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Full-Text Articles in Medical Sciences

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee Jan 2020

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …


The Effects Of Autophagy And Senescence On Sensitivity To Cisplatin In Head And Neck Cancer, Zara H. Siddiqui Jan 2020

The Effects Of Autophagy And Senescence On Sensitivity To Cisplatin In Head And Neck Cancer, Zara H. Siddiqui

Theses and Dissertations

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 …


In Vivo Effects Of The Cb1 Allosteric Modulator Ldk1258, A Structural Analog Of Org-27569, Mohammed A. Mustafa Jan 2020

In Vivo Effects Of The Cb1 Allosteric Modulator Ldk1258, A Structural Analog Of Org-27569, Mohammed A. Mustafa

Theses and Dissertations

CB1 receptor allosteric modulators are an area of growing interest for their potential novel therapeutic actions. In the present study, we examined LDK1258 in a series of pharmacological in vivo tests sensitive to CB1 receptor stimulation. In the tetrad assay, LDK1258 produced significant decreases in locomotor activity and body temperature measures but did not produce either antinociception as measured in the tail-withdrawal assay or catalepsy as assessed in the bar test. These same effects were observed in both CB1 (-/-) and (+/+) mice. Moreover, LDK1258 failed to shift the dose-response curves of two orthosteric CB1 receptor agonists in the triad …