Molecular biology of testicular germ cell tumors.

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Gonzalez-Exposito, R; Merino, M; Aguayo, C

2016-06-01

Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

Role of Axumin PET Scan in Germ Cell Tumor

Science.gov (United States)

2018-05-01

Testis Cancer; Germ Cell Tumor; Testicular Cancer; Germ Cell Tumor of Testis; Germ Cell Tumor, Testicular, Childhood; Testicular Neoplasms; Testicular Germ Cell Tumor; Testicular Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Diseases; Germ Cell Cancer Metastatic; Germ Cell Neoplasm of Retroperitoneum; Germ Cell Cancer, Nos

Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

International Nuclear Information System (INIS)

Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

2013-01-01

DNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation. CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners. In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors. To achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses. The analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H 2 O 2 , the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased. Therefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to

"Mixed germ cell testicular tumor" in an adult female

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Udasimath Shivakumarswamy

2012-01-01

Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

Perinatal determinants of germ-cell testicular cancer in relation to histological subtypes

OpenAIRE

Richiardi, L; Akre, O; Bellocco, R; Ekbom, A

2002-01-01

We aimed to investigate the role of perinatal determinants on the risk for germ-cell testicular cancer, with respect to the aetiological heterogeneity between seminomas and non-seminomas. A case?control study of 628 case patients with testicular cancer (308 seminomas and 320 non-seminomas) and 2309 individually matched controls was nested within a cohort of boys born from 1920 to 1980 in two Swedish regions (Uppsala-?rebro Health Care Region and Stockholm). Cases were diagnosed from 1958 to 1...

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

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Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

The emerging phenotype of the testicular carcinoma in situ germ cell

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Rajpert-De Meyts, Ewa; Bartkova, Jirina; Samson, Michel

2003-01-01

This review summarises the existing knowledge on the phenotype of the carcinoma in situ (CIS) cell. CIS is a common pre-invasive precursor of testicular germ cell tumours of adolescents and young adults. These tumours display a variety of histological forms. Classical seminoma proliferates along...... of differentiation and pluripotency, CIS cells found in adult patients seem to be predestined for further malignant progression into one or the other of the two main types of overt tumours. A new concept of phenotypic continuity of differentiation of germ cells along germinal lineage with a gradual loss of embryonic...

Maternal smoking and testicular germ cell tumors.

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McGlynn, Katherine A; Zhang, Yawei; Sakoda, Lori C; Rubertone, Mark V; Erickson, Ralph L; Graubard, Barry I

2006-10-01

Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.

Saudi Oncology Society clinical management guidelines for testicular germ cell tumors

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Mohammed Al Otaibi

2011-01-01

Full Text Available In this report, guidelines for the evaluation, medical and surgical management of transitional cell carcinoma of testicular germ cell tumors is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The recommendations are presented with supporting level of evidence.

Long-term cultures of testicular biopsies from boys with cryptorchidism: effect of FSH and LH on the number of germ cells

DEFF Research Database (Denmark)

Larsen, Hans-Peter Ejler; Thorup, Jørgen; Skovgaard, Lene Theil

2002-01-01

A long-term culture system of testicular biopsies from boys with undescended testes was established to evaluate the effect of gonadotrophins on germ cell survival and growth.......A long-term culture system of testicular biopsies from boys with undescended testes was established to evaluate the effect of gonadotrophins on germ cell survival and growth....

Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

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M. V. Nemtsova

2015-03-01

Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1(Ter/Ter) mice.

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Cook, Matthew S; Coveney, Douglas; Batchvarov, Iordan; Nadeau, Joseph H; Capel, Blanche

2009-04-15

A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1(Ter/Ter)) results in a significant early loss of primordial germ cells (PGCs) prior to colonization of the gonad in both sexes and all genetic backgrounds tested. The same mutation also leads to testicular teratomas only on the 129Sv/J background. Male mutants on other genetic backgrounds ultimately lose all PGCs with no incidence of teratoma formation. It is not clear how these PGCs are lost or what factors directly control the strain-specific phenotype variation. To determine the mechanism underlying early PGC loss we crossed Dnd1(Ter/Ter) embryos to a Bax-null background and found that germ cells were partially rescued. Surprisingly, on a mixed genetic background, rescued male germ cells also generated fully developed teratomas at a high rate. Double-mutant females on a mixed background did not develop teratomas, but were fertile and produced viable off-spring. However, when Dnd1(Ter/Ter) XX germ cells developed in a testicular environment they gave rise to the same neoplastic clusters as mutant XY germ cells in a testis. We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background.

Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

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Avilés-Salas Alejandro

2009-08-01

Full Text Available Abstract Background Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG. hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF. Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors. Methods We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP, and lactate dehydrogenase were measured prior to surgery. Vascular density (VD and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis. Results Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016, AFP ≥ 14.7 ng/mL (p = 0.0001, and hCG ≥ 25 mIU/mL (p = 0.0001. In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04. When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization (p Conclusion This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.

Birth order, sibship size, and risk for germ-cell testicular cancer.

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Richiardi, Lorenzo; Akre, Olof; Lambe, Mats; Granath, Fredrik; Montgomery, Scott M; Ekbom, Anders

2004-05-01

Several studies have reported an inverse association between birth order and testicular cancer risk, but estimates vary greatly and the biologic mechanism underlying the association is not established. We have evaluated the effect of birth order, sibship size, and the combined effect of these 2 variables in relation to risk for testicular cancer in a large, nested case-control study. Specifically, we compared 3051 patients with germ-cell testicular cancer (diagnosed between 1958 and 1998 and identified through the Swedish Cancer Registry) with 9007 population control subjects. Using record linkage with the Multi-Generation Register and the Census, we obtained information on number, order, and sex of the subjects' siblings, parental age, and paternal socioeconomic status. Both birth order and sibship size had an inverse and monotonically decreasing association with testicular cancer risk after adjusting for parental age, paternal socioeconomic status, and twin status. The associations were modified by subjects' cohort of birth and were not present among those born after 1959. The odds ratio for having at least 3 siblings, compared with none, was 0.63 (95% confidence interval = 0.53-0.75) among subjects born before 1960. Stratified analyses showed that birth order and number of younger siblings had a similar inverse association with the risk for testicular cancer. Sibship size, and not only birth order, is associated with testicular cancer risk. This suggests a higher prevalence of parental subfertility among patients with testicular cancer.

Polymorphic variation in the androgen receptor gene: association with risk of testicular germ cell cancer and metastatic disease

DEFF Research Database (Denmark)

Västermark, Åke; Giwercman, Yvonne Lundberg; Hagströmer, Oskar

2011-01-01

Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR...... of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between...

Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

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Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

2017-01-01

The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

Testis sparing surgery for treatment of small testicular lesions: Is it feasible even in germ cell tumors?

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Bojanic, Nebojsa; Bumbasirevic, Uros; Bojanic, Gordana; Vukovic, Ivan; Milojevic, Bogomir; Pekmezovic, Tatjana

2017-03-01

To evaluate the results of testis-sparing surgery (TSS) in patients, with small testicular lesions and a normal contralateral testicle. In all, 28 patients were treated with TSS for small testicular lesions and a normal contralateral testicle. TSS was considered in patients with testicular lesions smaller than 2 cm and no evidence of metastatic disease. The mean age of patients was 35.3 ± 7.3 years, while the mean diameter of the testicular lesions was 11.4 ± 3.7 mm. After pathological examination, 18 patients (64.3%) were diagnosed with stromal tumors and miscellaneous lesions, while 10 (35.7%) had a germ cell tumor. The median follow-up time for the former group was 33 months and no recurrences were observed. In one patient with germ cell tumor, immediate orchiectomy was performed, while the remaining nine were followed-up (median time, 45 months). One patient developed local recurrence after 39 months. Excellent outcomes for benign lesions could be achieved using TSS. TSS could be offered safely in highly selected patients with germ cell tumors, specifically within a clinical trial but there is more data needed regarding the potential risks and benefits. J. Surg. Oncol. 2017;115:287-290. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Testicular cancer

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... Germ cell tumor; Seminoma testicular cancer; Nonseminoma testicular cancer; Testicular neoplasm ... Philadelphia, PA: Elsevier Saunders; 2014:chap 86. National Cancer Institute. PDQ testicular cancer treatment. Updated February 17, 2016. www.cancer. ...

Testicular germ cell cancer incidence in an immigration perspective, Denmark, 1978 to 2003

DEFF Research Database (Denmark)

Schmiedel, Sven; Schüz, Joachim; Skakkebaek, Niels E

2010-01-01

The incidence rate of testicular germ cell cancer in Denmark increased up to the 1990s to become among the highest in the world. Since recently rate stabilization was suggested, we determined whether it is due to an increasing number of immigrants at lower risk for this cancer....

The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia in cryptorchid boys and the subsequent risk of testicular cancer in men with prepubertal surgery for syndromic or non-syndromic cryptorchidism.

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Osterballe, Lene; Clasen-Linde, Erik; Cortes, Dina; Engholm, Gerda; Hertzum-Larsen, Rasmus; Reinhardt, Susanne; Thorup, Jorgen

2017-04-01

Cryptorchidism is a risk factor for testicular cancer in adult life. It remains unclear how prepubertal surgery for cryptorchidism impacts later development of adult testicular cancer. The aim of study was to investigate tools to identify the cryptorchid boys who later develop testicular cancer. The study cohort consisted of 1403 men operated prepubertally/pubertally for undescended testis between 1971 and 2003. At surgery testicular biopsies were taken from the cryptorchid testes. The boys were followed for occurrence of testicular cancer. The testicular cancer risk was compared to the risk in the Danish Population. Testicular biopsies from the boys who developed testicular cancer during follow-up underwent histological examination with specific diagnostic immunohistochemical markers for germ cell neoplasia. The cohort was followed for 33,627 person years at risk. We identified 16 cases with testicular cancer in adulthood. The standardized incidence ratio was 2.66 (95% CI: 1.52-4.32). At time of primary surgery in prepubertal/pubertal age Intratubular Germ Cell Neoplasia (ITGCN) was diagnosed in 5 cases and the boys were unilaterally orchiectomized. At follow-up new immunohistochemical staining indicated ITGCN in two of the 16 cancer cases at reevaluation of the original biopsies from time of prepubertal/pubertal surgery. One had syndromic cryptorchid and developed seminoma, and another showed nonsyndromic cryptorchidism and developed embryonic teratocarcinoma. Totally, ITGCN was diagnosed in 0.5% (7/1403) of prepubertal cryptorchid boys, whereof 57% (4/7) in syndromic-cryptorchidism. ITGCN is predominantly observed prepubertally in boys with syndromic-cryptorchidism. In nonsyndromic cryptorchidism testicular cancer develops postpubertally, generally not based on dormant germ cells of ITGCN caused by an early fetal maldevelopment. LEVEL I. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship

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Christensen, Jesper F; Bandak, Mikkel; Campbell, Anna

2015-01-01

BACKGROUND: Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy...

Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene

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Nylen, P; Johnson, A C; Hoeglund, G; Ebendal, T; Eriksdotter-Nilsson, M; Henschen, A; Olson, L; Hansson, T; Kronevi, T; Kvist, U

1989-07-01

Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy. (orig.).

Baldness, acne and testicular germ cell tumors

Science.gov (United States)

Trabert, Britton; Sigurdson, Alice J.; Sweeney, Anne M.; Amato, Robert J.; Strom, Sara S.; McGlynn, Katherine A.

2013-01-01

Androgen levels during critical periods of testicular development may be involved in the etiology of testicular germ cell tumors (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls (OR, 0.6; 95% CI, 0.4, 1.0). Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR, 0.5; 95% CI, 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake. PMID:21128977

Extragonadal Germ Cell Cancer (EGC)

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The Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell tumors. That is, the tumors originate in the sperm forming cells in the testicles ( ...

K-RAS and N-RAS mutations in testicular germ cell tumors

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Bekir Muhammet Hacioglu

2017-05-01

Full Text Available Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55% pure seminoma cases and 19 (45% non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen. In total, a RAS mutation was present in 12 patients (27%: 7 seminoma (29% and 5 non-seminoma cases (26% [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.

N-cadherin Expression in Testicular Germ Cell and Gonadal Stromal Tumors

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Daniel J. Heidenberg, Joel H. Barton, Denise Young, Michael Grinkemeyer, Isabell A. Sesterhenn

2012-01-01

Full Text Available Neural-cadherin is a member of the cadherin gene family encoding the N-cadherin protein that mediates cell adhesion. N-cadherin is a marker of Sertoli cells and is also expressed in germ cells of varying stages of maturation. The purpose of this study was to determine the presence and distribution of this protein by immunohistochemistry in 105 germ cell tumors of both single and mixed histological types and 12 gonadal stromal tumors. Twenty-four germ cell tumors consisted of one cell type and the remaining were mixed. Of the 23 seminomas in either pure or mixed tumors, 74% were positive. Two spermatocytic seminomas were positive. Of the 83 cases with yolk sac tumor, 99% were positive for N-cadherin. The teratomas were positive in 73% in neuroectodermal and / or glandular components. In contrast, 87% of embryonal carcinomas did not express N-cadherin. Only 17% of the syncytiotrophoblastic cells were positive for N-cadherin. In conclusion, N-cadherin expression is very helpful in the identification of yolk sac tumors. In addition to glypican-3 and Sal-like protein 4, N-cadherin can be beneficial for the diagnosis and classification of this subtype of testicular germ cell tumor. Nine of the 12 gonadal stromal tumors were positive to a variable extent.

Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Almstrup, K; Nielsen, J E

2005-01-01

AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG...... expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences...

Metachronous Testicular Cancer After Orchiectomy: A Rare Case.

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Arda, Ersan; Cakiroglu, Basri; Cetin, Gizem; Yuksel, Ilkan

2017-11-09

Testicular cancer represents approximately 1% of all cancers diagnosed in males. The prevalence of bilateral testicular germ cell tumor cases varies from 1% to 5%. Intratubular germ cell neoplasia (ITGCN) is a precursor for almost all testicular germ cell tumors (TGCT) and is one of the highest risks of developing contralateral testicular cancer. The radical orchiectomy is still preferred for the treatment of testicular cancer. However, in some cases like solitary testis, bilateral cancer or if the tumor size is under 30% percent of the testicular extent, organ-sparing surgery can be an option. There are just a few published reports of metachronous contralateral testicular cancer, developed after orchiectomy with the histopathology of the intratubular germ cell neoplasia.

Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors

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Erika Di Zazzo

2016-12-01

Full Text Available Testicular germ cell tumors (TGCTs derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the PRDM2 gene, belonging to the Positive Regulatory domain gene (PRDM family, is located. Expression of PRDM2 gene is shifted in different human tumors, where the expression of the two principal protein forms coded by PRDM2 gene, RIZ1 and RIZ2, is frequently unbalanced. Therefore, PRDM2 is actually considered a candidate tumor suppressor gene in different types of cancer. Although recent studies have demonstrated that PRDM gene family members have a pivotal role during the early stages of testicular development, no information are actually available on the involvement of these genes in TGCTs. In this article we show by qRT-PCR analysis that PRDM2 expression level is modulated by proliferation and differentiation agents such as estradiol, whose exposure during fetal life is probably an important risk factor for TGCTs development in adulthood. Furthermore in normal and cancer germ cell lines, PRDM2 binds estradiol receptor α (ERα and influences proliferation, survival and apoptosis, as previously reported using MCF-7 breast cancer cell line, suggesting a potential tumor-suppressor role in TGCT formation.

Intratubular germ cell neoplasms of the testis and bilateral testicular tumors: Clinical significance and management options

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Michael C Risk

2010-01-01

Full Text Available Objectives : Intratubular germ cell neoplasia (ITGCN is the precursor lesion for invasive testicular germ cell tumors (TGCTs of adolescents and young adults. The rising incidence of these tumors has prompted a rigorous investigation of the etiology, diagnosis and management of ITGCN. Bilateral testicular cancer is closely linked with ITGCN, as patients with unilateral testicular cancer are at the highest risk for a future malignancy in the contralateral testicle. Methods : A literature review directed at ITGCN and bilateral testis cancer was performed using the Medline/PubMed database. Our review focused on the pathogenesis, risk factors, diagnosis and treatment regimens utilized. Results : Major advances have been made in the understanding of ITGCN over the past 30 years. There is evidence that TGCTs arise from ITGCN, ITGCN is closely related to fetal gonocytes, and that events in pre- and perinatal period may result in abnormal persistence of fetal gonocytes leading to ITGCN and subsequent TGCT. Controversy exists regarding the need to biopsy men at increased risk of TGCT, as well as the best approach to managing patients with known ITGCN. Bilateral testicular cancer has excellent outcomes in the current era of platinum-based chemotherapy. Conclusion : The optimal management of patients at risk for ITGCN and future TGCT is still a matter of debate. Individualization of management, including biopsy and treatment, should be based on risk factors for TGCT, compliance with potential surveillance, and patient preferences particularly with regard to fertility.

Testicular Cancer—Health Professional Version

Science.gov (United States)

Most testicular cancers are germ cell tumors. Germ cell tumors are divided into seminomas and nonseminomas. Nonseminomas tend to grow and spread more quickly than seminomas. Find evidence-based information on testicular cancer treatment, screening, and statistics.

Carcinoma in situ testis, the progenitor of testicular germ cell tumours

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Rajpert-De Meyts, E; Daugaard, G

2005-01-01

Testicular germ cell tumours (TGCT), including seminomas, embryonal carcinomas, teratomas and yolk sac tumours, have a common precursor, the carcinoma in situ (CIS) cell. Recent gene expression studies displaying close similarity of CIS cells to embryonic stem cells support the longstanding theory...... should be made to obtain diagnosis at the CIS stage, as intervention is possible before an invasive tumour develops, thus reducing the necessity for intensive therapy. CIS may be suspected in patients with an assumed extragonadal GCT or cryptorchidism, and in intersex patients and selected cases...

Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

DEFF Research Database (Denmark)

Jørgensen, N; Rajpert-De Meyts, E; Graem, N

1995-01-01

study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental......-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first......-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester...

Late diagnosis of testicular germ cell tumors and its impact on prognosis

International Nuclear Information System (INIS)

Puskacova, J.; Kolenova, A.; Mocna, A.; Cechvalova, A.; Kaiserova, E.; Molcan, J.

2015-01-01

Introduction: Testicular tumors in children and adolescents are rare diseases with very good prognosis. Biological characteristics of germ cell tumors depends on the type of histology, stage and age at the time of diagnosis. Case report: 14 years old boy was urgently admitted to the hospital because of hemoptysis. Chest X ray showed round shaped lesions bilaterally. Surprisingly, extremely enlarged left testicle was found. Ultrasound confirmed tumor in left testicle, tumor markers were elevated and dissemination in lungs, retroperitoneal lymph nodes and CNS as well, was present. Despite three chemotherapeutic regimens the patient died 8 months from the diagnosis. Conclusions: Testicular tumors in adolescent boys are usually diagnosed in advanced stage after several months history of continuous enlargement. Whole body examination of patients and self examination of testicles in pubertal boys could lead to earlier diagnosis and improve the chance to cure. (author)

The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia in cryptorchid boys and the subsequent risk of testicular cancer in men with prepubertal surgery for syndromic or non-syndromic cryptorchidism

DEFF Research Database (Denmark)

Osterballe, Lene; Clasen-Linde, Erik; Cortes, Dina

2017-01-01

INTRODUCTION: Cryptorchidism is a risk factor for testicular cancer in adult life. It remains unclear how prepubertal surgery for cryptorchidism impacts later development of adult testicular cancer. The aim of study was to investigate tools to identify the cryptorchid boys who later develop...... testicular cancer. METHODS: The study cohort consisted of 1403 men operated prepubertally/pubertally for undescended testis between 1971 and 2003. At surgery testicular biopsies were taken from the cryptorchid testes. The boys were followed for occurrence of testicular cancer. The testicular cancer risk...... was compared to the risk in the Danish Population. Testicular biopsies from the boys who developed testicular cancer during follow-up underwent histological examination with specific diagnostic immunohistochemical markers for germ cell neoplasia. RESULTS: The cohort was followed for 33,627 person years at risk...

Anti-Ma2 paraneoplastic encephalitis associated with testicular germ cell tumor treated by carboplatin, etoposide and bleomycin.

Science.gov (United States)

Kimura, Masaki; Onozawa, Mizuki; Fujisaki, Akira; Arakawa, Takashi; Takeda, Katsuhiko; Dalmau, Joseph; Hattori, Kazunori

2008-10-01

Anti-Ma2-associated encephalitis is a paraneoplastic disorder that predominantly affects the limbic system, diencephalon and brainstem, and is usually associated with tumors of the testis. We report a 35-year-old man with a right testicular mass who presented with multiple neurological complains, and clinical, serological and radiological features compatible with anti-Ma2-associated encephalitis. After three courses of carboplatin, etoposide and bleomycin for metastatic testicular germ-cell tumor, all elevated tumor markers normalized and the retroperitoneal metastases disappeared, but the neurological disorder deteriorated. To our knowledge, this is the first case in which orchiectomy followed by carboplatin, etoposide and bleomycin for a testicular tumor with anti-Ma2 encephalitis was performed.

CYTOGENETIC ANALYSIS OF THE MATURE TERATOMA AND THE CHORIOCARCINOMA COMPONENT OF A TESTICULAR MIXED NONSEMINOMATOUS GERM-CELL TUMOR

NARCIS (Netherlands)

DEGRAAFF, WE; OOSTERHUIS, JW; DEJONG, B; VANECHTENARENDS, J; WIERSEMABUIST, J; KOOPS, HS; SLEIJFER, DT

1992-01-01

We karyotyped two histologically distinct components with different metastatic behavior of a testicular nonseminomatous germ cell tumor. The two components showed an almost identical chromosomal pattern. These almost identical karyotypes of the two components with different metastatic potential

The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

International Nuclear Information System (INIS)

Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

2015-01-01

Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

Energy Technology Data Exchange (ETDEWEB)

Li, Wei [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Fu, Jianfang [Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Shun [Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Zhao, Jie [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Xie, Nianlin, E-mail: xienianlin@126.com [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Cai, Guoqing, E-mail: firstchair@fmmu.edu.cn [Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

2015-06-01

Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

Science.gov (United States)

Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

2016-09-07

Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

From embryonic stem cells to testicular germ cell cancer-- should we be concerned?

DEFF Research Database (Denmark)

Almstrup, Kristian; Sonne, Si Brask; Hoei-Hansen, Christina E

2006-01-01

that initial hypothesis but also indicating that CIS cells have a striking phenotypic similarity to embryonic stem cells (ESC). Many cancers have been proposed to originate from tissue-specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS may be a very good example of a CSC......, but with exceptional features due to the retention of embryonic pluripotency. In addition, considering the fact that pre-invasive CIS cells are transformed from early fetal cells, possibly due to environmentally induced alterations of the niche, we discuss potential risks linked to the uncontrolled therapeutic use......Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell for the vast majority of germ cell tumours -- it has been proposed that CIS cells could be derived from transformed primordial germ cells or gonocytes. Here, we review recent discoveries not only substantiating...

Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

Science.gov (United States)

2013-01-15

Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

DEFF Research Database (Denmark)

Rajpert-De Meyts, E; Hørding, U; Nielsen, H W

1994-01-01

sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace......Epidemiological features suggest that the risk of testicular cancer may be related to exposure to unknown infectious agents, including viruses. Therefore a series of twenty specimens of testicular germ cell tumours, including preinvasive carcinoma in-situ, were tested for the presence of DNA...... of EBV DNA was revealed in one of two experiments. These samples were examined by immunohistochemical staining with specific antibodies raised against the EBV protein products and in-situ hybridization with specific molecular probes, and were confirmed to be negative. The study indicates...

Changes in the profile of simple mucin-type O-glycans and polypeptide GalNAc-transferases in human testis and testicular neoplasms are associated with germ cell maturation and tumour differentiation

DEFF Research Database (Denmark)

Rajpert-De Meyts, E; Poll, S N; Goukasian, I

2007-01-01

Testicular germ cell tumours (TGCT) exhibit remarkable ability to differentiate into virtually all somatic tissue types. In this study, we investigated changes in mucin-type O-glycosylation, which have been associated with somatic cell differentiation and cancer. Expression profile of simple mucin......-glycosylation pattern in haploid germ cells suggests a role in their maturation or egg recognition/fertilization warranting further studies in male infertility, whereas the findings in TGCT provide new diagnostic tools and support our hypothesis that testicular cancer is a developmental disease of germ cell...

Anxiety and depression in long-term testicular germ cell tumor survivors.

Science.gov (United States)

Vehling, S; Mehnert, A; Hartmann, M; Oing, C; Bokemeyer, C; Oechsle, K

2016-01-01

Despite a good prognosis, the typically young age at diagnosis and physical sequelae may cause psychological distress in germ cell tumor survivors. We aimed to determine the frequency of anxiety and depression and analyze the impact of demographic and disease-related factors. We enrolled N=164 testicular germ cell tumor survivors receiving routine follow-up care at the University Cancer Center Hamburg and a specialized private practice (mean, 11.6 years after diagnosis). Patients completed the Generalized Anxiety Disorder Screener-7, the Patient Health Questionnaire-9 and the Memorial Symptom Assessment Scale-Short Form. We found clinically significant anxiety present in 6.1% and depression present in 7.9% of survivors. A higher number of physical symptoms and having children were significantly associated with higher levels of both anxiety and depression in multivariate regression analyses controlling for age at diagnosis, cohabitation, socioeconomic status, time since diagnosis, metastatic disease and relapse. Younger age at diagnosis and shorter time since diagnosis were significantly associated with higher anxiety. Although rates of clinically relevant anxiety and depression were comparably low, attention toward persisting physical symptoms and psychosocial needs related to a young age at diagnosis and having children will contribute to address potential long-term psychological distress in germ cell tumor survivors. Copyright © 2016 Elsevier Inc. All rights reserved.

Burned-Out Testicular Tumor: A Case Report

Directory of Open Access Journals (Sweden)

N. Balalaa

2011-01-01

Full Text Available Germ cell tumors constitute the majority of all testicular tumors, which are relatively rare overall and are mainly encountered in young adults and teenagers. The term ‘burned-out’ germ cell tumor refers to the presence of a metastatic germ cell tumor with histological regression of the primary testicular lesion. Clinical examination of the testes and scrotal sonography is pivotal in the initial diagnosis of such neoplasms. We present a case of a 31-year-old male with a retroperitoneal mass and no palpable lesion on testicular examination.

Predicting retroperitoneal histology in postchemotherapy testicular germ cell cancer : A model update and multicentre validation with more than 1000 patients

NARCIS (Netherlands)

Vergouwe, Yvonne; Steyerberg, Ewout W.; Foster, Richard S.; Sleijfer, Dirk T.; Fossa, Sophie D.; Gerl, Arthur; de Wit, Ronald; Roberts, J. Trevor; Habbema, J. Dik F.

Objectives: Surgical resection of postchemotherapy retroperitoneal lymph nodes is often performed in patients with advanced nonseminomatous testicular germ cell cancer. We previously developed a model to predict the probability that the lymph nodes contain only necrotic or fibrotic (benign) tissue

Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

International Nuclear Information System (INIS)

Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

2013-01-01

Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

DEFF Research Database (Denmark)

Salonen, Jonna; Rajpert-De Meyts, E; Mannisto, Susanna

2010-01-01

Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular deve...... development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms....

Testicular Cancer—Patient Version

Science.gov (United States)

Testicular cancer most often begins in germ cells (cells that make sperm). It is rare and is most frequently diagnosed in men 20-34 years old. Most testicular cancers can be cured, even if diagnosed at an advanced stage. Start here to find information on testicular cancer treatment, screening, and statistics.

Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

Directory of Open Access Journals (Sweden)

Sigmund Brabrand

2015-02-01

Full Text Available Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs, is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors, of these three patients in whom both tumors were available (six tumors and two patients each with only one available tumor (two tumors. Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21, some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA, and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.

Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice.

Directory of Open Access Journals (Sweden)

Chun Fu

Full Text Available After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance protein. Fanconi anemia (FA proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2-3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line.

Genome-wide assessment of the association of rare and common copy number variations to testicular germ cell cancer

DEFF Research Database (Denmark)

Edsgard, Stefan Daniel; Dalgaard, Marlene Danner; Weinhold, Nils

2013-01-01

Testicular germ cell cancer (TGCC) is one of the most heritable forms of cancer. Previous genome-wide association studies have focused on single nucleotide polymorphisms, largely ignoring the influence of copy number variants (CNVs). Here we present a genome-wide study of CNV on a cohort of 212...... of rare CNVs related to cell migration (false-discovery rate = 0.021, 1.8% of cases and 1.1% of controls). Dysregulation during migration of primordial germ cells has previously been suspected to be a part of TGCC development and this set of multiple rare variants may thereby have a minor contribution...

Parental Occupational Exposure to Organic Solvents and Testicular Germ Cell Tumors in their Offspring

DEFF Research Database (Denmark)

Le Cornet, Charlotte; Fervers, Béatrice; Pukkala, Eero

2017-01-01

BACKGROUND: Testicular germ cell tumors (TGCT) were suggested to have a prenatal environmentally related origin. The potential endocrine disrupting properties of certain solvents may interfere with the male genital development in utero. OBJECTIVES: We aimed to assess the association between......-Nordic Occupational Cancer Study Job-Exposure Matrix. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, no association was found between prenatal maternal exposure to solvents and TGCT risk. In subset analyses using only mothers for whom...

Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors.

Science.gov (United States)

Klümper, Niklas; Syring, Isabella; Offermann, Anne; Shaikhibrahim, Zaki; Vogel, Wenzel; Müller, Stefan C; Ellinger, Jörg; Strauß, Arne; Radzun, Heinz Joachim; Ströbel, Philipp; Brägelmann, Johannes; Perner, Sven; Bremmer, Felix

2015-09-17

Testicular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes. Immunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software. In tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis. In conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15

Parental Occupational Exposure to Heavy Metals and Welding Fumes and Risk of Testicular Germ Cell Tumors in Offspring

DEFF Research Database (Denmark)

Togawa, Kayo; Le Cornet, Charlotte; Feychting, Maria

2016-01-01

BACKGROUND: Data are scarce on the association between prenatal/preconception environmental exposure and testicular germ cell tumor (TGCT) in offspring. We examined parental occupational exposures to heavy metals and welding fumes in relation to TGCT in offspring in a registry-based case-control ......BACKGROUND: Data are scarce on the association between prenatal/preconception environmental exposure and testicular germ cell tumor (TGCT) in offspring. We examined parental occupational exposures to heavy metals and welding fumes in relation to TGCT in offspring in a registry-based case......-control study (NORD-TEST Study). METHODS: We identified TGCT cases diagnosed at ages 14-49 years in Finland (1988-2012), Norway (1978-2010), and Sweden (1979-2011) through nationwide cancer registries. These cases were individually matched by country and year of birth to controls selected from population...... registries. Information on parental occupations was retrieved from censuses. From this, we estimated prenatal/preconception exposures of chromium, iron, nickel, lead, and welding fumes (all three countries), and cadmium (Finland only) for each parent using job-exposure matrices specifying prevalence (P...

Testicular germ cell tumours and parental occupational exposure to pesticides

DEFF Research Database (Denmark)

Le Cornet, Charlotte; Fervers, Béatrice; Oksbjerg Dalton, Susanne

2015-01-01

OBJECTIVES: A potential impact of exposure to endocrine disruptors, including pesticides, during intrauterine life, has been hypothesised in testicular germ cell tumour (TGCT) aetiology, but exposure assessment is challenging. This large-scale registry-based case-control study aimed to investigate...... controls per case were randomly selected from the general national populations, matched on year of birth. Information on parental occupation was collected through censuses or Pension Fund information and converted into a pesticide exposure index based on the Finnish National Job-Exposure Matrix. RESULTS......: A total of 9569 cases and 32 028 controls were included. No overall associations were found for either maternal or paternal exposures and TGCT risk in their sons, with ORs of 0.83 (95% CI 0.56 to 1.23) and of 1.03 (0.92 to 1.14), respectively. Country-specific estimates and stratification by birth cohorts...

Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

Science.gov (United States)

Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

2015-02-01

Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group

OpenAIRE

Kollmannsberger, C; Rick, O; Klaproth, H; Kubin, T; Sayer, H G; Hentrich, M; Welslau, M; Mayer, F; Kuczyk, M; Spott, C; Kanz, L; Bokemeyer, C

2002-01-01

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell...

Is the FSHR 2039A>G variant associated with susceptibility to testicular germ cell cancer?

DEFF Research Database (Denmark)

Bang, A K; Busch, A S; Almstrup, K

2018-01-01

Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It is believed that exogenous endocrine factors have a crucial role in governing neoplastic transformation but on a strong hereditary...... background. Follicle-stimulating hormone (FSH) is the major regulatory hormone of the Sertoli cells. FSH signalling-related single-nucleotide polymorphisms (SNPs) have previously been shown to affect FSH action in men at different levels. We aimed to investigate whether three FSH-related SNPs (FSHR 2039A......>G, FSHR -29G>A and FSHB -211G>T) are associated with development of TGCC. A total of 752 Danish and German patients with TGCC from two tertiary andrological referral centres were included. Three control groups comprising 2020 men from the general population, 679 fertile men and 417 infertile men, were...

Association of the polymorphism of the CAG repeat in the mitochondrial DNA polymerase gamma gene (POLG) with testicular germ-cell cancer

DEFF Research Database (Denmark)

Blomberg Jensen, M; Leffers, H; Petersen, J H

2008-01-01

BACKGROUND: A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study. The hypothesis was prompted by an earlier preliminary study proposing an association of the absence...

Association of Down's syndrome and testicular cancer.

Science.gov (United States)

Dieckmann, K P; Rübe, C; Henke, R P

1997-05-01

We present additional clinical evidence for the suspected association of Down's syndrome and testicular germ cell tumors. Four cases of Down's syndrome and testicular cancer are reported. The literature was reviewed for previous cases and analysis regarding common features. The 4 patients were 29 to 35 years old and had clinical stage I seminoma of the testis. Two patients received prophylactic abdominal radiotherapy, 1 is being followed and 1 received adjuvant carboplatin treatment. There was no relapse at followup of 1 to 8 years. One patient also had contralateral cryptorchidism. A total of 16 cases with the association of Down's syndrome and testicular germ cell cancer was documented previously. Evidence for the suspected association of Down's syndrome and testicular cancer is now accumulating. Etiologically it is suspected that, along with genetically determined malformations in many other organs in trisomy 21, the gonads also undergo maldevelopment, thus creating the conditions for step 1 of germ cell tumor oncogenesis in utero. Physicians caring for patients with Down's syndrome should be aware of the possible association with testicular neoplasms.

Testicular growth and development in puberty.

Science.gov (United States)

Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

2017-06-01

To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

Epigenetic: a molecular link between testicular cancer and environmental exposures?

Directory of Open Access Journals (Sweden)

Aurelie eVega

2012-11-01

Full Text Available In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters (EDs exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the Testicular Dysgenesis Syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Futhermore, infertility has been stated as a risk factor for testicular cancer. The incidence of testicular cancer has been increasing over the past decades. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS from fetal germ cells (primordial germ cell or gonocyte. During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications plays an important role in normal development as well as in various diseases, including testicular cancer.Here we will review chromatin modifications which can affect testicular physiology leading to the development of testicular cancer; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells.

Science.gov (United States)

Spade, Daniel J; Bai, Cathy Yue; Lambright, Christy; Conley, Justin M; Boekelheide, Kim; Gray, L Earl

2018-06-15

In utero exposure to certain phthalate esters results in testicular toxicity, characterized at the tissue level by induction of multinucleated germ cells (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in a decrease in testicular testosterone in rats. The anti-androgenic effects of phthalates have been more thoroughly quantified than testicular pathology due to the significant time requirement associated with manual counting of MNGs on histological sections. An automated counting method was developed in ImageJ to quantify MNGs in digital images of hematoxylin-stained rat fetal testis tissue sections. Timed pregnant Sprague Dawley rats were exposed by daily oral gavage from gestation day 17 to 21 with one of eight phthalate test compounds or corn oil vehicle. Both the manual counting method and the automated image analysis method identified di-n-butyl phthalate, butyl benzyl phthalate, dipentyl phthalate, and di-(2-ethylhexyl) phthalate as positive for induction of MNGs. Dimethyl phthalate, diethyl phthalate, the brominated phthalate di-(2-ethylhexyl) tetrabromophthalate, and dioctyl terephthalate were negative. The correlation between automated and manual scoring metrics was high (r = 0.923). Results of MNG analysis were consistent with these compounds' anti-androgenic activities, which were confirmed in an ex vivo testosterone production assay. In conclusion, we have developed a reliable image analysis method that can be used to facilitate dose-response studies for the reproducible induction of MNGs by in utero phthalate exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

Management of germ cell testicular cancer with pulmonary metastases

International Nuclear Information System (INIS)

Schnorrer, M.; Carsky, S.; Ondrus, D.; Hornak, M.; Belan, V.; Kausitz, J.; Matoska, J.

1996-01-01

Twenty eight patients with germ cell testicular pulmonary metastases received primary chemotherapy including bleomycin, etoposide, and cisplatin. Complete response (CR) was achieved in 21 (75%) patients, in 11 of them CR was achieved following chemotherapy alone. Post-chemotherapy surgery of residual mass performed in 12 (42.9%) patients with normalized serum tumor markers. Retroperitoneal lymph node dissection was performed in one patient, pulmonary surgery in four, and both post-chemotherapy treatments in 7 patients. Overall cure rate was 89.3%, 26 (92.9%) patients are still alive at a mean follow-up of 19.7+ months (range, 3-34+ months) after the treatment start. Two (7.1%) died: one of them due to disease progression during chemotherapy, and the second one due to postoperative complication (acute respiratory failure). Relapse of disease was observed in one patient 21 months following CR achievement, and sequential chemotherapy was introduced. Authors recommend surgical remove of all radiologically detected residual deposits, because the available imaging methods are not adequate for determining the histologic composition of residual mass, which is decisive for further therapy and has prognostic value. (author)

An Uncommon Presentation of a Metachronous Testicular Primary Nonseminoma and Seminoma Separated by Two Decades and a Testicular Cancer Literature Review

Directory of Open Access Journals (Sweden)

Dennis Andrew Buck

2017-09-01

Full Text Available Introduction: Testicular cancer is the most common malignancy in men aged 15–40 years [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Its incidence comprises 0.8% of all male cancers worldwide, with a mortality rate of 0.1%. The incidence has nearly doubled from 1975 to 2007 leading to the concern of environmental causes [Thomas: Am J Epidemiol 2013; 178: 1240–1245]. Testicular cancer presents as a painless testicular mass without transillumination. Testicular cancer is subcategorized under germ cell testicular cancer or sex cord-stromal tumors. Of the germ cell tumors, approximately 90% originate in the testis, with the other 10% being extragonadal [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Typically, if a patient presents with a testicular mass and is 50 years old or older, the diagnosis of a primary lymphoma is considered until proven otherwise [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Germ cell testicular cancer is further divided into the subtypes of seminomatous and nonseminomatous; each presents with a unique histology and differing treatment implications. Discussion: Given the uniqueness of our patient’s metachronous second testicular primary, we sought to compare our case findings to available historic publications. We sought to address the issues of the incidence of a second primary testicular malignancy with regard to varying histology, age of incidence, and timing of a second primary testicular cancer, the presence of bowel involvement, and finally a brief discussion of testosterone replacement therapy. Conclusion: A review of our case presents several unique factors. The above varying literature has shown our patient to have met the odds of a contralateral testicular primary development in that he had a nonseminomatous primary, followed by a second testicular primary seminoma. Our patient exceeded the 15-year

An Uncommon Presentation of a Metachronous Testicular Primary Nonseminoma and Seminoma Separated by Two Decades and a Testicular Cancer Literature Review.

Science.gov (United States)

Buck, Dennis Andrew; Smith, Tristan Dean; Montana, Wilbur Nelson

2017-01-01

Testicular cancer is the most common malignancy in men aged 15-40 years [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Its incidence comprises 0.8% of all male cancers worldwide, with a mortality rate of 0.1%. The incidence has nearly doubled from 1975 to 2007 leading to the concern of environmental causes [Thomas: Am J Epidemiol 2013; 178: 1240-1245]. Testicular cancer presents as a painless testicular mass without transillumination. Testicular cancer is subcategorized under germ cell testicular cancer or sex cord-stromal tumors. Of the germ cell tumors, approximately 90% originate in the testis, with the other 10% being extragonadal [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Typically, if a patient presents with a testicular mass and is 50 years old or older, the diagnosis of a primary lymphoma is considered until proven otherwise [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Germ cell testicular cancer is further divided into the subtypes of seminomatous and nonseminomatous; each presents with a unique histology and differing treatment implications. Given the uniqueness of our patient's metachronous second testicular primary, we sought to compare our case findings to available historic publications. We sought to address the issues of the incidence of a second primary testicular malignancy with regard to varying histology, age of incidence, and timing of a second primary testicular cancer, the presence of bowel involvement, and finally a brief discussion of testosterone replacement therapy. A review of our case presents several unique factors. The above varying literature has shown our patient to have met the odds of a contralateral testicular primary development in that he had a nonseminomatous primary, followed by a second testicular primary seminoma. Our patient exceeded the 15-year cumulative risk of contralateral metachronous testicular cancer of 1

Mendelian randomisation analysis provides no evidence for a relationship between adult height and testicular cancer risk.

Science.gov (United States)

Levy, M; Hall, D; Sud, A; Law, P; Litchfield, K; Dudakia, D; Haugen, T B; Karlsson, R; Reid, A; Huddart, R A; Grotmol, T; Wiklund, F; Houlston, R S; Turnbull, C

2017-09-01

Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10 -57 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10 -10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10 -6 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors

Immunoreactive neuron-specific enolase (NSE) is expressed in testicular carcinoma-in-situ

DEFF Research Database (Denmark)

Kang, J L; Rajpert-De Meyts, E; Skakkebaek, N E

1996-01-01

Neuron-specific enolase (NSE) is a well-known marker of tumours that have neuroendocrine origin. High levels of NSE have also been described in various types of testicular germ cell neoplasms, particularly in seminomas. To evaluate the presence of NSE in testicular carcinoma-in situ (CIS), a prei...... are evidence against a relationship between NSE and N-myc in testicular germ cell tumours. The high expression of NSE in CIS and overt germ cell tumours may be due to the increased gene dosage effect associated with the overrepresentation of isochromosome 12p....

Long-term unmaintained remissions after agressive multidisciplinary treatment of advanced non-seminomatous testicular germ cell tumors.

Science.gov (United States)

Carey, R W; Weitzman, S A; Wilkins, E W; Chu, A M; Prout, G R

1977-10-01

Five patients with disseminated non-seminomatous testicular germ cell tumors are described. These patients have been clinically free of disease for 25 to more than 99 months and may be cured, since the interval after last treatment ranges from 13 to more than 76 months. Two patients, including 1 with pure choriocarcinoma, represent chemotherapeutic successes. In 3 patients the advantages of an individualized, multidisciplinary approach with surgery, radiotherapy and chemotherapy are shown. The benefits of continued aggressive treatment using residual therapeutic modalities despite prior failure with other therapy are documented.

Tributyltin chloride induced testicular toxicity by JNK and p38 activation, redox imbalance and cell death in sertoli-germ cell co-culture.

Science.gov (United States)

Mitra, Sumonto; Srivastava, Ankit; Khandelwal, Shashi

2013-12-06

The widespread use of tributyltin (TBT) as biocides in antifouling paints and agricultural chemicals has led to environmental and marine pollution. Human exposure occurs mainly through TBT contaminated seafood and drinking water. It is a well known endocrine disruptor in mammals, but its molecular mechanism in testicular damage is largely unexplored. This study was therefore, designed to ascertain effects of tributyltin chloride (TBTC) on sertoli-germ cell co-culture in ex-vivo and in the testicular tissue in-vivo conditions. An initial Ca(2+) rise followed by ROS generation and glutathione depletion resulted in oxidative damage and cell death. We observed p38 and JNK phosphorylation, stress proteins (Nrf2, MT and GST) induction and mitochondrial depolarization leading to caspase-3 activation. Prevention of TBTC reduced cell survival and cell death by Ca(2+) inhibitors and free radical scavengers specify definitive role of Ca(2+) and ROS. Sertoli cells were found to be more severely affected which in turn can hamper germ cells functionality. TBTC exposure in-vivo resulted in increased tin content in the testis with enhanced Evans blue leakage into the testicular tissue indicating blood-testis barrier disruption. Tesmin levels were significantly diminished and histopathological studies revealed marked tissue damage. Our data collectively indicates the toxic manifestations of TBTC on the male reproductive system and the mechanisms involved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Induction and persistence of abnormal testicular germ cells following gestational exposure to di-(n-butyl) phthalate in p53-null mice.

