Asian Pacific Journal of Cancer Prevention

Wang, Shi-Yong;Yang, Zhen-Jun;Zhang, Zhe;Zhang, Hui 10045

https://doi.org/10.7314/APJCP.2014.15.23.10045 PDF KSCI

Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

Yildirim, Julide Gulizar;Arabaci, Zeynep 10053

https://doi.org/10.7314/APJCP.2014.15.23.10053 PDF KSCI

The human papilloma virus (HPV) is the main aetiological agent for cervical cancer, one of the most frequent cancers observed in women throughout the world. There are effective programs for reducing the incidence of cervical cancer with HPV vaccination. The objective of this study was to discuss the applicability of the HPV vaccination and the role of nurses in prevention of cervical cancer. Use of bivalent and quadrivalent vaccines has been initiated against the types of HPV which are the primary cause of cancer. The quadrivalent HPV vaccination has entered into the routine vaccination schedule in many European countries for use in children and adolescents between 9-15 years of age and for women between 16-26 years of age, whereas it has been proposed that the bivalent vaccination should be given to girls between 9-18 years of age. While cervical cancer is among the cancers that can be prevented, it is essential to continue screening tests while introducing vaccination in a systematic manner for protection. On this subject, among the most important roles of nurses is to implement the screening programs by fulfilling the caregiving, training and consultancy roles for the society and especially, for high risk groups and to increase the awareness of the people.

uz Zaman, Maseeh;Fatima, Nosheen;Sajjad, Zafar;Zaman, Unaiza;Tahseen, Rabia;Zaman, Areeba 10057

https://doi.org/10.7314/APJCP.2014.15.23.10057 PDF KSCI

Positron emission tomography (PET) as the functional component of current hybrid imaging (like PET/CT or PET/MRI) seems to dominate the horizon of medical imaging in coming decades. $^{18}$Flourodeoxyglucose ($^{18}FDG$) is the most commonly used probe in oncology and also in cardiology and neurology around the globe. However, the major capital cost and exorbitant running expenditure of low to medium energy cyclotrons (about 20 MeV) and radiochemistry units are the seminal reasons of low number of cyclotrons but mushroom growth pattern of PET scanners. This fact and longer half-life of $^{18}F$ (110 minutes) have paved the path of a centralized model in which $^{18}FDG$ is produced by commercial PET radiopharmacies and the finished product (multi-dose vial with tungsten shielding) is dispensed to customers having only PET scanners. This indeed reduced the cost but has limitations of dependence upon timely arrival of daily shipments as delay caused by any reason results in cancellation or rescheduling of the PET procedures. In recent years, industry and academia have taken a step forward by producing low energy, table top cyclotrons with compact and automated radiochemistry units (Lab-on-Chip). This decentralized strategy enables the users to produce on-demand doses of PET probe themselves at reasonably low cost using an automated and user-friendly technology. This technological development would indeed provide a real impetus to the availability of complete set up of PET based molecular imaging at an affordable cost to the developing countries.

Salcedo, Mauricio;Pina-Sanchez, Patricia;Vallejo-Ruiz, Veronica;Monroy-Garcia, Alberto;Aguilar-Lemarroy, Adriana;Cortes-Gutierrez, Elva I.;Santos-Lopez, Gerardo;Montoya-Fuentes, Hector;Grijalva, Renan;Madrid-Marina, Vicente;Apresa-Garcia, Teresa;Hernandez, Dulce M.;Jave-Suarez, Luis F.;Romero, Pablo;Poot, Albros;Salgado, Eduardo;Ramos-Gonzalez, Patricia;Gonzalez-Hernandez, Rigoberto;Canton, Juan C.;Jimenez-Aranda, Lucio;Parra-Melquiadez, Miriam;Paniagua, Lucero;Mendoza, Monica;Arreola, Hugo;Villegas, Vanesa;Torres-Poveda, Kirvis;Bahena-Roman, Margarita;Gonzalez-Yebra, Beatriz;Taniguchi, Keiko;Rodea, Carlos;Mantilla-Morales, Alejandra;Mora-Garcia, Maria L.;Velazquez-Velazquez, Cindy K.;Cordova-Uscanga, Candelaria;Peralta, Raul;Lopez-Romero, Ricardo;Marrero, Daniel;Bandala, Cindy;Reyes-Leyva, Julio;Furuya, Maria E.;Almeida, Eduardo;Galvan, Maria E.;Grijalva, Israel 10061

https://doi.org/10.7314/APJCP.2014.15.23.10061 PDF KSCI

Background: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. Materials and Methods: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. Results: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. Conclusions: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Tabrizi, Ali Dastranj;Melli, Manijeh Sayyah;Foroughi, Meraj;Ghojazadeh, Morteza;Bidadi, Sanam 10067

https://doi.org/10.7314/APJCP.2014.15.23.10067 PDF KSCI

Background: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. Materials and Methods: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. Results: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. Conclusions: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.

Bayrami, Roghieh;Taghipour, Ali;Ebrahimipour, Hossein 10071

https://doi.org/10.7314/APJCP.2014.15.23.10071 PDF KSCI

Background: Cervical cancer has become a major public health problem worldwide. Iran, like other developing countries, is facing a number of challenges in managing the disease. This qualitative study documents challenges encountered in cervical cancer preventing programs in Iran. Materials and Methods: In-depth interviews were conducted with 28 participants including eleven patients with cervical cancer, three gynecologic oncologists, five specialists in Obstetrics and Gynecology, five midwives, three health care managers and one epidemiologist in Mashhad Iran, between May and December of 2012. The sample was selected purposively until data saturation was achieved. Data credibility verified via allocated sufficient time for data collection, using member checking and peer debriefing. Data analysis was carried out using conventional content analysis approach with ATLAS. ti software. Results: Findings from data analysis demonstrated 2 major themes and 6 categories about challenges of providing cervical cancer prevention programs including: individual and social challenges (cognitive/behavioral challenges and socio/cultural challenges) and health system challenges (stewardship, financing, competency of health care providers and access to services). Each category included some subcategories. Conclusions: Managing the cervical cancer prevention programs need to include the consideration of individuals, health care providers and health system challenges. Addressing the low level of knowledge, negative attitudes, socio cultural challenges, Poor intersectional collaboration and coordination and intra-sectional management, financing and competency of health care providers are essential steps toward significantly reducing the burdens of cervical cancer.

Zhang, Hao-Jie;Qian, Wei-Qing;Chen, Ran;Sun, Zhong-Quan;Song, Jian-Da;Sheng, Lu 10079

https://doi.org/10.7314/APJCP.2014.15.23.10079 PDF KSCI

Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasis and invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancer cells. Materials and Methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells. Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was used to estimate invasion and signaling pathways were studied by Western blotting. Results: ET-1 mRNA and protein in ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively. ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells. From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least related to some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 and MMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective than single treatment. Conclusions: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3 cells, but combined treatment might be a better therapeutic schedule.

Han, Jian-Jun;Xue, De-Wen;Han, Qiu-Rong;Liang, Xiao-Hong;Xie, Li;Li, Sheng;Wu, Hui-Yong;Song, Bao 10085

https://doi.org/10.7314/APJCP.2014.15.23.10085 PDF KSCI

Background: The insulin-like growth factor (IGF) system comprises a group of proteins that play key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. The aim of this study was to investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in hepatocellular carcinoma. Materials and Methods: Expression of IGF2, IGFBP3, and PTEN was analyzed by qRT-PCR. Lentivirus vectors were used to overexpress IGFBP3 in hepatocellular carcinoma cell (HCC) lines. The effect of IGFBP3 on proliferation was investigated by MTT and colony formation assays. Results: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells. Conclusions: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells.

Bravo, Eduardo Francisco;Saint-Pierre, Gustavo Enrique;Yaikin, Pabla Javiera;Meier, Martina Jose 10091

https://doi.org/10.7314/APJCP.2014.15.23.10091 PDF KSCI

Easter Island is a small island of $180km^2$, located 3,800 km from the Chilean coast and one of the most isolated inhabited places in the world. Since the mid-twentieth century, it has been undergoing an epidemiological transition in relation to the causes of death, from a predominance of infectious to non-communicable diseases (NCDs) such as cardiovascular ailments and cancer. The aim of this study is to describe the causes of death to Easter Island between 2000 and 2012, so the statistical records of Hanga Roa Hospital and death certificates were reviewed. The period under review of 13 years there was a total of 252 deaths, an average to 19.3 deaths per year. The most frequent causes of death found in the general population of Easter Island were cardiovascular diseases (25.4%), followed by neoplasms (23.4%), accidents (18.6%). Related to Rapa Nui people, cardiovascular and neoplastic diseases (both 26.7%) predominate, while in the population without belonging to the ethnic group the main causes were traumatic (25%) and cardiovascular (22.2%). Comparing the leading causes of death of Easter Island with mainland Chile, it can be seen how they resemble. Taking the island death profile, it is necessary to work on public health strategies aimed to this, considering that some of the causes are completely preventable.

Ozturk, Ahmet;Unalan, Demet;Guleser, Gulsum Nihal 10095

https://doi.org/10.7314/APJCP.2014.15.23.10095 PDF KSCI

Background: The present study was conducted to determine knowledge level of technicians working in hospitals about testicular cancer (TC) and self-examination of testicles (TSE) and to determine levels of consciousness and implementation status about TSE. Materials and Methods: This cross-sectional study was conducted with technicians working in hospitals (n=243) between $2^{nd}$ January-$31^{st}$ May 2012 at private and governmental hospitals in urban Kayseri. Healthy control subjects (n=235) who were similar to technicians in terms of age, education level and income status were also included to the study. Chi-square test was used in comparison of categorical variables. Results: Technicians were significantly more aware of TC than controls, but the latter were found to have significantly more information about TSE. There was no significant difference between the two groups in terms of knowing how to do TSE and 80% of both groups were unaware this exam. Of technicians, 19.8% and of controls, 25.5% did TSE, the difference being statistically insignificant. First reason for not doing TSE was "not-knowing" among technicians (48.1%) while it was "ignorance" among controls (66.8%). Of technicians doing TSE, 37.5% did as it came to their mind while 51.7% of controls performed TSE several times in the previous year. Technicians were significantly more afraid of getting TC than controls (p=0.037). Conclusions: It was determined in the present study that rates of TSE were similar between technicians and controls. However compliance with the recommended frequency and right method was low. Consequently, public health education should be planned and applied in order to increase the knowledge of TC and TSE.

Jung, Su Mi;Jo, Heui-Sug 10101

https://doi.org/10.7314/APJCP.2014.15.23.10101 PDF KSCI

The purpose of this study was to identify factors of intrinsic motivation that affect regular breast cancer screening and contribute to development of a program for strategies to improve effective breast cancer screening. Subjects were residing in South Korea Gangwon-Province and were female over 40 and under 69 years of age. For the investigation, the Intrinsic Motivation Inventory (IMI) was modified to the situation of cancer screening and was used to survey 905 inhabitants. Multinominal logistic regression analyses were conducted for regular breast cancer screening (RS), one-time breast cancer screening (OS) and non-breast cancer screening (NS). For statistical analysis, IBM SPSS 20.0 was utilized. The determinant factors between RS and NS were "perceived effort and choice" and "stress and strain" - internal motivations related to regular breast cancer screening. Also, determinant factors between RS and OS are "age" and "perceived effort and choice" for internal motivation related to cancer screening. To increase regular screening, strategies that address individual perceived effort and choice are recommended.

Bai, Rong-Pan;Weng, Yu;Su, Li-Ling;Jin, Ming-Juan;Xu, Zheng-Ping;Lu, Li-Qin;Chen, Guang-Di 10107

https://doi.org/10.7314/APJCP.2014.15.23.10107 PDF KSCI

MicroRNA-27a is highly expressed in cancers and has been identified as an oncogenic microRNA. A genetic variant in pre-miR-27a (rs895819) with a transition of A to G has been demonstrated to be associated with cancer risk; however, the results of these studies remain conflicting rather than conclusive. Therefore, we performed a meta-analysis to derive a more precise estimation. Through searching PubMed or other databases up to March 2014 using the following MeSH terms and keywords, "miR-27a", "polymorphism" and "cancer", seventeen case-control studies were identified in this meta-analysis, including 7,813 cases and 9,602. Crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to investigate the association strength between rs895819 and the susceptibility of cancer. The results of the overall meta-analysis did not suggest any association between rs895819 polymorphism and cancer susceptibility, and this remained in Asians as a subgroup. In Caucasians, however, the rs895819 was associated with a reduced cancer risk in heterozygous (OR, 0.83; 95%CI, 0.75-0.93) and dominant models (OR, 0.84; 95%CI, 0.76-0.93), and the [G] allele of rs895819 showed a protective effect (OR, 0.90, 95%CI, 0.84-0.97). Further studies showed a significant association between the [G] allele of rs895819 and decreased risk of breast cancer (0.91; 95%CI, 0.85-0.98), and stratified analyses indicated a protective effect of the [G] allele in Caucasians (OR, 0.89; 95%CI, 0.82-0.98), younger breast cancer cases (OR, 0.87; 95%CI, 0.79-0.96), and in the group of unilateral breast cancer patients (OR, 0.90; 95%CI, 0.83-0.97). These findings suggest an association between pre-miR-27a polymorphism rs895819 and cancer risk in Caucasians. The protective effect of rs895819 [G] allele in younger breast cancer and in the group of unilateral breast cancer patients await further confirmation since the included studies in this meta-analysis were limited.

