Identification of microRNAs involved in the radioresistance of esophageal cancer cells.

Radioresistance is considered as the most important reason for local tumour recurrence. This study investigates the role of miRNAs in radioresistant human esophageal cancer cells. Human miRNA microarray has been used to detect the differential expressed microRNAs between radioresistant esophageal cell line KYSE-150R and the parental cell line KYSE-150. The relative expression of some candidate miRNAs was measured by quantitative real-time PCR (qRT-PCR). Potential mRNA targets were analysed bioinformatically. Significant upregulation of 10 microRNAs and downregulation of 25 microRNAs were detected. The statistical significance of downregulation in hsa-miR-301a, hsa-miR-141 and hsa-miR-18b expression (P < 0.05) were confirmed by qRT-PCR. The correlation of the predicted microRNA target genes to apoptosis (63 genes), cell cycle (67 genes), DNA damage and repair (18 genes) were confirmed by functional annotation. The downregulation of hsa-miR-301a promoted radioresistance in KYSE-150R through the upregulation of wnt1, indicating that wnt/ß-catenin signal pathway might be important in radioresistance. In conclusion, a unique set of miRNAs and their expression profiles in radiation resistance have been identified, providing a solid basis for future studies to investigate the target genes of these miRNAs and their function.

Postoperative chemoradiotherapy for advanced gastric cancer after D2 gastrectomy.

BACKGROUND/AIMS: The purpose of this study is to investigate the role of postoperative chemoradiotherapy with paclitaxel and cisplatin in the multimodality treatment of locally advanced gastric cancer after D2 gastrectomy. METHODOLOGY: Sixty-five patients underwent D2 gastrectomy with stage IB-IV (M0) gastric cancers were enrolled. A postoperative radiotherapy dose of 46 Gy in 23 fractions with concurrent chemotherapy of paclitaxel and cisplatin were delivered to the patients. Chemotherapy was administrated with paclitaxel 135mg/ m2 at day 1 and 21, cisplantin 20mg/ m2 at day 1-3 and day 29-31 during the radiotherapy course. Sixty-three out off 65 eligible patients were irradiated to a total dose of 46Gy and completed two cycles of full-dose chemotherapy. Thirty-three patients died at the time of analysis. RESULTS: The median follow-up was 68.0 months (range 1.9-119.1). The 3-year overall survival (OS) and disease-free survival (DFS) were 78.5% and 73.2%, respectively. The 5-year OS and DFS were 57.4% and 54.8%, respectively. Toxicity was tolerant. The main toxicities were gastrointestinal disorder, hematologic toxicity and hair loss. CONCLUSION: This novel postoperative chemoradiotherapy regimen for patients with gastric cancer after D2 gastrectomy had a tolerable toxicity, however, it did not decrease the local recurrence rate.

Concurrent paclitaxel/cisplatin chemoradiotherapy with or without consolidation chemotherapy in high-risk early-stage cervical cancer patients following radical hysterectomy: preliminary results of a phase III randomized study.

A phase III randomized study on the efficacy and safety of consolidation chemotherapy with paclitaxel plus cisplatin following radical hysterectomy and adjuvant chemoradiotherapy (CRT) in the treatment of high risk early-stage cervical cancer were reported. 146 eligible patients were randomized to arm A receiving concurrent CRT or arm B receiving CRT plus consolidation chemotherapy, respectively. An interim analysis showed a trend of improvement on disease-free survival (DFS) and overall survival (OS) in arm B with hazard ratios (HR) of 1.25 (95% CI = 0.60-2.60, p = 0.55) and 1.43 (95% CI = 0.64-3.20, p = 0.38) for DFS and OS, respectively. The 3-year DFS and OS were 82.0% vs.74.3%, and 86.6% vs. 78.3% for patients receiving CRT plus consolidation chemotherapy and CRT alone, respectively. There was significant difference between the two arms in distant alone recurrence (p = 0.048). Multivariate analysis indicated that pathologic type was a significant prognostic factor for OS (p = 0.045), positive pelvic nodes were significantly associated with both OS ( p=0.02) and DFS (P=0.03). Grade 2 to 4 gastrointestinal disorder (p = 0.95), radiation enteritis (P=0.48), radiation cystitis (p = 0.27) and radioepidermitis (p = 0.46) were similar in the two arms. Overall rates of grade 0-2/3-4 myelosuppression were 87.7%/12.3% for arm A and 74.6%/25.4% for arm B, respectively, but this difference was not statistically significant (p = 0.05). In conclusion, concurrent CRT plus consolidation chemotherapy may play a potential role in further improving survival outcomes for high-risk early stage cervical cancer patients compared CRT alone.

