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1.
Contemp Oncol (Pozn) ; 27(4): 284-291, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38405214

RESUMO

Introduction: Assessment of renal tumour masses is based on conventional imaging studies (computer tomography or magnetic resonance), which does not allow characterisation of the histopathological type. Moreover, the prediction of prognosis in localised and metastatic renal cell carcinoma requires improvement as well. Analysis of circulating free DNA (cfDNA) in blood is one of the variants of liquid biopsy that may improve diagnostics and prognosis issues of patients with renal tumour masses suspected to be renal cell carcinoma. The aim of the study was to assess the diagnostic and prognostic role of preoperative cfDNA concentration in the plasma samples of clear cell renal cell carcinoma (ccRCC) patients. Material and methods: The preoperative plasma cfDNA concentration was assessed in ccRCC patients (n = 46) and healthy individuals (control group) (n = 17). The circulating free DNA concentration was reflected by the 90 bp DNA fragments determined by real-time polymerase chain reaction. Results: The median cfDNA concentration was significantly higher in ccRCC patients (n = 46) compared to the control g roup (n = 17) (2588 ±2554 copies/ml vs. 960 ±490 copies/ml, p < 0.01). In multivariate analysis, the preoperative plasma cfDNA concentration was the significant factor increasing the probability of ccRCC detection (OR: 1.003; 95% CI: 1.001-1.005). The median cfDNA concentration depended on the stage of ccRCC; it was higher in metastatic ccRCC patients (n = 11) compared to non-metastatic ccRCC patients (n = 35) (3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml, p < 0.03). Kaplan-Meier survival analysis demon-strated that patients with high cfDNA values (above 2913 copies/ml) had significantly worse cancer-specific survival (HR: 4.5; 95% CI: 1.3-16.9, log-rank Mantel-Cox test p = 0.015). Conclusions: Preoperative plasma cfDNA concentration has diagnostic and prognostic potential in ccRCC pa-tients.

2.
Mol Carcinog ; 56(11): 2414-2423, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28543713

RESUMO

The involvement of Grainyhead-like (GRHL) transcription factors in various cancers is well documented. However, little is known about their role in clear cell renal cell carcinoma (ccRCC). We discovered that the expression of two of these factors-GRHL1 and GRHL2-are downregulated in ccRCC samples, and their expression is correlated with the expression of VHL gene. This suggests a functional link between the GRHL transcription factors and one of the best known tumor suppressors. Although the GRHL genes are not mutated in ccRCC, some of the single nucleotide polymorphisms in these genes may indicate an increased risk of ccRCC development and/or may allow to assess patients' prognoses and predict their responses to various forms of therapy. Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of ccRCC. These changes support the potential role for GRHL2 as a suppressor of ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Rim/patologia , Fatores de Transcrição/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Feminino , Inativação Gênica , Humanos , Rim/metabolismo , Neoplasias Renais/patologia , Masculino , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética
3.
BMC Cancer ; 15: 518, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26169495

RESUMO

BACKGROUND: VHL inactivation is the most established molecular characteristic of clear cell renal cell carcinoma (ccRCC), with only a few additional genes implicated in development of this kidney tumor. In recently published ccRCC gene expression meta-analysis study we identified a number of deregulated genes with limited information available concerning their biological role, represented by gene transcripts belonging to transmembrane proteins family (TMEMs). TMEMs are predicted to be components of cellular membranes, such as mitochondrial membranes, ER, lysosomes and Golgi apparatus. Interestingly, the function of majority of TMEMs remains unclear. Here, we analyzed expression of ten TMEM genes in the context of ccRCC progression and development, and characterized these proteins bioinformatically. METHODS: The expression of ten TMEMs (RTP3, SLC35G2, TMEM30B, TMEM45A, TMEM45B, TMEM61, TMEM72, TMEM116, TMEM207 and TMEM213) was measured by qPCR. T-test, Pearson correlation, univariate and multivariate logistic and Cox regression were used in statistical analysis. The topology of studied proteins was predicted with Metaserver, together with PSORTII, Pfam and Localizome tools. RESULTS: We observed significant deregulation of expression of 10 analyzed TMEMs in ccRCC tumors. Cluster analysis of expression data suggested the down-regulation of all tested TMEMs to be a descriptor of the most advanced tumors. Logistic and Cox regression potentially linked TMEM expression to clinical parameters such as: metastasis, Fuhrman grade and overall survival. Topology predictions classified majority of analyzed TMEMs as type 3 and type 1 transmembrane proteins, with predicted localization mainly in ER. CONCLUSIONS: The massive down-regulation of expression of TMEM family members suggests their importance in the pathogenesis of ccRCC and the bioinformatic analysis of TMEM topology implies a significant involvement of ER proteins in ccRCC pathology.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas de Membrana/genética , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Carcinoma de Células Renais/patologia , Análise por Conglomerados , Biologia Computacional , Progressão da Doença , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Família Multigênica , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Transporte Proteico , Carga Tumoral
4.
Contemp Oncol (Pozn) ; 19(1): 1-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26199563

