TNM staging of colorectal cancer should be reconsidered by T stage weighting

AIM:To verify that the T stage has greater weight than the N stage in the staging of colorectal cancer.METHODS:Open data from the Surveillance,Epidemiology,and End Results program were reviewed and analyzed according to the T stage,N stage,and patients’observed survival(OS).The relative weights of the T and N stages were calculated by multiple linear regressions based on their impact on survival.Risk scores for25 TN categories were then calculated from the T and N stage relative weights,and a rearranged tumor node metastasis(TNM)staging system was proposed via a cluster analysis of the TN scores.RESULTS:Both T and N stages significantly affect the OS of patients with colorectal cancer.Moreover,the T stage has greater weight than the N stage in the TNM staging system of colorectal cancer.For colon cancer,the relative T and N stage weights were 0.58 and 0.42,respectively,and for rectal cancer,the relative T and N stage weights were 0.61 and 0.39,respectively.On the basis of cluster analysis of the TN scores,T1N1a was classified to stageⅠ,and T2N1a-1b and T1N1b-2a were classified to stageⅡin our revised TNM staging system for both colon and rectal cancer.For colon cancer,T4bN0 was classified to stageⅢa,but for rectal cancer,it was classified to stageⅢb.CONCLUSION:As the T stage affects colorectal cancer survival more significantly than the N stage,the TNM staging should be revised by relative T stage weight.

Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer:a multicenter,randomized,double-blinded,placebo-controlled,phaseⅡclinical trial

Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal

Effect of SNC19/ST14qene overexpression on invasion of colorectal cancer cells

AIM: To study the effect of SNC19/ST14gene overexpression on invasion in vitro of colorectal cancer cells.METHODS: The adhesion of SNC19/ST14gene-transfected cells to ECM was measured by MTT assay. The cell movement was evaluated by wound healing assay. Cell invasion and migration were determined by invasion assay in vitro.RESULTS: SNC19/ST14 gene overexpression could enhance invasion of colorectal cancer cells in vitro significantly and influence early cell adherence to ECM,but could not change cell movement significantly.CONCLUSION: SNC19/ST14 gene overexpression increases the local invasion of colorectal cancer cells in vitro.

Proteomic analysis of primary colon cancer-associated fibroblasts using the SELDI-ProteinChip platform

Objective: Cancer-associated fibroblasts (CAFs) are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods: Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was conducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip platform. Results: Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of α-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio (m/z) 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin β-4-like protein 3, and tight junction-associated protein 1. Conclusions: Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.

舒尼替尼对结肠成纤维细胞体内外抑制机制研究(英文)

研究目的:探索小分子酪氨酸激酶抑制剂舒尼替尼(sunitinib)对结肠肿瘤微环境中的肿瘤相关成纤维细胞的作用及其机制。创新要点:舒尼替尼通过抑制肿瘤间质成纤维细胞的生长,间接发挥抗肿瘤效应,为结肠癌综合治疗的提供新途径。研究方法:通过细胞周期分析和细胞增殖测定进行舒尼替尼体外抑制肿瘤细胞的研究。采用Western-blot检测磷酸化血小板衍生生长因子β受体(PDGFR-β)、蛋白激酶B(Akt)及细胞外信号调节蛋白激酶(ERK)的蛋白水平。通过注射肠腺癌细胞株SW620和结肠成纤维细胞构建的裸鼠移植瘤模型来研究舒尼替尼的体内抑瘤效果。重要结论:舒尼替尼可有效抑制结肠癌来源的原代结肠成纤维细胞生长,该抑制作用主要通过抑制血小板衍生生长因子(PDGF)信号通路得以实现。

Short-term outcomes following purse-string versus conventional closure of ileostomy wounds in Chinese colorectal cancer patients-a single center retrospective study

Background Nearly 15%colorectal cancer(CRC)patients received ileostomy,while surgical site infection(SSI)is a common complication after ileostomy wound closure.Purse-string closure was reported to reduce SSI rate in ileostomy wound closure compared with conventional linear closure,but had never been systematically reported in CRC patients.The present study aimed to compare the short-term outcomes between purse-string and conventional closure in Chinese CRC patients.Patients and methods A total of 57 CRC patients underwent ileostomy wounds closure in the Second Affiliated Hospital of Zhejiang University during November,2015 and October,2017 were retrospectively reviewed.Twenty-nine received purse-string closure while the others received conventional closure.The short-term outcomes including SSI rate,scar length,pain score and hospital stay were reviewed and analyzed.Results There were no significant differences in the characteristics of the patients between two groups.The SSI rate was similar within two groups(10.3%vs 10.7%,p=1.000).The purse-string closure group had a significantly short scar length(1.66 cm vs 5.30 cm,p<0.0001),but had no difference in operation time,hospital stay and postoperative pain.Conclusion The present study did not find superiority of Purse-string closure in SSI rate control.It seemed only had a cosmetic effect according to its shorter scar length.