Science.gov (United States)

Saffarini, Camelia M; Heger, Nicholas E; Yamasaki, Hideki; Liu, Tao; Hall, Susan J; Boekelheide, Kim

2012-01-01

Phthalate esters are commonly used plasticizers found in many household items, personal care products, and medical devices. Animal studies have shown that in utero exposure to di-(n-butyl) phthalate (DBP) within a critical window during gestation causes male reproductive tract abnormalities resembling testicular dysgenesis syndrome. Our studies utilized p53-deficient mice for their ability to display greater resistance to apoptosis during development. This model was chosen to determine whether multinucleated germ cells (MNG) induced by gestational DBP exposure could survive postnatally and evolve into testicular germ cell cancer. Pregnant dams were exposed to DBP (500 mg/kg/day) by oral gavage from gestational day 12 until birth. Perinatal effects were assessed on gestational day 19 and postnatal days 1, 4, 7, and 10 for the number of MNGs present in control and DBP-treated p53-heterozygous and null animals. As expected, DBP exposure induced MNGs, with greater numbers found in p53-null mice. Additionally, there was a time-dependent decrease in the incidence of MNGs during the early postnatal period. Histologic examination of adult mice exposed in utero to DBP revealed persistence of abnormal germ cells only in DBP-treated p53-null mice, not in p53-heterozygous or wild-type mice. Immunohistochemical staining of perinatal MNGs and adult abnormal germ cells was negative for both octamer-binding protein 3/4 and placental alkaline phosphatase. This unique model identified a role for p53 in the perinatal apoptosis of DBP-induced MNGs and provided insight into the long-term effects of gestational DBP exposure within a p53-null environment.

When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome?

Science.gov (United States)

Van Saen, D; Vloeberghs, V; Gies, I; Mateizel, I; Sermon, K; De Schepper, Jean; Tournaye, H; Goossens, E

2018-06-01

When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome (KS)? In KS, germ cell loss is not observed in testicular tissue from fetuses in the second semester of pregnancy but present at a prepubertal age when the testicular architecture is still normal, while fibrosis is highly present at an adolescent age. Most KS patients are azoospermic at adult age because of a massive germ cell loss. However, the timing when this germ cell loss starts is not known. It is assumed that germ cell loss increases at puberty. Therefore, testicular sperm extraction (TESE) at an adolescent age has been suggested to increase the chances of sperm retrieval at onset of spermatogenesis. However, recent data indicate that testicular biopsies from peripubertal KS patients contain only a few germ cells. In this study, we give an update on fertility preservation in adolescent KS patients and evaluate whether fertility preservation would be beneficial at prepubertal age. The possibility of retrieving testicular spermatozoa by TESE was evaluated in adolescent and adult KS men. The presence of spermatogonia and the degree of fibrosis were also analysed in testicular biopsies from KS patients at different ages. The patients were divided into four age groups: foetal (n = 5), prepubertal (aged 4-7 years; n = 4), peripubertal (aged 12-16 years; n = 20) and adult (aged 18-41 years; n = 27) KS patients. In peripubertal and adult KS patients, retrieval of spermatozoa was attempted by semen analysis after masturbation, vibrostimulation, electroejaculation or by TESE. MAGE-A4 immunohistochemistry was performed to evaluate the presence of germ cells in testicular biopsies from foetal, prepubertal, peripubertal and adult KS patients. Tissue morphology was evaluated by haematoxylin-periodic acid Schiff (H/PAS) staining. Testicular spermatozoa were collected by TESE in 48.1% of the adult KS patients, while spermatozoa were recovered after TESE in only one peripubertal patient (5

Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia

DEFF Research Database (Denmark)

Rajpert-De Meyts, E; Jørgensen, N; Brøndum-Nielsen, K

1998-01-01

Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal...... development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low...... frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We...

Epigenetic: a molecular link between testicular cancer and environmental exposures.

Science.gov (United States)

Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A; Volle, David H

2012-01-01

In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

Perspectives on testicular sex cord-stromal tumors and those composed of both germ cells and sex cord-stromal derivatives with a comparison to corresponding ovarian neoplasms.

Science.gov (United States)

Roth, Lawrence M; Lyu, Bingjian; Cheng, Liang

2017-07-01

Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2% to 5% of cases. Both genetic and epigenetic factors account for the differences in frequency and histologic composition between testicular and ovarian SCSTs. For example, large cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing Sertoli cell neoplasia occur in the testis but have not been described in the ovary. In this article, we discuss recently described diagnostic entities as well as inconsistencies in nomenclature used in the recent World Health Organization classifications of SCSTs in the testis and ovary. We also thoroughly review the topic of neoplasms composed of both germ cells and sex cord derivatives with an emphasis on controversial aspects. These include "dissecting gonadoblastoma" and testicular mixed germ cell-sex cord stromal tumor (MGC-SCST). The former is a recently described variant of gonadoblastoma that sometimes is an immediate precursor of germinoma in the dysgenetic gonads of patients with a disorder of sex development. Although the relationship of dissecting gonadoblastoma to the previously described undifferentiated gonadal tissue is complex and not entirely resolved, we believe that it is preferable to continue to use the term undifferentiated gonadal tissue for those cases that are not neoplastic and are considered to be the precursor of classical gonadoblastoma. Although the existence of testicular MGC-SCST has been challenged, the most recent evidence supports its existence; however, testicular MGC-SCST differs significantly from ovarian examples due to both genetic and epigenetic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

Energy Technology Data Exchange (ETDEWEB)

Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

2008-01-18

Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

Nontesticular cancers in relatives of testicular germ cell tumor (TGCT) patients from multiple-case TGCT families

Science.gov (United States)

McMaster, Mary L; Heimdal, Ketil R; Loud, Jennifer T; Bracci, Janet S; Rosenberg, Philip S; Greene, Mark H

2015-01-01

Testicular germ cell tumors (TGCT) exhibit striking familial aggregation that remains incompletely explained. To improve the phenotypic definition of familial TGCT (FTGCT), we studied an international cohort of multiple-case TGCT families to determine whether first-degree relatives of FTGCT cases are at increased risk of other types of cancer. We identified 1041 first-degree relatives of TGCT cases in 66 multiple-case TGCT families from Norway and 64 from the United States (combined follow-up of 31,556 person-years). We collected data on all cancers (except nonmelanoma skin cancers) reported by the family informant in these relatives, and we attempted to verify all reported cancer diagnoses through medical or cancer registry records. We calculated observed-to-expected (O/E) standardized incidence ratios, together with 95% confidence intervals (CI), for invasive cancers other than TGCT. We found no increase in risk of cancer overall (Norway O/E = 0.8; 95% CI: 0.6–1.1 and United States O/E = 0.9; 95% CI: 0.7–1.3). Site-specific analyses pooled across the two countries revealed a leukemia excess (O/E = 6.5; 95% CI: 3.0–12.3), deficit of female breast cancer (O/E = 0.0; 95% CI: 0.0–0.6) and increased risk of soft tissue sarcoma (O/E = 7.2; 95% CI: 2.0–18.4); in all instances, these results were based on small case numbers and statistically significant only in Norway. While limited by sample size and potential issues relating to completeness of cancer reporting, this study in multiple-case TGCT families does not support the hypothesis that cancers other than testis cancer contribute to the FTGCT phenotype. PMID:25882629

Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations

DEFF Research Database (Denmark)

Skakkebaek, N E; Rajpert-De Meyts, Ewa; Jørgensen, N

2007-01-01

Recently a worldwide rise in the incidence of testicular germ cell cancer (TGCC) has been repeatedly reported. The changing disease pattern may signal that other testicular problems may also be increasing. We have reviewed recent research progress, in particular evidence gathered in the Nordic...... countries, which shows strong associations between testicular cancer, undescended testis, hypospadias, poor testicular development and function, and male infertility. These studies have led us to suggest the existence of a testicular dysgenesis syndrome (TDS), of which TGCC, undescended testis, hypospadias...... in TGCC rates of a population may be 'whistle blowers' of other reproductive health problems. As cancer registries are often of excellent quality - in contrast to registries for congenital abnormalities - health authorities should consider an increase in TGCC as a warning that other reproductive health...

Accuracy of Prader orchidometer in measuring testicular volume

African Journals Online (AJOL)

2012-10-21

Oct 21, 2012 ... testicular volumes were then determined by water displacement of the testis. ... tubules and germ cells. ... in a warm room after application of a heating pad (we used ... This mean difference in testicular volume between Prader.

Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.

Science.gov (United States)

Litchfield, Kevin; Levy, Max; Orlando, Giulia; Loveday, Chey; Law, Philip J; Migliorini, Gabriele; Holroyd, Amy; Broderick, Peter; Karlsson, Robert; Haugen, Trine B; Kristiansen, Wenche; Nsengimana, Jérémie; Fenwick, Kerry; Assiotis, Ioannis; Kote-Jarai, ZSofia; Dunning, Alison M; Muir, Kenneth; Peto, Julian; Eeles, Rosalind; Easton, Douglas F; Dudakia, Darshna; Orr, Nick; Pashayan, Nora; Bishop, D Timothy; Reid, Alison; Huddart, Robert A; Shipley, Janet; Grotmol, Tom; Wiklund, Fredrik; Houlston, Richard S; Turnbull, Clare

2017-07-01

Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis. Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT.

Infertility with Testicular Cancer.

Science.gov (United States)

Ostrowski, Kevin A; Walsh, Thomas J

2015-08-01

Testicular germ cell cancer is one of the most curable cancers. Most patients are treated during their reproductive years, making infertility a significant quality of life issue after successful treatment. This focused review evaluates the factors that contribute to infertility and specific fertility risks with the various testicular cancer treatments. Timing of patient discussions and current fertility treatments are reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis

DEFF Research Database (Denmark)

Giwercman, Alexander; Andrews, P W; Jørgensen, N

1993-01-01

Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic...

Undetectable inhibin B serum levels in men after testicular irradiation

DEFF Research Database (Denmark)

Petersen, P M; Andersson, A M; Rørth, M

1999-01-01

A group of men treated with testicular irradiation for carcinoma in situ in the remaining testis after orchidectomy for unilateral testicular germ cell cancer was used as a model to study of the effect of selective eradication of germ cells on the levels of serum inhibin B in the human male....... Thirteen men with verified spermatogenesis and detectable preirradiation levels of serum inhibin B (median, 55; range, 23-193 pg/mL) were investigated before and after testicular irradiation (14-20 Gy). All patients had undetectable levels of inhibin B 2-12 months (median, 5 months) after radiotherapy (...

Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours

DEFF Research Database (Denmark)

Bush, J M; Gardiner, D W; Palmer, J S

2011-01-01

Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated...... in canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model...... and characterized using human classification criteria. Histopathological and immunohistological analysis of PLAP, KIT, DAZ and DMRT1 expression revealed that canine seminomas closely resemble human spermatocytic seminomas. In addition, a relatively frequent concomitant presence of somatic cell tumours was noted...

Comet assay on mice testicular cells

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Anoop Kumar Sharma

2015-05-01

Full Text Available Heritable mutations may result in a variety of adverse outcomes including genetic disease in the offspring. In recent years the focus on germ cell mutagenicity has increased and the “Globally Harmonized System of Classification and Labelling of Chemicals (GHS” has published classification criteria for germ cell mutagens (Speit et al., 2009. The in vivo Comet assay is considered a useful tool for investigating germ cell genotoxicity. In the present study DNA strand breaks in testicular cells of mice were investigated. Different classes of chemicals were tested in order to evaluate the sensitivity of the comet assay in testicular cells. The chemicals included environmentally relevant substances such as Bisphenol A, PFOS and Tetrabrombisphenol A. Statistical power calculations will be presented to aid in the design of future Comet assay studies on testicular cells. Power curves were provided with different fold changes in % tail DNA, different number of cells scored and different number of gels (Hansen et al., 2014. An example is shown in Figure 1. A high throughput version of the Comet assay was used. Samples were scored with a fully automatic comet assay scoring system that provided faster scoring of randomly selected cells.

Testicular dysgenesis syndrome and the origin of carcinoma in situ testis.

Science.gov (United States)

Sonne, Si Brask; Kristensen, David Møbjerg; Novotny, Guy W; Olesen, Inge Ahlmann; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2008-04-01

Recent increases in male reproductive disorders have been linked to exposure to environmental factors leading to the testicular dysgenesis syndrome (TDS). Testicular cancer is the most severe condition in TDS and studies have shown a clear correlation between risk of testicular cancer and other components of TDS and that the geographical location of the mother during pregnancy can be a risk factor. This suggests that the dysgenesis has its origin in utero and that TDS is initiated by environmental factors, including possibly hormone-disrupting compounds that act on the mother and the developing foetus, but the genetic background may also play a role. The morphological similarity of carcinoma in situ (CIS) cells (the precursor of the majority of invasive testicular cancers) with primordial germ cells and gonocytes, and overlap in expression of protein markers suggests an origin of CIS from primordial germ cells or gonocytes. CIS cells and germ cell-derived cancers of the human type have so far not been described in any animal model of TDS, which could be caused by species differences in the development of the male gonad. Regardless of this, it is plausible that the dysgenesis, and hence the development of CIS cells, is a result of disturbed signalling between nurse cells and germ cells that allow embryonic germ cells to survive in the pre-pubertal and adult testis. The post-pubertal proliferation of CIS cells combined with aberrant signalling then leads to an accumulation of genetic changes in the CIS cells, which eventually results in the development of invasive testicular cancer in the adult.

Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors.

Science.gov (United States)

Franke, F E; Pauls, K; Kerkman, L; Steger, K; Klonisch, T; Metzger, R; Alhenc-Gelas, F; Burkhardt, E; Bergmann, M; Danilov, S M

2000-12-01

Retained fetal expression of angiotensin I-converting enzyme (ACE, CD143) has recently been shown in intratubular germ cell neoplasms (IGCN) and invasive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a characteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determined by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraffin-embedded tissue sections, supplemented by mRNA expression analysis using in situ hybridization. These data were compared with those obtained by germ cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employing an uniform score system for the evaluation of immunoreactivity (IRS; possible values from 0 to 12). Expression of sACE and PIAP was found in all 87 analyzed IGCN (IRS > 4, median IRS of 12). Heterogeneous staining patterns were not related to the type of adjacent GCT but correlated with low expression in adjacent seminomas (P =.032 for sACE; P =.005 for PIAP). Both sACE and PIAP often showed a decreased and more heterogeneous but still moderate expression in 91 classic seminomas (median IRS of 8) and were completely absent in tumor cells of spermatocytic seminomas. Despite all similarities, we found sACE and PIAP differently regulated during GCT progression. This was documented by a well-preserved expression of either sACE or PIAP or both in all classic seminomas, low PIAP immunoreactivity in metastasis of seminomas, and completely diverging expression patterns in nonseminomatous GCT. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous differentiated tumors. HUM PATHOL 31:1466-1476. Copyright 2000 by W.B. Saunders Company

Reporting and Staging of Testicular Germ Cell Tumors: The International Society of Urological Pathology (ISUP) Testicular Cancer Consultation Conference Recommendations.

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Verrill, Clare; Yilmaz, Asli; Srigley, John R; Amin, Mahul B; Compérat, Eva; Egevad, Lars; Ulbright, Thomas M; Tickoo, Satish K; Berney, Daniel M; Epstein, Jonathan I

2017-06-01

The International Society of Urological Pathology held a conference devoted to issues in testicular and penile pathology in Boston in March 2015, which included a presentation and discussion led by the testis microscopic features working group. This conference focused on controversies related to staging and reporting of testicular tumors and was preceded by an online survey of the International Society of Urological Pathology members. The survey results were used to initiate discussions, but decisions were made by expert consensus rather than voting. A number of recommendations emerged from the conference, including that lymphovascular invasion (LVI) should always be reported and no distinction need be made between lymphatic or blood invasion. If LVI is equivocal, then it should be regarded as negative to avoid triggering unnecessary therapy. LVI in the spermatic cord is considered as category pT2, not pT3, unless future studies provide contrary evidence. At the time of gross dissection, a block should be taken just superior to the epididymis to define the base of the spermatic cord, and direct invasion of tumor in this block indicates a category of pT3. Pagetoid involvement of the rete testis epithelium must be distinguished from rete testis stromal invasion, with only the latter being prognostically useful. Percentages of different tumor elements in mixed germ cell tumors should be reported. Although consensus was reached on many issues, there are still areas of practice that need further evidence on which to base firm recommendations.

Raman spectroscopic analysis identifies testicular microlithiasis as intratubular hydroxyapatite.

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De Jong, B W D; De Gouveia Brazao, C A; Stoop, H; Wolffenbuttel, K P; Oosterhuis, J W; Puppels, G J; Weber, R F A; Looijenga, L H J; Kok, D J

2004-01-01

As diagnosed by ultrasonography, testicular microlithiasis is associated with various benign and malignant conditions. The molecular constitution of these microliths is largely unknown. Raman spectroscopy provides detailed in situ information about the molecular composition of tissues and to our knowledge it has not been applied to gonadal microliths. We analyzed the molecular composition of gonadal microlithiasis and its surrounding region using Raman spectroscopy in malignant and benign conditions. Multiple microliths from 6 independent samples diagnosed with gonadal microlithiasis by ultrasound and histologically confirmed were investigated by Raman spectroscopy. The samples included 4 testicular parenchyma samples adjacent to a germ cell tumor (4 seminomas), a gonadoblastoma of a dysgenetic gonad and testicular biopsy of a subfertile male without malignancy. Raman spectroscopic mapping demonstrated that testicular microliths were located within the seminiferous tubule. Glycogen surrounded all microliths in the samples associated with germ cell neoplasm but not in the benign case. The molecular composition of the 26 microliths in all 6 conditions was pure hydroxyapatite. Microliths in the testis are located in the seminiferous tubules and composed of hydroxyapatite. In cases of germ cell neoplasm they co-localize with glycogen deposits.

Clinical and genetic aspects of testicular germ cell tumours

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Holzik Martijn

2008-02-01

Full Text Available Abstract In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs. TGCT is the most common type of malignant disorder in men aged 15-40 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.

Clinical and genetic aspects of testicular germ cell tumours.

Science.gov (United States)

Lutke Holzik, Martijn F; Sijmons, Rolf H; Hoekstra-Weebers, Josette Ehm; Sleijfer, Dirk T; Hoekstra, Harald J

2008-02-15

In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs). TGCT is the most common type of malignant disorder in men aged 1540 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.

Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer

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Timothy M. Pierpont

2017-11-01

Full Text Available Summary: Testicular germ cell tumors (TGCTs are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. : Using a mouse testicular germ cell tumor model, Pierpont et al. establish that male germ cells are susceptible to malignant transformation during a restricted window of embryonic development. The cancer stem cells of the resulting testicular cancers demonstrate genotoxin hypersensitivity, rendering these malignancies highly responsive to conventional chemotherapy. Keywords: testicular germ cell tumor, TGCT, cancer stem cells, CSCs, chemotherapy, embryonal carcinoma, EC, DNA damage response, DDR

Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

Science.gov (United States)

2013-03-25

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo

DEFF Research Database (Denmark)

Blomberg Jensen, Martin; Jørgensen, Anne; Nielsen, John Erik

2012-01-01

and express pluripotency factors (NANOG/OCT4). Vitamin D (VD) is metabolized in the testes, and here, we examined VD metabolism in TGCT differentiation and pluripotency regulation. We established that the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human fetal germ cells, CIS, and invasive......) treatment in vivo. These novel findings show that VD metabolism is involved in the mesodermal transition during differentiation of cancer cells with embryonic stem cell characteristics, which points to a function for VD during early embryonic development and possibly in the pathogenesis of TGCTs.......Testicular germ cell tumors (TGCTs) are classified as either seminomas or nonseminomas. Both tumors originate from carcinoma in situ (CIS) cells, which are derived from transformed fetal gonocytes. CIS, seminoma, and the undifferentiated embryonal carcinoma (EC) retain an embryonic phenotype...

A Case of Lung Abscess during Chemotherapy for Testicular Tumor

OpenAIRE

林, 裕次郎; 宮後, 直樹; 武田, 健; 山口, 唯一郎; 中山, 雅志; 新井, 康之; 垣本, 健一; 西村, 和郎

2014-01-01

32-year-old man was seen in a clinic because ofprolonged cough and slight-fever. Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal lymph node metastases from right testicular tumor was suspected by positron emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ cell tumor (embryonal carcinoma＋seminoma, pT2N1M1b), and classified into the intermediate risk group according to International Germ Cell Cancer Collaborative Group. He underwen...

IMPACT OF BEP OR CARBOPLATIN CHEMOTHERAPY ON TESTICULAR FUNCTION AND SPERM NUCLEUS OF SUBJECTS WITH TESTICULAR GERM CELL TUMOR

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Marco eGhezzi

2016-05-01

Full Text Available Young males have testicular germ cells tumours (TGCT as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO, the treatment of TGCT may include surveillance, radiotherapy or chemotherapy (CT, basing on tumour histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide and cisplatin (BEP, after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group, 54 with carboplatin (Carb group and 58 were just surveilled (S-group. All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0 and after 12 (T1 and 24 months (T2 from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones and testicular volume at baseline were not different between groups. At T1 we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S- group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S group and Carb group. These alterations were persistent after two years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after one and two years from the end of treatment

Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects

DEFF Research Database (Denmark)

Sharpe, R.M.; Skakkebæk, Niels Erik

2008-01-01

Reproductive disorders of newborn (cryptorchidism, hypospadias) and young adult males (low sperm counts, testicular germ cell cancer) are common and/or increasing in incidence. It has been hypothesized that these disorders may comprise a testicular dysgenesis syndrome (TDS) with a common origin...

Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

Science.gov (United States)

2011-07-14

Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

Familial testicular cancer and developmental anomalies

International Nuclear Information System (INIS)

Ondrus, D.; Kuba, D.; Chrenova, S.; Matoska, J.

1997-01-01

Familial occurrence belongs to factors followed in etiology and pathogenesis of testicular germ-cell tumors. Association with abnormal testicular development, or with other risk factors is relatively frequent. In our material 650 patients had been treated for testicular cancer in the period of 1981-1995. Familial occurrence was observed 7-times (1.08), most frequently in combination with cryptorchidism. Individual families were analyzed in details, including HLA typing. On basis of the observations the supplementation of initial examination of each patient with suspicious testicular cancer with detailed familiar history aimed also at the occurrence of urogenital developmental anomalies and tumors has been recommended. The knowledge about familial tumor occurrence in the first-degree relatives in combination with thorough testicular self-examination is being considered of great importance in the secondary prevention. (author)

DEMONSTRATION OF THE GENUINE ISO-12P CHARACTER OF THE STANDARD MARKER CHROMOSOME OF TESTICULAR GERM-CELL TUMORS AND IDENTIFICATION OF FURTHER CHROMOSOME-12 ABERRATIONS BY COMPETITIVE INSITU HYBRIDIZATION

NARCIS (Netherlands)

SUIJKERBUIJK, RF; VANDEVEEN, AY; VANECHTEN, J; BUYS, CHCM; DEJONG, B; OOSTERHUIS, JW; WARBURTON, DA; CASSIMAN, JJ; SCHONK, D; VANKESSEL, AG

The recently developed competitive in situ hybridization (CISH) strategy was applied to the analysis of chromosome 12 aberrations in testicular germ cell tumors (TGCTs). DNAs from two rodent-human somatic cell hybrids, containing either a normal chromosome 12 or the p arm of chromosome 12 as their

GESTATIONAL AGE AT BIRTH AND RISK OF TESTICULAR CANCER

Science.gov (United States)

Crump, Casey; Sundquist, Kristina; Winkleby, Marilyn A.; Sieh, Weiva; Sundquist, Jan

2011-01-01

Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973–1979, including 19,214 born preterm (gestational age testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio 3.95; 95% CI, 1.67–9.34) after adjusting for other perinatal factors, family history of testicular cancer, and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth, or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life. PMID:22314417

Carcinoma in situ testis displays permissive chromatin modifications similar to immature foetal germ cells

DEFF Research Database (Denmark)

Almstrup, K; Nielsen, J E; Mlynarska, O

2010-01-01

The majority of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS) stage. The CIS cell is a neoplastic counterpart of foetal germ cells. During their development, foetal germ cells undergo extensive and essential epigenetic modifications, but little is known about...

Treatment Option Overview (Extragonadal Germ Cell Tumors)

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... Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk of extragonadal germ cell ... Headache. Change in bowel habits. Feeling very tired. Trouble walking. Trouble in seeing or moving the eyes. ...

General Information about Extragonadal Germ Cell Tumors

Science.gov (United States)

... Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk of extragonadal germ cell ... Headache. Change in bowel habits. Feeling very tired. Trouble walking. Trouble in seeing or moving the eyes. ...

Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

Science.gov (United States)

Shenoy, Niraj; Dronca, Roxana; Quevedo, Fernando; Boorjian, Stephen A; Cheville, John; Costello, Brian; Kohli, Manish; Witzig, Thomas; Pagliaro, Lance

2017-08-01

The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-1α (HIF-1α) expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.

Cancer treatment in childhood and testicular function: the importance of the somatic environment

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Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Hutka, Marsida

2018-01-01

Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment. PMID:29351905

Adult Immunohistochemical Markers Fail to Detect Intratubular Germ Cell Neoplasia in Prepubertal Boys with Cryptorchidism

DEFF Research Database (Denmark)

Kvist, Kolja; Clasen-Linde, Erik; Cortes, Dina

2013-01-01

Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. It is characterized by large germ cells with large nuclei with a hyperchromatic, coarse chromatin pattern, large prominent nucleoli and abundant pale cytoplasm. In prepubertal boys these cells are located both...

The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

International Nuclear Information System (INIS)

Schrader, Mark; Burger, Angelika M; Müller, Markus; Krause, Hans; Straub, Bernd; Schostak, Martin; Schulze, Wolfgang; Lauke, Heidrun; Miller, Kurt

2002-01-01

The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT). Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients. High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression. These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status

The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

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Schulze Wolfgang

2002-11-01

Full Text Available Abstract Background The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT, which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT. Methods Telomerase activity (TA was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients. Results High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome showed no telomerase activity and only minimal hTERT expression. Conclusions These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status.

Polygenic susceptibility to testicular cancer

DEFF Research Database (Denmark)

Litchfield, Kevin; Mitchell, Jonathan S; Shipley, Janet

2015-01-01

BACKGROUND: The increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic...... known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme. RESULTS: The area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having...

[Polymorphisms of KITLG, SPRY4, and BAK1 genes in patients with testicular germ cell tumors and individuals with infertility associated with AZFc deletion of the Y chromosome].

Science.gov (United States)

Nemtsova, M V; Ivkin, E V; Simonova, O A; Rudenko, V V; Chernykh, V B; Mikhaylenko, D S; Loran, O B

2016-01-01

Testicular cancer is the most common form of solid cancer in young men. Testicular cancer is represented by testicular germ cell tumors (TGCTs) derived from embryonic stem cells with different degrees of differentiation in about 95% of cases. The development of these tumors is related to the formation of a pool of male germ cells and gametogenesis. Clinical factors that are predisposed to the development of germ-cell tumors include cryptorchidism and testicular microlithiasis, as well as infertility associated with the gr/gr deletion within the AZFс locus. KITLG, SPRY4, and BAK1 genes affect the development of the testes and gametogenesis; mutations and polymorphisms of these genes lead to a significant increase in the risk of the TGCT development. To determine the relationship between gene polymorphisms and the development of TGCTs, we developed a system for detection and studied the allele and genotype frequencies of the KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), and BAK1 (rs210138) genes in fertile men, patients with TGCTs, and patients with infertility that have the AZFс deletion. A significant association of rs995030 of the KITLG gene with the development of TGCTs (p = 0.029 for the allele G, p = 0.0124 for the genotype GG) was revealed. Significant differences in the frequencies of the studied polymorphisms in patients with the AZFc deletion and the control group of fertile men were not found. We showed significant differences in the frequencies for the combination of all high-risk polymorphisms in the control group, patients with the AZFc deletion and patients with TGCTs (p (TGCTs-AZF-control) = 0.0207). A fivefold increase in the frequency of the combination of all genotypes in the TGCT group (p = 0.0116; OR = 5.25 [1.44-19.15]) and 3.7-fold increase was identified in patients with the AZFc deletion (p = 0.045; OR = 3.69 [1.11-12.29]) were revealed. The genotyping of patients with infertility caused by the AZFc deletion can be used to

Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors.

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Figueroa, Jonine D; Sakoda, Lori C; Graubard, Barry I; Chanock, Stephen; Rubertone, Mark V; Erickson, R Loren; McGlynn, Katherine A

2008-11-01

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma.

Expression of the glycolipid globotriaosylceramide (Gb3) in testicular carcinoma in situ

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Kang, J L; Rajpert-De Meyts, E; Wiels, J

1995-01-01

of the globo-series core-structure, globotriaosylceramide (Gb3) was investigated in the preinvasive stage of testicular germ cell tumours, carcinoma in situ (CIS). Seventeen tissue specimens with CIS and 12 samples of overt testicular tumours were immunostained with anti-Gb3 monoclonal antibody 38...

Anti-MIC2 as a tool in examination of testicular biopsies

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Visfeldt, J; Cortes, Dina; Thorup, J M

1999-01-01

MIC2 is a pseudoautosomal gene localized on X and Y chromosomes. The MIC2 gene product is a glycoprotein expressed on the cell membranes of a number of somatic cells, including Sertoli cells of the testis, but not on the cell membranes of germ cells. In cases of cryptorchidism, a testicular biopsy...... transverse section is lower than 1% of the lowest normal age-matched value. Besides Sertoli cells the seminiferous tubules in undescended testes contain only a few germ cells, and it may be difficult to pinpoint the germ cells in small biopsies. Especially in nonpalpable testes their number may be heavily...... reduced. A reliable identification of germ cells may also be difficult in cultures of testicular biopsies from undescended testes. Against this background, we tried the use of an immunohistochemical method with DAKO antibody to the MIC2 gene product (MIC2, 12 E7, code no. M3601) in order to obtain...

Expression of testicular angiotensin-converting enzyme in adult spontaneously hypertensive rats.

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Genka Krasteva

2009-05-01

Full Text Available Recent studies demonstrated that one isoform of angiotensin-converting enzyme named testicular or germinal (tACE is localized in postmeiotic male germ cells and is essential for fertilizing ability of spermatozoa. Hypertension in spontaneously hypertensive rats (SHR is androgen-dependent and reduction in male gametes is reported in this experimental conditions. Expression of tACE was not studied under conditions of spontaneous hypertension. The aim of this work is to characterize immuno-expression of tACE in the testis of adult (16-week-old SHR rats in relation to the changes in blood pressure and serum testosterone level. In 82% of adult SHR, the immuno-expression of tACE followed the normal stage-specific pattern. Destructive testicular changes, germ cells depletion have been observed in 18% of 16-week-old SHR and stronger expression of tACE in stages 8-11 compared to controls was detected. As a result stage specificity in SHR was not as evident as in control. No reaction was found in germ cell depleted tubules in which elongated spermatids were absent. Degenerating germ cells exhibited strong immunostaining comparable to that in residual bodies. The blood pressure was significantly higher in SHR and testosterone levels were more than twice but non-significantly elevated. There was no clear correlation between testicular structural changes, blood pressure level values or serum testosterone levels. Expression of tACE in postmeiotic germ cells, specifically altered by SHR, suggested possible involvement of components of renin-angiotensin system in the process of spermiogenesis. Loss of enzyme expression we found in germ cell depleted tubules in SHR is due to absence of corresponding stages of spermatid differentiation. Therefore, tACE can be used as a marker for germ cell depletion due to hypertension and other pathological conditions.

Cervical mature teratoma 17 years after initial treatment of testicular teratocarcinoma: report of a late relapse

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Alavion Mina

2007-01-01

Full Text Available Abstract Background Late relapses of testicular germ cell tumor are uncommon. We report a case of cervical mature teratoma appeared 17 years after treatment of testicular teratocarcinoma. Case presentation A 20- year- old patient underwent left sided orchiectomy followed by systemic therapy and retroperitoneal residual mass resection in 1989. He remained in complete remission for 200 months. In 2005 a huge left supraclavicular neck mass with extension to anterior mediastinum appeared. Radical surgical resection of the mass was performed and pathologic examination revealed mature teratoma. Conclusion This is one of the longest long-term reported intervals of a mature teratoma after treatment of a testicular nonseminoma germ cell tumor. This case emphasizes the necessity for follow up of testicular cancer throughout the patient's life.

The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

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Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

2011-01-01

This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

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Athanasiou, A. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Institut Curie, Paris (France)], E-mail: alexandra.athanasiou@curie.net; Vanel, D. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Istituti Ortopedici Rizzoli, Bologna (Italy); El Mesbahi, O. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Theodore, C. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Department of Oncology, Hopital Foch, Suresnes (France); Fizazi, K. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France)

2009-02-15

Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

Testicular histology in cryptorchid boys - aspects of fertility

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Cortes, Dina; Thorup, jørgen; Petersen, BL

2007-01-01

, testis, infertility, germ cells. Correspondence: Jorgen M. Thorup MD, PhD. Department of Paediatric Surgery and Department of Pathology, Rigshospitalet University of Copenhagen, 2100 Copenhagen O, DENMARK. e-mail: j-thorup@rh.dk Introduction Cryptorchidism is associated with infertility. Early surgery...... who had surgery for cryptorchidism with simultaneous successful testicular biopsy, between Januar 1971 and March 2006. Excluded were patients who had undergone prior inguinal surgery or exhibited retractile testes, those with a uterus, tuba uterina, testicular neoplasia or known X chromosome...... fertility potential (2, 18, 20), but is notable that lack of germ cells may result in infertility even in unilateral cryptorchidism. This may be because the same pathological mechanisms are operating in both testes. Our results emphasize the importance of performing orchiopexy before 15 month of age...

Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

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Rudolph, Christiane; Melau, Cecilie; Nielsen, John E; Vile Jensen, Kristina; Liu, Dekang; Pena-Diaz, Javier; Rajpert-De Meyts, Ewa; Rasmussen, Lene Juel; Jørgensen, Anne

2017-08-01

Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. The expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined. MMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p cisplatin sensitivity. This study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in

Anti-MIC2 as a tool in examination of testicular biopsies

DEFF Research Database (Denmark)

Visfeldt, J; Cortes, D; Thorup, J M

1999-01-01

MIC2 is a pseudoautosomal gene localized on X and Y chromosomes. The MIC2 gene product is a glycoprotein expressed on the cell membranes of a number of somatic cells, including Sertoli cells of the testis, but not on the cell membranes of germ cells. In cases of cryptorchidism, a testicular biopsy...... testes which had been cultured in vitro for 7, 14 or 21 days. In all cases the immunohistochemical method with DAKO antibody to the MIC2 gene product was helpful for identification of Sertoli cells and germ cells, and we therefore recommend the use of anti-MIC2 in all testicular biopsies where...

Testicular cancer from diagnosis to epigenetic factors

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Boccellino, Mariarosaria; Vanacore, Daniela; Zappavigna, Silvia; Cavaliere, Carla; Rossetti, Sabrina; D’Aniello, Carmine; Chieffi, Paolo; Amler, Evzen; Buonerba, Carlo; Di Lorenzo, Giuseppe; Di Franco, Rossella; Izzo, Alessandro; Piscitelli, Raffaele; Iovane, Gelsomina; Muto, Paolo; Botti, Gerardo; Perdonà, Sisto; Caraglia, Michele; Facchini, Gaetano

2017-01-01

Testicular cancer (TC) is one of the most common neoplasms that occurs in male and includes germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Diagnosis of TC involves the evaluation of serum tumor markers alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, but clinically several types of immunohistochemical markers are more useful and more sensitive in GCT, but not in teratoma. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C) and LIN28. Gene expression in GCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TG-subtypes that reflect the normal developmental switch in primordial germ cells from an under- to normally methylated genome. The main purpose of this review is to illustrate the findings of recent investigations in the classification of male genital organs, the discoveries in the use of prognostic and diagnostic markers and the epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and microRNAs (miRNAs). PMID:29262668

Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism

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Cortes, Dina; Visfeldt, J; Thorup, J M

2001-01-01

In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10-40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33-100% risk of inferti...

Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes

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Rajpert-De Meyts, Ewa; Jørgensen, N; Müller, Jørn

1996-01-01

conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects...... expressed Kit at a later developmental age than controls, in which no Kit protein was detectable beyond the 15th week of gestation. This finding may indicate a disturbance of the chronology of germ cell development, or it may suggest a change of the regulation of c-kit expression in subjects with disorders...

The Expression of Markers for Intratubular Germ Cell Neoplasia in Normal Infantile Testes

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Kolja Kvist

2018-06-01

Full Text Available BackgroundPositive immunohistochemical expression of testicular cancer markers is often reported beyond 12 months of age in cryptorchid testes, which is assumed to indicate delayed maturation of the fetal germ cells, or neoplastic changes. These findings allowed for questions as to the extent of positive reaction in normal testes. The aim of the study was to clarify the expression of these markers in a normal material up to 2 years.MethodsTesticular material from 69 boys aged 1–690 days, who died of causes with no association of testicular pathology. Histology sections were incubated with primary antibodies including anti-placental-like alkaline phosphatase (PLAP, anti-C-Kit, anti-D2–40, and anti-Oct3/4. The mean germ cell number per tubular transverse section (G/T was calculated based on the G/T of both testes of every boy.ResultsThe mean G/T declined through the 690 days. PLAP appeared stably expressed throughout the ages studied. The likelihood of a positive reaction for C-Kit waned with increasing age within the study period. Positive staining for D2–40 and Oct3/4 was demonstrated up to 6 and 9 months respectively.ConclusionUp to 1 or 2 years of age, normal infantile testes contain germ cells positive for the immunohistochemical markers commonly utilized to aid in the detection of testicular cancer. This finding supports the concept of germ cells undergoing a continuous maturational process in a heterogeneous fashion, and that this process is not complete by 2 years of age.

[A case of lung abscess during chemotherapy for testicular tumor].

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Hayashi, Yujiro; Miyago, Naoki; Takeda, Ken; Yamaguchi, Yuichiro; Nakayama, Masashi; Arai, Yasuyuki; Kakimoto, Ken-ichi; Nishimura, Kazuo

2014-05-01

32-year-old man was seen in a clinic because of prolonged cough and slight-fever. Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal lymph node metastases from right testicular tumor was suspected by positron emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ cell tumor (embryonal carcinoma + seminoma, pT2N1M1b), and classified into the intermediate risk group according to International Germ Cell Cancer Collaborative Group. He underwent 4 cycles of chemotherapy with bleomycin, etoposide and cisplatin (BEP therapy). During BEP therapy, sputum with foul odor appeared and chest CT scan revealed lung abscess with a necrotic lesion of metastatic tumor. The lung abscess was treated successfully with antibiotics.

Prospective assessment of MRI for imaging retroperitoneal metastases from testicular germ cell tumours

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Sohaib, S.A. [Department of Radiology, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey (United Kingdom)], E-mail: aslam.sohaib@rmh.nhs.uk; Koh, D.M. [Department of Radiology, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Barbachano, Y. [Department of Computing and Statistics, Royal Marsden Hospital, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Parikh, J.; Husband, J.E.S. [Department of Radiology, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Dearnaley, D.P.; Horwich, A.; Huddart, R. [Department of Academic Urology Unit, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey (United Kingdom)

2009-04-15

Aim: To determine the sensitivity of magnetic resonance imaging (MRI) in the detection of retroperitoneal lymph nodes in patients with testicular germ cell tumours (TGCT). Methods and materials: A prospective study of 52 patients (mean age 34 years, range 18-54 years) was performed. Imaging of the retroperitoneum was performed using multidetector computed tomography (CT) and 1.5 T MRI systems. The CT and MRI images were read independently by three observers. The number, size, and site of enlarged nodes ({>=}10 mm maximum short axis diameter) were recorded. Retroperitoneal nodal detection on MRI was compared to CT. Results: Twenty-two (42%) of the 52 patients had no retroperitoneal disease; in remaining 30 patients 51 enlarged nodes were identified. On a per patient basis readers 1, 2, and 3 identified nodal disease in 28 of 29, 29 of 30, and 24 of 30 patients, respectively, using MRI compared to CT. Thus for experienced radiologists (readers 1 and 2) MRI is comparable to CT for nodal detection (i.e., this study excludes MRI being inferior to CT with 80% power and 5% type 1 error). Conclusion: MRI offers an alternative method for staging the retroperitoneum in young patients being followed for TGCT and has the major advantage of avoiding exposure to ionizing radiation.

Genetic changes associated with testicular cancer susceptibility.

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Pyle, Louise C; Nathanson, Katherine L

2016-10-01

Testicular germ cell tumor (TGCT) is a highly heritable cancer primarily affecting young white men. Genome-wide association studies (GWAS) have been particularly effective in identifying multiple common variants with strong contribution to TGCT risk. These loci identified through association studies have implicated multiple genes as associated with TGCT predisposition, many of which are unique among cancer types, and regulate processes such as pluripotency, sex specification, and microtubule assembly. Together these biologically plausible genes converge on pathways involved in male germ cell development and maturation, and suggest that perturbation of them confers susceptibility to TGCT, as a developmental defect of germ cell differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Serum hormones that regulate the reproductive axis in men with testicular germ cell cancer and its impact on fertility].

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Tovar-Rodríguez, José María; Chávez-Zúñiga, Irma; Bañuelos-Ávila, Leticia; Vargas-Hernández, Víctor Manuel; Acosta-Altamirano, Gustavo

2014-01-01

Epidemiological studies treat testicular germ cancer as a single disease, the behavior of the two histological types of cancer; seminoma and nonseminoma have differences in reproductive hormone secretion and impair fertility differently. To demonstrate that the serum concentration of pituitary hormones involved in fertility and spermatogenesis in the affected male is different in the two histological types. Were determined by radioimmunoassay or inmunoradiometric assay, luteinizing hormone, follicle stimulating hormone, total testosterone, prolactin, estradiol, human chorionic gonadotropin and alpha fetoprotein in 37 patients with germ cell cancer (15 seminoma and 22 nonseminoma) and 35 controls. We analyzed the semen of patients, and were questioned about paternity before the cancer diagnosis. Age was higher in patients with seminoma cancer, showed decreased luteinizing hormone, follicle stimulating hormone, and testosterone and increased estradiol and prolactin in nonseminoma compared with seminoma. In patients with nonseminoma they had 9 children, 5 were oligozoospermic, 3 azoospermic and 6 normal concentration, 8 did not provide sample, seminoma group they had eight children, only one azoospermic, nine normal concentration, and 5 did not provide sample . The hormonal behavior is different in men with nonseminoma compared with seminoma, so that the negative impact on the reproductive axis and fertility is higher in cases of non-seminoma.

A possible new syndrome with growth-hormone secreting pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familial testicular germ cell malignancy: A case report

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Mai Phuong L

2007-03-01

Full Text Available Abstract Background Germ-cell testicular cancer has not been definitively linked to any known hereditary cancer susceptibility disorder. Familial testicular cancer in the presence of other findings in affected and unaffected family members might indicate a previously-unidentified hereditary cancer syndrome. Case presentation The patient was diagnosed with a left testicular seminoma at age 28, and treated with left orchiectomy followed by adjuvant cobalt radiation. His family history is significant for testicular seminoma in his son, bladder cancer in his sister, and lipomatosis in his father. His evaluation as part of an etiologic study of familial testicular cancer revealed multiple colon polyps (adenomatous, hyperplastic, and hamartomatous first found in his 50 s, multiple lipomas, multiple hyperpigmented skin lesions, left kidney cancer diagnosed at age 64, and a growth-hormone producing pituitary adenoma with associated acromegaly diagnosed at age 64. The patient underwent genetic testing for Cowden syndrome (PTEN gene, Carney complex (PRKAR1A gene, and multiple endocrine neoplasia syndrome type 1 (MEN1 gene; no deleterious mutations were identified. Discussion The constellation of benign and malignant neoplasms in the context of this patient's familial testicular cancer raised the possibility that these might be manifestations of a known hereditary susceptibility cancer syndrome; however, genetic testing for the three syndromes that were most likely to explain these findings did not show any mutation. Alternatively, this family's phenotype might represent a novel neoplasm susceptibility disorder. This possibility cannot be evaluated definitively on the basis of a single case report; additional observations and studies are necessary to investigate this hypothesis further.

N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes.

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Ji, Yan-Li; Wang, Hua; Zhang, Cheng; Zhang, Ying; Zhao, Mei; Chen, Yuan-Hua; Xu, De-Xiang

2013-03-01

Cadmium (Cd) is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum (ER) stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine (NAC), an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 (2.0 mg kg(-1)). As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling (TUNEL). However, the administration of NAC alleviated Cd-induced germ cell apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 (GRP78), an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2α (eIF2α), a downstream target of the double-stranded RNA-activated kinase-like ER kinase (PERK) pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein (XBP)-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response (UPR). Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein (CHOP) and phosphorylation of c-Jun N-terminal kinase (JNK), two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.

[Primary testicular rhabdomyosarcoma: A case report].

