Primary retroperitoneal extraovarian granulosa cell tumor

Extraovarian granulosa cell tumors (GCTs) develop from ectopic gonadal tissue situated along the embryonal route of the genital ridge. Primary retroperitoneal tumors are extremely rare, with an incidence of 02% -06% and 80-85% probability of malignancy. Only eight such case reports have been published previously. We herein, report a rare case of extraovarian retroperitoneal GCT in a 55-year-old woman who presented with intermittent left lumbar region pain of one-year duration. She had a history of hysterectomy and bilateral salpingo-oophorectomy 8 years ago for uterine leiomyoma. Laparotomy revealed a retroperitoneal mass measuring 8cm x 10cm x 20cm in size, solid cystic with areas of necrosis and hemorrhage. The gross features, classical histopathology, and positive immunostaining of the retroperitoneal mass with inhibin, calretinin, PR, WT1 and immunonegativity for EMA were characteristic of adult-type GCT. Excluding any previous history of primary ovarian GCT in this patient, a de-novo retroperitoneal diagnosis was established.

External quality assessment of prenatal screening for maternal serum inhibin A in second trimester / 中华围产医学杂志

Objective To eva1uate the external quality assessment results of prenatal screening for maternal serum inhibin A in the second trimester in 2018 and to improve the accuracy of prenatal screening.Methods National Center for Clinical Laboratories provided three batches of quality control urine sample (Lot:201811-201813) to 94 prenatal screening laboratories nationwide in March 2018.Laboratories participated in the assessment voluntarily and reported the results,methods,equipment,reagents and other related information as required.Clinet EQA and Microsoft Excel 2010 were used for statistical analysis of the laboratory test results and for descriptive evaluation of the accuracy rate.Results A total of 55 laboratories submitted their testing results giving a return rate of 58.5％ (55/94),of which 52 (94.5％) were consistent with the expected results,while none of the results submitted by the other three laboratories was accurate.At the mean time,the bias of all three batches in each laboratory fell into the same side (two laboratories showed negative bias and one positive bias).Conclusions The results of the external quality assessment of prenatal screening for maternal serum inhibin A are generally satisfactory except for a few laboratories.It is necessary to incorporate prenatal screening for maternal serum inhibin A in the second trimester into the formal external quality assessment plan and regularly monitor the level of its detection quality.

Study on the prediction of premature rupture of membranes with inhibin A / 中国医师进修杂志

Objective To explore the relationship between the level of the pregnant women serum inhibin A and premature rupture of membranes.Methods Thirty-two pregnant women with the gestational age 36-37+6weeks were selected,including 18 cases with premature rupture of membranes (premature rupture of membranes group) and 14 cases without premature rupture of membranes (none premature rupture of membranes group).The serum level of inhibin A was measured by enzyme-linked immunosorbent assay method.Results The serum level of inhibin A in premature rupture of membranes group was significantly higher than that in none premature rupture of membranes group(1 253.5 ng/L vs.698.1 ng/L), and there was statistical difference (P<0.05).The receiver-operating characteristic curve analysis result showed that the optimal cut-off value of serum level of inhibin A to predict premature rupture of membranes was 984.45 ng/L,with a sensitivity of 72.2% and a specificity of 78.6%,and the area under the curve was 0.77(95% CI 0.59-0.95).Conclusions The serum level of inhibin A has a certain predictive value for premature rupture of membranes.

How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency / Como os marcadores polimórficos contribuem para as doenças genéticas em diferentes populações? O estudo da inibina A para insuficiência ovariana prematura

