The Mechanism Underlying the Promoting Effect of Cancer-associated Fibroblasts on Chemoresistance / 中国生物化学与分子生物学报

The carcinogenesis and progression of cancer not only depend on the feature of tumor cell themselves, but also rely on the tumor microenvironment (TME). Numerous studies have shown that TME plays a crucial role in tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are important stromal cells in TME containing multiple functions, such as remodeling the extracellular matrix, regulating angiogenesis, interacting with adjacent tumor cells, and releasing a variety of molecules (such as cytokines, growth factors and exosomes) to regulate cell proliferation, invasion and metastasis. CAFs exhibit heterogeneity of origin and phenotype, and play dual roles in tumor progression. Recent studies have shown that CAFs are also involved in chemoresistance, suggesting that CAFs themselves and their downstream molecules and signal pathways could be the potential therapeutic target for cancer treatment. In this review, we summarized the role of CAFs in chemoresistance and underlying mechanism, and discussed the potential of targeting CAFs in overcoming drug resistance. However, the exploration of strategy for targeting CAFs is still at an early stage and requires further in-depth research.

Research Improvements and Related Hot Issues of Surgical Treatment on Locally Advanced Rectal Cancer / 肿瘤防治研究

Surgical resection is one of the main steps in the treatment of locally advanced rectal cancer. With the popularization of total mesorectal resection and laparoscopic minimally invasive techniques, related current research on surgical treatment has now entered a relatively high-level stage. In this article, we review the research frontiers of surgical treatment on rectal cancer, including reduction of trocars, specimen retrieval through natural orifices, robotic surgery, high definition/3D/indocyanine fluorescence green surgery, surgical approach and key surgery technology. Based on the current environment of evidence-based medicine, colorectal surgeons should adapt to the changes of the times, actively absorb cutting-edge scientific concepts and technologies and integrate them with surgical equipment and instruments, and carry out rigorous and innovative large-scale prospective clinical trials.

Anatomy research on Denonvilliers fascia and its significance in nerve-preservation rectal cancer surgery / 中华胃肠外科杂志

Urinary and sexual dysfunctions due to intraoperative pelvic autonomic nerve injury have become the most common complications of rectal cancer surgery, seriously affecting postoperative quality of life. How to protect the nerve and urogenital function while ensuring radical resection for rectal cancer has become the focus of research. We previously carried out a series of systematic studies on Denonvilliers fascia, an important anatomical structure closely related to protection of pelvic autonomic nerve, and demonstrated the importance of Denonvilliers fascia in preservation of intraoperative pelvic autonomic nerve and protection of postoperative urogenital function from aspects of anatomy, physiology, tissue, operation practice and so on. Meanwhile, based on the interim results of our multicenter randomized controlled study, we confirmed that total mesorectal excision with preservation of Denonvilliers fascia (innovative TME, iTME) could effectively reduce the incidence of postoperative urinary and sexual dysfunctions in male patients with mid-low rectal cancer, without sacrificing oncologic outcome. In this article, combined with our research results, we review the literature on anatomy research progress of Denonvilliers fascia to demonstrate the significance and research prospect of Denonvilliers fascia in the pelvic autonomic nerve preservation surgery for rectal cancer.

The Demographic Profile and Operative Findings after Conventional Surgery in Rectal Cancer Patients

Objective: In this study our main goal is to evaluate thedemographic profile and operative findings after conventionalsurgery in rectal cancer patients.Method: This quasi experimental study was carried out at Thedepartment of General Surgery and Colorectal unit ofBangabandhu Sheikh Mujib Medical University (BSMMU),Dhaka and Somorita Hospital, Dhaka from July 2005 to June2007 where patients who having carcinoma involving themiddle and lower third of the rectum were evaluated. Duringthe study patients were divided into two groups: Group A:Patients undergone total mesorectal excision (TME) and GroupB: Patients undergone conventional operative method. Allpatients were operated under general anesthesia, placed inLloyd- Davies position.Result: In the study, most of the patients belong to 21 - 30years age group and 46.7% patients of Group-A and 56.6% ofGroup-B were males. The rest 52.8% of Group-A and 43.4% ofGroup-B were females. Sexual function preoperatively wellmaintained in 50 (94.3%) patients of group A and 51 (96.2%)patients of group B. Also, local recurrence rate in Group A ratewas 5.7% and in group B was 20.8%.Conclusion: We can conclude that, for management of rectalcancer conventional surgery has some limitation which canaffect the patient’s recovery and health condition. Further studyis needed for better outcome.

Roles of microRNAs in the tumor progression promoted by cancer-associated fibroblasts / 中国肿瘤生物治疗杂志

@#Cancer-associated fibroblasts (CAFs) are one of the major cellularcomponents in tumor microenvironment (TME), which play an important role in cancer progression. MicroRNAs (miRNAs) could participate in the process of CAFs, transformation and metabolism reprogramming, affect the stemness of CAFs, and regulate CAFs-mediated tumor cell proliferation, invasion and chemotherapy resistance; and studies have shown that miRNAs play an important role in CAFs formation and the regulation of CAFs on tumors. The miRNAs released by CAFs can be used as reference indicators for tumor diagnosis, prognosis and drug selection. Thus, exploring the role of miRNAs in the interaction between CAFs and tumor cells and underlining the mechanism, is of great significancefor understanding the occurrence and development of tumors, as well as providing novel strategy for cancer treatment. This review will summarize the role of miRNAs in the formation of CAFs and the regulation of CAFs on tumor cells.

Risk factors of anastomotic leakage in the procedures of trans-abdominal and transanal total mesorectal excision for rectal cancer / 中华胃肠外科杂志

Anastomotic leakage is one of the most serious complications following traditional trans-abdominal total mesorectal excision of rectal cancer. Anastomotic leakage not only affects the postoperative recovery of patients, but also affects their long-term survival. Transanal total mesorectal excision (taTME) is a new surgical procedure developed in recent years. Its anastomosis is different from traditional trans-abdominal total mesorectal excision surgery. The risk of anastomotic leakage and related risk factors are also different. Anastomotic leakage of taTME has many risk factors, such as male gender, smoking, large tumor size, obesity, diabetes, methods of anastomosis, duration of surgery, and so on. Surgeons should analyze the risk of anastomotic leakage for every patient with rectal cancer based on patient characteristics, evidence-based medicine, and intraoperative status before deciding on whether diverting colostomy should be performed. In case of postoperative anastomotic leakage, surgeons should carefully select the best timing of performing diverting stoma to minimize the risks caused by the anastomotic leakage of the taTME procedure.

Advances of research in cancer-associated inflammation and tumor microenvironments / 中国肿瘤临床

Cancer-associated inflammation is one of the key features of cancer. Many cytokines are involved in inflammation and its regulation and play important roles in many factors affecting tumor biology. Inflammation participates in the construction of tumor mi-croenvironments (TMEs) by changing the homeostasis of tumor tissues. The interaction of cytokines secreted by TME-infiltrating cells forms a complex network of cytokines that play a role in tumor progression through various mechanisms such as inflammation promo-tion, immune editing, and immune escape. This review aims at analyzing the research progress on the relationship between inflamma-tion, cytokine networks, and TMEs

Prognostic significance of myocardial markers and echocardiography in elderly patients with sepsis / 中国医师杂志

Objective To explore the relationship between those myocardial markers serum cardiac troponin T (cTNT),serum cardiac troponin I (cTNI),N-terminal pro-brain natriuretic peptide (NT-proBNP),echocardiography and myocardial injury in the oldest-old septic patients,as well as to evaluate prognosis in the oldest-old septic patients.Methods 140 oldest-old septic patients hospitalized in Beijing Friendship Hospital from January 1 st,2015 to Jun 31st,2017 were collected and analyzed retrospectively.They were divided into survival group (90 cases) death group (50 cases)according to their survival time.Serum cTNT,cTNI and NT-proBNP level at 1,3 and 7d post-diagnosis were collected and echocardiography left ventricular diastolic diameter (EDD),left ventricular systolic diameter (ESD),right ventricular diameter (RV),left ventricular ejection fraction (EF) was performed.Results 140 oldest-old septic patients were enrolled in the analysis.There were 90 cases in survival group and 50 cases in death group.Mean values of cTNT,cTNI,NT-proBNP,EDD,ESD in survival group were obviously higher than those in death group (P ＜ 0.05),left ventricular ejection fraction (LVEF) in survival group was lower than that in death group (P ＜ 0.01).But there were no difference in E/A and RV between survival group and death group (P ＞ 0.05).There were positive correlation between cTNT,cTNI,NT-proBNP and EDD,ESD (P ＜ 0.05),negative correlation between cTNT,cTNI,NT-proBNP and LVEF (P ＜ 0.05),and no correlation between cTNT,cTNI,NT-proBNP and E/A,RV (P ＞0.05).There were obviously correlation between cTNT,cTNI,NT-proBNP,EDD,ESD and mortality rate (OR ＞ 1,P ＜ 0.05).It was shown the prognosis value of cTNT,cTNI,NT-proBNP,EDD,ESD to mortality rate in oldest-old septic patient.The prognosis value was cTNT ＞ NT-proBNP ＞ cTNI ＞ EDD ＞ ESD.Conclusions There were obviously correlation between cT NT,cTNI,NT-proBNP,EDD,ESD and myocardium restrain,heart dysfunction as well as mortality rate.cTNT was the best prognosis indicator in sensitivity,and NT-proBNP was the best prognosis indicator in specificity.The combination of cTNT and NT-proBNP can better forecast the prognosis of the oldest-old septic patient.

Research progress of tumor-associated neutrophils / 实用肿瘤学杂志

Tumor growth depends on the tumor microenvironment(TME).Tumor-associated neutrophils(TANs)are important inflammatory cells in TME.TANs are divided intoN1type with anti-tumor effect andN2type of tumor-promoting effect.Therefore,TANs have both beneficial and harmful aspects of the body.A large number of studies have been shown that TANs affect tumor formation,metastasis,angiogenesis and immune response,regulated by the secretion of cytokines and chemokines.This review will summarize the biological characteristics of TANs,and tumor development,prognosis and treatment of tumor as well as research progress of the relationship between TANs and tumor.

As LER/DORT e os fatores psicossociais / The RSI/WMSD and the psychosocial factors / Las LER/ TME y los factores psicosociales

As Lesões por Esforço Repetitivo/Distúrbios Osteomusculares Relacionados ao Trabalho (LER/DORT) provocam sequelas irreversíveis aos trabalhadores, podendo acarretar invalidez permanente. Além das despesas previdenciárias e do custo organizacional, os trabalhadores enfrentam um intenso sofrimento psíquico, estresse e insatisfação com o trabalho. O objetivo deste artigo, apoiado em uma revisão da literatura, é analisar a complexidade dos fatores psicossociais associados às LER/DORT e discutir a fragmentação das pesquisas na área. As LER/DORT são um fenômeno multifatorial (fatores: biomecânicos, organizacionais e psicossocais) e multidimensional (dimensões: individual, grupal e social). Um desafio para a pesquisa é compreender como os fatores e as dimensões interagem entre si para produzir ou potencializar os sintomas e como impactam na reabilitação e prevenção. As pesquisas indicam que o fator biomecânico, por si só, não é suficiente para a compreensão do fenômeno

The Repetitive Strain Injury/ Work Related Musculoskeletal Disorders (RSI/WMSD) cause irreversible consequences to workers and can result in permanent disability. In addition to the pension costs and organizational costs, workers face an intense psychological distress, stress and job dissatisfaction. The purpose of this article, which is supported by a literature review, is to analyze the complexity of the psychosocial factors associated with RSI/WMSD and to discuss the fragmentation of research in this area. RSI/WMSD is a multifactorial phenomenon (the factors are: biomechanical, organizational and psychosocial) and multidimensional (the dimensions are: individual, group and social). A challenge for research is to understand how these factors and dimensions interact with each other to bring on the symptoms and how they impact upon rehabilitation and prevention. Research indicates that the biomechanical factor by itself is not sufficient for understanding the phenomenon

Las Lesiones por Esfuerzos Repetidos/ Trastornos Músculoesqueléticos Vinculados con el Trabajo (LER/TME) provocan secuelas irreversibles a los trabajadores, y pueden provocar discapacidad permanente. Además de los costos de la seguridad social y los costos de organización, los trabajadores enfrentan un sufrimiento psíquico intenso, el estrés y la insatisfacción con el trabajo. El objetivo de este artículo, basado en una revisión de la literatura, es analizar la complejidad de los factores psicosociales asociados a LER/TME y discutir la fragmentación de la investigación en el área. Las LER/TME son un fenómeno multifactorial envuelve factores biomecánicos, organizacionales y psicosocialesy multidimensional - de dimensiones individual, grupal y social. Un reto para la investigación es entender cómo los factores y las dimensiones interactúan entre sí para producir o potenciar los síntomas. La investigación indica que el factor biomecánico por sí solo no es suficiente para la comprensión del fenómeno

Correlation between ginsenoside accumulation and SQS and SQE gene expression in different organs of Panax quinquefolius / 中草药

Objective: To examine the biological accumulation of total ginsenosides and their monomers, and determine their relationships with the expression of squalene synthase (SQS) and squalene epoxidase (SQE) genes that are involved in the ginsenoside biosynthetic pathway in different organs of Panax quinquefolius. Methods: Fourteen organs of four year-old P. quinquefolius were used as materials. Total ginsenosides were extracted using the Soxhlet ginsenoside extraction method, and the contents of total ginsenosides and their monomers Rg1, Re, Rb1, Rc Rb2 and Rd in the organs were determined by the Vanillin-sulfuric Colorimetry and HLPC methods, respectively. The expressions of the SQS and SQE genes in the organs were profiled by real-time quantitative PCR. Results: The biological accumulation of total ginsenosides and each of their monomers varied significantly (P<0.01) in different parts of P. quinquefolius.Except for ginsenoside monomer Rb 2, there were significantly positive correlations between total ginsenoside and monomers Re, Rg1, Rb1 and Rd (P<0.01). The expressions of both SQS and SQE genes were extremely significantly different among the 14 plant parts (P<0.01) and significantly positively correlated with the biological accumulation of total ginsenoside and monomers, Re, Rg 1, Rb1 and Rd (P<0.05). Conclusion: The results indicate that the SQS and SQE genes play the important roles in the biosynthesis of total gingenosides and their monomers.

Cirurgia por orifícios naturais transcolônica: acesso NOTES peri-retal (PNA) para excisão mesoretal total / Transcolonic natural orifice surgery: peri-rectal NOTES access (PNA) for total mesorectal excision

OBJETIVOS: Cirurgia por orifícios naturais tem sido recentemente aplicada em series clínicas para cirurgia abdominal. Apesar de potenciais vantagens do acesso NOTES transcolônico para doenças colorretais, este ainda não havia sido utilizado clinicamente. O presente trabalho descreve a primeira aplicação bem-sucedida de NOTES transcolônico da literatura, em uma nova abordagem de excisão mesoretal total (TME) para cancer de reto. MÉTODOS: Foi obtida aprovação de Comitê de Ética em Pesquisa para cirurgias por orifícios naturais, e o paciente assinou termo de consentimento informado. Em um paciente de 54 anos portador de adenocarcinoma de reto, o procedimento de retossigmoidectomia e linfadenectomia, com excisão mesoretal total foi realizada utilizando um acesso posterior transcolônico pouco acima da borda anal. A dissecção mesorretal foi conseguida utilizando um colonoscópio flexível e instrumentos endoscópicos, com assistência laparoscópica. O espécime foi retirado via transanal, e anastomose foi transorificial, com estoma proximal de proteção. RESULTADOS: O tempo operatório foi de 350 min, não ocorrendo complicações operatórias. A evolução pós-operatória foi favorável, e o paciente recebeu alta no sexto dia de pós-operatório com dieta plena. CONCLUSÃO: Este primeiro relato bem sucedido de cirurgia NOTES transcolônica traz potencialmente novas fronteiras de aplicações clínicas na cirurgia minimamente invasiva. O tratamento de doenças colorretais utilizando o novo acesso flexível PNA (Perirectal NOTES Access) é uma promissora nova abordagem, paralelamente à laparoscopia e cirurgia aberta, para melhoria do tratamento dos pacientes.

OBJECTIVES: Clinical natural orifice surgery has been applied for abdominal surgery in recent years. Despite potential advantages of transcolonic NOTES for colorectal diseases, it was since now not yet clinically applied. The study describes the first successful human application of transcolonic NOTES in the literature, in a new transrectal TME procedure for rectal cancer. METHODS: IRB approval was obtained at the institution for the study, and the patient signed informed consent. In a 54yrs-old male patient with a rectal adenocarcinoma, total mesorectal resection and rectosigmoidectomy with lymphadenectomy was performed using a posterior transcolonic access 3cm from the anal verge. Mesorectal dissection was achieved using a flexible colonoscope and endoscopic instrumentation and laparoscopic assistance. The specimen was extracted transanally, and transorificial anastomosis was performed, with proximal stoma. RESULTS: Operative time was 350 min, no intraoperative complications occurred. The postoperative course was uneventful, patient was discharged after 6 days. CONCLUSION: Successful first human report on Transcolonic NOTES potentially brings new fronteers and applications for minimally invasive surgery. The treatment of colorectal diseases through a flexible Perirectal NOTES Access (PNA) is a promising new approach besides existing laparoscopic and open surgery to improve patient care.

