The Effects of Autophagy and Senescence on Sensitivity to Cisplatin in Head and Neck Cancer - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Effects of Autophagy and Senescence on Sensitivity to Cisplatin in Head and Neck Cancer write by Zara Hafeez Siddiqui. This book was released on 2020. The Effects of Autophagy and Senescence on Sensitivity to Cisplatin in Head and Neck Cancer available in PDF, EPUB and Kindle. While current treatments in cancer, such as chemotherapy and radiation, can generally be effective in eliminating disease in patients, there also exists the possibility of recurrence of cancer cells over time. In patients diagnosed with locally advanced head and neck carcinoma, about 50-60% develop a loco-regional recurrence within two years, and 20-30% of patients develop metastatic disease at distant sites in the body [5]. On a cellular level, one mechanism for this survival may be that natural mechanisms such as autophagy and senescence play a role in allowing cells to survive after undergoing treatment. One standard of care chemotherapy for head and neck cancer is cisplatin, which was used as the primary treatment in this project. HN12 cells (head and neck tumor cells; p53-null) showed significant growth arrest and decreased viability in response to 5 [mu]M cisplatin treatment, but proliferative recovery over time. It was found that apoptosis did not play a significant role in this growth arrest, as assessed by annexin V/propidium iodide assays to measure apoptotic cell death. Additionally, cisplatin was shown to induce significant levels of autophagy in head and neck tumor cells with acridine orange staining and western blot analysis; however, pharmacological inhibition of autophagy with either chloroquine (5 [mu]M), bafilomycin (5 nM), or 3-methyladenine (1 mM) did not sensitize cells to treatment with cisplatin, indicating a nonprotective role of autophagy. Additionally, HN12 cells showed significant levels of senescence, a form of cellular growth arrest, as indicated by beta-galactosidase upregulation, flattened morphology, and cell cycle arrest. Targeting of senescent cells with the senolytic ABT-263, a Bcl-2/Bcl-xl inhibitor, was effective in sensitizing cells to treatment with cisplatin, but cellular proliferation still occurred over time. Additionally, the HN30 cell line (p53 wild type) was compared to the HN12 line and experiments suggested that p53 status did not play a significant role in induction of autophagy or the sensitization to the senolytic, although more work needs to be done. Overall, these studies provide evidence that autophagy is nonprotective in the HN12 cell line in response to cisplatin treatment, and that senescence plays a role in allowing cells to survive over time. Further, ABT-263 is effective in targeting the remaining population of senescent cells after cisplatin treatment and may be a potential therapeutic mechanism in preventing the recurrence of head and neck cancers.
Autophagy and Senescence in Cancer Therapy
Autophagy and Senescence in Cancer Therapy - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Autophagy and Senescence in Cancer Therapy write by . This book was released on 2021-04-13. Autophagy and Senescence in Cancer Therapy available in PDF, EPUB and Kindle. Advances in Cancer Research, Volume 150, the latest release in this ongoing series, covers the relationship(s) between autophagy and senescence, how they are defined, and the influence of these cellular responses on tumor dormancy and disease recurrence. Specific sections in this new release include Autophagy and senescence, converging roles in pathophysiology, Cellular senescence and tumor promotion: role of the unfolded protein response, autophagy and senescence in cancer stem cells, Targeting the stress support network regulated by autophagy and senescence for cancer treatment, Autophagy and PTEN in DNA damage-induced senescence, mTOR as a senescence manipulation target: A forked road, and more. Addresses the relationship between autophagy and senescence in cancer therapy Covers autophagy and senescence in tumor dormancy Explores autophagy and senescence in disease recurrence
Cytoprotective Versus Non-protective Autophagy Induced by Radiation in Head and Neck Cancer Cells
Cytoprotective Versus Non-protective Autophagy Induced by Radiation in Head and Neck Cancer Cells - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Cytoprotective Versus Non-protective Autophagy Induced by Radiation in Head and Neck Cancer Cells write by Duaa Mohamed Bakhshwin. This book was released on 2014. Cytoprotective Versus Non-protective Autophagy Induced by Radiation in Head and Neck Cancer Cells available in PDF, EPUB and Kindle. The primary treatment options for head and neck cancer are radiation therapy or surgery, or both combined; chemotherapy is often used as an additional, or adjuvant, treatment. Patients treated with radiotherapy are exposed to a high cumulative dose of radiation over a period of time and there is a 17-33% chance of recurrence. High cumulative doses of radiation, a long time course of treatment, side effects and the possibility of recurrence provide the rationale for developing approaches for radiation sensitization, which could be helpful to patients in decreasing the dose, duration of radiation, side effects, or the chance of recurrence. Radiation induces autophagy, which is a catabolic process involving the degradation of the cell's own components to generate energy under conditions of stress. Autophagy can be cytoprotective helping the cell to survive during stress such as nutrient deprivation or it can be cytotoxic, leading the cell toward death. We investigated whether blocking autophagy by the use of the antimalarial drug, chloroquine, could sensitize head and neck cancer cells to radiation. Studies were performed using the HN30 human head and neck cancer line (p53 wild type) derived from the pharynx as well as HN6 human cells (p53 mutant) derived from the base of the tongue. Cell viability was determined by cell counting and clonogenic survival assays, autophagy was monitored based on acridine orange staining accompanied by flow cytometry, while western blotting, DAPI and TUNEL staining and PI/annexin/FACS were utilized for determination and quantification of apoptosis. Senescence was monitored by beta-galactosidase staining/ FACS analysis. Radiation alone produced a transient growth arrest followed by proliferative recovery in both the HN30 and HN6 cancer cells. Radiation also promoted autophagy in both cell lines. The combination of chloroquine with radiation inhibited autophagy and promoted apoptotic cell death and suppression of proliferative recovery for the HN30 cells, but had little effect on sensitivity to radiation and proliferative recovery in the HN6 cells. The data suggest that autophagy induced by radiation serves a protective function in the HN30 cells and that a blockade to autophagy by chloroquine drives the cell toward apoptosis and death. In contrast, autophagy in HN6 cells appears to be non-protective as a pharmacological blockade did not sensitize the HN6 cells to radiation. These studies support the premise that autophagy induction by radiation need not necessarily have a cytoprotective function and further indicates that caution should be exercised in efforts to sensitize head and neck cancer to radiation through the clinical suppression of autophagy.
Basic Principles of Cancer Chemotherapy
Basic Principles of Cancer Chemotherapy - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Basic Principles of Cancer Chemotherapy write by Kenneth Charles Calman. This book was released on 1980. Basic Principles of Cancer Chemotherapy available in PDF, EPUB and Kindle.
Metronomic Chemotherapy
Metronomic Chemotherapy - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Metronomic Chemotherapy write by Guido Bocci. This book was released on 2014-09-04. Metronomic Chemotherapy available in PDF, EPUB and Kindle. This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.