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Mejía-Salas, Jesús Alberto; Sánchez-Corona, Hugo; Priego-Niño, Alejandro; Cárdenas-Rodríguez, Edgar; Sánchez-Galindo, José Antonio

Rhabdomyosarcoma is the most common sarcoma of soft tissues in childhood and adolescence, with an annual incidence of 4-7 cases per million children aged 15. Embryonal rhabdomyosarcoma is common in adults younger than 30 years, and are usually presented as a large painless, palpable mass (> 5cm). Survival in the case of paratesticular sarcoma in men is approximately 50%. Male 27 years of age with no history of importance, was seen in a clinic with an increased, painless, left testicular volume 3 years onset. Intrascrotal left testicle increased volume, with dimensions of 20×12×8cm, a stone and left inguinal node in induratum measuring 2×2cm. Microscopically, it showed a pattern of an embryonal rhabdomyosarcoma with left inguinal node metastases. Early diagnosis of testicular tumours, and especially of primary intratesticular rhabdomyosarcomas, and aggressive surgical treatment in combination with chemotherapy reduces the incidence of local recurrence and may improve the rate of disease-free survival and overall survival in adult patients with metastases. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Urethral metastasis from non-seminomatous germ cell tumor: a case report

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Joffe Johnathan

2011-01-01

Full Text Available Abstract Introduction We present a case of nonseminomatous germ cell tumor of the testes with acute urinary retention secondary to urethral metastasis. This presentation, and similar cases of urethral metastasis from this tumor, have not been reported previously. Case presentation A 35-year-old Caucasian man presented to hospital with a history of acute urinary retention. On examination he was found to have right testicular enlargement with raised β-human chorionic gonadotrophin, serum α-fetoprotein and lactate dehydrogenase levels. He underwent radical left inguinal orchidectomy and histology confirmed a nonseminomatous germ cell tumor of the testes. Cystoscopy carried out due to urinary retention showed penile metastasis and the biopsy confirmed metastatic malignant undifferentiated teratoma. Staging computed tomography scan and magnetic resonance imaging of the pelvis showed pulmonary, pelvic nodal, ischial and penile metastasis. The diagnosis of the International Germ Cell Cancer Collaborative Group of poor prognosis metastatic nonseminomatous germ cell tumor was made, following which he received four cycles of bleomycin, etoposide and cisplatin chemotherapy with curative intent. He had a complete marker and an excellent radiological response. He is currently under follow up. Conclusion The unusual presentation of lymphovascular spread in this case of nonseminomatous germ cell tumor highlights the need to include routine pelvic imaging in the assessment and follow up of testicular cancer.

Postnatal risk factors for testicular cancer: The EPSAM case-control study.

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Moirano, Giovenale; Zugna, Daniela; Grasso, Chiara; Mirabelli, Dario; Lista, Patrizia; Ciuffreda, Libero; Segnan, Nereo; Merletti, Franco; Richiardi, Lorenzo

2017-11-01

Testicular cancer is considered to originate from an impaired differentiation of fetal germ cells, but puberty could represent another time window of susceptibility. Our study aimed at investigating the association between environmental exposures acting during puberty/adolescence (13-19 years of age) and the risk of testicular cancer. We used data of the EPSAM study, a case-control study on germ-cell testicular cancer conducted in the province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Histologically confirmed cases (n = 255) and controls (n = 459) completed a postal questionnaire focusing in particular on the pubertal period (namely age 13 years) with questions on physical activity (competitive sports, gardening), lifestyle (alcohol consumption, smoking), occupational history and medical conditions. All analyses were adjusted for the matching variables, cryptorchidism and educational level. Having done at least one competitive sport during puberty (odds ratio [OR]: 0.72, 95% confidence interval: 0.52-1.00), gardening activities during puberty (OR: 0.62, 0.42-0.94) and having a lower weight than peers during puberty (OR: 0.64, 0.42-0.97) were all inversely associated with the risk of testicular cancer. No evidence of association between smoking or alcohol consumption during puberty and the risk of testicular cancer was observed. Regarding agriculture-related occupations, we found an association with the risk of testicular cancer both for occasional jobs during puberty (OR: 2.40, 95% CI: 1.08-5.29) and ever employment in adolescence (OR: 2.59, 95% CI: 0.83-8.10). Our results suggest that postnatal exposures could play a role in testicular cancer aetiology, at least when acting in puberty or adolescence. © 2017 UICC.

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

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Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

2014-01-01

to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

Human testicular insulin-like factor 3: in relation to development, reproductive hormones and andrological disorders

DEFF Research Database (Denmark)

Bay, K; Andersson, A-M

2011-01-01

the endocrine regulation of this process. INSL3 is, along with testosterone, a major secretory product of testicular Leydig cells. In addition to its crucial function in testicular descent, INSL3 is suggested to play a paracrine role in germ cell survival and an endocrine role in bone metabolism. INSL3...

Towards Optimal Diagnosis of Type II Germ Cell Tumors

NARCIS (Netherlands)

J.A. Stoop (Hans)

2011-01-01

textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies

Endogenous biotin expression in renal and testicular tumours and literature review.

Science.gov (United States)

Fahmy, Nader; Woo, Mark; Alameldin, Mona; Lee, Joe King; MacDonald, Kyle; Goneau, Lee W; Cadieux, Peter; Burton, Jeremy; Pautler, Stephen

2014-07-01

The aim of this study was to examine endogenous biotin levels in tumour specimens collected from patients with renal and testicular tumours and compare them to the surrounding non-neoplastic surgical margin. Frozen samples were obtained from the Ontario Tumour Bank. Renal and testicular tumour tissue were included in this study. Normal tissue from the negative surgical margins of each tumour served as a control. Biotin detection in tissue specimens was determined using immunohistochemistry (IHC). Specimens collected from 56 patients (36 men and 20 women) were included in this study. Histopathology of the 52 renal tumours included 31 (60%) conventional type RCC, 5 (10%) chromophobe RCC, 5 (10%) papillary RCC, 1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4 testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non seminomatous germ cell tumours. No biotin signal was perceived in all tested tumour samples. Endogenous biotin expression was detected in the matching non-neoplastic surgical margin of tested renal tissues. This lack of staining may prove to be a valuable tool in future studies.

Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer

DEFF Research Database (Denmark)

Hammer, Niels A; Hansen, Thomas v O; Byskov, Anne Grete

2005-01-01

prompted us to examine their possible involvement in testicular neoplasia. IMPs were detected primarily in germ-cell neoplasms, including preinvasive testicular carcinoma in situ, classical and spermatocytic seminoma, and nonseminomas, with particularly high expression in undifferentiated embryonal...... carcinoma. The relative expression of IMP1, IMP2 and IMP3 varied among tumor types and only IMP1 was detected in all carcinoma in situ cells. Thus IMPs, and in particular IMP1, may be useful auxiliary markers of testicular neoplasia....

[Treatment of testicular cancer].

Science.gov (United States)

Droz, Jean-Pierre; Boyle, Helen; Culine, Stéphane; Fizazi, Karim; Fléchon, Aude; Massard, Christophe

2013-12-01

Germ-cell tumours (GCTs) are the most common type of cancer in young men. Since the late 1970s, disseminated GCT have been a paradigm for curable metastatic cancer and metastatic GCTs are highly curable with cisplatin-based chemotherapy followed by surgical resection of residual masses. Patients' prognosis is currently assessed using the International Germ-Cell Consensus Classification (IGCCC) and used to adapt the burden of chemotherapy. Approximately 20% of patients still do not achieve cure after first-line cisplatin-based chemotherapy, and need salvage chemotherapy (high dose or standard dose chemotherapy). Clinical stage I testicular cancer is the most common presentation and different strategies are proposed: adjuvant therapies, surgery or surveillance. During the last three decades, clinical trials and strong international collaborations lead to the development of a consensus in the management of GCTs.

Onco-testicular sperm extraction: birth of a healthy baby after fertility preservation in synchronous bilateral testicular cancer and azoospermia.

Science.gov (United States)

Roque, M; Sampaio, M; Salles, P G de Oliveira; Geber, S

2015-05-01

Testicular germ cell tumours (TGCT) represent 1%-1.5% of all male neoplasms, and they have the highest prevalence among men between 15 and 35 years old. Synchronous bilateral disease is a rare presentation, and the ratio of metachronous to synchronous bilateral disease is about 4 : 1. Several studies have suggested a correlation between male infertility and testicular cancer, with a 20-fold increase in the incidence of testicular cancer in infertile patients compared with the general population. At the time of diagnosis, 50%-75% of patients with unilateral TGCT present with subfertility; almost 13% of the patients are azoospermic before treatment, and up to two-thirds of patients become azoospermic following adjuvant cancer therapies. Therefore, fertility preservation should be considered in all oncological treatments. The only available option to preserve the reproductive potential in azoospermic patients with testicular cancer is to perform an onco-testicular sperm extraction (onco-TESE) before cancer treatment. In this paper, we describe a rare case of a patient with synchronous bilateral testicular cancer and azoospermia who was submitted to onco-TESE, sperm cryopreservation, and which was followed by the delivery of a healthy baby after intracytoplasmic sperm injection (ICSI), emphasising the importance of fertility preservation in oncology patients. © 2014 Blackwell Verlag GmbH.

Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development

DEFF Research Database (Denmark)

Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders

2015-01-01

in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which......Development of human gonads is a sex-dimorphic process which evolved to produce sex-specific types of germ cells. The process of gonadal sex differentiation is directed by the action of the somatic cells and ultimately results in germ cells differentiating to become functional gametes through...

Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information

DEFF Research Database (Denmark)

Edsgärd, D; Scheel, M; Hansen, N T

2011-01-01

-associated genes among loci targeted by CNVs. The top-ranked candidate, RLN1, encoding a Relaxin-H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular...... GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome-wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed....... Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population-wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible role...

Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information

DEFF Research Database (Denmark)

Edsgard, Stefan Daniel; Scheel, M.; Hansen, Niclas Tue

2011-01-01

‐associated genes among loci targeted by CNVs. The top‐ranked candidate, RLN1, encoding a Relaxin‐H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular...... GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome‐wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed...... and spermatids. Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population‐wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible...

Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats.

Science.gov (United States)

Kilarkaje, Narayana; Mousa, Alyaa M; Al-Bader, Maie M; Khan, Khalid M

2013-10-01

To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction. In vivo study. Research laboratory. Adult male and female Sprague-Dawley rats. The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se). Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period. At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels. The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer

Science.gov (United States)

Turnbull, Clare; Rapley, Elizabeth A.; Seal, Sheila; Pernet, David; Renwick, Anthony; Hughes, Deborah; Ricketts, Michelle; Linger, Rachel; Nsengimana, Jeremie; Deloukas, Panagiotis; Huddart, Robert A.; Bishop, D Timothy; Easton, Douglas F.; Stratton, Michael R.; Rahman, Nazneen

2013-01-01

We conducted a genome-wide association study for testicular germ cell tumor genotyping 298,782 SNPs in 979 cases and 4,947 controls from the UK and replicating associations in a further 664 cases and 3,456 controls. We identified three novel susceptibility loci, two of which include genes that are involved in telomere regulation. We identified two independent signals within the TERT-CLPTM1L locus on chromosome 5 which has been associated with multiple other cancers (rs4635969, OR=1.54 (95%CI 1.33-1.79), P=1.14×10−23 and rs2736100, OR 1.33 (1.18-1.50) P=7.55 ×10−15). We also identified a locus on chromosome 12 (rs2900333, OR=1.27 (95%CI 1.12-1.44), P=6.16×10−10) that contains ATF7IP, a regulator of TERT expression. Finally we identified a locus on chromosome 9 (rs755383, OR=1.37 (95%CI 1.21-1.55), P=1.12×10−23) containing the sex determination gene DMRT1, which has been linked with teratoma susceptibility in mice. PMID:20543847

Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.

Science.gov (United States)

Pierpont, Timothy M; Lyndaker, Amy M; Anderson, Claire M; Jin, Qiming; Moore, Elizabeth S; Roden, Jamie L; Braxton, Alicia; Bagepalli, Lina; Kataria, Nandita; Hu, Hilary Zhaoxu; Garness, Jason; Cook, Matthew S; Capel, Blanche; Schlafer, Donald H; Southard, Teresa; Weiss, Robert S

2017-11-14

Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Germ cell transplantation in an azoospermic Klinefelter bull.

Science.gov (United States)

Joerg, Hannes; Janett, Fredi; Schlatt, Stefan; Mueller, Simone; Graphodatskaya, Daria; Suwattana, Duangsmorn; Asai, Mika; Stranzinger, Gerald

2003-12-01

Germ cell transplantation is a technique that transfers donor testicular cells into recipient testes. A population of germ cells can colonize the recipient testis, initiate spermatogenesis, and produce sperm capable of fertilization. In the present study, a nonmosaic Klinefelter bull was used as a germ cell recipient. The donor cell suspension was introduced into the rete testis using ultrasound-guided puncture. A pulsatile administration of GnRH was performed to stimulate spermatogenesis. The molecular approach to detect donor cells was done by a quantitative polymerase chain reaction with allele discrimination based on a genetic mutation between donor and recipient. Therefore, a known genetic mutation, associated with coat-color phenotype, was used to calculate the ratio of donor to recipient cells in the biopsy specimens and ejaculates for 10 mo. After slaughtering, meiotic preparations were performed. The injected germ cells did not undergo spermatogenesis. Six months after germ cell transplantation, the donor cells were rejected, which indicates that the donor cells could not incorporate in the testis. The hormone stimulation showed that the testosterone-producing Leydig cells were functionally intact. Despite subfertility therapy, neither the recipient nor the donor cells underwent spermatogenesis. Therefore, nonmosaic Klinefelter bulls are not suitable as germ cell recipients. Future germ cell recipients in cattle could be mosaic Klinefelters, interspecies hybrids, bulls with Sertoli cell-only syndrome, or bulls with disrupted germ cell migration caused by RNA interference.

Lifetime growth and risk of testicular cancer.

Science.gov (United States)

Richiardi, Lorenzo; Vizzini, Loredana; Pastore, Guido; Segnan, Nereo; Gillio-Tos, Anna; Fiano, Valentina; Grasso, Chiara; Ciuffreda, Libero; Lista, Patrizia; Pearce, Neil; Merletti, Franco

2014-08-01

Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (testicular cancer for tall (>180 cm) vs. short (testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence. © 2013 UICC.

Diagnostic markers for germ cell neoplasms

DEFF Research Database (Denmark)

Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E

2015-01-01

This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic diff...... of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up....

Effects of chemical-induced DNA damage on male germ cells

Energy Technology Data Exchange (ETDEWEB)

Holme, J.A.; Bjoerge, C.; Trbojevic, M.; Olsen, A.K.; Brunborg, G.; Soederlund, E.J. [National Inst. of Public Health, Oslo (Norway). Dept. of Environmental Medicine; Bjoeras, M.; Seeberg, E. [National Hospital, Oslo (Norway). Dept. of Microbiology; Scholz, T.; Dybing, E.; Wiger, R. [National Hospital, Oslo (Norway). Inst. for Surgical Research and Surgical Dept. B

1998-12-31

Several recent studies indicate declines in sperm production, as well as increases in the incidence of genitourinary abnormalities such as testicular cancer, cryptorchidism and hypospadias. It is not known if these effects are due to exposure to chemical pollutants or if other ethiological factors are involved. Animal studies indicate that chemicals will induce such effects by various genetic, epigenetic or non-genetic mechanisms. Recently, much attention has been focused on embryonic/fetal exposure to oestrogen-mimicking chemicals (Toppari et al., 1996). However, the possibility that chemicals may cause reproductive toxicity by other mechanisms such as interactions with DNA, should not be ignored. DNA damage in germ cells may lead to the production of mutated spermatozoa, which in turn may result in spontaneous abortions, malformations and/or genetic defects in the offspring. Regarding the consequences of DNA alterations for carcinogenesis it is possible that genetic damage may occur germ cells, but the consequences are not expressed until certain genetic events occur in postnatal life. Transmission of genetic risk is best demonstrated by cancer-prone disorders such as hereditary retinoblastoma and the Li-Fraumeni syndrome. A number of experiments indicate that germ cells and proliferating cells may be particularly sensitive to DNA damaging agents compared to other cells. Furthermore, several lines of evidence have indicated that one of the best documented male reproductive toxicants, 1,2-dibrome-3-chloropropane (DBCP), causes testicular toxicity through DNA damage. It is possible that testicular cells at certain maturational stages are more subject to DNA damage, have less efficient DNA repair, or have different thresholds for initiating apoptosis following DNA damage than other cell types. (orig.)

Germ cell neoplasia in situ (GCNIS)

DEFF Research Database (Denmark)

Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad

2016-01-01

The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagr......The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity...... and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce...

Apparent diffusion coefficient values and dynamic contrast enhancement patterns in differentiating seminomas from nonseminomatous testicular neoplasms

Energy Technology Data Exchange (ETDEWEB)

Tsili, Athina C., E-mail: a_tsili@yahoo.gr [Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Sylakos, Anastasios, E-mail: anasylakos@yahoo.gr [Department of Urology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Ntorkou, Alexandra, E-mail: alexdorkou@yahoo.com [Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Stavrou, Sotirios, E-mail: s.sotiris@yahoo.gr [Department of Urology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Astrakas, Loukas G., E-mail: astrakas@uoi.gr [Department of Medical Physics, Medical School, University of Ioannina, 45110 Ioannina (Greece); Sofikitis, Nikolaos, E-mail: akrosnin@hotmail.com [Department of Urology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Argyropoulou, Maria I., E-mail: margyrop@cc.uoi.gr [Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina (Greece)

2015-07-15

Highlights: • Functional MRI in the characterization of testicular germ cell tumors was assessed. • ADC values proved useful in the characterization of testicular germ cell tumors. • Testicular germ cell tumors had similar enhancement patterns of dynamic MRI. - Abstract: Introduction: The aim of this study is to investigate the role of apparent diffusion coefficient (ADC) values and dynamic contrast enhancement (DCE) patterns in differentiating seminomas from nonseminomatous germ cell tumors (NSGCTs). Materials and methods: The MRI examinations of the scrotum of 26 men with histologically proven testicular GCTs were reviewed. DWI was performed in all patients, using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b-values of 0 and 900 s/mm{sup 2}. Subtraction DCE-MRI was performed in 20 cases using a 3D fast-field echo sequence after gadolinium administration. Time-signal intensity curves were created and semi-quantitative parameters (peak enhancement, time to peak, wash-in and wash-out rate) were calculated. The Student's t-test was used to compare the mean values of ADC, peak enhancement, time to peak, wash-in and wash-out rate between seminomas and NSGCTs. ROC analysis was also performed. Results: Histopathology disclosed the presence of 15 seminomas and 11 NSGCTs. The mean ± s.d. of ADC values (× 10{sup −3} mm{sup 2}/s) of seminomas (0.59 ± 0.009) were significantly lower than those of NSGCTs (0.90 ± 0.33) (P = 0.01). The optimal ADC cut-off value was 0.68 × 10{sup −3} mm{sup 2}/s. No differences between the two groups were observed for peak enhancement (P = 0.18), time to peak (P = 0.63) wash-in rate (P = 0.32) and wash-out rate (P = 0.18). Conclusions: ADC values may be used to preoperatively differentiate seminomas from NSGCTs.

Apparent diffusion coefficient values and dynamic contrast enhancement patterns in differentiating seminomas from nonseminomatous testicular neoplasms

International Nuclear Information System (INIS)

Tsili, Athina C.; Sylakos, Anastasios; Ntorkou, Alexandra; Stavrou, Sotirios; Astrakas, Loukas G.; Sofikitis, Nikolaos; Argyropoulou, Maria I.

2015-01-01

Highlights: • Functional MRI in the characterization of testicular germ cell tumors was assessed. • ADC values proved useful in the characterization of testicular germ cell tumors. • Testicular germ cell tumors had similar enhancement patterns of dynamic MRI. - Abstract: Introduction: The aim of this study is to investigate the role of apparent diffusion coefficient (ADC) values and dynamic contrast enhancement (DCE) patterns in differentiating seminomas from nonseminomatous germ cell tumors (NSGCTs). Materials and methods: The MRI examinations of the scrotum of 26 men with histologically proven testicular GCTs were reviewed. DWI was performed in all patients, using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b-values of 0 and 900 s/mm 2 . Subtraction DCE-MRI was performed in 20 cases using a 3D fast-field echo sequence after gadolinium administration. Time-signal intensity curves were created and semi-quantitative parameters (peak enhancement, time to peak, wash-in and wash-out rate) were calculated. The Student's t-test was used to compare the mean values of ADC, peak enhancement, time to peak, wash-in and wash-out rate between seminomas and NSGCTs. ROC analysis was also performed. Results: Histopathology disclosed the presence of 15 seminomas and 11 NSGCTs. The mean ± s.d. of ADC values (× 10 −3 mm 2 /s) of seminomas (0.59 ± 0.009) were significantly lower than those of NSGCTs (0.90 ± 0.33) (P = 0.01). The optimal ADC cut-off value was 0.68 × 10 −3 mm 2 /s. No differences between the two groups were observed for peak enhancement (P = 0.18), time to peak (P = 0.63) wash-in rate (P = 0.32) and wash-out rate (P = 0.18). Conclusions: ADC values may be used to preoperatively differentiate seminomas from NSGCTs

Long-term cultures of testicular biopsies from boys with cryptorchidism

DEFF Research Database (Denmark)

Larsen, Hans-Peter Ejler; Thorup, Jørgen; Skovgaard, Lene Theil

2002-01-01

BACKGROUND: A long-term culture system of testicular biopsies from boys with undescended testes was established to evaluate the effect of gonadotrophins on germ cell survival and growth. METHODS: Biopsies from 25 boys with cryptorchidism, aged 1.1-9.9 years, were obtained at the time of surgery. ...

DNA repair studies in mammalian germ cells

International Nuclear Information System (INIS)

Sega, G.A.; Owens, J.G.

1984-01-01

In submammalian test systems, nitrosocarbamates (NEC) are 100-fold more mutagenic than are their corresponding nitrosourea homologues. To learn more about its interaction with germ-cell DNA in the mouse testis, male mice were given i.p. injections of NEC. Testicular injections of [ 3 H]dThd were given along with the NEC. Sixteen days after treatment, sperm were recovered from the caudal epididymides and assayed for an unscheduled-DNA-synthesis

Cigarette smoking during early pregnancy reduces the number of embryonic germ and somatic cells

DEFF Research Database (Denmark)

Mamsen, Linn; Lutterodt, M C; Andersen, Elisabeth Anne Wreford

2010-01-01

BACKGROUND: Cigarette smoking during pregnancy is associated with negative reproductive consequences for male fetuses in adult life such as reduced testicular volume and sperm concentration. The present study evaluates the number of germ and somatic cells present in human embryonic first-trimeste......BACKGROUND: Cigarette smoking during pregnancy is associated with negative reproductive consequences for male fetuses in adult life such as reduced testicular volume and sperm concentration. The present study evaluates the number of germ and somatic cells present in human embryonic first......-trimester gonads in relation to maternal smoking. METHODS: The study includes 24 human first-trimester testes, aged 37-68 days post-conception, obtained from women undergoing legal termination of pregnancy. A questionnaire was used to obtain information about smoking and drinking habits during pregnancy. Validated...... confounders such as alcohol and coffee consumption (P = 0.002). The number of germ cells in embryonic gonads, irrespective of gender, was also significantly reduced by 41% (95% CI 58-19%, P = 0.001) in exposed versus non-exposed embryonic gonads. CONCLUSIONS: Prenatal exposure to maternal cigarette smoke...

The Danish Testicular Cancer database

DEFF Research Database (Denmark)

Daugaard, Gedske; Kier, Maria Gry Gundgaard; Bandak, Mikkel

2016-01-01

AIM: The nationwide Danish Testicular Cancer database consists of a retrospective research database (DaTeCa database) and a prospective clinical database (Danish Multidisciplinary Cancer Group [DMCG] DaTeCa database). The aim is to improve the quality of care for patients with testicular cancer (TC......) in Denmark, that is, by identifying risk factors for relapse, toxicity related to treatment, and focusing on late effects. STUDY POPULATION: All Danish male patients with a histologically verified germ cell cancer diagnosis in the Danish Pathology Registry are included in the DaTeCa databases. Data...... collection has been performed from 1984 to 2007 and from 2013 onward, respectively. MAIN VARIABLES AND DESCRIPTIVE DATA: The retrospective DaTeCa database contains detailed information with more than 300 variables related to histology, stage, treatment, relapses, pathology, tumor markers, kidney function...

Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

Energy Technology Data Exchange (ETDEWEB)

Jiang, Xin; Bai, Yang; Zhang, Zhiguo [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Xin, Ying, E-mail: xiny@jlu.edu.cn [KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021 (China); Cai, Lu, E-mail: l0cai001@louisville.edu [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States)

2014-09-01

Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

International Nuclear Information System (INIS)

Jiang, Xin; Bai, Yang; Zhang, Zhiguo; Xin, Ying; Cai, Lu

2014-01-01

Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

Characterization of testicular germ cell tumors: Whole-lesion histogram analysis of the apparent diffusion coefficient at 3T.

Science.gov (United States)

Min, Xiangde; Feng, Zhaoyan; Wang, Liang; Cai, Jie; Yan, Xu; Li, Basen; Ke, Zan; Zhang, Peipei; You, Huijuan

2018-01-01

To assess the values of parameters derived from whole-lesion histograms of the apparent diffusion coefficient (ADC) at 3T for the characterization of testicular germ cell tumors (TGCTs). A total of 24 men with TGCTs underwent 3T diffusion-weighted imaging. Fourteen tumors were pathologically confirmed as seminomas, and ten tumors were pathologically confirmed as nonseminomas. Whole-lesion histogram analysis of the ADC values was performed. A Mann-Whitney U test was employed to compare the differences in ADC histogram parameters between seminomas and nonseminomas. Receiver operating characteristic analysis was used to identify the cutoff values for each parameter for differentiating seminomas from nonseminomas; furthermore, the area under the curve (AUC) was calculated to evaluate the diagnostic accuracy. The median of 10th, 25th, 50th, 75th, and 90th percentiles and mean, minimum and maximum ADC values were all significantly reduced for seminomas compared with nonseminomas (phistogram analysis of ADCs might be used for preoperative characterization of TGCTs. Copyright © 2017 Elsevier B.V. All rights reserved.

Preliminary Study on Testicular Germ Cell Transplantation of Endemic Species Oryzias celebensis

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Andriani, I.; Agustiani, F.; Hassan, M.; Parenrengi, A.; Inoue, K.

2018-03-01

The research has been conducted to study some technical steps for male germ-plasm from endemic fish species such as some species of Oryzias fish in Indonesia to preserve and propagate through germ cell transplantation technology. For preliminary research, the study was started with germ cell characterization of testes, cryopreservation of TGC and the transplantation of Oryzias celebensis as candidates for surrogate broodstock of Oryzias fish male germ plasm. The data analized included the potential number of TGC as donor, the viability of cryopreserved TGC in two types of cryoprotectans and the survival rate of O.celebensis larvae as recipient after transplantation. The result showed that the average amount of TGC yielded after dissociation was 131000 ± 31349 with 74.2 % viability of TGC each. Cryoprotectan10% DMSO +glucose yielded higher viable of TGC. More than 80 % of O.celebensis larvae survived after transplantation. In conclusion, these preliminary data of O.celebensis as surrogate broodstock candidate will support the application of TGC transplantation technology in Oryzias endemic species.

Testicular dysgenesis syndrome and the origin of carcinoma in situ testis

DEFF Research Database (Denmark)

Sonne, Si Brask; Kristensen, David Møbjerg; Novotny, Guy W

2008-01-01

foetus, but the genetic background may also play a role. The morphological similarity of carcinoma in situ (CIS) cells (the precursor of the majority of invasive testicular cancers) with primordial germ cells and gonocytes, and overlap in expression of protein markers suggests an origin of CIS from...

Clinical characteristics and oncological outcomes of testicular cancer patients registered in 2005 and 2008: the first large-scale study from the Cancer Registration Committee of the Japanese Urological Association.

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Miki, Tsuneharu; Kamoi, Kazumi; Fujimoto, Hiroyuki; Kanayama, Hiro-omi; Ohyama, Chikara; Suzuki, Kazuhiro; Nishiyama, Hiroyuki; Eto, Masatoshi; Naito, Seiji; Fukumori, Tomoharu; Kubota, Yoshinobu; Takahashi, Satoru; Mikami, Kazuya; Homma, Yukio

2014-08-01

To describe the clinical and pathological characteristics and oncological outcomes of testicular cancer diagnosed in Japan, we report the results of the testicular cancer registration carried out by the Japanese Urological Association. Testicular cancer survey was conducted by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. The survey included details such as age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, initial treatment and clinical outcomes. We analyzed 1121 cases of testicular primary germ cell tumor among 1157 registered patients. The median age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for 61.9% and 38.1%, respectively. Measurements of tumor markers were documented in 98.6% of the patients; however, there was an unsatisfactory uniform measurement of human chorionic gonadotropin, which made it difficult to evaluate the International Germ Cell Consensus Classification in all patients. The 1- and 3-year overall survival rates from the entire cohort were 98.3% and 96.8%, respectively. According to the International Germ Cell Consensus Classification, 3-year overall survival rates in the good, intermediate, and poor prognosis group were 99.1%, 100% and 79.9%, respectively. The present report is the first large-scale study of the characteristics and survival of testicular cancer patients in Japan based on multi-institutional registry data, and showed a good prognosis even in an advanced stage. The improved survival attributed substantially to accurate diagnosis and effective multimodal treatment. © 2014 The Japanese Urological Association.

Risk stratification for venous thromboembolism in patients with testicular germ cell tumors.

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Angelika Bezan

Full Text Available Patients with testicular germ cell tumors (TGCT have an increased risk for venous thromboembolism (VTE. We identified risk factors for VTE in this patient cohort and developed a clinical risk model.In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich.Venous thromboembolic events occurred in 34 (5.2% patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS and a retroperitoneal lymphadenopathy (RPLN were the strongest predictors of VTE (p<0.0001. As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence: cS IA-B 8/463 patients (1.7%, cS IS-IIB 5/86 patients (5.9%, cS IIC 3/21 patients (14.3% and cS IIIA-C 15/70 patients (21.4%. This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence: cS IA-B (0.5%, cS IS-IIB (6.0%, cS IIC (11.1% and cS IIIA-C (19.1%. Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007.According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy.

Association of Torsion With Testicular Cancer: A Retrospective Study.

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Uguz, Sami; Yilmaz, Sercan; Guragac, Ali; Topuz, Bahadır; Aydur, Emin

2016-02-01

Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported with the association of torsion in surgical specimens, and the published data remain scant on the association of torsion with testicular tumors. By retrospective medical record review, we identified 32 patients who had been diagnosed with testicular torsion, 20 of whom had undergone orchiectomy. Of these 20 patients, 2 were diagnosed with a malignancy. Our study, the largest case series to date, has shown an association between testicular torsion and testicular cancer of 6.4%. Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported in association with torsion in surgical specimens. However, the published data remain scant on the association between torsion and the presence of testicular tumors. The present retrospective study explored the association between torsion and testicular cancer in patients with testicular torsion undergoing orchiectomy during scrotal exploration. A medical record review was performed of patients who had had a diagnosis of testicular torsion from January 2003 to February 2015. The clinicopathologic characteristics of the patients were recorded. A total of 32 patients were identified. Their mean age was 21.1 years (range, 7-39 years). All the patients had unilateral testicular torsion, which affected the left side in 17 and the right side in 15. Manual detorsion was successful in 6 patients, and 26 patients underwent emergency surgery with testicular detorsion (6 fixation surgery and 20 orchiectomy). The type of incision was scrotal in 6, inguinal in 10, and unspecified in 4. Pathologic examination of the orchiectomy specimens showed malignancy in 2 cases (seminoma and malign mixed germ cell tumor). To the best of our knowledge, the present single-center case series is the largest case series to date of

Secondary malignant neoplasms in testicular cancer survivors.

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Curreri, Stephanie A; Fung, Chunkit; Beard, Clair J

2015-09-01

Testicular cancer is the most common cancer among men aged 15 to 40 years, and the incidence of testicular cancer is steadily increasing. Despite successful treatment outcomes and the rate of survival at 5 to 10 years being 95%, survivors can experience late effects of both their cancer and the treatment they received, including secondary malignant neoplasms (SMNs). We discuss the development of non-germ cell SMNs that develop after diagnosis and treatment of testicular cancer and their effect on mortality. Patients diagnosed with testicular cancer frequently choose postoperative surveillance if they are diagnosed with clinical stage I disease. These patients may experience an increased risk for developing SMNs following radiation exposure from diagnostic imaging. Similarly, radiotherapy for testicular cancer is associated with increased risks of developing both solid tumors and leukemia. Studies have reported that patients exposed to higher doses of radiation have an increased risk of developing SMNs when compared with patients who received lower doses of radiation. Patients treated with chemotherapy also experience an increased risk of developing SMNs following testicular cancer, though the risk following chemotherapy and radiation therapy combined is not well described. A large population-based study concluded that the rate ratios for both cancer-specific and all-cause mortality for SMNs among testicular cancer survivors were not significantly different from those of matched first cancers. Although it is known that patients who receive adjuvant chemotherapy or radiotherapy or who undergo routine diagnostic or follow-up imaging for a primary testicular cancer are at an increased risk for developing SMNs, the extent of this risk is largely unknown. It is critically important that research be conducted to determine this risk and its contributing factors as accurately as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

Testicular development in mice lacking receptors for follicle stimulating hormone and androgen.

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Peter J O'Shaughnessy

Full Text Available Post-natal testicular development is dependent on gonadotrophin and androgen stimulation. Follicle stimulating hormone (FSH acts through receptors (FSHR on the Sertoli cell to stimulate spermatogenesis while androgens promote testis growth through receptors (AR on the Sertoli cells, Leydig cells and peritubular myoid cells. In this study we have examined the effects on testis development of ablating FSHRs (FSHRKO mice and/or ARs ubiquitously (ARKO mice or specifically on the Sertoli cells (SCARKO mice. Cell numbers were measured using stereological methods. In ARKO mice Sertoli cell numbers were reduced at all ages from birth until adulthood. FSHR ablation also caused small reductions in Sertoli cell numbers up to day 20 with more marked effects seen in the adult. Germ cell numbers were unaffected by FSHR and/or AR ablation at birth. By day 20 ubiquitous AR or FSHR ablation caused a marked reduction in germ cell numbers with a synergistic effect of losing both receptors (germ cell numbers in FSHRKO.ARKO mice were 3% of control. Germ cell numbers in SCARKO mice were less affected. By adulthood, in contrast, clear synergistic control of germ cell numbers had become established between the actions of FSH and androgen through the Sertoli cells. Leydig cell numbers were normal on day 1 and day 5 in all groups. By day 20 and in adult animals total AR or FSHR ablation significantly reduced Leydig cell numbers but Sertoli cell specific AR ablation had no effect. Results show that, prior to puberty, development of most testicular parameters is more dependent on FSH action than androgen action mediated through the Sertoli cells although androgen action through other cells types is crucial. Post-pubertally, germ cell numbers and spermatogenesis are dependent on FSH and androgen action through the Sertoli cells.

Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ

DEFF Research Database (Denmark)

Rajpert-De Meyts, E; Kvist, Majbrit; Skakkebaek, N E

1996-01-01

Testicular carcinoma in situ (CIS) is the precursor of germ cell tumours in adults, except for spermatocytic seminoma. The mechanism of the progression from premalignant CIS to invasive and overt tumours is largely unknown. There are currently two main hypotheses: one is that CIS can progress dir...

Leydig cell function in boys following treatment for testicular relapse of acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Blatt, J.; Sherins, R.J.; Niebrugge, D.; Bleyer, W.A.; Poplack, D.G.

1985-01-01

Current practice for achieving local control of testicular relapse in males with acute lymphoblastic leukemia (ALL) includes the use of 2,400-rad testicular radiation. Although this therapy is known to cause germ cell depletion, it has been assumed that it does not alter testicular secretion of testosterone. To test this assumption, the authors measured gonadotropin and testosterone levels in seven boys with ALL who had been treated with radiation for clinically apparent testicular relapse. In four of seven boys, testicular relapse was bilateral with overt involvement of one testicle and microscopic involvement of the other. Three of these four boys demonstrated delayed sexual maturation, and in addition to elevated follicle-stimulating hormone (FSH) concentrations, testosterone levels were low and luteinizing hormone levels were elevated compared with controls. These data indicate that boys with overt testicular leukemia who are treated with 2,400-rad testicular radiation are at risk for Leydig cell dysfunction. However, the relative contributions of radiation, prior chemotherapy, and leukemic infiltration to this dysfunction remain to be clarified

Dependence of serum hormones (T, FSH, LH) on morphometric testicular findings recorded from patients after chemotherapy and radiotherapy for malignant testicular tumours

International Nuclear Information System (INIS)

Barth, V.; Schoenfelder, M.

1990-01-01

Correlations which exist between morphometric parameters of remaining testicular tissue, on the one hand, and serum hormones on the other (testosterone = T, follicle-stimulating hormone = FSH, luteinising hormone = LH), depending on therapeutic action taken on patients for malignant testicular tumours, seem to suggest that decline in epithelial thickness together with increase in wall thickness leads to rise in FSH. No unambiguous relations, on the other hand, were found to exist between testosterone or luteotrophic hormone and morphometric findings. Hence, FSH seems to characterize the severity of damage to germ epithelium and thus the degree of impairment to spermatogenesis. FSH may be accepted as a criterion for fertility disorders in sexually active men. (author)

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation.

Science.gov (United States)

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation. Copyright 2009 Wiley-Liss, Inc.

Impaired testicular function in patients with carcinoma-in-situ of the testis

DEFF Research Database (Denmark)

Petersen, P M; Giwercman, A; Hansen, S W

1999-01-01

for testicular cancer. Biopsy of the contralateral testis had showed CIS in a group of 24 patients and no evidence of CIS in the other group of 30 patients. Semen quality and serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were compared in these two groups of men...... after orchidectomy but before further treatment for testicular cancer. RESULTS: Significantly higher LH levels (median, 8.1 IU/L v 4.8 IU/L; P ...PURPOSE: To elucidate the biologic association between germ cell neoplasia and testicular dysfunction, through investigation of Leydig cell function and semen quality in men with carcinoma-in-situ (CIS) of the testis. PATIENTS AND METHODS: We examined two groups of men, unilaterally orchidectomized...

Alveolar Soft Part Sarcoma of Urinary Bladder Occurring as a Second Primary Malignancy: A Case Report and Literature Review

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Manint Usawachintachit

2016-01-01

Full Text Available We report a case of bladder alveolar soft part sarcoma in an 18-year-old Thai male patient who had been treated with testicular radiation and systemic chemotherapy for acute lymphoblastic leukemia with testicular relapse. He presented with recurrent dysuria and gross hematuria. Cystoscopy revealed a 2-centimeter irregular sessile mass at the bladder base adjacent to left ureteral orifice. Transurethral resection of the tumor was performed. The histopathological diagnosis was alveolar soft part sarcoma. Chest and abdominal computed tomography showed no evidence of metastasis. He was treated with partial cystectomy and left ureteral reimplantation with negative surgical margin. No evidence of recurrence was found during a 28-month follow-up period with surveillance cystoscopy and computed tomography of the chest and abdomen.

Unusually Located Stroke After Chemotherapy in Testicular Germ Cell Tumors

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Braulio Alexander Martinez MD

2015-06-01

Full Text Available Testicular cancer is a type of malignancy that affects young adults and has high rates of cure; however, as any malignancy, it is associated with an increased risk of ischemic or hemorrhagic cerebrovascular disease, given the systemic tumor effects or side effects of chemotherapy, which in turn increases morbidity, functional impairment, and additional risk of early death.

Influence of vitamin D on cisplatin sensitivity in testicular germ cell cancer-derived cell lines and in a NTera2 xenograft model

DEFF Research Database (Denmark)

Jørgensen, Anne; Blomberg Jensen, Martin; Nielsen, John Erik

2013-01-01

The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has anti-proliferative, pro-apoptotic, and pro-differentiating effects in somatic cancer cells in vitro and in vivo. 1,25(OH)(2)D(3) also augments the anti-tumor effects of several chemotherapeutic agents, including...... cisplatin, which may have clinical relevance. Given the pro-differentiation effect of vitamin D recently demonstrated in testicular germ cell tumors (TGCTs), we hypothesized that 1,25(OH)(2)D(3) could be a beneficial adjunctive to existing chemotherapy regime used to treat these tumors. In this study, cell...... survival effects of 1,25(OH)(2)D(3), another pro-differentiation compound, retinoic acid and cisplatin were investigated in TGCT-derived cell lines in vitro. 1,25(OH)(2)D(3) augmented the effect of cisplatin in an embryonal carcinoma-derived cell line (NTera2), possibly through downregulation...

Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

International Nuclear Information System (INIS)

Takubo, Keiyo; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio

2006-01-01

Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16 Ink4a activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16 Ink4a -mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16 Ink4a -mediated senescence

Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours

DEFF Research Database (Denmark)

Sonne, Si Brask; Herlihy, Amy S; Hoei-Hansen, Christina E

2006-01-01

Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis. PDPN encodes podoplanin (Aggrus...... gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has...

Quantitative histology of germ cells in the undescended testes of human fetuses, neonates and infants

DEFF Research Database (Denmark)

Cortes, D; Thorup, J M; Beck, B L

1995-01-01

PURPOSE: We investigated the number of germ cells per tubular cross section and testicular weight in cryptorchid fetuses, neonates and infants, and characterized additional abnormalities. MATERIALS AND METHODS: Our series comprised 35 fetuses and 58 boys with cryptorchidism, and 22 normal fetuses...

The attractive Achilles heel of germ cell tumours : an inherent sensitivity to apoptosis-inducing stimuli

NARCIS (Netherlands)

Spierings, DCJ; de Vries, EGE; Vellenga, E; de Jong, S

Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin-containing chemotherapy. The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin. In fact,

The Effects of α-Lipoic Acid against Testicular Ischemia-Reperfusion Injury in Rats

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Seda Ozbal

2012-01-01

Full Text Available Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of α-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.

Thrombosis of abdominal aorta during cisplatin-based chemotherapy of testicular seminoma - a case report

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Gehrckens Ralf

2009-12-01

Full Text Available Abstract Background Vascular complications occurring during cisplatin-based chemotherapy of germ cell tumours are inadequately recognized to date. Case Presentation A 49 year old man with advanced seminoma underwent two courses of chemotherapy according to the PEB regimen. Upon restaging, two thrombotic deposits were noted in the descending part of the thoracic aorta and in the infrarenal abdominal aorta, respectively. Although thrombotic plaques caused aortic occlusion of about 30%, no clinical signs of malperfusion of limbs were registered. The patient was placed on anticoagulant therapy. Six months after completion of chemotherapy, thrombotic deposits had completely resolved. In the absence of other predisposing factors, it must be assumed that cisplatin-based chemotherapy represented a strong stimulus for arterial thrombosis in the aorta. Conclusions This is the first case of endo-aortic thrombosis during chemotherapy for testicular germ cell cancer. Providers of chemotherapy must be aware of arterial thrombosis even in young patients with testicular cancer.

Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology.

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Pérez, Cecilia V; Gómez, Leticia G; Gualdoni, Gisela S; Lustig, Livia; Rabinovich, Gabriel A; Guazzone, Vanesa A

2015-07-30

Galectin-1 (Gal-1), a proto-type member of galectin family, is highly expressed in immune privileged sites, including the testis. However, in spite of considerable progress the relevance of endogenous and exogenous Gal-1 in testis pathophysiology have not yet been explored. Here we evaluated the in vivo roles of Gal-1 in experimental autoimmune orchitis (EAO), a well-established model of autoimmune testicular inflammation associated with subfertility and infertility. A significant reduction in the incidence and severity of EAO was observed in mice genetically deficient in Gal-1 (Lgals1(-/-)) versus wild-type (WT) mice. Testicular histopathology revealed the presence of multifocal testicular damage in WT mice characterized by an interstitial mononuclear cell infiltrate and different degrees of germ cell sloughing of seminiferous tubules. TUNEL assay and assessment of active caspase-3 expression, revealed the prevalence of apoptotic spermatocytes mainly localized in the adluminal compartment of seminiferous tubules in EAO mice. A significant increased number of TUNEL-positive germ cells was detected in EAO testis from WT compared with Lgals1(-/-) mice. In contrast, exogenous administration of recombinant Gal-1 to WT mice undergoing EAO attenuated the severity of the disease. Our results unveil a dual role of endogenous versus exogenous Gal-1 in the control of autoimmune testis inflammation.

Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish.

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Lin, Qiaohong; Mei, Jie; Li, Zhi; Zhang, Xuemei; Zhou, Li; Gui, Jian-Fang

2017-11-01

Spermatogenesis is a fundamental process in male reproductive biology and depends on precise balance between self-renewal and differentiation of male germ cells. However, the regulative factors for controlling the balance are poorly understood. In this study, we examined the roles of amh and dmrt1 in male germ cell development by generating their mutants with Crispr/Cas9 technology in zebrafish. Amh mutant zebrafish displayed a female-biased sex ratio, and both male and female amh mutants developed hypertrophic gonads due to uncontrolled proliferation and impaired differentiation of germ cells. A large number of proliferating spermatogonium-like cells were observed within testicular lobules of the amh -mutated testes, and they were demonstrated to be both Vasa- and PH3-positive. Moreover, the average number of Sycp3- and Vasa-positive cells in the amh mutants was significantly lower than in wild-type testes, suggesting a severely impaired differentiation of male germ cells. Conversely, all the dmrt1 -mutated testes displayed severe testicular developmental defects and gradual loss of all Vasa-positive germ cells by inhibiting their self-renewal and inducing apoptosis. In addition, several germ cell and Sertoli cell marker genes were significantly downregulated, whereas a prominent increase of Insl3-positive Leydig cells was revealed by immunohistochemical analysis in the disorganized dmrt1 -mutated testes. Our data suggest that amh might act as a guardian to control the balance between proliferation and differentiation of male germ cells, whereas dmrt1 might be required for the maintenance, self-renewal, and differentiation of male germ cells. Significantly, this study unravels novel functions of amh gene in fish. Copyright © 2017 by the Genetics Society of America.