RESUMO

In recent years, significant development in the treatment of prostate cancer has taken place. One of the most documented methods of treatment in patients characterised by a high risk of progression is a combination of radiotherapy (RT) with long-term hormone therapy (HT). In this group of patients, neither RT alone nor HT alone allows satisfactory outcomes to be achieved, and therefore as monotherapy they are not recommended as optimal methods of treatment. In this review, we summarise arguments for combining radiotherapy with hormonal therapy in high-risk prostate cancer, with an emphasis on the results of phase III trials.

5.
Tumour Biol ; 35(3): 2607-17, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24318988

RESUMO

In this paper, we provide a comprehensive summary of available clear cell renal cell carcinoma (ccRCC) microarray data in the form of meta-analysis of genes differentially regulated in tumors as compared to healthy tissue, using effect size to measure the strength of a relationship between the disease and gene expression. We identified 725 differentially regulated genes, with a number of interesting targets, such as TMEM213, SMIM5, or ATPases: ATP6V0A4 and ATP6V1G3, of which limited or no information is available in terms of their function in ccRCC pathology. Downregulated genes tended to represent pathways related to tissue remodeling, blood clotting, vasodilation, and energy metabolism, while upregulated genes were classified into pathways generally deregulated in cancers: immune system response, inflammatory response, angiogenesis, and apoptosis. One hundred fifteen deregulated genes were included in network analysis, with EGLN3, AP-2, NR3C1, HIF1A, and EPAS1 (gene encoding HIF2-α) as points of functional convergence, but, interestingly, 610 genes failed to join previously identified molecular networks. Furthermore, we validated the expression of 14 top deregulated genes in independent sample set of 32 ccRCC tumors by qPCR and tested if it could serve as a marker of disease progression. We found a correlation of high fucosyltransferase 11 (FUT11) expression with non-symptomatic course of the disease, which suggests that FUT11's expression might be potentially used as a biomarker of disease progression.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/genética , Fucosiltransferases/genética , Neoplasias Renais/genética , Transcriptoma , Biomarcadores Tumorais/genética , Progressão da Doença , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase
6.
Contemp Oncol (Pozn) ; 18(2): 85-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24966789

RESUMO

Metastatic prostate cancer, which shows progression despite castration testosterone levels, was previously defined as hormone-refractory. This definition has recently been changed to the one presently used - castrate-resistant prostate cancer. Numerous fundamental studies have provided evidence that the development of hormone-refractory prostate cancer is constantly dependent on the concentration of androgens. The aim of the metastatic castrate-resistant prostate cancer (mCRPC) treatment is currently to obtain the lowest possible androgen concentration. The effectiveness of such management has been proven by the results of clinical studies on the latest hormonal and chemotherapeutic medications. In the last two decades, new effective chemotherapeutics have become available on the market: abiraterone, enzalutamide, docetaxel, cabazitaxel, zoldronic acid, denosumab and alpharadin They significantly contribute to extending patients' survival and to improving their quality of life. Therefore, the question arises whether using luteinizing hormone-releasing hormone (LHRH) analogues is still a necessary element of the therapy. A detailed analysis of study regimens involving the above-mentioned medications and of available publications supports the view that LHRH analogues are the basic strategy in the treatment of patients with mCRPC. All clinical trials evaluating new therapies still followed the principle of obtaining castration testosterone levels as a result of using LHRH analogues simultaneously with the new medications.

