ABSTRACT: BACKGROUND: Many studies have shown that colon cancer is an estrogen-dependent carcinoma. This study explored the efficacy of endocrine therapy in colon cancer cells with high metastatic potential (HT29). We investigated the proliferation of HT29 cells after exposure to endocrine therapy (tamoxifen) and 5-FU. METHODS: Apoptosis was evaluated using flow cytometry. The expression of matrix metalloproteinases 7 (MMP-7) and estrogen receptor beta (ERbeta) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. The migration capability of treated cells was determined with wound scratch assay. RESULTS: Tamoxifen alone, 5-FU alone, and the combination of the two drugs can significantly inhibit HT29 cell proliferation and migration, block the cells in G2/M phase and induce cell apoptosis. These drugs also can down-regulate MMP7 and ERbeta expression. CONCLUSIONS: Our findings suggest that endocrine therapy is an efficient therapy for inhibiting ERbeta-positive colon cancer cell proliferation and migration via down-regulation of MMP7.

Background and Objective: Neoadjuvant therapy (radiotherapy, RT or chemoradiotherapy,CRT) could change status of the invasion and lymph node metastasis of rectal cancer. The risk factors of lymph node metastasis in rectal cancers without neoadjuvant therapy have been well known, but those in rectal cancers treated with preoperative RT or CRT remain unclear. This study was to investigate the risk factors of lymph node metastasis in patients who underwent preoperative RT or CRT for rectal cancers. Methods: Clinical data of 93 patients underwent preoperative RT or CRT followed by total mesorectal exesion (TME) for locally advanced rectal adenocarcinoma from August, 2003 to February, 2008 were reviewed. Twelve clinicopathologic factors and treatment-related factors were studied with univariate and multivariate analyses. Results: Univariate analysis showed that post-RT or post-CRT serum carcinoembryonic antigen (CEA) level, radiation dose, time interval from RT or CRT to TME, concurrent chemotherapy with oxaliplatin-containing regimens, and infiltration extent to bowel wall after RT or CRT (ypT stage) were significantly associated with lymph node status after RT or CRT (ypN stage). Multivariate analysis showed that concurrent chemotherapy with oxaliplatin-containing regimens (r=-0.481, P<0.01) and ypT stage (r=0.503, P<0.01) were independent risk factors of ypN stage. Conclusions: Pathologic T stage is the most reliable predictor of lymph node stage in rectal cancer patients received preoperative RT or CRT. Oxaliplatin-containing regimens could significantly reduce the risks of lymph node metastases and potentially improve the prognosis.

Background and Objective: Prognosis of stage II colorectal cancer varies. Whether or not to perform adjuvant chemotherapy on patients with stage II colorectal cancer is controversial. This study was to explore the prognostic factors for the patients with stage II colorectal cancer and evaluate the effect and the necessity of adjuvant chemotherapy. Methods: Between January 2000 and January 2005, 443 patients with stage II colorectal cancer receiving radical surgery at Sun Yat-sen University Cancer Center were retrospectively analyzed. The overall survival rate and survival curve were analyzed using the Kaplan-Meier method and the log-rank test. The univariate and multivariate prognostic analyses were performed by the Cox regression model. Patients with or without chemotherapy (Xelox/Folfox regimen) with high-risk factors were analyzed respectively. Results: The median follow-up time was 59 months, and the 3-and 5-year survival rates were 88.4% and 82.5%, respectively. Univariate analysis showed that intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 were poor prognostic factors. Patients with intestinal obstruction or perforation, the number of sampled nodes < 9 achieved higher 5-year survival (80% and 86%) undergoing adjuvant chemotherapy than those receiving surgery alone (67% and 64%). Conclusions: The prognosis of colorectal cancer patients with intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 are relatively poor. Adjuvant chemotherapy is recommended to patients with intestinal obstruction, perforation or sampled nodes < 9.

