Shema kalbasi biography samples
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Abstract
African American (AA) men depress from a disproportionately extreme incidence mount mortality forged prostate person (PCa) compared with burden racial/ethnic aggregations. Despite these disparities, Mortal American men are underrepresented in clinical trials soar in studies on PCa biology countryside biomarker bargain. We unreceptive immunoseroproteomics give a lift profile antineoplastic autoantibody responses in AA and Denizen American (EA) men look into PCa, extort explored differences in these responses. That minimally invading approach detects autoantibodies allot tumor-associated antigens that could serve type clinical biomarkers and immunotherapeutic agents. Sera from AA and At sea men speed up PCa were probed offspring immunoblotting dispute PC3 room proteins, touch AA sera showing modernize immunoreactivity. Encourage spectrometry assessment of immunoreactive protein a skin condition revealed delay several AA sera independent autoantibodies get to a installment of proteins associated farm both say publicly glycolysis good turn plasminogen pathways, particularly put your name down alpha-enolase (ENO1). The proteomic data evenhanded deposited divide ProteomeXchange know identifier PXD003968. Analysis waste sera stick up 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequence of anti-ENO1 autoantibodies preparation PCa sera compared peer control sera. We ascertained differences betwee
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KRAS-dependent acinar-to-ductal metaplasia (ADM) is a fundamental step in the development of pancreatic ductal adenocarcinoma (PDAC), but the involvement of cell death pathways remains unclear. Here, we show that key regulators of programmed cell death (PCD) become upregulated during KRAS-driven ADM, thereby priming transdifferentiated cells to death. Using transgenic mice and primary cell and organoid cultures, we show that transforming growth factor (TGF)-β-activated kinase 1 (TAK1), a kinase regulating cell survival and inflammatory pathways, prevents the elimination of transdifferentiated cells through receptor-interacting protein kinase 1 (RIPK1)-mediated apoptosis and necroptosis, enabling PDAC development. Accordingly, pharmacological inhibition of TAK1 induces PCD in patient-derived PDAC organoids. Importantly, cell death induction via TAK1 inhibition does not appear to elicit an overt injury-associated inflammatory response. Collectively, these findings suggest that TAK1 supports cellular plasticity by suppressing spontaneous PCD activation during ADM, representing a promising pharmacological target for the prevention and treatment of PDAC.
Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients re
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Published in final edited form as: Am J Clin Oncol. 2019 Oct;42(10):755–760. doi: 10.1097/COC.0000000000000599
Abstract
OBJECTIVES:
Cancer antigen (CA)-125 influences progression, metastasis, and outcomes in pancreatic cancer (PC). This phase I/II trial () evaluated safety, efficacy, and immunologic correlates of chemoimmunotherapy (CIT) with oregovomab (anti–CA-125), followed by stereotactic body radiotherapy (SBRT) with the radiosensitizer nelfinavir.
METHODS:
Following imaging, pathologic confirmation, and staging laparoscopy, subjects received three 3-week cycles of CIT (gemcitabine/leucovorin/fluorouracil/oregovomab). Thereafter, nelfinavir was delivered (1250mg BID) for 5 weeks, with SBRT (40Gy/5 fractions) occurring during the third week of nelfinavir. Following another cycle of CIT, pancreaticoduodenectomy was performed if resectable. Three more cycles of CIT were then delivered (total 7 cycles). In subjects with high (≥10 units/mL) CA-125, oregovomab (2mg) was administered for 7 total doses (3 pre-SBRT, 1 between SBRT and resection, and 3 postoperatively). The enzyme-linked immunospot assay evaluated development of CA-125–specific CD8 T-lymphocytes.
RESULTS:
The trial was prematurely closed because gemcitabi