Adolescent ; Child ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Killer Cells, Natural ; pathology ; Leukocyte Common Antigens ; analysis ; Lymphoma, T-Cell ; genetics ; immunology ; Male ; Microtubule-Associated Proteins ; genetics

Objective To explore the relationship between physical activity(PA) and the risk of colon cancer. Methods Cohort studies on physical activity and risk of colon cancer were identified by searching MEDLINE, EMBASE, Chinese Bio-medicine and Chinese Wanfang databases from January 1979 to December 2009. Results from the individual studies were synthetically combined in our study. Inverse variance weighting was used in fixed effects model and the random effects estimate was based on the DerSimonian-Laird method. Variance-weighted least squares method was used for trend test of summarized dose-response data. Results A total of 28 studies were included in our analysis. An inverse association between physical activities and the risk of colon cancer was observed with the relative risks (RR) as 0.75 [95% confidence interval (CI): 0.66-0.86] in males and 0.85(95%CI: 0.76-0.95)in females, respectively. However, the findings from those documents with high quality showed significant and borderline significant associations between PA and colon cancer in both males (RR=0.74, 95% CI: 0.61-0.90) and females (RR=0.99, 95% CI: 0.95-1.02). Meanwhile, the dose-response trend was not observed either in males (P=0.142) or in females (P=0.417). For men, the pooled RRs differed by subsites were 0.62(95%CI:0.45-0.85) and 0.74 (95%CI:0.56-0.99)for highest level PA, compared with lowest level PA in proximal colon and distal colon cancer,respectively. For women, the pooled RRs were 0.84 (95%CI: 0.69-1.01 ) in proximal colon and 0.75(95%CI: 0.53-1.05)in distal colon cancer, respectively. Conclusion These results added to the evidence for the protective effects in colon cancer among men and women.

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, ¹H NMR, and ¹³C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

OBJECTIVETo investigate the association between anthropometry and risk of breast cancer among pre-and post-menopausal women in urban Shanghai.

METHODSA total of 73 461 female residents aged 40 to 70 years in urban Shanghai were recruited in a prospective cohort study (the Shanghai women's health study) during 1997 through 2000, and were actively followed up biennially. During mean follow-up period of 5.66 years, 432 incident cases of breast cancer were identified in the cohort. Cox regression model was used to estimate the adjusted relative risks (RRs) and 95% confidence intervals (CIs).

RESULTSAfter adjustment for some potential confounding factors, baseline weight, body mass index(BMI), waist-to-hip ratio(WHR) and weight gain since age 20 were positively associated with the increased risk of breast cancer among postmenopausal women. The positive association between height and breast cancer was found among premenopausal women. Among them, those with height taller than 161 cm at age 20 experienced 1.84 fold increased risk (95% CI: 1.30-2.61) of breast cancer compared to their counterpart with height shorter than 157.1 cm. Women who were either much heavier or lighter than average at age 20 were at reduced risk. Further analyses mutually adjusted for BMI and WHR did not substantially alter the positive association for both BMI and WHR. After further adjustment for BMI, weight gain since age 20 was significantly associated to an increased risk for postmenopausal breast cancer (RR = 1.61, 95% CI: 1.09-2.37).

CONCLUSIONSWeight gain and central obesity seemed to be strong predictors for the risk of breast cancer among postmenopausal women. Controlling weight and decreasing fat around waist were effective means to prevent postmenopausal breast cancer and height might serve as a risk factor for premenopausal breast cancer.

Adult ; Aged ; Anthropometry ; Breast Neoplasms ; epidemiology ; China ; epidemiology ; Female ; Humans ; Middle Aged ; Obesity, Abdominal ; Postmenopause ; Risk ; Urban Population ; Weight Gain

OBJECTIVETo evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.

METHODSThe clinical data of 2173 consecutive early-stage breast cancer patients treated by surgery treatments were retrospectively reviewed in order to clarify the indications and contraindications of different modalities. Therapeutic outcome of different surgical treatment modes were compared in terms of recurrence-free survival ( RFS) , disease-free survival ( DFS) , overall survival (OS). The cosmetic results of breast conservation and reconstruction were also evaluated .

RESULTSThe median age of these patients was 51 years ranging from 18 to 91. Of 2173 patients, 547 had stage 0- I lesions and 1626 stage II , and 1155 (53. 2% ) premenopausal. The proportion of patients who received radical surgery, breast conservation and reconstruction after mastectomy was 83. 6% (1817/2173), 10. 5% (229/2173) and 2. 5% (55/2173) , respectively. Younger and premenopausal patients prefer conservative and reconstructive surgeries, which are reasonable for stage 0-I and non-invasive breast cancer patients. Conservative surgery was not suitable for Paget's disease of breast (P = 0. 004) , mastectomy followed by reconstruction in this type of cancer was up to 38. 5%. The recurrence and metastasis rate of conservation or mastectomy were similar with a comparable 3-year RFS of 97. 4% and 95. 4% , respectively; there were also no significant differences in RFS(P =0. 2435) , DFS( P =0. 1395) and OS(P =0. 9406) after having been followed for 3 to 64 months. Similarly, immediate reconstruction did not show any negative effects with only 1 recurrence and 1 metastasis. Aesthetic outcomes were assessed as excellent or good in 90. 0% of breast conservation surgery, and the acceptability of reconstruction was 94. 5%.

