Chemotherapeutic Resistance Genes of Breast Cancer Patients – An Overview

Purpose: Cancer is the leading challenge to human health since the dawn of early Egyptian manuscripts, where they found tumour from fossils in the modernized twentieth century. Increasing rate of incidence and death from cancer in the past few years is thought provoking. Among all type of cancers, breast cancer is very common among women and diverse in character. Drug resistance is the challenging aspect for traditional chemotherapy. Methods: Data was collected from online platform without any time restriction. After screening and evaluation, 66 articles were considered for this study. This review is a summarized collection of information from published studies on human genes associated with drug resistance in breast cancer treatment. Results: Analysis of these findings highlights the importance of MAP kinase and ABC gene families in creating resistance barriers. Genes involved in cell cycle alteration, apoptosis, and hippo pathway were also linked with drug resistance particularly in breast cancer. Conclusion: The exact mechanism of chemotherapy resistance is still unresolved and unexplained the drug resistance seen in breast cancer patients were multifactorial. Drug induced up regulation or down regulation of genes contributes unusual protein expression and ultimately leads to resistance. The ultimate focus of this review is to identify the genes having pivotal role in chemotherapy resistance in breast cancer.

Bengamide Analogues Show A Potent Antitumor Activity against Colon Cancer Cells: A Preliminary Study

The limited success and side effects of the current chemotherapeutic strategies against colorectal cancer (CRC), the third most common cancer worldwide, demand an assay with new drugs. The prominent antitumor activities displayed by the bengamides (Ben), a family of natural products isolated from marine sponges of the Jaspidae family, were explored and investigated as a new option to improve CRC treatment. To this end, two potent bengamide analogues, Ben I (5) and Ben V (10), were selected for this study, for which they were synthesized according to a new synthetic strategy recently developed in our laboratories. Their antitumor effects were analyzed in human and mouse colon cell lines, using cell cycle analysis and antiproliferative assays. In addition, the toxicity of the selected analogues was tested in human blood cells. These biological studies revealed that Ben I and V produced a significant decrease in CRC cell proliferation and induced a significant cell cycle alteration with a greater antiproliferative effect on tumor cell lines than normal cells. Interestingly, no toxicity effects were detected in blood cells for both compounds. All these biological results render the bengamide analogues Ben I and Ben V as promising antitumoral agents for the treatment of CRC.

ET-11 ANALYSIS OF ANTI-GLIOMA EFFECT BY PROINFLAMMATORY CYTOKINES

OBJECT Antiglioma activity of proinflammatory cytokines, (TNF-alpha, IL-2, IL-12 related cytokines, IL-18, IL-32) are analyzed. Most effective combinations of cytokines are investigated. MATERIAL & METHOD Antitumor activity against U373MG, U87MG were measured by co-culture with PBMC and by nude mouse subcutaneous transplantation model. Cytokine receptors on PBMC and glioma cell lines were examined by IHC and mRNA expression. Anti-tumor activity was measured by local injection and systemic administration of proinflammatory cytokines. Cell cycle alteration and expression of apoptosis-related genes after cytokine administration was analyzed. Serum concentraion of cytokines is measured by ELISA. RESULT Cytokine receptors were not expressed on glioma cells but were present on intratmoral mononuclear cells. Anti-tumor activity against transplanted tumor is strongly observed by focal administration. Expression of apoptosis-related genes were augmented. IFN-gamma was strongly induced by TNF-alpha, IL-2 and IL-12 administration. IFN-gamma, IL-17, TNF-alpha were also induced. IL-27 and IL-32 per se did not induce IFN-gamma. Simultaneous IL-27 and IL-12 induced strong IFN-gamma induction. Anti-glioma activity of IL-12 and IL-23 were higher than the same dose of exogenous IFN-gamma. IFN-gamma, IL-2 plus IL-12 in U373MG, and IFN-gamma, IL-2 plus IL-18 in U87MG seemed to be the best combination. CONCLUSIONS Strong anti-glioma activity was induced by proinflammatory cytokines at least partially through IFN-gamma. There may be another factors. IL-2 and IL-23 showed anti-tumor activity through IFN-gamma, IL-17, TNF-alpha. IFN-gamma + IL-2 + IL-12/-18 seems to be the best combination.