Yang, Hui-Ying;Qu, Rong-Mei;Lin, Xiao-Shan;Liu, Tong-Xin;Sun, Quan-Quan;Yang, Chun;Li, Xiao-Hong;Lu, Wei;Hu, Xiao-Fang;Dai, Jing-Xing;Yuan, Lin 10115

https://doi.org/10.7314/APJCP.2014.15.23.10115 PDF KSCI

Purpose: The aim of this study was to investigate effects of adipose-derived mesenchymal stem cells (AMSCs) on radioresistance of breast cancer cells. Materials and Methods: MTT assays were used to detect any influence of AMSC supernatants on proliferation of breast cancer cells; cell migration assays were used to determine the effect of breast cancer cells on the recruitment of AMSCs; the cell survival fraction post-irradiation was assessed by clonogenic survival assay; ${\gamma}$-H2AX foci number post-irradiation was determined via fluorescence microscopy; and expression of IGF-1R was detected by Western blotting. Results: AMSC supernatants promoted proliferation and radioresistance of breast cancer cells. Breast cancer cells could recruit AMSCs, especially after irradiation. IGF-1 derived from AMSCs might be responsible for the radioresistance of breast cancer cells. Conclusions: Our results suggest that AMSCs in the tumor microenvironment may affect the outcome of radiotherapy for breast cancer in vitro.

Pishkuhi, Mahin Ahmadi;Salmaniyan, Soraya;Nedjat, Saharnaz;Zendedel, Kazem;Lari, Mohsen Asadi 10121

https://doi.org/10.7314/APJCP.2014.15.23.10121 PDF KSCI

Background: Cancers impose an increasing burden on health of the populations and individuals, but little is known about cancer patient satisfaction with care. The aim of this study was to assess the psychometric properties of the Persian version of European Organisation for Research and Treatment of Cancer (EORTC) In-Patsat32, as a recently developed questionnaire to assess cancer patient satisfaction with care and information provided during hospital admission. Materials and Methods: Complying with EORTC protocols, the Persian version of Inpatsat32 was translated and piloted in a small group of patients, then applied to 380 cancer patients admitted to different oncology wards in Tehran. Validity (convergent, discriminant, and divergent) and reliability of the tool was assessed through using multitrait analysis, factor analysis, intraclass correlations, Chronbach's alpha and test-retest (on a sample of 70 patients). Results: Good acceptance and high sensitivity of the questionnaire with low floor and ceiling effects were recognized, indicating power of the instrument to detect differences between groups with heterogeneous levels of satisfaction. Multitrait scaling analyses supported the convergent validity of the majority of scales (correlation coefficient >0.4) and favorable discriminant validity (item own scale correlation >0.8). There was no correlation between In-patsat32 scales and the EORTC-C30, which measures different concepts, confirming divergent validity of the tool. Internal consistency for all domains was high (${\alpha}$ >0.70) except for the hospital access score and the test-retest reliability was excellent (r=0.86-0.96). There was a weak responsiveness to change except for nurses technical skills. Principle component analysis confirmed five domains with much improved internal consistency (${\alpha}$ >0.9). Conclusions: The Persian version of the EORTC-in-patsat32 module is a reliable and valid instrument to measure cancer patient satisfaction with care received during their hospitalization period and can be utilized in clinical cancer research.

Tiwari, Ram Vinod;Megalamanegowdru, Jayachandra;Gupta, Anjali;Agrawal, Ankush;Parakh, Abhinav;Pagaria, Sulabh;Sahu, Abhishek 10129

https://doi.org/10.7314/APJCP.2014.15.23.10129 PDF KSCI

Background: Tobacco is a leading preventable cause of deaths worldwide; the situation is particularly serious in the developing countries. Tobacco use amongst the children and adolescents is already a pandemic and they are vulnerable targets of tobacco industry. This is also the case in India. Objectives: 1) Document and monitor the prevalence of tobacco use including smoked, smokeless and other forms of tobacco; 2) Understand student knowledge and attitudes related to tobacco use and its health impact; 3) Assess the impact of tobacco on the oral health status of school-going children in India. Materials and Methods: The sample was 1,500 school children of the age group 12-15 years age. A pretested, close ended questionnaire was administered in the form of extensive face to face interview to understand student knowledge, attitudes and behavior related to tobacco use and its health impact and to assess the prevalence of tobacco use including smoked, smokeless and other forms of tobacco. Oral health status was assessed using the Community Periodontal Index (CPI). Frequency distribution, Chi-square tests and Odd's ratio was calculated. Results: Prevalence of tobacco usage amongst the prevalence was 20.4%: 9.2% reported smoking, 15.8% used tobacco in the chewable form and 25.3% children were involved in consuming betel nut/areca nuts. The OR (Odd's ratio) for calculus formation was highest for guthka chewers (OR=14.322), paan masala chewers had the highest odds of developing bleeding on probing when compared to the others. Conclusions: There is an urgent need to launch school-based tobacco prevention programs for community awareness of children and the public, as preventing the initiation of a habit is far easier than stopping it.

Kelotra, Seema;Jain, Meeta;Kelotra, Ankit;Jain, Ish;Bandaru, Srinivas;Nayarisseri, Anuraj;Bidwai, Anil 10137

https://doi.org/10.7314/APJCP.2014.15.23.10137 PDF KSCI

Apoptosis is a general phenomenon of all multicellular organisms and caspases form a group of important proteins central to suicide of cells. Pathologies like cancer, Myocardial infarction, Stroke, Sepsis, Alzheimer's, Psoriasis, Parkinson and Huntington diseases are often associated with change in caspase 3 mediated apoptosis and therefore, caspases may serve as potential inhibitory targets for drug development. In the present study, two series of synthetic acetylated tetrapeptides containing aldehyde and fluromethyl keto groups respectively at the C terminus were proposed. All these compounds were evaluated for binding affinity against caspase 3 structure. In series 1 compound Ac-DEHD-CHO demonstrated appreciable and high binding affinity (Rerank Score: -138.899) against caspase 3. While in series 2 it was Ac-WEVD-FMK which showed higher binding affinity (Rerank Score: -139.317). Further these two compounds met ADMET properties and demonstrated to be non-toxic.

Zhang, Shao-Kai;Guo, Lan-Wei;Chen, Qiong;Zhang, Meng;Liu, Shu-Zheng;Quan, Pei-Liang;Lu, Jian-Bang;Sun, Xi-Bin 10143

https://doi.org/10.7314/APJCP.2014.15.23.10143 PDF KSCI

Background and Aim: No firm evidence of HPV infection in esophageal cancer has been established to date. The aim of this meta-analysis was to investigate the prevalence of HPV 16 in esophageal cancer in China, which had a high burden of the disease. Materials and Methods: Studies on HPV infection and esophageal cancer were identified and a random-effects model was used to pool the summary prevalence and corresponding 95% confidence intervals (CIs). Results: A total of 3,429 esophageal cancer cases were evaluated from 26 eligible studies in this meta-analysis. The summary estimate for HPV16 prevalence was 0.381 (95% CI: 0.283, 0.479). The prevalence varied by geographical areas of the study, publication year, HPV detection method and types of specimen. In sensitivity analysis, HPV 16 prevalence ranged from 0.368 (95% CI: 0.276, 0.460) to 0.397 (95% CI: 0.286, 0.508). Conclusions: The results indicate a relatively high level of HPV 16 prevalence in esophageal cancer among Chinese population, although there was variation between different variables. Further studies are needed to elucidate the role of HPV in esophageal carcinogenesis with careful consideration of study design and laboratory detection method, providing more accurate assessment of the HPV status in esophageal cancer.

Li, Yao-Ping;Tian, Fu-Guo;Shi, Peng-Cheng;Guo, Ling-Yun;Wu, Hai-Ming;Chen, Run-Qi;Xue, Jin-Ming 10151

https://doi.org/10.7314/APJCP.2014.15.23.10151 PDF KSCI

4-Hydroxynonenal (4-HNE) is a stable end product of lipid peroxidation, which has been shown to play an important role in cell signal transduction, while increasing cell growth and differentiation. 4-HNE could inhibit phosphatase and tensin homolog (PTEN) activity in hepatocytes and increased levels have been found in human invasive breast cancer. Here we report that 4-HNE increased the cell growth of breast cancer cells as revealed by colony formation assay. Moreover, vascular endothelial growth factor (VEGF) expression was elevated, while protein levels of hypoxia inducible factor 1 alpha (HIF-$1{\alpha}$) were up-regulated. Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, is reported to destabilize HIF-$1{\alpha}$. Here, 4-HNE could inhibit the deacetylase activity of SIRT3 by thiol-specific modification. We further demonstrated that the regulation by 4-HNE of levels of HIF-$1{\alpha}$ and VEGF depends on SIRT3. Consistent with this, 4-HNE could not increase the cell growth in SIRT3 knockdown breast cancer cells. Additionally, 4-HNE promoted angiogenesis and invasion of breast cancer cells in a SIRT3-dependent manner. In conclusion, we propose that 4-HNE promotes growth, invasion and angiogenesis of breast cancer cells through the SIRT3-HIF-$1{\alpha}$-VEGF axis.

Donnelly, Tam Truong;Al Khater, Al-Hareth;Al-Bader, Salha Bujassoum;Al Kuwari, Mohammed Ghaith;Malik, Mariam;Al-Meer, Nabila;Singh, Rajvir;Fung, Tak 10157

https://doi.org/10.7314/APJCP.2014.15.23.10157 PDF KSCI

Background: Breast cancer is the most common cancer among women in the State of Qatar. Due to low participation in breast cancer screening (BCS) activities, women in Qatar are often diagnosed with breast cancer at advanced stages of the disease. Findings indicate that low participation rates in BCS activities are significantly related to women's low level of awareness of breast cancer screening. The objectives of this study were to: (1) determine the factors that influence Qatari women's awareness of breast cancer and its screening activities: and (2) to find ways to effectively promote breast cancer screening activities among Arabic speaking women in Qatar. Materials and Methods: A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) female Qatari citizens and non-Qatari Arabic-speaking residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Outcome measures included participant awareness levels of the most recent national recommended guidelines of BCS, participation rates in BCS activities, and factors related to awareness of BCS activities. Results: While most participants (90.7%) were aware of breast cancer, less than half had awareness of BCS practices (28.9% were aware of breast self-examination and 41.8% of clinical breast exams, while 26.4% knew that mammography was recommended by national screening guidelines. Only 7.6% had knowledge of all three BCS activities). Regarding BCS practice, less than one-third practiced BCS appropriately (13.9% of participants performed breast self-examination (BSE) monthly, 31.3% had a clinical breast exam (CBE) once a year or once every two years, and 26.9% of women 40 years of age or older had a mammogram once every year or two years). Awareness of BCS was significantly related to BCS practice, education level, and receipt of information about breast cancer and/or BCS from a variety of sources, particularly doctors and the media. Conclusions: The low levels of participation rates in BCS among Arab women in this study indicate a strong need to increase awareness of the importance of breast cancer screening in Qatari women. Without this awareness, compliance with the most recent breast cancer screening recommendations in Qatar will remain low. An increased effort to implement mass media and public health campaigns regarding the impact of breast cancer on women's health and the benefits of early detection of breast cancer must be coupled with an enhanced participation of health care providers in delivering this message to Qatar population.