CONCLUSIONBreast conserving surgery not only has comparable survival as mastectomy, but also has better cosmetic outcomes. Immediate breast reconstruction can be a suitable option without compromising survival. It is very important in the management for early breast cancer by selecting the most suitable surgery mode for every individual patient not only to cure her disease but also to satisfy the patient psychologically. Conservation should be preferred prior to reconstruction whenever possible.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; surgery ; Carcinoma, Ductal, Breast ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paget's Disease, Mammary ; pathology ; surgery ; Reconstructive Surgical Procedures ; Retrospective Studies

Adult ; Brain ; anatomy & histology ; diagnostic imaging ; Female ; Humans ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the application of fluorescence in-situ hybridization (FISH) in detection of gene translocation in paraffin-embedded tissue samples of synovial sarcoma.

METHODSInterphase FISH was carried out in paraffin-embedded tissue of 42 cases of synovial sarcoma and 9 cases of non-synovial sarcoma, using a LSI SYT (18q11.2) dual color break-apart probe. In all of the cases studied, the gene fusion product SYT-SSX was also analyzed by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSPositive signals were detected in 37 cases (88.1%) of synovial sarcoma by FISH, as compared with 35 cases (83.8%) by RT-PCR and 39 cases (92.9%) by both techniques. Of the 39 positive cases, 33 cases (78.5%) revealed SYT gene translocation.

CONCLUSIONSFISH may serve as an adjunctive diagnostic tool in problematic cases of synovial sarcoma and can be applied in paraffin-embedded tissue samples. As compared with RT-PCR, FISH is also sensitive and reliable. The methodology is less labor intensive and time consuming. FISH has great potential in molecular diagnosis of soft tissue tumors.

Adolescent ; Adult ; Biomarkers, Tumor ; genetics ; Child ; Child, Preschool ; Chromosome Aberrations ; Female ; Head and Neck Neoplasms ; genetics ; metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Lower Extremity ; pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Paraffin Embedding ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoma, Synovial ; genetics ; metabolism ; Soft Tissue Neoplasms ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the effects of San Baoxin on myocardial injury induced by ischemia-reperfusion (MI/R) and thrombogenesis in rats in vivo and ex vivo.

METHODThe experimental model was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 180 min. The Chandler method was used to produced ex vivo thrombosis and an electrical stimulation of common carotid artery was adopted to form in vivo thrombosis respectively, the effect of antithrombosis induced by San Baoxin was observed.

RESULTSan Baoxin significantly decreased the content of malondialdehyde (MDA), obviously elevated the activity of superoxide dismutase (SOD) and increased the amount of NO of the serum simultaneously. The San Baoxin at the dosage of 10 g x kg(-1) could remarkably lengthen the OT ( P < 0.05). All San Baoxin dosages could inhibit the formation of ex vivo thrombosis.

CONCLUSIONSan Baoxin protects the myocardium from injury of ischemic and reperfusion. The protective effect of San Baoxin may be due to that it can dilate vessels, increase the activity of clearance enzyme of free radical and inhibit lipid peroxidation and the formation of ex vivo and in vivo thrombosis.

Animals ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Male ; Malondialdehyde ; blood ; Myocardial Ischemia ; blood ; pathology ; Myocardial Reperfusion Injury ; blood ; pathology ; Nitric Acid ; blood ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Superoxide Dismutase ; blood ; Thrombosis ; pathology

AIM: To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety. METHODS: All of the key intermediates were synthesized from stevioside, and the target compounds were obtained through glycosylation of the 4-carboxyl group. The cytotoxicity of the target compounds against six human cancer cell lines, HepG2, Bel-7402, A549, U251, MCF-7 and MDA-MB-231, were evaluated by the MTT assay. RESULTS: Compound 1b was more effective than the positive control adriamycin against the HepG2, Bel-7402, A549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 0.12, 0.91, 0.35, 0.08, and 0.07 μmol·L(-1), respectively. Moreover, compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line (IC50, 0.01 μmol·L(-1)). CONCLUSION Compounds 1b and 3c could be considered as potential anticancer candidates for further study.
Antineoplastic Agents ; chemistry ; toxicity ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Kaurane ; chemistry ; toxicity ; Drug Evaluation, Preclinical ; Glycosylation ; Humans ; Molecular Structure

D-alanine (D-Ala) is an essential amino acid that has a key role in bacterial cell wall synthesis. Alanine racemase (Alr) is a unique enzyme that interconverts L-alanine and D-alanine in most bacteria, making this enzyme a potential target for antimicrobial drug development. Streptococcus mutans is a major causative factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Alr in S. mutans. We constructed alr mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that alr deletion was lethal to S. mutans. A minimal supplement of D-Ala (150μg·mL?1) was required for the optimal growth of the alr mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the alr mutant strain. We also determined the compromised competitiveness of the alr mutant strain relative to the wild-type S. mutans against other oral streptococci (S. sanguinis or S. gordonii), demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of alr to the growth and competitiveness of S. mutans, Alr may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.