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1.
J Mol Recognit ; 36(8): e3044, 2023 08.
Article in English | MEDLINE | ID: mdl-37322568

ABSTRACT

Mitochondria are the main sites of oxidative metabolism and energy release of sugars, fats and amino acids in the body. According to studies, malignant tumor occurrence and development have been linked to abnormal mitochondrial energy metabolism (MEM). However, the feasible role of abnormal MEM in colon adenocarcinoma (COAD) is poorly understood. In this work, we obtained COAD patient data from The Cancer Genome Atlas (TCGA) as the training set, and GSE103479 from Gene Expression Omnibus (GEO) as the validation set. Combined with the mitochondrial energy metabolic pathway (MEMP)-related genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) database, a risk prognostic model was constructed by utilizing Cox regression analysis to identify 6 feature genes (CYP4A11, PGM2, PKLR, PPARGC1A, CPT2 and ACAT2) that were significantly associated with MEMP in COAD. By stratifying the samples based on riskscore, two distinct groups, namely the high- and low-risk groups, were identified. The model demonstrated accurate assessment of the prognosis risk in COAD patients and exhibited independent prognostic capability, as evidenced by the survival curve and receiver operating characteristic (ROC) curve analysis. A nomogram was plotted based on clinical information and riskscore. We proved it could predict the survival time of COAD patients effectively combined with the calibration curve of risk prediction. Subsequently, based on the immune evaluation and mutation frequency analysis performed on COAD patients, patients in high-risk group had observably higher immune scores, immune activity and PDCD1 expression level than low-risk group. In general, the prognostic model developed using MEMP-related genes served as a valuable biomarker for forecasting the prognosis of COAD patients, which offered a reference for the prognosis evaluation and clinical cure of COAD patients.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Colonic Neoplasms/genetics , Prognosis , Clinical Relevance , Adenocarcinoma/genetics , Mitochondria/genetics
2.
Oncol Res ; 30(6): 277-288, 2022.
Article in English | MEDLINE | ID: mdl-37303491

ABSTRACT

Introduction: Siva-1, as a pro-apoptotic protein, has been shown to induce extensive apoptosis in a number of different cell lines. In our previous study, we showed that overexpressed Siva-1 decreased the apoptosis of gastric cancer cells. So, we believe that it can also work as an anti-apoptotic protein. The present study aimed to determine the specific role of Siva-1 in anticancer drug resistance in gastric cancer in vivo and in vitro and preliminarily reveal the mechanism. Materials and Methods: A vincristine-resistant MKN-28/VCR gastric cancer cell line with stably downregulated Siva-1 was established. The effect of Siva-1 downregulation on chemotherapeutic drug resistance was assessed by measuring the IC50 and pump rate of doxorubicin. Proliferation, apoptosis of cells, and cell cycle were detected via colony formation assay and flow cytometry, respectively. Additionally, migration and invasion of cells was detected via wound healing and transwell assays. Moreover, we determined in vivo effects of LV-Siva-1-RNAi on tumor size, and apoptotic cells in tumor tissues were detected using TUNEL and hematoxylin and eosin staining. Results: Siva-1 downregulation reduced the pump rate of doxorubicin and enhanced the response to drug treatment. Siva-1 negatively regulated proliferation and promoted apoptosis of cells by potentiality G2-M phase arresting. Inhibition of Siva-1 expression in MKN-28/VCR cells significantly weakened wound healing ability and decreased invasion ability. Poly(C)-binding protein 1 (PCBP1) was identified as a Siva-1-interacting protein in yeast two-hybrid screening. Semiquantitative RT-PCR and western blotting revealed that Siva-1 downregulation could inhibit expression of PCBP1, Akt, and NF-κB and eventually decrease the expression of MDR1 and MRP1. Conclusion: he current study demonstrated that the downregulation of Siva-1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells by inhibiting PCBP1/Akt/NF-κB signaling pathway expression, enhanced the sensitivity of gastric cancer cells to certain chemotherapies.


