Journal of Carcinogenesis最新文献

Colorectal cancer (CRC) is an important cause of mortality and morbidity in North America. Screening using a fecal occult blood test, flexible sigmoidoscopy, or colonoscopy reduces CRC mortality through the detection and treatment of precancerous polyps and early stage CRC. Although CRC screening participation has increased in recent years, large inequities still exist. Minorities, new immigrants, and those with lower levels of education or income are much less likely to be screened. This review provides an overview of the commonly used tests for CRC screening, disparities in CRC screening, and promising methods at the individual, provider, and system levels to reduce these disparities. Overall, to achieve high CRC participation rates and reduce the burden of CRC in the population, a multi-faceted approach that uses strategies at all levels to reduce CRC screening disparities is urgently required.

The incidence of esophageal cancer remains on the rise worldwide and despite aggressive research in the field of gastrointestinal oncology, the survival remains poor. Much remains to be defined in esophageal cancer, including the development of an effective screening tool, identifying a good tumor marker for surveillance purposes, ways to target esophageal cancer stem cells as well as circulating tumor cells, and developing minimally invasive protocols to treat early-stage disease. The goal of this chapter is to highlight some of the recent advances and ongoing research in the field of esophageal cancer.

Background: The present study observed the expression levels of epidermal growth factor receptor (EGFR), p53, Bcl2, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (cox-2), cyclin D1, human epidermal receptor-2 (HER-2) and Ki-67 in gallbladder carcinoma (GBC) and their association with clinicopathological profiles and disease outcomes.

Materials and methods: Fifty consecutive samples of cholecystectomy/biopsies from GB bed (archived formalin fixed paraffin embedded tissue blocks of different stages of GBC) were included, and patient details related to their demographic profile, investigations, tumor profile, treatment, and follow-up were recorded. Immunohistochemistry was performed to study the expression levels.

Results: Overexpression of EGFR, p53, Bcl2, VEGF, cox-2, cyclin D1 and HER-2 was observed as 74%, 44%, 8%, 34%, 66%, 64%, and 4%, respectively. Association of Bcl2 overexpression in mucinous morphology (40%, P = 0.045), cox-2 overexpression in early stage (I/II) tumors (87.5%, P = 0.028) and VEGF overexpression in alive patients (47.1%, P = 0.044) was observed. Co-expression of EGFR and p53 were statistically significant (P = 0.033). Ki-67 labeling index was significantly higher in patients in age group <40 years (P = 0.027), and poorly differentiated tumors (P = 0.023). Advanced disease and poorly differentiated tumors showed a significantly poor median survival (P < 0.05).

Conclusion: EGFR, cox-2 and cyclin D1 were largely overexpressed. Advanced tumor stages and poorly differentiated tumors are predictors of poor survival.

Backgrounds: Doenjang is traditional Korean fermented soybean paste and widely known for its various health benefits including anticancer effect. In this study, we manufactured doenjang with the grain-type meju using probiotic mixed starter cultures of Aspegillus oryzae, Bacillus subtilis-SKm, and Lactococcus lactis-GAm to improve the qualities and beneficial properties of doenjang.

Materials and methods: The inhibitory effects of the doenjang prepared with the grain-type meju using mixed starter cultures were investigated in azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced colon carcinogenesis mice model. AOM and DSS colon carcinogenesis was induced in female C57BL/6 mice, and doenjang was orally administered for 4 weeks. Body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically evaluated. The serum levels of proinflammatory cytokines as well as the expression of inflammation- and apoptosis-related genes in colonic tissue were also analyzed.

Results: Administration of the doenjang using probiotic mixed starter cultures ameliorated the symptoms of colon cancer, and reduced the incidence of neoplasia, and reduced the levels of serum proinflammatory cytokines such as interleukin-6, and tumor necrosis factor-α and inducible nitric oxide synthase and cycloooxygenase-2 expression levels in colonic tissue. In addition, it increased Bax and reduced Bcl-2 expression levels and increased p21 and p53 expression in the colonic tissues.

Conclusion: These findings indicate that the doenjang attenuated colon carcinogenesis induced by AOM and DSS by ameliorating the symptoms of colon cancer, reducing the occurrence of neoplasia, regulating proinflammatory cytokine levels, and controlling the expressions of inflammation- and apoptosis-related genes in the colonic tissue.

