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1.
Anticancer Res ; 39(12): 6939-6943, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810965

RESUMO

BACKGROUND/AIM: In spite of early detection, appoximately 15% of the small renal cell carcinomas (RCC) will develop metastasis within 5 years follow-up. The aim of this study was to identify new biomarkers to estimate the postoperative relapse of the most common conventional RCC. PATIENTS AND METHODS: Tissue multi arrays of conventional RCC without metastasis at the time of operation from a cohort of 634 patients were analysed by immunohistochemistry for expression of the chitinase 3-like protein 2 (CHI3L2). Cancer specific survival of patients was estimated with Kaplan-Meier analysis, univariate and multivariate Cox regression models. RESULTS: Kaplan-Meier analysis estimated a shorter cancer-free survival for patients with CHI3L2 positive tumors. In multivariate analysis, the CHI3L2 positivity associated with a 3.5 times higher risk for tumor relapse (p<0.001). CONCLUSION: Expression of CHI3L2 in tumor cells of conventional RCC define a group of patients at high risk for postoperative progression.


Assuntos
Carcinoma de Células Renais/metabolismo , Quitinases/metabolismo , Neoplasias Renais/metabolismo , Macrófagos/metabolismo , Recidiva Local de Neoplasia/metabolismo , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/cirurgia , Quitinases/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Nefrectomia , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos , Regulação para Cima
2.
Anticancer Res ; 38(12): 6663-6667, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30504374

RESUMO

BACKGROUND/AIM: The association of Wilms' tumor (WT), papillary renal cell tumor (PRCT) and mucinous tubular and spindle cell carcinoma (MTSCC) with embryonal rests has already been documented, but the cellular origin of metanephric adenoma (MA) is not yet known. The aim of this study was to understand their developmental evolution and find diagnostic markers. MATERIALS AND METHODS: CD57, KRT7, AMACR, SCEL, WT1 and CDH17 expression was analysed by immunohistochemistry in the four types of tumors and the associated pre-neoplastic lesions. RESULTS: Immunohistochemistry was able to differentiate WT, MA, MTSCC and PRCT. A phenotypic correlation between MA and perilobar nephrogenic rest associated with WT was identified. CONCLUSION: Perilobar nephrogenic rest and MA arise from differentiation arrested cells of the proximal domain of the S-shape body. We propose that WT1, MA, MTSCC and PRCT derive from different forms of maturation arrested embryonal rests.


Assuntos
Adenoma/diagnóstico , Adenoma/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Rim/embriologia , Néfrons/embriologia , Adenoma/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/patologia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Diferenciação Celular , Diagnóstico Diferencial , Embrião de Mamíferos , Feminino , Feto/metabolismo , Feto/patologia , Humanos , Imuno-Histoquímica , Rim/metabolismo , Rim/patologia , Neoplasias Renais/metabolismo , Néfrons/metabolismo , Néfrons/patologia , Gravidez , Análise Serial de Tecidos , Tumor de Wilms/diagnóstico , Tumor de Wilms/metabolismo , Tumor de Wilms/patologia
3.
Int J Biol Sci ; 14(7): 784-790, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29910688

RESUMO

We have suggested that papillary renal cell tumor (PRCT) of the kidney arises from nephrogenic rest-like lesions. To approve our hypothesis, we worked up 14 kidneys bearing papillary and 14 ones with conventional renal cell carcinoma (CRCC) histologically and found 42 papillary lesions in average per kidney bearing PRCT. PRCTs are characterized by loss of the Y chromosome and trisomy of chromosomes 7 and 17. The MET and HNF1B are localized to chromosome 7q31 and 17q21 and are frequently amplified in PRCT. We have analyzed the expression of the mutant MET in hereditary PRCTs and precursor lesions and found duplication and expression of the mutated allele. Because both genes are involved in early stage of nephron development, we have analyzed the expression of MET and HNF1B by immunohistochemistry in fetal kidneys, precursor lesions and PRCTs. We detected strong expression of MET and HNF1B in distal compartment of S-shaped body of fetal kidneys and in nephrogenic rest-like precursor lesions. Our finding suggests an association between expression of MET and HNF1B in precursor lesions and development of PRCT. We propose a model involving chromosomal clonal evolution and corresponding gene expression for development of PRCTs from embryonic rests due to impaired differentiation. Our model suggests that PRCT have a natural history distinct from that of most common CRCC.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Alelos , Carcinogênese/genética , Carcinogênese/patologia , Transformação Celular Neoplásica/genética , Feminino , Fator 1-beta Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/metabolismo , Humanos , Rim/metabolismo , Masculino
4.
Anticancer Res ; 37(3): 1185-1189, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28314280

