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Medical Genetics
Mechanisms of inherited cancer susceptibility
Shirley HODGSON
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 1-4.   https://doi.org/10.1631/jzus.B073001
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A small proportion of many cancers are due to inherited mutations in genes, which result in a high risk to the individual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes, oncogenes, genes encoding proteins involved in DNA repair and cell cycle control, and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.
HER2 over-expression and response to different chemotherapy regimens in breast cancer
Jin ZHANG, Yan LIU
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 5-9.   https://doi.org/10.1631/jzus.B073003
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Purpose: To exam the relationship between HER2 over-expression and different adjuvant chemotherapies in breast cancer. Patients and Methods: A total of 1625 primary breast cancer patients who received post-surgery adjuvant chemotherapy in Tianjin Cancer Hospital, China, from July 2002 to November 2005 were included in the study. Among them, 600 patients were given CMF (CTX+MTX+5-Fu) regimen, 600 given CEF (CTX+E-ADM+5-Fu) regimen, and 425 given anthracyclines plus taxanes regimen, with mean follow-up time of 42 months. Results: In CMF treatment group, the 3-year disease free survival (DFS) in HER2 over-expressed patients was lower than that of the HER2-negative ones (89.80% vs 91.24%, P=0.0348); in node-positive subgroup, the 3-year DFS was 84.72% in HER2 over-expressed patients, and 90.18% in the HER-2-negative ones (P=0.0271). Compared to CMF regimen, anthracyclines and anthracyclines plus taxanes regimens are more effective (P<0.05) in node-positive HER2 over-expression than those in the node-negative. Conclusion: HER2 over-expression is an independent index for predicting poor prognosis and short DFS for breast cancer patients. HER2 over-expressed patients are resistant to CMF regimen chemotherapy, but sensitive to anthracyclines-based or anthracyclines plus taxanes regimen. HER2 expression can be taken as a marker for therapies in breast cancer.
Genetics in medical school curriculum: A look at the University of Rochester School of Medicine and Dentistry
Deanne M. ROBINSON, Chin-To FONG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 10-15.   https://doi.org/10.1631/jzus.B073004
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Genetics is assuming an increasingly important role in medicine. As a result, the teaching of genetics should also be increased proportionally to ensure that future physicians will be able to take advantage of the new genetic technology, and to understand the associated ethical, legal and social issues. At the University of Rochester School of Medicine and Dentistry, we have been able to incorporate genetic education into a four-year medical curriculum in a fully integrated fashion. This model may serve as a template for other medical curriculum still in development.
Biomedicine
A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells
Zuo-fu PENG, Lin-xiang LAN, Fang ZHAO, Jing LI, Qiang TAN, Han-wei YIN, Hui-hui ZENG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 16-21.   https://doi.org/10.1631/jzus.B071605
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Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich’s ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.
Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect
Si-yuan LI, Jun-ling CAO, Zhong-li SHI, Jing-hong CHEN, Zeng-tie ZHANG, Clare E. HUGHES, Bruce CATERSON
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 22-33.   https://doi.org/10.1631/jzus.B071322
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Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD), the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA), soluble CD44 (sCD44), IL-1β and TNF-α levels in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was determined by flow cytometry (FCM). CD44, hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13, 3-B-3(−) and 2-B-6 epitopes in the cartilage reconstructed in vitro. Results: T-2 toxin inhibited CD44, HAS-2, and aggrecan mRNA expressions, but promoted aggrecanase-2 mRNA expression. Meanwhile, CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition, ELISA results indicated that there were higher sCD44, IL-1β and TNF-α levels in T-2 toxin group. Similarly, higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore, using monoclonal antibodies BC-13, 3-B-3 and 2-B-6, strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin, whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. Conclusion: T-2 toxin could inhibit aggrecan synthesis, promote aggrecanases and pro-inflammatory cytokines production, and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage, inducing aggrecan loss in the end, which may be the initiation of the cartilage degradation.