Ordu, Cetin;Pilanci, Kezban Nur;Koksal, Ulkuhan Iner;Okutur, Kerem;Saglam, Sezer;Tecimer, Coskun;Demir, Gokhan 10165

https://doi.org/10.7314/APJCP.2014.15.23.10165 PDF KSCI

Background: Megestrol acetate (MA) is a steroid origin medicine often used for control of cachexia in oncologic palliative care. Thrombosis is a common problem in oncology patients. One question is whether MA can cause thrombosis. This retrospective, registry-based analysis was therefore conducted to assess thrombotic processes in oncology patients using MA concurrent with chemotherapy. Materials and Methods: Data on oncology patients at the metastatic stage using MA were obtained from the archives of our center. Outcomes of patients were evaluated for thromboembolic events (VTEs) during treatment. Results: Ninety-seven oncology patients with a median age of 62 (33-84) years were included. During the median follow-up of 17 months, 58 (59.8%) died leaving 39 (31.2%) still alive. Median overall survival (OS) was 19 months (6-180). Mean time of MA use was 8.69 months(${\pm}3.53$), with a median dose of 160mg (range 160-480mg). Eleven VTEs were detected after MA use, 4 of these in pancreatic cancer cases. The patients with thrombosis non-significantly had worse OS, than those without thrombosis (p=0.106). Conclusions: This trial revealed that the 11.3% of all patients developed thrombosis,who had been treated with MA and chemotherapy concomittantly. There was no statistically significant difference regarding to occurrence of thrombotic process, among the patients receiving different chemotherapy regimens with MA concomittantly. Pancreatic cancer seemed to be related to thrombosis rather than MA use.

Motono, Nozomu;Ueno, Masakatsu;Tanaka, Makoto;Machida, Yuichiro;Usuda, Katsuo;Sakuma, Tsutomu;Sagawa, Motoyasu 10171

https://doi.org/10.7314/APJCP.2014.15.23.10171 PDF KSCI

Background: The purpose of this study was to determine the prognostic significance of the maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients undergoing surgical treatment for non-small cell lung cancer. Materials and Methods: Seventy-eight consecutive patients (58 with adenocarcinomas, 20 with squamous cell carcinomas) treated with potentially curative surgery were retrospectively reviewed. Results: The SUVmax was significantly higher in the patients with recurrent than with non-recurrent adenocarcinoma (p<0.01). However, among the patients with squamous cell carcinoma, there were no differences with or without recurrence (p=0.69). Multivariate analysis indicated that the SUVmax of adenocarcinoma lesions was a significant predictor of disease-free survival (p=0.04). In addition, an SUVmax of 6.19, the cut-off point based on ROC curve analysis of the patients with pathological IB or more advanced stage adenocarcinomas, was found to be a significant predictor of disease-free survival (p<0.01). Conclusions: SUVmax is a useful predictor of disease-free survival in patients with resected adenocarcinoma, but not squamous cell carcinoma. Patients with adenocarcinoma exhibiting an SUVmax above 6.19 are candidates for more intensive adjuvant therapy.

Du, Shu-Li;Geng, Ting-Ting;Feng, Tian;Chen, Cui-Ping;Jin, Tian-Bo;Chen, Chao 10175

https://doi.org/10.7314/APJCP.2014.15.23.10175 PDF KSCI

Background: The association between the RTEL1 rs6010620 single nucleotide polymorphism (SNP) and glioma risk has been extensively studied. However, the results remain inconclusive. To further examine this association, we performed a meta-analysis. Materials and Methods: A computerized search of the PubMed and Embase databases for publications regarding the RTEL1 rs6010620 polymorphism and glioma cancer risk was performed. Genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analyses, tests of heterogeneity, cumulative meta-analyses, and assessments of bias were performed in our meta-analysis. Results: Our meta-analysis confirmed that risk with allele A is lower than with allele G for glioma. The A allele of rs6010620 in RTEL1 decreased the risk of developing glioma in the 12 case-control studies for all genetic models: the allele model (OR=0.752, 95%CI: 0.715-0.792), the dominant model (OR=0.729, 95%CI: 0.685-0.776), the recessive model (OR=0.647, 95%CI: 0.569-0.734), the homozygote comparison (OR=0.528, 95%CI: 0.456-0.612), and the heterozygote comparison (OR=0.761, 95%CI: 0.713-0.812). Conclusions: In all genetic models, the association between the RTEL1 rs6010620 polymorphism and glioma risk was significant. This meta-analysis suggests that the RTEL1 rs6010620 polymorphism may be a risk factor for glioma. Further functional studies evaluating this polymorphism and glioma risk are warranted.

Lian, Hai-Wei;Zhou, Yun;Jian, Zhi-Hong;Liu, Ren-Zhong 10181

https://doi.org/10.7314/APJCP.2014.15.23.10181 PDF KSCI

Background: MicroRNAs, small noncoding RNA molecules, can regulate mammalian cell growth, apoptosis and differentiation by controlling the expression of target genes. The aim of this study was to investigate the function of miR-323-5p in the glioma cell line, U251. Materials and Methods: After over-expression of miR-323-5p using miR-323-5p mimics, cell growth, apoptosis and migration were tested by MTT, flow cytometry and cell wound healing assay, respectively. We also assessed the influence of miR-323-5p on the mRNA expression of IGF-1R by quantitative real-time reverse transcriptase PCR (qRT-PCR), and on the protein levels by Western blot analysi. In addition, dual-luciferase reporter assays were performed to determine the target site of miR-323-5p to IGF-1R 3'UTR. Results: Our findings showed that over-expression of miR-323-5p could promote apoptosis of U251 and inhibit the proliferation and migration of the glioma cells. Conclusions: This study demonstrated that increased expression of miR-323-5p might be related to glioma progression, which indicates a potential role of miR-323-5p for clinical therapy.

Khenjanta, Chakkaphan;Thanan, Raynoo;Jusakul, Apinya;Techasen, Anchalee;Jamnongkan, Wassana;Namwat, Nisana;Loilome, Watcharin;Pairojkul, Chawalit;Yongvanit, Puangrat 10187

https://doi.org/10.7314/APJCP.2014.15.23.10187 PDF KSCI

Cytochrome P450 (CYP) enzymes are a large family of constitutive and inducible mono-oxygenase enzymes that play a central role in the oxidative metabolism of both xenobiotic and endogenous compounds. Several CYPs are involved in metabolism of oxysterols, which are cholesterol oxidation products whose expression may be dysregulated in inflammation-related diseases including cancer. This study focused on CYP39A1, which can metabolize 24-hydroxycholesterol (24-OH) that plays important roles in the inflammatory response and oxidative stress. We aimed to investigate the expression status of CYP39A1 and its transcription factor (RUNX2) in relation to clinical significance in cholangiocarcinoma (CCAs) and to determine whether 24-OH could induce oxidative stress in CCA cell lines. Immunohistochemistry showed that 70% and 30% of CCA patients had low and high expression of CYP39A1, respectively. Low expression of CYP39A1 demonstrated a significant correlation with metastasis. Our results also revealed that the expression of RUNX2 had a positive correlation with CYP39A1. Low expression of both CYP39A1 (70%) and RUNX2 (37%) was significantly related with poor prognosis of CCA patients. Interestingly, oxidized alpha-1 antitrypsin (ox-A1AT), an oxidative stress marker, was significantly increased in CCA tissues in which CYP39A1 and RUNX2 were down regulated. Additionally, immunocytochemistry showed that 24-OH could induce ox-A1AT in CCA cell lines. In conclusion, our study revealed putative roles of the CYP39A1 enzyme in prognostic determination of CCAs.

Nikfarjam, Zahra;Massoudi, Toktam;Salehi, Maryam;Salehi, Mahta;Khoshroo, Fahimeh 10193

https://doi.org/10.7314/APJCP.2014.15.23.10193 PDF KSCI

Background: Cancer is a major cause of mortality in developing countries and correct and valid information about the epidemiology of this disease is the first step in the planning of health care in each region. The aim of this study was to determine the relative frequency, mean age and sex ratio of the most 10 common non-skin cancers in the world and Iran, among patients referred to an oncology clinic. Materials and Methods: This descriptive study was conducted in Mashhad, north east of Iran. The data obtained from the records of patients referred to the private oncology center between the years of 1985-2012". According to the latest report of GLOBOCAN study commonest malignancies included were lung, breast, colorectal, prostate, stomach, liver, cervix, esophageal, bladder cancers and Non-Hodgkin lymphoma. Results: A total of 4,606 cases were analyzed. The mean age was $55.5{\pm}13.8years$ (male: $59.5{\pm}13.9$, female: $52.6{\pm}12.9$). Overall, breast cancer (1,264 cases, relative frequency of 27.4%) was the most prevalent cancer; however the mean ages of diagnosis were not significantly different between 5-year time period divisions (p=0.290). The most common cancer in men was esophageal cancer (26.3%).The lowest mean age was related to women diagnosed with breast cancer ($48.5{\pm}11.8$) and men with non-Hodgkins lymphoma ($48.4{\pm}17.8$). There were statistically significant differences between the mean age of men and women with gastric (p=0.003) and esophageal cancers (p<0.001). Male to female sex ratios in our study for bladder, lung and stomach cancers were 6.57, 2.60 and 2.50 respectively. Conclusions: The results showed that breast cancer tends to be found in younger female patients and bladder cancer appears more often in men. Screening in target population in addition to early diagnosis may reduce death and disability.

Kudubes, Asli Akdeniz;Bektas, Murat;Ugur, Ozlem 10199

https://doi.org/10.7314/APJCP.2014.15.23.10199 PDF KSCI

Background: This study was planned in an attempt to develop scales for the assessment of fatigue in pediatric oncology patients aged 7-12 as well as for their parents. Materials and Methods: In collecting the study data, we used the Child and Parent Information Form, Visual Fatigue Scale, Scale for the Assessment of Fatigue in Pediatric Oncology Patients Aged 7-12 and the Scale for the Assessment of Fatigue in Pediatric Oncology Patients Aged 7-12 for Parents. We also used Pearson correlation analysis, the Cronbach Alpha coefficient, Factor Analysis and ROC Analysis for the study data. Results: In this study, the total Cronbach alpha value of the parent form was 0.95, the total factor load was 0.52-0.95 and the total variance being explained was 85.7%. The cutoff point of the parent form was 82 points. The total Cronbach alpha value of the child form was 0.98, the total factor load was 0.71-0.94 and the total variance being explained was 84.7%. The cutoff point of the child form was 75 points. Conclusions: This study suggests that our scales for the assessment of fatigue in pediatric oncology patients aged 7-12 and their parents are valid and reliable instruments.

Jeng, Jen-Eing;Wu, Hui-Fang;Tsai, Meng-Feng;Tsai, Huey-Ru;Chuang, Lea-Yea;Lin, Zu-Yau;Hsieh, Min-Yuh;Chen, Shinn-Chern;Chuang, Wan-Lung;Wang, Liang-Yen;Yu, Ming-Lung;Dai, Chia-Yen;Tsai, Jung-Fa 10209

https://doi.org/10.7314/APJCP.2014.15.23.10209 PDF KSCI

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

Liu, Hai-Ou;Wu, Qian;Liu, Wei-Si;Liu, Yi-Dong;Fu, Qiang;Zhang, Wei-Juan;Xu, Le;Xu, Jie-Jie 10217

https://doi.org/10.7314/APJCP.2014.15.23.10217 PDF KSCI

Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.

Qureshi, Z.;Mahjabeen, I.;Baig, R.M.;Kayani, M.A. 10225

https://doi.org/10.7314/APJCP.2014.15.23.10225 PDF KSCI

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

Heng, Suttichai;Benjapibal, Mongkol 10231

https://doi.org/10.7314/APJCP.2014.15.23.10231 PDF KSCI

This study aimed to evaluate the prevalence of preoperative thrombocytosis and its prognostic significance in Thai patients with endometrial cancer. We retrospectively reviewed the medical records of 238 cases who had undergone surgical staging procedures between January 2005 and December 2008. Associations between clinicopathological variables and preoperative platelet counts were analyzed using Pearson's chi square or two-tailed Fisher's exact tests. Survival analysis was performed with Kaplan-Meier estimates. Univariate and Cox-regression models were used to evaluate the prognostic impact of various factors including platelet count in terms of disease-free survival and overall survival. The mean preoperative platelet count was $315,437/{\mu}L$ (SD $100,167/{\mu}L$). Patients who had advanced stage, adnexal involvement, lymph node metastasis, and positive peritoneal cytology had significantly higher mean preoperative platelet counts when compared with those who had not. We found thrombocytosis (platelet count greater than $400,000/{\mu}L$) in 18.1% of our patients with endometrial cancer. These had significant higher rates of advanced stage, cervical involvement, adnexal involvement, positive peritoneal cytology, and lymph node involvement than patients with a normal pretreatment platelet count. The 5-year disease-free survival and overall survival were significantly lower in patients who had thrombocytosis compared with those who had not (67.4% vs. 85.1%, p=0.001 and 86.0% vs. 94.9%, p=0.034, respectively). Thrombocytosis was shown to be a prognostic factor in the univariate but not the multivariate analysis. In conclusion, presence of thrombocytosis is not uncommon in endometrial cancer and may reflect unfavorable prognostic factors but its prognostic impact on survival needs to be clarified in further studies.