RESUMO

BACKGROUND/AIM: Previous genetic and morphologic characterisation of mucinous tubular and spindle cell carcinoma (MTSCC) have yielded controversial results. The aim of this study was to explain the phenotypic heterogeneity of MTSCC diagnosed by genetic means. MATERIALS AND METHODS: We analyzed 7 MTSCC by array CGH and microsatellite allelotyping and by histology for morphological variation. We worked-up two entire kidneys with MTSCC to find microscopic alterations. RESULTS: We confirmed the diagnosis of MTSCC by detecting copy number changes at chromosomes 1, 4, 6, 8, 13, 14, 15, 18 and 22. We detected 13 small, microscopic precursor lesions in the two kidneys and found similar histological structures in precursor lesions and MTSCC. CONCLUSION: MTSCC develops from embryonal rest-like lesions of impaired differentiation which may explain its morphological variations. Until diagnosis of a "malignant" MTSCC" is not confirmed by genetic means, it should not be called carcinoma.


Assuntos
Adenocarcinoma Mucinoso/genética , Linhagem da Célula , Neoplasias Renais/genética , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Adulto , Alelos , Diferenciação Celular , Hibridização Genômica Comparativa , Feminino , Testes Genéticos , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Fenótipo , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia
5.
Histopathology ; 70(2): 273-280, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27501523

RESUMO

AIMS: The aims of this study were to investigate the potential of ß-catenin as a biomarker for predicting cancer-specific survival, and to find a reproducible mode of evaluation of immunohistochemistry. METHODS AND RESULTS: ß-Catenin expression was analysed by immunohistochemistry in a cohort of 488 patients with conventional renal cell carcinoma (RCC) operated on between 2000 and 2010. The association between ß-catenin expression and cancer-specific survival was assessed with univariate and multivariate Cox regression models in relation to conventional clinical pathological prognostic factors, and by Kaplan-Meier survival analysis with the log rank test. The univariate Cox regression model revealed an association of cytoplasmic ß-catenin positivity and pathological variables with cancer-specific death. The multivariate Cox regression model analysis of tumours without metastatic disease at the first presentation identified the T-classification (P < 0.001) and cytoplasmic ß-catenin positivity as risk factors for postoperative tumour progression. Specifically, cytoplasmic ß-catenin expression was an independent factor indicating an unfavourable prognosis, with a four-fold higher risk of cancer-specific death (relative risk 4.017; 95% confidence interval 2.489-6.482; P < 0.001). The median survival time for patients with tumours showing cytoplasmic accumulation of ß-catenin was 48 months, whereas the overall survival time was 166 months. CONCLUSIONS: Cytoplasmic ß-catenin expression is an independent prognostic factor for conventional RCC, and may help to identify patients with a high risk of cancer-specific death and to direct optimized active surveillance or adjuvant therapy.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , beta Catenina/biossíntese , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , Citoplasma/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise Serial de Tecidos , beta Catenina/análise
6.
Anticancer Res ; 36(5): 2169-73, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27127119

