Publications by authors named "Kaixiong Tao"

177 Publications

Role of Indole-3-Acetic Acid in NAFLD Amelioration After Sleeve Gastrectomy.

Obes Surg 2021 May 10. Epub 2021 May 10.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: This study aimed to investigate the weight-independent mechanism of sleeve gastrectomy on the relief of nonalcoholic fatty liver disease (NAFLD).

Methods: A total of 58 obese patients who had undergone sleeve gastrostomy (SG) were recruited. Plasma levels of indole-3-acetic acid (I3A), a metabolite from gut microbiota before and after SG were investigated. In addition, we had 78 C57BL/6J mice included in the study. High-fat diet (HFD) was used to induce obesity in mice. Sleeve gastrectomy (SG) was then performed. The liver of the mice was analyzed by HE and oil red staining to study lipid accumulation. Fluorescence-activated cell sorting (FACS) analysis was performed to study the phenotype of macrophages in the liver. The levels of I3A in serum, stool, and liver were tested by ELISA. Macrophages and hepatocytes were cultured in vitro and stimulated with I3A to study the effects on differentiation and proliferation/apoptosis.

Results: In human samples, I3A increased after SG and plasma I3A levels were positively correlated with liver CT values and negatively correlated with liver fat attenuation. In mice models, after surgery, the percentage of M2 macrophages significantly increased in the liver. Both oral gavage and in vitro stimulation of I3A could promote M2 differentiation and did not significantly affect the state of hepatocytes.

Conclusions: This study suggested that increased I3A from the intestine after SG could reduce the M1/M2 ratio in the liver and thus promote relief of NAFLD in obese individuals. Graphical Abstract.
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http://dx.doi.org/10.1007/s11695-021-05321-0DOI Listing
May 2021

Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.

Front Oncol 2021 1;11:648045. Epub 2021 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, and tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21 expression.
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http://dx.doi.org/10.3389/fonc.2021.648045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047315PMC
April 2021

Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A.

Life Sci 2021 Apr 5;277:119398. Epub 2021 Apr 5.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. The present study explored the effects of TF-miR-146b-3p axis on CRC and elucidated its downstream regulatory molecule.

Materials And Methods: The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.

Results: Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.

Conclusion: Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC.
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http://dx.doi.org/10.1016/j.lfs.2021.119398DOI Listing
April 2021

Radical resection versus local excision for low rectal gastrointestinal stromal tumor: A multicenter propensity score-matched analysis.

Eur J Surg Oncol 2021 Feb 3. Epub 2021 Feb 3.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: The surgical approaches and resection extent for rectal gastrointestinal stromal tumors (GISTs) are controversial due to the low incidence of this disease. A multicenter retrospective cohort study was conducted to compare the postoperative and oncologic outcomes of local excision (LE) and radical resection (RR) in patients with low rectal GIST.

Patients And Methods: The medical records of rectal GIST patients from 11 large-scale medical centers in China (January 2000-December 2019) were reviewed. All patients were divided into either the LE group or the RR group. Propensity score matching (PSM) was conducted to reduce confounders.

Results: A total of 280 patients with low rectal GIST were enrolled. After PSM, 144 patients were included (72 in each group). The LE group showed a higher anal preservation rate (100.0% vs. 76.4%, P < 0.001), shorter operation time (77.1 ± 68.4 min vs. 159.1 ± 83.6 min, P < 0.001), fewer complications (8.3% vs. 22.2%, P = 0.021) and shorter postoperative hospital stay (4.9 ± 4.1 d vs. 10.7 ± 8.1 d, P < 0.001) than the RR group. There was no significant difference in recurrence-free survival (RFS) between the RR and LE groups among patients with tumors ≤2 cm (P = 0.220), and the RR group had a superior RFS than the LE group in patients with tumors >2 cm (P = 0.046).

Conclusions: LE resulted in improved postoperative outcomes and comparable oncological safety with a low rectal GIST of ≤2 cm. However, for patients with a low rectal GIST of >2 cm, RR might be a more appropriate option with better RFS.
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http://dx.doi.org/10.1016/j.ejso.2021.01.027DOI Listing
February 2021

Comparative efficacy and tolerability of adjuvant systemic treatments against resectable colon cancer: a network meta-analysis.

Ther Adv Med Oncol 2020 14;12:1758835920974195. Epub 2020 Dec 14.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China.

Background: Currently, 6-month oxaliplatin-based chemotherapy has been recommended as the preferred adjuvant treatment against high-risk stage 2 and stage 3 colon cancer patients.

Methods: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society for Medical Oncology meeting libraries from inception to November 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. Disease-free survival was primary endpoint. Network calculation was based on a random-effects model, and relative ranking of each node was numerically indicated by score.