Subject(s)
Apoptosis Regulatory Proteins , Stomach Neoplasms , Humans , Apoptosis , DNA-Binding Proteins , Drug Resistance, Multiple/genetics , NF-kappa B , Proto-Oncogene Proteins c-akt , RNA-Binding Proteins/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics
3.
Am Surg ; 88(6): 1131-1136, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33517706

ABSTRACT

BACKGROUND: The role of the intersphincteric space in the pathogenesis of fistula-in-ano is being increasingly recognized. Submucosal and intersphincteric rectal abscesses have been surgically managed by laying open and draining the intersphincteric space as well as by the modified ligation of intersphincteric fistula tract (LIFT) procedure. In 2017, the transanal opening of intersphincteric space (TROPIS) technique was reported for the treatment of high, complex anal fistulae. AIM: We aim to investigate the advantages of performing the TROPIS procedure in patients with fistula-in-ano. METHODS: This was a prospective cohort study investigating the outcomes in patients who had undergone a procedure using the TROPIS technique for the treatment of fistula-in-ano. Preoperative magnetic resonance imaging scans and electronic colonoscopies were performed on all patients. A clinical database evaluating the following variables was constructed: age, gender, body mass index (BMI), previous fistula surgery, type of fistula, postoperative complications, duration of follow-up, success rate, and incontinence scores pre- and postoperatively. RESULTS: The TROPIS procedure was performed on 41 patients with fistula-in-ano with a follow-up time of 6-23 months. The characteristics of the patients were as follows: 36 males, 6 females, mean age 38.6±13.2 years, and mean BMI 23.5±3.9 kg·m-2. All patients (41) had transsphincteric fistulae, and 90.2% (37) had high fistula. Of the 41 patients, 22% (9) had recurrent fistulae, 29.27% (12) had horseshoe fistulae, 7.3% (3) had supralevator fistulae, and 14.6% (6) had an associated abscess. The fistula healed completely in 85.3% (35) of patients and failed to heal in 14.7% (6) of patients, and the healing of high fistula was 86.5% (32). Of those patients who had not healed completely, 2 were found to have contracted iatrogenic infections due to foreign residues and underwent surgery with the passing of a loose seton. The additional 4 patients who had not healed underwent a fistulotomy and healed completely thereafter. There were no significant changes in incontinence scores. The incontinence scores were .15 ± .36 preoperatively and .22 ± .47 3 months postoperatively (t = -1.438, P = .16). CONCLUSIONS: The TROPIS technique is a novel sphincter-preserving procedure, which can be effectively used in treating fistula-in-ano.


Subject(s)
Anus Diseases , Rectal Fistula , Abscess/etiology , Anal Canal/surgery , Anus Diseases/etiology , Female , Humans , Ligation/methods , Male , Prospective Studies , Rectal Fistula/etiology , Rectal Fistula/surgery , Recurrence , Treatment Outcome
4.
Gastrointest Endosc ; 94(3): 642-650, 2021 09.
Article in English | MEDLINE | ID: mdl-33798538

ABSTRACT

BACKGROUND AND AIMS: Now that the debate about the safety and effectiveness of laparoscopic versus open surgery is over, attention has turned to innovations that can verify whether minimizing the impact of laparoscopy on the abdominal wall can further reduce pain, improve patient comfort, lead to superior cosmesis, and reduce morbidity. The aim of this study was to further explore the application value of totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction (NOSE) and to evaluate the short-term efficacy of transcolonic NOSE surgery for resecting specimens of ascending colon cancer. METHODS: From January 2016 to May 2017, a retrospective study was conducted in Guangxi. Propensity score matching was used to minimize the bias from nonrandomized treatment assignment. Patients were followed up through May 2020. RESULTS: Forty-nine patients underwent totally laparoscopic right hemicolectomy with transcolonic NOSE and 116 patients laparoscopic right hemicolectomy with mini-laparotomy (ML) procedures at our institution. After propensity score matching, each group included 45 patients, and all covariate imbalances were alleviated. The transcolonic NOSE group and the ML group did not differ significantly in terms of baseline clinical characteristics. The transcolonic NOSE group was associated with a shorter time to first flatus (NOSE vs ML: 1.8 ± .5 vs 3.2 ± .8, P = .032), a shorter length of hospital stay (11.3 ± 2.5 days vs 13.0 ± 3.1 days, P = .034), a shorter time to first liquid intake (2.6 ± .8 vs 3.8 ± .9, P = .068), less pain (1.8 ± .8 vs 4.2 ± .7, P = .013), less analgesia requirement (6 [13.3%] vs 21 [46.7%], P = .001), and lower C-reactive protein levels on postoperative day 1 (3.6 ± 1.7 vs 8.2 ± 2.2, P = .001) and postoperative day 3 (NOSE 2.4 ± 1.4 vs M: 4.6 ± 1.7 [P = .013]) than the ML group. The median follow-up was 28.4 months (interquartile range, 18.0-36.0). The 3-year overall survival rates were similar between the transcolonic NOSE group and the ML group. CONCLUSIONS: In total, laparoscopic right hemicolectomy with transcolonic specimen extraction appears to be safe for selected patients with ascending colon cancer as a minimally invasive surgery.


