Cancer-Associated Fibroblasts Promote the Chemo-resistance in Gastric Cancer through Secreting IL-11 Targeting JAK/STAT3/Bcl2 Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Our aim was to detect the potential role of interleukin 11 (IL-11) in the development of chemo-resistance in gastric cancer and to reveal the mechanism involved in the process. MATERIALS AND METHODS: Here, we used flow cytometry to examine the percentage of cancer-associated-fibroblasts in tumor samples from chemo-resistant and -sensitive gastric cancer patients. Using MTT assay, we detected the cell viability under different conditions. Using quantitative real-time polymerase chain reaction and Western blotting, we determined the target expressions in mRNA and protein levels. We also performed immunohistochemistry and immunofluorescence to detect the target proteins under different conditions. Animal models were constructed to verify the potential role of IL-11 in chemo-resistant develop in vivo. RESULTS: Herein, we observed enriched cancer associated fibroblasts in drug resistant tumor tissues from gastric patients. Those fibroblasts facilitate the chemotherapeutic drugs resistance development through the secretion of IL-11, which activates the IL-11/IL-11R/gp130/JAK/STAT3 anti-apoptosis signaling pathway in gastric cancer cells. We found that the combination of chemotherapeutic drugs and JAK inhibitor overcomes the resistance and increases the survival of mice with gastric cancer xenografts. CONCLUSION: Ourresults demonstrated that IL-11 contributed to the obtain ofresistance to chemotherapy drugs through gp130/JAK/STAT3/Bcl2 pathway, and targeting the IL-11 signaling pathway induced by fibroblasts might be a promising strategy to overcome the multi-drugs resistant cancer in clinic.

Laparoscopic resection for gastric stromal tumors with sizes larger than 5 cm / 中华普通外科杂志

Objective To investigate the treatment efficacy,feasibility and safety of laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm.Methods The clinical data of 31 patients who underwent laparoscopic resection of large gastric GISTs between Jan 2010 and Jun 2017 at Sir Run Run Shaw Hospital and People's Hospital of Zhejiang Province were retrospectively analyzed.Results All operations were successful.Two patients were converted to open surgery.The mean tumor size was (7.2 ±0.5) cm.The mean operation time was (127 ± 12) min,intraoperative blood loss was (83 ±25) ml.The first flatus time was (2.2 ±0.8) days,the first diet resumption time was (2.4 ± 1.2) days,and the median postoperative hospital stay was (5.5 ± 1.5) days.The median follow-up time was 25 months.One patient developing liver metastasis 41 months after primary resection received oral mesylate imatinib therapy for 24 months and was still alive at the last follow-up.One patient died of lung cancer 33 months after primary operation without recurrence of gastric GIST.Conclusions Laparoscopic surgery for gastric GIST larger than 5 cm on laparoscopicaly accessible location is feasible and safe.

Laparoscopic radical antegrade modular pancreatosplenectomy for left-sided pancreatic adenocarcinoma: analysis of 12 cases / 中华外科杂志

Objective@#To evaluate the safety and feasibility of laparoscopic radical antegrade modular pancreatosplenectomy(Lap-RAMPS) for left-sided pancreatic adenocarcinoma.@*Methods@#Clinical data of total 12 patients underwent Lap-RAMPS for left-sided pancreatic adenocarcinoma at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital from March 2016 to August 2017 were reviewed retrospectively.There were 7 male patients and 5 female patients, with median age of 60.5 years old(47-68 years old). Abdominal enhanced CT, pancreatic MRI, PET-CT were performed on all patients to evaluate the lesion and exclude metastasis.Follow-up were done with out-patient clinic or telephone consultancy until October 2017.@*Results@#All patients underwent pure Lap-RAMPS.The medium operative time was 250 minutes(180-445 minutes), and the blood loss was 150 ml(50-500 ml). The medium first flatus time and diet resumption time were 3.0 days(1-5 days) and 3.5 days(1-7 days) respectively.The medium postoperative hospital stay was 9 days(4-18 days). Morbidity occurred in 8 patients with gastric empty delay(n=1), bleeding(n=1), fluid collection(n=3). There was no mortality.The medium overall number of retrived lymph nodes was 15.6 and the positive rate was 41.7%. The R0 rate was 100%.The medium follow-up was 10 months.One patient was diagnosed as liver metastasis after 8 months and accepted chemotherapy.One patient died after 14 months for tumor recurrence and metastasis.Others survived without tumor recurrence or metasitasis.@*Conclusion@#Lap-RAMPS is safe and feasible with accepted oncological outcomes for selected left side pancreatic adenocarcinoma under skilled hands.

