• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1833-1840
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• 2013

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), ${\gamma}$-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

• BMB Reports
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• 제48권3호
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• pp.127-128
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• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3539-3548
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• 2012

The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

• 대한두경부종양학회지
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• 제16권2호
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• pp.161-166
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• 2000

Objective: The nm23 gene has been identified as a potential metastasis suppressor gene in various human neoplasms. Both Bcl-2, which promotes cell survival, and Bax, which promotes cell death, have been considered as major factors in controlling the apoptotic pathway. This study was carried out to determine whether these markers are useful in distinguishing potential intrinsic differences in tumor virulence of papillary thyroid cancers. Material and Method: The expressions of nm23, Bcl-2 and Bax have been evaluated using immunohistochemical techniques in 100 pure papillary thyroid cancers and 20 metastatic lymphnodes. The intensity of immnunoreactivity was graded on arbitrary four point scale(grade 0 or 1 : negative reactivity, grade 2 or 3 positive reactivity). The immunoreactivities were analyzed in relation to TNM atage, AMES score, local recurrence and distant metastasis, and that of metastatic LNs was compared with the tumors. Results: The expression of Bcl-2 and bax did not show any statistical differences by TNM stage, AMES score, recurrence, distant metastasis and also between the tumor and metastatic LN. However, the nm23 showed higher expression of Ki67 in distant metastasis than in control group and in metastatic LNs than in the tumors(p<0.05). Conclusion: Although the expression of Bcl-2 and Bax protein showed no correlation with clinical parameters representing tumor virulence, the nm23 expression could be an useful prognostic factor, especially in predicting nodal or distant metastasis in papillary thyroid cancer.

• Journal of Korean Neurosurgical Society
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• 제50권3호
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• pp.216-223
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• 2011

Objective : The purposes of this study are to estimate postoperative survival and ambulatory outcome and to identify prognostic factors thereafter of metastatic spinal tumors in a single institute. Methods : We reviewed the medical records of 182 patients who underwent surgery for a metastatic spinal tumor from January 1987 to January 2009 retrospectively. Twelve potential prognostic factors (age, gender, primary tumor, extent and location of spinal metastases, interval between primary tumor diagnosis and metastatic spinal cord compression, preoperative treatment, surgical approach and extent, preoperative Eastern Cooperative Oncology Group (ECOG) performance status, Nurick score, Tokuhashi and Tomita score) were investigated. Results : The median survival of the entire patients was 8 months. Of the 182 patients, 80 (44%) died within 6 months after surgery, 113 (62%) died within 1 year after surgery, 138 (76%) died within 2 years after surgery. Postoperatively 47 (26%) patients had improvement in ambulatory function, 126 (69%) had no change, and 9 (5%) had deterioration. On multivariate analysis, better ambulatory outcome was associated with being ambulatory before surgery (p=0.026) and lower preoperative ECOG score (p=0.016). Survival rate was affected by preoperative ECOG performance status (p<0.001) and Tomita score (p<0.001). Conclusion : Survival after metastatic spinal tumor surgery was dependent on preoperative ECOG performance status and Tomita score. The ambulatory functional outcomes after surgery were dependent on preoperative ambulatory status and preoperative ECOG performance status. Thus, prompt decompressive surgery may be warranted to improve patient's survival and gait, before general condition and ambulatory function of patient become worse.

• Journal of Korean Biological Nursing Science
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• 제7권1호
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• pp.47-56
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• 2005

nm23-H1 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. However, its role with respect to the invasive behavior of central nervous system tumors has scarcely been addressed Because cell motility and invasion plays an essential role in metastatic dissemination, we have studied whether motile human glioma cell(U87MG) transfected with nm23-H1 complementary DNA have any alterations in their ability to migrate and invade. There was no significant changes in the shape and size of the cells following nm23-H1 transfection. The role of nm23-H1 in glioma migration and invasion have been evaluated by in vitro simple scratch technique and brain slice invasion model Basal migration ability of nm23-H1 transfectants cell(U87MG-pEGFP-nm23) were lesser than U87MG. Accordingly, U87MG-pEGFP-nm23 didn't migrate away apparently from the tumors implanted site comparing U87MG in brain slice invasion model. These results suggest that nm23-H1 may play an important role in suppressing the human glioma migration and invasion.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권2호
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• pp.81-93
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• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• 대한상부위장관⦁헬리코박터학회지
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• 제18권3호
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• pp.162-167
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• 2018

Cancer specimens obtained via surgical resection or biopsy are generally used to understand tumor-associated alterations; however, those approaches cannot always be performed because of their invasive nature, and they may fail to reflect current tumor dynamics and drug sensitivity, which may change during the therapeutic process. Therefore, many research groups have focused on developing a non-invasive biomarker with the ability to monitor tumor dynamics. Circulating tumor cells (CTCs) are metastatic cells released from the primary tumor into the bloodstream. Hematogenous spreading of CTCs is a crucial step in the metastatic cascade, which leads to the formation of overt metastases. CTCs have attracted considerable attention because of their easy accessibility and their superiority over conventional tumor markers. Detecting CTCs is considered a valuable modality to determine prognosis and monitor response to systemic therapies in patients with gastric cancer. Moreover, molecular analyses of CTCs may provide important biological information for individual patients with cancer, which may lead to the development of personalized cancer treatment. In this article, we review potential roles and clinical applications of CTCs in patients with gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1675-1679
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• 2014

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.155-160
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• 2016

Breast cancer (BC) is the second most common cancer in the world and by far the most frequent cancer among women, with an estimated 1.67 million new cancer cases diagnosed in 2012 (25% of all cancers). Polygene expression analysis is used to predict the prognosis and determine the most appropriate treatment regimen. The objective of this study was to examine the gene expression profiles of SIRT3, HRAS, LSP1, SCUBE2 and AP2A2 in Iranian women with BC.A total of 136 patients including healthy controls were categorized into three groups based on the relapse of the disease. Expression of desired genes in formalin-fixed, paraffin embedded tissues collected from all groups of participants was analyzed via the RT PCR method. RNA extraction and cDNA synthesis were performed then real-time quantitative PCR was carried out. Gene expression analysis revealed that the expression of SIRT3 was equal among patient and control groups. LSP1 was down regulated in all patient groups relative to controls but reduced expression in the metastatic group relative to the non-metastatic one was not significant. HRAS was significantly overexpressed in total and metastatic tumor samples versus normal but not in non-metastatic cases. SCUBE2 expression showed significant over-expression in both overall tumor samples and the non-metastatic group as compared to normal tissues. Gene expression level of AP2A2 in all groups was not detectable. Our data are compatible with a tumor suppressor role of LSP1 related to potential prognostic factor for tumor recurrence and outcome. This study for the first time assayed the prognostic value and changes in the expression of SIRT3, LSP1, HRAS, SCUBE2 and AP2A2 genes in women with breast cancer in the Iranian population and findings confirmed potential biomarker and prognostic capability of these genes. Such expression profiling data can critically improve prognosis and treatment decisions in cancer patients.