In Vitro Toxicity of TiO2:SiO2 Nanocomposites with Different Photocatalytic Properties

The enormous technological relevance of titanium dioxide (TiO2) nanoparticles (NPs) and the consequent concerns regarding potentially hazardous effects that exposure during production, use, and disposal can generate, encourage material scientists to develop and validate intrinsically safe design solution (safe-by-design). Under this perspective, the encapsulation in a silica dioxide (SiO2) matrix could be an effective strategy to improve TiO2 NPs safety, preserving photocatalytic and antibacterial properties. In this work, A549 cells were used to investigate the toxic effects of silica-encapsulated TiO2 having different ratios of TiO2 and SiO2 (1:1, 1:3, and 3:1). NPs were characterized by electron microscopy and dynamic light scattering, and cell viability, oxidative stress, morphological changes, and cell cycle alteration were evaluated. Resulting data demonstrated that NPs with lower content of SiO2 are able to induce cytotoxic effects, triggered by oxidative stress and resulting in cell necrosis and cell cycle alteration. The physicochemical properties of NPs are responsible for their toxicity. Particles with small size and high stability interact with pulmonary cells more effectively, and the different ratio among silica and titania plays a crucial role in the induced cytotoxicity. These results strengthen the need to take into account a safe(r)-by-design approach in the development of new nanomaterials for research and manufacturing.

Heterogeneity of γH2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors

The biomarker for DNA double stand breaks, gammaH2AX (γH2AX), holds a high potential as an intrinsic radiosensitivity predictor of tumors in clinical practice. Here, two published γH2AX foci datasets from in and ex vivo exposed human head and neck squamous cell carcinoma (hHNSCC) xenografts were statistically re-evaluated for the effect of the assay setting (in or ex vivo) on cellular geometry and the degree of heterogeneity in γH2AX foci. Significant differences between the nucleus areas of in- and ex vivo exposed samples were found. However, the number of foci increased linearly with nucleus area in irradiated samples of both settings. Moreover, irradiated tumor cells showed changes of nucleus area distributions towards larger areas compared to unexposed samples, implying cell cycle alteration after radiation exposure. The number of residual γH2AX foci showed a higher degree of intra-tumoral heterogeneity in the ex vivo exposed samples relative to the in vivo exposed samples. In the in vivo setting, the highest intra-tumoral heterogeneity was observed in initial γH2AX foci numbers (foci detected 30 min following irradiation). These results suggest that the tumor microenvironment and the culture condition considerably influence cellular adaptation and DNA damage repair.

Buckwheat and buckwheat enriched products exert an anti-inflammatory effect on the myofibroblasts of colon CCD-18Co

Buckwheat products ameliorated cell migration and cell cycle alteration of colon myofibroblasts in the presence of TNF-α.

Diethylnitrosamine Increases Proliferation in Early Stages of Hepatic Carcinogenesis in Insulin-Treated Type 1 Diabetic Mice

Diethylnitrosamine (DEN) induces hepatocarcinogenesis, increasing mitotic hepatocytes and leading to chronic inflammation. In addition, type 1 diabetes mellitus (T1DM) is also characterized by a proinflammatory state and by requiring insulin exogenous treatment. Given the association of diabetes, insulin treatment, and cell proliferation, our specific goal was to determine whether the liver in the diabetic state presents a greater response to DEN-induced cell cycle alteration, which is essential for the malignant transformation. Male C57BL/6 mice (four-week-old) were divided into 4 groups: C, C + DEN, T1DM, and T1DM + DEN. Mice were euthanized ten weeks after DEN injection. DEN per se produced an increase in liver lipid peroxidation levels. Besides, in T1DM + DEN, we found a greater increase in the proliferation index, in comparison with C + DEN. These results are in agreement with the increased expression observed in cell cycle progression markers: cyclin D1 and E1. In addition, a proapoptotic factor, such as activated caspase-3, evidenced a decrease in T1DM + DEN, while the Vascular Endothelial Growth Factor (VEGF) and the protooncogene p53 showed a higher increase with respect to C + DEN. Overall, the results allow us to highlight a major DEN response in T1DM, which may explain in part the greater predisposition to the development of hepatocarcinoma (HCC) during the diabetic state.