Bashir, Muhammad Naeem;Ahmad, Muhammad Riaz;Malik, Akram 10237

https://doi.org/10.7314/APJCP.2014.15.23.10237 PDF KSCI

Background: Prostate cancer is the third most commonly diagnosed cancer among males in Pakistan but very little is known about risk factors among the Pakistani population. Therefore a hospital-based, case-control study was carried out in Faisalabad to identify potential risk factors. Materials and Methods: This study was based on 140 prostate cancer cases and 280 normal controls. Logistic regression was used to estimate odds ratios and 95% confidence intervals for odds ratios to assess the relationship between prostate cancer and different risk factors. Results: Family history of prostate cancer, age, smoking, obesity, consumption of red meat and frequent use of fat items significantly increased the prostate cancer risk (odds ratios and 95% confidence intervals of: 7.32; 1.79-29.8; 16.9, 5.60-50.8; 2.47, 1.17-5.18; 5.79, 2.66-12.6; 2.71, 1.07-6.91; and 3.39, 1.47-7.83, respectively. On the other hand, more consumption of fruit, fluid intake and better lifestyle (physical activity) significantly reduced the risk of developing prostate cancer with odd ratios and corresponding 95% confidence intervals of: 0.27, 0.11-0.61; 0.05, 0.02-0.12; and 0.28, 0.13-0.58. Conclusions: The results of the present study suggested that age, family history of prostate cancer, smoking, obesity, fluid intake, frequent use of fat items, consumption of fruits and better lifestyle might be associated with prostate cancer among Pakistani males.

Liu, Jin;Huang, Xin-En 10241

https://doi.org/10.7314/APJCP.2014.15.23.10241 PDF KSCI

Objective: To investigate the efficacy and side effects of Bifidobacterium tetragenous viable bacteria tablets in treating cancer patients with functional constipation during chemotherapy. Methods: A consecutive cohort of 100 cancer patients with functional constipation were divided into two equal groups: patients in the experimental group were given Bifidobacterium tetragenous viable bacteria tablets combined with chemotherapy, while patients in the control group received chemotherapy alone. After 4 weeks, the efficacy and side effects in treating functional constipation were evaluated. Results: Constipation in 48 patients in experimental group was controlled (9 returned to normal), with a total response rate of 96%, and 1 patient reported diarrhea (2%). In contrast only 16 patients in the control group demonstrated improvement and 34 were still constipated after chemotherapy, with a response rate of 32%. The difference in response rate was statistically significant (P<0.05). Conclusion: This study suggested that Bifidobacterium tetragenous viable bacteria tablets are effective and safe in treating cancer patients with functional constipation during chemotherapy.

Meng, Xian-Guo;Yue, Shou-Wei 10245

https://doi.org/10.7314/APJCP.2014.15.23.10245 PDF KSCI

Background: Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. Materials and Methods: The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Results: Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Conclusions: Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.

George, Mathew;Asab, Nihad Abu;Varughese, Elizabeth;Irwin, Matthew;Oldmeadow, Christopher;Hollebone, Keith;Apen, Kenneth;Renner, Stefan 10251

https://doi.org/10.7314/APJCP.2014.15.23.10251 PDF KSCI

Uterine cancer is the most common invasive gynaecological cancer in Australia. Early detection is a key predictive factor achieved by increasing public awareness and participation in screening. This observational study measures awareness of gynaecological malignancies, particularly uterine, among women in two rural areas of New South Wales, Australia. Patients presenting to gynaecology clinics in January to March 2014 were invited to complete a structured questionnaire. Women with a history of cancer and incomplete questionnaires were excluded. Of the 382 patients invited to participate, 329 (86%) responded with complete feedback. Most respondents were younger than than 50 years (66%) and married with at least 2 children (74%). The majority (94%) of participants had no awareness of uterine cancer and many (46%) were unable to identify common risk factors including obesity, diabetes and hypertension. The ability to identify risk factors was correlated to age, marital status and obesity. The study identifies poor awareness on uterine malignancies in two typical areas of rural Australia. Although external validity is limited by sociological factors, poor awareness of uterine cancer among rural patients in this study represents a valid public health concern. It is imperative to improve awareness of uterine cancer and available screening programs to facilitate early detection and cure.

Ekalaksananan, Tipaya;Jungpol, Watcharapol;Prasitthimay, Chuthamas;Wongjampa, Weerayut;Kongyingyoes, Bunkerd;Pientong, Chamsai 10255

https://doi.org/10.7314/APJCP.2014.15.23.10255 PDF KSCI

High risk human papillomavirus (HR-HPV) E2 proteins play roles in transcriptional regulation and are commonly functionally disrupted when the HPV genome integrates into host chromosomes. Some 15-40% of cancer cases, however, contain an intact E2 gene or episomal HPV. In these cases, polymorphism of the E2 gene might be involved. This study aimed to determine polymorphisms of the E2 gene in episomal HPV16 detected in high grade squamous intraepithelial lesions and squamous cell carcinomas and altered functions compared to the E2 prototype. The E2 gene was amplified and sequenced. Two expression vectors containing E2 gene polymorphisms were constructed and transfected in SiHa and C33A cells, then E6 gene as well as Il-10 and TNF-${\alpha}$ expression was determined by quantitative RT-PCR. Expression vectors and reporter vectors containing the HPV16 long control region (LCR) were co-transfected and transcriptional activity was determined. The results showed that a total of 32 nucleotides and 23 amino acids were changed in all 20 cases of study, found in the transactivation (TA) domain, hinge (H) region and DNA binding (DB) domain with 14, 5 and 13 nucleotide positions. They mostly caused amino acid change. The expressing vectors containing different E2 gene polymorphisms showed E6 mRNA suppression, TNF-${\alpha}$ mRNA suppression and IL-10 induction but no statistically significant differences when compared to the E2 prototype. Moreover, promoter activity in HPV16 LCR was not affected by E2 protein with different gene polymorphisms, in contrast to nucleotide variations in LCR that showed an effect on transcription activity. These results demonstrated that E2 gene polymorphisms of episomal HPV16 did not affect transcriptional regulation and suggested that nucleotide variation as well as epigenetic modification of the LCR might play a role in inducing malignant transformation of cells containing episomal HPV16.

Phua, Chee Ee;Tang, Weng Heng;Yusof, Mastura Md.;Saad, Marniza;Alip, Adlinda;See, Mee Hoong;Taib, Nur Aishah 10263

https://doi.org/10.7314/APJCP.2014.15.23.10263 PDF KSCI

Background: The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test. Results: Between $1^{st}$ January 2002 and $31^{st}$ December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319). Conclusions: In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

Jing, Jie-Xian;Wang, Yan;Xu, Xiao-Qin;Sun, Ting;Tian, Bao-Guo;Du, Li-Li;Zhao, Xian-Wen;Han, Cun-Zhi 10267

https://doi.org/10.7314/APJCP.2014.15.23.10267 PDF KSCI

To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

Xu, Chong-De 10273

https://doi.org/10.7314/APJCP.2014.15.23.10273 PDF KSCI

Objective: To explore the clinical effects of nimotuzumab combined with chemotherapy in the treatment of late gastric cancer. Methods: A total of 34 reoccurrence or metastatic patients with late stage gastric cancer who were confirmed by histopathology and/or cytology were selected and randomly divided into observational and control groups, of 17 cases each. Patients in the control group were treated with the standard DCF plan, while patients in observational group additionally received nimotuzumab. The short-term and long-term efficacy and adverse reactions in the 2 groups were followed. Results: The objective response rate (ORR) and disease control rate (DCR) were 64.7% (11/17) and 82.4% (14/17) in observational group and 25.0%(4/16) and 37.5%(6/16) in the control group(ORR and DCR between 2 groups, ${\chi}^2=5.2412$, P=0.0221 and ${\chi}^2=6.9453$, P=0.0084). The median progression-free survival (PFS) time and median overall survival (OS) time were 6.50 months and 12.50 months in observational group and 4.50 months and 8.25 months in the control group (P=0.0212; P=0.0255). The main toxic and side effects in the 2 groups were reduced leukocytes and hemoglobin, gastrointestinal reactions and hair loss and these were relieved after symptomatic treatment and nutrition support therapy. There were no differences in the occurrence of toxic and side effects between the 2 groups. Conclusions: Nimotuzumab combined with DCF plan is effective in treating late stage gastric cancer. A larger scale study is now warranted for confirmation of the findings.

Petric, Militza;Martinez, Santiago;Acevedo, Francisco;Oddo, David;Artigas, Rocio;Camus, Mauricio;Sanchez, Cesar 10277

https://doi.org/10.7314/APJCP.2014.15.23.10277 PDF KSCI

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Barghi, Leila;Asgari, Davoud;Barar, Jaleh;Nakhlband, Aylar;Valizadeh, Hadi 10281

https://doi.org/10.7314/APJCP.2014.15.23.10281 PDF KSCI

Background: Development of a nanosized polymeric delivery system for erlotinib was the main objective of this research. Materials and Methods: Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) copolymers with different compositions were synthesized via ring opening polymerization. Formation of triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers with solvent displacement method. Results: Physicochemical properties of obtained polymeric nanoparticles were dependent on composition of used copolymers. Size of particles was decreased with decreasing the PCL/PEG molar ratio in used copolymers. Encapsulation efficiency of prepared formulations was declined by decreasing their particle size. Drug release behavior from the prepared nanoparticles exhibited a sustained pattern without a burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles is decreased by increase of CL/PEG molar ratio of prepared block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be $14.8{\mu}M$. Conclusions: From the obtained results, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as delivery system for erlotinib.

Bixofis, Regiane B.;Sassi, Laurindo Moacir;Patussi, Cleverson;Jung, Juliana E.;Ioshii, Sergio O.;Schussel, Juliana L. 10289

https://doi.org/10.7314/APJCP.2014.15.23.10289 PDF KSCI

Background: The involvement of HPV in oral and oropharyngeal carcinogenesis was first proposed in 2004, based on epithelial HPV tropism and detection of HPV genotypes in oral squamous cell carcinoma samples. While 60-70% of oropharynx tumors may be HPV-positive, only 10 to 19% of tumors of the oral cavity, larynx and hypopharynx appear to have HPV infection. The aim of the study was to evaluate HPV infection associated with oropharyngeal cancer. Materials and Methods: Seventy-eight cases were selected for p16 immunoexpression reactions, and demographic data were collected for comparisons. Results: Most patients were over 60 years old, and 64.1% were smokers. Immunohistochemistry results showed that 86.3% of cases stained positive for p16 protein. Conclusion: The oropharyngeal cancer profile at Erasto Gaertner Hospital presented a high index of smokers over 60 years as well a high number of p16+ tumors, for what we can not determinate the main etiologic factor, but can be aware of the number of patients that presented HPV infection. Since prevention is still the best way to deal with cancer disease, it is important to analyze the interaction of these two etiologic factors and how to detect lesions at an early stage.

Chu, Ke-Tan;Song, Yang;Zhou, Jian-Hong 10293

https://doi.org/10.7314/APJCP.2014.15.23.10293 PDF KSCI

Background: Previous epidemiologic studies on the association between energy intake and endometrial cancer risk have only generated contradictory results. The role of energy intake in endometrial carcinogenesis thus remains unclear. To quantitatively assess the potential association between energy intake and endometrial cancer, a meta-analysis of case-control and cohort studies was here conducted. Materials and Methods: Eligible studies were retrieved via both computerized searches and review of references. Fixed-or random-effect models were used to summarize the estimates of OR with 95%CIs. Stratified analyses on study design, region and macronutrients' calorie were performed. Results: Sixteen studies met the inclusion criteria of the meta-analysis. No association between total energy intake and endometrial cancer was observed in either overall group (OR=1.11, 95%CI 0.92-1.30) or subgroups stratified by study design and region. In the specific macronutrients' calorie analysis, higher fat energy intake was found to be associated with increased endometrial risk (OR=1.72, 95%CI 1.12-2.32) while energy from carbohydrate and protein was not related to endometrial cancer risk. Conclusions: Our analysis did not support that total energy intake is related to endometrial cancer risk, in contrast to fat energy.

