• Title, Summary, Keyword: Liver Diseases

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Mutation Analysis of KRAS and BRAF Genes in Metastatic Colorectal Cancer: a First Large Scale Study from Iran

  • koochak, Aghigh;Rakhshani, Nasser;Niya, Mohammad Hadi Karbalaie;Tameshkel, Fahimeh Safarnezhad;Sohrabi, Masoud Reza;Babaee, Mohammad Reza;Rezvani, Hamid;Bahar, Babak;Imanzade, Farid;Zamani, Farhad;Khonsari, Mohammad Reza;Ajdarkosh, Hossein;Hemmasi, Gholamreza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.603-608
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    • 2016
  • Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

  • Lu, Feng-Bin;Chen, Da-Zhi;Chen, Lu;Hu, En-De;Wu, Jin-Lu;Li, Hui;Gong, Yue-Wen;Lin, Zhuo;Wang, Xiao-Dong;Li, Ji;Jin, Xiao-Ya;Xu, Lan-Man;Chen, Yong-Ping
    • Molecules and Cells
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    • v.42 no.12
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    • pp.906-918
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    • 2019
  • MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Significance of Diffuse Lung Uptake of $^{99m}Tc-Tin$ Colloid in Liver Scanning (간스캔상 $^{99m}Tc-Tin$ Colloid의 미만성 폐섭취의 의의)

  • Sohn, In;Kwon, In-Soon;Park, Jung-Sik;Lee, Myung-Chul;Cho, Bo-Yeon;Koh, Chang-Soon;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.17 no.1
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    • pp.33-39
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    • 1983
  • Sixty-nine patients with diffuse lung uptake of $^{99m}Tc-tin$ colloid were evaluated to determine the kinds of associated diseases, the incidence of associated liver scan abnormalities, and prognosis. The results were as follows: 1) Diseases associated with diffuse lung uptake included malignancies in 31 patients, infectious diseases in 19, chronic liver diseases in 14, and others in 5. It appeared that the marked degree of lung uptake was associated with severe diseases. 2) Thirty-one of the 69 patients(45%) had abnormal liver size, 43(62%) had space occupying lesions or nonhomogeneity in liver image, 37(54%) had splenomegaly and 45(65%) had increased splenic uptake. Increased bone marrow uptake was found in 48(70%) and renal uptake in 15(22%). As the degree of lung uptake increased, there was a statistically significant (p<0.05) tendency for the incidences of the abnormal liver image and renal uptake to increase. 3) Sixty-two of the 69 patients were followed up for one to 439 days(mean 44 days) after liver scanning. Eleven(18%) were dead, 10(16%) were aggravated, and 13(21%) were improved. Most of improved patients had infectious diseases. It appeared that diffuse lung uptake of $^{99m}Tc-Tn$ colloid was found in the various diseases including malignancies, infections, and chronic liver diseases, and that it was strongly associated with other liver scan abnormalities, but was not necessarily associated with a poor prognosis, particularly when underlying diseases were infections.

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MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease

  • Ha, Tai-You
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.309-323
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    • 2011
  • MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases.

Analysis on Developmental Factors of the Liver Diseases in Ultrasound Diagnosis of Healthcare (종합검진 초음파검사에서 나타난 간질환과 건강관련 요인분석)

