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Sample records for epididymal clear cells

  1. Epididymitis

    Science.gov (United States)

    ... infection, including sexually transmitted infections (STIs), such as gonorrhea or chlamydia. Sometimes, a testicle also becomes inflamed — ... you urinate. Causes Causes of epididymitis include: STIs. Gonorrhea and chlamydia are the most common causes of ...

  2. Clear cell chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, R.; David, R.; Cierney, G. III

    1985-01-01

    The clinical, radiologic, and histopathologic features of three cases of clear cell chondrosarcoma are described. On radiographs, this rather benign-appearing tumor resembles a chondroblastoma when it occurs at the end of a long bone, and may occasionally show a calcified matrix. However, it has distinctive tumor cells with a centrally placed vesicular nucleus surrounded by clear cytoplasm. The lesion has a low-grade malignancy and is amenable to en bloc surgical resection, which results in a much better prognosis than that of conventional chondrosarcoma.

  3. Clear cell hidradenocarcinoma:

    OpenAIRE

    Lamovec, Janez; Pohar-Marinšek, Živa

    2003-01-01

    A case of eccrine clear cell hidradenocarcinoma of sweat gland origin is presented, disclosing its clinical behavior and morphologic characteristics asevidenced by fine needle aspiration biopsy and tissue section histology. Thepatient was a 53-years old male who had a tumor on his fifth toe for 16 years. The tumor recurred 18 months after excision and metastasized widely 17 months following the amputation of the toe due to the recurrence. In spite of chemotherapy the patient died 37 months af...

  4. Clear cell hidradenoma

    Directory of Open Access Journals (Sweden)

    Zabihollah Shahmoradi

    2013-01-01

    Full Text Available Clear cell hidradenoma or nodulocystic hidradenoma or acrospiroma are histologically distinct relatively rare tumors of sweat gland duct origin, found mainly in adults with a female preponderance. We report a case of eccrine hidradenoma in a 31-year-old man who presented with an asymptomatic, solitary nodule on occipital region. A few reports are available in literature regarding presence of this tumor on occipital region of young man and present case is being reported because of its rarity in this region of scalp and in this sex.

  5. Clear cells in acral melanoma.

    Science.gov (United States)

    Schmuth, M; Spötl, L; Zelger, B; Weinlich, G; Zelger, B

    2001-01-01

    Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.

  6. Direct binding of boar ejaculate and epididymal spermatozoa to porcine epididymal epithelial cells is also needed to maintain sperm survival in in vitro co-culture.

    Science.gov (United States)

    Yeste, Marc; Castillo-Martín, Míriam; Bonet, Sergi; Briz, Maria Dolors

    2012-04-01

    The aim of the present study was to compare the influence of cultured epididymal epithelial cells (EEC) from corpus, caput or cauda, oviductal epithelial cells (OEC) and non-reproductive epithelial cells (LLC-PK1) on function and survival of epididymal and ejaculated spermatozoa, in the latter case to determine whether such influence differed between morphologically normal and abnormal spermatozoa. For this purpose, either spermatozoa were directly co-cultured with EEC from caput, corpus, or cauda, OEC and LLC-PK1 cells (experiment 1) or a membrane-diffusible insert was included in these co-cultures (experiment 2). EEC cultured from the three epididymal regions did not differently affect the sperm parameters. Morphologically normal spermatozoa presented a higher ability to bind EEC, OEC, and LLC-PK1 than abnormal spermatozoa with cytoplasmic droplets or with tail/head malformations. Epididymal spermatozoa were more able to bind EEC during the first 24 h of co-culture, while ejaculated spermatozoa presented a higher capacity to bind OEC between 30 min and 3 h of co-incubation. In all cases, the ability to bind to epithelial cells was higher when they were co-cultured with EEC and OEC than with LLC-PK1. After 2 h of co-culture, the viability of epididymal spermatozoa was better maintained when they bound EEC than when they bound OEC. Conversely, the viability of ejaculated spermatozoa was better maintained when bound OEC than when bound EEC after 24 and 48 h of co-culture. Our work, apart from corroborating the involvement of morphologically normal spermatozoa in the formation of sperm reservoir, highlights the importance of direct contact spermatozoa-EEC in maintaining the sperm survival in in vitro co-culture, and also suggests that a specific binding between EEC and epididymal spermatozoa exists. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. High-resolution helium ion microscopy of epididymal epithelial cells and their interaction with spermatozoa.

    Science.gov (United States)

    Păunescu, Teodor G; Shum, Winnie W C; Huynh, Chuong; Lechner, Lorenz; Goetze, Bernhard; Brown, Dennis; Breton, Sylvie

    2014-10-01

    We examined the rat and mouse epididymis using helium ion microscopy (HIM), a novel imaging technology that uses a scanning beam of He(+) ions to produce nanometer resolution images of uncoated biological samples. Various tissue fixation, sectioning and dehydration methods were evaluated for their ability to preserve tissue architecture. The cauda epididymidis was luminally perfused in vivo to remove most spermatozoa and the apical surface of the epithelial lining was exposed. Fixed epididymis samples were then subjected to critical point drying (CPD) and HIM. Apical stereocilia in principal cells and smaller apical membrane extensions in clear cells were clearly distinguishable in both rat and mouse epididymis using this technology. After perfusion with an activating solution containing CPT-cAMP, a permeant analog of cAMP, clear cells exhibited an increase in the number and size of membrane ruffles or microplicae. In contrast, principal cells did not exhibit detectable structural modifications. High-resolution HIM imaging clearly showed the ultrastructure of residual sperm cells, including the presence of concentric rings on the midpiece, and of cytoplasmic droplets in some spermatozoa. Close epithelium-sperm interactions were also detected. We found a number of sperm cells whose heads were anchored within the epididymal epithelium. In certain cases, the surface of the sperm cytoplasmic droplet was covered with vesicle-like structures whose size is consistent with that of epididymosomes. In conclusion, we describe here the first application of HIM technology to the study of the structure and morphology of the rodent epididymis. HIM technology represents a major imaging breakthrough that can be successfully applied to study the epididymis and spermatozoa, with the goal of advancing our understanding of their structure and function. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All

  8. Characteristics of stallion epididymal spermatozoa at collection and effect of two refrigeration protocols on the quality of the frozen/thawed sperm cells.

    Science.gov (United States)

    Guimarães, T; Lopes, G; Ferreira, P; Leal, I; Rocha, A

    2012-12-01

    Cryopreservation of epididymal spermatozoa is a useful tool to preserve genetic material of valuable stallions after emergency castration or unexpected death. For that, testicles and epididymides are generally sent refrigerated to the laboratory. Collection of epididymal spermatozoa is a simple procedure that reduces the volume of the material to be shipped, and may improve the quality of the chilled epididymal sperm cells. In the present study we compared the characteristics of frozen/thawed epididymal spermatozoa after refrigeration of the epididymis or after direct refrigeration of the extended epididymal sperm cells. Ejaculated sperm samples were obtained from 10 healthy stallions with at least 15 days of sexual rest, before routine orchiectomies. Spermatozoa were recovered from the epididymal tail immediately after castration (EPI), after refrigeration of the epididymis for 24h at 4°C (EPI R) and recovered from epididymal tail immediately after castration and stored for 24h at 4°C (EPI RR). Total motility, straight-line velocity, percentage of rapid cells, viability and morphological defects were similar (p>0.05) among different treatments, and post-thaw viability was higher (psperm. The similarity of post-thaw parameters led us to conclude that immediate collection and refrigeration of the epididymal sperm cells or refrigeration of the whole epididymis are equally efficient as a means of transporting material for 24h before cryopreservation of epididymal spermatozoa. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Hyaluronidase 2: a novel germ cell hyaluronidase with epididymal expression and functional roles in mammalian sperm.

    Science.gov (United States)

    Modelski, Mark J; Menlah, Gladys; Wang, Yipei; Dash, Soma; Wu, Kathie; Galileo, Deni S; Martin-DeLeon, Patricia A

    2014-11-01

    To initiate the crucial cell adhesion events necessary for fertilization, sperm must penetrate extracellular matrix barriers containing hyaluronic acid (HA), a task thought to be accomplished by neutral-active hyaluronidases. Here we report that the ~57 kDa hyaluronidase 2 (HYAL2) that in somatic tissues has been highly characterized to be acid-active is present in mouse and human sperm, as detected by Western blot, flow cytometric, and immunoprecipitation assays. Immunofluorescence revealed its presence on the plasma membrane over the acrosome, the midpiece, and proximal principal piece in mice where protein fractionation demonstrated a differential distribution in subcellular compartments. It is significantly more abundant in the acrosome-reacted (P = 0.04) and soluble acrosomal fractions (P = 0.006) (microenvironments where acid-active hyaluronidases function) compared to that of the plasma membrane where neutral hyaluronidases mediate cumulus penetration. Using HA substrate gel electrophoresis, immunoprecipitated HYAL 2 was shown to have catalytic activity at pH 4.0. Colocalization and coimmunoprecipitation assays reveal that HYAL2 is associated with its cofactor, CD44, consistent with CD44-dependent HYAL2 activity. HYAL2 is also present throughout the epididymis, where Hyal2 transcripts were detected, and in the epididymal luminal fluids. In vitro assays demonstrated that HYAL2 can be acquired on the sperm membrane from epididymal luminal fluids, suggesting that it plays a role in epididymal maturation. Because similar biphasic kinetics are seen for HYAL2 and SPAM1 (Sperm adhesion molecule 1), it is likely that HYAL2 plays a redundant role in the catalysis of megadalton HA to its 20 kDa intermediate during fertilization. © 2014 by the Society for the Study of Reproduction, Inc.

  10. Single-layer centrifugation separates spermatozoa from diploid cells in epididymal samples from gray wolves, Canis lupus (L.).

    Science.gov (United States)

    Muñoz-Fuentes, Violeta; Linde Forsberg, Catharina; Vilà, Carles; Morrell, Jane M

    2014-09-15

    Sperm samples may be used for assisted reproductive technologies (e.g., farmed or endangered species) or as a source of haploid DNA or sperm-specific RNA. When ejaculated spermatozoa are not available or are very difficult to obtain, as is the case for most wild endangered species, the epididymides of dead animals (e.g., animals that have been found dead, shot by hunters or poachers, or that that require euthanasia in zoological collections) can be used as a source of sperm. Such epididymal sperm samples are usually contaminated with cellular debris, erythrocytes, leukocytes, and sometimes also bacteria. These contaminants may be sources of reactive oxygen species that damage spermatozoa during freezing or contribute undesired genetic material from diploid cells. We used single-layer centrifugation through a colloid formulation, Androcoll-C, to successfully separate wolf epididymal spermatozoa from contaminating cells and cellular debris in epididymal samples harvested from carcasses. Such a procedure may potentially be applied to epididymal sperm samples from other species. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Clear cell carcinoma of the palate.

    Science.gov (United States)

    Grenevicki, L F; Barker, B F; Fiorella, R M; Mosby, E L

    2001-10-01

    A case of minor salivary gland clear cell adenocarcinoma of the palate with metastasis to the lungs in a 53-year-old female is presented. Histologically, the cells were characterized by glycogen rich clear cells arranged in solid nests, trabeculae, surrounded by hyalinized fibrous stroma. We believe this represents an aggressive form of this type of tumor.

  12. Primary clear cell sarcoma of bone

    International Nuclear Information System (INIS)

    Choi, J.H.; Gu, M.J.; Kim, M.J.; Bae, Y.K.; Choi, W.H.; Shin, D.S.; Cho, K.H.

    2003-01-01

    Clear cell sarcoma is a rare soft tissue sarcoma of young adults with melanocytic differentiation. It occurs predominantly in the soft tissue of extremities, typically involving tendons and aponeuroses. Primary clear cell sarcoma of bone is extremely rare. We report a case of primary clear cell sarcoma of the right first metatarsal in a 48-year-old woman and provide a literature review of the entity. (orig.)

  13. Next Generation Sequencing Analysis Reveals Segmental Patterns of microRNA Expression in Mouse Epididymal Epithelial Cells

    Science.gov (United States)

    Nixon, Brett; Stanger, Simone J.; Mihalas, Bettina P.; Reilly, Jackson N.; Anderson, Amanda L.; Dun, Matthew D.; Tyagi, Sonika; Holt, Janet E.; McLaughlin, Eileen A.

    2015-01-01

    The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment is, in turn, created by the combined secretory and absorptive activity of the surrounding epithelium and displays an extraordinary level of regionalization. Although the regulatory network responsible for spatial coordination of epididymal function remains unclear, recent evidence has highlighted a novel role for the RNA interference pathway. Indeed, as noncanonical regulators of gene expression, small noncoding RNAs have emerged as key elements of the circuitry involved in regulating epididymal function and hence sperm maturation. Herein we have employed next generation sequencing technology to profile the genome-wide miRNA signatures of mouse epididymal cells and characterize segmental patterns of expression. An impressive profile of some 370 miRNAs were detected in the mouse epididymis, with a subset of these specifically identified within the epithelial cells that line the tubule (218). A majority of the latter miRNAs (75%) were detected at equivalent levels along the entire length of the mouse epididymis. We did however identify a small cohort of miRNAs that displayed highly regionalized patterns of expression, including miR-204-5p and miR-196b-5p, which were down- and up-regulated by approximately 39- and 45-fold between the caput/caudal regions, respectively. In addition we identified 79 miRNAs (representing ~ 21% of all miRNAs) as displaying conserved expression within all regions of the mouse, rat and human epididymal tissue. These included 8/14 members of let-7 family of miRNAs that have been widely implicated in the control of androgen signaling and the repression of cell proliferation and oncogenic pathways. Overall these data provide novel insights into the sophistication of the miRNA network that regulates the function of the male reproductive tract. PMID:26270822

  14. Effect of D-valine and cytosine arabinoside on [3H]thymidine incorporation in rat and rabbit epididymal epithelial cell cultures

    International Nuclear Information System (INIS)

    Orgebin-Crist, M.C.; Jonas-Davies, J.; Storey, P.; Olson, G.E.

    1984-01-01

    Epithelial cell enriched primary cultures were established from the rat and the rabbit epididymis. Epithelial cell aggregates, obtained after pronase digestion of minced epididymis, attached to the culture dish and after 72 h in vitro spread out to form discrete patches of cells. These cells have an epithelioid morphology and form a monolayer of closely apposed polygonal cells where DNA synthesis, as judged by [ 3 H]thymidine uptake, is very low. In L-valine medium the nonepithelial cell contamination was no more than 10% in rat and rabbit epididymal primary cultures. The labeling index of rat epididymal cells cultured in D-valine medium was significantly lower than that of cells cultured in L-valine medium. In contrast, the labeling index of rabbit epididymal cells cultured in D-valine medium was significantly higher than that of cells cultured in L-valine medium. Cytosine arabinoside decreased the number of labeled cells in both L-valine and D-valine cultures. From these results, it appears that D-valine is a selective agent for rat epididymal epithelial cells, but not for rabbit epithelial cells, and that cytosine arabinoside is a simple and effective means to control the proliferation of fibroblast-like cells in both rat and rabbit epididymal cell cultures

  15. Bovine epididymal spermatozoa: Resistance to cryopreservation and binding ability to oviductal cells.

    Science.gov (United States)

    Cunha, A T M; Carvalho, J O; Kussano, N R; Martins, C F; Mourão, G B; Dode, M A N

    2016-12-01

    In this study we examined quality, longevity and ability of epididymal sperm (EP) to bind to oviduct explants (OE) after cooling and cryopreservation. Ejaculated (EJ) and EP sperm from seven bulls were evaluated before, during and after cryopreservation for total (TM), progressive motility (PM), sperm morphology, plasma membrane integrity (PMI) and acrosome integrity (ACI). For longevity, cryopreserved EP, EJ and a third group of cells in which EP spermatozoa were incubated with seminal plasm (SP) for 10 min after thawing (EPP group), were compared, and the groups were analyzed at 0, 3, 6, and 24 h for all parameters. Sperm from each group were co-incubated with OE for 30 min, 6 h, and 24 h for binding evaluation. Data were analyzed by the generalized linear models SAS 9.1 (P sperm. However, a reduction in motility occurred in the EJ sperm after cooling, while in EP group such reduction occurred only after cryopreservation. At 6 h of incubation EP and EPP had higher PMI and ACI than EJ (P  0.05) for all groups either at 30 min or 24 h. We conclude that EP are more resistant to cooling than EJ, and can bind to OE similarly to EJ. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Imaging of ovarian clear cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Toshihiko; Sawano, Seishi; Yamada, Keiko [Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital] (and others)

    1999-12-01

    The aim of this study is to examine the appearance of ovarian clear cell adenocarcinoma (OCCA) on MR, CT, US. In 39 cases with OCCA, the imaging characteristics of OCCA were evaluated morphologically and classified into three groups, that was, monomural nodule type, multi-mural nodule type and predominantly solid type. Forty-three percent of the patients had endometriosis. Contrast material-enhanced MRI was the most useful method for diagnosis of OCCA. (author)

  17. Clear cell hidradenocarcinoma developing in pacemaker pocket.

    Science.gov (United States)

    Reyes, Cesar V

    2008-11-01

    An octagenerian woman developed clear cell hidradenocarcinoma, a rare neoplasm of eccrine sweat gland origin, 4 years following pacemaker implantation in her right lateral chest. The tumor immunohistochemically mimicked a metastatic lobular breast carcinoma, for example, strongly positive estrogen, weakly positive progesterone, and weakly reactive mammoglobin. A complete surgical excision of the tumor was complemented with ipsilateral dissection of involved adjacent axillary lymph nodes. Recommended irradiation was refused by the patient. Retrospective 3-year mammogram review, 2-year postsurgery follow-up, and complete postmortem evaluation failed to prove a primary breast malignancy or other metastatic lesion elsewhere.

  18. A case of clear cell sarcoma

    DEFF Research Database (Denmark)

    Juel, Jacob; Ibrahim, Rami Mossad

    2017-01-01

    INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour of the soft tissue often misdiagnosed, as it shares characteristics with malignant melanoma (MM). Previously, CCS has been characterised, as malignant melanoma of the soft tissue, contemporary immunohistochemical techniques, however, have made...... this designation obsolete. The true incidence remains unknown, but CCS is believed to represent less than one percent of all sarcomas. PRESENTATION OF CASE: A 22-year-old patient presented with a mass sized 2.6×2.7×2.7cm of the left gluteal region, pain, and malaise. Initially, the symptoms were interpreted...

  19. Phospholipase Cγ2 Is Required for Luminal Expansion of the Epididymal Duct during Postnatal Development in Mice

    Science.gov (United States)

    Ichise, Hirotake; Ichise, Taeko; Yoshida, Nobuaki

    2016-01-01

    Phospholipase Cγ2 (PLCγ2)-deficient mice exhibit misconnections of blood and lymphatic vessels, and male infertility. However, the cell type responsible for vascular partitioning and the mechanism for male infertility remain unknown. Accordingly, we generated a mouse line that conditionally expresses endogenous Plcg2 in a Cre/loxP recombination-dependent manner, and found that Tie2-Cre- or Pf4-Cre-driven reactivation of Plcg2 rescues PLCγ2-deficient mice from the vascular phenotype. By contrast, male mice rescued from the vascular phenotype exhibited epididymal sperm granulomas. As judged from immunostaining, PLCγ2 was expressed in clear cells in the epididymis. PLCγ2 deficiency did not compromise differentiation of epididymal epithelial cells, including clear cells, and tube formation at postnatal week 2. However, luminal expansion of the epididymal duct was impaired during the prepubertal period, regardless of epithelial cell polarity and tube architecture. These results suggest that PLCγ2-deficient clear cells cause impaired luminal expansion, stenosis of the epididymal duct, attenuation of luminal flow, and subsequent sperm granulomas. Clear cell-mediated luminal expansion is also supported by the observation that PLCγ2-deficient males were rescued from infertility by epididymal epithelium-specific reactivation of Plcg2, although the edematous and hemorrhagic phenotype associated with PLCγ2 deficiency also caused spontaneous epididymal sperm granulomas in aging males. Collectively, our findings demonstrate that PLCγ2 in clear cells plays an essential role in luminal expansion of the epididymis during the prepubertal period in mice, and reveal an unexpected link between PLCγ2, clear cells, and epididymal development. PMID:26950550

  20. Intraventricular metastatic clear cell renal carcinoma.

    Science.gov (United States)

    Sava, I; Sava, Anca; Şapte, Elena; Mihailov, Claudia; Dumitrescu, Gabriela; Poeată, I; Sava, Florina; Haba, Danisia

    2013-01-01

    Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.

  1. Malignant Clear Cell Hidradenoma of the Breast.

    Science.gov (United States)

    Chambers, Isaac; Rahal, Ahmad K; Reddy, Pavan S; Kallail, K James

    2017-03-01

    A 58-year-old female had a mass in the right breast palpable beneath the areola. A mammogram revealed a 1.5-centimeter soft tissue density that was confirmed with a subsequent ultrasound. The patient underwent a core needle biopsy which was initially reported as a moderately differentiated invasive ductal carcinoma. Immunohistochemical analysis revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), mammaglobin, and gross cystic disease fluid protein 15 (GCDFP-15). A wide local excision of the mass was performed. The pathology report stated the tumor had an infiltrative growth pattern with a desmoplastic stromal response with enhanced epithelial atypia consistent with malignant transformation of a nodular clear cell hidradenoma. Clear cell hidradenoma is a very rare tumor originating from the sweat gland and has a propensity for the face and extremities. The malignant variant of this tumor is extremely rare and has been reported to originate from the breast in few cases. This case represents the difficulty in diagnosing this tumor along with the radiographic and histologic features that can distinguish this malignancy from other entities.

  2. Bilateral clear cell sarcoma of the kidney

    International Nuclear Information System (INIS)

    Zekri, W.; Yehia, D.; Alfaar, A.S.; Elshafie, M.M.; Younes, A.A.; Zaghloul, M.S.; El-Kinaai, N.; Taha, H.; Refaat, A.; Zekri, W.; Elshafie, M.M.; Zaghloul, M.S.; Taha, H.; Refaat, A.; Younes, A.A.; Alfaar, A.S.; Yehia, D.

    2015-01-01

    Clear cell sarcoma of the kidney (CCSK) accounts for 2-5% of all pediatric renal malignancies, and is known for its propensity to metastasize to bone and other sites. We are reporting two cases with bilateral CCSK that were diagnosed at our institution. One patient initially presented with bilateral renal masses, as well as pulmonary, hepatic and bone metastasis; while other present only with bilateral masses with no evident distant metastasis. Both patients received aggressive neo-adjuvant chemotherapy to decrease tumor size. One patient completed his designated treatment and initially showed complete remission (CR); eventually suffering from relapse. The other patient’s tumor progressed during the course of chemotherapy. Both cases manifested brain dissemination at the time of relapse or progression. This emphasizes the importance of staging stratification in CCSK. This also illustrates CCSK’s ability to metastasize to bone and other sites including the brain (a primary relapse site in our cases)

  3. Tris-egg yolk-glycerol (TEY) extender developed for freezing dog semen is a good option to cryopreserve bovine epididymal sperm cells.

    Science.gov (United States)

    Lopes, G; Soares, L; Ferreira, P; Rocha, A

    2015-02-01

    Cryopreservation of epididymal spermatozoa is often performed after shipping the excised testis-epididymis complexes, under refrigeration, to a specialized laboratory. However, epididymal spermatozoa can be collected immediately after excision of the epididymis and sent extended and refrigerated to a laboratory for cryopreservation. In this experiment, we evaluated the effect of both methods of cold storage bovine epididymal spermatozoa as well as of two different extenders on spermatozoa characteristics after freeze-thawing. For that, spermatozoa collected from the caudae epididymis of 19 bulls were extended and cryopreserved in either AndroMed(®) or a Tris-egg yolk (TEY)-based extender. Cryopreservation of sperm cells was performed immediately after castration (Group A, n = 9) or after cold storage for 24 h diluted in the two extenders and (Group B, n = 9) and also after cold storage for 24 h within the whole epididymis (Group C, n = 10). Sperm subjective progressive motility (light microscopy), plasma membrane integrity (hypoosmotic swelling test) and sperm viability (eosin-nigrosin) were evaluated. In vitro fertilization and culture (IVF) was performed to assess the blastocyst rate. No differences (p > 0.05) were observed on post-thaw sperm parameters between samples from Group A, B and C. TEY extended samples presented a higher (p sperm, than those extended in AndroMed(®) . Blastocyst rate after IVF differed only (p epididymal sperm can be shipped chilled overnight either within the epididymal tail or after dilution without deleterious effect on post-thaw sperm quality. TEY extender was more suitable for cold storage and freezing bovine epididymal sperm, than the commercial extender AndroMed®. © 2014 Blackwell Verlag GmbH.

  4. Toll-like Receptors 4 and 5 Cooperatively Initiate the Innate Immune Responses to Uropathogenic Escherichia coli Infection in Mouse Epididymal Epithelial Cells.

    Science.gov (United States)

    Cheng, Lijing; Chen, Qiaoyuan; Zhu, Weiwei; Wu, Han; Wang, Qing; Shi, Lili; Zhao, Xiang; Han, Daishu

    2016-03-01

    Uropathogenic Escherichia coli (UPEC) may cause epididymitis and impair male fertility. The mechanisms underlying the innate immune responses to UPEC infection in the epididymis are not fully understood. This study showed that UPEC induced innate immune responses in mouse epididymal epithelial cells (EECs) through the activation of Toll-like receptor 4 (TLR4) and TLR5. Infection with UPEC significantly induced the expression of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and monocyte chemoattractant protein 1, in EECs through the activation of nuclear factor kappa B. Moreover, UPEC induced the production of type 1 interferons by EECs through the activation of interferon regulatory factor 3. The UPEC-induced innate immune responses were significantly reduced in the EECs of Tlr4 or Tlr5 knockout mice. The innate immune responses were further reduced in Tlr4 and Tlr5 double-knockout EECs. Furthermore, we demonstrated that TLR4 and TLR5 cooperatively initiated the epididymal innate immune responses to UPEC infection in vivo. The results provide novel insights into the mechanisms underlying the epididymal innate immune responses to UPEC infection. © 2016 by the Society for the Study of Reproduction, Inc.

  5. Snail heterogeneity in clear cell renal cell carcinoma.

    Science.gov (United States)

    Zaldumbide, Laura; Erramuzpe, Asier; Guarch, Rosa; Pulido, Rafael; Cortés, Jesús M; López, José I

    2016-03-08

    Intratumor heterogeneity may be responsible of the unpredictable aggressive clinical behavior that some clear cell renal cell carcinomas display. This clinical uncertainty may be caused by insufficient sampling, leaving out of histological analysis foci of high grade tumor areas. Although molecular approaches are providing important information on renal intratumor heterogeneity, a focus on this topic from the practicing pathologist' perspective is still pending. Four distant tumor areas of 40 organ-confined clear cell renal cell carcinomas were selected for histopathological and immunohistochemical evaluation. Tumor size, cell type (clear/granular), Fuhrman's grade, Staging, as well as immunostaining with Snail, ZEB1, Twist, Vimentin, E-cadherin, β-catenin, PTEN, p-Akt, p110α, and SETD2, were analyzed for intratumor heterogeneity using a classification and regression tree algorithm. Cell type and Fuhrman's grade were heterogeneous in 12.5 and 60 % of the tumors, respectively. If cell type was homogeneous (clear cell) then the tumors were low-grade in 88.57 % of cases. Immunostaining heterogeneity was significant in the series and oscillated between 15 % for p110α and 80 % for Snail. When Snail immunostaining was homogeneous the tumor was histologically homogeneous in 100 % of cases. If Snail was heterogeneous, the tumor was heterogeneous in 75 % of the cases. Average tumor diameter was 4.3 cm. Tumors larger than 3.7 cm were heterogeneous for Vimentin immunostaining in 72.5 % of cases. Tumors displaying negative immunostaining for both ZEB1 and Twist were low grade in 100 % of the cases. Intratumor heterogeneity is a common event in clear cell renal cell carcinoma, which can be monitored by immunohistochemistry in routine practice. Snail seems to be particularly useful in the identification of intratumor heterogeneity. The suitability of current sampling protocols in renal cancer is discussed.

  6. DGCR8 Localizes to the Nucleus as well as Cytoplasmic Structures in Mammalian Spermatogenic Cells and Epididymal Sperm

    Directory of Open Access Journals (Sweden)

    Akane Nakano

    2013-01-01

    Full Text Available The localization of DGCR8 in spermatogenic cells and sperm from rat and mouse was studied by immunofluorescence and immunoelectron microscopy. Spermatogenic cells from these species yielded similar DGCR8 localization pattern. Immunofluorescence microscopy results showed that DGCR8 localized to both the cytoplasm and nucleus. In the cytoplasm, diffuse cytosolic and discrete granular staining was observed. Dual staining showed that DGCR8 colocalized to the granules with MAEL (a nuage marker. In the nucleus of spermatocytes, both the nucleoli and nucleoplasm were stained, whereas in the nucleus of early spermatids small spots were stained. In late spermatids, DGCR8 localized to the tip of their head and to small granules (neck granules of the neck cytoplasm. The neck granules were also observed in the neck of epididymal sperm. Immunoelectron microscopy results showed that DGCR8 localized to nuage structures. Moreover, DGCR8 localized to nonnuage structures in late spermatids. DGCR8 also localized to the nucleolus and euchromatin in spermatocytes and round spermatids and to small granules in the nucleus of late spermatids. The results suggest that in spermatogenic cells DGCR8 localizes not only to the nuclei but also to the cytoplasmic structures such as nuage and nonnuage structures. Furthermore, DGCR8 seems to be imported into the egg with neck granules in sperm during fertilization.

  7. Is lithium essential for epididymal sperm maturation?

    Science.gov (United States)

    Halder, Tanmoy; Datta, Uttam; Basu, Siddhartha; Mukherjee, Prasenjit

    2016-11-01

    A wider biological role of ultratrace element lithium in the mammalian reproduction has been reported, however, presence of lithium in the epididymal luminal fluid (ELF) and its influence on sperm during maturation events in the epididymal regions are still unknown. A pilot study was carried out in Jamunapari buck which revealed that levels of lithium in the ELF diminished gradually and significantly (Psperm were observed, except spermatozoan motility that was found absent in the caput epididymis. Therefore, we hypothesize that levels of lithium in the epididymal regions is one of the motility initiation and/or regulatory factor for epididymal sperm maturation essential for acquiring fertilizing competence of sperm cells, hence, lithium could also be considered as one of the biomarker of sperm maturation in any species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Applying the erythrocyte Pig-a assay concept to rat epididymal sperm for germ cell mutagenicity evaluation.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J

    2017-08-01

    The Pig-a assay, a recently developed in vivo somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)-anchored cell surface markers. We hypothesized that the erythrocyte Pig-a assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI-anchored CD59 as the Pig-a mutation marker and examined the frequency of CD59-negative sperm using flow cytometry. A reconstruction experiment that spiked un-labeled sperm (mutant-mimic) into labeled sperm at specific ratios yielded good agreement between the detected and expected frequencies of mutant-mimic sperm, demonstrating the analytical ability for CD59-negative sperm detection. Furthermore, this methodology was assessed in F344/DuCrl rats administered N-ethyl-N-nitrosourea (ENU), a prototypical mutagen, or clofibrate, a lipid-lowering drug. Rats treated with 1, 10, or 20 mg/kg body weight/day (mkd) ENU via daily oral garage for five consecutive days showed a dose-dependent increase in the frequency of CD59-negative sperm on study day 63 (i.e., 58 days after the last ENU dose). This ENU dosing regimen also increased the frequency of CD59-negative erythrocytes. In rats treated with 300 mkd clofibrate via daily oral garage for consecutive 28 days, no treatment-related changes were detected in the frequency of CD59-negative sperm on study day 85 (i.e., 57 days after the last dose) or in the frequency of CD59-negative erythrocytes on study day 29. In conclusion, these data suggest that the epidiymal sperm Pig-a assay in rats is a promising method for evaluating germ cell mutagenicity. Environ. Mol. Mutagen. 58:485-493, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Clear cell hepatocellular carcinoma: Back to the basics for diagnosis

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    Puja Sakhuja

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a common cancer world-wide with a higher incidence in Asia. Clear cell variant of HCC (CCHCC has a frequency ranging from 0.4% to 37%. The presence of 90-100% clear cells is rare. In the present case, a 35-year-old female patient presented with fever and a large abdominal mass in the right hypochondrium. Histology of the tumor revealed >95% clear cells and after taking multiple sections from different areas of tumor only few scattered cells with eosinophilic cytoplasm were found. Immunohistochemistry with Hep Par 1, Glypican 3 and polyclonal carcinoembryonic antigen were negative as were all other markers for metastatic clear cell tumors. Histological diagnosis was based on routine H and E sections showing a histological pattern of architecture with thickened trabeculae. We describe a rare case of CCHCC with >95% clear cells and no immunoreactivity in tumor cells in a non-cirrhotic liver.

  10. Novel algorithm for management of acute epididymitis.

    Science.gov (United States)

    Hongo, Hiroshi; Kikuchi, Eiji; Matsumoto, Kazuhiro; Yazawa, Satoshi; Kanao, Kent; Kosaka, Takeo; Mizuno, Ryuichi; Miyajima, Akira; Saito, Shiro; Oya, Mototsugu

    2017-01-01

    To identify predictive factors for the severity of epididymitis and to develop an algorithm guiding decisions on how to manage patients with this disease. A retrospective study was carried out on 160 epididymitis patients at Keio University Hospital. We classified cases into severe and non-severe groups, and compared clinical findings at the first visit. Based on statistical analyses, we developed an algorithm for predicting severe cases. We validated the algorithm by applying it to an external cohort of 96 patients at Tokyo Medical Center. The efficacy of the algorithm was investigated by a decision curve analysis. A total of 19 patients (11.9%) had severe epididymitis. Patient characteristics including older age, previous history of diabetes mellitus and fever, as well as laboratory data including a higher white blood cell count, C-reactive protein level and blood urea nitrogen level were independently associated with severity. A predictive algorithm was created with the ability to classify epididymitis cases into three risk groups. In the Keio University Hospital cohort, 100%, 23.5%, and 3.4% of cases in the high-, intermediate-, and low-risk groups, respectively, became severe. The specificity of the algorithm for predicting severe epididymitis proved to be 100% in the Keio University Hospital cohort and 98.8% in the Tokyo Medical Center cohort. The decision curve analysis also showed the high efficacy of the algorithm. This algorithm might aid in decision-making for the clinical management of acute epididymitis. © 2016 The Japanese Urological Association.

  11. Primary Clear Cell Sarcoma of the Dermis Mimicking Malignant Melanoma

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    Ifeyinwa E. Obiorah

    2018-03-01

    Full Text Available Background: Clear cell sarcoma is a rare malignant soft tissue neoplasm that typically involves tendons and aponeurosis. Clear cell sarcoma in the dermis is an extremely rare occurrence, and it is difficult to differentiate between this neoplasm and dermal malignant melanoma because they have similar morphologic and immunohistochemical features. Although rare, clear cell sarcoma of the skin typically occurs in the extremities. To our knowledge, there are no reported cases of primary clear cell sarcoma of the skin occurring in the neck. Here, we report an unusual case of clear cell sarcoma arising in the skin of the neck. Case Report: A 43-year-old female presented with a right neck lesion. Histologic sections of the lesion showed a nodular proliferation of spindle cells with pale cytoplasm with epithelioid features involving the entire dermis with no epidermal component. The tumour cells were positive for melanocytic markers, including S100 and Human Melanoma Black 45, which led to an initial diagnosis of malignant melanoma. Fluorescence in situ hybridization showed a rearrangement of the EWSR1 gene on chromosome 22q12, which led to a diagnosis of primary clear cell sarcoma in the skin. Conclusion: Because the treatments for clear cell sarcoma and conventional melanoma are different, fluorescence in situ hybridization for EWSR1 should be performed in any dermal lesions with melanocytic features that do not have an in situ component.

  12. Effect of Rabbit Epididymal Antimicrobial Peptide, REHbβP, on LPS-Induced Proinflammatory Cytokine Responses in Human Vaginal Cells In Vitro

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    K. V. R. Reddy

    2012-01-01

    Full Text Available Antimicrobial peptides (AMP’s protect epithelial surfaces including epididymis against pathogens and play a key role in orchestrating various defensive responses. Recently, we have identified one such AMP, rabbit epididymal hemoglobin-β subuit (REHbβP from the epididymal fluid of rabbit, Oryctologus cuniculus. The demonstration of a protective role of REHbβP in epididymal epithelial cells (EPEC’s led us to investigate: (1 the identification of LPS interactive domain in REHbβP, and (2 whether the REHbβP of rabbit origin mediates vaginal cellular immune responses of another species (human. HeLa-S3, human vaginal epithelial cells (hVECs were exposed to LPS or the LPS-stimulated cells treated with REHbβP or neutral peptide, nREHbβP. Effect of LPS and cytokines (IL-6 and IL-1α and chemokines (IL-8, MCP-1 levels was determined in the culture supernatants. In response to the LPS, hVECs synthesized these mediators and the levels were significantly higher than controls. This enhancing effect was ameliorated when the LPS-induced hVECs were treated with REHbβP. Similar results were obtained on NF-κB protein and hBD-1 mRNA expression. Confocal microscopy studies revealed that REHbβP attenuated the LPS-induced internalization of E. coli by macrophages. The chemotaxis studies performed using Boyden chamber Transwell assay, which showed elevated migration of U937 cells when the supernatants of LPS-induced hVECs were used, and the effect was inhibited by REHbβP. REHbβP was found to be localized on the acrosome of rabbit spermatozoa, suggesting its role in sperm protection beside sperm function. In conclusion, REHbβP may have the potential to develop as a therapeutic agent for reproductive tract infections (RTI’s.

  13. MCPIP1 contributes to clear cell renal cell carcinomas development.

    Science.gov (United States)

    Ligeza, Janusz; Marona, Paulina; Gach, Natalia; Lipert, Barbara; Miekus, Katarzyna; Wilk, Waclaw; Jaszczynski, Janusz; Stelmach, Andrzej; Loboda, Agnieszka; Dulak, Jozef; Branicki, Wojciech; Rys, Janusz; Jura, Jolanta

    2017-08-01

    Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development.

  14. Sperm ubiquitination in epididymal feline semen.

    Science.gov (United States)

    Vernocchi, Valentina; Morselli, Maria Giorgia; Varesi, Sara; Nonnis, Simona; Maffioli, Elisa; Negri, Armando; Tedeschi, Gabriella; Luvoni, Gaia Cecilia

    2014-09-01

    Ubiquitin is a 8.5-kDa peptide that tags other proteins for proteasomal degradation. It has been proposed that ubiquitination might be responsible for the elimination of defective spermatozoa during transit through the epididymis in humans and cattle, but its exact biological function in seminal plasma has not yet been clarified. In the domestic cat (Felis catus), the percentage of immature, unviable, and abnormal spermatozoa decreases during the epididymal transit, indicating the existence of a mechanism that removes defective spermatozoa. Magnetic cell separation techniques, based on the use of magnetic beads coated with anti-ubiquitin antibodies, may allow the selective capture of ubiquitinated spermatozoa from semen, thus contributing to the identification of a potential correlation between semen quality and ubiquitination process. Moreover, the selective identification of all the ubiquitinated proteins in different epididymal regions could give a better understanding of the ubiquitin role in feline sperm maturation. The aims of this study were as follows: (1) to verify the possibility of separating ubiquitinated spermatozoa with magnetic ubiquitin beads and identify the morphological and acrosomal differences between whole sample and unbound gametes, (2) to characterize all the ubiquitinated proteins in spermatozoa retrieved in the three epididymal regions by a proteomic approach. The data indicated the presence of ubiquitinated proteins in cat epididymal semen. However, a correlation between abnormal and ubiquitinated spermatozoa has not been found, and ubiquitin cannot be considered as a biomarker of quality of epididymal feline spermatozoa. To the author's knowledge, this is the first identification of all the ubiquitinated proteins of cat spermatozoa collected from different epididymal regions. The proteomic pattern allows a further characterization of cat epididymal semen and represents a contribute to a better understanding of the ubiquitin role in

  15. The epigenetic landscape of clear-cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Katarzyna Kluzek

    2015-05-01

    Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common subtype of all kidney tumors. During the last few years, epigenetics has emerged as an important mechanism in ccRCC pathogenesis. Recent reports, involving large-scale methylation and sequencing analyses, have identified genes frequently inactivated by promoter methylation and recurrent mutations in genes encoding chromatin regulatory proteins. Interestingly, three of detected genes (PBRM1, SETD2 and BAP1 are located on chromosome 3p, near the VHL gene, inactivated in over 80% ccRCC cases. This suggests that 3p alterations are an essential part of ccRCC pathogenesis. Moreover, most of the proteins encoded by these genes cooperate in histone H3 modifications. The aim of this review is to summarize the latest discoveries shedding light on deregulation of chromatin machinery in ccRCC. Newly described ccRCC-specific epigenetic alterations could potentially serve as novel diagnostic and prognostic biomarkers and become an object of novel therapeutic strategies.

  16. A new insight into the three-dimensional architecture of the Golgi complex: Characterization of unusual structures in epididymal principal cells.

    Science.gov (United States)

    Martínez-Martínez, Narcisa; Martínez-Alonso, Emma; Tomás, Mónica; Neumüller, Josef; Pavelka, Margit; Martínez-Menárguez, José A

    2017-01-01

    Principal epididymal cells have one of the largest and more developed Golgi complex of mammalian cells. In the present study, we have used this cell as model for the study of the three-dimensional architecture of the Golgi complex of highly secretory and endocytic cells. Electron tomography demonstrated the presence in this cell type of some unknown or very unusual Golgi structures such as branched cisternae, pocket-like cisternal invaginations or tubular connections. In addition, we have used this methodology and immunoelectron microscopy to analyze the close relationship between this organelle and both the endoplasmic reticulum and microtubules, and to describe in detail how these elements interact with compact and non-compact regions of the ribbon.

  17. Napsin A as a marker of clear cell ovarian carcinoma.

    Science.gov (United States)

    Skirnisdottir, Ingiridur; Bjersand, Kathrine; Akerud, Helena; Seidal, Tomas

    2013-11-05

    Clear cell carcinomas are aggressive tumors with a distinct biologic behaviour. In a genome-wide screening for genes involved in chemo-resistance, NAPA was over-expressed in cisplatin-resistant cells. The NAPA (protein) Napsin A was described to promote resistance to cisplatin by degradation of the tumor suppressor p53. Totally 131 patients were included in this study all in FIGO-stages I-II; 16 were clear cell tumors which were compared with 40 Type I tumors and 75 type II tumors according to the markers Napsin A, p21, p53 and p27 and some clinical features. For detection of the markers tissue microarrays and immunohistochemistry were used. Positivity for Napsin A was detected in 12 (80%) out of the 15 clear cell tumors available for analysis compared with 3 (4%) out of the Type I and II tumors in one group (pp53 status, and p21+p53- status were striking when clear cell tumors were compared with Type I, Type II, and Type I and II tumors in one group, respectively. The p21+p53-status was associated to positive staining of Napsin A (p=0.0015) and clear cell morphology (p=0.0003). In two separate multivariate logistic regression analyses with Napsin A as endpoint both clear cell carcinoma with OR=153 (95% C.I. 21-1107); (pp53- status with OR=5.36 (95% C.I. 1.6-17.5); (p=0.005) were independent predictive factors. ROC curves showed that AUC for Napsin A alone was 0.882, for p21+p53- it was 0.720 and for p21+p53-Napsin A+AUC was 0.795. Patients with clear cell tumors had lower (p=0.013) BMI than Type I patients and were younger (p=0.046) at diagnosis than Type II patients. Clear cell tumors had a higher frequency (p=0.039) of capsule rupture at surgery than Type I and II tumors. Positivity of Napsin A in an epithelial ovarian tumor might strengthen the morphological diagnosis of clear cell ovarian carcinoma in the process of differential diagnosis between clear cell ovarian tumors and other histological subtypes.

  18. Vaginal laparoscopically assisted radical trachelectomy in cervical clear cell adenocarcinoma.

    Science.gov (United States)

    Iacoponi, Sara; Diestro, Maria Dolores; Zapardiel, Ignacio; Serrano, María; Santiago, Javier De

    2013-01-01

    Adenocarcinoma of the cervix is a rare condition that has shown an increase in incidence, especially in the 20- to 34-year-old group. Adenocarcinoma represents about 5-10% of all tumours in this area, and, among these, the clear cell type accounts for 4-9%. This type of tumour affects mainly postmenopausal women but also occurs in young women with a history of prenatal exposure to diethylstilbestrol (DES). The prognosis for adenocarcinoma of the cervix is poor overall and worse for the clear cell variety. This article discusses a case of clear cell adenocarcinoma of the cervix, unrelated to intrauterine exposure to DES, in a woman of childbearing age who wished to preserve her fertility and was therefore treated by radical vaginal trachelectomy and pelvic lymphadenectomy.

  19. Treatment results and prognostic factors of clear cell ovarian carcinomas and ovarian carcinomas with clear cell component

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    M. D. Ahmedova

    2012-01-01

    Full Text Available The most important prognostic factors for clear cell carcinoma (CCC are clinical and morphological signs and clinical stage of the disease. Analyses of 5-year survival in patients with I stage of CCC is 69 %, in II stage – 55 %, in III stage – 14 % and in IV stage – 4 % patients. We analyzed distant results of treatment of 71 patients with CCC and of 25 patients with mixed malignant ovaries neoplasm with obligatory clear cell component taking into consideration main clinical and morphological sings of disease. On the base of performed reseal we revealed that morphological structure of the tumors and stage of the disease exerted heist influence on the exponent of survival of the patients with clear CCC ovaries neoplasm. Besides, there is a correlation between exponent of patients’ survival and radicalized of surgery, character of tumor growth, differentiation degree, cell anaplasia and mitotic activity of tumor cells.

  20. The Immunoexpression of FSH-R in the Ductuli Efferentes and the Epididymis of Men and Rat: Effect of FSH on the Morphology and Steroidogenic Activity of Rat Epididymal Epithelial Cells In Vitro

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    Małgorzata Świder-Al-Amawi

    2010-01-01

    Full Text Available The Sertoli cells were regarded as the only target for FSH in male reproductive system. The expression of FSH receptor (FSH-R was detected also in epithelial cells of the caput epididymis of rat and monkey. We showed in the immunohistochemistry study the expression of FSH-R in rat and human ductuli efferentes and the caput, corpus, and cauda epididymis, moreover, by Western blot analysis in the caput and cauda epididymis of rat. Additionally, we presented that the morphology of rat epididymal epithelial cells in vitro was affected by FSH, and FSH stimulation resulted in the increase of 17β-estradiol synthesis by rat caput epididymal cells in dose-depended manner. In conclusion, the identification of FSH receptors in human and rat epididymides supports our results that the epididymis is a target organ not only for LH but additionally for FSH. On the basis of the results we showed for the first time that morphology of epididymal epithelial cells and epididymal steroidogenesis can be regulated by FSH.

  1. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...

  2. Clear cell variant of syringoma as a rare case

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    Özben Yalçın

    2014-12-01

    Full Text Available Syringoma is a benign skin tumor derived from eccrine glands characterized by yellowish-pink color and firm papular lesions of the skin especially on the lower eyelid. Typical histopathological features of syringoma are dilated cystic eccrine sweat gland ducts. In this paper, we report a case of clear cell variant syringoma with neck and trunk lesions.

  3. Metastatic clear-cell hidradenocarcinoma of the vulva.

    Science.gov (United States)

    Messing, M J; Richardson, M S; Smith, M T; King, L; Gallup, D G

    1993-02-01

    Clear-cell hidradenocarcinoma is a malignant tumor of sweat gland origin. It is most often found on the trunk, head, and extremities. This case report describes a rare occurrence of this tumor on the vulva of a young woman. The discovery of metastatic disease reflects the potentially aggressive nature of this tumor.

  4. Clear cell syringofibroadenoma (of Mascaro) of the nail.

    Science.gov (United States)

    Fouilloux, B; Perrin, C; Dutoit, M; Cambazard, F

    2001-03-01

    Eccrine syringofibroadenoma (ESFA) is a rare disorder. We report the first case of ESFA of the nail apparatus, which presented as a yellow longitudinal onycholytic band of the left fourth finger over an intermittently painful subungual filamentous tumour. Histological examination showed features of ESFA with a digitate pattern of papillomatosis due to the specialized physiological longitudinal arrangement of the ridges in the nail bed. In addition, we describe a new feature of colloidal iron-positive clear cells. In our case, the presence of two types of cells with a central ductal differentiation and a significant amount of mucopolysaccharides in clear cells could suggest differentiation towards both the ductal and the secretory portion of the eccrine gland.

  5. Cerebellar clear cell ependymoma in a 10 year old girl

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    Thinzar Aye Nyein; Moon, Ah Rim; Hwang, Sun Chul; Hong, Hyun Sook; Lee, A Leum; Chang, Kee Hyun; Kim, Hee Kyung; Chin, Su Sie [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Park, Ji Sang [Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of)

    2016-01-15

    Clear cell ependymoma (CCE) is a histological rare variant (1–5%) of ependymoma, which is distinguished from other histological subtypes by the presence of fusiform cells arrayed radially around small blood vessels. These alleged perivascular pseudorosettes are significant characteristic features of ependymomas. About 95% of infratentorial ependymomas are found in the fourth ventricle and the remainder occurs as cerebellopontine angle lesions. In previous reports, the cerebellum is found to be a rare location for ependymoma. In this study we report one case of CCE originating from the cerebellar hemisphere, showing unusual morphology on 3T MRI.

  6. Sonographic appearance of epididymal microlithiasis.

    Science.gov (United States)

    Vandervelde, Clive; Varghese, Ajay; Mason, Althea; Howlett, David

    2007-09-01

    We report a case of epididymal microlithiasis that was diagnosed sonographically in a 75-year-old man undergoing scrotal sonographic examination to investigate right groin pain associated with an inguinal hernia. The sonographic appearance was that of multiple comet-shaped foci of microcalcification throughout both epididymides, with associated comet-tail artifacts. The testes had normal appearance with no evidence of testicular microlithiasis. The patient subsequently remained well after hernia repair. To our knowledge, epididymal microlithiasis has only previously been reported in a cadaveric study; the authors of that study hypothesized that the condition is caused by aging, with ischemia likely implicated in the pathogenesis. There are many other patterns of extratesticular calcification, including sperm granuloma, hematoma, and chronic epididymitis. We discuss how these differ in appearance from epididymal microlithiasis. Epididymal microlithiasis is a completely separate entity from testicular microlithiasis and should be recognized and dismissed by sonographers and radiologists. (c) 2007 Wiley Periodicals, Inc.

  7. A giant benign clear cell hidradenoma on the anterior trunk

    Directory of Open Access Journals (Sweden)

    Damlanur Sakiz

    2011-10-01

    Full Text Available Clear cell hidroadenoma (CCA is a uncommon variant of bening cutaneous adnexial tumors. These tumors are clinically asymptomatic, solitary dermal nodules. they occur most frequently on the scalp, face, abdomen and the extremities. Growth is slow and malignant change is rare. 45- year-old woman presented us with a nodule with a central ulceration and a minimal hemoragic discharge on her anterior abdomen wall which had begun 4 years ago as a small nodular asymptomatic lesion. On dermatological examination there was a 6.5x4x5 cm non-tender, soft reddish purple nodule with lobular appearence and ulceration. In the laboratory investigations, all the hematologic and biochemical tests were normal. A CT scan demonstrated a cyctic tumor with lobulated countour with contrast enhancement. The lesion excised totally. In histopathological examination the tumor was composed of biphasic  smaller dark polygonal cells and larger clera cells and coarse nuclear chromatine. There were duct like structures. Immunohistochemical investigation was done for the suspicion of malignancy. Cytoplasm of clear cells and duct like structures showed PAS positive and d-Pas resistant staining. There was a positive reactivity to epithelial membrane antigen and carcinoembrionic antigen. The mitotic index in Ki 67 examination was low. All these findings confirmed the diagnosis of bening CCA. 

  8. Why are epididymal tumours so rare?

    Science.gov (United States)

    Yeung, Ching-Hei; Wang, Kai; Cooper, Trevor G

    2012-01-01

    Epididymal tumour incidence is at most 0.03% of all male cancers. It is an enigma why the human epididymis does not often succumb to cancer, when it expresses markers of stem and cancer cells, and constitutively expresses oncogenes, pro-proliferative and pro-angiogenic factors that allow tumour cells to escape immunosurveillance in cancer-prone tissues. The privileged position of the human epididymis in evading tumourigenicity is reflected in transgenic mouse models in which induction of tumours in other organs is not accompanied by epididymal neoplasia. The epididymis appears to: (i) prevent tumour initiation (it probably lacks stem cells and has strong anti-oxidative mechanisms, active tumour suppressors and inactive oncogene products); (ii) foster tumour monitoring and destruction (by strong immuno-surveillance and -eradication, and cellular senescence); (iii) avert proliferation and angiogenesis (with persistent tight junctions, the presence of anti-angiogenic factors and misplaced pro-angiogenic factors), which together (iv) promote dormancy and restrict dividing cells to hyperplasia. Epididymal cells may be rendered non-responsive to oncogenic stimuli by the constitutive expression of factors generally inducible in tumours, and resistant to the normal epididymal environment, which mimics that of a tumour niche promoting tumour growth. The threshold for tumour initiation may thus be higher in the epididymis than in other organs. Several anti-tumour mechanisms are those that maintain spermatozoa quiescent and immunologically silent, so the low incidence of cancer in the epididymis may be a consequence of its role in sperm maturation and storage. Understanding these mechanisms may throw light on cancer prevention and therapy in general. PMID:22522502

  9. Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

    DEFF Research Database (Denmark)

    Mitchell, Thomas J.; Turajlic, Samra; Rowan, Andrew

    2018-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the...

  10. Molecular changes in endometriosis-associated ovarian clear cell carcinoma.

    Science.gov (United States)

    Worley, Michael J; Liu, Shubai; Hua, Yuanyuan; Kwok, Jamie Sui-Lam; Samuel, Anicka; Hou, Lei; Shoni, Melina; Lu, Shi; Sandberg, Evelien M; Keryan, Anna; Wu, Di; Ng, Shu-Kay; Kuo, Winston P; Parra-Herran, Carlos E; Tsui, Stephen K W; Welch, William; Crum, Christopher; Berkowitz, Ross S; Ng, Shu-Wing

    2015-09-01

    Endometriosis is frequently associated with and thought of having propensity to develop into ovarian clear cell carcinoma (OCCC), although the molecular transformation mechanism is not completely understood. We employed immunohistochemical (IHC) staining for marker expression along the potential progression continuum. Expression profiling of microdissected endometriotic and OCCC cells from patient-matched formalin-fixed, paraffin-embedded samples was performed to explore the carcinogenic pathways. Function of novel biomarkers was confirmed by knockdown experiments. PTEN was significantly lost in both endometriosis and invasive tumour tissues, while oestrogen receptor (ER) expression was lost in OCCC relative to endometriosis. XRCC5, PTCH2, eEF1A2 and PPP1R14B were significantly overexpressed in OCCC and associated endometriosis, but not in benign endometriosis (p ⩽ 0.004). Knockdown experiments with XRCC5 and PTCH2 in a clear cell cancer cell line resulted in significant growth inhibition. There was also significant silencing of a panel of target genes with histone H3 lysine 27 trimethylation, a signature of polycomb chromatin-remodelling complex in OCCC. IHC confirmed the loss of expression of one such polycomb target gene, the serous ovarian cancer lineage marker Wilms' tumour protein 1 (WT1) in OCCC, while endometriotic tissues showed significant co-expression of WT1 and ER. Loss of PTEN expression is proposed as an early and permissive event in endometriosis development, while the loss of ER and polycomb-mediated transcriptional reprogramming for pluripotency may play an important role in the ultimate transformation process. Our study provides new evidence to redefine the pathogenic programme for lineage-specific transformation of endometriosis to OCCC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Glycogen-rich clear cell carcinoma of the breast.

    Science.gov (United States)

    Markopoulos, Christos; Mantas, Dimitris; Philipidis, T; Kouskos, Efstatios; Antonopoulou, Zoi; Hatzinikolaou, Ml; Gogas, Helen

    2008-04-29

    Glycogen-rich carcinoma of the breast is a rare histological subtype of breast cancer, usually reported to have poor prognosis. We present the case of a 59-year-old woman who underwent a mastectomy for a 3.5 cm clinically palpable left breast carcinoma, originally diagnosed as fibroadenoma on a screening mammogram four years before presentation. Diagnosis of clear cell carcinoma was based on certain histological characteristics of the tumour and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA, cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin, Synaptophysin, S-100, SMA). No lymph node metastasis was found and as the tumour was ER positive and PgR negative, patient was treated only with an aromatase inhibitor upfront and remains free of disease 48 months now since operation. Glycogen-rich clear cell carcinoma of the breast is a rare tumor, its clinical behavior reported to be rather aggressive so far, might varies depending on special characteristics such as low grade and strongly positive ER expression.

  12. Clear Cell Adenocarcinoma of the Urethra: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2015-01-01

    Full Text Available Background. Clear cell adenocarcinoma of the urethra (CCAU is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour. Aims. To review the literature on CCAU. Methods. Various internet databases were used. Results/Literature Review. (i CCAU occurs in adults and in women in the great majority of cases. (ii It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v CCAU is aggressive with low 5-year survival rates. (vi There is no consensus opinion of treatment options that would improve the prognosis. Conclusions. Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.

  13. Glycogen-rich clear cell carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hatzinikolaou ML

    2008-04-01

    Full Text Available Abstract Background Glycogen-rich carcinoma of the breast is a rare histological subtype of breast cancer, usually reported to have poor prognosis. Case presentation We present the case of a 59-year-old woman who underwent a mastectomy for a 3.5 cm clinically palpable left breast carcinoma, originally diagnosed as fibroadenoma on a screening mammogram four years before presentation. Diagnosis of clear cell carcinoma was based on certain histological characteristics of the tumour and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA, cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin, Synaptophysin, S-100, SMA. No lymph node metastasis was found and as the tumour was ER positive and PgR negative, patient was treated only with an aromatase inhibitor upfront and remains free of disease 48 months now since operation. Conclusion Glycogen-rich clear cell carcinoma of the breast is a rare tumor, its clinical behavior reported to be rather aggressive so far, might varies depending on special characteristics such as low grade and strongly positive ER expression

  14. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    International Nuclear Information System (INIS)

    Cannon, Christopher P.; Nelson, Scott D.; Seeger, Leanne L.; Eckardt, Jeffrey J.

    2002-01-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  15. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Christopher P. [Department of Orthopaedic Surgery, Madigan Army Medical Center, Ft. Lewis, WA (United States); Nelson, Scott D. [Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, CA (United States); Seeger, Leanne L. [Department of Radiological Sciences, University of California, CA (United States); Eckardt, Jeffrey J. [Department of Orthopaedic Surgery, University of California, Los Angeles School of Medicine, CA (United States)

    2002-06-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  16. Clear Cell Adenocarcinoma Arising from Abdominal Wall Endometriosis

    Directory of Open Access Journals (Sweden)

    Thouraya Achach

    2008-01-01

    Full Text Available Endometriosis is a frequent benign disorder. Malignancy arising in extraovarian endometriosis is a rare event. A 49-year-old woman is presented with a large painful abdominal wall mass. She underwent a myomectomy, 20 years before, for uterus leiomyoma. Computed tomography suggested that this was a desmoid tumor and she underwent surgery. Histological examination showed a clear cell adenocarcinoma associated with endometriosis foci. Pelvic ultrasound, computed tomography, and endometrial curettage did not show any malignancy or endometriosis in the uterus and ovaries. Adjuvant chemotherapy was recommended, but the patient was lost to follow up. Six months later, she returned with a recurrence of the abdominal wall mass. She was given chemotherapy and then she was reoperated.

  17. SETD2 and PBRM1 inactivation in the development of clear cell renal cell carcinoma

    NARCIS (Netherlands)

    Li, Jun

    2016-01-01

    Kidney cancer of the clear cell type is often lethal and causes more than 100,000 deaths worldwide every year. Understanding the biology of this cancer type may help to develop better ways to diagnose and treat it. Damage in DNA (genes) is present in all cancer cells and clear cell kidney cancer is

  18. Thyroid metastasis as initial presentation of clear cell renal carcinoma.

    Science.gov (United States)

    Ramírez-Plaza, César Pablo; Domínguez-López, Marta Elena; Blanco-Reina, Francisco

    2015-01-01

    Metastatic tumors account for 1.4-2.5% of thyroid malignancies. About 25-30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles "suggestive" of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of "de novo" thyroid nodules in oncologic patients must be always considered and studied. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Epididymitis: revelations at the convergence of clinical and basic sciences

    Directory of Open Access Journals (Sweden)

    Vera Michel

    2015-01-01

    Full Text Available Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.

  20. cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit.

    Science.gov (United States)

    Krapf, Dario; Ruan, Ye Chun; Wertheimer, Eva V; Battistone, Maria A; Pawlak, John B; Sanjay, Archana; Pilder, Stephen H; Cuasnicu, Patricia; Breton, Sylvie; Visconti, Pablo E

    2012-09-01

    Changes that occur to mammalian sperm upon epididymal transit and maturation render these cells capable of moving progressively and capacitating. Signaling events leading to mammalian sperm capacitation depend on the modulation of proteins by phosphorylation and dephosphorylation cascades. Recent experiments have demonstrated that the Src family of kinases plays an important role in the regulation of these events. However, sperm from cSrc null mice display normal tyrosine phosphorylation associated with capacitation. We report here that, despite normal phosphorylation, sperm from cSrc null mice display a severe reduction in forward motility, and are unable to fertilize in vitro. Histological analysis of seminiferous tubules in the testes, caput and corpus epididymis do not reveal obvious defects. However, the cauda epididymis is significantly smaller, and expression of key transport proteins in the epithelial cells lining this region is reduced in cSrc null mice compared to wild type littermates. Although previously, we and others have shown the presence of cSrc in mature sperm from cauda epididymis, a closer evaluation indicates that this tyrosine kinase is not present in sperm from the caput epididymis, suggesting that this protein is acquired by sperm later during epididymal maturation. Consistent with this observation, cSrc is enriched in vesicles released by the epididymal epithelium known as epididymosomes. Altogether, these observations indicate that cSrc is essential for cauda epididymal development and suggest an essential role of this kinase in epididymal sperm maturation involving cSrc extracellular trafficking. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Diagnosis and treatment of clear cell hidradenocarcinoma of the scalp.

    Science.gov (United States)

    Shu, Kai; Xiao, Qungen; Büchele, Fabian; Zhang, Suojun; Jiang, Wei; Lei, Ting

    2012-12-01

    Clear cell hidradenocarcinoma (CCH) is an exceedingly rare and highly malignant tumor of the eccrine sweat glands. Its treatment is extremely difficult due to the characteristically aggressive clinical course including repeated local recurrence and uncontrollable distal metastasis coming along with a very poor prognosis. Most published case studies recommend a wide surgical excision followed by adjuvant conservative therapy, which is generally considered to be the standard treatment. Two cases of nodular CCH of the scalp either presenting as a singular primary lesion or at an already metastatic stage were analyzed retrospectively. Wide local excision of the tumor couldn't prevent the primary carcinoma from recurring and metastasizing. Both cases received various therapies but the results were unsatisfactory. Although most authors have recommended that early wide surgical excision of the tumor is a feasible therapeutic measurement, our results raise doubts on the efficacy of this treatment strategy. As alternative approaches (i.e. chemotherapy, radiotherapy) are similarly controversial, further studies and a wide exchange of clinical experiences are crucial.

