Single nucleotide polymorphisms (SNP) of chicken gonadotropin-releasing hormone receptor (GnRHR) and neuropeptide Y (NPY) were selected to identify the genotypes of Wenchang (Chinese indigenous breed) chicken ...Single nucleotide polymorphisms (SNP) of chicken gonadotropin-releasing hormone receptor (GnRHR) and neuropeptide Y (NPY) were selected to identify the genotypes of Wenchang (Chinese indigenous breed) chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production (NE), average days of continual laying (ADCL), and number of double-yolked eggs (DYE) traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 (Bpu1102 Ⅰ A) and 0.31 (Bpu1102 Ⅰ a) and for NPY 0.46 (Dra Ⅰ B) and 0.54 (Dra Ⅰ b). Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes' marker were found: for GnRHR and number of eggs (dominant; t= 2.67, df= 116) and NPY and number of eggs (additive; t= 1.97, df= 116). The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.展开更多
Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop...Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop- ment, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.展开更多
Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and de...Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coil strain BL21 StarTM (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.展开更多
The effects of fluoride exposure on thefunctions of reproductive and endocrine systemshave attracted widespread attention in academiccircle nowadays. However, it is unclear whether thegene-environment interaction may ...The effects of fluoride exposure on thefunctions of reproductive and endocrine systemshave attracted widespread attention in academiccircle nowadays. However, it is unclear whether thegene-environment interaction may modify thesecretion and activity of hypothalamus-pituitary-ovarian (HPO) axis hormones. Thus, the aim of thisstudy was to explore the influence of fluorideexposure and follicle stimulating hormone receptor(FSHR) gene polymorphism on reproductivehormones in Chinese women. A cross sectionalstudy was conducted in seven villages of HenanProvince, China during 2010-2011. A total of 679women aged 18-48 years were recruited throughcluster sampling and divided into three groups, i.e.endemic fluorosis group (EFG), defluoridationproject group (DFPG), and control group (CG) basedon the local fluoride concentration in drinkingwater. The serum levels of gonadotropin releasinghormone (GnRH), follicle stimulating hormone(FSH), luteinizing hormone (LH), and estradiol (E2)were determined respectively and the FSHRpolymorphism was detected by real time PCR assay.The results provided the preliminary evidenceindicating the gene-environment interaction onHPO axishormones in women.展开更多
This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor(ER), proges...This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor(ER), progesterone receptor(PR) and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry.Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2%(79/521), 26.9%(140/520) and 44.8%(225/502), respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5%(39/521), 13.3%(69/520) and 21.1%(106/502) of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7%(40/521), 13.6%(71/520)and 23.7%(119/502) of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.展开更多
[ Objective] To clone follicle-stimulating hormone receptor (FSHR) promoter in the Jintang black goat, study its transcriptional activity, and provide a basis for alternative splicing of FSHR gene. [Method] The tota...[ Objective] To clone follicle-stimulating hormone receptor (FSHR) promoter in the Jintang black goat, study its transcriptional activity, and provide a basis for alternative splicing of FSHR gene. [Method] The total DNA were extracted from the womb of Jintang black goat, and one pair of primers were designed for amplification of FSHR promoter fragments, then the sequences and homology were analyzed. The FSHR promoter fragment was inserted into the pcFSHRB1 expression vector to substitute the CMV promoter and construct the pcFSHRB2 expression vector. The pcFSHRB1 and pcFSHRB2 expression vectors were transformed into HEK293 cells, respectively. Then these cells were collected after 24 and 48 h treatment with 2 mlU/ml follicle-stimulating hormone (FSH), and the cAMP levels were detected. [Result] The FSHR promoter sequence of Jin- tang black goat had 34.2% homology to that of chicken and 41.6% to that of rat, respectively. The transcription initial site of FSHR was at -576 bp and its upstream sequences contained two TATA-boxes, four CAAT-boxes, one E-box and one Wl-box. After treating for 24 and 48 h, the cAMP levels of pcFSHRB2 were respectively 299.581 3 and 125.528 1 pmol/L; and that of pcFSHRB1 were respectively 120.057 1 and 109.940 7 pmoVL. [Conclusion] The FSHR promoter of Jintang black goat is a typical type 2 eukaryotic promoter, and it is also a strong promoter.展开更多