Results: A total of 30 trials were included, corresponding to 54,109 patients. Regarding disease-free survival, none of the analyzed regimens displayed significant superiority against common comparator 6-month capecitabine plus oxaliplatin (XELOX), while 12-month [network hazard ratio (HR) 0.81 (0.60-1.10); 0.79 (0.57-1.10)] and 3-month XELOX [0.95 (0.86-1.04); 0.93 (0.83-1.05)] were top-ranking regimens showing non-inferiority among overall and stage 3 patients. Moreover, by pairwise meta-analysis, 3-month XELOX demonstrated significant superiority against 6-month XELOX among low-risk stage 3 patients [pairwise HR 0.78 (0.63-0.97)]. Concerning adverse events, 3-month oxaliplatin-based chemotherapy was significantly better than the 6-month counterpart with respect to peripheral sensory neuropathy, thrombocytopenia and fatigue. The 12-month capecitabine monotherapy failed to display non-inferiority among other major adverse events.

Conclusions: The 3-month XELOX treatment could be an alternative option of the 6-month regimen among low-risk stage 3 patients. Among high-risk stage 3 patients, 6-month oxaliplatin-based regimens still seem more competitive. In addition, clinical application of 12-month capecitabine monotherapy should be cautious, despite its top rankings, especially among non-Asian countries.
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http://dx.doi.org/10.1177/1758835920974195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739130PMC
December 2020

Dysregulation of intercellular signaling by MOF deletion leads to liver injury.

J Biol Chem 2020 Dec 29. Epub 2020 Dec 29.

Medicine; Biochemistry and Molecular Medicine, University of Southern California, United States.

Epigenetic mechanisms that alter heritable gene expression and chromatin structure play an essential role in many biological processes, including liver function. Human MOF (males absent on the first) is a histone acetyltransferase that is globally downregulated in human steatohepatitis. However, the function of MOF in the liver remains unclear. Here, we report that MOF plays an essential role in adult liver. Genetic deletion of Mof by Mx1-Cre in liver leads to acute liver injury, with increase of lipid deposition and fibrosis akin to human steatohepatitis. Surprisingly, hepatocyte specific Mof deletion had no overt liver abnormality. Using the in vitro co-culturing experiment, we show that Mof deletion-induced liver injury requires coordinated changes and reciprocal signaling between hepatocytes and Kupffer cells, which enables feedforward regulation to augment inflammation and apoptotic responses. At the molecular level, Mof deletion induced characteristic changes in metabolic gene programs, which bore noticeable similarity to the molecular signature of human steatohepatitis. Simultaneous deletion of Mof in both hepatocytes and macrophages results in enhanced expression of inflammatory genes and NO signaling in vitro. These changes, in turn, lead to apoptosis of hepatocytes and lipotoxicity. Our work highlights the importance of histone acetyltransferase MOF in maintaining metabolic liver homeostasis and sheds light on the epigenetic dysregulation in liver pathogenesis.
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http://dx.doi.org/10.1074/jbc.RA120.016079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948572PMC
December 2020

RYGB increases postprandial gastric nesfatin-1 and rapid relieves NAFLD via gastric nerve detachment.

PLoS One 2020 10;15(12):e0243640. Epub 2020 Dec 10.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Roux-en-Y gastric bypass (RYGB) could reduce nonalcoholic fatty liver disease (NAFLD) ahead of the weight-loss effects. But the detailed mechanisms remain unclear.

Material And Methods: A high-fat diet (HFD) was fed to induce obesity. RYGB was then performed. Gastric nesfatin-1 was measured by enzyme-linked immunosorbent assay (ELISA) in portal vein and polymerase chain reaction (PCR) in gastric tissues. Modified surgeries including vagus-preserved bypass and vagectomy were performed and postprandial gastric nesfatin-1 were analyzed. The effects of nesfatin-1 on hepatocytes were studied by PCR and immunohistochemistry. Both intraperitoneal and intracerebroventricular injection (ICV) were performed to analyze the in vivo effects on liver lipid metabolism.

Results: Increased postprandial portal vein nesfatin-1 was observed in RYGB but not in control groups. This increase is mainly due to induction of gastric nesfatin-1. A modified RYGB in which the gastric vagus is preserved is conducted and, in this case, this nesfatin-1 induction effect is diminished. Mere vagectomy could also induce a similar nesfatin-1 increase pattern. The infusion of nesfatin-1 in the brain could inhibit the expression of gastric nesfatin-1, and the effects are diminished after gastric vagectomy. In vivo and in vitro nesfatin-1 stimulation in the liver resulted in improvements in lipid metabolism.

Conclusions: Severing the gastric vagus during RYGB could cut off the negative control from the central nervous system (CNS) and result in increased postprandial gastric nesfatin-1 post surgery, which in turn, improves NAFLD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243640PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728189PMC
February 2021

Robotic colorectal cancer surgery in China: a nationwide retrospective observational study.

Surg Endosc 2020 Nov 25. Epub 2020 Nov 25.

Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Background: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series.

Method: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed.

Results: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage.

Conclusion: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.
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http://dx.doi.org/10.1007/s00464-020-08157-4DOI Listing
November 2020

Procalcitonin as an Early Predictor of Intra-abdominal Infections Following Gastric Cancer Resection.

