Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two daughter cells. A model for the generation of trisomies by such asymmetrical cell division accurately predicted several features of clones having extra chromosomes in vivo, including the ratio between trisomies and tetrasomies and the observation that different trisomies found in the same tumor occupy identical proportions of cells and colocalize in tumor tissue. Our findings provide an experimentally validated model explaining how multiple trisomies can occur in tumor cells that still maintain accurate sister chromatid separation at metaphase-anaphase transition and thereby physiologically satisfy the SAC.
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PMID:Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis. 2105 55

A significant number of patients with germline mutations in the Wilms' tumour 1 (WT1) gene, a transcriptional factor essential for early renal and gonadal development, display cryptorchidism or non-scrotal testis position. We show here that WT1 is expressed during development in the mouse gubernacular ligament connecting the testis to the abdominal wall. Conditional inactivation of Wt1 in the gubernaculum (GU-WT1KO animals) resulted in abnormal differentiation of the gubernacula during development and, in about 40% of adult males, unilateral, always left-sided, cryptorchidism. At birth the right testis was positioned above the processus vaginalis and eventually moved into the developing scrotal pouch. In affected mutants the left testis was displaced from the normal position and the left processus vaginalis failed to form. The analysis of testicular descent at different stages of postnatal development suggests that unilateral cryptorchidism might be caused by asymmetry in the positions of the abdominal organs providing a higher degree of mobility for the left testis. Spermatogenesis in GU-WT1KO animals was blocked in cryptorchid testes located in a high pararenal position, but was maintained in testes located in a low abdominal position. Conditional inactivation of both Wt1 and androgen receptor (Ar) genes in the gubernaculum led to a bilateral asymmetrical cryptorchidism in all mutant males, with the left testis again located higher than the right one. The malformations induced by WT1 and AR deficiency in the gubernaculum and processus vaginalis, in combination with mechanical constraints on testis descent, determine the final position of the testes. In summary, our data indicate that WT1 is directly involved in gubernaculum differentiation. Taken together, the results of the study underline the complex nature of testicular descent, with an involvement in this process of several genetic factors and developmental events.
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PMID:Left-sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis. 2328 85

We demonstrate a 4-year-old girl who presented with progressive, asymmetrical, firm abdominal distention and was diagnosed with synchronous Wilms' tumor and left para-aortic ganglioneuroma (GN). Although synchronous tumors in the pediatric population are commonly associated with malignancy-predisposing syndromes, the patient in question was found to be otherwise healthy and had no clinical evidence nor family history of a syndrome. This case is the second one in the literature diagnosed with synchronous presentation of Wilms' tumor and GN in a previously healthy child. In addition, a GN foci presumed to be a previous metastasis of a neurogenic tumor that subsequently matured to GN was depicted within a left para-aortic lymph node. We aimed to emphasize an extremely rare synchronous occurrence of these embryonal tumors, increase the awareness of physicians, and discuss the radiologic differential diagnosis and management.
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PMID:Simultaneous Presentation of Wilms' Tumor and Contralateral Ganglioneuroma in a Child: Case Report and Literature Review. 2933 35