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1.
Pathol Res Pract ; 235: 153938, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35552086

ABSTRACT

Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that lack the ability to encode protein. Convincing studies have indicated that lncRNAs can act as oncogenes or tumor suppressors by regulating gene expression. The novel lncRNA NR2F1-AS1 was recently found to be abnormally expressed in various malignancies, including hepatocellular carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, lung cancer, thyroid cancer, esophageal squamous cell carcinoma, osteosarcoma, and neuroblastoma. NR2F1-AS1 can modify cell proliferation, invasion, migration, apoptosis, the cell cycle, and glycolysis through various mechanisms involving direct or indirect effects on pathways. Furthermore, NR2F1-AS1 may be a potential therapeutic target and prognostic marker in cancer, as it has been related to the clinicopathological characteristics of cancer patients. Here, we summarize and clarify recent research advances regarding the expression, function, molecular mechanisms, and clinical implications of NR2F1-AS1 in multiple malignant tumors.


Subject(s)
COUP Transcription Factor I , Neoplasms , RNA, Long Noncoding , Animals , COUP Transcription Factor I/genetics , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Humans , MicroRNAs/genetics , Neoplasms/genetics , Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
2.
Front Surg ; 9: 980056, 2022.
Article in English | MEDLINE | ID: mdl-36684316

ABSTRACT

Background and Objective: Postoperative pancreatic fistula (POPF) is the most common critical complication after pancreatoduodenectomy (PD) and is the primary reason for increased mortality and morbidity after PD. We aim to investigate the clinical significance of a novel approach, i.e., end-to-side one-layer continuous pancreaticojejunostomy, for patients with PD. Methods: The clinical data of 65 patients who underwent pancreatoduodenectomy at the Xiangya Hospital, Central South University, from September 2020 to December 2021 were retrospectively analyzed. Results: Forty patients underwent end-to-end invaginated pancreaticojejunostomy, and 25 underwent the novel end-to-side one-layer continuous pancreaticojejunostomy. No significant differences were observed in pancreatic fistula, intraperitoneal infection, intraperitoneal bleeding, reoperation, postoperative hospital stay, or perioperative death between the two groups. However, the novel end-to-side one-layer continuous pancreaticojejunostomy group had significantly shorter operation duration (32.6 ± 5.1 min vs. 8.3 ± 2.2 min, p < 0.001). The incidence of pancreatic fistula in the novel pancreaticojejunostomy group was 12%, including two cases of grade A POPF and only one case of grade B POPF. No cases of grade C POPF occurred. No deaths were observed during the perioperative period. Conclusions: The novel anastomosis method leads to a shorter operation duration than the traditional anastomosis method and does not increase postoperative complications. In conclusion, it is a simplified and feasible method for pancreatic anastomosis.

4.
Cancer Cell Int ; 20: 382, 2020.
Article in English | MEDLINE | ID: mdl-32782440

ABSTRACT

BACKGROUND: Pancreatic cancer is a common malignant tumor of the digestive tract. It has a high degree of malignancy and poor prognosis. Finding effective molecular markers has great significance for pancreatic cancer diagnosis and treatment. This study aimed to investigate DLGAP5 expression in pancreatic cancer and explore the possible mechanisms and clinical value of DLGAP5 in tumorigenesis and tumor development. METHODS: Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) data set GSE16515. Gene Ontology (GO)-based functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis were performed on the corresponding proteins of the above genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Kaplan-Meier Plotter database was used to analyze the relationship between differentially expressed genes and pancreatic cancer prognosis. The most prognostic gene, DLGAP5, was screened out, and the Oncomine and gene expression profiling interactive analysis (GEPIA) databases were used to analyze its expression in pancreatic cancer and other cancer tissues. The Cancer Genome Atlas (TCGA) database was used to analyze the overall survival of DLGAP5. Gene set enrichment analysis (GSEA) was performed to explore its possible molecular mechanisms in pancreatic cancer. Furthermore, the biological behavior of DLGAP5 in pancreatic cancer was verified by cell function experiments. RESULTS: A total of 201 significant upregulated differentially expressed genes and 79 downregulated genes were selected. The biological processes with significant enrichment of differential genes included cell adhesion, apoptosis, wound healing, leukocyte migration, angiogenesis. Pathways were mainly enriched in tumor-related signaling pathways such as cancer pathways, the extracellular matrix-receptor interaction pathway, and the p53 signaling pathway. DLGAP5 was significantly expressed in pancreatic cancer, and its expression level had a significant effect on patients' survival time and progression-free survival. GSEA results indicated that DLGAP5 had significantly enriched into signaling pathways such as the cell cycle, the p53 signaling pathway, and oocyte meiosis. The experimental results showed that when we knocked down the expression of DLGAP5 in pancreatic cancer cells, their proliferation ability was significantly inhibited, and their invasion and migration ability significantly decreased. CONCLUSIONS: DLGAP5 can be used as a prognostic indicator for pancreatic cancer and affect the occurrence and development of pancreatic cancer.

