Tumor microvessel including two modes,as one is classic vascular structures surrounded with vascular endothelial cells and the other is vasculogenic mimicry( VM) surrounded with cancer cells.Recent studies suggested that anti-angiogenic drugs can inhibit classic microvessel structure significantly, but can not inhibit VM formation and even promote VM formation further more.This is one of the reasons affecting its clinical effica-cy.However,basic research has shown that traditional chinese medicine,gene therapy and drugs which is targeting for VM formation have an unique advantage in anti-VM.In this review, we summarize the progress of cancer therapy on targeting vasculogenic mimicry,and provide a basic for the development of new drugs for cancer thera-py through targeting both angiogenesis and VM formation.

Objective To evaluate the safety and feasibility of laparoscopy in combination with fast track colorectal surgery (FTCS) in the treatment of colorectal cancer in the elderly.Methods A total of 123 patients were randomly divided into 3 groups:the laparoscopy plus FTCS group (n=41),the laparoscopy group (n=41) and the laparotomy group (n=41).Parameters for measuring surgical quality,recovery and postoperative complications were analysed.Results No significant differences were found in age,gender,tumor location,anesthesia ASA classification,American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) staging,Eastern Cooperative Oncology Group (ECOG) score or complications between the three groups (P＞0.05 for all).There were no differences in blood loss,operative time,time required to resume defecation or number of lymph nodes dissected between the laparoscopy plus FTCS group and the laparoscopy or laparotomy group (P＞0.05 for all),but time taken to initiate postoperative ambulation,time taken to resume flatulence,time taken to start intake of liquid food and length of hospital stay were shorter in the laparoscopy plus FTCS group than in the other groups (P ＜ 0.05 for all).The incidence of postoperative complications was 12.2％ or 5/41 in the laparoscopy plus FTCS group,which was lower than in the laparoscopy group (34.1％ or 14/41) and in the laparotomy group (68.3％ or 28/41) (x2 =5.549 and 28.826,P=0.018 and 0.01,respectively),a statistically significant difference was also found between the latter two groups (x2 =9.567,P =0.002).Conclusions Laparoscopy in combination with FTCS is safe and effective in the treatment of colorectal cancer in the elderly.

Objective To investigate the correlation of the expression of microRNA-424-5p (miR-424-5p) and orthodenticle homeobox 1 (OTX1) gene in colorectal cancer (CRC) tissue,and the effects of miR-424-5p on the proliferation,migration and invasion of CRC cells HCT116.Methods A total of 60 patients with CRC were collected from June 2017 to June 2018 in Department of Colorectal Surgery of Third Affiliated Hospital of Kunming Medical University.Real time quantitative PCR (RT-qPCR) was used to detect the expression of miR-424-5p and OTX1 mRNA in 60 cases of CRC tissues,para-carcinoma tissues and CRC cell lines.The correlation between the expression of miR-424-5p and OTX1 gene was further analyzed.miR-NC (miR-NC group) and miR-424-5p-mimic (miR-424-5p-mimic group) were transfected into HCT116 cells.CCK-8 assay,scratch assay and Transwell assay were used to detect the effects of miR-424-5p on the proliferation,migration and invasion of HCT116 cells.The effect of miR-424-5p on the expression of OTX1 protein was detected by Western blotting.The luciferase report assay was used to detect the influence of miR-424-5p on the luciferase activity of OTX1-3'UTR vector.Results The relative expressions of OTX1 mRNA in CRC tissues and para-carcinoma tissues were 1.049 ±0.446 and 0.639 ±0.178 (t =-6.583,P ＜0.001);and the relative expression of miR-424-5p in CRC tissues and para-carcinoma tissues were 0.865 ± 0.261 and 1.329 ± 0.387 (t =7.705,P ＜ 0.001),with statistically significant differences.Negative correlation was found between the expression of miR-424-5p and OTX1 mRNA in CRC tissues (r =-0.439,P =0.015).The absorbance values of HCT116 cells transfected with miR-424-5p-mimic were 0.813 ± 0.064,0.960 ± 0.098,1.287 ± 0.192 on 72,96 and 120 hours respectively,and those of HCT116 cells transfected with miR-NC were 1.163 ±0.158,1.645 ±0.117 and 2.043 ±0.236.The proliferation ability of miR-424-5p-mimic group was lower than that of miR-NC group and the differences between the two groups were statistically significant (t =3.538,P =0.024;t =7.778,P =0.001;t =4.257,P =0.013).The scratch assay showed that the migration of HCT116 cells in miR-424-5p-mimic group was inhibited as compared with miR-NC group.The numbers of cells permeating septum of miR-NC and miR-424-5p-mimic group were 177.104 ± 17.834 and 35.667 ± 13.634,and the difference was statistically significant (t =15.246,P ＜ 0.001).The relative expressions of OTX1 protein in miR-NC and miR-424-5p-mimic group were 0.862 ±0.121 and 0.342 ±0.103 respectively,and the difference was statistically significant (t =16.286,P ＜ 0.001).Luciferase report assay showed that the luciferase activities of wt-OTX1-3'UTR and mut-OTX1-3'UTR vector were 0.305 ± 0.095 and 0.898 ± 0.080 after over expression of miR-424-5p,and the difference was statistically significant (P ＜ 0.001).Conclusion The expressions of miR-424-5p and OTX1 mRNA are negatively correlated in CRC tissue.miR-424-5p can inhibit the proliferation,migration and invasion of CRC cells by down-regulating the expression of OTX1.

