Expression and clinical significance of dendritic cell and transforming growth factor-beta 1 in cervical cancer

Cervical cancer and precancerous cervical lesionsare major problems in women's health.Clinical,molecu-lar and epidemiological investigations have identifiedhuman papillomavirus(HPV)as a major cause of cer-vical cancer[1].Although HPV infection is very com…     

Maternal plasma transforming growth factor-beta1 concentrations in preeclamptic and normotensive pregnant Zimbabwean women.

OBJECTIVE: We examined the relationship between maternal plasma transforming growth factor-beta1 (TGF-beta1) concentrations and risk of preeclampsia among women delivering at Harare Maternity Hospital in Zimbabwe. We evaluated the relationship in the context of maternal systemic inflammation using plasma tumor necrosis factor-a soluble receptor p55 (sTNFp55) as a marker. METHODS: 132 women with preeclampsia and 180 controls were included in this case-control study analysis. Maternal post-diagnosis plasma TGF-beta1 and sTNFp55 concentrations were determined using immunoassays. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. RESULTS: A linear increase in preeclampsia risk was observed with increasing quartiles of TGF-beta1 concentrations (p<0.01). Women whose TGF-beta1 concentrations were >or=25.1 ng/ml (quartile 4) had a 2.5-fold (95% CI 1.2-5.6) increased risk of preeclampsia as compared with those women whose concentrations were <11.2 ng/ml (quartile 1). Relative to women with no evidence of systemic inflammation and no elevated TGF-beta1 concentrations, those women who were jointly positive for elevated TGF-beta1 and sTNFp55 concentrations experienced a 5.3-fold (95% CI 2.3-12.0) increased risk of preeclampsia. CONCLUSION: Overall, we noted that elevated TGF-beta1 is associated with an increased risk of preeclampsia. We also noted that the preeclampsia risk is exaggerated in the presence of maternal systemic inflammation.     

Correlation between overexpression of transforming growth factor-beta 1 in occluded fallopian tubes and postsurgical pregnancy among infertile women

Objective

To compare the expression profiles of transforming growth factor-beta 1 (TGF-β1) and its receptors in occluded tubes of infertile women with those of control patients and to evaluate the potential correlation with postsurgical pregnancy outcome.

Methods

The expression profiles of TGF-β1, TGF-β1R1, and TGF-β1R2 in occluded fallopian tubes were compared using immunohistochemistry between 60 infertile patients with adhered tubes and 60 control patients with normal tubes; potential correlations with postsurgical fertility were evaluated at 2-year follow up.

Results

Immunostainings of TGF-β1, TGF-β1R1, and TGF-β1R2 were all significantly elevated in patients with adhered tubes compared with normal specimens (P < 0.001). In adhered specimens, correlation analyses showed positive correlations between TGF-β1 and TGF-β1R1 (P = 0.008), and TGF-β1 and TGF-β1R2 (P = 0.035). At 2-year follow up, 32 of the 60 infertile women had achieved normal pregnancies, 5 had had ectopic pregnancies, and 23 remained infertile. Correlation analysis showed that TGF-β1 expression level was negatively correlated with pregnancy outcome (r = -0.445, P < 0.001), independent of adhesion severity or patient age.

Conclusion

TGF-β1 expression was independently correlated with the postsurgical pregnancy outcome among infertile women.     

Peritoneal fluid concentrations of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and transforming growth factor-beta in women with pelvic adhesions

OBJECTIVE: To establish whether the concentration of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-beta (TGF-beta) is influenced by the presence or absence of adhesions, and whether the concentration of these mediators vary throughout the menstrual cycle. DESIGN: Prospective case-control study. SETTING: Women undergoing laparoscopy in a university hospital in the United Kingdom. PATIENT(S): Women undergoing laparoscopy for benign gynecological conditions. INTERVENTION(S): Samples of peritoneal fluid were collected at diagnostic laparoscopy in one group, and at laparoscopy and serially during the first 48 hours after laparoscopic adhesiolysis in a second group. We correlated the concentrations of mediators in serially sampled peritoneal fluid during the 48 hours following laparoscopic adhesiolysis to the adhesion formation and reformation found during second-look laparoscopy. MAIN OUTCOME MEASURE(S): The concentrations of MMP-9, TIMP-1, and TGF-beta in peritoneal fluid. RESULT(S): MMP-9 concentration was lower in the follicular phase than the luteal phase of the menstrual cycle. MMP-9 concentration was significantly lower in women with pelvic adhesions than in women with a normal pelvis. The MMP-9/TIMP-1 ratio is significantly higher in women with significant adhesions at second-look laparoscopy compared to women with minimal or no adhesions. CONCLUSION(S): The components of extracellular matrix remodeling may play an important part in the adhesion formation/reformation process.     

