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Biomedical subjects

Fan Jin

Publications and source records attributed to Fan Jin.

At least 37 records · Page 2Linked to original sources

Genetic polymorphisms in glutathione-S-transferase genes (GSTM1, GSTT1, GSTP1) and survival after chemotherapy for invasive breast carcinoma.

BACKGROUND: It has been suggested that genetic polymorphisms in certain glutathione-S-transferase (GST) genes reduce the effectiveness of detoxifying cytotoxins generated by chemotherapeutic agents, potentially resulting in enhanced clinical responses to chemotherapy. METHODS: The authors evaluated common polymorphisms in the GSTM1, GSTT1, and GSTP1 genes for associations with overall survival in 1034 patients with invasive breast carcinoma who were recruited into the Shanghai Breast Cancer Study between 1996 and 1998, treated with chemotherapy, and followed for a median of 5.3 years. RESULTS: After adjusting for age, tumor stage, and the use of radiotherapy and tamoxifen, women who were homozygous for the variant GSTP1 105Val allele had a 60% reduction in mortality risk compared with women who were homozygous for the Ile allele (hazard ratio, 0.4; 95% confidence interval, 0.2-0.8). No association was found with respect to any of the GSTM1 or GSTT1 genotypes. CONCLUSIONS: The results of the current study indicate a potential role for GSTP1 polymorphism in predicting the clinical outcomes of patients with breast carcinoma who are treated with chemotherapy.

Acyltransferases↗

High frequency of Y chromosome microdeletions in idiopathic azoospermic men with high follicle-stimulating hormone levels.

Y chromosome microdeletions were detected in 33.3% (6 out of 18) of idiopathic azoospermic patients with high serum follicle-stimulating hormone (FSH) levels in the present study. The results suggest that it may be necessary to detect microdeletions in patients with azoospermia, especially for those with high serum FSH levels, before assisted reproductive technology (ART) is provided to them.

Adult↗

Up-regulation of DNA methyltransferase 3B expression in endometrial cancers.

OBJECTIVE: To understand the role of epigenetic regulation in the pathogenesis of endometrial cancer, we have characterized DNA methyltransferase 3B (DNMT3B) gene expression in normal, Grade I and Grade III endometrioid cancers, and examined DNMT3B promoter activities in endometrial cancer cell lines. METHODS: DNMT3B expression was measured in normal, Grade I, and Grade III endometrioid cancer samples. Real-time PCR and Western blot analysis were performed to compare DNMT3B mRNA and protein levels. DNMT3B levels were also compared among endometrial cell lines including those for Ishikawa, KLE, AN3, RL-95, HEC-1A, and HEC-1B. DNMT3B promoter reporter plasmids were constructed. Promoter activities in well and poorly differentiated cell lines were compared by in vitro reporter gene transfection. RESULTS: DNMT3B was significantly up-regulated in both Grade I and Grade III cancers as compared to normal controls. Western blot analysis confirmed the increased DNMT3B protein expression in cancer tissues. It was also found that the well-differentiated endometrial cell line, Ishikawa, expressed lower levels of DNMT3B than the poorly differentiated KLE cells, the expression patterns similar to those observed in tumor specimens. CONCLUSION: The results suggest that DNMT3B overexpression may play a significant role in endometrial cancer development. In addition, the transfection experiments indicated that DNMT3B promoters are more active in the poorly differentiated endometrial cancer cell lines, suggesting that the in vitro assay provides a useful model for studying the DNMT3B transactivation mechanism related to tumor transformation.

Carcinoma, Endometrioid↗

Human embryonic stem cell lines derived from the Chinese population.

Six human embryonic stem cell lines were established from surplus blastocysts. The cell lines expressed alkaline phosphatase and molecules typical of primate embryonic stem cells, including Oct-4, Nanog, TDGF1, Sox2, EBAF, Thy-1, FGF4, Rex-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. Five of the six lines formed embryoid bodies that expressed markers of a variety of cell types; four of them formed teratomas with tissue types representative of all three embryonic germ layers. These human embryonic stem cells are capable of producing clones of undifferentiated morphology, and one of them was propagated to become a subline. Human embryonic stem cell lines from the Chinese population should facilitate stem cell research and may be valuable in studies of population genetics and ecology.