J Surg Res 2021 02 24;258:352-361. Epub 2020 Oct 24.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: The purpose of this study was to investigate the prognostic value of postoperative procalcitonin (PCT) and C-reactive protein (CRP) for their ability to detect Intra-abdominal infections (IAIs) in patients after GC surgery.

Methods: Patients who underwent elective gastrectomy for primary GC were retrospectively enrolled between October 2018 and October 2019. The PCT and CRP levels and white blood cell (WBC) count were measured before surgery and on postoperative days (POD) 1, 3, 5, and 7. The differences in serum PCT, CRP, and WBC levels between IAIs and non-IAIs groups were compared. Diagnostic accuracy was determined by the area under the receiver operating characteristic curve. Univariate and multivariate logistic regression analyses identified independent clinical factors that predicted postoperative IAIs.

Results: A total of 155 patients who underwent GC surgery were enrolled. IAIs were observed in 12 patients (7.74%). The postoperative CRP and PCT values in the IAI group were higher than those in the non-IAI group. PCT had superior diagnostic accuracy on POD 3 (area under the curve 0.769) with an optimal cutoff value of 2.03 ng/mL, yielding 75% sensitivity, 87.4% specificity, and 97.6% negative predictive value. Multivariate analysis identified a PCT level of 2.03 mg/mL or greater on POD 3 as a significant predictive factor for IAIs after gastrectomy (odds ratio: 21.447, 95% confidence interval: 5.081-91.672).

Conclusions: PCT values less than 2.03 ng/mL on POD 3 is an excellent negative predictor of IAIs, which may ensure a safe early discharge after gastric cancer surgery.
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http://dx.doi.org/10.1016/j.jss.2020.08.037DOI Listing
February 2021

Prognostic Value of Surgical Site Infection in Patients After Radical Colorectal Cancer Resection.

Med Sci Monit 2020 Oct 11;26:e928054. Epub 2020 Oct 11.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

BACKGROUND This study aimed to evaluate the clinicopathological factors associated with surgical site infection (SSI) and the prognostic impact on patients after colorectal cancer (CRC) resection surgery. MATERIAL AND METHODS This retrospective study evaluated the relationships between SSI and various clinicopathological factors and prognostic outcomes in 326 consecutive patients with CRC who underwent radical resection surgery at Wuhan Union Hospital during April 2015-May 2017. RESULTS Among the 326 patients who underwent radical CRC resection surgery, 65 had SSIs, and the incidence rates of incisional and organ/space SSI were 16.0% and 12.9%, respectively. Open surgery, chronic obstructive pulmonary disease (COPD), and a previous abdominal surgical history were identified as risk factors for incisional SSI. During a median follow-up of 40 months (range: 5-62 months), neither simple incisional nor simple organ/space SSI alone significantly affected disease-free survival (DFS) or overall survival (OS), whereas combined incisional and organ/space SSI had a significant negative impact on both the 3-year DFS and OS (P<0.001). A multivariate analysis identified that age ≥60 years, lymph node involvement, tumor depth (T3-T4), and incisional and organ/space SSI were independent predictors of 3-year DFS and OS. In addition, adjuvant chemotherapy and a carbohydrate antigen-125 concentration ≥37 ng/ml were also independent predictors of OS. CONCLUSIONS We have identified several clinicopathological factors associated with SSI, and identified incisional and organ/space SSI is an independent prognostic factor after CRC resection. Assessing the SSI classification may help to predict the prognosis of these patients and determine further treatment options.
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http://dx.doi.org/10.12659/MSM.928054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559942PMC
October 2020

Development and validation of a prognostic nomogram to predict recurrence in high-risk gastrointestinal stromal tumour: A retrospective analysis of two independent cohorts.

EBioMedicine 2020 Oct 25;60:103016. Epub 2020 Sep 25.

Department of Gastrointestinal Surgery, Union Hospital Tongji Medical College Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province 430022, China. Electronic address:

Background: The risk of recurrence in localised, primary gastrointestinal stromal tumour (GIST) classified as high-risk after complete resection varies significantly. Thus, we aimed to develop a nomogram to predict the recurrence of high-risk GIST after surgery to aid patient selection.

Methods: We retrospectively evaluated patients (n = 424) with high-risk GIST who underwent curative resection as the initial treatment at two high-volume medical centres, between January 2005 and September 2019. The least absolute shrinkage and selection operator (LASSO) regression model was utilised to select potentially relevant features. Multivariate Cox proportional hazards analysis was used to develop a novel nomogram.

Findings: The nomogram comprised age, fibrinogen levels, prognostic nutritional index (PNI), platelet-lymphocyte ratio (PLR), mitotic counts and tumour size, which provided favourable calibration and discrimination in the training dataset with an AUC of 0•749 and a C-index of 0•742 (95%CI:0•689-0•804). Further, it showed acceptable discrimination in the validation cohort, with an AUC of 0•778 and C-index of 0•735 (95%CI:0•634-0•846). The time-dependant receiver operating characteristic (ROC) curves performed well throughout the observation period. Additionally, the nomogram could classify high-risk GISTs into 'very high-risk' and 'general high-risk' groups with a hazard ratio (HR) of 5•190 (95%CI: 3•202-8•414) and 5•438 (95%CI: 2•236-13•229) for the training and validation datasets, respectively.