  2. MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.

    Science.gov (United States)

    Zhu, Jie; Cui, Liang; Xu, Axiang; Yin, Xiaotao; Li, Fanglong; Gao, Jiangping

    2017-03-07

    Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1. MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells. By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (cc

  3. cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit

    OpenAIRE

    Krapf, Dario; Ruan, Ye Chun; Wertheimer, Eva V.; Battistone, Maria A.; Pawlak, John B.; Sanjay, Archana; Pilder, Stephen H.; Cuasnicu, Patricia; Breton, Sylvie; Visconti, Pablo E.

    2012-01-01

    Changes that occur to mammalian sperm upon epididymal transit and maturation render these cells capable of moving progressively and capacitating. Signaling events leading to mammalian sperm capacitation depend on the modulation of proteins by phosphorylation and dephosphorylation cascades. Recent experiments have demonstrated that the Src family of kinases plays an important role in the regulation of these events. However, sperm from cSrc null mice display normal tyrosine phosphorylation asso...

  4. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  5. IL-15 STIMULATED NATURAL KILLER CELLS CLEAR HIV-1 INFECTED CELLS FOLLOWING LATENCY REVERSAL EX VIVO.

    Science.gov (United States)

    Garrido, Carolina; Abad-Fernandez, Maria; Tuyishime, Marina; Pollara, Justin J; Ferrari, Guido; Soriano-Sarabia, Natalia; Margolis, David M

    2018-03-28

    Current efforts towards HIV eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate immune system, recognize and clear targets using different mechanisms than CD8 + T cells, offering an alternative or complementary approach for HIV clearance strategies. We assessed the impact of IL-15 treatment on NK cell function and the potential of stimulated NK cells to clear the HIV reservoir. We measured NK cell receptor expression, antibody-dependent cell-dependent cytotoxicity (ADCC), cytotoxicity, IFN-γ production and antiviral activity in autologous HIV replication systems. All NK cell functions were uniformly improved by IL-15, and more importantly, IL-15-treated NK cells were able to clear latently HIV infected cells after exposure to vorinostat, a clinically relevant latency reversing agent. We also demonstrate that NK cells from HIV infected individuals aviremic on antiretroviral therapy can be efficiently stimulated with IL-15. Our work opens a promising line of investigation towards future immunotherapies to clear persistent HIV infection using NK cells. IMPORTANCE In the search for an HIV cure, strategies to enhance immune function to allow recognition and clearance of HIV infected cells following latency reversal are being evaluated. Natural killer (NK) cells possess characteristics that can be exploited for immunotherapy against persistent HIV infection. We demonstrate that NK cells from HIV-positive donors can be strongly stimulated with IL-15, improving their antiviral and cytotoxic potential, and more importantly, clearing HIV infected cells after latency reversal with a clinically relevant drug. Our results encourage further investigation to design NK cell-based immunotherapies to achieve HIV eradication. Copyright © 2018 American Society for Microbiology.

  6. Localization of cathepsin D in mouse reproductive tissues and its acquisition onto sperm surface during epididymal sperm maturation.

    Science.gov (United States)

    Asuvapongpatana, Somluk; Saewu, Arpornrad; Chotwiwatthanakun, Charoonroj; Vanichviriyakit, Rapeepun; Weerachatyanukul, Wattana

    2013-06-01

    Sperm maturation in the epididymis involves multiple complex events, that include the adsorption of epididymal secretory proteins, re-organization and removal of sperm surface ligands. In this study, we investigated the existence and distribution of cathepsin D (CAT-D) transcripts and proteins in mouse reproductive tissues and proposed a transfer mechanism of CAT-D to the sperm surface. CAT-D transcripts were highly expressed in cultured Sertoli cells, but not in germ cells. The transcriptional level was relatively higher in the caput epididymis (CP) than in the cauda epididymis (CD). At the translational level, CAT-D was detected in testicular somatic cells and in the principal and basal cells in the CP. The expression of CAT-D was fairly specific to the clear cells in the CD. All forms of CAT-D were detected in ultracentrifuged epididymosomes. In conjunction with the expression levels in epididymal epithelium and epididymosomes, CAT-D expression level on the sperm surface was relatively high in CP sperm, but gradually declined toward the CD. Overall, our results indicated that CAT-D was not inherent to sperm themselves, but rather of epididymal origin and was presumably transported to the sperm surface via epididymosomes. Copyright © 2012 Elsevier GmbH. All rights reserved.

  7. Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

    Science.gov (United States)

    Cochrane, Dawn R; Tessier-Cloutier, Basile; Lawrence, Katherine M; Nazeran, Tayyebeh; Karnezis, Anthony N; Salamanca, Clara; Cheng, Angela S; McAlpine, Jessica N; Hoang, Lien N; Gilks, C Blake; Huntsman, David G

    2017-09-01

    Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Cryopreservation of epididymal stallion sperm.

    Science.gov (United States)

    Olaciregui, M; Gil, L; Montón, A; Luño, V; Jerez, R A; Martí, J I

    2014-02-01

    Any event that makes semen collection or mating impossible, such as death, castration, or injury, may terminate a stallion's breeding career. Fortunately, stallion sperm which are capable of fertilization can be harvested from the epididymis, and frozen for future use. However, the fertility of frozen-thawed epididymal sperm has been found to be lower than that of ejaculated sperm. Therefore, this study aimed to optimize the fertility of frozen epididymal stallion sperm by investigating the effects of different cryoprotectants and freezing protocols on sperm quality. Dimethylformamide was tested alone or combination with pasteurized egg yolk as substitute of fresh egg yolk. In addition, the effect of the pre-freeze stabilization on sperm quality was analyzed. Heterospermic samples obtained from stallion epididymis were collected and cryopreserved in lactose-egg-yolk extender or in the same extender with varying content of cryoprotectant and content of egg yolk, stabilized and no-stabilized. Sperm motility, viability, hypoosmotic swelling test (HOST) and acrosome integrity were evaluated post-thawing. No improvement was observed on the replacement of fresh yolk by pasteurized egg yolk, whereas the results suggest that dimethylformamide is a cryoprotectant suitable for cryopreservation of equine epididymal semen, even better than glycerol. In addition, we found that the stabilization before freezing on epididymal stallion sperm, can improve sperm quality parameters. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Computer approach to recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Kruk, Michal; Osowski, Stanislaw; Markiewicz, Tomasz; Slodkowska, Janina; Koktysz, Robert; Kozlowski, Wojciech; Swiderski, Bartosz

    2014-06-01

    To present a computerized system for recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma on the basis of microscopic images of the neoplasm cells in application of hematoxylin and eosin staining. The applied methods use combined gradient and mathematical morphology to obtain nuclei and classifiers in the form of support vector machine to estimate their Fuhrman grade. The starting point is a microscopic kidney image, which is subject to the advanced methods of preprocessing, leading finally to estimation of Fuhrman grade of cells and the whole analyzed image. The results of the numerical experiments have shown that the proposed nuclei descriptors based on different principles of generation are well connected with the Fuhrman grade. These descriptors have been used as the diagnostic features forming the inputs to the classifier, which performs the final recognition of the cells. The average discrepancy rate between the score of our system and the human expert results, estimated on the basis of over 3,000 nuclei, is below 10%. The obtained results have shown that the system is able to recognize 4 Fuhrman grades of the cells with high statistical accuracy and agreement with different expert scores. This result gives a good perspective to apply the system for supporting and accelerating the research of kidney cancer.

  10. Primary clear cell sarcoma of bone: a unique site of origin

    International Nuclear Information System (INIS)

    Gelczer, R.K.; Wenger, D.E.; Wold, L.E.

    1999-01-01

    Clear cell sarcoma is a rare soft tissue neoplasm, accounting for less than 1% of soft tissue sarcomas. We are presenting a case of a clear cell sarcoma of bone which, to our knowledge, is the only report of a primary clear cell sarcoma of bone. (orig.)

  11. Thiol changes during epididymal maturation: a link to flagellar angulation in mouse spermatozoa?

    Science.gov (United States)

    Ijiri, T W; Vadnais, M L; Huang, A P; Lin, A M; Levin, L R; Buck, J; Gerton, G L

    2014-01-01

    Caput epididymal wild-type spermatozoa and cauda epididymal spermatozoa from mice null for the adenylyl cyclase Adcy10 gene are immotile unless stimulated by a membrane-permeant cyclic AMP analogue. Both types of spermatozoa exhibit flagellar angulation where the head folds back under these conditions. As sperm proteins undergo oxidation of sulfhydryl groups and the flagellum becomes more stable to external forces during epididymal transit, we hypothesized that ADCY10 is involved in a mechanism regulating flagellar stabilization. Although no differences were observed in global sulfhydryl status between caput and cauda epididymal spermatozoa from wild-type or Adcy10-null mice, two-dimensional fluorescence difference gel electrophoresis was performed to identify specific mouse sperm proteins containing sulfhydryl groups that became oxidized during epididymal maturation. A-kinase anchor protein 4, fatty acid-binding protein 9 (FABP9), glutathione S-transferase mu 5 and voltage-dependent anion channel 2 exhibited changes in thiol status between caput and cauda epididymal spermatozoa. The level and thiol status of each of these proteins were quantified in wild-type and Adcy10-null cauda epididymal spermatozoa. No differences in the abundance of any protein were observed; however, FABP9 in Adcy10-null cauda epididymal spermatozoa contained fewer disulfide bonds than wild-type sperm cells. In caput epididymal spermatozoa, FABP9 was detected in the cytoplasmic droplet, principal piece, midpiece, and non-acrosomal area of the head. However, in cauda epididymal spermatozoa, this protein localized to the perforatorium, post-acrosomal region and principal piece. Together, these results suggest that thiol changes during epididymal maturation have a role in the stabilization of the sperm flagellum. PMID:24254994

  12. Thiol changes during epididymal maturation: a link to flagellar angulation in mouse spermatozoa?

    Science.gov (United States)

    Ijiri, T W; Vadnais, M L; Huang, A P; Lin, A M; Levin, L R; Buck, J; Gerton, G L

    2014-01-01

    Caput epididymal wild-type spermatozoa and cauda epididymal spermatozoa from mice null for the adenylyl cyclase Adcy10 gene are immotile unless stimulated by a membrane-permeant cyclic AMP analogue. Both types of spermatozoa exhibit flagellar angulation where the head folds back under these conditions. As sperm proteins undergo oxidation of sulfhydryl groups and the flagellum becomes more stable to external forces during epididymal transit, we hypothesized that ADCY10 is involved in a mechanism regulating flagellar stabilization. Although no differences were observed in global sulfhydryl status between caput and cauda epididymal spermatozoa from wild-type or Adcy10-null mice, two-dimensional fluorescence difference gel electrophoresis was performed to identify specific mouse sperm proteins containing sulfhydryl groups that became oxidized during epididymal maturation. A-kinase anchor protein 4, fatty acid-binding protein 9 (FABP9), glutathione S-transferase mu 5 and voltage-dependent anion channel 2 exhibited changes in thiol status between caput and cauda epididymal spermatozoa. The level and thiol status of each of these proteins were quantified in wild-type and Adcy10-null cauda epididymal spermatozoa. No differences in the abundance of any protein were observed; however, FABP9 in Adcy10-null cauda epididymal spermatozoa contained fewer disulfide bonds than wild-type sperm cells. In caput epididymal spermatozoa, FABP9 was detected in the cytoplasmic droplet, principal piece, midpiece, and non-acrosomal area of the head. However, in cauda epididymal spermatozoa, this protein localized to the perforatorium, post-acrosomal region and principal piece. Together, these results suggest that thiol changes during epididymal maturation have a role in the stabilization of the sperm flagellum. © 2013 American Society of Andrology and European Academy of Andrology.

  13. Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Wei, Xiaona; Choudhury, Yukti; Lim, Weng Khong; Anema, John; Kahnoski, Richard J; Lane, Brian; Ludlow, John; Takahashi, Masayuki; Kanayama, Hiro-Omi; Belldegrun, Arie; Kim, Hyung L; Rogers, Craig; Nicol, David; Teh, Bin Tean; Tan, Min-Han

    2017-08-04

    Clear cell renal cell carcinoma (ccRCC) has been previously classified into putative discrete prognostic subtypes by gene expression profiling. To investigate the robustness of these proposed subtype classifications, we evaluated 12 public datasets, together with a new dataset of 265 ccRCC gene expression profiles. Consensus clustering showed unstable subtype and principal component analysis (PCA) showed a continuous spectrum both within and between datasets. Considering the lack of discrete delineation and continuous spectrum observed, we developed a continuous quantitative prognosis score (Continuous Linear Enhanced Assessment of RCC, or CLEAR score). Prognostic performance was evaluated in independent cohorts from The Cancer Genome Atlas (TCGA) (n = 414) and EMBL-EBI (n = 53), CLEAR score demonstrated both superior prognostic estimates and inverse correlation with anti-angiogenic tyrosine-kinase inhibition in comparison to previously proposed discrete subtyping classifications. Inverse correlation with high-dose interleukin-2 outcomes was also observed for the CLEAR score. Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were associated with the CLEAR score. Application of the CLEAR score to independent expression profiling of intratumoral ccRCC regions demonstrated that average intertumoral heterogeneity exceeded intratumoral expression heterogeneity. Wider investigation of cancer biology using continuous approaches may yield insights into tumor heterogeneity; single cell analysis may provide a key foundation for this approach.

  14. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    cells were stained by antisera to carcinoembryonic antigen, keratin and epithelial membrane antigen, but not by antisera to alpha-lactalbumin, desmin or vimentin. Ultrastructurally, the epithelial derivation of the tumour was confirmed. Only a few intracytoplasmic lumina were demonstrated. The tumour...

  15. Targeting HIF2α Translation with Tempol in VHL-Deficient Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Ghosh, Manik C.; Ghosh, Sanchari; Yang, Youfeng; Gupta, Gopal; DeGraff, William; Krishna, Murali C.; Mitchell, James B.; Rouault, Tracey A.; Linehan, W. Marston

    2012-01-01

    The tumor suppressor gene, Von Hippel-Lindau (VHL), is frequently mutated in the most common form of kidney cancer, clear cell renal cell carcinoma (CCRCC). In hypoxic conditions, or when there is a VHL mutation, the hypoxia inducible factors, HIF1α and HIF2α, are stabilized and transcribe a panel of genes associated with cancer such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). Recent studies in clear cell kidney cancer have suggested that HIF2α, but not HIF1α, is the critical oncoprotein in the VHL pathway. Therefore, targeting HIF2α could provide a potential therapeutic approach for patients with advanced CCRCC. Since iron regulatory protein 1 (IRP1) is known to inhibit the translation of HIF2α, we investigated whether Tempol, a stable nitroxide that activates IRP1 towards IRE-binding, might have a therapeutic effect on a panel of human CCRCC cells expressing both HIF1α and HIF2α. We first evaluated the protein expression of HIF1α and HIF2α in 15 different clear cell renal carcinoma cell lines established from patient tumors in our laboratory. Tempol decreased the expression of HIF2α, and its downstream targets in all the cell lines of the panel. This effect was attributed to a dramatic increase of IRE-binding activity of IRP1. Several cell lines were found to have an increased IRP1 basal activity at 20% O2 compared to 5% O2, which may lower HIF2α expression in some of the cell lines in a VHL-independent manner. Taken together our data identify Tempol as an agent with potential therapeutic activity targeting expression of HIF2α in VHL-deficient clear cell kidney cancer and illustrate the importance of studying biochemical processes at relevant physiological O2 levels. PMID:23178531

  16. Role of WNT signaling in epididymal sperm maturation.

    Science.gov (United States)

    Cheng, Jin-Mei; Tang, Ji-Xin; Li, Jian; Wang, Yu-Qian; Wang, Xiu-Xia; Zhang, Yan; Chen, Su-Ren; Liu, Yi-Xun

    2018-02-01

    Spermatozoa maturation, a process required for spermatozoa to acquire progressive motility and the ability to fertilize ova, primarily occurs in the caput and corpus of the epididymis. Despite considerable efforts, the factor(s) promoting epididymal sperm maturation remains unclear. Recently, WNT signaling has been implicated in epididymal sperm maturation. To further investigate WNT signaling function in epididymal sperm maturation, we generated Wntless conditional knockout mice (Wls cKO), Wls flox/flox ; Lcn5-Cre. In these mice, WNTLESS (WLS), a conserved membrane protein required for all WNT protein secretion, was specifically disrupted in the principal cells of the caput epididymidis. Immunoblot analysis showed that WLS was significantly reduced in the caput epididymidis of Wls cKO mice. In the caput epididymidis of Wls cKO mice, WNT 10A and WNT 2b, which are typically secreted by the principal cells of the caput epididymis, were not secreted. Interestingly, sperm motility analysis showed that the WLS deficiency in the caput epididymidis had no effect on sperm motility. Moreover, fertility tests showed that Wls cKO male mice had normal fertility. These results indicate that the disruption of WLS in principal cells of the caput epididymidis inhibits WNT protein secretion but has no effect on sperm motility and male fertility, suggesting that WNT signaling in the caput epididymidis may be dispensable for epididymal sperm maturation in mice.

  17. Epididymosomes transfer epididymal sperm binding protein 1 (ELSPBP1) to dead spermatozoa during epididymal transit in bovine.

    Science.gov (United States)

    D'Amours, Olivier; Frenette, Gilles; Bordeleau, Louis-Jean; Allard, Nancy; Leclerc, Pierre; Blondin, Patrick; Sullivan, Robert

    2012-10-01

    Previously, we showed that epididymal sperm binding protein 1 (ELSPBP1) characterizes spermatozoa already dead before ejaculation in bovine. In this study, we investigated the presence of ELSPBP1 in bull genital tract as well as its acquisition by spermatozoa during epididymal transit. As assessed by real-time RT-PCR, ELSPBP1 was highly expressed in the caput and the corpus epididymis but was present in lower expression levels in the testis and the cauda epididymis. Immunohistochemistry revealed the same expression pattern. However, Western blot on tissue homogenates showed some discrepancies, as ELSPBP1 was found in a comparable concentration all along the epididymis. This difference was due to the presence of ELSPBP1 in the epididymal fluid. In both caput and cauda epididymal fluid, ELSPBP1 was associated with the epididymosomes, small membranous vesicles secreted by epithelial cells of the epididymis and implicated in the transfer of proteins to spermatozoa. As assessed by immunocytometry, ELSPBP1 was found on a subset of dead spermatozoa in caput epididymis but was found on all dead spermatozoa in cauda epididymis. To assess ELSPBP1 acquisition by spermatozoa, caput epididymal spermatozoa were incubated with cauda epididymosomes under various conditions. ELSPBP1 detection by immunocytometry assay revealed that only spermatozoa already dead before incubation were receptive to ELSPBP1 transfer by epididymosomes. This receptivity was enhanced by the presence of zinc in the incubation medium. This specificity for a sperm subpopulation suggests that an underlying mechanism is involved and that ELSPBP1 could be a tag for the recognition of dead spermatozoa during epididymal transit.

  18. Metastatic Clear Cell Renal Cell Carcinoma Presenting with a Gingival Metastasis

    OpenAIRE

    Ali, Rusha A.E.; Mohamed, Kamal E.H.

    2016-01-01

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation...

  19. Pathological Bases and Clinical Impact of Intratumor Heterogeneity in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    López, José I; Angulo, Javier C

    2018-01-27

    Intratumor heterogeneity is an inherent event in tumor development that is receiving much attention in the last years since it is responsible for most failures of current targeted therapies. The purpose of this review is to offer clinicians an updated insight of the multiple manifestations of a complex event that impacts significantly patient's life. Clear cell renal cell carcinoma is the most common renal tumor and a paradigmatic example of a heterogeneous neoplasm. Next-generation sequencing has demonstrated that intratumor heterogeneity encompasses genetic, epigenetic, and microenvironmental variability. Currently accepted protocols of tumor sampling seem insufficient in unveiling intratumor heterogeneity with reliability and need to be updated. This variability challenges the precise morphological diagnosis, its molecular characterization, and the selection of optimal personalized therapies in clear cell renal cell carcinoma, a neoplasm traditionally considered chemo- and radio-resistant. We review the state of the art of the different approaches to intratumor heterogeneity in clear cell renal cell carcinomas, from the simple morphology to the most sophisticated massive sequencing tools.

  20. Ultrastructural morphometry of nucleoli: potential usefulness for objective grading of clear cell renal cell carcinoma.

    Science.gov (United States)

    Lloreta-Trull, J; Bielsa-Galí, O; Domínguez-Solà, D; Arumí-Uría, M; Pavesi, M; Gelabert, A; Serrano-Figueras, S

    2001-01-01

    The authors attempted to determine the potential prognostic value of several ultrastructural morphometric parameters, including nuclear, nucleolar, and cytoplasmic features, that could be used in the objective and reproducible histological grading of clear cell renal cell carcinoma. Several nuclear and cytoplasmic parameters were assessed by ultrastructural morphometry in 26 consecutive cases of clear cell renal cell carcinoma. The nuclear and nucleolar sizes, the number of nucleoli per nuclear section and the number of marginated nucleoli, Fuhrman's nuclear grade, and Robson's stage were recorded. In addition, the proportion of cytoplasmic components was semiquantitatively estimated and compared to light microscopic appearance. Follow-up ranged from 5 to 15 years (mean = 10 years). Statistical evaluations were performed by means of the Pearson or Spearman correlation coefficient tests, and differences in survival were estimated, using the Mantel-Cox proportional risk method. Differences in survival among patients with a mean nuclear area over and under 160 microm2, and among those with a mean nucleolar area over and under 10 microm2, were statistically significant. (Cutoff points were selected at the median value for both parameters; Mantel-Cox test: chi2 = 7.102, p morphometric features, nucleolar area is the most useful in the reproducible and accurate grading of clear cell renal cell carcinoma.

  1. Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature.

    Science.gov (United States)

    Knez, Virginia M; Barrow, Willis; Lucia, M Scott; Wilson, Shandra; La Rosa, Francisco G

    2014-08-14

    The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diagnosis are tumors of Müllerian origin and metastatic lesions, such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear cell urothelial carcinoma is exceedingly rare, with only nine clinical cases described in the literature. We report the case of a 75-year-old Caucasian man who presented with intermittent hematuria, in whom a bladder tumor was identified. A final histopathology examination of a cystoprostatectomy specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder tumor consisted of sheets of malignant cells with severe nuclear atypia and abundant clear cytoplasm; no glandular or tubular structures were identified. Tumor cells were periodic acid-Schiff positive and negative after diastase treatment; additional mucicarmine and oil red O stains were negative. Immunohistochemical stains showed the tumor cells positive for cytokeratin 7 (CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45 (HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP), prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25 (CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all negative. The tumor marker profile was consistent with clear

  2. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal

    2014-01-01

    of published biomarkers to predict the survival of patients with clear cell kidney cancer in an independent patient cohort. Only one molecular test adds prognostic information to routine clinical assessments. This marker showed good and poor prognosis results within most individual cancers. Future biomarkers......BackgroundCandidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. ObjectiveTo validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising...... markers to guide biomarker optimisation. Design, setting, and participantsCancer-specific survival (CSS) for each of 28 identified genetic or transcriptomic biomarkers was assessed in 350 ccRCC patients. ITH was interrogated in a multiregion biopsy data set of 10 ccRCCs. Outcome measurements...

  3. Clear cell myoepithelial carcinoma of salivary glands showing EWSR1 rearrangement: molecular analysis of 94 salivary gland carcinomas with prominent clear cell component.

    Science.gov (United States)

    Skálová, Alena; Weinreb, Ilan; Hyrcza, Martin; Simpson, Roderick H W; Laco, Jan; Agaimy, Abbas; Vazmitel, Marina; Majewska, Hanna; Vanecek, Tomas; Talarčik, Peter; Manajlovic, Spomenka; Losito, Simona N; Šteiner, Petr; Klimkova, Adela; Michal, Michal

    2015-03-01

    This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary gland carcinomas with myoepithelial differentiation. A total of 94 salivary gland carcinomas with a prominent clear cell component included 51 cases of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign myoepithelioma were included as well. All the tumors in this spectrum were reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH) for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5 of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%) cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and CCMCexPAs shared similar histomorphology. They were arranged in nodules composed of compact nests of large polyhedral cells with abundant clear cytoplasm. Necrosis, areas of squamous metaplasia, and hyalinization were frequent features. Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%), and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in the 20% to 40% range. Clinical follow-up information was available in 21 cases (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to follow-up. Ten patients are alive with no evidence of recurrent or metastatic disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients are alive with recurrent and metastatic disease, and 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis appeared in 5 patients

  4. Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

    2018-02-23

    Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. [Late thyroid and pancreas metastases from a clear cell renal carcinoma. Report of two cases].

    Science.gov (United States)

    Urdiales-Viedma, Mariano; Luque, Rafael J; Elósegui-Martínez, Fernando; Martos-Padilla, Sebastián; López-Urdiales, Rafael

    2008-01-01

    To report two cases of late metastases of clear cell renal cell carcinoma. Two patients, a male and a female with history of nephrectomy 17 and 16 years before for renal cell carcinomas, presented new tumours in the thyroid and pancreas, which were excised. Pathology reported that both lesions were clear cell tumours and immunohistochemically they were consistent with metastases from clear renal cell carcinomas. 1) Previous history of any type of carcinoma should suggest the possibility of metastases when facing a thyroid or pancreatic nodule. 2) All-life follow-up should be made, nephrectomy (resection) for a renal cell carcinoma. 3) In the presence of a clear cell tumour of the thyroid or pan-creatic glands, the differential diagnosis must always include metastatic renal cell carcinoma. 4) The treatment of choice is surgical resection.

  6. Metastatic Clear Cell Renal Cell Carcinoma Presenting with a Gingival Metastasis.

    Science.gov (United States)

    Ali, Rusha A E; Mohamed, Kamal E H

    2016-04-26

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis.

  7. Metastatic clear cell renal cell carcinoma presenting with a gingival metastasis

    Directory of Open Access Journals (Sweden)

    Rusha A.E. Ali

    2016-06-01

    Full Text Available Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis.

  8. Testicular Involvement of Tuberculous Epididymitis : Sonographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jae Joon; Kim, Myeong Jin; Yoo, Hyung Sik; Lee, Jong Tae; Lee, Yong Hee [Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Joong Hwa [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Lee, Yeon Hee [Dankook University Hospital, Cheonan (Korea, Republic of)

    1996-12-15

    To report the sonographic findings of testicular involvement of tuberculous epididymitis. The sonographic findings of testicular involvement in twelve patients with histologically proven tuberculous epididymitis were retrospectively reviewed. The sonographic findings of testicular lesions are 1) an ill defined hypoechoic lesion (3 cases, 25.0%), 2) a well-demarcated hypoechoic lesion (3 cases, 25.0%),3) multiple and small hypoechoic nodules in the enlarged testis (2 cases, 16.7%), 4) indistinct margin between the testis and epididymis (2 cases, 16.7%) and 5) a diffusely enlarged testis with hypoechogenicity (2 cases, 16.7%).Nine patients had ipsilateral epididymitis, and 3 patients had bilateral epididymitis. Pus discharge through the draining sinus tract was noted in 4 cases (33.3%), and hydrocele in 8 cases (66.7%). No parenchymal calcification was seen in the involved testis. Sonographic findings of testicular involvement in tuberculous epididymitis were various

  9. Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas

    International Nuclear Information System (INIS)

    Yao, Masahiro; Murakami, Takayuki; Shioi, Koichi; Mizuno, Nobuhiko; Ito, Hiroki; Kondo, Keiichi; Hasumi, Hisashi; Sano, Futoshi; Makiyama, Kazuhide; Nakaigawa, Noboru; Kishida, Takeshi; Nagashima, Yoji; Yamanaka, Shoji; Kubota, Yoshinobu

    2014-01-01

    High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs

  10. Cytopathologic, Histopathologic, and Immunohistochemical Features of Intrahepatic Clear Cell Bile Duct Adenoma: A Case Report and Review of the Literature

    OpenAIRE

    William W. Wu; Mai Gu; Di Lu

    2014-01-01

    Intrahepatic clear cell bile duct adenoma is extremely rare, with only 3 previous cases reported in the literature. The cause of cytoplasmic clearing in clear cell bile duct adenoma has not been previously investigated. Distinguishing clear cell bile duct adenoma from other clear cell tumors, particularly clear cell cholangiocarcinoma, can be challenging. Previous studies have shown loss of CD10 expression and focal CD56 expression in cholangiocarcinoma. Expressions of CD10 and CD56 have not...

  11. Desialylation of Spermatozoa and Epithelial Cell Glycocalyx Is a Consequence of Bacterial Infection of the Epididymis*

    Science.gov (United States)

    Khosravi, Farhad; Michel, Vera; Galuska, Christina E.; Bhushan, Sudhanshu; Christian, Philipp; Schuppe, Hans-Christian; Pilatz, Adrian; Galuska, Sebastian P.; Meinhardt, Andreas

    2016-01-01

    Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. In men, pathogens can also spread to the genital tract via the continuous ductal system, eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis; however, the fertility of patients can be permanently impaired. Because a premature acrosome reaction was observed in an UPEC epididymitis mouse model, and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. In UPEC-elicited acute epididymitis in mice, a substantial loss of N-acetylneuraminic acid residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli-associated epididymitis. In vitro, such an UPEC induced N-acetylneuraminic acid release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after a premature acrosome reaction during acute epididymitis. PMID:27339898

  12. Desialylation of Spermatozoa and Epithelial Cell Glycocalyx Is a Consequence of Bacterial Infection of the Epididymis.

    Science.gov (United States)

    Khosravi, Farhad; Michel, Vera; Galuska, Christina E; Bhushan, Sudhanshu; Christian, Philipp; Schuppe, Hans-Christian; Pilatz, Adrian; Galuska, Sebastian P; Meinhardt, Andreas

    2016-08-19

    Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. In men, pathogens can also spread to the genital tract via the continuous ductal system, eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis; however, the fertility of patients can be permanently impaired. Because a premature acrosome reaction was observed in an UPEC epididymitis mouse model, and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. In UPEC-elicited acute epididymitis in mice, a substantial loss of N-acetylneuraminic acid residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli-associated epididymitis. In vitro, such an UPEC induced N-acetylneuraminic acid release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after a premature acrosome reaction during acute epididymitis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Imaging features of clear-cell ependymoma of the spinal cord

    International Nuclear Information System (INIS)

    Bapuraj, J.R.; Parmar, Hemant A.; Blaivas, Mila; Muraszko, Karin M.

    2007-01-01

    A 10-year-old girl presented with increasing lower back pain without gait or sphincter disturbances. MRI demonstrated a large, intramedullary tumor at the level of the conus. The imaging findings were unlike those of a classic ependymoma or astrocytoma. Histopathologic examination demonstrated clear-cell ependymoma, which is a distinct entity. We found three cases of clear-cell ependymoma of the spinal cord reported in the literature. Clear-cell ependymoma of the spinal cord can be resected completely and needs to be recognized for its imaging features, benign course and favorable prognosis. (orig.)

  14. Molecular changes and signaling events occurring in spermatozoa during epididymal maturation.

    Science.gov (United States)

    Gervasi, M G; Visconti, P E

    2017-03-01

    After leaving the testis, spermatozoa have not yet acquired the ability to move progressively and are unable to fertilize oocytes. To become fertilization competent, they must go through an epididymal maturation process in the male, and capacitation in the female tract. Epididymal maturation can be defined as those changes occurring to spermatozoa in the epididymis that render the spermatozoa the ability to capacitate in the female tract. As part of this process, sperm cells undergo a series of biochemical and physiological changes that require incorporation of new molecules derived from the epididymal epithelium, as well as post-translational modifications of endogenous proteins synthesized during spermiogenesis in the testis. This review will focus on epididymal maturation events, with emphasis in recent advances in the understanding of the molecular basis of this process. © 2017 American Society of Andrology and European Academy of Andrology.

  15. Molecular changes and signaling events occurring in sperm during epididymal maturation

    Science.gov (United States)

    Gervasi, Maria Gracia; Visconti, Pablo E.

    2017-01-01

    After leaving the testis, sperm have not yet acquired the ability to move progressively and are unable to fertilize oocytes. To become fertilization-competent they must go through an epididymal maturation process in the male, and capacitation in the female tract. Epididymal maturation can be defined as those changes occurring to sperm in the epididymis that render the sperm the ability to capacitate in the female tract. As part of this process, sperm cells undergo a series of biochemical and physiological changes that require incorporation of new molecules derived from the epididymal epithelium, as well as post-translational modifications of endogenous proteins synthesized during spermiogenesis in the testis. This review will focus on epididymal maturation events, with emphasis in recent advances in the understanding of the molecular basis of this process. PMID:28297559

  16. Chondroblastoma and clear cell chondrosarcoma: radiological and MRI characteristics with histopathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kaim, Achim H.; Huegli, Rolf [Institute of Diagnostic Radiology, University Hospital Basle (Switzerland); Bonel, Harald M. [Institute of Clinical Radiology, University Hospital, Munich-Grosshadern (Germany); Jundt, Gernot [Institute of Pathology, University Hospital Basle (Switzerland)

    2002-02-01

    Objective: To analyze and compare the radiological and magnetic resonance imaging (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with histopathological correlation. Design and patients: Twelve patients with histologically proven chondroblastoma and of another four patients with clear cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted sequences, intravenous gadolinium application). Additionally, the clinical and radiologic data of seven cases of clear cell chondrosarcoma without available MRI were considered. The localization, calcification of tumor matrix, periosteal reaction, cortical bone and patterns of bone destruction were analyzed according to the Lodwick radiological grading system (LRGS). The signal intensity on T1- and T2-weighted sequences, characteristics of contrast enhancement, associated bone marrow edema, soft tissue reaction and joint involvement were evaluated. Histopathological specimens were available in all cases. Results: The age of patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6 years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm, mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm, mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12) than the clear cell chondrosarcomas. All chondroblastomas and clear cell chondrosarcomas except one were classified as grade 1A or 1B according to the LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of the tumors on MRI was very heterogeneous in both groups. High signal intensity on T2-weighted MR images in chondroblastoma mostly corresponded to areas with aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be more intense with clear cell

  17. Clear cell hidradenocarcinoma of the eyelid: a case report with a review of the literature.

    Science.gov (United States)

    Singh, Gurcharan; Narasimha, Aparna; Kumar, Harendra; Datti, Narendra

    2013-04-01

    Clear cell hidradenocarcinomas are extremely rare neoplasms, with very few well-documented cases reported in the literature. The most common sites are the head and neck regions. These tumors are histologically malignant but are not always aggressive. They are known for recurrence and may metastasize widely. Treatment is wide local resection. We report on a case of clear cell hidradenocarcinoma occurring over the eyelid together with a review of the literature.

  18. Clear cell sarcoma of the abdominal wall with peritoneal sarcomatosis: CT features

    International Nuclear Information System (INIS)

    Sabate, J.M.; Fernandez, A.; Torrubia, S.; Villanueva, A.; Monill, J.M.

    1999-01-01

    Clear cell sarcoma, also called malignant melanoma of soft parts, is an uncommon neoplasm that involves tendons or aponeuroses of the lower extremity. The CT features of a clear cell sarcoma arising from the abdominal wall with later peritoneal dissemination are described. Peritoneal sarcomatosis from soft tissue sarcomas is a very rare condition previously unreported in the radiologic literature. Metastases to peritoneal surfaces must therefore be considered a possible site for systemic dissemination of soft tissue sarcomas. (orig.)

  19. Acetylcarnitine hydrolase activity in bovine caudal epididymal spermatozoa

    Energy Technology Data Exchange (ETDEWEB)

    Bruns, K.; Foster, R.A.; Casillas, E.R.

    1986-05-01

    Recently, the authors identified mM concentrations of acetylcarnitine in epidiymal fluids and have investigated the metabolism of acetylcarnitine by bovine and hamster caudal epididymal spermatozoa. (1-/sup 14/C)acetyl-L-carnitine is oxidized to /sup 14/CO/sub 2/ by washed, intact hamster and bovine sperm at maximal rates of 8.4 and 15.2 nmol/hr/10/sup 7/ cells respectively. Conversely, the carnitine moiety of acetyl-L-(/sup 3/H-methyl)carnitine is not accumulated by sperm under similar conditions. Hydrolysis of (/sup 3/H)acetyl-L-carnitine and competition of uptake of (/sup 3/H)acetate by unlabeled acetate was demonstrated in incubations of intact cells of both species. The amount of (/sup 3/H)acetate accumulated in the incubation medium is time-dependent and also depends on the concentration of unlabeled acetate. A partial solubilization of acetylcarnitine hydrolase activity from washed, intact bovine caudal epididymal spermatozoa in buffer or 0.01% Triton X-100 is observed. There is an enrichment of acetylcarnitine hydrolase activity in purified plasma membranes from bovine caudal epididymal spermatozoa when compared to the activity present in broken cell preparations or other cellular fractions. The results suggest that acetylcarnitine is a substrate for spermatozoa as they traverse the epididymis.

  20. A case of canine apocrine sweat gland adenoma, clear cell variant.

    Science.gov (United States)

    Nibe, K; Uchida, K; Itoh, T; Tateyama, S

    2005-03-01

    A cutaneous mass at the base of the retroauricular region of a 4-year-old, female Golden Retriever was examined pathologically. Histologically, the mass formed multiple nodules consisting of a proliferation of large clear cells with abundant cytoplasm. Mitotic figures among the neoplastic cells were very sparse. The large clear cells were intensely positive for cytokeratins (AE1/AE4, cytokeratin 8 and 18) and moderately positive for lysozyme and contained periodic acid-Schiff-positive granules in the cytoplasm. In addition, small flat cells lined the islands of neoplastic large clear cells, and these were strongly positive for alpha-smooth muscle actin and vimentin, and some were positive for cytokeratin (AE1/AE4), suggesting they were myoepithelial cells. No local recurrence or metastasis has been recognized during the 18 months since surgical excision. On the basis of these findings, the present tumor was diagnosed as apocrine sweat gland adenoma, clear cell variant. There have been few previous reports of canine apocrine adenomas showing a clear cell morphology.

  1. Epididymal lithiasis in roosters and efferent ductule and testicular damage.

    Science.gov (United States)

    Mahecha, G A B; Oliveira, C A; Balzuweit, K; Hess, R A

    2002-12-01

    Epididymal stones have been reported in roosters in the USA and Japan. The cause of this dysfunction, which is associated with low fertility, is not known. The hypothesis of the present study is that a potential cause is the aggressive selection of birds over many centuries based upon female egg laying traits, without concern for potential effects on the male. If this hypothesis is correct, one potential consequence would be the presence of epididymal stones only in domesticated fowl and this observation would be worldwide in distribution. The present study investigated epididymal lithiasis in Brazilian crossbreed roosters and two other fowl strains, in addition to several domestic and wild bird species. The efferent ductules contained stones in 94.3% of the roosters, but stones were absent in all other domestic and wild birds. The stones were irregular in shape, size and colour and consisted mainly of calcium. In affected roosters, the efferent ductules showed epithelial cell vacuolization and sloughing and peritubular mononuclear cell infiltration, culminating with atrophy. Signs of epithelial re-canalization were seen in ductules occluded by abnormal content, such as stones. In the testis, decrease in mass, sloughing of epithelium, mononuclear cell infiltration and tubular atrophy occurred. No correlation was found between the occurrence of stones and a positive test for ELISA IBV (infectious bronchitis virus), or between the number of stones and calcium concentration in water and food, indicating that IBV infection and calcium in the diet were not related to stones formation. This study confirms and extends information about the epididymal lithiasis, which appears to be unique for roosters but to occur around the world. The severity of the lesion points to potentially severe economical impact in the poultry industry.

  2. MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression.

    Science.gov (United States)

    Marona, Paulina; Górka, Judyta; Mazurek, Zofia; Wilk, Waclaw; Rys, Janusz; Majka, Marcin; Jura, Jolanta; Miekus, Katarzyna

    2017-09-15

    Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC. Cancer Res; 77(18); 4905-20. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis.

    Science.gov (United States)

    Dong, Baijun; Gao, Yujing; Kang, Xunlei; Gao, Hongchang; Zhang, Jin; Guo, Hua; You, Mingjian J; Xue, Wei; Cheng, Jinke; Huang, Yiran

    2016-12-06

    Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC. Moreover, SENP1 knockdown in RCC4/VHL cells downregulated expression of key glycolytic enzymes under normoxic and hypoxic conditions and inhibited cell proliferation under hypoxic conditions, possibly due to ineffective deSUMOylation and stablization of Hif-1α related to the SENP-1 deficiency. Finally, SENP1 expression correlated positively with tumor pathological grade and was an indicator of poor overall survival and advanced tumor progression in ccRCC. Altered VHL gene function is found in 60-90% ccRCC cases of ccRCC, but therapies targeting VHL-related signaling pathways have been ineffective, spurring exploration of alternative pathological signaling events. Our results provide a possible mechanistic explanation for the role of SENP1 in the initiation and development of ccRCC with normal VHL activity, and identifies SENP1 as a potential treatment target for the disease.

  4. A rare chest wall localized soft tissue sarcoma: Clear cell sarcoma

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    Ulaş Alabalık

    2013-03-01

    Full Text Available The clear cell sarcomas of soft tissue are rare tumorsoriginating from neural crest cells and presenting withpoor prognosis. By the reason of the resemblance ofhistological properties to malign melanoma (eg. the immunoreactivityto S100 and HMB45, the presence of melanosomesultrastructurally, these tumors are also definedas malign melanomas of soft tissue. But distinctivelyfrom cutaneous melanoma, clear cell sarcoma is almostalways deeply localized and the biological behaviour ofthe last one is also different. The differential diagnosisbetween clear cell sarcoma and desmoplastic or spindlecell malign melanoma may be more difficult because ofthe dermal localization of the last ones. In our case, itwas observed an infiltrative tumor composed of uniformseeming cells with vesicular nuclei, distinct nucleoli, paleeosinophilic and sometimes clear, scant cytoplasms, inaddition to necrotic areas. On immunohistochemical examination,the tumoral cells showed a positive immunoreactivityto vimentin, S100, HMB45, and SMA, while showingnegative immunoreactivity with CD34, PanCK, EMA,LCA, CD99 and desmin. Ki-67 proliferation index was determinedas approximately 50%. Because of deep localizationand different morphological-immunohistochemicalfindings of the tumor, the case was diagnosed as “clearcell sarcoma”. It was observed a tumor with similar morphologyin the biopsy sample taken from vertebra of thepatient one month later than the first material and this wascommented as the metastasis of the tumor to vertebra.Key words: Clear cell sarcoma, chest wall, metastasis,vertebral, HMB-45, S-100

  5. Acetylcarnitine metabolism and the partial purification and characterization of an acetylcarnitine hydrolase from bovine caudal epididymal spermatozoa

    Energy Technology Data Exchange (ETDEWEB)

    Bruns, K.A.

    1987-01-01

    Epididymal spermatozoa are capable of utilizing extracellular substrates for energy, but carbohydrates and free or esterified fatty acids are present in only very low concentrations in epididymal fluid. Acetyl-L-carnitine has been identified in epididymal fluid in low mM concentrations in several mammalian species and could possibly be an energy substrate for epididymal spermatozoa. Evidence that extracellular acetyl-L-carnitine can be used by intact caudal epididymal spermatozoa for energy, and a model for the metabolism of acetyl-L-carnitine by epididymal spermatozoa are presented here. Intact bovine and hamster caudal epididymal spermatozoa oxidized (1-{sup 14}C) acetyl-L-carnitine to {sup 14}CO{sub 2} in a time-, cell number-, and substrate concentration-dependent manner. No concomitant uptake of acetyl-D,L-(N-methyl-{sup 3}H) carnitine was observed by cells from the same preparations. Half-maximal rates of oxidation were observed at 8 mM and 4.5 mM acetyl-L-carnitine for the two species, respectively; the rates of oxidation at these concentrations were 15.3 nmol/10{sup 8} cells{centered dot}h and 2.9 nmol/10{sup 7} cells{centered dot}h. Intact spermatozoa in incubation with ({sup 3}H) acetyl-L-carnitine were observed to produce ({sup 3}H) acetate in the medium, and addition of sodium acetate competed for the uptake of radioactive acetate by these cells.

  6. Clear Cell Renal Cell Carcinoma Metastatic to the Gynecologic Tract: A Clinicopathologic Analysis of 17 Cases.

    Science.gov (United States)

    Fadare, Oluwole; Desouki, Mohamed M; Gwin, Katja; Hanley, Krisztina Z; Jarboe, Elke A; Liang, Sharon X; Quick, Charles M; Rawish, Kojo R; Roma, Andres A; Zheng, Wenxin; Hecht, Jonathan L; Parkash, Vinita; Osunkoya, Adeboye O

    2017-11-14

    Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seveteen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1β did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap

  7. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

    Science.gov (United States)

    Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

    2015-01-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

  8. Direct effects of ethane dimethanesulphonate on epididymal function in adult rats. An in vitro demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Klinefelter, G.L.; Roberts, N.L.; Suarez, J.D.

    1992-01-01

    It was recently demonstrated that the Leydig cell toxicant ethane dimethanesulphonate (EDS) produces multiple effects on the epididymis after a single in vivo exposure. To determine whether any of the perturbations were mediated by a direct action of the compound, we used a novel system for the coculture of epididymal epithelial cells and sperm from the caput epididymidis. This system maintains the morphologic integrity and cell polarity of the epididymal epithelial cells before and during coculture, and the sperm recovered after coculture have intact plasma and acrosomal membranes. In addition, several functions required for epididymal sperm maturation are expressed, including the secretion of protein by the epididymal epithelium, the association of secreted protein with the plasma membrane of cocultured sperm, and the acquisition of progressive motility by cocultured sperm. In vitro exposure of epididymal epithelial cells and sperm to EDS results in a significant decline in protein secretion by the epithelial cells during coculture, and in particular, a dose-dependent decline in a 36- to 38-kd protein (PI 4.0 to 4.5) and a 34- to 36-kd protein (PI 4.5 to 5.0). Moreover, these and other proteins are not recovered from the sperm membrane of cocultured sperm after EDS treatment. Finally, EDS results in a dose-dependent decline in the percentage of both motile and progressively motile sperm recovered after coculture compared with that of sperm from untreated cocultures.

  9. Imaging Nuclear Morphology and Organization in Cleared Plant Tissues Treated with Cell Cycle Inhibitors.

    Science.gov (United States)

    de Souza Junior, José Dijair Antonino; de Sa, Maria Fatima Grossi; Engler, Gilbert; Engler, Janice de Almeida

    2016-01-01

    Synchronization of root cells through chemical treatment can generate a large number of cells blocked in specific cell cycle phases. In plants, this approach can be employed for cell suspension cultures and plant seedlings. To identify plant cells in the course of the cell cycle, especially during mitosis in meristematic tissues, chemical inhibitors can be used to block cell cycle progression. Herein, we present a simplified and easy-to-apply protocol to visualize mitotic figures, nuclei morphology, and organization in whole Arabidopsis root apexes. The procedure is based on tissue clearing, and fluorescent staining of nuclear DNA with DAPI. The protocol allows carrying out bulk analysis of nuclei and cell cycle phases in root cells and will be valuable to investigate mutants like overexpressing lines of genes disturbing the plant cell cycle.

  10. GSTM1 genotype is an independent prognostic factor in clear cell renal cell carcinoma.

    Science.gov (United States)

    Coric, Vesna M; Simic, Tatjana P; Pekmezovic, Tatjana D; Basta-Jovanovic, Gordana M; Savic-Radojevic, Ana R; Radojevic-Skodric, Sanja M; Matic, Marija G; Suvakov, Sonja R; Dragicevic, Dejan P; Radic, Tanja M; Dzamic, Zoran M; Pljesa-Ercegovac, Marija S

    2017-06-01

    Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot. We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (Prisk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

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    Min Jee Park

    2015-01-01

    Full Text Available Background: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2 in tumorigenesis or progression of renal cell carcinoma (RCC. The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs. Methods: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0, mild (1+, moderate (2+, and strong (3+. Results: TG2 staining intensity was negative in 8.5% of CCRCC (n=54, 1+ in 32.6% (n=208, 2+ in 50.5% (n=322, and 3+ in 8.5% (n=54. Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011, high T category (p=.049, metastasis (p=.043 and male sex (p<.001 but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively. On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054. Conclusions: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

  12. Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

    Science.gov (United States)

    Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

    2017-10-01

    To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Novel biomarker candidates for the diagnosis of ovarian clear cell carcinoma

    Science.gov (United States)

    KOBAYASHI, HIROSHI; SUGIMOTO, HITOMI; ONISHI, SHUNSUKE; NAKANO, KAZUTOSHI

    2015-01-01

    Ovarian clear cell carcinoma can arise from endometriosis; however, it is distinct from other types of epithelial ovarian carcinoma in terms of its clinicopathological and molecular features. Cancer antigen 125 lacks the sensitivity and specificity required for accurate clinical diagnosis of clear cell carcinoma. Therefore, the aim of the current review was to identify novel biomarker candidates for the immunohistochemical and serological diagnosis of clear cell carcinoma. A search of the relevant English language literature published between 1966 and 2014 was conducted using the PubMed MEDLINE online database. High-throughput tissue microarray technology and proteomic screening combined with mass spectrometry may provide additional information regarding diagnostic biomarker candidates for ovarian clear cell carcinoma. The present review summarizes the characteristics of potential genomic alterations that activate cancer signaling pathways and, thus, contribute to carcinogenesis. The major signaling pathways activated in clear cell carcinoma are associated with cell cycle regulation (hepatitis A virus cellular receptor 1 and tumor protein D52), growth factor signaling (insulin-like growth factor binding protein 1; KiSS-1 metastasis-suppressor; erb-b2 receptor tyrosine kinase 2; and fibroblast growth factor receptor 2), anti-apoptosis and survival pathways [sialidase 3 (membrane sialidase)], metabolism (γ-glutamyltransferase 1), chemoresistance (napsin A aspartic peptidase, glutathione peroxidase 3; and aldehyde dehydrogenase 1 family, member A1), coagulation [coagulation factor III (thromboplastin, tissue factor); and tissue factor pathway inhibitor 2], signaling (lectin, galactoside-binding and soluble, 3), and adhesion and the extracellular matrix [cadherin 1, type 1, E-cadherin (epithelial); versican; and laminin, α 5]. The present review of the relevant literature may provide a basis for additional clinical investigation of the ovarian clear cell carcinoma

  14. Ultrastructure of epididymal epithelium and its interaction with the sperm in the soft-shelled turtle Pelodiscus sinensis.

    Science.gov (United States)

    Bian, Xunguang; Zhang, Linli; Yang, Li; Yang, Ping; Ullah, Shakeeb; Zhang, Qian; Chen, Qiusheng

    2013-01-01

    The epididymis of the soft-shelled turtle Pelodiscus sinensis was examined under light and transmission electron microscopes to determine the morphological characteristics, as well as their changes at different phases of the seasonal reproductive cycle. Three distinct regions, viz., cranial, middle and caudal were identified in the epididymis based on anatomical characteristics. The epididymal epithelium consists of five different cell types: principal, narrow, apical, clear and basal cells. Principal cells, which are the most abundant, together with basal cells are present along the entire length. Ultrastructural evidence suggests that all of the principal cells in each of the regions function in both absorption and secretion. Narrow cells and apical cells are rare and only confined to the cranial region. The clear cells, for the first time reported in the turtle epididymis, are confined to middle and caudal regions; these cells showed strong PAS-positive granulation in apical position, and secretory activity by a holocrine process, especially in the middle region. There was a significant difference in the epithelium height of all the regions between the reproductive season and the non-reproductive season. Sperm are stored in the epididymis throughout the year. Apart from the mature spermatozoa, immature spermatozoa with normal morphology are also observed. Under TEM, the immature spermatozoa showed a large amount of cytoplasm located eccentrically on the midpiece wrapped by plasma membrane, with some cytoplasm extended to the posterior of the head. Furthermore, the interactions of sperm with the epididymal epithelium were observed. Some sperm are associated with the secretory material in the lumen; other sperm are inserted into the intercellular space between the epithelial cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  16. Primary clear cell ductal adenocarcinoma of the pancreas: A case report and clinicopathologic literature review

    Directory of Open Access Journals (Sweden)

    Yashpal Modi

    2014-01-01

    Full Text Available We present a very rare, interesting case of a carcinoma of the pancreas with predominantly abundant clear cell morphology. According to the WHO classification, primary clear cell carcinoma of the pancreas is classified as a rare "miscellaneous" carcinoma. The tumor was observed in the distal body and tail of the pancreas of a 74-year-old woman. The histopathology of tumor cells showed well-defined cell membranes, clear cytoplasm, and prominent cell boundaries. Immunohistochemical (IHC staining showed positive reactions to antibodies against vimentin, cytokeratin 7 (CK-7, mucicarmine (MUC-1, periodic acid-Schiff (PAS, periodic acid-Schiff with diastase (PASD, carcinoembryonic antigen (CEA, and Carbohydrate Antigen 19-9 (CA 19-9. On the other hand, IHC staining was negative for alpha-fetoprotein (AFP, cytokeratin 20 (CK-20, HMB45, chromogranin, and synaptophysin. The patient was subsequently diagnosed with a primary solid-type pancreatic clear cell carcinoma with hepatic metastasis. Herein, we report this rare case and include a review of the current literature of this tumor.

  17. Clear cell sarcoma of soft tissue in right parapharyngeal region: report of a rare case.

    Science.gov (United States)

    Fan, Chuifeng; Yu, Juanhan; Yang, Lianhe; Lin, Xuyong; Wang, Enhua

    2015-01-01

    Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is a rare malignant neoplasm typically involving deep soft tissue of the extremities, in close proximity to tendons and aponeuroses. Here we describe a case of clear cell sarcoma of the right parapharyngeal region in a young female aged 20 years. MRI detected a mass about 4.4 cm×3.4 cm×3.0 cm, located in the right parapharyngeal area and between the external pterygoid and the medial pterygoid. Microscopically, most of the tumor cells were epithelioid with palely eocinophilic cytoplasm arranged in sheets. Pleophorism of tumor cells were not marked. Immunohistochemical analysis shows that the tumor cells were positive for vimentin, S-100, HMB45 and MelanA, and negative for AE1/AE3, actin-sm, desmin, CD117, TFE-3, and P63. Ki67 index was about 5%.

  18. Clear cell adenocarcinoma of urinary bladder: A case report and review

    Directory of Open Access Journals (Sweden)

    Somika Sethi

    2011-01-01

    Full Text Available Clear cell carcinoma is an uncommon but distinct variant of urinary bladder carcinoma histologically resembling the neoplasm in the female genital tract. The histogenesis of this neoplasm is uncertain. The clinicopathologic and histologic features are suggestive of a mullerian origin in some tumors, while some believe it to be glandular differentiation of urothelium or a unique vesicular adenocarcinoma of non-mullerian origin. [1] We present a case of clear cell adenocarcinoma in a 74-year-old woman with review of literature along with its differential diagnosis.

  19. An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Beatriz Martín-Martín

    2011-09-01

    Full Text Available Glycogen-rich clear cell (GRCC is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC. The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up.

  20. CD163-positive cancer cells are potentially associated with high malignant potential in clear cell renal cell carcinoma.

    Science.gov (United States)

    Ma, Chaoya; Horlad, Hasita; Ohnishi, Koji; Nakagawa, Takenobu; Yamada, Sohsuke; Kitada, Shohei; Motoshima, Takanobu; Kamba, Tomomi; Nakayama, Toshiyuki; Fujimoto, Naohiro; Takeya, Motohiro; Komohara, Yoshihiro

    2018-03-01

    CD163 is preferentially expressed by monocyte/macrophages; however, recent studies using immunohistochemistry (IHC) have reported that some cancer cells also express CD163. In the present IHC study, we investigated CD163 staining of cancer cells and macrophages in clear cell renal cell carcinoma (ccRCC) tissues and determined the relationship between cancer cell CD163 expression and clinical prognosis in patients with ccRCC. IHC for CD163 was performed in ccRCC tissues from 103 patients. CD163-positive cancer cells were detected in 35% of the patients (36/103); however, the positive signals on cancer cells were significantly lower than those on macrophages. CD163-positive cancer cells were preferentially detected in patients with high T classification, and females, and were significantly associated with shortened progression-free survival and a lower overall survival ratio. Notably, a high intensity of CD163-positive macrophage infiltration was detected in the CD163-positive cancer cell-high tumor areas. Although CD163 mRNA was detected in cultured macrophages, no CD163 mRNA was detected in two cultured RCC cell lines. The detailed mechanism by which a positive signal is detected on cancer cells has not been clarified. Detection of the CD163 antigen on cancer cells might be a useful marker for evaluating the clinical course of patients with ccRCC.

  1. Histomorphological changes by epididymal lithiasis in roosters

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    I Geraldo

    2014-03-01

    Full Text Available Epididymal lithiasis (EL histopathology is described using light and electronic microscopy in roosters (Gallus gallus domesticus naturally affected by EL in Minas Gerais, Brazil. The histologic and morphological changes by EL in roosters was performed regarding cellular and subcellular details through light and electron microscopy. Efferent ductules epithelium lysosomal increase in size and numbers, membrane rupture, cellular vacuolation, ciliary loss, basal membrane degeneration, inflammatory reaction with mononuclear infiltrations, edema, epithelial and vascular endothelium losses were described. All industrial and freerange chickens showed EL in varying degrees in the efferent ductules (ED. However, ED altered areas did not correlate with the presence of luminal stones. Non-ciliated ED epithelium cells presented several atypically large lysosomes. Plicae loss and basal vacuoles were observed in the epithelium of dilated regions. Cellular cilia loss and apical cytoplasmic membrane rupture resulted in leakage of the cytoplasmic contents to the ED lumen, and ED epithelium desquamation occurred with or without lesion to the basal membrane. Basal membrane alterations were associated with profound sub-epithelial connective tissue damage. Aggregations of desquamated epithelium and spermatozoa were seen in the lumen of ED and compact aggregates were considered the basis for calculi formation. The widespread occurrence and high severity of EL lesions are indicative of the importance of EL as a cause of infertility in male chickens.

  2. Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically.

    Science.gov (United States)

    Vilaseca, Antoni; Nguyen, Daniel P; Vertosick, Emily A; Corradi, Renato B; Musquera, Mireia; Pérez, Meritxell; Fossati, Nicola; Sjoberg, Daniel D; Farré, Ramon; Almendros, Isaac; Montserrat, Josep M; Benfante, Nicole E; Hakimi, A Ari; Skanderup, Anders J; Russo, Paul; Alcaraz, Antonio; Touijer, Karim A

    2017-01-01

    To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS). We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data. In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5-20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00-1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08). OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated.

  3. Clear cell sarcoma of the right lumbar region: A case report and review of the literature.

    Science.gov (United States)

    Yang, Xue-Li; Lu, San-Jun; Xue, Jie; Wu, Yan-Fen; Shi, Jun-Ling

    2014-10-01

    Clear cell sarcoma of soft tissues is a very rare, malignant soft tissue tumor that usually arises in the extremities, with a predilection for the lower limbs. This report presents a 45-year-old male with a painless mass in the right lumbar region for one year. Magnetic resonance imaging showed a 3.6×3.2×1.5-cm soft tissue mass of the right lumbar region. The tumoral cells had pleomorphic nuclei and large amounts of clear cytoplasm, and a proportion of the cells contained melanin. Immunohistochemical analysis was performed, which identified that the cells were positive for S-100, MITF and HMB-45 tumor markers. The patient underwent a postoperative chemotherapy protocol and had no local recurrences at one year post-surgery.

  4. High expression of HMGA2 predicts poor survival in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Na N

    2016-11-01

    Full Text Available Ning Na,1,* Tujie Si,2,* Zhengyu Huang,1,* Bin Miao,1 Liangqing Hong,1 Heng Li,1 Jiang Qiu,2 Jianguang Qiu3 1Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, 2Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, 3Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: High-mobility group AT-hook 2 (HMGA2 is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS of patients with non-metastatic clear cell renal cell carcinoma (ccRCC following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004. An IHC analysis revealed that HMGA2 was expressed in the nuclei of tumor cells in 146 (90.1% patients with ccRCC. The level of HMGA2 was positively correlated with tumor size, lymph node metastasis, and Fuhrman Grade. A Kaplan–Meier analysis with log-rank test found that patients with high HMGA2 expression had a poor outcome and that patients with low HMGA2 expression had better survival. Cox regression analysis showed that HMGA2 expression could serve as an independent prognostic factor for ccRCC patients. The efficacy of the following prognostic models was improved when HMGA2 expression was added: tumor node metastasis stage, UCLA Integrated Scoring System, Mayo Clinic stage, size, grade, and necrosis score. In summary, this study showed that HMGA2 expression is an independent prognostic factor for OS in patients with ccRCC. HMGA2 was found to be a valuable biomarker for ccRCC progression. Keywords: renal carcinoma, high-mobility group protein A

  5. Metastatic clear cell eccrine hidradenocarcinoma of the vulva: survival after primary surgical resection.

    Science.gov (United States)

    Massad, L S; Bitterman, P; Clarke-Pearson, D L

    1996-05-01

    A case of clear cell eccrine hidradenocarcinoma of the vulva metastatic to regional lymph nodes with long survival after surgical resection is presented. Like the only other case reported to date, this suggests that surgical therapy alone may be adequate, even when metastasis is present.

  6. A case report of the clear cell variant of gallbladder carcinoma

    Directory of Open Access Journals (Sweden)

    Ravi Maharaj

    2017-01-01

    Conclusion: In these cases, clinical case management should be personalized for increased survival with the possible incorporation of next generation sequencing approaches to guide therapeutic algorithms. We discuss this exceedingly rare case of the clear cell variant of gallbladder carcinoma in detail, highlighting some of the diagnostic, and clinical challenges.

  7. “Maxillary sinus -a poisoned chalice “- clear cell odontogenic ...

    African Journals Online (AJOL)

    Background: Malignant tumours in the nose and paranasal sinuses are challenging problems in the head and neck tumours. They represent the area of greatest histological diversity in the body with every tissue type represented. Clear cell odontogenic carcinoma (CCOC) is a rare neoplasm of the jaws and was first ...

  8. Clear Cell Carcinoma of the Breast: A Rare Breast Cancer Subtype - Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Vilma Ratti

    2015-11-01

    Full Text Available Background: Glycogen-rich clear cell breast carcinoma is a rare histological breast cancer subtype. Its prognosis may vary depending on specific clinical and pathological characteristics such as low grade, strong positivity of estrogen receptor (ER expression and early diagnosis. Case Presentation: We present the case of a 53-year-old woman with a bleeding 10-cm-diameter mass in the left breast. The histological examination showed a poorly differentiated tumor with malignant cells characterized by abundant clear cytoplasm. The diagnosis of clear cell carcinoma was based on the histological characteristics of the tumor, and a nonmammary origin was initially ruled out. The tumor was triple negative [i.e. ER, progesterone receptor (PR and HER2 negative]. Four months after the initial locoregional treatment, the patient developed lung and distant lymph node metastases. Conclusions: Glycogen-rich clear cell carcinoma of the breast is a rare tumor. Early diagnosis, absence of lymph node metastases and ER/PR positivity are associated with a better prognosis, as in other common breast cancer subtypes.

  9. p53 mutation is infrequent in clear cell carcinoma of the ovary.

