Oncology Commons^™

Concomitant Inhibition Of Flt3 And Mcl-1 In Flt3 Mutated Acute Myeloid Leukemia, Paul Panis

Dissertations & Theses (Open Access)

The MCL-1 inhibitor S63845 synergizes with the FLT3 inhibitor midostaurin for potent anti-leukemic effect in preclinical human models of FLT3-ITD mutated acute myeloid leukemia (AML). Acute Myeloid leukemia (AML) is a neoplastic blood disorder defined by a characteristically rapid growth rate and altered behavior of myeloid cells in the bone marrow. The FLT3 receptor is responsible for the upstream regulation of many key processes in hematopoietic cells. FLT3 internal tandem duplication (ITD) mutations are common in leukemia and have been observed in up to a third of newly diagnosed AML patients. FLT3-ITD have been implicated as a driver mutation partly …

Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim

Department of Biological & Biomedical Sciences

Objective: To investigate the anticancer effect of Illicium verum against human breast cancer MCF-7 cell line.
Methods: An experimental study was conducted in Multidisciplinary and Tissue Culture Laboratory, Aga Khan University in collaboration with Pharmacology Department of Bahria University Medical and Dental College, Karachi, Pakistan from January 2021 to June 2021. MCF-7 cells of Luminal-A breast cancer were seeded in 96-well plate and treated with I.verum methanol extract. After incubation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye was used for cell viability and cell proliferation assays to determine the number of dead and viable cells, and the absorbance was measured using an enzyme-linked …

The Innate Immune System In Cardiovascular Diseases And Its Role In Doxorubicin-Induced Cardiotoxicity, Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman

Student and Faculty Publications

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release …

Inhibition Of Cyclin Dependent Kinase 4/6 Overcomes Primary Resistance To Programmed Cell Death 1 Blockade In Malignant Mesothelioma, Hee-Jin Jang, Cynthia Y Truong, Eric M Lo, Hudson M Holmes, Daniela Ramos, Maheshwari Ramineni, Ju-Seog Lee, Daniel Y Wang, Massimo Pietropaolo, R Taylor Ripley, Bryan M Burt, Hyun-Sung Lee

Student and Faculty Publications

BACKGROUND: Despite the profound number of malignant pleural mesothelioma (MPM) patients now treated with programmed cell death 1 (PD-1) blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remains unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM.

METHODS: We generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and 4 nonresponders). We used The Cancer Genome Atlas MPM cohort (n = 73) to determine what genomic alterations were associated with the resistance signature. We tested …

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Student and Faculty Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …

Role Of Sam68 In Sunitinib Induced Renal Cell Carcinoma Apoptosis, Zeshen Wu, Yulu Peng, Longbin Xiong, Jun Wang, Zhen Li, Kang Ning, Minhua Deng, Ning Wang, Wensu Wei, Zhiyong Li, Pei Dong, Chunping Yu, Fangjian Zhou, Zhiling Zhang

Student and Faculty Publications

Sunitinib is one of the first-line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src-associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration-dependent manner and inhibited the expression of total and phosphorylated Sam68 (p-Sam68). Downregulation of Sam68 expression inhibited RCC cell …

The Phenomenon Of Multidrug Resistance In Glioblastomas, Alexandr N. Chernov, Diana A. Alaverdian, Elvira S. Galimova, Alessandra Renieri, Elisa Frullanti, Ilaria Meloni, Olga V. Shamova

Hematology/Oncology and Stem Cell Therapy

The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresistance and chemoresistance. In the current review, we discuss the phenomenon of multidrug resistance of GBM in the context of the expression of ABC family transporter proteins and the mechanisms of proliferation, angiogenesis, and recurrence. We focused on the search of molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes, and their single-nucleotide polymorphisms.

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …