Kejian Huang

Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro

BackgroundSignal transducer and activator of transcription 3 (Stat3) is a member of the Janus-activated kinase(Jak)/Stat signaling pathway. Abnormal activation of Stat3 plays a critical role in metastasis and invasion in varieties of human tumors including pancreatic cancer. This study aimed to investigate the mechanisms of activation and blocking of the Stat3 signaling pathway and its effects on invasion and metastasis of human pancreatic cancer cells.MethodsThe Jak inhibitor AG490 and interleukin-6 (IL-6) were added to the culture media of human pancreatic cancer cells SW1990 and Capan-2, respectively. Cell growth was measured by MTT assays. Western blotting and immunocytochemistry were performed to detect phosphorylated Stat3 (p-Stat3) protein, while VEGF and MMP-2 mRNA and protein expression were examined with fluorescence quantitative polymerase chain reaction and Western blotting, respectively. The invasion ability of SW1990 and Capan-2 cells was determined by cell invasion assay.ResultsStat3 was activated by IL-6 in Capan-2 cells; protein expression of p-Stat3 was increased significantly in Capan-2 cells. IL-6 remarkably promoted the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression were increased significantly. Also, IL-6 increased the invasion ability of Capan-2 cells. AG490 inhibited Stat3 activation in SW1990 cells. Western blotting and immunocytochemistry analysis showed that p-Stat3 protein expression was decreased significantly with AG490 treatment in SW1990 cells. AG490 remarkably inhibited the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression was decreased significantly. And AG490 decreased the invasion ability of SW1990 cells.ConclusionsAbnormal activation of Stat3 plays an important role in the invasion and metastasis of pancreatic cancer. Activation and blocking of the Stat3 signaling pathway can affect invasion ability and expression of the VEGF and MMP-2 genes in pancreatic cancer cells. The Stat3 signaling pathway may provide a novel therapeutic target for treatment of pancreatic cancer.

RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells

Signal transducers and activators of transcription‐3 (STAT3), a central cytoplasmic transcription factor, is frequently overexpressed and constitutively activated by tyrosine during malignant transformation. The overexpression and phosphorylation of STAT3 in pancreatic cancer has been described only recently, but the roles and mechanism still remain unclear. In this study, we elucidate the significance of the STAT3 signaling pathway in metastatic potentials of pancreatic cancer. We stably silence the expression of the STAT3 and p‐STAT3 by using RNA interference (RNAi) in the pancreatic cancer cell line SW1990, and then reduce its invasion capacity in vitro and metastasis capacity in vivo compared to parental cells or cells tansfected with a control vector. Furthermore, silencing SW1990 cells with the STAT3 gene by RNAi also led to a decrease of matrix metalloproteinases‐2 (MMP‐2) and vascular endothelial growth factor (VEGF) at the mRNA and protein level. Collectively, these studies suggest that activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer, and that silence of the STAT3 gene with RNAi may be a useful anti‐invasive therapeutic option in pancreatic cancer. (Cancer Sci 2007; 98: 1099–1106)

Laparoscopic and open resection for colorectal cancer: an evaluation of cellular immunity

BackgroundColorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality allover the world. Despite the promising clinical results recently, less information is available regarding the perioperative immunological effects of laparoscopic surgery when compared with the open surgery. This study aimed to compare the cellular immune responses of patients who underwent laparoscopic(LCR) and open resections(OCR) for colorectal cancer.MethodsBetween Mar 2009 and Sep 2009, 35 patients with colorectal carcinoma underwent LCR by laparoscopic surgeon. These patients were compared with 33 cases underwent conventional OCR by colorectal surgeon. Clinical data about the patients were collected prospectively. Comparison of the operative details and postoperative outcomes between laparoscopic and open resection was performed. Peripheral venous blood samples from these 68 patients were taken prior to surgery as well as on postoperative days(POD) 1, 4 and 7. Cell counts of total white blood cells, neutrophils, lymphocyte subpopulations, natural killer(NK) cells as well as CRP were determined by blood counting instrument, flow cytometry and hematology analyzer.ResultsThere was no difference in the age, gender and tumor status between the two groups. The operating time was a little longer in the laparoscopic group (P > 0.05), but the blood loss was less (P = 0.039). Patients with laparoscopic resection had earlier return of bowel function and earlier resumption of diet as well as shorter median hospital stay (P < 0.001). Compared with OCR group, cell numbers of total lymphocytes, CD4+T cells and CD8+T cells were significant more in LCR group (P < 0.05) on POD 4, while there was no difference in the CD45RO+T or NK cell numbers between the two groups. Cellular immune responds were similar between the two groups on POD1 and POD7.ConclusionsLaparoscopic colorectal resection gets less surgery stress and short-term advantages compared with open resection. Cellular immune respond appears to be less affected by laparoscopic colorectal resection when compared with open resection.