8.
Rep Pract Oncol Radiother ; 18(5): 304-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24416568

RESUMO

BACKGROUND: Radical nephrectomy is the gold standard for treatment of renal cell carcinoma (RCC), but even for localized disease the survival rates are still unsatisfactory. Identification of prognostic factorsl is the basis for future treatment strategies for an individual patient. AIM: The aim of our study was to assess the usefulness of the concentration of IL-6 and CRP as prognostic factors in patients after nephrectomy due to localized RCC. MATERIALS AND METHODS: Our prospective study included 89 patients (55 men and 34 women) who had been surgically treated for RCC. The examined group included patients with localized advanced disease (from T1 to T3) with no metastases in lymph nodes (N0), and with no distant metastases (M0). All patients had blood samples drawn three times during the study (one day before surgery, six days after surgery and 6 months after surgery) to evaluate the concentration of CRP and IL-6. In each patient RCC of the kidney was removed during radical nephrectomy. Statistical analysis was conducted using statistica v.7.0. RESULTS: Statistically significant relationships were found between the concentration of CRP before the operation and OS (p = 0.0001). CRP concentration at baseline was statistically significantly correlated with CSS (p = 0.0004). The level of IL-6 assessed before the surgery was significantly correlated with survival times such as OS (p = 0.0096) and CSS (p = 0.0002). The concentration of IL-6 and CRP measured 6 days after surgery and 6 months after surgery were not statistically significantly correlated with survival times. CONCLUSIONS: Results of our study showed that elevated levels of IL-6 and CRP in peripheral blood before surgery of RCC were correlated with worse OS and CSS.

9.
Am J Cancer Res ; 13(5): 1863-1883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293153

RESUMO

Due to their involvement in the development of various cancers Transmembrane Proteins (TMEMs) are the focus of many recent studies. Previously we reported TMEM de-regulation in clear cell Renal Cell Carcinoma (ccRCC) with TMEM213, 207, 116, 72 and 30B being among the most downregulated on mRNA level. TMEM down-regulation was also more pronounced in advanced ccRCC tumors and was potentially linked to clinical parameters such as: metastasis (TMEM72 and 116), Fuhrman grade (TMEM30B) and overall survival (TMEM30B). To further investigate these findings, first, we set off to prove experimentally that selected TMEMs are indeed membrane-bound as predicted in silico, we verified the presence of signaling peptides on their N-termini, orientation of TMEMs within the membrane and validated their predicted cellular localization. To investigate the potential role of selected TMEMs in cellular processes overexpression studies in HEK293 and HK-2 cell lines were carried out. Additionally, we tested TMEM isoform expression in ccRCC tumors, identified mutations in TMEM genes and examined chromosomal aberrations in their loci. We confirmed the membrane-bound status of all selected TMEMs, assigned TMEM213, and 207 to early endosomes, TMEM72 to early endosomes and plasma membrane, TMEM116 and 30B to the endoplasmic reticulum. The N-terminus of TMEM213 was found to be exposed to the cytoplasm, the C-terminus of TMEM207, 116 and 72 were directed toward the cytoplasm, and both termini of TMEM30B faced the cytoplasm. Interestingly, TMEM mutations and chromosomal aberrations were infrequent in ccRCC tumors, yet we identified potentially damaging mutations in TMEM213 and TMEM30B and found deletions in the TMEM30B locus in nearly 30% of the tumors. Overexpression studies suggested selected TMEMs may take part in carcinogenesis processes such as cell adhesion, regulation of epithelial cell proliferation, and regulation of adaptive immune response, which could indicate a link to the development and progression of ccRCC.

10.
Ginekol Pol ; 83(1): 67-70, 2012 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-22384643

RESUMO

Penile cancer occurs quite seldom, mostly in men around 60 years of age. However penile squamous cell carcinoma is also observed in younger men. Etiology remains unclear but we can recognize some risk factors such as poor hygiene for example. The authors report a case of a patient who refused treatment in early stages of the disease and was treated only after disease progression. Applied surgical treatment, unfortunately proved to be insufficient and the patient was transferred to complete therapy at the oncology department. This case inspired us to recall the basic diagnostic and therapeutic methods used at the time of diagnosis of the penile tumor


Assuntos
Amputação Cirúrgica , Carcinoma de Células Escamosas/cirurgia , Neoplasias Penianas/cirurgia , Pênis/cirurgia , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Penianas/patologia , Resultado do Tratamento
11.
Cancers (Basel) ; 13(3)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535553

RESUMO

Renal cell carcinoma (RCC) is one of the most common cancers worldwide with a nearly non-symptomatic course until the advanced stages of the disease. RCC can be distinguished into three subtypes: papillary (pRCC), chromophobe (chRCC) and clear cell renal cell carcinoma (ccRCC) representing up to 75% of all RCC cases. Detection and RCC monitoring tools are limited to standard imaging techniques, in combination with non-RCC specific morphological and biochemical read-outs. RCC subtype identification relays mainly on results of pathological examination of tumor slides. Molecular, clinically applicable and ideally non-invasive tools aiding RCC management are still non-existent, although molecular characterization of RCC is relatively advanced. Hence, many research efforts concentrate on the identification of molecular markers that will assist with RCC sub-classification and monitoring. Due to stability and tissue-specificity miRNAs are promising candidates for such biomarkers. Here, we performed a meta-analysis study, utilized seven NGS and seven microarray RCC studies in order to identify subtype-specific expression of miRNAs. We concentrated on potentially oncocytoma-specific miRNAs (miRNA-424-5p, miRNA-146b-5p, miRNA-183-5p, miRNA-218-5p), pRCC-specific (miRNA-127-3p, miRNA-139-5p) and ccRCC-specific miRNAs (miRNA-200c-3p, miRNA-362-5p, miRNA-363-3p and miRNA-204-5p, 21-5p, miRNA-224-5p, miRNA-155-5p, miRNA-210-3p) and validated their expression in an independent sample set. Additionally, we found ccRCC-specific miRNAs to be differentially expressed in ccRCC tumor according to Fuhrman grades and identified alterations in their isoform composition in tumor tissue. Our results revealed that changes in the expression of selected miRNA might be potentially utilized as a tool aiding ccRCC subclass discrimination and we propose a miRNA panel aiding RCC subtype distinction.

12.
J Biomed Biotechnol ; 2009: 625394, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19859572

RESUMO

AIM: To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. MATERIAL AND METHODS: Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. RESULTS: The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. CONCLUSIONS: The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Terapia Neoadjuvante , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Idoso , Antineoplásicos Hormonais/uso terapêutico , Flutamida/uso terapêutico , Gosserrelina/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/mortalidade , Polônia/epidemiologia , Estudos Prospectivos , Neoplasias da Próstata/mortalidade , Radioterapia Conformacional , Fatores de Risco
13.
Urol Int ; 83(4): 471-5, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19996657

RESUMO

PURPOSE: Ghrelin and its functional receptor are highly expressed in prostate cancer (PC) and ghrelin may activate proliferation of PC cell lines. This study was therefore designed to characterize the association between serum acylated and total ghrelin, and obestatin levels in patients with benign prostate hyperplasia (BPH) and PC. METHODS: Blood serum concentrations of active and total ghrelin and obestatin were estimated by EIA methods. RESULTS: Serum level of active ghrelin in PC was significantly higher compared to control and BPH groups. On the other hand, concentrations of total ghrelin and of obestatin did not differ between studied groups of patients. In the control group the ratio of active to total ghrelin concentrations amounted to 0.16, and it was similar in BPH (0.14), while it was notably elevated in PC (0.42). Also the ratio of active ghrelin to obestatin concentrations was higher in the group with PC than in the control and BPH groups. In all studied groups, the ratio of total circulating ghrelin to obestatin was similar. CONCLUSIONS: Obtained results suggest the link between elevated blood active ghrelin and PC, and we cannot exclude that elevated circulating active ghrelin may affect growth of malignant prostatic tissues.


Assuntos
Grelina/sangue , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
14.
Eur J Cancer Prev ; 17(1): 62-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18090912

RESUMO

Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed - both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9-27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5-12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1-11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9-51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.


Assuntos
Proteína BRCA1/genética , Mutação , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Efeito Fundador , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Linhagem , Polônia/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fatores de Risco
15.
Przegl Lek ; 64(10): 871-3, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-18409329

RESUMO

The association between tobacco intake, in different forms (smoking and smokeless tobacco), and frequency of urogenital disorders was analyzed. Based on wide bibliography the authors have concentrated especially on tobacco related urogenital neoplasm. Some types of neoplasm, like bladder carcinoma, were significantly tobacco dependent, others were not so clearly documented.


