Oncolytic adenoviruses (OA) are envisioned as a therapeutic option for patients with cancer, designed to preferentially replicate in cancer cells. However, the high number of genetic alterations in tumors can generate a context in which adenoviruses have difficulties replicating. Abnormal miRNAs expression is a trademark of pancreatic cancer, with several oncogenic miRNAs playing essential roles in cancer-associated pathways. The perturbed miRNome induces reprogramming of gene expression in host cells that can impact the complex interplay between cellular processes and viral replication. We have studied the effects of overexpressed miRNAs on oncolytic adenoviral activity and identified miRNAs modulators of adenoviral oncolysis in pancreatic cancer cells. Inhibition of the highly upregulated miR-222 sensitized cancer cells to oncolysis. To provide a therapeutic application to this insight, we engineered the oncolytic adenovirus AdNuPARmE1A with miR-222 binding sites, working as sponges to withdraw the miRNA from the cellular environment. AdNuPAR-E-miR222-S mediated-decrease of miR-222 expression in pancreatic cancer cells strongly improved the viral yield and enhanced the adenoviral cytotoxic effects. Antitumoral studies confirmed a high activity for AdNuPARmE1A-miR222-S in vivo, controlling tumor progression more effectively than the scrambled control virus in xenografts. We demonstrated that the increased antitumor potency of the novel oncolytic virus resulted from the combinatory effects of miR-222 oncomiR inhibition and the restoration of miR-222 target genes activity enhancing viral fitness.
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http://dx.doi.org/10.3390/cancers13133233 | DOI Listing |
Cancer Sci
December 2024
Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Patient-derived organoids represent a novel platform to recapitulate the cancer cells in the patient tissue. While cancer heterogeneity has been extensively studied by a number of omics approaches, little is known about the spatiotemporal kinase activity dynamics. Here we applied a live imaging approach to organoids derived from 10 pancreatic ductal adenocarcinoma (PDAC) patients to comprehensively understand their heterogeneous growth potential and drug responses.
View Article and Find Full Text PDFIran Biomed J
December 2024
Department of Anatomy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
World J Surg Oncol
December 2024
Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, 315048, Zhejiang, China.
Background: There is ongoing debate surrounding the optimal therapeutic strategy for hepatocellular carcinoma (HCC) patients achieving complete response (CR) after conversion therapy. This meta-analysis compares the prognostic outcomes of non-surgery strategies with hepatectomy.
Methods: The systematic searches were conducted up to April 11, 2024, across PubMed, Embase, Web of Science, and the Cochrane Library, analyzing progression-free survival (PFS) and overall survival (OS).
BMC Microbiol
December 2024
Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province, 250012, China.
Background: Smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). This study aimed to investigate the effects of smoking on the pancreatic microbiome and metabolome in resectable and unresectable male PDAC patients.
Methods: The pancreatic tissue samples were collected from resectable PDACs via surgery and unresectable PDACs via endoscopic ultrasound fine needle aspiration (EUS-FNA).
Int J Emerg Med
December 2024
Faculty of Medicine, University of Kalamoon, Al_Nabk, Syria.
Introduction: Non-cancer deaths are now becoming a significant threat to the health of cancer patients. Death from stomach and duodenal ulcer is linked to cancer due to the side effects of treatment and its pathogenesis. However, guidelines for identifying cancer patients at the highest risk of death from stomach and duodenal ulcer remain unclear.
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