scholarly journals Imatinib Regulates miR-483-3p and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors

2021 ◽  
Vol 22 (19) ◽  
pp. 10600
Author(s):  
Wen-Kuan Huang ◽  
Hao Shi ◽  
Pinar Akçakaya ◽  
Katarina Zeljic ◽  
Anastasia Gangaev ◽  
...  

Metabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the development of therapeutic strategies synergizing the efficacy of imatinib. In this study, we explored the role of microRNAs in regulating OXPHOS in GIST upon imatinib treatment. Using a microarray approach, we found that miR-483-3p was one of the most downregulated miRNAs in imatinib-treated tumors compared to untreated tumors. Using an extended series of GIST samples, we further validated the downregulation of miR-483-3p in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that miR-483-3p could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, miR-483-3p overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of miR-483-3p in regulating cell viability upon imatinib treatment.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Cicilia Marcella ◽  
Rui Hua Shi ◽  
Shakeel Sarwar

Aims. To review the clinical presentation, diagnosis, assessment of risk of malignancy, and recent advances in management (mainly focusing on the role of endoscopic resection) of gastrointestinal stromal tumors (GISTs) in upper GI.Method. We searched Embase, Web of science, and PubMed databases from 1993 to 2018 by using the following keywords: “gastrointestinal stromal tumors,” “GIST,” “treatment,” and “diagnosis.” Additional papers were searched manually from references of the related articles.Findings. The improvement of endoscopic techniques in treating upper gastrointestinal subepithelial tumors especially gastrointestinal tumors has reduced the need for invasive surgery in patients unfit for surgery. Many studies have concluded that modified endoscopic treatments are effective and safe. These treatments permit minimal tissue resection, better dissection control, and high rates of en bloc resection with an acceptable rate of complications.


2016 ◽  
Vol 10 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ryota Niikura ◽  
Takako Serizawa ◽  
Atsuo Yamada ◽  
Shuntaro Yoshida ◽  
Mariko Tanaka ◽  
...  

The number of cancer patients undergoing dialysis has been increasing, and the number of these patients on chemotherapy is also increasing. Imatinib is an effective and safe therapy for KIT-positive gastrointestinal stromal tumors (GIST), but the efficacy and safety of imatinib in dialysis patients remain unclear. Because clinical trials have not been conducted in this population, more investigations are required. We report on a 75-year-old Japanese man undergoing dialysis who presented with massive tarry stool from a duodenal GIST. The duodenal GIST was 14 cm in diameter with multiple liver and bone metastases. The patient underwent an urgent pancreaticoduodenectomy to achieve hemostasis. After surgery, he was administered imatinib 400 mg/day. No severe adverse event including myelosuppression, congestive heart failure, liver functional impairment, intestinal pneumonia, or Steven-Johnson syndrome occurred, and the liver metastasis remained stable for 4 months. During chemotherapy, hemodialysis continued three times per week without adverse events. We suggest that regular-dose imatinib is an effective and safe treatment in patients with GIST undergoing dialysis. In addition, we present a literature review of the effectiveness and safety of imatinib treatment in dialysis patients.


2018 ◽  
Author(s):  
Jen‑Shi Chen ◽  
Chun‑Nan Yeh ◽  
Chi‑Tung Cheng ◽  
Chueh‑Chuan Yen ◽  
Yen‑Yang Chen ◽  
...  

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