ABSTRACT Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

RESUMO Objetivo Verificar a incidência da mutação G679A no éxon 2 do gene da inibina alfa (INHA) em mulheres com amenorreia secundária e diagnóstico de insuficiência ovariana prematura e em controles. Métodos Uma amostra de 5mL de sangue periférico foi coletada de todos os participantes do estudo em tubo de EDTA e utilizada para a extração de DNA. Para o grupo de pacientes, foram coletados também 5mL de sangue em tubo contendo heparina para realização de cariótipo, e 5mL um tubo seco para dosagem de hormônio folículo-estimulante. As amostras de pacientes e controles foram inicialmente submetidas à análise da variante G679A no éxon 2 do gene INHA pela técnica de PCR-RFLP. As amostras de pacientes com insuficiência ovariana prematura após PCR-RFLP foram submetidas ao sequenciamento de Sanger dos éxons codantes 2 e 3. O sequenciamento foi realizado em equipamento ABI 3500 GeneticAnalyzer, e os resultados foram avaliados pelos programas SeqA and Variant Reporter. Resultados Foram avaliadas amostras de 70 mulheres com insuficiência ovariana prematura e de 97 controles férteis. A variante G769A foi encontrada em apenas uma paciente do Grupo Insuficiência Ovariana Prematura e em nenhum controle, e parece ser rara nas pacientes brasileiras com insuficiência ovariana prematura. Este polimorfismo foi previamente associado à insuficiência ovariana prematura em diversas populações no mundo. Conclusão O estudo evidenciou que há heterogeneidade genética quanto ao INHA em diferentes populações e entre as causas de insuficiência ovariana prematura.

The application value of INHB and AMH tests in assisted reproductive technology / 中华检验医学杂志

Inhibin B(INHB) and anti-Müllerian hormone(AMH) detection have important clinical significance in assisted reproductive technology.INHB for evaluation of male testis function is very meaningful,playing a guiding role in the treatment of oligospermatism.INHB has very high clinical diagnosis value for evaluation of ovarian reserve function,being an important indicator to predict the effect of controlled ovarian hyperstimulation.AMH for evaluation of women ovarian function is significant,and is a diagnosis index of reproductive domain related diseases such as polycystic ovary syndrome and one of the important indices for evaluation of assisted reproductive outcomes.

Evaluation of AMH and INHB in the diagnosis of polycystic ovary syndrome / 中华检验医学杂志

Objective To assess the clinical diagnosis value and treatment effect of anti-Müllerian hormone(AMH)and inhibin B(INHB)in polycystic ovary syndrome(PCOS)patients.Methods Total of 300 cases of PCOS patients were enrolled in this study from January 2014 to January 2016 in the First Affiliated Hospital,Hunan University of Chinese Medicine,and those patients were randomly divided into group A,group B and group C.There were 100 patients in every group.The patients in group A were interfered by traditional Chinese medicine.The patients in group B were treated with Western medicine and those in group C were treated with traditional Chinese medicine combined with western medicine.Total of 264 cases health volunteers were enrolled as the control group.The effect was evaluated.The level of AMH and INHB in serum of PCOS patients were detected by chemiluminescent assay before treatment and three months after treatment.Results The cutoffs of AMH and INHB were 6.98 ng/ml and 150 pg/ml,respectively.The AUC of AMH combined with INHB was significantly larger than that of AMH or INHB(0.945 vs.0.859,0.945 vs.0.784).In the PCOS group,the positive PCOS rate of AMH combined with INHB was significantly larger than that of AMH or INHB[87.00％(261/300)vs.83.33％(250/300)vs.93.67％(281/300),x2=15.593,P=0.000].The sensitivity[93.67％(281/300)],specificity[92.42％(244/264)],positive predictive value[93.36％(281/288)],negative predictive value[92.78％(244/264)]and Jordanian index(0.659)of AMH combined with INHB was significantly larger than that of AMH[87.00％(261/300),87.88％(232/264),89.08％(261/293),85.61％(232/271)and 0.612]or INHB[83.33％(250/300),90.15％(238/264),90.58％(250/276),82.64％(238/301)and 0.571].After treatment,AMH[(9.06±2.13)ng/ml vs.(6.34±1.12)ng/ml,t=10.595,P=0.000;(9.08±2.08)ng/ml vs.(6.02±1.02)ng/ml,t=13.209,P=0.000;(9.13±2.31)ng/ml vs.(3.53±0.83)ng/ml,t=22.814,P=0.000]and INHB[(173.13±14.22)pg/ml vs.(145.26±13.05)pg/ml,t=14.440,P=0.000;(174.28±13.82)pg/ml vs.(145.39±12.98)pg/ml,t=15.238,P=0.000;(174.98±13.77)pg/ml vs.(133.15±12.04)pg/ml,t=22.869,P=0.000]in 3 groups had decreased.After treatment,the AMH of group C [(3.53±0.83)ng/ml] was significantly lower than that of group A and B[(6.34±1.12)ng/ml and(6.02±1.02)ng/ml,F=237.936,P=0.000],and the level of AMH in group C [(133.15±12.04)pg/ml] was significantly lower than that in both group A and group B[(145.26±13.05)pg/ml and(145.39±12.98)pg/ml,F=30.645,P=0.000].Conclusions AMH combined with INHB can be used to diagnose PCOS.AMH and INHB can be used to evaluate PCOS efficacy.

