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Cheng A.,Zhejiang Province Peoples Hospital | Chen S.,Fudan University | Zhang Y.,Zhejiang University | Zhang Y.,Key Laboratory of Medical Molecular Imaging of Zhejiang Province | And 2 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2011

Purpose: This study evaluated the tolerance and therapeutic efficacy of rhenium-188 hydroxyethylidene diphosphonate ( 188Re-HEDP) in patients with different types of advanced cancer suffering from bone pain caused by osseous metastases. Methods: Sixty-four patients received a single injection of escalating doses of 188Re-HEDP with various dosages. Vital signs were observed before and after treatment for 8 weeks; adverse effects and rebound pain were recorded within 8 weeks after injection. Blood counts, biochemical parameters, and electrocardiogram were also measured over a period of 8 weeks. Clinical follow-up studies including the bone pain score and the Karnofsky performance score were performed. Pain response was scored by a four-point pain-rating scale as complete, marked, mild, and no response. Results: No adverse effects or clinically significant changes in vital signs, electrocardiograms, and biochemical parameters in patients were observed, and there was no statistical change in alkaline phosphate levels in patients before or after treatment. The overall nadir of thrombopenia was at week 4, leucopoenia at week 3, and anemia at week 8. At week 8, the mean level of platelets and leukocytes returned to baseline levels. The pain score descended from 8.11 to 7.74 on the day of therapy, with a nadir of 4.89 at week 4, and up to 6.67 at week 8 after therapy (p < 0.05). The Karnofsky performance score continually increased from 74.81 before therapy to 82.31 at 8 weeks (p < 0.05). Pain palliation was reported by 73.33% of patients, with a mean duration of 6.85 weeks and a mean start time of 4.05 days. Of the specific tumor types, pain relief was achieved in 84.62% of patients with prostate cancer, 78.57% with breast cancer, 62.50% with lung cancer, and 55.56% with liver cancer. Conclusions: 188Re-HEDP is a useful radiopharmaceutical agent for improving bone pain in patients with advanced cancer with painful bone metastases. © Copyright 2011, Mary Ann Liebert, Inc.

Ou Z.M.,Zhejiang University of Technology | Feng W.F.,Zhejiang Province Peoples Hospital
Advanced Materials Research | Year: 2013

(S)-tert-butyl 3-hydroxybutyrate was synthesized by asymmetric reduction of tert-butyl acetoacetate with Saccharomyces cerevisiae B5 as catalyst. The enantiometric excess of (S)-tert-butyl 3-hydroxybutyrate increased with addition of more amount of substrate. High optical purity of product can be obtained when 6 g/L chloroform was used as inhibitor. The optimum reduction time, temperature, and initial pH of reaction mixture were 60 h, 30 deg;C, and 6.2. Addition of more biomass and lower amount of substrate helped to get high conversion. Conversion and enantiometric excess of product reached 100% when initial substrate concentration and biomass were 2.0 g/L and 140 g/L with 6 g/L chloroform as inhibitor. © (2013) Trans Tech Publications, Switzerland.

Xu G.,Zhejiang University | Li Y.,Zhejiang Province Peoples Hospital | Jiang X.,Zhejiang University | Chen H.,Zhejiang University
Journal of Cellular Biochemistry | Year: 2016

Cholesterol gallstone disease (CGD) is a hepatobiliary disorder which results from a biochemical imbalance in the gallbladder bile. Here we show that loss of CAV1 sensitized mice to lithogenic diet-induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts. The combined effect of increased biliary cholesterol concentration and decreased biliary bile salt secretion in CAV1−/− mice led to an increased cholesterol saturation index and the formation of cholesterol crystals. At the signaling level, the ERK/AP-1 pathway seems to mediate the effects of CAV1 on biliary BA homeostasis and might be developed as a therapeutic target for CGD. We propose that CAV1 is an anti-lithogenic factor and that the CAV1−/− mice may offer a convenient CGD model to develop therapeutic interventions for this disease. J. Cell. Biochem. 117: 2118–2127, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dong S.,Zhejiang University | Xia Q.,Zhejiang Province Peoples Hospital | Wu Y.-J.,Zhejiang University
Otolaryngology - Head and Neck Surgery (United States) | Year: 2015

Objective. We aimed to identify whether thyroid peroxidase antibodies (TPOAb) are indicative of multifocal papillary thyroid cancer (PTC) in Hashimoto's thyroiditis (HT) patients and may help to determine necessity for total thyroidectomy. Study design. Retrospective cohort study. Setting:. Teaching hospital. Subjects. A total of 808 consecutive patients with HT alone or with HT and unifocal or multifocal PTC were included. Methods. Preoperative thyroid function tests, TPOAb determination, preoperative ultrasonography, intraoperative frozen biopsy, and postoperative routine pathologic examination to confirm thyroid nodules were performed for all patients. Patients with nodules or malignancy potential on ultrasound and fine-needle aspiration cytology were included. Patients with hyperthyroidism, concomitant chronic disease, a history of other malignant tumors, or history of major diseases were excluded. All patients underwent surgery, and HT and PTC were confirmed by postoperative pathologic results. Results. No significant differences were found in age and sex between groups (P >.05). TPOAb ≤1300 IU/mL were more prevalent in the HT + unifocal PTC group than in the other groups (99.57% vs 15.52% and 60.75%, P<.001). TPOAb >1300 IU/mL were more prevalent in the HT + multifocal PTC group than in the other groups (84.48% vs 0.43% and 39.25%; P < .001). Compared to the other groups, the HT + multifocal PTC group had higher percentages of patients with elevated thyroid-stimulating hormone and positive central lymph node (LN) metastasis (elevated thyroid-stimulating hormone: 8.7% vs 3.2% and 6.5%, P = .008; positive central LN metastasis: 74.57% vs 67.38% and 0%, P<.001). Conclusion. High TPOAb levels (>1300 IU/mL) are definitive indicators of multifocal PTC in HT patients, which may support surgical treatment with total thyroidectomy. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

Jiang X.,Zhejiang University | Guo H.,Zhejiang University | Wu J.,Zhejiang University | He Q.,Zhejiang Province Peoples Hospital | And 9 more authors.
Haematologica | Year: 2014

Germinal center lymphoma is a heterogeneous human lymphoma entity. Here we report that constitutive activity of SHP2 (PTPN11) and its downstream kinase ERK is essential for the viability of germinal center lymphoma cells and disease progression. Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma. Furthermore, SHP2/ERK signaling is required to maintain the CD19/c-Myc loop, which preferentially promotes survival of a distinct subtype of germinal center lymphoma cells carrying the MYC/IGH translocation. These findings demonstrate a critical function for SHP2/ERK signaling upstream of c-Myc in germinal center lymphoma cells and provide a rationale for targeting SHP2 in the therapy of germinal center lymphoma. © 2014 Ferrata Storti Foundation.

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