    Science.gov (United States)

    Ho, E S; Lai, C R; Hsieh, Y T; Chen, J T; Lin, A J; Hung, M H; Liu, F S

    2001-02-01

    p53 gene alteration has been extensively studied in epithelial ovarian cancer. However, its occurrence in clear cell carcinoma, an infrequent histologic subtype of epithelial ovarian cancer, is rarely reported. The aim of this study is to determine the status of p53 gene alteration in this distinct type of ovarian carcinoma. Paraffin blocks of tumors from 38 patients with primary or recurrent ovarian clear cell carcinoma were studied for p53 alteration. All these tumors were subjected to immunohistochemical and molecular analysis. Two monoclonal antibodies (DO-7 and PAb 1801) were used for immunohistochemical staining. Genomic DNAs extracted from paraffin blocks of the 38 tumors were subscribed for a nested polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) analysis. Tumors showing band shift on SSCP were further prepared for DNA sequencing to determine the site of mutation. Overexpression of p53 was observed in only one stage III clear cell carcinoma. However, focal positive p53 staining was noted in another five tumors. Of the six tumors showing positive immunohistochemistry, p53 alterations were noted in four tumors. Three tumors revealed a missense point mutation: two were in exon 7 (TCT(227) --> TTT and GGC(245) --> AGC) and one was in exon 5 (CGC(156) --> CAC). Another tumor revealed a 12-bp deletion in two possible ways: it might involve the last four codons at the 3' end of exon 4 (nucleotides 12,288-12,299) or it might cross over the splice junction between exon 4 and intron 4 (nucleotides 12,290-12,301). The former would result in a predicted protein product of 389 amino acids whereas the latter would cause a frameshift in the gene sequence and would result in a truncated protein. Mutations in p53 appear to be much less frequent in clear cell carcinoma than in other histologic types of epithelial ovarian cancer. We suggest that p53 alterations may not play an important role in the development of clear cell carcinoma.

  10. Epididymal research: more warp than weft?

    Science.gov (United States)

    Cooper, Trevor G

    2015-01-01

    From a review of some aspects of epididymal structure, function and research done largely in my research area over the last 50 years, I conclude that more is known than is understood of sperm maturation and storage in the epididymis. Highly qualified technicians have not always applied sophisticated modern techniques in well-considered experiments to physiologically relevant and properly-prepared samples, so that our understanding of the biological problem of the nature of the epididymal epithelial influence on maturing epididymal spermatozoa has not kept pace with the outpouring of data generated, much of which is difficult to interpret. We stand at a crossroads of where to aim our limited resources and personnel: should we continue new technology-led studies in many directions, backtrack to test hypotheses and fill in gaps in our knowledge, or consider more biological directions to our research?

  11. Epididymal research: more warp than weft?

    Directory of Open Access Journals (Sweden)

    Trevor G Cooper

    2015-01-01

    Full Text Available From a review of some aspects of epididymal structure, function and research done largely in my research area over the last 50 years, I conclude that more is known than is understood of sperm maturation and storage in the epididymis. Highly qualified technicians have not always applied sophisticated modern techniques in well-considered experiments to physiologically relevant and properly-prepared samples, so that our understanding of the biological problem of the nature of the epididymal epithelial influence on maturing epididymal spermatozoa has not kept pace with the outpouring of data generated, much of which is difficult to interpret. We stand at a crossroads of where to aim our limited resources and personnel: should we continue new technology-led studies in many directions, backtrack to test hypotheses and fill in gaps in our knowledge, or consider more biological directions to our research?

  12. Epididymal research: more warp than weft?

    Science.gov (United States)

    Cooper, Trevor G

    2015-01-01

    From a review of some aspects of epididymal structure, function and research done largely in my research area over the last 50 years, I conclude that more is known than is understood of sperm maturation and storage in the epididymis. Highly qualified technicians have not always applied sophisticated modern techniques in well-considered experiments to physiologically relevant and properly-prepared samples, so that our understanding of the biological problem of the nature of the epididymal epithelial influence on maturing epididymal spermatozoa has not kept pace with the outpouring of data generated, much of which is difficult to interpret. We stand at a crossroads of where to aim our limited resources and personnel: should we continue new technology-led studies in many directions, backtrack to test hypotheses and fill in gaps in our knowledge, or consider more biological directions to our research? PMID:25652625

  13. Outcome of papillary versus clear cell renal cell carcinoma varies significantly in non-metastatic disease.

    Directory of Open Access Journals (Sweden)

    Nina Wagener

    Full Text Available Renal cell carcinoma (RCC comprises a heterogenous group of tumors. Traditionally, papillary RCC (pRCC is associated with a favorable outcome compared to clear cell RCC (ccRCC, while other series report equivalent or worse prognosis. In this paper we comparatively evaluate outcome of pRCC versus ccRCC in two large multi-institutional databases (cohort study, including distribution of pRCC subtypes 1 and 2. Retrospective data of 1,943 surgically treated pRCC patients from 17 European/ North American centers between 1984-2015 were compared to 5,600 ccRCC patients from a database comprising 11 European/ North American centers (1984-2011. Median follow-up was 64.6 months. Differences between pRCC, subtypes, and ccRCC were compared with t-tests, Chi^2-tests, and exact Fisher tests. Cancer-specific mortality was analyzed with cumulative incidence curves and Cox cause-specific hazard models. The robustness of our results was examined with sensitivity analyses. We present that cancer-specific mortality rates and variables as stage, lymph node, and distant metastasis differ significantly between groups. Furthermore, we demonstrate that patients with non-metastatic pRCC had a significantly better cancer-specific mortality (HR 0.76, p = 0.007, when compared to ccRCC. Additionally, pRCC type 2 versus ccRCC exhibited no difference in cancer-specific mortality (HR 0.9, p = 0.722, whereas pRCC type 1 versus ccRCC displayed a risk of death reduced by 69% (p = 0.044. Taken together, outcome of pRCC versus ccRCC varies significantly in non-metastatic disease. Furthermore, pRCC type 2 exhibited no difference in cancer-specific mortality, whereas pRCC type 1 displayed a significantly reduced risk of death. Consequently, there is urgent need to respect histopathological entities and their subtypes, when assigning follow-up or targeted therapy to RCC patients.

  14. Canine cutaneous clear cell adnexal carcinoma: histopathology, immunohistochemistry, and biologic behavior of 26 cases.

    Science.gov (United States)

    Schulman, F Y; Lipscomb, T P; Atkin, T J

    2005-09-01

    Thirty tumors including 27 distinctive cutaneous neoplasms and 3 metastatic tumors from 26 dogs were collected from diagnostic submissions to 3 laboratories. Characteristic histopathologic features included location in the subcutis or dermis (or both); lobular, nodular, and nest-like architecture; and a component of epithelioid cells with clear cytoplasm. Additional features present in most cases included follicular dermal papilla-like structures, low mitotic index, nuclear pleomorphism, necrosis, and mineralization. Cytoplasmic periodic acid Schiff-positivity, which was abolished by pretreatment with diastase, indicated the presence of glycogen in all cases. The oil red O stain did not demonstrate cytoplasmic lipid. Melanin granules, accentuated by the Fontana-Masson method, were observed infrequently. A sparsely cellular mucinous stroma and stromal cartilaginous differentiation were uncommon. By immunohistochemistry, neoplastic cells stained positively for cytokeratin (29 of 29), vimentin (28 of 28), S-100 protein (24 of 29), and melan A (8 of 12); results were negative for smooth muscle actin and calponin in all cases. Clinical follow-up information was obtained on all 26 dogs. One tumor recurred, 1 metastasized to a regional lymph node, and 1 metastasized to regional lymph nodes twice. In another case, possible pulmonary metastasis was noted radiographically. The findings are consistent with a poorly differentiated, low-grade, adnexal carcinoma of the skin. Similar canine cutaneous neoplasms have been reported as "clear-cell hidradenocarcinoma" and "follicular stem cell carcinoma." The authors propose the designation "cutaneous clear cell adnexal carcinoma."

  15. Trisomy 19 ependymoma, a newly recognized genetico-histological association, including clear cell ependymoma

    Directory of Open Access Journals (Sweden)

    Lacroix Catherine

    2007-07-01

    Full Text Available Abstract Ependymal tumors constitute a clinicopathologically heterogeneous group of brain tumors. They vary in regard to their age at first symptom, localization, morphology and prognosis. Genetic data also suggests heterogeneity. We define a newly recognized subset of ependymal tumors, the trisomy 19 ependymoma. Histologically, they are compact lesions characterized by a rich branched capillary network amongst which tumoral cells are regularly distributed. When containing clear cells they are called clear cell ependymoma. Most trisomy 19 ependymomas are supratentorial WHO grade III tumors of the young. Genetically, they are associated with trisomy 19, and frequently with a deletion of 13q21.31-31.2, three copies of 11q13.3-13.4, and/or deletions on chromosome 9. These altered chromosomal regions are indicative of genes and pathways involved in trisomy 19 ependymoma tumorigenesis. Recognition of this genetico-histological entity allows better understanding and dissection of ependymal tumors.

  16. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    International Nuclear Information System (INIS)

    Cai, Demin; Li, Hongji; Zhou, Bo; Han, Liqiang; Zhang, Xiaomei; Yang, Guoyu; Yang, Guoqing

    2012-01-01

    Highlights: ► Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. ► Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. ► Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor α (TNFα) and the positive regulator Peroxisome Proliferator-Activated Receptor-γ (PPARγ) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  17. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  18. Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Weber T

    2014-05-01

    Full Text Available Thomas Weber,1,2 Matthias Meinhardt,3 Stefan Zastrow,1 Andreas Wienke,4 Kati Erdmann,1 Jörg Hofmann,1 Susanne Fuessel,1 Manfred P Wirth11Department of Urology, Technische Universität Dresden, Dresden, Germany; 2Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany; 3Institute of Pathology, Technische Universität Dresden, Dresden, Germany; 4Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale, GermanyPurpose: To enhance prognostic information of protein biomarkers for clear cell renal cell carcinomas (ccRCCs, we analyzed them within prognostic groups of ccRCC harboring different tumor characteristics of this clinically and molecularly heterogeneous tumor entity.Methods: Tissue microarrays from 145 patients with primary ccRCC were immunohistochemically analyzed for VHL (von Hippel-Lindau tumor suppressor, Ki67 (marker of proliferation 1, p53 (tumor protein p53, p21 (cyclin-dependent kinase inhibitor 1A, survivin (baculoviral IAP repeat containing 5, and UEA-1 (ulex europaeus agglutinin I to assess microvessel-density.Results: When analyzing all patients, nuclear staining of Ki67 (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04–1.12 and nuclear survivin (nS; HR 1.04, 95% CI 1.01–1.08 were significantly associated with disease-specific survival (DSS. In the cohort of patients with advanced localized or metastasized ccRCC, high staining of Ki67, p53 and nS predicted shorter DSS (Ki67: HR 1.07, 95% CI 1.02–1.11; p53: HR 1.05, 95% CI 1.01–1.09; nS: HR 1.08, 95% CI 1.02–1.14. In organ-confined ccRCC, patients with high p21-staining had a longer DSS (HR 0.96, 95% CI 0.92–0.99. In a multivariate model with stepwise backward elimination, tumor size and p21-staining showed a significant association with DSS in patients with "organ-confined" ccRCCs. The p21-staining increased the concordance index of tumor size from

  19. Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma.

    Science.gov (United States)

    Wang, Yiying; Mang, Maggie; Wang, Yue; Wang, Lijie; Klein, Robert; Kong, Beihua; Zheng, Wenxin

    2015-01-01

    Current research has strongly proposed that contrary to prior beliefs, many ovarian epithelial cancers (OECs) do not, as their name suggests, originate in the ovaries. Recent findings regarding both high-grade and low-grade serous carcinomas has implicated the fallopian tube as a cell source for these OECs, but until now, there has been little insight into the cellular source for clear cell and endometrioid carcinomas. In this commentary review article, we aimed to discuss the new findings that support the possible contribution from the fallopian tube in clear cell and endometrioid carcinomas. Specifically, we have provided results that showcased ovarian surface epithelia (OSE) and ovarian epithelial inclusions (OEIs) as having mesothelial and tubal origins and have strongly recognized the secondary müllerian system and the ability for tubal epithelia to implant upon the ovarian surface as contributing to fallopian tube-derived OEIs (F-OEIs). We have provided initial indications of these F-OEIs and their relationship to endometriosis and then clear cell and endometrioid carcinomas and subsequently offer our new proposal of a probable tubal origin. This new proposal is a paradigm that drastically changes the understanding behind the origin of these OECs and has significant clinical implications in the near future.

  20. Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma.

    Science.gov (United States)

    Utsumi, Fumi; Kajiyama, Hiroaki; Nakamura, Kae; Tanaka, Hiromasa; Hori, Masaru; Kikkawa, Fumitaka

    2014-01-01

    Ovarian clear cell carcinoma (CCC) is a histological type of epithelial ovarian cancer that is less responsive to chemotherapy and associated with a poorer prognosis than serous and endometrioid carcinoma. Non-thermal atmospheric pressure plasma which produces reactive species has recently led to an explosion of research in plasma medicine. Plasma treatment can be applied to cancer treatment to induce apoptosis and tumor growth arrest. Furthermore, recent studies have shown that a medium exposed to plasma also has an anti-proliferative effect against cancer in the absence of direct exposure to plasma. In this study, we confirmed whether this indirect plasma has an anti-tumor effect against CCC, and investigated whether this efficacy is selective for cancer cells. Non-thermal atmospheric pressure plasma induced apoptosis in CCC cells, while human peritoneal mesothelial cells remained viable. Non-thermal atmospheric pressure plasma exhibits selective cytotoxicity against CCC cells which are resistant to chemotherapy.

  1. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Guo, Guangwu; Gui, Yaoting; Gao, Shengjie

    2012-01-01

    We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of similar to 1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the u...... of the hypoxia regulatory network....

  2. Opposite prognostic roles of HIF1β and HIF2β expressions in bone metastatic clear cell renal cell cancer

    DEFF Research Database (Denmark)

    Szendroi, Attila; Szász, A. Marcell; Kardos, Magdolna

    2016-01-01

    BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1β/HIF2β and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2β was lower in mRCC both at m...

  3. Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

    DEFF Research Database (Denmark)

    Schnack, Tine H; Høgdall, Estrid; Thomsen, Lotte Nedergaard

    2017-01-01

    OBJECTIVES: Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according...... to endometriosis status. METHODS: Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic...... regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. RESULTS: Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher...

  4. Seborrheic Keratosis With Prominent Clear Cell Changes-A Rare But Important Diagnostic Variant.

    Science.gov (United States)

    Long, Thomas H; Zlotnick, David; Hurst, Stanley L; Argenyi, Zsolt

    2018-03-01

    Seborrheic keratoses, although exceedingly common, occasionally have morphologic similarities to other lesions that complicate a typically straightforward diagnosis. The authors present a case of a 69-year-old man with a left shoulder lesion that displayed characteristic clinical and microscopic features of seborrheic keratosis on biopsy. However, diffuse and prominent clear cells were also noted. These stained strongly with Periodic acid-Schiff and were diastase sensitive, suggestive of glycogen accumulation and possible trichilemmal differentiation. This case is presented to demonstrate a unique and striking example of clear cell change within a seborrheic keratosis and to briefly review the published literature on this finding, which is rarely reported and demands close examination to exclude more aggressive neoplasms.

  5. Post-radiotherapy locoregional recurrence of hyalinizing clear cell carcinoma of palate

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Clear cell carcinoma of the salivary glands is a rare tumor that represents less than 1% of all salivary tumors and is a new disease that is only recognized in recent years. It is rare and the standard treatment is still under investigation. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. Recurrence of the hyalinizing clear cell carcinoma (HCCC after complete surgical resection is uncommonly documented. We hereby report a case of post-radiotherapy locoregional recurrence of HCCC of the palate and recommend further clinicopathological study and long-term follow-up to document the biological behavior of this entity along with highlighting the role of special stains and immunohistochemistry in its diagnosis.

  6. Solitary intrathyroidal metastasis of renal clear cell carcinoma in a toxic substernal multinodular goiter

    Directory of Open Access Journals (Sweden)

    Dionigi Gianlorenzo

    2008-10-01

    Full Text Available Abstract Introduction Thyroid gland is a rare site of clinically detectable tumor metastasis. Case report A 71-year-old woman was referred to our department for an evaluation of toxic multinodular substernal goiter. She had a history of renal clear cell carcinoma of the left kidney, which had been resected 2 years previously. US confirmed the multinodular goiter. Total thyroidectomy with neuromonitoring was performed on March 2008. A histological examination revealed a solitary metastasis of a clear cell renal cancer in a diffuse multinodular goiter. No distant metastases are detected. Conclusion Although uncommon, it is important for the endocrine surgeon and endocrine oncologist to be able to recognize and differentiate intrathyroid metastases from more primary common thyroid neoplasms. The diagnosis can be suspected if the patient has a thyroid tumor and a past history of extrathyroid cancer. These tumors, on the whole, tend to behave more aggressively and, in most cases, the use of multimodality therapy is recommended.

  7. [Clear cell sarcoma of the chest wall; report of a case].

    Science.gov (United States)

    Fujiwara, K; Nanjou, S; Ishihara, S

    2006-11-01

    Clear cell sarcoma is a rare malignant soft tissue neoplasm that usually arises adjacent to tendons or aponeuroses. The principal sites of this neoplasm are the extremities, but tumors do occur in the trunk on rare occasions. A case had a checkup for chest bachache with a 21-year-old woman, and it was diagnosed as the right chest wall tumor. We performed the en bloc resection of parts of the 7th and 8th ribs. Composix mesh was fixed to cover a deficit in the chest wall. The pathological diagnosis was clear cell sarcoma of the chest wall. The postoperative course was uneventful. She has shown no symptoms or signs of recurrence during 14 months of follow-up.

  8. Synchronous Bilateral Clear Cell Carcinoma and Papillary Serous Cystadenocarcinoma of the Ovaries

    Directory of Open Access Journals (Sweden)

    Bhavna Nayal

    2014-02-01

    Full Text Available The presence of synchronous bilateral ovarian malignancy with similar histology is well recognized. The presence of two tumours with different pathology in both the ovaries is extremely uncommon and pose a diagnostic and therapeutic challenge. Only one such case has been reported in a postmenopausal lady. We present second such case with synchronous presence of high grade serous and clear cell carcinoma in a premenopausal woman. [J Interdiscipl Histopathol 2014; 2(1.000: 52-55

  9. Undifferentiated pulmonary adenocarcinoma of clear cells associated to hypertrophic osteopathy in a dog

    OpenAIRE

    Rossetto, Victor José Vieira [UNESP; Rahal, Sheila Canevese [UNESP; Pardini, Luciana Moura Campos [UNESP; Fabris, Viciany Erique [UNESP; Mamprim, Maria Jaqueline [UNESP; Ribeiro, Sergio Marrone [UNESP

    2015-01-01

    Background: Most of the primary pulmonary tumors in dogs are malignant and from epithelial origin, being bronchioalveolar tumors more prevalent. Adenocarcinoma of clear cells, however, is a very rare pulmonary tumor and its origin is still unknown. It is related to several clinical abnormalities, including hypertrophic osteopathy, an unusual paraneoplastic syndrome characterized by a periosteal reaction along the shaft of long bones. Because of the unusual presentation of the pulmonary adenoc...

  10. Lymph node location of a clear cell hidradenoma: report of a patient and review of literature.

    Science.gov (United States)

    Tingaud, Claire; Costes, Valérie; Frouin, Eric; Delfour, Christophe; Cribier, Bernard; Guillot, Bernard; Szablewski, Vanessa

    2016-08-01

    Cutaneous clear cell hidradenoma is an uncommon benign adnexal tumor which is not supposed to metastasize, contrary to its rare malignant counterpart, hidradenocarcinoma. We report the case of a 49-year-old man, who had had a stable inguinal lymph node enlargement for 6 years. An excision was performed and revealed an intra-nodal tumor, made of large clear cells with abundant cytoplasm and round nuclei without atypia or mitosis. The immunohistochemical staining showed diffuse positivity for keratin AE1/AE3, keratin 5/6 and p63, and focal staining with keratin 7, epithelial membrane antigen (EMA) and carcinous epithelial antigen (CEA), which underlined some ductular structures. Tumor cells were negative for renal markers PAX8 and CD10. Ki67 stained less than 1% of tumor cells. A translocation involving MAML2 gene was evidenced by fluorescence in situ hybridization (FISH) analysis. No primary cutaneous tumor was found after extensive examination. Altogether, these results are in favor of an isolated nodal hidradenoma, for which we discuss two hypothesis: a primary nodal lesion, or a 'benign metastasis' of a cutaneous tumor. Cases of morphologically benign hidradenoma with lymph node involvement are exceptional. Our case, similar to every other reported case, was associated with an excellent prognosis, supporting the idea that these patients should not be overtreated. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Thymomas With Extensive Clear Cell Component:  A Clinicopathologic and Immunohistochemical Study of Nine Cases.

    Science.gov (United States)

    Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar A

    2016-07-01

    Nine cases of thymomas with an extensive clear cell component are presented. The patients were six men and three women aged between 45 and 62 years (mean, 52 years). Presenting symptoms included shortness of breath, chest pain, and cough. Diagnostic imaging revealed anterior mediastinal masses in all patients, and all underwent thymectomy. Grossly, the tumors varied from 3 to 9 cm in the greatest dimension. Four cases were invasive and five encapsulated. Histologically, the tumors were characterized by an epithelial cell component with extensive clear cell change, admixed with lymphocytes in varying proportions. Immunohistochemically, the tumors demonstrated the typical immunophenotype of thymomas characterized by positive staining of the epithelial cells for pancytokeratin and cytokeratin 5/6, absent expression of CD5 and c-kit, and reactivity of the lymphocytes for terminal deoxynucleotidyl transferase. Clinical follow-up available for six patients showed that all were alive and well 12 to 24 months after surgical resection. The cases herein presented highlight an unusual feature in thymoma that has more commonly been ascribed to thymic carcinoma. They also emphasize the importance of correct diagnosis to determine the appropriate treatment strategy and to accurately predict prognosis. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature

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    Zhang C

    2016-09-01

    Full Text Available Chengsheng Zhang,1,2 Wei Zhang,1,2 Dianbin Mu,1 Xuetao Shi,1 Lei Zhao1,2 1Department of Hepatobiliary Surgery, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, 2School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China Abstract: An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9 and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL, whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL. Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients. Keywords: gallbladder, clear cell adenocarcinoma, hepatoid differentiation 

  13. Clear cell carcinoma of the ovary: Is there a role of histology-specific treatment?

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    Takano Masashi

    2012-06-01

    Full Text Available Abstract Several clinical trials to establish standard treatment modality for ovarian cancers included a high abundance of patients with serous histologic tumors, which were quite sensitive to platinum-based chemotherapy. On the other hand, ovarian tumor with rare histologic subtypes such as clear cell or mucinous tumors have been recognized to show chemo-resistant phenotype, leading to poorer prognosis. Especially, clear cell carcinoma of the ovary (CCC is a distinctive tumor, deriving from endometriosis or clear cell adenofibroma, and response rate to platinum-based therapy is extremely low. It was implied that complete surgical staging enabled us to distinguish a high risk group of recurrence in CCC patients whose disease was confined to the ovary (pT1M0; however, complete surgical staging procedures could not lead to improved survival. Moreover, the status of peritoneal cytology was recognized as an independent prognostic factor in early-staged CCC patients, even after complete surgical staging. In advanced cases with CCC, the patients with no residual tumor had significantly better survival than those with the tumor less than 1 cm or those with tumor diameter more than 1 cm. Therefore, the importance of achieving no macroscopic residual disease at primary surgery is so important compared with other histologic subtypes. On the other hand, many studies have shown that conventional platinum-based chemotherapy regimens yielded a poorer prognosis in patients with CCC than in patients with serous subtypes. The response rate by paclitaxel plus carboplatin (TC was slightly higher, ranging from 22% to 56%, which was not satisfactory enough. Another regimen for CCC tumors is now being explored: irinotecan plus cisplatin, and molecular targeting agents. In this review article, we discuss the surgical issues for early-staged and advanced CCC including possibility of fertility-sparing surgery, and the chemotherapy for CCC disease.

  14. Clear cell hidradenocarcinoma--a case report with unusual in situ malignant changes.

    Science.gov (United States)

    Al-Irhayim, B

    1984-05-01

    Clear cell hidradenocarcinoma is a rare tumour, the histogenesis of which has been much debated in the past. However, it is now considered a tumour of sweat gland origin. Presented herewith is a report of a case with unusual histological features of in situ malignant changes within sweat glands. These changes very closely simulate lobular cancerisation of the breast. On reviewing the English literature on the histopathology of sweat gland tumours, we have not found similar histological findings. These histological findings provide supportive evidence of the sweat gland origin of these tumours.

  15. Clear cell adenocarcinoma of the ulterine cervix in a 15 year old girl: A case report

    International Nuclear Information System (INIS)

    Choi, Seung Joon; Kim, Jee Eun; KIm, Hyung Sik; Choi, Hye Young

    2013-01-01

    Cervical cancer is rare in the pediatric population. In cases of cervical cancer, adenocarcinoma is predominantly reported. Clear cell adenocarcinoma (CCAC) of the uterine cervix is a very rare tumor and accounts for only 4% of all adenocarcinomas of the uterine cervix. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor. This study reports the imaging finding of primary uterine cervical tumor in a 15-year-old girl, who was finally diagnosed with CCAC, with no maternal history of DES exposure in utero.

  16. Clear cell adenocarcinoma of the ulterine cervix in a 15 year old girl: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Jee Eun; KIm, Hyung Sik; Choi, Hye Young [Dept. of Radiology, Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2013-10-15

    Cervical cancer is rare in the pediatric population. In cases of cervical cancer, adenocarcinoma is predominantly reported. Clear cell adenocarcinoma (CCAC) of the uterine cervix is a very rare tumor and accounts for only 4% of all adenocarcinomas of the uterine cervix. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor. This study reports the imaging finding of primary uterine cervical tumor in a 15-year-old girl, who was finally diagnosed with CCAC, with no maternal history of DES exposure in utero.

  17. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

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    Ilson Sepúlveda

    2013-08-01

    Full Text Available We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.

  18. Novel treatment strategies in clear-cell metastatic renal cell carcinoma.

    NARCIS (Netherlands)

    Spronsen, D.J. van; Weijer, K.J.M. de; Mulders, P.F.A.; Mulder, P.H.M. de

    2005-01-01

    Metastatic renal-cell carcinoma (mRCC) is highly resistant to cytotoxic agents or hormones and is currently mainly treated with cytokine-based therapy. Transient responses and moderate survival advantages have been achieved in a subset of patients with these aspecific biological response modifiers.

  19. Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors.

    Science.gov (United States)

    Diniz, Gulden; Karadeniz, Tugba; Sayhan, Sevil; Akata, Talya; Aydiner, Fatma; Ayaz, Duygu; Solakoglu Kahraman, Dudu; Akman, Tulay

    2017-01-01

    Human Epididymal Secretory Protein 4 was firstly described as an epididymis-specific protein but more recently it has been demonstrated to be a putative serum tumor marker for different malignancies, especially ovarian epithelial cancers. The aim of this study is to investigate the association between tissue Human Epididymal Secretory Protein 4 expression and the clinicopathological features of uterine cervical tumors. This retrospective study was designed to evaluate the differences of tissue expressions of Human Epididymal Secretory Protein 4 protein in a spectrum of cervical neoplasms. One hundred and seven patients recently diagnosed as having cervical intraepithelial neoplasm or invasive squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma based on pathology databases. Decreased or negative Human Epididymal Secretory Protein 4 expressions were determined in both normal cervical epithelia and in intraepithelial carcinomas, while increased HE4 expression was observed in invasive tumors. This study demonstrated that altered expression of Human Epididymal Secretory Protein 4 may involve in tumorigenesis in the uterine cervix. Our findings also suggested the presence of a correlation between Human Epididymal Secretory Protein 4 expression and the invasive potential of uterine tumors. Therefore it may be thought that the tissue expression of HE4 can be used to differentiate high grade intraepithelial tumors from carcinomas.

  20. Clear Cell Carcinoma Compared to Serous Carcinoma in Early Ovarian Cancer: Same Prognosis in a Large Randomized Trial

    NARCIS (Netherlands)

    Timmers, P. J.; Zwinderman, A. H.; Teodorovic, I.; Vergote, I.; Trimbos, J. B.

    2009-01-01

    BACKGROUND:: An analysis was performed comparing survival of patients with clear cell carcinoma (CCC) to patients with serous adenocarcinoma (SAC) in early ovarian cancer. Furthermore, a literature search was done to clarify the clinical and histopathological features of clear cell tumors of the

  1. Epididymal lithiasis in Gallus gallus domesticus

    Directory of Open Access Journals (Sweden)

    JM Rocha Jr.

    2009-03-01

    Full Text Available A study on the occurrence of epididymal lithiasis (EL in Gallus gallus domesticus of different breeds and from different geographical regions of Brazil was carried out. Forty breeding roosters were collected in the states Santa Catarina, São Paulo, Minas Gerais, Espírito Santo and Goiás, representing two specific pathogen free Leghorn lines (SPF, one commercial Leghorn layer breeder (Hy-Line line, two commercial broiler breeder lines (Ross and Cobb, and two backyard chicken flocks. In commercial poultry breeders, EL was observed mainly after 55 weeks of age, and lithus resulted in lower fertility caused by inadequate maturation of spermatozoa and testicular atrophy, which evolved to more severe testicular dysfunction at 100 weeks of age. One hundred percent of the sampled roosters of the evaluated SPF lines presented epididymal lithiasis, which was also observed in all commercial genetic lines. The analysis of EL occurrence revealed no differences among regions and breeds: all regions and genetic lines presented epididymal calculi and the occurrence seemed higher in the more intensively-reared chickens. As for the backyard roosters, 50% presented calculi. Considering the occurrence of EL in the SPF flocks, its primary association with infectious bronchitis virus (IBV infection was discarded, despite its contribution to fertility loss.

  2. Hepatocellular Carcinoma with Foamy Histiocyte-Like Appearance: A Deceptively Clear Cell Carcinoma Appearing Variant

    Directory of Open Access Journals (Sweden)

    Takuji Noro

    2010-08-01

    Full Text Available Hepatocellular carcinoma (HCC shows many pathological features, and it varies architecturally and cytologically. There have been many reports and discussions of the morphological features of HCC. A 63-year-old man was found to have a solitary tumor in liver segment 7 that was diagnosed as HCC. A partial resection of liver segment 7 was performed. Microscopically, the tumor lesion showed a moderately differentiated HCC. There was also a lesion with foamy histiocyte-like cells corresponding to the white lesion in the face of the cut tumor. Immunohistochemical staining showed that they were negative for CD68, S-100, vimentin, and HMB-45. The cytoplasm itself was negative on periodic acid Schiff (PAS and Sudan staining. Without immunohistological analysis, it is difficult to distinguish this HCC variant from clear cell carcinoma or metastases of renal cell carcinoma. It is important to recognize this type as a specific cytological variant of HCC that requires confirmation by immunohistochemistry. This report describes the case of a patient with a morphologically distinctive pattern of HCC with prominent cell cytoplasm that had a foamy histiocyte-like appearance. To the best of our knowledge, this is the first report of this HCC variant.

  3. [Diagnostic value of combined detection of HNF-1β and Napsin A in the diagnosis of ovarian clear cell carcinoma].

    Science.gov (United States)

    Wang, Jinsong; Li, Qing; Cheng, Xue; Xiong, Kemei; Qi, Qiong; Huang, Wenbin

    2015-12-01

    To study the diagnostic value of HNF-1β and Napsin A for ovarian clear cell carcinomas, serous carcinomas, endometrioid adenocarcinomas and metastatic Krukenberg tumors. Immunohistochemical EnVision method was used to detect the expression of HNF-1β and Napsin A in 38 cases of ovarian clear cell carcinoma, 30 cases of high-grade serous carcinoma, 22 cases of endometrioid adenocarcinoma and 16 cases of metastatic Krukenberg tumor. Expression of HNF-1β and Napsin A were compared, and sensitivity and specificity of clear cell carcinoma of the ovary were analysed. The positive rate of HNF-1β in the ovarian clear cell carcinoma was 100%(38/38), higher than those in high-grade serous carcinoma and endometrioid adenocarcinoma (P0.05). Napsin A expressed in 97.4% (37/38) of ovarian clear cell carcinoma, 6.7% (2/30) of high-grade serous carcinoma, 22.7% (5/22) of endometrioid adenocarcinoma. Napsin A expression in clear cell carcinoma was higher than those in high-grade serous carcinoma and endometrioid adenocarcinoma (P0.05). The sensitivity and specificity of HNF-1β in the diagnosis of ovarian clear cell carcinoma were 100% and 52.9%, those of Napsin A were 97.4% and 91.2%, those of both HNF-1β and Napsin A were 97.4% and 91.2%, respectively. The sensitivity and specificity of HNF-1β or Napsin A in the diagnosis of ovarian clear cell carcinoma were 100% and 52.9%, respectively. HNF-1β is a more sensitive marker for the diagnosis of ovarian clear cell carcinoma, whereas Napsin A is a more specific marker. The combined detection of HNF-1β and Napsin A may be helpful for the diagnosis of clear cell carcinoma of the ovary.

  4. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

    Directory of Open Access Journals (Sweden)

    Ronald M Bukowski

    2010-03-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

  5. Notch signaling in the epididymal epithelium regulates sperm motility and is transferred at a distance within epididymosomes.

    Science.gov (United States)

    Murta, D; Batista, M; Silva, E; Trindade, A; Henrique, D; Duarte, A; Lopes-da-Costa, L

    2016-03-01

    Spermatozoa undergo sequential maturation changes during their transit along the epididymis. These changes are modulated by the epididymal epithelium and require a finely tuned gene expression. The Notch cell signaling pathway is a major regulator of cell fate decisions in several tissues, including the testis. Here, we evaluated the transcription and expression patterns of Notch components (Notch1-3, Dll1, Dll4, and Jagged1) and effectors (Hes1-2 and Hes5) in the adult mouse epididymis, and evaluated the role of Notch signaling in the epididymis through its in vivo blockade following administration of an inhibitor (DAPT). Notch components and effectors were dynamically transcribed and expressed in the epididymis and vas deferens, each segment exhibiting a specific combination of epithelial receptor/ligand/effector expression patterns. Nuclear detection of Notch effectors indicates that Notch signaling was active. Notch components (but not effectors) were identified in the cytoplasmic droplet of spermatozoa, in a dynamic and specific pattern along the epididymis. In addition, Notch components were identified within large and small vesicles in the epididymal lumen. A purified population of these membranous vesicles from different epididymal segments was obtained, and through dot blot analysis, it was confirmed that Notch components were carried within these vesicles in a dynamic pattern along the epididymal lumen. We hypothesize that these vesicles (epididymosomes) allow Notch signaling at distance from epididymal epithelial cells to spermatozoa. DAPT-induced in vivo Notch signaling blockade, although showing a low efficiency, disrupted the expression patterns of Notch components and effectors in the epididymal epithelium and in spermatozoa, and significantly decreased sperm motility, although not affecting male fertility. These results prompt for a regulatory role of Notch signaling in epididymal epithelial function and sperm maturation. © 2016 American Society of

  6. Vaginal brachytherapy for early stage uterine papillary serous and clear cell endometrial cancer.

    Science.gov (United States)

    Townamchai, Kanokpis; Berkowitz, Ross; Bhagwat, Mandar; Damato, Antonio L; Friesen, Scott; Lee, Larissa J; Matulonis, Ursula; O'Farrell, Desmond; Viswanathan, Akila N

    2013-04-01

    To report clinical outcomes following adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) for early-stage uterine papillary serous (UPSC) and clear cell (CC) endometrial cancer. A retrospective study of Stage I and II papillary serous and clear cell endometrial cancer treated with post-operative HDR VB between October 2005 and May 2012 was performed. A total of 37 patients were identified, 26 with UPSC, 9 with CC and 2 with mixed UPSC/CC. After total hysterectomy and bilateral salpingo-oophorectomy, VB was administered without external-beam radiation with a dose of 24 Gy in 6 fractions prescribed to the vaginal surface. Chemotherapy was given to 30 patients (75%). The median follow up time was 24.8 months (range, 2.0 to 71.5 months). Four patients relapsed, 2 with UPSC and 2 with CC. The initial site of relapse was concurrent vagina, pelvic/para-aortic nodes and abdominal wall (1), pelvic/para-aortic nodes (1) and para-aortic nodes alone (2). The 2-year vaginal-control rate was 96.8%. The pelvic-control rate including vaginal and nodal relapse was 93.5%. The 2-year disease-free and overall survival rates were 89.3% and 100%, respectively. HDR VB as the sole adjuvant treatment modality for early-stage UPSC/CC is associated with a low rate of vaginal relapse and excellent survival outcomes. This novel low-dose regimen for VB is safe and effective. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress in the epididymis and epididymal sperm of adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Latchoumycandane, C.; Chitra, K.C.; Mathur, P.P. [School of Life Sciences, Pondicherry University, 605 014, Pondicherry (India)

    2003-05-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent environmental contaminants, which has been shown to induce oxidative stress in testis and epididymal sperm of rats. However, the nature and mechanism of action of TCDD on the epididymis is not clear. The aim of the present study was to investigate whether induction of oxidative stress in epididymal sperm was direct effect of TCDD on epididymis. In the present studies, TCDD (0.1, 1.0 and 10 {mu}g/kg body weight per day) was administered orally to rats for 4 days. Twenty-four hours after the last treatment the animals were killed using anesthetic ether. Both epididymides were dissected out and epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F-12 medium at 35 C. The epididymal sperm and caput, corpus and cauda epididymides were homogenized and used for biochemical studies. Epididymal sperm counts did not decrease in the rats treated with TCDD. Administration of TCDD increased the production of reactive oxygen species such as hydrogen peroxide while the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were found to be decreased in the epididymal sperm as well as in cauda epididymides. Lipid peroxidation also increased in the epididymal sperm and in the various regions of the epididymides after exposure to TCDD. The results indicated that TCDD induces oxidative stress in the epididymis and epididymal sperm by decreasing the antioxidant enzymes through induction of reactive oxygen species. Thus, the adverse effects of TCDD on the epididymal sperm were due to direct effect of TCDD on epididymis. (orig.)

  8. Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Hossein Tezval

    2012-10-01

    Full Text Available Clear cell variants of transitional cell carcinomas (TCC of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

  9. Clear cell carcinoma of the uterine cervix: clinical characteristics and feasibility of fertility-preserving treatment

    Directory of Open Access Journals (Sweden)

    Jiang X

    2014-01-01

    Full Text Available Xiang Jiang, Ying Jin, Yan Li, Hui-Fang Huang, Ming Wu, Keng Shen, Ling-Ya Pan Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: The objective of this retrospective study was to analyze the clinical characteristics and prognosis of clear cell adenocarcinoma (CCA in the post-diethylstilbestrol (DES era and to evaluate the feasibility of fertility-preserving treatment. The records of 32 patients with CCAs who were treated at Peking Union Medical College Hospital from August 1986 to June 2012 were retrospectively reviewed. Three of the patients had undergone fertility-preserving treatment. The incidence of CCA among cervical adenocarcinomas was 15.2%. The median age was 38 years: 11 patients (34.4% were diagnosed before 30 years of age and two (6.3% after 70 years of age. Ten patients (31.2% were nulliparous. No patient had been exposed to DES. Twenty-nine patients (90.6% presented with obvious symptoms, and the cervix appeared abnormal in 26 patients (81.3%. Cervical Papanicolaou (Pap tests were abnormal in all four patients in whom they were performed (three had high-grade squamous intraepithelial lesions and one had atypical squamous cells of undetermined significance. The distribution by stage was 56.3% stage I, 34.4% stage II, 6.3% stage III, and 3.1% stage IV. Treatments mainly included surgery for patients with stage I to IIA CCA and radiochemotherapy for patients with advanced CCA. The overall 5-year progression-free survival was 72.2%. Patients with stage I to IIA CCA had better 5-year progression-free survival than did patients with stage IIB to IV CCA (81.5% versus 40.0%, P=0.003. The three patients who had undergone fertility-preserving treatment had no recurrences. CCA may also affect adolescents and children without prior DES exposure, who are often misdiagnosed as having functional uterine

  10. Alveolar architecture of clear cell renal carcinomas (≤5.0 cm) show high attenuation on dynamic CT scanning

    International Nuclear Information System (INIS)

    Fujimoto, Hiroyuki; Wakao, Fumihiko; Moriyama, Noriyuki; Tobisu, Kenichi; Kakizoe, Tadao; Sakamoto, Michiie

    1999-01-01

    To establish the correlation between tumor appearance on CT and tumor histology in renal cell carcinomas. The density and attenuation patterns of 96 renal cell carcinomas, each ≤5 cm in greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of contrast medium using dynamic CT. The density and attenuation patterns and pathological maps of each tumor were individually correlated. High attenuated areas were present in 72 of the 96 tumors on early enhanced dynamic CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on early enhanced scanning included three clear cell, nine granular cell, six papillary, five chromophobe and one collecting duct type. With respect to tumor architecture, all clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. Clear cell renal cell carcinomas of alveolar architecture show high attenuation on early enhanced dynamic CT scanning. A larger number of patients are indispensable to obtaining clear results. However, these findings seem to be an important clue to the diagnosis of renal cell carcinomas as having an alveolar structure. (author)

  11. Epididymal protein Rnase10 is required for post-testicular sperm maturation and male fertility

    Science.gov (United States)

    Krutskikh, Anton; Poliandri, Ariel; Cabrera-Sharp, Victoria; Dacheux, Jean Louis; Poutanen, Matti; Huhtaniemi, Ilpo

    2012-01-01

    Eutherian spermatozoa are dependent on the environment of the proximal epididymis to complete their maturation; however, no specific epididymal factors that mediate this process have so far been identified. Here, we show that targeted disruption of the novel gene Rnase10 encoding a secreted proximal epididymal protein in the mouse results in a binding defect in spermatozoa and their inability to pass through the uterotubal junction in the female. The failure to gain the site of fertilization in the knockout spermatozoa is associated with a gradual loss of ADAM3 and ADAM6 proteins during epididymal transit. In the distal epididymis, these spermatozoa appear to lack calcium-dependent associations with the immobilizing glutinous extracellular material and are released as single, vigorously motile cells that display no tendency for head-to-head agglutination and lack affinity to the oviductal epithelium. In sperm-egg binding assay, they are unable to establish a tenacious association with the zona pellucida, yet they are capable of fertilization. Furthermore, these sperm show accelerated capacitation resulting in an overall in vitro fertilizing ability superior to that of wild-type sperm. We conclude that the physiological role of sperm adhesiveness is in the mechanism of restricted sperm entry into the oviduct rather than in sperm-egg interaction.—Krutskikh, A., Poliandri, A., Cabrera-Sharp, V., Dacheux, J. L., Poutanen, M., Huhtaniemi, I. Epididymal protein Rnase10 is required for post-testicular sperm maturation and male fertility. PMID:22750516

  12. Identification of intranuclear inclusions is useful for the cytological diagnosis of ovarian clear cell carcinoma.

    Science.gov (United States)

    Naka, Masaki; Ohishi, Yoshihiro; Kaku, Tsunehisa; Watanabe, Sumiko; Tamiya, Sadafumi; Ookubo, Fumihiko; Kato, Kiyoko; Oda, Yoshinao; Sugishima, Setsuo

    2015-11-01

    The aim of this study was to clarify the diagnostic significance of the presence of intranuclear inclusions in clear cell carcinoma (CCC). We analyzed 98 imprint specimens and 53 ascites specimens from 98 ovarian carcinoma cases [28 CCCs, 37 serous carcinomas (SCs), 22 endometrioid carcinomas (ECs), and 11 mucinous carcinomas (MCs)]. We examined (1) frequency of intranuclear inclusion-positive cases of each ovarian carcinoma subtype, using imprint specimens, (2) frequency of intranuclear inclusion-positive cells of each ovarian carcinoma subtype, using imprint specimens, (3) frequency of intranuclear inclusion-positive cases of each ovarian carcinoma subtype, using ascites specimens, and (4) sensitivity and specificity of the presence of intranuclear inclusions for the cytological diagnosis of CCC. (1) The frequency of intranuclear inclusion-positive cases in CCC (96.4%) was significantly higher than in SC (13.5%), EC (13.6%), and MC (18.2%) (P < 0.001). Two or more intranuclear inclusions in a single nucleus were observed only in CCC. (2) The frequency of intranuclear inclusion-positive cells in CCC (median, 0.41%) was significantly higher than in non-CCC subtypes (0.010%) (P < 0.001). (3) Using ascites specimens, the frequency of intranuclear inclusion-positive cases in CCC (78.6%) was significantly higher than in SC (10.3%), EC (0%), and MC (0%) (P < 0.001). (4) The sensitivity of intranuclear inclusions was 96.4%, and the specificity was 85.7%. The identification of intranuclear inclusions, in particular a high frequency and multiple intranuclear inclusions in a single nucleus, is useful for the cytological diagnosis of CCC. Furthermore, these results may be applicable to ascites cytology. © 2015 Wiley Periodicals, Inc.

  13. Epididymal Inflammatory Pseudotumor: A Case Report

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2013-04-01

    Full Text Available Inflammatory pseudotuomr refers to a group of benign tumor like lesions that they are composed of a mixed inflammatory infiltrates. The diagnosis of these lesions and differentiation of them from malignant process may be difficult. We report on a 35-yearoldman who presented with multiple painless palpable masses in his right hemiscrotum for about 6 months. Right epididymal involvement with intact testicle and spermatic cord were observed during scrotal exploration. After classic right epididymectomy, histopathologic studies revealed inflammatory pseudotumor of the right epididymis.No remarkable abnormal signs and symptoms were observed in the follow up visits after 8 months.

  14. The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

    NARCIS (Netherlands)

    Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

    Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

  15. Morphology of the testes and epididymal ducts in the pampas cat Leopardus colocolo (Molina, 1782

    Directory of Open Access Journals (Sweden)

    Mahmoud Mehanna

    Full Text Available ABSTRACT: The pampas cat Leopardus colocolo (Molina, 1782 is a species of the Felidae family, widely distributed in South America, included on CITES Appendix II and classified as Near Threatened on the IUCN Red List, with population trend decreasing. Based on this information, the objective of this study is to describe morphologically the testes and epididymal ducts of pampas cat. The animal, coming from the Federal University of Mato Grosso Zoo, Brazil, had died after anesthesia procedure and the male reproductive system was dissected to collect the testicles. The samples taken were fragmented and histologically examined. From the microscopic analysis of the testes were identified: vaginal and tunica albuginea, formed by dense connective tissue modeled with large amount of collagen fibers. The tunica albuginea fibrous septa emits into the body. The seminiferous tubules are coiled and coated internally by spermatogenic epithelium consisting of Sertoli cells, surrounded by a basement membrane in the presence of myoid cells. The interstitial tissue between the seminiferous tubules, is composed of loose connective tissue, blood and lymph vessels, and Leydig cells in polyhedral shape. The epididymal ducts showed pseudostratified columnar epithelium with secretory cells of which stereocilia design, situated on a basement membrane filled by myoid cells. This epithelium has principal and basal cells, the main cell design stereocilia toward the lumen of the epididymal duct.

  16. Pentoxifylline effects on capacitation and fertility of stallion epididymal sperm

    NARCIS (Netherlands)

    Guasti, P. N.; Monteiro, G. A.; Maziero, R. R.D.; Carmo, M. T.; Dell'Aqua, J. A.; Crespilho, A. M.; Rifai, E. A.; Papa, F. O.

    2017-01-01

    The aims of this study were to determinate whether pentoxifylline (PTX) increases the motion parameters of fresh and frozen-thawed equine epididymal spermatozoa, to evaluate the tyrosine phosphorylation of frozen-thawed epididymal sperm in the presence of PTX and to determine whether the

  17. Dose-dependent effects of homologous seminal plasma on motility and kinematic characteristics of post-thaw stallion epididymal spermatozoa.

    Science.gov (United States)

    Neuhauser, S; Dörfel, S; Handler, J

    2015-05-01

    Preservation of epididymal spermatozoa is important to save genetic material of endangered species and breeds, or in case of unexpected injury, which will end the breeding career of valuable sires. Seminal plasma (SP) influences sperm quality in a dose-dependent manner and its addition to preserved semen immediately before insemination may be beneficial for sperm fertility. Increased plasma membrane stability of epididymal spermatozoa reduces freezing injury of cells, and the addition of SP after freezing and thawing might have activating and protecting effects on spermatozoa within the female genital tract. In this study, epididymal spermatozoa were harvested by retrograde flush of the epididymal cauda immediately after routine castration and frozen. Seminal plasma was collected from other six stallions. Homologous SP (SP from the same species, but from a different animal) was added to frozen-thawed epididymal spermatozoa at concentrations of 0, 5, 20, 50 and 80% SP. Addition of SP increased sperm motility and influenced kinematic values in a dose-dependent manner (p sperm motility among SP from six different donor stallions regardless of the concentrations of SP (p > 0.05). Total and progressive motility of ten frozen-thawed epididymal spermatozoa samples collected from different stallions after dilution with extender and 5, 20, 50 or 80% SP differed significantly (p epididymal spermatozoa immediately improved motility in a dose-dependent manner regardless of semen quality of SP donor stallions. This might positively influence fertility when SP is added before insemination. Moreover, there seems to be a threshold level of SP concentration for optimal improvement of sperm motility. © 2015 American Society of Andrology and European Academy of Andrology.

  18. In vitro fertilization using frozen-thawed feline epididymal spermatozoa from corpus and cauda regions.

    Science.gov (United States)

    Kunkitti, Panisara; Axnér, Eva; Bergqvist, Ann-Sofi; Sjunnesson, Ylva

    2016-10-01

    Epididymal sperm preservation offers a potential for rescuing genetic material from endangered or valuable animals after injury or death. Spermatozoa from corpus, as well as from cauda, have the capability to be motile and to undergo capacitation and can thus potentially be preserved for assisted reproductive technologies. In the present study, feline frozen-thawed epididymal spermatozoa from corpus and cauda regions were investigated for their ability to fertilize homologous oocytes and further embryo development in vitro. Epididymal spermatozoa from corpus and cauda of seven cats were cryopreserved and used for IVF. Cumulus-oocyte complexes (n = 419) were obtained from female cats after routine spaying. Frozen-thawed corpus epididymal spermatozoa showed similar properties of acrosome integrity, membrane integrity, and chromatin integrity as frozen-thawed spermatozoa from cauda except corpus spermatozoa showed lower motility (P epididymal spermatozoa was confirmed by similar number of embryos developing to the two- and four-cell stages compared with sperm from cauda (32.03% vs. 33.33%). However, oocytes fertilized with corpus spermatozoa had lower potential to develop to the blastocyst stage (6.79%) and had lower cell numbers compared to oocytes fertilized with cauda spermatozoa (14.08%). In conclusion, spermatozoa from corpus epididymis had a similar capability to fertilize homologous oocytes in vitro as sperm from cauda but resulted in fewer embryos developing to the blastocyst stage compared to spermatozoa from the cauda. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney

    Science.gov (United States)

    Roy, Angshumoy; Kumar, Vijetha; Zorman, Barry; Fang, Erica; Haines, Katherine M.; Doddapaneni, HarshaVardhan; Hampton, Oliver A.; White, Simon; Bavle, Abhishek A.; Patel, Nimesh R.; Eldin, Karen W.; John Hicks, M.; Rakheja, Dinesh; Leavey, Patrick J.; Skapek, Stephen X.; Amatruda, James F.; Nuchtern, Jed G.; Chintagumpala, Murali M.; Wheeler, David A.; Plon, Sharon E.; Sumazin, Pavel; Parsons, D. Williams

    2015-01-01

    The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of 27 (85%) pediatric clear cell sarcomas of the kidney (CCSK) from two independent cohorts. We profile CCSK tumours using a combination of whole-exome, transcriptome and targeted sequencing. Identical ITD mutations are found in primary and relapsed tumour pairs but not in adjacent normal kidney or blood. Mutant BCOR transcripts and proteins are markedly upregulated in ITD-positive tumours. Transcriptome analysis of ITD-positive CCSKs reveals enrichment for PRC2-regulated genes and similarity to undifferentiated sarcomas harbouring BCOR–CCNB3 fusions. The discovery of recurrent BCOR ITDs defines a major oncogenic event in this childhood sarcoma with significant implications for diagnostic and therapeutic approaches to this tumour. PMID:26573325

  20. Clear cell sarcoma of the kidney: patients' characteristics and improved outcome in developing countries.

    Science.gov (United States)

    Zekri, Wael; Alfaar, Ahmad Samir; Yehia, Dina; Elshafie, Maged M; Zaghloul, Mohamed Saad; El-Kinaai, Naglaa; Taha, Hala; Refaat, Amal; Younes, Alaa A

    2014-12-01

    Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive tumor accounting for 5% of pediatric renal tumors with an incidence of 20 patients per year in the USA. It is bone metastasizing with poor prognosis. Our aim was to show characteristics of patients in relation to improved outcome in one of the developing countries. We included all patients diagnosed as CCSK in the period between July 2007 and March 2012 at Children's Cancer Hospital, Egypt. Patients' demographics, clinical presentation, pathology, and management were reviewed. Follow up was continued until April 2013. Twenty-five patients were identified in the defined time interval, accounting for 7% all renal tumors diagnosed at the hospital. Mean age was 36 months. Abdominal swelling and hematuria were the most common presentations. Stages I, II, III, IV, and V represented 9 (36%), 3 (12%), 8 (32%), 3 (12%), and 2 (8%), respectively. Twenty-four patients had radical nephrectomy either upfront or after neo-adjuvant chemotherapy. Surgery was followed by adjuvant chemotherapy. Abdominal radiotherapy was given for local stages II and III. Twenty-two patients reached complete remission, while one patient had stationary disease and two patients died due to progression and relapse. Overall survival was 88.5% and event-free survival was 87.8% at 45 months. Although previous studies indicate poor prognosis of CCSK, our experience shows that those patients can be treated using extensive chemotherapy combined with proper local control. © 2014 Wiley Periodicals, Inc.

  1. Reappraising hyalinizing clear cell carcinoma: A population-based study with molecular confirmation.

    Science.gov (United States)

    Hernandez-Prera, Juan C; Kwan, Ricky; Tripodi, Joseph; Chiosea, Simion; Cordon-Cardo, Carlos; Najfeld, Vesna; Demicco, Elizabeth G

    2017-03-01

    Hyalinizing clear cell carcinoma (HCCC) is a rare malignancy, characterized by EWSR1-ATF1 gene fusion, whose behavior is poorly understood, as it was for many years considered a diagnosis of exclusion. All available salivary gland carcinomas (n = 594) from our institution were reviewed. Diagnosis of HCCC was confirmed by fluorescence in situ hybridization (FISH) for EWSR1. Literature review was performed. We found 15 patients with HCCCs (10 women, 5 men), 13 with EWSR1 rearrangement. Median age at diagnosis was 57 years (range, 31-87 years). Oral cavity (n = 9) and base of tongue (n = 4) were the most frequent primary sites. Combining our cases with those identified in literature review, the 10-year risk of local recurrence and locoregional nodal metastasis were 49% and 15%, respectively. Molecularly confirmed HCCC accounted for 2.5% of salivary gland malignancies at our institution. HCCCs are indolent tumors with a propensity for locoregional recurrence. © 2016 Wiley Periodicals, Inc. Head Neck 39: 503-511, 2017. © 2016 Wiley Periodicals, Inc.

  2. Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database.

    Science.gov (United States)

    Nieto, Karina; Adams, William; Pham, Nghia; Block, Alec M; Grover, Surbhi; Small, William; Harkenrider, Matthew M

    2018-01-01

    To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC). 4298 patients treated from 1998 to 2011 with Stage I-IVA CCC were identified within the National Cancer Database. FIGO 2009 staging system was used. Adjuvant groups included: hysterectomy (HYS); HYS+vaginal brachytherapy (VBT); HYS+chemotherapy (CT); HYS+external beam radiation therapy (EBRT); HYS+CT+EBRT; and HYS+CT+VBT. Univariable (UVA) and multivariable (MVA) frailty survival analyses were performed. On UVA, higher stage was associated with an increased risk of death. Compared to stage I-IA, the risk of death for stage IB was HR 1.75 (95% CI, 1.50-2.04; pgeographic education attainment (p=0.001), greater comorbidity score (p=0.001), increasing age (pNational Cancer Center Database. Given the aggressive nature of the disease, clinical trials are required to determine the optimal adjuvant therapy in patients with non-metastatic CCC to improve clinical outcomes. Published by Elsevier Inc.

  3. Canine epididymal spermatozoa: A hidden treasure with great potential.

    Science.gov (United States)

    Luvoni, G C; Morselli, M G

    2017-04-01

    The hidden treasure represented by epididymal spermatozoa has great potential in the current reproductive technologies in dogs. In case of azoospermia or when a donor male accidentally dies or undergoes orchiectomy, the retrieval of epididymal spermatozoa opens new possibilities to generate progeny. Spermatozoa can be collected by different techniques from ex vivo or in vivo testicles and can be cryopreserved for a future use. Freeze tolerance of canine epididymal spermatozoa seems lower than that of ejaculated spermatozoa; however, puppies were born after artificial insemination with frozen epididymal semen, other than with fresh and chilled. Even though several aspects need to be further investigated, advances have been recently made in the use of epididymal spermatozoa in assisted reproduction in dogs. © 2016 Blackwell Verlag GmbH.

  4. Comparison of two different extenders for cryopreservation of epididymal dog sperm.

    Science.gov (United States)

    Martins, Mim; Justino, R C; Sant'anna, M C; Trautwein, L G C; Souza, F F

    2012-12-01

    The collection of epididymal sperm is an option for preservation of germplasm of genetically superior animals that need to be orchiectomized or have died. The extender type used to freeze sperm is important to avoid spermatozoal membrane damage and to preserve semen quality after cryopreservation. The objective of this study was to verify the effects of a commercial bovine extender (Bovimix(®); Nutricell, Campinas) and a traditional TRIS-citric acid-glucose-egg yolk-7% glycerol extender on cryopreservation of canine epididymal sperm. The testes of 13 adult dogs were kept at 5 °C for 24 h in saline solution, and epididymal sperm was recovered in Ringers solution without lactate and were evaluated for motility. Samples with ≥ 80% motility were pooled and then divided before dilution and packaging in 0.5 ml plastic straws, equilibration at 4 °C for 1 h, freezing in nitrogen vapour for 20 min and storing at -196 °C. The straws were thawed at 56 °C for 10 s and were evaluated for motility by computer assisted analysis (CASA). The semen parameters, sperm movement index, linearity, total motility and rapid progressive motility were statistically higher in Bovimix(®) than TRIS. In contrast, amplitude of lateral head displacement, slow sperm and static sperm were lower in Bovimix(®). Despite the high percentage of sperm defects in epididymal cells, regardless of the extender, we concluded that Bovimix(®) is a viable alternative for the freezing of canine epididymal sperm. © 2012 Blackwell Verlag GmbH.

  5. Mismatch repair status and PD-L1 expression in clear cell carcinomas of the ovary and endometrium.

    Science.gov (United States)

    Willis, Brian C; Sloan, Emily A; Atkins, Kristen A; Stoler, Mark H; Mills, Anne M

    2017-11-01

    Clear cell carcinoma represents a distinct histologic type of müllerian carcinoma that is resistant to conventional chemotherapy. Expression of programmed cell death ligand (PD-L1) has been associated with immune evasion in numerous tumor types and may be used to identify patients who will benefit from targeted immunotherapy, particularly in the setting of mismatch repair defects. We evaluated PD-L1 expression in 23 ovarian clear cell carcinomas and 21 endometrial clear cell carcinomas, and correlated expression with mismatch repair status. Tumor PD-L1 staining was seen in 43% of ovarian tumors and 76% of endometrial tumors, including 71% of cases (67% of ovarian and 75% of endometrial) with mismatch repair defects. Extensive tumoral staining (>50%) was seen in only one case (an endometrial case with MSH6 loss). However, tumoral PD-L1 expression remained common in mismatch repair-intact tumors and mismatch repair status was not significantly correlated with PD-L1 expression. The increased incidence of PD-L1 positivity in tumor cells (P=0.04) in endometrial vs ovarian clear cell carcinomas suggests differences in the tumor microenvironment of these histologically and molecularly similar tumors that may inform treatment options. These results suggest that clear cell histology may be a useful susceptibility marker for immunotherapy targeting the PD-1/PD-L1 axis irrespective of mismatch repair status, particularly in endometrial carcinomas.

  6. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

    Science.gov (United States)

    Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

    2017-11-01

    Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

  7. Adenoma clear cell carcinoma of prostatic utricle. Report of a case. Literature Review

    International Nuclear Information System (INIS)

    Cataldi, S.; Castillo, L.; Rodrígue, R.

    2004-01-01

    The prostatic utricle (UP) is a rudimentary structure derived from the Müllerian ducts (paramesonephric), which gives rise to the female genital tract in its portion flow and Wollfianos products (mesonephric), which causes the male seminal tubes urogenital sinus and in the caudal segment. It is located in the central portion of the prostatic urethra. UP pathology is rare in the literature and only few isolated cases have been reported and rare reviews. UP neoplasms are extremely rare. The first report on the literature is the year 1967 in a man 66 years in which the diagnosis was incidental in a piece of prostatectomy. Objective: The aim of this paper is to review the literature on this rare condition from the report of a clinical case. Case report: Male patient, 15 years who presented with hematuria. the tomography showed right renal agenesis, hypertrophic left kidney and a solid mass retrovesical in prostate topography. The transrectal ultrasound guided biopsy remains informed embryonic kidney blastoma and immunohistochemical profile is specific to urothelial epithelium and glomerular (BPM CK7 strongly positive). It is involved, resecting the tumor whose pelvic pathology (AP) corresponded to clear cell adenocarcinoma UP. Pursuing a post-operative complications and remains without clinical tomographic control locoregional relapse was diagnosed 5 months after. Get chemotherapy type adriamycin-cisplatin with complete clinical response after the 2nd cycle of treatment and rapid lesion progression at the end of the 6th cycle. Was re hospitalized resecting one laterovesical mass right, leaving in situ a left laterovesical similar mass. the AP was similar to the original. Currently, the patient underwent a left nephrostomy is planned initiation of palliative chemotherapy of weekly Docetaxel type. Conclusions: Given the rarity of the disease, and little literature there is no data on evolution and sensitivity to treatment. In the case of this patient highlight the high

  8. Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma.

    Science.gov (United States)

    Matsuo, Koji; Hasegawa, Kosei; Yoshino, Kiyoshi; Murakami, Ryusuke; Hisamatsu, Takeshi; Stone, Rebecca L; Previs, Rebecca A; Hansen, Jean M; Ikeda, Yuji; Miyara, Akiko; Hiramatsu, Kosuke; Enomoto, Takayuki; Fujiwara, Keiichi; Matsumura, Noriomi; Konishi, Ikuo; Roman, Lynda D; Gabra, Hani; Fotopoulou, Christina; Sood, Anil K

    2015-09-01

    We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P<0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P=0.006). Advanced OCCC (hazard ratio [HR] 3.38, P<0.0001), thrombocytosis (HR 1.42, P=0.032) and elevated IL-6 (HR 8.90, P=0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P<0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P<0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P=0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P=0.07). Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis.