[摘 要] 缺氧和免疫逃逸是肿瘤的两大特征，缺氧是促进肿瘤发生免疫逃逸的重要因素。近年来的研究结果表明，缺氧诱导的长链非编码RNA（HIL）是介导缺氧促进免疫逃逸的关键因子，是肿瘤诊断、治疗和预后评估的潜在标志物，具有较好的研究和临床转化价值，有望成为肿瘤免疫治疗的潜在靶点。本文综述了HIL在肿瘤发生发展及预后中最新的研究进展，讨论了HIL通过诱导上皮间质转化发生、血管生成、肿瘤干细胞形成、糖酵解、免疫细胞浸润、免疫因子释放、干扰抗原提呈机制和免疫检查点表达上调等多种机制诱导肿瘤发生免疫逃逸，探讨双靶向HIL与免疫检查点的联合肿瘤治疗新策略的可能性及临床意义，分析了HIL领域中关于普适性和组织特异性关键HIL及其调控肿瘤免疫机制的鉴定、HIL与肿瘤免疫治疗及疗效之间关系的明确，以及肿瘤联合治疗新策略临床转化的实现等关键问题及可能的解决办法，为实现靶向HIL与免疫检查点的肿瘤免疫治疗策略提供了理论基础。

Objective: To investigate the molecular mechanism of chemokine CCL20/CCR6 in promoting invasion and migration of colon cancer SW480 cells. Methods: Colorectal cancer SW480 cells with high expression of CCR6 receptor were screened by immunochemistry (IHC). After co-culture with recombinant human CCL20, the invasion and migration of SW480 cells were detected by Transwell assay and Wound-Healing assay, respectively. Expressions of EMT markers, AKT signal protein and target protein MMP3 were detected by immunofluorescence (IF) and WB. AKT signaling pathway as the key mechanism was confirmed by MK2206 blocking assay. The expressions of CCL20 and MMP3 in colorectal cancer tissues as well as their correlation were analyzed by TCGAdatabase resources (https://portal.gdc.cancer.gov/). Results: CCL20 promoted the invasion and migration ability of SW480 cells significantly (all P <0.01), and this was induced by activation of AKT signaling and up-regulation of downstream target protein MMP3, instead of EMT. Blocking AKT signaling could significantly inhibit the invasion and migration of SW480 cells, and down-regulate MMP3 expression (P<0.05). TCGA platform data showed that the expressions of CCL20 and MMP3 in colorectal cancer tissues were significantly higher than those in normal mucosa tissues (P<0.05 or P<0.01), and an evidently positive correlation was found between CCL20 and MMP3 (r =0.051, P<0.01). Conclusion: The chemokine CCL20 promotes the invasion and migration of SW480 cells throughAKT/MMP3 signal axis, but not the EMT.

OBJECTIVETo evaluate systematically the short- and long-term outcomes between laparoscope-assisted transanal total mesorectal excision (LA-taTME) and laparoscopic total mesorectal excision (L-TME) in the treatment of mid and low rectal cancer.

METHODSLiteratures comparing LA-taTME with L-TME published from January 2014 to January 2018 were systematically selected through searching PubMed, Ovid, EMbase, Cochrane Library, CNKI and Wanfang databases. Literature screening and methodology quality evaluation were carried out by two surgeons independently. Randomized controlled trial (RCT) was evaluated by the modified Jadad rating scale, in which 1 to 3 and 4 to 7 were considered as low and high quality,respectively(total scores: 7). Non-randomized controlled trial (NRCT) was assessed by the modified Newcastle Ottawa Scale (NOS), in which 1 to 3, 4 to 6, and 7 to 9 were defined as low, moderate, and high quality, respectively (total score: 9). Ratio of incomplete mesorectum, positive rate of circumferential resection margin (CRM), number of harvested lymph node, distance of distal resection margin, operation time, intraoperative blood loss, morbidity of postoperative complication, conversion rate, hospital stay, recurrence, 2-year disease-free survival (DFS) and 2-year overall survival (OS) were compared and analyzed by using Stata/SE12.0 software.

