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Hangzhou, China

The optimal radiotherapy technique and combination with systemic therapy in locally advanced gastric cancer patients are far from being resolved despite the fact that radiochemotherapy is becoming more attractive in contemporary clinical practice. 40 patients with locally advanced gastric cancer received intensity-modulated radiotherapy (IMRT) at a dosage of 45-50.4 Gy concurrent with chemotherapy using S-1 solely or with a combination of oxaliplatin. Surgery was recommended for those who were evaluated as resectable. Sequential chemotherapy with various regimens was adopted based on the efficacy and tolerance of radiochemotherapy. The overall response rate was 75% according to Response Evaluation Criteria in Solid Tumors and Japanese Gastric Cancer Association criteria. 24 finally underwent surgery, with 22 (91.7%) receiving an R0 resection (resection for cure or complete remission). The overall pathological response rate was 37.5% (9/24). Patients receiving an R0 resection had a higher 2-year overall survival rate (64.7 vs. 16.2%, p = 0.001) and local relapse-free survival rate (90.2 vs. 29.3%, p = 0.000), while there was no difference in distant metastasis-free survival rate (66.1 and 48.1% p = 0.231). Hematological and gastrointestinal toxicities of grade 1 or grade 2 were relatively common. The high rate of R0 resections and low rate of locoregional recurrence suggest that IMRT combined with S-1-based chemotherapy is an effective treatment for locally advanced gastric cancer patients.

Shi H.,Red Cross | Chen L.,Sir Run Run Shaw Hospital | Wang H.,University of Miami | Zhu S.,University of Miami | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

HDAC inhibitors are under clinical development for the treatment of hypertrophic cardiomyopathy and heart failure although the mechanisms of protection are incompletely understood. Micro-RNA 126, an endothelium-specific miR has been assigned essential developmental roles in the heart by activating survival kinases ERK1/2 and Akt and increasing pro-angiogenic signaling. Here we provide the first evidence that hypoxia and HDAC inhibitors selectively and synergistically stimulate expression of miR-126 in cardiac myocytes. MiR-126 expression was increased 1.7-fold (p<. 0.05) after 1. h of hypoxic exposure and this was further enhanced to 3.0-fold (p<. 0.01) by simultaneously blocking HDAC with the pan-HDAC inhibitor Tricostatin A (TSA). TSA alone did not increase miR-126. In parallel, hypoxia and TSA synergistically increased p-ERK and p-Akt without effecting VEGF-A level. Knockdown of miR-126 with si-RNA eliminated inductions of p-ERK and p-Akt by hypoxia, whereas miR-126 overexpression mimicked hypoxia and amplified p-ERK and p-Akt in parallel with miR-126. The results suggest that miR-126 is a hypoxia-inducible target of HAT/HDAC and its activation in cardiac myocytes may contribute to cardioprotection by activating cell survival and pro-angiogenic pathways selectively during ischemia. © 2012 Elsevier Inc.

Wu Y.-L.,Guangdong Academy of Medical science | Lee J.S.,National Cancer Center | Thongprasert S.,Maharaj Nakorn Chiang Mai Hospital | Yu C.-J.,National Taiwan University Hospital | And 27 more authors.
The Lancet Oncology | Year: 2013

Background: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m2 on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m2 on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779. Findings: From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2-8·3], vs 6·0 months [5·6-7·1], hazard ratio [HR] 0·57 [0·47-0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3-20·8) and 15·2 months (12·7-17·5), respectively (HR 0·79 [0·64-0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9-20·4] vs 6·9 months [5·3-7·6], HR 0·25 [0·16-0·39]; p<0·0001; median overall survival 31·4 months [22·2-undefined], vs 20·6 months [14·2-26·9], HR 0·48 [0·27-0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). Interpretation: Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. Funding: F Hoffmann-La Roche. © 2013 Elsevier Ltd.

Hu X.-T.,Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province | He C.,Sir Run Run Shaw Hospital
Chinese Journal of Cancer | Year: 2013

Gastric cancer is one of the most common malignancies and a leading cause of cancer mortality worldwide. The pathogenesis mechanisms of gastric cancer are still not fully clear. Inactivation of tumor suppressor genes and activation of oncogenes caused by genetic and epigenetic alterations are known to play significant roles in carcinogenesis. Accumulating evidence has shown that epigenetic silencing of the tumor suppressor genes, particularly caused by hypermethylation of CpG islands in promoters, is critical to carcinogenesis and metastasis. Here, we review the recent progress in the study of methylations of tumor suppressor genes involved in the pathogenesis of gastric cancer. We also briefly describe the mechanisms that induce tumor suppressor gene methylation and the status of translating these molecular mechanisms into clinical applications.

Guo Z.,Zhejiang Cancer Hospital | Yu P.,Harvard University | Liu Z.,Sir Run Run Shaw Hospital | Liu Z.,University of Wisconsin - Madison | And 2 more authors.
Clinical Endocrinology | Year: 2013

Background Conducting total thyroidectomy (TT) or subtotal thyroidectomy (ST) in patients with Graves' disease remains controversial. We performed a meta-analysis based on the published randomized controlled trials to evaluate the complications of TT vs ST. Methods We searched multiple electronic databases for prospective, randomized, controlled trials related to safety and effectiveness of TT vs ST. Relative risk (RR) was estimated with 95% confidence interval (CI) based on an intention-to-treat analysis. We considered the following outcomes: recurrent hyperthyroidism, ophthalmopathy progression, temporary and permanent hypoparathyroidism, temporary and permanent recurrent laryngeal nerve palsy (RLNP) and post-operative bleeding. Results Four trials with 674 patients (342 with TT, 332 with ST) were analysed. Although the overall rates of ophthalmopathy progression were similar between TT and ST (RR 0·92, 95% CI = 0·50-1·71; P = 0·80), TT was associated with a significant reduction in recurrent hyperthyroidism (RR 0·14, 95% CI = 0·05-0·41; P < 0·01). The pooled RR of post-operative bleeding for TT was similar to that for ST (RR 0·32, 95% CI = 0·05-1·96; P = 0·22). However, comparing with ST, the RR of temporary hypoparathyroidism was significantly higher for TT (RR 2·66, 95% CI = 1·89-3·73; P < 0·01). There was no significant difference in permanent hypoparathyroidism (RR 2·30, 95% CI = 0·78-6·76; P = 0·13), temporary (RR 1·08, 95% CI = 0·47-2·48; P = 0·85) and permanent RLNP (RR 1·54, 95% CI = 0·41-5·73; P = 0·52) between the two groups. Conclusions With regard to ophthalmopathy progression, post-operative bleeding, permanent hypoparathyroidism, temporary and permanent RLNP, TT is consistent with ST in patients with Graves' disease. However, TT is associated with a reduced incidence of recurrent hyperthyroidism and results in an increase in temporary hypoparathyroidism. Therefore, TT should be proposed for the treatment of Graves' disease. © 2013 John Wiley & Sons Ltd.

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