    Science.gov (United States)

    Paik, E Sun; Kim, Tae Joong; Choi, Chel Hun; Kim, Byoung Gie; Bae, Duk Soo; Lee, Jeong Won

    2018-03-01

    The aim of this investigation is to compare outcomes of patients according to the presence of cancer arising from endometriosis in ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC). This study retrospectively investigated 224 CCC and EC patients treated in Samsung Medical Center from 2001 to 2015 to identify cancer arising from endometriosis according to Sampson and Scott criteria. Propensity score matching was performed to compare patients arising from endometriosis to patients without endometriosis (ratio 1:1) according to stage, age, lymph node metastasis (LNM), cancer antigen (CA)-125 level, and residual status after debulking surgery. Forty-five cases arising from endometriosis were compared with 179 cases without endometriosis. CCC and EC arising from endometriosis tended to present with early age (mean, 45.2 vs. 49.2 years; p=0.003), early-stage (stages I and II, 92.7% vs. 62.3%; p<0.001), lower CA-125 level (mean, 307.1 vs. 556.7; p=0.041), higher percentages of no gross residual disease after surgery (87.8% vs.56.8%; p=0.001), and higher percentages of negative LNM (82.9% vs. 59.0%; p=0.008) compared to cases without endometriosis. Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS) showed better outcomes for groups with cancer arising from endometriosis (p=0.014 for PFS; and p=0.010 for OS). However, the association with endometriosis was not significant in multivariate analysis. Also, after propensity score matching, survival differences between the 2 groups were not significant. CCC and EC arising from endometriosis are diagnosed at an earlier age and stage. However, cancer arising from endometriosis was not a significant prognostic factor. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  10. Is the presence of endometriosis associated with a survival benefit in pure ovarian clear cell carcinoma?

    Science.gov (United States)

    Sahin, Hanifi; Sari, Mustafa Erkan; Cuylan, Zeliha Firat; Haberal, Asuman Nihan; Sirvan, Levent; Coban, Gonca; Yalcin, Ibrahim; Güngör, Tayfun; Celik, Husnu; Meydanli, Mehmet Mutlu; Ayhan, Ali

    2018-01-30

    The purpose of this study was to compare the prognoses of women with pure ovarian clear cell carcinoma (OCCC) arising from endometriosis to those of women with pure OCCC not arising from endometriosis treated in the same manner. A dual-institutional, retrospective database review was performed to identify patients with pure OCCC who were treated with maximal or optimal cytoreductive surgery (CRS) followed by paclitaxel/carboplatin chemotherapy between January 2006 and December 2016. Patients were divided into two groups according to the detection of cancer arising in endometriosis or not, on the basis of pathological findings. Demographic, clinicopathological, and survival data were collected, and prognosis was compared between the two groups. Ninety-three women who met the inclusion criteria were included. Of these patients, 48 (51.6%) were diagnosed with OCCC arising in endometriosis, while 45 (48.4%) had no concomitant endometriosis. OCCC arising in endometriosis was found more frequently in younger women and had a higher incidence of early stage disease when compared to OCCC patients without endometriosis. The 5-year overall survival (OS) rate of the patients with OCCC arising in endometriosis was found to be significantly longer than that of women who had OCCC without endometriosis (74.1 vs. 46.4%; p = 0.003). Although univariate analysis revealed the absence of endometriosis (p = 0.003) as a prognostic factor for decreased OS, the extent of CRS was identified as an independent prognostic factor for both recurrence-free survival (hazard ratio (HR) 8.7, 95% confidence interval (CI) 3.15-24.38; p < 0.001) and OS (HR 11.7, 95% CI 3.68-33.71; p < 0.001) on multivariate analysis. Our results suggest that endometriosis per se does not seem to affect the prognosis of pure OCCC.

  11. PAI-1 expression and its regulation by promoter 4G/5G polymorphism in clear cell renal cell carcinoma.

    Science.gov (United States)

    Choi, Jung-Woo; Lee, Ju-Han; Park, Hong Seok; Kim, Young-Sik

    2011-10-01

    To characterise patients with high plasminogen activator inhibitor-1 (PAI-1) expression as oral PAI-1 antagonists are currently in preclinical trials, and to determine whether the PAI-1 promoter 4G/5G polymorphism regulates PAI-1 expression in clear cell renal cell carcinoma (CCRCC). PAI-1 expression was examined by immunohistochemistry in 69 CCRCC specimens. In addition, the promoter 4G/5G polymorphism was investigated by both allele-specific PCR and direct DNA sequencing. PAI-1 was overexpressed in 25/69 (36.2%) patients with CCRCC. PAI-1 staining was intense in tumour cells with a high Fuhrman nuclear grade and in spindle-shaped tumour cells. PAI-1 expression was significantly associated with older age at diagnosis (p=0.027), high nuclear grade (p5G and 31.9% (22/69) 5G/5G. The homozygous 4G/4G or 5G/5G group showed a tendency for a high nuclear grade (p=0.05) but the 4G/5G polymorphism was not related to other prognostic parameters. PAI-1 expression was poorly correlated with its promoter 4G/5G polymorphism (Spearman ρ=0.088). CCRCC with high PAI-1 expression is characterised by older age, high nuclear grade, advanced stage, distant metastasis and/or shortened disease-free survival. PAI-1 expression is not affected by the promoter 4G/5G polymorphism.

  12. Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Peio Errarte

    Full Text Available The discovery of the intrarenal renin-angiotensin system (iRAS, which regulates angiogenesis, cell differentiation and proliferation, has opened new perspectives in the knowledge of kidney carcinogenesis. In this study we analyzed the immunohistochemical expression and fluorimetric activity of four key peptidases of iRAS in tumor tissue (n = 144 and serum samples (n = 128 from patients with renal neoplasms. Neutral endopeptidase (NEP/CD10, Angiotensin-converting enzyme-2 (ACE2, and aminopeptidase A (APA were expressed in tumor cells whilst Angiotensin-converting enzyme (ACE was expressed in the endothelial cells of intratumor blood vessels. The expression of ACE, ACE2 and NEP/CD10 was highest in clear cell renal cell carcinoma (CCRCC and papillary renal cell carcinoma (PRCC. The expression of these enzymes correlated with CCRCC aggressiveness. In addition, NEP/CD10 correlated with 15-year overall survival. On the other hand, APA expression was decreased in CCRCC with higher grade and stage. The loss of expression of APA independently correlated with a worse 15-year overall survival. Serum activity of ACE2, NEP/CD10 and APA was significantly higher in renal tumor patients than in healthy subjects. Serum ACE activity was lower in high grade and metastatic CCRCC patients, and NEP/CD10 activity was negatively correlated with UISS (UCLA Integrated Staging System and SSIGN (Mayo Clinic stage, size, grade and necrosis model scores and with overall survival of CCRCC patients. These results suggest a metabolic imbalance of iRAS in renal tumors. This finding should be taken into account in the search of new diagnostic, prognostic and therapeutic tools for this disease.

  13. The adult boar testicular and epididymal transcriptomes

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    Guyonnet Benoît

    2009-08-01

    Full Text Available Abstract Background Mammalians gamete production takes place in the testis but when they exit this organ, although spermatozoa have acquired a specialized and distinct morphology, they are immotile and infertile. It is only after their travel in the epididymis that sperm gain their motility and fertility. Epididymis is a crescent shaped organ adjacent to the testis that can be divided in three gross morphological regions, head (caput, body (corpus and tail (cauda. It contains a long and unique convoluted tubule connected to the testis via the efferent ducts and finished by joining the vas deferens in its caudal part. Results In this study, the testis, the efferent ducts (vas efferens, VE, nine distinct successive epididymal segments and the deferent duct (vas deferens, VD of four adult boars of known fertility were isolated and their mRNA extracted. The gene expression of each of these samples was analyzed using a pig generic 9 K nylon microarray (AGENAE program; GEO accession number: GPL3729 spotted with 8931 clones derived from normalized cDNA banks from different pig tissues including testis and epididymis. Differentially expressed transcripts were obtained with moderated t-tests and F-tests and two data clustering algorithms based either on partitioning around medoid (top down PAM or hierarchical clustering (bottom up HCL were combined for class discovery and gene expression analysis. Tissue clustering defined seven transcriptomic units: testis, vas efferens and five epididymal transcriptomic units. Meanwhile transcripts formed only four clusters related to the tissues. We have then used a specific statistical method to sort out genes specifically over-expressed (markers in testis, VE or in each of the five transcriptomic units of the epididymis (including VD. The specific regional expression of some of these genes was further validated by PCR and Q-PCR. We also searched for specific pathways and functions using available gene ontology

  14. Pentoxifylline effects on capacitation and fertility of stallion epididymal sperm.

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    Guasti, P N; Monteiro, G A; Maziero, R R D; Carmo, M T; Dell'Aqua, J A; Crespilho, A M; Rifai, E A; Papa, F O

    2017-04-01

    The aims of this study were to determinate whether pentoxifylline (PTX) increases the motion parameters of fresh and frozen-thawed equine epididymal spermatozoa, to evaluate the tyrosine phosphorylation of frozen-thawed epididymal sperm in the presence of PTX and to determine whether the PTX-treatment of stallion epididymal sperm prior to freezing improves the fertility response of mares to a reduced number of spermatozoa per insemination dose. Fifty epididymis were flushed with a skim milk based extender with or without PTX. The pre-treatment with PTX enhanced the sperm motility after being harvested (Psperm kinematics between control and treated samples (P>0.05). Plasma membrane integrity did not differ between control and PTX group after recovery and after thawing (P>0.05), as observed in tyrosine phosphorylation, which the PTX treatment did not alter the percentage of tail-associated immunofluorescence of cryopreserved epididymal sperm (P>0.05). For the fertility trial, different insemination groups were tested: 800×10 6 epididymal sperm (C800); 100×10 6 epididymal sperm (C100); 100×10 6 epididymal sperm recovered in an extender containing PTX (PTX100). The conception rates for C800; C100 and PTX100 were 68.7% (11/16); 31.5% (5/16) and 50% (8/16), respectively. The conception rate did not differ among groups (P>0.05), however, a low number of animals was used in this study. A trend toward significance (P=0.07) was observed between C800 and C100 groups. In conclusion, PTX has no deleterious effect on sperm motility, viability and capacitation of cryopreserved stallion epididymal sperm. The conventional artificial insemination with 100×10 6 sperm recovered with PTX ensures acceptable conception rates and maximize the limited number of doses of cryopreserved stallion epididymal sperm. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Clinicopathologic characteristics and prognosis of glycogen-rich clear cell carcinoma of the breast.

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    Ma, Xiangmin; Han, Yunwei; Fan, Yu; Cao, Xuchen; Wang, Xin

    2014-01-01

    Glycogen-rich clear cell carcinoma (GRCC) of the breast is a rare type of breast carcinoma. Knowledge about the characteristics of this type is fragmentary, and the prognosis is on debate. In this study, we aimed to summarize the clinical, pathologic, and biologic characteristics of GRCC of the breast and analyze the survival. We reviewed the cases of breast cancer in our hospital between January 1999 and December 2009 and identified 28 patients as GRCC of the breast. The routine hematoxylin-eosin staining, periodic acid-Schiff (PAS) staining, and diastase PAS staining were performed on the tumor tissues. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), Ki67 and P53 were evaluated by immunohistochemistry. Tumors with a HER-2 score of 2+ were confirmed by fluorescent in situ hybridization test. Each GRCC case, who had complete follow-up data, was compared with four cases of usual invasive ductal carcinomas as controls in the same database and matched with age, year of diagnosis, tumor size, nodal status, and immunophenotype. The chi-squared test and the Fisher's exact test were used to compare the characteristics of GRCC cases and controls. The univariate analysis was used to study the prognosis, and Kaplan-Meier method was used to compare the survival of two groups. The clinicopathologic and imaging features were analyzed in the GRCC cases. Tumor sizes ranged from 0.8 to 7.5 cm (mean, 3.2 cm). Thirteen cases (46.4%) had positive lymph nodes. The positivity of ER and PR was 61.5% (16 of 26). HER-2 was positive for three cases (12%). The positivity of Ki67 and P53 were 87.5% and 45.8%, respectively. Twenty-four cases were followed up from 19 to 158 months. The prognosis of GRCC of the breast was significantly related with the number of positive lymph nodes (p free survival (p = 0.900) between GRCC of the breast and the usual invasive ductal carcinomas. GRCC of the breast may not have a worse

  16. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    International Nuclear Information System (INIS)

    Collins, Mark S.; Koyama, Takashi; Swee, Ronald G.; Inwards, Carrie Y.

    2003-01-01

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  17. Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

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    Mijušković Mirjana

    2016-01-01

    Full Text Available Background/Aim. Kidney injury molecule-1 (KIM-1 and aquaporin-1 (AQP-1 are potential early urinary biomarkers of clear renal cell carcinoma (cRCC. The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1 and urinary AQP-1 (uAQP-1 were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr] were significantly greater compared with controls (healthy volunteers (0.210 ± 0.082 ng/mgUcr (p = 0.0227. Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively. The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr compared with the control group (0.202 ± 0.078 ng/mgUcr (p = 0.0014. Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018

  18. LCN6, a novel human epididymal lipocalin

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    Soundararajan Rama

    2003-11-01

    Full Text Available Abstract Background The lipocalin (LCN family of structurally conserved hydrophobic ligand binding proteins is represented in all major taxonomic groups from prokaryotes to primates. The importance of lipocalins in reproduction and the similarity to known epididymal lipocalins prompted us to characterize the novel human epididymal LCN6. Methods and Results LCN6 cDNA was identified by database analysis in a comprehensive human library sequencing program. Macaca mulatta (rhesus monkey cDNA was obtained from an epididymis cDNA library and is 93% homologous to the human. The gene is located on chromosome 9q34 adjacent LCN8 and LCN5. LCN6 amino acid sequence is most closely related to LCN5, but the LCN6 beta-barrel structure is best modeled on mouse major urinary protein 1, a pheromone binding protein. Northern blot analysis of RNAs isolated from 25 human tissues revealed predominant expression of a 1.0 kb mRNA in the epididymis. No other transcript was detected except for weak expression of a larger hybridizing mRNA in urinary bladder. Northern hybridization analysis of LCN6 mRNA expression in sham-operated, castrated and testosterone replaced rhesus monkeys suggests mRNA levels are little affected 6 days after castration. Immunohistochemical staining revealed that LCN6 protein is abundant in the caput epithelium and lumen. Immunofluorescent staining of human spermatozoa shows LCN6 located on the head and tail of spermatozoa with the highest concentration of LCN6 on the post-acrosomal region of the head, where it appeared aggregated into large patches. Conclusions LCN6 is a novel lipocalin closely related to Lcn5 and Lcn8 and these three genes are likely products of gene duplication events that predate rodent-primate divergence. Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility.

  19. MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs.

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    Haowei He

    Full Text Available This study aims to profile dysregulated microRNA (miRNA expression in clear cell renal cell carcinoma (ccRCC and to identify key regulatory miRNAs in ccRCC.miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452 and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429 were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3' untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes.This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429 may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

  20. Clear cell hidradenocarcinoma of the ear helix: report of primary ear helix adnexal carcinoma with regional lymph node metastasis.

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    Bae, Tae Hui; Kang, Shin Hyuk; Kim, Han Koo; Kim, Woo Seob; Kim, Mi Kyung

    2014-07-01

    Clear cell hidradenocarcinoma is a rare tumor of eccrine sweat gland origin that has a predilection for the head and neck. It has an indolent growth pattern and a higher incidence of regional and distant metastases. Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. We report a case of an 89-year-old female patient with clear cell hidradenocarcinoma manifesting in the right ear helix that metastasized to the right parotid gland who was treated by wide local excision and radiation therapy.

  1. Clear Cell Carcinoma Presented as a Large Polypoid Mass Expanding the Vaginal Fornix: Report of Two Cases

    International Nuclear Information System (INIS)

    Kim, Ji Young; Cho, Jae Ho

    2012-01-01

    Primary clear cell carcinoma of the vagina or uterine cervix is a very rare tumor. We report radiologic findings of two cases of clear cell carcinoma, arising in the vagina and uterine cervix in a 16-year-old and a 26-year-old female. These were presented as a large polypoid mass with a stalk and expanding the vaginal fornix. One case with ultrasonography showed relatively homogeneous echoic solid mass; the other case with a CT showed heterogeneously and strongly enhancing mass. All of the two cases showed non-specific signal intensity with heterogeneous and strong enhancement on MRI.

  2. Clear Cell Carcinoma Presented as a Large Polypoid Mass Expanding the Vaginal Fornix: Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Young; Cho, Jae Ho [Dept. of Radiology, College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2012-11-15

    Primary clear cell carcinoma of the vagina or uterine cervix is a very rare tumor. We report radiologic findings of two cases of clear cell carcinoma, arising in the vagina and uterine cervix in a 16-year-old and a 26-year-old female. These were presented as a large polypoid mass with a stalk and expanding the vaginal fornix. One case with ultrasonography showed relatively homogeneous echoic solid mass; the other case with a CT showed heterogeneously and strongly enhancing mass. All of the two cases showed non-specific signal intensity with heterogeneous and strong enhancement on MRI.

  3. Seminal plasma aids the survival and cervical transit of epididymal ram spermatozoa.

    Science.gov (United States)

    Rickard, J P; Pini, T; Soleilhavoup, C; Cognie, J; Bathgate, R; Lynch, G W; Evans, G; Maxwell, W M C; Druart, X; de Graaf, S P

    2014-11-01

    Seminal plasma purportedly plays a critical role in reproduction, but epididymal spermatozoa are capable of fertilisation following deposition in the uterus, calling into question the biological requirement of this substance. Through a combination of direct observation of spermatozoa in utero using probe-based Confocal Laser Endomicroscopy, in vivo assessment of sperm fertility and in vitro analysis of various sperm functional parameters, this study investigated the role of seminal plasma in spermatozoa transit through the cervix of the ewe. Following deposition in the cervical os, epididymal spermatozoa previously exposed to seminal plasma displayed an enhanced ability to traverse the cervix as evidenced by both significantly higher pregnancy rates and numbers of spermatozoa observed at the utero-tubal junction when compared with epididymal spermatozoa not previously exposed to seminal plasma. The beneficial effect of seminal plasma on sperm transport was clearly localised to transit through the cervix as pregnancy rates of spermatozoa deposited directly into the uterus were unaffected by exposure to seminal plasma. This phenomenon was not explained by changes to sperm motion characteristics, as seminal plasma had no effect on the motility, kinematic parameters or mitochondrial membrane potential of spermatozoa. Rather, in vitro testing revealed that seminal plasma improved the ability of epididymal spermatozoa to penetrate cervical mucus recovered from ewes in oestrus. These results demonstrate that the survival and transport of ram spermatozoa through the cervix of the ewe is not linked to their motility or velocity but rather the presence of some cervical penetration trait conferred by exposure to seminal plasma. © 2014 Society for Reproduction and Fertility.

  4. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

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    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  5. Prognostic significance of overexpressed long non-coding RNA TUG1 in patients with clear cell renal cell carcinoma.

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    Wang, P-Q; Wu, Y-X; Zhong, X-D; Liu, B; Qiao, G

    2017-01-01

    The long non-coding RNAs (lncRNAs) study has gradually become one of the hot topics in the field of RNA biology. However, little is known about the pathological role of lncRNA TUG1 in clear cell renal cell carcinoma (ccRCC) patients. This study attempted to investigate the association of lncRNA TUG1 expression with progression and prognosis in ccRCC patients. Using qRT-PCR, the expression of TUG1 was measured in 203 ccRCC tissues and 45 adjacent non-cancerous tissues. Then, the relationships between TUG1 level and the clinicopathological factors of patients with ccRCC were analyzed. The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. The relative level of TUG1was significantly higher in ccRCC tissues compared to the adjacent non-tumor tissues (p TUG1 was associated significantly with histological grade, tumor stage, lymph node metastasis and distant metastasis (all p TUG1 expression levels were associated with a shorter overall survival (p TUG1 expression was an independent prognostic marker of poor outcome. These findings suggested that TUG1 may act as a tumor promoter in ccRCC and could serve as a potential therapeutic target for this tumor.

  6. Systematic expression analysis of the mitochondrial complex III subunits identifies UQCRC1 as biomarker in clear cell renal cell carcinoma.

    Science.gov (United States)

    Ellinger, Jörg; Gromes, Arabella; Poss, Mirjam; Brüggemann, Maria; Schmidt, Doris; Ellinger, Nadja; Tolkach, Yuri; Dietrich, Dimo; Kristiansen, Glen; Müller, Stefan C

    2016-12-27

    Mitochondrial dysfunction is common in cancer, and the mitochondrial electron transport chain is often affected in carcinogenesis. So far, few is known about the expression of the mitochondrial complex III (ubiquinol-cytochrome c reductase complex) subunits in clear cell renal cell carcinoma (ccRCC). In this study, the NextBio database was used to determine an expression profile of the mitochondrial complex III subunits based on published microarray studies. We observed that five out of 11 subunits of the complex III were downregulated in at least three microarray studies. The decreased mRNA expression level of UQCRFS1 and UQCRC1 in ccRCC was confirmed using PCR. Low mRNA levels UQCRC1 were also correlated with a shorter period of cancer-specific and overall survival. Furthermore, UQCRFS1 and UQCRC1 were also decreased in ccRCC on the protein level as determined using Western blotting and immunohistochemistry. UQCRC1 protein expression was also lower in ccRCC than in papillary and chromophobe subtypes. Analyzing gene expression and DNA methylation in The Cancer Genome Atlas cohort revealed an inverse correlation of gene expression and DNA methylation, suggesting that DNA hypermethylation is regulating the expression of UQCRC1 and UQCRFS1. Taken together, our data implicate that dysregulated UQCRC1 and UQCRFS1 are involved in impaired mitochondrial electron transport chain function.

  7. High perirenal fat thickness predicts a poor progression-free survival in patients with localized clear cell renal cell carcinoma.

    Science.gov (United States)

    Huang, Haichao; Chen, Shi; Li, Wei; Wu, Xiurong; Xing, Jinchun

    2018-01-04

    The aim of the study was to assess the association between the progression-free survival (PFS) and perirenal fat thickness (PFT) in a population of histopathologically confirmed, localized clear cell renal cell carcinoma (ccRCC) patients. We retrospectively enrolled 174 patients with localized ccRCC at our center between December 2009 and December 2015. The preoperative visceral fat area (VFA), PFT, and subcutaneous fat area (SFA) were evaluated. Kaplan-Meier curves were used to assess the differences in PFS between the high and the low PFT groups within sexes. Potential independent prognostic factors of PFS were identified by univariable and multivariable Cox analyses. During the follow-up period (median, 38 months), 27 patients (21 with high PFT and 6 with low PFT) experienced tumor progression. Kaplan-Meier curves revealed that high PFT was associated with a worse PFS than low PFT (P = 0.005). In the univariable Cox analyses, high VFA, high PFT, T stage, and the presence of sarcomatoid differentiation were significantly associated with a poor PFS. Moreover, both high PFT and VFA retained significance in the multivariable analysis. We first report the evidence that high PFT presents as an independent risk factor of tumor progression in localized ccRCC. We suggest that this noninvasive and readily available preoperative parameter may help in the risk stratification of ccRCC patients before surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Hypermethylation of the 16q23.1 Tumor Suppressor Gene ADAMTS18 in Clear Cell Renal Cell Carcinoma

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    Ben Xu

    2015-01-01

    Full Text Available To identify tumor suppressor genes (TSGs silenced by hypermethylation and discover new epigenetic biomarkers for early cancer detection. ADAMTS18, located at 16q23.1, has been reported to be a critical TSG in multiple primary tumors; however, this has not yet been verified in clear cell renal cell carcinoma (ccRCC. We explored epigenetic alterations in this gene in ccRCC and analyzed possible clinicopathological associations. We examined ADAMTS18 gene expression and methylation by semi-quantitative reverse transcription PCR (RT-PCR and methylation-specific polymerase chain reaction (MSP in 5 ccRCC-derived cell lines before and after treatment with 5-aza-2'-deoxycytidine (5-AzaC. MSP was further performed for 101 ccRCC primary tumors and 20 adjacent normal tissues. Some cell lines and specimens were examined by subsequent bisulfite genomic sequencing (BGS and real-time PCR. Further, we analyzed the relationship between the ADAMTS18 gene methylation and clinicopathological features, including short-term disease-free survival (DFS, in patients with ccRCC. ADAMTS18 down-regulation and hypermethylation were detected in the ccRCC-derived cell lines using RT-PCR and MSP. Treatment with 5-AzaC reversed the hypermethylation of the ADAMTS18 gene and restored its expression. Hypermethylation was further detected in 44 of 101 (43.6% primary tumors and 3 of 20 (15.0% adjacent normal tissues. However, a significant difference between both groups was observed (p = 0.02. BGS analysis and real-time PCR were subsequently performed to confirm the results of RT-PCR and MSP. Furthermore, the methylation status of ADAMTS18 was not significantly associated with gender, age, location, tumor diameter, pathological stage, nuclear grade or short-term DFS in patients with ccRCC (p > 0.05. The ADAMTS18 gene is often down-regulated by hypermethylation in ccRCC-derived cell lines and primary tumors, indicating its critical role as a TSG in ccRCC. We conclude that ADAMTS18

  9. NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1

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    Lei Wang

    2017-11-01

    Full Text Available Background Clear cell renal cell carcinoma (ccRCC is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone 1 alpha subcomplex 4-like 2 (NDUFA4L2 was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated. Methods The Gene Expression Omnibus (GEO and The Cancer Genome Atlas (TCGA data were mined to verify the change of NDUFA4L2 expression level in ccRCC tissues. The correlation between expression level of NDUFA4L2 and cell proliferation/apoptosis was explored by Gene Set Enrichment Analysis (GSEA. Protein-protein interaction (PPI network of NDUFA4L2 was constructed. Biological process and involved pathways of NDUFA4L2 were analyzed by gene ontology (GO and the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway. The transcription factors (TFs which can induce the expression of NDUFA4L2 were explored in clinical samples by correlation analysis and its regulation on the expression of NDUFA4L2 was verified by knockdown experiment. Results NDUFA4L2 was verified to be overexpressed in ccRCC tissues and its expression level was increased accordingly as the American Joint Committee on Cancer (AJCC stage progressed. A high NDUFA4L2 level predicted the poor prognosis of ccRCC patients and correlated with enhanced cell proliferation and anti-apoptosis. NDUFA4L2 may interact with 14 tumor-related proteins, participate in growth and death processes and be involved in ccRCC-related pathways, such as insulin-like growth factor 1 (IGF-1, mammalian target of Rapamycin (mTOR and phosphoinositide 3 kinase serine/threonine protein kinase (PI3K/AKT. ETS domain-containing protein ELK1 level positively correlated with the level of NDUFA4L2 in ccRCC tissues and ELK1 could regulate

  10. Differentiation of Renal Oncocytoma and Renal Clear Cell Carcinoma Using Relative CT Enhancement Ratio

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    An Ren

    2015-01-01

    Full Text Available Background: The difference between renal oncocytomas (RO and renal clear cell carcinomas (RCCs presents the greatest diagnostic challenge. The aim of this study was to retrospectively determine if RO and RCCs could be differentiated on computed tomography (CT images on the basis of their enhancement patterns with a new enhancement correcting method. Methods: Forty-six patients with a solitary renal mass who underwent total or partial nephrectomy were included in this study. Fourteen of those were RO and 32 were RCCs. All patients were examined with contrast-enhanced CT. The pattern and degree of enhancement were evaluated. We selected the area that demonstrated the greatest degree of enhancement of the renal lesion in the corticomedullary nephrographic and excretory phase images. Regions of interest (ROI were also placed in adjacent normal renal cortex for normalization. We used the values of the normal renal cortex that were measured at the same time as divisors. The ratios of lesion-to-renal cortex enhancement were calculated for all three phases. The Student′s t-test and Pearson′s Chi-square test were used for statistical analyses. Results: All RCCs masses showed contrast that appeared to be better enhanced than RO on all contrast-enhanced phases of CT imaging, but there was no significant difference in absolute attenuation values between these two diseases (P > 0.05. The ratio of lesion-to-cortex attenuation in the corticomedullary phase showed significantly different values between RO and RCCs. The degree of contrast enhancement in RCCs was equal to or greater than that of the normal renal cortex, but it was less than that of the normal cortex in RO in the corticomedullary phase. The ratio of lesion-to-cortex attenuation in the corticomedullary phase was higher than the cut off value of 1.0 in most RCCs (84%, 27/32 and lower than 1.0 in most RO (93%, 13/14 (P < 0.05. In the nephrographic phase, the ratio of lesion-to-cortex attenuation

  11. Kinase Gene Expression Profiling of Metastatic Clear Cell Renal Cell Carcinoma Tissue Identifies Potential New Therapeutic Targets.

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    Pooja Ghatalia

    Full Text Available Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR and mammalian target of rapamycin (mTOR improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC, but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T, matched normal kidney (N and metastatic tumor tissue (M may assist in identifying drivers of metastasis and prioritizing therapeutic targets. We compared the expression of 519 kinase genes using NanoString in T, N and M in 35 patients to discover genes over-expressed in M compared to T and N tissue. RNA-seq data derived from ccRCC tumors in The Cancer Genome Atlas (TCGA were used to demonstrate differential expression of genes in primary tumor tissue from patients that had metastasis at baseline (n = 79 compared to those that did not develop metastasis for at least 2 years (n = 187. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Of 10 kinase genes overexpressed in metastases compared to primary tumor in the discovery cohort, 9 genes were also differentially expressed in TCGA primary tumors with metastasis at baseline compared to primary tumors without metastasis for at least 2 years: EPHB2, AURKA, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7 and MAP3K8; p<0.001. The top pathways overexpressed in M tissue were pyridoxal 5'-phosphate salvage, salvage pathways of pyrimidine ribonucleotides, NF-kB signaling, NGF signaling and cell cycle control of chromosomal replication. The 9 kinase genes validated to be over-expressed in metastatic ccRCC may represent currently unrecognized but potentially actionable therapeutic targets that warrant functional validation.

  12. Analysis of epididymal sperm maturation by MALDI profiling and top-down mass spectrometry.

    Science.gov (United States)

    Labas, Valérie; Spina, Lucie; Belleannee, Clémence; Teixeira-Gomes, Ana-Paula; Gargaros, Audrey; Dacheux, Françoise; Dacheux, Jean-Louis

    2015-01-15

    The fertilization ability of male gametes is achieved after their transit through the epididymis where important post-gonadal differentiation occurs in different cellular compartments. Most of these maturational modifications occur at the protein level. The epididymal sperm maturation process was investigated using the ICM-MS (Intact Cell MALDI-TOF MS) approach on boar spermatozoa isolated from four different epididymal regions (immature to mature stage). Differential and quantitative MALDI-TOF profiling for whole cells or sub-cellular fractions was combined with targeted top-down MS in order to identify endogenous biomolecules. Using this approach, 172m/z peaks ranging between 2 and 20kDa were found to be modified during maturation of sperm. Using top-down MS, 62m/z were identified corresponding to peptidoforms/proteoforms with post-translational modifications (MS data are available via ProteomeXchange with identifier PXD001303). Many of the endogenous peptides were characterized as N-, C-terminal sequences or internal fragments of proteins presenting specific cleavages, suggesting the presence of sequential protease activities in the spermatozoa. This is the first time that such proteolytic activities could be evidenced for various sperm proteins through quantification of their proteolytic products. ICM-MS/top-down MS thus proved to be a valid approach for peptidome/degradome studies and provided new contributions to understanding of the maturation process of the male gamete involved in the development of male fertility. This peptidomic study (i) characterized the peptidome of epididymal spermatozoa from boar (Sus scrofa); (ii) established characteristic molecular phenotypes distinguishing degrees of maturation of spermatozoa during epididymal transit, and (iii) revealed that protease activities were at the origin of numerous peptides from known and unknown proteins involved in sperm maturation and/or fertility processes. Copyright © 2014 Elsevier B.V. All

  13. Assessment of resistive index in acute epididymitis on doppler sonography

    International Nuclear Information System (INIS)

    Jung, Seung Mun; Cho, Kyoung Sik; Choi, Hyo Kyeong; Lee, Moon Gyu; Auh, Yong Ho; Kim, Chung Soo

    1995-01-01

    This study was aimed to review findings of gray-scale ultrasonography and to assess the diagnostic value of the resistive index (RI) in patients with acute epididymitis by comparing with that in normal volunteers. Gray-scale ultrasonogram was reviewed in nine patients with acute epididymitis for echogenicity, size and reactive hydrocele. Normal values of resistive index (RI) were obtained in 20 epididymides from 10 volunteers (aged 20-28, mean 23.7). Nine patients of epididymitis (aged 18-67, mean 37.2) were examinated with color Doppler sonography and RI was measured at 11 sites on epididymal arteries. For the prediction of acute epididymitis, accuracy, sensitivity and specificity were calculated at the cut-off value of RI in 0.65 and 0.70. Gray-scale ultrasonography showed echogenicity that was variable among the 9 cases (hyperechoic 2 cases, isoechoic 2, hypoechoic 5), enlargement of epididymis in 8, and reactive hydrocele in 8 cases. Normal volunteers displayed color Doppler signals in 14 out of 20. The range of RI in normal volunteers were between 0.64 and 1.00 (mean, 0.79 ± SD 0.10). In patients with acute epididymitis, color Doppler signals were detected in all patients. The range of RI in epididymitis were 0.40-0.68 (mean, 0.56 ± SD 0.10). At cut-off RI value of 0.65, accuracy was 88%, sensitivity 81.1%, and specificity 92.7%. At cut-off value of 0.70 accuracy was 92%, sensitivity 100%, and specificity 85.7%. In addition to the findings of gray-scale ultrasonography, resistive index and color flow changes are valuable in diagnosing acute epididymitis

  14. Assessment of resistive index in acute epididymitis on doppler sonography

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seung Mun; Cho, Kyoung Sik; Choi, Hyo Kyeong; Lee, Moon Gyu; Auh, Yong Ho; Kim, Chung Soo [Asan Medical Center University of Ulsan, College of Medicine, Seoul (Korea, Republic of)

    1995-06-15

    This study was aimed to review findings of gray-scale ultrasonography and to assess the diagnostic value of the resistive index (RI) in patients with acute epididymitis by comparing with that in normal volunteers. Gray-scale ultrasonogram was reviewed in nine patients with acute epididymitis for echogenicity, size and reactive hydrocele. Normal values of resistive index (RI) were obtained in 20 epididymides from 10 volunteers (aged 20-28, mean 23.7). Nine patients of epididymitis (aged 18-67, mean 37.2) were examinated with color Doppler sonography and RI was measured at 11 sites on epididymal arteries. For the prediction of acute epididymitis, accuracy, sensitivity and specificity were calculated at the cut-off value of RI in 0.65 and 0.70. Gray-scale ultrasonography showed echogenicity that was variable among the 9 cases (hyperechoic 2 cases, isoechoic 2, hypoechoic 5), enlargement of epididymis in 8, and reactive hydrocele in 8 cases. Normal volunteers displayed color Doppler signals in 14 out of 20. The range of RI in normal volunteers were between 0.64 and 1.00 (mean, 0.79 {+-} SD 0.10). In patients with acute epididymitis, color Doppler signals were detected in all patients. The range of RI in epididymitis were 0.40-0.68 (mean, 0.56 {+-} SD 0.10). At cut-off RI value of 0.65, accuracy was 88%, sensitivity 81.1%, and specificity 92.7%. At cut-off value of 0.70 accuracy was 92%, sensitivity 100%, and specificity 85.7%. In addition to the findings of gray-scale ultrasonography, resistive index and color flow changes are valuable in diagnosing acute epididymitis.

  15. Genome-wide profiling of peroxisome proliferator-activated receptor γ in primary epididymal, inguinal, and brown adipocytes reveals depot-selective binding correlated with gene expression

    DEFF Research Database (Denmark)

    Siersbæk, Majken; Loft, Anne; Jørgensen, Mads Malik Aagaard

    2012-01-01

    epididymal, inguinal, and brown adipose tissues. While these PPARγ binding profiles are overall similar, there are clear depot-selective binding sites. Most PPARγ binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPARγ binding...... sites that are specific to the primary cells, and these tend to be located in closed chromatin regions in 3T3-L1 adipocytes. The depot-selective binding of PPARγ is associated with highly depot-specific gene expression. This indicates that PPARγ plays a role in the induction of genes characteristic...... of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPARγ lineage-specific recruitment even when differentiated in vitro....

  16. Acute epididymitis in Greek children: a 3-year retrospective study.

    Science.gov (United States)

    Sakellaris, George S; Charissis, Giorgos C

    2008-07-01

    The aim of the study was to compare historical features, physical examination findings, and testicular color Doppler ultrasound in pediatric patients with epididymitis compared to testicular torsion and torsion of the appendix testes. A retrospective review of the medical records of 66 boys presenting with clinical aspects of acute scrotum over a 3-year period was performed. Sixty-six patients were included in the study (29 with epididymitis, 8 with testicular torsion and 12 with torsion of the appendix testis, 4 with scrotal abscesses, 5 with scrotal swelling, and 1 with inflamed epididymal cyst). The duration of symptoms ranged from 6 h to 4 days with a peak on the second day. Urine cultures and viral testes were negative in all patients. Color Doppler ultrasound was diagnostic for epididymitis in 28 patients (96.6%). Systemic intravenous antibiotics were given in all 29 patients with epididymitis. No patient showed signs of testicular atrophy in the follow-up. The increasing incidence of epididymitis should question the policy of routine exploration of the acute scrotum in children. The history and physical examination cannot reliably identify those boys who can be managed conservatively. Color Doppler ultrasound is a useful adjunct in the evaluation of the acute scrotum when physical findings are equivocal but it can also be misleading.

  17. Quality of canine spermatozoa retrieved by percutaneous epididymal sperm aspiration.

    Science.gov (United States)

    Varesi, S; Vernocchi, V; Faustini, M; Luvoni, G C

    2013-02-01

    To investigate the feasibility of percutaneous epididymal sperm aspiration in dogs and whether it might provide a population of epididymal spermatozoa similar to the population that can be obtained by processing isolated epididymis caudae. Concentration and total sperm number, motility, morphology and acrosomal integrity of spermatozoa retrieved by percutaneous epididymal sperm aspiration, in vitro aspiration and mincing of the cauda of the epididymis were compared. Percutaneous epididymal sperm aspiration is a feasible procedure to retrieve a population of spermatozoa in dogs. Quality is similar to that of spermatozoa collected in vitro, although a wide variation amongst animals was observed. In case of ejaculation failure due to pathological conditions in dogs, the collection of spermatozoa from the cauda of the epididymis could be an option for providing gametes for assisted reproductive technologies. Percutaneous epididymal sperm aspiration can be used in dogs with compromised reproductive performance, in which orchiectomy cannot be performed for medical or owner reasons. Further studies aimed to investigate whether the percutaneous epididymal sperm aspiration technique might be feasible for repeated semen collection and to accurately evaluate side effects are required. © 2013 British Small Animal Veterinary Association.

  18. Clear retainer

    Directory of Open Access Journals (Sweden)

    Priyakorn Chaimongkol

    2017-01-01

    Full Text Available A clear retainer is a removable retainer that is popular in the present day. Compared with conventional fixed and removable orthodontic retainers, it is a more esthetic, comfortable, and inexpensive appliance. Although several studies have been published about clear retainers, it could be difficult to interpret the results because of the variety of study designs, sample sizes, and research methods. This article is intended to compile the content from previous studies and discuss advantages, disadvantages, fabrication, insertion, and adjustment. Moreover, the effectiveness in maintaining dental position, occlusion, retention protocols, thickness, and survival rate of clear retainers is discussed.

  19. Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns?

    Directory of Open Access Journals (Sweden)

    Duygu Kankaya

    2016-01-01

    Full Text Available Introduction: The aim of this study was to assess whether epidermal growth factor receptor (EGFR overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC and whether its prognostic significance was affected by immunohistochemical expression patterns. Materials and Methods: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG as low-NG (NG1, 2 or high NG (NG3, 4, and by pathological stage as localized (pT1, 2, or locally invasive (pT3, 4. Clinical disease was grouped by clinical stage as early stage (stage I, II, or late stage (stage III, IV. Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt , and membranous (EGFR Mem staining. Results: EGFR Cyt correlated with high NG (P = 0.001, lymphovascular invasion (P = 0.028, regional lymph node involvement (P = 0.027, metastasis (P = 0.001, late stage (P = 0.003, cancer-specific death (P = 0.036, and was a predictor for disease-specific survival (P = 0.012 whereas EGFR Mem correlated with only local invasion (P = 0.021 and perirenal invasion (P = 0.009 and did not show any correlation with cancer-specific death or disease specific survival. Conclusion: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients.

  20. Application of the Stage, Size, Grade, and Necrosis (SSIGN) Score for Clear Cell Renal Cell Carcinoma in Contemporary Patients.

    Science.gov (United States)

    Parker, William P; Cheville, John C; Frank, Igor; Zaid, Harras B; Lohse, Christine M; Boorjian, Stephen A; Leibovich, Bradley C; Thompson, R Houston

    2017-04-01

    The tumor stage, size, grade, and necrosis (SSIGN) score was originally defined using patients treated with radical nephrectomy (RN) between 1970 and 1998 for clear cell renal cell carcinoma (ccRCC), excluding patients treated with partial nephrectomy (PN). To characterize the original SSIGN score cohort with longer follow-up and evaluate a contemporary series of patients treated with RN and PN. Retrospective single-institution review of 3600 consecutive surgically treated ccRCC patients grouped into three cohorts: original RN, contemporary (1999-2010) RN, and contemporary PN. RN or PN. The association of the SSIGN score with risk of death from RCC was assessed using a Cox proportional hazards regression model, and predictive ability was summarized with a C-index. The SSIGN scores differed significantly between the original RN, contemporary RN, and contemporary PN cohorts (pcontemporary RN, and 1.70 for contemporary PN; all pcontemporary RN, and contemporary PN, respectively. After accounting for an era-specific improvement in survival among RN patients (HR: 0.53 for contemporary vs original RN; pcontemporary RN and PN patients, the score retained strong predictive ability. These results should assist in patient counseling and help guide surveillance for ccRCC patients treated with RN or PN. We evaluated the validity of a previously described tool to predict survival following surgery in contemporary patients with kidney cancer. We found that this tool remains valid even when extended to patients significantly different than were initially used to create the tool. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  1. Promoter Methylation of CDO1 Identifies Clear-Cell Renal Cell Cancer Patients with Poor Survival Outcome.

    Science.gov (United States)

    Deckers, Ivette A G; Schouten, Leo J; Van Neste, Leander; van Vlodrop, Iris J H; Soetekouw, Patricia M M B; Baldewijns, Marcella M L L; Jeschke, Jana; Ahuja, Nita; Herman, James G; van den Brandt, Piet A; van Engeland, Manon

    2015-08-01

    In this era of molecular diagnostics, prediction of clear-cell renal cell cancer (ccRCC) survival requires optimization, as current prognostic markers fail to determine individual patient outcome. Epigenetic events are promising molecular markers. Promoter CpG island methylation of cysteine dioxygenase type 1 (CDO1), which was identified as prognostic marker for breast cancer, is studied as a potential marker for ccRCC survival. We collected primary tissues of 365 ccRCC cases identified within the prospective Netherlands Cohort Study (NLCS). In this population-based series, CDO1 promoter methylation was observed in 124 of 324 (38.3%) patients with successful methylation-specific PCR analysis. Kaplan-Meier curves and Wilcoxon tests were used to evaluate 10-year ccRCC-specific survival. Cox regression analysis was used to obtain crude and multivariate HRs and 95% confidence intervals (CI). The relative prognostic value of multivariate models with and without CDO1 promoter methylation was compared using likelihood-ratio tests. Patients with CDO1 promoter methylation have a significantly poorer survival than those without (Wilcoxon P = 0.006). Differences in survival were independent of other prognostic factors, including age and sex (HR, 1.66; 95% CI, 1.12-2.45) and TNM stage, tumor size, and Fuhrman grade (HR, 1.89; 95% CI, 1.25-2.85). Multivariate models performed better with than without CDO1 promoter methylation status (likelihood-ratio P = 0.003). Survival curves were validated in an independent series of 280 ccRCC cases from The Cancer Genome Atlas (TCGA; Wilcoxon P promoter methylation may not substitute common prognostic makers to predict ccRCC survival, but offers additional, relevant prognostic information, indicating that it might be a novel molecular marker to determine ccRCC prognosis. ©2015 American Association for Cancer Research.

  2. Differing von Hippel Lindau genotype in paired primary and metastatic tumors in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Susan A.J. Vaziri

    2012-05-01

    Full Text Available In sporadic clear cell renal cell carcinoma (CCRCC, the von Hippel Lindau (VHL gene is inactivated by mutation or methylation in the majority of primary (P tumors. Due to differing effects of wild-type (WT and mutant (MT VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization (CGH analysis studies have reported genetic differences between paired P and metastatic (M tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s in patients with CCRCC. Using paraffin embedded specimens, genomic DNA from microdissected samples (>80% tumor of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GeneBank Accession No. AF010238. Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40% patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC.

  3. MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma

    Science.gov (United States)

    Winter, Stefan; Rausch, Steffen; Hennenlotter, Jörg; Nies, Anne T.; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Kruck, Stephan; Schwab, Matthias; Schaeffeler, Elke

    2015-01-01

    Cluster of differentiation 147 (CD147/BSG) is a transmembrane glycoprotein mediating oncogenic processes partly through its role as binding partner for monocarboxylate transporter MCT4/SLC16A3. As demonstrated for MCT4, CD147 is proposed to be associated with progression in clear cell renal cell carcinoma (ccRCC). In this study, we evaluated the prognostic relevance of CD147 in comparison to MCT4/SLC16A3 expression and DNA methylation. Methods CD147 protein expression was assessed in two independent ccRCC-cohorts (n = 186, n = 59) by immunohistochemical staining of tissue microarrays and subsequent manual as well as automated software-supported scoring (Tissue Studio, Definien sAG). Epigenetic regulation of CD147 was investigated using RNAseq and DNA methylation data of The Cancer Genome Atlas. These results were validated in our cohort. Relevance of prognostic models for cancer-specific survival, comprising CD147 and MCT4 expression or SLC16A3 DNA methylation, was compared using chi-square statistics. Results CD147 protein expression generated with Tissue Studio correlated significantly with those from manual scoring (P BSG promoter was not associated with expression. Comparison of prognostic relevance of CD147/BSG and MCT4/SLC16A3, showed higher significance for MCT4 expression and superior prognostic power for DNA methylation at specific CpG-sites in the SLC16A3 promoter (e.g. CD147 protein: P = 0.7780, Harrell's c-index = 53.7% vs. DNA methylation: P = 0.0076, Harrell's c-index = 80.0%). Conclusions Prognostic significance of CD147 protein expression could not surpass that of MCT4, especially of SLC16A3 DNA methylation, corroborating the role of MCT4 as prognostic biomarker for ccRCC. PMID:26384346

  4. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  5. Vitamin D3 and androgen receptors in testis and epididymal region of roosters (Gallus domesticus) as affected by epididymal lithiasis.

    Science.gov (United States)

    Oliveira, André G; Dornas, Rubem A P; Kalapothakis, Evanguedes; Hess, Rex A; Mahecha, Germán A B; Oliveira, Cleida A

    2008-12-01

    Epididymal lithiasis is a dysfunction characterized by formation of calcium-rich stones in the epididymal region of roosters, associated with decreased serum testosterone and loss of fertility. The segment most affected by the lithiasis is the efferent ductules, which, in birds, are responsible for reabsorption of calcium and luminal fluid. Therefore, we postulated that epididymal lithiasis could result from local impairment of calcium or fluid homeostasis, culminating in initiation of stone formation. Transepithelial calcium transport depends on vitamin D3 and vitamin D3 receptor (VDR). Based on the fact that VDR are present in efferent ductules, possible changes in the pattern of VDR in roosters affected by the epididymal lithiasis was investigated, to start to gain an understanding of the molecular mechanisms involved in the development of calcium stones. To evaluate the potential impact of androgen reduction, changes in androgen receptor (AR) were also investigated. Both VDR and AR were increased in specific segments of the epididymal region, whereas no alterations were found in the testes of affected animals. The increase in VDR was most likely due to an increase in the number of VDR-positive mononuclear leukocyte infiltrates found in the connective tissue followed by an increase in epithelial receptors. The AR were increased, however, mainly in the epididymal duct epithelium. These results suggest that the vitamin D3 and androgen responsive system may be directly/indirectly involved in the development of the disease.

  6. Sperm treatment affects capacitation parameters and penetration ability of ejaculated and epididymal boar spermatozoa.

    Science.gov (United States)

    Matás, C; Sansegundo, M; Ruiz, S; García-Vázquez, F A; Gadea, J; Romar, R; Coy, P

    2010-11-01

    This work was designed to study how this ability is affected by different sperm treatments routinely used for in vitro fertilization (IVF) assay. In this study, boar sperm samples from epididymal or ejaculated origin were processed by three different methods: left unwashed (NW group), washed in Dulbecco's phosphate-buffered saline supplemented with 0.1% BSA (BSA group), and washed on a Percoll(®) gradient (PERCOLL group). After preparation of semen samples, changes in motility patterns were studied by CASA, calcium uptake by spectrofluorimetry, and ROS generation, spontaneous acrosome reaction, and lipid disorder by means of flow cytometry. Finally IVF assays were also performed with the different semen samples and penetrability results evaluated at 2 and 4 h post insemination (hpi). Independently of the sperm treatment, epididymal spermatozoa showed higher values of progressive motility, percentage of live cells with low lipid disorder, and penetration ability at 4 hpi than the corresponding ejaculated spermatozoa. Ejaculated spermatozoa showed higher levels of calcium uptake, ROS generation and percentage of spontaneous acrosome reaction than epididymal sperm. Regarding sperm treatments, PERCOLL group showed the highest values for some motility parameters (linearity of the curvilinear trajectory, straightness, and average path velocity/curvilinear velocity), ROS generation and penetration ability at 2 and 4 hpi; however this same group showed the lowest values for sperm curvilinear velocity and lateral head displacement. From all experimental groups, ejaculated-PERCOLL-treated spermatozoa showed the highest fertilization ability after 2 hpi. Results suggest that capacitation pathways can be regulated by suitable treatments making the ejaculated sperm able to reach capacitation and fertilize oocytes in similar levels than epididymal spermatozoa, although most of the studied capacitation-associated changes do not correlate with this ability. Copyright © 2010

  7. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

    Science.gov (United States)

    Hampras, Shalaka S.; Sucheston-Campbell, Lara E.; Cannioto, Rikki; Chang-Claude, Jenny; Modugno, Francesmary; Dörk, Thilo; Hillemanns, Peter; Preus, Leah; Knutson, Keith L.; Wallace, Paul K.; Hong, Chi-Chen; Friel, Grace; Davis, Warren; Nesline, Mary; Pearce, Celeste L.; Kelemen, Linda E.; Goodman, Marc T.; Bandera, Elisa V.; Terry, Kathryn L.; Schoof, Nils; Eng, Kevin H.; Clay, Alyssa; Singh, Prashant K.; Joseph, Janine M.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Cook, Linda S.; Cramer, Daniel W.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; du Bois, Andreas; Dürst, Matthias; Easton, Doug; Eccles, Diana; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hogdall, Claus; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Klapdor, Rüdiger; Kolomeyevskaya, Nonna; Krakstad, Camilla; Kjaer, Susanne K.; Kruszka, Bridget; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashikant; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Liu, Song; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valeria; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Moes-Sosnowska, Joanna; Narod, Steven A.; Nedergaard, Lotte; Nevanlinna, Heli; Nickels, Stefan; Olson, Sara H.; Orlow, Irene; Weber, Rachel Palmieri; Paul, James; Pejovic, Tanja; Pelttari, Liisa M.; Perkins, Barbara; Permuth-Wey, Jenny; Pike, Malcolm C.; Plisiecka-Halasa, Joanna; Poole, Elizabeth M.; Risch, Harvey A.; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schmitt, Kristina; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Tangen, Ingvild L.; Teo, Soo-Hwang; Thompson, Pamela J.; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; Tyrer, Jonathan; van Altena, Anna M.; Vergote, Ignace; Vierkant, Robert A.; Walsh, Christine; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Gayther, Simon A.; Ramus, Susan J.; Sellers, Thomas A.; Schildkraut, Joellen M.; Phelan, Catherine M.; Berchuck, Andrew; Chenevix-Trench, Georgia; Cunningham, Julie M.; Pharoah, Paul P.; Ness, Roberta B.; Odunsi, Kunle; Goode, Ellen L.; Moysich, Kirsten B.

    2016-01-01

    Background Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. Methods In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. Results The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with (p = 0.001) and clear cell EOC. Gene associations with histotypes at< 0.05 included:(p = 0.005 and = 0.008, serous and high-grade serous, respectively), (p = 0.035, endometrioid and mucinous), (p = 0.03, mucinous), (p = 0.022, clear cell), (p = 0.021 endometrioid) and (p = 0.017 and = 0.025, endometrioid and mucinous, respectively). Conclusions Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients. PMID:27533245

  8. Rsp5/Nedd4 clears cells of heat-damaged proteins.

    Science.gov (United States)

    Sommer, Thomas; Weber, Annika; Jarosch, Ernst

    2014-12-01

    Protein quality control systems protect cells from proteotoxicity caused by the accumulation of aberrantly folded polypeptides. The Rsp5 ubiquitin ligase (mammalian homologue Nedd4) is now identified as a major constituent of a clearance pathway that degrades misfolded cytosolic proteins after exposure to heat.

  9. Rsp5/Nedd4 clears cells of heat-damaged proteins

    OpenAIRE

    Sommer, T.; Weber, A.; Jarosch, E.

    2014-01-01

    Protein quality control systems protect cells from proteotoxicity caused by the accumulation of aberrantly folded polypeptides. The Rsp5 ubiquitin ligase (mammalian homologue Nedd4) is now identified as a major constituent of a clearance pathway that degrades misfolded cytosolic proteins after exposure to heat.

  10. Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    Full Text Available Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC. This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened

  11. Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

    Science.gov (United States)

    Thiesen, H-J; Steinbeck, F; Maruschke, M; Koczan, D; Ziems, B; Hakenberg, O W

    2017-01-01

    Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

  12. Stratification of clear cell renal cell carcinoma (ccRCC genomes by gene-directed copy number alteration (CNA analysis.

    Directory of Open Access Journals (Sweden)

    H-J Thiesen

    Full Text Available Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs presented in 48 clear cell renal cell carcinoma (ccRCC genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25 and 20 G3 (ratio 0.58. Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes has been successfully validated on published Swiss data (GSE19949 leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and

  13. Methylation of 10 miRNA genes in clear cell renal cell carcinoma and their diagnostic value

    Directory of Open Access Journals (Sweden)

    V. I. Loginov

    2017-01-01

    Full Text Available Introduction. Clear cell renal cell carcinoma (ccRCC is characterized by the high (30–40 % of cases frequency of lethal outcomes which at metastasis reaches 90 %. Lack of efficient diagnostics at early stages of a disease indicates the need of searching on new ccRCC markers.Objective: for definition of methylation role of some tumor suppressor microRNA (miRNA genes in ccRCC pathogenesis and progression and marker identification for ccRCC diagnostics and metastasis predictions.Materials and methods. The alterations of methylation status of 10 miRNA genes were determined by methylation specific polymerase chain reaction in tumor DNA samples and matched histologically unchanged tissues from 70 patients with ccRCC, as well as in DNA samples of kidney tissues from 19 post-mortal individuals without cancer history. Methylation of MIR MIR-107, -130b and -148a genes in ccRCC was studied for the first time.Results. It was shown that 8 miRNA genes (MIR-9-1/3, -34b/c, -124a-1/2/3, -129-2, -130b were methylated in ccRCC tumors with significantly higher frequency than in the matched histologically unchanged kidney tissues. It was established the association of methylation of 4 miRNA genes (MIR-107, -124a-3, -129-2, -130b with ccRCC progression (stage, tumor size, differentiation grade, including metastasis in the lymph nodes or distant organs, revealed for MIR-107 and -129-2. The association of MIR-107 and -130b methylation with progression of ccRCC is shown for the first time. Potential marker systems are made for ccRCC diagnostics using tumor biopsy; according to the ROC analysis, systems from 4 and 5 genes (MIR-9-1, -4b/c, -124a-3, -129-2/with addition of MIR-130b are characterized by high clinical sensitivity of 90 % and specificity of 94 % (area under ROC curve 0.93 and 0.94. Conclusion. The received results will form the basis of noninvasive ccRCC diagnostics further development. To conclude, it is shown the association of methylation of 9

  14. New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus).

    Science.gov (United States)

    Dacheux, Jean-Louis; Dacheux, Francoise; Labas, Valerie; Ecroyd, Heath; Nixon, Brett; Jones, Russell C

    2009-01-01

    The platypus epididymal proteome is being studied because epididymal proteins are essential for male fertility in mammals and it is considered that knowledge of the epididymal proteome in an early mammal would be informative in assessing the convergence and divergence of proteins that are important in the function of the mammalian epididymis. Few of the epididymal proteins that have been identified in eutherian mammals were found in platypus caudal epididymal fluid, and the major epididymal proteins in the platypus (PXN-FBPL, SPARC and E-OR20) have never been identified in the epididymis of any other mammal.

  15. L1CAM expression associates with poor outcome in endometrioid, but not in clear cell ovarian carcinoma.

    Science.gov (United States)

    Soovares, Piret; Pasanen, Annukka; Bützow, Ralf; Lassus, Heini

    2017-09-01

    Our aim was to study the expression of L1CAM in endometrioid and clear cell ovarian carcinomas and to evaluate its correlation with clinical parameters and patient prognosis. Tissue microarray -based immunohistochemical analysis of L1CAM expression was performed in 249 endometrioid and 140 clear cell ovarian carcinomas. Concurrent endometrial carcinoma was found in 57 of these patients. L1CAM expression was found in 15% of endometrioid and 23% of clear cell ovarian carcinomas. L1CAM expression was strongly associated with poor disease-specific overall survival and poor disease-free survival in endometrioid (povarian carcinomas. Significant association of L1CAM expression with poor overall survival was observed in grade 1-2 carcinomas (povarian carcinomas, L1CAM expression was associated with aggressive tumor characteristics, such as higher grade and stage, and incomplete response to primary therapy. However, L1CAM expression was not an independent prognostic factor for overall or disease-free survival. Of the 57 patients with concurrent endometrial carcinoma L1CAM positivity was found in 4 cases both in the ovarian and endometrial tumors, and in 3 cases only in the endometrial tumor. All these seven patients with L1CAM positive tumors had poor outcome. L1CAM expression could serve as a biomarker for predicting clinical outcome and response to therapy in patients with endometrioid ovarian carcinoma, but not in clear cell carcinomas. L1CAM positivity also predicts poor outcome in patients with concurrent endometrioid ovarian and endometrial carcinomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection.

    Directory of Open Access Journals (Sweden)

    Babs E Verstrepen

    Full Text Available A single correlate of effective vaccine protection against chronic HCV infection has yet to be defined. In this study, we analyzed T-cell responses in four chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b. Viral clearance was observed in one animal, while the other three became chronically infected. In the animal that cleared infection, NS3-specific CD8 T-cell responses were observed to be more potent in terms of frequency and polyfunctionality of cytokine producing cells. Unique to this animal was the presence of killing-competent CD8 T-cells, specific for NS3 1258-1272, being presented by the chimpanzee MHC class I molecule Patr-A*03∶01, and a high affinity recognition of this epitope. In the animals that became chronically infected, T-cells were able to produce cytokines against the same peptide but no cytolysis could be detected. In conclusion, in the animal that was able to clear HCV infection not only cytokine production was observed but also cytolytic potential against specific MHC class I/peptide-combinations.

  17. Study on the incidence of testicular and epididymal appendages in patients with cryptorchidism

    Directory of Open Access Journals (Sweden)

    Favorito Luciano A.

    2004-01-01

    Full Text Available OBJECTIVE: To study the incidence of testicular and epididymal appendages in patients with cryptorchidism. MATERIALS AND METHODS: We studied 65 patients with cryptorchidism, totalizing 83 testes and 40 patients who had prostate adenocarcinoma and hydrocele (control group, totalizing 55 testes. The following situations were analyzed: I absence of testicular and epididymal appendages, II presence of testicular appendage only, III presence of epididymal appendage, IV presence of testicular and epididymal appendage, V presence of 2 epididymal appendages and 1 testicular appendage and VI presence of paradidymis or vas aberrans of Haller. RESULTS: In patients with cryptorchidism we found testicular appendages in 23 cases (41.8%, epididymal appendages in 9 (16.3%, testicular and epididymal appendage in 8 (14.5%, 2 epididymal appendages and 1 testicular in 1 (1.8% and absence of appendages in 14 (25.4%. In the control group, we found testicular appendages in 29 (34.9%, epididymal appendages in 19 (22.8%, testicular and epididymal appendage in 7 (8.4%, and absence of appendages in 28 (33.7%, we did not find 2 epididymal appendages in this group, and none of the patients in the 2 groups presented paradidymis or vas aberrans of Haller. CONCLUSION: The occurrence of testicular and epididymal appendages is quite variable. There was no statistically significant difference in the incidence and distribution of the testicular and epididymal appendages between patients with cryptorchidism and those from the control group.

  18. Identification of peroxiredoxin-5 in bovine cauda epididymal sperm.

    Science.gov (United States)

    Nagdas, Subir K; Buchanan, Teresa; Raychoudhury, Samir

    2014-02-01

    Developing spermatozoa require a series of posttesticular modifications within the luminal environment of the epididymis to achieve maturation; this involves several surface modifications including changes in plasma membrane lipids, proteins, carbohydrates, and alterations in the outer acrosomal membrane. Epididymal maturation can therefore allow sperm to gain forward motility and fertilization capabilities. The objective of this study was to identify maturation-dependent protein(s) and to investigate their role with the production of functionally competent spermatozoa. Lectin blot analyses of caput and cauda sperm plasma membrane fractions identified a 17.5 kDa wheat germ agglutinin (WGA)-binding polypeptide present in the cauda sperm plasma membrane not in the caput sperm plasma membrane. Among the several WGA-stained bands, the presence of a 17.5 kDa WGA-binding polypeptide band was detected only in cauda epididymal fluid not in caput epididymal fluid suggesting that the 17.5 kDa WGA-binding polypeptide is secreted from the cauda epididymis and binds to the cauda sperm plasma membrane during epididymal transit. Proteomic identification of the 17.5 kDa polypeptide yielded 13 peptides that matched the sequence of peroxiredoxin-5 (PRDX5) protein (Bos Taurus). We propose that bovine cauda sperm PRDX5 acts as an antioxidant enzyme in the epididymal environment, which is crucial in protecting the viable sperm population against the damage caused by endogeneous or exogeneous peroxide.

