Background Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors. Methods We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed antitumor response and the safety and tolerability of the drug. Pharmacokinetics were assessed in a subgroup of patients. Results A total of 147 patients were randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79 patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had stable disease, and for technical reasons, response could not be evaluated in 7 patients (4.8 percent). No patient had a complete response to the treatment. The median duration of response had not been reached after a median follow...

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Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.

Diagnosis of gastrointestinal stromal tumors: A consensus approach.

Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)60500-6.pdf

Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial.

ObjectiveTo analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively.Summary Background DataA GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of tre

https://ink.library.smu.edu.sg/cgi/viewcontent.cgi?article=1016&context=soe_research

Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.

Background: Gabapentin, originally an antiepileptic agent, was found to have anti-cancer activity on multiple cancer cells. How-ever, its eﬀects on hepatocellular carcinoma (HCC) and associated molecular mechanisms are unclear. Objectives: In this study, we investigated the anti-cancer eﬀects of gabapentin against HCC cells in vitro and in vivo. Methods: Human HCC cells were inoculated with various levels of gabapentin for 24 and 48 h. We utilized the MTT assay to detect the proliferation of HCC cells after gabapentin treatment. The eﬀect of gabapentin on the migration of HCC cells was detected by transwell migration assay. We established a model of subcutaneously transplanted HCC in nude mice and observed the impact of gabapentin on HCC cell tumorigenicity in vivo. The changes in RNA expression in gabapentin-treated HCC cells were evaluated by RNA sequencing analysis, and the results were analyzed and further validated by qRT-PCR. Results: Gabapentin signiﬁcantly inhibited the proliferation of a variety of human HCC cells in a time- and dose-dependent approach. After treatment with 10 mM gabapentin for 12 h, the transendothelial migration of HCC cells via membrane remarkably reduced. Three weeks after the hypodermic transplanting of HCC in nude mice with Huh7 cell line, the gabapentin-treated group hadadramaticdecreaseinmeantumorvolumeandweightrelativetothecontrols. RelativetothenormalHuh7cellline,theresults of RNA sequencing of Huh7 cells treated with gabapentin for 24 h showed the diﬀerential enrichment of genes involved in "energy metabolism","cancers","signaltransduction",and"folding,sorting,anddegradation". Thegenes CDH11 and ARHGAP15 relatedtocell migration were further veriﬁed by qRT-PCR. Conclusions: Our results suggested that gabapentin has an inhibitory eﬀect on the growth, migration, and tumor formation of hepatomacells,andthemechanismof gabapentin’sinhibitiononHCCcellsmayberelatedtosomesignalingpathways,whichwill lay a foundation for the future studies on branched-chain aminotransferase 1 (BCAT1) as a target for HCC treatment.

Inhibitory Eﬀects of Gabapentin on the Proliferation and Cell Motility of Hepatocellular Carcinoma Cells

Background: Gabapentin, originally an antiepileptic agent, was found to have anti-cancer activity on multiple cancer cells. However, its effects on hepatocellular carcinoma (HCC) and associated molecular mechanisms are unclear. Objectives: In this study, we investigated the anti-cancer effects of gabapentin against HCC cells in vitro and in vivo. Methods: Human HCC cells were inoculated with various levels of gabapentin for 24 and 48 h. We utilized the MTT assay to detect the proliferation of HCC cells after gabapentin treatment. The effect of gabapentin on the migration of HCC cells was detected by transwell migration assay. We established a model of subcutaneously transplanted HCC in nude mice and observed the impact of gabapentin on HCC cell tumorigenicity in vivo. The changes in RNA expression in gabapentin-treated HCC cells were evaluated by RNA sequencing analysis, and the results were analyzed and further validated by qRT-PCR. Results: Gabapentin significantly inhibited the proliferation of a variety of human HCC cells in a time- and dose-dependent approach. After treatment with 10 mM gabapentin for 12 h, the transendothelial migration of HCC cells via membrane remarkably reduced. Three weeks after the hypodermic transplanting of HCC in nude mice with Huh7 cell line, the gabapentin-treated group had a dramatic decrease in mean tumor volume and weight relative to the controls. Relative to the normal Huh7 cell line, the results of RNA sequencing of Huh7 cells treated with gabapentin for 24 h showed the differential enrichment of genes involved in "energy metabolism", "cancers", "signal transduction", and "folding, sorting, and degradation". The genes CDH11 and ARHGAP15 related to cell migration were further verified by qRT-PCR. Conclusions: Our results suggested that gabapentin has an inhibitory effect on the growth, migration, and tumor formation of hepatoma cells, and the mechanism of gabapentin’s inhibition on HCC cells may be related to some signaling pathways, which will lay a foundation for the future studies on branched-chain aminotransferase 1 (BCAT1) as a target for HCC treatment.