Sheyhidin, Ilyar;Hasim, Ayshamgul;Zheng, Feng;Ma, Hong 10299

https://doi.org/10.7314/APJCP.2014.15.23.10299 PDF KSCI

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

Kayilioglu, Selami Ilgaz;Dinc, Tolga;Sozen, Isa;Senol, Kazim;Katar, Kagan;Karabeyoglu, Melih;Tez, Mesut;Coskun, Faruk 10307

https://doi.org/10.7314/APJCP.2014.15.23.10307 PDF KSCI

Background: The Bethesda System for Reporting Thyroid Cytopathology is one of the main classification systems for thyroid nodules. It expects that 7% of all fine needle aspiration biopsies will be reported as atypia or follicular lesions of undetermined significance, and 5-15% of these undetermined nodules are malignant. Our study is a retrospective analysis of variables that may be associated with outcome in patients with indeterminate thyroid nodules. Materials and Methods: Patients who underwent thyroidectomy in our institution between 2010 and 2014 were retrieved from the institutional records database. Patient demographics and medical histories were recorded. All ultrasonography reports were examined for nodule features and biochemical blood levels, hormone levels and complete blood counts were recorded. Results: A total of 103 patient cytopathology reports were regarded as belonging to the undetermined category. Some 35% of patients had malignant nodules. Median preoperative red cell distribution width (RDW) level was 13.6 inthe benign group, while it was 14.3 in patients with malignancy, demonstrating a significant correlation (p=0.003). Only calcification presence was significantly different between benign and malignant groups on ultrasonography (p=0.034). Conclusions: Ultrasonography is one of the primary tools for this matter. RDW levels may become another promising tool to predict malignancy.

Gravena, Angela Andreia Franca;Brischiliari, Sheila Cristina Rocha;Gil, Lais Moraes;Lopes, Tiara Cristina Romeiro;Demitto, Marcela De Oliveira;Agnolo, Catia Millene Dell;Borghesan, Deise Helena Pelloso;Carvalho, Maria Dalva De Barros;Pelloso, Sandra Marisa 10313

https://doi.org/10.7314/APJCP.2014.15.23.10313 PDF KSCI

Background: The purpose of the article was to analyze the years of potential life lost (YPLL) of women who died from breast and cervical cancer in the State of Paran$\acute{a}$, Southern Brazil. This was a temporal trend study (2000 to 2010) about the coefficients of mortality and the years of potential life lost in women aged 20 to 70 years. Materials and Methods: Data were obtained through the database of the Department of the Unified Health System (DATASUS) and the National Mortality Information System. Results: There was a loss of 125.075 YPLL due to breast cancer, with an average of 11.370 YPLL. Regarding cervical cancer, the figure obtained was 91.625 YPLL from 2000 to 2010, with an average of 8.329 YPLL. Increased risk of death from breast cancer was observed for women aged 50 to 59 years, with a significant increase among those in the age group from 40 to 49 years. There was an increased rate of cervical cancer among women 40 to 69 years. Conclusions: The risk of death grows with increasing age, being higher from 40 years. Prevention is paramount for both cancers. Thus, preventive measures are required and a reassessment of political strategies should be adopted.

Zahir, Shokouh Taghipour;Vakili, Mahmood;Navabii, Hossein;Rahmani, Koorosh 10319

https://doi.org/10.7314/APJCP.2014.15.23.10319 PDF KSCI

Background: The incidence rate of brain tumors has increased more than 40% in the past 20 years, especially in adults. We aimed to study the clinical and pathological findings of central nervous system (CNS) tumor patients and to evaluate their 5 year survival rates. Materials and Methods: The archives of all patients with CNS tumors in 6 health care centers in Yazd, Iran, from 2006 to 2013, were studied. Patients data were extracted using a checklist which included age, sex, date of reference and diagnosis, date of death, clinical signs, radiography findings, pathology report, size and location of tumor, patient treatment and grade of tumor. Results: A total of 306 patient records were studied in the 8 year period. The most prevalent type of tumor was astrocytoma (n=113, 36.9%). The frequency of almost all tumor types was statistically higher in male patients (p=0.025). In most cases surgery with radiotherapy was the treatment of choice (49.3%). The most frequent symptom reported was headache (in 60.8% of patients) followed by convulsions (15.7%). Most of the tumors were located in the right hemisphere (46.1%) and the frontal and parietal lobe (26% and 12%, respectively). Radiography findings displayed edema with a nonhomogeneous lesion in majority of the patients (87%). The survival fraction of the patients with malignant tumors decreased over time (0.807 in the first year and 0.358 at the end of the $5^{th}$ year). Conclusions: Astrocytoma was the more common CNS tumor with male predominance. Overall survival rates of malignant tumors decreased over time and this was in relation with tumor grade.

Huang, Ying-Ze;Wu, Wei;Wu, Kun;Xu, Xiao-Ning;Tang, Wen-Ru 10325

https://doi.org/10.7314/APJCP.2014.15.23.10325 PDF KSCI

RASSF1A, regarded as a candidate tumor suppressor, is frequently silenced and inactivated by methylation of its promoter region in many human tumors. However, the association between RASSF1A promoter methylation and lung cancer risk remains unclear. To provide a more reliable estimate we conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in lung carcinogenesis. Relevant studies were identified by searches of PubMed, Web of Science, ProQest and Medline databases using the following key words: 'lung cancer or lung neoplasm or lung carcinoma', 'RASSF1A methylation' or 'RASSF1A hypermethylation'. According to the selection standard, 15 articles were identified and analysised by STATA 12.0 software. Combined odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and lung cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant relationship between RASSF1A promoter methylation and lung cancer risk (OR, 16.12; 95%CI, 11.40-22.81; p<0.001) with no between-study heterogeneity. In subgroup analyses, increased risk of RASSF1A methylation in cases than controls was found for the NSCLC group (OR, 13.66, 95%CI, 9.529-19.57) and in the SCLC group (OR, 314.85, 95%CI, 48.93-2026.2).

Zhang, En-Jiao;Cui, Zhi-Gang;Xu, Zhong-Fei;Duan, Wei-Yi;Huang, Shao-Hui;Tan, Xue-Xin;Yin, Zhi-Hua;Sun, Chang-Fu;Lu, Li 10329

https://doi.org/10.7314/APJCP.2014.15.23.10329 PDF KSCI

Background: To systematically summarize the association between the X-ray repair cross complementing 3 (XRCC3) gene polymorphism and oral cancer susceptibility by meta-analysis. Materials and Methods: Databases including PubMed, EMbase, CNKI, VIP and WanFang Data were searched to identify case-control studies concerning the association between an XRCC3 gene polymorphism and the risk of oral cancer from the inception to June 2014. Two reviewers independently screened the literature according to the criteria, extracted the data and assessed the quality. Then meta-analysis was performed using Stata 11.0 software. Results: Seven published case-control studies including 775 patients with oral cancer and 1922 controls were selected. Associations between the rs861539 polymorphism and overall oral cancer risk were not statistically significant in all kinds of comparison models (CT vs CC: OR=0.94, 95%CI=0.74-1.18; TT vs CC: OR=0.94, 95%CI=0.64-1.38; dominant model: OR=0.95, 95%CI=0.76-1.18; recessive model: OR=0.94, 95%CI=0.69-1.29; allele T vs C: OR=0.97, 95%CI=0.84-1.11). In the stratified analysis by ethnicity, no significant associations were found among Asians and Caucasians. On stratification by tumor type, no significant associations were found for cancer and oral premalignant lesions. Conclusions: The XRCC3 gene polymorphism was not found to be associated with the risk of oral cancer. Considering the limited quality of the included case-control studies, more high quality studies with large sample size are needed to verify the above conclusion.

Kavousi, Amir;Bashiri, Yousef;Mehrabi, Yadollah;Etemad, Korosh;Teymourpour, Amir 10335

https://doi.org/10.7314/APJCP.2014.15.23.10335 PDF KSCI

Background: Gastric cancer is considered as the second most prevalent cancer in Iran. The present research sought to identify high risk clusters of gastric cancer with mapping using space-time scan statistics. Materials and Methods: The present research is of descriptive type. The required data were gathered from the registered cancer reports of Cancer Control Office in the Center for Non Communicable Disease of the Ministry of Health (MOH). The data were extracted at province level in the time span of 2004-9. Sat-Scan software was used to analyse the data and to identify high risk clusters. ArcGIS10 was utilized to map the distribution of gastric cancer and to demonstrate high risk clusters. Results: The most likely clusters were found in Ardabil, Gilan, Zanjan, East-Azerbaijan, Qazvin, West-Azerbaijan, Kurdistan, Hamadan, Tehran and Mazandaran between 2007 and 2009. It was statistically significant at the p-value below 0.05. Conclusions: High risk regions included Northern, West-North and central provinces, particularly Ardabil, Kurdistan, Mazandaran and Gilan. More screening tests are suggested to be conducted in high risk regions along with more frequent epidemiological studies to enact gastric cancer prevention programs.

Pornour, Majid;Ahangari, Ghasem;Hejazi, Seyed Hesam;Ahmadkhaniha, Hamid Reza;Akbari, Mohamad Esmail 10339

https://doi.org/10.7314/APJCP.2014.15.23.10339 PDF KSCI

Breast cancer is the most common cancer among females worldwide and a most prevalent malignancy in Iranian women. Chronic stress may make an important contribution to cancer, especially in the breast. Numerous studies showed roles of neurotransmitters in the occurrence and progression of cancers which are mediated by their various types of receptors. This study was conducted to evaluate alterations in the expression profile of dopamine receptor genes in peripheral blood mononuclear cells (PBMC) as stress factors in breast cancer patients and the human breast cancer cell line (MCF-7). Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total mRNA was extracted from PBMC and MCF-7 cells and RT-PCR was performed to confirm the presence of five dopamine receptors (DRD1-DRD5). Expression changes of dopamine receptor genes were evaluated by real time PCR. We observed that DRD2-DRD4 in PBMCs of breast cancer patients were increased compared to healthy individuals. In addition, all dopamine receptor subtypes but DRD1 were expressed in MCF-7 cells. Therefore, alterations of these receptors as stress factors should be assessed for selecting appropriate drugs such as D2-like agonists for treatment of breast cancer after performing complimentary tests. Determining the expression profile of dopamine receptor genes thus seems promising.

Usha, Talambedu;Goyal, Arvind Kumar;Lubna, Syed;Prashanth, H.P.;Mohan, T. Madhan;Pande, Veena;Middha, Sushil Kumar 10345

https://doi.org/10.7314/APJCP.2014.15.23.10345 PDF KSCI

Background: Punica granatum (family: Lythraceae) is mainly found in Iran, which is considered to be its primary centre of origin. Studies on pomegranate peel have revealed antioxidant, anti-inflammatory, anti-angiogenesis activities, with prevention of premature aging and reducing inflammation. In addition to this it is also useful in treating various diseases like diabetes, maintaining blood pressure and treatment of neoplasms such as prostate and breast cancer. Objectives: In this study we identified anti-cancer targets of active compounds like corilagin (tannins), quercetin (flavonoids) and pseudopelletierine (alkaloids) present in pomegranate peel by employing dual reverse screening and binding analysis. Materials and Methods: The potent targets of the pomegranate peel were annotated by the PharmMapper and ReverseScreen 3D, then compared with targets identified from different Bioassay databases (NPACT and HIT's). Docking was then further employed using AutoDock pyrx and validated through discovery studio for studying molecular interactions. Results: A number of potent anti-cancerous targets were attained from the PharmMapper server according to their fit score and from ReverseScreen 3D server according to decreasing 3D scores. Conclusion: The identified targets now need to be further validated through in vitro and in vivo studies.

Chen, Yang;Liu, Zhong-Jing;Liu, Jia;Liu, Li-Kun;Zhang, Er-Shao;Li, Wei-Ling 10351

https://doi.org/10.7314/APJCP.2014.15.23.10351 PDF KSCI

Background: Rosa Roxburghii Tratt is a promising wild fruit crop in Southwest China. Its extracts have been used as traditional Chinese medicine, which benefit immune responses and cure various health disorders. However, whether Rosa Roxburghii Tratt polysaccharides could inhibit metastasis and invasion of ovarian cancer cells remains unknown. Materials and Methods: Effects of crude polysaccharides from Rosa Roxburghii Tratt on the viability of ovarian cancer A2780 cells were detected by MTT assay. Ovarian carcinoma cell migration and invasion after exposure to Rosa Roxburghii Tratt polysaccharides were quantified by wound healing and Transwell assays, respectively. Western blotting was applied to assess protein levels of MMP-9. Results: The results indicated that Rosa Roxburghii Tratt polysaccharides significantly reduced wound closure rate of A2780 cells, inhibited their migration and invasion, and suppressed the expression of MMP-9. Conclusions: Our findings indicated that Rosa Roxburghii Tratt polysaccharides have potential for develop as anti-metastatic cancer drug preparations for ovarian cancer patients.