  19. Progression of Epididymal Maldevelopment Into Hamartoma-like Neoplasia in VHL Disease

    Directory of Open Access Journals (Sweden)

    Gautam U. Mehta

    2008-10-01

    Full Text Available Inactivation of the von Hippel-Lindau (VHL gene and activation of the hypoxia-inducible factor (HIF in susceptible cells precedes formation of tumorlets and frank tumor in the epididymis of male VHL patients. We performed detailed histologic and molecular pathologic analysis of tumor-free epididymal tissues from VHL patients to obtain further insight into early epididymal tumorigenesis. Four epididymides from two VHL patients were serially sectioned to allow for three-dimensional visualization of morphologic changes. Areas of interest were genetically analyzed by tissue microdissection, immunohistochemistry for HIF and markers for mesonephric differentiation, and in situ hybridization for HIF downstream target vascular endothelial growth factor. Structural analysis of the epididymides revealed marked deviations from the regular anatomic structure resulting from impaired organogenesis. Selected efferent ductules were represented by disorganized mesonephric cells, and the maldeveloped mesonephric material was VHL-deficient by allelic deletion analysis. Furthermore, we observed maldeveloped mesonephric material near cystic structures, which were also VHL-deficient and were apparent derivatives of maldeveloped material. Finally, a subset of VHL-deficient cells was structurally integrated in regular efferent ductules; proliferation of intraductular VHL-deficient cells manifests itself as papillary growth into the ductular lumen. Furthermore, we clarify that that there is a pathogenetic continuum between microscopic tumorlets and formation of tumor. In multiple locations, three-dimensional reconstruction revealed papillary growth to extend deeply into ductular lumina, indicative of progression into early hamartoma-like neoplasia. We conclude epididymal tumorigenesis in VHL disease to occur in two distinct sequential steps: maldevelopment of VHL-deficient mesonephric cells, followed by neoplastic papillary proliferation.

  20. Crosstalk between PI3K and Ras pathways via protein phosphatase 2A in human ovarian clear cell carcinoma.

    Science.gov (United States)

    Takai, Masaaki; Nakagawa, Takatoshi; Tanabe, Akiko; Terai, Yoshito; Ohmichi, Masahide; Asahi, Michio

    2015-01-01

    Hypoxia-inducible factor-1 (HIF-1) is one of the most promising pharmacological targets for all types of cancer, including ovarian cancer. Ovarian clear cell carcinoma (OCCC) has poor prognosis because of its insensitivity to chemotherapy. To elucidate the characteristics of this troublesome cancer, we examined HIF-1α expression under normoxia or hypoxia in various ovarian cancer cell lines. HIF-1α was highly expressed under normoxia only in RMG-1, an OCCC cell line. To examine whether HIF-1 is involved in the tumorigenesis of RMG-1 cells, we established HIF-1α-silenced cells, RMG-1HKD. The proliferation rate of RMG-1HKD cells was faster than that of RMG-1 cells. Furthermore, the activity of MEK/ERK in the Ras pathway increased in RMG-1HKD cells, whereas that of mTOR in the PI3K pathway did not change. Activation of the Ras pathway was attributable to the increase in phosphorylated MEK via PP2A inactivation. To confirm the crosstalk between the PI3K and Ras pathways in vivo, RMG-1 or RMG-1HKD cells were transplanted into the skin of nude mice with rapamycin (an inhibitor of mTOR), PD98059 (an inhibitor of MEK), or both. RMG-1HKD cells showed higher sensitivity to PD98059 than that observed in RMD-1 cells, whereas the combination therapy resulted in synergistic inhibition of both cells. These findings suggest that inhibition of HIF-1, a downstream target of mTOR in the PI3K pathway, activates the Ras pathway on account of the increase in MEK phosphorylation via PP2A inactivation, and the crosstalk between the 2 pathways could be applied in the combination therapy for HIF-1-overexpressing cancers such as OCCC.

  1. Hematopoietic stem cells exhibit a specific ABC transporter gene expression profile clearly distinct from other stem cells.

    NARCIS (Netherlands)

    Tang, L.; Bergevoet, S.M.; Gilissen, C.F.H.A.; Witte, T.J.M. de; Jansen, J.H.; Reijden, B.A. van der; Raymakers, R.A.P.

    2010-01-01

    BACKGROUND: ATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. Earlier we showed that many ABC transporters are highly expressed in hematopoietic stem cells (HSCs) compared to more committed progenitor cells. The ABC

  2. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Liou Louis S

    2010-04-01

    Full Text Available Abstract Background MicroRNA regulate mRNA levels in a tissue specific way, either by inducing degradation of the transcript or by inhibiting translation or transcription. Putative mRNA targets of microRNA identified from seed sequence matches are available in many databases. However, such matches have a high false positive rate and cannot identify tissue specificity of regulation. Results We describe a simple method to identify direct mRNA targets of microRNA dysregulated in cancers from expression level measurements in patient matched tumor/normal samples. The word "direct" is used here in a strict sense to: a represent mRNA which have an exact seed sequence match to the microRNA in their 3'UTR, b the seed sequence match is strictly conserved across mouse, human, rat and dog genomes, c the mRNA and microRNA expression levels can distinguish tumor from normal with high significance and d the microRNA/mRNA expression levels are strongly and significantly anti-correlated in tumor and/or normal samples. We apply and validate the method using clear cell Renal Cell Carcinoma (ccRCC and matched normal kidney samples, limiting our analysis to mRNA targets which undergo degradation of the mRNA transcript because of a perfect seed sequence match. Dysregulated microRNA and mRNA are first identified by comparing their expression levels in tumor vs normal samples. Putative dysregulated microRNA/mRNA pairs are identified from these using seed sequence matches, requiring that the seed sequence be conserved in human/dog/rat/mouse genomes. These are further pruned by requiring a strong anti-correlation signature in tumor and/or normal samples. The method revealed many new regulations in ccRCC. For instance, loss of miR-149, miR-200c and mir-141 causes gain of function of oncogenes (KCNMA1, LOX, VEGFA and SEMA6A respectively and increased levels of miR-142-3p, miR-185, mir-34a, miR-224, miR-21 cause loss of function of tumor suppressors LRRC2, PTPN13, SFRP1

  3. Prognostic and Predictive Values of Subcellular Localisation of RET in Renal Clear-Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC presents a poor prognosis and an unpredictable course. To date, no validated biomarkers can predict the outcome of RCC. Ongoing efforts are conducted to identify the molecular markers of RCC progression, as well as the targets for novel therapeutic approaches. RET is a tyrosine kinase receptor which has been investigated as a possible target in other cancers because it is involved in oncogenic activation. To evaluate the predictive and prognostic functions of RET in ccRCC, a tissue microarray study was conducted on 273 ccRCC patients. Results showed that both RET cytoplasmic and nuclear expression were independently associated with PFS and OS, and the combined RET cytoplasmic and nuclear statuses demonstrated that the ratio of high nuclear RET and cytoplasmic RET was the strongest predictor of both PFS and OS. The high cytoplasmic RET expression retained its independent poor prognostic value in targeted drug treated patients. The RET nuclear expression was associated with distant metastasis. Moreover, the RET nuclear expression was an independent predictor of ccRCC postoperative metastasis. In conclusion, RET may be useful in prognostication and can be used at initial diagnosis to identify patients with high potential to develop metastasis.

  4. New insights into epididymal function in relation to sperm maturation.

    Science.gov (United States)

    Dacheux, Jean-Louis; Dacheux, Françoise

    2014-02-01

    Testicular spermatozoa acquire fertility only after 1 or 2 weeks of transit through the epididymis. At the end of this several meters long epididymal tubule, the male gamete is able to move, capacitate, migrate through the female tract, bind to the egg membrane and fuse to the oocyte to result in a viable embryo. All these sperm properties are acquired after sequential modifications occurring either at the level of the spermatozoon or in the epididymal surroundings. Over the last few decades, significant increases in the understanding of the composition of the male gamete and its surroundings have resulted from the use of new techniques such as genome sequencing, proteomics combined with high-sensitivity mass spectrometry, and gene-knockout approaches. This review reports and discusses the most relevant new results obtained in different species regarding the various cellular processes occurring at the sperm level, in particular, those related to the development of motility and egg binding during epididymal transit.

  5. A Study to Isolate and Test Circulating Tumor Cells Using the ClearCell® FX EP+ System

    Science.gov (United States)

    2018-03-20

    Lung Cancer; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Carcinoma, Non-small-cell Lung; Adenocarcinoma; Squamous Cell Carcinoma

  6. Iodine quantification to distinguish clear cell from papillary renal cell carcinoma at dual-energy multidetector CT: a multireader diagnostic performance study.

    Science.gov (United States)

    Mileto, Achille; Marin, Daniele; Alfaro-Cordoba, Marcela; Ramirez-Giraldo, Juan Carlos; Eusemann, Christian D; Scribano, Emanuele; Blandino, Alfredo; Mazziotti, Silvio; Ascenti, Giorgio

    2014-12-01

    To investigate whether dual-energy multidetector row computed tomographic (CT) imaging with iodine quantification is able to distinguish between clear cell and papillary renal cell carcinoma ( RCC renal cell carcinoma ) subtypes. In this retrospective, HIPAA-compliant, institutional review board-approved study, 88 patients (57 men, 31 women) with diagnosis of either clear cell or papillary RCC renal cell carcinoma at pathologic analysis, who underwent contrast material-enhanced dual-energy nephrographic phase study between December 2007 and June 2013, were included. Five readers, blinded to pathologic diagnosis, independently evaluated all cases by determining the lesion iodine concentration on color-coded iodine maps. The receiving operating characteristic curve analysis was adopted to estimate the optimal threshold for discriminating between clear cell and papillary RCC renal cell carcinoma , and results were validated by using a leave-one-out cross-validation. Interobserver agreement was assessed by using an intraclass correlation coefficient. The correlation between tumor iodine concentration and tumor grade was investigated. A tumor iodine concentration of 0.9 mg/mL represented the optimal threshold to discriminate between clear cell and papillary RCC renal cell carcinoma , and it yielded the following: sensitivity, 98.2% (987 of 1005 [95% confidence interval: 97.7%, 98.7%]); specificity, 86.3% (272 of 315 [95% confidence interval: 85.0%, 87.7%]); positive predictive value, 95.8% (987 of 1030 [95% confidence interval: 95.0%, 96.6%]); negative predictive value, 93.7% (272 of 290 [95% confidence interval: 92.8%, 94.7%]); overall accuracy of 95.3% (1259 of 1320 [95% confidence interval: 94.6%, 96.2%]), with an area under the curve of 0.923 (95% confidence interval: 0.913, 0.933). An excellent agreement was found among the five readers in measured tumor iodine concentration (intraclass correlation coefficient, 0.9990 [95% confidence interval: 0. 9987, 0.9993). A

  7. Demographic Clinical and Prognostic Factors of Primary Ovarian Adenocarcinomas of Serous and Clear Cell Histology—A Comparative Study

    DEFF Research Database (Denmark)

    Schnack, Tine H; Høgdall, Estrid; Nedergaard, Lotte

    2016-01-01

    OBJECTIVE: To compare clinical demographic and prognostic factors as well as overall survival in a nationwide cohort of patients diagnosed with ovarian clear cell carcinoma (oCCC) and high grade ovarian serous adenocarcinoma (oSAC) during 2005 to 2013. MATERIALS AND METHODS: Population......SAC cases. Furthermore, our findings confirm that advanced stages of oCCC have a poorer prognosis compared with oSAC probably because of the resistance toward adjuvant chemotherapy. The observed differences highlight the need for subtype-specific research and individualized treatment within ovarian cancer....

  8. Single-layer centrifugation through colloid selects improved quality of epididymal cat sperm.

    Science.gov (United States)

    Chatdarong, K; Thuwanut, P; Morrell, J M

    2010-06-01

    The objectives were to determine the: 1) extent of epithelial and red blood cell contamination in epididymal cat sperm samples recovered by the cutting method; 2) efficacy of simple washing, single-layer centrifugation (SLC), and swim-up for selecting epididymal cat sperm; and 3) effects of freezing and thawing on cat sperm selected by various techniques. Ten unit samples were studied; each contained sperm from the cauda epididymides of four cats (total, approximately 200 x 10(6) sperm) and was equally allocated into four treatments: 1) simple washing, 2) single-layer centrifugation through colloid prior to cryopreservation (SLC-PC), 3) single-layer centrifugation through colloid after cryopreservation (SLC-AC), and 4) swim-up. Centrifugation (300 x g for 20 min) was done for all methods. The SLC-PC had a better recovery rate than the SLC-AC and swim-up methods (mean+/-SD of 16.4+/-8.7, 10.7+/-8.9, and 2.3+/-1.7%, respectively; Pblood cell contamination than simple washed samples (0.02+/-0.01, 0.02+/-0.04, 0.03+/-0.04, and 0.44+/-0.22 x 10(6) cells/mL, respectively; P0.05), SLC-PC yielded the highest percentage of sperm with normal midpieces and tails (P0.05). In conclusion, both SLC-PC and swim-up improved the quality of epididymal cat sperm, including better morphology, membrane and DNA integrity, and removal of cellular contamination. However, SLC had a better sperm recovery rate than swim-up. 2010 Elsevier Inc. All rights reserved.

  9. Viability of postmortal epididymal mouse spermatozoa during long-term hypothermic storage and cryopreservation.

    Science.gov (United States)

    Shishova, N V; Gakhova, E N; Mel'nikova, E V

    2011-08-01

    The study examined the effect of long-term hypothermic (4°C) storage of mouse carcasses on motility, cell membrane damage, in vitro survival and capacitation of epididymal spermatozoa before and after cryopreservation. It was shown that the number of spermatozoa with rectilinear forward motion decreased with increasing storage time. There were no significant changes in the total sperm motility and integrity of their plasmalemma. Pronounced effects of hypothermia and long-term storage of the mouse carcasses on cryocapacitation of spermatozoa during cryoconservation were demonstrated.

  10. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Arias-González

    2013-06-01

    Full Text Available Extracellular signal-regulated kinase 5 (ERK5, also known as big mitogen-activated protein kinase (MAPK 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.

  11. RNA PROFILES IN RAT AND MOUSE EPIDIDYMAL SPERMATOZOA

    Science.gov (United States)

    RNA PROFILES IN RAT AND MOUSE EPIDIDYMAL SPERMATOZOA Kary E. Thompson1, Hongzu Ren1, Judith E. Schmid1 and David J. Dix11Reproductive Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, RTP, NC. Mature spermatozoa are transcriptionally inactive...

  12. A Patient Presenting with Concurrent Testis Torsion and Epididymal Leiomyoma

    Directory of Open Access Journals (Sweden)

    E. Arpali

    2013-01-01

    Full Text Available Leiomyomas are the second most common tumors of epididymis. Patients with leiomyomas are sometimes misdiagnosed with testicular tumors. A Case of a patient with a scrotal mass presenting with testicular torsion is reported. Concurrent occurrence of testicular torsion and epididymal leiomyoma is an extremely rare condition.

  13. Nonpathological extracellular amyloid is present during normal epididymal sperm maturation.

    Directory of Open Access Journals (Sweden)

    Sandra Whelly

    Full Text Available Amyloids are aggregated proteins characterized by a specific cross-β-sheet structure and are typically associated with neurodegenerative diseases including Alzheimer's disease. Recently, however, several nonpathological amyloids have been found in intracellular organelles of normal mammalian tissues suggesting that amyloid may also carry out biological functions. We previously have shown that the epididymal cystatin CRES (cystatin-related epididymal spermatogenic, cst8, a reproductive-specific member of the cystatin superfamily of cysteine protease inhibitors, forms amyloid in vitro suggesting that CRES amyloid may also form in vivo within the epididymal lumen. Here we show that amyloid structures containing CRES are a component of the normal mouse epididymal lumen without any apparent cytotoxic effects on spermatozoa and that these structures change along the length of the tubule. These studies suggest the presence of a functional amyloid structure that may carry out roles in sperm maturation or maintenance of the luminal milieu and which itself may undergo maturational changes along the epididymis. In contrast to previous examples of functional amyloid which were intracellular, our studies now show that nonpathological/functional amyloid can also be extracellular. The presence of an extracellular and nonpathological amyloid in the epididymis suggests that similar amyloid structures may be present in other organ systems and may carry out distinctive tissue-specific functions.

  14. Antioxidative effect of epichlorohydrin on rat cauda epididymal ...

    African Journals Online (AJOL)

    The aim of the study was to evaluate the effect of epichlorohydrin (ECH) on the antioxidant system of rat cauda epididymal sperm. Fresh epididymides of adult male rats were obtained from JIPMER, (Pondicherry) were collected by chopping the epididymis in modified Ringer's phosphate solution (RPS medium). After several ...

  15. Cryoprotectant-free freezing of the goat epididymal sperm.

    Science.gov (United States)

    Katanbafzadeh, H; Barati, F; Tabandeh, M

    2014-01-01

    Cryoprotectant free approach successfully removed the impact of physical and chemical damages in preserving human sperm in a vitrification protocol. There is no any report on this technology in farm animal sperm freezing. The aim of the present study was to find the efficacy of cholesterol-loaded cyclodextrin (CLC; 1 mg per 60 million) and sucrose (0.1 and 0.2 M) on freezing of the goat epididymal sperm. Caudal epididymides (n=5 pairs) were dissected, incised and incubated in the Tris-BSA solution for 15 min, followed by swim-up at room temperature. Sperm was loaded in 0.25 mL French straws and cooled on nitrogen vapor for 3 min then immersed in liquid nitrogen and remained for 48 h. Then the straws thawed by immersing in 37 degree C waterbath for 30 sec and analyzed. The results showed the impact of freezing on the goat epididymal sperm motility, viability and DNA fragmentation that were improved by incorporation of CLC and sucrose (0.2 M). In conclusion, the goat epididymal sperm was frozen in a cryoprotectant-free freezing model. CLC and 0.4 M sucrose protected the goat epididymal sperm against freezing-induced damages.

  16. Vesicular transfer of membrane components to bovine epididymal spermatozoa.

    Science.gov (United States)

    Schwarz, A; Wennemuth, G; Post, H; Brandenburger, T; Aumüller, G; Wilhelm, B

    2013-09-01

    Epididymosomes (apocrine secreted epididymal vesicles) are assumed to play a crucial role in sperm maturation. Our aim has been to analyze the fusogenic properties of bovine epididymosomes and their involvement in the transfer of membrane components (lipids, proteins, plasma membrane Ca(2+)-ATPase 4 [PMCA4]) into bovine sperm. The fusogenic properties of epididymosomes with spermatozoa were investigated in vitro by using octadecyl rhodamine-B (R18)-labeled epididymosomes. Spermatozoa isolated from the epididymal caput showed a higher fusion rate than those taken from the cauda. The fusion rate was dependent on pH and time. Furthermore, the lipid and protein content in spermatozoa changed during epididymal transit and after in vitro fusion with epididymosomes. Following the in vitro fusion of caput spermatozoa with epididymosomes, the cholesterol/total phospholipid ratio of the sperm plasma membrane decreased. The effect was comparable with the cholesterol/total phospholipid ratio of native cauda spermatozoa. Co-incubation experiments of spermatozoa with biotinylated epididymosomes additionally revealed that proteins were transferred from epididymosomes to sperm. To examine the potential transfer of epididymis-derived PMCA4 to spermatozoa, immunofluorescence analysis and Ca(2+)-ATPase activity assays were performed. In caput spermatozoa, the PMCA4 fluorescence signal was slightly raised and Ca(2+)-ATPase activity increased after in vitro fusion. Thus, our experiments indicate significant changes in the lipid and protein composition of epididymal sperm following interaction with epididymosomes. Moreover, our results substantiate the presumption that PMCA4 is transferred to spermatozoa via epididymosomes.

  17. Cystatin-related epididymal spermatogenic subgroup members are part of an amyloid matrix and associated with extracellular vesicles in the mouse epididymal lumen.

    Science.gov (United States)

    Whelly, Sandra; Muthusubramanian, Archana; Powell, Jonathan; Johnson, Seethal; Hastert, Mary Catherine; Cornwall, Gail A

    2016-11-01

    2 were primarily found in the initial segment and intermediate zone of the epididymis and were profoundly downregulated in epididymides from CRES KO mice, suggesting integrated functions. Except for CRES3, which was only detected in a particulate form, proteins were present in the epididymal lumen in both soluble and particulate forms including in a film-like matrix and in extracellular vesicles. The use of amyloid-specific reagents determined that all CRES subgroup members were present as amyloids and colocalized to a common amyloid matrix present in the epididymal lumen. Negative stain EM, dot blot analysis and ThT plate assays showed that recombinant CRES2, CRES3 and cystatin E2 formed amyloid in vitro, albeit with different aggregation properties. Together, our studies demonstrate that a unique amyloid matrix composed of the CRES family of reproductive-specific cystatins and cystatin C is a normal component of the mouse epididymal lumen and may play a functional role in sperm maturation by coordinating interactions between the luminal fluid and spermatozoa. The structures examined in our studies were isolated from luminal fluid obtained by puncture of the epididymis and therefore we cannot rule out some contamination by epithelial cells. Although our studies show CRES family members are associated with extracellular vesicles, we have yet to determine if proteins are present on the surface or are within the vesicles. We also have not established if narrow/apical cells are the source of the CRES family extracellular vesicles. CRES and CRES2 have been previously found in the human epididymis and associated with spermatozoa; however, we have yet to determine if the human CRES subgroup proteins are amyloidogenic and if an amyloid matrix is present in the human epididymal lumen. Understanding the regulation and biological roles of amyloids, such as the CRES subgroup amyloid matrix that functions without causing pathology, could have broad implications for

  18. Quantitative Glycopeptide Changes in Rat Sperm During Epididymal Transit.

    Science.gov (United States)

    Villaverde, Ana Izabel Silva Balbin; Hetherington, Louise; Baker, Mark A

    2016-04-01

    Mammalian spermatozoa acquire fertilizing potential as they undergo a series of changes during epididymal transit. One major facet of such is the alterations in the sperm glycome. Modifications of the sialic acid content within glycan moieties are known to regulate epitope presentation and cellular adhesion and signaling, all of which may be critical for sperm to successfully reach and fertilize the egg. To date, there is paucity of information regarding the sialic acid changes that occur on spermatozoa during epididymal transit. Therefore, the aim of this study was to identify N-linked sialylated glycoproteins in rat epididymal sperm and investigate whether they are regulated during epididymal transit. Sialylated glycopeptides from caput, corpus, and cauda spermatozoa were enriched using titanium dioxide beads. Bound N-linked glycopeptides were released by enzymatic deglycosylation using PNGase F and then analyzed by liquid chromatography tandem-mass spectrometry. A total of 92 unique N-linked sialylated glycopeptides were identified from 65 different proteins. These included members of the disintegrin and metalloproteinase domain-containing protein family (ADAM), Basigin, and Testis-expressed protein 101 (TEX101). Remarkably, label-free quantification showed that more than half of these peptides (48/92) were regulated during epididymal transit. Of interest, the protein TEX101 exhibited PNGase F-resistant deglycosylation under the conditions used in this study. The results from this study showed that changes in the N-linked sialoglycoprotein profile is a major hallmark of sperm maturation in rats. © 2016 by the Society for the Study of Reproduction, Inc.

  19. Individual Bromodomains of Polybromo-1 Contribute to Chromatin Association and Tumor Suppression in Clear Cell Renal Carcinoma.

    Science.gov (United States)

    Porter, Elizabeth G; Dykhuizen, Emily C

    2017-02-17

    The architecture of chromatin is governed, in part, by ATP-dependent chromatin remodelers. These multiprotein complexes contain targeting domains that recognize post-translational marks on histones. One such targeting domain is the bromodomain (BD), which recognizes acetyl-lysines and recruits proteins to sites of acetylation across the genome. Polybromo1 (PBRM1), a subunit of the Polybromo-associated BRG1- or hBRM-associated factors (PBAF) chromatin remodeler, contains six tandem BDs and is frequently mutated in clear cell renal cell carcinoma (ccRCC). Mutations in the PBRM1 gene often lead to the loss of protein expression; however, missense mutations in PBRM1 have been identified and tend to cluster in the BDs, particularly BD2 and BD4, suggesting that individual BDs are critical for PBRM1 function. To study the role of these six BDs, we inactivated each of the six BDs of PBRM1 and re-expressed these mutants in Caki2 cells (ccRCC cells with the loss of function mutation in PBRM1 ). Four of the six BDs abrogated PBRM1 tumor suppressor function, gene regulation, and chromatin affinity with the degree of importance correlating strongly to the rate of missense mutations in patients. Furthermore, we identified BD2 as the most critical for PBRM1 and confirmed BD2-mediated association to histone H3 peptides acetylated at lysine 14 (H3K14Ac), validating the importance of this specific acetylation mark for PBRM1 binding. From these data, we conclude that four of the BDs act together to target PBRM1 to sites on chromatin; when a single BD is mutated, PBRM1 no longer controls gene expression properly, leading to increased cell proliferation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Reduced Fertility and Altered Epididymal and Sperm Integrity in Mice Lacking ADAM7.

    Science.gov (United States)

    Choi, Heejin; Han, Cecil; Jin, Sora; Kwon, Jun Tae; Kim, Jihye; Jeong, Juri; Kim, Jaehwan; Ham, Sera; Jeon, Suyeon; Yoo, Yung Joon; Cho, Chunghee

    2015-09-01

    The mammalian epididymis is a highly convoluted tubule that connects the testis to the vas deferens. Its proper functions in sperm transport, storage, and maturation are essential for male reproduction. One of the genes predominantly expressed in the epididymis is ADAM7 (a disintegrin and metalloprotease 7). Previous studies have shown that ADAM7 synthesized in the epididymis is secreted into the epididymal lumen and is then transferred to sperm membranes, where it forms a chaperone complex that is potentially involved in sperm fertility. In this study, we generated and analyzed mice with a targeted disruption in the Adam7 gene. We found that the fertility of male mice was modestly but significantly reduced by knockout of Adam7. Histological analyses revealed that the cell heights of the epithelium were dramatically decreased in the caput of the epididymis of Adam7-null mice, suggesting a requirement for ADAM7 in maintaining the integrity of the epididymal epithelium. We found that sperm from Adam7-null mice exhibit decreased motility, tail deformation, and altered tyrosine phosphorylation, indicating that the absence of ADAM7 leads to abnormal sperm functions and morphology. Western blot analyses revealed reduced levels of integral membrane protein 2B (ITM2B) and ADAM2 in sperm from Adam7-null mice, suggesting a requirement for ADAM7 in normal expression of sperm membrane proteins involved in sperm functions. Collectively, our study demonstrates for the first time that ADAM7 is required for normal fertility and is important for the maintenance of epididymal integrity and for sperm morphology, motility, and membrane proteins. © 2015 by the Society for the Study of Reproduction, Inc.

  1. Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.

    Directory of Open Access Journals (Sweden)

    Yoriko Yamashita

    Full Text Available Clear cell adenocarcinoma of the ovary (OCC is a chemo-resistant tumor with a relatively poor prognosis and is frequently associated with endometriosis. Although it is assumed that oxidative stress plays some role in the malignant transformation of this tumor, the characteristic molecular events leading to carcinogenesis remain unknown. In this study, an array-based comparative genomic hybridization (CGH analysis revealed Met gene amplification in 4/13 OCC primary tumors and 2/8 OCC cell lines. Amplification of the AKT2 gene, which is a downstream component of the Met/PI3K signaling pathway, was also observed in 5/21 samples by array-based CGH analysis. In one patient, both the Met and AKT2 genes were amplified. These findings were confirmed using fluorescence in situ hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemistry. In total, 73 OCC cases were evaluated using real-time quantitative PCR; 37.0% demonstrated Met gene amplification (>4 copies, and 8.2% had AKT2 amplification. Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse survival than patients without Met gene amplification (p<0.05. Met knockdown by shRNA resulted in reduced viability of OCC cells with Met amplification due to increased apoptosis and cellular senescence, suggesting that the Met signaling pathway plays an important role in OCC carcinogenesis. Thus, we believe that targeted inhibition of the Met pathway may be a promising treatment for OCC.

  2. Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

    DEFF Research Database (Denmark)

    Arildsen, Nicolai Skovbjerg; Jönsson, Jenny-Maria; Bartuma, Katarina

    2017-01-01

    OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyondARID1A, which...... and ultimately improve patient outcome. METHODS: Gene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1;n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays...... ovarian cancer subtypes. However, overexpression ofERBB2was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct...

  3. CLINICAL VALUE OF THE MARKERS OF PROLIFERATION AND APOPTOSIS IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-07-01

    Full Text Available Renal cell carcinoma (RCC is a heterogeneous disease in which the patients survive for months to years. At the present time the prognostic models have no sufficient information or exact prognostic value. Cell proliferation and apoptosis play a key role in cell cycle regulation; and impairment in these processes is commonly detected in different human tumors. The investigation enrolled 76 patients (49 men, 27 women aged 32 to 73 years (mean age 56 ± 7.6 years diagnosed with RCC. The follow-up was 8 to 116 months (mean 36.5 months. All the patients underwent nephrectomy; antibodies against р53, Bcl-2, and Ki-67 were investigated by immunohistochemistry. The expression of p53 and none or reduced expression of Bcl-2 are poor prognostic factors and associated with the metastatic potential of a tumor and with low relapse-free survival. High Ki-67 levels are a risk factor for metastases. A combination of p53 expression and high proliferative activity reflects the aggressive potential of a tumor and suggests the high risk of metastases just at the disease diagnosis and early tumor dissemination. 

  4. Minimal volume vitrification of epididymal spermatozoa results in successfulin vitrofertilization and embryo development in mice.

    Science.gov (United States)

    Horta, Fabrizzio; Alzobi, Hamida; Jitanantawittaya, Sutthipat; Catt, Sally; Chen, Penny; Pangestu, Mulyoto; Temple-Smith, Peter

    2017-01-01

    This study compared three cryopreservation protocols on sperm functions, IVF outcomes, and embryo development. Epididymal spermatozoa cryopreserved using slow-cooling (18% w/v raffinose, RS-C) were compared with spermatozoa vitrified using 0.25 M sucrose (SV) or 18% w/v raffinose (RV). The motility, vitality, and DNA damage (TUNEL assay) of fresh control (FC) spermatozoa were compared with post-thawed or warmed RS-C, RV, and SV samples. Mouse oocytes (n = 267) were randomly assigned into three groups for insemination: RV (n = 102), RS-C (n = 86), and FC (n = 79). The number and the proportion of two-cell embryos and blastocysts from each treatment were assessed. Sperm motility (P spermatozoa. However, DNA fragmentation was significantly reduced in spermatozoa vitrified using sucrose (15 ± 1.8% [SV] vs 26 ± 2.8% [RV] and 27 ± 1.2% [RS-C]; P spermatozoa was not significantly different, the number of blastocysts produced from two-cell embryos using RV spermatozoa was significantly higher than FC spermatozoa (P = 0.0053). This simple, small volume vitrification protocol and standard insemination method allows successful embryo production from small numbers of epididymal spermatozoa and may be applied clinically to circumvent the need for ICSI, which has the disadvantage of bypassing sperm selection.

  5. Diagnostic value of dual detection of hepatocyte nuclear factor 1 beta (HNF-1β) and napsin A for diagnosing ovarian clear cell carcinoma.

    Science.gov (United States)

    Li, Qing; Zeng, Xin; Cheng, Xue; Zhang, Jingmin; Ji, Jie; Wang, Jinsong; Xiong, Kemei; Qi, Qiong; Huang, Wenbin

    2015-01-01

    We evaluated the diagnostic value of hepatocyte nuclear factor 1 beta (HNF-1β) and napsin A for diagnosing ovarian clear cell carcinoma. Immunohistochemical EnVision was used to measure HNF-1β and napsin A expression in 38 cases of ovarian clear cell carcinoma, 30 cases of high-grade serous carcinoma, 22 cases of endometrioid adenocarcinoma, and 16 metastatic Krukenberg tumor cases. Then we found that HNF-1β appeared in all ovarian clear cell carcinoma and was less common in high-grade serous and endometrioid adenocarcinoma (P carcinoma and metastatic Krukenberg tumor was found (P > 0.05). Napsin A was expressed in 97.4% of ovarian clear cell carcinoma, 6.7% high-grade serous carcinoma, 22.7% endometrioid adenocarcinoma, and 0% metastatic Krukenberg tumors. Napsin A in clear cell carcinoma was greater than that found in high-grade serous carcinoma, endometrioid adenocarcinoma, and metastatic Krukenberg tumor (P ovarian clear cell carcinoma was 100% and 54.4%, and 97.4% and 89.7%, respectively. Sensitivity and specificity of HNF-1β and napsin A for diagnosing ovarian clear cell carcinoma was 97.4% and 91.2%, respectively. So it is concluded that HNF-1β and napsin A are more sensitive than currently used markers for diagnosing ovarian clear cell carcinoma. Moreover, napsin A is more specific than HNF-1β. Combining HNF-1β and napsin A may distinguish clear cell carcinoma from high-grade serous carcinoma, endometrioid adenocarcinoma and metastatic Krukenberg tumors.

  6. MicroRNAs and altered metabolism of clear cell renal cell carcinoma: Potential role as aerobic glycolysis biomarkers.

    Science.gov (United States)

    Morais, Mariana; Dias, Francisca; Teixeira, Ana L; Medeiros, Rui

    2017-09-01

    Warburg Effect is a metabolic switch that occurs in most of cancer cells but its advantages are not fully understood. This switch is known to happen in renal cell carcinoma (RCC), which is the most common solid cancer of the adult kidney. RCC carcinogenesis is related to pVHL loss and Hypoxia Inducible Factor (HIF) activation, ultimately leading to the activation of several genes related to glycolysis. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level and are also deregulated in several cancers, including RCC. This review focuses in the miRNAs that direct target enzymes involved in glycolysis and that are deregulated in several cancers. It also reviews the possible application of miRNAs in the improvement of clinical patients' management. Several miRNAs that direct target enzymes involved in glycolysis are downregulated in cancer, strongly influencing the Warburg Effect. Due to this strong influence, FDG-PET can possibly benefit from measurement of these miRNAs. Restoring their levels can also bring an improvement to the current therapies. Despite being known for almost a hundred years, the Warburg Effect is not fully understood. MiRNAs are now known to be intrinsically connected with this effect and present an opportunity to understand it. They also open a new door to improve current diagnosis and prognosis tests as well as to complement current therapies. This is urgent for cancers like RCC, mostly due to the lack of an efficient screening test for early relapse detection and follow-up and the development of resistance to current therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Synthesis and secretion of proteins by perifused caput epididymal tubules, and association of secreted proteins with spermatozoa

    Energy Technology Data Exchange (ETDEWEB)

    Klinefelter, G.R.; Hamilton, D.W.

    1985-11-01

    We have used perifusion organ culture of proximal and distal caput epididymal tubules of the rat to study the secretion of proteins by epididymal epithelium and uptake of the luminal radioactive proteins by sperm. The amount of incorporation of L-(35S)methionine into luminal fluid proteins was time dependent and completely inhibited by cycloheximide. The association of labeled proteins with cultured sperm was also dependent on time and continuous, with sperm still acquiring labeled luminal proteins after protein synthesis was arrested. A Mr = 46,000 molecule was found to be heavily labeled in luminal fluid and sperm extracts. Fluorograms of all L-(35S)methionine extracts immunoprecipitated using an antiepididymal alpha-lactalbumin antibody (Klinefelter and Hamilton, 1984) showed labeling of an Mr = 18,000 molecule and, in addition, the Mr = 46,000 molecule, but immunostaining was specific only for the Mr = 18,000 molecule and the heavy chain of the immunoglobulin. We suggest that the Mr = 46,000 molecule may be galactosyltransferase. Galactose oxidase-NaB(3H)4 labeling of the cultured caput sperm cell surface revealed a Mr = 23,000 molecule that was able to be immunoprecipitated with antiepididymal alpha-lactalbumin antibody. Our data suggest that this cell surface molecule is similar to one component of the fluid epididymal alpha-lactalbumin-like complex and, in addition, show that glycosylation of the sperm surface can occur in the caput epididymidis.

  8. Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

    Directory of Open Access Journals (Sweden)

    Marcelo Zerati

    2013-07-01

    Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

  9. Glycoproteins of bovine epididymal spermatozoa--a cytochemical study.

    Science.gov (United States)

    Sinowatz, F; Friess, A E; Wrobel, K H

    1984-01-01

    Modifications in bull sperm plasmamembrane during epididymal passage were investigated by the use of four different lectins: Concanavalin A (Con A); Ricinus communis I (RCA1); Wheat germ agglutinin (WGA); Ulex europaeus agglutinin I (UEA1). During sperm passage from caput to cauda epididymidis agglutination by RCA1 and WGA distinctly increased. Similar but somewhat less pronounced difference in the agglutinability was found for Con A. No agglutination was observed with UEA1. Ultrastructural examination of Con A binding sites on sperm plasma membrane with a Con A-horseradish peroxidase-gold technique (Con A-HRP-G) revealed a significant increase in the number of gold granules on the sperm tails during the epididymal passage of spermatozoa. No change in WGA-binding sites was observed between caput and cauda spermatozoa using a WGA-peroxidase method.

  10. Etiologic significance of bacterial isolates from rams with palpable epididymitis.

    Science.gov (United States)

    Lozano, E A

    1986-05-01

    Identified and partly identified bacterial isolates were obtained from 48 rams of various breeds that had unilateral or bilateral epididymitis. Most of the animals were approximately 1 year of age; a few were older. Brucella ovis, Actinobacillus spp, Corynebacterium spp, Haemophilus spp, Acinetobacter spp, Escherichia coli, Moraxella spp, Staphylococcus spp, Pasteurella spp, Streptococcus spp, and Chlamydia psittaci were isolated. A vaccine strain of B ovis, isolated species of bacteria, and mixtures of isolates of tissue homogenates containing all isolates except B ovis and C psittaci were inoculated via the mucous membranes of the eyes, nares, and prepuce. Palpable epididymitis was not produced by the inoculations. The vaccine strain of B ovis induced complement-fixation reaction in 11 of 20 rams.

  11. Morphological and acrosomal changes of canine spermatozoa during epididymal transit.

    Science.gov (United States)

    Varesi, Sara; Vernocchi, Valentina; Faustini, Massimo; Luvoni, Gaia Cecilia

    2013-02-26

    During epididymal transit, functional and structural modifications leading to full maturation enable male gametes to reach, recognize and fertilize the oocytes. In dogs, little is known on the modifications of spermatozoa during the passage in the epididymis. The aim of this study was to describe the motility, morphology and acrosomal patterns of canine spermatozoa retrieved from the epididymis caput, corpus and cauda. After the dilution required for the collection of epididymal content, sperm motility was significantly higher (Pepididymal regions. A significantly increased prevalence of tail defects, mainly represented by single bent tails, was observed in the corpus compared to caput (Psperm with cytoplasmic droplets decreased from the proximal to the distal region of the epididymis. Particularly, proximal cytoplasmic droplets were more frequently found in spermatozoa collected from the caput epididymis than in the corpus (Pepididymal regions.

  12. Functional Studies on Primary Tubular Epithelial Cells Indicate a Tumor Suppressor Role of SETD2 in Clear Cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jun Li

    2016-06-01

    Full Text Available SET domain-containing 2 (SETD2 is responsible for the trimethylation of histone H3 lysine36 (H3K36me3 and is one of the genes most frequently mutated in clear cell renal cell carcinoma (ccRCC. It is located at 3p21, one copy of which is lost in the majority of ccRCC tumors, suggesting that SETD2 might function as a tumor suppressor gene. However, the manner in which loss of SETD2 contributes to ccRCC development has not been studied in renal primary tubular epithelial cells (PTECs. Therefore, we studied the consequences of SETD2 knockdown through lentiviral shRNA in human PTECs. Consistent with its known function, SETD2 knockdown (SETD-KD led to loss of H3K36me3 in PTECs. In contrast to SETD2 wild-type PTECs, which have a limited proliferation capacity; the SETD2-KD PTECs continued to proliferate. The expression profiles of SETD2-KD PTECs showed a large overlap with the expression profile of early-passage, proliferating PTECs, whereas nonproliferating PTECs showed a significantly different expression profile. Gene set enrichment analysis revealed a significant enrichment of E2F targets in SETD2-KD and proliferating PTECs as compared with nonproliferating PTECs and in proliferating PTEC compared with SETD2-KD. The SETD2-KD PTECs maintained low expression of CDKN2A and high expression of E2F1, whereas their levels changed with continuing passages in untreated PTECs. In contrast to the nonproliferating PTECs, SETD2-KD PTECs showed no β-galactosidase staining, confirming the protection against senescence. Our results indicate that SETD2 inactivation enables PTECs to bypass the senescence barrier, facilitating a malignant transformation toward ccRCC.

  13. Expression of Opa interacting protein 5 (OIP5) is associated with tumor stage and prognosis of clear cell renal cell carcinoma.

    Science.gov (United States)

    Gong, Mancheng; Xu, Yangyang; Dong, Wenjing; Guo, Guiying; Ni, Wenjun; Wang, Yan; Wang, Yongquan; An, Ruihua

    2013-10-01

    Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, the biological function and clinical significance of OIP5 in human Clear Cell Renal Cell Carcinoma (CCRCC) remains unknown. In the present study, we found the expression of OIP5 was markedly upregulated in surgical CCRCC specimens and CCRCC cell lines. Immunohistochemical analysis revealed that paraffin-embedded archival CCRCC specimens exhibited higher levels of OIP5 expression than normal renal tissues. Further statistical analysis suggested the upregulation of OIP5 was positively correlated with the Fuhrman grade (P = 0.02), T classification (P = 0.015), N classification (P = 0.018) and clinical stage (P = 0.035). Also, patients with high OIP5 expression dramatically exhibited shorter survival time (P = 0.001). In addition, the OIP5 expression was an independent prognostic marker of overall survival of CCRCC patients in a multivariate analysis (P = 0.008). Experimentally, we demonstrated that silencing OIP5 in CCRCC cell lines by specific siRNA clearly inhibited cell growth. In conclusion, our findings suggested that OIP5 could be a valuable marker of CCRCC progression and prognosis, and a promising therapeutic target for CCRCC. Copyright © 2013 Elsevier GmbH. All rights reserved.

  14. Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy.

    Science.gov (United States)

    Li, Mengjiao; Li, Haoran; Liu, Fei; Bi, Rui; Tu, Xiaoyu; Chen, Lihua; Ye, Shuang; Cheng, Xi

    2017-02-10

    It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC). Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored. The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar

  15. Biochemical and binding characteristics of boar epididymal fluid proteins

    Czech Academy of Sciences Publication Activity Database

    Maňásková-Postlerová, Pavla; Davidová, Nina; Jonáková, Věra

    2011-01-01

    Roč. 879, č. 1 (2011), s. 100-106 ISSN 1570-0232 R&D Projects: GA ČR(CZ) GA303/09/1285; GA MŠk(CZ) 1M06011; GA ČR(CZ) GD523/08/H064 Institutional research plan: CEZ:AV0Z50520701 Keywords : epididymal proteins * RP HPLC * biotin-labeled ligands Subject RIV: CE - Biochemistry Impact factor: 2.888, year: 2011

  16. Painless inter epididymal testicular torsion of the spermatic cord

    Directory of Open Access Journals (Sweden)

    Salomon V. Romano

    2007-02-01

    Full Text Available Inter epididymal testicular torsion of the spermatic cord is extremely rare and usually diagnosed at surgery. We present an unusual case of spermatic cord torsion in a 14-year-old male patient. It is important to highlight that the torsion occurred only on the distal half of the epididymis leaving the head untwisted and edematous. In addition, the fact that this condition was painless made this case extremely rare and motivated our presentation.

  17. Painless inter epididymal testicular torsion of the spermatic cord

    OpenAIRE

    Salomon V. Romano; Haime S. Hernan; Norberto Fredotovich

    2007-01-01

    Inter epididymal testicular torsion of the spermatic cord is extremely rare and usually diagnosed at surgery. We present an unusual case of spermatic cord torsion in a 14-year-old male patient. It is important to highlight that the torsion occurred only on the distal half of the epididymis leaving the head untwisted and edematous. In addition, the fact that this condition was painless made this case extremely rare and motivated our presentation.

  18. Abdominoscrotal hydrocele in infancy with incorporated epididymal tissue.

    Science.gov (United States)

    Park, James; Gioia, Kevin; Wasnick, Robert J

    2010-04-01

    Abdominoscrotal hydrocele is a rare condition where a large hydrocele is connected to a preperitoneal space through the inguinal canal. We present a case of a young male with an abdominoscrotal hydrocele who showed gross absence of an epididymis upon hydrocele removal. Upon pathological examination, epididymal tissue was found to be incorporated into the wall of the hydrocele sac. Copyright © 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  19. Fatty acid content in epididymal fluid and spermatozoa during sperm maturation in dogs.

    Science.gov (United States)

    Ramos Angrimani, Daniel S; Nichi, Marcilio; Losano, João Diego A; Lucio, Cristina F; Lima Veiga, Gisele A; Franco, Márcia V M Junqueira; Vannucchi, Camila I

    2017-01-01

    During sperm maturation, there is a reorganization of fatty acids from plasmatic membrane of the spermatozoa, which allows higher membrane integrity and acquisition of sperm motility. However, the fatty acid profile during sperm maturation remains unclear in dogs. Thus, the aim of this study was to identify the fatty acids from the epididymal spermatozoa and plasma during the sperm maturation, and observed changes in the motility and plasmatic membrane parameters. Twenty one adult dogs were used, subsequently to bilateral orchiectomy and epididymal storage, sperm samples were collected from the different segments of the epididymis. Samples were evaluated for conventional microscopy, computer-assisted motility analysis, sperm plasma membrane permeability and the fatty acid analysis (lipids were extracted, transmethylated and analyzed by chromatography). Caput and corpus sperm showed lower values for the motility variables evaluated and plasmatic membrane integrity, indicating different levels of the fatty acids organization. Saturated, monounsaturated and polyunsaturated fatty acids were in higher concentrations in the spermatozoa from epididymis cauda. Highlighting the presence of caprylic, stearic and docosahexaenoic acids. These findings demonstrate the influence of the fatty acid profile during sperm maturation, assigning physical and chemical changes in sperm cells, essential for fertilization.

  20. Laboratory handling of epididymal and testicular spermatozoa: What can be done to improve sperm injections outcome.

    Science.gov (United States)

    Esteves, Sandro C; Varghese, Alex C

    2012-09-01

    Spermatozoa from azoospermic males can be retrieved from either the epididymis or the testis, depending on the type of azoospermia, using different surgical methods such as percutaneous epididymal sperm aspiration (PESA), testicular sperm aspiration (TESA), testicular sperm extraction (TESE), and microsurgical testicular sperm extraction (micro- TESE). After collecting the epididymal fluid or testicular tissue, laboratory techniques are used to remove contaminants, cellular debris, noxious microorganisms, and red blood cells. Processed spermatozoa may be used for intracytoplasmic sperm injection or eventually be cryopreserved. However, spermatozoa collected from either the epididymis or the testis are often compromised and more fragile than ejaculated ones. Therefore, sperm processing techniques should be used with great caution to avoid jeopardizing the sperm fertilizing potential in treatment cycles. In this review, we describe the current methods for processing surgically-retrieved specimens, either fresh or frozen- thawed, and provide the tips and pitfalls for facilitating the handling of such specimens. In addition, we present the available laboratory tools to aid in the identification of viable immotile spermatozoa to be used in conjunction with assisted reproductive techniques. Review of the literature was carried out using PubMed and Science Direct search engines.

  1. Laboratory handling of epididymal and testicular spermatozoa: What can be done to improve sperm injections outcome

    Directory of Open Access Journals (Sweden)

    Sandro C Esteves

    2012-01-01

    Full Text Available Spermatozoa from azoospermic males can be retrieved from either the epididymis or the testis, depending on the type of azoospermia, using different surgical methods such as percutaneous epididymal sperm aspiration (PESA, testicular sperm aspiration (TESA, testicular sperm extraction (TESE, and microsurgical testicular sperm extraction (micro- TESE. After collecting the epididymal fluid or testicular tissue, laboratory techniques are used to remove contaminants, cellular debris, noxious microorganisms, and red blood cells. Processed spermatozoa may be used for intracytoplasmic sperm injection or eventually be cryopreserved. However, spermatozoa collected from either the epididymis or the testis are often compromised and more fragile than ejaculated ones. Therefore, sperm processing techniques should be used with great caution to avoid jeopardizing the sperm fertilizing potential in treatment cycles. In this review, we describe the current methods for processing surgically-retrieved specimens, either fresh or frozen- thawed, and provide the tips and pitfalls for facilitating the handling of such specimens. In addition, we present the available laboratory tools to aid in the identification of viable immotile spermatozoa to be used in conjunction with assisted reproductive techniques. Review of the literature was carried out using PubMed and Science Direct search engines.

  2. The Clinicopathologic Significance of p53 and BAF-250a (ARID1A) Expression in Clear Cell Carcinoma of the Endometrium

    OpenAIRE

    Fadare, Oluwole; Gwin, Katja; Desouki, Mohamed M.; Crispens, Marta A.; Jones, Howard W.; Khabele, Dineo; Liang, Sharon X.; Zheng, Wenxin; Mohammed, Khaled; Hecht, Jonathan L.; Parkash, Vinita

    2013-01-01

    TP53 mutation (and associated p53 protein overexpression) is probably a negative prognostic marker in endometrial cancers, but its relevance in the rarer histologic subtypes, including clear cell carcinomas, has not been delineated. Preclinical studies suggest functional interactions between p53 and the BAF250a protein, the product of a tumor suppressor gene ARID1A that is frequently mutated in ovarian clear cell carcinoma. In this study, we evaluated the significance of p53 and BAF250a expre...

  3. DNA integrity of fresh and frozen canine epididymal spermatozoa.

    Science.gov (United States)

    Varesi, Sara; Vernocchi, Valentina; Morselli, Maria Giorgia; Luvoni, Gaia Cecilia

    2014-12-01

    The aims of this study were to evaluate: (1) the effect of cryopreservation on DNA fragmentation of canine epididymal spermatozoa, and (2) the potential protective effect of melatonin on post-thaw sperm quality (motility, morphology, acrosomal and DNA integrity). Epididymal spermatozoa were collected after orchiectomy of ten dogs. Sperm samples were frozen in the presence or absence of melatonin (1mM). DNA fragmentation index (percentage of spermatozoa with fragmented DNA) was similar in fresh samples (3.3±3.6) and samples frozen with (4.2±3.8) or without (3.6±3.7) melatonin. Sperm motility was significantly (psperm motility. Proportions of spermatozoa with normal morphology were similar in fresh and frozen samples, irrespective of the presence of melatonin in the extender. Acrosome integrity was significantly decreased (pepididymal spermatozoa was not affected by the freezing procedure, and the presence of melatonin did not preserve motility and acrosome integrity which were adversely affected by cryopreservation. The evaluation of DNA status of thawed gametes is particularly relevant for epididymal spermatozoa since these spermatozoa are usually stored and used in assisted reproductive techniques. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. Different extenders in the cryopreservation of bovine epididymal spermatozoa.

    Science.gov (United States)

    Papa, Patrícia M; Papa, Frederico O; Oliveira, Letícia A; Guasti, Priscilla N; Castilho, Caliê; Giometti, Ines Cristina

    2015-10-01

    The objective of this study was to evaluate the effects of two different egg yolk extenders incubated with or without Sperm Talp on the motility and plasma membrane integrity of cryopreserved bovine epididymal spermatozoa after freezing. Twenty-five testicles with epididymides from mature bulls were collected at the abattoir. Epididymal sperm recovery was performed by retrograde flushing using a skim milk-extender (Botu-Semen™). After recovery, sperm were incubated either without or with Sperm Talp and then submitted to centrifugation. For the freezing process, half of the testes were processed with Tris egg yolk extender, and half were processed with Botu-Bov™ egg yolk extender. Samples incubated in Sperm Talp exhibited better results than epididymal spermatozoa that were incubated without Sperm Talp (psperm from the bovine epididymides if the sperm were previously incubated with Sperm Talp. The extenders examined in this work did not differ in their effect on plasma membrane integrity after freezing. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study.

    Science.gov (United States)

    Kim, Hee Seung; Choi, Hwa-Young; Lee, Maria; Suh, Dong Hoon; Kim, Kidong; No, Jae Hong; Chung, Hyun Hoon; Kim, Yong Beom; Song, Yong Sang

    2016-01-01

    We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC). The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes. Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted non-complete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

  6. Evaluation of Lasting Effects of Heat Stress on Sperm Profile and Oxidative Status of Ram Semen and Epididymal Sperm

    Directory of Open Access Journals (Sweden)

    Thais Rose dos Santos Hamilton

    2016-01-01

    Full Text Available Higher temperatures lead to an increase of testicular metabolism that results in spermatic damage. Oxidative stress is the main factor responsible for testicular damage caused by heat stress. The aim of this study was to evaluate lasting effects of heat stress on ejaculated sperm and immediate or long-term effects of heat stress on epididymal sperm. We observed decrease in motility and mass motility of ejaculated sperm, as well as an increase in the percentages of sperm showing major and minor defects, damaged plasma and acrosome membranes, and a decrease in the percentage of sperm with high mitochondrial membrane potential in the treated group until one spermatic cycle. An increased enzymatic activity of glutathione peroxidase and an increase of stressed cells were observed in ejaculated sperm of the treated group. A decrease in the percentage of epididymal sperm with high mitochondrial membrane potential was observed in the treated group. However, when comparing immediate and long-term effects, we observed an increase in the percentage of sperm with low mitochondrial membrane potential. In conclusion, testicular heat stress induced oxidative stress that led to rescuable alterations after one spermatic cycle in ejaculated sperm and also after 30 days in epididymal sperm.

  7. Phosphopeptide analysis of rodent epididymal spermatozoa.

    Science.gov (United States)

    Baker, Mark A; Hetherington, Louise; Weinberg, Anita; Velkov, Tony

    2014-12-30

    Spermatozoa are quite unique amongst cell types. Although produced in the testis, both nuclear gene transcription and translation are switched off once the pre-cursor round cell begins to elongate and differentiate into what is morphologically recognized as a spermatozoon. However, the spermatozoon is very immature, having no ability for motility or egg recognition. Both of these events occur once the spermatozoa transit a secondary organ known as the epididymis. During the ~12 day passage that it takes for a sperm cell to pass through the epididymis, post-translational modifications of existing proteins play a pivotal role in the maturation of the cell. One major facet of such is protein phosphorylation. In order to characterize phosphorylation events taking place during sperm maturation, both pure sperm cell populations and pre-fractionation of phosphopeptides must be established. Using back flushing techniques, a method for the isolation of pure spermatozoa of high quality and yield from the distal or caudal epididymides is outlined. The steps for solubilization, digestion, and pre-fractionation of sperm phosphopeptides through TiO2 affinity chromatography are explained. Once isolated, phosphopeptides can be injected into MS to identify both protein phosphorylation events on specific amino acid residues and quantify the levels of phosphorylation taking place during the sperm maturation processes.

  8. Identification and validation of mouse sperm proteins correlated with epididymal maturation

    OpenAIRE

    Ijiri, Takashi W.; Merdiushev, Tanya; Cao, Wenlei; Gerton, George L.

    2011-01-01

    Sperm need to mature in the epididymis to become capable of fertilization. To understand the molecular mechanisms of mouse sperm maturation, we conducted a proteomic analysis using saturation dye labeling to identify proteins of caput and cauda epididymal sperm that exhibited differences in amounts or positions on two-dimensional gels. Of eight caput epididymal sperm-differential proteins, three were molecular chaperones and three were structural proteins. Of nine cauda epididymal sperm-diffe...

  9. Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynecologic malignancies

    Science.gov (United States)

    Wu, Ren-Chin; Ayhan, Ayse; Maeda, Daichi; Kim, Kyu-Rae; Clarke, Blaise A.; Shaw, Patricia; Chui, M. Herman; Rosen, Barry; Shih, Ie-Ming; Wang, Tian-Li

    2014-01-01

    Up-regulated expression of telomerase reverse transcriptase (TERT) and subsequent maintenance of telomere length are essential in tumor development. Recent studies have implicated somatic gain-of-function mutations at the TERT promoter as one of the mechanisms that promote transcriptional activation of TERT; however, it remains unclear whether this genetic abnormality is prevalent in gynecologic neoplasms. We performed mutational analysis in a total of 525 gynecological cancers, and correlated TERT promoter mutations with clinicopathological features. With the exception of ovarian clear cell carcinomas, in which mutations were found in 37 (15.9%) of 233 cases, the majority of gynecologic malignancies were wild-type. TERT promoter mutation does not appear to be an early event during oncogenesis, as it was not detected in the contiguous endometriosis associated with ovarian clear cell carcinoma. Ovarian clear cell carcinoma cell lines with TERT promoter mutations exhibited higher TERT mRNA expression than those with wild-type sequences (p = 0.0238). TERT promoter mutation tended to be mutually exclusive with loss of ARID1A protein expression (p= 4.4×10−9) and PIK3CA mutation (p= 0.0019) in ovarian clear cell carcinomas. No associations with disease-specific survival were observed for ovarian clear cell carcinoma. The above results, in conjunction with our previous report showing longer telomeres in ovarian clear cell carcinomas relative to other types of ovarian cancer, suggests that aberrations in telomere biology may play an important role in the pathogenesis of ovarian clear cell carcinoma. PMID:24338723

  10. Epididymal lithiasis in roosters: in the middle of the way there was a stone.

    Science.gov (United States)

    Oliveira, André G; Oliveira, Cleida A

    2011-10-10

    The epididymal region plays an important role in the reproduction of roosters, as it is the site of functions important in the maintenance of fertility, including fluid and calcium reabsorption and sperm surface modifications. About 10 years ago, a reproductive dysfunction characterized by the formation of luminal calcium stones in the epididymal region of roosters was described. This anomaly, known as epididymal lithiasis, is associated with a significant decrease in the fertility of affected roosters. This reproductive anomaly has been observed in multiple countries and is thought to negatively impact the poultry industry; however, the cause of epididymal lithiasis has not been fully determined. Several hypotheses have been proposed to explain the origin of epididymal lithiasis, including the presence of an infectious agent within the epididymal region, an autoimmune response, increased dietary calcium and vitamin D3 intake and the presence of genetic susceptibility factors; however, none of these has been proven to be the primary cause of the calcium stone formation. Nonetheless, considerable evidence suggests that regardless of the primary cause of epididymal lithiasis, this anomaly could result from a hormonal imbalance or a local impairment of calcium homeostasis in the epididymal region. The objectives of this mini-review are to 1) summarize the reproductive alterations observed in animals affected by epididymal lithiasis, 2) discuss the hypotheses proposed to explain the cause of luminal stone formation and 3) provide perspectives for future studies of this reproductive disorder. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study.

    Science.gov (United States)

    Gooskens, S L; Furtwängler, R; Spreafico, F; van Tinteren, H; de Kraker, J; Vujanic, G M; Leuschner, I; Coulomb-L'Herminé, A; Godzinski, J; Schleiermacher, G; Stoneham, S; Bergeron, C; Pritchard-Jones, K; Graf, N; van den Heuvel-Eibrink, M M

    2014-07-15

    Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%). In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.

  12. The Role of Vaginal Brachytherapy in the Treatment of Surgical Stage I Papillary Serous or Clear Cell Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barney, Brandon M., E-mail: barney.brandon@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Mariani, Andrea; Dowdy, Sean C.; Bakkum-Gamez, Jamie N. [Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota (United States); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2013-01-01

    Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic and paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.

  13. Diagnostic Impacts of Serum CA-125 Levels, Pap Smear Evaluation, and Endometrial Sampling in Women with Endometrial Clear Cell Carcinoma.

    Science.gov (United States)

    Cetinkaya, Nilufer; Selcuk, İlker; Ozdal, Bulent; Meydanli, Mehmet M; Gungor, Tayfun

    2016-01-01

    Endometrial clear cell carcinoma (ECCC) is a rare variant of endometrial cancer with an unfavorable prognosis. The aim of this study was to determine the relationships, if any, between preoperative serum cancer antigen 125 (CA-125) levels, the last Papanicolaou (Pap) smear, the results of endometrial biopsy and tumor histology, and disease-stage according to permanent histopathology. The data of 26 women with ECCC were collected from their medical records to compare demographics, preoperative serum CA-125 levels, Pap test results, histological diagnosis of the endometrial biopsy, and tumor histology, as well as the disease stage according to permanent histopathology. The mean age at diagnosis was 64.0 years. There were 17 (65.3%) women with pure ECCC and 8 (30.7%) women with a mixed histology. Stage III-IV disease was diagnosed in 12 (46.2%) women and occurred more frequently in pure ECCC (n = 11, 91.7%). CA-125 values were significantly higher in advanced stage disease. Cytological evaluation indicated the presence of 71.4% (10/14) cytological abnormalities in pure ECCC. The overall sensitivity of endometrial sampling for the detection of malignancy was 92.3% (24/26), whereas the accurate diagnosis of ECCC was only 34.7% (8/23) with the Pipelle sampler. Pap test abnormalities are frequent in ECCC. Although it is less accurate in the diagnosis of ECCC than in the detection of malignancy, endometrial sampling is still the main procedure for the diagnosis of ECCC. Higher preoperative CA-125 concentrations imply the presence of advanced stage ECCC. © 2016 S. Karger GmbH, Freiburg.

  14. Puma (Puma concolor) epididymal sperm morphometry.

    Science.gov (United States)

    Cucho, Hernán; Alarcón, Virgilio; Ordóñez, César; Ampuero, Enrique; Meza, Aydee; Soler, Carles

    2016-01-01

    The Andean puma (Puma concolor) has not been widely studied, particularly in reference to its semen characteristics. The aim of the present study was to define the morphometry of puma sperm heads and classify their subpopulations by cluster analysis. Samples were recovered postmortem from two epididymides from one animal and prepared for morphological observation after staining with the Hemacolor kit. Morphometric data were obtained from 581 spermatozoa using a CASA-Morph system, rendering 13 morphometric parameters. The principal component (PC) analysis was performed followed by cluster analysis for the establishment of subpopulations. Two PC components were obtained, the first related to size and the second to shape. Three subpopulations were observed, corresponding to elongated and intermediate-size sperm heads and acrosomes, to large heads with large acrosomes, and to small heads with short acrosomes. In conclusion, puma spermatozoa showed no uniform sperm morphology but three clear subpopulations. These results should be used for future work in the establishment of an adequate germplasm bank of this species.

  15. Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate.

    Science.gov (United States)

    Nilsson, H; Lindgren, D; Mandahl Forsberg, A; Mulder, H; Axelson, H; Johansson, M E

    2015-01-08

    Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-producing metabolic pathways. One exception seems to be the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most other pathways than that of glycolysis has been shown to be reduced. This makes ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of the disease. However, few studies have so far addressed this issue. In this report, we show a strikingly reduced mitochondrial respiratory capacity of primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in established ccRCC cell lines, a finding that highlights the importance of using biologically relevant models in the search for new candidate cancer therapies. 3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been shown to be well tolerated in vivo, should be further analyzed for the possible development of selective treatment strategies for patients with ccRCC.

  16. A simplified method to detect epididymal sperm aneuploidy (ESA) in mice using three-chromosome fish

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, X.; O`Hogan, S.; Wyrobek, A. [Lawrence Livermore National Lab., CA (United States)

    1995-11-01

    We developed a new method (ESA) to detect aneuploidy and polyploidy in epididymal sperm of mice using three-chromosome FISH. In comparison to a previous method (TSA-testicular spermatid aneuploidy), which required late-step spermatids, the ESA method utilizes epididymal sperm, which are easier to collect than testicular cells. The ESA method also provides a homogenous population of cells, which significantly speeds up the scoring procedure. A total of 6 mice were investigated by the ESA method and results compared with those obtained by the TSA method: 2 mice each of Robertsonian (8.14) heterozygotes, Rb(8.14) homozygotes and B6C3F1. About 10,000 sperm were scored per mouse. For the ESA method, epididimides were cut into small pieces and filtered. Sperm were prepared for hybridization by sonication and a modification of the DTT/LIS method previously described. Sperm aneuploidy was detected by multi-color FISH using three DNA probes specific for mouse chromosomes X, Y and 8. The sex ratio of X8(49.7%) and Y8(49.6%) did not differ from the expected 1:1. The efficiency of ESA was very high; -0.3% of the cells showed no hybridization domain. Hyperhaploidy frequencies for chromosomes X, Y and 8 compared well between the ESA and TSA methods for Rb(8.14) heterozygous (p=0.79) and B6C3F1 mice (p>0.05). The data obtained from Rb(8.14) homozygotes were similar to those from B6C3F1, as predicted (p=0.3). This highly efficient ESA assay is therefore, recommended for future studies of the mechanism of induction of aneuploidy in male germ cells. It also lays a solid foundation for automated scoring.