Effect of prohibitin on hepatitis C virus replication / 临床肝胆病杂志

ObjectiveTo investigate the effect of prohibitin (PHB) on hepatitis C virus (HCV) replication. MethodsHuman hepatocarcinoma Huh-7.5 cells were transfected with the full-length genome HCV RNA in vitro to establish the full-length genome cell model of HCV, and the supernatants were collected 24, 48, 72, and 96 hours later to measure HCV copies. The indirect immunofluorescence assay was used to measure the expression of HCV core proteins, and a transmission electron microscope was used to observe the changes in the ultrastructure of HCV-infected Huh-7.5 cells and identify the full-length genome cell model of HCV. Quantitative real-time PCR and Western Blot were used to measure the expression of PHB in HCV-infected Huh-7.5 cells, and the RNA interference technique was used to measure the replication of HCV RNA. The t-test was used for comparison between groups. ResultsThe results of identification showed that the HCV full-length genome cell model was successfully established. At 24 and 48 hours after Huh-7.5 cells were transfected with HCV RNA, the mRNA expression level of PHB was 13.41±1.35 and 16.45±1.76, respectively, which differed significantly from that in the control group (101±057 and 101±087，t=29540 and 31361，both P＜0.01), and the 24- and 48-hour transfection groups showed a significantly higher expression level of PHB than the control group (both P＜0.01). At 24 and 48 hours after Huh-7.5 cells were transfected with the RNA interference plasmids of PHB, the level of HCV RNA was 64.32±5.49 and 84.45±7.06, respectively, significantly higher than that in the control group (shRNA-control group; 10.52±1.57 and 16.34±2.97, t=29538 and 25908，all P＜0.01). ConclusionIn HCV-infected Huh-7.5 cells, the increased expression of PHB is closely related to HCV RNA infection, and to a certain extent, PHB can inhibit the replication of HCV RNA.

Significance of serum levels of inhibin B in women with polycystic ovary syndrome during controlled ovarian stimulation / 中国基层医药

Objective To explore the dynamic variation of inhibin B(INHB)in patients with polycystic ovary syndrome(PCOS)in the course of controlled ovarian stimulation(COS).To analyze the correlation between the increment of serum INHB and the dosage of Gn and the number of oocytes in PCOS.Methods Immunohistochemistry was performed to assess the level of INHB in 90 patients with PCOS and 20 normal childbearing period women in the course of COS.We collected the blood samples of all the patients on the third day of the menstrual(day 3),the day start to administrate exogenous gonadotropin(Gn day),five days later of the Gn day(Gn5 day)and the day of HCG injection(HCG day),respectively.Results Compared with the control group,the serum level of INHB was higher in the PCOS group,regardless day3,Gn day,Gn5 day and HCG day,the difference was statistically significant(P <0.01).In the course of COS,the level of serum INHB in the tow groups was increased.In the PCOS group,the greater the ΔINHB(the growth of the serum level of INHB on Gn5 day),the less of the Gn dosage,and the more number of oocytes retrieved.Conclusion In the process of COS,the serum level of INHB has obvious change.The serum levels of INHB reduce after pituitary down -regulation,then increase after COS.