子痫前期患者胎盘组织中转化生长因子β1、血管细胞黏附分子1及E选择素表达的研究

目的探讨子痫前期患者胎盘组织中转化生长因子β1(TGF-β1)、血管细胞黏附分子1(VCAM-1)和E选择素(E-selectin)的表达变化及其意义。方法用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(SP)法,对20例正常孕妇(对照组)和40例子痫前期患者(子痫前期组,其中轻度16例、重度24例)的胎盘组织进行TGF-β1、VCAM-1和E-selectin定位,并用计算机图像分析系统进行定量分析比较。结果(1)1FGF-β1在胎盘绒毛合体滋养细胞的表达,子痫前期组为70．7±0．5,对照组为70．3±0．6,两组比较,差异有统计学意义(P<0．05)。VCAM-1的表达,子痫前期组为82．5±0．5,对照组为82．8±0．3;E-selectin的表达,子痫前期组为53．5±0．5,对照组为53．8±0．4;两组分别比较,差异均有统计学意义(P<0．05)。TGF-β1、VCAM-1、E-selectin在轻度子痫前期患者胎盘组织合体滋养细胞中的表达分别为70．6±0．6、82．4±0．6、53．4±0．5,在重度子痫前期患者胎盘组织中的表达分别为70．8±0．4、82．6±0．5、53．6±0．5,轻度与重度子痫前期患者TGF-β1、VCAM-1、E- selectin表达水平比较,差异均无统计学意义(P>0．05)。(2)E-selectin在胎盘绒毛毛细血管内皮细胞的表达,子痫前期组为63．0±0．5,对照组为62．6±0．4,两组比较,差异有统计学意义(P<0．05);轻度子痫前期患者为63．2±0．4、重度子痫前期为62．9±0．5,二者比较,差异无统计学意义(P> 0．05)。结论TGF-β1、VCAM-1和E-selectin在胎盘组织中的表达变化,在子痫前期发病中有重要作用。     

The promoter region (-800, -509) polymorphisms of transforming growth factor-beta1 (TGF-beta1) gene and recurrent spontaneous abortion

Recurrent spontaneous abortion (RSA) is regarded as a common pregnancy complication in southern Iran. The exact causes of RSA are not yet known. Transforming growth factor-beta1 (TGF-beta1) is produced by T regulatory lymphocytes (Treg), which play an important role in the physiology of pregnancy. Several polymorphisms of the TGF-beta1 gene have been reported, some with important correlation with disease severity. In this investigation, the polymorphism of the TGF-beta1 gene at promoter region positions -800 (G/A) and -509 (C/T) was studied in 111 RSA and 110 normal female subjects from southern Iran by PCR-RFLP. Results indicated that at position -800 (G/A) polymorphism, 75.7% of RSA cases and 77.3% of normals were homozygote GG. In addition, 23.4% of cases and 22.7% of normal individuals were heterozygote AG. Only one of the patients appeared to be homozygote AA. None of the normal individuals were found to be homozygote AA at this position. In the case of the -509 (C/T) polymorphism, 38.7% of patients and 28.2% of controls were homozygote CC. While 40.6% of cases and 50.9% of normal individuals were heterozygote CT, 20.7% of RSA cases and 20.9% of controls were homozygote TT. The results indicate that there are no statistically significant differences of genotype distribution and allele frequency between RSA cases and controls at both polymorphic sites. In conclusion, the promoter region polymorphisms of TGF-beta1 at positions -800 (G/A) and -509 (C/T) may not be associated with RSA.     

