Low-level laser selectively inhibiting colorectal cancer cell metabolic activity and inducing apoptosis for delaying the development of intestinal cancer.

Low-level laser irradiation (LLLI) is a novel approach that shows promise for the treatment of colorectal cancer (CRC). However, the molecular mechanisms underlying its biochemical effects and gene expression remain unclear. Here, LLLI (632.8 nm) was used to treat CRC RKO cells and normal small intestinal NCM460 cells. LLLI showed a significant dose- and time-dependent effect on cell viability, in which a single dose of irradiation at 15 J/cm2 selectively inhibited the growth of RKO cells but largely unaffected the activity of NCM460 cells. And then, LLLI produced an internal response, effectively reducing the level of H2O2 in tumor cells, downregulating the mitochondrial membrane potential, and improving the efficiency of apoptosis in CRC, but no internal response was observed in NCM460 cells under the same conditions. Furthermore, the expression of several important genes in the classical WNT pathway was significantly downregulated, and the pathway was inactivated after LLLI intervention, thereby inhibiting tumor cell growth. Simultaneously, TNF-α was effectively activated to stimulate the caspase family members of the death effector to initiate apoptosis led by the extrinsic pathway. LLLI successfully achieves tumor cell normalization while delivering a potent anticancer effect, expected to be a novel therapeutic modality for CRC.

Tumor-derived extracellular vesicles confer 5-fluorouracil resistance in esophageal cancer via long noncoding RNA AC116025.2 delivery.

5-Fluorouracil (5-FU) resistance is one of the main causes for treatment failure in esophageal cancer (EC). Here, we intended to elucidate the mechanism of tumor-derived extracellular vesicles (TEVs)-encapsulated long noncoding RNAs (lncRNAs) AC116025.2 in 5-FU resistance in EC. EVs were isolated from the serum samples of EC patients and HEEC, TE-1, and TE-1/5-FU cells, followed by RT-qPCR detection of AC116025.2 expression in EVs. The relationship among AC116025.2, microRNA (miR)-4496, and SEMA5A was evaluated. Next, EC cells were cocultured with EVs, followed by lentivirus transduction and plasmid transfection for studying the role of TEVs-AC116025.2 in EC cells in relation to miR-4496 and SEMA5A. Tumor formation in nude mice was applied for in vivo confirmation. Elevated AC116025.2 expression was seen in the EVs from the serum of 5-FU insensitive patients and from 5-FU-resistant EC cells. Mechanistically, AC116025.2 bound to miR-4496 that inversely targeted SEMA5A in EC cells. EVs-oe-AC116025.2 augmented EC cell viability, colony formation, and 5-FU resistance, but diminished their apoptosis through miR-4496-mediated SEMA5A. Furthermore, EVs-oe-AC116025.2 augmented tumor formation and 5-FU resistance of EC cells in vivo. Conclusively, our data offered evidence of the promoting mechanism of TEVs in the 5-FU resistance of EC by delivering AC116025.2.

Optimal adjuvant chemotherapy completion time for stage III colon cancer: a cohort study.

BACKGROUND: Adjuvant chemotherapy for 6 months following surgery is the standard treatment plan for stage III colon cancer. The aim of the present study was to determine whether the adjuvant chemotherapy completion time for stage III colon cancer had an effect on prognosis and cut-off time that affected the prognosis. METHODS: This was a retrospective study of stage III colon cancer patients who completed adjuvant chemotherapy at Guangzhou Red Cross Hospital from January 2010 to December 2017. Univariate and multivariate analyses were used to determine the association between adjuvant chemotherapy completion time and the 3-year disease-free survival (DFS). The restricted cubic spline model was used to analyze the cut-off time that affected the 3-year DFS. RESULTS: A total of 431 patients were included in the study. The 3-year DFS was associated with a combination of obstruction or perforation, preoperative serum carcino-embryonic antigen (CEA) concentration, T stage, N stage, pathological stage, and adjuvant chemotherapy completion time in the univariate analysis (P<0.05). A combination of obstruction or perforation, preoperative serum CEA concentration, N stage, and adjuvant chemotherapy completion time were independent prognostic factors in the multivariate analysis (P<0.05). The cut-off time was 28 weeks for adjuvant chemotherapy completion time in the restricted cubic spline model analysis. For those whose adjuvant chemotherapy completion time was >28 weeks, the risk of 3-year recurrence was 1.428 times higher compared with those whose adjuvant chemotherapy completion time was ≤28 weeks. [P=0.032, 95% confidence interval (CI): 1.034-2.055]. CONCLUSIONS: The 3-year DFS of stage III colon cancer was related to the adjuvant chemotherapy completion time. For those who completed adjuvant chemotherapy >28 weeks, the risk of 3-year recurrence increased.