Inhibitory Effects of Gabapentin on the Proliferation and Cell Motility of Hepatocellular Carcinoma Cells


 Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancers. There is urgent need for discovery of biomarkers of prognostic significance, predictive value and as well as therapeutic targets in patients with pancreatic cancer. In this study, we examined the relative expression and prognostic significance of all HER family members and the type III EGFR mutant (EGFRvIII) in patients with pancreatic ductal adenocarcinoma (PDC). The expression levels of wild-type EGFR (wtEGFR), HER2, HER3, HER4 and EGFRvIII were determined in tumor specimens from 43 patients by immunohistochemistry using antibodies DAK-H1-WT, Neu 3B5, SP71, HFR1 and NBP2-50599 respectively. The staining was scored based on the percentage of positive tumor cells, the intensity (i.e. strong 3+, moderate 2+, weak 1+) and the cellular location of immunostaining (i.e. membranous, cytoplasmic or nuclear). The association between the expression level of the biomarkers and patient overall survival was evaluated using Chi-squared, Kaplan-Meier survival curves and log rank test. At cut-off value of above 5%, we found weak to moderate expression of wtEGFR, HER2, HER3, HER4 and EGFRvIII in 4.7%, 14%, 14%, 20.9% and 2.3% of the cases examined respectively. The cellular location of wtEGFR and HER2 was found to be predominantly cytoplasmic, HER-3 membranous and cytoplasmic whereas HER4 expression was found to be mainly nuclear. There was no statistically significant association between the expression level of these markers and patient overall survival. The expression levels of the above biomarkers were also evaluated in tissue microarrays (TMAs) from 40 cases of pancreatic ductal adenocarcinoma. Interestingly, at the same cut-off value, 62.5%, 75%, 0%, 55% and 5% of the TMAs were positive for wtEGFR, HER2, HER3, HER4 and EGFRvIII respectively. Overall, we found that the expression pattern of HER family members was heterogenous, and with EGFRvIII expression being very low in both whole tumor sections and TMAs from patients with pancreatic cancer. Taken together, our results provide support for more detailed studies of co-expression of all HER family members in a larger group of pancreatic cancer patients. Such studies should help to unravel their potential as targets for therapeutic interventions as well as their prognostic significance and predictive value for response to therapy.
 Citation Format: Tanzeel Khan, Said A. Khelwatty, Izhar Bagwan, Alan Seddon, Angus Dalgleish, Satvinder Mudan, Helmout Modjtahedi. Expression pattern and prognostic significance of HER family members and EGFRvIII in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2691.

Salvinder S. Mudan

Papers

Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.

Inhibitory Eﬀects of Gabapentin on the Proliferation and Cell Motility of Hepatocellular Carcinoma Cells

Inhibitory Effects of Gabapentin on the Proliferation and Cell Motility of Hepatocellular Carcinoma Cells

Abstract 2691: Expression pattern and prognostic significance of HER family members and EGFRvIII in pancreatic cancer