Animals↗

Longitudinal study of soy food intake and blood pressure among middle-aged and elderly Chinese women.

BACKGROUND: Several small-scale clinical trials have suggested a potential beneficial effect of short-term soy consumption on blood pressure (BP). Data are scanty on long-term effects of the usual intake of soy foods on BP in general populations. OBJECTIVE: Our aim was to examine the association between usual intake of soy foods and BP. DESIGN: The usual intake of soy foods was assessed at baseline, and BP was measured 2-3 y after the baseline survey among 45 694 participants of the Shanghai Women's Health Study aged 40-70 y who had no history of hypertension, diabetes, or cardiovascular disease at recruitment. Multiple regression models were used to estimate mean differences in BP associated with various intakes of soy foods. RESULTS: Soy protein intake was inversely associated with both systolic BP (P for trend = 0.01) and diastolic BP (P for trend = 0.009) after adjustment for age, body mass index, and lifestyle and other dietary factors. The adjusted mean systolic BP was 1.9 mm Hg lower (95% CI: -3.0, -0.8 mm Hg) and the diastolic BP was 0.9 mm Hg lower (-1.6, -0.2 mm Hg) in women who consumed > or =25 g soy protein/d than in women consuming <2.5 g/d. The inverse associations became stronger with increasing age (P for interaction < 0.05 for both BPs). Among women >60 y old, the corresponding differences were -4.9 mm Hg (95% CI: -8.0, -1.9 mm Hg) for systolic BP and -2.2 mm Hg (95% CI: -3.8, -0.6 mm Hg) for diastolic BP. CONCLUSION: Usual intake of soy foods was inversely associated with both systolic and diastolic BPs, particularly among elderly women.

Adult↗

Association of breast cancer risk with a common functional polymorphism (Asp327Asn) in the sex hormone-binding globulin gene.

Sex hormones play a central role in the development of breast cancer. Sex hormone-binding globulin (SHBG) modulates the bioavailability of circulating sex hormones and regulates their signaling system in the breast tissue. We evaluated the association of a common functional polymorphism (Asp327Asn) in the SHBG gene with breast cancer risk in a population-based case-control study (1,106 cases and 1,180 controls) conducted in Shanghai, China. The variant Asn allele was associated with a reduced breast cancer risk in postmenopausal women [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.53-0.99], but not in premenopausal women (OR, 1.03; 95% CI, 0.82-1.27). The protective association was much stronger in postmenopausal women with a low body mass index (BMI; OR, 0.46; 95% CI, 0.29-0.75) or waist-to-hip ratio (OR, 0.51; 95% CI, 0.32-0.83) than those with a high BMI or waist-to-hip ratio (P for interaction < 0.05). Furthermore, the association was stronger for estrogen receptor-positive (OR, 0.64; 95% CI, 0.42-0.98) than for estrogen receptor-negative breast cancer (OR, 0.85; 95% CI, 0.50-1.45). Among postmenopausal controls, blood SHBG levels were 10% higher in carriers of the variant Asn allele than noncarriers (P = 0.06). Postmenopausal control women with the Asn allele and low BMI or waist-to-hip ratio had 20% higher SHBG levels (P < 0.05). This study suggests that the Asn allele in the SHBG gene may be related to a reduced risk of breast cancer among postmenopausal women by increasing their blood SHBG levels.

Adult↗

Energy balance and breast cancer risk.

