Value of HE4 combined with cancer Antigen 125 in the diagnosis of Endometrial Cancer

Objective: To investigate the clinical significance of human epididymal secretory protein E4 [HE4] in combination with cancer antigen 125 [CA125] in the diagnosis of endometrial cancer

Methods: One hundred and fifty patients with endometrial cancer who were admitted to Binzhou People's Hospital, Shandong, China, between June 2013 and July 2014, were enrolled and set as an endometrial cancer group; another one hundred patients with benign uterine diseases and one hundred healthy females were also enrolled, The serum was collected from the subjects for the detection of HE4 level

The level of CA125 was detected using electrochemiluminescence assay [ELISA]. Receiver Operating Characteristic [ROC] curve was drawn to analyze the cutoff points of HE4 and CA125 levels for the diagnosis of endometrial cancer. The diagnostic efficacy based on the detection of the two indexes separately and jointly was evaluated

Results: The area under curve [AUC] for diagnosis of endometrial cancer based on HE4 was superior to that based on CA125 [0.819 vs 0.757]

The optimal diagnosis cutoff point of HE4 and CA125 on the ROC curves was 92.21 pmol/Land 31.32KU/L, respectively. The sensitivity, Youden index, coincidence rate and negative predicted value of diagnosing endometrial cancer with HE4 in combination with CA125 [73.2%, 0.641 , 83.5% and 83,4%] were significantly higher than those of diagnosing endometrial cancer with the two indexes separately. The ROC- AUC value of serum HE4 and CA125 was 0.749 and 0.528 respectively, much lower than that of HE4 in combination with CA125 [0.794; P<0.05]

Conclusion: Serum HE4 and CA125 are the ideal marker combination for the diagnosis of endometrial cancer. HE4 combined with CA125 is beneficial to the diagnosis of endometrial cancer; hence it is worth promotion in clinical practice

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.

DHEA: el andrógeno más producido pero el menos entendido / DHEA: the androgen produced but least understood

Dehidroepiandrosterona (DHEA) y su derivada sulfatada (DHEAS) son los esteroides más abundantes en el cuerpo humano, pero aún se deconoce su mecanismo de acción y sus implicancias fisiológicas. Se le ha atribuido múltiples efectos antienvejecimiento, antiinflamatorio y antiarteriosclerótico entre otros y en EEUU se vende al público como complemento energético y para aumento del libido, sin restricción de la FDA...

Topografia de ligação de proteínas do plasma seminal à membrana de espermatozoides bovinos epididimários e ejaculados / Binding patterns of seminal plasma plasma proteins on bovine epididymal and ejaculated sperm membrane

The present study was designed to investigate the topographical distribution of seminal plasma (SP) proteins on epididymal and ejaculated bovine sperm. Using immunocytochemistry and confocal microscopy the binding patterns of bovine SP proteins BSP-A3, albumin, transferrin, prostaglandin D-synthase (PGDS) and nucleobindin in ejaculated and cauda epididymal sperm from adult bulls were evaluated. Experiments were performed using sperm from 5 males. Data showed a positive signal, only detected for anti-PGDS, in the acrosomal cap of epididymal and ejaculated sperm. In ejaculated sperm, a very weak signal for nucleobindin 2 in the midpiece and equatorial regions was detected, using the anti-rat nucleobindin. BSP-A3 was detected on all sperm regions studied, with a more evidenced signal in acrosome and midpiece. However, no binding was detected for albumin or transferrin in neither epididymal nor ejaculated sperm. In conclusion, PGDS, BSP-A3 and nucleobindin interact directly with bovine sperm, with specific topographic distribution. These findings may add to the knowledge of how these proteins modulate sperm functions, thus providing fundamental support for studies designed to evaluate how they influence sperm functions.