  17. The putative tumor suppressor, miR-199a, regulated by Snail, modulates clear cell renal cell carcinoma aggressiveness by repressing ROCK1.

    Science.gov (United States)

    Zhang, Xiao; Li, Peng; Ding, Zhen; Wang, Huili; Wang, Junye; Han, Lei; Ding, Shangwei

    2018-01-01

    Aberrant expression of miR-199a has been frequently reported in cancer studies; however, its role in renal cell carcinoma (RCC) has not been examined in detail. Here, we showed that miR-199a was downregulated in RCC and associated with poor prognostic phenotype. Using luciferase and western blot assays we identified that Rho-associated coiled coil-containing protein kinases 1 (ROCK1) was a direct target gene for miR-199a. miR-199a regulated proliferation, invasion, and apoptosis of clear cell renal cell carcinoma (ccRCC) cells by modulating ROCK1 expression. Interestingly, we also found that miR-199a was modulated by snail in ccRCC cells. Snail elevated ROCK1 expression by repressing miR-199a activity. Altogether, our results identify a crucial tumor suppressive role of miR-199a in the progression of ccRCC and suggest that miR-199a might be an anticancer therapeutic target for ccRCC patients.

  18. The effect of citric acid and citrate on protoplasmic droplet of bovine epididymal sperms

    Directory of Open Access Journals (Sweden)

    Keivan Abdy

    2011-11-01

    Full Text Available AbstractFor evaluation of citric acid and citrate effects on bovine epididymal protoplasmic droplets, fifty bovine testes were collected in the October 2007 till June 2008 from Urmia slaughterhouse and transported to the laboratory in a cool container filled with 5 °C ice pack. Caudal epididymis was incised and sperm cells were put into Petri dishes containing hams f10 media with 10% fetal calf serum (FCS, which were kept in 37 °C, CO2 incubator. Then sperm cells were counted and 50-milion per mL concentration was prepared. After this stage, three dilutions of citric acid (0.1, 0.2, 0.3 N and one dilution of citrate (1N, based on normal osmolarity and normal pH were added to a micro tube containing 25 milion per mL sperm. Then one-step eosin-nigrosin staining in 30-60-120-240-360 minutes was performed and slides were evaluated with 1000-x phase contrast microscope and 200 sperm cells per slide were counted. The results revealed significant difference between blank and citric acid 0.3 N. The proportion of protoplasmic droplet in group consisting of 0.3 N acid citric in 120-240-360 minutes, was significantly lower than that of blank (P < 0.05. There was no significant difference between citrate – blank and citric acid 0.1N-blank groups, but after 240 minutes significant difference was observed between blank & citric acid 0.2 N (P < 0.05. In conclusions citric acid based on dilution and time duration can reduce the proportion of bovine epididymal sperm cytoplasmic droplets.

  19. Characteristics of the Epididymal Luminal Environment Responsible for Sperm Maturation and Storage.

    Science.gov (United States)

    Zhou, Wei; De Iuliis, Geoffry N; Dun, Matthew D; Nixon, Brett

    2018-01-01

    The testicular spermatozoa of all mammalian species are considered functionally immature owing to their inability to swim in a progressive manner and engage in productive interactions with the cumulus-oocyte complex. The ability to express these key functional attributes develops progressively during the cells' descent through the epididymis, a highly specialized ductal system that forms an integral part of the male reproductive tract. The functional maturation of the spermatozoon is achieved via continuous interactions with the epididymal luminal microenvironment and remarkably, occurs in the complete absence of de novo gene transcription or protein translation. Compositional analysis of the luminal fluids collected from the epididymis of a variety of species has revealed the complexity of this milieu, with a diversity of inorganic ions, proteins, and small non-coding RNA transcripts having been identified to date. Notably, both the quantitative and qualitative profile of each of these different luminal elements display substantial segment-to-segment variation, which in turn contribute to the regionalized functionality of this long tubule. Thus, spermatozoa acquire functional maturity in the proximal segments before being stored in a quiescent state in the distal segment in preparation for ejaculation. Such marked division of labor is achieved via the combined secretory and absorptive activity of the epithelial cells lining each segment. Here, we review our current understanding of the molecular mechanisms that exert influence over the unique intraluminal environment of the epididymis, with a particular focus on vesicle-dependent mechanisms that facilitate intercellular communication between the epididymal soma and maturing sperm cell population.

  20. [Testicular and epididymal appendages. Contribution about it's embryology and pathogenesis].

    Science.gov (United States)

    Blesa, E; Moreno, C; Blesa, A; Rodríguez, L; Núñez, R; Cabrera, R

    2003-04-01

    The testicular appendages are structures with biologic activity and with the possibility to become ischaemic or to degenerate before determined stimulus. Laterly, we have seen an apparent increase in our cases of torsion of testicular appendages. The said, together with the questions about embriology and pathogenesis of this structures, encourage us to do this work. 1- Retrospective clinical study of patients operated of torsion of testicular appendages, from January 1984 to December 2001. We asses age, year of operation and clinical features. 2- Prospective clinical study of patients operated of torsion of testicular appendages, between March 1999 and March 2000. We asses age, time of evolution, degree of ischaemia, nutritional status, sexual maturity stage and testicular volume. 3- Inmunocytochemical study of testicular and epididymal appendages. We identified the oestrogen receptors. There is a meaningful increase in the yearly incidence of ischaemia of testicular appendages. The mean age of the patients was 9.3 +/- 2.5 years, similar alone of the study. In the patients of group 2, the mean time of evolution was 49.2 +/- 46.6 hours. The appendages showed oedema and several degrees of ischaemia in the absence of torsion (14/21). The body mass index was 19.5 +/- 3.7, and 90% of patients had stages I and II of Tanner. The mean of testicular volume was 2.1 +/- 1.6 ml. By means of inmunocytochemical study we identified oestrogen receptors in 7 of all testicular appendages studied and absence of oestrogen receptors in all epididymal appendages. The clinical syndrome of the acute scrotum in the majority of cases is due to oedema and ischemia of the appendages, in absence of torsion, probably related to its enlargement in response to hormonal stimulation, at least in some grade, in prepubertal boys. The difference found, related to oestrogen receptors, suggest a different origin for testicular and epididymal appendages.

  1. Differences between epididymal and ejaculated sperm characteristics in donkey.

    Science.gov (United States)

    Gloria, Alessia; Contri, Alberto; De Amicis, Ippolito; Robbe, Domenico; Carluccio, Augusto

    2011-10-01

    Spermatozoa acquire their motility and fertilizing ability during their passage through the epididymal canal. In the epididymal caput and corpus spermatozoa undergo several biochemical and metabolic changes while the cauda of the epididymis should be considered as the primarily site for storage of the spermatozoa. In the horse spermatozoa from cauda epididymis were collected and frozen, and the fertility of semen assessed. However, no studies have detailed semen characteristics of spermatozoa collected from the cauda epididymis in the jackass. In this study sperm characteristics of spermatozoa in the cauda epididymis of the donkey was reported and a comparison with ejaculated spermatozoal characteristics was performed. Samples from 10 Martina Franca jackasses were collected and analyzed for viability (Propidium iodide/Sybr-14® fluorescent stain), mitochondrial activity (Mitotraker® fluorescent stain), objective motility characteristics (by Computer Assisted Sperm Analyzer - CASA) and morphology. A higher viability and mitochondrial activity in the cauda epididymis samples were reported in this paper. Samples reported in this paper were identified and the percentage of total and progressive spermatozoa was comparable, but trajectories were more rapid (higher VCL) with less progressiveness (higher ALH and lower STR and LIN) in the cauda epididymis. Sperm morphology showed a pronounced variability between jackasses, with comparable values for all morphological subclasses. In this study the loss of the distal cytoplasmic droplets happen close to or after ejaculation because the percentage fell to nearly 0% after ejaculation. As suggested for bulls, the presence of a similar percentage in sperm with proximal cytoplasmic droplet in epididymal and ejaculated semen is likely to indicate a failure in the maturation process. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. DNA fragmentation and sperm head morphometry in cat epididymal spermatozoa.

    Science.gov (United States)

    Vernocchi, Valentina; Morselli, Maria Giorgia; Lange Consiglio, Anna; Faustini, Massimo; Luvoni, Gaia Cecilia

    2014-10-15

    Sperm DNA fragmentation is an important parameter to assess sperm quality and can be a putative fertility predictor. Because the sperm head consists almost entirely of DNA, subtle differences in sperm head morphometry might be related to DNA status. Several techniques are available to analyze sperm DNA fragmentation, but they are labor-intensive and require expensive instrumentations. Recently, a kit (Sperm-Halomax) based on the sperm chromatin dispersion test and developed for spermatozoa of different species, but not for cat spermatozoa, became commercially available. The first aim of the present study was to verify the suitability of Sperm-Halomax assay, specifically developed for canine semen, for the evaluation of DNA fragmentation of epididymal cat spermatozoa. For this purpose, DNA fragmentation indexes (DFIs) obtained with Sperm-Halomax and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) were compared. The second aim was to investigate whether a correlation between DNA status, sperm head morphology, and morphometry assessed by computer-assisted semen analysis exists in cat epididymal spermatozoa. No differences were observed in DFIs obtained with Sperm-Halomax and TUNEL. This result indicates that Sperm-Halomax assay provides a reliable evaluation of DNA fragmentation of epididymal feline spermatozoa. The DFI seems to be independent from all the measured variables of sperm head morphology and morphometry. Thus, the evaluation of the DNA status of spermatozoa could effectively contribute to the completion of the standard analysis of fresh or frozen semen used in assisted reproductive technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Clear Cell Carcinoma of the Endometrium: Evaluation of Prognostic Parameters in a Multi-institutional Cohort of 165 Cases.

    Science.gov (United States)

    Abdulfatah, Eman; Sakr, Sharif; Thomas, Sumi; Al-Wahab, Zaid; Mutch, David G; Dowdy, Sean; Bandyopadhyay, Sudeshna; Munkarah, Adnan; Elshaikh, Mohamed; Morris, Robert; Ali-Fehmi, Rouba

    2017-10-01

    Clear cell carcinoma (CCC) comprises a rare yet an aggressive subtype, accounting for less than 5% of all uterine carcinomas. Several clinicopathologic features have been predictive of poor prognosis; however, data remain controversial. The aim of this study was to evaluate the clinicopathologic features of a multi-institutional cohort of endometrial CCC in order to identify which, if any, have prognostic significance. Retrospective review of endometrial CCC diagnosed between 1995 and 2012 at 3 institutions was conducted to evaluate clinicopathologic parameters: age, race, tumor size, stage, myometrial invasion (MI), lymphovascular invasion, lymph node and adnexal involvement, adjuvant therapy, and outcomes. Data were analyzed using Fisher exact, Cox regression, and Kaplan-Meier analyses. Patients' ages ranged from 36 to 90 years (median, 67 years). The median tumor size was 3.6 cm. Inner-half MI was present in 44%, lymphovascular invasion in 34%, adnexal involvement in 16%, and lymph node metastasis in 30% of cases. Fifty-eight percent of the patients presented with early-stage disease. The 5-year overall survival (OS) was 58%. Shorter disease-free interval (DFI) was significantly associated with older age at diagnosis (>70 years), advanced-stage disease, adnexal involvement, and deep MI (P = 0.005, P = 0.001, P = 0.001, and P = 0.003, respectively). Patients who received adjuvant chemotherapy had a significantly worse DFI and 5-year OS (P = 0.001 and P = 0.001, respectively). A significantly shorter 5-year OS was noted with advanced stage (III-IV) and presence of adnexal involvement (P = 0.001 and P = 0.021, respectively). On Cox regression analysis, advanced-stage disease, older age, and adnexal involvement were significant independent predictors of worse DFI (P = 0.001, P = 0.005, and P = 0.019, respectively), whereas inner-half MI was a significant independent predictor of longer DFI (P = 0.004). Adjuvant radiotherapy alone was a significant independent

  4. Clear cell adenocarcinoma of the vagina and cervix. An update of the central Netherlands registry showing twin age incidence peaks.

    Science.gov (United States)

    Hanselaar, A; van Loosbroek, M; Schuurbiers, O; Helmerhorst, T; Bulten, J; Bernhelm, J

    1997-06-01

    The objective of this study was to update the registry of women in the Netherlands with clear cell adenocarcinoma (CCAC) of the cervix or vagina with or without intrauterine exposure to diethylstilbestrol (DES). From a nationwide search in PALGA, the automated pathology registry in the Netherlands, data were gathered on women with CCAC born after 1947. Information obtained from the clinical files of the patients included reported exposure to DES, patterns of complaints previous to diagnosis, the current status of the patients, and the results of cytopathologic examinations previous to histopathologic diagnosis. After review of the histopathologic slides, the specific pathologic characteristics of CCAC were determined. The age distribution of women born after 1947 was compared with that of women born before 1947. Information about possible exposure to DES during pregnancy was available for 73 of 88 women with CCAC born after 1947. Exposure to DES was reported for 47 (64%) of these women. The DES medication was most often reported as having started before the 18th week of pregnancy. Cytopathologic examination was informative in 81% of the cases of CCAC of the cervix, but only in 41% of the cases of CCAC of the vagina. Most patients had Stage I or II tumors at diagnosis. Tumor Stage III and IV and a high grade of nuclear atypia were related to unfavorable outcome. The age distribution of all patients with CCAC showed two distinct peaks; one at young age, (a mean age of 26 years), and one at older age (a mean age of 71 years). This bimodal age distribution still applied when the cases in which DES exposure was reported had been excluded. Despite the fact that DES has not been prescribed to pregnant women in the Netherlands in the last 20 years, CCAC is still relevant in our times. It is important to stay alert and periodically to update and evaluate the data of this registry, including data on women born outside the DES exposure period. The bimodal age distribution in

  5. Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Nicolai Skovbjerg Arildsen

    2017-05-01

    Full Text Available ObjectiveOvarian clear cell carcinomas (OCCCs constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30–50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome.MethodsGene expression profiling of formalin-fixed, paraffin-embedded (FFPE tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67 was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2. Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3 was used for validation by immunohistochemistry and chromogenic in situ hybridization.ResultsGene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors.ConclusionOCCCs appear

  6. Bilateral synchronous high-grade serous carcinoma and clear cell carcinoma in right and left ovaries with immunohistochemical confirmation: An exceptional finding

    Directory of Open Access Journals (Sweden)

    Agarwal Preeti

    2014-01-01

    Full Text Available Synchronous epithelial or mixed epithelial and germ cells tumors in the same ovary is a recognized event, however, having two different surface epithelial tumors in contra lateral ovaries is a rare occurrence; prognosis and pathogenesis of which is still not clear. We came across similar finding in a 60-year-old female with different types of surface epithelial neoplasm in right and left ovaries at the same time; both of which were malignant. Clinicoradiologically only the left ovary revealed tumor, right ovary was atrophic. To our surprise, left ovary revealed high grade serous carcinoma and the right ovary displayed clear cell carcinoma. We performed immunohistochemistry to rule out the possibility of clear cell variant of serous papillary carcinoma. On literature search, we found; only single case with synchronous presentation of two different surface epithelial ovarian tumors in the same patient, both of which were benign.

  7. HtrA3 is regulated by 15-deoxy-Δ12,14-prostaglandin J2 independently of PPARγ in clear cell renal cell carcinomas

    International Nuclear Information System (INIS)

    Theoleyre, Sandrine; Mottier, Stephanie; Masson, Damien; Denis, Marc G.

    2010-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) ligands have been shown to possess anti-proliferative effects in many types of cancer. In clear cell renal cell carcinoma (CCRCC), the targets involved in these effects are not known. In this study, we demonstrated that, in CCRCC cell lines, the endogenous PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) induces the expression, both at the mRNA and the protein levels, of the HtrA3 gene. This gene belongs to the High-Temperature Requirement Factor A family of serine proteases that repress signaling by TGF-β family members and inhibit cell migration. Rosiglitazone or ciglitazone, synthetic PPARγ agonists, did not induce HtrA3 expression, and the PPARγ antagonist GW9662 did not prevent 15dPGJ2 induction, suggesting that the up-regulation of HtrA3 by 15dPGJ2 is independent of PPARγ. The MEK/ERK inhibitor PD98059 dramatically repressed HtrA3 induction. Altogether, these data indicate that 15dPGJ2 is able to stimulate the expression of HtrA3 through an indirect mechanism involving the MEK/ERK pathway but independent of PPARγ. Our results provide a better understanding of the mechanisms involved in the regulation of HtrA3, a potential tumor suppressor gene.

  8. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship...... to CXCR4 and its ligand CXCL12 in ccRCC is unclear. By using reverse transcription PCR, immunofluorescence and immunohistochemistry, strong mRNA and protein expression of CXCR4, CXCL12, MMP2, MMP9 and MMP inhibitors TIMP1 and TIMP2 was found in VHL-null 786-O ccRCC cells. Loss of CXCR4/CXCL12 expression...... after restoration of VHL function in these cells was accompanied by a significant reduction of MMP2 and MMP9 expression, whereas neither TIMP1 nor TIMP2 expression was affected. Using real-time PCR analysis, higher MMP2 (p = 0.0134) and MMP9 (p = 0.067) mRNA expression levels were detected in primary cc...

  9. Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.

    Science.gov (United States)

    He, Y; Wu, A C; Harrington, B S; Davies, C M; Wallace, S J; Adams, M N; Palmer, J S; Roche, D K; Hollier, B G; Westbrook, T F; Hamidi, H; Konecny, G E; Winterhoff, B; Chetty, N P; Crandon, A J; Oliveira, N B; Shannon, C M; Tinker, A V; Gilks, C B; Coward, J I; Lumley, J W; Perrin, L C; Armes, J E; Hooper, J D

    2016-01-28

    Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC

  10. Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

    Science.gov (United States)

    Lalani, Aly-Khan A; Gray, Kathryn P; Albiges, Laurence; Callea, Marcella; Pignon, Jean-Christophe; Pal, Soumitro; Gupta, Mamta; Bhatt, Rupal S; McDermott, David F; Atkins, Michael B; Woude, G F Vande; Harshman, Lauren C; Choueiri, Toni K; Signoretti, Sabina

    2017-11-28

    In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

  11. Follow-up of children born after ICSI with epididymal spermatozoa

    NARCIS (Netherlands)

    Woldringh, G.H.; Horvers, M.; Janssen, A.J.W.M.; Reuser, J.J.C.M.; Groot, S.A. de; Steiner, K.; Hauwers, K.W.M. d'; Wetzels, A.M.M.; Kremer, J.A.M.

    2011-01-01

    BACKGROUND: To evaluate the safety of ICSI with epididymal sperm, this study compared children born after ICSI treatment with epididymal sperm and children conceived after IVF and ICSI with ejaculated sperm. Additionally, the results of a multidisciplinary, multicentre follow-up of the children

  12. Identification and validation of mouse sperm proteins correlated with epididymal maturation

    Science.gov (United States)

    Ijiri, Takashi W.; Merdiushev, Tanya; Cao, Wenlei; Gerton, George L.

    2012-01-01

    Sperm need to mature in the epididymis to become capable of fertilization. To understand the molecular mechanisms of mouse sperm maturation, we conducted a proteomic analysis using saturation dye labeling to identify proteins of caput and cauda epididymal sperm that exhibited differences in amounts or positions on two-dimensional gels. Of eight caput epididymal sperm-differential proteins, three were molecular chaperones and three were structural proteins. Of nine cauda epididymal sperm-differential proteins, six were enzymes of energy metabolism. To validate these proteins as markers of epididymal maturation, immunoblotting and immunofluorescence analyses were performed. During epididymal transit, heat shock protein 2 was eliminated with the cytoplasmic droplet and smooth muscle γ-actin exhibited reduced fluorescence from the anterior acrosome while the signal intensity of aldolase A increased, especially in the principal piece. Besides these changes, we observed protein spots, such as glutathione S-transferase mu 5 and the E2 component of pyruvate dehydrogenase complex, shifting to more basic isoelectric points, suggesting post-translational changes such dephosphorylation occur during epididymal maturation. We conclude that most caput epididymal sperm-differential proteins contribute to the functional modification of sperm structures and that many cauda epididymal sperm-differential proteins are involved in ATP production that promotes sperm functions such as motility. PMID:21805633

  13. Characteristics of the Epididymal Luminal Environment Responsible for Sperm Maturation and Storage

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2018-02-01

    Full Text Available The testicular spermatozoa of all mammalian species are considered functionally immature owing to their inability to swim in a progressive manner and engage in productive interactions with the cumulus–oocyte complex. The ability to express these key functional attributes develops progressively during the cells’ descent through the epididymis, a highly specialized ductal system that forms an integral part of the male reproductive tract. The functional maturation of the spermatozoon is achieved via continuous interactions with the epididymal luminal microenvironment and remarkably, occurs in the complete absence of de novo gene transcription or protein translation. Compositional analysis of the luminal fluids collected from the epididymis of a variety of species has revealed the complexity of this milieu, with a diversity of inorganic ions, proteins, and small non-coding RNA transcripts having been identified to date. Notably, both the quantitative and qualitative profile of each of these different luminal elements display substantial segment-to-segment variation, which in turn contribute to the regionalized functionality of this long tubule. Thus, spermatozoa acquire functional maturity in the proximal segments before being stored in a quiescent state in the distal segment in preparation for ejaculation. Such marked division of labor is achieved via the combined secretory and absorptive activity of the epithelial cells lining each segment. Here, we review our current understanding of the molecular mechanisms that exert influence over the unique intraluminal environment of the epididymis, with a particular focus on vesicle-dependent mechanisms that facilitate intercellular communication between the epididymal soma and maturing sperm cell population.

  14. Role of Dicer1-Dependent Factors in the Paracrine Regulation of Epididymal Gene Expression.

    Directory of Open Access Journals (Sweden)

    Olivia Jerczynski

    Full Text Available Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules such as microRNAs (miRNAs and endogenous small interfering RNAs (endo-siRNAs. These small non-coding RNAs are important regulators of post-transcriptional gene expression and participate in the control of male fertility. With the knowledge that 1 Dicer1-dependent factors are required for proper sperm maturation in the epididymis, and that 2 miRNAs are potent mediators of intercellular communication in most biological systems, we investigated the role of Dicer1-dependent factors produced by the proximal epididymis (initial segment/caput- including miRNAs- on the regulation of epididymal gene expression in the distal epididymis regions (i.e. corpus and cauda. To this end, we performed comparative microarray and ANOVA analyses on control vs. Defb41iCre/wt;Dicer1fl/fl mice in which functional Dicer1 is absent from the principal cells of the proximal epididymis. We identified 35 and 33 transcripts that displayed significant expression level changes in the corpus and cauda regions (Fold change > 2 or 2 or < -2; p < 0.01. These miRNAs are secreted via extracellular vesicles (EVs derived from the DC2 epididymal principal cell line, and their expression correlates with target transcripts involved in distinct biological pathways, as evidenced by in silico analysis. Albeit correlative and based on in silico approach, our study proposes that Dicer1-dependent factors trigger- directly or not-significant genes expression changes in distinct regions of this organ. The paracrine control of functions important to post-testicular sperm maturation by Dicer1-dependent factors may open new avenues for the identification of molecular targets important to male fertility control.

  15. Evaluation of the role of downregulation of SNF5/INI1 core subunit of SWI/SNF complex in clear cell renal cell carcinoma development.

    Science.gov (United States)

    Sarnowska, Elzbieta; Szymanski, Michal; Rusetska, Nataliia; Ligaj, Marcin; Jancewicz, Iga; Cwiek, Pawel; Skrodzka, Marta; Leszczynski, Marcin; Szarkowska, Joanna; Chrzan, Alicja; Stachowiak, Malgorzata; Steciuk, Jaroslaw; Maassen, Anna; Galek, Lech; Demkow, Tomasz; Siedlecki, Janusz A; Sarnowski, Tomasz J

    2017-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau ( VHL ) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 ( POLYBROMO1 ) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer. The evaluation of INI1 protein level in samples from 50 patients with diagnosed ccRCC, including three displaying rhabdoid features, showed the INI1 positive staining in rhabdoid cells while the conventional ccRCC cells exhibited reduced INI1 level. This indicated the rhabdoid component of ccRCC as distinct from other known rhabdoid tumors. The reduced INI1 protein level observed in all conventional ccRCC cases used in this study correlated with decreased SMARCB1 gene expression at the transcript level. Consistently, the overexpression of INI1 protein in A498 ccRCC cell line resulted in the elevation of endogenous SMARCB1 transcript level indicating that the INI1-dependent regulatory feedback loop controlling expression of this gene is affected in ccRCC Moreover, the set of INI1 target genes including i.e. CXCL12/CXCR7/CXCR4 chemokine axis was identified to be affected in ccRCC. In summary, we demonstrated that the inactivation of INI1 may be of high importance for ccRCC development and aggressiveness.

  16. Emergency Pancreatoduodenectomy with Preservation of Gastroduodenal Artery for Massive Gastrointestinal Bleeding due to Duodenal Metastasis by Clear Cell Renal Cell Carcinoma in a Patient with Celiac Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Kyriakos Neofytou

    2014-01-01

    Full Text Available Duodenal metastasis from renal cell carcinoma is rare, and even rarer is a massive gastrointestinal bleeding from such tumours. Coeliac occlusive disease, although rarely symptomatic, can lead to ischaemic changes with anastomotic dehiscence and leaks when a patient undergoes pancreatoduodenectomy. A 41-year-old man with known metastasis to the adrenal glands and the second part of the duodenum close to the ampulla of Vater from clear cell renal cell carcinoma was admitted to our department due to massive gastrointestinal bleeding from the duodenal metastasis. Endoscopic control of the bleed was not possible, while the bleeding vessel embolization was able to control the haemorrhage only temporarily. An angiography during the embolization demonstrated the presence of stenosis of the coeliac artery and also hypertrophic inferior pancreaticoduodenal arteries supplying the proper hepatic artery via the gastroduodenal artery (GDA. The patient underwent emergency pancreatoduodenectomy with preservation of the gastroduodenal artery. The patient had an uneventful recovery and did not experience further bleeding. Also the blood flow to the liver was compromised as shown by the normal liver function tests (LFTs postoperatively. To the best of our knowledge, this is the first report of a preservation of the GDA during an emergency pancreatoduodenectomy.

  17. Diagnosis value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Ma Zhoupeng; Zhou Jianjun; Liu Xueling; Wang Chun; Zhang Shunzhuang

    2012-01-01

    Objective: To explore the diagnostic value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma. Methods: Sixty patients who were suspected of clear cell renal cell carcinoma underwent non-enhanced CT and contrast enhancement CT of early interface-phase between cortex -medulla and parenchymal phase on a dual-energy CT. The true non-enhanced kidney CT (TNCT) was performed in a single-energy acquisition mode, but the dual-phase contrast enhancement CT were performed in a dual-energy mode of 80 kV and 140 kV respectively. The virtual non-enhanced CT (VNCT) images were derived from the data of early interface phase using liver virtual non-contrast software. The diagnose according to VNCT combined dual-phase contrast enhancement CT and dual-phase contrast enhancement CT only were made respectively and compared with χ 2 test. Between the true non-contrast CT and the virtual non-contrast CT, the image quality was compared with Wilcoxon test; The radiation dose of volume CT dose index (CTDIvol) and dose length product(DLP) in a single-phase and total examination, the mean CT HU values of the tumours were compared with t test. Results: The accuracy of VNCT combined dual-phase contrast enhancement CT was higher than that of dual-phase contrast enhancement CT only [93.3% (56/60) vs.78.3% (47/60); χ 2 =5.6, P<0.05]. The detective ability (score) of VNCT was near to that of TNCT and the difference was not obvious (Z=0.00, P>0.05). The radiation dose of volume CT dose index (CTDIvol) and dose length product (DLP) in a single phase and total examination of VNCT [(8.85 ± 1.28) mGy, (196.45 ±21.12) mGy·cm, (17.69±2.35) mGy, (392.90±42.25) mGy · cm] were lower than that of TNCT [(10.20 ± 1.44) mGy,(218.29 ± 29.60) mGy · cm, (30.61 ± 3.27) mGy and (654.86 ± 88.81) mGy ·cm], t=4.21, 3.58, 23.63, 16.12 respectively, P<0.05. The mean CT HU values of tumours on VNCT images was higher than that

  18. Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Andersen, Claus B.; Nielsen, John E

    2010-01-01

    The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal...

  19. Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets

    DEFF Research Database (Denmark)

    van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H

    2013-01-01

    The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We co...

  20. High Expression of KCa3.1 in Patients with Clear Cell Renal Carcinoma Predicts High Metastatic Risk and Poor Survival

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Oliván-Viguera, Aida; Hansen, Lars Koch

    2015-01-01

    BACKGROUND: Ca2+-activated K+ channels have been implicated in cancer cell growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA and protein expression of the intermediate-conductance Ca2+-activated K+ channel, KCa3.1, is a molecular marker of clear cell Renal Cell...... specific survival trended towards reduction in the subgroup of high-KCa3.1-expressing tumors (phigh-KCa3.1-expressing tumors (p... tumors). Immunohistochemistry revealed high protein expression of KCa3.1 in tumor vessels of ccRCC and oncocytoma and in a subset of ccRCC cells. Oncocytoma cells were devoid of KCa3.1 protein. In a primary ccRCC cell line and Caki-1/2-ccRCC cells, we found KCa3.1-protein as well as TRAM-34-sensitive KCa...

  1. ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Takafumi Kuroda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiating cells (CICs are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas by the ALDEFLUOR assay. ALDH1(high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high cells. ALDH1(high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

  2. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

    Directory of Open Access Journals (Sweden)

    Quiroga-Garza Gabriela

    2012-02-01

    Full Text Available Abstract Seven percent of renal cell carcinoma (RCC cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC and a tubulocystic renal carcinoma (TCRC in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR and distal tubule cell (CK19 markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2 of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3 showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283

  3. Maximum standardized uptake value of fluorodeoxyglucose positron emission tomography/computed tomography is a prognostic factor in ovarian clear cell adenocarcinoma.

    Science.gov (United States)

    Konishi, Haruhisa; Takehara, Kazuhiro; Kojima, Atsumi; Okame, Shinichi; Yamamoto, Yasuko; Shiroyama, Yuko; Yokoyama, Takashi; Nogawa, Takayoshi; Sugawara, Yoshifumi

    2014-09-01

    Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful for diagnosing malignant tumors. Intracellular FDG uptake is measured as the standardized uptake value (SUV), which differs depending on tumor characteristics. This study investigated differences in maximum SUV (SUVmax) according to histologic type in ovarian epithelial cancer and the relationship of SUVmax with prognosis. This study included 80 patients with ovarian epithelial cancer based on histopathologic findings at surgery and who had undergone PET/CT before treatment. Maximum SUV on PET/CT of primary lesions and histopathology were compared based on histologic type, and the prognosis associated with different SUVmax was evaluated. Clinical tumor stage was I in 35 patients, II in 8, III in 25, and IV in 12. Histologic type was serous adenocarcinoma (AC) in 33 patients, clear cell AC in 27, endometrioid AC in 15, and mucinous AC in 5. Median SUVmax was lower in mucinous AC (2.76) and clear cell AC (4.9) than in serous AC (11.4) or endometrioid AC (11.4). Overall, median SUVmax was lower in clinical stage I (5.37) than in clinical stage ≥II (10.3). However, in both clear cell AC and endometrioid AC, when histologic evaluation was possible, no difference was seen between stage I and stage ≥II. Moreover, in clear cell AC, the 5-year survival rate was significantly higher in the low-SUVmax group (100%) than in the high-SUVmax group (43.0%, P = 0.009). Maximum SUV on preoperative FDG-PET/CT in ovarian epithelial cancer differs according to histologic type. In clear cell AC, SUVmax may represent a prognostic factor.

  4. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

    NARCIS (Netherlands)

    Hampras, S.S.; Sucheston-Campbell, L.E.; Cannioto, R.; Chang-Claude, J.; Modugno, F.; Dork, T.; Hillemanns, P.; Preus, L.; Knutson, K.L.; Wallace, P.K.; Hong, C.C.; Friel, G.; Davis, W.; Nesline, M.; Pearce, C.L.; Kelemen, L.E.; Goodman, M.T.; Bandera, E.V.; Terry, K.L.; Schoof, N.; Eng, K.H.; Clay, A.; Singh, P.K.; Joseph, J.M.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Baker, H.; Bean, Y.; Beckmann, M.W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Cook, L.S.; Cramer, D.W; Cybulski, C.; Dansonka-Mieszkowska, A.; Dennis, J.; Despierre, E.; Dicks, E.; Doherty, J.A.; Bois, A. du; Durst, M.; Easton, D.; Eccles, D.; Edwards, R.P.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Gronwald, J.; Harrington, P.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.T.; Hogdall, C.; Hogdall, E.; Hosono, S.; Iversen, E.S.; Jakubowska, A.; Jensen, A.; Ji, B.T.; Karlan, B.Y.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.L.M.; Klapdor, R.; Kolomeyevskaya, N.; Krakstad, C.; Kjaer, S.K.; Kruszka, B.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Liu, S.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.A.G.; Matsuo, K.; McGuire, V.; et al.,

    2016-01-01

    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and

  5. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

    DEFF Research Database (Denmark)

    Hampras, Shalaka S; Sucheston-Campbell, Lara E; Cannioto, Rikki

    2016-01-01

    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases a...

  6. Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

    Science.gov (United States)

    Lu, Qing; Li, Cui-xian; Huang, Bei-jian; Xue, Li-yun; Wang, Wen-ping

    2015-02-01

    To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p 97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

  7. Simultaneous metastases of clear cell renal cell carcinoma to the urinary bladder and left retroperitoneal space: A case report and review of the literature.

    Science.gov (United States)

    Li, Hengping; Wang, Jianzhong; Wei, Qiang; Wang, Huan

    2016-07-01

    The present study describes an extremely rare case of simultaneous metastases of clear cell renal cell carcinoma (ccRCC) to the urinary bladder and left retroperitoneal space, occurring subsequent to an open radical nephrectomy. A review of the literature is also considered. A 70-year-old man presenting with diabetes mellitus and hypertension was referred to West China Hospital (Chengdu, China) with constant left flank pain that had been apparent for 2 months. Ultrasonography identified a heterogeneous tumor with a solid component measuring 4.4×3.4×5.0 cm, and computed tomography (CT) revealed a circumscribed and contrast-enhanced tumor in the left kidney. Subsequent pathological analysis of the specimen, obtained from an open radical nephrectomy, confirmed the presence of ccRCC. At 1 month after the radical nephrectomy, an abdominopelvic CT scan identified tumors located on the posterior bladder wall and also in the left retroperitoneal space, forming due to hematuria and acute urinary clot retention. There was no evidence of metastasis to the lungs, bones or other organs. A transurethral resection of the bladder tumor was performed and pathological analysis of the bladder specimen demonstrated metastatic ccRCC. Extensive hydrothorax and general anasarca presented half a month after the transurethral resection, with the patient subsequently succumbing 15 days later.

  8. Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma.

    Science.gov (United States)

    Lucca, Ilaria; de Martino, Michela; Hofbauer, Sebastian L; Zamani, Nura; Shariat, Shahrokh F; Klatte, Tobias

    2015-12-01

    Pretreatment measurements of systemic inflammatory response, including the Glasgow prognostic score (GPS), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) have been recognized as prognostic factors in clear cell renal cell carcinoma (CCRCC), but there is at present no study that compared these markers. We evaluated the pretreatment GPS, NLR, MLR, PLR and PNI in 430 patients, who underwent surgery for clinically localized CCRCC (pT1-3N0M0). Associations with disease-free survival were assessed with Cox models. Discrimination was measured with the C-index, and a decision curve analysis was used to evaluate the clinical net benefit. On multivariable analyses, all measures of systemic inflammatory response were significant prognostic factors. The increase in discrimination compared with the stage, size, grade and necrosis (SSIGN) score alone was 5.8 % for the GPS, 1.1-1.4 % for the NLR, 2.9-3.4 % for the MLR, 2.0-3.3 % for the PLR and 1.4-3.0 % for the PNI. On the simultaneous multivariable analysis of all candidate measures, the final multivariable model contained the SSIGN score (HR 1.40, P patients with clinically localized CCRCC, the GPS and the MLR appear to be the most relevant prognostic measures of systemic inflammatory response. They may be used as an adjunct for patient counseling, tailoring management and clinical trial design.

  9. CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method.

    Science.gov (United States)

    Huhdanpaa, Hannu; Hwang, Darryl; Cen, Steven; Quinn, Brian; Nayyar, Megha; Zhang, Xuejun; Chen, Frank; Desai, Bhushan; Liang, Gangning; Gill, Inderbir; Duddalwar, Vinay

    2015-10-01

    There are distinct quantifiable features characterizing renal cell carcinomas on contrast-enhanced CT examinations, such as peak tumor enhancement, tumor heterogeneity, and percent contrast washout. While qualitative visual impressions often suffice for diagnosis, quantitative metrics if developed and validated can add to the information available from standard of care diagnostic imaging. The purpose of this study is to assess the use of quantitative enhancement metrics in predicting the Fuhrman grade of clear cell RCC. 65 multiphase CT examinations with clear cell RCCs were utilized, 44 tumors with Fuhrman grades 1 or 2 and 21 tumors with grades 3 or 4. After tumor segmentation, the following data were extracted: histogram analysis of voxel-based whole lesion attenuation in each phase, enhancement and washout using mean, median, skewness, kurtosis, standard deviation, and interquartile range. Statistically significant difference was observed in 4 measured parameters between grades 1-2 and grades 3-4: interquartile range of nephrographic attenuation values, standard deviation of absolute enhancement, as well as interquartile range and standard deviation of residual nephrographic enhancement. Interquartile range of nephrographic attenuation values was 292.86 HU for grades 1-2 and 241.19 HU for grades 3-4 (p value 0.02). Standard deviation of absolute enhancement was 41.26 HU for grades 1-2 and 34.66 HU for grades 3-4 (p value 0.03). Interquartile range was 297.12 HU for residual nephrographic enhancement for grades 1-2 and 235.57 HU for grades 3-4 (p value 0.02), and standard deviation of the same was 42.45 HU for grades 1-2 and 37.11 for grades 3-4 (p value 0.04). Our results indicate that absolute enhancement is more heterogeneous for lower grade tumors and that attenuation and residual enhancement in nephrographic phase is more heterogeneous for lower grade tumors. This represents an important step in devising a predictive non-invasive model to predict the

  10. Induction of oxidative stress in rat epididymal sperm after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Latchoumycandane, C.; Chitra, K.C.; Mathur, P.P. [School of Life Sciences, Pondicherry University (India)

    2002-03-01

    The ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to induce oxidative stress in various tissues of animals has been reported. The nature and mechanism of action of TCDD on the antioxidant system of sperm has not been studied. In the present study we have sought to investigate whether TCDD induces oxidative stress in the epididymal sperm of rats. Subchronic doses of TCDD (1, 10, and 100 ng/kg body weight per day) were administered orally to male Wistar strain rats for 45 days. After 24 h of the last treatment the rats were killed using diethyl ether. The epididymides were removed and cleared from the adhering tissues. Epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F12 medium, and counted using a hemocytometer. The epididymal sperm counts in the TCDD-treated groups decreased in a dose-dependent manner from the control value of 8.2{+-}0.14 x 10{sup 8} to 5.31{+-}0.15 x 10{sup 8}. Since a positive correlation (r=0.95; n=24) was observed between sperm count and DNA content of the epididymal sperm, DNA content was routinely used as an indicator of sperm count, and the results were expressed in terms of both protein and DNA. There was a significant decline in the activities of superoxide dismutase (40{+-}2.17 to 27.1{+-}0.76/mg protein and 32.41 to 18.07{+-}0.76/mg DNA), catalase (2.49{+-}0.13 to 2.03{+-}0.05/mg protein and 2.01{+-}0.05 to 1.35{+-}0.05/mg DNA), glutathione reductase (71.2{+-}3.87 to 48{+-}1.79/mg protein and 57.58{+-}1.52 to 31.94/mg DNA) and glutathione peroxidase (22.4{+-}1.43 to 16.9{+-}1.57/mg protein and 18.08{+-}0.61 to 11.38{+-}1.22/mg DNA) while there were increases in the levels of hydrogen peroxide (20.8{+-}1.96 to 55.3{+-}0.88/ mg protein and 16.18{+-}1.88 to 36.87{+-}0.88/ mg DNA) and lipid peroxidation (2.17{+-}0.2 to 6.08/mg protein and 1.75{+-}0.12 to 4.05{+-}0.12/mg DNA) in the epididymal sperm. The results suggest that graded doses of TCDD elicit depletion of antioxidant defense system

  11. Clear cell adenocarcinoma of the cervix in second generation young women who are without maternal exposure to diethylstilbestrol: A case report

    Directory of Open Access Journals (Sweden)

    Tanitra Tantitamit

    2017-05-01

    Full Text Available Clear cell adenocarcinoma of the cervix (CCAC is a rare type of gynecological cancer. The risk factors and pathogenesis have yet to be clearly determined. This is a case report of a 19-year-old woman, who was never exposed to DES from her mother, who had gone for an examination for vaginal bleeding. A polypoid mass measured at 3 cm presenting in her cervix was discovered. Histological diagnosis following cervical biopsy proved the tumor to be a clear cell carcinoma. The patient was then referred to our hospital. A loop electrosurgical excision procedure (LEEP was done and the pathological diagnosis was confirmed for clear cell carcinoma with a positive endocervical margin. Radical hysterectomy, pelvic lymphadenectomy and incidental appendectomy were achieved without any complications. The microscopic findings had revealed no residual tumor. The patient did not require adjuvant treatment. No sign of recurrence has been detected throughout 6 months of follow-up. We have performed the literature review on the clinical presentation, pathogenesis, pathology, diagnosis, treatment, and prognosis of this unusual tumor.

  12. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

  13. Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ewelina Pośpiech

    2015-01-01

    Full Text Available The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR=1.688, 95% CI: 1.104–2.582, P=0.016 and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P=0.012 to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P=0.036. Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P=0.041, which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P=0.008 as well as revealing interactions between GNAS1 and EPAS1 (P=0.016, GNAS1 and MC1R (P=0.031, GNAS1 and VDR (P=0.032, and MC1R and VDR (P=0.035.

  14. Impact of the Processes of Total Testicular Regression and Recrudescence on the Epididymal Physiology of the Bat Myotis nigricans (Chiroptera: Vespertilionidae.

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    Mateus R Beguelini

    Full Text Available Myotis nigricans is a species of vespertilionid bat, whose males show two periods of total testicular regression within the same annual reproductive cycle in the northwest São Paulo State, Brazil. Studies have demonstrated that its epididymis has an elongation of the caudal portion, which stores spermatozoa during the period of testicular regression in July, but that they had no sperm during the regression in November. Thus, the aim of this study was to analyze the impact of the total testicular regression in the epididymal morphophysiology and patterns of its hormonal regulation. The results demonstrate a continuous activity of the epididymis from the Active to the Regressing periods; a morphofunctional regression of the epididymis in the Regressed period; and a slow recrudescence process. Thus, we concluded that the processes of total testicular regression and posterior recrudescence suffered by M. nigricans also impact the physiology of the epididymis, but with a delay in epididymal response. Epididymal physiology is regulated by testosterone and estrogen, through the production and secretion of testosterone by the testes, its conduction to the epididymis (mainly through luminal fluid, conversion of testosterone to dihydrotestosterone by the 5α-reductase enzyme (mainly in epithelial cells and to estrogen by aromatase; and through the activation/deactivation of the androgen receptor and estrogen receptor α in epithelial cells, which regulate the epithelial cell morphophysiology, prevents cell death and regulates their protein expression and secretion, which ensures the maturation and storage of the spermatozoa.

  15. Impact of the Processes of Total Testicular Regression and Recrudescence on the Epididymal Physiology of the Bat Myotis nigricans (Chiroptera: Vespertilionidae)

    Science.gov (United States)

    Beguelini, Mateus R.; Góes, Rejane M.; Rahal, Paula; Morielle-Versute, Eliana; Taboga, Sebastião R.

    2015-01-01

    Myotis nigricans is a species of vespertilionid bat, whose males show two periods of total testicular regression within the same annual reproductive cycle in the northwest São Paulo State, Brazil. Studies have demonstrated that its epididymis has an elongation of the caudal portion, which stores spermatozoa during the period of testicular regression in July, but that they had no sperm during the regression in November. Thus, the aim of this study was to analyze the impact of the total testicular regression in the epididymal morphophysiology and patterns of its hormonal regulation. The results demonstrate a continuous activity of the epididymis from the Active to the Regressing periods; a morphofunctional regression of the epididymis in the Regressed period; and a slow recrudescence process. Thus, we concluded that the processes of total testicular regression and posterior recrudescence suffered by M. nigricans also impact the physiology of the epididymis, but with a delay in epididymal response. Epididymal physiology is regulated by testosterone and estrogen, through the production and secretion of testosterone by the testes, its conduction to the epididymis (mainly through luminal fluid), conversion of testosterone to dihydrotestosterone by the 5α-reductase enzyme (mainly in epithelial cells) and to estrogen by aromatase; and through the activation/deactivation of the androgen receptor and estrogen receptor α in epithelial cells, which regulate the epithelial cell morphophysiology, prevents cell death and regulates their protein expression and secretion, which ensures the maturation and storage of the spermatozoa. PMID:26057377

  16. FINE NEEDLE ASPIRATION CYTOLOGY OF EPIDIDYMAL SWELLINGS IN RIMS HOSPITAL, IMPHAL: A FIVE-YEAR STUDY

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    Rajesh Singh Laishram

    2016-06-01

    Full Text Available BACKGROUND Epididymal nodules are frequently encountered in surgical practice. They are easily accessible to fine needle aspiration cytology (FNAC. Clinically, these nodules present as worrisome nodules to the patients as well to the patients. This study was conducted to study the clinico-pathological profile of patients presenting with epididymal nodule using fine needle aspiration cytology (FNAC. METHODS A retrospective study was done by critically analysing the FNAC reports of palpable epididymal swellings in last five years (January 2010 to December 2015 at the Department of Pathology, Regional Institute of Medical Sciences (RIMS Hospital, Imphal, Manipur. Review of all the reports were done and diagnosis was made according to standard guidelines and correlated with patient’s age, sex, and side of involvement to explore the disease pattern. RESULTS A total of 71 cases were retrieved and divided as follows: Tuberculous epididymitis 20(28.17%, spermatocoele 11(15.49%, non-specific chronic epididymitis 10(14.08%, spermatic granulomas 6(8.45%, acute epididymitis 6(8.45%, hydrocoele 5 (7.04%, adenomatoid tumour 4(6.63% and microfilaria 1(1.41%. FNAC material was inadequate for opinion in 8 cases (11.28% cases. CONCLUSION FNAC has a definite important role in the differential diagnosis of epididymal nodules as it can identify neoplastic and nonneoplastic conditions. FNAC can thus be used to segregate the group of patients requiring a surgical intervention and a biopsy

  17. Epididymal anomalies associated with patent processus vaginalis in hydrocele and cryptorchidism.

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    Han, Chang Hee; Kang, Sung Hak

    2002-01-01

    The epididymal anomalies and patent processus vaginalis are frequently seen in patients with cryptorchidism or hydrocele. We performed a prospective study on the relationship between the epididymal anomalies and the patency of the processus vaginalis in boys with hydrocele (190 cases) or cryptorchidism (89 cases) who were treated from August 1997 to February 2000 (mean age, 51 months; range, 12 to 152 months). The epididymal anomalies were observed with an overall frequency of 48%. Closed, partially closed, and open processus vaginalis were associated with an epididymal anomaly in 14, 38, and 65% of cases, respectively. The epididymal anomalies were more common in association with undescended (61%) than with descended (43%) testes without statistical significance (p=0.415). Incomplete attachment of the caput epididymis was the most common anomaly (35%), followed by detachment of caput and cauda epididymis (31%), cauda epididymis (24%), and long looping epididymis (10%). These data showed that the epididymal anomalies were strongly associated with the patency of the processus vaginalis irrespective of testicular descent (p<0.001), and they provide further evidence for the hypothesis that a common stimulus, possibly androgens, may be required for the epididymal development and obliteration of the processus vaginalis. PMID:12378019

  18. Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma.

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    Liang Zhou

    2010-12-01

    Full Text Available With the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC using massively parallel sequencing technology.The expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients.A total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206 play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122 without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e.g., cell cycle and apoptosis pathways and cell communication (e.g., focal adhesion and ECM-receptor interaction were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of ∼50 ccRCC patients.Our study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC.

  19. Fertility of undiluted ram epididymal spermatozoa stored for several days at 4°C.

    Science.gov (United States)

    Abella, D Fernández; Da Costa, M; Guérin, Y; Dacheux, J L

    2015-02-01

    In vitro preservation of the male gamete is a challenge in the development of artificial insemination techniques for domestic animals. Specific strategies and diluents have been developed for the preservation of the fertilizing ability of the semen for each species. However, the epididymal medium has been demonstrated to be the best sperm environment to maintain sperm viability over several days and weeks for mammals. The aims of this study were to evaluate the motility and in vivo fertility of ram epididymal spermatozoa when the semen was stored for up to 4 days at 4°C undiluted in epididymal plasma. The study was undertaken with two ovine breeds (Ile de France and Corriedale). The motility of epididymal spermatozoa was better preserved in the undiluted epididymal fluid than when epididymal spermatozoa were diluted in classic ovine extender such as skim milk. During storage, the decrease in the percentage of motile sperm was lower if the epididymal spermatozoa were collected immediately after epididymal sampling than 24 h after castration or animal death. The fertility obtained after cryopreservation of the stored sperm and subsequent intrauterine insemination ranged from 55% to 24% following 24 to 96-h sperm storage. There was a linear regression relationship between fertility and the number of motile sperm inseminated for both breeds. These results show that it is possible to keep epididymal sperm motile and fertile for several days without dilution. Such a method of sperm preservation could be a final possibility for animals of high genetic value or for endangered species when the collection of semen before death of the animal is not possible.

  20. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome.

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    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p 3 fold, p sperm cryopreservation.

  1. Epididymal contraction and sperm parameters are affected by clonidine.

    Science.gov (United States)

    da Silva Júnior, E D; de Souza, B P; Vilela, V V; Rodrigues, J Q D; Nichi, M; de Agostini Losano, J D; Dalmazzo, A; Barnabe, V H; Jurkiewicz, A; Jurkiewicz, N H

    2014-11-01

    The use of clonidine, a selective agonist of α2-adrenoceptors, is related to the fertility impairment. Thus, it has been described that changes in the epididymal function are related to the loss of fertility. Therefore, this study was sought to further evaluate the effects of clonidine in the rat distal cauda epididymis contractions and its consequence in the sperm parameters. The in vitro effects of clonidine in the isolated distal cauda epididymis were evaluated by pharmacological experiments. The consecutive contractile responses for clonidine in distal cauda epididymis showed desensitization. The noradrenaline-induced contractions were desensitized after in vitro clonidine pre-treatment (10(-5) M for 10 min). Clonidine was unable to alter the noradrenaline contractions if the in vitro pre-treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist), whereas prazosin (α1-adrenoceptor antagonist) was ineffective. Moreover, the in vitro clonidine pre-treatment increased frequency and amplitude of spontaneous contraction of distal cauda epididymis. In addition, to induce in vivo desensitization of α2-adrenoceptors, male Wistar rats were treated with crescent doses of clonidine and distal cauda of epididymis contraction and sperm parameters were analyzed. The in vivo treatment with clonidine diminished the potency of the contractions induced by adrenergic agonists and augmented the frequency and amplitude of spontaneous contraction of distal cauda epididymis. This treatment also altered the sperm transit time in epididymis, epididymal sperm reserves, sperm lipid peroxidation, and antioxidant enzymes activity. The results suggest that clonidine was able to affect the sperm quantity and quality by decreasing the transit time related to the increase in the frequency and amplitude of spontaneous contractions in epididymis, although the contractions induced by adrenergic agonists were desensitized. © 2014 American Society of Andrology and European

  2. CRYOPRESERVATION OF ONAGER (EQUUS HEMIONUS ONAGER) EPIDIDYMAL SPERMATOZOA.

    Science.gov (United States)

    Pablos, María Teresa Prieto; Saragusty, Joseph; Santiago-Moreno, Julián; Stagegaard, Julia; Göritz, Frank; Hildebrandt, Thomas Bernd; Hermes, Robert

    2015-09-01

    Genetic diversity is a primary component of adaptive evolution, and its loss or reduction can decrease the long-term survival probability of populations. Utilization of cryopreserved semen may be considered a perfect tool to improve genetic diversity, reduce inbreeding, and avoid animal translocation for breeding. The present study aimed at finding a reliable epididymal sperm freezing protocol for the critically endangered onager (Equus hemionus onager). Six testicles from three animals were processed postmortem. The effects of two transportation temperatures (22°C and 4°C; testicles submerged in saline), two cryopreservation techniques (conventional liquid nitrogen vapor freezing in straws and directional freezing in 8-ml HollowTubes(TM)), and two postthaw incubation temperatures (22°C and 37°C; evaluated after 0.5, 1, 2, and 3 hr) were tested in a 2×2×2 experimental design. Sperm samples were evaluated for motility, viability, acrosome integrity, and sperm morphology. The resulting optimal freezing protocol includes transportation of testicles at 4°C, cryopreservation by directional freezing, and, if needed, postthaw incubation at 22°C. With this combination of transportation temperature and cryopreservation technique, the authors obtained the following postthaw values normalized to prefreezing values: 60.3±8.8% motility, 60.7±13.3% viability, 75.3±9.5% acrosome integrity, and 94.7±2.9% normal morphology (excluding defects due to the epididymal origin of the sperm). After incubation at 22°C, motility values for the above combination were 40±5.7%, 30.3±5.2%, 28.3±4.4%, and 16.7±4.4% for 0.5, 1, 2, and 3 hr, respectively. In conclusion, with this protocol, good quality semen can be stored for future use in artificial inseminations when and where needed.

  3. High Expression of Colony-Stimulating Factor 1 Receptor Associates with Unfavorable Cancer-Specific Survival of Patients with Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Yang, Liu; Liu, Yidong; An, Huimin; Chang, Yuan; Zhang, Weijuan; Zhu, Yu; Xu, Le; Xu, Jiejie

    2016-03-01

    Colony-stimulating factor 1 receptor (CSF-1R), a single-pass type III transmembrane tyrosine-protein kinase, is mainly involved in inflammation and immune regulation to facilitate the progression of solid tumors. This study aimed to evaluate the impact of CSF-1R expression on clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) after surgery. We retrospectively enrolled 268 patients with ccRCC undergoing nephrectomy between 2001 and 2004. Clinicopathologic features and cancer-specific survival (CSS) were collected. Western blot analysis was performed in the pairwise comparisons of CSF-1R expression in peritumor and tumor tissues of patients with ccRCC. Immunohistochemistry was conducted to determine CSF-1R expression level in tumor specimens. Survival analysis was performed by the Kaplan-Meier method. Cox regression models were used to evaluate the impact of prognostic factors on CSS. A concordance index was calculated to measure prognostic accuracy. A prognostic nomogram was constructed on the basis of the identified independent prognostic factors. CSF-1R expression in tumor tissues was higher than in peritumor tissues in 71.4% (5 of 7) patients. CSF-1R expression of tumor tissues was positively associated with metastasis, tumor, node, metastasis classification system (TNM) stage, Eastern Cooperative Oncology Group performance status score and poor CSS. CSF-1R expression was determined as an independent prognostic factor for CSS in patients with ccRCC. Furthermore, extension of the well-established prognostic models with CSF-1R expression presented significantly improved prognostic accuracy. An efficient prognostic nomogram was constructed on the basis of the independent prognostic factors. High CSF-1R expression is a potential independent adverse prognostic factor for CSS in patients with ccRCC.

  4. Gender-specific association of methylenetetrahydrofolate reductase genotype and haplotype with the aggressiveness and prognosis of clear cell renal cell carcinoma in Japanese patients.

    Science.gov (United States)

    Sakano, Shigeru; Hinoda, Yuji; Okayama, Naoko; Kawai, Yoshihisa; Ito, Hideaki; Nagao, Kazuhiro; Hara, Takahiko; Matsuyama, Hideyasu

    2010-08-01

    To determine if the two common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect tumour aggressiveness or prognosis of clear cell renal cell carcinoma (CCRCC) in Japanese patients. MTHFR C677T and A1298C polymorphisms have been reported to cause decreased enzyme activity, which reduces the quantity of methyl groups available for DNA methylation and leads to mis-incorporation of uracil into DNA, resulting in single-strand DNA breaks. These effects might induce the accumulation of several genetic changes, leading to the development and progression of CCRCC. Therefore, we investigated the associations between MTHFR genotypes and haplotypes and the clinicopathological characteristics and survival rates in 240 Japanese patients with histopathologically confirmed CCRCC. MTHFR C677T and A1298C were genotyped and haplotypes were analysed using appropriate software. The variant genotypes of MTHFR A1298C were significantly associated with some advanced characteristics of CCRCC in all patients, and these associations were stronger among men. However, among women, the variant genotypes of MTHFR C677T were associated with some advanced characteristics of CCRCC and the C677T variant genotypes or the 677T-1298A haplotype was significantly associated with decreased overall survival (P = 0.007 and P = 0.009, respectively). To our knowledge, this is the first report on the association between MTHFR polymorphisms and CCRCC aggressiveness or prognosis. These results suggest that the MTHFR genotypes and haplotype might be useful, in a gender-specific manner, as predictive factors for the clinical course of CCRCC. Furthermore, these findings will contribute to the understanding of the mechanisms underlying CCRCC progression.

  5. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Coric, Vesna M; Simic, Tatjana P; Pekmezovic, Tatjana D; Basta-Jovanovic, Gordana M; Savic Radojevic, Ana R; Radojevic-Skodric, Sanja M; Matic, Marija G; Dragicevic, Dejan P; Radic, Tanja M; Bogdanovic, Ljiljana M; Dzamic, Zoran M; Pljesa-Ercegovac, Marija S

    2016-01-01

    The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and prisk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.

  6. Type 1 plasminogen activator inhibitor (PAI-1 in clear cell renal cell carcinoma (CCRCC and its impact on angiogenesis, progression and patient survival after radical nephrectomy

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    Seidal Tomas

    2010-12-01

    Full Text Available Abstract Background To examine the expression of type 1 plasminogen inhibitor (PAI-1 in clear cell renal cell carcinoma (CCRCC, and its possible association with microvessel density (MVD, the expression of thrombospondin-1 (TSP-1, nuclear grade, tumour stage, continuously coded tumour size (CCTS and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy. Methods A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43% died of RCC, while 47 patients (29% died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%. Results Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046 and directly with advanced stage (p = 0.008, high NG (3+4 (p = 0.002, tumour size (p = 0.011, microvessel density (p = 0.049 and disease progression (p = 0.002. In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS (p Conclusions PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.

  7. Keap1/Nrf2 pathway in kidney cancer : frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma

    NARCIS (Netherlands)

    Fabrizio, Federico Pio; Costantini, Manuela; Copetti, Massimiliano; la Torre, Annamaria; Sparaneo, Angelo; Fontana, Andrea; Poeta, Luana; Gallucci, Michele; Sentinelli, Steno; Graziano, Paolo; Parente, Paola; Pompeo, Vincenzo; De Salvo, Laura; Simone, Giuseppe; Papalia, Rocco; Picardo, Francesco; Balsamo, Teresa; Flammia, Gerardo Paolo; Trombetta, Domenico; Pantalone, Angela; Kok, Klaas; Paranita, Ferronika; Muscarella, Lucia Anna; Fazio, Vito Michele

    2017-01-01

    The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal

  8. Clear Cell Adenocarcinoma Arising from Endometriosis in the Groin: Wide Resection and Reconstruction with a Fascia Lata Tensor Muscle Skin Flap

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    Shozo Yoshida

    2018-01-01

    Full Text Available We herein report a case of clear cell carcinoma arising from endometriosis in the groin in a 53-year-old woman. The findings of MRI and FDG/PET-CT indicated a malignant tumor, and surgical biopsy confirmed adenocarcinoma of the female genital tract. The tumor including a part of the abdominal rectus muscle and rectus sheath, subcutaneous fat, skin, and the right inguinal ligament was resected en bloc. The defect in the abdominal wall was reconstructed with a fascia lata tensor muscle skin flap. The tumor was composed of clear cell adenocarcinoma arising from extrapelvic endometriosis. The patient received chemotherapy with gemcitabine and carboplatin for 6 cycles and had no evidence of recurrence 7 months after the treatment. We herein described the diagnosis and surgical management of endometriosis-associated carcinoma in the groin.

  9. Clear cell sarcoma of tendons and aponeuroses of the parapharyngeal space: an unusual localization of a rare tumor (a case report and review of the literature).

    Science.gov (United States)

    Abdellah, Aissa; Soufiane, Berhili; Amine, Bazine; Sanaa, El Majjaoui; Hanan, Elkacemi; Ijlal, Kharbaoui; Rachida, Latib; Basma, El Khannoussi; Tayeb, Kebdani; Noureddine, Benjaafar

    2014-01-01

    The clear cell sarcoma of tendons and aponeuroses (CCSTA) is a rare soft tissue sarcoma in the head and neck region and parapharyngeal space. Over 95% of CCSTAs present in the extremities, with the head and neck region (1.9%) being an unusual site. This study presents an additional case of CCSTA of the head and neck region involving the parapharyngeal space in a 48-year-old men and review of the literature on CCSTA.

  10. Testis Morphometry and Stages of the Seminiferous Epithelium Cycle in an Epididymal Sperm-storing Neotropical Vespertilionid, Myotis levis (Chiroptera).

    Science.gov (United States)

    Farias, T O; Notini, A A; Talamoni, S A; Godinho, H P

    2015-10-01

    Yellowish myotis, Myotis levis, is a seasonal, epididymal sperm-storing Neotropical vespertilionid. In the dry season, males show simultaneous testis regression and sperm storage in cauda epididymis, enabling them to mate during this season. In this study, we investigated seasonal variations in body mass, diameter and height of seminiferous tubules and nuclei of Leydig cells in a population of southeastern Brazil. We also determined the frequencies of the stages of the seminiferous epithelium cycle (SEC) of mature individuals of this population. Body mass and diameter of Leydig cell nuclei showed no significant differences between dry and rainy seasons and stages of annual reproductive cycle; however, all other morphometric parameters varied significantly. The relative cumulative frequency of pre-meiotic stages of the SEC (1-3) was 51%, of meiotic stage (4) was 2% and of post-meiotic stages (5-8) was 47%. We confirmed that the yellowish myotis presents seasonal sperm production as revealed by testis regression and epididymal sperm storage during the dry season. © 2014 Blackwell Verlag GmbH.

  11. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of {sup 10}B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  12. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    International Nuclear Information System (INIS)

    Andoh, T.; Fujimoto, T.; Sudo, T.; Fujita, I.; Imabori, M.; Moritake, H.; Sugimoto, T.; Sakuma, Y.; Takeuchi, T.; Kawabata, S.; Kirihata, M.; Akisue, T.; Yayama, K.; Kurosaka, M.; Miyatake, S.; Fukumori, Y.; Ichikawa, H.