Laparoscopic pancreaticoduodenectomy: a report of 233 cases by a single team / 中华外科杂志

Objective@#To summary the experience of 233 cases of laparoscopic pancreaticoduodenectomy (LPD) performed by a single surgical team.@*Methods@#Data of patients undergoing LPD from September 2012 to October 2016 were reviewed. There were 145 males and 88 females with the mean age of(60.3±13.0)years old, ranging from 19 to 92 years old, and the mean body mass index of (22.8±3.5)kg/m2, ranging from 16.3 to 36.8 kg/m2. There were 195 patients with clinical manifestation and 54 patients who had the history of abdominal surgery.@*Results@#LPD were performed on 233 patients by same surgical team consecutively. The mean operative time was(368.0±57.4)minutes. Mean blood loss was(203.8±138.6)ml. The postoperative morbidity rate was 33.5%, with 6.9% of grade B or C pancreatic fistula and 9.9% of bleeding. The reoperation rate was 5.6%. The mortality during 30 days after operation was 0.9%. Mean postoperative hospital stay was (18.1±11.2)days. Mean tumor size was (3.9±2.4)cm, and the mean number of lymph nodes harvested was 21.3±11.9.One hundred and sixty-three patients were diagnosed as malignant tumor, including pancreatic adenocarcinoma(n=84), cholangiocarcinoma(n=17), ampullary adenocarcinoma(n=55), duodenal adenocarcinoma(n=5), gastric cancer(n=1)and duel cancer (n=1) located in distal stomach and duodenum.@*Conclusion@#The key point to make laparoscopic pancreaticduodenectomy a routine safe procedure is to operate the procedure under skilled hands in selected patients via suitable surgical approaches.

DRP1-mediated overactive mitophagy increases the sensitivity of gastric cancer cell MKN-45 to oxaliplatin / 中华普通外科杂志

Objective To investigate the effects of DRP1 gene silencing on the chemosensitivity of human gastric cancer MKN-45 cells to oxaliplatin.Methods A lentiviral vector containing short hairpin RNA (shRNA) targeting DRP1 was constructed and cotransfected to MKN-45 cells.Levels of DRP1mRNA was detected by quantitative RT-PCR,With a final concentration of 0.5,1.0,2.0,4.0,8.0,16.0 and 32.0 μg/ml of oxaliplatin processing Lv-shRNA-DRPI group (experimental group),negative control group (NC group),and blank control group (CON group) respectively.Cellular proliferation was determined by MTT assay and calculate half maximal inhibitory concentration (IC5o).Celluar apoptosis was analyzed by flowcytometry.Using Western blot to detect LC3-Ⅱ and p62 expression.Results DRP1mRNA levels in experimental group (0.087 ± 0.025) was significantly inhibited as compared with NC group (1.040 ± 0.020) and CON group (1.027 ± 0.021) (P ＜ 0.001).Cellular survival rate decreased in a oxaliplatin dose-dependent manner (all P ＜ 0.001).IC50 value in experimental group (14.1 ± 0.4) μg/ml dropped compared with NC group (20.0 ± 1.1) μg/ml and CON group (20.0 ± 1.8) pg/ml (both P ＜ 0.01).Celluar apoptosis rates in experimental group (9.4％ ± 1.1％) elevated in contrast with NC group (6.4％ ± 0.8％) and CON group (6.5％ ± 1.0％) (both P ＜ 0.05),expression of LC3 in experimental group(0.36 ± 0.03) dropped compared with NC group (0.62 ± 0.04) and CON group (0.59 ± 0.07) (both P ＜ 0.05),expression of P62 in experimental group (0.58 ±-0.04) increased in contrast with NC group (0.39±0.04) and CON group (0.36 ±0.04) (both P＜0.05).Conclusions DRP1-mediated overactive mitophagy plays a vital role in increasing the sensitivity of gastric cancer cell MKN-45 to oxaliplatin.

