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Filename: drivers/Session_files_driver.php
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Filename: controllers/Detail.php
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Function: insertAPISummary
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Introduction: The PI3K signaling pathway drives tumor cell proliferation and survival in gastrointestinal stromal tumor (GIST). We tested the in vivo efficacy of three PI3K inhibitors (PI3Ki) in patient-derived GIST xenograft models.
Experimental Design: One hundred and sixty-eight nude mice were grafted with human GIST carrying diverse KIT genotypes and PTEN genomic status. Animals were dosed orally for two weeks as follows: control group (untreated); imatinib (IMA); PI3Ki (BKM120-buparlisib, BEZ235, or BYL719) or combinations of imatinib with a PI3Ki. Western blotting, histopathology, and tumor volume evolution were used for the assessment of treatment efficacy. Furthermore, tumor regrowth was evaluated for three weeks after treatment cessation.
Results: PI3Ki monotherapy showed a significant antitumor effect, reflected in tumor volume reduction or stabilization, inhibitory effects on mitotic activity, and PI3K signaling inhibition. The IMA+PI3Ki combination remarkably improved the efficacy of either single-agent treatment with more pronounced tumor volume reduction and enhanced proapoptotic effects over either single agent. Response to IMA+PI3Ki was found to depend on the KIT genotype and specific model-related molecular characteristics.
Conclusion: IMA+PI3Ki has significant antitumor efficacy in GIST xenografts as compared with single-agent treatment, resulting in more prominent tumor volume reduction and enhanced induction of apoptosis. Categorization of GIST based on KIT genotype and PI3K/PTEN genomic status combined with dose optimization is suggested for patient selection for clinical trials exploring such combinations.
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http://dx.doi.org/10.1158/1078-0432.CCR-14-1823 | DOI Listing |
J Nanobiotechnology
December 2024
Cancer Stem Cells and Fibroinflammatory Microenvironment Group, Instituto de Investigaciones Biomédicas (IIBm) Sols-Morreale CSIC-UAM, 28029, Madrid, Spain.
Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis.
View Article and Find Full Text PDFCell Death Dis
December 2024
Department of Obstetrics and Gynaecology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Ovarian cancer (OC) is prone to adipose tissue metastasis. However, the underlying molecular mechanisms remain elusive. Here, we observed that omental adipocytes were induced into cancer-associated adipocytes (CAAs) by OC-derived TGF-β1 to establish a pre-metastatic niche (PMN) through collagen and fibronectin secretion.
View Article and Find Full Text PDFWei Sheng Yan Jiu
November 2024
Shanghai University of Medicine & Health Sciences, Shanghai 200237, China.
Objective: To investigate the protective effect of lycopene on lung oxidative damage induced by atmospheric fine particulate matter(PM_(2.5)) in rats.
Methods: Sixty 7-week-old male Sprague-Dawley rats were randomly divided into six groups: normal control group, PM_(2.
J Adolesc Young Adult Oncol
December 2024
Facultad de Medicina, Centro de Desarrollo de Investigación 360, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Germ cell tumors (GCTs) are chemosensitive neoplasms with high cure rates; however, a small group of patients present tumors with refractory chemotherapy, with a dismal prognosis and few effective management options. Although immune checkpoint inhibitors (ICIs) are approved for use in chemotherapy refractory GCT, the evidence supporting this indication remains scarce. Original research studies were included on patients with GCTs refractory to chemotherapy treated with ICI up to December 2023.
View Article and Find Full Text PDFMamm Genome
December 2024
Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), No. 61# Jiefang West Road, Changsha, 410005, Hunan, China.
Exonuclease 1 (EXO1) is an evolutionarily conserved exonuclease, which have function on maintaining genomic stability. Elevated expression of EXO1 has been reported in certain cancers. However, a comprehensive pan-cancer analysis of EXO1 is still lacking and its role in human cancer development remains poorly understood.
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