Short-term and medium-term clinical outcomes of laparoscopic-assisted and open surgery for colorectal cancer: a single center retrospective case-control study

BackgroundLaparoscopic procedure is a rapid developed technique in colorectal surgery. In this investigation we aim at assessing the diversities of short-term and medium-term clinical outcomes of laparoscopic-assisted versus open surgery for colorectal cancer.MethodsA total number of 519 patients with non-metastatic colorectal cancer were enrolled for this study. The patients underwent either laparoscopic-assisted surgery (LAP) (n = 254) or open surgery (OP) (n = 265). Surgical techniques, perioperative managements and clinical follow-ups were standardized. Short-term perioperative data and medium-term recurrence and survival were compared and analyzed between the two groups.ResultsThere were no differences in perioperative parameters between the two groups except in regards to a trend of faster recovery in laparoscopic procedures. There was no statistically significant difference in postoperative complications, reoperation rate, or perioperative mortality. Statistically significant differences in a faster return of gastrointestinal function and shorter hospital stay were identified in favor of laparoscopic-assisted resection. In colon and rectal cancer cases separately, the overall survival, cancer-free survival and recurrence rate were similar in two groups. There was also no tendency of significant differences in overall survival, cancer-free survival and recurrence in stage I-II and stage III patients in two cancer categories between the two groups, respectively. pT, lymph node metastasis, and clinical stage were independent predictors of overall death risk, while pT, pN, lymph node metastasis and clinical stage were found to be the independent predictors of recurrence risk in enrolled patients database.ConclusionsLaparoscopic-assisted procedure has more benefits on postoperative recovery, while has the same effects on medium-term recurrence and survival compared with open surgery in the treatment of non-metastatic colorectal cancer.

STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo.

Signal transducers and activators of transcription 3 (STAT3) is a central cytoplasmic transcription factor that is activated by phosphorylation in response to extracellular signals and oncogenes. STAT3 regulates a number of pathways important in tumorigenesis including cell cycle progression, apoptosis, tumor angiogenesis, invasion and metastasis, and tumor cell evasion of the immune system. Our studies demonstrated that constitutively activated STAT3 plays an important role in the angiogenesis of pancreatic cancer. The objective of this study was to evaluate the potential use of RNA interference (RNAi) to knock down the STAT3 gene and the effect on angiogenesis of human pancreatic cancer cells in vitro and in vivo. We stably inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3) using RNAi in the SW1990 pancreatic cancer cell line. Furthermore, RNAi for STAT3 inhibited STAT3-induced HUVEC cell migration and cell proliferation, and significantly suppressed the levels of secreted vascular endothelial growth factor (VEGF) and matrix metalloproteinases-2 (MMP-2) of SW1990 cells. In vivo experiments showed that RNAi for STAT3 significantly suppressed tumor growth and angiogenesis of SW1990 cells. Furthermore, silencing the STAT3 gene in SW1990 cells by RNAi also led to a decrease of VEGF and MMP-2 at the mRNA and protein levels. Collectively, these results demonstrate that the STAT3 signaling pathway plays an important role in the angiogenesis of pancreatic cancer and that knockdown of the STAT3 gene using the RNAi technique may be a novel therapeutic option for the treatment of pancreatic cancer.

SMAD4 and its role in pancreatic cancer

Transforming growth factor-β (TGF-β) regulates cell functions and has key roles in pancreatic cancer development. SMAD4, as one of the Smads family of signal transducer from TGF-β, mediates pancreatic cell proliferation and apoptosis and is specifically inactivated in half of advanced pancreatic cancers. In recent years, many advances concerning SMAD4 had tried to unravel the complex signaling mechanisms of TGF-β and its dual role of tumor-suppressive and tumor-promoting efforts in pancreatic cancer initiation and progression through SMAD4-dependent TGF-β signaling and SMAD4-independent TGF-β signaling pathways. Meanwhile, its potential prognostic value based on immunohistochemical expression in surgical sample was variably reported by several studies and short of a systematic analysis. This review aimed to discuss the structure, functions, and regulation of this principal protein and its effects in determining the progression and prognosis of pancreatic cancer.

Down-regulation of STAT3 expression by vector-based small interfering RNA inhibits pancreatic cancer growth

AIM To evaluate the effect of RNA interference (RNAi) mediated silence of signal transduction and activation of transcription (STAT)3 on the growth of human pancreatic cancer cells both in vitro and in vivo. METHODS STAT3 specific shRNA was used to silence the expression of STAT3 in pancreatic cancer cell line SW1990. The anti-growth effects of RNAi against STAT3 were studied in vitro and in experimental cancer xenografts in nude mice. The potential pathways involved in STAT3 signaling were detected using reverse transcription polymerase chain reaction and western blotting. RESULTS The expression of the STAT3 was inhibited using RNAi in SW1990 cells. RNAi against STAT3 inhibited cell proliferation, induced cell apoptosis and significantly reduced the levels of CyclinD1 and Bcl-xL when compared with parental and control vector-transfected cells. In vivo experiments showed that RNAi against STAT3 inhibited the tumorigenicity of SW1990 cells and significantly suppressed tumor growth when it was directly injected into tumors. CONCLUSION STAT3 signaling pathway plays an important role in the progression of pancreatic cancer, and silence of STAT3 gene using RNAi technique may be a novel therapeutic option for treatment of pancreatic cancer.