Effects of chronic arsenic poisoning on serum inhibin-B and testosterone in male rats / 中华地方病学杂志

Objective To evaluate the effects of chronic arsenic poisoning on serum inhibin-B (INH-B) and testosterone of male rats.Methods Forty Sprague-Dawley rats in cleanliness grad were randomly divided into four groups according to body weight:high-dose,middle-dose,low-dose arsenic exposure groups and control group,10 animals in each group.Rats in high-dose,middle-dose,and low-dose groups were administered with arsenic in concentrations of 10.0,5.0,2.5,0.0 mg/kg in distilled water,respectively.Rats in control group were fed with distilled water freely.After 9 months,serum INH-B and testosterone were tested using an ELISA Kit.Results Serum INH-B and testosterone levels in the above mentioned four groups,respectively,were (66.31 ± 37.21),(75.13 ± 29.88),(119.02 ± 36.10),(133.04 ± 38.67)ng/L and (1.292 ± 0.715),(1.757 ± 0.649),(2.359 ± 0.675),(2.817 ± 0.890)μg/L,and the differences between different groups were statistically significant (F=84.88,8.214,all P ＜ 0.05).Serum INH-B and testosterone levels in high-dose and middle-dose groups were significantly lower than that of control group(all P＜ 0.05),whereas no significant difference was found between low-dose group and control group (all P ＞ 0.05).Conclusion Chronic arsenic poisoning has led to decreased concentration of serum INH-B and testosterone in male rats.

Efficiency of quadruple test including inhibin-A in second-trimester screening for Down syndrome / 中华围产医学杂志

ObjectiveTo establish the reference value of inhibin-A in the serum of pregnant women with gestational age from 15 to 20+6 weeks in Guangdong province,and assess the efficiency of inhibin-A and quadruple test in Down syndrome screening.Methods A total of 2802 singleton pregnancies receiving triple test screening in Guangzhou Women and Children's Medical Center from March 2008 to December 2010 were included in this study.Inhibin-A was measured by automatic enzyme-linked immunosorbent chemiluminescence assay. The concentration of inhibin-A was expressed as multiples of the median (MoM),and adjusted with maternal weight and gestational age.Parameters of SURUSS were used to recalculate the risk of Down syndrome.The efficacy of single marker and combination were evaluated by receiver operating characteristic curve and the area under the curve. Results(1) In normal singleton pregnancies,the median concentration of inhibin-A was 286.60,267.10,249.10,243.40,242.30 and 256.60 pg/ml respectively for each week of gestational age from 15 to 20+6 weeks.The distribution of inhibin-A in each gestational week was relatively stable.The mean concentration [(852.83±370.04) pg/ml] and MoM (2.82) of inhibin-A in twelve pregnant mothers with Down syndrome fetuses were significantly higher than those without [(293.28±149.46) pg/ml (t=5.37,P＜0.05) and 1,respectively].(2) The detection rate was 83.3％ (10/12) by using the quadruple test including free human chorionic gonadotropin-β,alphafetoprotein,unconjugated estriol and inhibin-A at false positive rate of 5.8％; while when the detection rate of triple test including alpha-fetoprotein,free human chorionic gonadotropin-β and unconjugated estriol was 83.3％,the false positive rate was 7.7％.When the false positive rate was set to 5.0％,the area under the curve of inhibin-A,alpha-fetoprotein,free human chorionic gonadotropin-β and unconjugated estriol was 63.7％,20.5％,46.1％ and 4.8％,respectively,and the relative area under the curve of routine triple test and quadruple test was 45.5％ and 63.1％,respectively.ConclusionsInhibin-A is suggested to be the most effective marker used for secondtrimester screening,which could be used for second trimester Down syndrome screening in Chinese population combined with existing three markers.

Anti-thrombotic effect and pharmacokinetics of a novel factor Xa inhibitor Bg115-2 in mice / 中国药理学与毒理学杂志

