Downregulation of GSTM2 enhances gemcitabine chemosensitivity of pancreatic cancer in vitro and in vivo

Peng, Lisi; Zhuang, Lu; Lin, Kun; Yao, Yao; Zhang, Yang; Arumugam, Thiruvengadam; Fujii, Tozo; Jiang, Hui; Sun, Lixia; Jin, Zhendong; Li, Zhao‐Shen; Logsdon, Craig D.; Ji, Baoan; Huang, Haojie

doi:10.1016/j.pan.2020.12.008

Cited by 12 publications

(13 citation statements)

References 21 publications

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“…The most recent meta-analysis by Li et al [ 35 ] reporting on the relationship between the use of different SAs and the occurrence of POPF stands in stark contrast with the above-mentioned previous meta-analysis, concluding that SA prophylaxis significantly reduces the POPF incidence as well as overall morbidity but not mortality. However, several biases may have again affected the results of this study.…”

Section: Discussionmentioning

confidence: 84%

“…Second, the FRS was proposed by Callery et al [ 5 ] to stratify patients who might require SA prophylaxis by risk, with prophylaxis provided to those with higher scores, as also recommended by the current ISGPS position statement [ 15 ]. However, despite the fact that the FRS has been used in the past to evaluate the effectiveness of SA prophylaxis, no RCT has yet used it to stratify patients and evaluate the effectiveness of SA prophylaxis [ 35 ], especially in high-risk patients.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we only considered patients treated with somatostatin, as it historically represents the most commonly used SA at our institution as well as the most economically viable one. Both of the most recent meta-analyses mentioned above [ 31 , 35 ] are limited by their consideration of all SAs indifferently, and thus far, there have been no randomized trials comparing two or more different analogues. Every SA has always been studied individually, with different and controversial results.…”

Section: Discussionmentioning

confidence: 99%

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Somatostatin administration following pancreatoduodenectomy: a case-matched comparison according to surgical technique, body mass index, American Society of Anesthesiologists’ score and Fistula Risk Score

et al. 2020

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Purpose This study evaluated the controversial role of somatostatin after pancreatoduodenectomy (PD), stratifying patients for the main risk factors using the most recent postoperative pancreatic fistula (POPF) classification and including only patients who had undergone PD with the same technique of pancreatojejunostomy. Methods Between November 2010 and February 2020, 218 PD procedures were carried out via personal modified pancreatojejunostomy (mPJ-PD). Somatostatin was routinely administered between 2010 and 2016, while from 2017, 97 mPJ-PD procedures without somatostatin (WS) were performed. The WS group was retrospectively compared with a control (C) group obtained with one-to-one case–control matching according to the body mass index, American Society of Anesthesiologists’ score, and Fistula Risk Score (FRS). Results A total of 144 patients (72 WS group versus 72 C group) were compared. In the WS group. 6 patients (8.3%) developed clinically relevant POPF, compared with 8 patients (11.1%) in the C group (p = 0.656). In addition, on analyzing the subgroup of high-risk patients according to the FRS, we did not note any significant differences in POPF occurrence. Furthermore, no marked differences in the morbidity or mortality were found. Digestive bleeding and diabetes onset rates were higher in the WS group than in the control group, but not significantly so. Conclusions The results of the present study confirm no benefit with the routine administration of somatostatin after PD to prevent POPF, even in high-risk patients. However, a possible role in the prevention of postoperative digestive bleeding and diabetes was observed.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Somatostatin administration following pancreatoduodenectomy: a case-matched comparison according to surgical technique, body mass index, American Society of Anesthesiologists’ score and Fistula Risk Score

et al. 2020

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“…As a fatal malignant tumor, PDAC causes a huge social health burden and patients could neither be directly diagnosed in the early stage nor be accurately predicted the clinical outcome. At this point, the prognostic marker is in great need for the treatment of patients with PDAC [ 15 ]. In this study, we used bioinformatic and statistical methods to screen the biomarkers with great prognostic sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Three PDAC Subtypes and Individualized GSVA Immune Pathway-Related Prognostic Risk Score Formula in Pancreatic Ductal Adenocarcinoma Patients