Short- and mid-term outcomes of transanal versus laparoscopic total mesorectal excision for low rectal cancer: a meta-analysis.

PURPOSE: The current meta-analysis combining mid and low rectal cancer with no meta-analysis only for low rectal cancer was seen. This meta-analysis was to compare the short- and mid-term outcomes of the transanal total mesorectal excision (TaTME) vs. laparoscopic total mesorectal excision (LaTME) for low rectal cancer. METHODS: A systematic literature search was conducted using the web-based databases; China National Knowledge Infrastructure, Chinese BioMedical Database, PubMed, Embase, Cochrane Central Register of Controlled Trials, and Wanfang Database. Randomized controlled trials (RCTs) were evaluated using the Jadad scale and non-RCTs (NRCs) were evaluated using the Newcastle-Ottawa Scale. RESULTS: Ten studies (2 RCTs and 8 NRCs) involving 772 patients were included. Among them, 378 patients underwent TaTME and 394 patients underwent LaTME. Compared with the LaTME group, the conversion rate was low (risk ratio [RR], 0.25; 95% confidence interval [CI], 0.11-0.54; P < 0.001), the circumferential resection margin (CRM) involvement was low (RR, 0.48; 95% CI, 0.27-0.86; P = 0.010), and the hospital stay was short (mean difference, -1.72; 95% CI, -2.89 to -0.55; P = 0.004) in the TaTME group. No significant differences were seen in the mesorectal resection quality, CRM distance, distal resection margin (DRM) involvement, DRM distance, local R1 resection, intraoperative complications, morbidity, anastomotic leakage, severe morbidity, mortality, operative time, intraoperative blood loss, harvested lymph nodes, and local recurrence rate (P > 0.05). CONCLUSION: The TaTME is a promising surgical technique and is fully a safe and efficacious option in managing low rectal cancer.

Comparison of short-term efficacy of transanal total mesorectal excision and laparoscopic total mesorectal excision in low rectal cancer.

BACKGROUND/OBJECTIVE: The transanal total mesorectal excision(TaTME) of rectal malignancies is largely referred to as treatment of mid to low, especially low rectal cancer. This study was to compare the short-term efficacy of TaTME and laparoscopic total mesorectal excision (LaTME) for low rectal cancer. METHODS: A prospective study of patients with low rectal cancer who underwent laparoscopic radical surgery at the General Surgery of Guangzhou Red Cross Hospital from January 2017 to December 2019 was performed. The general information, perioperative results and pathological results of the two groups were compared. RESULTS: A total of 64 patients were included in the study, 32 in the TaTME group and 32 in the LaTME group. The clinical characteristics of the two groups was comparable (P > 0.05). The operation time in the TaTME group was longer than that in the LaTME group (212.59 ± 28.71min vs 187.66 ± 27.15min, P = 0.001), no significant differences were seen in the conversion rate, intraoperative complications, morbidity, serious morbidity, anastomotic leak, unplanned reoperation and hospital stay(P > 0.05). The circumferential resection margin (CRM) distance in the TaTME group was longer than that in the LaTME group (6.81 ± 2.99 mm vs 5.21 ± 3.06 mm, P = 0.039). The inter-group difference in terms of harvested lymph nodes, mesorectum integrity, CRM involvement, DRM distance, R1 resection, complete remission, pathological T stage, pathological N stage and pathological TNM stage was not significant (P > 0.05). CONCLUSIONS: TaTME is a promising surgical technique and maybe offers a safe and feasible alternative to LaTME in managing low rectal cancer.