DRP1-mediated overactive mitophagy increases the sensitivity of gastric cancer cell MKN-45 to oxaliplatin / 中华普通外科杂志

Objective To investigate the effects of DRP1 gene silencing on the chemosensitivity of human gastric cancer MKN-45 cells to oxaliplatin.Methods A lentiviral vector containing short hairpin RNA (shRNA) targeting DRP1 was constructed and cotransfected to MKN-45 cells.Levels of DRP1mRNA was detected by quantitative RT-PCR,With a final concentration of 0.5,1.0,2.0,4.0,8.0,16.0 and 32.0 μg/ml of oxaliplatin processing Lv-shRNA-DRPI group (experimental group),negative control group (NC group),and blank control group (CON group) respectively.Cellular proliferation was determined by MTT assay and calculate half maximal inhibitory concentration (IC5o).Celluar apoptosis was analyzed by flowcytometry.Using Western blot to detect LC3-Ⅱ and p62 expression.Results DRP1mRNA levels in experimental group (0.087 ± 0.025) was significantly inhibited as compared with NC group (1.040 ± 0.020) and CON group (1.027 ± 0.021) (P ＜ 0.001).Cellular survival rate decreased in a oxaliplatin dose-dependent manner (all P ＜ 0.001).IC50 value in experimental group (14.1 ± 0.4) μg/ml dropped compared with NC group (20.0 ± 1.1) μg/ml and CON group (20.0 ± 1.8) pg/ml (both P ＜ 0.01).Celluar apoptosis rates in experimental group (9.4％ ± 1.1％) elevated in contrast with NC group (6.4％ ± 0.8％) and CON group (6.5％ ± 1.0％) (both P ＜ 0.05),expression of LC3 in experimental group(0.36 ± 0.03) dropped compared with NC group (0.62 ± 0.04) and CON group (0.59 ± 0.07) (both P ＜ 0.05),expression of P62 in experimental group (0.58 ±-0.04) increased in contrast with NC group (0.39±0.04) and CON group (0.36 ±0.04) (both P＜0.05).Conclusions DRP1-mediated overactive mitophagy plays a vital role in increasing the sensitivity of gastric cancer cell MKN-45 to oxaliplatin.

Laparoscopic gastrectomy for gastric stump cancer: analysis of 7 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of laparoscopic gastrectomy for gastric stump cancer.</p><p><b>METHODS</b>Clinical and follow-up data of 7 patients who underwent laparoscopic gastrectomy for gastric stump cancer in our department from January 2008 to July 2015 were analyzed retrospectively.</p><p><b>RESULTS</b>There were 5 male and 2 female patients, with a mean age of (62.1±10.7) years. Initial gastrectomy was performed for gastric cancer in 3 patients and peptic ulceration in 4. The initial surgery was B-II( gastrojejunostomy in 6 patients and Roux-en-Y gastrojejunostomy in 1. Duration between primary gastrectomy and occurrence of gastric stump cancer was ranged from 6-30 years for peptic ulceration, and from 11-15 years for gastric cancer. During the operation, adhesiolysis and exploration to locate the tumor were performed. Following total remnant gastrectomy and lymphadenectomy, intracorporeal anastomosis was accomplished by Roux-en-Y reconstruction. The methods of intracorporeal esophagojejunostomy were end-to-side approach using a circular stapler in 1 patient, side-to-side approach using an endoscopic linear staple in 2 patients, and hand-sewn technique in 4 patients. The operation time was (247.1±17.5) minutes and the intraoperative blood loss was (100.0±30.8) ml without transfusion. The number of retrieved lymph node was 19.1±4.8. The first flatus time, diet resumption time, postoperative hospital stay were (3.3±1.5) days, (3.7±0.8) days, (9.4±2.6) days, respectively. One patient experienced gastrointestinal bleeding that was managed conservatively and ultimately cured. Seven patients were followed up till January 2016. After follow-up from 6 to 38 months, 1 patient died of peritoneal metastasis 17 months after surgery, and 1 patient died of Alzheimer's disease 19 months after surgery. The other 5 patients were still alive without metastasis or recurrence.</p><p><b>CONCLUSION</b>Laparoscopic gastrectomy for gastric stump cancer is feasible and safe.</p>