Interpretation: The nomogram independently predicted post-operative recurrence-free survival (RFS) in high-risk GIST and showed favourable discrimination and calibration values. It may be a useful clinical tool for identifying 'very high-risk' GIST, by allowing treatment strategy optimisation in these patients.

Funding: National Natural Science Foundation of China (No. 81702386 and 81874184).
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http://dx.doi.org/10.1016/j.ebiom.2020.103016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522759PMC
October 2020

Tert-butylhydroquinone mitigates Carbon Tetrachloride induced Hepatic Injury in mice.

Int J Med Sci 2020 29;17(14):2095-2103. Epub 2020 Jul 29.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Tert-butylhydroquinone (tBHQ) is an antioxidant compound that exhibits cytoprotective effect in many tissues under pathological condition. However, its role in carbon tetrachloride (CCL4) induced liver injury is still unclear. Here we established a carbon tetrachloride induced hepatic injury model in mice to determine whether tBHQ can mitigate CCL4 induced liver damage. In our study, we found tBHQ exhibited protective effects in CCL4 treated mice model. TBHQ markedly improved hepatic function and decreased hepatic histopathological damage . In addition, tBHQ reduced levels of pro-inflammatory cytokines in mice model. Moreover, tBHQ mitigated apoptosis of hepatocytes, oxidative stress and lipid peroxidation and . We also found the possible mechanism of protective effects of tBHQ was associated with activation of Nrf2/ heme oxygenase-1 (HO-1) pathway. In conclusion, our study revealed tBHQ can be a potential therapeutic drug in treatment of acute hepatic injury.
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http://dx.doi.org/10.7150/ijms.45842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484658PMC
July 2020

The MDM2 ligand Nutlin-3 differentially alters expression of the immune blockade receptors PD-L1 and CD276.

Cell Mol Biol Lett 2020 31;25:41. Epub 2020 Aug 31.

RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.

Background: The links between the p53/MDM2 pathway and the expression of pro-oncogenic immune inhibitory receptors in tumor cells are undefined. In this report, we evaluate whether there is p53 and/or MDM2 dependence in the expression of two key immune receptors, CD276 and PD-L1.

Methods: Proximity ligation assays were used to quantify protein-protein interactions in situ in response to Nutlin-3. A panel of p53-null melanoma cells was created using CRISPR-Cas9 guide RNA mediated genetic ablation. Flow cytometric analyses were used to assess the impact of or gene ablation, as well as the effects of Nutlin-3 and an ATM inhibitor on cell surface PD-L1 and CD276. Targeted siRNA was used to deplete CD276 to assess changes in cell cycle parameters by flow cytometry. A T-cell proliferation assay was used to assess activity of CD4+ T-cells as a function of genotype.

Results: CD276 forms protein-protein interactions with MDM2 in response to Nutlin-3, similar to the known MDM2 interactors p53 and HSP70. Isogenic HCT116 p53-wt/null cancer cells demonstrated that CD276 is induced on the cell surface by Nutlin-3 in a p53-dependent manner. PD-L1 was also unexpectedly induced by Nutlin-3, but PD-L1 does not bind MDM2. The ATM inhibitor KU55993 reduced the levels of PD-L1 under conditions where Nutlin-3 induces PD-L1, indicating that MDM2 and ATM have opposing effects on PD-L1 steady-state levels. PD-L1 is also up-regulated in response to genetic ablation of in A375 melanoma cell clones under conditions in which CD276 remains unaffected. A549 cells with a deletion in the gene up-regulated only PD-L1, further indicating that PD-L1 and CD276 are under distinct genetic control.

Conclusion: Genetic inactivation of , or the use of the MDM2 ligand Nutlin-3, alters the expression of the immune blockade receptors PD-L1 and CD276. The biological function of elevated CD276 is to promote altered cell cycle progression in response to Nutlin-3, whilst the major effect of elevated PD-L1 is T-cell suppression. These data indicate that gene status, ATM and MDM2 influence PD-L1 and CD276 paralogs on the cell surface. These data have implications for the use of drugs that target the p53 pathway as modifiers of immune checkpoint receptor expression.
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http://dx.doi.org/10.1186/s11658-020-00233-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457494PMC
August 2020