[Prognostic value of lymph node ratio and N stage in stage III colorectal cancer].

OBJECTIVE: To compare the prognostic value of lymph node ratio and N staging in stage III colorectal cancer. METHODS: The clinicopathologic factors and follow-up data of 304 cases with stage III colorectal cancer from January 1998 to December 2011 were analyzed retrospectively. Multivariate analysis was performed using Cox proportional hazard regression model in forward stepwise regression. Patients were divided into different subgroups according to the number of lymph nodes sample. RESULTS: LNR and N stage were independent risk factors for stage III colorectal cancer, the prognostic value of LNR was better than that of N stage [Odds ratio were 1.838(95% CI:1.563~2.161) vs. 1.625 (95% CI:1.392~1.898)]. Subgroup analysis showed that, when the number of lymph nodes sample was less than 13, the prognostic value of LNR was better than that of N stage (Odds ratio were 1.836 vs. 1.639). But when the number of lymph nodes sample was more than 13, they were comparable (Odds ratio were 1.876 vs. 1.853). CONCLUSIONS: The prognostic value of LNR and N stage were comparable for stage III colorectal cancer, but when the number of lymph nodes sample was less than 13, LNR was more valuable.

[Clinical significance of tumor budding detection in stage II colon cancer].

OBJECTIVE: To investigate the association of tumor budding with recurrence and survival of patients with stage II colon cancer, in order to identify patients with high-risk recurrence who may benefit from adjuvant therapy. METHODS: Clinical data of 112 stage II colon cancer patients in Guangzhou Red Cross Hospital between 1998 and 2007 were analyzed retrospectively. The degree of tumor budding was assessed by two observers and classified according to the number of tumor buds in the area with the greatest budding intensity on HE stain slides, as high-grade budding (≥10, n=30) and low-grade budding (≤9, n=82). Progression-free and cancer-specific survival were analyzed using the Kaplan-Meier method and Cox regression. RESULTS: All the patients were followed up and the median follow-up was 78 months. The 5-year progression-free survival rates for patients with high-grade and low-grade budding were 65.3% and 90.7% respectively (P=0.008). The 5-year cancer-specific survival rates were 72.1% and 93.8% respectively (P=0.001). Cox regression analysis demonstrated tumor budding was an independent predictor of disease progression (RR=4.572, 95%CI:2.218-11.746, P=0.002) and cancer-related death (RR=4.116, 95%CI:1.657-10.384, P=0.012). CONCLUSION: Tumor budding is a strong prognostic index for adverse outcome in stage II colon cancer patients,which may serve as a prognostic marker to identify patients with high risk of recurrence who may benefit from adjuvant therapy.

Prognostic value of the lymph node ratio in stage III colorectal cancer.

The nodal stage of colorectal cancer is based on the number of positive nodes. It is inevitably affected by the number of removed lymph nodes, but lymph node ratio can be unaffected. We investigated the value of lymph node ratio in stage III colorectal cancer in this study. The clinicopathologic factors and follow-up data of 145 cases of stage III colorectal cancer between January 1998 and December 2008 were analyzed retrospectively. The Pearson and Spearman correlation analyses were used to determine the correlation coefficient, the Kaplan-Meier method was used to analyze survival, and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression. We found that lymph node ratio was not correlated with the number of removed lymph nodes (r = -0.154, P = 0.065), but it was positively correlated with the number of positive lymph nodes (r = 0.739, P < 0.001) and N stage (r = 0.695, P < 0.001). Kaplan-Meier survival analysis revealed that tumor configuration, intestinal obstruction, serum carcinoembryonic antigen (CEA) concentration, T stage, N stage, and lymph node ratio were associated with disease-free survival of patients with stage III colorectal cancer (P < 0.05). Multivariate analysis showed that serum CEA concentration, T stage, and lymph node ratio were prognostic factors for disease-free survival (P < 0.05), whereas N stage failed to achieve significance (P = 0.664). We confirmed that lymph node ratio was a prognostic factor in stage III colorectal cancer and had a better prognostic value than did N stage.