Testicular immunohistochemical and Ultrastructural changes associated with chronic cholestasis in rats: Effect of ursodeoxycholic acid.

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Mahmoud, Yomna I

2015-09-01

Testicular atrophy has been commonly reported in patients with chronic liver diseases. Ursodeoxycholic acid is the most widely used drug for the treatment of many liver diseases. However, its effect on testicular ultrastructure associated with chronic cholestasis has never been studied. Thus, this study aimed to assess how chronic obstructive jaundice affects the testicular ultrastructure and whether it affects the androgen receptor or the proliferating cell nuclear antigen. The role of ursodeoxycholic acid was also investigated. Cholestasis was induced by bile duct ligation. Samples were collected 4weeks postoperative. Testicular changes were assessed using immunohistochemistry and transmission electron microscopy. Chronic cholestasis resulted in testicular atrophy evidenced by shrinkage and deformation of seminiferous tubules, thickening of peritubular boundaries, vacuolation, disorganization of germ cells, and maturation arrest. This was accompanied by decreased immunoreactivity of androgen receptors and proliferating cell nuclear antigen. Administration of ursodeoxycholic acid improved the testicular morphology and reversed cholestasis-induced immunohistochemical and ultrastructural changes. Ursodeoxycholic acid can improve the testicular ultrastructure and restore the spermatogenic process in rats with chronic cholestasis. These findings support the clinical application of ursodeoxycholic acid in cholestatic patients especially those with hypogonadism. Copyright © 2015. Published by Elsevier Inc.

EMMPRIN/CD147-encriched membrane vesicles released from malignant human testicular germ cells increase MMP production through tumor-stroma interaction.

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Milia-Argeiti, Eleni; Mourah, Samia; Vallée, Benoit; Huet, Eric; Karamanos, Nikos K; Theocharis, Achilleas D; Menashi, Suzanne

2014-08-01

Elevated levels of EMMPRIN/CD147 in cancer tissues have been correlated with tumor progression but the regulation of its expression is not yet understood. Here, the regulation of EMMPRIN expression was investigated in testicular germ cell tumor (TGCTs) cell lines. EMMPRIN expression in seminoma JKT-1 and embryonal carcinoma NT2/D1 cell lines was determined by Western blot, immunofluorescence and qRT-PCR. Membrane vesicles (MVs) secreted from these cells, treated or not with EMMPRIN siRNA, were isolated by differential centrifugations of their conditioned medium. MMP-2 was analyzed by zymography and qRT-PCR. The more aggressive embryonic carcinoma NT2/D1 cells expressed more EMMPRIN mRNA than the seminoma JKT-1 cells, but surprisingly contained less EMMPRIN protein, as determined by immunoblotting and immunostaining. The protein/mRNA discrepancy was not due to accelerated protein degradation in NT2/D1 cells, but by the secretion of EMMPRIN within MVs, as the vesicles released from NT2/D1 contained considerably more EMMPRIN than those released from JKT-1. EMMPRIN-containing MVs obtained from NT2/D1, but not from EMMPRIN-siRNA treated NT2/D1, increased MMP-2 production in fibroblasts to a greater extent than those from JKT-1 cells. The data presented show that the more aggressive embryonic carcinoma cells synthesize more EMMPRIN than seminoma cells, but which they preferentially target to secreted MVs, unlike seminoma cells which retain EMMPRIN within the cell membrane. This cellular event points to a mechanism by which EMMPRIN expressed by malignant testicular cells can exert its MMP inducing effect on distant cells within the tumor microenvironment to promote tumor invasion. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Candidate Genes for Testicular Cancer Evaluated by In Situ Protein Expression Analyses on Tissue Microarrays

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Rolf I. Skotheim

2003-09-01

Full Text Available By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.

Cardiac Murmur Prompting Diagnosis of Metastatic Nonseminomatous Germ Cell Testicular Neoplasia in an 18-Year-Old Patient

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Steve Y. Chung

2005-01-01

Full Text Available Most retroperitoneal tumors such as renal cell carcinoma have been associated with tumor thrombus extending into the renal vein, inferior vena cava (IVC, and heart. The retroperitoneal metastatic potential of testicular tumors is well known. We report here the first instance of a cardiac murmur prompting diagnosis of metastatic testicular neoplasia in an 18-year-old patient. Chemotherapy was delayed and after successful surgical resection of the ventricular mass, the patient recovered uneventfully. This case underscores the need to pursue abnormal cardiac exams in newly diagnosed testicular cancer patients.

Surveillance for stage I nonseminoma testicular cancer

DEFF Research Database (Denmark)

Daugaard, Gedske; Gundgaard, Maria Gry; Mortensen, Mette Saksø

2014-01-01

PURPOSE: To describe treatment results in a large cohort with stage I nonseminoma germ cell cancer (NSGCC) treated in a surveillance program. PATIENTS AND METHODS: From January 1, 1984, to December 31, 2007, 1,226 patients with stage I NSGCC, including high-risk patients with vascular invasion......, were observed in a surveillance program. RESULTS: The relapse rate after orchiectomy alone was 30.6% at 5 years. Presence of vascular invasion together with embryonal carcinoma and rete testis invasion in the testicular primary identified a group with a relapse risk of 50%. Without risk factors....... Relapses after 5 years were seen in 0.5% of the whole cohort or in 1.6% of relapsing patients. The majority of relapses (94.4%) belonged to the good prognostic group according to the International Germ Cell Cancer Collaborative Group classification. The disease-specific survival at 15 years was 99...

Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

Science.gov (United States)

Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Hornick, Jason L; Woda, Bruce; Yu, Hongbo

2016-08-01

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

Testicular microlithiasis and testicular cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Rafaelsen, Søren Rafael; Møller, Henrik

2016-01-01

Purpose To perform a systematic literature review to assess whether the occurrence of testicular microlithiasis (TML) in conjunction with other risk factors is associated with testicular cancer. Methods A systematic literature search was performed of original articles in English published 1998...... In total, 282 abstracts in were identified. Based on title and abstract the eligibility was assessed and 31 studies were included. Five conditions in relation to TML and testicular cancer emerged: Down syndrome, McCune–Albright syndrome, cryptorchidism, infertility and familial disposition of testicular...... cancer. Conclusion Data support the conclusion that TML is not an independent risk factor for testicular cancer but associated with testicular cancer through other conditions. In male infertility, TML appears to be related to an increased risk of testicular cancer possibly as part of a testicular...

Cisplatin in cancer therapy: molecular mechanisms of action

OpenAIRE

Dasari, Shaloam; Tchounwou, Paul Bernard

2014-01-01

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA da...

Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

Directory of Open Access Journals (Sweden)

Michelle Welsh

2010-10-01

Full Text Available Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO. Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

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Zhang, Shun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Jiang, Chunyang [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Department of Thoracic Surgery, Tianjin Union Medicine Centre, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin (China); Liu, Hongliang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Guan, Zhizhong [Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou (China); Zeng, Qiang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Cui, Yushan; Yu, Linyu [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Wang, Zhenglun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Wang, Aiguo, E-mail: wangaiguo@mails.tjmu.edu.cn [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China)

2013-09-01

Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress. �

Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

International Nuclear Information System (INIS)

Zhang, Shun; Jiang, Chunyang; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Zhenglun; Wang, Aiguo

2013-01-01

Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress. �

Extragonadal germ cell tumors. Clinicaopathologic findings, staging and treatment experience in 14 patients

Energy Technology Data Exchange (ETDEWEB)

Berkmen, F.; Peker, A.F.; Ayyildiz, A.; Basay, S.; Arik, A.I.; Ugur, I. [Ankara Oncology Education and Research Hospital, Dept. of Urologic Oncology and Radiotherapy, Ankara (Turkey)

2000-09-01

Extragonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR), one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. Our modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The necessity of a uniform staging system and treatment programs are discussed.

Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism

DEFF Research Database (Denmark)

Cortes, D; Visfeldt, J; Thorup, J M

2001-01-01

of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found......: Erythropoietin (Eprex) 100 IU/kg were administered subcutaneously weekly for 3 months prior to surgery in two cryptorchid boys, 6 months old and 1 year 9 months old, respectively, with renal function impairment. RESULTS: The number of spermatogonia per tubular cross-section in testicular biopsies was unusually...... that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells. MATERIALS AND METHODS...

Lindane induces testicular apoptosis in adult Wistar rats through the involvement of Fas-FasL and mitochondria-dependent pathways

International Nuclear Information System (INIS)

Saradha, B.; Vaithinathan, S.; Mathur, P.P.

2009-01-01

Lindane, an organochlorine pesticide, is known to impair testicular functions and fertility. To elucidate the mechanism(s) underpinning the gonadal effects of lindane, we sought to investigate the levels of apoptosis-related proteins, namely cytochrome c, caspase-3 and-9, Fas and FasL in the testis of adult rats. Furthermore, the study aims to delineate whether nuclear factor kappa B (NF-κB) is involved in meditating the testicular effects of lindane. Animals were administered with a single dose of lindane (5 mg/kg body weight) and sacrificed at specific post-treatment intervals (0, 3, 6, 12, 24 and 72 h). Significant elevations in the levels of cytosolic cytochrome c with a parallel increase in pro-caspase-9 were observed as early as 6 h following exposure. Time-dependent elevations in the levels of Fas, FasL and caspase-3 were observed. Immunofluorescence studies revealed increased colocalization of Fas and caspase-3 in peritubular germ cells. FasL levels were increased in Sertoli and peritubular germ cells. The cytoplasmic levels of NF-κB p65 decreased from 3 h following exposure with a maximal decline at 12 and 24 h. Changes in the localization of NF-κB were observed with maximal nuclear translocation in germ cells at 12 and 24 h. Terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) assay revealed a time-dependent increase in the number of apoptotic cells. Taken together, the data illustrate induction of testicular apoptosis in adult rats following exposure to a single dose of lindane. Early activation of NF-κB in contrast to late increase in Fas expression suggests a pro-apoptotic role of NF-κB in testicular response to lindane

Significant calendar period deviations in testicular germ cell tumors indicate that postnatal exposures are etiologically relevant.

Science.gov (United States)

Speaks, Crystal; McGlynn, Katherine A; Cook, Michael B

2012-10-01

The current working model of type II testicular germ cell tumor (TGCT) pathogenesis states that carcinoma in situ arises during embryogenesis, is a necessary precursor, and always progresses to cancer. An implicit condition of this model is that only in utero exposures affect the development of TGCT in later life. In an age-period-cohort analysis, this working model contends an absence of calendar period deviations. We tested this contention using data from the SEER registries of the United States. We assessed age-period-cohort models of TGCTs, seminomas, and nonseminomas for the period 1973-2008. Analyses were restricted to whites diagnosed at ages 15-74 years. We tested whether calendar period deviations were significant in TGCT incidence trends adjusted for age deviations and cohort effects. This analysis included 32,250 TGCTs (18,475 seminomas and 13,775 nonseminomas). Seminoma incidence trends have increased with an average annual percentage change in log-linear rates (net drift) of 1.25 %, relative to just 0.14 % for nonseminoma. In more recent time periods, TGCT incidence trends have plateaued and then undergone a slight decrease. Calendar period deviations were highly statistically significant in models of TGCT (p = 1.24(-9)) and seminoma (p = 3.99(-14)), after adjustment for age deviations and cohort effects; results for nonseminoma (p = 0.02) indicated that the effects of calendar period were much more muted. Calendar period deviations play a significant role in incidence trends of TGCT, which indicates that postnatal exposures are etiologically relevant.

Ketoconazole-induced testicular damage in rats reduced by Gentiana extract.

Science.gov (United States)

Amin, Amr

2008-04-01

Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. The protective effect of Gentiana (GEN) extract (Gentiana lutea) against KET-induced testicular damage was evaluated in male Wistar rats. GEN extract was administered orally (1g/kgbwt/day) for 26 days. Three weeks after extract administration, KET was co-administered intraperitoneally at a dose of 100mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. KET also induced severe testicular histopathological lesions such as degeneration of the seminiferous tubules and depletion of germ cells. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidants (catalase (CAT) and superoxide dismutase (SOD)) were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of GEN extract. This study suggests a protective role of GEN extract that could be attributed to its antioxidant properties.

Two Case Reports of Benign Testicular Mesothelioma and Review of the Literature

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Cristobal Ramirez Sevilla

2017-01-01

Full Text Available Mesothelioma is usually diagnosed in people over the age of 50 with large history of asbestos-related exposure. It is frequently located in pleural cavity, peritoneum, and pericardium. At the testicles the mesothelioma had been reported first in 1957 like a malignant non-germ-cells tumor. The objective is to present two case reports of benign testicular mesothelioma and review of the literature.

Secondary Malignancy As A Manifestation Of Late Toxicity Of Curative Treatment For Testicular Cancer

International Nuclear Information System (INIS)

Reckova, M.; Kakalejcik, M.; Beniak, J.; Boljesikova, E.

2008-01-01

The case presents the patient with a diagnosis of bladder carcinosarcoma. He was diagnosed 42 years after adjuvant middle abdominal and pelvic radiotherapy for testicular seminoma. We discuss the problem of late toxicity of oncology treatment in patients with potentially curative germ cell tumors of testes together with diagnosis and treatment of patients with bladder carcinoma and carcinosarcoma. (author)

Prevalence of small testicular hyperechogenic foci in subgroups of 382 non-vasectomized, azoospermic men

DEFF Research Database (Denmark)

Fedder, Jens

2017-01-01

Testicular hyperechogenic foci (THF) are associated with Klinefelter’s syndrome, cryptorchidism, infertility, and testicular germ cell neoplasia. The aims of the study were to evaluate THF in relation to etiology of azoospermia and to Sertoli cell dysfunction. The structures inside the scrotum...... technique for detection of cytokeratin-18 (CK-18). The prevalence of THF was 13.4%. uTHF was found in 11 men (2.9%), the pattern was bilateral in four while other four had bTHF in the other testis. pTHF was detected in eight cases (2.1%), and except for one case with Klinefelter’s syndrome, pTHF was in all...

Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43.

Science.gov (United States)

Sarkar, D; Singh, S K

2017-07-01

Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose

ASSESSMENT OF MALE INFERTILITY BY TESTICULAR BIOPSY IN SOUTHERN ODISHA

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Sujata Naik

2017-10-01

Full Text Available BACKGROUND Infertility continues to be a significant problem since ages. Studies suggest that the problem affects 8-12% of couples across the globe, and among these affected couples, approximately 50% cases are contributed by the male partner. Semen analysis is the first investigation that indicates towards male factor in infertility. Finding the cause of infertility in cases of severe oligozoospermia and azoospermia by evaluating testicular biopsies has now become essential with the availability of Assisted Reproductive Techniques (ART, which gives information about the level of spermatogenesis. The present study was undertaken to detect the histological findings in cases of male infertility in this geographic region. MATERIALS AND METHODS A prospective cross-sectional study was undertaken in which testicular biopsies received from 52 infertile male patients with seminogram impressions of very severe oligozoospermia and azoospermia constituted the study group. Detailed clinical data including the LH. FSH and testosterone hormone levels were recorded. Tissue samples were routinely processed and Haematoxylin and Eosin stained were made. Modified Johnsen scoring was used to categorise each case. RESULTS 86.5% cases in the study group were found to have azoospermia and rest 13.5% cases had severe oligozoospermia. All the cases were histologically classified into six categories- obstructive pathology 25 of 52 cases (48.1%, pure germ cell aplasia 14 of 52 cases (26.9%, maturation arrest 7 of 52 cases (13.5%, atrophic testis 4 of 52 cases (7.7%, hypospermatogenesis 1 of 52 cases (1.9% and inconclusive in 1 of 52 cases. Serum FSH and serum LH levels were found significantly raised in cases of pure germ cell aplasia and atrophic testis in contrast cases of obstructive aetiology had normal levels. Modified Johnsen scoring values were 9 in cases with obstructive pathology, 1/2 only in cases of pure germ cell aplasia and atrophic testes and 3 to 6 in cases

Pathogenesis of Testicular Germ Cell Tumors from a Developmental Point of View

NARCIS (Netherlands)

K. Biermann (Katharina)

2010-01-01

textabstractCurrent classification systems of human germ cell tumors (GCTs) are based on histological composition. In the group of nonseminomas, different variants of teratoma (somatic differentiation), yolk sac tumor and choriocarcinoma (extra-embryonic differentiation), are recognized, as well

Diffusion-weighted magnetic resonance imaging in the characterization of testicular germ cell neoplasms: Effect of ROI methods on apparent diffusion coefficient values and interobserver variability

Energy Technology Data Exchange (ETDEWEB)

Tsili, Athina C., E-mail: a_tsili@yahoo.gr [Department of Clinical Radiology, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece); Ntorkou, Alexandra, E-mail: alexdorkou@hotmail.com [Department of Clinical Radiology, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece); Astrakas, Loukas, E-mail: astrakas@uoi.gr [Department of Medical Physics, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece); Xydis, Vasilis, E-mail: vxydis@cc.uoi.gr [Department of Clinical Radiology, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece); Tsampalas, Stavros, E-mail: stamp@gmail.com [Department of Urology, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece); Sofikitis, Nikolaos, E-mail: akrosnin@hotmail.com [Department of Urology, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece); Argyropoulou, Maria I., E-mail: margyrop@cc.uoi.gr [Department of Clinical Radiology, Medical School, University of Ioannina, University Campus, 45110, Ioannina (Greece)

2017-04-15

Highlights: • Seminomas have lower mean ADC compared to NSGCNs. • Round ROI is accurate in characterizing TGCNS. • ROI shape has no significant effect on interobserver variability. - Abstract: Introduction: To evaluate the difference in apparent diffusion coefficient (ADC) measurements at diffusion-weighted (DW) magnetic resonance imaging of differently shaped regions-of-interest (ROIs) in testicular germ cell neoplasms (TGCNS), the diagnostic ability of differently shaped ROIs in differentiating seminomas from nonseminomatous germ cell neoplasms (NSGCNs) and the interobserver variability. Materials and methods: Thirty-three TGCNs were retrospectively evaluated. Patients underwent MR examinations, including DWI on a 1.5-T MR system. Two observers measured mean tumor ADCs using four distinct ROI methods: round, square, freehand and multiple small, round ROIs. The interclass correlation coefficient was analyzed to assess interobserver variability. Statistical analysis was used to compare mean ADC measurements among observers, methods and histologic types. Results: All ROI methods showed excellent interobserver agreement, with excellent correlation (P < 0.001). Multiple, small ROIs provided the lower mean ADC in TGCNs. Seminomas had lower mean ADC compared to NSGCNs for each ROI method (P < 0.001). Round ROI proved the most accurate method in characterizing TGCNS. Conclusion: Interobserver variability in ADC measurement is excellent, irrespective of the ROI shape. Multiple, small round ROIs and round ROI proved the more accurate methods for ADC measurement in the characterization of TGCNs and in the differentiation between seminomas and NSGCNs, respectively.

Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

Directory of Open Access Journals (Sweden)

De Gendt Karl

2009-08-01

Full Text Available Abstract Background Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM. Methods This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs on the Sertoli cells (SCARKO, mice with a ubiquitous loss of androgen ARs (ARKO, hypogonadal (hpg mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO and ARKO (hpg.ARKO mice. Results Microscopic TM was seen in 94% of hpg.ARKO mice (n = 16 and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n = 11 of hpg testes (mean 2 +/- 0.5 per testis and 30% (n = 10 of hpg.SCARKO testes (mean 8 +/- 6 per testis. No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice. Conclusion We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression.

Autophagy-associated proteins BAG3 and p62 in testicular cancer.

Science.gov (United States)

Bartsch, Georg; Jennewein, Lukas; Harter, Patrick N; Antonietti, Patrick; Blaheta, Roman A; Kvasnicka, Hans-Michael; Kögel, Donat; Haferkamp, Axel; Mittelbronn, Michel; Mani, Jens

2016-03-01

Testicular germ cell tumors (TGCT) represent the most common malignant tumor group in the age group of 20 to 40-years old men. The potentially curable effect of cytotoxic therapy in TGCT is mediated mainly by the induction of apoptosis. Autophagy has been discussed as an alternative mechanism of cell death but also of treatment resistance in various types of tumors. However, in TGCT the expression and role of core autophagy-associated factors is hitherto unknown. We designed the study in order to evaluate the potential role of autophagy-associated factors in the development and progression of testicular cancers. Eighty-four patients were assessed for autophagy (BAG3, p62) and apoptosis (cleaved caspase 3) markers using immunohistochemistry (IHC) on tissue micro- arrays. In addition, western blot analyses of frozen tissue of seminoma and non-seminoma were performed. Our findings show that BAG3 was significantly upregulated in seminoma as compared to non-seminoma but not to normal testicular tissue. No significant difference of p62 expression was detected between neoplastic and normal tissue or between seminoma and non-seminoma. BAG3 and p62 showed distinct loco‑regional expression patterns in normal and neoplastic human testicular tissues. In contrast to the autophagic markers, apoptosis rate was significantly higher in testicular tumors as compared to normal testicular tissue, but not between different TGCT subtypes. The present study, for the first time, examined the expression of central autophagy proteins BAG3 and p62 in testicular cancer. Our findings imply that in general apoptosis but not autophagy induction differs between normal and neoplastic testis tissue.

Effects of intratesticular zinc gluconate treatment on testicular dimensions, echodensity, histology, sperm production, and testosterone secretion in American black bears (Ursus americanus).

Science.gov (United States)

Brito, Leonardo F C; Sertich, Patricia L; Rives, William; Knobbe, Marc; Del Piero, Fabio; Stull, Gordon B

2011-05-01

Eight adult American black bears were used to evaluate the effects of chemical castration by intratesticular zinc gluconate treatment on testicular dimensions, echodensity, histology, sperm production, and testosterone secretion. Treatment did not affect testicular dimensions and did not result in decreased resting or GnRH-stimulated testosterone secretion. Multifocal hyperchoic areas in the testicular parenchyma were observed on ultrasound examination, and white foci were observed on gross pathology examination after zinc gluconate treatment. Histologically, there were normal seminiferous tubules containing either round or elongated spermatids, along with abnormal tubules in all bears after treatment. Vacuolation of the seminiferous epithelium, sloughing of germ cells into the tubules' lumen, presence of multinuclear giant cells, and reduced height of the seminiferous epithelium with missing generations of germ cells were commonly observed. The most severe testicular changes were multifocal and included fibrosis, complete degeneration of the seminiferous epithelium with shrinkage of the tubule, and sperm stasis. Epididymal sperm reserve was 982.74 ± 654.16 × 10(6) sperm (mean ± SEM) and motile sperm were observed in the epididymis of all but one of the bears. In conclusion, although intratesticular zinc gluconate treatment in black bears resulted in testicular degenerative changes detected by ultrasound and histology examinations, sperm production was not completely ablated. We inferred that normal fertility might have been compromised, but treatment unlikely resulted in sterility. Copyright © 2011. Published by Elsevier Inc.

Testicular Microlithiasis: Is It Associated with Testicular Cancer?

Science.gov (United States)

... Is there a link between testicular microlithiasis and testicular cancer? Answers from Erik P. Castle, M.D. Testicular microlithiasis (tes-TIK-yoo- ... studies show a relationship between testicular microlithiasis and testicular cancer. However, it remains unclear whether having testicular microlithiasis ...

Extra gonadal germ cell tumors. Clinico pathologic findings, staging and treatment experience in 14 patients

Energy Technology Data Exchange (ETDEWEB)

Berkmen, F.; Peker, F.; Ayyildiz, A.; Basay, S.; Arik, A.I.; Ugur, I. [Ankara, Oncology Education and Research Hospital, Dept. of Urologic Oncology and Radiotherapy (Turkey)

2000-09-01

Extra gonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR), one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. The modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The necessity of a uniform staging system and treatment programs are discussed.

Importance of photoperiods in determining temporal pattern of annual testicular events in rose-ringed parakeet (Psittacula krameri).

Science.gov (United States)

Maitra, S K; Dey, M

1992-01-01

Male rose-ringed parakeets (Psittacula krameri) were transferred to a long photoperiod (LP; LD 16:8) or a short photoperiod (SP; LD 8:16) for 45 or 90 days on four dates corresponding to the beginnings of different reproductive phases in an annual testicular cycle, and testicular responsiveness was evaluated by comparison with the testicular volume, weight, seminiferous tubular diameter, and germ cell profiles of birds in a natural photoperiod (NP). Exposure of birds to LP during the progressive phase (November) led to precocious maturation of testes after 45 days, but induced regression at 90 days. After showing retarded gametogenic functions at 45 days, parallel (November) SP birds exhibited an accelerated rate of germ cell formation at day 90. During the prebreeding phase (January), there were no remarkable differences in any features of testes among NP. LP, and SP birds at 45 days, but gonadal involution in LP parakeets and active spermatogenesis in SP birds occurred after 90 days. The testes did not show any response to LP or SP for 45 and 90 days when the birds were transferred to altered photoperiods during the breeding (March) and preparatory (June) phases, indicating that the parakeets were photorefractory for at least 6 months (March through September). The results also suggest that initiation and termination of seasonal gametogenic activity in parakeets are possibly functions of endogenous rhythmicity or extraphotoperiodic environmental factors. Duration of light may have certain influences on the attainment of annual peak in spermatogenesis, but in all probability the species has a low photoperiod threshold for induction of testicular growth.

Do environmental factors play a role in the aetiology of carcinoma in situ testis and the testicular dysgenesis syndrome?

Science.gov (United States)

Sonne, S B; Hoei-Hansen, C E; Fisher, J S; Leffers, H; Rajpert-de Meyts, E; Skakkebaek, N E

2004-01-01

The hypothesis of the Testicular Dysgenesis Syndrome (TDS), first suggested in 2001, propose that several disorders of the male reproductive system such as infertility, hypospadias, cryptorchidism and testicular cancer are all symptoms of TDS, which is most likely initiated during early foetal development, and may be provoked by external factors such as endocrine disruptors in addition to genetic predisposition. Testicular germ cell tumours (TGCTs), considered the most severe symptom of TDS, have increased in incidence during the last 60 years, to become the most common malignancy in young Caucasian men aged 17-45 years. TGCTs of young men originate from carcinoma in situ (CIS) cells. In the last few years, progress has been made identifying candidate genes involved in the neoplastic development of CIS, which may elucidate the timing of the initiation of CIS, currently thought to originate in foetal life from primordial germ cells or early gonocytes. Histological dysgenetic features are frequently seen in testes affected with the TDS components testis cancer or cryptorchidism. A TDS-like phenotype can be induced in male rats by in utero exposure to high concentrations of dibutyl phthalate (DBP) suggesting that ubiquitously present environmental endocrine disruptors may play a role in the aetiology of human TDS. So far, no animal model has been able to mimick all the symptoms of TDS including TGCTs although CIS-like cells have been found in a spontaneous testicular neoplasm in a rabbit.

Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort.

Science.gov (United States)

Pathak, Anand; Adams, Charleen D; Loud, Jennifer T; Nichols, Kathryn; Stewart, Douglas R; Greene, Mark H

2015-10-01

Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1-23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6-48.6). Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. ©2015 American Association for Cancer Research.

Prospectively-Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort

Science.gov (United States)

Pathak, Anand; Adams, Charleen D.; Loud, Jennifer T.; Nichols, Kathryn; Stewart, Douglas R.; Greene, Mark H.

2015-01-01

Background Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly-penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. Methods We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Results Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR=11.9; 95% confidence interval [CI]=5.1–23.4; excess absolute risk=7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR=13.4; 95%CI=1.6–48.6). Conclusions Our data are the first indicating that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Impact Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. PMID:26265202

Human HRAD9B and testicular cancer

International Nuclear Information System (INIS)

Hopkins, K.M.; Wang, X.; Berlin, A.; Thaker, H.M.; Lieberman, H.B.

2003-01-01

Full text: The HRAD9 gene mediates radioresistance and regulates the G2/M cell cycle checkpoint induced by ionizing radiation. In this report, we describe the isolation of the human paralog of HRAD9, called HRAD9B. Furthermore, we demonstrate that, like HRAD9 protein, the HRAD9B gene product can coimmunoprecipitate with HRAD1, HRAD9, HHUS1 and HHUS1B proteins. However, HRAD9B is expressed predominantly in testis, whereas its paralog is expressed more universally in different tissues. And most notably, we demonstrate that HRAD9B exhibits markedly and consistently reduced expression in testicular seminomas, high levels of expression in normal adult testis, yet also shows expression in fetal testis cells where meiosis is not performed. These results suggest that HRAD9B could at the least serve as a marker for testicular cancer, and its expression may be causally related to the disease. Further studies are under way to determine the cause of the reduced expression of HRAD9B in germ cell tumors

A subfertile patient diagnosed with testicular carcinoma in situ by immunocytological staining for AP-2gamma in semen samples

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Rajpert-De Meyts, E; Carlsen, E

2005-01-01

patients, including patients with testicular cancer and subfertility. Cells positive for AP-2gamma were found only in semen samples from patients diagnosed a priori with testicular neoplasms and, surprisingly, in a 23 year old control subject with oligozoospermia and no symptoms of a germ cell tumour......, simple method based on immunocytological staining of a semen sample for AP-2gamma, a novel marker for CIS. The value of this method for diagnostic use in the clinic requires further careful validation in a large series of patients and controls, but the preliminary results are promising....

Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer

DEFF Research Database (Denmark)

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders

2017-01-01

BACKGROUND: Little is known about preorchiectomy Leydig cell function in patients with testicular germ cell cancer (TGCC). The aim was to estimate the prevalence of preorchiectomy Leydig cell dysfunction and evaluate factors associated with this condition in a cohort of patients with TGCC. PATIENTS...... AND METHODS: We evaluated luteinizing hormone (LH), total testosterone (TT), calculated free T (cFT), estradiol, and sex hormone-binding globulin (SHBG) preorchiectomy in 561 patients with TGCC and compared with 561 healthy controls. We calculated TT/LH and cFT/LH ratios and constructed bivariate charts of TT...

Lonidamine affects testicular steroid hormones in immature mice

International Nuclear Information System (INIS)

Traina, Maria Elsa; Guarino, Maria; Natoli, Alessia; Romeo, Antonella; Urbani, Elisabetta

2007-01-01

The effects on the hypothalamus-pituitary-testicular axis of the well-known antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the present study, the possible changes of the testicular steroid hormones were evaluated in immature mice for a better characterization of the LND adverse effects both in its use as antitumoral agent and male contraceptive. Male CD1 mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on PND42 (1 and 2 weeks after the administration, respectively). Severe testicular effects were evidenced in the LND treated groups, including: a) significant testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease (more than 50% of the control) on PND29-32; c) damage of the tubule morphology primarily on the Sertoli cell structure and germ cell exfoliation. All these reproductive endpoints were recovered on PND42. At the same time, a significant impairment of the testicular steroid balance was observed in the treated mice, as evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while the testicular content of 17β-estradiol (E2) was unchanged. The hormonal balance was not completely restored afterwards, as levels of T, ADIONE and 17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 and PND42. These data showed for the first time that LND affects intratesticular steroids in experimental animals. However further data are needed both to elucidate the mechanism responsible for the impairment of these metabolic pathways and to understand if the androgens decrease observed after LND administration could be partially involved in the testicular damage

Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

DEFF Research Database (Denmark)

Kristensen, David M; Nielsen, John E; Skakkebaek, Niels E

2008-01-01

UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 and REX-1 during...... human gonadal development and in TGCT....

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

Science.gov (United States)

Nayan, Madhur; Jewett, Michael A S; Hosni, Ali; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Hansen, Aaron R; Chung, Peter; Warde, Padraig; Sweet, Joan; O'Malley, Martin; Atenafu, Eshetu G; Hamilton, Robert J

2017-01-01

Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. To determine cRR in CSI testicular cancer. We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Deltamethrin-induced testicular apoptosis in rats: the protective effect of nitric oxide synthase inhibitor.

Science.gov (United States)

El-Gohary, M; Awara, W M; Nassar, S; Hawas, S

1999-01-01

This study is the first to examine and characterize the testicular apoptosis which might be induced due to exposure of male rats to deltamethrin. Furthermore, the role which might be played by nitric oxide (NO), as well as the other reactive oxygen species (ROS) in controlling this testicular apoptosis was assessed. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis and cellular morphology on testicular tissue sections. It was found that administration of deltamethrin (1 mg/kg daily for 21 days) to animals resulted in characteristic DNA migration patterns (laddering), thereby providing evidence that apoptosis is the major mechanism of cell death in the testicular tissues. In addition, histopathological examination of testicular tissue sections showed that apoptosis was confined to the basal germ cells, primary and secondary spermatocytes. These changes, in addition to the appearance of Sertoli cell vacuoles in deltamethrin-intoxicated animals, indicates the suppression of spermatogenesis. At the same time, the plasma levels of both NO and lipid peroxides measured as malondialdehyde (MDA) were found to be significantly increased in deltamethrin-treated animals. Administration of NO synthase (NOS) inhibitors such as N(G)-nitro monomethyl L-arginine hydrochloride (L-NMMA, 1 mg/kg) to rats 2 h before exposure to deltamethrin was effective in the reduction of the typically testicular apoptotic DNA fragmentation pattern and the associated histopathological changes. These findings may suggest that deltamethrin-induced testicular apoptosis is mediated by NO. Therefore, the pharmacological manipulation of apoptosis by selective NOS inhibitors such as L-NMMA may offer new possibilities for the control of deltamethrin-induced testicular dysfunction and infertility in the future.

Serum organochlorine pesticide residues and risk of testicular germ cell carcinoma: a population-based case-control study.

Science.gov (United States)

Biggs, Mary L; Davis, Mark D; Eaton, David L; Weiss, Noel S; Barr, Dana B; Doody, David R; Fish, Sherianne; Needham, Larry L; Chen, Chu; Schwartz, Stephen M

2008-08-01

Testicular germ cell carcinoma (TGCC) is the most common malignancy among men ages 20 to 34 years. Although the pathogenesis of TGCC is poorly understood, suboptimal androgen levels or impaired androgen signaling may play a role. Some persistent organochlorine pesticides commonly found in human tissue possess antiandrogenic properties. We examined whether the risk of TGCC is associated with serum levels of 11 organochlorine pesticides, including p,p'-DDE, and whether the p,p'-DDE-TGCC association is modified by CAG or GGN repeat polymorphisms in the androgen receptor gene. We conducted a population-based case-control study among 18- to 44-year-old male residents of three Washington State counties. Cases (n = 246) were diagnosed during 1999 to 2003 with a first, primary TGCC. Controls (n = 630) were men of similar age with no history of TGCC from the same population identified through random-digit telephone dialing. Questionnaires elicited information on demographic, medical, and lifestyle factors. A blood specimen provided serum for gas chromatography-high-resolution mass spectrometry analysis of organochlorine pesticide residues and DNA for genotyping. We observed no clear patterns between TGCC risk and concentrations of any of the organochlorines measured, nor did we observe that the risk associated with p,p'-DDE was modified by androgen receptor CAG ( or =23 repeats) or GGN ( or =17 repeats) genotype. This study does not provide support for the hypothesis that adult exposure to organochlorine pesticides is associated with risk of TGCC. Due to uncertainty regarding how well organochlorine levels measured in adulthood reflect exposures during early life, further research is needed using exposure measurements collected in utero or during infancy.

Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

DEFF Research Database (Denmark)

Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

2013-01-01

This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome pr...

Tumour lysis syndrome: A rare acute presentation of locally advanced testicular cancer – Case report and review of literature

Directory of Open Access Journals (Sweden)

Marcus Chow

2016-01-01

Full Text Available Tumour lysis syndrome (TLS is a potentially fatal complication of malignancy or its treatment. This uncommon syndrome comprises laboratory findings of hyperuricaemia, hypocalcaemia, hyperkalaemia and hyperphosphataemia. A literature search revealed a total of eight patients, with testicular cancer, who had TLS. All these patients had metastatic disease. We present a unique case of a 47-year-old gentleman we saw in clinic, who presented with a rapidly growing right groin mass and acute breathlessness, and discuss the diagnosis and management of TLS. TLS is extremely rare in testicular cancer but necessitates the awareness of urologists. TLS can occur spontaneously in testicular malignancy. Cell lysis in a rapidly proliferating germ cell tumour is a possible mechanism. The prompt identification and institution of management for TLS is crucial to improve clinical outcomes.

Testicular germ cell tumors and related research from a historical point of view

DEFF Research Database (Denmark)

Damjanov, Ivan; Albrechtsen, Nicolai Jacob Wewer

2013-01-01

and histogenesis have been elucidated in part by contributions in the field of experimental pathology and developmental biology. Correlation between clinical oncologic findings, pathology and experimental studies of germ cell tumors and related topics ushered the era of cellular and genetic engineering that have...

Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer

DEFF Research Database (Denmark)

Kier, Maria G; Hansen, Merete K; Lauritsen, Jakob

2016-01-01

radiotherapy (RT); bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment (MTOL). Main Outcomes and Measures: Cumulative incidence and hazard ratios (HRs) for SMN and death calculated by the Cox proportional hazards model were compared with those of age-matched controls. Results: The study......Importance: Patients given systemic treatment for testicular germ cell cancer (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous studies on SMN and causes of death lacked information on the exact treatment applied or were based on patients receiving former treatment options....... Objective: To evaluate the treatment-specific risks for SMN and death in a nationwide population-based cohort of patients with GCC treated with current standard regimens. Design, Setting, and Participants: This study examined a Danish nationwide cohort of 5190 men with GCC who entered the Danish Testicular...

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer.

Science.gov (United States)

Pietzak, Eugene J; Tasian, Gregory E; Tasian, Sarah K; Brinster, Ralph L; Carlson, Claire; Ginsberg, Jill P; Kolon, Thomas F

2015-11-01

Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach. We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values. A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6 months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation. The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The value of prognostic factors in the management of Stage I nonseminomatous germ cell testicular tumors (NSGCTT)

International Nuclear Information System (INIS)

Ondrus, D.; Goncalves, F.; Kausitz, J.; Matoska, J.; Belan, V.

1996-01-01

The prospective study, carried out from February 1992 to January 1996, included 49 patients in clinical Stage I nonseminomatous germ cell testicular tumors (NSGCTT). They are aged 16-40 years (mean, 25 years). Patients were stratified to different risk-adapted therapeutic approaches according to histopathologic findings of primary tumor removed by inguinal orchiectomy. Eleven patients of the first group with vascular invasion and majority of embryonal carcinoma components in the primary tumor were treated with adjuvant chemotherapy (2 cycles of BEP). None of them had disease progression after the follow-up of 4-43+ months (mean, 20.9 months) after orchiectomy. Five patients of the second group with vascular invasion and majority of teratoma elements in the primary tumor were treated with primary retroperitoneal lymph node dissection (RPLND). They were followed-up 29-445+ months (mean, 33.4 months) after orchiectomy. Two of them (40%) had pathologic Stage II after RPLND and underwent subsequent BEP chemotherapy. One of them died due to disease progression in disseminated stage 29 months after orchiectomy. The second on lives with no evidence of the disease (NED). Thirty three patients in the third group without vascular invasion were kept under surveillance. They were followed-up 3-48+ months (mean, 22.3 months) after orchiectomy. Disease progression was observed in 5 of them (15.1%), 7-10 months (mean, 8.8 months) following orchiectomy. These patients were treated with BEP chemotherapy and live with NED 1-16+ months (mean, 9.2 months) after completion of the therapy. The overall survival rate in clinical Stage I patients was 97.9%. The authors recommend the surveillance policy only in clinical Stage NSGCTT patients without vascular invasion in the primary tumor. (author)

Functional phosphodiesterase 11A mutations may modify the risk of familial and bilateral testicular germ cell tumors

Science.gov (United States)

Horvath, Anelia; Korde, Larissa; Greene, Mark H.; Libe, Rosella; Osorio, Paulo; Faucz, Fabio Rueda; Raffin-Sanson, Marie Laure; Tsang, Kit Man; Drori-Herishanu, Limor; Patronas, Yianna; Remmers, Elaine F; Nikita, Maria-Elena; Moran, Jason; Greene, Joseph; Nesterova, Maria; Merino, Maria; Bertherat, Jerome; Stratakis, Constantine A.

2009-01-01

Inactivating germline mutations in phosphodiesterase 11A (PDE11A) have been implicated in adrenal tumor susceptibility. PDE11A is highly-expressed in endocrine steroidogenic tissues, especially the testis, and mice with inactivated Pde11a exhibit male infertility, a known testicular germ cell tumor (TGCT) risk factor. We sequenced the PDE11A gene-coding region in 95 patients with TGCT from 64 unrelated kindreds. We identified 8 non-synonymous substitutions in 20 patients from 15 families: four (R52T; F258Y; G291R; V820M) were newly-recognized, three (R804H; R867G; M878V) were functional variants previously implicated in adrenal tumor predisposition, and one (Y727C) was a known polymorphism. We compared the frequency of these variants in our patients to unrelated controls that had been screened and found negative for any endocrine diseases: only the two previously-reported variants, R804H and R867G, known to be frequent in general population, were detected in these controls. The frequency of all PDE11A-gene variants (combined) was significantly higher among patients with TGCT (P=0.0002), present in 19% of the families of our cohort. Most variants were detected in the general population, but functional studies showed that all these mutations reduced PDE activity, and that PDE11A protein expression was decreased (or absent) in TGCT samples from carriers. This is the first demonstration of a PDE gene’s involvement in TGCT, although the cAMP signaling pathway has been investigated extensively in other reproductive organs and their diseases. In conclusion, we report that PDE11A-inactivating sequence variants may modify the risk of familial and bilateral TGCT. PMID:19549888

Parental Occupational Exposure to Organic Solvents and Testicular Germ Cell Tumors in their Offspring: NORD-TEST Study.

Science.gov (United States)

Le Cornet, Charlotte; Fervers, Béatrice; Pukkala, Eero; Tynes, Tore; Feychting, Maria; Hansen, Johnni; Togawa, Kayo; Nordby, Karl-Christian; Oksbjerg Dalton, Susanne; Uuksulainen, Sanni; Wiebert, Pernilla; Woldbæk, Torill; Skakkebæk, Niels E; Olsson, Ann; Schüz, Joachim

2017-06-30

Testicular germ cell tumors (TGCT) were suggested to have a prenatal environmentally related origin. The potential endocrine disrupting properties of certain solvents may interfere with the male genital development in utero . We aimed to assess the association between maternal and paternal occupational exposures to organic solvents during the prenatal period and TGCT risk in their offspring. This registry-based case control study included TGCT cases aged 14–49 y ( n =8,112) diagnosed from 1978 to 2012 in Finland, Norway, and Sweden. Controls ( n =26,264) were randomly selected from the central population registries and were individually matched to cases on year and country of birth. Occupational histories of parents prior to the child’s birth were extracted from the national censuses. Job codes were converted into solvent exposure using the Nordic job-Nordic Occupational Cancer Study Job-Exposure Matrix. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, no association was found between prenatal maternal exposure to solvents and TGCT risk. In subset analyses using only mothers for whom occupational information was available in the year of or in the year prior to the child’s birth, there was an association with maternal exposure to aromatic hydrocarbon solvents (ARHC) (OR=1.53; CI: 1.08, 2.17), driven by exposure to toluene (OR=1.67; CI: 1.02, 2.73). No association was seen for any paternal occupational exposure to solvents with the exception of exposure to perchloroethylene in Finland (OR=2.42; CI: 1.32, 4.41). This study suggests a modest increase in TGCT risk associated with maternal prenatal exposure to ARHC. https://doi.org/10.1289/EHP864.

Testicular Cancer Screening

Science.gov (United States)

... undescended testicle) is a risk factor for testicular cancer. Testicular cancer is a disease in which malignant (cancer) ... Testicular Cancer Treatment for more information about testicular cancer. Testicular cancer is the most common cancer in men ...

Differential expression of miRNAs in the seminal plasma and serum of testicular cancer patients.