5.
J Cell Biochem ; 120(12): 19358-19370, 2019 12.
Article in English | MEDLINE | ID: mdl-31490563

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. With the deepening of people's understanding of CRC at the molecular level, the survival and prognosis of CRC have been significantly improved with the help of surgery, radiotherapy, and chemotherapy, molecular targeted biological therapy and early detection of diseases. The research of different disciplines and the development of multihistological analysis in recent years have proved that the occurrence and development of CRC is a complex biological process with the common action of multiple factors, which involves the huge changes of various histological levels such as the genome, transcriptome, and epigenome. At present, the abnormal expression of protein products in the transcription process has attracted more and more attention. Based on the sensitivity and timeliness of its changes, it has become a hot topic to study the occurrence and development mechanism of CRC through transcriptome changes, so as to provide markers for early diagnosis and prognosis. In recent years, competitive endogenous RNA (ceRNA) has become one of the hot topics in cancer research. The ceRNA hypothesis holds that transcripts such as long noncoding RNA can competitively bind microRNA (miRNA), thus preventing miRNA from binding to messenger RNA (mRNA) and thereby regulating the expression of mRNA. At present, the interaction mechanism of ceRNA in CRC is still unclear, and exploring its interaction relationship is of great significance to elucidate the occurrence and development mechanism of CRC. In this study, we used The Cancer Genome Atlas (TCGA) RNA - seq data of colorectal Cancer and microRnas - seq data to construct colorectal Cancer ceRNA topology network to mine key RNAs that influence the prognosis of colorectal cancer, providing potential RNA biomarkers.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism
6.
Pancreatology ; 19(7): 935-940, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31558390

