Quality of life in patients after radical orchiectomy

Testikulární nádory představují sice jen 1% všech maligních onemocnění, které postihují mužskou populaci, ale ve věkové skupině 20-44 let dosahuje jejich podíl 23%. Představují nejčastěji se vyskytující nádor bílé populace v této věkové skupině. Orchiektomie má zásadní význam jak v diagnostice tak v léčbě testikulárních nádorů. Je téměř nemožné zkoumat pacienty z pouhého hlediska důsledků radikální orchiektomie, jelikož jen malá skupina pacientů prodělá pouze tento operační zákrok. Téměř nedílnou součástí následné terapie je adjuvantní radioterapie a chemoterapie (které značně ovlivňují pacienta). Dále samotné nádorové onemocnění působí negativně na organizmus. Z těchto důvodů nelze na kvalitu života pacientů nahlížet pouze z hlediska radikální orchiektomie, ale musíme se na kvalitu života pacientů po orchiektomii dívat z komplexního pohledu testikulárních nádorů. Musíme zvážit důsledky i ostatních terapeutických modalit. Skupina pacientů, kteří přežili testikulární nádorové onemocnění (v anglickém jazyce-testicular cancer survivors-TCS) představují zajímavou skupinu ke sledovaní kvality života z několika důvodů. Léčba testikulárních nádorů je v 90% úspěšná a následně mají TCS stejnou predikovanou dobu dožití jako stejně staří muži ze zdravé populace. TCS mají také určitá specifika v otázkách fertility a...Although testicular tumors represent only 1% of all malignancies that affect the male population , but in the age group of 20-44 years reaching their share of 23%. They represent the most frequent tumor of the white population in that age group. Orchiectomy is critical both in diagnosis and in treatment testicular tumors . It is almost impossible to examine the patient merely from the point of view consequences of radical orchiectomy , since only a small group of patients will experience only this surgery . Almost an integral part of the subsequent therapy is adjuvant radiotherapy and chemotherapy ( which significantly affect patient). Furthermore itself cancer has a negative effect on the organism. For these reasons, the quality of life of patients seen only in terms of radical orchiectomy , but We have the quality of life of patients after orchiectomy look of a comprehensive Looking testicular tumors . We must consider the consequences of other therapeutic modalities. The group of patients who survived testicular cancer ( in English - testicular - cancer survivors TCS) are an interesting group to monitor the quality of life for several reasons. Treatment of testicular tumors in 90 % successful and consequently have the same TCS predicted life expectancy as well old men from the healthy population. TCS...Urologická klinikaDepartment of UrologyThird Faculty of Medicine3. lékařská fakult

Úloha evolučně konzervovaných proteinů BIR-1/Survivin a SKP-1 v regulaci genové exprese

Souhrn SKIP a BIR/Survivin jsou evolučně zachovalé proteiny. SKIP je známý transkripční a sestřihový kofaktor a BIR-1/Survivin reguluje bunečné dělení, genovou expresi a vývoj. Inaktivace SKP-1 a BIR-1 indukuje podobné vývojové fenotypy. K odhalení možných interakcí SKP-1 a BIR-1 jsme použili kvasinkový dvojhybridní systém a knihovnu kompletní mRNA C. elegans. Tyto experimenty identifikovaly částečně se překrývající kategorie proteinů jako interaktory proteinů SKP-1 a BIR-1. Identifikované interagující proteiny zahrnovaly ribozomální proteiny, transkripční faktory, translační faktory, cytoskeletální a motorové proteiny. Tyto výsledky naznačují jejich možnou účast v mnohočetných proteinových komplexech. Pomocí krátkodobé nadměrné exprese BIR-1 jsme sledovali účinek BIR-1 na proteom C. elegans v larválním stádiu L1. To způsobilo dramatickou změnu v celém proteomu což naznačuje, že BIR-1 má schopnost změnit chromatografický profil mnohočetných cílových proteinů včetně těch, které jsme již dříve identifikovali jako interagující proteiny v experimentach s kvasinkovým dvouhybridním systému. Výsledky jsme následně potvrdili pro RPS-3, RPL-5, myosin (non-muscle myosin) a TAC-1 (transkripční kofaktor a protein asociovaný s centrosomy). Tyto výsledky naznačují, že SKP-1 a BIR-1 jsou multifunkční proteiny, které jsou...SKIP and BIR/Survivin are evolutionarily conserved proteins. SKIP is a known transcription and splicing cofactor while BIR-1/Survivin regulates cell division, gene expression and development. Loss of function of C. elegans SKIP (SKP-1) and BIR-1 induces overlapping developmental phenotypes. In order to uncover the possible interactions of SKP-1 and BIR-1 on the protein level, we screened the complete C. elegans mRNA library using the yeast two-hybrid system. These experiments identified partially overlapping categories of proteins as SKP-1 and BIR-1 interactors. The interacting proteins included ribosomal proteins, transcription factors, translation factors and cytoskeletal and motor proteins suggesting involvement of the two studied proteins in multiple protein complexes. To visualize the effect of BIR-1 on the proteome of C. elegans we induced a short time pulse BIR-1 overexpression in synchronized L1 larvae. This led to a dramatic alteration of the whole proteome pattern indicating that BIR-1 alone has the capacity to alter the chromatographic profile of many target proteins including proteins found to be interactors in yeast two hybrid screens. The results were validated for ribosomal proteins RPS-3, RPL-5, non-muscle myosin and TAC-1, a transcription cofactor and a centrosome associated...Ústav buněčné biologie a patologie 1. LF UKInstitute of Cell Biology and Pathology First Faculty of Medicine Charles UniversityFirst Faculty of Medicine1. lékařská fakult