Circulating tumor cell (CTC) measurement in peripheral blood of patients with breast cancer offers prognostic information. In this review, we will try to identify evidence that could be used for prognosis, predictive power to draw this tool to clinical utility. We reviewed 81 manuscripts, and categorized those in discovery datasets, prognostic factors in metastatic breast cancer, identification of clinical utility in early breast cancer and in novel approaches. With each patient responding differently to chemotherapy, more efficient markers would improve clinical outcome. Current CTC diagnostic techniques use epithelial markers predominantly; however, the most appropriate method is the measurement of circulating DNA. It has been hypothesized that micrometastasis occurs early in the development of tumors. That implies the presence of CTCs in nonmetastatic setting. The origin of stimulus for malignant transformation is yet unknown. The role of microenvironment as a stimulus is also being investigated. It has been shown that CTCs vary in numbers with chemotherapy. The markers, which are followed-up in the primary tumors, are also being studied on the CTCs. There is discordance of the human epidermal growth factor receptor-2 status between the primary tumor and CTCs. This review summarizes our current knowledge about the CTCs. With genetic profiling and molecular characterization of CTCs, it is possible to overcome the diagnostic difficulties. Evidence for clinical utility of CTC as prognostic and predictive marker is increasing. Appropriate patient stratification according to CTC determination among other tests, would make personalized cancer therapy more feasible.

Context: Aristolochia tagala (AT) and Curcuma caesia (CC) have been used traditionally by local herbal practitioners for cancer treatment and as chief ingredients of many polyherbal formulations for various types of ailments. However, there is void in scientific study to evaluate their anti-cancer property.

Aims: The aim of this study was to evaluate the anti-carcinogenic properties of the crude methanolic extracts of roots of AT and rhizomes of CC in BALB/c mice exposed to a hepatocarcinogen, diethylnitrosamine (DEN).

Settings and design: (I) Toxicity of herbal plant extracts (HPE); (II) Anticancer studies; (III) Histological studies; and (IV) Biochemical studies.

Materials and methods: To evaluate the effects of these two HPE either alone or following DEN exposure, serum transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]), alkaline phosphatase (ALP), and cancer marker enzyme acetylcholine esterase (AChE) were assayed in mice. In addition, histological study was also carried out under similar conditions. The antioxidant potentials of the HPE were evaluated by monitoring the activity of antioxidant enzymes and metabolites, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH).

Statistical analysis used: Statistical analysis was performed by GraphPad Prism 6 Software using one-way analysis of variance followed by the Tukey's multiple comparisons test. Significance was set at P < 0.05.

Results: Our findings show that DEN administration elevated AST, ALT, ALP, and AChE activities. CC or AT extracts attenuated the increased activities of these marker enzymes. The activities of antioxidant enzymes, which were decreased following DEN administration, were significantly increased in mice treated with CC or AT.

Conclusions: The present study clearly documents anticarcinogenic and antioxidant properties of AT and CC in DEN-induced mouse liver cancer in vivo.

Prostate cancer (PCa) is a leading cause of cancer mortality in men and despite high cure rates with surgery and/or radiation, 30-40% of patients will eventually develop advanced disease. Androgen deprivation is the first line therapy for standard of care for men with advanced disease. Eventually however all men will progress to castration-resistant prostate cancer (CRPC). Insight into the molecular mechanisms of androgen resistance has led to the development of alternative novel hormonal agents. Newer hormonal agents such as abiraterone, enzalutamide and TOK-001; and the first cancer vaccine, Sipuleucel T have been approved for use in men with CRPC. The recognition of the importance of bone health and morbidity associated with skeletal related events has led to the introduction of the receptor activator of nuclear factor kappa-B-ligand inhibitor denosumab. Other molecularly targeted therapies have shown promise in pre-clinical studies, but this has not consistently translated into clinical efficacy. It is increasingly evident that CRPC is a heterogeneous disease and an individualized approach directed at identifying primary involvement of specific pathways could maximize the benefit from targeted therapies. This review focuses on targeted therapy for PCa with special emphasis on therapies that have been Food and Drug Administration approved for use in men with CRPC.

Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR), there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings.

Increased understanding of cancer pathogenesis has identified several pathways that serve as potential targets for novel targeted agents in development. The selection of targeted cancer therapy based on biomarkers has instigated a new era of personalized medicine and changed the way we practice oncology. Many targeted agents are approved for treatment of gastrointestinal malignancies most targeting tumor angiogenesis, and many more are in different phases of development. Here we briefly summarize nine different targeted agents that are approved currently in the U.S. and several other agents currently being studied in various gastrointestinal cancers.