  • Lee, Mi-Yeon;Jung, Hong-Ryang;Lim, Chang-Hwan
    • Journal of radiological science and technology
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    • v.32 no.1
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    • pp.79-86
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    • 2009
  • The study found out developmental factors of the liver diseases in 29, 531 cases of the healthy adults who were diagnosed by using ultrasound at domestic healthcare centers in 6 cities. The results are as follows. Based on the result of the study, the liver diseases diagnosed by using ultrasound was revealed to show 43.1% of prevalence, and the occurrence was significantly higher in male (23.3%) than in female (19.8%). The prevalence of hepatic diseases related to the BMI was revealed to show highest prevalence of the fatty liver in obese group (BMI $\geqq$ 25) by recording 44.3%. Smoking contributed to the high prevalence of all liver diseases. Although the fatty liver was the most frequently occurred form of liver diseases by recording the prevalence of 49.1% (22.2% in male, 26.9% in female), the significant difference was found only in female (p < 0.05), but male group did not show significant difference (p > 0.05). The prevalence of hepatic diseases related to the hypertension was revealed to show highest prevalence of the fatty liver in hypertension group by recording 67.7%. The prevalence of hepatic diseases related to the diabetes was revealed to show highest prevalence of the fatty liver in diabetes group by recording 66.2%. The high prevalence of all hepatic diseases was related to diabetes mellitus with statistical significance (p < 0.001). The multiple regression analysis for the related factors which affect the prevalence of the liver diseases showed the higher prevalence by age. Sex, obesity and diabetes mellitus were positively related to the prevalence (p < 0.05) while hypertension and smoking showed no significant relationship to the prevalence of the disease (p > 0.05).

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Experimental Applications of in situ Liver Perfusion Machinery for the Study of Liver Disease

  • Choi, Won-Mook;Eun, Hyuk Soo;Lee, Young-Sun;Kim, Sun Jun;Kim, Myung-Ho;Lee, Jun-Hee;Shim, Young-Ri;Kim, Hee-Hoon;Kim, Ye Eun;Yi, Hyon-Seung;Jeong, Won-Il
    • Molecules and Cells
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    • v.42 no.1
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    • pp.45-55
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    • 2019
  • The liver is involved in a wide range of activities in vertebrates and some other animals, including metabolism, protein synthesis, detoxification, and the immune system. Until now, various methods have been devised to study liver diseases; however, each method has its own limitations. In situ liver perfusion machinery, originally developed in rats, has been successfully adapted to mice, enabling the study of liver diseases. Here we describe the protocol, which is a simple but widely applicable method for investigating the liver diseases. The liver is perfused in situ by cannulation of the portal vein and suprahepatic inferior vena cava (IVC), with antegrade closed circuit circulation completed by clamping the infrahepatic IVC. In situ liver perfusion can be utilized to evaluate immune cell migration and function, hemodynamics and related cellular reactions in each type of hepatic cells, and the metabolism of toxic or other compounds by changing the composition of the circulating media. In situ liver perfusion method maintains liver function and cell viability for up to 2 h. This study also describes an optional protocol using density-gradient centrifugation for the separation of different types of hepatic cells, allowing the determination of changes in each cell type. In summary, this method of in situ liver perfusion will be useful for studying liver diseases as a complement to other established methods.

Risk Factors Analysis of Alcoholic Liver Diseases by Ultrasonography (초음파검사에 의한 알코올성 간질환의 위험요인 분석)

  • Lee, Man-Koo;Han, Nam-Sook;Lim, Cheong-Hwan;Jung, Hong-Ryang;Cho, Jung-Keun
    • The Journal of the Korea Contents Association
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    • v.9 no.3
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    • pp.185-194
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    • 2009
  • This research attempted to find risk factors of alcoholic liver diseases by ultrasonography at the K image medicine clinic center located in Kwangju city, Kyunggi-Do from March to May, 2007. Six risk factors were selected for this study, age, sex, frequency of alcohol drinking, body mass index(BMI), cholesterol and GPT. The data collected from 353 patients of aged between 20 and 69. This study found the relationships between liver diseases and alcohol drinking style by liver ultrasonography. The results of the analyses showed that the male were 2.12 times more likely to have liver diseases than the female. The persons drinking alcohol more than 3 times per week had 2.37 times higher likelihood of showing liver diseases than below 2 times per week or non drinking at all.. The persons with normal body mass index have 0.52 times lower probability of liver diseases than the persons with abnormal BMI. The persons with abnormal cholesterol level have 9.13 times higher probability of liver diseases. The persons with abnormal GPT have 4.66 times higher probability of liver diseases. The results of this study suggested applying ultrasonography in health promotion programs for diagnosis of liver diseases.

