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Satoh T.,Kinki University | Doi T.,National Cancer Center Hospital East | Ohtsu A.,National Cancer Center Hospital East | Tsuji A.,Kochi Health science Center | And 15 more authors.
Journal of Clinical Oncology | Year: 2014

Purpose: In Asian countries, paclitaxel once per week is used as second-line treatment in advanced gastric cancer, including human epidermal growth factor receptor 2 (HER2) -positive tumors. The role of anti-HER2 agents, including lapatinib, in this setting and population is unclear. Patients and Methods: TyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m2 or paclitaxel alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), time to progression (TTP), overall response rate (ORR), time to response, response duration, and safety. Analyses were based on immunohistochemistry (IHC) and gastrectomy status, prior trastuzumab therapy, and regional subpopulations. Results: Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044), with no significant difference in median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001). Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%). Conclusion: Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population. © 2014 by American Society of Clinical Oncology. Source

Zhang Z.-S.,Jiangyan Peoples Hospital | Chen L.-X.,Cancer Hospital of Jiangsu Province
Chinese Journal of Cancer Prevention and Treatment | Year: 2012

OBJECTIVE: To compare the effectiveness and toxicity effect of combine chemotherapy regimen of irinotecan plus carboplatin (IC) and EP regimen in the treatment of SCLC. METHORDS: Seventy-three defined SCLC patients were randomly divided into IC group (n=36) and EP group (n=37). All the patients were given more than two chemotherapy cycles and compare the rate of CR, PR, SD, PD, RR of the two groups. RESULTS: The overall response rate was 58.3% in IC group and 62.2% in EP group. The complete remission was 25.0%(9/36) in IC group and 21.6%(8/37) in EP group. There was no significant difference in the response rate between the two groups (P>0.05). In terms of hematlogic toxicity, neutropenia were more frequent in EP group than those in IC group (P=0.002 5) but there was no significant difference in thrombocytopenia rate (P=0.960 7), leucopenia (P=0.150 0) and anemia rate(P=0.077 5). In terms of toxicity in the gastrointestinal tract there was no significant difference in > III degree diarrhea incidence (P=0.404 7), severe vomiting (P=0.965 0), elevated liver enzymes (P=0.969 6) between the two groups. In nephrotoxicity there was no significant difference in > III degree of hematuria, BUN and creatinine increase rate. Peripheral neuritis, phlebitis, baldness was rarely observed. There was no chemotherapy-related death. CONCLUSION: IC regimen was equally effective and safe for SCLC comparing with EP regimen, we can choose them it for clinical application. Source

Shi Y.,Nanjing Medical University | Liu Y.,Taixing Peoples Hospital | Wang J.,Nanjing Medical University | Jie D.,Nanjing Medical University | And 5 more authors.
PLoS ONE | Year: 2015

BRAF activated non-coding RNA (BANCR), a long non-coding RNA (lncRNA), is crucial for cell migration in melanoma cells and non-small cell lung cancer (NSCLC) cells. However, little is known regarding the role of this gene in the proliferation of colorectal cancer. Therefore, we investigated the involvement of BANCR in the proliferation of colorectal cancer cells. In this study, we show that BANCR expression was significantly down-regulated in colorectal cancer tissues compared with normal tissues, and overexpression of BANCR suppressed colorectal cancer cell growth in vitro and in vivo. We also determined that pCDNA-BANCR-mediated colorectal cancer cell proliferation was associated with induction of G0/G1 cell-cycle arrest and apoptosis enhancement through regulation of p21, and its effects were most likely posttranscriptional. Taken together, our findings suggest that down-regulation of BANCR contributes to the proliferation of colorectal cancer cells, at least in part, through the regulation of p21 protein. © 2015 Shi et al. Source

Zhang C.,Nanjing University | Wang C.,Nanjing University | Chen X.,Nanjing University | Yang C.,Nanjing University | And 13 more authors.
Clinical Chemistry | Year: 2010

BACKGROUND: Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker. METHODS: Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe - based stem - loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls. RESULTS: The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls. CONCLUSIONS: This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC. © 2010 American Association for Clinical Chemistry. Source

Chen X.,Nanjing University | Hu Z.,Nanjing Medical University | Wang W.,U.S. Center for Disease Control and Prevention | Ba Y.,Tianjin Medical University | And 16 more authors.
International Journal of Cancer | Year: 2012

The detection of nonsmall cell lung cancer (NSCLC) at an early stage presents a daunting challenge due to the lack of a specific noninvasive marker. The discovery of microRNAs (miRNAs), particularly those found in serum, has opened a new avenue for tumor diagnosis. To determine whether the expression profile of serum miRNAs can serve as a NSCLC fingerprint, we performed Taqman probe-based quantitative RT-PCR assay to selected differentially expressed serum miRNAs from a sample set including 400 NSCLC cases and 220 controls, and risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. After a two-phase selection and validation process, 10 miRNAs were found to have significantly different expression levels in NSCLC serum samples compared with the control serum samples. Risk score analysis showed that this panel of miRNAs was able to distinguish NSCLC cases from controls with high sensitivity and specificity. Under ROC curves, the AUC for tumor identification in training set and validation set were 0.966 and 0.972, respectively. Furthermore, the expression profile of the 10-serum miRNAs was correlated with the stage of NSCLC patients, especially in younger patients and patients with current smoking habits. More importantly, the serum miRNA-based biomarker for early NSCLC detection was supported by a retrospective analysis in which the 10-serum miRNA profile could accurately classify serum samples collected up to 33 months ahead of the clinical NSCLC diagnosis. Taken together, we demonstrate that the profiling of 10-serum miRNAs provides a novel noninvasive biomarker for NSCLC diagnosis. Copyright © 2011 UICC. Source

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