We evaluated the hypothesis that a pattern of behavioral exposures indicating positive energy balance [i.e., less exercise/sport activity, high body mass index (BMI), or high energy intake] would be associated with an increased breast cancer risk in the Shanghai Breast Cancer Study, a population-based study of 1,459 incident breast cancer cases and 1,556 age frequency-matched controls. Participants completed in-person interviews that collected information on breast cancer risk factors, usual dietary intake and physical activity in adulthood. Anthropometric indices were measured. Odds ratios and 95% confidence intervals were estimated by logistic regression to describe the individual and joint effects of the exposures on breast cancer risk. Lack of exercise/sport activity, low occupational activity, and high BMI were all individually associated with increased risk of breast cancer [odds ratios (OR) ranged from 1.49 to 1.86]. In general, women with lower exercise/sport activity level and higher BMI, or those with higher energy intake, were at an increased risk compared with women who reported more exercise/sport activities, had lower BMIs, or reported less energy intake. There was a significant multiplicative interaction (P = 0.02) between adult exercise/sport activity and BMI, with inactive women in the upper BMI quartile being at increased risk (OR, 2.16; 95% confidence interval, 1.25-3.74) compared with their active and lean counterparts. This association was stronger in postmenopausal than in premenopausal women, and non-exercising postmenopausal women with higher BMIs were at substantially increased risk (OR, 4.74; 95% confidence interval, 2.05-12.20). Our study suggests that promotion of behavior patterns that optimize energy balance (weight control and increasing physical activity) may be a viable option for breast cancer prevention.

Adult↗

[Polymorphism in insulin receptor gene exon 17 in women with polycystic ovary syndrome].

OBJECTIVE: To investigate insulin receptor (INSR) genotype exon 17 frequencies in women with polycystic ovary syndrome (PCOS) and to elucidate its role in the pathogenesis of PCOS. METHODS: The study involved 33 women with PCOS and 28 healthy control women who were genotyped for polymorphism of INSR gene exon 17 by single strand conformation polymorphism (SSCP) analysis. Body mass index (BMI), insulin sensitive index (ISI), the expression of INSR beta subunit, and serum concentration of luteinizing hormone (LH), total testosterone between the genotypes were compared. RESULTS: (1) The T-to-C mutation was observed in the INSR gene exon 17 (1008 bp). The frequency of the C/C genotype was significantly higher in patients (39%) than in the controls (11%) (P < 0.05). There was no significant difference in the distribution of genotypes between obese PCOS and non-obese PCOS, and between PCOS with insulin resistance (IR) and PCOS without IR. (2) In comparison of mutation genotype groups with wild genotype (T/T), ISI was significantly decreased (C/C genotype, P < 0.01; C/T genotype, P < 0.05), and no significant difference was observed in the other indices. CONCLUSIONS: There is polymorphism in INSR gene exon 17 in patients with PCOS. This variant leads to increased risk of IR in women with PCOS. It does not influence the expression of INSR beta subunit.

Adult↗

Effects of preimplantation embryos on expressions of DNA methyltransferase 1 in mouse oviduct epithelial cells.

OBJECTIVE: To investigate the effects of mouse preimplantation embryos on the expressions of DNA methyltransferase 1(Dnmt1) of mouse oviduct epithelial cells. METHODS: The histological location of Dnmt1 protein was detected by immunohistochemical staining and the expression levels of Dnmt1 mRNA and protein in mouse oviduct were assayed by real-time reverse transcription-PCR(RT-PCR) and Western blotting in both pregnant and pseudopregnant mice at the 2-cell, 4-cell and 8-cell stages. RESULTS: The expressions of Dnmt1 protein were mainly located in the epithelial cells of mouse oviduct. It was found that during all three stages, the expression levels of Dnmt1 mRNA in the epithelial cells of the pregnant mice were significantly lower than those in the pseudopregnant mice (P< 0.05), and the level of Dnmt1 protein expression in the pregnant mice was significantly decreased as compared with that in pseudopregnant mice at the 4-cell stage. CONCLUSION: Expressions of both Dnmt1 mRNA and protein in the epithelial cells of mouse oviduct could be regulated by mouse preimplantation embryos, which might play an important role in the expression changes of some genes in oviduct epithelial cells during the preimplantation period.

Animals↗

[Expression patterns of GCN5 and HDAC1 in preimplantational mouse embryos and effects of in-vitro cultures on their expressions].