Is laparoscopic colorectal cancer surgery associated with an increased risk in obese patients? A retrospective study from China

BackgroundThe impact of obesity on surgical outcomes after laparoscopic colorectal cancer resection in Chinese patients is still unclear.MethodsWe retrospectively reviewed the prospectively collected data from 527 consecutive colorectal cancer patients who under went laparoscopic resection from January 2008 to September 2013. Patients were categorized into three groups: nonobese (body mass index (BMI) <25.0 kg/m2), obese I (BMI 25.0 = to 29.9 kg/m2) and obese II (BMI ≥30.0 kg/m2). Clinical characteristics, surgical outcomes and postoperative complications were compared between nonobese, obese I and obese II patients.ResultsFrom among the 527 patients, there were 371 patients with in the nonobese group, 142 patients in the obese I group and 14 patients in the obese II group. The patients were well-matched for age, sex and American Society of Anesthesiologists class, except for BMI (P = 0.001). The median operative time correlated highly significantly with increasing weight (median: nonobese = 135 minutes, obese I = 145 minutes, obese II = 162.5 minutes; P = 0.001). There appeared to be a slight tendency toward grade III complications (rated according to the Clavien-Dindo Classification of Surgical Complications) in the obese II group, but this difference was not significant (nonobese = 5.1%, obese I = 3.5% and obese II = 14.3%; P = 0.178). None of the grade III complications which occurred in the obese II group were wound dehiscences that required a stitch. Other aspects, such as estimated blood loss, harvested lymph nodes, operation type, pathological results, conversion rate and overall postoperative complications, were not statistically significant.ConclusionWith sufficient experience, laparoscopic colorectal cancer surgery is feasible and safe in obese Chinese patients.

Prognostic Significance of Complications after Laparoscopic Colectomy for Colon Cancer

Aims This study sought to evaluate the prognostic significance of postoperative complications for colon cancer patients undergoing laparoscopic surgery. Methods From May 2006 to May 2009, a total 224 patients who underwent laparoscopic curative resection (R0) for colon cancer were included in our retrospective study. Postoperative complications were evaluated according to a standardized grading system. The main outcome measurements of our study were overall survival (OS) and relapse-free survival (RFS), which were then compared between the no complication and complication groups. Univariate and multivariate analysis were used to assess the correlation between complications and prognosis. Results Fifty-nine postoperative complications occurred in 43 patients. The overall morbidity rate was 26.3%. The 5-year OS in the complication group was 41.4% compared with 78.5% in the no complication group (P<0.001). The cumulative incidence of relapse was also more aggressive in patients with complications (5-year RFS: complication group 40.9% vs. no complication group 82.1%, P<0.001). Multivariate analysis identified complications as a significant factor increasing the risk for both OS (RR 2.737; 95% CI 1.512–4.952; P = 0.001) and RFS (RR 4.247; 95% CI 2.291–7.876; P<0.001). Conclusion Postoperative complications could pose a significant adverse impact not only on OS but also on RFS in patients with colon cancer even when laparoscopic R0 resection is available.

Application of International Videoconferences for Continuing Medical Education Programs Related to Laparoscopic Surgery

BACKGROUND Continuing medical education (CME) is an effective way for practicing physicians to acquire up-to-date clinical information. MATERIALS AND METHODS We conducted four CME seminars in 2007-2010 endorsed by the Chinese Medical Association Council on Medical Education. Overseas telelectures and live case demonstrations were introduced in each seminar via telemedicine based on a digital video transport system. Network stability and packet loss were recorded. An anonymous mini-questionnaire was conducted to evaluate the satisfaction of attendees regarding the image and sound quality, content selection, and overall evaluation. RESULTS Four telelectures and five live case demonstrations were successfully conducted. Stability of the network was maintained during each videoconference. High-quality videos of 720 × 480 pixels at the rate of 30 frames per second were shown to the entire group of attendees. The time delay between Shanghai and Fukuoka, Japan, was only 0.3 s, and the packet loss was 0%. We obtained 129 valid responses to the mini-questionnaire from a total of 146 attendees. The majority of the attendees were satisfied with the quality of transmitted images and voices and with the selected contents. The overall evaluation was ranked as excellent or good. CONCLUSIONS Videoconferences are excellent channels for CME programs associated with laparoscopic training.