OBJECTIVETo evaluate antithrombotic efficacy and preliminary pharmacokinetics of Bg115-2.METHODSProthrombin time (PT) and activated partial thromboplastin time (APTT) in vitro were determined using assay kits,respectively.The effect on venous thrombosis was evaluated with the model of inferior sinus venous thrombosis in mice.Bleeding reaction was measured by tail bleeding time test.Preliminary pharmacokinetic study was conducted using FXa activity assay.RESULTSBg115-2 (sc) 0.75 -3.0 mg·kg-1 prolonged PT (P＜0.05,P＜0.01) and APTT (P ＜ 0.01) dose-dependently. In the inferior sinus venous thrombosis model,Bg115-20.19 - 3.0 mg· kg-1 significantly reduced thrombus mass with ID50 of 0.19 mg· kg-1.Interestingly,Bg115-2 (ig) 1.5 -6.0 mg·kg-1 also significantly reduced venous thrombus mass (P ＜0.01 ).Bg115-2 was similar to nadroparin calcium in bleeding reaction,and ED2/ID50 reached up to 26.8.Furthermore,Bg115-2 3.0 mg· kg-1 displayed a pharmacokinetic character with a two-compartment model.t1/2,cmax and AUC were (6.18 + 1.45 ) h,(5.20 + 0.66) mg·L-1 and (43.75 +8.20)mg·L-1 ·h,respectively.CONCLUSIONBg115-2 is a potent and oral effective inhibitor of venous thrombosis in mice with slight bleeding side-effect.It has longer t1/2 and the distribution character of a twocompartment model.

Serum biomarkers for predicting pregnancy outcome in women undergoing IVF: human chorionic gonadotropin, progesterone, and inhibin A level at 11 days post-ET / 대한생식의학회지

OBJECTIVE: This study was performed to assess the prognostic value of serum hCG, progesterone, and inhibin A levels measured at 11 days post-ET for predicting pregnancy outcome in women participating in IVF. METHODS: Between May 2005 and April 2008, sera were obtained from 70 infertile women who underwent IVF-ET at 11 days post-ET and stored. HCG, progesterone, and inhibin A levels were measured by commercial enzyme-linked immunosorbent assay kits. The predictive accuracy of hCG, progesterone, and inhibin A levels for establishment of intrauterine pregnancy and ongoing pregnancy was calculated by receiver-operating characteristic curve analysis. RESULTS: For the prediction of intrauterine and ongoing pregnancy, serum hCG was better than progesterone and inhibin A. The predictive performance of progesterone and inhibin A was similar. The serum progesterone and inhibin A levels were significantly correlated each other (r=0.915, p=0.010). CONCLUSION: A single measurement of the serum hCG level is sufficient to predict pregnancy outcome in IVF-ET patients.

Serum myostatin levels and malnutrition in patients with chronic obstructive pulmonary disease / 中华内科杂志

Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.

Aplicações das dosagens de inibinas em Ginecologia e Obstetrícia / Clinical usefulness of inhibin assays in Gynecology and Obstetrics

Na mulher, a principal fonte de inibina B são as células da granulosa de folículos em crescimento, enquanto a inibina A é secretada principalmente pelo corpo lúteo e pela placenta. Em mulheres inférteis submetidas a terapias de reprodução assistida, a inibina B se mostrou útil para predizer má resposta ovulatória, embora não tenha superado o desempenho de outros marcadores. No rastreamento pré-natal da síndrome de Down, a utilidade da inibina A foi repetidamente confirmada no segundo trimestre e começa a ser considerada também na bateria de testes do primeiro trimestre. Além das duas aplicações acima, a dosagem de inibina total pode contribuir para a identificação de casos de insuficiência ovariana autoimune. A inibina total também pode ser um marcador auxiliar no diagnóstico de tumores epiteliais do ovário, enquanto a dosagem de inibina B auxilia no diagnóstico de tumores de células da granulosa. O uso da inibina A pode se estender à avaliação de gestantes com ameaça de abortamento, com história de abortamento de repetição, com risco aumentado de pré-eclâmpsia, ou ainda nos primeiros dias de seguimento pós-esvaziamento de mola hidatiforme. Todas essas aplicações continuam em estudo, mas com possibilidade real de virem a ampliar o espectro diagnóstico das dosagens de inibinas em Ginecologia e Obstetrícia.

The main source of inhibin B in women is the growing follicle granulosa cells, while inhibin A is mainly produced by the corpus luteum and the placenta. In infertile women submitted to therapies of assisted reproduction, inhibin B has shown to be useful to predict a poor ovulatory response, though it has not yet overcome the performance of other markers. In the pre-natal screening of the Down syndrome, inhibin A has been repeatedly confirmed as useful in the second trimester and has also started to be considered in the first trimester test battery. Besides the two applications above, the dosage of total inhibin may contribute to the identification of cases of autoimmune ovarian insufficiency. Total inhibin may also be an auxiliary marker in the diagnosis of ovarian epithelial tumors, while the amount of inhibin B helps in the diagnosis of granulosa cells tumors. The use of inhibin A may be extended to the evaluation of pregnant women with risk of abortion, with a history of repeated abortion, with increased risk of pre-eclampsia, or even in the first days of follow-up of hydatiform mole post-emptying. All those applications are still under study, but with a real possibility of helping to extend the diagnostic spectrum of inhibin dosage in Gynecology and Obstetrics.