To investigate the expression patterns of histone acetyltransferase (GCN5) and histone deacetylase 1 (HDAC1) in preimplantation mouse embryos and the effects of in-vitro cultures on their expressions, immunocytochemistry was used to detect the expressions of GCN5 and HDAC1 in mouse embryos at the stages of two-cell, four-cell, eight-cell, morula and blastocyst in both in-vivo and invitro groups. In in-vivo group, the obvious expressions of GCN5 were observed in the cytoplasm of all kinds of mouse embryos but blastocysts. Meanwhile, HDAC1 was highly expressed in the nuclei of four and eight-cell embryos and morula but mainly seen in the cytoplasm of two-cell embryos. In blastocysts, the HDAC1 fluorescence was limited to the nuclei of trophoblast cells. In in-vitro group, there were no obvious GCN5 expressions in all kinds of embryos and the expression of HDAC1 was significantly reduced although its expression pattern was similar to that of in-vivo group. Those results showed that in -vitro culture environments could inhibit GCN5 expression and decrease the expression of HDAC1 in mouse preimplantation embryos, which might affect the correct embryonic gene expression.

Animals↗

Passive smoking and breast cancer risk among non-smoking Chinese women.

Our purpose was to evaluate whether passive exposure to cigarette smoke may be related to breast cancer risk. Data from the Shanghai Breast Cancer Study, a large population-based study of 1459 breast cancer cases and 1556 controls aged 25-64 years, were analyzed. Respective response rates were 91.1% and 90.3%. Passive smoking questions were added to all face-to-face interviews 7 months into the study. Women were asked about exposure to their husbands' smoke at home as well as exposure in the workplace. Analyses were restricted to the 1013 cases and 1117 controls with passive tobacco smoke exposure data who had never actively smoked. Over 60% of controls reported some exposure to a husband's smoke and over 40% reported exposure to passive smoke in the workplace. Overall, there was no apparent association between any passive smoke exposure or exposure to a husband's smoke and breast cancer risk. There was some evidence of an elevated breast cancer risk associated with passive smoking exposure of 5 hr or more per day in the workplace (OR = 1.6, 95% confidence interval 1.0-2.4; p for trend = 0.02). This association warrants further investigation.

Adult↗

[The expression of integrin beta3 in mice's endometrium during the implantation window based on different ovarian stimulation protocols].

OBJECTIVE: To compare the uterine receptivity with different ovarian stimulation protocols, the endometrial expression of Integrin beta3 in mice's during the implantation window underwent different ovarian stimulation were studied. METHODS: Forty mice were randomly allocated into 4 groups of 10 mice. (1) GnRHant group, gonadotropin-releasing hormone antagonist (GnRHant) was given first for desensitizing the pituitary, then the pregnant mare's serum gonadotrophin (PMSG) was added for ovarian stimulation. (2) gonadotropin-releasing hormone agonist (GnRHa) group, GnRHa was given first for desensitizing the pituitary, then PMSG was added for ovarian stimulation. (3) PMSG group, injected with PMSG only; and (4) control group, given with saline of the same volume. Human chorionic gonadotropin (HCG) was injected to the mice of the GnRHant, GnRHa, and PMSG groups. Forty-eight hours after the mice of the control group the mice were killed. Their uteri were taken. RT-polymerase chain reaction (RT-PCR) was used to detect the expression of integrin beta3 mRNA. Immunohistochemistry (SP method) was used to locate and semiquantitatively measure the integrin beta3 in the endometrium during implantation window. RESULTS: (1) Immunohistochemistry: showed that the staining intensity of integrin beta3 was 3.74 +/- 0.15 in GnRHa group, 3.22 +/- 0.19 in the GnRHant group, and 3.24 +/- 0.18 in the PMSG group, all significantly lower than that in the control group (3.90 +/- 0.11, P = 0.023, 0.001, and 0.001). with a significant difference between the GnRHa group and the PMSG group (P = 0.001) and without a significant difference between the. GnRHant group and PMSG groups (P = 0.768). (2) RT-PCR showed that the relative quantity of integrin beta3 mRNA expression was 1.14 +/- 0.16 in the GnRHa group, 0.76 +/- 0.33 in the GnRHant group, and 0.73 +/- 0.26 in the PMSG group, all significantly lower than that in the control group (1.4 +/- 0.3, P = 0.045, 0.001, and 0.001). with a significant difference between the GnRHant and PMSG groups (P = 0.001) and without a significant difference between the GnRHant and PMSG groups (P = 0.857). CONCLUSION: All of the ovarian stimulation protocols do harm to the mice's uterine receptivity. Ovarian stimulation combining GnRHa protocol in mice is better than PMSG alone protocol, because it can improve the uterine receptivity. Ovarian stimulation combining GnRHant protocol in mice decrease the uterine receptivity as well as the PMSG alone protocol.