A pilot study of combination intraperitoneal recombinant human endostatin and chemotherapy for refractory malignant ascites secondary to ovarian cancer.

The management of refractory malignant ascites (MA) due to ovarian cancer (OC) remains a difficult clinical problem. A total of 23 eligible patients with refractory MA due to OC were treated with combined intraperitoneal therapy repeated 4 weeks, which consisted of paclitaxel 100 mg m(-2) (over 3 h) on day 1, 5-FU 600 mg m(-2) on day 1-3 followed by recombinant human endostatin 60 mg on day 4. The objective response rate was 60.9 % (14/23). The median time to progression and overall survival was 5.8 and 12.9 months, respectively. Treatment-related toxicities were uncommon and manageable without therapy-associated deaths. The mean Karnofsky performance status score was significantly improved from 60.0 ± 1.89 at enrollment to 70.0 ± 2.59 at 2 weeks after the first cycle of therapy (P = 0.000). Moreover, the mean score of overall ascites-associated symptoms was also increased significantly from 5.1 ± 0.32 to 4.0 ± 0.20 (P = 0.002). There were remarkable improvements in 7 out of 9 individual ascites-associated symptoms including well being, anxiety, abdominal distention, vomiting, anorexia, fatigue, and dyspnea as well (all P < 0.05). These results suggest that combination intraperitoneal recombinant human endostatin and chemotherapy is effective and safe in patients with refractory MA secondary to OC and significantly improves patients' quality of life with encouraging survival, which might highlight more effective treatment for this challenging disease and merits further investigation.

Association between single nucleotide polymorphisms of the transforming growth factor-ß1 gene and overall survival in unresectable locally advanced non-small-cell lung cancer patients treated with radio(chemo)therapy in a Chinese population.

The outcome is variable for unresectable locally advanced non-small-cell lung cancer (ULANSCLC) patients treated with radio(chemo)therapy. The aim of this study is to investigate whether single-nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 (TGF-ß1) gene are associated with overall survival (OS) in ULANSCLC patients treated with definitive radio(chemo)therapy. A total of 109 patients who had available blood samples and complete clinical and follow-up information were enrolled. DNA from blood was genotyped for two SNPs: TGF-ß1 C-509T and T+869C. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used to evaluate associations between genotypes and OS. Log-rank test showed that TGF-ß1 C-509T significantly correlated with OS (pooled P = 0.017). Both univariate and multivariate analyses showed that TGF-ß1 C-509T CC genotype was significantly associated with better OS than CT or TT genotypes. These results indicate that TGF-ß1 C-509T CC genotype is significantly associated with better OS in ULANSCLC patients treated with radio(chemo)therapy as a potential independent survival predictor.

Adjuvant combined systemic chemotherapy and intraperitoneal chemotherapy for locally advanced gastric cancer.