Evaluation of Endoscopic Characteristics of Upper Gastrointestinal Polyps in Patients with Familial Adenomatous Polyposis

  • Fatemi, Seyed Reza;Safaee, Azadeh;Pasha, Sara;Pourhoseingholi, Mohamad Amin;Bahrainei, Rasool;Molaei, Mahsa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6945-6948
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    • 2014
  • Background: Familial adenomatous polyposis (FAP) is a disease inherited in an autosomal dominant fashion. Most FAP patients develop upper gastrointestinal polyps; especially those in the antrum and duodenum are usually neoplastic. The aim of this study was to evaluate the prevalence of gastroduodenal polyps in Iranian FAP patients. Materials and Methods: 28 patients affected by FAP underwent front-view and side-view endoscopy. Papillary biopsies were performed in all patients. Location of polyps, their number and size, pathology study, patient general information (gender, age, family history of FAP or colorectal cancer and gastroduodenal polyps) were analyzed. Results: Gastric polyps were seen in 39.3 % of patients. Some 72.7% of the affected individuals had fundic gland polyps and 36.36% had hyperplastic polyps. Duodenal adenoma was observed in 25% of patients. While 57% of patients had tubular adenoma with low grade dysplasia, 42.8% showed tubulovillous adenoma with low grade dysplasia. Conclusions: Findings of this study indicated that the prevalence of gastroduodenal polyps in FAP patients is high and dysplasia may be evident in duodenal polyps. Therefore, it appears that routine gastroduodenal endoscopy in FAP patients is necessary.

The Prostaglandin Synthase 2/cyclooxygenase 2 (PTGS2/COX2) rs5277 Polymorphism Does not Influence Risk of Colorectal Cancer in an Iranian Population

  • Khorshidi, Fatemeh;Haghighi, Mahdi Montazer;Mojarad, Ehsan Nazemalhosseini;Azimzadeh, Pedram;Damavand, Behzad;Vahedi, Mohsen;Almasi, Shohreh;Aghdaei, Hamid Asadzadeh;Zali, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3507-3511
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    • 2014
  • Background: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. Materials and Methods: We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). Conclusions: Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC.

Intronic Polymorphisms of the SMAD7 Gene in Association with Colorectal Cancer

  • Damavand, Behzad;Derakhshani, Shaghayegh;Saeedi, Nastaran;Mohebbi, Seyed Reza;Milanizadeh, Saman;Azimzadeh, Pedram;Aghdaie, Hamid Asadzadeh;Zali, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.41-44
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    • 2015
  • Based on genome-wide association studies (GWAS) a linkage between several variants such as single nucleotide polymorphisms (SNPs) in intron 3 of SMAD7 (mothers against decapentaplegic homolog7) were, rs12953717, rs4464148 and rs4939827 has been noted for susceptibility to colorectal cancer (CRC). In this study we investigated the relationship of rs12953717 and rs4464148 with risk of CRC among 487 Iranian individuals based on a case-control study. Genotyping of SNPs was performed by PCR-RFLP and for confirming the outcomes, 10% of genotyping cases were sequenced with RFLP. Comparing the case and control group, we have found significant association between the rs4464148 SNP and lower risk of CRC. The AG genotype showed decreased risk with and odds ratio of 0.635 (adjusted OR=0.635, 95% CI: 0.417-0.967, p=0.034). There was no significant difference in the distribution of SMAD7 gene rs12953717 TT genotype between two groups of the population evaluated (adjusted OR=1.604, 95% CI: 0.978-2.633, p=0.061). On the other hand, rs12953717 T allele showed a statistically significant association with CRC risk (adjusted OR=1.339, 95% CI: 1.017-1.764, p=0.037). In conclusion, we found a significant association between CRC risk and the rs4464148 AG genotype. Furthermore, the rs12953717 T allele may act as a risk factor. This association may be caused by alternative splicing of pre mRNA. Although we observed a strong association with rs4464148 GG genotype in affected women, we did not detect the same association in CRC male patients.