Animals↗

Transcription enhancer factor-5 and a GATA-like protein determine placental-specific expression of the Type I human 3beta-hydroxysteroid dehydrogenase gene, HSD3B1.

The enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3betaHSD) is required for the biosynthesis of all active steroid hormones. It exists as multiple isoforms in humans and rodents, each a product of a distinct gene. Two isoforms, 3betaHSD I and II, are expressed in a tissue-specific manner in humans. 3betaHSD I is the only isoform expressed in the placenta, where it is required for the biosynthesis of progesterone and thus essential for the maintenance of pregnancy. We recently identified two transcription factors, activating protein-2gamma (AP-2gamma) and the homeodomain protein, distaless-3 (Dlx-3), that are expressed in both human and mouse trophoblast cells that were shown to be required for trophoblast-specific expression of the orthologous murine 3betaHSD, 3betaHSD VI. Although we identified specific binding sites for AP-2gamma and Dlx-3 in the distal promoter of the human 3betaHSD I gene, HSD3B1, it was found that these transcription factors were not involved in determining placental-specific expression of human 3betaHSD I. Instead, a 53-bp placental-specific enhancer element located between -2570 and -2518 of the HSD3B1 promoter was identified. Within this 53-bp element, two potential placental transcription factor binding sites were found. EMSAs with a 20-bp oligonucleotide containing these two potential placental-specific binding sites identified one of the binding sites specific for the transcription enhancer factor (TEF)-5, which is highly expressed in human placenta and in placental choriocarcinoma-derived JEG-3 cells and the other overlapping binding site, specific for a GATA-like protein. Site-specific mutations in either the TEF-5 binding site or in the GATA binding site, each resulted in complete loss of enhancer activity. The data indicate that TEF-5 and the GATA-like protein act in a coordinate manner to determine the placental-specific expression of the human 3betaHSD I enzyme and therefore are critical for placental progesterone production required for the maintenance of pregnancy.

17-Hydroxysteroid Dehydrogenases↗

Evaluation of the synergistic effect of insulin resistance and insulin-like growth factors on the risk of breast carcinoma.

BACKGROUND: The purpose of the current study was to investigate the association between insulin resistance (which was measured using fasting blood C-peptide) and its joint association with insulin-like growth factors (IGF-1, IGF-2, and IGF binding protein-3 [IGFBP-3]) on the risk of breast carcinoma. METHODS: Included in the current study were 400 case-control pairs from the Shanghai Breast Cancer Study. Pretreatment biospecimens and interview data were collected from all breast carcinoma cases and their individually matched controls. RESULTS: Breast carcinoma risk was found to be statistically significantly increased when higher blood levels of C-peptide and IGFs were noted in a dose-response manner. There was a statistically significant twofold to threefold increased risk of breast carcinoma for women in the highest quartile of C-peptide, IGF-1, or IGFBP-3 compared with women in the lowest quartiles. Women with high levels of both C-peptide and IGF-1 or IGFBP-3 also were found to have a substantially higher risk of breast carcinoma than those women with a high level of only one of these molecules. The adjusted odds ratios (ORs) were 3.79 (95% confidence interval [95% CI], 2.03-7.08) for those with a higher level of both C-peptide and IGF-1 and 4.03 (95% CI, 2.06-7.86) for those with a higher level of both C-peptide and IGFBP-3. CONCLUSIONS: The results of the current study suggest that insulin resistance and IGFs may synergistically increase the risk of breast carcinoma.

Adult↗

Genetic polymorphisms in the TGF-beta 1 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study.