Postanal Retrieval and Anastomosis in Laparoscopic Rectal Surgery: Report of 3 Cases

Laparoscopic surgery is popular and widely accepted method for colorectal cancer today. Especially in rectal cancer, laparoscopic TME made surgery safe and feasible with good outcome. But there are still some limits and difficulties in resection and anastomosis of low rectal cancer. We combined laparoscopic TME and posterior approach. Surgery was performed in three low rectal cancer patients. They were prepared in supine position and laparoscopic TME to pelvic floor muscles was performed. After changing the patient to Jack-knife position, post-anal median incision (between the external sphincter and coccyx) and distal rectal resection was done. Through this surgical window, proximal stump was retrieved and resected with the safety margin, and anastomosis with leak test was performed. After a drain keeping, patient's position was changed back to supine again and laparoscopic irrigation and inspection of operation field was done finally. In the course of recovery, two patients were uneventful, but the rest with FAP experienced postoperative anastomotic leakage and got perineal resection and permanent ileostomy. According to our experience, posterior approach after laparoscopic TME permit right angle resection of distal rectum which is difficult in laparoscopic transabdominal approach. In addition, manual anastomosis with various instruments, Lembert suture, easy drain keeping, accurate fibrin glue apply can also be achieved. No incision on abdomen adds cosmetic advantage. But frequent position changes, need of patience-demanding intracorporeal mesenteric dissection to anastomotic site, and wound discomfort during sitting position right after the operation remain as challenges to consider and solve.

TME or TSD with pelvic autonomic nerve preserving operation for 247 patients with advanced rectal cancer / 肿瘤研究与临床

Objective To investigate effects of rectal cancer to undergo total mesorectal excision (TME)or three space dissection(TSD)with pelvic autonomic nerve preservation(PANP).Methods TME or/ and TSD was applied in 247 Patients with advanced rectal cancer in which 185 cases (74.9 %) underwent PANP(Group P)including TME-PANP(Group Pro)139 cases and TSD-PANP(Group Ps)46 cases.The other 62 cases underwent none-PANP(Group P-)due to tumor invasion.Results There were no death cases for operation inall patients.Group Pm was better than Group Ps in the operation time and the difficulty of proce- dure(P0.05).Conclusion The procedure with TME to preserve pelvic autonomic nerves adapts to the majority of rectal cancer patients.TSD procedure is more complex than TME.Statistically,the survival differ- ence between Patients with TSD and with TME is no defective.The survival time is determined to the tumor's earlier diagnosis and therapy.

Clinical research of the effect of pedicled greater omentum on the anastomotic fistula after total mesorectal excision of rectal carcinoma / 重庆医科大学学报

0.05)was observed between the research group and the control.Conclusion:Pedicled greater omentum efficaciously reduced the incidence rate of anastomotic fistula in TME of rectal carcinoma.

Advances in surgery of rectal cancer / 中国癌症杂志

To introduce the advances in surgery of rectal cancer and to discuss some of its critical issues. Preserving the anus, diminishing the damage of urinary and sexual function and reducing recurrence are the three major difficulties in surgery of rectal cancer. The surgical margin, the concept of TME, the indication of local surgery, the necessity of pelvic lymphonodectomy and the reconstruction of the colonic sack are important problems in the surgery of rectal cancer.The surgery for preserving the anal function should not go against the fundamental principle of radical surgery. The distal and circumferential margin must be enough. The impairment of urinary and sexual function can be reduced by protecting the pelvic autonomic nerves. There are many factors contributing to the relapse of rectal cancer. TME can reduce markedly recurrence of rectal cancer. The trend of either over-expanding or over-shrinking the indication of local surgery of rectal cancer should be avoided. The extensive dissection of pelvic lymph nodes should be selective. The reconstruction of the colonic sack is valuable to some extent.[