Science.gov (United States)

Pelloni, Marianna; Coltrinari, Giulia; Paoli, Donatella; Pallotti, Francesco; Lombardo, Francesco; Lenzi, Andrea; Gandini, Loredana

2017-09-01

Various microRNAs from the miR-371-3 and miR-302a-d clusters have recently been proposed as markers for testicular germ cell tumours. Upregulation of these miRNAs has been found in both the tissue and serum of testicular cancer patients, but they have never been studied in human seminal plasma. The aim of this study was, therefore, to assess the differences in the expression of miR-371-3 and miR-302a-d between the seminal plasma and serum of testicular cancer patients, and to identify new potential testicular cancer markers in seminal plasma. We investigated the serum and seminal plasma of 28 pre-orchiectomy patients subsequently diagnosed with testicular cancer, the seminal plasma of another 20 patients 30 days post-orchiectomy and a control group consisting of 28 cancer-free subjects attending our centre for an andrological check-up. Serum microRNA expression was analysed using RT-qPCR. TaqMan Array Card 3.0 platform was used for microRNA profiling in the seminal plasma of cancer patients. Results for both miR-371-3 and the miR-302 cluster in the serum of testicular cancer patients were in line with literature reports, while miR-371and miR-372 expression in seminal plasma showed the opposite trend to serum. On array analysis, 37 miRNAs were differentially expressed in the seminal plasma of cancer patients, and the upregulated miR-142 and the downregulated miR-34b were validated using RT-qPCR. Our study investigated the expression of miRNAs in the seminal plasma of patients with testicular cancer for the first time. Unlike in serum, miR-371-3 cannot be considered as markers in seminal plasma, whereas miR-142 levels in seminal plasma may be a potential marker for testicular cancer.

[Fertility preservation in boys: spermatogonial stem cell transplantation and testicular grafting].

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Goossens, E; Tournaye, H

2013-09-01

Spermatogonial stem cells (SSC) are the founder cells of spermatogenesis and are responsible for the lifelong production of spermatozoa. The cryopreservation and transplantation of these cells has been proposed as a fertility preservation strategy for young boys at risk for stem cell loss, i.e. patients undergoing chemotherapy for cancer or as a conditioning treatment for bone marrow transplantation. To prevent lifelong sterility in boys, two fertility restoration strategies are being developed: the injection of SSC and the grafting of testicular tissue containing SSC. Depending on the disease of the patient one of these two approaches will be applicable. Grafting has the advantage that SSC can reside within their natural niche, preserving the interactions between germ cells and their supporting cells and may therefore be regarded as the first choice strategy. However, in cases where the risk for malignant contamination of the testicular tissue is real, e.g. leukemia, transplantation of SSC by injection is preferable over grafting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Diagnosis and management of testicular cancer the European point of view

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Krege, Susanne

2015-01-01

This book presents the views of leading European experts on the diagnosis and management of testicular cancer, with coverage of current hot topics in the field. It opens by providing an overview of the recommendations in the most recent consensus paper from the European Germ Cell Cancer Consensus Group, which is based on interdisciplinary cooperation among urologists, medical oncologists, radio-oncologists, pathologists, and basic scientists. The remainder of the book focuses on areas of controversy in the diagnosis, treatment, and follow-up of testicular cancer. In each case the evidence base is discussed and results from the most recent studies are reviewed, drawing attention to new findings that might alter treatment recommendations. The treatment-related chapters cover a broad range of issues, including the best approach in patients with poor-prognosis and recurrent disease and those with long-term toxicities. Relevant aspects of survivorship care are also addressed. The book will help clinicians and prac...

Animacroxam, a Novel Dual-Mode Compound Targeting Histone Deacetylases and Cytoskeletal Integrity of Testicular Germ Cell Cancer Cells.

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Steinemann, Gustav; Dittmer, Alexandra; Kuzyniak, Weronika; Hoffmann, Björn; Schrader, Mark; Schobert, Rainer; Biersack, Bernhard; Nitzsche, Bianca; Höpfner, Michael

2017-11-01

Novel approaches for the medical treatment of advanced solid tumors, including testicular germ cell tumors (TGCT), are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual-mode compound animacroxam for TGCT treatment. Animacroxam consists of an HDAC-inhibitory hydroxamate moiety coupled to a 4,5-diarylimidazole with inherent cytoskeleton disrupting potency. Animacroxam revealed pronounced antiproliferative, cell-cycle arresting, and apoptosis-inducing effects in TGCT cell lines with different cisplatin sensitivities. The IC 50 values of animacroxam ranged from 0.22 to 0.42 μmol/L and were not correlated to the cisplatin sensitivity of the tumor cells. No unspecific cytotoxicity of animacroxam was observed in either cisplatin-sensitive or resistant TGCT cells, even at doses as high as 10 μmol/L. Furthermore, animacroxam induced the formation of actin stress fibers in cancer cells, thereby confirming the cytoskeleton-disrupting and antimigratory properties of its imidazole moiety. When compared with the clinically established HDAC inhibitor vorinostat, the novel dual-mode compound animacroxam exhibited superior antitumoral efficacy in vitro Animacroxam also reduced the tumor size of TGCT tumors in vivo , as evidenced by performing xenograft experiments on tumor bearing chorioallantoic membranes of fertilizes chicken eggs (CAM assay). The in vivo experiments also revealed a very good tolerability of the compound, and hence, animacroxam may be a promising candidate for innovative treatment of TGCT in general and the more so for platinum-insensitive or refractory TGCT. Mol Cancer Ther; 16(11); 2364-74. ©2017 AACR . ©2017 American Association for Cancer Research.

Adult testicular cancer: Two decades of Saudi national data.

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Abomelha, Mohammed

2017-01-01

There is a paucity of data regarding testicular cancer among Saudis as well as the nonexistent of published national data. Furthermore, a substantial increase of the incidence of testicular cancer among Saudis was lately noted. The aim of the study is to determine the trends and patterns of testicular cancer among adult Saudis using national data over a period of 20 years. The national database of the Saudi Cancer Registry (SCR) on testicular cancer over the last two decades was studied including epidemiological and histological patterns. The 1004 cases of testicular cancer among adult Saudis reported by the SCR will be the subject of this study. From 1994 to 2013, 1004 cases of testicular cancer among adult Saudis were reported to the SCR, with a steadily significant increase in incidence rate reaching an annual rate of 94 cases in 2013. Age of the patients ranged 15-93 years with a mean of 34.5 years. The most affected age group was 20-34 years, where 51% of all testicular cancer accumulated. Around 85% of testicular cancer is germ cell tumors, while paratesticular and gonadal stromal tumors represent 15%. Of all testicular cancer, seminomas were seen in 40.7%, nonseminomas in 44.6%. Notably, 70.4% of the cases in the first decade were seminomas, while in the second decade 65.9% of the cases were nonseminomas. The subtypes of the nonseminomas were a mixed tumor in 51.6%, embryonal carcinoma in 19.9%, yolk sac tumor in 12.3%, germinomas in 6.7%, teratomas in 6%, and choriocarcinomas in 3.6%. Lymphomas (34.7%) and rhabdomyosarcomas (23.6%) are on the top of the paratesticular tumor group. The Surveillance Epidemiology and End Results summary stage of seminomas was localized in 61.6%, regional in 19.8%, and distant in 12.6%, while of nonseminomas was 48%, 15.5%, and 28.5%, respectively. Localized and distant status of seminomas improved over the studied period by 12% and 4% respectively, while this trend was not seen in nonseminomas. The incidence rate is on rising

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

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Moch, Holger; Cubilla, Antonio L; Humphrey, Peter A; Reuter, Victor E; Ulbright, Thomas M

2016-07-01

The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "blue book"), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, acquired cystic disease-associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non-GCNIS-related tumours in the 2016 WHO classification. The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All

Testicular microlithiasis and testicular cancer: review of the literature.

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Pedersen, Malene Roland; Rafaelsen, Søren Rafael; Møller, Henrik; Vedsted, Peter; Osther, Palle Jörn

2016-07-01

To perform a systematic literature review to assess whether the occurrence of testicular microlithiasis (TML) in conjunction with other risk factors is associated with testicular cancer. A systematic literature search was performed of original articles in English published 1998 to 2015. Relevant studies were selected by reading the title and abstract by two of the authors. Studies were included if TML was diagnosed by ultrasonography and a risk condition was reported. Studies were only eligible if the particular risk condition was reported in more than one article. In total, 282 abstracts in were identified. Based on title and abstract the eligibility was assessed and 31 studies were included. Five conditions in relation to TML and testicular cancer emerged: Down syndrome, McCune-Albright syndrome, cryptorchidism, infertility and familial disposition of testicular cancer. Data support the conclusion that TML is not an independent risk factor for testicular cancer but associated with testicular cancer through other conditions. In male infertility, TML appears to be related to an increased risk of testicular cancer possibly as part of a testicular dysgenesis syndrome.

Temporal trends in management and outcomes of testicular cancer: A population-based study.

Science.gov (United States)

Leveridge, Michael J; Siemens, D Robert; Brennan, Kelly; Izard, Jason P; Karim, Safiya; An, Howard; Mackillop, William J; Booth, Christopher M

2018-04-16

Treatment guidelines for early-stage testicular cancer have increasingly recommended de-escalation of therapy with surveillance strategies. This study was designed to describe temporal trends in routine clinical practice and to determine whether de-escalation of therapy is associated with inferior survival in the general population. The Ontario Cancer Registry was linked to electronic records of treatment to identify all patients diagnosed with testicular cancer treated with orchiectomy in Ontario during 2000-2010. Treatment after orchiectomy was classified as radiotherapy (RT), retroperitoneal lymph node dissection (RPLND), chemotherapy, or none. Surveillance was defined as no identified treatment within 90 days of orchiectomy. Overall survival (OS) and cancer-specific survival (CSS) were measured from the date of orchiectomy. The study population included 1564 and 1086 cases of seminomas and nonseminoma germ cell tumors (NSGCTs), respectively. Among patients with seminomas, there was a significant increase in the proportion of patients with no treatment within 90 days of orchiectomy (from 56% to 84%; P testicular cancer in routine practice since 2000. Long-term survival in routine practice is excellent and has not decreased with the uptake of surveillance strategies. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Sperm Cryopreservation before Testicular Cancer Treatment and Its Subsequent Utilization for the Treatment of Infertility

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Jana Žáková

2014-01-01

Full Text Available Aims. In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. Methods. Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5% was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. Results. A total of 557 men have decided to freeze their semen before cancer treatment. Azoospermia was diagnosed in 34 men (6.1%, and semen was cryopreserved in 532 patients. Seminoma was diagnosed in 283 men (54.1% and nonseminomatous germ cell tumors in 240 men (45.9%. 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. Conclusion. The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

Science.gov (United States)

Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

2014-08-01

The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Teaching about Testicular Cancer and Testicular Self-examination.

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Marty, Phillip J.; McDermott, Robert J.

1983-01-01

Because testicular cancer is one of the most commonly diagnosed cancers in young men, it is important that they become informed about it. This paper reviews the pathology and epidemiology of testicular cancer, the technique of testicular self-examination, and some suggestions for teaching about this subject. (Authors/JMK)

Intra-Abdominal Testicular Seminoma in a Woman with Testicular Feminization Syndrome

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Darshana D. Rasalkar

2011-01-01

Full Text Available We report a case of intra-abdominal testicular tumor in a 36-year-old married lady presenting with chief complaints of primary amenorrhea. The patient was later diagnosed with testicular feminization syndrome, a form of male pseudohermaphroditism. This testicular tumor was histologically proven as seminoma. Due to rarity, imaging findings in patients with testicular feminization syndrome and intraabdominal testicular tumor have been poorly documented. So far, only one case report had described the combined role of CT and MR imaging in intraabdominal testicular sex-cord stromal tumor. To our knowledge, this case is first to document USG and MR imaging in addition to MR spectroscopy features in intraabdominal testicular seminoma.

Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

2017-01-01

Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

Predictors of sperm recovery after cryopreservation in testicular cancer

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James M Hotaling

2016-01-01

Full Text Available Our objective was to identify predictors of improved postthaw semen quality in men with testicular cancer banking sperm for fertility preservation. We reviewed 173 individual semen samples provided by 67 men with testicular germ cell tumor (TGCT who cryopreserved sperm before gonadotoxic treatment between 1994 and 2010 at our tertiary university medical center. Our main outcomes measures were independent predictors for the greater postthaw total motile count (TMC in men with TGCT. Men with NSGCT were more likely to be younger (P median fresh TMC each had increased odds of a postthaw TMC greater than median postthaw TMC. Interestingly, age, advanced cancer stage (II or III, rapid freezing protocol, and motility enhancer did not show increased odds of improved postthaw TMC in our models. In conclusion, men with TGCT or poor fresh TMC should consider preserving additional vials (at least 15 vials before oncologic treatment. Density gradient purification should be routinely used to optimize postthaw TMC in men with TGCT. Larger, randomized studies evaluating cancer stage and various cryopreservation techniques are needed to assist in counseling men with TGCT regarding fertility preservation and optimizing cryosurvival.

Residual tumor size and IGCCCG risk classification predict additional vascular procedures in patients with germ cell tumors and residual tumor resection: a multicenter analysis of the German Testicular Cancer Study Group.

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Winter, Christian; Pfister, David; Busch, Jonas; Bingöl, Cigdem; Ranft, Ulrich; Schrader, Mark; Dieckmann, Klaus-Peter; Heidenreich, Axel; Albers, Peter

2012-02-01

Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p=0.0047) and residual tumor size (3.7% size risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Testicular Microlithiasis

DEFF Research Database (Denmark)

Pedersen, Malene Roland Vils; Osther, Palle Jørn Sloth; Sørensen, Flemming Brandt

2016-01-01

factors (testicular atrophy (N=1) and previous testicular cancer (N=4)), but no cases of testicular malignancy were found in the follow-up period. Conclusion: The low patient compliance conflicts with the ESUR Scrotal Imaging Subcommittee guidelines that recommend scrotal US follow-up annually for TML...

Effect of Physalis peruviana L. on cadmium-induced testicular toxicity in rats.

Science.gov (United States)

Othman, Mohamed S; Nada, Ahmed; Zaki, Hassan S; Abdel Moneim, Ahmed E

2014-06-01

Cadmium (Cd) stimulates the production of reactive oxygen species and causes tissue damage. We investigated here the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced testes toxicity in rats. Twenty-eight Wistar albino rats were used. They were divided into four groups (n=7). Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg body weight (bwt) of cadmium chloride for 5 days. Group 3 was orally treated with 200 mg/kg bwt of methanolic extract of physalis (MEPh). Group 4 was pretreated with MEPh before cadmium for 5 days. Changes in body and testes weights were determined. Oxidative stress markers, antioxidant enzymes, and testosterone level were measured. Histopathological changes of testes were examined, and the immunohistochemical staining for the proapoptotic (caspase-3) protein was performed. The injection of cadmium caused a significant decrease in body weight, while a significant increase in testes weight and testes weight index was observed. Pretreatment with MEPh was associated with significant reduction in the toxic effects of Cd as shown by reduced testicular levels of malondialdehyde, nitric oxide, and caspase-3 expression and increased glutathione content, and the activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and testosterone were also increased. Testicular histopathology showed that Cd produced an extensive germ cell apoptosis, and the pretreatment of MEPh in Cd-treated rats significantly reduced Cd-induced testicular damage. On the basis of the above results, it can be hypothesized that P. peruviana L. has a protective effect against cadmium-induced testicular oxidative stress and apoptosis in the rat.

Bone sarcomas

International Nuclear Information System (INIS)

Mudry, P.

2008-01-01

Bone sarcomas are malignancies with peak incidence in adolescents and young adults. The most frequent are osteosarcoma and Ewing sarcoma/PNET, in an older adults are seen chondrosarcomas, other ones are rare. In general, biology of sarcomas is closely related to pediatric malignancies with fast growth, local aggressiveness, tendency to early hematogenic dissemination and chemo sensitivity. Diagnostics and treatment of bone sarcomas should be done in well experienced centres due to low incidence and broad issue of this topic. An interdisciplinary approach and staff education is essential in due care of patients with bone sarcoma. If these criteria are achieved, the cure rate is contemporary at 65 - 70 %, while some subpopulation of patients has chance for cure up to 90 %. Osteosarcoma and Ewing sarcoma/PNET are discussed below as types of most frequent bone sarcoma. (author)

Maternal hormone levels and risk of cryptorchism among populations at high and low risk of testicular germ cell tumors.

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McGlynn, Katherine A; Graubard, Barry I; Nam, Jun-Mo; Stanczyk, Frank Z; Longnecker, Matthew P; Klebanoff, Mark A

2005-07-01

Cryptorchism is one of the few well-described risk factors for testicular cancer. It has been suggested that both conditions are related to increased in utero estrogen exposure. The evidence supporting the "estrogen hypothesis" has been inconsistent, however. An alternative hypothesis suggests that higher in utero androgen exposure may protect against the development of cryptorchism and testicular cancer. In order to examine both hypotheses, we studied maternal hormone levels in two populations at diverse risks of testicular cancer; Black Americans (low-risk) and White Americans (high-risk). The study population of 200 mothers of cryptorchid sons and 200 mothers of noncryptorchid sons was nested within the Collaborative Perinatal Project, a cohort study of pregnant women and their children. Third trimester serum levels of estradiol (total, free, bioavailable), estriol, testosterone (total, free, bioavailable), sex hormone-binding globulin, alpha-fetoprotein, and the ratios of estradiols to testosterones were compared between the case and control mothers. The results found no significant differences in the levels of testosterone (total, free, bioavailable), alpha-fetoprotein, sex hormone-binding globulin, or in the ratios of estrogens to androgens. Total estradiol, however, was significantly lower in the cases versus the controls (P = 0.03) among all mothers and, separately, among White mothers (P = 0.05). Similarly, estriol was significantly lower among all cases (P = 0.05) and among White cases (P = 0.05). These results do not support either the estrogen or the androgen hypothesis. Rather, lower estrogens in case mothers may indicate that a placental defect increases the risk of cryptorchism and, possibly, testicular cancer.

Anchoring ethinylestradiol induced gene expression changes with testicular morphology and reproductive function in the medaka.

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Hilary D Miller

Full Text Available Environmental estrogens are ubiquitous in the environment and can cause detrimental effects on male reproduction. In fish, a multitude of effects from environmental estrogens have been observed including altered courting behavior and fertility, sex reversal, and gonadal histopathology. However, few studies in fish assess the impacts of estrogenic exposure on a physiological endpoint, such as reproduction, as well as the associated morphologic response and underlying global gene expression changes. This study assessed the implications of a 14 day sub-chronic exposure of ethinylestradiol (EE2; 1.0 or 10.0 µg/L EE2 on male medaka fertility, testicular histology and testicular gene expression. The findings demonstrate that a 14 day exposure to EE2 induced impaired male reproductive capacity and time- and dose-dependent alterations in testicular morphology and gene expression. The average fertilization rate/day following the exposure for control, 1.0 and 10.0 µg/L EE2 was 91.3% (±4.4, 62.8% (±8.3 and 28.8% (±5.8, respectively. The testicular morphologic alterations included increased germ cell apoptosis, decreased germinal epithelium and thickening of the interstitium. These changes were highly associated with testicular gene expression changes using a medaka-specific microarray. A pathway analysis of the differentially expressed genes emphasized genes and pathways associated with apoptosis, cell cycle and proliferation, collagen production/extracellular matrix organization, hormone signaling, male reproduction and protein ubiquitination among others. These findings highlight the importance of anchoring global gonadal gene expression changes with morphology and ultimately with tissue/organ function.

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

International Nuclear Information System (INIS)

Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

2014-01-01

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

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Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

2014-11-04

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: a case report.

Science.gov (United States)

Iwatsuki, Shoichiro; Naiki, Taku; Kawai, Noriyasu; Etani, Toshiki; Iida, Keitaro; Ando, Ryosuke; Nagai, Takashi; Okada, Atsushi; Tozawa, Keiichi; Sugiyama, Yosuke; Yasui, Takahiro

2016-05-05

Patients with a primary pure seminoma in the testis who have elevated serum alpha-fetoprotein are rare and should be treated as patients with nonseminomatous germ cell tumors. However, nonpalpable testicular tumors in this condition have never been reported. We describe a case of nonpalpable pure testicular seminoma with elevated serum alpha-fetoprotein presenting retroperitoneal metastasis. A 29-year-old Asian man was referred to our hospital with right flank pain. Computed tomography showed a mass located between his aorta and inferior vena cava, but a testicular tumor was not detected. His serum levels of lactate dehydrogenase, alpha-fetoprotein, and DUPAN-2 were high. Although no tumor or nodule was palpable in his testis, ultrasonography revealed multiple low echoic lesions in his right testicular parenchyma. He was diagnosed with right testicular cancer with retroperitoneal lymph node metastasis and underwent right high orchiectomy. A pathological examination revealed pure seminoma and no nonseminomatous components were found in the specimen. Three courses of induction systemic chemotherapy (cisplatin, etoposide, and bleomycin) normalized his serum alpha-fetoprotein and DUPAN-2 levels. Three additional courses of chemotherapy (etoposide and bleomycin) were performed, and treatment was completed with laparoscopic retroperitoneal lymph node dissection. Pathology of the dissected specimen showed fibrous and necrotic tissue with no viable cells. He is alive without recurrence 54 months after orchiectomy. We report a case of pure testicular seminoma with elevated serum alpha-fetoprotein and DUPAN-2 presenting retroperitoneal metastasis. We recommend an ultrasound examination of bilateral testes when large retroperitoneal tumors are detected in young men, even if a mass is not palpable in the scrotum.

Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer

NARCIS (Netherlands)

de Haas, Esther C.; Zwart, Nynke; Meijer, Coby; Nuver, Janine; Boezen, H. Marike; Suurmeijer, Albert J. H.; Hoekstra, Harald J.; van der Steege, Gerrit; Sleijfer, Dirk Th.; Gietema, Jourik A.

2008-01-01

Purpose Response to chemotherapy may be determined by gene polymorphisms involved in metabolism of cytotoxic drugs. A plausible candidate is the gene for bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, an essential component of chemotherapy regimens for disseminated testicular

Prenatal and perinatal risk factors and testicular cancer: a hospital-based case-control study.

Science.gov (United States)

Sonke, Gabe S; Chang, Shine; Strom, Sara S; Sweeney, Anne M; Annegers, J Fred; Sigurdson, Alice J

2007-01-01

Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight 4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.

AiGERM: A logic programming front end for GERM

Science.gov (United States)

Hashim, Safaa H.

1990-01-01

AiGerm (Artificially Intelligent Graphical Entity Relation Modeler) is a relational data base query and programming language front end for MCC (Mission Control Center)/STP's (Space Test Program) Germ (Graphical Entity Relational Modeling) system. It is intended as an add-on component of the Germ system to be used for navigating very large networks of information. It can also function as an expert system shell for prototyping knowledge-based systems. AiGerm provides an interface between the programming language and Germ.

A novel rapid access testicular cancer clinic: prospective evaluation after one year.

Science.gov (United States)

Carey, K; Davis, N F; Elamin, S; Ahern, P; Brady, C M; Sweeney, P

2016-02-01

Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa). To present our experience after 12 months. All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa. Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology. The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.

A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation

DEFF Research Database (Denmark)

Dalgaard, Marlene D; Weinhold, Nils; Edsgard, Stefan Daniel

2012-01-01

controls with excellent reproductive health. Furthermore, they developed a novel integrative method that combines GWAS data with other TDS-relevant data types and identified additional TDS markers. The most significant findings were replicated in an independent cohort of 671 Nordic men. Results Markers......Background Testicular dysgenesis syndrome (TDS) is a common disease that links testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis. The incidence of these disorders has increased over the last few decades...... located in the region of TGFBR3 and BMP7 showed association with all TDS phenotypes in both the discovery and replication cohorts. An immunohistochemistry investigation confirmed the presence of transforming growth factor β receptor type III (TGFBR3) in peritubular and Leydig cells, in both fetal...

Excessive apoptosis and defective autophagy contribute to developmental testicular toxicity induced by fluoride

International Nuclear Information System (INIS)

Zhang, Shun; Niu, Qiang; Gao, Hui; Ma, Rulin; Lei, Rongrong; Zhang, Cheng; Xia, Tao; Li, Pei; Xu, Chunyan; Wang, Chao; Chen, Jingwen; Dong, Lixing; Zhao, Qian; Wang, Aiguo

2016-01-01

Fluoride, a ubiquitous environmental contaminant, is known to impair testicular functions and fertility; however the underlying mechanisms remain obscure. In this study, we used a rat model to mimic human exposure and sought to investigate the roles of apoptosis and autophagy in testicular toxicity of fluoride. Sprague–Dawley rats were developmentally exposed to 25, 50, or 100 mg/L sodium fluoride (NaF) via drinking water from pre-pregnancy to post-puberty, and then the testes of offspring were excised on postnatal day 56. Our results demonstrated that developmental NaF exposure induced an enhanced testicular apoptosis, as manifested by a series of hallmarks such as caspase-3 activation, chromatin condensation and DNA fragmentation. Further study revealed that fluoride exposure elicited significant elevations in the levels of cell surface death receptor Fas with a parallel increase in cytoplasmic cytochrome c, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. Intriguingly, fluoride treatment also simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II but not Beclin1. Unexpectedly, the expression of p62, a substrate that is degraded by autophagy, was also significantly elevated, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation rather than increased formation. Importantly, these were associated with marked histopathological lesions including spermatogenic failure and germ cell loss, along with severe ultrastructural abnormalities in testes. Taken together, our findings provide deeper insights into roles of excessive apoptosis and defective autophagy in the aggravation of testicular damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity. - Highlights: • Rats were developmentally exposed to fluoride from pre-pregnancy to post-puberty. • Both excessive apoptosis and defective autophagy are involved in

Recovery of testicular blood flow following ligation of testicular vessels

International Nuclear Information System (INIS)

Pascual, J.A.; Villanueva-Meyer, J.; Salido, E.; Ehrlich, R.M.; Mena, I.; Rajfer, J.

1989-01-01

To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133-xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

DEFF Research Database (Denmark)

Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B

2013-01-01

development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

Kaposi's Sarcoma

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... Name: Category: Share: Yes No, Keep Private Kaposi’s Sarcoma Share | Kaposi’s sarcoma (KS) is a vascular neoplasm of the skin ... symptoms of HIV infection. This type of Kaposi's sarcoma progresses slowly, with new lesions appearing every few ...

Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment

DEFF Research Database (Denmark)

Bartkova, Jirina; Hoei-Hansen, Christina E; Krizova, Katerina

2014-01-01

The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier ...... checkpoints in intracranial tumorigenesis, with implications for the differential biological responses of diverse tumor types to endogenous stress as well as to genotoxic treatments such as ionizing radiation or chemotherapy....

Loss of heterozygosity of CDKN2A (p16INK4a) and RB1 tumor suppressor genes in testicular germ cell tumors

International Nuclear Information System (INIS)

Vladusic, Tomislav; Hrascan, Reno; Pecina-Slaus, Nives; Vrhovac, Ivana; Gamulin, Marija; Franekic, Jasna; Kruslin, Bozo

2010-01-01

Testicular germ cell tumors (TGCTs) are the most frequent malignances in young adult men. The two main histological forms, seminomas and nonseminomas, differ biologically and clinically. pRB protein and its immediate upstream regulator p16INK4a are involved in the RB pathway which is deregulated in most TGCTs. The objective of this study was to evaluate the occurrence of loss of heterozygosity (LOH) of the CDKN2A (p16INK4a) and RB1 tumor suppressor genes in TGCTs. Forty TGCTs (18 seminomas and 22 nonseminomas) were analyzed by polymerase chain reaction using the restriction fragment length polymorphism or the nucleotide repeat polymorphism method. LOH of the CDKN2A was found in two (6%) out of 34 (85%) informative cases of our total TGCT sample. The observed changes were assigned to two (11%) nonseminomas out of 18 (82%) informative samples. Furthermore, LOH of the RB1 was detected in two (6%) out of 34 (85%) informative cases of our total TGCT sample. Once again, the observed changes were assigned to two (10.5%) nonseminomas out of 19 (86%) informative samples. Both LOHs of the CDKN2A were found in nonseminomas with a yolk sac tumor component, and both LOHs of the RB1 were found in nonseminomas with an embryonal carcinoma component. The higher incidence of observed LOH in nonseminomas may provide a clue to their invasive behavior

Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours

DEFF Research Database (Denmark)

Mosbech, Christiane Hammershaimb; Svingen, Terje; Nielsen, John Erik

2014-01-01

Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline....

AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours

DEFF Research Database (Denmark)

Gueler, B; Sonne, S B; Zimmer, J

2012-01-01

are believed to originate from fetal gonocytes.METHODSDDX3Y protein expression was analysed during development in different tissues by western blotting. The localization of DDX3Y in normal fetal and prepubertal testis tissue of different ages as well as in a series of distinct TGCT tissue samples (CIS......, classical seminoma, spermatocytic seminoma, teratoma and embryonal carcinoma) was performed by immunohistochemistry.RESULTSGerm cell-specific expression of DDX3Y protein was revealed in fetal prospermatogonia but not in gonocytes and not before the 17th gestational week. After birth, DDX3Y was expressed......, but not in somatically differentiated non-seminomas, consistent with its germ-cell specific function.CONCLUSIONSThe fetal germ cell DDX3Y expression suggests a role in early spermatogonial proliferation and implies that, in men with AZFa deletion, germ cell depletion may begin prenatally. The strong expression of DDX3Y...

Two new loci and gene sets related to sex determination and cancer progression are associated with susceptibility to testicular germ cell tumor.

Science.gov (United States)

Kristiansen, Wenche; Karlsson, Robert; Rounge, Trine B; Whitington, Thomas; Andreassen, Bettina K; Magnusson, Patrik K; Fosså, Sophie D; Adami, Hans-Olov; Turnbull, Clare; Haugen, Trine B; Grotmol, Tom; Wiklund, Fredrik

2015-07-15

Genome-wide association (GWA) studies have reported 19 distinct susceptibility loci for testicular germ cell tumor (TGCT). A GWA study for TGCT was performed by genotyping 610 240 single-nucleotide polymorphisms (SNPs) in 1326 cases and 6687 controls from Sweden and Norway. No novel genome-wide significant associations were observed in this discovery stage. We put forward 27 SNPs from 15 novel regions and 12 SNPs previously reported, for replication in 710 case-parent triads and 289 cases and 290 controls. Predefined biological pathways and processes, in addition to a custom-built sex-determination gene set, were subject to enrichment analyses using Meta-Analysis Gene Set Enrichment of Variant Associations (M) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (I). In the combined meta-analysis, we observed genome-wide significant association for rs7501939 on chromosome 17q12 (OR = 0.78, 95% CI = 0.72-0.84, P = 1.1 × 10(-9)) and rs2195987 on chromosome 19p12 (OR = 0.76, 95% CI: 0.69-0.84, P = 3.2 × 10(-8)). The marker rs7501939 on chromosome 17q12 is located in an intron of the HNF1B gene, encoding a member of the homeodomain-containing superfamily of transcription factors. The sex-determination gene set (false discovery rate, FDRM cancer and apoptosis, was associated with TGCT (FDR utero are implicated in the development of TGCT. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Testicular cancer and male infertility.

Science.gov (United States)

Paduch, Darius A

2006-11-01

Testicular cancer and infertility affect a similar age group of patients and have common biologic, epidemiologic, and environmental backgrounds. In this review, we provide current literature on links between infertility and testicular cancer, and new developments in the management of testicular cancer aimed at improving quality of life in men with testicular cancer. In-utero environmental exposure to endocrine disruptors modulates the genetically determined fate of primitive gonad and results in testicular dysgenesis syndrome, which may result in infertility and testicular cancer. Excellent response of testicular cancer to radiation and chemotherapy results in over 90% of survival and quality of life--fertility and sexual function--is of significant concern to patients and clinicians. The testicular-sparing management of testicular masses emerges as a sound alternative to radical orchiectomy and allows for preservation of spermatogenesis and hormonal function, and at the same time achieving similar survival rates. Secondary malignancies, pulmonary, and cardiovascular complications are recognized as late complications of treatment for testicular cancer. Better understanding of common mechanisms involved in infertility and testicular cancer, and scientifically driven evidence-based treatment options should improve quality of life in young men faced with this potentially life-threatening disease.

Endocrine testicular function and spermatogenesis persist in calves after partial scrotal resection but not Burdizzo castration.

Science.gov (United States)

Pieler, D; Wohlsein, P; Peinhopf, W; Aurich, J E; Erber, R; Ille, N; Baumgärtner, W; Aurich, C

2014-06-01

Bull calves for fattening are often castrated during the first weeks of life. Because androgens stimulate growth, there is an interest in males that are infertile but exposed to endogenous testicular steroids. Such a situation occurs in cryptorchids and has been imitated by shortening the scrotum to an extent that the testes are located in a near-inguinal position. In this study, effects of partial scrotal resection (SR) and Burdizzo castration (BZ) on endocrine testicular function, testes histology and on weight at slaughter were studied and compared to orchidectomized (OR) and gonad-intact calves (CO; n = 10 per group; age at castration, 54 ± 3 days; fattening period, 474 ± 11 days). Plasma testosterone concentrations were determined repeatedly, and testes were collected for histopathology at slaughter. We hypothesized that SR inhibits spermatogenesis without loss of testicular steroidogenesis. Group SR animals gained more weight than groups OR and BZ (P < 0.01). Plasma testosterone concentration increased in groups SR and CO (P < 0.01 vs. BZ and OR). Histologically, in all SR animals, testicular and epididymal tissue was identified with a seminiferous epithelium of up to three-cell layers in two animals. Germ cells including elongated spermatids were present in three animals. Shortening of the scrotum thus induced varying degrees of testicular degeneration but 3/10 animals had to be suspected as fertile. In one BZ animal, spermatids were identified whereas in the remaining BZ animals, testes and epididymides consisted of sclerotic fibrous tissue. Partial SR thus induced a cryptorchid-like status but fertility in individual animals must be assumed. Copyright © 2014 Elsevier Inc. All rights reserved.

Excessive apoptosis and defective autophagy contribute to developmental testicular toxicity induced by fluoride.

Science.gov (United States)

Zhang, Shun; Niu, Qiang; Gao, Hui; Ma, Rulin; Lei, Rongrong; Zhang, Cheng; Xia, Tao; Li, Pei; Xu, Chunyan; Wang, Chao; Chen, Jingwen; Dong, Lixing; Zhao, Qian; Wang, Aiguo

2016-05-01

Fluoride, a ubiquitous environmental contaminant, is known to impair testicular functions and fertility; however the underlying mechanisms remain obscure. In this study, we used a rat model to mimic human exposure and sought to investigate the roles of apoptosis and autophagy in testicular toxicity of fluoride. Sprague-Dawley rats were developmentally exposed to 25, 50, or 100 mg/L sodium fluoride (NaF) via drinking water from pre-pregnancy to post-puberty, and then the testes of offspring were excised on postnatal day 56. Our results demonstrated that developmental NaF exposure induced an enhanced testicular apoptosis, as manifested by a series of hallmarks such as caspase-3 activation, chromatin condensation and DNA fragmentation. Further study revealed that fluoride exposure elicited significant elevations in the levels of cell surface death receptor Fas with a parallel increase in cytoplasmic cytochrome c, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. Intriguingly, fluoride treatment also simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II but not Beclin1. Unexpectedly, the expression of p62, a substrate that is degraded by autophagy, was also significantly elevated, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation rather than increased formation. Importantly, these were associated with marked histopathological lesions including spermatogenic failure and germ cell loss, along with severe ultrastructural abnormalities in testes. Taken together, our findings provide deeper insights into roles of excessive apoptosis and defective autophagy in the aggravation of testicular damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Epidemic Kaposi Sarcoma

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... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Classic Kaposi Sarcoma

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... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Gonadal germ cell tumors in children and adolescents

Directory of Open Access Journals (Sweden)

Giovanni Cecchetto

2014-01-01

Full Text Available Pediatric germ cell tumors (GCT are rare tumors: 80% are benign, 20% malignant (2-3% of all malignant pediatric tumors. The gonadal sites (ovary and testis account for 40% of cases. Ovarian GCTs: Represent 30% of GCTs and 70% of neoplastic ovarian masses, being the most common ovarian neoplasms in children and teenagers. Benign and immature forms (teratomas constitute about 80% of all ovarian GCTs, malignant forms represent 20% increasing during adolescence. The most common malignant entity in children is the yolk sac tumors (YST; dysgerminoma is frequent during adolescence and being bilateral in 10% of cases. Presentation is similar in malignant and benign lesions; abdominal pain (70-80% and lower abdominal mass are common symptoms. Evaluation of alpha-fetoprotein (αFP or beta subunit of human chorionic gonadotropin (βHCG is essential to address the nature of the tumors: Their elevation means presence of malignancy. Surgery includes intraoperative staging procedures and requires ovariectomy or ovarosalpingectomy for malignant lesions, but may be conservative in selected benign tumors. Since malignant GCTs are very chemosensitive, primary chemotherapy is recommended in metastatic or locally advanced tumors. Testicular GCT: Represent 10% of pediatric GCT, and about 30% of malignant GCT with two age peaks: Children <3 years may experience mature teratoma and malignant GCTs, represented almost exclusively by YST, while adolescents may also show seminomas or other mixed tumors. The main clinical feature is a painless scrotal mass. Surgery represents the cornerstone of the management of testicular GCTs, with an inguinal approach and a primary high orchidectomy for malignant tumors, while a testis-sparing surgery can be considered for benign lesions. A retroperitoneal lymph node (LN biopsy may be necessary to define the staging when the involvement of retroperitoneal LN is uncertain at imaging investigations. Conclusion: Patients with gonadal

Positive Oct -3/4 and D2-40 Immunohistochemical Expression in Germ Cells and Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with Cryptorchidism Vanish after the Age of 2 Years

DEFF Research Database (Denmark)

Thorup, Jorgen; Clasen-Linde, Erik; Cortes, Dina

2017-01-01

of repeat biopsy with anti-stem cell factor (SCF) receptor.  Results  The prevalence of Oct-3/4 and D2-40-positive staining of germ cells in testicular biopsies were in age groups less than 6 months, 100% and 50%; 6-12 months, 60% and 17%; and 1-2 years, 12% and 4%. A 1 year, 1-month-old boy with Prader-Willi...... syndrome treated with growth hormone had ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases, 8 months, 8 months and 1-year-old, a histological pattern in accordance with ITGCN was found. These three boys had a repeat biopsy from both testes performed at the age of 3 years, 4......, but no increased risk of malignancy.  Materials and Methods  Histology sections from 373 testicular biopsies from 289 boys aged 1 month to 2 years operated for cryptorchidism were incubated with primary antibodies including anti-placental-like-alkaline phosphatase, antiOct-3/4, anti-C-kit, anti-D2-40, and in case...

Hypothalamic-pituitary-testicular system following testicular X-irradiation

International Nuclear Information System (INIS)

Verjans, H.L.; Eik-Nes, K.B.

1976-01-01

Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, precded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increase in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats be regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature. (author)

The Epidemiology of Sarcoma

Directory of Open Access Journals (Sweden)

Burningham Zachary

2012-10-01

Full Text Available Abstract Sarcomas account for over 20% of all pediatric solid malignant cancers and less than 1% of all adult solid malignant cancers. The vast majority of diagnosed sarcomas will be soft tissue sarcomas, while malignant bone tumors make up just over 10% of sarcomas. The risks for sarcoma are not well-understood. We evaluated the existing literature on the epidemiology and etiology of sarcoma. Risks for sarcoma development can be divided into environmental exposures, genetic susceptibility, and an interaction between the two. HIV-positive individuals are at an increased risk for Kaposi’s sarcoma, even though HHV8 is the causative virus. Radiation exposure from radiotherapy has been strongly associated with secondary sarcoma development in certain cancer patients. In fact, the risk of malignant bone tumors increases as the cumulative dose of radiation to the bone increases (p for trend

Testicular calculus: A rare case.

Science.gov (United States)

Sen, Volkan; Bozkurt, Ozan; Demır, Omer; Tuna, Burcin; Yorukoglu, Kutsal; Esen, Adil

2015-01-01

Testicular calculus is an extremely rare case with unknown etiology and pathogenesis. To our knowledge, here we report the third case of testicular calculus. A 31-year-old man was admitted to our clinic with painful solid mass in left testis. After diagnostic work-up for a possible testicular tumour, he underwent inguinal orchiectomy and histopathologic examination showed a testicular calculus. Case hypothesis: Solid testicular lesions in young adults generally correspond to testicular cancer. Differential diagnosis should be done carefully. Future implications: In young adults with painful and solid testicular mass with hyperechogenic appearance on scrotal ultrasonography, testicular calculus must be kept in mind in differential diagnosis. Further reports on this topic may let us do more clear recommendations about the etiology and treatment of this rare disease.

Identification of a Novel Androgen Receptor Mutation in a Family With Multiple Components Compatible With the Testicular Dysgenesis Syndrome

DEFF Research Database (Denmark)

Lottrup, Grete; Jørgensen, Anne; Nielsen, John E.

2013-01-01

showed features consistent with insufficient testis development and TDS.Conclusion: The presence of all hallmarks of TDS, including germ cell cancer, in a family with a novel AR mutation causing a partial decrease in AR function is in line with the concept that reduced androgen signaling may contribute......, cryptorchidism, hypospadias, and testicular cancer, caused by a novel AR mutation.Objective: The aim of this study was to describe the phenotype of the affected males, characterize functionally the novel AR mutation, and discuss the significance of partial androgen insufficiency in the pathogenesis of TDS...... analysis of the mutation in a gene-reporter assay showed a 50% reduction in AR-induced transcriptional activity. The affected males had elevated LH and T in accordance with decreased AR signaling. The histology and immunohistochemical profile of the testis tissue from the 2 patients with testicular cancer...

Synchronous bilateral testicular seminoma. Presentation of a clinical case and review of the literature

International Nuclear Information System (INIS)

Roldán, G.; Musé, I.

2004-01-01

Introduction: The patients with testicular germ cell tumors (TGT) present in the contralateral tumor development in approximately 3% of the cases. A small subset presenting with synchronous bilateral tumors (TBS). Case report: Patient is a 41-year study of infertility in who have performed bilateral testicular biopsies. Using ultrasound bilateral testicular nodules were diagnosed predominantly right. It performs a bilateral orchiectomy evidencing bilateral pure classic seminoma (T1 and T4). Staging the regional nodal involvement and distance rule and visceral with normal tumor markers. Receive adjuvant radiotherapy (3060 cGy) including inguinal lymph node chains, and pelvic and lumbo-aortic remaining free of disease at 33 months after surgery. Discussion: 85% of all bilateral TGT metachronous are presented as 15% synchronously. TBS represent less than 1% of the most representative series. In most cases they are seminomas and have been associated with infertility and history Family suggestive of genetic predisposition. Bilateral orchiectomy is local treatment of choice and subsequent planned strategy is according the loco-regional extension stressing the importance of hormone replacement and psychological support. Conclusions: In patients with a family history suggestive or infertile should be evaluated for TBS, especially if it carries a seminoma. the bilateral orchiectomy is local treatment of choice. We found no evidence seminomatous TBS have a worse prognosis compared with patients with unilateral or bilateral metachronous tumors of similar size lesional

Generation of juvenile rainbow trout derived from cryopreserved whole ovaries by intraperitoneal transplantation of ovarian germ cells.

Science.gov (United States)

Lee, Seungki; Katayama, Naoto; Yoshizaki, Goro

2016-09-23

Cryopreservation of fish sperm offers the practical applications in the selective breeding and biodiversity conservation. However, because of the lack of cryopreservation methods for fish eggs and embryos, maternally inherited cytoplasmic compartments cannot be successfully preserved. We previously developed an alternative method to derive functional eggs and sperm from cryopreserved whole testis by transplanting testicular cells into female and male recipients. However, if target fish had ovaries, the previous method employing male-derived germ cells would be ineffective. Here, we aimed to generate functional gametes from cryopreserved whole ovaries by transplanting ovarian germ cells into peritoneal cavity of sterile hatchlings. Cryopreservation conditions for rainbow trout ovaries (1.0 M DMSO, 0.1 M trehalose, and 10% egg yolk) were optimized by testing several different cryoprotective agents. Ovarian germ cells from thawed ovaries were intraperitoneally transplanted into allogeneic triploid hatchlings. Transplanted germ cells migrated toward and were incorporated into recipient gonads, where they underwent gametogenesis. Transplantation efficiency of ovarian germ cells remained stable after cryopreservation period up to 1185 days. Although all triploid recipients that did not undergo transplantation were functionally sterile, 5 of 25 female recipients and 7 of 25 male recipients reached sexual maturity at 2.5 years post-transplantation. Inseminating the resultant eggs and sperm generated viable offspring displaying the donor characteristics of orange body color, green fluorescence, and chromosome numbers. This method is thus a breakthrough tool for the conservation of endangered fish species that are crucial to cryopreserve the genetic resources of female fish. Copyright © 2016 Elsevier Inc. All rights reserved.

Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro?

Science.gov (United States)

Mincheva, M; Sandhowe-Klaverkamp, R; Wistuba, J; Redmann, K; Stukenborg, J-B; Kliesch, S; Schlatt, S

2018-02-01

interacted and contributed to cord-like structure formation. Not applicable. Owing to scarcity of normal human testicular tissue, testes from gender dysphoria patients were used in the study. The regressed status might influence the experimental responses of primary cells. We observed basic morphological features resembling in vivo testicular cords, however, the proof of functionality (e.g. support of germ cells) will need further studies. The proposed in vitro culture system may open opportunities for examination of testicular cell interactions during testicular tubulogenesis. Further refinement of our approach may enable initiation of ex vivo spermatogenesis. The work was supported by EU-FP7-PEOPLE-2013-ITN 603568: 'Growsperm'. No conflict of interests is declared. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Studies of testicular function after treatment for testicular tumor, 1

International Nuclear Information System (INIS)

Furuhata, Akihiko; Ogawa, Katsuaki; Hosaka, Masahiko; Sugawara, Toshimichi.