[Impact of perioperative chemotherapy on prognosis of colorectal cancer: a report of 82 cases].

BACKGROUND & OBJECTIVE: Recently, some scholars advocate perioperative chemotherapy for colorectal cancer. This study aimed to investigate the impact of perioperative chemotherapy on the prognosis of colorectal cancer. METHODS: From Aug. 2001 to Aug. 2003, 167 patients with Dukes'B or C colorectal cancer were randomized into two groups: 82 in trial group received perioperative chemotherapy using 5-fluorouracil (5-FU), while 85 in control group received no perioperative chemotherapy. All patients received adjuvant chemotherapy of 5-FU/leucovorin regimen. The adverse events, recurrence rate and survival rate were compared between these two groups. RESULTS: There was no difference in adverse events between the two groups. The overall recurrence rate was 42.5%û it was significantly lower in trial group than in control group (34.6% vs. 49.4%, P=0.038). The overall 1-, 3-, and 4-year survival rates were 97.6%, 74.7% and 61.8%û they were significantly higher in trial group than in control group (100% vs. 95.3%, 82.7% vs. 67.1%, and 69.1% vs. 54.8%, P=0.046). CONCLUSION: Perioperative chemotherapy can improve the prognosis of colorectal cancer.

[Multivariate regressive analysis of prognosis of liver metastases from colorectal cancer].

BACKGROUND & OBJECTIVE: It is not very clear about the factors that affect the prognosis of liver metastases from colorectal cancer. This study was to investigate the clinicopathologic factors related to the prognosis of liver metastases from colorectal cancer. METHODS: The clinicopathologic factors and follow-up data of 197 patients with liver metastases from colorectal cancer, treated from Jan. 1996 to Dec. 2000, were analyzed retrospectively. The prognostic index (PI) of patients was calculated based on the results of multivariate analysis and patients were classified into different hazard groups accordingly. RESULTS: The overall 1-, 3-, and 5-year survival rates were 59.04%, 17.73%, and 11.48%. Univariate analysis revealed that extrahepatic invasion, primary tumor resection, liver metastasis resection, type of primary tumor, serum CEA concentration, number and size of liver metastases, and distribution of liver metastases were associated with prognosis. Multivariate analysis identified that the resection of liver metastases, serum CEA concentration, number and size of liver metastases were prognostic factors. The patients were classified into high risk, moderate risk, and low risk groups according to the PI value, and there was significant difference in survival rates between each two groups. CONCLUSIONS: Liver metastasis resection, serum CEA concentration, number and size of liver metastases are important prognostic factors for liver metastases from colorectal cancer. In order to improve the survival rate, liver metastases should be resected for suitable patients. Moreover, PI value could be used to predict the prognosis of patients with liver metastases from colorectal cancer.

[Inhibitory effect of angiogenesis inhibitor YH-16 on liver metastases from colorectal cancer].