ABSTRACT

BACKGROUND: Multidrug-resistant organisms (MDROs) is becoming a serious worldwide threat to public health. However, the impact of MDROs on the outcomes of the patients with infected pancreatic necrosis (IPN) remains unclear. This study aims to evaluate the roles of MDROs in IPN. METHODS: A prospectively maintained database of 188 patients with IPN between January 2010 and May 2019 was analyzed. The microbiology profile of organisms isolated from wall-off necrosis (WON) was specifically investigated to correlate with the outcomes of the patients. RESULTS: Of the 188 patients with IPN, 108 patients (57.4%) had MDROs detected in aspirates from WON. Carbapenem-resistant Klebsiella pneumoniae (CRKP) accounted for 43.5% of the MDROs isolated (60/138), followed by Carbapenem-resistant Acinetobacter baumanii (CRAB) (34.8%, 48/138) and Escherichia coli producing an extended-spectrum beta-lactamase (ESBLp) (6.5%, 9/138). MDROs infection was associated with higher mortality (35.2% vs 11.3%, P < 0.001), higher rate of hemorrhage (36.1% vs 11.3%, P < 0.001), longer intensive care unit (ICU) stay (23 vs 12 days, P < 0.001), longer hospital stay (68 vs 51 days, P = 0.001) and more hospitalization expenses (45,190 ±â€¯31,680 vs 26,965 ±â€¯17,167 $, P < 0.001). Multivariate analysis of predictors of mortality indicated that MDROs infection (OR = 2.6; 95% confidence interval [CI], 1.0-6.5; P = 0.042), age ≥ 50 years (OR = 2.6; 95% CI, 1.2-5.8; P = 0.016), severe category (OR = 2.9; 95% CI, 1.1-8.0; P = 0.035), bloodstream infection (OR = 3.4; 95% CI, 1.5-7.6; P = 0.049), step-down surgical approach (OR = 2.7; 95% CI, 1.1-6.2; P = 0.023) were significant factors. CONCLUSIONS: MDROs infection was prevalent among patients with IPN and associated with adverse clinical outcomes and increased mortality.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/microbiology , Drug Resistance, Multiple, Bacterial , Pancreatitis, Acute Necrotizing/microbiology , Adult , Aged , Bacteria/drug effects , Female , Humans , Male , Middle Aged , Odds Ratio , Pancreatitis, Acute Necrotizing/mortality , Retrospective Studies
7.
Dig Liver Dis ; 51(11): 1580-1585, 2019 11.
Article in English | MEDLINE | ID: mdl-31079936

ABSTRACT

BACKGROUND: Patients with critical acute pancreatitis (CAP) have the highest risk of mortality. However, there have been no studies specifically designed to evaluate the prognostic factors of CAP. AIMS & METHODS: This was a prospective observational cohort study involving patients with CAP. Three aspects including organ failure, (peri)pancreatic necrotic fluid cultures and surgical interventions were analyzed specifically to identify prognostic factors. RESULTS: Of the 102 consecutive patients with CAP, 83 patients (81.4%) received step-up surgical treatment, the mortality of the step-up group was 25.3% (21/83). 19 patients (18.6%) underwent step-down surgical treatment, the mortality of the step-down group was 57.9% (11/19). Overall mortality in the whole cohort was 31.4% (32/102). Multivariate analysis of death predictors indicated that multiple organ failure (MOF) (OR = 5.3; 95% CI, 1.5-18.2; p = 0.008), long duration (≥5 days) of organ failure (OR = 6.4; 95% CI, 1.2-54.3; p = 0.029), multidrug-resistant organisms (MDROs) infection (OR = 4.6; 95% CI, 1.3-15.8; p = 0.013), OPN (OR = 3.7; 95% CI, 1.5-8.8; p = 0.004) and step-down surgical treatment (OR = 3.5; 95% CI, 1.2-10.1; p = 0.019) were significant factors. CONCLUSION: Among patients with CAP, MOF, long duration (≥5 days) of organ failure, MDROs infection, OPN and step-down surgical treatment were identified as the predictors of mortality.


Subject(s)
Multiple Organ Failure/etiology , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/mortality , Pancreatitis, Acute Necrotizing/surgery , Acute Disease , Adult , China/epidemiology , Critical Illness , Disease Progression , Drug Resistance, Multiple , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Factors
8.
J Cell Physiol ; 234(9): 15407-15419, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30693518

ABSTRACT

Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1-AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR-142/HIF-1α axis under hypoxic condition; however, FEZF1-AS1 failed to affect the protein levels of HIF-1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1-AS1 could target miR-133a to inhibit its expression; under the normoxic condition, FEZF1-AS1 exerted its effect on PC cell lines through miR-133a/EGFR axis. Taken together, FEZF1-AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.