The female internal sex organs develop from the paramesonephric (Mullerian) duct. In male embryos, the regression of the Mullerian duct is caused by the anti-Mullerian hormone (AMH), which plays an important role ...The female internal sex organs develop from the paramesonephric (Mullerian) duct. In male embryos, the regression of the Mullerian duct is caused by the anti-Mullerian hormone (AMH), which plays an important role in the process of testicular descent. The physiological remnant of the Mullerian duct in males is the appendix testis (AT). In our previous study, we presented evidence for the decreased incidence of AT in cryptorchidism with intraoperative surgery. In this report, the expression of the anti-Mullerian hormone receptor type 2 (AMHR2), the specific receptor of AMH, on the AT was investigated in connection with different urological disorders, such as hernia inguinalis, torsion of AT, cysta epididymis, varicocele, hydrocele testis and various forms of undescended testis. The correlation between the age of the patients and the expression of the AMHR2 was also examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect the receptor's mRNA and protein levels, respectively. We demonstrate that AMHR2 is expressed in the ATs. Additionally, the presence of this receptor was proven at the mRNA and protein levels. The expression pattern of the receptor correlated with neither the examined urological disorders nor the age of the patients; therefore, the function of the AT remains obscure.展开更多
Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of M...Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of MC1R gene and alpaca coat color.The MC1R gene from white alpaca was cloned successfully and sequence analysis verified that the MC1R gene,encoding 317 amino acids,was 1081 bp in length.Compared with the existing sequence in GenBank,sequence identity was 99.9%and 7 mutations were found.Primers,designed from the sequence obtained,were used to assess the relative expression of MC1R in alpacas of different coat color using QRT-PCR and SPSS 13.0 software.Relative expression of MC1R in the skin of brown alpacas was 4.32 times higher than that in white alpacas after normalization with GAPDH(P【0.01),indicating that MC1R expression may be related to coat color of alpacas.展开更多
The aim of this study was to determine the expression of growth hormone receptor(GHR) in patients with pri-mary gastric adenocarcinoma.We investigated 48 specimens of primary gastric adenocarcinoma and their cor-res...The aim of this study was to determine the expression of growth hormone receptor(GHR) in patients with pri-mary gastric adenocarcinoma.We investigated 48 specimens of primary gastric adenocarcinoma and their cor-responding normal gastric mucosa.Immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the expression of GHR.Immunohistochemical analyses revealed that GHR was expressed in human primary gastric adenocarcinoma(36/48,75.0%) and appeared to be upregulated,compared to the normal mucosa(28/48,58.3%,P 〈 0.001).A significant correlation was found between GHR expression and tumor stage(P 〈 0.001) and tumor differentiation(P 〈 0.001).The average positive rate of ki-67 in GHR-positive tumors was 16.06%,while the positive rate in GHR-negative tumors was 6.17%(P 〈 0.01).The average apoptosis index(AI) of GHR-positive tumors was 3.36%,which was significantly lower than that(7.33%) of GHR-negative tumors.In addition,27 of 48 cases of tumors had GHR mRNA expression,while only 17 of all 48 cases of normal mucosa did so.Our results indicate that the frequency of GHR was significantly higher in primary gastric adeno-carcinoma than that in normal gastric mucosa.GHR expression was significantly correlated with tumor differen-tiation and tumor grade.This finding supported a possible role of growth hormone in primary gastric adenocarci-noma pathophysiology.展开更多
To explore and enrich the molecular mechanisms of thyroid hormone receptors (TRs) in the metamorphosis of amphibians, the cDNA sequences of TRa and TRβ in Microhyla fissipes were cloned and characterized. TRa was 1...To explore and enrich the molecular mechanisms of thyroid hormone receptors (TRs) in the metamorphosis of amphibians, the cDNA sequences of TRa and TRβ in Microhyla fissipes were cloned and characterized. TRa was 1 706 bp in length with an open reading frame (ORF) of 1 257 bp encoding a predicted protein of 418 amino acids and TRβ was 1 422 bp with an ORF of 1 122 bp encoding a predicted protein of 373 amino acids. Their protein sequences contained 4 conserved domains of the nuclear receptor superfamily with two highly conserved cysteine-rich zinc fingers in the DNA-binding domain, whereas TRβ was 42 amino acids shorter in its A/B domain than TRot. Highly-conserved sequences and structures indicated their conserved functions during metamorphosis. TRa expression reached peak at 12 h and then decreased from 12 h to 48 h. While dramatically up-regulated TRβ was observed after exposure of T3 within 24 h, and it was down-regulated from 24 h to 48 h. The expression pattern of TRβ is similar to that in the natural metamorphosis. Furthermore, tadpoles treated 24 h also resembled the climax of metamorphosis tadpoles and TRβ expression had higher responsiveness than TRa to T3 in M. fissipes. These results suggest M. fissipes may serve as the model to assay environmental compounds on TH signaling disruption.展开更多
The human ovarian mucinous cystadenocarcinoma (hOMC) cells were co-cultured with antisense oligodeoxynucleotide (antisense ODN), nonsense ODN, and follicle-stimulating hormone (FSH) at different concentrations f...The human ovarian mucinous cystadenocarcinoma (hOMC) cells were co-cultured with antisense oligodeoxynucleotide (antisense ODN), nonsense ODN, and follicle-stimulating hormone (FSH) at different concentrations for the purpose of observing the effects of antisense ODN to FSH receptor (FSHR) on the proliferation and apoptosis of cultured hOMC cells in vitro. The inhibitory rates of growth were measured by using MTT method on the 2nd, 4th, 6th, 8th and 10th days after the interference of antisense ODN, nonsense ODN, and FSH, respectively. The apoptotic rates and the cell cycles were determined by means of flow cytometry, the apoptosis indexes were detected by using TUNEL, and the expression of caspase-3 was measured by using SP immunohistochemistry. Compared with that in the control group, the proliferative