Ontogenetic Profile of the Expression of Thyroid Hormone Receptors in Rat and Human Corpora Cavernosa of the Penis

Introduction. In the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones on the penis. Aim. To study the spatiotemporal distribution of mRNA for the thyroid hormone nuclear receptors (TR) alpha 1, alpha 2 and beta in the penis and smooth muscle cells (SMCs) of the corpora cavernosa of rats and humans during development. Methods. We used several molecular biology techniques to study the TR expression in whole tissues or primary cultures from human and rodent penile tissues of different ages. Main Outcome Measure. We measured our data by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) amplification, Northern blot and immunohistochemistry. Results. We found that TR alpha 1 and TR alpha 2 are both expressed in the penis and in SMCs during ontogenesis without development-dependent changes. However, in the rodent model, TR beta shows an increase from 3 to 6 days post natum (dpn) to 20 dpn, remaining high in adulthood. The same expression profile was observed in humans. While the expression of TR beta is strictly regulated by development, TR alpha 1 is the principal isoform present in corpora cavernosa, suggesting its importance in SMC function. These results have been confirmed by immunohistochemistry localization in SMCs and endothelial cells of the corpora cavernosa. Conclusions. The presence of TRs in the penis provides the biological basis for the direct action of thyroid hormones on this organ. Given this evidence, physicians would be advised to investigate sexual function in men with thyroid disorders. Carosa E, Di Sante S, Rossi S, Castri A, D'Adamo F, Gravina GL, Ronchi P, Kostrouch Z, Dolci S, Lenzi A, and Jannini EA. Ontogenetic profile of the expression of thyroid hormone receptors in rat and human corpora cavernosa of the penis. J Sex Med 2010;7:1381-1390

Hormonal signaling in cnidarians : do we understand the pathways well enough to know whether they are being disrupted?

Author Posting. © The Author, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 5-13, doi:10.1007/s10646-006-0121-1.Cnidarians occupy a key evolutionary position as basal metazoans and are ecologically important as predators, prey and structure-builders. Bioregulatory molecules (e.g., amines, peptides and steroids) have been identified in cnidarians, but cnidarian signaling pathways remain poorly characterized. Cnidarians, especially hydras, are regularly used in toxicity testing, but few studies have used cnidarians in explicit testing for signal disruption. Sublethal endpoints developed in cnidarians include budding, regeneration, gametogenesis, mucus production and larval metamorphosis. Cnidarian genomic databases, microarrays and other molecular tools are increasingly facilitating mechanistic investigation of signaling pathways and signal disruption. Elucidation of cnidarian signaling processes in a comparative context can provide insight into the evolution and diversification of metazoan bioregulation. Characterizing signaling and signal disruption in cnidarians may also provide unique opportunities for evaluating risk to valuable marine resources, such as coral reefs

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

The role of evolutionarily conserved proteins BIR-1/Survivin and SKP-1 in the regulation of gene expression

SKIP and BIR/Survivin are evolutionarily conserved proteins. SKIP is a known transcription and splicing cofactor while BIR-1/Survivin regulates cell division, gene expression and development. Loss of function of C. elegans SKIP (SKP-1) and BIR-1 induces overlapping developmental phenotypes. In order to uncover the possible interactions of SKP-1 and BIR-1 on the protein level, we screened the complete C. elegans mRNA library using the yeast two-hybrid system. These experiments identified partially overlapping categories of proteins as SKP-1 and BIR-1 interactors. The interacting proteins included ribosomal proteins, transcription factors, translation factors and cytoskeletal and motor proteins suggesting involvement of the two studied proteins in multiple protein complexes. To visualize the effect of BIR-1 on the proteome of C. elegans we induced a short time pulse BIR-1 overexpression in synchronized L1 larvae. This led to a dramatic alteration of the whole proteome pattern indicating that BIR-1 alone has the capacity to alter the chromatographic profile of many target proteins including proteins found to be interactors in yeast two hybrid screens. The results were validated for ribosomal proteins RPS-3, RPL-5, non-muscle myosin and TAC-1, a transcription cofactor and a centrosome associated..

Quality of life in patients after radical orchiectomy

Although testicular tumors represent only 1% of all malignancies that affect the male population , but in the age group of 20-44 years reaching their share of 23%. They represent the most frequent tumor of the white population in that age group. Orchiectomy is critical both in diagnosis and in treatment testicular tumors . It is almost impossible to examine the patient merely from the point of view consequences of radical orchiectomy , since only a small group of patients will experience only this surgery . Almost an integral part of the subsequent therapy is adjuvant radiotherapy and chemotherapy ( which significantly affect patient). Furthermore itself cancer has a negative effect on the organism. For these reasons, the quality of life of patients seen only in terms of radical orchiectomy , but We have the quality of life of patients after orchiectomy look of a comprehensive Looking testicular tumors . We must consider the consequences of other therapeutic modalities. The group of patients who survived testicular cancer ( in English - testicular - cancer survivors TCS) are an interesting group to monitor the quality of life for several reasons. Treatment of testicular tumors in 90 % successful and consequently have the same TCS predicted life expectancy as well old men from the healthy population. TCS..