The optimal adjuvant treatment modality for gastric cancer has not been well defined. The aim of this study was to evaluate the efficacy and feasibility of adjuvant combined systemic and intraperitoneal chemotherapy (ACSIP) in high-risk patients with locally advanced gastric cancer. Between June 2003 and December 2008, 62 eligible patients with serosa-infiltrating and/or node-positive gastric cancer following curative gastrectomy with D2 lymphadenectomy received ACSIP, consisting of intravenous oxaliplatin 85 mg/m(2) on day 1 followed by leucovorin (LV) 200 mg/m(2) and 5-fluorouracil (5-FU) 450 mg/m(2) on days 1-3, intraperitoneal 5-FU 600 mg/m(2) on days 4-5 and cisplatin (CDDP) 40 mg/m(2) on day 5. Survival rates, the sites of first treatment failure and safety were analyzed. At a median follow-up of 45 months (range 7-101), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 66.1 and 74.2%, respectively. Initial peritoneal and hepatic failures were found in 6 (24.0%) and 3 (12.0%) of the 25 patients with recurrence, respectively. Neutropenia, gastrointestinal side effects and peripheral neuropathy were the most common grade 3-4 toxicities; however, they were all infrequent and manageable. No serious surgical complications or treatment-related mortality was observed. The results of this study indicate that ACSIP is effective and feasible for locally advanced gastric cancer with encouraging survival rates and possibly decreased peritoneal and hepatic recurrences. The benefits of this promising combined adjuvant treatment modality warrant further studies.

Simultaneous modulated accelerated radiation therapy and concurrent weekly Paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma.

OBJECTIVES: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) and concurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. METHODS: Forty- one patients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrent weekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV) and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of 45 mg/m2 was administered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeks after the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). RESULTS: All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patients due to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patients completed the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course. Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The median follow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS), and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and T or N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively. CONCLUSION: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approach in the treatment of locally advanced NPC.

[Improved methods of isolation and purification of rat islets and its viability research].

OBJECTIVE: The purity and activity of islets will greatly affect the outcome of xenotransplantation therapy of type 1 diabetes mellitus. To set up an improved method of the isolation and purification of rat islets, which can obtain high-purity, high-yield, and high-viability islets. METHODS: Ten healthy and adult male SD rats, weighing 250-300 g were used as organ donors. Collagenase V was perfused into pancreas via pancreatic duct. Pancreas was digested with collagenase in water bath at 38 degrees C about 15 minutes, islet purification was performed using two techniques: with Ficoll 400 density gradient (group A), and Ficoll-Paque PLUS (group B). Dithizone (DTZ) was utilized for identifying islets, counting islets equivalent quantity (IEQ) and islets' purity. Trypan blue staining was used to detect the viability of islets. Islets of group B was encapsulated with alginate/poly-L-lysine/alginate (APA). Islets function of microencapsulated and nonmicroencapsulated was evaluated by the insulin release test. RESULTS: DTZ staining showed that islets shape were round, ellipse and irregular with a clear edge and a diameter range of 50-300 microm. The IEQ values were 338.04 +/- 76.61 and 834.80 +/- 54.00 in groups A and B, respectively, showing significant difference (P < 0.05). The purities were 88.31% +/- 2.67% and 95.63% +/- 1.96% in groups A and B, respectively, showing no significant difference (P > 0.05). The activities of islets were 67.40% +/- 5.15% and 86.05% +/- 2.52% in groups A and B, showing significant difference (P < 0.05). Islet APA microcapsules had round shape, unified size, and its diameter was between 1.5 and 2.0 mm. Each microcapsule was encapsulated of 1 to 3 islets. The result of insulin release assay was that the concentrations of insulin secretion with islets of microencapsulated and nonmicroencapsulated were (5.53 +/- 1.64) ng/mL and (4.76 +/- 0.26) ng/mL in low glucose, and its concentrations of insulin secretion in high glucose were (11.95 +/- 2.07) ng/mL and (14.34 +/- 3.18) ng/mL. Stimulated insulin secretion in high glucose was 2 times more than that in low glucose (P < 0.05), but there was no significant difference (P > 0.05) in the stimulation index between group A (2.16 +/- 0.30) and group B (3.01 +/- 0.59). CONCLUSION: The method of islets isolation and purification using Ficoll-Paque PLUS own the virtues of more convenient, high islet yield, and high islet purity. Both microencapsulated and nonmicroencapsulated islets show high-viability while culture in vitro.