Wang, Ning;Xu, Zhi-Wen;Wang, Kun-Hao 10355

https://doi.org/10.7314/APJCP.2014.15.23.10355 PDF KSCI

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

Ozyalvacli, Gulzade;Yesil, Cemile;Kargi, Ertugrul;Kizildag, Betul;Kilitci, Asuman;Yilmaz, Fahri 10363

https://doi.org/10.7314/APJCP.2014.15.23.10363 PDF KSCI

Background: The aim of this study was to determine diagnostic and prognostic roles of the neutrophil to lymphocyte ratio (NLR) in breast cancer patients. To date, data are limited on associations of primary breast carcinoma (PBC) and benign proliferative breast disease (BPBD) with preoperative NLR values. Materials and Methods: Our study covered of 120 female patients with PBC and 50 with BPBD. Diagnostic values of NLR were estimated using sensitivity, specificity and areas under receiver operating characteristic curves (AUC). Results: NLR values were significantly higher in the PBC patients than in those with BPBD, with an AUC of 0.668 in the PBC case. The optimal cut-off for NLR was 2.96 and this was validated in the testing set, giving a sensitivity and a specificity of 79.7% and 76.2%, respectively, in PBC patients. Conclusions: Preoperative high NLR is a significant diagnostic predictor of distinction of breast cancer from BPBD and elevated NLR is also an important prognostic marker for primary invasive breast cancer.

Jongudomkarn, Darunee;Macduff, Colin 10367

https://doi.org/10.7314/APJCP.2014.15.23.10367 PDF KSCI

Background: Cancer and non-communicable diseases are a major issue not only for the developed but also developing countries. Public health and primary care nursing offer great potential for primary and secondary prevention of these diseases through community and family-based approaches. Within Thailand there are related established educational curricula but less is known about how graduate practitioners enact ideas in practice and how these can influence policy at local levels. Aim: The aim of this inquiry was to develop family nursing practice in primary care settings in the Isaan region or Northeastern Thailand and to distill what worked well into a nursing model to guide practice. Materials and Methods: An appreciative inquiry approach involving analysis of written reports, focus group discussions and individual interviews was used to synthesize what worked well for fourteen family nurses involved in primary care delivery and to build the related model. Results: Three main strategies were seen to offer a basis for optimal care delivery, namely: enacting a participatory action approach mobilizing families' social capital; using family nursing process; and implementing action strategies within communities. These were distilled into a new conceptual model. Conclusions: The model has some features in common with related community partnership models and the World Health Organization Europe Family Health Nurse model, but highlights practical strategies for family nursing enactment. The model offers a basis not only for planning and implementing family care to help prevent cancer and other diseases but also for education of nurses and health care providers working in communities. This articulation of what works in this culture also offers possible transference to different contexts internationally, with related potential to inform health and social care policies, and international development of care models.

Duran, Ayse Ocak;Karaca, Halit;Besiroglu, Mehmet;Bayoglu, Ibrahim Vedat;Menekse, Serkan;Yapici, Heves Surmeli;Yazilitas, Dogan;Bahceci, Aykut;Uysal, Mukremin;Sevinc, Alper;Hacibekiroglu, Ilhan;Aksoy, Asude;Tanriverdi, Ozgur;Arpaci, Erkan;Inanc, Mevlude;Dane, Faysal;Ozkan, Metin 10375

https://doi.org/10.7314/APJCP.2014.15.23.10375 PDF KSCI

Background: XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev) treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this study was to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC. Materials and Methods: A total of 409 patients with mCRC who received chemotherapy were included and divided into 2 groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made in terms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity. Results: Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in 29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%), stable disease in 88 (29.5%) and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively. Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months, 95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) for Group 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4% in Group 1 and 26.1% in Group 2 (p<0.001). Conclusions: First-line XELOX-Bev is more effective with a better response rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.

Li, Pei-Hua;Wu, Jin-Xia;Zheng, Jun-Nian;Pei, Dong-Sheng 10381

https://doi.org/10.7314/APJCP.2014.15.23.10381 PDF KSCI

SKI-II has been reported as an inhibitor of sphingosine kinase 1 and has been extensively used to prove the involvement of sphingosine kinase and sphingosine-1-phosphate (Sphk1) in cellular processes. In the current study, we investigated the effects of SKI-II and its potential mechanisms in human gastric cancer SGC7901 cells. After treatment with SKI-II, cell growth, cell cycle distribution, apoptosis, expression of Sphk1, NF-${\kappa}B$, Bcl-2, Bax and p27 were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western-blot assay, respectively. Our results showed that SKI-II markedly inhibited SGC7901 cell survival in a dose-dependent manner, reduced cell proliferation with accumulation of cells in the G0/G1 phase and induced apoptosis in the tumor cells. Furthermore, Western blotting and immunocytochemistry showed that the expression of p27 and Bax was increased significantly, but the expression of NF-${\kappa}B$, Bcl-2 and Sphk1 decreased by different degrees. These results indicate that SKI-II induced cell growth arrest and apoptosis. The increased apoptotic sensitivity of SGC7901 was correlated with NF-${\kappa}B$ or Bcl-2/Bax activation.

Wang, Shuang-Shuang;Guo, Hai-Yan;Dong, Lin-Li;Zhu, Xiang-Qian;Ma, Liang;Li, Wen;Tang, Jian-Xin 10387

https://doi.org/10.7314/APJCP.2014.15.23.10387 PDF KSCI

Background: This study aimed to identify any association between the p73 gene G4C14-to-A4T14 polymorphism and risk of non-small cell lung cancer (NSCLC) in the south of China. Materials and Methods: We genotyped the p73 gene polymorphism of peripheral blood DNA from 168 patients with NSCLC and 195 normal controls using HRM (high resolution melting) and PCR-CTPP (polymerase chain reaction with confronting two-pair primers). Results: The results of genotyping by HRM and PCR-CTPP were consistent with direct sequencing, the p73 genotype distribution in 168 lung cancer patients being as follows: GC/GC 101 cases (60.1%), GC/AT 59 cases (35.1%), AT/AT 8 cases (4.8%). The carriers of AT/AT genotype had a significantly reduced risk of NSCLC (OR=0.370; 95%CI: 0.170-0.806; p=0.010) as compared with non-carriers. However, we found no relations between p73 genotypes and histological type (p=0.798, $x^2=0.452$), tumor stage (p=0.806, $x^2=0.806$), or lymph node metastasis (p=0.578, $x^2=1.098$). Conclusions: Our findings suggest that the p73 G4C14-to-A4T14 polymorphism may be a modifier of NSCLC susceptibility in the Chinese population.

Kafshdooz, Leila;Tabrizi, Ali Dastranj;Mohaddes, Seyyed Mojtaba;Kafshdooz, Tayebeh;Akbarzadeh, Abolfazl;Ghojazadeh, Morteza;Gharesouran, Jalal 10393

https://doi.org/10.7314/APJCP.2014.15.23.10393 PDF KSCI

Background: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival. In this study, we aimed to investigate the association between HIF-1 1772 C/T polymorphisms and endometrial cancer. Materials and Methods: 75 patients with endometrial carcinoma and 75 patients whose underwent hysterectomy for non tumoral indication selected for evaluation of HIF-1 1772 C/T polymorphisms by PCR-RFLP and sequencing. Results: For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with endometrial cancer risk. Conclusions: Our results suggest that the C1772T polymorphism of the HIF-1a may be associated with endometrial cancers.

Banjerdpongchai, Ratana;Wudtiwai, Benjawan;Pompimon, Wilart 10397

https://doi.org/10.7314/APJCP.2014.15.23.10397 PDF KSCI

Stigmalactam, an aristolactam-type alkaloid extracted from Orophea enterocarpa, exerts cytotoxicity against several human and murine cancer cell lines, but the molecular mechanisms remain elusive. The aims of this study were to identify the mode and mechanisms of human cancer cell death induced by stigmalactam employing human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells as models, compared to normal murine fibroblasts. It was found that stigmalactam was toxic to HepG2 and MDA-MB-231 cells with $IC_{50}$ levels of $23.0{\pm}2.67{\mu}M$ and $33.2{\pm}4.54{\mu}M$, respectively, using MTT assays. At the same time the $IC_{50}$ level towards murine normal fibroblast NIH3T3 cells was $24.4{\pm}6.75{\mu}M$. Reactive oxygen species (ROS) production was reduced in stigmalactam-treated cells dose dependently after 4 h of incubation, indicating antioxidant activity, measured by using 2',7',-dichlorohydrofluorescein diacetate and flow cytometry. Caspase-3 and caspase-9 activities were increased in a dose response manner, while stigmalactam decreased the mitochondrial transmembrane potential dose-dependently in HepG2 cells, using 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, indicating mitochondrial pathway-mediated apoptosis. In conclusion, stigmalactam from O. enterocarpa was toxic to both HepG2 and MDA-MB-231 cells and induced human cancer HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway.

Mammadov, Elnur;Aslan, Guven;Tuna, Burcin;Bozkurt, Ozan;Yorukoglu, Kutsal 10401

https://doi.org/10.7314/APJCP.2014.15.23.10401 PDF KSCI

Background: Molecular prognostic markers have been under investigation for the last decade and no validated marker to date has been proven to be used in daily clinical practice for urinary bladder cancers. The aim of the present study is to evaluate the significance of HYAL-1 expression in prediction of recurrence and progression in pT1 urothelial carcinomas. Materials and Methods: Eighty-nine urothelial carcinoma cases staged as T1 according to 2004 WHO classification were studied. Representative sections from every case were stained immunohistochemically for HYAL-1 and scored between 0 and +3, according to staining density, and graded as low and high for the scores 0-1 and 2-3, respectively. Results: Of the 89 pT1 bladder cancer patients, HYAL-1 expression was high in 92.1% (82 patients; 72 patients +3 and 10 patients +2) and low in 7.9% (only 7 patients; 6 patients +1 and 1 patient 0) of the cases. Of the 89 patients, 38 (42.7%) had recurrence and 22 (24.7%) showed progression. HYAL-1 staining did not show significant characteristics for tumor grade, accompanying CIS, multiplicity, tumor size, age and sex. HYAL-1 expression did not have any prognostic value in estimating recurrence or progression. Conclusions: HYAL-1 expression was found to be high, but did not have any prognostic importance in T1 bladder urothelial carcinomas.

Li, Chen-Long;Chang, Liang;Guo, Lin;Zhao, Dan;Liu, Hui-Bin;Wang, Qiu-Shi;Zhang, Ping;Du, Wen-Zhong;Liu, Xing;Zhang, Hai-Tao;Liu, Yang;Zhang, Yao;Xie, Jing-Hong;Ming, Jian-Guang;Cui, Yu-Qiong;Sun, Ying;Zhang, Zhi-Ren;Jiang, Chuan-Lu 10407

https://doi.org/10.7314/APJCP.2014.15.23.10407 PDF KSCI

Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

Liu, Wen;Gao, Fang-Fang;Li, Qun;Lv, Jia-Wei;Wang, Ying;Hu, Peng-Chao;Xiang, Qing-Ming;Wei, Lei 10413

https://doi.org/10.7314/APJCP.2014.15.23.10413 PDF KSCI

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

Fallahzadeh, Hosein;Cheraghi, Maria;Amoori, Neda;Alaf, Mehrangiz 10421

https://doi.org/10.7314/APJCP.2014.15.23.10421 PDF KSCI

Background: While the incidence of non-Hodgkins lymphoma (NHL) has been rising worldwide, the reasons remain undefined. Recent research has focused on effect of red andf processed meat intake as a risk factor, but with inconclusive results. We therefore conducted a meta-analysis of data published to date, to ascertain the overall association between intake and NHL. Materials and Methods: A published literature search was performed through Pubmed, Cochrane Library, Medline, and Science Citation Index Expanded databases for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using Chi-square and I2 statistics. Dissemination bias was evaluated by funnel plot analysis.We performed a formal meta-analysis using summary measures from these studies. Results: In total, 11 published studies were included in the final analysis. The combined analysis revealed that there was significant association between the red meat and NHL risk (OR=1.10, 95%CI: 1.02 to 1.19, p=0.01). Additionally, there was showed significance association between processed red meat and NHL risk (OR=1.17, 95%CI: 1.06 to 1.29, p=0.001). In subgroup analysis, a statistical significant association was noted between diffuse large B-cell lymphoma (DLBCL) (OR=1.20, 95%CI: 1.04 to 2.37, P=0.01) and red meat intake. Conclusions: In this meta-Analysis, there was evidence for association between consumption of red meat, or processed meat and risk of NHL, particularly with the DLBCL subtype in the red meat case.