Subject(s)
Colonic Neoplasms , Laparoscopy , China , Colectomy , Colon, Ascending , Colonic Neoplasms/surgery , Humans , Laparotomy , Length of Stay , Propensity Score , Retrospective Studies , Treatment Outcome
5.
Dis Markers ; 2016: 9421571, 2016.
Article in English | MEDLINE | ID: mdl-27190429

ABSTRACT

MUC1, a member of the mucin family, is expressed in tumors of various human organs and may function as an antiadhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis, and served as a potential biomarker of tumor progression in early gastric cancer. However, its prognostic significance in gastric cancer is still in dispute. We performed a meta-analysis to evaluate the relationship between MUC1 expression and prognosis of gastric cancer. A total of ten eligible studies with 834 cases and 548 controls were included. MUC1 positive cases were highly positive in intestinal-type carcinomas (OR = 1.76, 95% CI: 1.27-2.44, P = 0.0008 fixed-effect), higher rate of vascular invasion (OR = 1.64, 95% CI: 1.13-2.39, P = 0.009 fixed-effect), and lymph node metastasis (OR = 2.10, 95% CI: 1.20-3.67, P = 0.01 random-effect), as well as lower 5-year survival rate (HR = 0.27, 95% CI: 0.11-0.66, P = 0.004 random-effect). However, the presence of MUC1 was not associated with gender, tumor size, histologic differentiation, and clinical stage. In summary, MUC1 is a prognostic factor in gastric cancer, which acts as a marker of poor outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of MUC1 in clinical practice.


Subject(s)
Mucin-1/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Female , Humans , Lymphatic Metastasis , Male , Prognosis , Stomach Neoplasms/mortality , Survival Analysis , Tumor Burden
7.
Pathol Oncol Res ; 21(1): 19-27, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25430561

ABSTRACT

In lower rectal cancer, postoperative outcome is still subject of controversy between the advocates of abdominoperineal resection (APR) and low anterior resection (LAR). Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. Publications were identified which assessed the differences comparing 5-year survival, local recurrence, circumferential resection margin rate, complications and so on. A meta-analysis was performed to clarify the safety and feasibility of the two procedures with several types of outcome measures. A total of 13 studies met the inclusion criteria, and comprised 6,850 cases. Analysis of these data showed that LAR group was highly correlated with 5-year survival (pooled OR = 1.73, 95%CI: 1.30-2.29, P = 0.0002 random-effect). And local recurrence rate of APR group was significantly higher than that in LAR group (pooled OR = 0.63, 95%CI: 0.53-0.75, P < 0.00001 fixed-effect). Also, the circumferential resection margin (CRM) were high involved in APR group than in LAR group. (5 trials reported the data, pooled OR = 0.43, 95%CI: 0.36-0.52, P < 0.00001 fixed-effect). Besides, the incidents of overall complications of APR group was higher compared with LAR group (pooled OR = 0.52, 95%CI: 0.29-0.92, P = 0.03 random-effect). Patients treated by APR have a higher rate of CRM involvement, a higher local recurrence, and poorer prognosis than LAR. And there is evidence that in selected low rectal cancer patients, LAR can be used safely with a better oncological outcome than APR. due to the inherent limitations of the present study, for example, the trails available for this systematic review are limited and the finite retrospective data, future prospective randomized controlled trials will be useful to fully investigate these outcome measures and to confirm this conclusion.


Subject(s)
Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Animals , Digestive System Surgical Procedures/methods , Humans , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Rectal Neoplasms/mortality , Retrospective Studies , Treatment Outcome
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