Comparison of an SMS text messaging and phone reminder to improve attendance at a health promotion center: A randomized controlled trial
Zhou-wen CHEN, Li-zheng FANG, Li-ying CHEN, Hong-lei DAI
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 34-38.   https://doi.org/10.1631/jzus.B071464
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Objective: To compare the efficacy of a short messaging service (SMS) text messaging and phone reminder to improve attendance rates at a health promotion center. Methods: A total of 1 859 participants who had scheduled appointments in the health promotion center of our hospital from April 2007 to May 2007 were enrolled in the study and randomly assigned into 3 groups: control (no reminder) group, SMS text messaging reminder group and telephone reminder group. Attendance rates and costs of interventions were collected. Results: A total of 1848 participants were eligible for analysis. Attendance rates of control, SMS and telephone groups were 80.5%, 87.5% and 88.3%, respectively. The attendance rates were significantly higher in SMS and telephone groups than that in the control group, with odds ratio 1.698, 95% confidence interval 1.224 to 2.316, P=0.001 in the SMS group, and odds ratio 1.829, 95% confidence interval 1.333 to 2.509, P<0.001 in the telephone group. However, there was no difference between the SMS group and the telephone group (P=0.670). The cost effectiveness analysis showed that the cost per attendance for the SMS group (0.31 Yuan) was significantly lower than that for the telephone group (0.48 Yuan). Conclusion: SMS and telephone are effective reminders for improving attendance rate at a health promotion center. SMS reminder may be more cost-effective compared with the telephone reminder.
Breast metastasis from small cell lung carcinoma
Shi-ping LUH, Chih KUO, Thomas Chang-yao TSAO
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 39-43.   https://doi.org/10.1631/jzus.B072258
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Breast metastases from extramammary neoplasms are very rare. We presented a 66 year-old female with metastasis of small cell lung carcinoma to the breast. She presented with consolidation over the left upper lobe of her lung undetermined after endobronchial or video-assisted thoracoscopic surgery (VATS) biopsy, and this was treated effectively after antibiotic therapy at initial stage. The left breast lumps were noted 4 months later, and she underwent a modified radical mastectomy under the impression of primary breast carcinoma. However, the subsequent chest imaging revealed re-growing mass over the left mediastinum and hilum, and cells with the same morphological and staining features were found from specimens of transbronchial brushing and biopsy. An accurate diagnosis to distinguish a primary breast carcinoma from metastatic one is very important because the therapeutic planning and the outcome between them are different.
Biotechnology
Effects of over-expressing resistin on glucose and lipid metabolism in mice
You LIU, Qun WANG, Ying-bin PAN, Zhi-jie GAO, Yan-fen LIU, Shao-hong CHEN
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 44-50.   https://doi.org/10.1631/jzus.B071479
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Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.
Optimization of acidic extraction of astaxanthin from Phaffia rhodozyma
Hui NI, Qi-he CHEN, Guo-qing HE, Guang-bin WU, Yuan-fan YANG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 51-59.   https://doi.org/10.1631/jzus.B061261
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Optimization of a process for extracting astaxanthin from Phaffia rhodozyma by acidic method was investigated, regarding several extraction factors such as acids, organic solvents, temperature and time. Fractional factorial design, central composite design and response surface methodology were used to derive a statistically optimal model, which corresponded to the following optimal condition: concentration of lactic acid at 5.55 mol/L, ratio of ethanol to yeast dry weight at 20.25 ml/g, temperature for cell-disruption at 30 °C, and extraction time for 3 min. Under this condition, astaxanthin and the total carotenoids could be extracted in amounts of 1294.7 μg/g and 1516.0 μg/g, respectively. This acidic method has advantages such as high extraction efficiency, low chemical toxicity and no special requirement of instruments. Therefore, it might be a more feasible and practical method for industrial practice.