Progression of the FLT3 Inhibitor in acute myeloid leukemia / 白血病·淋巴瘤

FLT3, a tyrosine kinase receptor, is the most common mutation in AML and has two classes of mutations: internal tandem duplications in the juxtamembrane domain (FLT3-ITDs) and point mutations in the tyrosine kinase domain (FLT3-TKDs). AML patients with FLT3 mutations tend to have a poor prognosis. As an independent factor, the presences of FLT3 mutations play an important role in the origin and development of AML and have prognostic value. Molecular targeted therapy represents a novel and popular therapeutic approach in the world. In this review, we explain clinical value of the FLT3 mutations, mechanism and research progression of the FLT3 inhibitor;and discuss difficulties and perspectives in the research of the FLT3 inhibitor.

The relationship of inhibin-B in serum and endometrium / 中国医师杂志

Objective To detect the frequency and tissue distribution pattern of inhibin subunits in normal endometrium and periph-eral blood, and investigate the precise action in endometrium. Methods Normal cndometrial tissues were obtained from 16 women in the proliferative phase with salpingo-infertility, 11 women in the early secretory phase and 17 women in the late secretory phase with cervical cancer from Jan to Dee 2006. Expression of INH subunits were detected by immunohistochcmistry. INH-B in the blood samples were detec-ted. None of patients took any steroid drugs before 6 months of giving the samples. Results Immunohistochemistry showed that INH sub-units expressed in normal endometrial tissues. The expression intensity of INH subunits gradually increased in different menstrual phases. The level of inhibin-B in proliferative phase was higher than that in late secretory phase. Conclusions The relationship of inhibin-B level in serum and expression of inhibin subunits in endometrium showed that inhibin could be involved in autocrine/paracrine signaling and contrib-ute to several aspects of endometrial maturation.

Correlation between serum inhibin B level afar treatment with gonadotropin releasing hormone agonist and outcome of in vitro fertilization-embryo transfer / 中华妇产科杂志

Objective To evaluate the decreased level of serum inhibin B(INHB)treated by gunadotropin releasing hormone agonist(GNRH-a)in predicting ovarian response and pregnancy in in vitro fertilization-embryo transfer(IVF-ET).Methods The prospective study enrolled 124 women given by GnRH-a+recombine follicle stimulating hormone(rFSH)+human chorionic gonadotrophin(hCG)long term stimulation protocol undergone their first cycle of IVF-ET treatment.The following predictive factors were collected and analyzed,such as age,basal level of follicle stimulating hormone(FSH),the ratio of FSH/luteinizing hormone(LH),the concentration of INHB after down-regulation,total number of antral follicle count(AFC)and mean ovarian volume. Ovarian response was evaluated by the number of oecytes obtained.A multiple regression analysis and logistic regression model were used for all possible prognostic variables to evaluate the value of difierent hormones in predicting ovariall response and pregnancy after IVF-ET.Receiver operating characteristic(ROC) analysis was used to evaluate the level of INHB in predicting the number of oocytes obtained.The sensitivity and specificity were calculated at the discriminating cut-off point Results The concentration of INHB after down-regulation showed a highly significant positive correlations with the number of oocytes obtained(r=0.435,P<0.01).The multiple regression analyses showed INHB was the most significant predictor of the number of retrieved oocytes,but INHB was not associated with IVF-ET outcome significantly(P>0.05).ROC analyses showed INHB after down-regulation had the largest area under curve(AUC)0.933(95%CI:0.878-0.988).When a threshold of 15 ng/L of INHB was established,95.5%sensitivity and 50.0% specificity in ovarian response were observed.Conclusions The level of INHB Was the best factor in predicting ovarian response in IVF-ET.Decreased level of INHB Was the early sign of ovarian reserve function failure,however,useless in predicting IVF-ET outcome.

