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DCLK1 Inhibition Sensitizes Colorectal Cancer Cells to Radiation Treatment
Int J Mol Cell Med. 2021 Winter;10(1):23-33. doi: 10.22088/IJMCM.BUMS.10.1.23. Epub 2021 May 22.ABSTRACTColorectal cancer (CRC) is one of the most prevalent diagnosed cancers and a common cause of cancer-related mortality. Despite effective clinical responses, a large proportion of patients undergo resistance to radiation therapy. Therefore, the identification of efficient targeted therapy strategies would be beneficial to overcome cancer radioresistance. Doublecortin-like kinase 1 (DCLK1) is an intestinal and pancreatic stem cell marker that showed overexpression in a variety of cancers. The transfection of DCLK1 siRNA to...
Source: Molecular Medicine - July 16, 2021 Category: Molecular Biology Authors: Chiman Mohammadi Ali Mahdavinezhad Massoud Saidijam Fatemeh Bahreini Abdolazim Sedighi Pashaki Mohammad Hadi Gholami Rezvan Najafi Source Type: research

Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer Molecular Bases of Disease
In this study, we investigated whether the chronological aging of normal human fibroblasts (NHFs), a previously underappreciated area in pancreatic cancer research, influences the progression and therapeutic outcomes of PDAC. Results from experiments with murine xenografts and 2D and 3D co-cultures of NHFs and PDAC cells revealed that older NHFs stimulate proliferation of and confer resistance to radiation therapy of PDAC. MS-based metabolite analysis indicated that older NHFs have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,...
Source: Journal of Biological Chemistry - May 14, 2020 Category: Chemistry Authors: Ehab H. Sarsour, Jyung Mean Son, Amanda L. Kalen, Wusheng Xiao, Juan Du, Matthew S. Alexander, Brianne R. O'Leary, Joseph J. Cullen, Prabhat C. Goswami Tags: Cell Biology Source Type: research

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Abstract 3326: Targeting lysophosphatidic acid receptor 1 (LPAR1) radiosensitizes poor prognosis cancers
Therapies for poor prognosis cancers, such as lung cancer and glioblastoma, are limited due to radio-resistance and tumor recurrence. Development of molecular targeted therapy can serve as a potential method to improve the efficacy of radiation therapy in both glioblastoma and lung cancer. Ionizing radiation (IR) can activate a series of pro-survival pathways which contributes to the pathogenesis of cancer cells. Among these pathways, cytosolic phospholipase A2 (cPLA2) is an integral component which is activated by IR. Following activation, cPLA2 cleaves arachidonic acid to form phosphatidylcholine (PC) and yields lysophos...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Khudanyan, A., Dadey, D., Karvas, R., Kotipatruni, R., Hallahan, D., Thotala, D. Tags: Tumor Biology Source Type: research

Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1.
In this study, we found that infection with the oncolytic H-1 parvovirus decreased HIF-1α protein levels in pancreatic cancer cells under CoCl2 or hypoxia. The H-1 virus-induced decrease of HIF-1α was regulated by a proteasome-mediated pathway. Suppression of VHL, an E3 ligase and a critical regulator of HIF-1α, or enforced expression of UCP, an E2 ubiquitin-conjugating enzyme, failed to inhibit the H-1 virus-induced decrease of HIF-1α. Furthermore, siRNA-mediated suppression of RACK1, another regulator of HIF-1α, did not prevent H-1 viral infection from lowering HIF-1α protein levels. Although decrease of HIF-1α wa...
Source: International Journal of Oncology - March 9, 2015 Category: Cancer & Oncology Authors: Cho IR, Kaowinn S, Moon J, Soh J, Kang HY, Jung CR, Oh S, Song H, Koh SS, Chung YH Tags: Int J Oncol Source Type: research

Novel treatment approaches for locally advanced pancreatic cancer.
This study shows encouraging results from a phase I investigation of a regionally delivered siRNA that targets the K-rasG12D mutation. Investigation of novel approaches such as those presented here holds the greatest promise for improving treatment of this deadly disease. PMID: 24618426 [PubMed - in process]
Source: JOP - March 14, 2014 Category: Gastroenterology Authors: Gorovets D, Saif MW, Huber K Tags: JOP Source Type: research