Zhang

Wang

Peng

et al. 2021

Journal of Oncology

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Background. With the progress of precision medicine treatment in pancreatic ductal adenocarcinoma (PDAC), individualized cancer-related medical examination and prediction are of great importance in this high malignant tumor and tumor-immune microenvironment with changed pathways highly enrolled in the carcinogenesis of PDAC. Methods. High-throughput data of pancreatic ductal adenocarcinoma were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. After batch normalization, the enrichment pathway and relevant scores were identified by the enrichment of immune-related pathway signature using gene set variation analysis (GSVA). Then, cancerous subtype in TCGA and GEO samples was defined through the NMF methods by cancertypes packages in R software, respectively. Subsequently, the significance between the characteristics of each TCGA sample and cancer type and the significant prognosis-related pathway with risk score formula is calculated through t-test and univariate Cox analysis. Next, the prognostic value of gained risk score formula and each significant prognosis-related pathway were validated in TCGA and GEO samples by survival analysis. The pivotal hub genes in the enriched significant prognosis-related pathway are identified and validated, and the TIMER database was used to identify the potential role of hub genes in the PDAC immune environment. The potential role of hub genes is promoting the transdifferentiation of cancer-associated fibroblasts. Results. The enrichment pathway and relevant scores were identified by GSVA, and 3 subtypes of pancreatic ductal adenocarcinoma were defined in TCGA and GEO samples. The clinical stage, tumor node metastasis classification, and tumor grade are strongly relative to the subtype above in TCGA samples. A risk formula about GSVA significant pathway “GSE45365_WT_VS_IFNAR_KO_CD11B_DC_MCMV_INFECTION_DN ∗ 0.80 + HALLMARK_GLYCOLYSIS ∗ 16.8 + GSE19888_CTRL_VS_T_CELL_MEMBRANES_ACT_MAST_CELL_DN ∗ 14.4” was identified and validated in TCGA and GEO samples through survival analysis with significance. DCN, VCAN, B4GALT7, SDC1, SDC2, B3GALT6, B3GAT3, SDC3, GPC1, and XYLT2 were identified as hub genes in these GSVA significant pathways and validated in silico. Conclusions. Three pancreatic ductal adenocarcinoma subtypes are identified, and an individualized GSVA immune pathway score-related prognostic risk score formula with 10 hub genes is identified and validated. The predicted function of the 10 upregulated hub genes in tumor-immune microenvironment was promoting the infiltration of cancer-associated fibroblasts. These findings will contribute to the precision medicine of pancreatic ductal adenocarcinoma treatment and tumor immune-related basic research.

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“…[21] GSTM2 downregulation was reported to bring enhanced drug sensitivity. [22] GSTO1 is overexpressed in some cancer types that equip them elevated aggression and increased resistance against chemical treatment; [23] so, its specific inhibitors were stated as good tools for lowering the survival rate of breast cancer cell line MDA-MB-43 in chemotherapeutic applications. [24] Thiophene derivatives would be both the target and the modulator of GSTs in cancer treatment and the current study focuses on this fact to reveal the metabolic fate of an benzothiophene derivative which has selective cytotoxicity against some prostat, liver and colorectal cancer lines.…”

Section: Introductionmentioning

confidence: 99%

A Thiophene Derivative, 2‐Bromo‐5‐(2‐(methylthio)phenyl)thiophene, Has Effective Anticancer Potential with Other Biological Properties

et al. 2022

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Thiophene derivatives are studied intensively due to their anticancer, antimicrobial, antioxidant and some other clinically important properties. In this study, the biological properties of a new thiophene derivative, so called BMPT, with a moderate drug score of 0.29 were tested. BMPT showed selective cytotoxicity for LnCap, HepG2 and Caco‐2 cancer cell lines with EC50 values of 138.573 μM, 185.931 μM, and 108.657 μM, respectively, but not on the control cell line HEK293. The increased expressions were detected for caspase3, caspase8, caspase9 and Bax; but Bcl‐2 expressions were decreased at cancer cell lines. BMPT decreased the total thiol content and total GST activities at HepG2 47 % and 40 %, respectively, and, molecular docking supported inhibitory models for GSTP1‐1, GSTA1‐1 and GSTM2‐2 were mixed, uncompetitive and uncompetitive, respectively. BMPT also showed potent antibacterial activity against Staphylococcus aureus. Related with its selective inhibition on GST activities, BMPT is proposed to have significant apoptotic effect leaded by changes, especially, in caspase 3, Bcl‐2 and Bax expressions.

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Downregulation of GSTM2 enhances gemcitabine chemosensitivity of pancreatic cancer in vitro and in vivo

Cited by 12 publications

References 21 publications

Somatostatin administration following pancreatoduodenectomy: a case-matched comparison according to surgical technique, body mass index, American Society of Anesthesiologists’ score and Fistula Risk Score

Somatostatin administration following pancreatoduodenectomy: a case-matched comparison according to surgical technique, body mass index, American Society of Anesthesiologists’ score and Fistula Risk Score

Identification and Validation of Three PDAC Subtypes and Individualized GSVA Immune Pathway-Related Prognostic Risk Score Formula in Pancreatic Ductal Adenocarcinoma Patients

A Thiophene Derivative, 2‐Bromo‐5‐(2‐(methylthio)phenyl)thiophene, Has Effective Anticancer Potential with Other Biological Properties

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