activity of hOMC cells was increased obviously in FSH groups (P〈0.05 or P〈0.01), decreased distinctly in antisense ODN groups (P〈0.05 or P〈0.01), and unchanged in nonsense ODN groups, respectively. Meanwhile, antisense ODN could significantly antagonize the FSH-promoted cell proliferative activity (P〈0.01). Compared with those in the control group, the apoptotic rates and the expression of caspase-3 were dramatically increased in the mid- and high-dose antisense ODN groups (P〈0.05 or P〈0.01), while the number of cells in G1/G0 phase was significantly decreased and that in S phase distinctly increased (P〈0.01), There was no change in nonsense ODN groups (P〉0.05), It was suggested that FSH may improve the development of hOMC cells, However, antisense ODN could inhibit proliferative activity and the FSH-promoted proliferative activity in hOMC cells, at the same time, antisense ODN could inhibit hOMC cell growth by inducing apoptosis.展开更多
Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- yea...Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- year survival rate through stratification and multivariatc analysis. The results showed that histologic tumor type and grading, lymphnode status, ER value and patient age took more important role in patient survival, and SR, especially, conferred survival advantage in advanced cases with tumor size larger than 2 cm, node involved, or TNM Stage Ⅱ-Ⅲ.展开更多
An easy and reliable method was developed for construction and quantification of competitive templates, which shared the same sequence as the amplified target DNA except for a 20 bp insertion in the middle by recombi...An easy and reliable method was developed for construction and quantification of competitive templates, which shared the same sequence as the amplified target DNA except for a 20 bp insertion in the middle by recombinant polymerase chain reaction (PCR). Among the advantages of competitive PCR is that any predictable or unpredictable variable that affects amplification has the same effect on both target and competitor species and that the final ratio of amplified products reflects exactly the initial targets. The utilization of a thermostable reverse transcriptase in the RT step was proposed to overcome the problem of the efficiency of target cDNA synthesis. In addition, to obtain reliable measurements, it was recommended to perform four PCR with amounts of competitive template flanking the concentration of the target mRNA.展开更多
[ Objective] To study the polymorphism of follicle-stimulating hormone receptor (FSHR) gene in Ningxia Tan sheep and thus to provide a theoretical basis for breeding. I Methodl Genotypes of 111 healthy Ningxia Tan s...[ Objective] To study the polymorphism of follicle-stimulating hormone receptor (FSHR) gene in Ningxia Tan sheep and thus to provide a theoretical basis for breeding. I Methodl Genotypes of 111 healthy Ningxia Tan sheep were examined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). [ResultS] A 306-bp fragment was amplified. The PCR products digested with restriction enzyme Alu I showed polymorphism with three genotypes, L e., GG, CG and CC. The genotypic frequencies of GG, CG and CC were 0.135 1 ( 15 individuals), 0.666 7 (74 individuals) and 0.198 2 (22 individuals), respectively. The allele frequencies of G and C were 0.468 5 and 0.531 5, respectively.[ Conclusion] FSHR aene is Dolvmomhic in Ninaxia Tan Sheeo.展开更多
Background Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent h...Background Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β(TRβ). We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and other laboratory tests were analysed. TFTs of his family's members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones (FT4 and FT3) and normal thyroid-stimulating hormone (TSH) concentrations. He felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.展开更多
Background: In the current society, infertility related to age has become a social problem. The in vitro fertilization (IVF) success rate in women with poor ovarian response (POR) is very low. Dandelion extract T...Background: In the current society, infertility related to age has become a social problem. The in vitro fertilization (IVF) success rate in women with poor ovarian response (POR) is very low. Dandelion extract T-1 (DE-T1) is an effective component of the extract from the leaves and stems of Traxacum officinale, which is one of the medicines used in some patients with POR, but its molecular mechanism remains unclear. Methods: Following IVF, ovarian granulosa cells (GCs) of sixty patients were extracted and divided into normal ovarian response (NOR) and POR groups. GCs were cultured in a dose-dependent and time-dependent manner with DE-TI, proliferation of GCs was determined by Cell Counting Kit-8 assay, and mRNA levels of insulin-like growth factor 1 receptor (IGF-1R), luteotropic hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), LHR, and CYP19A1 (aromatase) were determined by quantitative polymerase chain reaction. Progesterone and estradiol (E2) concentrations were determined by enzyme-linked immunosorbent assay. Results: The cell viability gradually increased with the progressive increase in the DE-T1 concentration. Compared with the control group (without DE-T1), the mRNA expressions of FSHR, LHR, IGF-IR, and CYPIgAI were upregulated after the addition of DE-T l, especially in the 2.5% DE-T 1 group (P 〈 0.01 ). The expression of IGF- 1R was upregulated approximately 25 times (24.97 ± 4.02 times) in the POR group with 2.5% DE-T1. E2 and progesterone levels increased with the increasing DE-T1 concentration. There were highly significant differences in the E2 and progesterone secretion between the NOR and POR groups (P 〈 0.01). Conclusion: DE-TI may promote steroid hormone synthesis by promoting GC proliferation and upregulating GC receptor expression, thereby improving ovarian endocrine function.展开更多
Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulati...Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer.展开更多
Background Follicle stimulating hormone is necessary for normal reproduction in men.The biochemical actions of follicle stimulating hormone result from binding to the follicle stimulating hormone receptor in the plasm...Background Follicle stimulating hormone is necessary for normal reproduction in men.The biochemical actions of follicle stimulating hormone result from binding to the follicle stimulating hormone receptor in the plasma membrane of Sertoli cells.Here,we investigated the expression of the follicle stimulating hormone receptor in different testicular histological phenotypes of patients with idiopathic azoospermia.Methods Fifty-seven cases of idiopathic azoospermia were classified into three groups according to the results of testicular biopsy:patients with hypospermatogenesis,patients with maturation arrest,and patients with Sertoli cell-only syndrome.Thirteen azoospermic patients identified by testicular biopsy as being capable of completing spermatogenesis acted as the control group.Immunohistochemistry and real-time quantitative reverse-transcriptase polymerase chain reaction were performed in each case,and the serum hormone level was also measured in all patients.Results The serum follicle stimulating hormone level in patients with Sertoli cell-only syndrome was significantly higher than in patients with hypospermatogenesis,maturation arrest,and complete spermatogenesis (P<0.01).The serum follicle stimulating hormone level in patients with maturation arrest was significantly higher than in patients with hypospermatogenesis and complete spermatogenesis (P<0.05).There was no difference in serum follicle stimulating hormone levels in patients with hypospermatogenesis and complete spermatogenesis.The follicle stimulating hormone receptor expression level of testicular samples with Sertoli cell-only syndrome was significantly higher than in those with hypospermatogenesis,maturation arrest,and complete spermatogenesis (P<0.05),but no significant difference was observed among hypospermatogenesis,maturation arrest,and complete spermatogenesis testicular samples.Conclusions Different serum follicle stimulating hormone levels and follicle stimulating hormone receptor expression were found in the different testicular histology phenotypes in azoospermic patients.Differential follicle stimulating hormone receptor expression in testicular tissue of patients with idiopathic azoospermia may be associated with the degree of spermatogenesis.展开更多
Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in...Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC.From the“AI(aromatase inhibitor)era”represented by aromatase inhibitors,we have gradually entered the“post-AI era”represented by fulvestrant.Under the guidance of research on the molecular mechanism of endocrine therapy resistance,the“combination of endocrine therapy and targeted therapy”era is approaching.The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors,histone deacetylase inhibitors,and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)pathway,providing new strategies for HR-positive MBC.Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.展开更多
Thyroid hormone receptors (TR), ligand-mediated transcription factors, regulate cell growth, differentiation, and apoptosis. In humans, two different genes encode TR-α and TR-β and they are often co-expressed in v...Thyroid hormone receptors (TR), ligand-mediated transcription factors, regulate cell growth, differentiation, and apoptosis. In humans, two different genes encode TR-α and TR-β and they are often co-expressed in various tissues at different levels. To explore the role of TR in esophageal cancer, we analyzed expression of TR-β1 mRNA (most abundantly expressed in the majority of normal cells) in normal and malignant esophageal tissue specimens using in situ hybridization. The TR-β1 mRNA was detected in 92.3% (96 of 104) of normal esophageal mucosa, whereas TR-β1 mRNA was only detected in 55.8% (58 of 104 cases) of esophageal squamous cell carcinoma specimens (P〈 0.00001). Expression of TR-β1 mRNA was associated with well-differentiated cancers (P〈 0.001). Furthermore, we determined whether the loss of heterozygosity (LOH) in TR-β1 gene locus would be responsible for the lost TR-β1 expression. Analysis of 73 esophageal tissue specimens generated 39 informative cases, 17 of which showed LOH (43.6%) but only 9 of these 17 cases were correlated with lost TR-β1 expression. This study demonstrated that expression of TR-β1 mRNA was lost in esophageal cancer tissues, which may be due to multiple mechanisms.展开更多
文摘Single nucleotide polymorphisms (SNP) of chicken gonadotropin-releasing hormone receptor (GnRHR) and neuropeptide Y (NPY) were selected to identify the genotypes of Wenchang (Chinese indigenous breed) chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production (NE), average days of continual laying (ADCL), and number of double-yolked eggs (DYE) traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 (Bpu1102 Ⅰ A) and 0.31 (Bpu1102 Ⅰ a) and for NPY 0.46 (Dra Ⅰ B) and 0.54 (Dra Ⅰ b). Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes' marker were found: for GnRHR and number of eggs (dominant; t= 2.67, df= 116) and NPY and number of eggs (additive; t= 1.97, df= 116). The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.