Hassona, Y.;Scully, C.;Almangush, A.;Baqain, Z.;Sawair, F. 10427

https://doi.org/10.7314/APJCP.2014.15.23.10427 PDF KSCI

Background: To determine the prevalence, types, and risk factors of oral potentially malignant disorders (OPMDs) among a group of Arab Jordanian dental patients, and to evaluate their awareness and attitudes toward early diagnosis and treatment. Materials and Methods: A total of 1,041 patients attending a University Hospital for dental care were examined for the presence of OPMDs. Histopathological examination was performed on all cases clinically diagnosed and patients were directly interviewed to evaluate their knowledge and attitudes toward early detection and treatment of oral cancer. Results: The prevalence of OPMDs overall was 2.8%. Lichen planus/lichenoid lesions were the most common lesions (1.8%) followed by leukoplakias (0.48%), chronic hyperplastic candidiosis (0.38%), and erythroplakia (0.096%). Smoking, alcohol, and age (>40 years) were the main identifiable risk factors. Patients with OPMDs displayed a general lack of awareness and negative attitudes towards early diagnosis and treatment. Conclusions: OPMDs among Arab dental patients are relatively uncommon and awareness about oral cancer among Jordanian dental patients is low. Interventions to improve public knowledge about oral cancer and attitudes toward early diagnosis and treatment are urgently indicated.

Yacoub, Haitham Ahmed;Mahmoud, Wael Mahmoud;El-Baz, Hatim Alaa-Eldeen El-Din;Eid, Ola Mohamed;El-Fayoumi, Refaat Ibrahim;Mahmoud, Maged Mostafa;Harakeh, Steve;Abuzinadah, Osama H.A. 10433

https://doi.org/10.7314/APJCP.2014.15.23.10433 PDF KSCI

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

Shi, Liang;Chen, Zhan-Guo;Wu, Li-li;Zheng, Jian-Jian;Yang, Jian-Rong;Chen, Xiao-Fei;Chen, Zeng-Qiang;Liu, Cun-Li;Chi, Sheng-Ying;Zheng, Jia-Ying;Huang, Hai-Xia;Lin, Xiang-Yang;Zheng, Fang 10439

https://doi.org/10.7314/APJCP.2014.15.23.10439 PDF KSCI

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

Xiao, Yang;Liu, Jun;Huang, Xin-En;Ca, Li-Hua;Ma, Yi-Min;Wei, Wei;Zhang, Rong-Xia;Huang, Xiao-Hong;Chang, Juan;Wu, Yi-Jia 10445

https://doi.org/10.7314/APJCP.2014.15.23.10445 PDF KSCI

Objective: To observe treatment effects and safety of fluvoxamine combined with oxycodone prolonged-release tablets in treating patients with moderate to severe cancer pain. Methods: Patients confirmed pathologically with cancer and complicated with moderate to severe pain, were divided into control and experimental groups. Oxycodone prolonged-release tablets, with or without fluvoxamine, were administrated to all study patients until pain relief. Degree of pain relief, dose of oxycodone prolonged-release tablets, side effects and quality of life were compared before and after treatment. Results: In total, 120 patients were recruited. No statistically significant difference was detected regarding age, gender, types of cancer, KPS between two groups of patients (P>0.05). Baseline pain score of patients with moderate pain in treatment and control group was $4.9{\pm}0.8$ and $5.1{\pm}0.8$, respectively; and decreased to $1.8{\pm}1.1$ and $1.2{\pm}1.1$ after treatment, respectively. Pain intensity was significantly reduced in the treatment group (P=0.028). Average daily consumption of oxycodone prolonged-release tablets was ($54.0{\pm}19.6$) mg and ($44.7{\pm}18.7$) mg respectively, which is lower in treatment grpup than in control group, but the difference was not statistically significant (P=0.065). Baseline pain score of patients with severe pain in treatment and control groups were $8.3{\pm}1.1$ and $8.3{\pm}1.1$, respectively; and pain intensity after treatment decreased to $2.9{\pm}1.0$ and $2.3{\pm}1.0$. Pain intensity was significantly reduced in the treatment group, with statistical significance (P=0.026). Average daily consumption of oxycodone prolonged-release tablets was ($132.0{\pm}42.2$) mg and ($110.7{\pm}33.9$) mg, respectively, which is lower in treatment group than in control group, and the difference was statistically significant (P=0.035). In terms of quality of life, patients in treatment group had better performance status, daily activity, mood, and sleep than that in control group (P < 0.05). Patients in two groups had similar side effects, eg., constipation, nausea/vomiting, lethargy, dizziness, itchy skin, dysuria, and ataxia. Lower incidence of nausea/vomiting, lethargy, was obtained from patients in treatment than in control group, while significant low constipation was observed in treatment than in control group (35.0% vs 49.2%, P=0.026). Conclusion: Fluvoxamine combined with oxycodone prolonged-release tablets could be more effective in treating patients with cancer pain, and could reduce the dosage of oxycodone prolonged-release tablets and thus be associated with lower side effects, and improved quality of life.

Gamsizkan, Mehmet;Yilmaz, Ismail;Buyukbabani, Nesimi;Demirkesen, Cuyan;Demiriz, Murat;Cetin, Emel Dikicioglu;Ince, Umit;Akalin, Taner;Demirkan, Nese Calli;Lebe, Banu;Erdem, Ozlem;Gokoz, Ozay;Sakiz, Damlanur;Demireli, Peyker Temiz;Astarci, Hesna Muzeyyen;Adim, Saduman Balaban;Zemheri, Itir Ebru;Acikalin, Arbil;Yaman, Banu;Aydin, Ovgu;Bassorgun, Cumhur Ibrahim 10451

https://doi.org/10.7314/APJCP.2014.15.23.10451 PDF KSCI

Background: We defined melanoma distribution in a large series of Turkish patients and evaluated the prognostic parameters of melanomas. Materials and Methods: A total of 1574 patients' data was retrospectively collected at 18 centers in Turkey. Demographic characteristics were questioned and noted. Prognostic parametres were evaluated based on sentinel lymph node involvement. Results: Mean age was 56.7 (4-99) years. While 844 (53.6%) cases were male, 730 (46.4%) cases were female. One thousand four hundred forty-seven (92%) cases were invasive melanoma and 127 (8%) cases were in-situ melanoma. The most common histopathological form was the superficial spreading melanoma (SSM) which was found in 549 patients (37.9%). It was followed by nodular melanoma in 379 (26.2%), acral lentiginous melanoma (ALM) in 191 (13.2%) and lentigo maligna melanoma in 132 (9.1%), respectively. On univariate analysis, lymphovascular invasion (p<0.001), tumor thickness (p<0.001), histopathological subtype (p<0.001), Clark level (p=0.001), ulceration (p<0.001), ${\geq}6/mm^2$ mitosis (p=0.005), satellite formation (p=0.001) and gender (p=0.03) were found to be associated with sentinel lymph node positivity. Regression was associated with sentinel lymph node negativity (p=0.017). According to multivariate analysis, lymphovascular invasion and tumor thickness were significant independent predictive factors of SLN positivity. Patient age, tumor localization, precursor lesions, lymphocytic infiltration and neurotropism were not related with sentinel lymph node involvement. Conclusions: In this retrospective analysis, it was found that the prevalence of SSM is at a lower rate while the prevalence of ALM is at a higher rate when compared to western countries. According to Breslow index; most of the melanoma lesions' thickness were greater than 2 mm, corresponding Clark IV. Vascular invasion and tumor thickness are the most important factors for sentinel lymph node involvement.

Kayani, Mahmood Akhtar;Khan, Sumeera;Baig, Ruqia Mehmood;Mahjabeen, Ishrat 10457

https://doi.org/10.7314/APJCP.2014.15.23.10457 PDF KSCI

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

Yothaisong, Supak;Thanee, Malinee;Namwat, Nisana;Yongvanit, Puangrat;Boonmars, Thidarut;Puapairoj, Anucha;Loilome, Watcharin 10463

https://doi.org/10.7314/APJCP.2014.15.23.10463 PDF KSCI

Opisthorchis viverrini (Ov) infection is the major etiological factor for cholangiocarcinoma (CCA), especially in northeast Thailand. We have previously reported significant involvement of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin in human CCA tissues. The present study, therefore, examined the expression and activation of PI3K/AKT/PTEN and $Wnt/{\beta}$-catenin signaling components during Ov-induced cholangiocarcinogenesis in a hamster animal model. Hamsters were divided into two groups; non-treated and Ov plus NDMA treated. The results of immunohistochemical staining showed an upregulation of PI3K/AKT signaling as determined by elevated expression of the $p85{\alpha}$-regulatory and $p110{\alpha}$-catalytic subunits of PI3K as well as increased expression and activation of AKT during cholangiocarcinogenesis. Interestingly, the staining intensity of activated AKT (p-AKT) increased in the apical regions of the bile ducts and strong staining was detected where the liver fluke resides. Moreover, PTEN, a negative regulator of PI3K/AKT, was suppressed by decreased expression and increased phosphorylation during cholangiocarcinogenesis. We also detected upregulation of $Wnt/{\beta}$-catenin signaling as determined by increased positive staining of Wnt3, Wnt3a, Wnt5a, Wnt7b and ${\beta}$-catenin, corresponded with the period of cholangiocarcinogenesis. Furthermore, nuclear staining of ${\beta}$-catenin was observed in CCA tissues. Our results suggest the liver fluke infection causes chronic inflammatory conditions which lead to upregulation of the PI3K/AKT and $Wnt/{\beta}$-catenin signaling pathways which may drive CCA carcinogenesis. These results provide useful information for drug development, prevention and treatment of CCA.

Yuan, Hong-Liang;Liu, Xiao-Lei;Liu, Ying-Jie 10469

https://doi.org/10.7314/APJCP.2014.15.23.10469 PDF KSCI

Background: Solanum nigrum L. has been used in traditional Chinese medicine because of its diuretic and antipyretic effects. The present research concerned effects of crude polysaccharides isolated from Solanum nigrum L. on erythrocyte membranes of tumor-bearing $S_{180}$ and $H_{22}$ in mice. Materials and Methods: Fluorescence-labeled red blood cell membranes were used with DPH fluorescence spectrophotometry to examine erythrocyte membrane fluidity, and colorimetry to determine degree of erythrocyte surface membrane blocking. Extent of reaction by tumor-bearing mice with the enzyme erythrocyte membrane bubble shadow detection of red cell membrane variation in the degree of closure before and after administration. Results: Solanum nigrum polysaccharide could significantly improve the $S_{180}$ and $H_{22}$ tumor-bearing mice erythrocyte membrane fluidity, compared with the control group, the difference was significant (p<0.01), SNL can significantly improve the red blood cell membrane and then $S_{180}$ tumor-bearing mice sealing ability, compared with the negative control group, the difference was significant(p<0.05, p<0.01). $H_{22}$ tumor-bearing mice can increase red cell membrane and then sealing ability, the difference was significant (p<0.05). Solanum nigrum polysaccharide degree of fluidity and blocking two transplanted tumors in mice restored the ability to raise the red cell membrane has a significant effect. Conclusions: Solanum nigrum L.-type mice transplanted tumor can affect the red blood cell membrane fluidity and re-closed, through the red cell membrane of red blood cells to enhance the immune function of the possibility of erythrocyte immunity against tumor formation garland provide experimental basis.

Zhang, Ya-Li;Sun, Feng-Ting;Zhang, Ze;Chen, Xiao-Xu;Liu, Ai-Xiang;Pan, Jing-Jing;Peng, Fei;Zhou, Shuai;Sun, Li-Jun 10475

https://doi.org/10.7314/APJCP.2014.15.23.10475 PDF KSCI

Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.