9.
Biomed Pharmacother ; 106: 523-531, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29990840

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and resistance to cytotoxic chemotherapy is the major cause of mortality in PDAC patients. miR-125a-3p was found to be down-regulated in PDAC cells; however, the function of miR-125a-3p in PDAC has been elusive. Here, we explored the role of miR-125a-3p in chemosensitivity in PDAC cells. METHODS: We used qRT-PCR to detect miR-125a-3p expression in two PDAC cell lines. And we measured cell viability and apoptosis by MTT assay and flow cytometry, respectively. Scratch wound healing assay and transwell invasion assay were used to test the effects of miR-125a-3p and Fyn on cell EMT process. In addition, we validated the interaction of miR-125a-3p and Fyn by dual luciferase reporter assay. qRT-PCR and western blot were used to detect the mRNA and protein expressions of E-cadhrein, N-cadhrein, Snail and Fyn. RESULTS: We found that miR-125a-3p was down-regulated in a time-dependent manner following treatment with gemcitabine in PDAC cells. Meanwhile, we found that overexpression of miR-125a-3p significantly increased chemosensitivity to gemcitabine and suppressed epithelial-mesenchymal transition (EMT) of PDAC cells. Mechanistically, miR-125a-3p directly targeted Fyn and decreased the expression of Fyn that functions to promote EMT process in PDAC. Furthermore, overexpression of Fyn could partially reverse the effects of miR-125a-3p on chemosensitivity to gemcitabine. CONCLUSION: Our study is the first to show that miR-125a-3p is responsible for chemosensitivity in PDAC and could inhibit epithelial-mesenchymal transition by directly targeting Fyn. This provides a novel potential therapeutic strategy to overcome chemoresistance in PDAC.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Carcinoma, Pancreatic Ductal/drug therapy , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm , Epithelial-Mesenchymal Transition/drug effects , MicroRNAs/metabolism , Pancreatic Neoplasms/drug therapy , Apoptosis/drug effects , Carcinoma, Pancreatic Ductal/enzymology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Pancreatic Neoplasms/enzymology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins c-fyn/genetics , Proto-Oncogene Proteins c-fyn/metabolism , Signal Transduction/drug effects , Time Factors , Gemcitabine
10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 21(7): 761-765, 2018 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-30051443

ABSTRACT

OBJECTIVE: To explore the appropriate operative strategy in recurrent groin hernia repair. METHODS: Clinical and follow-up data of 82 patients with recurrent groin hernia undergoing operation at Department of Pancreatobiliary Surgery, Xiangya Hospital of Central South University from April 2010 to April 2017 were analyzed retrospectively. The operative approaches included laparoscopic transabdominal preperitoneal (TAPP) hernia repair, Lichtenstein repair and hybrid repair. Surgical method selection was based on the basis of European Hernia Society guidelines, combined with hernia histories, preoperative examination results and intra-operative results: (1) When an anterior approach (Lichtenstein, Bassini or Shouldice surgery) was adopted in the previous operation, TAPP was preferred for the recurrent groin hernia. (2) When the previous operation was an posterior approach [TAPP or total extraperitoneal hernioplasty (TEP)], Lichtenstein method was preferred. Moreover, Lichtenstein surgery with local anesthesia or nerve block was also selected when the patient could not tolerate general anesthesia. (3) When extensive preperitoneal adhesions were found in patients with previous anterior approach repair during laparoscopic exploration, especially in patients who had relapsed after multiple operations or had previous biochemical glues injection, hybrid surgery was preferred. RESULTS: All 82 patients completed operations smoothly. TAPP, Lichtenstein and hybrid operation were applied in 74, 4 and 4 patients, respectively, with median operative time of 70 minutes (40-130 minutes) in TAPP, 60 minutes (40-90 minutes) in Lichtenstein and 120 minutes (70-150 minutes) in hybrid operation, respectively. The median numerical rating scales (NRS) score was 2 (0-6) on postoperative day 1. The incidences of postoperative seroma, pain and urinary retention were 4.9% (4/82), 2.4% (2/82) and 1.2% (1/82) respectively. The median postoperative hospital stay was 2 days (1-6 days). Seventy-two patients were followed-up from 11 to 87 months. The median follow-up period was 27 months. The median inguinal pain questionnaire (IPQ) score was 2 (0-8) month after operation. One recurrent case was reported 1 year after operation. No incision or mesh infection and long-term inguinal chronic pain were observed. CONCLUSIONS: For recurrent patients with previous open anterior approach, TEP and TAPP repair are equivalent surgical techniques, and the choice should be tailored to the surgeon's expertise. For those with previous TAPP or TEP repair, Lichtenstein technique is recommended. For those with adhesions both in anterior transverse fascia and pre-peritoneum, hybrid operation may be the preferable choice according to adhesion conditions.