Immunolocalization of transforming growth factor-beta 3 in pregnant human myometrium

BACKGROUND: Transforming growth factor-beta 3 is a cytokine which is involved in cell growth regulation and differentiation, stimulation of extracellular matrix and modulation of immune responses. The goal of this study was to detect the presence of this cytokine in the myometrium of preterm and term, nonlaboring and laboring patients, and to measure serum levels of interleukin-1 beta (IL-1 beta), IL-6 and IL-8 before cesarean section. METHODS: In this prospective study, we obtained samples of myometrium from the lower uterine segment during elective and emergency cesarean sections (term non-laboring, n=8; term laboring, n=7; preterm non-laboring, n=3; and preterm laboring, n=19) and stained for transforming growth factor-beta 3. Blood was also sampled from the same patients to determine IL-1 beta, IL-6 and IL-8 levels. RESULTS: Different intensities of staining were detected in preterm laboring, term nonlaboring and term laboring groups, but there was no staining in preterm nonlaboring group. We also found a statistically significant difference in IL-6 levels between laboring and nonlaboring groups (p=0.028). CONCLUSION: Different intensities of TGF-beta 3 which appeared in different stages of myometrium made us consider that TGF-beta 3 might prepare myometrium to labor, and IL-6 was more important than the other interleukins in initiation of labor.     

Reversal of Adriamycin-impaired wound healing by transforming growth factor-beta

Impaired wound healing remains an important clinical problem. Treatment with systemic Adriamycin (doxorubicin) is known to impair wound healing in patients, and it has been used to produce animal models of impaired healing. The results of previous studies have shown that local treatment of incisions in normal rats with transforming growth factor beta (TGF-beta) or epidermal growth factor (EGF) stimulated early increases in tensile strength of surgical incisions in normal rats. We investigated the effects of locally applied, biosynthetic TGF-beta or EGF on the tensile strength of standardized incisions in rats treated with Adriamycin. Systemic Adriamycin treatment (8 milligrams per kilogram) produced significant decreases in wound tear strength (WTS) and wound tear energy (WTE) when compared with that of normal rats at seven and ten days (p less than 0.01). A single dose of TGF-beta (2 micrograms) in a collagen vehicle stimulated a reversal of this wound healing impairment at ten days (p less than 0.05), returning the WTS and WTE to near normal levels. A single dose of EGF (50 micrograms) in hyaluronic acid failed to increase tensile strength, probably because of formulation of EGF in a vehicle that does not prolong its release in incisions. These results suggest that exogenous growth factors may be clinically useful in stimulating healing in incisions in healing impaired conditions.     

Plasma and placental levels of interleukin-10, transforming growth factor-beta1, and epithelial-cadherin in preeclampsia

OBJECTIVE: To investigate the plasma and placental levels of interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1), and epithelial-cadherin (E-cadherin) in normotensive and preeclamptic pregnancies. METHODS: The study population consisted of 33 women with normotensive pregnancy and 35 women with preeclampsia. Peripheral venous blood samples were collected before labor (35.3 +/- 1.1 and 34.2 +/- 3.4 weeks' gestation for normotensive and preeclamptic pregnancies, respectively), and placental tissues were obtained after delivery. Maternal plasma and placental homogenate IL-10, TGF-beta1, and E-cadherin levels were determined by enzyme-linked immunosorbent assay. RESULTS: The mean plasma and placental levels of IL-10, TGF-beta1, and E-cadherin were significantly higher in preeclamptic than normotensive patients (P <.001). The plasma and placental levels of IL-10, TGF-beta1, and E-cadherin significantly increased with the increments in diastolic blood pressure (P <.001). CONCLUSION: IL-10, TGF-beta1, and E-cadherin may be involved in the pathologic process of preeclampsia. The pathophysiologic changes associated with preeclampsia may stem in part from the overproduction of these placental mediators.     

The association of transforming growth factor-beta 1 with myometrial invasion of endometrial carcinomas through effects on matrix metalloproteinase

OBJECTIVE: The association of transforming growth factor-beta 1 (TGF-beta 1) with a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase (TIMP), as well as myometrial invasion of endometrial cancer was studied. METHODS: The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity, and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancer patients with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta receptor Type I in tumor tissue from the same patients also was detected. RESULTS: Invasiveness, gelatinase activity, and the expression of TIMP-1 were higher in KLE cells than in Ishikawa cells, and they were increased by treatment with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1. The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage-Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were ubiquitous. CONCLUSIONS: Myometrial invasion of endometrial cancers involves an increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an autocrine or paracrine fashion.     