Differences in the expression of inhibin receptors and activin receptors in normal human ovaries and their significance / 中华妇产科杂志

Objective To explore the differences in the expression of inhibin(INH)receptors and activin (ACT)receptors in the follicular/luteinic phase in normal human ovaries and their relationship with female endocrine hormone levels.Methods Real time PCR and immunohistochemistry were used to determine the expression of inhibin receptors(INHR)genes,activin receptors(ACTR)genes.Serum estradiol(E2),follicle stimulating hormone(FSH),luteinizing hormone(LH),INHB,ACTA levels were determined by a solid quantitative sandwich enzyme immunoassay technique(Sandwich ELISA)in 21 women during follicular phase and another 21 women during luteinic phase,the correlations between each gene and each hormone were analyzed.Results(1)ACT type Ⅰ and Ⅱ receptors genes(ACTR Ⅰ A,ACTR Ⅰ B,ACTRⅡA,ACTR Ⅱ B)and INH receptor β-glycan genes were expressed higher in the follicular phase than in the luteinic phase:ACTR Ⅰ A(0.50±0.17 vs 0.36±0.18;P＜0.05),ACTR Ⅰ B(0.050±0.019 vs0.036±0.020;P＜0.05),ACTRⅡ A(0.10±0.04 vs 0.07±0.04;P＜0.05),ACTR Ⅱ B(0.28±0.10vs 0.19±0.11;P＜0.05),β-glycan(0.26±0.10 vs 0.17±0.09;P＜0.01).(2)The intensities of ACTR I A,ACTR Ⅱ A,β-glycan immunostaining in human normal ovaries in the follicular phase were significantly stronger compared to those in luteinic phase.In the follicular phase β-glycan expression was positively correlated with serum E2,FSH,LH,INHB levels.The correlation coefficient was 0.53(P＜0.05).0.74(P＜0.01),0.85(P＜0.01)and 0.76(P＜0.01)respectively.Conclusion In normal human ovary in the follicular phase INH and ACT bind their receptors and down-regulate or up-regulate FSH,thus influencing the follicular development.

The Immunoexpressions and Prognostic Significance of Inhibin Alpha and Beta Human Chorionic Gonadotrophins (hCG) in Breast Carcinomas / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Pregnancy and hCG treatments are considered essential for inhibiting breast cancer. The effect of hCG is accompanied by the synthesis of inhibin, a transforming growth factor involved in cell differentiation and proliferation. Inhibin is considered a tumor suppressor, but its role in the breast is unclear. The aim of this study was to determine the frequency and tissue distribution of the expressions of inhibin-alpha and beta-hCG in breast cancer, and their prognostic relevance with other biological parameters. MATERIALS AND METHODS: 334 of formalin-fixed, paraffin embedded tissue blocks were selected, and then immunostained for inhibin-alpha and beta-hCG. The inhibin-alpha expression was compared with those of beta-hCG, ER, PR and HER-2/neu, as well as the tumor characteristics and recurrences. RESULTS: Inhibin-alpha and beta-hCG were expressed in 87 (26.0%) and 44 cases (13.2%), respectively. Inhibin-alpha was found in 25.1% of infiltrating ductal carcinomas (67/267), 26.7% of intraductal carcinomas (8/30), 33.3% of lobular tumors (3/9), 80.0% of apocrine carcinomas (4/5) and 21.7% of the other types (5/23). Inhibin-alpha was correlated with beta-hCG (p<0.0001), PR (p=0.010) and HER-2/ neu (p=0.021). HCG was focally expressed in the cytoplasm of the conventional types, but the apocrine type displayed diffusely intense cytoplasmic staining, which correlated with histological tumor types (p<0.001). CONCLUSION: Inhibin was significantly correlated with the expressions of hCG, PR and HER-2/neu. Therefore, it might be a useful marker in the prevention and hormonal treatment of breast cancer, such as hCG and progesterone. HCG was expressed significantly higher in the apocrine type than the conventional types, suggesting it can be a useful adjunct in differentiating other cancer types.