Investigou-se a distribuição topográfica da ligação de proteínas seminais à membrana de espermatozoides bovinos epididimários e ejaculados. Utilizando imunocitoquímica e microscopia confocal, avaliaram-se a topografia de ligação das proteínas BSP-A3, albumina, transferrina, prostaglandina D sintetase (PGDS) e nucleobindina 2 (NUC2) à membrana espermática. Os experimentos foram realizados utilizando espermatozoides de cinco touros. Os resultados mostraram que, para espermatozoides epididimários, somente detectou-se a PGDS na crista do acrossomo. Nos espermatozoides ejaculados, a PGDS ligou-se de forma mais intensa à crista acrossômica, enquanto a NUC2 apresentou sinal bastante fraco na peça intermediária e região equatorial. A BSP-A3 ligou-se a todas as regiões estudadas, de forma mais intensa na peça intermediária e acrossomo. Nenhum sinal foi detectado para albumina ou transferrina, seja em espermatozoides epididimários ou ejaculados. Concluiu-se que PGDS, BSP-A3 e NUC2 interagem diretamente com espermatozoides bovinos, e mostrou distribuição topográfica específica. Estes achados permitem melhor compreensão sobre o papel desempenhado por essas proteínas na regulação da função espermática e da fertilidade.

Effect of human epididymis protein 4 gene silencing on the malignant phenotype in ovarian cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown.</p><p><b>METHODS</b>In this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro.</p><p><b>RESULTS</b>HE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro.</p><p><b>CONCLUSION</b>HE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion.</p>

Identification of M(r)22 000 protein in rat epididymal luminal fluid / 中华男科学杂志

<p><b>OBJECTIVE</b>To identify the specific protein in the epididymal luminal fluid that may play a role in sperm epididymal maturation or modification on the surface of spermatozoa.</p><p><b>METHODS</b>We compared the differential protein components in the lumen fluids from the caput and cauda segments of the epididymis of normal rats as well as from the cauda segment of experimental left varicocele (ELV) rats by SDS-PAGE or 2D-electrophoresis. The protein spots of interest were selected for MS identification, and the target proteins further characterized by immuno-blot assay.</p><p><b>RESULTS</b>MS analysis showed that one of the most prominent proteins, M(r) 22 000, was identical to the phosphatidylethanolamine-binding protein (PBP), and it was further identified as PBP by immuno-blot assay.</p><p><b>CONCLUSION</b>PBPs were present in a variety of molecular forms in the epididymal luminal fluid, including the glycosylated form, and ELV markedly elevated the PBP level in the cauda luminal fluid of the rats. Thus, the association of this molecule with sperm surface modification remains an interest for future investigation.</p>

Advances in researches on epididymal WFDC-type serine protease inhibitors / 中华男科学杂志

Sperm maturation in the epididymis is regulated by changes of luminal ion concentration and processing of sperm surface membrane by several glycosidases and proteases, and the actions of the proteases are controlled by protease inhibitors present in specific areas of the epididymis. WFDC-type serine protease inhibitors that are highly expressed in the epididymis play an important role in natural immunity and male reproduction. This paper gives an overview of the structure and function of the protein and its application prospects in the development of drugs for male reproductive tract infection and immunocontraception.

Specialized gene expression and regulation in the epididymis / 中华男科学杂志

The epididymis is a single and highly convoluted tubule system in mammals. The epithelium is the major compartment for epididymal function. Proteins synthesized and secreted by epididymal epithelium provide a special and ever-changing luminal fluid environment for sperm as they progress through the epididymis, which makes sperm achieve motility and ultimately results in sperm functional maturation. Specialized genes expressed in the epididymis have regional-specific characteristics. They are regulated by androgen and/or testicular factors and present spatial and tempel-specialized expression pattern in postnatal development, all these hint that they play important and unique roles in epididymis.

Rodent epididymal cDNAs identified by sequence homology to human and canine counterparts / 亚洲男科学杂志(英文版)

<p><b>AIM</b>Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat.</p><p><b>METHODS</b>"Electronic screening" of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis.</p><p><b>RESULTS</b>Rodent ESTs and genomic sequences homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and the "full-length" rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively. mRNA expression patterns were analysed in rats, including rat HE1 and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis. Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens.</p><p><b>CONCLUSION</b>The novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.</p>