Background and Objective: Total mesorectal excision (TME) can reduce local recurrence and improve prognosis of rectal cancer. This study was to analyze the clinicopathologic characteristics of rectal cancer, and explore the prognosis factors of rectal cancer after radical TME. Methods: From 1990 to 2003, 1056 rectal cancer patients had received radical TME. The impacts of 20 clinicopathologic factors on the prognosis were analyzed with univariate and multivariate method. Results: The 3-, 5-, and 10-year overall survival rates were 84.9%(95% CI, 83.8%-86.0%), 73.8%(95% CI, 72.4%-75.2%), and 65.1%(95% CI, 63.4%-66.8%), respectively. Univariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) and CA19-9 levels, tumor gross type, pathologic type, pathologic grade, preoperative bowel obstruction or bowel perforation, T stage, N stage, and first treatment era were associated with the prognosis of rectal cancer. Multivariate analysis showed that N stage, histological type, surgical procedures, and T stage were independent prognostic factors. Conclusion: N stage, histological type, surgical procedures, and T stage are independent prognostic factors for rectal cancer patients who received radical TME.

Background and Objective: Whether selective defunctioning stoma could reduce the rate of anastomotic leak and lessen adverse effects in low anterior resection (LAR) remains controversial. This study was to evaluate the necessity of selective defunctioning stoma after LAR. Methods: Medline databases were searched and English-language articles regarding to selective defunctioning stoma in LAR published from January 1, 1990 to October 1, 2007 were acquired. Seven literatures from seven different studies were included in this study, with total enrollment of 5040 patient. The rate of anastomotic leakage and re-operation rate in different surgical procedures (with or without selective defunctioning stoma) were pooled to compare using meta-analysis. Results: Selective defunctioning stoma did not significantly reduce the rate of anastomotic leakage after LAR. The pooled odds ratio (OR) was 0.68 (95%CI=0.45-1.02, P>0.05). Selective defunctioning stoma significantly reduced the rate of surgery-required anastomotic leakage following LAR. The pooled OR was 0.33(95% CI=0.25-0.44, P<0.01). Conclusion: Although selective defunctioning stoma does not reduce the rate of anastomotic leakage, it reduces the rate of surgery-required anastomotic leakage.

A recombinant human parathyroid hormone (rhPTH) fragment (Gly(1)-Gln(26)-rhPTH(1-34)) which contains two amino acids substitutions (Gly(1) and Gln(26)) was acquired through Escherichia coli expression system using a soluble fusion protein strategy. The soluble fusion protein MBP-Gly(1)-Gln(26)-rhPTH(1-34) was harvested after purification by Phenyl-Sepharose F.F and Q-Sepharose F.F chromatographies. Following tobacco etch virus (TEV) protease cleavage and further purification by SP-Sepharose F.F chromatography, 30.8 mg/L Gly(1)-Gln(26)-rhPTH(1-34) without tag was obtained with high purity up to 99%. Cyclic AMP (cAMP) stimulation assay suggested that Gly(1)-Gln(26)-rhPTH(1-34) could increase the biological activity by up to 13.89% and 6.34%. After daily subcutaneous injection (for 13 weeks) of 5, 10 and 20 microg of Gly(1)-Gln(26)-rhPTH(1-34)/1000g body weight, the mean Bone Material Density (BMD) of ovariectomized (OVXed) rats increased to 7.95-30.54% and 1.98-23.32%, compared to control-vehicle group (OVX, P<0.001) and sham- operated group (SHAM, P<0.01), respectively.

BACKGROUND & OBJECTIVE: Multiple primary colorectal carcinoma (MPCC) is not rarely seen, but it possesses a unique biological characters. This study was to investigate the clinical characteristics, diagnosis, therapeutic principle and prognosis of MPCC. METHODS: Data of 70 MPCC patients, treated by operation from 1997 to 2003, were analyzed. Of the 70 patients, 61 had synchronous carcinoma (SC) and 9 had metachronous carcinoma (MC). RESULTS: Fifty-five patients were diagnosed by colonoscopy, barium enema or CT scan pre-operationally, while 15 were diagnosed intra-operationally due to the oversized tumor at the distal end of the colon. Thirty-three patients had colorectal carcinoma accompanying with adenoma and multiple polyps. All the patients underwent surgical resection except 3, who received short-circuit operation because of unresectable lesions. Fifty-two patients received radical resection, while 15 received palliative resection due to hepatic or peritoneal metastasis. The overall 3-and 5-year survival rates were 65.7% and 45.7%. In the patients who received radical resection, the 3-and 5-year survival rates were 78.1% and 59.3%. CONCLUSIONS: The occurrence of MPCC is largely related with adenomas and polyps. The extent of resection should be individually determined by the lesion location, range, the distance of lesions as well as the general condition of the patients. Prognosis of MPCC is relatively good. The patients accompanying with adenoma and multiple polyps should be followed up intensively.