RESULTSFourteen studies including 1 RCT and 13 NRCTs were enrolled finally. Among them, the RCT with a score of 6 was considered to be of high quality; all NRCTs (2 with 6 stars, 5 with 7 stars, and another 6 with 8 stars) were indicative of moderate to high quality; 450 patients underwent LA-taTME and 498 patients underwent L-TME. No significant differences were observed in terms of age, gender, tumor location and TNM stage between two approaches (all P>0.05). Compared to L-TME, LA-taTME had lower ratio of incomplete mesorectum (RR=0.53, 95%CI: 0.31 to 0.93, P=0.026), lower positive rate of CRM (RR=0.50, 95%CI: 0.29 to 0.86, P=0.012), lower conversion rate(RR=0.48, 95%CI: 0.26 to 0.86, P=0.014), lower morbidity of postoperative complication (RR=0.81, 95%CI: 0.67 to 0.99, P=0.036) and less intraoperative blood loss (SMD=-0.38, 95%CI:-0.68 to -0.08, P=0.013). While the differences between two groups had no statistical significance in terms of operative duration, number of harvested lymph node, distance of distal resection margin, hospital stay, overall recurrence, 2-year DFS and 2-year OS (all P>0.05).

CONCLUSIONThe short- and long-term outcomes of LA-taTME and L-TME for the treatment of mid and low rectal cancer are comparable, while LA-taTME can reduce the ratio of incomplete mesorectum, positive rate of CRM, conversion rate, and morbidity of postoperative complication, and intraoperative blood loss.

Humans ; Laparoscopes ; Laparoscopy ; Neoplasm Recurrence, Local ; Postoperative Complications ; Randomized Controlled Trials as Topic ; Rectal Neoplasms ; surgery ; Rectum ; surgery ; Transanal Endoscopic Surgery ; Treatment Outcome

OBJECTIVE: To compare the application among intensity-modulated radiotherapy (IMRT), three-dimensional conformal radiotherapy(3D-CRT) and conventional radiotherapy (CRT) for locally advanced middle-low rectal cancer. METHODS: From January 2015 to December 2016, 93 locally advanced middle-low rectal cancer patients with clinical stage cT3N+M0 or cT4N0/+M0 who underwent preoperative concurrent chemoradiotherapy at Department of Colorectal Surgery, the Third Affiliated Hospital of Kunming Medical University and had complete data were enrolled in this retrospective cohort study. Patients were divided into IMRT group (17 cases), 3D-CRT group (28 cases) and CRT group (48 cases) according to different radiotherapy methods. The frequency and dose of CRT were 1 time/day, 5 times/week, for a total of 5 weeks, with a single dose of 2.0 Gy, the total dose was 50 Gy. Frequency and dose of 3D-CRT and IMRT were 1 time/day, 5 times/week, for a total of 23 to 28 times, with a single dose of 1.8 to 2.0 Gy, and a total dose of 45.0 to 50.4 Gy. The chemotherapy regimen was performed with capecitabine tablets at a dose of 825 mg/m twice a day for 5 days every week, at the same time during radiotherapy. The efficacy, chemotherapy adverse reactions and immune function of the three groups were compared. RESULTS: There was no significant difference in the baseline data among the three groups (all P>0.05). The proportion of patients receiving permanent ostomy in the IMRT group and the 3D-CRT group was 29.4%(5/17) and 32.1%(9/28) respectively, which was lower than 58.3%(28/48) in CRT group, and the difference was statistically significant (χ²=7.982, P=0.030), while this proportion was not significantly different between IMRT and 3D-CRT group(χ²=0.037, P=0.848). The pathologic complete response(pCR) rate was 23.7%(22/93) in the whole study, and the pCR rate was 39.3%(11/28) in the 3D-CRT group, which was higher than that of CRT group and IMRT group [12.5%(6/48) and 29.4%(5/17)], and the difference was statistically significant (χ²=7.407, P=0.025), while there was no significant difference in pCR rate between CRT group and IMRT group (χ²=2.554, P=0.110). There was no adverse reaction of grade 3 or above in all three groups. No significant difference in the incidence of bone marrow suppression, abnormal liver and kidney function markers, digestive tract reaction or radiation dermatitis was found(all P>0.05). After receiving concurrent chemoradiotherapy, the proportion of CD3/CD4 cells in the IMRT group and the CRT group decreased compared with that before treatment(23.1±9.3 vs. 31.1±10.9, 27.4±10.7 vs. 33.6±7.2, respectively); the proportion of CD3/CD8 cells was up-regulated (36.1±15.2 vs. 24.8±10.9, 30.9±14.4 vs. 24.0±8.3,respectively), and the differences were statistically significant (both P<0.05), while the above indexes before and after treatment were not significantly different in the 3D-CRT group(all P>0.05). After treatment, the proportion of CD4/CD8 cells in IMRT group decreased (0.8±0.6 vs. 1.6±1.0, t=3.838, P=0.003), while this proportion was not significantly different in CRT group and 3D-CRT group(all P>0.05). CONCLUSIONS IMRT and 3D-CRT can reduce the rate of permanent stoma. 3D-CRT can increase pCR rate. No obvious advantage is shown in IMRT as compared with 3D-CRT in the short-term efficacy. On the contrary, an immunosuppressive status may occur. Therefore, 3D-CRT is recommended as the best preoperative treatment strategy for patients with locally advanced middle-low rectal cancer, especially for those with immunosuppression status.
Humans ; Radiotherapy ; methods ; standards ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; standards ; Radiotherapy, Intensity-Modulated ; standards ; Rectal Neoplasms ; radiotherapy ; Retrospective Studies