ObjectiveTo investigate the inhibition of telomerase activity of colorectal cancer by chemotherapeutic drugs.MethodsBy using telomerase repeat amplification protocol (TRAP) combined with PAGE silver staining, we detected the telomerase activity of human colorectal cancer cell line HT-29 under the effect of cisplatin, doxorubicin, pirarubicin, mitomycin C, and 5-FU.ResultsIn high doses,no inhibition of tolemerase activity was found when cells were collected after only 4 hours of drug treatment, but the telomerase activity was completely inhibited by cisplatin when the drug was removed and cells were reculured for 20 hours. However, doxorubicin, pirarubicin, mitomycin C, 5-FU had no such effect. ConclusionCisplatin inhibits telomerase activity of human colon cancer cell HT-29, while other drugs had no such effect.

Objective To investigate the correlation between VEGF-C and COX-2 expression in human rectal cancers and its significance in cancer metastasis. Methods VEGF-C expression was detected with Western blot in LOVO cells treated with NS-398 or PGE2. VEGF-C and COX-2 expression in 45 rectal adenocarcinomas was tested with immunohistochemistry. Results NS-398 inhibited the VEGF-C expression, and PGE2 up-regulated the expression of VEGF-C in a dosage-dependent way in LOVO cells. VEGF-C expression was significantly higher in adenocarcinomas with lymph node metastasis, and was related with the expression of COX-2 in 45 rectal adenocarcinomas. Conclusion COX-2 up-regulates VEGF-C and VEGF-C plays an important role in lymphatic metastasis of rectal cancers.

OBJECTIVES To analyse the diagnosis and treatment of 24 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds and report mismatch repair gene mutations. METHODS The diagnosis, treatment and follow-up of 24 HNPCC kindreds were reviewed retrospectively, cancer incidence and spectrum were recorded. Clinical characteristics and treatment were analyzed. Peripherial blood and genomic DNA were extracted from family members who had provided informed consent. PCR and SSCP were used to screen coding regions of the hMLH1 and hMSH2 genes. Variant bands were sequenced by 377 DNA sequencer after purification. RESULTS One hundred and 25 malignant neoplasms were diagnosed in 75 patients (multiple cancers in 24) with an average age of 51 years in 24 pedigrees. The onset of the disease occurred earlier than expected with the passing of each generation within large kindreds. The neoplasm mainly included colonic cancer (63 patients), rectal cancer(21), stomach cancer(13), endometric cancer(7), and esophageal cancers(6). 84% patients received radical operations. Of 64 patients with colorectal cancer 16 had metachronous colorectal cancer. 24% colorectal patients developed metachronous cancer within 10 years after initial operation and received re-operation. In 3 detected families with germline hMSH2 and hMLH1 mutations resulting in truncated protein, 12 carriers were found. CONCLUSIONS The main characteristics of hereditary nonpolyposis colorectal cancer include early onset and frequence of cancer; predominance of colorectal cancer, especially right-sided colonic cancer; frequency of multiple primary cancer, especially colorectal cancer; and age anticipation in large HNPCC pedigrees. Segmental resection of colorectal cancer is not suitable for colorectal cancer patient in HNPCC kindred. Intensive follow-up is important for all patients and possible gene carriers.
Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Carrier Proteins ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; therapy ; DNA-Binding Proteins ; Female ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Mutation ; Neoplasm Proteins ; genetics ; Nuclear Proteins ; Proto-Oncogene Proteins ; genetics

Objective To investigate the quality of life before and after the protective neostomy of patients with rectal cancer undergoing neoadjuvant radiotherapy.Methods A total of 81 cases with low rectal cancer were selected between March 201 2 and March 201 4 from the Colorectal Surgery Center of Beijing Cancer Hospital.Experimental group contained 40 cases of low rectal cancer with protective neostomy after neoadjuvant the rapyand control group contained 41 cases of low rectal cancer undergoing permanent colostomy.The life quality of patients in two groups were surveyed via questionnaire at 6th month after permanent colostomy,before and 6th month after protective neostomy.The differences between two groups were analyzed.Results The life-quality of the patients with low rectal cancer who received neoadjuvant therapy and protective neostomy were better than the patients with permanent colostomy (P <0.05).However,the quality of life was not significantly improved after the apotheosis of ileal stoma.Conclusions The life-quality of patients with low rectal cancer are not significantly improved by performing protective neostomy.Specific nursing measures should be carried out at these patients.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.