Boonyarat, Chantana;Yenjai, Chavi;Vajragupta, Opa;Waiwut, Pornthip 10483

https://doi.org/10.7314/APJCP.2014.15.23.10483 PDF KSCI

Heptaphylline derivatives are carbazoles in Clausena harmandiana, a medicinal plant that is utilized for headache, stomach ache, and other treatments of illness. The present study examined the effects of heptaphylline and 7-methoxyheptaphylline on apoptosis of human colon adenocarcinoma cells (HT-29 cell line). Quantification of cell viability was performed using cell proliferation assay (MTT assay) and of protein expression through immunoblotting. The results showed that only heptaphylline, but not 7-methoxyheptaphylline, significantly significantly activated cleaved of caspase-3 and poly (ADP-ribose) polymerase (PARP-1) which resulted in HT-29 cell death. We found that heptaphylline activated BH3 interacting-domain death agonist (Bid) and Bak, proapoptotic proteins. In contrast, it suppressed X-linked inhibitor-of-apoptosis protein (XIAP), Bcl-xL and survivin, inhibitors of apoptosis. In addition, heptaphylline inhibited activation of NF-${\kappa}B$/p65 (rel), a regulator of apoptotic regulating proteins by suppressing the activation of Akt and $IKK{\alpha}$, upstream regulators of p65. The findings suggested that heptaphylline induces apoptosis in human colon adenocarcinoma cells.

Yen, Rachel Lai Siaw;Telisinghe, Pemasari Upali;Cunningham, Anne;Abdullah, Muhd Syafiq;Chong, Chee Fui;Chong, Vui Heng 10489

https://doi.org/10.7314/APJCP.2014.15.23.10489 PDF KSCI

Background: Gastric cancer is the second most common gastrointestinal cancer and is largely attributed to Helicobacter pylori (H. pylori) infection. In addition, studies have also shown association with Epstein-Barr virus (EBV) in 10% of gastric cancers. This study assessed the characteristics of EBV associated gastric cancers (EBVaGC) in Brunei Darussalam. Materials and Methods: This study included gastric cancers diagnosed between 2008 and 2012, registered with the Department of Pathology RIPAS Hospital, Brunei Darussalam. Clinical case notes were systematically reviewed. Histology specimens were all stained for EBV and also assessed for intestinal metaplasia and H. pylori. Results: There were a total of 81 patients (54 male and 27 females) with a mean age of $65.8{\pm}14.8years$ included in the study. Intestinal metaplasia and active H. pylori infection were detected in 40.7% and 30.9% respectively. A majority of the tumors were proximally located (55.6%), most poorly differentiated (well differentiated 16%, moderately differentiated 30.9% and poorly differentiated 53.1%) and the stages at diagnosis were; stage I (44.4%), stage II (23.5%), stage III (8.6%) and stage IV (23.5%). EBV positivity (EBVaGC) was seen in 30.9%. Between EBVaGC and EBV negative gastric cancers, there were no significant differences (age, gender, ethnic group, presence of Intestinal metaplasia, tumor locations, stages of disease and degree of tumor differentiation). Conclusions: This study showed that a third of gastric cancers in Brunei Darussalam were positive for EBV, higher than what have been reported in the literature. However, there were no significant differences between EBVaGC and EBV negative gastric cancers. This suggests that the role of EBV in gastric cancer may be mostly incidental rather than any causal relation. However, further studies are required.

Ding, Da-Wei;Zhang, Yong-Hong;Huang, Xin-En;An, Qing;Zhang, Xun 10495

https://doi.org/10.7314/APJCP.2014.15.23.10495 PDF KSCI

Background: To evaluate the effects of bufalin in A549 human lung adenocarcinoma epithelial cells in vitro and assess the underlying mechanisms. Materials and Methods: Human A549 non-small cell lung cancer (NSCLC) cells were treated with various concentrations of bufalin. Cell proliferation was measured by CCK-8 assay, apoptotic cell percentage was calculated by flow cytometry and morphological change was observed by inverted phase contrast microscopy/transmission electron microscopy. In addition, the membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay, and the related protein expression of cytochrome C and caspase-3 was analyzed by Western blotting. Results: Bufalin could inhibit the proliferation of A549 cells via induction of apoptosis, with the evidence of characteristic morphological changes in the nucleus and mitochondria. Furthermore, bufalin decreased the mitochondrial membrane potential with up-regulation of cytochrome C in the cytosol, and activation of caspase-3. Conclusions: Bufalin inhibits the proliferation of A549 cells and triggers mitochondria-dependent apoptosis, pointing to therapeutic application for NSCLC.

Li, Jia-Ying;Li, Ying;Jiang, Zheng;Wang, Rui-Tao;Wang, Xi-Shan 10501

https://doi.org/10.7314/APJCP.2014.15.23.10501 PDF KSCI

Background: Colon cancer is the second most common cancer in developed countries. Activated platelets play a key role in inflammation and atherothrombosis, with mean platelet volume (MPV) is an early marker of platelet activation. The aim of the study was to clarify the relevance of MPV in patients with colon cancer. Materials and Methods: We measured MPV levels in 128 patients with colon cancer before and after surgery, and 128 controls matched for age, gender, body mass index (BMI) and smoking status. The odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer were calculated using multivariate logistic regression analyses across MPV quartiles. Results: Patients with colon cancer had higher MPV compared with controls. Surgical tumor resection resulted in a significant decrease in MPV levels (11.4 fL vs 10.7 fL; p<0.001). A positive correlation between MPV and tumor-nodule-metastases (TNM) stage was found. Furthermore, after adjusting for other risk factors, the ORs (95%CIs) for colon cancer according to MPV quartiles were 1.000, 2.238 (1.014-4.943), 3.410 (1.528-7.613), and 5.379 (2.372-12.198), respectively. Conclusions: The findings show that patients with colon cancer have higher MPV levels compared with controls, and these are reduced after surgery. In addition, MPV was found to be independently associated with the presence of colon cancer. Further studies are warranted to assess the utility of MPV as a novel diagnostic screening tool for colon cancer.

Kongsiang, Apichat;Tangvoraphonkchai, Vorachai;Jirapornkul, Chananya;Promthet, Supannee;Kamsa-ard, Siriporn;Suwanrungruang, Krittika 10505

https://doi.org/10.7314/APJCP.2014.15.23.10505 PDF KSCI

Background: Breast cancer is an important cause of death among women. One way of classifying different forms of breast cancer is by molecular features, usually in terms of the four subtypes: luminal A, luminal B, HER2-enriched, and triple negative. Objectives: This study aimed to investigate the association between molecular subtypes and survival among breast cancer patients treated with radiotherapy. Materials and Methods: A retrospective cohort study was conducted. The subjects were 272 breast cancer patients who had received treatment in the radiotherapy unit at Srinagarind Hospital, Thailand, between 1 January, 1999, and 31 May, 2009. The end of the study was 1 June, 2014. Overall survival was defined as the time elapsing between initial registration at the radiotherapy unit and death or the end of the study. Survival curves were estimated by the Kaplan-Meier method, and a multivariate analysis was performed using Cox's proportional hazard regression model. Results: The patient mean age was $47.5{\pm}10.4$ at the time of diagnosis. Of the 272 patients, 146 (53.7%) were classified as luminal A, 12 (4.4%) as luminal B, 30 (11.0%) as HER2-enriched, and 84 (30.9%) as triple negative. The overall survival rates at 1, 3 and 5 years were 87.1%, 68.4% and 59.2%, respectively. According to molecular subtypes, HER2-enriched patients had the lowest 5-year survival rate (30.0 %, 95%CI: 15.02-46.55). The median follow-up time was 8.37 years. In the Cox model analysis a higher risk of death was found for patients with HER2-enriched ($HR_{adj}=3.34$, 95%CI:1.96-5.67), triple negative ($HR_{adj}=2.17$, 95%CI: 1.44-3.27), and stage IIlB ($HR_{adj}=2.20$, 95%CI: 1.16-4.17) cancers. Conclusions: The worst survival rates were among patients classified as HER2-enriched, triple negative and at stage IIIB. Early detection and an advanced treatment modality are needed to help these patients.

Zhuang, Bo;Lv, Deng-Kun;Gao, Si-Ju;Meng, Jing-Jing 10509

https://doi.org/10.7314/APJCP.2014.15.23.10509 PDF KSCI

Objective: To investigate the differential features of CT images in children with neuroblastomas (N) and ganglioneuroblastomas (G). Materials and Methods: Clinical data of 12 children in group G and 15 in group N undergoing CT examination and definitely diagnosed by pathology were retrospectively analyzed. The focal conditions were observed and compared in the two groups, including location, size, boundaries, morphology, enhanced degree and mode, abdominal vascular involvement, presence or absence of spanning the midline, infiltration of peripheral organs, angiography manifestations in tumors or surroundings, presence or absence of calcification and vascular tumor emboli as well as metastases of distal organs and lymph nodes. Results: In group N, the incidence of tumors in the adrenal area was conspicuously higher than in group G (P<0.05), while that of tumors with regular morphology and clear boundaries was significantly lower than in group G (P<0.01); Angiography manifestation rate and incidences of vascular embedding, lymph node metastasis, infiltration and organic metastasis in group N were all markedly higher than in group G (P<0.05). There was no statistical significance between the two groups in terms of focal size, presence or absence of calcification and spanning the midline, and enhanced degree and mode, as well as vascular tumor emboli (P>0.05). Conclusions: Mostly located in adrenal areas and with vascular embedding as a primary manifestation, the neuroblastoma extremely readily metastases to lymph nodes and other organs as well as infiltrating local tissues, with dilation on angiography frequent in or around the tumors. With vascular displacement as a primary manifestation, ganglioneuroblastoma has a regular morphology and clear boundaries.

Fang, Ting-Ting;Sun, Xiao-Jing;Chen, Jie;Zhao, Yan;Sun, Rui-Xia;Ren, Ning;Liu, Bin-Bin 10513

https://doi.org/10.7314/APJCP.2014.15.23.10513 PDF KSCI

Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

Kim, Jae-Hyun;Park, Eun-Cheol;Yoo, Ki-Bong 10525

https://doi.org/10.7314/APJCP.2014.15.23.10525 PDF KSCI

Objective: To investigate the relationship between the perception of cancer risk and likelihood of having undergone cancer screening. Materials and Methods: We used data from the Korean Health Panel Survey from December 2011 onward. Of 3,390 patients who visited a hospital during the previous year, we included data from 2,466 individuals; 924 samples were excluded due to missing data. Logistic regression analysis and the chi square test were used to investigate the association between perceived cancer risk and the likelihood of having undergone cancer screening. Results: For patients who perceived their risk of developing cancer during the next 10 years to be 30-40%, the odds ratio was increased 1.65 fold (95%CI: 1.223, 2.234) compared with those who perceived their risk to be almost zero. Although the difference was not statistically significant, perceiving cancer risk as either extremely low or extremely high appears to be associated with a reduced likelihood of having undergone cancer screening, resulting in an inverted U-shaped relationship. Conclusions: Physicians and researchers should be aware of the importance of the affective component of risk perception. Policies addressing the influence of cancer risk perception should be implemented in South Korea and worldwide.

Kim, Jae-Hyun;Park, Eun-Cheol 10531

https://doi.org/10.7314/APJCP.2014.15.23.10531 PDF KSCI

Background: To examine whether offspring improve or reduce quality of life (QOL) among cancer patients and survivors. Materials and Methods: We used data from the Korean Longitudinal Study of Aging (KLoSA) from 2008 to 2011. There were 490 research subjects in our study: 245 cancer patients and survivors and 245 controls matched using propensity scores. Results: For cancer patients and survivors with no offspring, the QOL estimate was -2.831 lower (SE: 5.508, p-value: 0.623) than that of those with two offspring, while for those with five or more offspring, the QOL estimate was 7.336 higher (SE: 2.840, p-value: 0.036). For non-cancer patients and survivors with one child, the QOL estimate was -11.258 lower (SE: 2.430, p-value: 0.002) than that of those with two offspring, while for those with five or more offspring, the QOL estimate was -4.881 lower (SE: 2.484, p-value: 0.090). Conclusions: This article provides evidence for a beneficial effect of offspring upon QOL in cancer patients and survivors, indicating that offspring are important for them.

Xie, Nan-Nan;Hu, Liang;Li, Tai-Hui 10539

https://doi.org/10.7314/APJCP.2014.15.23.10539 PDF KSCI

A method to predict the risk of lung cancer is proposed, based on two feature selection algorithms: Fisher and ReliefF, and BP Neural Networks. An appropriate quantity of risk factors was chosen for lung cancer risk prediction. The process featured two steps, firstly choosing the risk factors by combining two feature selection algorithms, then providing the predictive value by neural network. Based on the method framework, an algorithm LCRP (lung cancer risk prediction) is presented, to reduce the amount of risk factors collected in practical applications. The proposed method is suitable for health monitoring and self-testing. Experiments showed it can actually provide satisfactory accuracy under low dimensions of risk factors.

Asian Pacific Journal of Cancer Prevention

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Asian Pacific Journal of Cancer Prevention

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