子宫内膜异位症患者腹腔液白细胞介素6,8及转化生长因子β1 …

OBJECTIVE: To investigate the role of cytokines in peritoneal fluid on pathogenesis of endometriosis (EM). METHODS: Interleukin-6 (IL-6), interleukin-8(IL-8) and transforming growth factor-beta 1 (TGF-beta 1) contents in peritoneal fluid (PF) of 31 cases with EM were detected by enzyme linked immunoabsorbent assay (ELISA) and compared with the counterparts of 22 cases without EM (controls). The correlation analyses between cytokine concentrations in peritoneal fluid of EM patients and the severity of EM or dysmenorrhea score were performed. RESULTS: The peritoneal fluid from patients with EM contained significantly greater amounts of IL-6 [(1.8 +/- 0.4) ng/L] and IL-8 [(1.7 +/- 0.5) ng/L] than those in controls [(1.2 +/- 0.2) ng/L and (1.4 +/- 0.3) ng/L respectively, P < 0.05]. However, in the amounts of TGF-beta 1 there were no significant difference (P > 0.05) between the two groups. The highest PF IL-6 and IL-8 concentrations were found in stage II, III and stag I, II EM respectively. A significant correlation between PF IL-6 content and the severity of disease was noted but there were no evidences of a relationship between concentrations of IL-8 and TGF-beta 1 and the severity of EM as well as between concentrations of three cytokines and dysmenorrhea score. CONCLUSION: Unusual levels of IL-6 and IL-8 in PF of EM patients partly account for imbalance of the immunologically dynamic environment in peritoneal cavity of EM patients.     

Pregnancy outcomes and superiorities of prophylactic cervical cerclage and therapeutic cervical cerclage in cervical insufficiency pregnant women

Purpose

To compare the clinical effect of prophylactic cervical cerclage and therapeutic cervical cerclage on pregnancy outcome and operative factors in cervical insufficiency pregnant women.

Methods

A retrospective study was conducted between June 2014 and September 2016 in a maternity ward, which included women who have had a single pregnancy and have been carried out a McDonald cerclage. All maternal medical records were reviewed. The efficacy of cerclage for preventing late foetal loss was assessed using multivariable logistic regression analysis.

Results

The results showed that there were significant associations between cerclage operations and pregnancy outcomes in the duration of pregnancy prolongation in terms of live births, gestation age, live birth and cesarean section rate. In prophylactic cervical cerclage, compared with therapeutic cervical cerclage, cervical length before surgery was significantly longer (32.7?±?5.8 vs 19.9?±?7.3 mm, p?<?0.0001). Mean operative duration and postoperative length of hospital stay in prophylactic cervical cerclage were shorter than those in therapeutic cervical cerclage (22.1?±?10.3 vs 28.9?±?13.0 min, p?=?0.0241 and 5.6?±?1.8 vs 7.0?±?2.8 days, p?=?0.0354), respectively. Compared with therapeutic cerclage, prophylactic cerclage had more advantages in gestational age at delivery (35.2?±?5.5 and 31.7?±?6.5 weeks, p?=?0.0061), deliveries?<?37 gestational weeks (40 vs 69.2%, p?=?0.0159), live births (93.3 vs 69.2%, p?=?0.0143) and the duration of pregnancy prolongation in terms of live births (19.5?±?5.0 vs 12.0?±?8.2 weeks, p?=?0.0002). There was a higher cesarean section rate in prophylactic group than that in therapeutic group (50 vs 25.6%, p?=?0.0383). The logistic analysis showed that the cervical length before surgery was the only independent prognostic factor [OR 2.860 (1.425, 5.742) p?=?0.0031] for pregnancy outcome, and that is the cervical length before surgery affected late foetal loss.

Conclusions

Our study suggests that, both prophylactic cervical cerclage and therapeutic cervical cerclage reduce the incidence of recurrent abortion or preterm birth and efficiently extend the length of the pregnancy with live births. The prophylactic cervical cerclage has more advantages in operative time, length of hospital stay after surgery, gestational age at delivery, live births and preterm birth. The length of the cervical before surgery is an independent risk factor for pregnancy outcomes when pregnant women appear in the cervical shortening is less than normal. Cervical cerclage is an effective surgical technique to prevent recurrent abortion or late foetal loss.

