Spermatogenesis and testicular tumours in ageing dogs

Spermatogenesis was examined in testes from 74 dogs of various breeds without clinically detected testicular disease. A modified Johnsen score system was used to determine whether spermatogenesis deteriorates with ageing. The diameter of seminiferous tubules was measured in dogs without testicular disease to examine other possible effects of ageing on tubular performance. There appeared to be no relation between age and these variables. The influence of testicular tumours on spermatogenesis was also investigated in both affected and unaffected testes. The testes of 28 dogs with clinically palpable tumours and 21 dogs with clinically non-palpable tumours were investigated. In cases of unilateral occurrence of a tumour, impairment of spermatogenesis was observed only in the affected testis of dogs with clinically detected tumours. Bilateral occurrence of tumours, whether detected clinically or non-clinically, was associated with severe impairment of spermatogenesis. The prevalence of tumours increased during ageing. Eighty-six per cent of the clinically detected and 57% of the non-clinically detected tumours were found in old dogs. Multiple types of tumour and bilateral occurrence were very common. Seminomas and Leydig cell tumours were more frequent than Sertoli cell tumours. It was concluded that spermatogenesis per se did not decrease during ageing in dogs but the occurrence of testicular tumours increased with ageing and affected spermatogenesis significantly, as reflected by a lower Johnsen score.     

Malignant tumours in patients with HIV infection.

One of the most important though somewhat neglected aspects of research in HIV infection concerns the development, clinicopathological characteristics, and treatment of malignant tumours in infected patients. With the improved survival of patients with AIDS owing to the better prevention and treatment of infectious complications there may well be an increase in AIDS related malignancies. This paper reviews the epidemiology, pathology, and treatment of malignant tumours in patients with HIV.     

Aurora B expression in post-puberal testicular germ cell tumours

Aurora/Ipl1-related kinases are a conserved family of proteins that are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumours and have been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy, and genomic instability. Previous studies of our group have shown that Aurora B expression is restricted to specific germinal cells. In this study, we have evaluated by immunohistochemical analysis Aurora B expression in post-puberal testicular germ cell tumours (22 seminomas, 2 teratomas, 15 embryonal carcinomas, 5 mixed germinal tumours with a prominent yolk sac tumour component and 1 choriocarcinoma). The Aurora B protein expression was detected in all intratubular germ cell tumours, seminomas and embryonal carcinomas analysed but not in teratomas and yolk sac carcinomas. The immunohistochemical data were further confirmed by Western blot analysis. In addition, the kinase Aurora B was vigorously expressed in GC-1 cells line derived from murine spermatogonia. The block of Aurora B function induced by a pharmacological inhibitor significantly reduced the growth of GC-1 cells suggesting that Aurora B is a potential therapeutic target. J. Cell. Physiol. 221: 435–439, 2009. © 2009 Wiley-Liss, Inc.     

Loss of heterozygosity in hypotriploid cell cultures from testicular tumours

Summary We have established cell lines with a hypotriploid chromosome number from four testicular tumours. Each line had at least one Y chromosome and most of the informative centromere and enzyme markers were heterozygous implying that the tumours originated from germ cells before the first meiotic division. The small metacentric marker chromosome (i12p), specific for testicular tumours, was present in all tumour cell lines and up to three copies were found in some lines. Rearrangements of chromosome 1 and 11 were each found in three out of four tumours. The rearrangements of chromosome 1 all resulted in duplication of 1q and deletion of short-arm material from the same chromosome giving loss of heterozygosity for enzyme markers on 1p. Loss of satellite material from chromosome 13 and the centromere region of chromosome 9 were found in single cases. This study shows that even where the chromosome number of tumour cells is near triploid, regions of the genome can be deleted. The chromosomes most frequently involved in rearrangements, 1, 11, and 12 all contain sites of ras oncogenes and it is suggested that loss of normal alleles could result in homozygosity for mutant oncogenes which may play a part in tumour progression.     

Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours

Metastatic cancer in adults usually has a fatal outcome. In contrast, advanced testicular germ cell tumours are cured in over 80% of patients using cisplatin-based combination chemotherapy [1]. An understanding of why these cells are sensitive to chemotherapeutic drugs is likely to have implications for the treatment of other types of cancer. Earlier measurements indicate that testis tumour cells are hypersensitive to cisplatin and have a low capacity to remove cisplatin-induced DNA damage from the genome [2] [3]. We have investigated the nucleotide excision repair (NER) capacity of extracts from the well-defined 833K and GCT27 human testis tumour cell lines. Both had a reduced ability to carry out the incision steps of NER in comparison with extracts from known repair-proficient cells. Immunoblotting revealed that the testis tumour cells had normal amounts of most NER proteins, but low levels of the xeroderma pigmentosum group A protein (XPA) and the ERCC1-XPF endonuclease complex. Addition of XPA specifically conferred full NER capacity on the testis tumour extracts. These results show that a low XPA level in the testis tumour cell lines is sufficient to explain their poor ability to remove cisplatin adducts from DNA and might be a major reason for the high cisplatin sensitivity of testis tumours. Targeted inhibition of XPA could sensitise other types of cells and tumours to cisplatin and broaden the usefulness of this chemotherapeutic agent.     

Expression of histone deacetylases 1, 2 and 3 in histological subtypes of testicular germ cell tumours

In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in testicular germ cell tumours (GCT) and to analyse differences between the histological subtypes of testicular GCT. 325 testicular GCT were included in a tissue microarray with each histological subtype of the tumour being separately represented on this array. Expression of class I HDAC isoforms 1, 2 and 3 was assessed by immunohistochemistry. While HDAC2 and 3 were highly expressed in all histological subtypes of GCT, HDAC1 was almost consistently expressed at lower levels. We observed significant differences in the expression of the respective HDACs between seminoma and non-seminoma GCT tissue components. Interestingly, choriocarcinomas showed generally high expression values for all three class I HDAC isoforms. Relevant correlations with clinicopathological parameters could not be demonstrated. Contrasting published findings on other tumour entities, no immediate practical diagnostic or prognostic value for HDAC1-3 in GCT could be inferred. However, the high expression levels might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies.     

Incidence of carcinoma in situ of germ cells in contralateral testis of men with testicular tumours.

Biopsy specimens from the contralateral testicle in 50 consecutive patients with germinal testicular cancer were examined for carcinoma in situ. Three out of 21 men with seminomas and one out of 29 with other types of germinal cancer (8%) had carcinoma in situ in the contralateral testicle without any clinical signs. One of these men developed early invasive germ-cell cancer 46 months after carcinoma in situ was first diagnosed. The others have been followed up for less than a year without signs of tumour growth. If these results are confirmed routine biopsy of the contralateral testicle in patients with germinal cancer may be indicated.