Early experience of laparoscopic pancreaticoduodenectomy on 66 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and safety of laparoscopic pancreaticoduodenectomy(LPD).</p><p><b>METHODS</b>Data of 66 patients from Sir Run Run Shaw Hospital undergoing LPD from September 2012 to September 2014 were reviewed. There were 44 male and 22 female with the mean age of (58.7±10.3) years and mean body mass index of (23.5±3.9)kg/m(2). Forty-five patients presented the symptoms and four of all had the history of abdominal surgery, including 2 cases of laparoscopic pancreatic surgery.</p><p><b>RESULTS</b>Of 66 patients underwent laparoscopic procedure, 1 patient underwent LPD combined with right hepatic resection, 1 patient underwent laparoscopic distal gastrectomy with LPD, and 1 patient underwent LPD after laparoscopic distal pancreatectomy. The mean operative time was (367±49) minutes. The mean blood loss was(193±126)ml. The rate of overall postoperative complications was 36.4%(24/66), with 4.5%(3/66) of B or C pancreatic fistula and 7.6% (5/66) of bleeding. The mean postoperative hospital stay was (18.9±12.1) days. Mean tumor size was (3.8±2.3) cm, and the mean number of lymph nodes harvested was (20.3±10.9). Forty-severn patients were diagnosed as pancreatic adenocarcinoma(n=18), cholangiocarcinoma(n=7), ampullary adenocarcinoma(n=21), and gastric cancer(n=1), respectively.</p><p><b>CONCLUSION</b>LPD is feasible and safe under the skilled hand.</p>

A retrospective study comparing perioperative results and long-term survival between laparoscopy-assisted gastrectomy and open procedures for gastric cancer / 中华普通外科杂志

Objective To evaluate the short-and long-term outcomes of laparoscopy-assisted gastrectomy (LAG) for gastric cancer.Methods After studying the patients' demographic data,extent of gastrectomy and lymphadenectomy,as well as differentiation and tumor TNM stage,85 patients who underwent LAG were individually matched to 85 patients who underwent open surgery (OG) between October 2004 and March 2008.The operative time,intraoperative blood loss,postoperative recovery,complications,pathological findings,and follow-up data were compared between the two groups.Results The mean operative time was significantly longer in the LAG group than in the OG group (277 ± 62) min vs.(211 ±46) min,t =7.882,P ＜0.05,whereas intraoperative blood loss was significantly lower (161 ±90) ml vs.(267 ± 141) ml,t =-5.854,P ＜0.05.In addition,there was a significant reduction in the time to first flatus and postoperative hospital stay (3.7 ± 1.3) days vs.(4.2 ± 1.1) days and (10 ± 3) days vs.(12 ± 6) days,respectively t =-2.318,-2.325,P ＜ 0.05.There was no significant difference between the LAG group and OG group with regard to the number of harvested lymph nodes and overall postoperative complications.The 5-year disease-free survival rates and overall survival rates were 76％,78％,respectively,in LAG group and 75％,73％,respectively in OG group (all P ＞ 0.05).Conclusions LAG is suitable and minimally invasive for treating gastric cancer.Compared to OG,the LAG will not increase the risk of recurrence and mortality after surgery.