Subject(s)
Hernia, Inguinal/surgery , Herniorrhaphy , Laparoscopy , Groin , Humans , Recurrence , Retrospective Studies , Surgical Mesh , Treatment Outcome
11.
Dis Markers ; 2018: 6857042, 2018.
Article in English | MEDLINE | ID: mdl-30595764

ABSTRACT

Given the low resection rate and chemoresistance of patients with pancreatic cancer (PC), their survival rates are typically poor. Long noncoding RNAs (lncRNAs) have recently been shown to play an important role in tumourigenesis and human cancer progression, including in PC. In this study, we aimed to investigate the role of taurine-upregulated gene 1 (TUG1) in PC. A quantitative polymerase chain reaction was used to analyse TUG1 expression in PC tissues and peritumoural normal tissues. TUG1 was overexpressed in PC tissues compared with that in peritumoural normal tissues, and the high expression of TUG1 was associated with the poor prognosis of patients with PC. Furthermore, TUG1 knockdown significantly inhibited the proliferation and invasion of PC cells both in vitro and in vivo, while overexpression TUG1 promoted tumour cell proliferation, migration, and invasion. TUG1 directly targeted miR-29c, a tumour suppressor in several cancers. TUG1 knockdown significantly increased the expression of miR-29c and subsequently induced the downregulation of integrin subunit beta 1 (ITGB1), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9). The downregulation of miR-29c abolished the TUG1 knockdown-mediated inhibition of tumour growth in vitro and in vivo, whereas the upregulation of miR-29c enhanced the effects of TUG1 knockdown on PC cells. In conclusion, we demonstrate for the first time the oncogenic role of TUG1 in PC. The downregulation of TUG1 significantly inhibited the growth and migratory ability of PC cells in vitro and in vivo by targeting miR-29c. Our study provides a novel potential diagnostic biomarker and therapeutic target for PC.


Subject(s)
MicroRNAs/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , RNA, Long Noncoding/genetics , Adult , Aged , Animals , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Mice, Nude , Middle Aged , Xenograft Model Antitumor Assays
12.
Gastroenterol Res Pract ; 2014: 364549, 2014.
Article in English | MEDLINE | ID: mdl-25435873

ABSTRACT

The aim of this study was to reveal the associations of microRNA miR-15a and miR-16 dysregulation with clinicopathological characteristics and prognosis in patients with colorectal cancer. As a result, we found that miR-15a and miR-16 expression, detected by quantitative real time-PCR, were both significantly downregulated in colorectal cancer tissues compared with adjacent colorectal mucosa (both P < 0.001). Particularly, the expression levels of miR-15a in colorectal cancer tissues were positively correlated with those of miR-16 significantly (Spearman correlation coefficient r = 0.652, P < 0.001). In addition, miR-15a and/or miR-16 downregulation were all significantly associated with advanced TNM stage (all P < 0.05), poorly histological grade (all P < 0.05), and positive lymph node metastasis (all P < 0.05). Moreover, the survival analysis identified miR-15a expression, miR-16 expression, and miR-15a/miR-16 combination as independent predictors of both unfavorable overall survival and disease-free survival. Interestingly, the prognostic value of miR-15a/miR-16 combination was more significant than miR-15a or miR-16 expression alone. Collectively, the aberrant expression of miR-15a and miR-16 could be used to stratify patients with aggressive tumor progression of colorectal cancer. The combined pattern of miR-15a and miR-16 downregulation has a significant value for distinguishing patients with a worse prognosis of colorectal cancer after surgery.

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