Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis

Ravegnini, Gloria; Sammarini, Giulia; Nannini, Margherita; Pantaleo, Maria A.; Biasco, Guido; Hrelia, Patrizia; Angelini, Sabrina

doi:10.1080/15548627.2016.1256522

Cited by 56 publications

(39 citation statements)

References 102 publications

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“…Changes in autophagy and apoptosis play an essential role in the development of cancer, and autophagy and apoptosis often interact in a complex manner . Autophagy can inhibit or promote cell apoptosis due to different cell types, environments and stimuli .…”

Section: Discussionmentioning

confidence: 99%

Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway

Yang

Tang

et al. 2020

Cancer Science

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Head and neck cancer is the sixth most common cancer diagnosed globally. 1 Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. 2 There are more than 350 000 new cases of OSCC every year in the world, and approximately 170 000 people die from OSCC annually. 3 OSCC has a poor prognosis. Currently, the main methods of treatment for OSCC are surgical resection, adjuvant radiotherapy and chemotherapy. Although surgical techniques, radiotherapy and chemotherapy have made great progress over the past 30 years, the 5-year survival rate of OSCC patients has remained at approximately 50% and has not increased significantly. 4-6 AbstractCurrent studies have shown that the clock gene Period 1 (Per1) is downregulated in various tumors and plays an important role in promoting tumor progression.However, the biological functions and mechanism of Per1 in tumors remain largely unknown. In this study, 86 specimens of oral squamous cell carcinoma (OSCC) tissues and adjacent noncancerous tissues were collected to determine the Per1 expression level and the clinical significance of Per1 expression. Per1 was stably inhibited or overexpressed in OSCC cells to investigate its function and mechanism in vitro and in vivo. We found that Per1 was remarkably downregulated in OSCC and that low Per1 expression was significantly associated with TNM clinical stage and poor prognosis of OSCC patients. Per1 overexpression in SCC15 OSCC cells (Per1-OE SCC15 cells) significantly promoted autophagy and apoptosis while inhibiting proliferation and the AKT/mTOR pathway. However, the results obtained in Per1-silenced TSCCA OSCC cells were opposite those obtained in Per1-OE SCC15 cells. After addition of the AKT activator SC79 to Per1-OE SCC15 cells, the increased autophagy and apoptosis as well as decreased proliferation were remarkably rescued. Furthermore, increased apoptosis was significantly rescued in Per1-OE SCC15 cells treated with the autophagy inhibitor autophinib. In vivo tumorigenicity assays also confirmed that Per1 overexpression suppressed tumor growth. Taken together, our findings demonstrate for the first time that Per1 promotes OSCC progression by inhibiting autophagy-mediated cell apoptosis and enhancing cell proliferation in an AKT/mTOR pathway-dependent manner, and Per1 could be used as a valuable therapeutic target for OSCC. K E Y W O R D Sautophagy, carcinogenesis, oral cancer, period 1, prognosis | 1543 YANG et Al.

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Section: Discussionmentioning

confidence: 99%

Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway

Yang

Tang

et al. 2020

Cancer Science

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“…However, the role of autophagy in CaOx kidney stones remains largely unknown. Moreover, it has been recently documented that nanomaterials could induce cell death through the crosstalk between autophagy and apoptosis, the two main mechanisms of programmed cell death . Thus, this study aims to investigate the occurrence of autophagy induced by CaOx nanocrystals in a human renal proximal tubular epithelial cell line HK‐2.…”

Section: Introductionmentioning

confidence: 99%

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Chen

Wei

Meng

et al. 2019

Part & Part Syst Charact

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Calcium oxalate (CaOx) stone is the most common type of kidney stone, with a formation process comprising supersaturation, nucleation, growth, aggregation to crystals, and adhesion on renal tubular epithelial cells. CaOx stones generally lead to renal injury; however, the underlying mechanism remains poorly understood. Accumulating evidence suggests that nanosized materials could induce much greater toxicity than bulk materials with the same components. As aggregation to nanocrystals is necessary to form CaOx stones and nanocrystals have been widely reported to elicit either prodeath or prosurvival autophagy, the aim is to address the precise role of autophagy in CaOx‐ nanocrystal‐induced cytotoxicity. Clinical CaOx stones from patients are collected followed by ball milling. As a result, CaOx nanocrystals significantly reduce renal cell viability in a dose‐ and time‐dependent manner. Further study shows that CaOx nanocrystals possess an autophagy‐inducing capacity and autophagic flux is complete. Autophagy abrogation by specific chemical inhibitor wortmannin or chloroquine obviously attenuates cytotoxicity, strongly suggesting that prodeath autophagy contributes to CaOx nanocrystals‐elicited cytotoxicity. Finally, it is revealed that autophagy is an essential signaling pathway participating in apoptosis regulation. Collectively, the findings demonstrate the role of autophagy in CaOx‐nanocrystal‐elicited cytotoxicity, and harnessing autophagy can be helpful to design promising strategies for attenuating kidney injury in nephrolithiasis.

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“…According to literature reviews and our clinical experience, we found that patients with GIST were generally well-tolerated with imatinib (19). DeMatteo and colleagues conducted a randomized phase III, double-blind, placebo-controlled, multicenter trial about patients with GIST treated with imatinib (20), showing that grade I and II adverse events were common and mostly involved gastrointestinal effects, headache, rash, edema, fatigue, and myalgias/arthralgias.…”

Section: Introductionmentioning

confidence: 99%

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors

Zhang

Qian

et al. 2018

Molecular Cancer Therapeutics

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Gastrointestinal stromal tumors (GIST) are the most prevalent mesenchymal tumors of the digestive tract. To investigate the association of imatinib mesylate plasma concentration with adverse drug reactions (ADRs) and influences of genetic polymorphisms on ADRs in GIST patients taking imatinib, a cohort of GIST patients consecutively treated with imatinib were included in the observational study. Clinical, pathologic and genotype information was recorded at enrollment and blood samples were collected at time as design. The plasma concentration of the imatinib was detected by LC-MS/MS. A questionnaire was used to evaluate the ADRs at each visit. SNPs in 13 genes were analyzed for a possible association with ADRs. The mean plasma trough concentration of 129 patients taking imatinib was 1.45 AE 0.79 mg/ml, average peak concentration was 2.63 AE 1.07 mg/ml. The imatinib concentration in patients treated with 600 mg/day was significantly higher than other dosage groups (P < 0.05). The ADRs were mostly mild. Edema, vomiting, and fatigue were significantly correlated with imatinib concentration (P < 0.05). Mutations of IL13 rs1800925 and CXCL14 rs7716492 were related with the incidence of leukopenia and rash in our research, separately (P < 0.05). We confirmed that with the increase of imatinib concentration, the incidence of edema, vomiting, and fatigue rises as well. Mutations of IL13 rs1800925 and CXCL14 rs7716492 may be the promising biomarkers to predict the ADRs of imatinib. The results of the study are of guiding significance for the use of imatinib in patients with GIST.

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Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis

Cited by 56 publications

References 102 publications

Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway

Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors

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