BACKGROUND & OBJECTIVE: YH-16, a new recombinant angiogenesis inhibitor, has demonstrated synergetic effects with chemotherapy in non-small-cell lung cancer treatment in stage II clinical trial. This study was to investigate the effect of YH-16 on liver metastases from colon cancer. METHODS: Inhibitory concentration 50% (IC(50)) of YH-16 on vascular endothelial cells and colon cancer cell line CT26 was determined by MTT assay. Furthermore, the mouse mode of colon cancer liver metastases was established by inoculating CT26 cells into the subcapsule of spleen. 60 mice were randomly divided into four groups: control group (0 mg/kg), low-dose YH-16 group (0.40 mg/kg), medium-dose YH-16 group (0.75 mg/kg) and high-dose YH-16 group (1.5 mg/kg). The numbers of liver metastases were examined 2 weeks after drug injection. The expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method in liver metastases, and tumor microvessel density (MVD) was measured by immunostaining using factor VIII monocolonal antibody. RESULTS: Proliferation of CT26 and vascular endothelial cells was inhibited by YH-16, which the IC(50) was (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg /ml, respectively. In vivo, the liver metastasis rates in control, low-dose, medium-dose and high-dose groups were 100%, 92.3%, 80% and 73.3%, respectively (P<0.05). However, YH-16 did not inhibit the growth of spleen tumors of which median volumes were 1.180 cm(3), 1.201 cm(3), 0.887 cm(3) and 0.781 cm(3), respectively (P>0.05). There was no difference of VEGF expression in liver metastases among the four groups. Moreover, MVD was 65.00+/-9.58, 58.15+/-8.81, 51.60+/-7.10 and 44.53+/-11.47 in the four groups. MVD in medium-dose and high-dose YH-16 groups was lower than that in control group and MVD was lower in high-dose group than that in medium-dose and low-dose groups (P<0.05). CONCLUSION: Angiogenesis inhibitor YH-16 can inhibit liver metastases from colorectal cancer.

[Univariate and multivariate regression analyses of recurrence and metastasis of colon cancer after radical resection].

BACKGROUND & OBJECTIVE: The prognosis of colon cancer after radical resection has seldom been reported, and the results are different. This study aimed to investigate the clinicopathologic factors related to recurrence and metastasis of colon cancer after radical resection. METHODS: The clinicopathologic and follow-up data of 152 patients with colon cancer, treated with radical resection from Jan. 1999 to Dec. 2000, were analyzed retrospectively. RESULTS: The overall recurrence and metastasis rate was 19.74%, and the liver metastasis rate was 9.87%. Univariate analysis showed that blood transfusion, disease duration, tumor size, tumor movement, histological differentiation, Dukesostage, and lymph node involvement were correlated to recurrence and metastasis of colon cancer after operation; blood transfusion, serum concentration of carcinoembryonic antigen (CEA), tumor movement, histological differentiation, Dukesostage, and lymph node involvement were correlated to liver metastasis. Multivariate analysis showed that tumor movement, histological differentiation, and lymph node involvement were prognostic factors for recurrence and metastasis, while serum concentration of CEA, histological differentiation, and lymph node involvement were prognostic factors for liver metastasis. CONCLUSIONS: Tumor movement, histological differentiation, and lymph node involvement are important prognostic factors for recurrence and metastasis of colon cancer after radical resection. Patients with high serum concentration of CEA, poor histological differentiation, and lymph node involvement have increased risk of liver metastasis.

[Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer].

OBJECTIVE: To study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer. METHODS: In vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group. The number of liver metastases, the size of primary tumor and the toxicity were examined after 2 weeks postoperatively. The expression of vascular endothelial growth factor (VEGF) in liver metastases was detected by immunohistochemistry, and tumor microvessel density (MVD) was measured by immunostaining with CD34 and factor VIII (monoclonal antibodies. RESULTS: In vitro, YH-16 inhibited the growth of colon cancer cells and vascular endothelial cells, with the IC50 at (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg/ml respectively. In vivo high-dose YH-16 and 5-FU had a remarkable inhibitory effect on liver metastasis, and the combination group showed significant enhancement on this effect (P< 0.05). The combination group and 5-FU group could inhibit the growth of primary tumor, but not found in YH-16 group. The toxicity of YH-16 was lower than that of 5-FU (P< 0.05), and the difference was not found in the toxicity between combination group and 5-FU group (P > 0.05). Expression of VEGF in liver metastases was clearly inhibited by YH-16 in combination with 5-FU or 5-FU alone compared to the control group, and MVD in middle-dose and high-dose YH-16 group, 5-FU group and combination group was lower than that in control group (P< 0.05). CONCLUSIONS: The angiogenesis inhibitor YH-16 can inhibit liver metastasis of colorectal cancer through inhibiting the growth of vascular endothelial cells. YH-16 in combination with 5-FU has additive effect on inhibitory activity against liver metastasis.