基金Supported by Research Award from KaroBio AB, Sweden (to Parini P)
文摘Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop- ment, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.
基金This study was supported by the National Key Technologies R and D Program (No. 2012BAI31B07 and No. 2006BAI03B12), the National Science Foundationof China (No. 81172694). This project was also funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coil strain BL21 StarTM (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.
基金supported by the National Natural Science Foundation of China(No.81072247)the Education Department of Henan Province,China(No.13A330653)
文摘The effects of fluoride exposure on thefunctions of reproductive and endocrine systemshave attracted widespread attention in academiccircle nowadays. However, it is unclear whether thegene-environment interaction may modify thesecretion and activity of hypothalamus-pituitary-ovarian (HPO) axis hormones. Thus, the aim of thisstudy was to explore the influence of fluorideexposure and follicle stimulating hormone receptor(FSHR) gene polymorphism on reproductivehormones in Chinese women. A cross sectionalstudy was conducted in seven villages of HenanProvince, China during 2010-2011. A total of 679women aged 18-48 years were recruited throughcluster sampling and divided into three groups, i.e.endemic fluorosis group (EFG), defluoridationproject group (DFPG), and control group (CG) basedon the local fluoride concentration in drinkingwater. The serum levels of gonadotropin releasinghormone (GnRH), follicle stimulating hormone(FSH), luteinizing hormone (LH), and estradiol (E2)were determined respectively and the FSHRpolymorphism was detected by real time PCR assay.The results provided the preliminary evidenceindicating the gene-environment interaction onHPO axishormones in women.
基金supported by National Natural Science Foundation of China (NSFC) (81372851)
文摘This study was designed to investigate the effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki67 in Chinese female breast cancer patients. The expression of estrogen receptor(ER), progesterone receptor(PR) and Ki67 among 525 neoadjuvant chemotherapy cases was studied by immunohistochemistry.Differences between specimens made through preoperative core needle biopsy and excised tissue biopsy were observed. The positive rates of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy were 65.3% and 63.2%, 51.0% and 42.6%, 65.6% and 43.4%, respectively. The expression of ER, PR and Ki67 in core needle biopsy and excised tissue biopsy had no statistically significant difference. However, after neoadjuvant chemotherapy, the discordance rates of ER, PR and Ki67 were 15.2%(79/521), 26.9%(140/520) and 44.8%(225/502), respectively. The ER, PR and Ki67 status changed from positive to negative in 7.5%(39/521), 13.3%(69/520) and 21.1%(106/502) of the patients, whereas ER, PR and Ki67 status changed from negative to positive in 7.7%(40/521), 13.6%(71/520)and 23.7%(119/502) of the patients, respectively. These results showed that the status of some biomarkers changes after neoadjuvant chemotherapy and biomarker status needs to be reexamined to optimize adjuvant systemic therapy and better prognosis assessment.
基金supported by Poultry and Aqua Breeding Project of Sichuan Province
文摘[ Objective] To clone follicle-stimulating hormone receptor (FSHR) promoter in the Jintang black goat, study its transcriptional activity, and provide a basis for alternative splicing of FSHR gene. [Method] The total DNA were extracted from the womb of Jintang black goat, and one pair of primers were designed for amplification of FSHR promoter fragments, then the sequences and homology were analyzed. The FSHR promoter fragment was inserted into the pcFSHRB1 expression vector to substitute the CMV promoter and construct the pcFSHRB2 expression vector. The pcFSHRB1 and pcFSHRB2 expression vectors were transformed into HEK293 cells, respectively. Then these cells were collected after 24 and 48 h treatment with 2 mlU/ml follicle-stimulating hormone (FSH), and the cAMP levels were detected. [Result] The FSHR promoter sequence of Jin- tang black goat had 34.2% homology to that of chicken and 41.6% to that of rat, respectively. The transcription initial site of FSHR was at -576 bp and its upstream sequences contained two TATA-boxes, four CAAT-boxes, one E-box and one Wl-box. After treating for 24 and 48 h, the cAMP levels of pcFSHRB2 were respectively 299.581 3 and 125.528 1 pmol/L; and that of pcFSHRB1 were respectively 120.057 1 and 109.940 7 pmoVL. [Conclusion] The FSHR promoter of Jintang black goat is a typical type 2 eukaryotic promoter, and it is also a strong promoter.