Assuntos
Fumar/efeitos adversos , Tabaco sem Fumaça/efeitos adversos , Neoplasias Urogenitais/etiologia , Humanos , Neoplasias Renais/etiologia , Masculino , Neoplasias Penianas/etiologia , Neoplasias da Próstata/etiologia , Neoplasias da Bexiga Urinária/etiologia
16.
Oncotarget ; 8(17): 28558-28574, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28212566

RESUMO

BACKGROUND: Mutation analysis and cytogenetic testing in clear cell renal cell carcinoma (ccRCC) is not yet implemented in a routine diagnostics of ccRCC. MATERIAL AND METHODS: We characterized the chromosomal alterations in 83 ccRCC tumors from Polish patients using whole genome SNP genotyping assay. Moreover, the utility of next generation sequencing of cell free DNA (cfDNA) in patients plasma as a potential tool for non-invasive cytogenetic analysis was tested. Additionally, tumor specific somatic mutations in PBRM1, BAP1 and KDM5C were determined. RESULTS: We confirmed a correlation between deletions at 9p and higher tumor size, and deletion of chromosome 20 and the survival time. In Fuhrman grade 1, only aberrations of 3p and 8p deletion, gain of 5q and 13q and gains of chromosome 7 and 16 were present. The number of aberrations increased with Fuhrman grade, all chromosomes displayed cytogenetic changes in G3 and G4. ccRCC specific chromosome aberrations were observed in cfDNA, although discrepancies were found between cfDNA and tumor samples. In total 12 common and 94 rare variants were detected in PBRM1, BAP1 and KDM5C, with four potentially pathogenic variants. We observed markedly lower mutation load in PBRM1. CONCLUSIONS: Cytogenetic analysis of cfDNA may allow more accurate diagnosis of tumor aberrations and therefore the correlation between the chromosome aberrations in cfDNA and clinical outcome should be studied in larger cohorts. The functional studies on in BAP1, KDM5C, PBRM1 mutations in large, independent sample set would be necessary for the assessment of their prognostic and diagnostic potential.


Assuntos
Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Aberrações Cromossômicas , DNA Tumoral Circulante , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Proteínas de Ligação a DNA , Feminino , Histona Desmetilases/genética , Humanos , Biópsia Líquida , Masculino , Mutação , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Polônia/epidemiologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
17.
Int J Mol Med ; 18(4): 615-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16964413

RESUMO

Leptin is an adipose tissue-secreted hormone that acts via specific receptors (Ob-R), of which six isoforms are at present recognized (from Ob-Ra to Ob-Rf). Ob-Rb is the only isoform able to activate JAK-STAT and MAPK signaling cascades. A large body of evidence suggests that leptin and its receptors are involved in prostate physiology and pathophysiology in humans, but studies on the leptin system in the rat prostate are lacking. Reverse transcription-polymerase chain reaction showed the expression of mRNAs of leptin, Ob-Ra, Ob-Rb, Ob-Rc, Ob-Re and Ob-Rf in adult rat seminal vesicles and prostate (coagulating, dorsal, ventral and lateral lobes). Western blotting demonstrated the presence in these specimens of the Ob-Rb protein, and immunocytochemistry revealed that Ob-Rb was mainly located in their epithelial-cell component. Collectively, these findings strongly suggest that leptin and Ob-R may be involved in the autocrine-paracrine functional regulation of the epithelial cells of adult rat seminal vesicles and prostate.


Assuntos
Leptina/genética , Próstata/metabolismo , Receptores de Superfície Celular/genética , Glândulas Seminais/metabolismo , Animais , Western Blotting , Imuno-Histoquímica , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Superfície Celular/metabolismo , Receptores para Leptina , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Int J Mol Med ; 18(6): 1097-100, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17089013

RESUMO

We have recently demonstrated the expression of leptin and leptin receptor (Ob-R) isoforms a, b, c, e and f in the rat seminal vesicles and prostate. The aim of the present study was to provide a semiquantitative real-time PCR estimation of leptin/Ob-R isoform mRNA expression in the seminal vesicles and individual components of rat prostate, and to ascertain the in vitro effects of leptin on prostate acid phosphatase release. The highest expression of the leptin and Ob-R genes was in the seminal vesicles and lateral prostate lobe, respectively. Of the various isoforms, Ob-Rb displayed the highest and Ob-Re the lowest expression. Leptin (10(-8) and 10(-6) M) enhanced acid phosphate release from seminal vesicles, and (10(-6) M) decreased it from the coagulating lobe. Taken together, our findings support the contention that leptin may be involved in the autocrine-paracrine functional regulation of rat seminal vesicles and prostate. The physiological relevance of the marked heterogeneity of the different prostate lobes in both their leptin/Ob-R expression and functional response to leptin remains to be addressed.