Keratinase production and keratin degradation by a mutant strain of Bacillus subtilis
Cheng-gang CAI, Bing-gan LOU, Xiao-dong ZHENG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 60-67.   https://doi.org/10.1631/jzus.B061620
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A new feather-degrading bacterium was isolated from a local feather waste site and identified as Bacillus subtilis based on morphological, physiochemical, and phylogenetic characteristics. Screening for mutants with elevated keratinolytic activity using N-methyl-N′-nitro-N-nitrosoguanidine mutagenesis resulted in a mutant strain KD-N2 producing keratinolytic activity about 2.5 times that of the wild-type strain. The mutant strain produced inducible keratinase in different substrates of feathers, hair, wool and silk under submerged cultivation. Scanning electron microscopy studies showed the degradation of feathers, hair and silk by the keratinase. The optimal conditions for keratinase production include initial pH of 7.5, inoculum size of 2% (v/v), age of inoculum of 16 h, and cultivation at 23 °C. The maximum keratinolytic activity of KD-N2 was achieved after 30 h. Essential amino acids like threonine, valine, methionine as well as ammonia were produced when feathers were used as substrates. Strain KD-N2, therefore, shows great promise of finding potential applications in keratin hydrolysis and keratinase production.
Determination of potential management zones from soil electrical conductivity, yield and crop data
Yan LI, Zhou SHI, Ci-fang WU, Hong-yi LI, Feng LI
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 68-76.   https://doi.org/10.1631/jzus.B071379
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One approach to apply precision agriculture to optimize crop production and environmental quality is identifying management zones. In this paper, the variables of soil electrical conductivity (EC) data, cotton yield data and normalized difference vegetation index (NDVI) data in an about 15 ha field in a coastal saline land were selected as data resources, and their spatial variabilities were firstly analyzed and spatial distribution maps constructed with geostatistics technique. Then fuzzy c-means clustering algorithm was used to define management zones, fuzzy performance index (FPI) and normalized classification entropy (NCE) were used to determine the optimal cluster numbers. Finally one-way variance analysis was performed on 224 georeferenced soil and yield sampling points to assess how well the defined management zones reflected the soil properties and productivity level. The results reveal that the optimal number of management zones for the present study area was 3 and the defined management zones provided a better description of soil properties and yield variation. Statistical analyses indicate significant differences between the chemical properties of soil samples and crop yield in each management zone, and management zone 3 presented the highest nutrient level and potential crop productivity, whereas management zone 1 the lowest. Based on these findings, we conclude that fuzzy c-means clustering approach can be used to delineate management zones by using the given three variables in the coastal saline soils, and the defined management zones form an objective basis for targeting soil samples for nutrient analysis and development of site-specific application strategies.
Medium optimization for enhanced production of cytosine-substituted mildiomycin analogue (MIL-C) by Streptoverticillium rimofaciens ZJU 5119
Dan YE, Zhi-nan XU, Pei-lin CEN
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(1): 77-84.   https://doi.org/10.1631/jzus.B071372
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Cytosine-substituted mildiomycin analogue (MIL-C) was produced effectively by supplementing cytosine into the culture of Streptoverticillium rimofaciens. In order to improve the yield of MIL-C, statistically-based experimental designs were applied to optimize the fermentation medium for S. rimofaciens ZJU 5119. Fifteen culture conditions were examined for their significances on MIL-C production using Plackett-Burman design. The Plackett-Burman design and one-variable-at-a-time design indicated that glucose and rice meal as the complex carbon sources, and peanut cake meal and NH4NO3 as the complex nitrogen sources were beneficial for MIL-C production in S. rimofaciens ZJU 5119. The results of further central composition design (CCD) showed that the optimal concentration of glucose, rice meal and peanut cake meal were 18.7 g/L, 64.8 g/L and 65.1 g/L, respectively. By using this optimal fermentation medium, the MIL-C concentration was increased up to 1336.5 mg/L, an approximate 3.8-fold improvement over the previous concentration (350.0 mg/L) with un-optimized medium. This work will be very helpful to the large-scale production of MIL-C in the future.
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