Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

<b>Background</b>: 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.<BR/> <b>Methods</b>: 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.<BR/> <b>Results</b>: 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.<BR/> <b>Conclusions</b>: 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

Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: Confirmation of OCT3/4 specificity for germ cell tumours

Background: OCT3/4 (POU5F1) is an established diagnostic immunohistochemical marker for specific histological variants of human malignant germ cell tumours (GCTs), including the seminomatous types and the stem cell component of non-seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of pluripotency and the self-renewal of normal embryonic stem-and germ cells. Detection of expression of this transcription factor is complicated by the existence of multiple pseudogenes and isoforms. Various claims have been made about OCT3/4 expression in non-GCTs, possibly related to using nonspecific detection methods. False-positive findings undermine the applicability of OCT3/4 as a specific diagnostic tool in a clinical setting. In addition, false-positive findings could result in misinterpretation of pluripotency regulation in solid somatic cancers and their stem cells. Of the three identified isoforms-OCT4A, OCT4B and OCT4B1-only OCT4A proved to regulate pluripotency. Up until now, no convincing nuclear OCT4A protein expression has been shown in somatic cancers or tissues. Methods: This study investigates expression of the various OCT3/4 isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ cell) cancers, including representative cell lines and xenografts. Results: Using specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in undifferentiated GCTs. The OCT4B variant shows no difference in expression between GCTs (either differentiated or undifferentiated) and somatic cancers. In spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no OCT3/4

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP-RTSG 2016 protocol

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours-the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in childre

20 years of semen cryopreservation: feasibility and referral behavior

Treatment of cancer can affect spermatogenesis resulting in infertility. Semen cryopreservation prior to gonadotoxic treatment can be offered to secure future fertility in male cancer patients. During 20\xc2\xa0years 1,018 patients referred for semen cryopreservation in fertile age with Hodgkin disease (n\xe2\x80\xaf= 194), non-Hodgkin lymphoma (n\xe2\x80\xaf= 110), leukemia (n\xe2\x80\xaf= 126) and testicular germ cell tumor (n\xe2\x80\xaf= 588) were followed up. Incidence of these cancers and incidence of regional semen cryopreservation was used to calculate a\xc2\xa0referral rate. Semen cryopreservation was successful in 856 of 1,018 patients (84.1%). Median yearly referral rate was respectively 17% and 31% in hematological malignancies and testicular germ cell tumor. Regional referral rate in hematological malignancies dropped dramatically after 2005 to a\xc2\xa0minimum of 2% in 2009. The incidence of TGCT and referral rate for fertility preservation in these patients increased over time. Our result show that referral of for semen cryopreservation in patients with hematological malignancies in fertile age is suboptimal.Behandeling van kanker kan de spermatogenese aantasten, met infertiliteit tot gevolg. Semencryopreservatie voorafgaand \naan gonadotoxische behandeling kan de vruchtbaarheid van mannelijke kankerpati\xc3\xabnten veiligstellen. Gedurende 20 jaar \nzijn 1.018 pati\xc3\xabnten tussen 12 en 50 jaar oud, met Hodgkin-lymfoom (n= 194), non-Hodgkin lymfoom (n=110), leukemie \n(n= 126) of testiculaire kiemceltumoren (n= 588) verwezen naar \xc3\xa9\xc3\xa9n centrum voor semencryopreservatie. De incidentie \nvan deze kankertypen in het adherentiegebied en de incidentie van regionale semencryopreservatie werd gebruikt om een \nverwijsratio te berekenen. Semencryopreservatie was succesvol bij 856 van de 1.018 pati\xc3\xabnten (84,1%). De mediane \njaarlijkse verwijsratio bij hematologische maligniteiten en testiculaire stamceltumoren was respectievelijk 17% en 31%. \nDe regionale verwijzing bij hematologische maligniteiten daalde na 2005 fors, tot een minimum van 2% in 2009, terwijl \ndeze toenam bij testiculaire kiemceltumoren. Onze resultaten tonen aan dat verwijzing voor semencryopreservatie bij \npati\xc3\xabnten met een hematologische maligniteit in de fertiele leeftijd suboptimaal is