1985-01-01

Recently, the treatment for testicular tumor has improved. Preservation of testicular function in the treatment of testicular tumor is important, because the majority of the patients are young. We investigated the testicular function of patients with testicular tumor before, during and after treatment. As a part of this study, the fertility of patients with testicular tumor before and after treatment was evaluated. 1. Fourteen of 78 married patients (18 %) showed sterility for two or more years before treatment. 2. When semen was examined in 31 patients before treatment, only seven patients (23 %) showed normal sperm counts of more than 40 x 10 6 /ml, and 19 (61.3 %) showed oligospermia or azoospermia with sperm counts of less than 10 x 10 6 /ml. 3. Of 20 patients who underwent retroperitoneal lymphnode dissection, 15 developed ejaculation deficiency. Four other patients also developed ejaculation deficiency but recovered, and three of them rendered their wives pregnant. 4. Of 23 patients given radiotherapy, nine produced children both before and after treatment, nine produced children before treatment but showed sterility after treatment, and five showed sterility both before and after treatment. 5. Examination of semen was performed in 17 patients given radiotherapy and in five given chemotherapy. Many patients developed oligospermia or azoospermia after the treatments, but revealed a tendency to recover with time. Based on the results mentioned above, it is inferred that the ability to produce sperm in patients with testicular tumor after treatment decreases but the decrease tends to recover to normal with time. (author)

Sarcomas cutâneos primários Primary cutaneous sarcomas

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Luiz Fernando Fróes Fleury Jr

2006-06-01

Full Text Available Os sarcomas com apresentação cutânea primária são tumores raros e de grande heterogeneidade histológica. Com a evolução da oncologia cutânea e da cirurgia dermatológica, os dermatologistas têm sido cada vez mais requisitados para o diagnóstico e orientação terapêutica de tumores menos freqüentes. Este artigo de revisão analisa os sarcomas cutâneos primários observando suas características clínicas, etiopatogênicas e histológicas, bem como aspectos do tratamento e evolução. Enfatiza os sarcomas de maior relevância para o dermatologista, como angiossarcoma, dermatofibrossarcoma protuberans, fibroxantoma atípico, leiomiossarcoma, lipossarcoma, tumor maligno de bainha de nervo periférico e sarcoma epitelióide. O sarcoma de Kaposi não é abordado devido a suas características individuais específicas.Soft tissue tumors represent a heterogeneous group of mesenchymal and neural lesions. The cutaneous presentation of these tumours is rare. With the evolution of dermatologic surgery and cutaneous oncology, dermatologists have emerged as specialists for skin cancer management. This article reviews primary cutaneous sarcomas with particular emphasis on the epidemiologic, clinical, and histological features of diagnosis, as well as treatment modalities and prognosis. The most frequent cutaneous sarcomas were reviewed, including angiosarcoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, leiomyosarcoma, liposarcoma, malignant nerve sheath tumor, and epithelioid sarcoma. Kaposi's sarcoma, due to specific characteristics, was omitted from this review.

Desenvolvimento testicular, espermatogênese e concentrações hormonais em touros Angus Testicular development, spermatogenesis and hormonal concentrations in Angus bulls

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Gyselle Viana Aguiar

2006-08-01

and in seminiferous epithelium of Angus bulls between 10 and 38 weeks of age. Samples of testicular parenchyma and blood were collected from 25 animals castrated in 4 week intervals. Traits associated to testicular development and quantitative aspects of spermatogenesis and hormonal concentrations were transformed by logarithm before analyses of variance. Changes in testis and seminiferous tubule diameter and testis weight were more pronounced after 26 weeks of age. The percentage of testicular parenchyma occupied by seminiferous tubules increased from 49.3 to 75.2% from 10 to 38 weeks. Most tubules (>90% had only Sertoli cells at 10 and 14 weeks, but the number of tubules with gonocytes and A spermatogonia increased at 18 (13.8±1.7% and 22 weeks (19±1%. Tubules with B and intermediate spermatogonia became predominant at 26 weeks (24.5±8.2% and those with spermatocytes as the most advanced germ cell type were more evident at 30 weeks (42.3±9.9%. Round spermatids were detected at 26 weeks and at 38 weeks of age, 62.3±1.5% of all tubules had either elongate or mature spermatids. Variations in testis growth (specially testis weight after 26 weeks were coincident with the establishment of meiosis in the seminiferous tubules, morphological alterations in nucleus and nucleolus of the Sertoli cells (indicators of Sertoli cell differentiation, lower levels of androstenedione and significant increases in testosterone and estradiol 17beta. Associations between testis development and concentrations of FSH and LH were less evident.

Kaposi's sarcoma

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Kirova, Y.M.; Belembaogo, E.; Frikha, H.; Yu, S.J.; Le Bourgeois, J.P.

1997-01-01

Moriz Kaposi was the first who, in 1872, described five patients presenting with 'sarcoma idiopathicum multiple hemorrhagicum'. In 1912 Sternberg termed this disease Kaposi's sarcoma. Since then various forms of this rare disease have been observed. In 1914 Hallenberg described the first cases of African or endemic Kaposi's sarcoma. In the 1960's the first reports discussing Kaposi's sarcoma following organ transplantation and immunosuppressive therapy were published. After 1981, the epidemic form associated with the acquired immunodeficiency syndrome (AIDS) was described. All these forms, their history, treatment methods and the role of radiation therapy in the management of this rare malignancy are discussed, and the literature is reviewed. (authors)

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling

DEFF Research Database (Denmark)

Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute

2004-01-01

in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported......Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly...

Isolated eyeball metastasis of non-seminomatous germ cell testicular tumor.

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Bojanić, Nebojsa; Nale, Djordje; Mićić, Sava; Janicić, Aleksandar; Vuksanović, Aleksandar; Vuković, Ivan

2011-11-01

Testicular tumors most frequently metastasize to regional lymph nodes. Non-seminomatous tumor metastasis of testicle (NSGCTT) to the eyeball is rare. We presented a 24-year old man, referred to the ophthalmologist due to acute pain and abrupt loss of sight in the left eye accompanied by its enlargement. Orbital and endocranial computerized tomography (CT) was carried out, indicating the tumor in the left eye. His previous medical history provided the information that the right testicle was painlessly enlarged for 8 months. Ultrasonography showed a completely tumorously altered testis. Abdominal and chest CT failed to reveal any secondary deposits in visceral organs and lymph glands. Tumor markers (AFP - alpha-fetoproteins, beta hCG - human choronic gonadotropin beta) were elevated. Right radical orchiactomy was performed (showed NSGCTT), followed by polychemotherapy with cisplatinum 100 mg/m2, etoposide 120 mg/m2, bleomycin 15 mg/m2 (PEB x 4), resulting in normalization of tumor marker values and significant regression of the left eyeball. Next, the left eye enucleation and ocular prosthesis implantation was carried out. Pathohistological evaluation indicated fibrosis and necrosis only. In a 5-year follow-up period, the patient was free of recurrence. Isolated hematogenous metastasis of the NSGCTT to the eye is rare. In our case, the left eye was the only metastatic localization. After chemotherapy and eye enucleation the patient was in a 4-year follow-up period free of the recurrence.

microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients.

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van Agthoven, Ton; Eijkenboom, Wil M H; Looijenga, Leendert H J

2017-08-01

α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up. We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers. At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma. The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.

The Danish Testicular Cancer database.

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Daugaard, Gedske; Kier, Maria Gry Gundgaard; Bandak, Mikkel; Mortensen, Mette Saksø; Larsson, Heidi; Søgaard, Mette; Toft, Birgitte Groenkaer; Engvad, Birte; Agerbæk, Mads; Holm, Niels Vilstrup; Lauritsen, Jakob

2016-01-01

The nationwide Danish Testicular Cancer database consists of a retrospective research database (DaTeCa database) and a prospective clinical database (Danish Multidisciplinary Cancer Group [DMCG] DaTeCa database). The aim is to improve the quality of care for patients with testicular cancer (TC) in Denmark, that is, by identifying risk factors for relapse, toxicity related to treatment, and focusing on late effects. All Danish male patients with a histologically verified germ cell cancer diagnosis in the Danish Pathology Registry are included in the DaTeCa databases. Data collection has been performed from 1984 to 2007 and from 2013 onward, respectively. The retrospective DaTeCa database contains detailed information with more than 300 variables related to histology, stage, treatment, relapses, pathology, tumor markers, kidney function, lung function, etc. A questionnaire related to late effects has been conducted, which includes questions regarding social relationships, life situation, general health status, family background, diseases, symptoms, use of medication, marital status, psychosocial issues, fertility, and sexuality. TC survivors alive on October 2014 were invited to fill in this questionnaire including 160 validated questions. Collection of questionnaires is still ongoing. A biobank including blood/sputum samples for future genetic analyses has been established. Both samples related to DaTeCa and DMCG DaTeCa database are included. The prospective DMCG DaTeCa database includes variables regarding histology, stage, prognostic group, and treatment. The DMCG DaTeCa database has existed since 2013 and is a young clinical database. It is necessary to extend the data collection in the prospective database in order to answer quality-related questions. Data from the retrospective database will be added to the prospective data. This will result in a large and very comprehensive database for future studies on TC patients.

How valid is the prenatal estrogen excess hypothesis of testicular germ cell cancer? A case control study on hormone-related factors.

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Dieckmann, K P; Endsin, G; Pichlmeier, U

2001-12-01

The prenatal estrogen excess hypothesis postulates abnormally high estrogen levels during pregnancy which predispose the developing gonad to testicular germ cell cancer (GCT) in adulthood. As no direct measurements are possible to support this hypothesis, evidence must come from clinical and epidemiological observations. The present study looked to surrogate parameters that purportedly point to high estrogenic influence in utero. In a case-control study design, 418 cases with GCT were compared to 636 controls having fractures, injuries or nephrolithiasis. A second comparison was done with 120 men suffering from malignant melanoma. The following factors were investigated: maternal and paternal age at birth of proband, birth-order, distribution of brothers and sisters in sibs of patients, sibship size, status of being a twin, status of being a singleton child, handedness, and frequency of breast cancer in mothers and sisters. Status of being a twin was significantly associated with GCT risk (OR 2.41; 95% CI 1.04- 5.63) if compared to men with fractures or stones. Comparison with melanoma controls showed only a nonsignificant trend. Frequency of breast cancer was insignificantly higher in mothers of GCT patients. Maternal age above 30 years was associated with decreased risk of GCT, which is contradictory to the hypothesis. No other parameter was significantly different in cases and controls. The present investigation failed to produce evidence for the estrogen excess hypothesis. Obviously, the parameters tested are only weak indicators of estrogenic influence during embryogenesis. Thus, the sample size and statistical power of the trial might have been too low to show any significant association. But, assessing the negative results of this study in light of equally negative results in previous investigations, the estrogen excess hypothesis still remains to be hypothetic.

Is Radiotherapy Necessary for Stage 1 Testicular Seminoma?

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Lee, Jung Ae; Park, Won; Lim, Do Hoon; Ahn, Yong Chan; Huh, Seung Jae; Yu, Jeong Il; Choi, Han Yong; Lee, Hyun Moo; Cho, Eun Yoon

2009-01-01

To report on the clinical outcome of patients with stage I testicular seminoma by postoperative radiotherapy (PORT) or surveillance after radical inguinal orchiectomy. This study is a retrospective review of 32 stage I pure seminoma patients treated between 1996 and 2005 at the Samsung Medical Center. Twenty two of the patients were treated by PORT, which was directed at the paraaortic lymphatics with a median dose of 25.2 Gy in 14 fractions for 3 weeks. The 10 remaining patients were managed by surveillance. The median follow-up period was 96 months with a range of 24 to 155 months. Clinically, most patients presented with a testicular mass or discomfort. Two of the patients had a history of undescended testes. Pathologically, 23 of the patients had intratubular germ cell neoplasia with seminoma. Both recurrence-free survival (RFS) and overall survival (OS) rates of patients treated by PORT were 100%. In the control group, 1 of the 10 patients suffered a para-aortic lymph node relapse. The RFS and OS rates of the surveillance group were 88.9% and 100%, respectively. No difference in survival was observed between the two groups. Moreover, symptom recurrence was only observed in 1 patient in the control group. The use of PORT may reduce the risk of relapse. With the availability of effective diagnostic and salvage modalities, surveillance monitoring may be considered for patients in good compliance

A Meta-Analysis of the Relationship between Testicular Microlithiasis and Incidence of Testicular Cancer.

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Wang, Tao; Liu, LuHao; Luo, JinTai; Liu, TaiSheng; Wei, AnYang

2015-04-29

There are many recent observational studies on testicular microlithiasis (TM) and risk of testicular cancer. Whether TM increases the risk of testicular cancer is still inconclusive. The objective of this updated meta-analysis was to synthesize evidence from clinical observational studies that evaluated the association between TM and testicular cancer. We identified eligible studies by searching the PubMed, Embase and Cochrane Library before March 2014. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-or fixed-model. A total of 14 studies involving 35,578 participants were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale systematic review, eleven studies were identified as relatively high-quality. TM was strong association with an increased incidence of testicular cancer (RR = 12.70, 95% CI: 8.18-19.71, P testicular cancer. More researches are warranted to clarify an understanding of the association between TM and risk of testicular cancer.

Targeted therapy for sarcomas

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Forscher C

2014-03-01

Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

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Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute; Blake, Jonathon; Schwager, Christian; Ansorge, Wilhelm; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2004-07-15

Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

Intracardiac Low-grade Sarcoma Following Treatment for Ewing Sarcoma.

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Ortiz, Michael V; Magnan, Heather; Slotkin, Emily K; Ambati, Srikanth R; Chou, Alexander J; Wexler, Leonard H; Meyers, Paul A; Walsh, Michael F; Heaton, Todd; Girardi, Leonard N; Wolden, Suzanne L; Price, Anita P; Kennedy, Jennifer A; Zehir, Ahmet; Hameed, Meera; Berger, Michael F; Kentsis, Alex; Shukla, Neerav

2017-11-01

A 16-year-old male was diagnosed with Ewing sarcoma of the ribcage with pulmonary metastases. Six months after completion of scheduled therapy, he was found to have a new intracardiac mass, presumed recurrent Ewing sarcoma. EWSR1 fusion was not detected by droplet digital polymerase chain reaction from blood plasma. After no improvement with salvage chemotherapy, he underwent surgical resection that identified a low-grade spindle cell sarcoma. Despite the near-synchronous presentation of 2 unrelated sarcomas, extensive genomic analyses did not reveal any unifying somatic or germline mutations nor any apparent cancer predisposition. This case also highlights the potential role of utilizing plasma cell-free DNA for diagnosing tumors in locations where biopsy confers high morbidity.

Salicornia ramosissima: Secondary metabolites and protective effect against acute testicular toxicity

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Daniela Ferreira

2018-01-01

Full Text Available Salicornia ramosissima J. Woods is a salt tolerant plant currently used in the human diet, whose genus not only displays great potential as a crop plant in deserts and highly saline soils, but also has value in traditional medicine and exhibits promising biological activities. The present study was designed to evaluate the effect of S. ramosissima ethanolic extract on carbon tetrachloride (CCl4-induced testicular damage in a mouse model and identify secondary metabolites present in the tested extract. The histopathological analysis showed that the treatment with the ethanolic extract prior to CCl4 administration prevented significantly the architectural disorder of seminiferous epithelium and germ cell exfoliation. The phytochemical study allowed the identification of known phenolic and aliphatic compounds [ethyl linolenoate (1, sitostanol (2, octadecyl (3 and eicosanyl (4 (E-ferulates, ethyl (E-2-hydroxycinnamate (5, scopoletin (6, a triacylglycerol of tetracosanoic acid (7], and three new compounds: saliramoester, a long chain triester (8, saliramophenone, a propiophenone derivative (9 and saliramopyrrole a pyrrole-3-carbaldehyde derivative (10. Their chemical structures were elucidated using detailed spectroscopic studies (1D and 2D NMR and MS. These results enhance the value of S. ramosissima as an excellent source of structurally interesting phytochemicals and as protective agent against testicular toxicity.

Testicular microlithiasis in patients with testicular cancer in the United Kingdom and in Denmark

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Horsfield, Catherine; Foot, Oliver

2018-01-01

INTRODUCTION: Testicular cancer is the most common type of cancer in young Caucasian men. It has been suggested that testicular microlithiasis (TML) is a premalignant condition. This study's objective was to investigate TML histology prevalence in testicular cancer patients in two European...... populations. METHODS: We analysed archived histopathology orchiectomy specimens from 152 patients diagnosed with testicular cancer at Fredericia Hospital in Denmark from 2004 to 2014, and 106 patients diagnosed at St Thomas' Hospital in London from 2011 to 2015. RESULTS: The Danish patients' median age was 37...... in seminomas than in non-seminomas.
 CONCLUSIONS: The English testicular cancer patients had a statistically significantly higher TML prevalence than the Danish patients. This observation questions the hypothesised biological association between TML and testicular 
cancer. FUNDING: The Region of Southern...

Management of testicular seminoma. Our experience.

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Sperlongano, P; Pisaniello, D; Di Mauro, U; Pone, D; Casoli, E

2000-01-01

The authors report their experience in the management of seminomas. They examine 12 cases of seminoma among a series of 19 patients with testicular germ cell tumours observed at the Second Surgical Department of the Second University of Naples. Their results showed a better prognosis for patients in early stage of the disease who underwent surgery and adjuvant prophylactic radiotherapy; good survival rates for patients in advanced stages of the disease were achieved by the combined use of surgery, adjuvant radiotherapy and chemotherapy. The authors discuss risk factors, clinical and diagnostic features of seminomas, relating their prognosis with the combined use of both surgery and adjuvant therapies. They consider total orchiectomy, followed by prophylactic radiotherapy, the treatment of choice, especially in stages IA and IIA. They don't perform the routine retroperitoneal lymphadenectomy, differently from American authors, who always achieve it to stage the disease. The authors stress the improvement in the prognosis of seminoma, which has actually reached the 98% of five-year survival rate, for stages I and II.

A survey of Sertoli cell differentiation in men after gonadotropin suppression and in testicular cancer

DEFF Research Database (Denmark)

Tarulli, Gerard A; Stanton, Peter G; Loveland, Kate L

2013-01-01

It is widely held that the somatic cell population that is responsible for sperm development and output (Sertoli cells) is terminally differentiated and unmodifiable in adults. It is postulated, with little evidence, that Sertoli cells are not terminally differentiated in some phenotypes of infer...... tubules with CIS and the emergence of strong JAM-A reactivity in seminoma. These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia....... of infertility and testicular cancer. This study sought to compare markers of Sertoli cell differentiation in normospermic men, oligospermic men (undergoing gonadotropin suppression) and testicular carcinoma in situ (CIS) and seminoma samples. Confocal microscopy was used to assess the expression of markers...... of proliferation (PCNA and Ki67) and functional differentiation (androgen receptor). As additional markers of differentiation, the organization of Sertoli cell tight junction and associated proteins were assessed in specimens with carcinoma in situ. In normal men, Sertoli cells exhibited a differentiated phenotype...

Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

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Zhao Junfeng

2012-03-01

Full Text Available Abstract The testicular yolk sac tumor (TYST is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14

Science.gov (United States)

Ruark, Elise; Seal, Sheila; McDonald, Heather; Zhang, Feng; Elliot, Anna; Lau, KingWai; Perdeaux, Elizabeth; Rapley, Elizabeth; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Shipley, Janet; Bishop, D. Timothy; Stratton, Michael R; Easton, Douglas F; Huddart, Robert A; Rahman, Nazneen; Turnbull, Clare

2013-01-01

Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks1,2. To date, six loci associated with TGCT have been reported3-7. From GWAS analysis of 307,291 SNPs in 986 cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci showing association with TGCT (P<5×10−8), at 1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3, which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification8 whilst DAZL, at 3p24.3, is required for regulation of germ cell development9. Furthermore, PITX1, at 5q31.1 regulates TERT expression, and is the third TGCT locus implicated in telomerase regulation10. PMID:23666240

Testicular cancer update.

Science.gov (United States)

Adra, Nabil; Einhorn, Lawrence H

2017-05-01

The advances seen in the treatment of testicular cancer are among the great achievements in modern medicine. These advances were made possible by the collaborative efforts of cancer researchers around the world. Investigators have been able to address many questions regarding the treatment of patients with disease limited to the testis, those with metastasis to the retroperitoneum only, and those with advanced metastatic disease. Questions answered include the chemotherapeutic agents to be used and in what combinations, the proper intensity of treatment and appropriate dosing, the optimal number of cycles of chemotherapy according to validated risk stratification, appropriate surgical approaches that preserve sexual function, the treatment of relapsed disease, what supportive care measures to take, and survivorship issues following treatment of testicular cancer. Today, cure is achievable in 95% of all patients with testicular cancer and 80% of those who have metastatic disease. Despite remarkable results with frontline and salvage combination chemotherapy, metastatic testicular cancer remains incurable in approximately 10% of patients, and novel treatment approaches are warranted. This review highlights past and recent discoveries in the treatment of patients with testicular cancer.

Ewing sarcoma

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Bone cancer - Ewing sarcoma; Ewing family of tumors; Primitive neuroectodermal tumors (PNET); Bone neoplasm - Ewing sarcoma ... to the lungs and other bones. At the time of diagnosis, spread is seen in about one- ...

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

Science.gov (United States)

Malkin, D; Li, F P; Strong, L C; Fraumeni, J F; Nelson, C E; Kim, D H; Kassel, J; Gryka, M A; Bischoff, F Z; Tainsky, M A

1990-11-30

Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

Clinical practice guideline: 2006 update of recommendations for the radiotherapeutic management of patients with soft tissue sarcoma (sarcoma of the extremity, uterine sarcoma and retroperitoneal sarcoma)

International Nuclear Information System (INIS)

Le Pechoux, C.; Pautier, P.; Le Cesne, A.; Delannes, M.; Bui, B.N.; Blay, J.Y.; Bonichon, F.; Bonvalot, S.; Morice, P.; Chevalier-Place, A.; Taieb, S.; Coindre, J.M.; Ray-Coquard, I.; Stoeckle, E.

2006-01-01

Context. - The National French Federation of Comprehensive Cancer Centres (FNCLCC) initiated the update of clinical practice guideline for the management of patients with soft tissue sarcoma in collaboration with the French Sarcoma Group (GSF-GETO), specialists from French public universities, general hospitals and private clinics and with the French National Cancer Institute. This work is based on the methodology developed in the 'Standards, Options and Recommendations' (SOR) project. Objectives - To update SOR guidelines for the management of patients with oft tissue sarcoma previously validated in 1995. Methods. -The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. Results. - This article presents the updated recommendations for radiotherapeutic management. The main recommendations are: 1) irradiation before or after surgical treatment is the standard for soft tissue sarcoma of the extremity and uterine sarcoma; 2) no systematic irradiation should be done in case of retroperitoneal sarcoma. (author)

Testicular self-examination and testicular cancer: a cost-utility analysis.

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Aberger, Michael; Wilson, Bradley; Holzbeierlein, Jeffrey M; Griebling, Tomas L; Nangia, Ajay K

2014-12-01

The United States Preventive Services Task Force (USPSTF) has recommended against testicular self-examinations (TSE) or clinical examination for testicular cancer screening. However, in this recommendation there was no consideration of the significant fiscal cost of treating advanced disease versus evaluation of benign disease. In this study, a cost-utility validation for TSE was performed. The cost of treatment for an advanced-stage testicular tumor (both seminomatous and nonseminomatous) was compared to the cost of six other scenarios involving the clinical assessment of a testicular mass felt during self-examination (four benign and two early-stage malignant). Medicare reimbursements were used as an estimate for a national cost standard. The total treatment cost for an advanced-stage seminoma ($48,877) or nonseminoma ($51,592) equaled the cost of 313-330 benign office visits ($156); 180-190 office visits with scrotal ultrasound ($272); 79-83 office visits with serial scrotal ultrasounds and labs ($621); 6-7 office visits resulting in radical inguinal orchiectomy for benign pathology ($7,686) or 2-3 office visits resulting in treatment and surveillance of an early-stage testicular cancer ($17,283: seminoma, $26,190: nonseminoma). A large number of clinical evaluations based on the TSE for benign disease can be made compared to the cost of one missed advanced-stage tumor. An average of 2.4 to 1 cost benefit ratio was demonstrated for early detected testicular cancer versus advanced-stage disease. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Testicular Busulfan Injection in Mice to Prepare Recipients for Spermatogonial Stem Cell Transplantation Is Safe and Non-Toxic.

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Qin, YuSheng; Liu, Ling; He, YaNan; Wang, Chen; Liang, MingYuan; Chen, XiaoLi; Hao, HaiSheng; Qin, Tong; Zhao, XueMing; Wang, Dong

2016-01-01

Current methods of administering busulfan to remove the endogenous germ cells cause hematopoietic toxicity, require special instruments and a narrow transplantation time. We use a direct testicular injection of busulfan method for preparing recipients for SSC transplantation. Male ICR mice (recipients) were divided into four groups, and two experimental groups were treated with a bilateral testicular injection of 4 or 6 mg/kg/side busulfan (n = 60 per concentration group). Mice received an intraperitoneal injection (i.p.) of 40 mg/kg busulfan (n = 60, positive control) and bilateral testicular injections of 50% DMSO (n = 60, negative control). Donor SSCs from RFP-transgenic C57BL/6J mice were introduced into the seminiferous tubules of each recipient testis via efferent duct injection on day 16-17 after busulfan treatment. Recipient mice mated with mature female ICR mice and the number of progeny was recorded. The index detected at day 14, 21, 28, 35 and 70 after busulfan treatment. Blood analysis shows that the toxicity of busulfan treated groups was much lower than i.p. injection groups. Fertility was restored in mice treated with busulfan and donor-derived offspring were obtained after SSC transplantation. Our study indicated that intratesticular injection busulfan for the preparation of recipients in mice is safe and feasible.

Testicular Busulfan Injection in Mice to Prepare Recipients for Spermatogonial Stem Cell Transplantation Is Safe and Non-Toxic.

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YuSheng Qin

Full Text Available Current methods of administering busulfan to remove the endogenous germ cells cause hematopoietic toxicity, require special instruments and a narrow transplantation time. We use a direct testicular injection of busulfan method for preparing recipients for SSC transplantation. Male ICR mice (recipients were divided into four groups, and two experimental groups were treated with a bilateral testicular injection of 4 or 6 mg/kg/side busulfan (n = 60 per concentration group. Mice received an intraperitoneal injection (i.p. of 40 mg/kg busulfan (n = 60, positive control and bilateral testicular injections of 50% DMSO (n = 60, negative control. Donor SSCs from RFP-transgenic C57BL/6J mice were introduced into the seminiferous tubules of each recipient testis via efferent duct injection on day 16-17 after busulfan treatment. Recipient mice mated with mature female ICR mice and the number of progeny was recorded. The index detected at day 14, 21, 28, 35 and 70 after busulfan treatment. Blood analysis shows that the toxicity of busulfan treated groups was much lower than i.p. injection groups. Fertility was restored in mice treated with busulfan and donor-derived offspring were obtained after SSC transplantation. Our study indicated that intratesticular injection busulfan for the preparation of recipients in mice is safe and feasible.

Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation

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Dorothy A. Lerit

2017-01-01

Full Text Available The primordial germ cells (PGCs specified during embryogenesis serve as progenitors to the adult germline stem cells. In Drosophila, the proper specification and formation of PGCs require both centrosomes and germ plasm, which contains the germline determinants. Centrosomes are microtubule (MT-organizing centers that ensure the faithful segregation of germ plasm into PGCs. To date, mechanisms that modulate centrosome behavior to engineer PGC development have remained elusive. Only one germ plasm component, Germ cell-less (Gcl, is known to play a role in PGC formation. Here, we show that Gcl engineers PGC formation by regulating centrosome dynamics. Loss of gcl leads to aberrant centrosome separation and elaboration of the astral MT network, resulting in inefficient germ plasm segregation and aborted PGC cellularization. Importantly, compromising centrosome separation alone is sufficient to mimic the gcl loss-of-function phenotypes. We conclude Gcl functions as a key regulator of centrosome separation required for proper PGC development.

Testicular germinal tumors

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Fresco, R.

2010-01-01

This work is about diagnosis, treatment and monitoring of testicular germinal tumors. The presumed diagnosis is based in the anamnesis, clinical examination, testicular ultrasound and tumor markers. The definitive diagnosis is obtained through the inguinal radical orchidectomy

Disrupting the male germ line to find infertility and contraception targets.

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Archambeault, Denise R; Matzuk, Martin M

2014-05-01

Genetically-manipulated mouse models have become indispensible for broadening our understanding of genes and pathways related to male germ cell development. Until suitable in vitro systems for studying spermatogenesis are perfected, in vivo models will remain the gold standard for inquiry into testicular function. Here, we discuss exciting advances that are allowing researchers faster, easier, and more customizable access to their mouse models of interest. Specifically, the trans-NIH Knockout Mouse Project (KOMP) is working to generate knockout mouse models of every gene in the mouse genome. The related Knockout Mouse Phenotyping Program (KOMP2) is performing systematic phenotypic analysis of this genome-wide collection of knockout mice, including fertility screening. Together, these programs will not only uncover new genes involved in male germ cell development but also provide the research community with the mouse models necessary for further investigations. In addition to KOMP/KOMP2, another promising development in the field of mouse models is the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-Cas technology. Utilizing 20 nucleotide guide sequences, CRISPR/Cas has the potential to introduce sequence-specific insertions, deletions, and point mutations to produce null, conditional, activated, or reporter-tagged alleles. CRISPR/Cas can also successfully target multiple genes in a single experimental step, forgoing the multiple generations of breeding traditionally required to produce mouse models with deletions, insertions, or mutations in multiple genes. In addition, CRISPR/Cas can be used to create mouse models carrying variants identical to those identified in infertile human patients, providing the opportunity to explore the effects of such mutations in an in vivo system. Both the KOMP/KOMP2 projects and the CRISPR/Cas system provide powerful, accessible genetic approaches to the study of male germ cell development in the mouse. A

Public awareness of testicular cancer and testicular self-examination in academic environments: a lost opportunity

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Henry A. A. Ugboma

2011-01-01

Full Text Available BACKGROUND: Although testicular cancer is the most common cancer among 18- to 50-year-old males, healthcare providers seldom teach testicular self-examination techniques to clients, thus potentially missing opportunities for early detection. This form of cancer is easily diagnosable by testicular self-examination and is 96% curable if detected early. Periodic self-examination must be performed for early detection. Knowledge deficits and sociocultural norms contribute to low levels of health-related knowledge in most patients, resulting in undue delays before seeking medical advice. OBJECTIVE: Our aim is to assess the level of awareness of testicular cancer and the prevalence of the practice of testicular self-examination in academic environments to enable appropriate interventions. METHOD: A cross-sectional survey was administered to 750 consecutive males aged 18-50 years in three tertiary institutions in Port Harcourt from October 2008 to April 2009. RESULT: Knowledge or awareness of testicular cancer was poor. Almost all of the respondents were unaware that testicular lumps may be signs of cancer. A lump was typically construed as a benign carbuncle or something that could resolve spontaneously. The main factor contributing to respondents' lack of knowledge of testicular cancer was that few reported that they were "ever taught about testicular self-examination." CONCLUSION: Young adult men are unaware of their risk for testicular cancer, which is the most common neoplasm in this age group. Healthcare providers are not informing them of this risk, nor are they teaching them the simple early detection technique of self-examination of the testes.

Stages of Ewing Sarcoma

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... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

The Danish Sarcoma Database

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Jørgensen, Peter Holmberg; Lausten, Gunnar Schwarz; Pedersen, Alma B

2016-01-01

AIM: The aim of the database is to gather information about sarcomas treated in Denmark in order to continuously monitor and improve the quality of sarcoma treatment in a local, a national, and an international perspective. STUDY POPULATION: Patients in Denmark diagnosed with a sarcoma, both...... skeletal and ekstraskeletal, are to be registered since 2009. MAIN VARIABLES: The database contains information about appearance of symptoms; date of receiving referral to a sarcoma center; date of first visit; whether surgery has been performed elsewhere before referral, diagnosis, and treatment; tumor...... of Diseases - tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System). Data quality and completeness are currently secured. CONCLUSION: The Danish Sarcoma Database is population based and includes sarcomas occurring...

Endosulfan and flutamide impair testicular development in the juvenile Asian catfish, Clarias batrachus

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Rajakumar, A.; Singh, R.; Chakrabarty, S.; Murugananthkumar, R.; Laldinsangi, C.; Prathibha, Y.; Sudhakumari, C.C.; Dutta-Gupta, A. [Department of Animal Sciences, School of Life Sciences-Centre for Advanced Studies, University of Hyderabad, P. O. Central University, Hyderabad 500046, Andhra Pradesh (India); Senthilkumaran, B., E-mail: bsksl@uohyd.ernet.in [Department of Animal Sciences, School of Life Sciences-Centre for Advanced Studies, University of Hyderabad, P. O. Central University, Hyderabad 500046, Andhra Pradesh (India)

2012-04-15

Highlights: Black-Right-Pointing-Pointer Endosulfan and/or flutamide retard(s) testicular differentiation in juvenile fish. Black-Right-Pointing-Pointer Endosulfan and/or flutamide target(s) cfGnRH-Tph2 axis, either directly or indirectly. Black-Right-Pointing-Pointer Effects of endosulfan and/or flutamide on plasma androgen levels. Black-Right-Pointing-Pointer Compared changes in testis-related transcripts with testis germ cell distribution. Black-Right-Pointing-Pointer Our study on endosulfan endorse its prompt and complete phase-out/ban. - Abstract: Endosulfan and flutamide, a widely used pesticide and a prostate cancer/infertility drug, respectively, have an increased risk of causing endocrine disruption if they reach water bodies. Though many studies are available on neurotoxicity/bioaccumulation of endosulfan and receptor antagonism of flutamide, only little is known about their impact on testicular steroidogenesis at molecular level. Sex steroids play an important role in sex differentiation of lower vertebrates including fishes. Hence, a small change in their levels caused by endocrine disruptors affects the gonadal development of aquatic vertebrates significantly. The aim of this study was to evaluate the effects of endosulfan and flutamide on testis-related transcription factor and steroidogenic enzyme genes with a comparison on the levels of androgens during critical period of catfish testicular development. We also analyzed the correlation between the above-mentioned genes and catfish gonadotropin-releasing hormone (cfGnRH)-tryptophan hydroxylase2 (tph2). The Asian catfish, Clarias batrachus males at 50 days post hatch (dph) were exposed to very low dose of endosulfan (2.5 {mu}g/L) and flutamide (33 {mu}g/L), alone and in combination for 50 days. The doses used in this study were far less than those used in the previous studies of flutamide and reported levels of endosulfan in surface water and sediments. Sampling was done at end of the treatments (100

Imaging Ewing's sarcoma

International Nuclear Information System (INIS)

Henk, C.B.; Grampp, S.; Kainberger, F.; Breitenseher, M.; Imhof, H.; Mostbeck, G.H.

1998-01-01

Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and 201 thallium scanning has been shown to be sensitive in the monitoring of treatment response. Today, computed tomography is not longer used to image the tumor site; however, spiral CT of the lungs plays a central role as a staging and follow-up tool. (orig.) [de

Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

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Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

2015-01-01

Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse......, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal...

Varicocele and testicular function

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Alexander W Pastuszak

2015-01-01

Full Text Available Testicular varicocele, a dilation of the veins of the pampiniform plexus thought to increase testicular temperature via venous congestion, is commonly associated with male infertility. Significant study has clarified the negative impact of varicocele on semen parameters and more recent work has shed light on its detrimental effects on the molecular and ultrastructural features of sperm and the testicular microenvironment, as well as more clearly defined the positive impacts of treatment on couples′ fertility. The relationship between varicocele and testicular endocrine function, while known for some time based on histologic evaluation, has become more apparent in the clinical setting with a growing link between varicocele and hypogonadism. Finally, in the pediatric setting, while future study will clarify the impact of varicocele on fertility and testicular function, recent work supports a parallel effect of varicocele in adolescents and adults, suggesting a re-evaluation of current treatment approaches in light of the progressive nature of the condition and potential increased risk of future disease.

Glial cell line-derived neurotrophic factor and endothelial cells promote self-renewal of rabbit germ cells with spermatogonial stem cell properties.

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Kubota, Hiroshi; Wu, Xin; Goodyear, Shaun M; Avarbock, Mary R; Brinster, Ralph L

2011-08-01

Previous studies suggest that exogenous factors crucial for spermatogonial stem cell (SSC) self-renewal are conserved among several mammalian species. Since glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are critical for rodent SSC self-renewal, we hypothesized that they might promote self-renewal of nonrodent SSCs. Therefore, we cultured testicular germ cells from prepubertal rabbits in the presence of GDNF and FGF2 and found they proliferated indefinitely as cellular clumps that displayed characteristics previously identified for rodent SSCs. The rabbit germ cells could not be maintained on mouse embryonic fibroblast (STO) feeders that support rodent SSC self-renewal in vitro but were rather supported on mouse yolk sac-derived endothelial cell (C166) feeder layers. Proliferation of rabbit germ cells was dependent on GDNF. Of critical importance was that clump-forming rabbit germ cells colonized seminiferous tubules of immunodeficient mice, proliferated for at least 6 mo, while retaining an SSC phenotype in the testes of recipient mice, indicating that they were rabbit SSCs. This study demonstrates that GDNF is a mitogenic factor promoting self-renewal that is conserved between rodent and rabbit SSCs; with an evolutionary separation of ∼ 60 million years. These findings provide a foundation to study the mechanisms governing SSC self-renewal in nonrodent species.

Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer.

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Kurkure, Purna; Prasad, Maya; Dhamankar, Vandana; Bakshi, Ganesh

2015-11-09

Infertility is a known side-effect of oncotherapy in cancer survivors, and often compromises the quality of life. The present study was undertaken to detect very small embryonic-like stem cells (VSELs) in testicular biopsies from young adult survivors of childhood cancer who had azoospermia. VSELs have been earlier reported in human and mouse testes. They resist busulphan treatment in mice and potentially restore spermatogenesis when the somatic niche is restored by transplanting Sertoli or mesenchymal cells. VSELs also have the potential to differentiate into sperm in vitro. The study had clearance from Institutional review board (IRB). Seven azoospermic survivors of childhood cancer were included in the study after obtaining their informed consent. Semen analysis was done to confirm azoospermia prior to inclusion in the study. Testicular biopsies were performed at the Uro-oncology Unit of the hospital and then used for various studies to detect VSELs. Hematoxylin and Eosin stained tubular sections confirmed azoospermia and smears revealed the presence of very small, spherical VSELs with high nucleo-cytoplasmic ratio, in addition to the Sertoli cells. Immuno-localization studies on testicular smears showed that the VSELs were CD133+/CD45-/LIN-, expressed nuclear OCT-4, STELLA and cell surface SSEA-4. Pluripotent transcripts Oct-4A, Nanog and Sox-2 were detected in azoospermic samples whereas marked reduction was observed in germ cell markers Oct-4 and Boule. The present study demonstrates the presence of pluripotent VSELs in the testicular biopsy of azoospermic adult survivors of childhood cancer. It is likely that these persisting VSELs can restore spermatogenesis as demonstrated in mice studies. Therefore, pilot studies need to be undertaken using autologous mesenchymal cells with a hope to restore testicular function and fertility in cancer survivors. The results of this study assume a great significance in the current era, where cryopreservation of testicular

Genotoxic and biochemical effects of Yohimbe after short-term treatment in somatic and germ cells of Swiss Albino Mice

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Al-Yahya, Abdulaziz A.

2006-01-01

Yohimbe was evaluated for its effects on cytological and biochemical toxicity in male Swiss albino mice. Adult male mice were mice were treated with different doses (750, 1500 and 3000 mg yohombe/kg., body weight/day) in form of an aqueous suspension for 7 consecutive days by gavage. The following parameters were evaluated: (i) cytological studies on micronucleus test, (ii) cytological analysis of spermatozoa abnormalities, (iii) Cytogentic analysis of meiotic chromosomes in the tests, (iv) quantification of proteins, ribose nucleic acid (RNA) and deoxyribose nucleic acid (DNA) in hepatic and testicular cells and (v) estimation of malondialdehyde (MDA) and nonprotein sulfhydryl (NP-SH) in hepatic and testicular cells. The treatment caused significant changes in the frequency of micronuclei in the femoral cells and induced spermatozoal abnormalities and testicular chromosomal aberrations. The study on biochemical parameters showed an increase of MDA and depletion of NP-SH, proteins, RNA and DNA in both hepatic and testicular cells. The data elucidated the role of free radical species in cytological and biochemical changes in both somatic and germ cells of Swiss albino mice. The exact mechanism of the genesis of lipid peroxides is not known, however, this might be related to the influence of yohimbine (the principal constituent of yohimbe) to enhance some catecholamines, including norepineprine which possess destructive stimuli on biological systems. It is suggested that, in view of the observed cytological and biochemical effects of yohimbe, it may be subjected to a thorough evaluation of toxicity before making it available for human use. (author)

Kaposi sarcoma

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... please enable JavaScript. Kaposi sarcoma is a cancerous tumor of the connective tissue, and is often associated with HIV/AIDS . Causes Before the HIV/AIDS epidemic, Kaposi sarcoma was seen mainly in older Italian ... this group, the tumors developed slowly. In people with HIV/AIDS, the ...

Uterine sarcoma Part II—Uterine endometrial stromal sarcoma: The TAG systematic review

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Huann-Cheng Horng

2016-08-01

Full Text Available Endometrial stromal tumors are rare uterine tumors (<1%. Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS, and uterine undifferentiated sarcoma (UUS. This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS. Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.

Testicular cancer: A narrative review of the role of socioeconomic position from risk to survivorship

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Richardson, Lisa C.; Neri, Antonio J.; Tai, Eric; Glenn, Jeffrey D.

2015-01-01

Background Testicular cancer (TC) is one of the most curable cancers. Given survival rates of close to 100% with appropriate therapy, ensuring proper treatment is essential. We reviewed and summarized the literature on the association of socioeconomic position (SEP) along the cancer control spectrum from risk factors to survivorship. Methods We searched PubMed from 1966 to 2011 using the following terms: testicular cancer, testicular neoplasm, poverty, and socioeconomic factors, retrieving 119 papers. After excluding papers for the non-English (10) language and non-relevance (46), we reviewed 63 papers. We abstracted information on socioeconomic position (SEP), including occupation, education, income, and combinations of the 3. Five areas were examined: risk factors, diagnosis, treatment, survival, and survivorship. Results Most studies examined area-based measures, not individual measures of SEP. The majority of studies found an increased risk of developing TC with high SEP though recent papers have indicated increased risk in low-income populations. Regarding diagnosis, recent papers have indicated that lower levels of education and SEP are risk factors for later-stage TC diagnosis and hence higher TC mortality. For treatment, 1 study that examined the use of radiation therapy (RT) in stage I seminoma reported that living in a county with lower educational attainment led to lower use of RT. For survival (mortality), several studies found that men living in lower SEP geographic areas experience lower survival and higher mortality. Conclusion The strongest evidence for SEP impact on testicular germ cell tumor (TGCT) was found for the risk of developing cancer as well as survival. The association of SEP with TGCT risk appears to have changed over the last decade. Given the highly curable nature of TGCT, more research is needed to understand how SEP impacts diagnosis and treatment for TGCT and to design interventions to address disparities in TGCT outcomes and SEP

Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

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Comish, Paul B; Drumond, Ana Luiza; Kinnell, Hazel L; Anderson, Richard A; Matin, Angabin; Meistrich, Marvin L; Shetty, Gunapala

2014-01-01

Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

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Paul B Comish

Full Text Available Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1 mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2% and to 80% in the male offspring of L1 (control value 33%. These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i DNA damage is a common mechanism leading to induction of testicular cancer, ii increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

Epidemiology of testicular cancer: an overview.

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Garner, Michael J; Turner, Michelle C; Ghadirian, Parviz; Krewski, Daniel

2005-09-01

Testicular cancer is a rare disease, accounting for 1.1% of all malignant neoplasms in Canadian males. Despite the low overall incidence of testicular cancer, it is the most common malignancy among young men. The incidence rate of testicular cancer has been increasing since the middle of the 20th century in many western countries. However, the etiology of testicular cancer is not well understood. A search of the peer-reviewed literature was conducted to identify important articles for review and inclusion in this overview of the epidemiology of testicular cancer. Most of the established risk factors are related to early life events, including cryptorchidism, carcinoma in situ and in utero exposure to estrogens. Occupational, lifestyle, socioeconomic and other risk factors have demonstrated mixed associations with testicular cancer. Although there are few established risk factors for testicular cancer, some appear to be related to hormonal balance at various life stages. Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, although they are not likely involved in cancer initiation. In addition to summarizing the current epidemiologic evidence on risk factors for testicular cancer, we suggest future research directions that may elucidate the etiology of testicular cancer.