     

TGF-β1通过诱导代谢重组促进子宫内膜异位症内膜间质细胞的迁移和侵袭

目的:探讨转化生长因子β1(TGF-β1)是否具有诱导子宫内膜间质细胞发生代谢重组的效应,及该效应对内膜间质细胞生物学行为的影响及其可能作用机制。方法:收集子宫内膜异位症(EMs)患者的异位病灶及在位内膜。免疫组化法分析标本组织内无氧糖酵解标志分子单羧酸转运蛋白1和4(MCT1、MCT4)等表达。体外分离和培养获得原代内膜间质细胞。原代培养的内膜间质细胞用TGF-β1(2ng/ml)干预12h,检测培养液中乳酸浓度。siRNA沉默MCT4基因表达。qRT-PCR和Western blot法检测无氧糖酵解相关基因和蛋白的表达水平,Transwell小室检测细胞迁移和侵袭能力。结果:内异症异位病灶组织内无氧糖酵解标志分子MCT1、MCT4表达显著增加。相较无干预细胞组,外源性TGF-β1作用后内膜间质细胞无氧糖酵解标志分子MCT1、MCT4和乳酸脱氢酶A(LDHA)表达均显著上调(P均0.05);同时TGF-β1干预促进内膜间质细胞的乳酸分泌及迁移和侵袭(P均0.05),但MCT4基因沉默可显著逆转上述效应。结论:TGF-β1通过诱导内膜间质细胞无氧糖酵解、乳酸分泌促进了细胞的迁移和侵袭,且MCT4在其中发挥了关键性作用。     

Transforming growth factor-beta1 in fetal serum correlates with insulin-like growth factor-I and fetal growth

OBJECTIVE: To estimate whether transforming growth factor-beta1 in fetal serum obtained by umbilical cord sampling at delivery is correlated with fetal growth. We also estimated whether transforming growth factor-beta1 is correlated with insulin-like growth factor-I and insulin-like growth factor binding protein-1, which have been shown to correlate with fetal growth. METHODS: The active form of transforming growth factor-beta1 was analyzed in serum from cord blood from 68 fetuses by the enzyme-linked immunosorbent assay technique. Of the 68 pregnant women, 12 had preeclampsia, 14 had preeclampsia and intrauterine growth restriction, 15 had intrauterine growth restriction alone, and seven had fetuses that were large for gestational age (LGA). Twenty pregnancies with fetuses appropriate for gestational age (AGA) served as controls. RESULTS: Transforming growth factor-beta1 concentrations were significantly correlated with birth weight. The average transforming growth factor-beta1 concentration in the following groups were: intrauterine growth restriction, 22.4 +/- 2.7 microg/L; intrauterine growth restriction plus preeclampsia, 22.9 +/- 2.0 microg/L; preeclampsia without intrauterine growth restriction, 28.8 +/- 2.1 microg/L; LGA, 30.3 +/- 4.3 microg/L; and AGA, 36.8 +/- 2.0 microg/L. Transforming growth factor-beta1 levels were significantly lower in pregnancies complicated by intrauterine growth restriction and showed a positive correlation with birth weight (r = 0.48, P <.001). Furthermore, there was a positive correlation between insulin-like growth factor-I levels and birth weight (r = 0.36, P <.01) and a negative correlation between insulin-like growth factor binding protein-1 and birth weight (r = -0.32, P <.01). There was also a correlation between transforming growth factor-beta1 and insulin-like growth factor-I (r = 0.29, P <.05) and between transforming growth factor-beta1 and insulin-like growth factor binding protein-1 (r = -0.25, P <.05). CONCLUSION: Transforming growth factor-beta1 might be related to fetal growth in pregnancy. The results also support previous data showing that insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to fetal growth.     

