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Liu Y.,Zhejiang University | Zheng X.,Zhejiang University | Yu Q.,Zhejiang University | Wang H.,Cancer Hospital of Zhejiang Province | And 6 more authors.
Science Translational Medicine | Year: 2016

Renal cell carcinoma (RCC) is known for its multidrug resistance. Using data obtained from the cancer transcriptome database Oncomine and the proteome database The Human Protein Atlas, we identified the repression of organic cation transporter OCT2 as a potential factor contributing to oxaliplatin resistance in RCC. By analyzing OCT2 expression in collected patient tissues and commercial tissue microarray specimens, we demonstrated OCT2 repression in RCC at both transcription and protein levels. Epigenetic analysis revealed that the repressed OCT2 promoter in RCC is characterized by hypermethylated CpG islands and the absence of H3K4 methylation. Further mechanistic studies showed thatDNAhypermethylation blockedMYCactivation of OCT2 by disrupting its interaction with the E-Box motif, which prevented MYC from recruiting MLL1 to catalyze H3K4me3 at the OCT2 promoter and resulted in repressed OCT2 transcription. Targeting thismechanism, we designed a sequential combination therapy and demonstrated that epigenetic activation of OCT2 by decitabine sensitizes RCC cells to oxaliplatin both in vitro and in xenografts. Our study highlights the potential of translating "omics" data into the development of targeted therapies.

Shi X.,Cancer Hospital of Zhejiang Province
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To observe the clinical efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer (NSCLC). Seventy patients aged 70 years or over with stage IIIb-IV NSCLC were equally and randomly divided into pemetrexed plus cisplatin group (PC) and gemcitabine plus carboplatin group (GC). Patients in the PC group received pemetrexed (PEM) 500 mg/m(2) on day 1, and carboplatin (CBP) AUC5 on day 1 for 21-day cycle. Patients in the GC group received gemcitabine 1000 mg/m(2) on days 1 and 8, CBP AUC5 on day 1 for a 21-day cycle. In the PC and GC groups, CR 0 and 0, PR 10 and 8, response rates 28.6% and 22.9% were observed, respectively. There was no statistically significant difference between the two groups (χ(2) = 0.299, P = 0.584). The 1-year and 2-year survival rates of the PC and GC groups were 48.6% vs. 45.7% and 11.4% vs. 11.4%, respectively, with a median survival of 11.00 and 10.00 months, without a statistically significant difference between the two groups (χ(2) = 0.01, P = 0.919). Regarding toxicities, the incidences of neutropenia/thrombocytopenia, nausea and vomiting (grade III ∼ IV) in the GC group were significantly higher than those in the PC group (P < 0.05). According to the observer scale of lung cancer symptoms, the post-treatment scores improved in both the two groups, and with no significant difference between them (P > 0.05). PC and GC show similar efficacy for elderly NSCLC patients, however, the toxicities in PC patients are lower than those in GC patients. Thus, pemetrexed combined with carboplatin is an effective chemotherapeutic regimen for advanced NSCLC in elderly patients.

Xu Y.-J.,Cancer Hospital of Zhejiang Province | Zheng X.,Cancer Hospital of Zhejiang Province
Chinese Journal of Cancer Biotherapy | Year: 2010

Radiotherapy combined with chemotherapy is the standard therapy strategy for locally advanced unresectable non-small cell lung cancer (NSCLC); however, this treatment is intolerable for some NSCLC patients and its therapy outcome seems to have reached a "platform". Epidermal growth factor receptor (EGFR) inhibitors may enhance radiosensitivity of NSCLC cells by increasing the cells in G2/M phase, reducing the cells in S phase, inhibiting phosphorylation of multi proteins in EGFR signal transduction pathway, and inhibiting the proliferation of NSCLC cells. The initial clinical results of radiotherapy or chemoradiotherapy in combination with EGFR-TKI show certain efficacy, but the long-term outcome is uncertain. Gefitinib combined with chemoradiotherapy resulted in a longer median survival and higher 2-year survival rate than the single therapy group; further randomized phase III trials are needed to validate the efficacy of the combination treatment. Above all, radiotherapy or chemoradiotherapy combined with EGFR inhibitors has great potential for patients with locally advanced unresectable non-small cell lung cancer and is worthy of further study.

Wang J.,Cancer Hospital of Zhejiang Province | Fang J.,Cancer Hospital of Zhejiang Province
Journal of medical case reports | Year: 2014

INTRODUCTION: Ectopic thyroid is characterized by the presence of thyroid tissue in a site other than in its usual pretracheal region. It is a rare condition among the thyroid diseases. Dural ectopic thyroid present in the cervical and anterior mediastinal has not been reported.CASE PRESENTATION: A 45-year-old Chinese woman presented with a nonfunctional ectopic thyroid located both in the cervical and anterior mediastinum. The ectopic thyroid was removed under video-assisted thoracoscopic surgery using a transverse neck incision and her postoperative period has been uneventful thus far.CONCLUSIONS: Ectopic thyroid is a rare condition among the thyroid diseases, and its location in the anterior mediastinum is even more uncommon. Less than 15 cases have been reported in the last four decades. This is the first case of ectopic thyroid to appear in both the cervical and anterior mediastinum at same time. Masses in the anterior mediastinal are usually thymoma, lymphoma, pheochromocytoma and germ cell tumors. Ectopic thyroid in this area is quite rare so this case enhances our understanding of the diagnosis of mediastinal masses.

Wang Y.,Cancer Hospital of Zhejiang Province | Wang Y.,Zhejiang University | Ding L.,Zhejiang University | Wang X.,Zhejiang University | And 7 more authors.
American Journal of Translational Research | Year: 2012

As a nature phytoalexin found in grapes, resveratrol has been proposed as a potential drug for cancer chemoprevention and treatment. However, its poor bioavailability limits its potential clinical application. Pterostilbene, the natural dimethylated analog of resveratrol with greater bioavailability, was confirmed to inhibit tumor growth both in vivo and in vitro, demonstrating its potential for further clinical application. In the current study, we found that pterostilbene could markedly inhibit the growth of two independent breast cancer cell lines. Both apoptosis and cell cycle arrest as well as the inhibition of wnt singling was induced by pterostilbene. The dominant-active mutant of β- catenin could reverse the growth inhibitory effect of pterostilbene, indicating that the inhibition of wnt signaling is important to the growth inhibitory effect of pterostilbene. Interestingly, pterostilbene induced autophagy and blockage of autophagy augmented pterostilbene-induced growth inhibition, suggesting that the combination of autophagy inhibitors with pterostilbene and other therapeutics such as endocrine drugs could serve as a new and promising strategy for the treatment of breast cancer cells.

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