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

J Cell Mol Med 2020 10 31;24(20):11828-11836. Epub 2020 Aug 31.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Colorectal cancer (CRC) mostly arises from progressive accumulation of somatic mutations within cells. Most commonly mutated genes like TP53, APC and KRAS can promote survival and proliferation of cancer cells. Although the molecular alterations and landscape of some specific mutations in CRC are well known, the presence of a somatic mutation signature related to genomic regions and epigenetic markers remain unclear. To find the signatures from a random distribution of somatic mutations in CRCs, we carried out enrichment analysis in different genomic regions and identified peaks of epigenetic markers. We validated that the mutation frequency in miRNA is dramatically higher than in flanking genomic regions. Moreover, we observed that somatic mutations in CRC and colon cancer cell lines are significantly enriched in CTCF binding sites. We also found these mutations are enriched for H3K27me3 in both normal sigmoid colon and colon cancer cell lines. Taken together, our findings suggest that there are some common somatic mutations signatures which provide new directions to study CRC.
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http://dx.doi.org/10.1111/jcmm.15799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579689PMC
October 2020

Study of the gastrointestinal tumor progression during the COVID-19 epidemic in Wuhan.

Br J Surg 2020 Oct 28;107(11):e502-e503. Epub 2020 Aug 28.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1002/bjs.11965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461452PMC
October 2020

Gearing back to normal clinical services in Wuhan: frontline experiences and recommendations from mental health perspective.

Br J Surg 2020 10 10;107(11):e455. Epub 2020 Aug 10.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1002/bjs.11912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436552PMC
October 2020

Comment on "Approaching Surgical Triage During the COVID-19 Pandemic": Triage Outpatients of Surgical Departments for Hospitalization During Post-COVID-19 Era-Experience and Recommendations From Frontline Surgeons in Wuhan.

Ann Surg 2020 Jul 24. Epub 2020 Jul 24.

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

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http://dx.doi.org/10.1097/SLA.0000000000004290DOI Listing
July 2020

Expression of DCP1a in gastric cancer and its biological function and mechanism in chemotherapy resistance in gastric cancer cells.

Dig Liver Dis 2020 11 6;52(11):1351-1358. Epub 2020 Jul 6.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei, PR China. Electronic address:

Aims: To detect the role of DCP1a in gastric cancer. To estimate the effect of DCP1a in gastric cancer cells on proliferation, invasion, migration and anti-drug behavior in vitro by down-regulating its expression.

Methods: Using IHC staining and Western blot to check the expression of DCP1a in tissues and the cell lines. SGC7901 and BGC823 cells were transfected with DCP1a siRNA, and the expression of DCP1a protein and mRNA were detected. The cell proliferation rate was detected by MTT assay and plate cloning assay. Transwell assay was used to detect the change of cell metastasis. The inhibition rates of cells to chemotherapy were detected by MTT assay. And signal pathways were also detected.

Results: The expression of DCP1a in cancer tissues is higher (p < 0.05), and higher expression of DCP1a is related to poor prognosis. After down-regulating the expression of DCP1a in cells, the proliferation rates, migration abilities and chemotherapy resistance decrease. We find that the expression of MRP-1 and the activation of AKT and STAT3 pathways might be involved in regulation.

Conclusion: The high expression of DCP1a might be associated with cancer development and prognosis. Down-regulating the expression of DCP1a will help to reduce chemotherapy resistance, which will help with further improvement of chemotherapy in gastric cancer.
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http://dx.doi.org/10.1016/j.dld.2020.06.031DOI Listing
November 2020

DNA methylation profiling to predict recurrence risk in stage Ι lung adenocarcinoma: Development and validation of a nomogram to clinical management.

J Cell Mol Med 2020 07 12;24(13):7576-7589. Epub 2020 Jun 12.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Increasing evidence suggested DNA methylation may serve as potential prognostic biomarkers; however, few related DNA methylation signatures have been established for prediction of lung cancer prognosis. We aimed at developing DNA methylation signature to improve prognosis prediction of stage I lung adenocarcinoma (LUAD). A total of 268 stage I LUAD patients from the Cancer Genome Atlas (TCGA) database were included. These patients were separated into training and internal validation datasets. GSE39279 was used as an external validation set. A 13-DNA methylation signature was identified to be crucially relevant to the relapse-free survival (RFS) of patients with stage I LUAD by the univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox proportional hazard analysis in the training dataset. The Kaplan-Meier analysis indicated that the 13-DNA methylation signature could significantly distinguish the high- and low-risk patients in entire TCGA dataset, internal validation and external validation datasets. The receiver operating characteristic (ROC) analysis further verified that the 13-DNA methylation signature had a better value to predict the RFS of stage I LUAD patients in internal validation, external validation and entire TCGA datasets. In addition, a nomogram combining methylomic risk scores with other clinicopathological factors was performed and the result suggested the good predictive value of the nomogram. In conclusion, we successfully built a DNA methylation-associated nomogram, enabling prediction of the RFS of patients with stage I LUAD.
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http://dx.doi.org/10.1111/jcmm.15393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339160PMC
July 2020

DNA methylation profiling to predict overall survival risk in gastric cancer: development and validation of a nomogram to optimize clinical management.

