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Wang X.,Jilin University | Zhu W.,Jilin University | Zhao X.,Jilin Province Cancer Hospital | Wang P.,Jilin University
International Journal of Molecular Medicine

The expression levels of the copper transporter P-type adenosine triphosphatase (ATP7B) are known correlate with tumor cell sensitivity to cisplatin. However, the mechanisms underlying cisplatin resistance remained poorly understood. Therefore, in the present study, we treated Hep-2 cells and in-house-developed vincristine-resistant Hep-2v cells with 50, 100, or 200 M cisplatin and assessed cell viability after 24 or 48 h. Hep-2v cells were shown to be resistant to 50-200 M cisplatin. Furthermore, using immunofluorescence staining and western blot analysis, we noted that ATP7B, but not copper-transporting ATPase 1 (ATP7A), expression was significantly increased in Hep-2v cells, and this increase was maintained at a higher level compared with Hep-2 cells. As ATP7B is a target of microRNA 133a (miR133a), the ability of miR133a to influence cisplatin sensitivity in Hep-2v cells was then assessed by CCK-8 assay. We noted that miR133a expression was lower in both Hep-2 and Hep-2v cells compared with epithelial NP69 cells. Following treatment with 50 M cisplatin, in Hep-2v cells expressing exogenous miR133a we noted reduced ATP7B expression, and these cells had a significantly lower survival rate compared with the control. The present study demonstrates that miR133a enhances the sensitivity of multidrug-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression. Source

Yang J.-J.,Shandong Academy of Sciences | Huang C.,Fujian Province Cancer Hospital | Chen G.-Y.,Heilongjiang Province Cancer Hospital | Song Y.,Nanjing General Hospital | And 4 more authors.
BMC Cancer

Background: Recent advances have shown that histology and genetic biomarkers are important in patient selection, which have led to significantly better outcomes for lung cancer patients. However, most new treatments only apply to adenocarcinoma or non-squamous, and in squamous carcinoma there is little breakthrough. In a phase III trial nab-paclitaxel plus carboplatin showed superior response rate over paclitaxel and carboplatin. In subgroup analysis the squamous histology appeared to be a predictive factor to nab-paclitaxel treatment.Methods/Design: This is an open-label, randomized, active controlled phase II trial. A total of 120 untreated advanced squamous lung cancer patients are randomized at a 1:1 ratio to receive nab-paclitaxel (135 mg/m2, d1, 8, q3w) plus carboplatin (AUC 5, d1, q3w) or gemcitabine (1,250 mg/m2, d1, 8, q3w) and carboplatin (AUC 5, d1, q3w). The primary endpoint is objective response rate and the second endpoints are progression free survival, overall survival, safety and biomarkers associated with nab-paclitaxel. The treatment will continue up to six cycles or intolerable toxicity.Discussion: This ongoing trial will be the first prospective randomized trial to explore the efficacy of nab-paclitaxel as the first-line treatment specifically in squamous carcinoma of lung.Study number: CTONG1002. Trial Registration: Clinicaltrials.gov reference: NCT01236716. © 2014 Yang et al.; licensee BioMed Central Ltd. Source

Qin S.,Peoples Liberation Army Cancer Center | Cheng Y.,Jilin Province Cancer Hospital | Liang J.,Qingdao University | Shen L.,Peking University | And 11 more authors.

Background. The EACH study assessed the efficacy of oxali-platin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) compared with doxorubicin alone in terms of overall survival (OS), progression-free survival (PFS), and safety in patients with advanced hepatocellular carcinoma (HCC). We present the results of this study in Chinese patients.Methods. In a multicenter, open-label, randomized, phase III study (NCT00471965), 371 patients (279 patients from the People’s Republic of China) were randomized 1:1 to receive either FOLFOX4 or doxorubicin until disease progression, intolerable toxicity, death, or surgical resection.Results. Baseline characteristics of the Chinese patients enrolled in the study were similar for the 2 treatment groups and in comparison with the whole EACH cohort. Median OS at the prespecified time point of treatment was 5.7 months with FOLFOX4 and 4.3 months with doxorubicin (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.55-0.98; p 5.03). At the end of the follow-up period, median OS was 5.9 months with FOLFOX4 and 4.3 months with doxorubicin (HR: 0.75; 95% CI: 0.58-0.98; p 5.03). Median PFS was 2.4 months and 1.7 months in the FOLFOX4 and doxorubicin groups, respectively (HR: 0.55; 95% CI: 0.45-0.78;p 5.0002).The response rate (RR) and disease control rate (DCR) were significantly higher in the FOLFOX4group than in the doxorubicin group (RR: 8.6% vs. 1.4%, p 5.006; DCR: 47.1% vs. 26.6%, p 5.0004). Hematological toxicity was more frequently reported in the FOLFOX4 group.Conclusion. For Chinese HCC patients enrolled in the EACH study, FOLFOX4 significantly improved the RR and DCR and prolonged survival compared with doxorubicin. Systemic chemotherapy with oxaliplatin-based regimens may play an important role in the treatment of Chinese patients with advanced HCC. © AlphaMed Press 2014. Source

Wang X.,Jilin University | Zhao X.,Jilin Province Cancer Hospital | Zhu W.,Jilin University
Oncology Letters

Adult laryngeal hemangioma is an extremely rare and slowly progressing vascular tumor. The present study describes the first reported case of a male with a large laryngeal hemangioma that was treated by ultrasonic scalpel. A 61‑year‑old male presented to our hospital with a recurrent pharyngeal foreign body sensation, without hoarseness, hemoptysis, expectoration or dyspnea. A blue‑black mass was detected in the right pyriform sinus, with a morular surface and a wide pedicle positioned lateral to the right arytenoid cartilage and aryepiglottic fold under electronic laryngoscopy. Following tracheotomy under local anesthesia, right superior laryngeal artery ligation and laryngeal hemangioma resection via a lateral neck hypopharyngeal approach were performed under general anesthesia using an ultrasonic scalpel. Pathological examination verified that the tumor was a cavernous hemangioma. On day 11, subsequent to post‑operative anti‑inflammatory and symptomatic treatment, electronic laryngoscopy showed that the arytenoid mucosal edema had decreased and that the movement of the arytenoid was good. There was no recurrence of hemangioma during a 2‑year follow‑up period. Therefore, it is recommended that complete surgical resection using an ultrasonic scalpel should be considered for similar cases involving large laryngeal hemangiomas. © 2015, Spandidos Publications. All Rights Reserved. Source

Shi Y.,Peking Union Medical College | Shi Y.,Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs | Zhang L.,Sun Yat Sen University | Liu X.,307 Hospital of the Academy of Military Medical science | And 29 more authors.
The Lancet Oncology

Background: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods: In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings: 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Interpretation: Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding: Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program. © 2013 Elsevier Ltd. Source

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