Therapeutic Approaches to Increase the Survival Rate of Cancer Patients in the Younger and Older Population.

galpattu, India Abstract: Various developments have been observed in the treatment of cancer patients, such as higher survival rates and better treatment outcomes. However, expecting similar outcomes in older patients remains a challenge. The main reason for this conclusion is the exclusion of older people from clinical trials for cancer drugs, as well as other factors, such as comorbidity, side effects, age-related frailties and their willingness to undergo multiple treatments. However, the discovery of new techniques and drug combinations has led to a significant improvement in the survival of the elderly population after the onset of the disease. On the other hand, cancer treatments have not become more complex for the younger population when compared to the older population, as the younger population tends to respond well to treatment trials and their physiological conditions are stable in response to treatments. In summary, this review correlates recent cancer treatment strategies and the corresponding responses and survival outcomes of older and younger patients.

The epigenetic correlation among ovarian cancer, endometriosis and PCOS: A review.

Ovarian cancer is a frequent malignancy that affects a large percentage of women. Endometriosis is a chronic condition, where there is a production of benign lesions were observed in the uterine environment. PCOS is a metabolic disorder characterized by the presence of numerous cysts in the ovaries. The relation between ovarian malignancies and PCOS, by an increased ratio of ovarian stromal tissues in PCOS patients. The direct correlation is not yet confirmed among the three disorders, but it is often noted that they share risk factors, such as obesity, hormonal imbalances. Epigenetic factors have shown to be an important reason for cancer progression. Our findings at the epigenetic level includes a comparative analysis, point mutations in genes, overactivation of signaling pathways. This review paper, highlight the possible correlation between the three disorders in terms of genetic and epigenetic factors and how it could together trigger the cancer progression and metastasis.

Pleiotropic effects of DCLK1 in cancer and cancer stem cells.

Doublecortin-like kinase 1 (DCLK1), a protein molecule, has been identified as a tumor stem cell marker in the cancer cells of gastrointestinal, pancreas, and human colon. DCLK1 expression in cancers, such as breast carcinoma, lung carcinoma, hepatic cell carcinoma, tuft cells, and human cholangiocarcinoma, has shown a way to target the DCLK1 gene and downregulate its expression. Several studies have discussed the inhibition of tumor cell proliferation along with neoplastic cell arrest when the DCLK1 gene, which is expressed in both cancer and normal cells, was targeted successfully. In addition, previous studies have shown that DCLK1 plays a vital role in various cancer metastases. The correlation of DCLK1 with numerous stem cell receptors, signaling pathways, and genes suggests its direct or an indirect role in promoting tumorigenesis. Moreover, the impact of DCLK1 was found to be related to the functioning of an oncogene. The downregulation of DCLK1 expression by using targeted strategies, such as embracing the use of siRNA, miRNA, CRISPR/Cas9 technology, nanomolecules, specific monoclonal antibodies, and silencing the pathways regulated by DCLK1, has shown promising results in both in vitro and in vivo studies on gastrointestinal (GI) cancers. In this review, we will discuss about the present understanding of DCLK1 and its role in the progression of GI cancer and metastasis.

Stem Cell-Derived Exosomes Potential Therapeutic Roles in Cardiovascular Diseases.

Owing to myocardial abnormalities, cardiac ailments are considered to be the major cause of morbidity and mortality worldwide. According to a recent study, membranous vesicles that are produced naturally, termed as "exosomes", have emerged as the potential candidate in the field of cardiac regenerative medicine. A wide spectrum of stem cells has also been investigated in the treatment of cardiovascular diseases (CVD). Exosomes obtained from the stem cells are found to be cardioprotective and offer great hope in the treatment of CVD. The basic nature of exosomes is to deal with the intracellular delivery of both proteins and nucleic acids. This activity of exosomes helps us to rely on them as the attractive pharmaceutical delivery agents. Most importantly, exosomes derived from microRNAs (miRNAs) hold great promise in assessing the risk of CVD, as they serve as notable biomarkers of the disease. Exosomes are small, less immunogenic, and lack toxicity. These nanovesicles harbor immense potential as a therapeutic entity and would provide fruitful benefits if consequential research were focused on their upbringing and development as a useful diagnostic and therapeutic tool in the field of medicine.

Tamoxifen induces stem-like phenotypes and multidrug resistance by altering epigenetic regulators in ERα+ breast cancer cells.

BACKGROUND: To understand the mechanism underlying tamoxifen-induced multidrug resistance (MDR) and stem-like phenotypes in breast cancer cells, we treated the MCF-7 cells with 4-hydroxy-tamoxifen (TAM) for 6 months continuously and established MCF-7 tamoxifen resistance (TR) phenotypes. METHODS: In the present study, the following methods were used: cell viability assay, colony formation, cell cycle analysis, ALDEFLUOR assay, mammosphere formation assay, chromatin immunoprecipitation (ChIP) assay, PCR array, western blot analysis and quantitative reverse transcription polymerase chain reaction (QRT-PCR). RESULTS: The expression of ERα was significantly higher in MCF7-TR cells when compared with parental MCF-7 cells. MCF7-TR cells exposed to TAM showed a significant increase in the proliferation and rate of colony formation. The number of cancer stem cells was higher in MCF7-TR cells as observed by the increase in the number of ALDH+ cells. Furthermore, the number of mammospheres formed from the FACS-sorted ALDH+ cells was higher in MCF7-TR cells. Using PCR array analysis, we were able to identify that the long-term exposure of TAM leads to alterations in the epigenetic and MDR stem cell marker genes. Furthermore, western blot analysis demonstrated elevated levels of Notch-1 expression in MCF-TR cells compared with MCF-7 cells. Chromatin immunoprecipitation (ChIP) assay revealed that Notch-1 enhanced the cyclin D1 expression significantly in these cells. In addition, we observed that MCF7-TR cells were resistant to doxorubicin but not the MCF-7 cells. CONCLUSIONS: In the present study, we conclude that the treatment with tamoxifen induces multiple epigenetic alterations that lead to the development of MDR and stem-like phenotypes in breast cancers. Therefore, our study provides better insights to develop novel treatment regime to control the progression of breast cancer.