The expressions of Sema4D and HER-2 proteins in breast cancers and their clinical significance / 中国医师杂志

Objective To investigate the expressions of Sema4D and HER-2 in breast cancers and their relationship with microlymphtic vessel density (MLVD).Methods MLVD and expressions of Sema4D and HER-2 were detected in 110 cases of breast cancer tissues by immunohistochemistry.The relationship of Sema4D and HER-2 expressions with clinicopathologic parameters was analyzed.Results The positive expression rate of Sema4D and HER-2 was 71.82％ (79/110) and 33.64％ (37/110),respectively,with a statistically significant differences compared to those in the control group ( P ＜0.01 ).The positive expression rates of Sema4D and MLVD in cases with lymphatic metastasis were higher than that without lymphatic metastasis ( P ＜ 0.01 ).The expressions of Sema4D and HER-2 were closely correlated with the histological grade,TNM stage,lymph node metastasis,and expression of ER of breast cancers ( P ＜0.05),but were not related to tumor size and expression of PR (P ＞ 0.05 ).On univariate analysis,the disease-free survival rate of patients with Sema4D positive expression was better than those with its negative expression ( P ＜ 0.05).Sema4D expression was positively correlated with the HER-2 expression ( r =0.535,P ＜ 0.01 ).Conclusions Sema4D may play important roles in the carcinogenesis and development of a breast cancer.

Meta-analysis on laparoscopy-assisted total gastrectomy for gastric cancer / 中华普通外科杂志

Objective To evaluate the safety and efficacy of laparoscopy-assisted total gastrectomy (LATG) for gastric cancer by systematic review and meta-analysis.Methods The literature database before February,2012 was extensively searched to retrieve the comparative studies of LATG and open total gastrectomy(OTG) with a relevance of study goal.The inclusion and exclusion criteria were formulated.Aftera quality evaluation,the data was extracted.The Cochrane collaboration RevMan 5.1 version software was used for meta-analysis.Results There are ten studies meeting the inclusion criteria for meta-analysis.The total sample size of these studies was 942 cases.Compared to OTG,LATG experienced longer operation time [weighted mean difference(WMD) =41.12 min,95％ confidence interval(CI):20.62-61.63,P ＜0.01)],less blood loss(WMD =-198.36 ml,95％ CI:-300.94--95.78,P ＜ 0.01),earlier time to flatus(WMD =-0.80 days,95％ CI:-1.17--0.42,P＜0.01),shorter hospital stay(WMD =-4.02days,95％ CI:-6.03--2.01,P ＜ 0.01) and decrease in overall complications [relative risk (RR) =0.55,95％ CI:0.40-0.76,P ＜ 0.01)].The number of dissected lymph nodes,proximal or distal resection margin and mortality were similar between the two groups.Conclusions Laparoscopy-assisted total gastrectomy is a safe and feasible procedure with less blood loss,less overall complications and quick recovery.

Discussion on National Advanced Training Course of Traditional Chinese Orthopedic and Traumatology in Anatomy Experiment / 中华医学教育探索杂志

National advanced training course of traditional Chinese orthopedic and traumatology in anatomy experiment is a short-term courses designed for grassroots doctors.Special training content and methods are designed for the multi-level cadets in the short-term courses.How to use teaching staff advantage to optimize course setting and improve the teaching effects will be discussed in this article.

Study on activation of mouse peritoneal macrophage by Astragalus Saponin / 中国免疫学杂志

Objective:To investigate the immunomodulatory effect of Astragalus Saponin on macrophages and explore the mechanisms of its immunomodulation.Methods:By adding different concentrations of AS into cultured mice peritoneal macrophages,the influence of AS on synthesis of nitro oxide(NO)was observed by NO Kit(enzymic method).MTT assay was used to determine the cytotoxicity of macrophages induced by AS.The morphological changes of the macrophages were identified by Transmission Electron Microscope.LSCM and specificity fluorescent probe Fluo-3/AM were applied to observe the change of Ca2+ in the macrophages induced by AS.Results:AS could significantly increase NO synthesis,enhance the capacity of mice peritoneal macrophages for cytotoxicity to carcinoma cells.The surface projections of the macrophages were exhibited multiplicating,thickening and extenting via Transmission Electron Microscope.Augmented intracellular Ca2+ in the macrophage was observed by LSCM.Conclusion:AS can enhance the immune functions of macrophages,the increase of intracellular Ca2+ be one of the mechanisms of its immunomodulatory effects.