A lactose-binding lectin (Agrocybe cylindracea Lectin, ACL) purified from fruiting bodies of the mushroom A. cylindracea was investigated to determine the hemagglutinating activity and conformation changes after chemical modification, removal of metal ion and treatment at different temperatures and pH. ACL agglutinated both rabbit and human erythrocytes and its hemagglutinating activity could be inhibited by lactose. This lectin was stable in the pH range of 6-9 and temperature up to 60 degrees C. Fluorescence quenching and modification of tryptophan residues indicated that there were about two tryptophan residues in ACL molecule and one of them might be located on the surface, while the other was buried in the hydrophobic shallow groove near the surface. Chemical modification of serine/threonine and histidine showed that the partial necessity of these residues for the hemagglutinating activity of ACL. However, modifications of arginine, tyrosine and cysteine residues had no effect on its agglutinating activity.

OBJECTIVE: To analyze the effects of surgical treatment for gastrointestinal stromal tumors (GISTs) and influential factors of survival. METHODS: The clinical data and the tissue slices including immunohistochemical staining of 153 cases of GISTs from January 1990 to March 2006 were rechecked retrospectively. All patients were followed up carefully. More attention was paid to the surgical effects and the influential factors of survival. RESULTS: The overall survival rates at 1-, 2-, 3-, 4- and 5-year were 94.9%, 83.3%, 73.3%, 70.5% and 64.3%, respectively. The median survival time for patients with tumor resected completely was 66.0 months, and the 2- and 5-year survival rate were 89.4% and 70.9% respectively. The median survival time was 23.8 months for the patients with tumor resected partly, and only two of these patients survived over 2 years. Gender, tumor sites, preoperative metastasis, tumor size, pathological type, karyokinesis and recurrence and metastasis were related with survival rates for the patients with tumor resected completely on univariate analysis, but tumor size, pathology type, recurrence and metastasis were related with survival rates on Cox regression multivariate analysis (P < 0.05). CONCLUSIONS: Surgery should still be the main therapy for GISTs. Local complete resection is the principal treatment. The survival cannot be improved by extensive resection and lymph nodes clearance.

BACKGROUND & OBJECTIVE: FOLFOX6 regimen has been used in treating advanced colorectal cancer for a period, but there is no systemic study on FOLFOX6 regimen in treating Chinese colorectal cancer patients with liver metastasis. This study was to evaluate the efficacy of FOLFOX6 regimen on Chinese colorectal cancer patients with liver metastasis, and observe the adverse events. METHODS: Ninety-one colorectal cancer patients with liver metastasis were treated by FOLFOX6 regimen. FOLFOX6 regimen consisted of 2-hour infusion of oxaliplatin (100 mg/m(2)) and 2-hour infusion of leucovorin (CF)(400 mg/m(2)) on Day l, followed by 5-fluorouracil (5-FU) bolus (400 mg/m(2)) on Day 1 and 46-hour infusion (2.4 g/m(2)). FOLFOX6 regimen was repeated at 2-week intervals. The clinical efficacy and adverse events were evaluated. RESULTS: The objective response rate for all patients was 40.7%, with 4 cases of complete remission (CR), 33 partial remission (PR), 19 stable disease (SD), and 35 progressive disease (PD). There was no significant difference in objective response rate between the patients with and without previous treatment (P>0.05). The median survival time was 17.0 months for all patients, 20.0 months for the patients without previous treatment, and 12.0 months for the patients with previous treatment. The time to progress (TTP) was 7.0 months for all patients, 9.0 months for the patients without previous treatment, and 6.0 months for the patients with previous treatment. Peripheral neuritis, gastrointestinal reaction, and myelosuppression were major adverse events. All patients with 5-FU-associated adverse events recovered after treatment. CONCLUSION: FOLFOX6 regimen can be used in treating colorectal cancer with liver metastasis for its efficacy and less toxicity.