文摘The female internal sex organs develop from the paramesonephric (Mullerian) duct. In male embryos, the regression of the Mullerian duct is caused by the anti-Mullerian hormone (AMH), which plays an important role in the process of testicular descent. The physiological remnant of the Mullerian duct in males is the appendix testis (AT). In our previous study, we presented evidence for the decreased incidence of AT in cryptorchidism with intraoperative surgery. In this report, the expression of the anti-Mullerian hormone receptor type 2 (AMHR2), the specific receptor of AMH, on the AT was investigated in connection with different urological disorders, such as hernia inguinalis, torsion of AT, cysta epididymis, varicocele, hydrocele testis and various forms of undescended testis. The correlation between the age of the patients and the expression of the AMHR2 was also examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect the receptor's mRNA and protein levels, respectively. We demonstrate that AMHR2 is expressed in the ATs. Additionally, the presence of this receptor was proven at the mRNA and protein levels. The expression pattern of the receptor correlated with neither the examined urological disorders nor the age of the patients; therefore, the function of the AT remains obscure.
基金supported by the National Natural Science Foundation of China(No.30501070)Shanxi Natural Science Foundation(No.20041099)President Foundation of Agricultural University of Hebei (BS2007023)
文摘Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of MC1R gene and alpaca coat color.The MC1R gene from white alpaca was cloned successfully and sequence analysis verified that the MC1R gene,encoding 317 amino acids,was 1081 bp in length.Compared with the existing sequence in GenBank,sequence identity was 99.9%and 7 mutations were found.Primers,designed from the sequence obtained,were used to assess the relative expression of MC1R in alpacas of different coat color using QRT-PCR and SPSS 13.0 software.Relative expression of MC1R in the skin of brown alpacas was 4.32 times higher than that in white alpacas after normalization with GAPDH(P【0.01),indicating that MC1R expression may be related to coat color of alpacas.
文摘The aim of this study was to determine the expression of growth hormone receptor(GHR) in patients with pri-mary gastric adenocarcinoma.We investigated 48 specimens of primary gastric adenocarcinoma and their cor-responding normal gastric mucosa.Immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the expression of GHR.Immunohistochemical analyses revealed that GHR was expressed in human primary gastric adenocarcinoma(36/48,75.0%) and appeared to be upregulated,compared to the normal mucosa(28/48,58.3%,P 〈 0.001).A significant correlation was found between GHR expression and tumor stage(P 〈 0.001) and tumor differentiation(P 〈 0.001).The average positive rate of ki-67 in GHR-positive tumors was 16.06%,while the positive rate in GHR-negative tumors was 6.17%(P 〈 0.01).The average apoptosis index(AI) of GHR-positive tumors was 3.36%,which was significantly lower than that(7.33%) of GHR-negative tumors.In addition,27 of 48 cases of tumors had GHR mRNA expression,while only 17 of all 48 cases of normal mucosa did so.Our results indicate that the frequency of GHR was significantly higher in primary gastric adeno-carcinoma than that in normal gastric mucosa.GHR expression was significantly correlated with tumor differen-tiation and tumor grade.This finding supported a possible role of growth hormone in primary gastric adenocarci-noma pathophysiology.
基金funded by the Important Research Project of Chinese Academy of Sciences (KJZG-EW-L13)2015 Western Light Talent Culture Project of the Chinese Academy of Sciences (Y6C3021)the Basic Application Project of Sichuan Province (2017JY0339)
文摘To explore and enrich the molecular mechanisms of thyroid hormone receptors (TRs) in the metamorphosis of amphibians, the cDNA sequences of TRa and TRβ in Microhyla fissipes were cloned and characterized. TRa was 1 706 bp in length with an open reading frame (ORF) of 1 257 bp encoding a predicted protein of 418 amino acids and TRβ was 1 422 bp with an ORF of 1 122 bp encoding a predicted protein of 373 amino acids. Their protein sequences contained 4 conserved domains of the nuclear receptor superfamily with two highly conserved cysteine-rich zinc fingers in the DNA-binding domain, whereas TRβ was 42 amino acids shorter in its A/B domain than TRot. Highly-conserved sequences and structures indicated their conserved functions during metamorphosis. TRa expression reached peak at 12 h and then decreased from 12 h to 48 h. While dramatically up-regulated TRβ was observed after exposure of T3 within 24 h, and it was down-regulated from 24 h to 48 h. The expression pattern of TRβ is similar to that in the natural metamorphosis. Furthermore, tadpoles treated 24 h also resembled the climax of metamorphosis tadpoles and TRβ expression had higher responsiveness than TRa to T3 in M. fissipes. These results suggest M. fissipes may serve as the model to assay environmental compounds on TH signaling disruption.