Cryptorchidism and testicular germ cell tumors: comprehensive meta-analysis reveals that association between these conditions diminished over time and is modified by clinical characteristics

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Kimberly eBanks

2013-02-01

Full Text Available Introduction: Risk of testicular germ cell tumors (TGCT is consistently associated with a history of cryptorchidism (CO in epidemiologic studies. Factors modifying the association may provide insights regarding etiology of TGCT and suggest a basis for individualized care of CO. To identify modifiers of the CO-TGCT association, we conducted a comprehensive, quantitative evaluation of epidemiologic data.Materials and Methods: Human studies cited in PubMed or ISI Web of Science indices through December 2011 and selected unpublished epidemiologic data were reviewed to identify 35 articles and one unpublished dataset with high-quality data on the CO-TGCT association. Association data were extracted as point and 95% confidence interval estimates of odds ratio (OR or standardized incidence ratio (SIR, or as tabulated data. Values were recorded for each study population, and for subgroups defined by features of study design, CO and TGCT. Extracted data were used to estimate summary risk ratios (sRR and evaluate heterogeneity of the CO-TGCT association between subgroups.Results: The overall meta-analysis showed that history of CO is associated with four-fold increased TGCT risk (RR=4.1(95%CI=3.6-4.7. Subgroup analyses identified five determinants of stronger association: bilateral CO, unilateral CO ipsilateral to TGCT, delayed CO treatment, TGCT diagnosed before 1970, and seminoma histology. Conclusions: Modifying factors may provide insight into TGCT etiology and suggest improved approaches to managing CO. Based on available data, cryptorchidism patients and their parents or caregivers should be made aware of elevated TGCT risk following orchidopexy, regardless of age at repair, unilateral versus bilateral nondescent, or position of undescended testes.

Fluoride-elicited developmental testicular toxicity in rats: roles of endoplasmic reticulum stress and inflammatory response.

Science.gov (United States)

Zhang, Shun; Jiang, Chunyang; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Zhenglun; Wang, Aiguo

2013-09-01

Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague-Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

Testicular biopsy in psittacine birds (Psittaciformes): impact of endoscopy and biopsy on health, testicular morphology, and sperm parameters.

Science.gov (United States)

Hänse, Maria; Krautwald-Junghanns, Maria-Elisabeth; Reitemeier, Susanne; Einspanier, Almuth; Schmidt, Volker

2013-12-01

Histologic examination of a testicular biopsy sample may be required to evaluate the reproductive status of male psittacine birds. The purpose of this study was to evaluate the viability of testicular sampling from live birds by assessing the impact on the birds' health, testicular integrity, and sperm quality. Testicular biopsy samples were obtained by endoscopy 4 times during 12 months from 9 cockatiels (Nymphicus hollandicus) and 7 rose-ringed parakeets (Psittacula krameri). Only 2 of 16 birds showed testicular cicatrization or divided testicular tissue after a single endoscopy. Further complications, such as damage to the air sacs or bleeding, predominantly occurred in subsequent endoscopies. In both species, endoscopy and testicular biopsy caused only minor or transient effects on sperm production and sperm quality. These results support that a single testicular biopsy is a viable method for evaluating the reproductive status of male psittacine birds.

Epidemiology and therapies for metastatic sarcoma

Directory of Open Access Journals (Sweden)

Amankwah EK

2013-05-01

Full Text Available Ernest K Amankwah,1 Anthony P Conley,2 Damon R Reed2 1Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Sarcoma Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma, adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. Keywords: chemotherapy, pediatric sarcoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, synovial sarcoma

The Histological, Histomorphometrical and Histochemical Changes of Testicular Tissue in the Metformin Treated and Untreated Streptozotocin-Induced Adult Diabetic Rats

Directory of Open Access Journals (Sweden)

Davoud Kianifard

2011-03-01

Full Text Available In this investigation, diabetes was induced in adult male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin (STZ at 45 mg kg-1 of body weight. A group comprised of 8 diabetic rats was treated with metformin at 100 mg kg-1 of body weight for reducing the elevated blood glucose level. The results revealed that, in the untreated diabetic rats, the body and testicular weight reduced in comparison with the control rats (P < 0.05 , the metformin treated diabetic rats showed body weight loss in comparison with the control group (P < 0.05. In the untreated diabetic rats, the blood glucose level significantly increased in comparison with control and metformin treated diabetic rats. Histomorphological examinations revealed a reduction in testicular capsule diameter, seminiferous tubules (STs and germinal epithelium height, increase of amorphous material of interstitial tissue, germ cell depletion, decrease in cellular population and activity and disruption of spermatogenesis in the untreated diabetic rats in comparison with control group. In metformin treated diabetic rats, the histomorphological alterations were seen in lesser part in comparison with untreated diabetic group. The results from this study proved that, there was a direct relationship between increased levels of blood glucose as a result of STZ-induced diabetes and the histomorphological changes of testicular tissue.

General Information about Kaposi Sarcoma

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... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Immunosuppressive Therapy-Related Kaposi Sarcoma

Science.gov (United States)

... Sarcoma Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma Go to Health Professional Version Key Points Kaposi ...

Primary Testicular B-cell Lymphoma

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Aykut Buğra Şentürk

2015-12-01

Full Text Available Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

Intermittent Testicular Torsion

African Journals Online (AJOL)

2017-06-02

Jun 2, 2017 ... had prior episodes of testicular pain, suggesting that they may have had intermittent torsion before .... None of the patients had antecedent history of sexual exposure, fever, or urinary tract infection .... torsion of the spermatic cord portends an increased risk of acute testicular infarction. J Urol 2008;180 4 ...

Uterine sarcoma – current perspectives

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Benson C

2017-08-01

Full Text Available Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade, undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. Keywords: sarcoma, leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyoma

Synovial sarcoma

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Sucari S.C. Vlok

2014-12-01

Full Text Available Synovial sarcoma is a malignant, predominantly juxta-articular, soft-tissue tumour representing approximately 10% of all soft-tissue sarcomas. Frequently initially incorrectly diagnosed as a benign lesion, it should be considered as a diagnosis when a young adult patient presents with a calcified juxta-articular soft-tissue mass of insidious onset.

Selecting Infants With Cryptorchidism and High Risk of Infertility for Optional Adjuvant Hormonal Therapy and Cryopreservation of Germ Cells: Experience From a Pilot Study

Directory of Open Access Journals (Sweden)

Jorgen Thorup

2018-06-01

Full Text Available IntroductionOrchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk.Materials and methodsWe included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur® 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent’s choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing.ResultsTwo out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S. Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not.ConclusionBased on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure

Testicular Cancer and Testicular Self-Examination; Knowledge, Attitudes and Practice in Final Year Medical Students in Nigeria

Science.gov (United States)

Ugwumba, Fred O; Ekwueme, Osa Eloka C; Okoh, Agharighom D

2016-11-01

The testicular cancer (TCa) incidence is increasing in many countries, with age-standardized incidence rates up to 7.8/100,000 men in the Western world, although reductions in mortality and increasingly high cure rates are being witnessed at the same time. In Africa, where rates are lower, presentation is often late and morbidity and mortality high. Given this scenario, awareness of testicular cancer and practice of testicular self-examination among future first response doctors is very important. This study was conducted to determine knowledge and attitude to testicular cancer, and practice of testicular self-examination (TSE) among final (6th) year medical students. In addition, the effect of an intervention in the form of a single PowerPoint® lecture, lasting 40 minutes with image content on testicular cancer and testicular self examination was assessed. Pre and post intervention administration of a self-administered structured pre tested questionnaire was performed on 151 medical students, 101 of whom returned answers (response rate of 66.8%). In the TC domain, there was a high level of awareness of testicular cancer, but poor knowledge of the age group most affected, with significant improvement post intervention (ptesticular self-examination pre-intervention was found considering the nature of the study group..Respondents had surprisingly weak/poor responses to the question “How important to men’s health is regular testicular self-examination?” Answers to the questions “Do you think it is worthwhile to examine your testis regularly?” and “Would you be interested in more information on testicular cancer and testicular self-examination?” were also suboptimal, but improved post intervention ptesticular cancer in the curricula of medical schools and other training institutions for health care personnel. Creative Commons Attribution License

Clinical management of soft tissue sarcomas

International Nuclear Information System (INIS)

Pinedo, H.M.; Verweij, J.

1986-01-01

This book is concerned with the clinical management of soft tissue sarcomas. Topics covered include: Radiotherapy; Pathology of soft tissue sarcomas; Surgical treatment of soft tissue sarcomas; and Chemotherapy in advanced soft tissue sarcomas

Soft Tissue Sarcoma

Science.gov (United States)

... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

Science.gov (United States)

Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

2017-03-01

Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor induced testicular function in dogs.

Directory of Open Access Journals (Sweden)

Vanmathy R Kasimanickam

Full Text Available Spermatogenesis is a multistep synchronized process. Diploid spermatogonia differentiate into haploid spermatozoa following mitosis, meiosis and spermiogenesis. Division and differentiation of male germ cells is achieved through the sequential expression of several genes. Numerous mRNAs in the differentiating germ cells undergo post-transcriptional and translational regulation. MiRNAs are powerful negative regulators of mRNA transcription, stability, and translation and recognize their mRNA targets through base-pairing. Retinoic acid (RA signaling is essential for spermatogenesis and testicular function. Testicular RA level is critical for RA signal transduction. This study investigated the miRNAs modulation in an RA- induced testicular environment following the administration of all-trans RA (2 µM and CYP26B1- inhibitor (1 µM compared to control. Eighty four canine mature miRNAs were analyzed and their expression signatures were distinguished using real-time PCR based array technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c, Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f, miR-125 (cfa-miR-125a and cfa-miR-125b, miR-146 (cfa-miR-146a and cfa-miR-146b, miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c, miR-23 (cfa-miR-23a and cfa-miR-23b, cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa-miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down-regulated. This study explored information regarding chromosome distribution, human orthologous sequences and the interaction of target genes of miRNA families significantly distinguished in this study using prediction algorithms. This study importantly identified dysregulated miRNA species resulting from RA-induced spermatogenesis. The present

Adaptive planning using megavoltage fan-beam CT for radiation therapy with testicular shielding

International Nuclear Information System (INIS)

Yadav, Poonam; Kozak, Kevin; Tolakanahalli, Ranjini; Ramasubramanian, V.; Paliwal, Bhudatt R.; Welsh, James S.; Rong, Yi

2012-01-01

This study highlights the use of adaptive planning to accommodate testicular shielding in helical tomotherapy for malignancies of the proximal thigh. Two cases of young men with large soft tissue sarcomas of the proximal thigh are presented. After multidisciplinary evaluation, preoperative radiation therapy was recommended. Both patients were referred for sperm banking and lead shields were used to minimize testicular dose during radiation therapy. To minimize imaging artifacts, kilovoltage CT (kVCT) treatment planning was conducted without shielding. Generous hypothetical contours were generated on each “planning scan” to estimate the location of the lead shield and generate a directionally blocked helical tomotherapy plan. To ensure the accuracy of each plan, megavoltage fan-beam CT (MVCT) scans were obtained at the first treatment and adaptive planning was performed to account for lead shield placement. Two important regions of interest in these cases were femurs and femoral heads. During adaptive planning for the first patient, it was observed that the virtual lead shield contour on kVCT planning images was significantly larger than the actual lead shield used for treatment. However, for the second patient, it was noted that the size of the virtual lead shield contoured on the kVCT image was significantly smaller than the actual shield size. Thus, new adaptive plans based on MVCT images were generated and used for treatment. The planning target volume was underdosed up to 2% and had higher maximum doses without adaptive planning. In conclusion, the treatment of the upper thigh, particularly in young men, presents several clinical challenges, including preservation of gonadal function. In such circumstances, adaptive planning using MVCT can ensure accurate dose delivery even in the presence of high-density testicular shields.

Adaptive planning using megavoltage fan-beam CT for radiation therapy with testicular shielding

Science.gov (United States)

Yadav, Poonam; Kozak, Kevin; Tolakanahalli, Ranjini; Ramasubramanian, V.; Paliwal, Bhudatt R.; Welsh, James S.; Rong, Yi

2012-01-01

This study highlights the use of adaptive planning to accommodate testicular shielding in helical tomotherapy for malignancies of the proximal thigh. Two cases of young men with large soft tissue sarcomas of the proximal thigh are presented. After multidisciplinary evaluation, preoperative radiation therapy was recommended. Both patients were referred for sperm banking and lead shields were used to minimize testicular dose during radiation therapy. To minimize imaging artifacts, kilovoltage CT (kVCT) treatment planning was conducted without shielding. Generous hypothetical contours were generated on each “planning scan” to estimate the location of the lead shield and generate a directionally blocked helical tomotherapy plan. To ensure the accuracy of each plan, megavoltage fan-beam CT (MVCT) scans were obtained at the first treatment and adaptive planning was performed to account for lead shield placement. Two important regions of interest in these cases were femurs and femoral heads. During adaptive planning for the first patient, it was observed that the virtual lead shield contour on kVCT planning images was significantly larger than the actual lead shield used for treatment. However, for the second patient, it was noted that the size of the virtual lead shield contoured on the kVCT image was significantly smaller than the actual shield size. Thus, new adaptive plans based on MVCT images were generated and used for treatment. The planning target volume was underdosed up to 2% and had higher maximum doses without adaptive planning. In conclusion, the treatment of the upper thigh, particularly in young men, presents several clinical challenges, including preservation of gonadal function. In such circumstances, adaptive planning using MVCT can ensure accurate dose delivery even in the presence of high-density testicular shields. PMID:21925866

Adaptive planning using megavoltage fan-beam CT for radiation therapy with testicular shielding

Energy Technology Data Exchange (ETDEWEB)

Yadav, Poonam [Department of Human Oncology, University of Wisconsin, Madison, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, Madison, WI (United States); School of Advance Sciences, Vellore Institue of Technology University, Vellore, Tamil Nadu (India); Kozak, Kevin [Department of Human Oncology, University of Wisconsin, Madison, Madison, WI (United States); Tolakanahalli, Ranjini [Department of Human Oncology, University of Wisconsin, Madison, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, Madison, WI (United States); Ramasubramanian, V. [School of Advance Sciences, Vellore Institue of Technology University, Vellore, Tamil Nadu (India); Paliwal, Bhudatt R. [Department of Human Oncology, University of Wisconsin, Madison, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, Madison, WI (United States); University of Wisconsin, Riverview Cancer Centre, Wisconsin Rapids, WI (United States); Welsh, James S. [Department of Human Oncology, University of Wisconsin, Madison, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, Madison, WI (United States); Rong, Yi, E-mail: rong@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin, Madison, Madison, WI (United States); University of Wisconsin, Riverview Cancer Centre, Wisconsin Rapids, WI (United States)

2012-07-01

This study highlights the use of adaptive planning to accommodate testicular shielding in helical tomotherapy for malignancies of the proximal thigh. Two cases of young men with large soft tissue sarcomas of the proximal thigh are presented. After multidisciplinary evaluation, preoperative radiation therapy was recommended. Both patients were referred for sperm banking and lead shields were used to minimize testicular dose during radiation therapy. To minimize imaging artifacts, kilovoltage CT (kVCT) treatment planning was conducted without shielding. Generous hypothetical contours were generated on each 'planning scan' to estimate the location of the lead shield and generate a directionally blocked helical tomotherapy plan. To ensure the accuracy of each plan, megavoltage fan-beam CT (MVCT) scans were obtained at the first treatment and adaptive planning was performed to account for lead shield placement. Two important regions of interest in these cases were femurs and femoral heads. During adaptive planning for the first patient, it was observed that the virtual lead shield contour on kVCT planning images was significantly larger than the actual lead shield used for treatment. However, for the second patient, it was noted that the size of the virtual lead shield contoured on the kVCT image was significantly smaller than the actual shield size. Thus, new adaptive plans based on MVCT images were generated and used for treatment. The planning target volume was underdosed up to 2% and had higher maximum doses without adaptive planning. In conclusion, the treatment of the upper thigh, particularly in young men, presents several clinical challenges, including preservation of gonadal function. In such circumstances, adaptive planning using MVCT can ensure accurate dose delivery even in the presence of high-density testicular shields.

Testicular Torsion (For Parents)

Science.gov (United States)

... Parents Kids Teens Hernias Ultrasound: Scrotum Undescended Testicles Male Reproductive System PQ: I have a lump on one of ... to Do a Testicular Self-Exam (Slideshow) Varicocele Male Reproductive System Testicular Torsion View more About Us Contact Us ...

General Information about Ewing Sarcoma

Science.gov (United States)

... adults. Ewing sarcoma has also been called peripheral primitive neuroectodermal tumor, Askin tumor (Ewing sarcoma of the ... Ewing sarcoma are usually done at the same time. The following tests and procedures may be used ...

Treatment Option Overview (Ewing Sarcoma)

Science.gov (United States)

... Ewing Sarcoma Treatment Osteosarcoma Treatment Research Ewing Sarcoma Treatment (PDQ®)–Patient Version General Information About Ewing Sarcoma ... started or in another part of the body. Treatment Option Overview Key Points There are different types ...

Cryopreservation of testicular tissue before long-term testicular cell culture does not alter in vitro cell dynamics

NARCIS (Netherlands)

Baert, Yoni; Braye, Aude; Struijk, Robin B.; van Pelt, Ans M. M.; Goossens, Ellen

2015-01-01

To assess whether testicular cell dynamics are altered during long-term culture after testicular tissue cryopreservation. Experimental basic science study. Reproductive biology laboratory. Testicular tissue with normal spermatogenesis was obtained from six donors. None. Detection and comparison of

Epidemiology and therapies for metastatic sarcoma

Science.gov (United States)

Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

2013-01-01

Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

Relaxin affects cell organization and early and late stages of spermatogenesis in a coculture of rat testicular cells.

Science.gov (United States)

Pimenta, M T; Francisco, R A R; Silva, R P; Porto, C S; Lazari, M F M

2015-07-01

Relaxin and its receptor RXFP1 are co-expressed in Sertoli cells, and relaxin can stimulate proliferation of Sertoli cells. In this study, we investigated a role of relaxin in spermatogenesis, using a short-term culture of testicular cells of the rat that allowed differentiation of spermatogonia to spermatids. Sertoli, germ, and peritubular myoid cells were the predominant cell types in the culture. Sertoli and germ cells expressed RXFP1. Cultures were incubated without (control) or with 0.5% fetal bovine serum (FBS) or 100 ng/mL H2 relaxin (RLN) for 2 days. Cell organization, number, and differentiation were analyzed after 2 (D2), 5 (D5) or 8 (D8) days of culturing. Although the proportion of germ cells decayed from D2 to D5, the relative contribution of HC, 1C, 2C, and 4C germ cell populations remained constant in the control group during the whole culture. RLN did not affect the proportion of germ cell populations compared with control, but increased gene and/or protein expression of the undifferentiated and differentiated spermatogonia markers PLZF and c-KIT, and of the post-meiotic marker Odf2 in D5. RLN favored organization of cells in tubule-like structures, the arrangement of myoid cells around the tubules, arrangement of c-KIT-positive spermatogonia at the basal region of the tubules, and expression of the cell junction protein β-catenin close to the plasma membrane region. Knockdown of relaxin with small interfering RNA (siRNA) reduced expression of β-catenin at the cell junctions, and shifted its expression to the nucleus. We propose that relaxin may affect spermatogenesis by modulating spermatogonial self renewal and favoring cell contact. © 2015 American Society of Andrology and European Academy of Andrology.

Association of testicular echogenicity, scrotal circumference, testicular volume and testosterone concentration in buffaloes

Directory of Open Access Journals (Sweden)

Henry D.M. Ayala

2016-12-01

Full Text Available ABSTRACT. Ayala H.D.M., Ribeiro H.F.L., Rolim Filho S.T., Silva E.V.C. & Vale W.G. Association of testicular echogenicity, scrotal circumference, testicular volume and testosterone concentration in buffaloes. [Associação entre a ecogenicidade, circunferência escrotal, volume testicular e concentração de testosterona em búfalos.] Revista Brasileira de Medicina Veterinária, 38(4:334-340, 2016. Programa de Pós-Graduação em Ciencia Animal, Universidade Federal do Pará, Rua Augusto Corrêa 1, Campus Universitário do Guamá, Belém, PA 66075-110, Brazil. E-mail wm.vale@hotmail.com This article aimed to discuss the changes in the testicular parenchyma, analyzed by the use of ultrasonography, and correlates them with the testicular biometric parameters and testosterone concentration in crossed Murrah x Mediterranean buffaloes. Nineteen buffaloes, with initial ages between 11 and 59 months,were submitted to fortnightly collections of semen for a period of six months. At each collection the testicular biometry and testicular echogenicity were evaluated as well as blood samples were also collected to measure the plasma testosterone levels. The data were submitted to analysis of variance by the GLM procedure, considering the age group fixed effect. The average data obtained were compared by the Duncan test, at 5% significance. There was a significant growth (P<0.05 of the scrotal circumference, which varied from 12.88±0.51 cmto 31.18±0.75 cm among animals aged 12 to 60 months, as well as testicular volume, which ranged from 30.28±17.37 to 611.96±38.69 cm³ among the animals. The echogenic intensity of the testicular parenchyma varied in pixels from 78.67±6.36 to 109.24±3.13 in animals aged 12 to 60 months respectively. In the animals with ages between 12 and 19 months was observed levels of testosterone considered being low, whereas in the animals from 20 to 21 months there was a progressive increase in the testosterone levels, which

Interdisciplinary evidence-based recommendations for the follow-up of early stage seminomatous testicular germ cell cancer patients

Energy Technology Data Exchange (ETDEWEB)

Souchon, Rainer [Universitaetsklinikum Tuebingen (Germany). Dept. of Radiation Oncology; Hartmann, Michael [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Dept. of Urology; Krege, Susanne [Krankenhaus Maria-Hilf GmbH, Krefeld (Germany). Dept. of Urology; Lorch, Anja [Universitaetsklinikum Marburg (Germany). Dept. of Oncology; Mayer, Frank [Universitaetsklinikum Tuebingen (Germany). Dept. of Oncology; Santis, Maria de [KFJ-Spital, ACR-ITR VIEnna/CEADDP and LBI-ACR VIEnna-CTO, Vienna (Austria). Dept. of Oncology; Gillessen, Silke [Kantonsspital St. Gallen (Switzerland). Dept. of Medical Oncology; Beyer, Joerg [Vivantes Klinikum am Urban, Berlin (Germany). Dept. of Hemato-Oncology; Cathomas, Richard [Kantonsspital Graubuenden, Chur (Switzerland). Medical Oncology

2011-03-15

Purpose: To provide guidance regarding follow-up procedures after initial treatment of early stage testicular seminoma (clinical stages (CS) I-II A/B) based on current published evidence complemented by expert opinion. Methods and Material: An interdisciplinary, multinational working group consisting of urologists, medical oncologists, and radiation oncologists analyzed the published evidence regarding follow-up procedures in various stages of seminomatous and nonseminomatous testicular cancers. Focusing on radiooncological aspects, the recommendations contained herein are restricted to early stage seminoma (with radiotherapy being a standard treatment option). In particular, extent, frequency, and duration of imaging at follow-up were analyzed concerning relapse patterns, risk factors, and mode of relapse detection. Results: Active surveillance, adjuvant carboplatin or radiotherapy are equally accepted options for CS I seminoma but they result in different relapse rates and patterns. Usually relapses occur within the first 2(-6) years. Routinely performed follow-up using computerized tomography (CT) after adjuvant treatment yield only low detection rates of recurrences. Therefore, there is no evidence to maintain routine examinations every 3-4 months. After treatment of stage IIA/B, detection rates of relapses or progression identified solely by routinely performed CT during follow-up are low. Conclusion: Considering lifelong cure rates of up to 99% for patients treated for seminoma CS I-IIA/B, the negative impact of unnecessary ionizing radiation exposure has to be considered. The presented recommendations for various follow-up scenarios for early stage seminoma strongly promote the restrictive use of imaging procedures that utilize ionizing radiation (especially CT), due to its potential to induce secondary malignancies. (orig.)

Impalpable Testicular Seminoma Identified on Sonoelastography

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Eric M. Ghiraldi

2015-09-01

Full Text Available The role of sonoelastography in diagnosing cancerous masses has increased since the advent of elastography as an ultrasound modality. Its ability to display differences in the mechanical properties of cancerous masses compared to normal surrounding tissue has shown benefit in increasing the accuracy of diagnosing malignant breast and thyroid masses and has shown early potential in accomplishing better targeted prostate biopsies. To date, the literature is limited in the number of studies describing the use of sonoelastography for testicular masses. We describe a 34-year-old man who presented with an incidental finding of an impalpable hypoechoic testicular mass on grayscale ultrasound during an infertility work-up. Sonoelastography was performed displaying intermediate testicular elastic properties. Upon frozen section of the mass during surgical exploration, classic testicular seminoma was diagnosed and subsequent radical orchiectomy was performed. We would like to use this atypical presentation of testicular seminoma to review the potential role of elastography for diagnosing testicular cancer.

The Danish Sarcoma Database

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Jorgensen PH

2016-10-01

Full Text Available Peter Holmberg Jørgensen,1 Gunnar Schwarz Lausten,2 Alma B Pedersen3 1Tumor Section, Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, 2Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Aim: The aim of the database is to gather information about sarcomas treated in Denmark in order to continuously monitor and improve the quality of sarcoma treatment in a local, a national, and an international perspective. Study population: Patients in Denmark diagnosed with a sarcoma, both skeletal and ekstraskeletal, are to be registered since 2009. Main variables: The database contains information about appearance of symptoms; date of receiving referral to a sarcoma center; date of first visit; whether surgery has been performed elsewhere before referral, diagnosis, and treatment; tumor characteristics such as location, size, malignancy grade, and growth pattern; details on treatment (kind of surgery, amount of radiation therapy, type and duration of chemotherapy; complications of treatment; local recurrence and metastases; and comorbidity. In addition, several quality indicators are registered in order to measure the quality of care provided by the hospitals and make comparisons between hospitals and with international standards. Descriptive data: Demographic patient-specific data such as age, sex, region of living, comorbidity, World Health Organization's International Classification of Diseases – tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System. Data quality and completeness are currently secured. Conclusion: The Danish Sarcoma Database is population based and includes sarcomas occurring in Denmark since 2009. It is a valuable tool for monitoring sarcoma incidence and quality of treatment and its improvement, postoperative

Protective effects of red grape (Vitis vinifera) juice through restoration of antioxidant defense, endocrine swing and Hsf1, Hsp72 levels in heat stress induced testicular dysregulation of Wister rat.

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Halder, Soma; Sarkar, Mrinmoy; Dey, Sananda; Kumar Bhunia, Sujay; Ranjan Koley, Alok; Giri, Biplab

2018-01-01

Ability of red grape juice (RGJ), a known antioxidant, on testis of adult Wister rat to protect from oxidative stress induced damages by heat stress has been investigated in this study. Heat stress was induced maintaining body and testicular temperature at 43°C for 30min/day for 15 days using a hyperthermia induction chamber. Four groups of rats (n=6 per group) comprising of Group-I (control) -kept at 32°C, Group-II -exposed to heat stress alone, Group-III received RGJ (0.8ml/rat/day) alone and Group-IV -exposed to heat stress and received RGJ at same dose. Analysis of blood and testicular tissue exhibited significant reduction in serum testosterone, testicular superoxide dismutase, testicular catalase and testicular glutathione (all p rise in the level of serum corticosteroid, testicular lipid peroxidase and the apoptotic enzyme caspase-3 of testis (all p < 0.001) were observed along with substantial increase in testicular Hsp72 and Hsf-1, and decrease in 17β-HSD3 were noted in heat stressed rats compared to controls. In Group-IV rats, RGJ administration could restore these parameters to normal levels. The signs of retention were clear in Group-IV rats and found to be significantly different as compared to that of the Group-II rats. In testicular histology of rats exposed to heat stress alone revealed remarkable germ cell degeneration and tubular deformations which were prevented by RGJ treatment (Group-IV). The reduced number of sperm level in Group-II also restored in RGJ treatment (Group-IV). The above results indicate that consumption of RGJ may substantially protect testis from heat stress induce dysfunctions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The pineal gland, but not melatonin, is associated with the termination of seasonal testicular activity in an annual reproductive cycle in roseringed parakeet Psittacula krameri.

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Sengupta, Anamika; Kumar Maitra, Saumen

2006-01-01

The role of the pineal gland and its hormone melatonin in the regulation of annual testicular events was investigated for the first time in a psittacine bird, the roseringed parakeet (Psittacula krameri). Accordingly, the testicular responsiveness of the birds was evaluated following surgical pinealectomy with or without the exogenous administration of melatonin and the experimental manipulations of the endogenous levels of melatonin through exposing the birds to continuous illumination. An identical schedule was followed during the four reproductive phases, each characterizing a distinct testicular status in the annual cycle, namely, the phases of gametogenic quiescence (preparatory phase), seasonal recovery of gametogenesis (progressive phase), seasonal initiation of sperm formation (pre-breeding phase), and peak gametogenic activity (breeding phase). In each reproductive phase, the birds were subjected to various experimental conditions, and the effects were studied comparing the testicular conditions in the respective control birds. The study included germ cell profiles of the seminiferous tubules, the activities of steroidogenic enzymes 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and Delta(5)3beta-hydroxysteroid dehydrogenase (Delta(5)3beta- HSD) in the testis, and the serum levels of testosterone and melatonin. An analysis of the data reveals that the pineal gland and its hormone melatonin may play an inhibitory role in the development of the testis until the attainment of the seasonal peak in the annual reproductive cycle. However, in all probability, the termination of the seasonal activity of the testis or the initiation of testicular regression in the annual reproductive cycle appears to be the function of the pineal gland, but not of melatonin.

[Demographic Analysis of Patients with Osteosarcoma, Chonddrosarcoma, Ewing's Sarcoma from one Sarcoma Center in Switzerland].

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Hodel, Sandro; Seeli, Franziska; Fuchs, Bruno

2015-06-17

Retrospective analysis of presentation, diagnosis and outcome of patients with osteosarcoma, chondrosarcoma and Ewing's sarcoma was performed for a single Sarcoma Center in Zurich at the University Hospital Balgrist. 201 patients were included. Overall survival at five and ten years were 74 ± 6%, 69 ± 7% for osteosarcoma (n = 85, since 2000), 85 ± 7%, 80 ± 9% for Ewing's sarcoma (n = 43, since 1990) and 86 ± 5%, 78 ± 9% for chondrosarcoma (n = 73, since 2000). The here presented overall survival rates from a single Sarcoma Center in Switzerland appear to be equivalent to other large international monocenter studies. The presentation and epidemiology of these patients are in accordance with large multicenter epidemiological studies. A nationwide sarcoma database (SwissSARCOS; www.sarcoma.ch) seems indispensable for more detailed analysis and quality management in such rare diseases.

Guidelines on testicular cancer

NARCIS (Netherlands)

Albers, Peter; Albrecht, Walter; Algaba, Ferran; Bokemeyer, Carsten; Cohn-Cedermark, Gabriella; Horwich, Alan; Klepp, Olbjoern; Laguna, M. Pilar; Pizzocaro, Giorgio

2005-01-01

To up-date the 2001 version of the EAU testicular cancer guidelines. A non-structured literature review until January 2005 using the MEDLINE database has been performed. Literature has been classified according to evidence-based medicine levels. Testicular cancer is a highly curable disease.

Primary Intradural Extraosseous Ewing's Sarcoma

OpenAIRE

Kim, Seok Won; Shin, Ho

2009-01-01

Ewing's sarcoma usually arises from skeletal bone, but rarely may have an extraskeletal origin. However, Ewing's sarcoma that originates around the spinal column, especially, the intradural extramedullary type is extremely rare. We report a rare case of primary intraspinal extraskeletal Ewing's sarcoma.

Chemotherapy refractory testicular germ cell tumor is associated with a variant in Armadillo Repeat gene deleted in Velco-Cardio-Facial syndrome (ARVCF

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Chunkit eFung

2012-12-01

Full Text Available Introduction: There is evidence that inherited genetic variation affects both testicular germ cell tumor (TGCT treatment outcome and risks of late-complications arising from cisplatin-based chemotherapy. Using a candidate gene approach, we examined associations of three genes involved in the cisplatin metabolism pathway, GSTP1, COMT, and TPMT, with TGCT outcome and cisplatin-induced neurotoxicity. Material and Methods: Our study population includes a subset of patients (n=137 from a genome-wide association study at the University of Pennsylvania that evaluates inherited genetic susceptibility to TGCT. All patients in our study had at least one course of cisplatin-based chemotherapy with at least one year of follow up. A total of 90 markers in GSTP1, COMT and TPMT and their adjacent genomic regions (± 20 kb were analyzed for associations with refractory TGCT after first course of chemotherapy, progression-free survival (PFS, overall survival (OS, peripheral neuropathy, and ototoxicity. Results: After adjustment for multiple comparisons, one SNP, rs2073743, in the flanking region (± 20 kb of COMT was associated with refractory TGCT after initial chemotherapy. This SNP lies within the intron region of the Armadillo Repeat gene deleted in Velco-Cardio-Facial syndrome (ARVCF. The G allele of rs2073743 predisposed patients to refractory disease with a relative risk of 2.6 (95% CI 1.1, 6.3; P=0.03. Assuming recessive inheritance, patients with the GG genotype had 22.7 times higher risk (95% CI 3.3, 155.8; P=0.04 of developing refractory disease when compared to those with the GC or CC genotypes. We found no association of our candidate genes with peripheral neuropathy, ototoxicity, PFS and OS. Discussion: This is the first study to suggest that germline genetic variants of ARVCF may affect TGCT outcome. The result of this study is hypothesis generating and should be validated in future studies.

Acute testicular ischemia caused by incarcerated inguinal hernia.

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Orth, Robert C; Towbin, Alexander J

2012-02-01

Acute testicular ischemia caused by an incarcerated inguinal hernia usually affects infants. There are few reports of diagnosis using US, and the effect of long-standing reducible hernias on testicular growth in infants and children is unknown. The objectives of this study were to determine the incidence of testicular ischemia secondary to an incarcerated inguinal hernia at scrotal sonography and to determine the effect on testicular size at diagnosis. A hospital database was used to locate scrotal sonography examinations documenting an inguinal hernia, and images were reviewed for signs of testicular ischemia. Testicular volumes were compared using the Wilcoxon signed rank test. A total of 147 patients were identified with an inguinal hernia (age 1 day to 23 years, average 6 years). Ten patients (6.8%) had associated testicular ischemia (age 3 weeks to 6 months, average 9 weeks) and showed a statistically significant increase in ipsilateral testicular size compared to the contralateral testicle (P = 0.012). Patients without testicular ischemia did not show a significant difference in testicular size, regardless of patient age. An incarcerated inguinal hernia should be considered as a cause of acute testicular ischemia in infants younger than 6 months of age.

Uterine sarcoma - current perspectives.

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Benson, Charlotte; Miah, Aisha B

2017-01-01

Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases.

CT measurement of breast glandular tissue and its association with testicular cancer

Energy Technology Data Exchange (ETDEWEB)

Klang, Eyal [Tel Aviv University, Department of Radiology, Chaim Sheba Medical Center, Tel Aviv (Israel); The Chaim Sheba Medical Center, Tel Hashomer (Israel); Rozendorn, Noa; Raskin, Steve; Portnoy, Orith; Sklair, Miri; Marom, Edith M.; Konen, Eli; Amitai, Michal M. [Tel Aviv University, Department of Radiology, Chaim Sheba Medical Center, Tel Aviv (Israel)

2017-02-15

To evaluate the associations between breast glandular tissues diameters as determined by CT and b-hCG levels, histological types, tumour spread and prognosis in patients with testicular germ cell tumour. Ninety-four patients with pre-treatment CT scan and markers (b-hCG, AFP, LDH) were retrospectively collected. A radiologist measured diameters in all CT examinations and correlation between diameters and log (b-hCG) was assessed (Pearson's coefficient). The ability of measured diameters to predict lymphatic and distant haematogenous metastatic spread was evaluated (ROC curves). The associations between measured diameter cut-off values of 20 and 25 mm and International Germ Cell Cancer Collaborative Group (IGCCCG) classification, lymphatic and distant haematogenous metastatic spread and histological subtypes were evaluated (chi squared test). Breast glandular diameters correlated to log(b-hCG) (r = 0.579) and predicted distant haematogenous metastatic spread (AUC = 0.78). Worse prognosis (intermediate or poor IGCCCG) was shown for 20 mm (27.3 vs. 4.2 %, p = 0.005) and 25 mm (33.3 vs. 6.1 %, p = 0.014). A diameter of 25 mm was associated with non-seminoma (91.7 vs. 48.8 %, p = 0.005). Breast glandular tissue diameters correlated with log(b-hCG) and predicted distant haematogenous metastases. Twenty and 25 mm were associated with worse prognosis and 25 mm was able to distinguish between seminoma and non-seminoma. (orig.)

Germ killing by ultraviolet radiation

International Nuclear Information System (INIS)

Wawrik, O.

1975-01-01

Short-wave UV radiation, in particular the range about 250 nm, has a high germ reducing effect. Corresponding UV burners which above all emit radiation at the line of 254 nm can therefore be used effectively in all cases where the least possible content of germs in the air is aimed at. Apart from this it is also possible to reduce by this process the germs on surfaces and liquids. Especially in the most various ranges of pharmaceutical production one is steadily striving for efficient and last not least economic procedures by which it is possible to reduce the germs present in the air of a room. Numerous scientific investigations have sufficiently proved that short-wave UV radiation is extremely well appropriate for such purposes. Absolutely germ-free air in a room can only be obtained under laboratory conditions. In practice, however, the aim is not to achieve a 100 per cent killing of the germs present in a room but to make sure that the germ rate in certain rooms is constantly reduced to the lowest possible level. If in this connection it is referred to a germ reduction of 100 or 99 per cent this is but theory. (orig.) [de

Sarcomas: etiología y síntomas Sarcomas: etiology and symptoms

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Roberto Gabriel Albín Cano

2012-07-01

Full Text Available Debido a la amplia diversidad de sarcomas, casi son inexistentes los textos que incluyen todas las variedades de este tipo de cáncer. Generalmente, su descripción y revisión se incluyen en las del sistema de órganos afectados específicamente, y la literatura que los aborda está muy fragmentada en las diferentes especialidades médicas. Se realiza una revisión bibliográfica sobre la etiología y síntomas de la mayor parte de los diferentes tipos de sarcomas. Es objetivo de esta revisión, lograr unir la información más actual disponible acerca de la etiología y síntomas de los sarcomas. Se han identificado diferentes factores de riesgo y factores etiológicos, tanto genéticos, infecciosos, como ambientales. Los grandes descubrimientos en relación con los mecanismos genéticos involucrados en los diferentes tipos de sarcoma, han abierto un camino de inestimable valor para introducir nuevos tratamientos, que incluyen ensayos con anticuerpos monoclonales y nuevos fármacos de terapia génica.

Due to the wide diversity of sarcomas, almost no texts include all varieties of this type of cancer. Generally, their description and review is included in those of the specifically affected organ system, and the literature containing that information is very fragmented in different medical specialties. We performed a literature review on the etiology and symptoms of most types of sarcomas. It is aimed at achieving a recompilation of most current information available on the causes and symptoms of sarcomas. Different risks and etiologic factors have been identified regarding genetics, infections, and environment. The great discoveries regarding genetic mechanisms involved in different types of sarcomas, have opened an invaluable way to introduce new treatments, including monoclonal antibodies and new drugs of gene therapy.

Radiosensitivity of soft tissue sarcomas

International Nuclear Information System (INIS)

Hirano, Toru; Iwasaki, Katsuro; Suzuki, Ryohei; Monzen, Yoshio; Hombo, Zenichiro

1989-01-01

The correlation between the effectiveness of radiation therapy and the histology of soft tissue sarcomas was investigated. Of 31 cases with a soft tissue sarcoma of an extremity treated by conservative surgery and postoperative radiation of 3,000-6,000 cGy, local recurrence occurred in 12; 5 out of 7 synovial sarcomas, 4 of 9 MFH, one of 8 liposarcomas, none of 4 rhabdomyosarcomas and 2 of 3 others. As for the histological subtyping, the 31 soft tissue sarcomas were divided into spindle cell, pleomorphic cell, myxoid and round cell type, and recurrence rates were 75%, 33.3%, 16.7% and 0%, respectively. From the remarkable difference in recurrent rate, it was suggested that round cell and myxoid type of soft tissue sarcomas showed a high radiosensitivity compared to the spindle cell type with low sensitivity. Clarifying the degree of radiosensitivity is helpful in deciding on the management of limb salvage in soft tissue sarcomas of an extremity. (author)

Testicular Microlithiasis: Case Report and Literature Review

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Savić Goran

2017-09-01

Full Text Available Testicular microlithiasis is a condition characterized by the ultrasonographic findings with multiple microliths, with the prevalence of 0.6% to 9%. This is a condition of unknown etiology; however, in many cases it may be associated with cryptorchidism, Klinefelter syndrome, Down syndrome, varicocele, testicular torsion and male pseudohermaphroditism. Many retrospective studies point to the association between testicular microlithiasis and testicular cancer.

Postirradiation sarcoma in retinoblastoma. Induction or predisposition

International Nuclear Information System (INIS)

Schwarz, M.B.; Burgess, L.P.; Fee, W.E. Jr.; Donaldson, S.S.

1988-01-01

An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods.13 references

Targeted therapies for bone sarcomas

International Nuclear Information System (INIS)

Mudry, P.

2011-01-01

Therapy success in bone sarcoma is significantly better compared to history cohorts with 60 - 70 % overall survival to date. Unfortunately, there is yet no shift and movement in better survival of patients with relapsed and refractory bone sarcomas during last twenty years. This article reviews targeted therapeutics for bone sarcomas which are under investigation and which could give chance to patients suffering from relapsed and chemo resistant bone sarcomas. Majority of the targeted drugs are given as part of phase 1 or 2 studies. (author)

Postradiation sarcomas: importance of surgery

International Nuclear Information System (INIS)

Lagrange, J.L.; Ramaioli, A.; Chateau, M.C.; Pignol, J.P.; Marchal, C.; Resbeut, M.; Richaud, P.; Rambert, P.; Tortechaux, J.; Seng, S.H.; La Fontan, B. de; Reme-Saumon, M.; Roullet, B.; Bof, J.; Coindre, J.M.

1997-01-01

Purpose: To evaluate the role of surgery in the treatment of Post-radiation sarcomas Materials. Post-radiation sarcomas is a rare entity and large series have rarely been reported. In order to improve knowledge about this entity the Radiotherapist group of the French Cancer Centres (FNCLCC) decided to collect retrospectively the cases treated in their institutions. In order to be sure of the histology, all the cases were reviewed by a panel of pathologists of the FNCLCC Pathologist group. A total of 129 cases of sarcomas, and 108 were reviewed; analysis of 8 is in progress, and no material was obtained in the other 11 cases. The diagnosis of sarcomas was confirmed in 80 cases. All patients (60 F, 20 M) have received radiation therapy (median dose 50 Gy; 9-110 Gy) for the treatment of the primary tumor. At this time the age was 44 years (6-83 y). Diagnoses included: breast C. 42%, Lymphomas 11.5%, gynaecological C. 10% benign lesions 5% miscellaneous. Sarcomas developed after a mean interval of 12 years (3-64 y), in bone in 30% of the cases and in soft tissue in 70%. The majority of lesions (90%) developed in the irradiated field (dose received was between 50 Gy and 60 Gy). Histologically there were 29% Malignant HistiocytofibroSarcomas, 19% OsteoSarcomas, 15% FibroSarcomas, 9% LipoSarcomas, 6% LeiomyoSarcomas, miscellaneous sarcomas 22%. Treatment included: Surgery 28 cases, Surgery+Chemotherapy 17 cases, Chemotherapy only 16 cases, Radiation therapy only 1 case, surgery + Radiation therapy 5 cases, Radiation therapy +chemotherapy 6 cases, Surgery + Radiation therapy + Chemotherapy 7 cases, no treatment 5 cases. Results. The outcome is known for all but 3 patients. 51 patients have died (44 of their sarcoma, 4 of the primary tumour, 2 of other cause and 1 iatrogenic). Median survival is 23 months (95% confidence interval 16-29 mo) but 9 patients survived 5 yr or more. Median survival was 43 mo for patients treated by surgery (28p), 6 mo for chemotherapy group (16 p

Ewing sarcoma

International Nuclear Information System (INIS)

Hamanoue, Satoshi; Makimoto, Atsushi

2007-01-01

Ewing sarcoma is the second most frequent primary bone cancer affecting children or young adults. Advances in molecular biology have revealed common chromosomal translocations such as EWS-FLI1 among Ewing sarcoma and related diseases such as primitive neuroectodermal tumor (PNET), so these are considered as Ewing sarcoma family tumor (ESFT). Although fewer than 10% of patients with ESFT survived before establishment of modern multiagent chemotherapy, the multimodal therapeutic regimens including combination chemotherapy, radiotherapy, and surgery can cure 60% of patients with localized disease, due to the collaborative research in European-American or the international trials. The standard chemotherapy for localized ESFT now comprises vincristine, actinomycin D, cyclophosphamide and doxorubicin (VACD) in Europe or vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC-IE) in North America. Meanwhile, those with metastatic disease have a much worse outcome with an approximately 10-30% 5-year event-free survival rate. New American-European collaborative trials such as EURO-E.W.I.N.G. 99 are in progress for further improvement of the cure rate in localized and metastatic ESFT. In Japan, Japan Ewing Sarcoma Study Group (JESS) phase II clinical trial for localized ESFT, and some clinical trials including new drugs are ongoing and waiting for results. (author)

Concurrent development of testicular seminoma and choriocarcinoma of the superior mediastinum, presented as cervical mass: a case report and implications about pathogenesis of germ-cell tumours

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Bamias Aristotelis

2006-11-01

Full Text Available Abstract Background Synchronous presentation of more than one germ cell tumours of different histology in the same patient is considered to be very rare. In these cases of multiple germ cell tumours, strong theoretical and clinical data suggest an underlying common pathogenetic mechanism concerning genetic instability or abnormalities during the pluripotent embryonic differentiation and maturation of the germ cell. Case presentation A 25 year-old young man presented with an enlarging, slightly painful left cervical mass. Despite the initial disorientation of the diagnosis to a possible thyroid disorder, the patient underwent complete surgical resection of the mass revealing mediastinal choriocarcinoma. Subsequent ultrasound of the scrotum indicated the presence of a small lobular node in the upper pole of the left testicle and the patient underwent radical left inguinal orchiectomy disclosing a typical seminoma. Based on these results, the patient received 4 cycles of Bleomycin, Etoposide and Platinum chemotherapy experiencing only mild toxicity and resulting in complete ongoing clinical and biochemical remission. Conclusion The pathogenesis of concurrent germ cell tumours in the same patient remains an area of controversy. Although the genetic instability of the pluripotent germ cell offers an adequate explanation, the possibility of metastasis from the primary, less differentiated tumour to a distant location as a more mature subtype cannot be excluded. Possible development of a metastatic site of different histology and thus biological behaviour (e.g choriocarcinoma should be anticipated. Furthermore, urologists, pathologists and medical oncologists should be meticulous in the original pathological diagnosis in these patients, since there is a significant frequency of germ cell tumours with mixed or overlapping histological elements with diverse potential of evolution and differentiation.

Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

DEFF Research Database (Denmark)

Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.

2014-01-01

Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective...... of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference......). Changes in TNF-α correlated with pulmonary toxicity (P BEP display consistently elevated levels of systemic inflammatory markers compared with healthy...

Primary renal synovial sarcoma

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Girish D. Bakhshi

2012-03-01

Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

1800 MHz mobile phone irradiation induced oxidative and nitrosative stress leads to p53 dependent Bax mediated testicular apoptosis in mice, Mus musculus.

Science.gov (United States)

Shahin, Saba; Singh, Surya P; Chaturvedi, Chandra M

2018-09-01

Present study was carried out to investigate the effect of long-term mobile phone radiation exposure in different operative modes (Dialing, Receiving, and Stand-by) on immature male mice. Three-week old male mice were exposed to mobile phone (1800 MHz) radiation for 3 hr/day for 120 days in different operative modes. To check the changes/alteration in testicular histoarchitecture and serum testosterone level, HE staining and ELISA was performed respectively. Further, we have checked the redox status (ROS, NO, MDA level, and antioxidant enzymes: SOD, CAT, and GPx) by biochemical estimation, alteration in the expression of pro-apoptotic proteins (p53 and Bax), active executioner caspase-3, full length/uncleaved PARP-1 (DNA repair enzyme), anti-apoptotic proteins (Bcl-2 and Bcl-x L ) in testes by immunofluorescence and cytosolic cytochrome-c by Western blot. Decreased seminiferous tubule diameter, sperm count, and viability along with increased germ cells apoptosis and decreased serum testosterone level, was observed in the testes of all the mobile phone exposed mice compared with control. We also observed that, mobile phone radiation exposure in all the three different operative modes alters the testicular redox status via increasing ROS, NO, and MDA level, and decreasing antioxidant enzymes levels leading to enhanced apoptosis of testicular cells by increasing the expression of pro-apoptotic and apoptotic proteins along with decreasing the expression of anti-apoptotic protein. On the basis of results, it is conclude that long-term mobile phone radiation exposure induced oxidative stress leads to apoptosis of testicular cells and thus impairs testicular function. © 2018 Wiley Periodicals, Inc.

Testicular biopsy in prepubertal boys

DEFF Research Database (Denmark)

Faure, Alice; Bouty, Aurore; O'Brien, Mike

2016-01-01

No consensus exists regarding the precise role of testicular biopsy in prepubertal boys, although it is considered useful for assessing the potential consequences of undescended testes on fertility. Current scientific knowledge indicates that surgeons should broaden indications for this procedure...... for the preservation of fertility after gonadotoxic chemotherapy - even for prepubertal boys - are emerging. Cryopreservation of testicular tissue samples for the preservation of fertility - although still an experimental method at present - is appealing in this context. In our opinion, testicular biopsy...

Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

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Fatemeh Sheikhbahaei

2016-12-01

Full Text Available Background: Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ as a fraction of Nigella sativa on methotrexate (MTX- induced germ cell apoptosis in male mice. Materials and Methods: In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6. A single dose of MTX (20 mg/kg and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results: In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%, apoptotic index (AI; 2.3 ± 0.6%, as well as mRNA expression of p53 (P=0.008, caspase 8 (P=0.002, caspase 3 (P=0.005, caspase 9 (P=0.000, bax (P=0.004 and the ratio of bax/bcl-2 (P=0.000, whereas there was an decrease in the expression of bcl-2 (P=0.003, as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg. Conclusion: TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage-gated channels, methylation/acetylation, and transcription factors.

Science.gov (United States)

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic. Copyright 2009 Wiley-Liss, Inc.

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.)

Radio-induced sarcomas in survivors of Ewing sarcoma

International Nuclear Information System (INIS)

Boriani, S.; Sudanese, A.; Toni, A.; Monesi, M.; Ciaroni, D.; Mancini, A.; Frezza, G.; Barbieri, E.; Picci, P.; Bacci, G.

1988-01-01

Of 255 cases of Ewing's sarcoma recorded at the Bone Tumor Center of the Rizzoli Orthopaedic Institute, 78 patients (irradiated and with a follow-up of longer than3 years) were considered ''at risk'' for the development of a second radio-induced sarcoma (RIS). Three of the 78 patients developed an RIS in the irradiated field. Theoretical and statistical analyses were carried out considering different modalities of local treatment. Statistically, the only significant factor was related to the irradiation dose. Surgical resection seems to prevent RIS

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

Science.gov (United States)

2018-02-12

Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC

Lymphangiectatic Kaposi's sarcoma in a patient with AIDS Sarcoma de Kaposi linfangiectásico em paciente com Aids

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Mônica Santos

2013-04-01

Full Text Available Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma.O sarcoma de Kaposi é uma neoplasia originária do endotélio linfatico, que apresenta um amplo espectro de manifestações, com quatro formas clínicas: sarcoma de Kaposi clássico, endêmico, iatrogêncio e epidêmico ou associado ao HIV. Em pacientes imunocompetentes, a doença é tipicamente limitada às extremidades. Porém em pacientes imunideprimidos, o sarcoma de Kaposi é uma doença sistêmica multifocal. Apresenta cursos clínicos diferentes, desde simples lesões cutâneas isoladas até lesões agressivas e difusas, com ou sem envolvimento sistêmico. Lesões avançadas de sarcoma de Kaposi, principalmente as localizadas nas extremidades, podem apresentar linfedema. Neste trabalho, reportamos caso de paciente com forma rara de Sarcoma de Kaposi associado a Aids, chamada de sarcoma de Kaposi linfangiectásico.

Radiographic appearance of Ewing sarcoma of the hands and feet: report from the Intergroup Ewing Sarcoma Study

International Nuclear Information System (INIS)

Reinus, W.R.; Gilula, L.A.; Shirley, S.K.; Askin, F.B.; Siegal, G.P.

1985-01-01

Review of current data from the Intergroup Ewing Sarcoma Study (IESS) shows that Ewing sarcoma is rare in bones of the hands and feet. The 12 patients from the IESS protocols with hand or foot Ewing sarcoma are comparable to those already reported in the literature. With the exception of lesions in the calcaneus, the prognosis for disease-free survival is excellent. The radiographic features of hand and foot Ewing sarcoma are generally those of classic Ewing sarcoma: permeation, soft-tissue mass, and often, associated sclerotic reaction. However, with the exception of sclerosis, features suggesting bone reaction and slow tumor growth in these patients were distinctly uncommon compared with Ewing sarcoma in general. Apparently location of the lesion is important, since in the reported cases in the literature and in this series, lesions of the calcaneus fared poorly. The importance of this set of patients therefore relates to awareness and early recognition of an unusual appearance and location of Ewing sarcoma

Sertoli cell origin of testicular androgen-binding protein (ABP)

Energy Technology Data Exchange (ETDEWEB)

Hagenaes, L [Pediatric Endocrinology Unit, Stockholm; Ritzen, E M; Ploeen, L; Hansson, V; French, F S; Nayfeh, S N

1975-05-01

In this report it is suggested that the specific androgen-binding protein (ABP), previously shown to originate in the testes of rat and other species, is produced by the Sertoli cells. This suggestion is based upon the following experimental findings: (1) ABP was found in high concentrations in testicular efferent duct fluid but only in trace amounts in inter-tubular lymph. (2) ABP could be recovered from crude preparations of testes tubules, but not from Leydig cells from the same testes. (3) Testes whose germinal epithelium had been severely damaged by gamma irradiation showed no decrease in ABP content. The transport of ABP to epididymis was also preserved as judged from the levels of ABP in caput epididymis. (4) Testes that were completely devoid of germ cells following prenatal gamma irradiation showed high levels of ABP. These high levels approached zero following hypophysectomy, but could be restored by FSH administration to the hypophysectomized animals. ABP has been well characterized and now provides a valuable experimental tool as an indicator of Sertoli cell function.

Radiotherapy in stage 1 testicular seminoma: retrospective study and review of literature

International Nuclear Information System (INIS)

Bauduceau, O.; Le-Moulec, S.; Bernard, O.; Souleau, B.; Houlgatte, A.

2003-01-01

Introduction. - Seminoma accounts for about 40% of germ cell tumours of the testicle. In this retrospective analysis, we review literature concerning management of stage I seminoma. Materials and methods. - Between March 1987 and April 2001, 65 patients with stage I pure testicular seminoma received adjuvant radiotherapy with a 25 MV linear accelerator. Results. - Median age was 33 years. Testicular tumour has been found on the right testis in 39 patients and on the left one in 24 patients. Patients have been treated using an anterior-posterior parallel pair and have received 20-25 Gy in 10-14 fractions. The target volume consisted of paraaortic, and paraaortic + homolateral iliac lymph nodes in 17 and 46 patients, respectively. Acute toxicity was mainly digestive, 38% of patients presenting nausea and vomiting. Median follow-up time was 37 months. All patients are alive in complete remission. Discussion. - Because of good radio-sensitivity of seminoma, radiotherapy is regarded as standard adjuvant treatment (5 years relapse rate: 3-5%). Acute toxicity is dominated by moderate gastro-intestinal side effects. Secondary neoplasia represents one of the worst possible long-term complications of therapy. Waiting for ongoing randomized trials, the modern literature for seminoma reflects a trend toward lower radiation doses (20-25 Gy) and smaller treatment volumes (paraaortic field). Adjuvant chemotherapy with two courses of carbo-platin, might be equivalent to radiotherapy but must be investigated in randomized trials. A surveillance policy is one of the other management options less recommended. (author)

General Information about Testicular Cancer

Science.gov (United States)

... tumor markers are used to detect testicular cancer: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Tumor ... tumor markers are used in staging testicular cancer : Alpha-fetoprotein (AFP) Beta-human chorionic gonadotropin (β-hCG). Lactate ...

Inguinal metastases from testicular cancer

DEFF Research Database (Denmark)

Daugaard, Gedske; Karas, Vladimir; Sommer, Peter

2006-01-01

To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease.......To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease....

Radiation-induced soft-tissue and bone sarcoma

International Nuclear Information System (INIS)

Kim, J.H.; Chu, F.C.; Woodard, H.Q.; Melamed, R.; Huvos, A.; Cantin, J.

1978-01-01

From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed

Testicular Pain Associated With Minocycline Use

OpenAIRE

Kucherov, Victor; Hulbert, William; Wu, Guan

2015-01-01

Two males ages 16 and 23 years presented with new testicular pain while taking minocycline. Both patients experienced resolution of their symptoms only after minocycline discontinuation. Testicular pain with minocycline use has been previously described, however only in the setting of systemic autoimmune reactions (which were absent here). These cases represent probable rare adverse reactions to minocycline. For patients taking minocycline who experience otherwise unexplained testicular pain,...

New evidence for the origin of intracranial germ cell tumours from primordial germ cells

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Sehested, A; Juhler, M

2006-01-01

that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which...... germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children...... and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected...

CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells

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Kim, Jiyeon; Seandel, Marco; Falciatori, Ilaria; Wen, Duancheng; Rafii, Shahin

2010-01-01

Stem cells reside in specialized microenvironments created by supporting stromal cells that orchestrate self-renewal and lineage-specific differentiation. However, the precise identity of the cellular and molecular pathways that support self-renewal of stem cells is not known. For example, long-term culture of prototypical stem cells, such as adult spermatogonial stem and progenitor cells (SPCs), in vitro has been impeded by the lack of an optimal stromal cell line that initiates and sustains proliferation of these cells. Indeed, current methods, including the use of mouse embryonic fibroblasts (MEFs), have not been efficient and have generally led to inconsistent results. Here, we report the establishment of a novel CD34-positive cell line, referred to as JK1, derived from mouse testicular stromal cells that not only facilitated long-term SPC culture but also allowed faithful generation of SPCs and multipotent stem cells. SPCs generated on JK1 maintained key features of germ line stem cells, including expression of PLZF, DAZL, and GCNA. Furthermore, these feeders also promoted the long-term cultivation of other types of primitive cells including multi-potent adult spermatogonial-derived stem cells, pluripotent murine embryonic stem cells, and embryonic germ cells derived from primordial germ cells. Stem cells could be passaged serially and still maintained expression of characteristic markers such as OCT4 and NANOG in vitro, as well as the ability to generate all three germ layers in vivo. These results indicate that the JK1 cell line is capable of promoting long-term culture of primitive cells. As such, this cell line allows for identification of stromal-derived factors that support long-term proliferation of various types of stem cells and constitutes a convenient alternative to other types of feeder layers. PMID:18669907

Testicular dysgenesis syndrome

DEFF Research Database (Denmark)

Skakkebaek, N E; Rajpert-De Meyts, E; Main, K M

2001-01-01

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently...... summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental...

Promiscuous partnerships in Ewing's sarcoma.

Science.gov (United States)

Sankar, Savita; Lessnick, Stephen L

2011-07-01

Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing's sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing's sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing's sarcoma. However, in recent years there have been reports of rare fusions in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing's sarcoma and Ewing's-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

[Update on soft tissue sarcomas].

Science.gov (United States)

Bui, Binh Nguyen; Tabrizi, Reza; Dagada, Corinne; Trufflandier, Nathalie; St ckle, Eberhard; Coindre, Jean-Michel

2002-01-01

Important refinements have taken place in the diagnosis of soft tissue sarcoma with extensive use of immuno-histochemistry. New entities have been described, while malignant histiocytofibroma, the most diagnosed sarcoma type during the last two decades, has been dismembered. As for prognosis, the new UICC classification is effectively more discriminating in the definition of prognostic groups; but the usefullness of new biological or genetic markers remains to be assessed. Several breakthrough have taken place in the last years in the treatment of soft tissue sarcoma. Isolated limb perfusion with TNF, hyperthermia and melphalan have proven its efficacy, and is now an alternative to preoperative chemotherapy and/or radiotherapy for limb sparing treatment of the primary tumor site or to amputation. For systemic treatments, novel cytostatic drugs have been shown to be active in sarcomas, including ecteinascidine (ET743) and Glivec (STI571). This last drug has been shown to be remarkably active in c-kit+ stromal sarcoma of the gastro-intestinal tract. It can hopefully regarded as an example for targeted therapies, which may come with a better understanding of the molecular mechanisms triggered by the fundamental, specific genetic alterations shown in sarcoma.

Kaposi’s Sarcoma in Film

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Richard F. WAGNER

2016-04-01

Full Text Available Kaposi’s sarcoma, a historically rare, indolent cutaneous malignancy of elderly men emerged as a frequent and easily recognizable cutaneous manifestation of Acquired Immunodeficiency Syndrome in the 1980s. Since these tumors were often visible to the public, Kaposi’s sarcoma quickly became a stigmatizing marker for those infected, and predicted the high mortality risk from comorbid opportunistic infections. English language films released from 1985-2008 are analyzed for their depictions of Kaposi’s sarcoma, and the role(s it played in these films. With the advent of highly active antiretroviral therapy for those with HIV infection, Kaposi’s sarcoma has once again become relatively rare.

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Science.gov (United States)

2018-05-15

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans.

Science.gov (United States)

Mainpal, Rana; Nance, Jeremy; Yanowitz, Judith L

2015-10-15

Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the ∼300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation. © 2015. Published by The Company of Biologists Ltd.

10 non seminomatous testicular germ cell tumors: therapeutic results and behavior at the University Hospital in the last 10 years

International Nuclear Information System (INIS)

Martinez, A.; Xavier, F.; Cepellini, R.; Fresco, R.

2010-01-01

Objective: Retrospectively analyze about the characteristics, therapeutic behavior and treatment results in patients with non-seminomatous testicular germ cell tumours (NSGCT) Stage III assisted in the University Hospital. Materials and Methods: The medical records of patients (pts) with histologically reviewed of NSGCT assisted in the Department of Clinical Oncology, Hospital das Clinicas (H C), among January 2000 and December 2009. We analyzed in detail the clinico pathological features of those belonging to pts with stage III tumors TNM classification. Results: 23 pts were included; median age 24 years (range: 17-40); median follow-up: 19 months (range: 2-104). Stadiums: I: 9/23; II: 7/23; III: 7/23. Among ptes E III.They corresponded to: high risk: 3/7; means: 3/7; Low: 1/7. Only in 1 patient (pte) of the E III It is not explicitly consisted risk rating in history but, based on data present is able to allocate retrospectively. The chemotherapy was the first line chosen, PE B plan pts 6/7 and 1/7 VIP (pte. athlete). All patients received 4 sets of PE B / VIP (including low risk). Imaging responses post chemotherapy (Q T): Complete: 1/7; Partial: 5/7; Stabilization: 1/7. In the 7 pts M T post Q T were normal. In 4 of the 7 pts who achieved partial response and normalized MTwe proceeded to surgery residual mass. The current status of patients is alive: 6/23; Dead: 4/23; monitoring loss (PDS): 13/23. The patients E III: Live 2/7, 4/7 dead, PDS 1/7.4 E III patients were dead with diagnosis (high risk 3/4, 1/4 medium). He did not make the survival analysis given the low and high percentage of patients PDS. Conclusions: In the last 10 years only 7 patients with NSGCT E III attended the H C (0.7 / year). Overall front line management adjusted to the recommendations international but the management of patients with residual mass and not normal M T necessarily. While the number of patients is too low to definitive conclusions, the C R rate to Q T 1st line impresses be

Proximal-type epithelioid sarcoma - Case report Sarcoma epitelióide tipo proximal - Relato de caso

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Luciana Mendes dos Santos

2013-06-01

Full Text Available Epithelioid sarcoma, first described by Enzinger in 1970, is a rare soft-tissue sarcoma typically presenting as a subcutaneous or deep dermal mass in distal portions of the extremities of adolescents and young adults. In 1997, Guillou et al. described a different type of epithelioid sarcoma, called proximal-type epithelioid sarcoma, which is found mostly in the pelvic and perineal regions and genital tracts of young to middle-aged adults. It is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. In this paper we present a case of proximal-type epithelioid sarcoma with an aggressive clinical course, including distant metastasis and death nine months after diagnosis.O sarcoma epitelióide, primeiramente descrito por Enzinger, em 1970, é uma neoplasia de partes moles que ocorre principalmente nas extremidades distais de adolescentes e adultos jovens. Em 1997, Guillou e cols. descreveram um tipo diferente de sarcoma epitelióide, que afetava frequentemente a região pélvica, períneo e áreas genitais de pacientes de média idade, com exame histológico caracterizado pela proliferação de células com aspecto epitelióide. Neste trabalho, descreve-se caso de paciente que apresentava há três meses duas lesões na região glútea, cujo exame histológico confirmou diagnóstico de sarcoma epitelioide do tipo proximal, já com presença de metástases pulmonares e cerebrais e que foi a óbito nove meses após o diagnóstico.

Hypothesis: does ochratoxin A cause testicular cancer?

Science.gov (United States)

Schwartz, Gary G

2002-02-01

Little is known about the etiology of testicular cancer, which is the most common cancer among young men. Epidemiologic data point to a carcinogenic exposure in early life or in utero, but the nature of the exposure is unknown. We hypothesize that the mycotoxin, ochratoxin A, is a cause of testicular cancer. Ochratoxin A is a naturally occurring contaminant of cereals, pigmeat, and other foods and is a known genotoxic carcinogen in animals. The major features of the descriptive epidemiology of testicular cancer (a high incidence in northern Europe, increasing incidence over time, and associations with high socioeconomic status, and with poor semen quality) are all associated with exposure to ochratoxin A. Exposure of animals to ochratoxin A via the diet or via in utero transfer induces adducts in testicular DNA. We hypothesize that consumption of foods contaminated with ochratoxin A during pregnancy and/or childhood induces lesions in testicular DNA and that puberty promotes these lesions to testicular cancer. We tested the ochratoxin A hypothesis using ecologic data on the per-capita consumption of cereals, coffee, and pigmeat, the principal dietary sources of ochratoxin A. Incidence rates for testicular cancer in 20 countries were significantly correlated with the per-capita consumption of coffee and pigmeat (r = 0.49 and 0.54, p = 0.03 and 0.01). The ochratoxin A hypothesis offers a coherent explanation for much of the descriptive epidemiology of testicular cancer and suggests new avenues for analytic research.

Downregulation of Clusterin Expression in Human Testicular Seminoma

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Bianjiang Liu

2013-11-01

Full Text Available Background: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma. Methods: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups. Results: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification. Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis. Conclusion: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer.

TESTICULAR CAPILLARY HEMANGIOMA: DESCRIPTION OF A CASE

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A. S. Markova

2012-01-01

Full Text Available The paper describes a clinical case of testicular capillary hemangioma in a 24-year-old man undergone a partial resection of the testis with the intraoperative morphological examination. Testicular capillary hemangioma is a rare benign tumor of a vascular origin, which can be similar to malignant testicular tumors on the clinical presentation, as well as on the imaging methods, in particular to seminoma. The intraoperative histological study can assist in avoiding organ-removing surgical interventions in diagnostically ambiguous cases if a benign testicular tumor is diagnosed.

Sarcoma risk after radiation exposure

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Berrington de Gonzalez Amy

2012-10-01

Full Text Available Abstract Sarcomas were one of the first solid cancers to be linked to ionizing radiation exposure. We reviewed the current evidence on this relationship, focusing particularly on the studies that had individual estimates of radiation doses. There is clear evidence of an increased risk of both bone and soft tissue sarcomas after high-dose fractionated radiation exposure (10 + Gy in childhood, and the risk increases approximately linearly in dose, at least up to 40 Gy. There are few studies available of sarcoma after radiotherapy in adulthood for cancer, but data from cancer registries and studies of treatment for benign conditions confirm that the risk of sarcoma is also increased in this age-group after fractionated high-dose exposure. New findings from the long-term follow-up of the Japanese atomic bomb survivors suggest, for the first time, that sarcomas can be induced by acute lower-doses of radiation (

Uterine sarcoma – current perspectives

Science.gov (United States)

Benson, Charlotte; Miah, Aisha B

2017-01-01

Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. PMID:28919822

Screening for carcinoma in situ in the contralateral testicle in patients with testicular cancer

DEFF Research Database (Denmark)

Kier, M G G; Lauritsen, Jakob; Almstrup, Kristian

2015-01-01

population-based screening programme for contralateral CIS in patients with testicular cancer showed no significant difference in the risk for metachronous GCC between a screened and an unscreened cohort. Single-site biopsy including modern immunohistochemistry does not identify all cases of CIS.......BACKGROUND: Screening programmes for contralateral carcinoma in situ (CIS) testis in patients with unilateral germ-cell cancer (GCC) have never been evaluated. We investigated the effect of screening for contralateral CIS in a large nation-wide, population-based study. PATIENTS AND METHODS...... years was 1.9% in the screened cohort and 3.1% in the unscreened cohort (P = 0.097), hazard ratio (HR) for the unscreened cohort: 1.59 (P = 0.144). Expert revision with contemporary methodology of CIS-negative biopsy samples from patients with metachronous cancer revealed CIS in 17 out of 45 (38%) cases...

Case-control study of anthropometric measures and testicular cancer risk

Directory of Open Access Journals (Sweden)

Fabrizio eGiannandrea

2012-11-01

Full Text Available The etiology of testicular germ cell tumors (TGCTs is poorly understood. Recent epidemiological findings suggest that TGCT risk is determined very early in life, although the available data are still conflicting. The rapid growth of the testes during puberty may be another period of vulnerability. Body size has received increasing attention as possible risk factor for TC. To clarify the relation of body size and its anthropometric variables to TGCT risk, the authors analyzed data from 272 cases and 382 controls with regard to height (cm, weight (Kg and body mass index (BMI; kg/m2. Overall, participants in the highest quartile of height were more likely to be diagnosed with TGCTs than participants in the lowest quartile of height, OR 2.22 (95% confidence intervals (CI: 1.25-3.93; adjusted; ptrend = 0.033. Moreover, histological seminoma subgroup was significantly associated with tallness, very tall men (>182 cm having a seminoma TGCT risk of OR=2.44 (95% confidence intervals (CI: 1.19-4.97; adjusted; ptrend = 0.011. There was also a significant inverse association of TGCT with increasing BMI (ptrend = 0.001; age-adjusted analysis and this association was equally present in both histological subgroups. These preliminary results indicate that testicular cancer is inversely associated with BMI and positively associated with height, in particular with seminoma subtype. Several studies have reported similar findings on body size. As adult height is largely determined by high-calorie intake in childhood and influenced by hormonal factors at puberty, increased attention to postnatal exposures in this interval may help elucidate the etiology of TGCTs.

Testicular teratoma, mimicking a simple testicular cyst, in an infant.

Science.gov (United States)

Di Renzo, Dacia; Persico, Antonello; Sindici, Giulia; Lelli Chiesa, Pierluigi

2013-09-01

Prepubertal testicular tumors are rare, and teratoma is the second most frequent histologic type. Its typical features are those of a hard and painless scrotal mass at clinical examination, and nonhomogeneous, echoic, often with calcifications at ultrasonography. Rare but reported is the atypical presentation as a transilluminating scrotal mass, due to the presence of some internal cystic areas, detectable at ultrasonography. We report the case of an infant with a transilluminating scrotal mass, mimicking at ultrasonography and surgery a simple, fully liquid cyst, which the pathologic examination revealed to be mature cystic testicular teratoma. Copyright © 2013 Elsevier Inc. All rights reserved.

Exploring men's preferred strategies for learning about testicular disorders inclusive of testicular cancer: A qualitative descriptive study.

Science.gov (United States)

Saab, Mohamad M; Landers, Margaret; Hegarty, Josephine

2017-02-01

Men's awareness of testicular disorders is lacking and their intention to seek help for testicular symptoms is sub-optimal. Studies conducted to explore and raise men's awareness of testicular disorders did not address their preferred learning strategies and failed to include men who are at risk for health inequities. The aim of this study was to explore, in-depth, the preferred strategies for learning about testicular disorders inclusive of testicular cancer among men who self-identify as heterosexual, gay, or bisexual. Maximum variation and snowball sampling were used to recruit 29 men aged 18-47 years. Participation was sought from community and youth organizations and a university in the Republic of Ireland. Semi-structured individual interviews and focus groups were conducted. Interviews were audio-recorded and transcribed verbatim. Inductive analysis of manifest content was used. Seventeen informants self-identified as heterosexual, 11 as gay, and one as bisexual. Four main categories emerged, namely: strategies to enhance awareness (television, internet, campaigns, print media), educational dos and don'ts (tailoring effective messages, drawbacks of national initiatives, ineffective learning strategies), implications of raising awareness (risks and benefits of increasing awareness), and learning among gay and bisexual men (learning needs and strategies). Future studies promoting awareness of testicular disorders should take into account men's preferred learning strategies. National campaigns should be delivered frequently and altered occasionally in order to achieve a top-up effect. Clinicians are encouraged to educate young men about the seriousness of testicular symptoms and the importance of seeking timely medical attention for any abnormalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Testicular Pain Associated With Minocycline Use

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Victor Kucherov

2015-05-01

Full Text Available Two males ages 16 and 23 years presented with new testicular pain while taking minocycline. Both patients experienced resolution of their symptoms only after minocycline discontinuation. Testicular pain with minocycline use has been previously described, however only in the setting of systemic autoimmune reactions (which were absent here. These cases represent probable rare adverse reactions to minocycline. For patients taking minocycline who experience otherwise unexplained testicular pain, a trial discontinuation of this medication should be considered.

Long-term health effects among testicular cancer survivors.

Science.gov (United States)

Hashibe, Mia; Abdelaziz, Sarah; Al-Temimi, Mohammed; Fraser, Alison; Boucher, Kenneth M; Smith, Ken; Lee, Yuan-Chin Amy; Rowe, Kerry; Rowley, Braden; Daurelle, Micky; Holton, Avery E; VanDerslice, James; Richiardi, Lorenzo; Bishoff, Jay; Lowrance, Will; Stroup, Antoinette

2016-12-01

Testicular cancer is diagnosed at a young age and survival rates are high; thus, the long-term effects of cancer treatment need to be assessed. Our objectives are to estimate the incidence rates and determinants of late effects in testicular cancer survivors. We conducted a population-based cohort study of testicular cancer survivors, diagnosed 1991-2007, followed up for a median of 10 years. We identified 785 testicular cancer patients who survived ≥5 years and 3323 men free of cancer for the comparison group. Multivariate Cox regression analysis was used to compare the hazard ratio between the cases and the comparison group and for internal analysis among case patients. Testicular cancer survivors experienced a 24 % increase in risk of long-term health effects >5 years after diagnosis. The overall incidence rate of late effects among testicular cancer survivors was 66.3 per 1000 person years. Higher risks were observed among testicular cancer survivors for hypercholesterolemia, infertility, and orchitis. Chemotherapy and retroperitoneal lymph node dissection appeared to increase the risk of late effects. Being obese prior to cancer diagnosis appeared to be the strongest factor associated with late effects. Testicular cancer survivors were more likely to develop chronic health conditions when compared to cancer-free men. While the late effects risk was increased among testicular cancer survivors, the incidence rates of late effects after cancer diagnosis was fairly low.

Chemokines in Ewing sarcoma

NARCIS (Netherlands)

Sand, L.G.L.

2016-01-01

Ewing sarcoma is an aggressive primary malignant bone tumor with high degree of tumor vascularization and is the second most common sarcoma of bone in children and young adults. Patients with disseminated disease at diagnosis or early relapse have a poor prognosis. To identify novel therapies and

Early life risk factors for testicular cancer

DEFF Research Database (Denmark)

Piltoft, Johanne Spanggaard; Larsen, Signe Benzon; Dalton, Susanne Oksbjerg

2017-01-01

of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. METHODS: The study population consisted of 408 cases of testicular cancer identified by a government issued identification...... in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79-4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth......PURPOSE: One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective...

Testicular Volume: Size Does Matter

International Nuclear Information System (INIS)

Reyes Lobo, Alexander; Segovia Fuentes, Javier; Cerpa Reyes, Edgar

2011-01-01

Testicular volume is critical for semen production and, consequently, for fertility. Hence the importance of knowing the normal size ranges and the different methods for calculating size, in order to classify patients at risk and refer them for appropriate management. Ultrasound is the first-line diagnostic method for the evaluation of testicular pathology, and it is also the best tool for estimating the volume of both testicles, bearing in mind that a testicular volume below 15 cc results in fertility problems. Although there are many causes of infertility, varicocele is undoubtedly the most important of all, because of its frequency and because it is amenable to curative surgical treatment.

Testicular Metastases From Prostate Carcinoma

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Harrina Erlianti Rahardjo

2010-07-01

Full Text Available Metastasis of prostate carcinoma to the testis is seldom reported. The tumour may spread from the prostatic urethra by retrograde venous extension, arterial embolism or through direct invasion into the lymphatics and lumen of the vas deferens. Clinical manifestations of secondary testicular tumours from the prostate are most often unsuspected clinically and are instead detected incidentally during orchidectomy. Less frequently, a palpable mass is detected, which may be confused with a primary testicular neoplasm. We report a case of a 66-year-old patient with adenocarcinoma of the prostate, and a left testicular tumour that was diagnosed as metastases from prostate carcinoma after radical orchidectomy.

Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.

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Michael K Skinner

Full Text Available A number of environmental factors (e.g. toxicants have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation progeny in regards to the primordial germ cell (PGC epigenetic reprogramming of the F3 generation (i.e. great-grandchildren. The F3 generation germline transcriptome and epigenome (DNA methylation were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13 and after cord formation in the testis at embryonic day 16 (E16. A larger number of DNA methylation abnormalities (epimutations and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

International Nuclear Information System (INIS)

Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

2015-01-01

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

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Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

2015-08-01

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

Is testicular dysgenesis syndrome a genetic, endocrine, or environmental disease, or an unexplained reproductive disorder?

Science.gov (United States)

Xing, Jian-Sheng; Bai, Zhi-Ming

2018-02-01

Progressive increases in the incidence of male reproductive disorders inclusive of hypospadias, cryptorchidism, poor semen quality, and testicular germ cell cancer (TGCC) have been observed in recent times. The central hypothesis of this study asserted that these disorders may all collectively signify testicular dysgenesis syndrome (TDS). This review aimed to provide evidence verifying the reality of TDS based on four key aspects: environmental endocrine-disrupting chemicals (EDCs), genetic factors, intrauterine growth disorders and lifestyle factors. Although TDS might result from genetic polymorphisms or aberration, recent evidence has highlighted links indicating the conditions associations to both environmental and lifestyle factors due to the rapid temporal changes in the clinical symptoms observed over recent decades. Based on our review of genetic and environmental factors, a key observation of our study suggested that there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. At present, current research has yet to elucidate the mechanisms of TDS, in addition to the lack of genuine consideration of a variety of potentially key factors and TDS mechanisms. In conclusion, our study revealed that environmental exposures owing to modern lifestyles are primary factors involved in the associated trends of the syndrome, which are capable of affecting the adult endocrine system via direct means or through epigenetic mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Ewing`s Sarcoma

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Agnieszka Budny

2017-06-01

Full Text Available Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Clinical presentation is usually dominated by local bone pain and a mass. Magnetic resonance best defines the extent of the lesion. Patients diagnosed with Ewing's sarcoma within  last years show a improving  survival rate . Rehabilitation seems to be a crucial part of multimodal therapy.

Sarcoma de Kaposi clássico fatal Fatal outcome in classic Kaposi's sarcoma

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Eugênia Maria Damásio N. Ohe

2010-06-01

Full Text Available Descrito em 1872, o sarcoma de Kaposi é neoplasia multicêntrica rara originária de células endoteliais com manifestação cutânea e extracutânea. A forma clássica é muito mais frequente em homens idosos, com evolução prolongada e boa resposta a quimioterapia e radioterapia. Apresentaremos um caso de sarcoma de Kaposi clássico com comprometimento cutâneo e visceral em paciente do sexo feminino com rápida evolução fatal.First described in 1872, Kaposi's sarcoma is defined as a rare multifocal tumor that originates in the endothelial cells and presents with cutaneous and extracutaneous manifestations. The classic form is most common in elderly men and progression is slow. This tumor responds well to chemotherapy and radiotherapy. This report describes a classic case of Kaposi's sarcoma in a woman with skin and visceral manifestations in whom the disease rapidly progressed to a fatal outcome.

Familial testicular cancer in a single-centre population

NARCIS (Netherlands)

Sonneveld, DJA; Sleijfer, DT; Sijmons, RH; van der Graaf, WTA; Sluiter, WJ; Hoekstra, HJ; Schraffordt Koops, H.

Familial occurrence of testicular cancer suggests a genetic predisposition to the disease. A genetic susceptibility may also be reflected by the occurrence of bilateral testicular neoplasms and the high rates of urogenital developmental anomalies in families prone to testicular cancer. In this

Unusual termination of the right testicular vein | Woldeyes | Anatomy ...

African Journals Online (AJOL)

The testicular veins are formed by the veins emerging from the testis and epididymis forming the pampiniform venous plexus. The right testicular vein drains into inferior vena cava and the left testicular vein to the left renal vein. Testicular veins display a great variability with regard to their number, course and sites of ...

Microdissection of gonadal tissues for gene expression analyses

DEFF Research Database (Denmark)

Jørgensen, Anne; Dalgaard, Marlene Danner; Sonne, Si Brask

2011-01-01

Laser microdissection permits isolation of specific cell types from tissue sections or cell cultures. This may be beneficial when investigating the role of specific cells in a complex tissue or organ. In tissues with easily distinguishable morphology, a simple hematoxylin staining is sufficient...... phosphatase enzyme, such as fetal germ cells, testicular carcinoma in situ cells, and putatively also other early stem cell populations. We have applied these protocols for microdissection of rat Leydig cells, fetal human and zebrafish germ cells, and human testicular germ cell tumors, but the staining...

Technetium scanning in Kaposi's sarcoma and its simulators

International Nuclear Information System (INIS)

Gunnoe, R.; Kalivas, J.

1982-01-01

The clinical picture of ulcerated purple plaques on the legs often suggests several diagnoses: Kaposi's sarcoma, stasis dermatitis, atrophie blanche (livedoid vasculitis), and a poorly understood condition called acroangiodermatitis of Favre-Chaix (pseudo-Kaposi's sarcoma). Even the skin biopsy may not always be conclusive. We describe our experience with three patients with pseudo-Kaposi's sarcoma, one with true Kaposi's sarcoma and two with atrophie blanche. Clinical and histopathologic similarities among these three conditions pointed up the need for additional confirmatory studies, i.e., isotope scanning. The technetium scan was positive in both Kaposi's sarcoma and pseudo-Kaposi's sarcoma but negative in atrophie blanche

An unusual presentation of testicular tumor

International Nuclear Information System (INIS)

Amin, M.U.; Rahan, T.; Haq, A.U.; Aftab, P.

2006-01-01

A case of testicular choriocarcinoma is reported in which blood mixed stools and haemoptysis were the presenting manifestations as the patient never told about the testicular swelling to his parents. Orchidectomy was performed but the patient presented again with massive hematemesis due to gastric perforation secondary to gastric metastasis. The size of the testis at diagnosis was approximately 12 x 7cm. This was also unusual as testicular choriocarcinoma presents as a small mass. The patient eventually died of the complications within one month of diagnosis. (author)

MicroRNAs in Testicular Cancer Diagnosis and Prognosis.

Science.gov (United States)

Ling, Hui; Krassnig, Lisa; Bullock, Marc D; Pichler, Martin

2016-02-01

Testicular cancer processes a unique and clear miRNA expression signature. This differentiates testicular cancer from most other cancer types, which are usually more ambiguous when assigning miRNA patterns. As such, testicular cancer may represent a unique cancer type in which miRNAs find their use as biomarkers for cancer diagnosis and prognosis, with a potential to surpass the current available markers usually with low sensitivity. In this review, we present literature findings on miRNAs associated with testicular cancer, and discuss their potential diagnostic and prognostic values, as well as their potential as indicators of drug response in patients with testicular cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Synovial sarcoma of the abdominal wall

International Nuclear Information System (INIS)

Matushita, J.P.K.; Matushita, J.S.

1989-01-01

A case report of synovial sarcoma arising in the abdominal wall is presented. A brief review of the clinical and radiological features of synovial sarcoma is made. Pre-operative diagnosis of an abdominal wall synovial sarcoma is virtually impossible, but should be considered when a soft tissue swelling is found to show amorphous stippled calcification X-ray. (author) [pt

Convergent evolution of germ granule nucleators: A hypothesis.

Science.gov (United States)

Kulkarni, Arpita; Extavour, Cassandra G

2017-10-01

Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells. The discovery that in some animals, the gene products of a small number of lineage-specific genes initiate the assembly (also termed nucleation) of germ granules and/or germ plasm is the first step towards facilitating a better understanding of these complex biological processes. Here, we draw on research spanning over 100years that supports the hypothesis that these nucleator genes may have evolved convergently, allowing them to perform analogous roles across animal lineages. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of mode of administration of methyl methanesulfonate and triethylenemelamine on induction of unscheduled DNA synthesis in mouse germ cells

International Nuclear Information System (INIS)

Sheu, C.W.; Sega, G.A.; Owens, J.G.

1987-01-01

The effect of route of administration on induction of unscheduled DNA synthesis (UDS) in mouse germ cells in vivo was studied using two germ cell mutagens, methyl methanesulfonate (MMS) and triethylenemelamine (TEM). The chemicals were administered to male mice (C3Hf x 101)F 1 by IP injection or gavage using acute or 5-day subacute regimens. After completion of dosing, methyl-[ 3 H]thymidine ([ 3 H]TdR) was injected into the testes, and spermatozoa were collected 16 days later. The sperm heads were isolated, and UDS was determined by the amount of [ 3 H]TdR incorporated. Acute administration of MMS (2-100 mg/kg) induced a strong, dose-related UDS response. The response was slightly higher with IP injection than with gavage. Acute administration of TEM (0.05-4.0 mg/kg) by IP injection or gavage induced weak and variable responses. The study showed that gavage, as well as IP injection, can be used for the administration of test chemicals and that the subacute 5-day regimen induced a higher UDS response than the acute regimen. Furthermore, the testicular route may enhance the detection of weak UDS inducers

Roentgenologic examination in Kaposi's sarcoma

International Nuclear Information System (INIS)

Kossovoj, A.L.

1990-01-01

Review of roentgenologic investigations into Kaposi's sarcoma is presented. It is shown that Kaposi's sarcoma is a disease injuring skin, osteal system, lungs and mediastinum, gastroeuteric tract and lymphatic nodes. Roentgenologic changes of soft tissues of limbs, osteal system, chest and gastroenteric tract organs are described. Manifestations of a tumor of any localization are quite different which makes it more difficult to perform roentgenologic diagnosis. An increase of Kaposi's sarcoma occurrence in patients suffering from aids as the disease increases is indicated

Penile epithelioid sarcoma: MR imaging findings

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Sirikci, A.; Bayram, M.; Demirci, M. [Department of Radiology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey); Bakir, K. [Department of Pathology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey); Sarica, K. [Department of Urology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey)

1999-10-01

Magnetic resonance imaging findings of a 38-year-old man with epithelioid sarcoma of the penis is presented. It started as a firm, painless and slowly growing nodule at the base of his penis 6 months previously which caused pain radiating to the testis during coitus. It has been well known that sarcomas may well mimic reactive processes. Initial presentation of epithelioid sarcoma may provoke considerable diagnostic difficulty, and its differentiation from benign lesions, such as Peyronie`s disease and chronic inflammation, may be a clinical problem. In our present report the MR findings are compared with those of the epithelioid sarcomas of various locations reported in the literature and differential diagnosis of the entity is discussed. To our knowledge, this is the first report regarding the MR findings of the epithelioid sarcoma of penis. (orig.) With 3 figs., 16 refs.

Synovial sarcoma: MR evaluation in 23 patients

International Nuclear Information System (INIS)

Galant, J.; Marti-Bonmati, L.; Lafuente, J.; Hernandez, L.; Soler, R.; Saez, F.

1997-01-01

The synovial sarcoma is one of the most common soft tissue sarcomas. MR is the technique of choice to determine to local extension of malignant soft tissue tumors. To assess the clinical and MR imaging parameters associated with synovial sarcomas that aid in establishing their diagnosis. We review the clinical findings and images of 23 histologically confirmed synovial sarcomas that were studied by MR. Synovial sarcomas usually develop in young adults as soft tissue tumors, preferentially in the deep tissues of an extremity in close proximity to a joint. They are characterized as having a lobulated contour and septa, frequently infiltrating neighboring tissues at some point, and are heterogeneous. The presence of hemorrhage, as well as infiltration of the fascia in subcutaneous tumors, suggests the diagnosis of synovial sarcoma. The development of perilesional edema is not uncommon. Although, logically, the clinical and radiological features of synovial sarcomas can overlap with those of other soft tissue tumors, the findings described here are fairly characteristic of these lesions: thus, when present, they should serve to orient the diagnostic process. (Author) 16 refs