    2011-01-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  13. Bilateral Epididymal Cyst in 14 year-old Boy: a case report

    Directory of Open Access Journals (Sweden)

    Yiğit Akin

    2014-04-01

    Full Text Available Bilateral epididymal cysts are rare in childhood. Clinically they may present as acute scrotum and should be differentiated from other pathologies. Here in, we report bilateral epididymal cysts in a 14-year-old boy. He was admitted to emergency department with symptoms of acute left scrotum. There was no history of trauma or infection. Blood analyses, including testis tumor markers were unremarkable. Bilateral epididymal cysts were diagnosed on ultrasonography evaluation. Medical treatment did not stop his scrotal pain. During scrotal exploration, there was no evidence of testicular torsion or any other pathology. An excision of cyst was performed. Histopathologically, the cyst wall was lined by columnar epithelia. As a result of these findings, a pathological diagnosis of epididymal cyst was made. The synchronized evaluation of clinical and ultrasonography findings with an appropriate histopathological evaluation can usually diagnose this rare pathology.

  14. The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium.

    Science.gov (United States)

    Heckl, Marlene; Schmoeckel, Elisa; Hertlein, Linda; Rottmann, Miriam; Jeschke, Udo; Mayr, Doris

    2018-01-01

    The objective of this study was to evaluate the prognostic value of ARID1A, p53, p21, p16 and ß-Catenin in endometrioid and clear cell ovarian and endometrial carcinomas. 97 tumors were available for analysis of ARID1A, p53, p21, p16 and ß-Catenin with the techniques of tissue microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were endometrial carcinomas. Endometrioid ovarian carcinomas showed negative staining for ARID1A (a) and p21 (b), aberrant expression of p53 (c) and p16 (d) and ß-Catenin positive nuclear expression (e) respectively in 19% (a), 100% (b), 28.6% (c), 52.4% (d) and 4.8% (e) of all cases. In the group of clear cell ovarian carcinomas it was 63.6% (a), 100% (b), 81.8% (c), 54.5% (d) and 0% (e). For endometrioid uterine carcinomas it was 75.7% (a), 94.9% (b), 30.5% (c), 52.1% (d) and 6.8% (e) and for clear cell uterine carcinomas it was 8.6% (a), 100% (b), 50% (c), 100% (d) and 0% (e). Survival analysis showed that negative expression of ARID1A, p53 aberrant expression and ß-Catenin nuclear positive staining are independent negative prognosticators in both, clear cell and endometrioid carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis showed them again as negative prognostic factors. Furthermore, we found a significant correlation between ARID1A and ß-Catenin expression in endometrioid uterine tumors. The analyzed gynaecological carcinoma showed a distinct expression scheme of proteins that are associated with tumor suppression. We may conclude that ARID1A, p53 and ß-Catenin are the strongest prognostic factors by analyzing a subgroup of tumor suppressor genes in clear cell and endometrioid subtypes of ovarian and endometrial cancer and may be used along with traditional morphological and clinical characteristics for prognosis.

  15. The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium.

    Directory of Open Access Journals (Sweden)

    Marlene Heckl

    Full Text Available The objective of this study was to evaluate the prognostic value of ARID1A, p53, p21, p16 and ß-Catenin in endometrioid and clear cell ovarian and endometrial carcinomas.97 tumors were available for analysis of ARID1A, p53, p21, p16 and ß-Catenin with the techniques of tissue microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were endometrial carcinomas.Endometrioid ovarian carcinomas showed negative staining for ARID1A (a and p21 (b, aberrant expression of p53 (c and p16 (d and ß-Catenin positive nuclear expression (e respectively in 19% (a, 100% (b, 28.6% (c, 52.4% (d and 4.8% (e of all cases. In the group of clear cell ovarian carcinomas it was 63.6% (a, 100% (b, 81.8% (c, 54.5% (d and 0% (e. For endometrioid uterine carcinomas it was 75.7% (a, 94.9% (b, 30.5% (c, 52.1% (d and 6.8% (e and for clear cell uterine carcinomas it was 8.6% (a, 100% (b, 50% (c, 100% (d and 0% (e. Survival analysis showed that negative expression of ARID1A, p53 aberrant expression and ß-Catenin nuclear positive staining are independent negative prognosticators in both, clear cell and endometrioid carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis showed them again as negative prognostic factors. Furthermore, we found a significant correlation between ARID1A and ß-Catenin expression in endometrioid uterine tumors.The analyzed gynaecological carcinoma showed a distinct expression scheme of proteins that are associated with tumor suppression. We may conclude that ARID1A, p53 and ß-Catenin are the strongest prognostic factors by analyzing a subgroup of tumor suppressor genes in clear cell and endometrioid subtypes of ovarian and endometrial cancer and may be used along with traditional morphological and clinical characteristics for prognosis.

  16. Tumor-specific hypermethylation of epigenetic biomarkers, including SFRP1, predicts for poorer survival in patients from the TCGA Kidney Renal Clear Cell Carcinoma (KIRC project.

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    Christopher J Ricketts

    Full Text Available The recent publication of the TCGA Kidney Renal Clear Cell Carcinoma (KIRC project has provided an immense wealth and breadth of data providing an invaluable tool for confirmation and expansion upon previous observations in a large data set containing multiple data types including DNA methylation, somatic mutation, and clinical information. In clear cell renal cell carcinoma (CCRCC many genes have been demonstrated to be epigenetically inactivated by promoter hypermethylated and in a small number of cases to be associated with clinical outcome. This study created two cohorts based on the Illumina BeadChip array used to confirm the frequency of tumor-specific hypermethylation of these published hypermethylated genes, assess the impact of somatic mutation or chromosomal loss and provide the most comprehensive assessment to date of the association of this hypermethylation with patient survival. Hypermethylation of the Fibrillin 2 (FBN2 gene was the most consistent epigenetic biomarker for CCRCC across both cohorts in 40.2% or 52.5% of tumors respectively. Hypermethylation of the secreted frizzled-related protein 1 (SFRP1 gene and the basonuclin 1 (BNC1 gene were both statistically associated with poorer survival in both cohorts (SFRP1 - p = <0.0001 or 0.0010 and BNC1 - p = <0.0001 or 0.0380 and represented better independent markers of survival than tumor stage, grade or dimension in one cohort and tumor stage or dimension in the other cohort. Loss of the SFRP1 protein can potentially activate the WNT pathway and this analysis highlighted hypermethylation of several other WNT pathway regulating genes and demonstrated a poorer survival outcome for patients with somatic mutation of these genes. The success of demethylating drugs in hematological malignances and the current trials in solid tumors suggest that the identification of clinically relevant hypermethylated genes combined with therapeutic advances may improve the effectiveness and

  17. Inhibitors of the mitogen-activated protein kinase kinase 1/2 signaling pathway clear prion-infected cells from PrPSc.

    Science.gov (United States)

    Nordström, Elin K; Luhr, Katarina M; Ibáñez, Carlos; Kristensson, Krister

    2005-09-14

    Prions represent a unique class of infectious agents in which the normal cellular prion protein (PrPC) is converted to an abnormal isoform (PrPSc), which accumulates in the brain and constitutes the major, if not the only, component of the infectious particle. Factors that still remain to be identified may facilitate the conversion of PrPC to PrPSc. In the present study, we first demonstrated that a growth factor of the neurotrophin family, brain-derived neurotrophic factor (BDNF), stimulates the formation of PrPSc in a gonadotropin-releasing hormone-secreting neuronal cell line (GT1-1 cells) infected with the Rocky Mountain Laboratory (RML) strain of scrapie as determined by Western blot analysis. We then observed that the prion-infected cells can be cleared from PrPSc by treatment with three inhibitors of mitogen-activated protein kinase kinase 1/2 (MEK1/2) [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene and 2-(2-amino-3-methyoxyphenyl)-4H-1-benzopyran-4-one, as well as alpha-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl) benzeneacetonitrile, which passes the blood-brain barrier], a component of one of the intracellular signaling pathways activated by BDNF. The MEK1/2 inhibitors were also efficient in clearing PrPSc from prion-infected GT1-1 cells stimulated to accumulate high levels of PrPSc by enhanced serum concentrations in the medium or by the use of a serum-free neuron-specific neurobasal medium. PrPSc did not reappear in the cultures within 5 weeks after completion of treatment. We conclude that inhibitors of the MEK1/2 pathway can efficiently and probably irreversibly clear PrP(Sc) from prion-infected cells. The MEK pathway may therefore be a suitable target for therapeutic intervention in prion diseases.

  18. Effects of Cinnamon (C. zeylanicum) Bark Oil Against Taxanes-Induced Damages in Sperm Quality, Testicular and Epididymal Oxidant/Antioxidant Balance, Testicular Apoptosis, and Sperm DNA Integrity.

    Science.gov (United States)

    Sariözkan, Serpil; Türk, Gaffari; Güvenç, Mehmet; Yüce, Abdurrauf; Özdamar, Saim; Cantürk, Fazile; Yay, Arzu Hanım

    2016-01-01

    The aim of this study was to investigate whether cinnamon bark oil (CBO) has protective effect on taxanes-induced adverse changes in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular apoptosis, and sperm DNA integrity. For this purpose, 88 adult male rats were equally divided into 8 groups: control, CBO, docetaxel (DTX), paclitaxel (PTX), DTX+PTX, DTX+CBO, PTX+CBO, and DTX+PTX+CBO. CBO was given by gavage daily for 10 weeks at the dose of 100 mg/kg. DTX and PTX were administered by intraperitoneal injection at the doses of 5 and 4 mg/kg/week, respectively, for 10 weeks. DTX+PTX and DTX+PTX+CBO groups were treated with DTX during first 5 weeks and PTX during next 5 weeks. DTX, PTX, and their mixed administrations caused significant decreases in absolute and relative weights of all reproductive organs, testosterone level, sperm motility, concentration, glutathione level, and catalase activity in testicular and epididymal tissues. They also significantly increased abnormal sperm rate, testicular and epididymal malondialdehyde level, apoptotic germ cell number, and sperm DNA fragmentation and significantly damaged the histological structure of testes. CBO consumption by DTX-, PTX-, and DTX+PTX-treated rats provided significant ameliorations in decreased relative weights of reproductive organs, decreased testosterone, decreased sperm quality, imbalanced oxidant/antioxidant system, increased apoptotic germ cell number, rate of sperm with fragmented DNA, and severity of testicular histopathological lesions induced by taxanes. In conclusion, taxanes cause impairments in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular histopathological structure, and sperm DNA integrity, and long-term CBO consumption protects male reproductive system of rats.

  19. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Vesna M Coric

    Full Text Available The aim of this study was to evaluate specific glutathione S-transferase (GST gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC, independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(apyrene diolepoxide (BPDE-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively. Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04. Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02. Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05. GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.

  20. Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma.

    Science.gov (United States)

    Puente, Javier; Laínez, Nuria; Dueñas, Marta; Méndez-Vidal, María José; Esteban, Emilio; Castellano, Daniel; Martinez-Fernández, Mónica; Basterretxea, Laura; Juan-Fita, María José; Antón, Luis; León, Luis; Lambea, Julio; Pérez-Valderrama, Begoña; Vázquez, Sergio; Suarez, Cristina; Del Muro, Xavier Garcia; Gallardo, Enrique; Maroto, José Pablo; Samaniego, M Luz; Suárez-Paniagua, Beatriz; Sanz, Julián; Paramio, Jesús M

    2017-05-02

    Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response.

  1. Epididymal anomalies in boys with undescended testis or hydrocele: Significance of testicular location.

    Science.gov (United States)

    Kim, Sun-Ouck; Na, Seong Woong; Yu, Ho Song; Kwon, Dongdeuk

    2015-10-24

    Epididymal anomalies and patent processus vaginalis are frequently found in boys with cryptorchidism or hydrocele. We conducted this study to evaluate the association between epididymal anomalies and testicular location or patent processus vaginalis in boys with undescended testis or hydrocele. Children undergoing surgery with undescended testis (group A, 136 boys and 162 testes) or communicating hydrocele (group B, 93 boys and 96 testes) were included. Testicular locations and epididymal anomalies were investigated prospectively. An anomalous epididymis was defined as anomalies of epididymal fusion that consisted of loss of continuity between the testis, the epididymis, and the long looping epididymis. The epididymis was considered normal when a normal, firm attachment between the testis, the caput, and the cauda epididymis was present. The mean ages of groups A and B were 24.6 ± 19.7 (range, 8-52 months) and 31.4 ± 20.6 months (range, 10-59 months). The incidence of epididymal anomalies was significantly higher in group A than that in group B (65.4 % vs. 13.5 %, P hydrocele, and that these anomalies were more frequent when undescended testis was at a higher level. These results suggest that testicular location is associated with epididymal anomalies rather than patent processus vaginalis.

  2. Iron elevation and adipose tissue remodeling in the epididymal depot of a mouse model of polygenic obesity.

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    Xiaoya Ma

    Full Text Available Iron dysregulation is a potential contributor to the pathology of obesity-related metabolic complications. KK/HIJ (KK mice, a polygenic obese mouse model, have elevated serum iron levels. A subset of KK male mice display a bronzing of epididymal adipose tissue (eAT associated with >100-fold (p0.05. The eAT histology revealed iron retention, macrophage clustering, tissue fibrosis, cell death as well as accumulation of HIF-2α in the high iron eAT. qPCR showed significantly decreased Lep (leptin and AdipoQ (adiponectin, whereas Tnfα (tumor necrosis factor α, and Slc40a1 (ferroportin were up-regulated in HI (p<0.05. Elevated HIF-2α, oxidative stress and local insulin signaling loss was also observed.Our data suggest that deposition of iron in adipose tissue is limited to the epididymal depot in male KK mice. A robust adipose tissue remodeling is concomitant with the high iron concentration, which causes local adipose tissue insulin resistance.

  3. Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding.

    Science.gov (United States)

    Björkgren, Ida; Alvarez, Luis; Blank, Nelli; Balbach, Melanie; Turunen, Heikki; Laajala, Teemu Daniel; Toivanen, Jussi; Krutskikh, Anton; Wahlberg, Niklas; Huhtaniemi, Ilpo; Poutanen, Matti; Wachten, Dagmar; Sipilä, Petra

    2016-05-15

    During epididymal maturation, sperm acquire the ability to swim progressively by interacting with proteins secreted by the epididymal epithelium. Beta-defensin proteins, expressed in the epididymis, continue to regulate sperm motility during capacitation and hyperactivation in the female reproductive tract. We characterized the mouse beta-defensin 41 (DEFB41), by generating a mouse model with iCre recombinase inserted into the first exon of the gene. The homozygous Defb41(iCre/iCre) knock-in mice lacked Defb41 expression and displayed iCre recombinase activity in the principal cells of the proximal epididymis. Heterozygous Defb41(iCre/+) mice can be used to generate epididymis specific conditional knock-out mouse models. Homozygous Defb41(iCre/iCre) sperm displayed a defect in sperm motility with the flagella primarily bending in the pro-hook conformation while capacitated wild-type sperm more often displayed the anti-hook conformation. This led to a reduced straight line motility of Defb41(iCre/iCre) sperm and weaker binding to the oocyte. Thus, DEFB41 is required for proper sperm maturation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Fucosyl neoglycoprotein binds to mouse epididymal spermatozoa and inhibits sperm binding to the egg zona pellucida.

    Science.gov (United States)

    Oh, Y S; Ahn, H S; Gye, M C

    2013-12-01

    Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals, and this sugar coding plays an important role in cell-to-cell recognition processes. In this study, our aims were to determine the distribution of sperm receptors with activity for fucosyl- and galactosyl glycans and to address whether monosugar neoglycoproteins functionally mimic the binding between zona pellucida (ZP) glycoproteins and spermatozoa. In mouse epididymal spermatozoa with intact acrosomes, fucopyranosyl bovine serum albumin (BSA-Fuc) bound to the segment of the acrosome, the equatorial segment, and the postacrosome region of the sperm head. Galactosyl BSA (BSA-Gal) binding activity was similar to that of BSA-Fuc, but was weaker. In acrosome-reacted spermatozoa treated with the Ca(2+) ionophore A23187, BSA-zuc binding was lost in the apical segment of the acrosome but remained in the equatorial segment and postacrosome regions. BSA-Gal binding to the equatorial region was increased. In the presence of 2.5 μg ml(-1) BSA-Fuc, in vitro sperm-ZP binding was significantly decreased, indicating that fucosyl BSA functionally mimics ZP glycoproteins during sperm-egg ZP interactions. At the same concentration, BSA-Gal was not effective. Fucosyl BSA that efficiently inhibited the sperm-ZP binding can mimic the ZP glycoconjugate and has potential for use as a sperm fertility control agent in mouse. © 2012 Blackwell Verlag GmbH.

  5. MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): a multicenter correlative MRI-pathology study of 21 cases and literature review

    International Nuclear Information System (INIS)

    Beuckeleer, L.H. de; Schepper, A.M. de; Vandevenne, J.E.; Bloem, J.L.; Davies, A.M.; Oudkerk, M.; Hauben, E.; Marck, E. van; Somville, J.; Vanel, D.; Steinbach, L.S.; Guinebretiere, J.M.; Hogendoorn, P.C.W.; Mooi, W.J.; Verstraete, K.; Zaloudek, C.; Jones, H.

    2000-01-01

    Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts).Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study.Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody.Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images. (orig.)

  6. Dioxin-induced changes in epididymal sperm count and spermatogenesis Mudanças induzidas por dioxina na contagem epididimal de esperma e espermatogênese

    Directory of Open Access Journals (Sweden)

    Warren G. Foster

    2011-06-01

    Full Text Available A single in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD on gestation day 15 decreased epididymal sperm count in adult rats and thus was used to establish a tolerable daily intake for TCDD. However, several laboratories have been unable to replicate these findings. Moreover, conflicting reports of TCDD effects on daily sperm production suggest that spermatogenesis may not be as sensitive to the adverse effects of TCDD as previously thought. We performed a PubMed search using relevant search terms linking dioxin exposure with adverse effects on reproduction and spermatogenesis. Developmental exposure to TCDD is consistently linked with decreased cauda epididymal sperm counts in animal studies, although at higher dose levels than those used in some earlier studies. However, the evidence linking in utero TCDD exposure and spermatogenesis is not convincing. Animal studies provide clear evidence of an adverse effect of in utero TCDD exposure on epididymal sperm count but do not support the conclusion that spermatogenesis is adversely affected. The mechanisms underlying decreased epididymal sperm count are unknown; however, we postulate that epididymal function is the key target for the adverse effects of TCDD.Uma única exposição in utero a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD no 15º dia de gestação diminuiu a contagem de esperma epididimal em ratos adultos e por isso foi utilizada para estabelecer uma dosagem diária tolerável para TCDD. No entanto, diversos laboratórios não conseguiram reproduzir esses resultados. Além disso, relatórios conflitantes dos efeitos de TCDD na produção diária de esperma sugere que espermatogênese pode não ser tão sensível aos efeitos adversos do TCDD como antes se pensava. Foi feita uma pesquisa no PubMed usando termos de pesquisa relevantes, relacionados à exposição à dioxina com efeitos adversos na reprodução e na espermatogênese. Exposição em desenvolvimento ao TCDD

  7. Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, T., E-mail: fujitaku@hp.pref.hyogo.jp [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Andoh, T. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Division of Pediatrics, University of Miyazaki, Miyazaki 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi Medical School, Nangoku 783-8505 (Japan); Sonobe, H. [Department of Pathology, Chugoku Central Hospital, Fukuyama 720-0001 (Japan); Epstein, Alan L. [Department of Pathology, Keck School of Medicine,University of Southern California, Los Angeles,CA 90033 (United States); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Fukumori, Y.; Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies.

  8. Percutaneous radiofrequency ablation for a recurrent metastasis after resection of liver metastases from an ileal clear-cell sarcoma: Long-term local tumor control.

    Science.gov (United States)

    Seo, Jung Wook

    2017-12-01

    Clear-cell sarcomas (CCSs) in the gastrointestinal tract are extremely rare and aggressive tumors. We present the first case of a CCS arising in the ileum and metastasizing to the liver; our patient was a 60-year-old man. After the resection of the CCS and the liver metastases, a new liver metastasis developed, which was treated via percutaneous radiofrequency ablation only. At the 5-year follow-up, the ablated region was stable without local tumor progression. Percutaneous radiofrequency ablation is a viable local treatment option for recurrent metastases from an ileal CCS if they are detected when small and at an early stage in follow-up studies.

  9. Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Andersen, Claus B.; Nielsen, John E

    2010-01-01

    The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal...... the segmental location of expression, and clarify whether the reported loss of VDR in CCc is coincident with alterations of vitamin D metabolism....

  10. Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report.

    Science.gov (United States)

    Gunji-Niitsu, Yoko; Kumasaka, Toshio; Kitamura, Shigehiro; Hoshika, Yoshito; Hayashi, Takuo; Tokuda, Hitoshi; Morita, Riichiro; Kobayashi, Etsuko; Mitani, Keiko; Kikkawa, Mika; Takahashi, Kazuhisa; Seyama, Kuniaki

    2016-11-21

    Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2

  11. Multiple chromophobe and clear cell renal cancer in a patient affected by Birt-Hogg-Dubè syndrome: a case report.

    Science.gov (United States)

    Castellucci, Roberto; Marchioni, Michele; Valenti, Sergio; Sortino, Giuseppe; Borgonovo, Giulio; Pesenti, Nicola; Vismara, Alberto C A; Circo, Maria C; Sessa, Barbara; Micheli, Emanuele; Lembo, Antonino

    2017-04-28

    Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The syndrome is linked to mutations in the FLCN gene, which is preferentially expressed in the skin, kidney, and lung. The aim of our paper is to describe a case of multiple bilateral renal cancer in a patient affected by BHDS. Patient subjected to enucleoresection seven kidney tumors discovered right after ultrasound performed for other reasons. Definitive histologic examination were as follows: multifocal type chromophobe renal cell carcinoma and clear cell. After 1 month, the patient was readmitted for spontaneous pneumothorax. After about a year, the patient was again subjected to resection of multiple renal tumors left. Histological examination proved that it was multifocal renal cell carcinoma, clear cell varieties. The genome analysis highlighted positive for mutation c. 1379_1380 of FLCN gene, BHDS gene. Currently, the patient is under close follow-up. After 1 year, the chest computed tomography (CT) confirmed the presence of minute air bubbles scattered on both sides. Instead, the abdominal CT was positive for a small round lesion 6 mm exophytic. The BHDS is a rare syndrome whose management is extremely complex both in terms of oncological and functional. Kidney tumors associated with BHDS usually have a favorable clinical course. Present evidence suggests a close follow-up of the carriers of the genetic mutation patients whether or not they have expressed the lesions of disease given the high rate of recurrence of renal lesions.

  12. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    International Nuclear Information System (INIS)

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-01-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells

  13. Involvement of muscarinic acetylcholine receptors in chloride secretion by cultured rat epididymal epithelium.

    Science.gov (United States)

    Du, Jian-Yang; Zuo, Wu-Lin; Chen, Min-Hui; Xiang, Hui; Zhou, Wen-Liang

    2006-09-01

    The aim of our present study was to investigate the short-circuit current response to carbachol in cultured rat cauda epididymal epithelia and the signal transduction mechanisms involved. Carbachol added basolaterally induced a concentration-dependent increase in short-circuit current (Isc) across the epididymal epithelium consisting of a rapidly rising phase and a long term sustained response. The response was almost abolished by removing Cl(-) from the extracellular medium and blockable by pretreating the tissues with DPC, indicating a substantial contribution of Cl(-) secretion to the carbachol-induced response. The muscarinic acetylcholine receptor antagonist atropine inhibited the response, but the nicotinic acetylcholine receptors antagonist curarine had no effect, suggesting that only the muscarinic acetylcholine receptors mediated the secretory response of the basolateral side of rat cauda epididymal epithelium to carbachol. Addition of carbachol to the apical side of the tissue was found not to elicit an Isc response. These results suggested that muscarinic receptors are present in the basolateral side of rat cauda epididymal epithelium. Activation of these receptors by acetylcholine released from the nerve endings regulates epididymal transepithelial Cl(-) secretion. Cholinergic stimulation therefore contributes to the formation of luminal fluid microenvironment.

  14. Normozoospermic versus teratozoospermic domestic cats: differential testicular volume, sperm morphometry, and subpopulation structure during epididymal maturation.

    Science.gov (United States)

    Gutiérrez-Reinoso, Miguel Angel; García-Herreros, Manuel

    2016-01-01

    Teratozoospermia (sperm morphometric traits, and potential differences regarding the sperm subpopulational structure during epididymal sperm maturation in teratozoospermic feline donors. Epididymal sperm samples were collected from the caput (R1), corpus (R2), and cauda (R3) epididymidis in two donor groups (N: normozoospermic; T: teratozoospermic). Aliquots were assessed for concentration, viability, motility, and acrosomal integrity. Sperm morphometric descriptors from CASA-Morph analysis were analyzed by the Principal Component Analysis (PCA) and clustering analyses. Irrespective of the group analyzed, PCA revealed two Principal Components (PCs) for each epididymal region explaining more than the 93% of the variance. Surprisingly, the number of subpopulations remained constant in regions R1-R2-R3 irrespective of the donor group analyzed. However, the distribution of these subpopulations was found to be structurally different and strongly influenced by the epididymal region and the donor group. In conclusion, testicular morphometry and the sperm subpopulation structure were different in N and T donors. The alterations in subpopulations during epididymal maturation could be used as a potential clinical indicator of teratozoospermic individuals since an important influence of teratozoospermia on sperm subpopulation structure has been demonstrated.

  15. On the proluminal movement of sup 3 H-androgens across the rat epididymal epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Turner, T.T.; Jones, C.E.; Roddy, M.S. (Univ. of Virginia School of Medicine, Charlottesville (USA))

    1989-07-01

    3H-Androgens in rat epididymal interstitium have previously been shown to move into the epididymal lumen against a concentration gradient. This is true especially in the caput epididymidis. The present investigation used the technique of in vivo epididymal perifusion and tubule micropuncture to demonstrate that the proluminal movement of 3H-androgens is subject to competitive inhibition (unlabeled testosterone in the perifusion fluid at 10 times and 100 times the concentration of 3H-testosterone significantly reduced proluminal movement of isotope) and is not energy-dependent (1 mM 2,4-dinitrophenol in perifusion fluid did not reduce the proluminal movement of isotope). Additionally, dry-mount autoradiography demonstrated high intraluminal concentrations of isotope relative to interstitial concentrations after caput tubule incubation in 3H-dihydrotestosterone (3H-DHT), and showed that the high intraluminal concentrations of isotope were not dependent on the presence of spermatozoa, i.e. proluminal movement of 3H-androgens was not due to binding to intraluminal spermatozoa. Isolation of caput epididymidal sperm on filters followed by 3H-DHT binding experiments also failed to demonstrate the presence of specific binding of this androgen to spermatozoa. Finally, it was confirmed that electrophoresed epididymal lumen fluid contains a single 3H-DHT binding peak that is at its highest concentration in the caput epididymal fluid. These data are consistent with the conclusion that intraluminal androgen-binding protein is an important factor in transepithelial androgen movement.

  16. Viability of Bali bull epididymal spermatozoa preserved at 3–5oC in Tris extender with different lactose concentrations

    Directory of Open Access Journals (Sweden)

    Muhammad Rizal

    2009-06-01

    Full Text Available Cauda epididymal spermatozoa could be used as an alternative source of gamete in the application of various reproductive technologies, because the spermatozoa is motile and has ability for fertilizing the oocyte. The objective of this research was to examine the effectivity of lactose in maintaining viability of Bali bull epididymal spermatozoa preserved at 3–5oC. Five testis with epididymides of Bali bulls were obtained from slaughterhouse. Epididymal spermatozoa was collected by the combination of slicing, flushing and tissues pressure of cauda epididymides with physiological saline (0.9% NaCl. Collected-spermatozoa was divided in equal volume into three tubes and diluted with Tris extender containing 20% egg yolk (control, Tris extender + 0.3 g lactose/100 ml (L0.3, and Tris extender + 0.6 g lactose/100 ml (L0.6, respectively. Diluted-spermatozoa was stored in refrigerator at 3–5oC. Quality of diluted-spermatozoa including percentages of motile spermatozoa (MS, live spermatozoa (LS, and intact plasma membrane (IPM were evaluated every day during storage at 3–5oC for six days. Data were analyzed using completely randomized design with three treatments and five replications. Results of this study showed that mean spermatozoa concentration, percentage of MS, percentage of LS, percentage of abnormal spermatozoa, percentage of cytoplasmic droplet, and percentage of IPM of Bali bull fresh epididymal spermatozoa were 11,222.5 million cell/ml, 75, 86.75, 10.5, 14, and 86.75%, respectively. At day-7 storage, percentages of MS, LS, and IPM for L0.3 (39, 50.6, and 51.6% and L0.6 (39, 51.4, and 51.8% were significantly (P<0.05 higher than control (29, 41.8, and 42.4%. In conclusion, addition of lactose in Tris extender extended viability of Bali bull epididymal spermatozoa preserved at 3–5oC.

  17. MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jun [Foshan Maternal and Child Health Care Hospital, Foshan (China); Lei, Ting [Zhongshan People’s Hospital, Zhongshan (China); Xu, Congjie [Department of Urology, Pepole’s Hospital of Hainan Province, Haikou (China); Li, Huan; Ma, Wenmin; Yang, Yunxia; Fan, Shuming [Foshan Maternal and Child Health Care Hospital, Foshan (China); Liu, Yuchen, E-mail: s_ycliu1@stu.edu.cn [Anhui Medical University, Hefei (China)

    2013-08-23

    Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC.

  18. Blood epididymal barrier to [3H]-inulin in intact and vasectomized hamsters

    International Nuclear Information System (INIS)

    Turner, T.T.; D'Addario, D.A.; Howards, S.S.

    1981-01-01

    The net transport of [ 3 H]-inulin into the fluids of the hamster seminiferous and caput, corpus, and cauda epididymal tubules was examined in both intact animals and those vasectomized 10 months previously. Mean isotope concentrations in reproductive tract tubule fluids did not exceeded 10 per cent of blood plasma isotope concentrations during the experiment. There were no significant differences in net transport of [ 3 H]-inulin into any of the tubule fluids sampled. Ten months after vasectomy, the seminiferous tubule, and all regions of the epididymal tubule retain the capacity to exclude [ 3 H]-insulin. Thus in the hamster 10 months after vasectomy, the blood testis and blood epididymal barriers to inulin are intact

  19. Sage (Salvia officinalis) and fennel (Foeniculum vulgare) improve cryopreserved boar epididymal semen quality study.

    Science.gov (United States)

    Monton, A; Gil, L; Malo, C; Olaciregui, M; Gonzalez, N; de Blas, I

    2015-01-01

    The aim of this study was to evaluate the effect of fennel and sage extracts and the influence of the egg yolk source (fresh or pasteurized) on the success of freezing boar epididymal spermatozoa. In experiment 1, epididymal sperm was recovered by flushing and cryopreserved in a lactose-egg yolk solution supplemented with various concentrations (10, 5 and 2.5 g/L) of sage or fennel. Sperm quality was evaluated (motility, viability, HOST and acrosome integrity) at 0 h and 2 h after thawing. Fennel 10 g/L and sage 5 g/L and control (no extracts) were selected for experiment 2 which also compared fresh or pasteurized egg yolk in the freezing extender and measured DNA integrity of the frozen sperm. Results showed that the interaction between fennel and sage antioxidants with fresh egg yolk significantly improved post thaw sperm quality and protected boar epididymal spermatozoa from cryopreservation damage as a result of oxidative stress.

  20. Malignant mesothelioma of the tunica vaginalis testis: a malignancy associated with recurrent epididymitis?

    Directory of Open Access Journals (Sweden)

    Yen Ching-Heng

    2012-11-01

    Full Text Available Abstract A 53-year-old Taiwanese male had several episodes of left epididymitis with hydrocele refractory to antibiotic treatment. Partial epididymectomy plus preventive vasectomy were planned, and, incidentally, an ill-defined nodule was found lying on the tunica vaginalis near the epididymal head. The pathological diagnosis was malignant mesothelioma of the tunica vaginalis testis. Radical orchiectomy with wide excision of the hemi-scrotal wall was performed. So far, there is no evidence of recurrence after more than 3 years of follow-up. Malignant tumor should be considered in the case of recurrent epididymitis refractory to empirically effective antibiotic treatment. Although the nature of this tumor is highly fatal, the malignancy can possibly be cured by early and aggressive surgical treatment.

  1. Proteomic Analyses Reveal a Role of Cytoplasmic Droplets as an Energy Source during Epididymal Sperm Maturation

    Science.gov (United States)

    Yuan, Shuiqiao; Zheng, Huili; Zheng, Zhihong; Yan, Wei

    2013-01-01

    A small portion of cytoplasm is generally retained as the cytoplasmic droplet (CD) on the flagellum of spermatozoa after spermiation in mice. CDs are believed to play a role in osmoadaptation by allowing water entrance or exit. However, many lines of evidence suggest that CDs may have roles beyond osmoregulation. To gain more insights, we purified CDs from murine epididymal spermatozoa and conducted proteomic analyses on proteins highly enriched in CDs. Among 105 proteins identified, 71 (68%) were enzymes involved in energy metabolism. We also found that sperm mitochondria underwent a reactivation process and glycolytic enzymes were further distributed and incorporated into different regions of the flagellum during epididymal sperm maturation. Both processes appeared to require CDs. Our data suggest that the CD represents a transient organelle that serves as an energy source essential for epididymal sperm maturation. PMID:24155961

  2. 3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing.

    Science.gov (United States)

    Liu, Yuan-An; Chung, Yuan-Chiang; Pan, Shien-Tung; Hou, Yung-Chi; Peng, Shih-Jung; Pasricha, Pankaj J; Tang, Shiue-Cheng

    2012-05-15

    Morphological changes of interstitial cells of Cajal (ICC) have been proposed to characterize motility disorders. However, a global view of the network orientations of ICC subgroups has not been established to illustrate their three-dimensional (3-D) architectures in the human colon. In this research, we integrate c-kit immunostaining, 3-D microscopy with optical clearing, and image rendering to present the location-dependent network orientations with high definition. Full-depth colonic tissues were obtained from colectomies performed for nonobstructing carcinoma. Specimens of colon wall were prepared away from the tumor site. C-kit and nuclear fluorescent staining were used to identify the ICC processes and cell body. Optical clearing was used to generate transparent colon specimens, which led to panoramic visualization of the fluorescence-labeled ICC networks at the myenteric plexus (ICC-MY), longitudinal (ICC-LM) and circular (ICC-CM) muscles, and submucosal boundary (ICC-SM) up to 300 μm in depth via confocal microscopy with subcellular level resolution. We observed four distinct network patterns: 1) periganglionic ICC-MY that connect with ICC-LM and ICC-CM, 2) plexuses of ICC-LM within the longitudinal muscle and extending toward the serosa, 3) repetitive and organized ICC-CM layers running parallel to the circular muscle axis and extending toward the submucosa, and 4) a condensed ICC-SM layer lining the submucosal border. Among the four patterns, the orderly aligned ICC-CM layers provide an appropriate target for quantitation. Our results demonstrate the location-dependent network orientations of ICC subgroups and suggest a practical approach for in-depth imaging and quantitative analysis of ICC in the human colon specimen.

  3. Ejaculated mouse sperm enter cumulus-oocyte complexes more efficiently in vitro than epididymal sperm.

    Science.gov (United States)

    Li, Honggang; Hung, Pei-Hsuan; Suarez, Susan S

    2015-01-01

    The mouse is an established and popular animal model for studying reproductive biology. Epididymal mouse sperm, which lack exposure to secretions of male accessory glands and do not precisely represent ejaculated sperm for the study of sperm functions, have been almost exclusively used in studies. We compared ejaculated and epididymal sperm in an in vitro fertilization setting to examine whether ejaculated sperm enter cumulus-oocyte complexes more efficiently. In order to prepare sperm for fertilization, they were incubated under capacitating conditions. At the outset of incubation, ejaculated sperm stuck to the glass surfaces of slides and the incidences of sticking decreased with time; whereas, very few epididymal sperm stuck to glass at any time point, indicating differences in surface charge. At the end of the capacitating incubation, when sperm were added to cumulus-oocyte complexes, the form of flagellar movement differed dramatically; specifically, ejaculated sperm predominantly exhibited increased bending on one side of the flagellum (a process termed pro-hook hyperactivation), while epididymal sperm equally exhibited increased bending on one or the other side of the flagellum (pro-hook or anti-hook hyperactivation). This indicates that accessory sex gland secretions might have modified Ca2+ signaling activities in sperm, because the two forms of hyperactivation are reported to be triggered by different Ca2+ signaling patterns. Lastly, over time, more ejaculated than epididymal sperm entered the cumulus oocyte complexes. We concluded that modification of sperm by male accessory gland secretions affects the behavior of ejaculated sperm, possibly providing them with an advantage over epididymal sperm for reaching the eggs in vivo.

  4. CLEAR test facility

    CERN Multimedia

    Ordan, Julien Marius

    2017-01-01

    A new user facility for accelerator R&D, the CERN Linear Electron Accelerator for Research (CLEAR), started operation in August 2017. CLEAR evolved from the former CLIC Test Facility 3 (CTF3) used by the Compact Linear Collider (CLIC). The new facility is able to host and test a broad range of ideas in the accelerator field.

  5. EFFECT OF MALTOSE CONCENTRATION IN TRIS DILUTION ON EPIDIDYMAL SPERMATOZOA QUALITY OF BALI BULL PRESERVED AT 50C

    Directory of Open Access Journals (Sweden)

    J. Wattimena

    2014-10-01

    Full Text Available The objective of research was to evaluate the effect of maltose concentration in Tris dilution onepididymal spermatozoa quality of Bali bull that preserved at 50C. Five testis of Bali bull collected fromslaughter house were used in this study. Epididymal spermatozoa were collected through slicing andflushing methods, pressing cauda epididymal was conducted in NaCl physiology (NaCl 0.9% emulsion.Spermatozoa which collected were divided into three reaction tube and each diluted by Tris dilutioncontaining: Tris dilution + 20% of yolk (control; Tris dilution + 20% of yolk + 0.3 g of maltose/100ml(M0.3; and Tris dilution + 20% of yolk + 0.6 g maltose/100 ml (M0.6. Spermatozoa qualities observedwere motile spermatozoa (MS, live-spermatozoa (LS and intact-plasma membrane (IPM thatevaluated daily in refrigerator at temperature of 5oC. Completely Randomized Design with threetreatments and five replications was used in this study. Data was analyzed by analysis of variance.Examination on fresh spermatozoa showed that spermatozoa concentration was 11,222.5 million cell/ml,motile spermatozoa was 75.00%, live-sperm was 86.75%, abnormal spermatozoa was 10.50%,cytoplasmic droplet was 14.00% and IPM was 86.75%. At the seventh day of preservation, thepercentages of MS, LS and IPM in M0.3 were 37.0 %, 49.2% and 50.4%, respectively, and M0.6 were38.05%; 51.8 % and 52.0%, respectively that were significantly higher (P<0.05 than control (29.0%;41.8% and 42.4%, respectively. It was concluded that maltose added into Tris dilution could lengthenepididymal spermatozoa quality of Bali bull which persevered at 50C.

  6. Predictive Factors for Natural Pregnancy after Microsurgical Reconstruction in Patients with Primary Epididymal Obstructive Azoospermia

    Directory of Open Access Journals (Sweden)

    Mihai Harza

    2014-01-01

    Full Text Available Primary epididymal obstructive azoospermia (OA is the most prevalent form of OA in nonvasectomized patients and has been less studied. We aim to assess the results with microsurgical vasoepididymostomy used in the treatment of men diagnosed with primary epididymal obstructive azoospermia and to identify the factors associated with natural pregnancy occurring after microsurgical reconstruction. This prospective study included consecutive patients with epididymal OA who underwent microsurgical reconstruction in our center. Clinical and biological data were obtained every three months during follow-up. Occurrence of natural pregnancy was the primary study outcome. In total, 36 patients underwent microsurgical reconstruction. The mean age was 34±4.5 years (range 24–46 years. Median follow-up time was 15 [IQR 12–21] months. The total patency rate was 77.7% (n=28. During follow-up, 8 (22.2% natural pregnancies occurred. The overall live birth rate was 100%. Low FSH levels (HR: 0.22; 95% CI: 0.052–0.88; P=0.032 and higher total motile sperm count (TMSC (HR: 1.001; 95% CI 1–1.001; P=0.012 were associated with a higher rate of natural pregnancy. Our data suggest that microsurgical vasoepididymostomy is an effective therapy of primary epididymal OA. Baseline lower FSH and higher TMSC were independent predictors for natural pregnancy occurrence.

  7. Predictive factors for natural pregnancy after microsurgical reconstruction in patients with primary epididymal obstructive azoospermia.

    Science.gov (United States)

    Harza, Mihai; Voinea, Sebastian; Ismail, Gener; Gagiu, Cristian; Baston, Catalin; Preda, Adrian; Manea, Ioan; Priporeanu, Tiberiu; Sinescu, Ioanel

    2014-01-01

    Primary epididymal obstructive azoospermia (OA) is the most prevalent form of OA in nonvasectomized patients and has been less studied. We aim to assess the results with microsurgical vasoepididymostomy used in the treatment of men diagnosed with primary epididymal obstructive azoospermia and to identify the factors associated with natural pregnancy occurring after microsurgical reconstruction. This prospective study included consecutive patients with epididymal OA who underwent microsurgical reconstruction in our center. Clinical and biological data were obtained every three months during follow-up. Occurrence of natural pregnancy was the primary study outcome. In total, 36 patients underwent microsurgical reconstruction. The mean age was 34 ± 4.5 years (range 24-46 years). Median follow-up time was 15 [IQR 12-21] months. The total patency rate was 77.7% (n = 28). During follow-up, 8 (22.2%) natural pregnancies occurred. The overall live birth rate was 100%. Low FSH levels (HR: 0.22; 95% CI: 0.052-0.88; P = 0.032) and higher total motile sperm count (TMSC) (HR: 1.001; 95% CI 1-1.001; P = 0.012) were associated with a higher rate of natural pregnancy. Our data suggest that microsurgical vasoepididymostomy is an effective therapy of primary epididymal OA. Baseline lower FSH and higher TMSC were independent predictors for natural pregnancy occurrence.

  8. The effect of quercetin on fertility of frozen-thawed ram epididymal ...

    African Journals Online (AJOL)

    mz

    2017-03-13

    Mar 13, 2017 ... known that the in vivo fertility of epididymal sperm tends to be lower than that of ejaculated ones (Papa et al.,. 2015). While cryopreservation has deleterious effects on mammalian sperm, the extent of that damage varies across species and relies heavily on sperm resilience to the freezing-thawing process ...

  9. The effect of quercetin on fertility of frozen-thawed ram epididymal ...

    African Journals Online (AJOL)

    Epididymal spermatozoa were recovered from the caudal of epididymides by injecting Bracket and Oliphant's (BO) medium retrogradely through the ductus deferens and extended with a tris egg-yolk-based extender and supplemented with 0, 5, 10, 15, 20, and 50 μg/mL quercetin. Following equilibration, the straws were ...

  10. Low-density Lipoprotein Improves Motility and Plasma Membrane Integrity of Cryopreserved Canine Epididymal Spermatozoa

    Directory of Open Access Journals (Sweden)

    N. Prapaiwan

    2016-05-01

    Full Text Available Cryopreservation of caudal epididymal spermatozoa is an effective technique to conserve genetic potentials of superior dogs when it is not possible to collect ejaculated spermatozoa. Although hen egg yolk is commonly supplemented into the semen extender, active substances within the egg yolk which protect sperm against cryoinjury remain to be discovered. Among its compositions, low-density lipoprotein (LDL has been reported to have a cryoprotective property for sperm cryopreservation. However, the effects of LDL on dog epididymal spermatozoa during cryopreservation have not yet been investigated. This study aimed to investigate the effects of LDL on epididymal spermatozoa quality following cryopreservation and thawing. After routine castration of 12 dogs, caudal epididymides from individuals were separated from the testes and cut into a few pieces in a Tris-buffer. Spermatozoa recovered from each sample were examined at once for sperm quality and divided into six groups of extender: no LDL, 20% egg yolk, 4%, 8%, 16%, and 24% LDL, before cryopreservation. The sperm aliquots were then equilibrated and conventionally frozen. After thawing, sperm motility, morphology, plasma membrane integrity, and acrosome integrity were evaluated. The results revealed that 4% LDL and 20% egg yolk yielded significantly higher sperm motility (57.69% and 52.69%, respectively, p<0.05 than other LDLs. In addition, 4% LDL yielded the significantly highest plasma membrane integrity (70.54%, p<0.05. In conclusion, the supplementation of 4% LDL in Tris-glucose extender could be applied for cryopreservation of canine epididymal spermatozoa.

  11. L-carnitine Supplemented Extender Improves Cryopreserved-thawed Cat Epididymal Sperm Motility

    Directory of Open Access Journals (Sweden)

    S. Manee-in

    2014-06-01

    Full Text Available Cryopreservation of epididymal sperm is an effective technique to preserve genetic materials of domestic cats and wild felids when they unexpectedly die. However, this technique inevitably causes detrimental changes of cryopreserved-thawed spermatozoa, for example, by physical damage and excessive oxidative stress. L-carnitine is an antioxidant that has been used to improve sperm motility in humans and domestic animals. This study aimed to investigate the effects of L-carnitine on cat epididymal sperm quality following cryopreservation and thawing. After routine castration, cauda epididymides were collected from 60 cat testes. The epididymal spermatozoa from 3 cauda epididymides were pooled as 1 replicate. Spermatozoa samples (16 replicates were examined for spermatozoa quality and then randomly divided into 4 groups: 0 mM L-carnitine (control, 12.5 mM, 25 mM and 50 mM L-carnitine. The sperm aliquots were then equilibrated and conventionally frozen. After thawing, sperm motility, plasma membrane integrity, DNA integrity and acrosome integrity were evaluated. The 25 mM L-carnitine significantly improved sperm motility compared with a control group (p<0.05, although this was not significantly different among other concentrations. In conclusion, supplementation of 25 mM L-carnitine in freezing extender improves cauda epididymal spermatozoa motility. The effects of L-carnitine on the levels of oxidative stress during freezing and thawing remains to be examined.

  12. In vitro fertilizing potential of urethral and epididymal spermatozoa collected from domestic cats (Felis catus).

    Science.gov (United States)

    Prochowska, S; Niżański, W

    2017-03-28

    The aim of this study was to provide a comparative analysis of in vitro fertilizing potential of frozen-thawed urethral and epididymal feline spermatozoa. Both types of semen were collected from 7 cats and cryopreserved in liquid nitrogen. To perform in vitro fertilization, both urethral and epididymal samples from the same individual were thawed and spermatozoa were co-incubated with in vitro matured cat oocytes. Obtained embryos were cultured in vitro for 7 days in a commercial medium. Cleavage rate, morula rate and blastocyst rate were calculated. Experiment was run in 10 replicates. The examined parameters showed no significant differences between urethral and epididymal spermatozoa (p>0.05). Cleavage rate and embryo's development were highly variable between replicates, even for the different sperm samples collected from one individual. There was no significant correlation between fertilizing capacity of two types of spermatozoa collected from the same male. In this study we confirmed that cryopreserved urethral spermatozoa have equally good fertilizing potential as epididymal ones, and both can be successfully used for in vitro fertilization in cats with the use of commercial medium.

  13. Recovery of sperm after epididymal refrigeration from domestic cats using ACP-117c and Tris extenders

    Directory of Open Access Journals (Sweden)

    D.B.C. Lima

    2016-08-01

    Full Text Available ABSTRACT We aimed to compare fresh sperm and sperm cooled to 4ºC that had been recovered from the epididymides of cats using powdered coconut water (ACP-117c and Tris extenders. Sixty epididymides were divided into 6 groups: 10 fresh epididymides were recovered using Tris (T0h; 10 were kept at 4°C/2h and recovered using Tris (T2h; 10 were kept at 4°C/4h and recovered using Tris (T4h; 10 fresh were recovered using ACP-117c (A0h; 10 were kept at 4°C/2h and recovered using ACP-117c (A2h, and 10 were kept at 4°C/4h and recovered using ACP-117c (A4h. The testis-epididymis complexes (TEC control were not cooled. The others were cooled at 4°C for 2 or 4h. The epididymis was separated and the sperm was recovered by the modified flotation method. Sperm kinetic parameters were evaluated by a computer-system analysis, and vigor, viability, concentration, membrane function and morphology of the sperm were assessed under a light microscope. The progressive motility with ACP-117c declined after 2h of cooling, but did not differ between fresh and 4h. The vigor and membrane function were higher in A4h than A0h. The vigor at T2h and T4h were decreased compared to T0h. T0h was higher than A0h for vigor and sperm membrane function. However, after 4h of cooling, ACP-117c maintained a higher percentage of living cells. Feline epididymal sperm quality can be maintained to the degree necessary for artificial breeding programs following cooling and ACP-117c may be successfully used to recover cat sperm that have been cooled for up to 4h.

  14. Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

    Directory of Open Access Journals (Sweden)

    Bohonowych Jessica ES

    2011-12-01

    Full Text Available Abstract Background Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF function in a von Hippel-Lindau (VHL independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Methods Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC inhibitor LBH589. Results The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. Conclusions We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.

  15. Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

    International Nuclear Information System (INIS)

    Bohonowych, Jessica ES; Peng, Shuping; Gopal, Udhayakumar; Hance, Michael W; Wing, Shane B; Argraves, Kelley M; Lundgren, Karen; Isaacs, Jennifer S

    2011-01-01

    Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589. The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression

  16. Acute epididymitis in ultrasound: Results of a prospective study with baseline and follow-up investigations in 134 patients

    Energy Technology Data Exchange (ETDEWEB)

    Pilatz, A., E-mail: adrian.pilatz@chiru.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany); Wagenlehner, F., E-mail: florian.wagenlehner@chiru.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany); Bschleipfer, T., E-mail: thomas.bschleipfer@chiru.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany); Schuppe, H.-C., E-mail: hans-christian.schuppe@derma.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany); Diemer, T., E-mail: thorsten.diemer@chiru.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany); Linn, T., E-mail: thomas.linn@innere.med.uni-giessen.de [Clinical Research Unit, 3rd Medical Clinic and Policlinic, Justus-Liebig University Giessen, Klinikstrasse 33, 35392 Giessen (Germany); Weidner, W., E-mail: wolfgang.weidner@chiru.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany); Altinkilic, B., E-mail: bora.altinkilic@chiru.med.uni-giessen.de [Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim-Str. 7, 35392 Giessen (Germany)

    2013-12-01

    Objectives: To perform a comprehensive follow-up analysis of ultrasonographic scrotal features and associated signs in patients with acute epididymitis. Methods: Between 2007 and 2012, 134 adults (median age 54 years) with acute epididymitis underwent scrotal ultrasonography and palpation at first presentation and after 2 weeks and 3 months. Results: At first presentation, 61 patients (45.5%) had hydrocele, 63 (47.0%) concomitant orchitis, and 8 (5.9%) epididymal abscess. Epididymitis was predominantly located in 24 cases (17.9%) in the head, 52 cases (38.8%) in the tail, and 58 cases (43.3%) in both. On the affected side, testicular volume was 16.9 ± 6.8 ml and peak systolic velocity of the testicular artery was 23.7 ± 7.5 cm/s, compared to the healthy side with 12.3 ± 4.4 ml and 9.5 ± 3.6 cm/s respectively (P < 0.001). Concomitant orchitis was associated with hydrocele, testicular enlargement and pain (P < 0.01). Orchiectomy due to secondary testicular infarction was necessary in four cases, while in all other patients ultrasound parameters normalized. Only 16/90 patients (17.8%) showed a persistent epididymal swelling after 3 months. Conclusions: Common ultrasound features include hydrocele, epididymal enlargement, hyperperfusion, and testicular involvement. Under conservative treatment, ultrasound parameters normalize without evidence of testicular atrophy even in patients with epididymal abscess or concomitant orchitis.

  17. CD9-positive microvesicles mediate the transfer of molecules to Bovine Spermatozoa during epididymal maturation.

    Science.gov (United States)

    Caballero, Julieta N; Frenette, Gilles; Belleannée, Clémence; Sullivan, Robert

    2013-01-01

    Acquisition of fertilization ability by spermatozoa during epididymal transit occurs in part by the transfer of molecules from membranous vesicles called epididymosomes. Epididymosomes are heterogeneous in terms of both size and molecular composition. Exosomes and other related small membranous vesicles (30-120 nm) containing tetraspanin proteins on their surface are found in many biological fluids. In this study, we demonstrate that these vesicles are present in bovine cauda epididymal fluid as a subpopulation of epididymosomes. They contain tetraspanin CD9 in addition to other proteins involved in sperm maturation such as P25b, GliPr1L1, and MIF. In order to study the mechanism of protein transfer to sperm, DilC12-labeled unfractionated epididymosomes or CD9-positive microvesicles were coincubated with epididymal spermatozoa, and their transfer was evaluated by flow cytometry. CD9-positive microvesicles from epididymal fluid specifically transferred molecules to spermatozoa, whereas those prepared from blood were unable to do so. The CD9-positive microvesicles transferred molecules to the same sperm regions (acrosome and midpiece) as epididymosomes, with the same kinetics; however, the molecules were preferentially transferred to live sperm and, in contrast to epididymosomes, Zn(2+) did not demonstrate potentiated transfer. Tetraspanin CD9 was associated with other proteins on the membrane surface of CD9-positive microvesicles according to coimmunoprecipitation experiments. CD26 cooperated with CD9 in the molecular transfer to sperm since the amount of molecules transferred was significantly reduced in the presence of specific antibodies. In conclusion, CD9-positive microvesicles are present in bovine cauda epididymal fluid and transfer molecules to live maturing sperm in a tissue-specific manner that involves CD9 and CD26.

  18. Morphological studies on the seasonal changes in the epididymal duct of the one-humped camel (camelus dromedarius

    Directory of Open Access Journals (Sweden)

    Ahmed El-Zuhry Zayed

    2012-02-01

    Full Text Available The present work was carried out on 20 testes and epididymis of sexually mature camels to elucidate the gross anatomical, morphometerical, light microscopical and scanning electron microscopical features of the epididymis in different seasons. Anatomically, the epididymal duct of a camel consists of three parts head, body and tail. Histomorphologically, the epididymal duct is subdivided into initial, middle and terminal segments, of which the middle segment is further subdivided into proximal, intermediate and distal parts. There is a gradual decrease in the epithelial height of the epididymal duct from the initial to the terminal segments. This mechanically facilities passage of the sperms toward the terminal segment. High epithelium in the initial segment may indicate a more absorptive power of the epithelium in this segment. The seasonal reproductivety of the epididymal duct in the camel expressed by variations in the weight and volume of the epididymis, total diameter of the epididymal duct, epithelial height, length of the stereocilia, thickness of the muscular coat and cellular distributions in different segments. The spring months offer ideal circumstances for maximal reproductive activity in this species. The cellular components of the epididymal duct epithelium of the camel displays important morphological changes from season to another showing signs of increasing activity during spring in comparison to decreasing activity in other seasons. PAS positive granules are demonstrated in different segments of the epididymal duct and intraepithelial glands in different seasons. These granules are relatively more numerous in spring. The lamina propria surrounding the epididymal duct contains a layer of the elastic fibers which is very thick in winter, thick in spring and thin in other seasons. This increase in thickness of the elastic fibers predisposes for the increase in the total diameter of the epididymal duct in spring. It was conclude

  19. Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted ¹⁸F-DCFPyL PET/CT.

    Science.gov (United States)

    Rowe, Steven P; Gorin, Michael A; Hammers, Hans J; Som Javadi, M; Hawasli, Hazem; Szabo, Zsolt; Cho, Steve Y; Pomper, Martin G; Allaf, Mohamad E

    2015-12-01

    Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, ¹⁸F-fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose. Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer ¹⁸F-DCFPyL, an inhibitor of the prostate-specific membrane antigen at 60 min post injection. ¹⁸F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease. In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal ¹⁸F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. ¹⁸F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUVmax) for the identified lesions of 1.6-19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for ¹⁸F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9%). PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as ¹⁸F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with

  20. Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma.

    Science.gov (United States)

    Aman, Murasaki; Ohishi, Yoshihiro; Imamura, Hiroko; Shinozaki, Tomoko; Yasutake, Nobuko; Kato, Kiyoko; Oda, Yoshinao

    2017-06-01

    Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress up-regulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of ovarian endometrioid carcinoma (OEC) were also examined. No significant differences in the expression of cyclooxygenase-2 and inducible nitric oxide synthase were observed between OCCC and OEC. Sixty-two percent of the OCCC cases showed high 8-hydroxydeoxyguanosine expression, whereas all of the OEC cases showed almost negative immunoreactivities. The presence of endometriosis did not affect the expression of these oxidative stress markers or prognosis. High PAR-2 expression was observed in 20% (14/71) of the early International Federation of Gynecology and Obstetrics (FIGO) stage cases and 58% (14/24) of the advanced FIGO stage cases. High PAR-2 expression was significantly correlated with advanced FIGO stage and shorter overall survival. We found no correlations between PAR-2 expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an important role in the progression of OCCC. The expression of 8-hydroxydeoxyguanosine is a characteristic finding of OCCC, indicating that the injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The prognostic value of pretreatment CA-125 levels and CA-125 normalization in ovarian clear cell carcinoma: a two-academic-institute study.

    Science.gov (United States)

    Bai, Huimin; Sha, Guisha; Xiao, Meizhu; Gao, Huiqiao; Cao, Dongyan; Yang, Jiaxin; Chen, Jie; Wang, Yue; Zhang, Zhenyu; Shen, Keng

    2016-03-29

    The present study investigated the clinical implications of pretreatment carbohydrate antigen 125 (CA-125) levels and CA-125 normalization in patients with ovarian clear cell carcinoma (CCC), and it provides useful information for the improvement of monitoring strategies for this lethal disease. The medical records of patients with ovarian CCC who had undergone primary staging surgery or cytoreductive surgery followed by systemic chemotherapy were retrospectively reviewed. A range of clinico-pathological parameters were collected and examined. A total of 375 women were included in the analysis. FIGO stage (p CA-125 levels included advanced-stage disease, positive residual tumors and negative endometriosis (p CA-125 levels were not associated with relapse-free survival (RFS) or overall survival (OS) (p = 0.060 and p = 0.176, respectively). CA-125 normalization after chemotherapy exhibited a positive linear correlation with advanced stage (r = 0.97, p = 0.001) and residual tumor (r = 0.81, p = 0.027) and a negative relationship with 5-year RFS (r = -0.97, p = 0.002) and 5-year OS (r = -0.97, p= 0.001). Patients with CA-125 levels that normalized before cycle 2 of chemotherapy had a similar prognosis as patients whose CA-125 levels normalized prior to chemotherapy (RFS: p = 0.327; OS: p = 0.654). By contrast, patients with CA-125 levels that normalized after cycle 2 of chemotherapy or never normalized were significantly more likely to experience disease progression. Pretreatment CA-125 levels are not very useful for predicting clinical outcome. CA-125 levels following treatment are a valid indicator for treatment monitoring. CA-125 normalization after the completion of cycle 1 of chemotherapy represents a distinct inflection point for decreased RFS and OS.

  2. Does the Loss of ARID1A (BAF-250a Expression in Endometrial Clear Cell Carcinomas Have Any Clinicopathologic Significance? A Pilot Assessment

    Directory of Open Access Journals (Sweden)

    Oluwole Fadare, Idris L. Renshaw, Sharon X. Liang

    2012-01-01

    Full Text Available SWI/SNF chromatin-modification complexes use the energy of ATP hydrolysis to remodel nucleosomes and to affect transcription and several cellular processes. Accordingly, their loss of function has been associated with malignant transformation. ARID1A (the expression of whose product, BAF250a, a key complex component, is lost when mutated has recently been identified as a tumor suppressor gene that is mutated in 46-57% of ovarian clear cell carcinoma (CCC. The purposes of this study are to assess the frequency of loss of BAF250a expression in endometrial CCC and whether this loss has any discernable clinicopathologic implications. 34 endometrial carcinomas with a CCC component (including 22 pure CCC, 8 mixed carcinomas with a 10% CCC component, and 4 carcinosarcomas with a CCC epithelial component, were evaluated by immunohistochemistry using a monoclonal antibody directed against the human BAF250a protein. 5 (22.7% of the 22 pure CCC were entirely BAF250a negative, whereas the remainder showed diffuse immunoreactivity. None of 4 carcinosarcomas and only 1 (12.5% of the 8 mixed carcinomas were BAF250a negative. There was no discernable relationship between BAF250a immunoreactivity status and tumor architectural patterns (solid, papillary or tubulocystic areas or cell type (flat, hobnail or polygonal. Of the 22 patients with pure CCC, 14, 2, 3, and 3 were International Federation of Gynecology and Obstetrics stages 1, II, III and IV respectively. Interestingly, all 5 BAF250a negative cases were late stage [stages III or IV] as compared with 1 of 17 BAF250a positive cases (p=0.0002. Thus, 83% (5/6 of all late stage cases were BAF250a [-], as compared with 0 (0% of the 16 early stage (I or II cases (p=.0002. BAF250a negative and positive cases did not show any statistically significant difference regarding patient age and frequency of lymphovascular invasion or myometrial invasion. As may be anticipated from the concentration of late stage cases in

  3. Single blastocyst transfer after ICSI from ejaculate spermatozoa, percutaneous epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE)

    OpenAIRE

    Nilsson, Staffan; Waldenström, Urban; Engström, Ann-Britt; Hellberg, Dan

    2007-01-01

    Purpose: To investigate the outcome of IVF following intracytoplasmic sperm injection (ICSI) from ejaculate, percutaneous epididymal sperm aspiration (PESA) and testicular sperm extraction (TESE), with subsequent blastocyst culture and single blastocyst transfer.

  4. Influence of recovery method and centrifugation on epididymal sperm from collared peccaries (Pecari tajacu Linnaeus, 1758).

    Science.gov (United States)

    Bezerra, José Artur Brilhante; da Silva, Andréia Maria; Peixoto, Gislayne Christianne Xavier; da Silva, Mariana de Araújo; Franco de Oliveira, Moacir; Silva, Alexandre Rodrigues

    2014-05-01

    In order to establish protocols for gamete recovery from accidentally killed wild animals, or to take advantage of those slaughtered by captive breeders, we assess the influence of two methods on the recovery of epididymal sperm from collared peccaries, and verify the effect of centrifugation on such gametes. Genitalia from nine animals were used. For each animal, one epididymis was processed by flotation and the other was processed by retrograde flushing, both using a buffered media based on Tris. Following recovery, sperm were evaluated for motility, vigor, viability, functional membrane integrity, and morphology. A 1-mL aliquot of each sample was centrifuged, the supernatant removed, and the pellet suspended and evaluated as fresh samples. The sperm characteristics did not differ between the samples collected by flotation or retrograde flushing (P methods was affected by centrifugation. In conclusion, epididymal sperm from collared peccaries can be efficiently collected through flotation or retrograde flushing, but not when either is followed by centrifugation.