The effect of genetic polymorphisms in the TGF-beta1 gene at codon 10 (T+29C), codon 25 (G+74C), and the promoter region [C --> T at -509 from the transcription site, (C-509T)] on breast cancer survival was evaluated among a cohort of 1111 patients. The median follow-up time for the cohort was 5.17 years after cancer diagnosis. No DNA sequence variation at codon 25 of the TGF-beta1 gene was found, whereas polymorphisms in C-509T and T+29C were in strong linkage disequilibrium. Patients who carried the C allele of T+29C polymorphism had a reduced 5-year disease-free survival rate (75.6% for T/C, and 78.2% for C/C) compared with the T/T genotype (85.1%; P, 0.04); the age-adjusted hazard ratio was 1.5 (95% confidence interval, 1.1-2.2). Adjustment for clinical prognostic factors slightly attenuated the association (hazard ratio, 1.4, 95% confidence interval, 1.0-1.9). Our study suggests that genetic polymorphisms in the TGF-beta1 gene may play a role in breast cancer progression.

Adult↗

Impact of season of food frequency questionnaire administration on dietary reporting.

PURPOSE: Foods consumed near the time of food frequency questionnaire (FFQ) administration may prime the memory, such that FFQ responses emphasize recently consumed foods. This study investigates the effect of season of FFQ administration, a proxy for the recent diet, on FFQ responses. METHODS: FFQ data from 74,958 Shanghai Women's Health Study (SWHS) subjects were compared with FFQ data from these subjects by season of FFQ administration (i.e., winter, spring, summer, and fall). All analyses were adjusted for age, BMI, and energy intake. Furthermore, quintile categories derived from all study subjects were compared with categories derived from the distribution of subjects recruited in the same season. RESULTS: Compared with the study group as a whole, subjects completing the FFQ in winter reported higher intakes of meat (2.1%), vegetable (3.9%), fish (3.1%), and soy foods (4.1%), but lower fruit (- 3.9%) intake. Subjects completing the FFQ in summer reported lower than average meat (- 2.0%), vegetable (- 3.2%), fish (- 2.3%), and soy food (- 4.6%) intakes, but greater fruit intake (0.9%). Completion of the FFQ in spring and fall usually led to intermediate differences from the group average, although fruit intake was 5.9% higher among subjects completing the FFQ in the fall. Variations across macronutrients and micronutrients by season of FFQ administration were smaller. If seasonal FFQ reporting is ignored, up to 13% of subjects would be classified to a different diet intake exposure category. However, reclassification was always to an adjacent category. CONCLUSIONS: FFQ responses varied with season of FFQ administration, consistent with theory that current diet intake influences reporting of habitual past diet intake. However, season of FFQ administration did not alter dietary exposure category assignments sufficiently to effect interpretation of most epidemiologic studies.

Adult↗

Oral contraceptive use and risk of diabetes among Chinese women.

Oral contraceptive (OC) use has been associated with alterations in carbohydrate metabolism. We examined the effect of OC use on the risk of diabetes among Chinese women. A nested case-control study was conducted among 57,130 women screened for diabetes at enrollment for the Shanghai Women's Health Study, a population-based cohort study of Chinese women aged 40-70 years in Shanghai, China. Included in this study were 259 women newly diagnosed with diabetes and 2072 age-matched controls (8 controls per case), randomly selected from women who tested negative for urine glucose. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) were used to measure the strength of the association between OC use and diabetes risk. Overall, OC use was not associated with the risk of diabetes. Stratified analysis by menopausal status revealed a dose-response relationship between the duration of OC use and the risk of diabetes among premenopausal women (p for trend = 0.02), with a 3.2-fold elevated risk observed among those who used OC longer than 1 year. Risk of diabetes diminished with increasing time since last OC use (p = 0.02). Use of intrauterine devices was associated with a reduced risk of diabetes in both pre- and postmenopausal women (OR = 0.67, CI: 0.48-0.93). These findings suggest that recent use (within 5 years) and continued use (>1 year) of OCs may increase the risk of diabetes among Chinese women. However, the attributable risk for diabetes among OC users in the general population, if confirmed by further studies, appears to be small.

Adult↗