J Cancer 2020 27;11(15):4352-4365. Epub 2020 Apr 27.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

DNA methylation has been reported to serve an important role in the carcinogenesis and development of gastric cancer. Our aim was to systematically develop an individualized prediction model of the survival risk combing clinical and methylation factors in gastric cancer. A univariate Cox proportional risk regression analysis was used to identify the prognosis-associated methylation sites based on the differentially expressed methylation sites between early and advanced gastric cancer group, then we applied least absolute shrinkage and selection operator (LASSO) Cox regression model to screen candidate methylation sites. Subsequently, multivariate Cox proportional risk regression analysis was conducted to identify predictive signature according to the candidate sites. Relative operating characteristic curve (ROC) analysis manifested that an 11-methylation signature exhibited great predictive efficiency for 1-, 3-, 5-year survival events. Patients in the low-risk group classified according to 11-methylation signature-based risk score yield significantly better survival than that in high-risk group. Moreover, Cox regression analysis combing methylation-based risk score and other clinical factors indicated that 11-methylation signature served as an independent risk factor. The predictive value of risk score was validated in the testing dataset. In addition, a nomogram was constructed and the ROC as well as calibration plots analysis demonstrated the good performance and clinical application of the nomogram. In conclusion, the result suggested the 11-DNA methylation signature may be potentially independent prognostic marker and functioned as a significant tool for guiding the clinical prediction of gastric cancer patients' overall survival.
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http://dx.doi.org/10.7150/jca.44436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255367PMC
April 2020

Safety and feasibility of prolonged versus early laparoscopic cholecystectomy for acute cholecystitis: a single-center retrospective study.

Surg Endosc 2021 May 22;35(5):2297-2305. Epub 2020 May 22.

Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430022, Hubei, People's Republic of China.

Background: Laparoscopic cholecystectomy (LC) is the standard treatment for acute cholecystitis (AC), and it should be performed within 72 h of symptoms onset if possible. In many undesired situations, LC was performed beyond the golden 72 h. However, the safety and feasibility of prolonged LC (i.e., performed more than 72 h after symptoms onset) are largely unknown, and therefore were investigated in this study.

Methods: We retrospectively enrolled the adult patients who were diagnosed as AC and were treated with LC at the same admission between January 2015 and October 2018 in an emergency department of a tertiary academic medical center in China. The primary outcome was the rate and severity of adverse events, while the secondary outcomes were length of hospital stay and costs.

Results: Among the 104 qualified patients, 70 (67.3%) underwent prolonged LC and 34 (32.7%) underwent early LC (< 72 h of symptom onset). There were no differences between the two groups in mortality rate (none for both), conversion rates (prolonged LC 5.4%, and early LC 8.8%, P = 0.68), intraoperative and postoperative complications (prolonged LC 5.7% and early LC 2.9%, P ≥ 0.99), operation time (prolonged LC 193.5 min and early LC 198.0 min, P = 0.81), and operation costs (prolonged LC 8,700 Yuan, and early LC 8,500 Yuan, P = 0.86). However, the prolonged LC was associated with longer postoperative hospitalization (7.0 days versus 6.0 days, P = 0.03), longer total hospital stay (11.0 days versus 8.0 days, P < 0.01), and subsequently higher total costs (40,400 Yuan versus 31,100 Yuan, P < 0.01).

Conclusions: Prolonged LC is safe and feasible for patients with AC for having similar rates and severity of adverse events as early LC, but it is also associated with longer hospital stay and subsequently higher total cost.
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http://dx.doi.org/10.1007/s00464-020-07643-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057981PMC
May 2021

Evaluation of the application of laparoscopy in enhanced recovery after surgery (ERAS) for gastric cancer: a Chinese multicenter analysis.

Ann Transl Med 2020 Apr;8(8):543

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Background: Enhanced recovery after surgery (ERAS) has been successfully applied in general surgery, especially in colorectal resection. However, the effect of ERAS in gastric cancer resection in current studies are inconsistent and most of which were single center retrospective ones. Thus, our study was aimed to evaluate the application of laparoscopy in ERAS for gastric cancer based on Chinese multicenter data.

Methods: The clinical and pathological data of patients who underwent radical gastric cancer resection at three Chinese medical centers between January, 2015 and December, 2017 were retrospectively analyzed. The current application of laparoscopy in ERAS for gastric cancer was evaluated.

Results: A total of 1,434 patients were involved in the final analysis. The operation time was 265.7±79.1 min, blood loss was 200 [5-1,300] mL, and the number of lymph nodes dissected was 26.4±12.9. Time to first ambulation, flatus, and liquid food intake were 2.1±1.3, 4.4±2.7, and 6.1±3.6 days, respectively, and postoperative hospital stay was 9.0±1.5 days. The incidence of postoperative complications, Clavien-Dindo score ≥ II, was 10.0%, and the rate of readmission within 30 days of discharge was 1.4%. Of the patients who underwent total gastrectomy, those in the laparoscopic group had a higher number of lymph nodes retrieved than those in the open group (P<0.05), and also had earlier ambulation, oral intake and first flatus, as well as a shorter postoperative hospital stay time than the open group. There were no significant differences in intraoperative blood loss or postoperative complications between the two groups (P>0.05). Of the patients who underwent distal gastrectomy, the laparoscopic group had a lower volume of blood loss, shorter postoperative hospital stay time, and earlier ambulation, oral intake, and first flatus than the open group, and had a similar number of lymph nodes dissected compared to the open group (P>0.05).