文摘The human ovarian mucinous cystadenocarcinoma (hOMC) cells were co-cultured with antisense oligodeoxynucleotide (antisense ODN), nonsense ODN, and follicle-stimulating hormone (FSH) at different concentrations for the purpose of observing the effects of antisense ODN to FSH receptor (FSHR) on the proliferation and apoptosis of cultured hOMC cells in vitro. The inhibitory rates of growth were measured by using MTT method on the 2nd, 4th, 6th, 8th and 10th days after the interference of antisense ODN, nonsense ODN, and FSH, respectively. The apoptotic rates and the cell cycles were determined by means of flow cytometry, the apoptosis indexes were detected by using TUNEL, and the expression of caspase-3 was measured by using SP immunohistochemistry. Compared with that in the control group, the proliferative activity of hOMC cells was increased obviously in FSH groups (P〈0.05 or P〈0.01), decreased distinctly in antisense ODN groups (P〈0.05 or P〈0.01), and unchanged in nonsense ODN groups, respectively. Meanwhile, antisense ODN could significantly antagonize the FSH-promoted cell proliferative activity (P〈0.01). Compared with those in the control group, the apoptotic rates and the expression of caspase-3 were dramatically increased in the mid- and high-dose antisense ODN groups (P〈0.05 or P〈0.01), while the number of cells in G1/G0 phase was significantly decreased and that in S phase distinctly increased (P〈0.01), There was no change in nonsense ODN groups (P〉0.05), It was suggested that FSH may improve the development of hOMC cells, However, antisense ODN could inhibit proliferative activity and the FSH-promoted proliferative activity in hOMC cells, at the same time, antisense ODN could inhibit hOMC cell growth by inducing apoptosis.
文摘Clinical, pathological features and steroid hormone receptors (SR) including receptors of estrogen (ER), progesterone (PR) and androgen (AR) were observed in 58 cases of breast carcinoma, and related to patient 5- year survival rate through stratification and multivariatc analysis. The results showed that histologic tumor type and grading, lymphnode status, ER value and patient age took more important role in patient survival, and SR, especially, conferred survival advantage in advanced cases with tumor size larger than 2 cm, node involved, or TNM Stage Ⅱ-Ⅲ.
文摘An easy and reliable method was developed for construction and quantification of competitive templates, which shared the same sequence as the amplified target DNA except for a 20 bp insertion in the middle by recombinant polymerase chain reaction (PCR). Among the advantages of competitive PCR is that any predictable or unpredictable variable that affects amplification has the same effect on both target and competitor species and that the final ratio of amplified products reflects exactly the initial targets. The utilization of a thermostable reverse transcriptase in the RT step was proposed to overcome the problem of the efficiency of target cDNA synthesis. In addition, to obtain reliable measurements, it was recommended to perform four PCR with amounts of competitive template flanking the concentration of the target mRNA.
基金funded by the Natural Science Foundation of Ningxia of China (NZ0931)Natural Science Foundation of Ningxia University
文摘[ Objective] To study the polymorphism of follicle-stimulating hormone receptor (FSHR) gene in Ningxia Tan sheep and thus to provide a theoretical basis for breeding. I Methodl Genotypes of 111 healthy Ningxia Tan sheep were examined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). [ResultS] A 306-bp fragment was amplified. The PCR products digested with restriction enzyme Alu I showed polymorphism with three genotypes, L e., GG, CG and CC. The genotypic frequencies of GG, CG and CC were 0.135 1 ( 15 individuals), 0.666 7 (74 individuals) and 0.198 2 (22 individuals), respectively. The allele frequencies of G and C were 0.468 5 and 0.531 5, respectively.[ Conclusion] FSHR aene is Dolvmomhic in Ninaxia Tan Sheeo.
文摘Background Resistance to thyroid hormone (RTH) is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β(TRβ). We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests (TFTs) including magnetic resonance imaging (MRI) of pituitary and other laboratory tests were analysed. TFTs of his family's members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones (FT4 and FT3) and normal thyroid-stimulating hormone (TSH) concentrations. He felt worse when treated as hyperthyroidism (Grave disease) with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.