Assuntos
Expressão Gênica/efeitos dos fármacos , Leptina/genética , Leptina/farmacologia , Próstata/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Receptores de Superfície Celular/genética , Fosfatase Ácida , Animais , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/análise , Ratos , Receptores de Superfície Celular/metabolismo , Receptores para Leptina , Proteínas Recombinantes/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Pol Merkur Lekarski ; 16(95): 495-9, 2004 May.
Artigo em Polonês | MEDLINE | ID: mdl-15518437

RESUMO

Currently radical prostatectomy remains the standard mode of treatment for patients with locally and localized stage of prostate cancer. On the other hand, after radical prostatectomy approximately 50% of patients have postoperative positive margin. Therefore implementation of effective mode of adjuvant radiotherapy treatment after radical prostatectomy plays important role in clinic. Currently available data, which evaluated the effectiveness of radiotherapy after radical prostatectomy are based on retrospective studies. These studies indicated that post-operative radiotherapy reduced the local recurrence rate but the influence on the patient's survival is unknown. Generally, the following factors are considered as prognostic for failure: the presence of pathologic T3 (pT3), positive surgical margin, preoperative concentration of prostatic specific antigen (PSA) above 25ng/ml, metastases to lymph nodes, Gleason >7. Radiotherapy is performed as typical adjuvant radiotherapy in case of pT3 or positive margin without rising of PSA level. This mode of treatment is efficient and gives the excellent local control rate but without marked influence on overall survival of patients. Another strategy, which is considered after radical prostatectomy, is salvage radiotherapy. This mode of treatment is introduced when the rising level of PSA and/or the pathological recurrence mass in the tumor bed is occurred. The efficacy of the salvage radiotherapy is lower than classical adjuvant radiotherapy. Still remain questions about the following issues: timing of radiotherapy, optimal dose, treatment technique, involved target for radiotherapy, and the role of adjuvant hormonal therapy. The last issue now is evaluating in the randomized clinical trial. In summary, currently until outcomes from well conducted randomized trials will available patients after radical prostatectomy with adverse significant factors for local recurrence or/and increased level of PSA should be considered for postoperative radiotherapy.


Assuntos
Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Terapia de Salvação , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco
20.
Pathol Oncol Res ; 20(2): 453-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24272675

RESUMO

In search for novel molecular targets in benign prostate hyperplasia (BPH), a PCR Array based screening of 84 genes was performed. Of those, expression of ZFP91 (ZFP91 zinc finger protein) was notably upregulated. Limited data concerning the function of ZFP91 product show that it is a potential transcription factor upregulated in human acute myelogenous leukemia and most recently found to be the non-canonical NF-κB pathway regulator. In order to test this finding on a larger number of samples, prostate specimens were obtained from patients undergoing adenomectomy for BPH (n = 21), and as a control, from patients undergoing radical cystectomy for bladder cancer (prostates unchanged pathologically, n = 18). Similar studies were performed on cultured human prostate cancer cell lines: LNCaP, DU145, 22Rv1, PC-3; as well as normal prostate epithelial cells-PrEC. Methods employed included: Human Obesity PCR Array (Qiagen), QPCR and Western blotting. QPCR studies confirmed significant overexpression of ZFP91 in BPH samples. On a protein level, however, comparison between normal and BPH prostates revealed insignificant differences. As for prostate cell lines examined, all expressed ZFP91 mRNA. Western blotting analysis showed markedly higher protein levels of ZFP91 in all cancer cell lines in comparison with normal (PrEC) cells. In conclusion, the upregulated ZFP91 mRNA in BPH, not accompanied by parallel changes in ZFP91 protein levels, together with ZFP91 protein abundance in prostate cancer cell lines suggest ZFP91 involvement in these prostate diseases.


Assuntos
Próstata/patologia , Ubiquitina-Proteína Ligases/genética , Células Epiteliais/patologia , Humanos , Masculino , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , Células Tumorais Cultivadas , Regulação para Cima/genética
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