Conclusions: Laparoscopic surgery combined with ERAS can shorten the time to early ambulation, oral intake, and first flatus, and shorten the length of hospital stay. Laparoscopic surgery can achieve the same oncological outcomes as open surgery and is safe and feasible without increasing the incidence of postoperative complications.
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http://dx.doi.org/10.21037/atm-20-2556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214879PMC
April 2020

Which size is the best cutoff for primary small gastric gastrointestinal stromal tumor?

J Gastrointest Oncol 2020 Apr;11(2):402-410

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510000, China.

Background: The biological behavior of primary small gastric gastrointestinal stromal tumor (gGIST) is indolent. The cutoff size categorizing small gGIST continues to be controversial. To date, there is no consensus regarding whether it should be 1 cm, 2 cm, or another size. We aimed to find a new cutoff size.

Methods: Retrospective clinicopathological and prognosis data of patients with small gGIST from January 1998 to January 2015 were collected among five medical centers in southern China. Tumor size was divided into two groups: <1 cm (Mirco group) and 1-2 cm (Small group). We compared the clinicopathological index and prognosis between these two groups and identified a new cutoff size to define small gGIST.

Results: During this 18-year period, there were 276 patients with primary small gGIST treated at these five medical centers. The range of tumor size was 0.2-2.0 cm. The median tumor size was 1.0 cm. The range of the mitotic count was 0-70/50 high power fields (HPFs) with counts ≤5/50 HPFs in 259 patients (93.8%), 5< counts ≤10/50 HPFs in 7 patients (2.5%), and counts >10/50 HPFs in 10 patients (3.6%). The median follow-up time was 38 months (3-156 months). The 5-year overall survival rate was 98.7% in the entire group. Using Pearson correlation analysis, there was a positive correlation between the mitotic count and tumor size as a continuous variable (r=0.164, P=0.006). There were 137 patients in the Micro group and 139 cases in the Small group. In the Micro group, mitotic counts were ≤5/50 HPFs in 134 patients, 5< counts ≤10/50 HPFs in 0 patients, and counts >10/50 HPFs in 3 patients; mitotic counts in the Small group were counts ≤5/50 HPFs in 125 patients, 5< counts ≤10/50 HPFs in 7 patients, >10/50 HPFs in 7 patients. There was a statistically significant difference between these two groups (P=0.002); the Small group had more intermediate/high-risk cases. Using the receiver operating characteristic curve (ROC curve), we observed that 1.15 cm was the new cutoff size to separate low-risk cases and intermediate/high-risk cases (AUC =0.707, P=0.004, sensitivity =0.824, 1-specificity =0.429).

Conclusions: Primary small gGIST has a good prognosis; gGIST <1 cm can be regarded as benign tumors that only requires endoscopic ultrasonography (EUS) follow-up. The proportion of potential intermediate/high-risk disease is high for patients with 1-2 cm gGIST. These patients should be treated with caution and the tumors should be resected if necessary. These results indicate that 1.15 cm may be the new cutoff size to separate small gGIST from large gGIST, but further studies are needed for verification.
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http://dx.doi.org/10.21037/jgo.2020.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212102PMC
April 2020

Interferon regulatory factor-1 suppresses DNA damage response and reverses chemotherapy resistance by downregulating the expression of RAD51 in gastric cancer.

Am J Cancer Res 2020 1;10(4):1255-1270. Epub 2020 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, Hubei, P. R. China.

Recent studies have shown that IRF-1 plays a significant role in various tumour-induced chemoresistance, but its role and mechanism in gastric cancer-associated chemoresistance are not clear. Our study showed that IRF-1 expression could reverse gastric cancer-related chemoresistance. Dysregulated DNA repair is an important cause of chemoresistance. We established a chemoresistant gastric cancer cell line and found that drug-resistant gastric cancer cells had increased DNA repair ability and that IRF-1 regulated DNA damage repair. Further studies showed that IRF-1 inhibited the expression of RAD51 directly by binding to the RAD51 promoter to affect DNA damage repair; this binding reversed resistance. However, restoring the expression of RAD51 halted the inhibitory effect of IRF-1 partially. Also, we revealed that the overexpression of IRF-1 in a mouse model synergized with chemotherapeutic drugs to inhibit tumour growth. Finally, IRF-1 expression correlated with RAD51 expression in gastric cancer specimens. The expression of IRF-1 and RAD51 are both related to the survival duration of patients with gastric cancer. These results suggest that targeting IRF-1-RAD51 could be an effective approach to reversing multidrug resistance in gastric cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191096PMC
April 2020

Characteristics of Household Transmission of COVID-19.