Regulation of invasion of epithelial ovarian cancer by transforming growth factor-beta

OBJECTIVE: The metastatic process in epithelial ovarian cancer is thought to involve surface shedding and subsequent dissemination of ovarian cancer cells, facilitated by localized proteolysis at the interface between ovarian cancer cells and peritoneal surfaces. The factors regulating the metastatic process, however, are not well understood. Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that elicits numerous cellular effects pertinent to the metastatic process. The purpose of this study was to evaluate the regulatory role of TGF-beta on metastasis in ovarian cancer. METHOD: We evaluated the effect of TGF-beta on the metastatic characteristics (adhesion, invasion, motility, proteolysis) of five ovarian cancer cell lines (DOV-13 and OVCA 420, 429, 432, and 433), two short-term primary ovarian cancer cell cultures (OVCA 10 and OVCA 208), and five normal ovarian surface epithelial (NOSE) cell cultures (OSE 133, 185, 186, 188, and 189). The effect of TGF-beta on invasion and proteolysis was quantified using a modified Boyden chamber invasion assay, zymography, a coupled colorimetric activity assay, and an HPLC-based quantitation of synthetic substrate cleavage. RESULTS: TGF-beta significantly increased invasion in five of seven ovarian cancer cell lines in amounts ranging from 2- to 20-fold. In contrast, TGF-beta significantly decreased invasion in two of five NOSE isolates by 50 to 80% and had no significant effect on invasion in three. TGF-beta treatment increased matrix metalloproteinase (MMP) expression in OVCA 420 and 433 and DOV-13, resulting in MMP-dependent collagen cleavage and invasive activity. Addition of the MMP inhibitor GI12947 neutralized the enhancing effect of TGF-beta on invasion. TGF-beta had no effect on ovarian cancer cell motility and only increased adhesion in DOV-13. CONCLUSIONS: These data suggest that TGF-beta may enhance the invasiveness of ovarian cancers through induction of MMP activity.     

子宫颈鳞状细胞癌中TGF-β1表达与血管生成的关系

目的　研究转化生长因子 (transforminggrowthfactor - β1 ,TGF - β1 )在子宫颈鳞状细胞癌中的表达 ,及其与血管内皮生长因子 (VEGF)表达和肿瘤内微血管密度 (MVD)的关系。　方法　应用免疫组织化学方法检测 4 3例子宫颈鳞状细胞癌中TGF - β1、VEGF的表达和MVD值。 结果　子宫颈鳞状细胞癌中TGF - β1和VEGF阳性表达率分别为 34 9%和 6 2 8% ,MVD值为 1 7 2～ 1 1 4 6 ,平均值为 5 7 4 2± 2 3 1 5。TGF - β1的表达与肿瘤的淋巴结转移和临床分期密切相关 (P <0 0 5 ) ,而与肿瘤的病理分级无关 (P >0 0 5 ) ,TGF - β1表达与VEGF的表达呈正相关 (P <0 0 5 ) ,而与肿瘤的MVD无明显相关性 (P >0 0 5 )。结论　TGF - β1可能通过上调VEGF的表达间接刺激血管生成而促进子宫颈鳞状细胞癌的进展     

Interleukins-1, -4, -6, -10, tumor necrosis factor, transforming growth factor-beta, FAS, and mannose-binding protein C gene polymorphisms in Australian women: Risk of preterm birth

OBJECTIVE: The purpose of this study was to examine the relationship between preterm birth and 22 single nucleotide polymorphisms in genes that encode cytokines and mediators of apoptosis and host defense. STUDY DESIGN: Two hundred two white women with a spontaneous preterm birth of <35 weeks of gestation were compared with 185 white women with term births. Genotyping was performed with polymerase chain reaction and sequence specific primers. Multivariable analyses included demographic and genetic variables. RESULTS: Alcohol (multivariable odds ratio, 2.3; P = .001] and substance use (multivariable odds ratio, 3.7; P = .01) were associated with preterm birth at <35 weeks of gestation. Smoking (multivariable odds ratio, 2.3; P = .03), haplotypes IL10 -1082A/-819T/-592A (multivariable odds ratio, 2.1; P = .04), tumor necrosis factor ( TNF )+488A/-238G/-308G (multivariable odds ratio, 2.4; P = .04), and IL4 -509C/C (multivariable odds ratio, 3.4; P = .02), and the presence of MBL2 codon 54Asp (multivariable odds ratio, 2.3; P = .02) were associated independently with preterm birth at <29 weeks of gestation. Homozygosity for IL10 -1082G/-819C/-592C haplotype (multivariable odds ratio, 1.9; P = .02) was more common in women with preterm premature rupture of membranes. CONCLUSION: Polymorphisms in immunoregulatory genes may influence susceptibility to preterm birth or premature rupture of membranes.