  5. In‑depth mapping of human testicular and epididymal proteins and their functional association with spermatozoa.

    Science.gov (United States)

    Liu, Xuexia; Liu, Fujun

    2015-07-01

    The mammalian testis and epididymis are responsible for spermatozoa production and maturation, which contributes to male fertility. Predominantly expressed proteins in the testis and epididymis were suggested to be involved in the key functions or pathways in spermatogenesis and sperm maturation. To further investigate these proteins and their associations with sperm, large protein profiles of human testis and epididymis were mapped. Predominantly‑expressed testicular (173) and epididymal (244) secreted proteins were further screened and functionally characterized. Differential expression levels of solute carrier family 2 (facilitated glucose transporter), member 3, solute carrier family 25 (carnitine/acylcarnitine translocase), member 20, WAP‑type four‑disulfide core domain protein 8 and prostate and testis expressed 1 were validated using western blot and immunohistochemical analyses. The results may provide novel insight into the understanding of testicular and epididymal physiology and function, and facilitate sperm maturation research.

  6. In-depth mapping of human testicular and epididymal proteins and their functional association with spermatozoa

    Science.gov (United States)

    LIU, XUEXIA; LIU, FUJUN

    2015-01-01

    The mammalian testis and epididymis are responsible for spermatozoa production and maturation, which contributes to male fertility. Predominantly expressed proteins in the testis and epididymis were suggested to be involved in the key functions or pathways in spermatogenesis and sperm maturation. To further investigate these proteins and their associations with sperm, large protein profiles of human testis and epididymis were mapped. Predominantly-expressed testicular (173) and epididymal (244) secreted proteins were further screened and functionally characterized. Differential expression levels of solute carrier family 2 (facilitated glucose transporter), member 3, solute carrier family 25 (carnitine/acylcarnitine translocase), member 20, WAP-type four-disulfide core domain protein 8 and prostate and testis expressed 1 were validated using western blot and immunohistochemical analyses. The results may provide novel insight into the understanding of testicular and epididymal physiology and function, and facilitate sperm maturation research. PMID:25760095

  7. Characteristics and in Vitro Fertilization Ability of Ram Spermatozoa: Comparison of Epididymal and Ejaculated Spermatozoa

    OpenAIRE

    Pamungkas, F; Setiadi, M A; Karja, N W.K

    2012-01-01

    The characteristics and in vitro fertilization (IVF) ability of ram spermatozoa collected from cauda epididymal was examined. Ejaculated spermatozoa was used as control group in this experiment. Characteristics of spermatozoa including the percentage of progressive motility, viability, abnormality and membrane integrity were evaluated before and after freezing. Fertilization ability of post-thawed spermatozoa in both group was examined based on the pronucleus formation after IVF of in vitro m...

  8. Association of sexual experience with isolation of various bacteria in cases of ovine epididymitis.

    Science.gov (United States)

    Bulgin, M S; Anderson, B C

    1983-02-15

    Testicles from rams in flocks experiencing ram epididymitis in Idaho and eastern Oregon were cultured. Twenty-six breeding rams from 6 flocks were cultured and only Brucella ovis was isolated. Virgin rams (65) harbored numerous species of small fastidious gram-negative rods, including Actinobacillus actinomycetemcomitans, Haemophilus spp, Moraxella spp, and Pasteurella spp. Thus, there appeared to be 2 separate disease entities, dependent on sexual experience of the animal.

  9. L-carnitine Supplemented Extender Improves Cryopreserved-thawed Cat Epididymal Sperm Motility

    OpenAIRE

    S. Manee-in; S. Parmornsupornvichit; S. Kraiprayoon; T. Tharasanit; P. Chanapiwat; K. Kaeoket

    2014-01-01

    Cryopreservation of epididymal sperm is an effective technique to preserve genetic materials of domestic cats and wild felids when they unexpectedly die. However, this technique inevitably causes detrimental changes of cryopreserved-thawed spermatozoa, for example, by physical damage and excessive oxidative stress. L-carnitine is an antioxidant that has been used to improve sperm motility in humans and domestic animals. This study aimed to investigate the effects of L-carnitine on cat epididy...

  10. The influence of canine brucellosis on morphofunctional features of epididymal spermatozoa: case report

    OpenAIRE

    Angrimani, D.S.R.; Lúcio, C.F.; Losano, J.D.A.; Brito, M.M.; Silva Júnior, R.A.; Keid, L.B.; Nichi, M.; Vannucchi, C.I.

    2016-01-01

    ABSTRACT The present work reports a clinical case of a mongrel dog, with serological diagnosis of brucellosis, from which epididymal sperm analysis was performed. Sperm samples were collected from different segments of the epididymis (tail, corpus, and caput). Sperm samples were evaluated for computer-assisted motility analysis (CASA), spermatic morphology, mitochondrial activity and sperm plasmatic membrane and acrosomal integrity. Changes in sperm movement patterns were found (progressive m...

  11. Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats.

    Science.gov (United States)

    Cavariani, Marilia Martins; de Almeida Kiguti, Luiz Ricardo; de Lima Rosa, Josiane; de Araújo Leite, Gabriel Adan; Silva, Patrícia Villela E; Pupo, André Sampaio; De Grava Kempinas, Wilma

    2015-09-01

    Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg(-1), 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg(-1) increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg(-1) bupropion impaired sperm quality increasing the incidence of non-progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Microsurgical and Percutaneous Epididymal Sperm Aspiration for Sperm Collection from Live Mice.

    Science.gov (United States)

    Boersma, Auke; Olszanska, Olga; Walter, Ingrid; Rülicke, Thomas

    2015-09-01

    Spermatozoa for in vitro fertilization of mouse oocytes and other methods of assisted reproduction typically are collected from the cauda epididymis of euthanized male mice. As an alternative to this terminal protocol, we developed and examined 2 methods for collecting sperm from anesthetized male mice without decreasing subsequent fertility: microsurgical epididymal sperm aspiration and, as a refinement, percutaneous epididymal sperm aspiration. Collected sperm was evaluated in terms of motility, concentration and in vitro fertilization ability. After recovery, both treated and untreated control male mice underwent in vivo fertility testing and subsequent histologic analysis of the treated male reproductive tract (epididymis and testis). In vitro fertilization using sperm recovered by the 2 collection methods was successfully achieved in all cases. The in vivo fertility test and the histologic analysis revealed no impairment of fertility and no permanent histologic alteration in the treated mice. Therefore, we recommend both techniques as simple and effective methods for recovering high-quality epididymal mouse sperm without having to euthanize fertile male mice.

  13. Effect of nonylphenol on male reproduction: Analysis of rat epididymal biochemical markers and antioxidant defense enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Aly, Hamdy A.A., E-mail: hamdyaali@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah (Saudi Arabia); Domènech, Òscar [Department of Physical Chemistry, Faculty of Pharmacy, Barcelona University (Spain); Banjar, Zainy M. [Department of Medical Biology, School of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia)

    2012-06-01

    The mechanism by which nonylphenol (NP) interferes with male reproduction is not fully elucidated. Therefore, the present study was conducted to evaluate the effect of NP on male reproductive organ's weight, sperm characteristics, and to elucidate the nature and mechanism of action of NP on the epididymis. Adult male Wistar rats were gavaged with NP, dissolved in corn oil, at 0, 100, 200 or 300 mg/kg/day for 30 consecutive days. Control rats were gavaged with vehicle (corn oil) alone. Body weight did not show any significant change while, absolute testes and epididymides weights were significantly decreased. Sperm count in cauda and caput/corpus epididymides, and sperm motility was significantly decreased. Daily sperm production was significantly decreased in a dose-related manner. Sperm transit time in cauda epididymis was significantly decreased by 300 mg/kg, while in the caput/corpus epididymis it was significantly decreased by 200 and 300 mg/kg of NP. Plasma LDH was significantly increased while; plasma testosterone was significantly decreased in a dose-related pattern. In the epididymal sperm, NP decreased acrosome integrity, Δψm and 5′-nucleotidase activity. Hydrogen peroxide (H{sub 2}O{sub 2}) production and LPO were significantly increased in a dose-related pattern. The activities of SOD, CAT and GPx were significantly decreased in the epididymal sperm. In conclusion, this study revealed that NP treatment impairs spermatogenesis and has a cytotoxic effect on epididymal sperm. It disrupts the prooxidant and antioxidant balance. This leads oxidative stress in epididymal sperms of rat. Moreover, the reduction in sperm transit time may affect sperm quality and fertility potential. -- Highlights: ► The nature and mechanism of action of NP on rat epididymis were elucidated. ► NP decreased sperm count, motility, daily sperm production and sperm transit time. ► NP decreased sperm acrosome integrity, Δψm and 5′-nucleotidase activity. ► Plasma

  14. A Systematic Analysis of a Deep Mouse Epididymal Sperm Proteome

    Energy Technology Data Exchange (ETDEWEB)

    Chauvin, Theodore; Xie, Fang; Liu, Tao; Nicora, Carrie D.; Yang, Feng; Camp, David G.; Smith, Richard D.; Roberts, Kenneth P.

    2012-12-21

    Spermatozoa are highly specialized cells that, when mature, are capable of navigating the female reproductive tract and fertilizing an oocyte. The sperm cell is thought to be largely quiescent in terms of transcriptional and translational activity. As a result, once it has left the male reproductive tract, the sperm cell is essentially operating with a static population of proteins. It is therefore theoretically possible to understand the protein networks contained in a sperm cell and to deduce its cellular function capabilities. To this end we have performed a proteomic analysis of mouse sperm isolated from the cauda epididymis and have confidently identified 2,850 proteins, which is the most comprehensive sperm proteome for any species reported to date. These proteins comprise many complete cellular pathways, including those for energy production via glycolysis, β-oxidation and oxidative phosphorylation, protein folding and transport, and cell signaling systems. This proteome should prove a useful tool for assembly and testing of protein networks important for sperm function.

  15. Roosters affected by epididymal lithiasis present local alteration in vitamin D3, testosterone and estradiol levels as well as estrogen receptor 2 (beta) expression.

    Science.gov (United States)

    Oliveira, André G; Dornas, Rubem A P; Praes, Lílian C; Hess, Rex A; Mahecha, Germán A B; Oliveira, Cleida A

    2011-09-01

    Epididymal lithiasis is a reproductive dysfunction of roosters that is associated with loss of fertility and is characterized by the formation of calcium stones in the lumen of the efferent ductules of the epididymal region. The efferent ductules of birds are responsible for the reabsorption of the fluid coming from the testis as well as luminal calcium. It has been hypothesized that the epididymal stone formation may be related to the impairment of local fluid or calcium homeostasis, which depends on hormones such as estradiol (E(2)). Therefore, this study aimed to investigate possible alterations in the expression of ERα (ESR1) and ERβ (ESR2) in the epididymal region of roosters affected by epididymal lithiasis. The study was performed by immunohistochemistry and western blotting assays. In addition, the concentrations of E(2), vitamin D3, and testosterone, which are also key hormones in maintenance of calcium homeostasis, were determined in the plasma and epididymal region, by ELISA. It was observed that ESR2 expression is increased in all segments of the epididymal region of affected roosters, whereas ESR1 levels are not altered. Moreover, the hormone concentration profiles were changed, as in the epididymal region of roosters with lithiasis the E(2) levels were increased and vitamin D3 as well as testosterone concentrations were significantly decreased. These results suggest that a hormonal imbalance may be involved with the origin and progression of the epididymal lithiasis, possibly by affecting the local fluid or calcium homeostasis.

  16. Sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured rat caput epididymal epithelium.

    Science.gov (United States)

    Zuo, Wu-Lin; Li, Sheng; Huang, Jie-Hong; Yang, Deng-Liang; Zhang, Geng; Chen, Si-Liang; Ruan, Ye-Chun; Ye, Ke-Nan; Cheng, Christopher H K; Zhou, Wen-Liang

    2011-01-01

    The epithelium lining the epididymis provides an optimal acidic fluid microenvironment in the epididymal tract that enable spermatozoa to complete the maturation process. The present study aims to investigate the functional role of Na(+)/HCO(3)(-) cotransporter in the pH regulation in rat epididymis. Immunofluorescence staining of pan cytokeratin in the primary culture of rat caput epididymal epithelium showed that the system was a suitable model for investigating the function of epididymal epithelium. Intracellular and apical pH were measured using the fluorescent pH sensitive probe carboxy-seminaphthorhodafluor-4F acetoxymethyl ester (SNARF-4F) and sparklet pH electrode respectively to explore the functional role of rat epididymal epithelium. In the HEPES buffered Krebs-Henseleit (KH) solution, the intracellular pH (pHi) recovery from NH(4)Cl induced acidification in the cultured caput epididymal epithelium was completely inhibited by amiloride, the inhibitor of Na(+)/H(+) exchanger (NHE). Immediately changing of the KH solution from HEPES buffered to HCO(3)(-) buffered would cause another pHi recovery. The pHi recovery in HCO(3)(-) buffered KH solution was inhibited by 4, 4diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), the inhibitor of HCO(3)(-) transporter or by removal of extracellular Na(+). The extracellular pH measurement showed that the apical pH would increase when adding DIDS to the apical side of epididymal epithelial monolayer, however adding DIDS to the basolateral side had no effect on apical pH. The present study shows that sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured caput epididymal epithelium.

  17. 77 FR 21277 - Customer Clearing Documentation, Timing of Acceptance for Clearing, and Clearing Member Risk...

    Science.gov (United States)

    2012-04-09

    ..., 23, 37, et al. Customer Clearing Documentation, Timing of Acceptance for Clearing, and Clearing..., 38, and 39 RIN 3038-0092, -0094 Customer Clearing Documentation, Timing of Acceptance for Clearing... Protection Act. These rules address: The documentation between a customer and a futures commission merchant...

  18. Artificial neural networks for the definition of kinetic subpopulations in electroejaculated and epididymal spermatozoa in the domestic cat.

    Science.gov (United States)

    Contri, Alberto; Zambelli, Daniele; Faustini, Massimo; Cunto, Marco; Gloria, Alessia; Carluccio, Augusto

    2012-09-01

    This study was designed for the identification of different sperm kinetic subpopulations in feline semen using artificial neural networks (ANNs) and for the evaluation of the effect of ejaculation on motility patterns of these subpopulations. Seven tomcats presented for routine orchiectomy were electroejaculated, and after 5 days, orchiectomized and epididymal tail sperms were collected. Sperm motility characteristics were evaluated using a computer-assisted sperm analyzer that provided individual kinetic characteristics of each spermatozoon. A total of 23 400 spermatozoa for electroejaculated and 9200 for epididymal tail samples were evaluated using a multivariate approach, comprising principal component analysis and ANN classification. The multivariate approach allowed the identification and characterization of three different and well-defined sperm subpopulations. There were significant differences before (epididymal tail spermatozoa) and after (electroejaculated sperm) ejaculation in sperm kinetic subpopulation characteristics. In both epididymal and ejaculated samples, the majority of subpopulation was characterized by high velocity and progressiveness; however, the electroejaculated samples showed significantly higher values, suggesting that the microenvironment of the epididymal tail could affect the sperm motility or, alternatively, seminal plasma could increase the kinetic characteristics of the spermatozoa, indicating that only after ejaculation, the spermatozoa express their motility potential. Nevertheless, further studies are required to clarify the functional significance of each kinetic subpopulation.

  19. Identification and characterisation of the epididymal proteins in the lizard, Eutropis carinata (Reptilia, Squamata) (Schneider, 1801).

    Science.gov (United States)

    Medini, R; Bhagya, M; Samson, S

    2018-04-01

    Lizards are seasonal breeders. Cyclic reproductive nature makes lizard as a useful model for the study of the reproductively active protein secretions in the epididymis. During breeding season, the epididymides of the lizard secret proteins that mixes with the spermatozoa and create a favourable environment for sperm maturation. In this spectrum, the aim of this study is to identify and characterize proteins which are present in the lumen of the epididymis of the lizard, E. carinata during the active phase of reproduction. The identification and analysis of the proteins are done through the proteomic approaches. The epididymal luminal fluid sample was taken from the reproductively active and inactive phase and these are subjected to the size exclusion chromatography. Two major peaks (peak 1 and peak 2) were obtained in the epididymal luminal fluid sample taken during the reproductively active phase. On the other hand, the sample from the reproductively inactive phase showed one peak (peak 1) whereas, peak 2 is not present during this phase. The peak 2 belong to reproductively active phase was later subjected to the proteomic analysis. Appropriate gel electrophoresis separation and purification methods are combined with LC-MS/MS in order to identify and characterize the proteins that are presented during the reproductively active phase. Further, in this work, nine proteins are identified including three enzymes and three heat shock proteins. Among the identified proteins, bioinformatics analysis predicts that majority of them are localized in the cytoplasm. In addition to this, an observation is made in the endoplasmic reticulum where it is seen that a close protein-protein interaction network of three molecular chaperones are involved in protein processing. Overall, this paper opens up a new dimension search for epididymal markers for the first time in reptiles, particularly lizards. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The ability of feline spermatozoa in different epididymal regions to undergo capacitation and acrosome reaction.

    Science.gov (United States)

    Kunkitti, Panisara; Bergqvist, Ann-Sofi; Sjunnesson, Ylva; Axnér, Eva

    2015-10-01

    The sperm maturation process that occurs in the epididymis is a necessary process for spermatozoa to acquire motility and the ability to undergo capacitation, which is an important key for fertilization. The aim of this study was to evaluate the ability of feline spermatozoa from different regions of the epididymis to undergo capacitation and acrosome reaction. Experiment I: epididymal spermatozoa from caput, corpus and cauda regions were placed in phosphate buffered saline (control medium) and in vitro fertilization medium (capacitating conditions). Sperm motility, motility patterns, plasma membrane integrity and tyrosine phosphorylation were evaluated at time 0 and 60min after incubation. Experiment II: spermatozoa were treated with 2μM of calcium ionophore (A23187) to induce the acrosome reaction and acrosome reaction was evaluated. The results showed a significant effect of region with a higher percentage of tyrosine phosphorylation in spermatozoa from the cauda than in the caput or corpus regions (P=0.0061; P=0.0088). Spermatozoa from corpus and cauda showed higher values in the majority of the measured motility parameters than spermatozoa from the caput (Pepididymal regions can undergo the acrosome reaction in vitro in response to induction by calcium ionophore with no difference between regions (P>0.05). Spermatozoa from all epididymal regions were able to undergo capacitation. Higher percentage of tyrosine phosphorylation in spermatozoa from the cauda reflect that they more easily underwent capacitation compared to spermatozoa from caput and corpus which required more time of incubation for capacitation. In conclusion feline epididymal spermatozoa from all regions can undergo capacitation and acrosome reaction in vitro and do not require incubation under capacitating conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Predictors of patency after two-stitch invagination vaso-epididymal anastomosis for idiopathic obstructive azoospermia

    Directory of Open Access Journals (Sweden)

    G Gautam

    2005-01-01

    Full Text Available Objectives: Anastomotic patency with return of sperm in the ejaculate following microsurgical vasoepididymostomy (VEA is not universal and may be delayed. The ability to predict the result of VEA based on preoperative or intra-operative parameters would enable the surgeon to offer the best treatment to the infertile couple. We used the two-stitch invagination technique of VEA in patients of idiopathic obstructive azoospermia and prospectively analyzed factors that could predict a patent anastomosis. While such studies have previously been done for patients undergoing VEA for secondary infertility following a vasectomy, to the best of our knowledge this is the first study analyzing these parameters for patients with primary infertility and idiopathic obstruction. Methods and materials: Over a 2-year period, 29 men underwent the 2-suture invagination VEA for idiopathic obstructive azoospermia. Twenty-four patients provided at least one postoperative semen sample. Preoperative and intra-operative parameters were compared between patients with a patent anastomosis with sperm in ejaculate (n = 12 and those with no sperm in the ejaculate (n = 12 using the t-test, Fisher′s exact test or chi-square test, as appropriate and a multivariate statistical analysis to determine any significant difference. Results: The mean follow up of the 24 patients was 7.6 months (2-30 months. A significantly greater number of patients with patent anastomosis had motile epididymal sperms (P = 0.034 and higher surgeon′s technical satisfaction with the procedure (P = 0.034. However, this difference was seen only on a univariate analysis and did not persist when a multivariate analysis was used. Conclusions: The presence of motile sperms in the epididymal fluid and a high level of technical satisfaction with the anastomosis may indicate a higher likelihood of success following a vaso-epididymal anastomosis for idiopathic obstruction. However, these parameters are not

  2. Characterization of functional variables in epididymal alpaca (Vicugna pacos) sperm using imaging flow cytometry.

    Science.gov (United States)

    Santiani, Alexei; Ugarelli, Alejandra; Evangelista-Vargas, Shirley

    2016-10-01

    Epididymal alpaca sperm represent an alternative model for the study of alpaca semen. The objective of this study was to characterize the normal values of some functional variables in epididymal alpaca sperm using imaging flow cytometry. Alpaca testicles (n=150) were processed and sperm were recovered from the cauda epididymides. Only 76 samples with acceptable motility and sperm count were considered for assessment by imaging flow cytometry. Acrosome integrity and integrity/viability were assessed by FITC-PSA/PI and FITC-PNA/PI. Mitochondrial membrane potential (MMP) was assessed by MitoTracker CMXRos and MitoTracker Deep Red FM. Lipid peroxidation was evaluated using BODIPY 581/591 C11. Results show that the mean values for acrosome-intact sperm were 95.03±6.39% and 93.34±7.96%, using FITC-PSA and FITC-PNA, respectively. The mean values for acrosome-intact viable sperm were 60.58±12.12% with FITC-PSA/PI and 58.81±12.94% with FITC-PNA/PI. Greater MMP was detected in 65.03±15.92% and 59.52±19.19%, using MitoTracker CMXRos and MitoTracker Deep Red FM, respectively. Lipid peroxidation was 0.84±0.95%. Evaluation of acrosome-intact and acrosome-intact viable sperm with FITC-PSA/PI compared with. FITC-PNA/PI or MMP with MitoTracker CMXRos compared with MitoTracker Deep Red FM were correlated (Psperm motility (r=0.3979). This report provides a basis for future research related to alpaca semen using the epididymal sperm model. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Junctional adhesion molecule A: expression in the murine epididymal tract and accessory organs and acquisition by maturing sperm.

    Science.gov (United States)

    Wu, Kathie Z; Li, Kun; Galileo, Deni S; Martin-DeLeon, Patricia A

    2017-02-10

    . Epididymosomes were isolated by ultracentrifugation of the ELF after it was clarified to remove cells and tissue fragments, and the proteins western blotted for JAM-A and pJAM-A, and exosomal biochemical markers. FACS analysis was used to quantify the amount of JAM-A present on caput and caudal sperm, as well as the amount of JAM-A acquired in vitro after their co-incubation with ELF. Western blots revealed that JAM-A is expressed in all three regions of the epididymis, the prostate and seminal vesicles. As confirmed by indirect immunofluorescence, a western blot showed that JAM-A has a higher expression in the corpus and caudal regions, where it is significantly (P sperm proteins showed a significant (P sperm. Flow-cytometric analysis confirmed the increase in JAM-A in caudal sperm where it was 1.4-fold higher than in caput ones. Co-incubation of caput and caudal sperm with ELF demonstrated ~2.3- and ~1.3-fold increases, respectively, in JAM-A levels indicating that epididymosomes transfer more JAM-A to caput sperm that are less saturated with the protein than caudal ones. Not applicable. First, although the ELF was clarified prior to ultracentrifugation for epididymosome isolation, we cannot rule out contamination of the epididymosomal proteins by those from epididymal epithelial cells. Second, the JAM-A detected in the prostate and seminal vesicles might not necessarily be secreted from those organs and may only be present within the tissues, where it would be unable to impact sperm in the ejaculate. Although performed in the mouse the study has implications for humans, as the highly conserved JAM-A is a signaling protein in human sperm. There is physiological significance to the finding that JAM-A, which regulates sperm motility and intracellular Ca

  4. Effect of low temperature on metabolism of rat liver slices and epididymal fat pads.

    Science.gov (United States)

    Hillyard, L. A.; Entenman, C.

    1973-01-01

    Study of low temperature effects on the metabolism of radioisotope-tagged glucose and palmitate in rat liver slices and epididymal fat pads. The obtained data suggest that the oxidative capacity of rat liver and adipose tissue is maintained at low temperatures to a greater degree than the synthetic capacity. It was concluded that sufficient energy can be produced at 17 C for maintenance of essential tissue functions by these two tissues but that the energy requirements may not be met at 7 C.

  5. Cadmium inhibits testis and epididymal acidification in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Caflisch, C.r.p; DuBose, T.D. Jr.

    1986-03-01

    The testis is known to be highly sensitive to functional impairment by cadmium, a widely distributed trace metal. Both vascular compromise and inhibition of Leydig cell androgen production may result in impaired sperm maturation and motility. Recent studies by our laboratory have confirmed the presence of an acid mileau in the testis and epididymis which may play an important role in sperm maturation. In this study the effect of cadmium on luminal acidification was assessed in rat seminiferous tubules, caput and cauda epididymis by glass membrane double-barrelled pH microelectrodes in vivo. Four Sprague-Dawley rats received CdCl/sub 2/ (0.015 mM/kg s.c.) 24 hrs. prior to micropuncture and 4 rats served as controls. Arterial blood gas values were within the normal range and were not different in the two groups. Cadmium resulted in marked alkalinization of seminiferous tubule fluid compared to controls (7.30 +/- 0.01 (15) vs 6.97 +/- 0.01 (25)) (p < 0.001). Similarly, the pH in proximal caput after CdCl/sub 2/ was 7.07 +/- 0.02 (19) a value significantly more alkaline (p < 0.001) than 6.58 +/- 0.02 (24) in untreated animals. In contrast, however, pH in the distal caput was 6.90 +/- 0.03 (19), a value indistinguishable from that observed in controls. In summary, CdCl/sub 2/ administration is associated with marked impairment of acidification in the testis and proximal epididymus while acidification in the distal epididymus remains intact.

  6. Low differentiated microvascular density and low expression of platelet-derived growth factor-BB (PDGF-BB) predict distant metastasis and poor prognosis in clear cell renal cell carcinoma.

    Science.gov (United States)

    Qi, Lifeng; Du, Jun; Zhang, Zhenting; Diao, Lei; Chen, Xusheng; Yao, Xin

    2013-08-01

    To examine the prognostic significance of the expression of platelet-derived growth factor-BB (PDGF-BB) and differentiated microvascular density (MVD) in patients with clear cell renal cell carcinoma (ccRCC). We used the vascular marker cluster of differentiation 34 (CD34) to identify tumour blood vessels. The expression of PDGF-BB and CD34 was detected by immunohistochemistry (IHC) in tissue microarrays (TMAs) from 100 ccRCCs. Prognostic effects of individual parameters were calculated using Cox regression models and Harrell's concordance index (c-index). Higher grade and more advanced stage ccRCCs had significantly less PDGF-BB expression and differentiated MVD (P BB expression was an independent prognostic factor for longer survival, and moreover, the final model built by the addition of PDGF-BB expression improved the predictive accuracy for disease-free survival (c-index 0.707) compared with the clinicopathological-based model (c-index 0.695). PDGF-BB expression was positively associated with differentiated MVD assessed by Spearman correlation and factor analysis (r = 0.634, P BB is as a novel and promising prognostic marker and antiangiogenic therapeutic target for the treatment of ccRCC. © 2013 The Authors. BJU International © 2013 BJU International.

  7. Identification of New Epididymal Luminal Fluid Proteins Involved in Sperm Maturation in Infertile Rats Treated by Dutasteride Using iTRAQ

    Directory of Open Access Journals (Sweden)

    Shu-Wu Xie

    2016-05-01

    Full Text Available Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39, which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.

  8. A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma [version 2; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    José I. Lopez

    2016-04-01

    Full Text Available Intratumor heterogeneity (ITH is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far.  Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection.

  9. Cholangiocarcinoma presenting as a solitary epididymal metastasis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Bailey David M

    2007-08-01

    Full Text Available Abstract Background Solid tumor metastasis to the epididymis is a rare occurrence and is mostly discovered incidentally at autopsy or after therapeutic orchidectomy for prostate cancer. Other primary carcinomas that have been demonstrated to metastasize to the paratesticular region include those originating in the stomach, kidney, ileum, and colon. Case presentation A 72-year-old gentleman presented with a firm and tender mass involving the right epididymis. On examination, he was jaundiced. Computed tomography of the abdomen demonstrated an obstructive stricture of the extra-hepatic bile ducts, in keeping with a cholangiocarcinoma, through which a metal stent was endoscopically inserted for symptomatic relief. Subsequent right radical orchidectomy yielded a diffusely infiltrative adenocarcinoma obliterating the epididymis, extending into the rete testis, vas deferens and spermatic cord and showing widespread vascular and perineural invasion. Residual epididymal, rete, and testicular tubules showed no in situ neoplasia. Morphologically and immunohistochemically the features were in keeping with a metastasis from a primary cholangiocarcinoma. Conclusion Only two cases of bile duct carcinoma metastasising to the male genital tract have previously been reported in the literature, the testis being the main site of metastasis in both cases. To our knowledge, this is the first described case of cholangiocarcinoma metastasising primarily to the epididymis, and presenting as a solitary epididymal metastasis in the absence of disseminated disease. It serves to highlight the importance of performing a thorough examination of the male external genitalia both clinically, in the follow up of cancer patients, and at autopsy.

  10. Testicular and Related Size Evaluations in Nigerian Sahel Goats with Optimal Cauda Epididymal Sperm Reserve.

    Science.gov (United States)

    Abba, Y; Igbokwe, I O

    2015-01-01

    Testicular sizes of animals are important for identification of those with adequate sperm production. The aim of this study was to define the testicular and related size estimates that would be associated with optimal cauda epididymal sperm counts (ESC) in Sahel goats based on postmortem evaluations. A stratified quota sample population of 125 male goats inclusive of all testicular sizes was taken at a slaughterhouse in Maiduguri, Nigeria. The bucks were aged 18-30 months and weighed 17.04 ± 2.99 (12-25) kg. Body, testicular, and epididymal weights of each goat with other related size measurements were estimated. ESC was determined from homogenized tissue using a manual cytometer. At the cut-off ESC of >1.1 × 10(9) sperm heads, 66 (52.80%) of the goats had optimal ESC which was associated with testicular weight of 59.90 ± 16.10 (31.40-86.20) g, gonadosomatic index of 3.51 ± 0.69 (2.00-4.50) g/kg, and scrotal circumference of 19.07 ± 1.29 (17.00-21.80) cm. The size variables of the scrotum and testis correlated with one another and with the ESC. These findings provide data that may be used to anticipate adequate antemortem sperm reserve based on testicular size during preliminary selection of sires for breeding from a sexually mature Sahel buck population.

  11. Cryopreservation of canine epididymal sperm using ACP-106c and TRIS.

    Science.gov (United States)

    Mota Filho, Antônio Cavalcante; Silva, Herlon Victor Rodrigues; Nunes, Thalles Gothardo Pereira; de Souza, Mírley Barbosa; de Freitas, Luana Azevedo; de Araújo, Airton Alencar; da Silva, Lúcia Daniel Machado

    2014-08-01

    The objective was to cryopreserve sperm recovered from the canine epididymal cauda immediately after an orchiectomy. The sperm was stored for 12h at 4 °C using ACP-106c and TRIS as extenders. Sixty adult male dogs were used. The testis-epididymis complex (TEC) was removed, immersed in 0.9% saline and transported to the laboratory. The 60 TEC were divided into groups according to the 4 °C cooling time (0 h or 12 h) and according to the extender used for sperm recovery (ACP-106c or TRIS), forming 4 experimental groups: G0h-ACP, G12h-ACP, G0h-TRIS and G12h-TRIS. The sperm were recovered from the epididymal cauda using the retrograde flow technique. Next, 1.0 mL of ACP-106c or 1.0 mL of TRIS (preheated to 37 °C for 5 min) was added to the sperm of each epididymis. One week later, the sperm was thawed at 37 °C for 1 min, and its morphology, functionality and total and progressive sperm motilities were analyzed. Other parameters were obtained by Computer Assisted Semen Analysis (CASA). The data were submitted to multivariate analysis of variance (MANOVA) (Psperm motility was observed after 12h of cooling for both extenders (Pepididymal sperm, and the freezing procedure must be performed immediately after sperm recovery. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Sperm maturation in dogs: sperm profile and enzymatic antioxidant status in ejaculated and epididymal spermatozoa.

    Science.gov (United States)

    Angrimani, D S R; Lucio, C F; Veiga, G A L; Silva, L C G; Regazzi, F M; Nichi, M; Vannucchi, C I

    2014-09-01

    Spermatozoa become more susceptible to the attack of reactive oxygen species during maturation. To avoid oxidative damage, the epididymis must provide the necessary antioxidant protection. The aim of this study was to compare the canine sperm profile and the enzymatic antioxidant status of the ejaculated fractions and samples collected from the different segments of the epididymis (caput, corpus and cauda). Five adult dogs were used, and after 1-3 weeks, subsequently to bilateral orchiectomy and epididymal storage, sperm samples were collected from the different segments of the epididymis. Samples were evaluated for conventional microscopy and computer-assisted motility analysis: sperm plasma membrane permeability and the activity of the antioxidant enzymes catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD). Samples collected from the caput and corpus showed lower values for most of the motility variables evaluated, indicating different levels of immaturity. Catalase activity was observed only in ejaculated samples. Conversely, GPx activity was higher in the cauda epididymidis. Correlations were found between SOD and GPx and SOD and sperm motility in the epididymal cauda and corpus, highlighting the importance of the enzymes for the protection of spermatozoa during the transit along the epididymis. © 2013 Blackwell Verlag GmbH.

  13. Comprehensive Immunophenotypic Characterization of Adult and Fetal Testes, the Excretory Duct System, and Testicular and Epididymal Appendages.

    Science.gov (United States)

    Magers, Martin J; Udager, Aaron M; Chinnaiyan, Arul M; French, Diana; Myers, Jeffrey L; Jentzen, Jeffrey M; McHugh, Jonathan B; Heider, Amer; Mehra, Rohit

    2016-08-01

    The immunophenotype of a normal testis and the excretory duct system has not been studied comprehensively in fetal and adult patients without testicular disease or hormonal manipulation so far. In addition, testicular (TA) and epididymal (EA) appendages are frequent paratesticular structures without previously reported comprehensive immunophenotypic studies. Immunohistochemistry for multiple markers, including the androgen receptor (AR), the estrogen receptor (ER), the progesterone receptor (PR), the prostate-specific antigen, the prostate-specific membrane antigen, PAX8, WT1, calretinin, CK7, CK20, OCT4, SALL4, and CD117, was performed on full sections of testicular/paratesticular tissue from a large cohort of adult and fetal autopsy patients. In contrast to adult germ cells (GC), fetal GC strongly express OCT4 and CD117, although the expression of these proteins is lost in the early postnatal period; SALL4, in contrast, is expressed in both fetal and adult GC, with only weak and focal expression in adult patients. Fetal Sertoli cells (SC) express WT1 and calretinin strongly and diffusely, in contrast to adult SC. Both fetal and adult excretory duct systems express CK7 and PAX8 with frequent AR coexpression, and all 3 main segments of the excretory duct system (ductuli efferentes, epididymis, and vas deferens) have unique immunophenotypes. The rete testis also has a unique immunohistochemical expression pattern, which includes strong expression of CK7, PAX8, WT1, calretinin, and AR. Finally, of the adult autopsy patients examined, 80% had a TA, and 60% had an EA; these paratesticular structures occurred at stereotypical locations, demonstrated reproducible morphologic features, and had a unique immunophenotype relative to other studied structures, with strong CK7, PAX8, WT1, AR, ER, and PR coexpression. The testis and the paratestis may be involved by diverse neoplastic and non-neoplastic processes, and knowledge of the immunophenotypic expression spectrum of

  14. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial.

    Science.gov (United States)

    Choueiri, Toni K; Larkin, James; Oya, Mototsugu; Thistlethwaite, Fiona; Martignoni, Marcella; Nathan, Paul; Powles, Thomas; McDermott, David; Robbins, Paul B; Chism, David D; Cho, Daniel; Atkins, Michael B; Gordon, Michael S; Gupta, Sumati; Uemura, Hirotsugu; Tomita, Yoshihiko; Compagnoni, Anna; Fowst, Camilla; di Pietro, Alessandra; Rini, Brian I

    2018-03-09

    The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma. The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751. Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the

  15. Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael; Madhuranthakam, Ananth J.; Margulis, Vitaly; Cadeddu, Jeffrey A.; Brugarolas, James; Kapur, Payal; Pedrosa, Ivan

    2018-01-01

    To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K trans ), rate constant (K ep ) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

  16. Low-grade metastases in high-grade clear cell renal cell carcinomas: A clinicopathologic study of 4 cases with an insight into the role of mesenchymal-to-epithelial transition process.

    Science.gov (United States)

    López, José I; Mosteiro, Lorena; Guarch, Rosa; Larrinaga, Gorka; Pulido, Rafael; Angulo, Javier C

    2016-02-01

    Clear cell renal cell carcinoma (CCRCC) frequently develops distant metastases. However, high-grade primary CCRCC rarely leads to low-grade metastases. Cellular changes occurring during neoplastic progression known as epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions explain this apparent contradiction. Four high-grade CCRCCs, which lead to low-grade metastases, are analyzed in this study, with the focus on epithelial-to-mesenchymal and mesenchymal-to-epithelial processes. Clinicopathologic data have been collected retrospectively and immunohistochemistry has been performed with E-cadherin, N-cadherin, vimentin, and WT-1. Three cases had organ-confined disease (2 pT2 and 1 pT1b). Three cases were G3 and 1 case was G4. Lung (3 cases), bone (2 cases), and pancreas (1 case) were the metastatic organs (2 patients developed multiple metastases). Metastases were G1 in all the cases. Average elapsed time between the primary tumor and the metastasis was 35.5 months. Three patients died of disease after 36, 120, and 180 months of follow-up, respectively. One patient is alive without disease after 75 months of follow-up. E-cadherin and N-cadherin showed concordant immunostaining patterns between primaries and metastases but inverse when correlated with Fuhrman grade. Hence, E-cadherin was positive in G3 cases and negative in G4, whereas N-cadherin was negative in G3 and positive in G4. Vimentin was positive in primaries and metastases only in 2 cases. WT-1 was consistently negative in all cases. In conclusion, pathologists must remember that high-grade CCRCC may develop low-grade metastases. Cadherin switching seems to be related to Fuhrman grade in this group of cases. This preliminary observation must be confirmed in longer studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Madhuranthakam, Ananth J. [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Margulis, Vitaly; Cadeddu, Jeffrey A. [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); Brugarolas, James [UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Internal Medicine, Dallas, TX (United States); Kapur, Payal [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Pathology, Dallas, Texas (United States); Pedrosa, Ivan [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States)

    2018-01-15

    To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K{sup trans}), rate constant (K{sub ep}) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

  18. 77 FR 37803 - Customer Clearing Documentation, Timing of Acceptance for Clearing, and Clearing Member Risk...

    Science.gov (United States)

    2012-06-25

    ... Documentation, Timing of Acceptance for Clearing, and Clearing Member Risk Management; Core Principles and Other Requirements for Designated Contract Markets; Correction AGENCY: Commodity Futures Trading Commission. ACTION... of April 9, 2012, and June 19, 2012, regarding Customer Clearing Documentation, Timing of Acceptance...

  19. Recovery and cryopreservation of epididymal sperm from agouti (Dasiprocta aguti) using powdered coconut water (ACP-109c) and Tris extenders.

    Science.gov (United States)

    Silva, M A; Peixoto, G C X; Santos, E A A; Castelo, T S; Oliveira, M F; Silva, A R

    2011-10-01

    The objective was to compare the use of powdered coconut water (ACP-109c; ACP Biotecnologia, Fortaleza, CE, Brazil) and Tris extenders for recovery and cryopreservation of epididymal sperm from agouti. The caudae epididymus and proximal ductus deferens from 10 sexually mature agoutis were subjected to retrograde washing using ACP-109c (ACP Biotecnologia) or Tris. Epididymal sperm were evaluated for motility, vigor, sperm viability, membrane integrity, and morphology. Samples were centrifuged, and extended in the same diluents plus egg yolk (20%) and glycerol (6%), frozen in liquid nitrogen, and subsequently thawed at 37°C for 1 min, followed by re-evaluation of sperm characteristics. The two extenders were similarly efficient for epididymal recovery, with regard to the number and quality of sperm recovered. However, for both extenders, sperm quality decreased (P Biotecnologia) group, which was significantly better than 9.7 ± 2.6% motile sperm with 1.2 ± 0.3 vigor in Tris. In conclusion, agouti epididymal sperm were successfully recovered using either ACP-109c (ACP Biotecnologia) or Tris extenders; however, ACP-109c (ACP Biotecnologia) was a significantly better extender for processing and cryopreserving these sperm. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Pregnancy outcomes using stallion epididymal sperm stored at 5 °C for 24 or 48 hours before harvest.

    Science.gov (United States)

    Stawicki, R J; McDonnell, S M; Giguère, S; Turner, R M

    2016-03-01

    The cryopreservation of epididymal sperm can be useful in a variety of circumstances for ensuring genetic preservation of a valued stallion. Although early studies have reported pregnancy rates significantly lower than those achieved with cryopreserved ejaculated sperm, two recent studies report over 60% one-cycle pregnancy rates with epididymal sperm stored for 24 hours at 5 °C before harvest and cryopreservation. The aims of this study were to: (1) attempt to replicate the one-cycle pregnancy rate of over 60% using epididymal sperm cooled and stored within the epididymis for 24 hours before harvest and cryopreservation and (2) evaluate pregnancy outcome with sperm cooled and stored within the epididymis for 48 hours before sperm harvest and cryopreservation. Testicles were obtained from 13 stallions undergoing routine castration. The epididymides were stored at 5 °C for either 24 or 48 hours before sperm harvest and cryopreservation in an egg yolk and dimethylformamide-based freezing extender. Thirteen mares were bred on one cycle with cryopreserved epididymal sperm stored for 24 hours before harvest, and 10 of those 13 mares were also bred on a previous or subsequent cycle with samples from the same stallion that had been stored for 48 hours before harvest. Pregnancy occurred in 7 of the 13 inseminations of sperm stored for 24 hours before harvest, and in 4 of the 10 inseminations of sperm stored for 48 hours before harvest. The pregnancy rate using epididymal sperm stored for 24 hours before harvest is consistent with that of previous reports. In addition, these results provide evidence that pregnancies can be achieved when the epididymides are cooled and stored for 48 hours before sperm harvest and cryopreservation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Clear aligners in orthodontic treatment.

    Science.gov (United States)

    Weir, T

    2017-03-01

    Since the introduction of the Tooth Positioner (TP Orthodontics) in 1944, removable appliances analogous to clear aligners have been employed for mild to moderate orthodontic tooth movements. Clear aligner therapy has been a part of orthodontic practice for decades, but has, particularly since the introduction of Invisalign appliances (Align Technology) in 1998, become an increasingly common addition to the orthodontic armamentarium. An internet search reveals at least 27 different clear aligner products currently on offer for orthodontic treatment. The present paper will highlight the increasing popularity of clear aligner appliances, as well as the clinical scope and the limitations of aligner therapy in general. Further, the paper will outline the differences between the various types of clear aligner products currently available. © 2017 Australian Dental Association.

  2. Addressing the best treatment for non-clear cell renal cell carcinoma: A meta-analysis of randomised clinical trials comparing VEGFR-TKis versus mTORi-targeted therapies.

    Science.gov (United States)

    Ciccarese, Chiara; Iacovelli, Roberto; Brunelli, Matteo; Massari, Francesco; Bimbatti, Davide; Fantinel, Emanuela; De Marco, Vincenzo; Porcaro, Antonio Benito; Martignoni, Guido; Artibani, Walter; Tortora, Giampaolo

    2017-09-01

    Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous group of malignancies that profoundly differ in terms of morphology, genetic profile, clinical behaviour and prognosis. The optimal treatment algorithm for nccRCC is still unknown and derived mainly from evidence available for ccRCC, being therefore represented by targeted agents against vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to compare the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of nccRCC patients. Searching the MEDLINE/PubMed, Cochrane Library and American Society of Clinical Oncology Meeting abstracts prospective studies were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The measured outcomes were progression-free survival (PFS), overall survival (OS) and the overall response rate (ORR). Four randomised controlled trials were selected for final analysis, with a total of 332 patients evaluable for PFS. Treatment with TKi significantly reduced the risk of progression compared with mTORi (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.60-0.84; p < 0.0001). This difference remained significant when sunitinib was compared with everolimus in first-line setting (HR = 0.67; 95% CI, 0.56-0.80; p < 0.00001). In the 332 patients evaluable for OS, no significant difference was found between TKi and mTORi (HR = 0.86; 95% CI, 0.67-1.12; p = 0.27). In the 176 evaluable patients, TKis therapy did not improve the ORR when compared with mTORi (relative risk [RR] = 2.21; 95% CI, 0.87-5.60; p = 0.09), even if treatment with sunitinib doubled the probability of achieving a tumour response. Treatment with TKis significantly improves PFS, but not OS, when compared with mTORi. Moreover, sunitinib as first-line therapy reduces the risk of

  3. The demand for central clearing: to clear or not to clear, that is the question

    OpenAIRE

    Bellia, Mario; Panzica, Roberto; Pelizzon, Loriana; Peltonen, Tuomas

    2018-01-01

    This paper analyses whether the post-crisis regulatory reforms developed by global-standard-setting bodies have created appropriate incentives for different types of market participants to centrally clear Over-The-Counter (OTC) derivative contracts. Beyond documenting the observed facts, we analyze four main drivers for the decision to clear: 1) the liquidity and riskiness of the reference entity; 2) the credit risk of the counterparty; 3) the clearing member’s portfolio net exposure with the...

  4. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Alleman, Wade G; Tabios, Ray L; Chandramouli, Gadisetti V R; Aprelikova, Olga N; Torres-Cabala, Carlos; Mendoza, Arnulfo; Rogers, Craig; Rodgers, Craig; Sopko, Nikolai A; Linehan, W Marston; Vasselli, James R

    2004-10-15

    Clear cell renal carcinoma (ccRCC) is strongly associated with loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is functionally lost through hypermethylation in up to 19% of sporadic ccRCC cases. We theorized that re-expressing VHL silenced by methylation in ccRCC cells, using a hypo-methylating agent, may be an approach to treatment in patients with this type of cancer. We test the ability of two hypo-methylating agents to re-express VHL in cell culture and in mice bearing human ccRCC and evaluate the effects of re-expressed VHL in these models. Real-time reverse transcription-PCR was used to evaluate the ability of zebularine and 5-aza-2'-deoxycytidine (5-aza-dCyd) to re-express VHL in four ccRCC cell lines with documented VHL gene silencing through hypermethylation. We evaluated if the VHL re-expressed after hypo-methylating agent treatment could recreate similar phenotypic changes in ccRCC cells observed when the VHL gene is re-expressed via transfection in cell culture and in a xenograft mouse model. Finally we evaluate global gene expression changes occurring in our cells, using microarray analysis. 5-Aza-dCyd was able to re-express VHL in our cell lines both in culture and in xenografted murine tumors. Well described phenotypic changes of VHL expression including decreased invasiveness into Matrigel, and decreased vascular endothelial growth factor and glucose transporter-1 expression were observed in the treated lines. VHL methylated ccRCC xenografted tumors were significantly reduced in size in mice treated with 5-aza-dCyd. Mice bearing nonmethylated but VHL-mutated tumors showed no tumor shrinkage with 5-aza-dCyd treatment. Hypo-methylating agents may be useful in the treatment of patients having ccRCC tumors consisting of cells with methylated VHL.

  5. Purification and characterization of a sperm motility inhibiting factor from caprine epididymal plasma.

    Directory of Open Access Journals (Sweden)

    Sujoy Das

    Full Text Available Several studies have been reported on the occurrence of sperm motility inhibiting factors in the male reproductive fluids of different mammalian species, but these proteins have not been adequately purified and characterized. A novel sperm motility inhibiting factor (MIF-II has been purified from caprine epididymal plasma (EP by Hydroxylapatite gel adsorption chromatography, DEAE-Cellulose ion-exchange chromatography and chromatofocusing. The MIF-II has been purified to apparent homogeneity and the molecular weight estimated by Sephacryl S-300 gel filtration is 160 kDa. MIF-II is a dimeric protein, made up of two subunits each having a molecular mass of 80 kDa as shown by SDS-PAGE. The isoelectric point of MIF-II is 5.1 as determined by chromatofocusing and isoelectric focusing. It is a heat labile protein and maximal active at the pH 6.9 to 7.5. The sperm motility inhibiting protein factor at 2 microg/ml (12.5 nM level showed maximal motility-inhibiting activity. The observation that the epididymal plasma factor lowered the intracellular cAMP level of spermatozoa in a concentration-dependent manner suggests that it may block the motility of caprine cauda spermatozoa by interfering the cAMP dependent motility function. The results revealed that the purified protein factor has the potential of sperm motility inhibition and may serve as a vaginal contraceptive. The antibody raised against the MIF-II has the potential for enhancement of forward motility of cauda-spermatozoa. This antibody may thus be useful for solving some of the problems of male infertility due to low sperm motility.

  6. The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation.

    Science.gov (United States)

    Nixon, Brett; Stanger, Simone J; Mihalas, Bettina P; Reilly, Jackson N; Anderson, Amanda L; Tyagi, Sonika; Holt, Janet E; McLaughlin, Eileen A

    2015-10-01

    In recent years considerable effort has been devoted to understanding the epigenetic control of sperm development, leading to an increased appreciation of the importance of RNA interference pathways, and in particular miRNAs, as key regulators of spermatogenesis and epididymal maturation. It has also been shown that sperm are endowed with an impressive array of miRNA that have been implicated in various aspects of fertilization and embryo development. However, to date there have been no reports on whether the sperm miRNA signature is static or whether it is influenced by their prolonged maturation within the male reproductive tract. To investigate this phenomenon, we employed next-generation sequencing to systematically profile the miRNA signature of maturing mouse spermatozoa. In so doing we have provided the first evidence for the posttesticular modification of the sperm miRNA profile under normal physiological conditions. Such modifications include the apparent loss and acquisition of an impressive cohort of some 113 and 115 miRNAs, respectively, between the proximal and distal epididymal segments. Interestingly, the majority of these changes occur late in maturation and include the uptake of novel miRNA species in addition to a significant increase in many miRNAs natively expressed in immature sperm. Because sperm are not capable of de novo transcription, these findings identify the epididymis as an important site in establishing the sperm epigenome with the potential to influence the peri-conceptual environment of the female reproductive tract, contribute to the inheritance of acquired characteristics, and/or alter the developmental trajectory of the resulting offspring. © 2015 by the Society for the Study of Reproduction, Inc.

  7. Viability of Frozen-Thawed Epididymal Sperm of Garut Ram Cryopreserved with Modified Tris Extender

    Directory of Open Access Journals (Sweden)

    MUHAMMAD RIZAL

    2005-06-01

    Full Text Available Sperm collected from cauda epididymis is a source of male gametes. The purposes of this study was to evaluate an quality of frozen-thawed sperm of garut ram which was collected from cauda epididymis and cryopreserved with modified Tris extender, i.e: Tris extender (control, KT, Tris extender + 60 mM lactose (LS, and Tris extender + 60 mM lactose + 0.05% glutathione (GL. Quality of collected sperm including concentration, motility, live sperm, abnormality, cytoplasmic droplet, intact acrosomal cap (IAC, and intact plasma membrane (IPM were evaluated. Results showed that mean of sperm concentration, percentages of motility, live sperm, abnormality, cytoplasmic droplet, IAC, and IPM of fresh epididymal sperm were 13,993.33 million/ml, 70.83, 82.83, 10.83, 8.5, 85.83, and 81.33%, respectively. Sperm quality after equilibration for LS and GL were significantly (P<0.05 higher than KT. Mean percentages of post thawing sperm motility, live sperm, IAC, and IPM for GL (45, 54.5, 47.83, and 48.83% were significantly (P<0.05 higher than LS (40, 49.17, 43.83, and 44.5%, and KT (35, 42.5, 39.17, and 41.5%. Mean percentages of post thawing sperm motility, live sperm, IAC, and IPM for LS were significantly (P<0.05 higher than those of KT. Hence, frozen-thawed epididymal sperm of garut ram after slaughter and cryopreserved with Tris extender + 60 mM lactose (LS and Tris extender + 60 mM lactose + 0.05% glutathione (GL possibly can be used for artificial insemination (AI or in vitro embryo production program.

  8. Daya Hidup Spermatozoa Epididimis Sapi Persilangan yang Dipreservasi dengan Air Kelapa Muda pada Suhu 5oC (VIABILITY OF EPIDIDYMAL SPERMATOZOA CROSSBREED CATTLE PRESERVED WITH COCONUT WATER AT 5oC

    Directory of Open Access Journals (Sweden)

    Muhammad Rizal

    2018-01-01

    Full Text Available The objective of this research was to examine the effectiveness of coconut water with various egg yolk concentrations in maintaining the viability of epididymal spermatozoa of crossbreed cattle preserved at 5oC. Five testis with epididymides of crossbreed cattle were obtained from slaughterhouse. Epididymal spermatozoa was collected by the combination of slicing, flushing and tissues pressure methods of cauda epididymides with saline solution (0.9% NaCl. Collected-spermatozoa was equally divided in volume into four tubes and diluted with lactose extender containing 20% egg yolk (control, 90% coconut water + 10% egg yolk (CWEY10, 85% coconut water + 15% egg yolk (CWEY15, and 80% coconut water + 20% egg yolk (CWEY20, repectively. Diluted-spermatozoa was stored in refrigerator at 5oC. Quality of dilutedspermatozoa including percentages of motile spermatozoa (MS, live spermatozoa (LS, spermatozoa with intact plasma membrane (IPM were evaluated every day during four days of storage. Data were analyzed by using completely randomized design with four treatments and five replicates. Means were compared with significant difference test at 0.05 significant level. Results of this study showed that mean of spermatozoa concentration, percentage of MS, percentage of LS, percentage of spermatozoa abnormal, and percentage of IPM of crossbreed cattle fresh epididymal spermatozoa were 1,414 million cell/ml, 72%, 85%, 9%, and 90%, respectively. At day-4 of the storage, percentages of MS, LS, and IPM of control (43, 52.2, 59.2% and CWEY20 (42, 52, 59% were significantly (P<0.05 higher than CWEY10 (33, 45.4, 52.8% and CWEY15 (37, 50, 54.6%. In conclusion, lactose and CWEY20 extenders could be maintaining the quality of epidydimal spermatozoa of crossbreed cattle for three days preservation at 5oC and two days for CWEY10 and CWEY15.

  9. Comparative morphometric and glycohistochemical studies on the epididymal duct in the donkey (Equus asinus) and dromedary camel (Camelus dromedarius).

    Science.gov (United States)

    Alkafafy, Mohamed; Ebada, Safwat; Rashed, Reda; Attia, Hossam

    2012-09-01

    The present study was undertaken to compare morphometric and glycohistochemical differences in the epididymal duct of the donkey and the dromedary camel. Paraffin-embedded sections from the different regions of the duct (caput, corpus and cauda) of both species were stained conventionally for general histology and histomorphometry and also with fluorescein isothiocyanate (FITC) conjugated lectins for glycohistochemical mapping. Morphometric data (means ± SE) showed that the luminal diameter was widest (1029.76 ± 15.04 μm) in the donkey cauda and narrowest (179.80 ± 3.27 μm) in the camel corpus. The thickness of the peritubular muscle coat had the highest (74.32 ± 1.85 μm) and the lowest (24.32 ± 0.74 μm) values in the donkey cauda and corpus respectively. The greatest (94.44 ± 2.08 μm) and the least (21.48 ± 0.66 μm) values of epithelial height were reported respectively in the camel caput and in the donkey cauda. The length of stereocilia of principal cells in the camel was greatest (21.88 ± 0.57 μm) and lowest (6.68 ± 0.28 μm) in the caput and cauda. Binding sites for only six out of eight lectins could be found. The distribution pattern of binding sites of different lectins showed significant variations in both a species-specific and also region-specific manner. Distinct labeling was found in the Golgi zone, apical cytoplasm and on stereocilia of principal cells in the camel (WGA and DBA) and donkey (DBA) caput region, while other lectins exhibited variable reactivity in the other regions in both species. The basal cells showed variable binding to most of the lectins, however, they displayed distinct binding to WGA and PSA throughout the duct in camel and donkey respectively. In conclusion, both morphometric and glycohistochemical findings displayed regional species-specific and potentially functional relevant characteristics. Copyright © 2011 Elsevier GmbH. All rights reserved.

  10. EPIDIDIMITE CRÔNICA POR Enterobacter cloacae EM CÃO CHRONIC EPIDIDYMITIS FOR Enterobacter cloacae IN DOG

    Directory of Open Access Journals (Sweden)

    Fabiano José Ferreira de Sant’ana

    2008-10-01

    Full Text Available

    Este relato descreve os aspectos clínicos, anatomopatológicos e microbiológicos de um caso de epididimite crônica em cão causada por Enterobacter cloacae. Um cão macho, Boxer, de três anos de idade, com histórico de tumefação unilateral na bolsa escrotal foi submetido à avaliação citopatológica. Após o diagnóstico citológico, sugestivo de orquite ou epididimite bacteriana, indicou-se a castração do animal. Macroscopicamente, o epidídimo direito estava muito aumentado de volume, firme e com superfície de corte irregular. Coletaram-se amostras de epidídimo e testículo para exames histopatológico e microbiológico, os quais revelaram epididimite crônica, degeneração testicular e identificação de E. cloacae. Diagnóstico diferencial foi realizado principalmente com orquite e neoplasias testiculares ou epididimárias. Esse parece ser o primeiro caso descrito de epididimite em cão associada à infecção por E. cloacae.

     

    PALAVRAS-CHAVES: Cão, epididimite, Enterobacter cloacae

    This report describes the clinic, anatomopathological and microbiological aspects of a case of chronic epididymitis in dog caused by Enterobacter cloacae. A three-year-old Boxer male dog with a history of scrotum unilateral swelling was submitted to cytopathologic examination. After cytologic diagnosis sugestive of bacterial orchitis/ epididymitis was indicated the castration. Grossly, the right epididymis was very firm and enlarged with irregular cut surface. Epididymis and testicle samples were collected to histologic and microbiologic exams. Histologic diagnosis of chronic epididymitis and testicular degeneration were confirmed. In the bacteriological valuation, E. cloacae was identified. Diferential diagnosis was realized especially with orchitis and testicular/epididymal

  11. Methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C and G1793A polymorphisms: association with risk for clear cell renal cell carcinoma and tumour behaviour in men.

    Science.gov (United States)

    Safarinejad, M R; Shafiei, N; Safarinejad, S

    2012-05-01

    Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated whether MTHFR C677T, A1298C and G1793A polymorphisms modified clear cell renal cell carcinoma (CCRCC) risk independently as well as in combination with serum total homocysteine (Hcy) and folate levels. A case-control study of 152 cases (men) and 304 age-matched healthy controls was conducted in one geographical area of Iran. Genotyping of MTHFR gene polymorphisms was carried out using a polymerase chain reaction restriction fragment length polymorphism technique. Serum levels of total Hcy, folate and vitamin B12 were also determined. The MTHFR 677T and 1298C allele frequencies were 42.8 and 47.4% in cases, compared with 33.7 and 33.1% in controls. After controlling for confounding factors, a significant increase in CCRCC risk was found among carriers of the 677CT genotype compared with those with the 677CC genotype (odds ratio 2.21, 95% confidence interval 1.31-3.76), with a significant trend (P=0.014). Statistically significant odds ratios were also found in patients homozygous for MTHFR C677T, who have a 1.58-fold higher risk of developing CCRCC (95% confidence interval=1.21-2.44; P=0.024). Compared with the MTHFR 677CC genotype, the odds ratio (95% confidence interval) for the MTHFR 677TT genotype was 6.18 (95% confidence interval=4.75-8.34) for stage IV cancer and 4.68 (95% confidence interval=2.72-6.54) for grade 3 CCRCC (both P=0.0001). After adjustment for selected variants, the MTHFR 1298AC genotype showed a significantly increased risk of CCRCC compared with the wild-type (odds ratio=3.71, 95% confidence interval=2.22-5.33; P=0.001), and the 1298C allele carrier showed a positive association with the risk of CCRCC compared with the wild-type (odds ratio=3.9, 95% confidence interval=2.55-6.02; P=0.001). Furthermore, subjects carrying at least one copy of the variant allele showed a 4.4 times

  12. [Obstructive azoospermia in men who wish to father children; initial clinical results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved epididymal semen

    NARCIS (Netherlands)

    Woldringh, G.H.; Kremer, J.A.M.; Wetzels, A.M.M.; Meuleman, E.J.H.; Ramos, L.; Schoot, D.K.E. van der; Braat, D.D.M.

    2003-01-01

    OBJECTIVE: To evaluate the results of intracytoplasmatic sperm injection (ICSI) with surgically retrieved epididymal semen. DESIGN: Prospective, descriptive. METHODS: Patients with an obstructive azoospermia confirmed by cytological examination of a testis biopsy, and conforming to the regular

  13. Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization.

    Science.gov (United States)

    Ren, Xiaojiao; Fu, Xiaojian; Zhang, Xinhua; Chen, Shiqiang; Huang, Shuguang; Yao, Lun; Liu, Guoquan

    2017-09-15

    Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS)-induced M1 polarization, but has no direct effect on adipocyte differentiation. Cellular signaling studies indicate that testosterone regulates macrophage polarization through the inhibitory regulative G-protein (Gαi) mainly, rather than via androgen receptors, and phosphorylation of Akt. Moreover, testosterone inhibits pre-adipocyte differentiation induced by M1 macrophage medium. Lowering of serum testosterone in mice by injecting a luteinizing hormone receptor (LHR) peptide increases epididymal white adipose tissue. Testosterone supplementation reverses this effect. Therefore, our findings indicate that testosterone inhibits pre-adipocyte differentiation by switching macrophages to M2 polarization through the Gαi and Akt signaling pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. ISR clearing current monitoring system

    International Nuclear Information System (INIS)

    Groebner, O.; Strubin, P.

    1977-01-01

    Clearing electrodes remove electrons produced by ionization of the residual gas in the ISR. The clearing current from a section of length L is related to the beam current I and the absolute pressure P by I/sub C/ = 0.76 I L P. The described monitoring system measures clearing currents from over 300 electrodes with a sensitivity of 20 pA, adequate to observe pressure changes of 5 x 10 -14 Torr. As compared with conventional UHV gauges which measure only locally, clearing currents yield the integrated pressure along the beam. For maximum flexibility and to cope with future extensions, the control and data acquisition system was designed around a microprocessor unit connected through an existing CAMAC link to the central ISR computer. Measurements were performed of the pressure stability in the presence of high intensity beams and of the secondary ionization rate by electrons trapped in local neutralization pockets. At several occasions, large clearing currents were observed which were explained tentatively by ionization of metal atoms sputtered from the vacuum chamber

  15. Epididymal and sex accessory gland secretions in transfusion-dependent beta-thalassemic patients: evidence of an impaired prostatic function.

    Science.gov (United States)

    Carpino, A; De Sanctis, V; Siciliano, L; Maggiolini, M; Vivacqua, A; Pinamonti, A; Sisci, D; Andó, S

    1997-01-01

    Neutral alpha-glucosidase levels as epididymal marker, fructose levels as vesicular marker, zinc, citric acid and prostate specific antigen levels as prostatic markers were measured in the seminal plasma of eight transfusion-dependent beta-thalassemic patients in order to