文摘Background: In the current society, infertility related to age has become a social problem. The in vitro fertilization (IVF) success rate in women with poor ovarian response (POR) is very low. Dandelion extract T-1 (DE-T1) is an effective component of the extract from the leaves and stems of Traxacum officinale, which is one of the medicines used in some patients with POR, but its molecular mechanism remains unclear. Methods: Following IVF, ovarian granulosa cells (GCs) of sixty patients were extracted and divided into normal ovarian response (NOR) and POR groups. GCs were cultured in a dose-dependent and time-dependent manner with DE-TI, proliferation of GCs was determined by Cell Counting Kit-8 assay, and mRNA levels of insulin-like growth factor 1 receptor (IGF-1R), luteotropic hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), LHR, and CYP19A1 (aromatase) were determined by quantitative polymerase chain reaction. Progesterone and estradiol (E2) concentrations were determined by enzyme-linked immunosorbent assay. Results: The cell viability gradually increased with the progressive increase in the DE-T1 concentration. Compared with the control group (without DE-T1), the mRNA expressions of FSHR, LHR, IGF-IR, and CYPIgAI were upregulated after the addition of DE-T l, especially in the 2.5% DE-T 1 group (P 〈 0.01 ). The expression of IGF- 1R was upregulated approximately 25 times (24.97 ± 4.02 times) in the POR group with 2.5% DE-T1. E2 and progesterone levels increased with the increasing DE-T1 concentration. There were highly significant differences in the E2 and progesterone secretion between the NOR and POR groups (P 〈 0.01). Conclusion: DE-TI may promote steroid hormone synthesis by promoting GC proliferation and upregulating GC receptor expression, thereby improving ovarian endocrine function.
文摘Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer.
基金This work was supported by the grants from Zhejiang Provincial Natural Science Foundation (No.J20110339) and the National Key Technology Support Program (No.2012BAI32B04).
文摘Background Follicle stimulating hormone is necessary for normal reproduction in men.The biochemical actions of follicle stimulating hormone result from binding to the follicle stimulating hormone receptor in the plasma membrane of Sertoli cells.Here,we investigated the expression of the follicle stimulating hormone receptor in different testicular histological phenotypes of patients with idiopathic azoospermia.Methods Fifty-seven cases of idiopathic azoospermia were classified into three groups according to the results of testicular biopsy:patients with hypospermatogenesis,patients with maturation arrest,and patients with Sertoli cell-only syndrome.Thirteen azoospermic patients identified by testicular biopsy as being capable of completing spermatogenesis acted as the control group.Immunohistochemistry and real-time quantitative reverse-transcriptase polymerase chain reaction were performed in each case,and the serum hormone level was also measured in all patients.Results The serum follicle stimulating hormone level in patients with Sertoli cell-only syndrome was significantly higher than in patients with hypospermatogenesis,maturation arrest,and complete spermatogenesis (P<0.01).The serum follicle stimulating hormone level in patients with maturation arrest was significantly higher than in patients with hypospermatogenesis and complete spermatogenesis (P<0.05).There was no difference in serum follicle stimulating hormone levels in patients with hypospermatogenesis and complete spermatogenesis.The follicle stimulating hormone receptor expression level of testicular samples with Sertoli cell-only syndrome was significantly higher than in those with hypospermatogenesis,maturation arrest,and complete spermatogenesis (P<0.05),but no significant difference was observed among hypospermatogenesis,maturation arrest,and complete spermatogenesis testicular samples.Conclusions Different serum follicle stimulating hormone levels and follicle stimulating hormone receptor expression were found in the different testicular histology phenotypes in azoospermic patients.Differential follicle stimulating hormone receptor expression in testicular tissue of patients with idiopathic azoospermia may be associated with the degree of spermatogenesis.
基金a grant from the Capital Clinical Feature Project of Beijing(No.Z181100001718215).
文摘Increasing numbers of targeted drugs are used in hormone receptor(HR)-positive metastatic breast cancer(MBC)to overcome or delay resistance to endocrine therapy.This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC.From the“AI(aromatase inhibitor)era”represented by aromatase inhibitors,we have gradually entered the“post-AI era”represented by fulvestrant.Under the guidance of research on the molecular mechanism of endocrine therapy resistance,the“combination of endocrine therapy and targeted therapy”era is approaching.The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors,histone deacetylase inhibitors,and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)pathway,providing new strategies for HR-positive MBC.Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.
文摘Thyroid hormone receptors (TR), ligand-mediated transcription factors, regulate cell growth, differentiation, and apoptosis. In humans, two different genes encode TR-α and TR-β and they are often co-expressed in various tissues at different levels. To explore the role of TR in esophageal cancer, we analyzed expression of TR-β1 mRNA (most abundantly expressed in the majority of normal cells) in normal and malignant esophageal tissue specimens using in situ hybridization. The TR-β1 mRNA was detected in 92.3% (96 of 104) of normal esophageal mucosa, whereas TR-β1 mRNA was only detected in 55.8% (58 of 104 cases) of esophageal squamous cell carcinoma specimens (P〈 0.00001). Expression of TR-β1 mRNA was associated with well-differentiated cancers (P〈 0.001). Furthermore, we determined whether the loss of heterozygosity (LOH) in TR-β1 gene locus would be responsible for the lost TR-β1 expression. Analysis of 73 esophageal tissue specimens generated 39 informative cases, 17 of which showed LOH (43.6%) but only 9 of these 17 cases were correlated with lost TR-β1 expression. This study demonstrated that expression of TR-β1 mRNA was lost in esophageal cancer tissues, which may be due to multiple mechanisms.