Clin Infect Dis 2020 11;71(8):1943-1946

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Since December 2019, SARS-CoV-2 has extended to most parts of China with >80 000 cases and to at least 100 countries with >60 000 international cases as of 15 March 2020. Here we used a household cohort study to determine the features of household transmission of COVID-19.

Methods: A total of 105 index patients and 392 household contacts were enrolled. Both index patients and household members were tested by SARS-CoV-2 RT-PCR. Information on all recruited individuals was extracted from medical records and confirmed or supplemented by telephone interviews. The baseline characteristics of index cases and contact patients were described. Secondary attack rates of SARS-CoV-2 to contact members were computed and the risk factors for transmission within the household were estimated.

Results: Secondary transmission of SARS-CoV-2 developed in 64 of 392 household contacts (16.3%). The secondary attack rate to children was 4% compared with 17.1% for adults. The secondary attack rate to the contacts within the households with index patients quarantined by themselves since onset of symptoms was 0% compared with 16.9% for contacts without quarantined index patients. The secondary attack rate to contacts who were spouses of index cases was 27.8% compared with 17.3% for other adult members in the households.

Conclusions: The secondary attack rate of SARS-CoV-2 in household is 16.3%. Age of household contacts and spousal relationship to the index case are risk factors for transmission of SARS-CoV-2 within a household. Quarantine of index patients at home since onset of symptoms is useful to prevent the transmission of SARS-Co-2 within a household.
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http://dx.doi.org/10.1093/cid/ciaa450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184465PMC
November 2020

Endoscopic diagnosis and treatment of complete anastomosis stenosis after colorectal resection without protective ileostomy: report of two cases and literature review.

J Int Med Res 2020 Apr;48(4):300060520914833

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

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http://dx.doi.org/10.1177/0300060520914833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153199PMC
April 2020

A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer.

Onco Targets Ther 2020 28;13:1797-1807. Epub 2020 Feb 28.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Gastric cancer is one of the most common malignant tumors, and it is also one of the leading causes of cancer death worldwide. Because of its insidious symptoms and lack of early dictation screening, many cases of gastric cancer are at late stages which make it more complicated to cure. For these advanced-stage gastric cancers, combination therapy of surgery, chemotherapy, radiotherapy and target therapy would bring more benefit to the patients. However, the drug-resistance to the chemotherapy restricts its effect and might lead to treatment failure. In this review article, we discuss the mechanisms which have been found in recent years of drug resistance in gastric cancer. And we also want to find new approaches to counteract chemotherapy resistance and bring more benefits to the patients.
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http://dx.doi.org/10.2147/OTT.S239336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053652PMC
February 2020

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis.

Cancer Sci 2020 May 30;111(5):1582-1595. Epub 2020 Apr 30.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.
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http://dx.doi.org/10.1111/cas.14372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226208PMC
May 2020

Diagnostic accuracy of procalcitonin as an early predictor of infection after radical gastrectomy for gastric cancer: A prospective bicenter cohort study.

Int J Surg 2020 Mar 22;75:3-10. Epub 2020 Jan 22.

Department of Gastrointestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China; Department of Orthopedics, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. Electronic address:

Objective: To investigate the diagnostic accuracy of procalcitonin (PCT) as an early predictor of infection following radical gastrectomy to treat gastric cancer (GC).

Methods: A prospective, observational, cohort study was conducted in two high-volume tertiary centers (registered under ClinicalTrials.gov). A total of 552 consecutive adult patients undergoing radical gastrectomy for GC from June 2018 to July 2019 were included. Routine blood tests (white blood cell count (WBC); neutrophil count; the neutrophil:WBC ratio, N%) and PCT were measured on post-operative day (POD) 3 and 5. Post-operative infection was recorded based on the criteria of the Center for Disease Control. The area under the curve (AUC) summarizing receiver-operating characteristic was calculated and compared for each biomarker measured.

Results: Ninety three adverse events occurred in 70 patients (12.7%), with infections being the most common (n = 37, 6.7%). With cutoff values of 0.695 ng/mL at POD 3 and 0.515 ng/mL at POD 5, specificity and negative predictive value for infections were 0.656 and 96.3%, 0.816 and 96.1%, respectively. PCT had a better AUC than the WBC and neutrophil count to detect post-operative complications, especially infections (AUC: 0.678, 0.600, 0.592, P = 0.028 and 0.017, respectively) at POD 3, but which were comparable at POD 5. Additionally, 4 of the 8 patients with PCT levels ≥3 ng/mL on POD 5 were confirmed to have an infection.

Conclusion: PCT is a more reliable predictor than WBC and neutrophil count to detect infections following radical gastrectomy for GC. PCT levels <0.695 ng/mL at POD 3 and < 0.515 ng/mL at POD 5 makes post-operative infections very unlikely but extreme high PCT levels should alert the surgeon to the possibility of infections.
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http://dx.doi.org/10.1016/j.ijsu.2020.01.019DOI Listing
March 2020