RESUMO

BACKGROUND/AIM: The canonical ß-catenin pathway is involved in the development of Wilms' tumor, but its role in adult renal cell tumors (RCT) of embryonal origin is not yet known. MATERIALS AND METHODS: We sequenced the catenin beta 1 (CTNNB1) gene in papillary RCTs, applied the TOPflash/FOPflash reporter plasmid system on cell lines, and examined the ß-catenin protein expression by immunohistochemistry. RESULTS: The absence of mutations in CTNNB1 and low TOPflash/FOPflash ratio in tumor cell lines indicated the absence of active Wingless-type MMTV integration site family (WNT) signaling in RCTs. The weakly cytoplasmic tending towards membranous expression of ß-catenin in RCT is analogous to cellular differentiation in the embryonal kidney rather than tumorigenic activation of WNT signaling. CONCLUSION: The localization of ß-catenin in papillary RCT, metanephric adenoma and mucinous tubular and spindle-cell carcinoma corresponds to that of emerging tubules of kidney at distinct stage of maturation, indicating their embryonal origin.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Embrionárias de Células Germinativas/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Células HEK293 , Humanos , Neoplasias Renais/patologia , Neoplasias Embrionárias de Células Germinativas/patologia
7.
J Mol Neurosci ; 59(2): 177-83, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26454744

RESUMO

Numerous studies investigated the localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in different tumors and described the effects of analogs on tumor growth to show its potential role in oncogenesis. Recently, our research group has found significantly lower levels of PACAP27-like immunorreactivity (LI) and PACAP38-LI in different human samples of primary small cell lung cancer and colon cancer compared to normal healthy tissues. There are only few human studies showing the presence of PACAP and its receptors in urogenital tumors; therefore, the aim of the present study was to compare PACAP-LI in different healthy and pathological human samples from urogenital organs (kidney, urinary bladder, prostate, testis) with radioimmunoassay (RIA) method. Similar to our earlier observations, the PACAP27-LI was significantly lower compared to PACAP38-LI in all samples. We did not find significant alterations in PACAP-LI between healthy and tumoral samples from the urinary bladder and testis. On the other hand, we found significantly lower PACAP38-LI level in kidney tumors compared with healthy tissue samples, and we showed higher PACAP27-LI in prostatic cancer compared to samples from benign prostatic hyperplasia. These data indicate that PACAP levels of different tissue samples are altered under pathological conditions suggesting a potential role of PACAP in the development of different urogenital tumors.


Assuntos
Neoplasias Renais/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias Testiculares/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Estudos de Casos e Controles , Humanos , Masculino , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética
8.
Virchows Arch ; 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26475151

RESUMO

There are no adequate immunohistochemical markers for papillary renal cell tumours. The aim of this study was to establish a gene expression profile of papillary renal cell tumours using an expression microarray approach. Through hierarchical clustering and significant analysis of microarrays, we have selected the best 13 genes and analysed their expression by real-time polymerase chain reaction (RT-PCR). Of these genes, we selected SCEL as potential marker of interest. Immunohistochemical staining of tissue microarrays containing all major types of kidney cancers revealed positive staining for sciellin in 87 of 114 papillary renal cell tumours and in 13 of 19 precursor lesions. No other renal tumour types were positive for sciellin. Our study indicates that although not all tumours express sciellin, its expression may help to confirm the diagnosis papillary renal cell tumour.

9.
Brain Res ; 1002(1-2): 110-9, 2004 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-14988040

RESUMO

Our recent results showed that angiotensin II or III (AII, AIII) microinjected into the zona incerta (ZI) significantly increased water intake. The most effective doses of AII and AIII were also defined. The two neuropeptides had their effects differently on drinking via different receptors. AII bound to AT(1) that was blocked by AT(1) receptor antagonist Losartan and the effect of AIII was eliminated by prior application of AT(2) receptor antagonist PD 123319. After different hydrational challenges, the effects of AII and AIII in the ZI have never been experimented, however. In the present experiments, the previously defined effective doses of AII (100 ng) or AIII (200 ng) were microinjected into the ZI after different types of challenges: (1). lowered thirst motivation when animals ingested approximately 40% of their daily fluid need during the consequent 60-min-daily-drinking period before the injection, (2). 48-h water deprivation, (3). intracellular dehydration and (4). extracellular dehydration. In all of the cases, incertally injected AII increased the animals' water ingestion. While Losartan could block these effects, PD 123319 was ineffective. Experiments were repeated by AIII, but in none of the cases differences were experienced between the groups. The finding that following hydrational challenges water intake increased only after AII injections and it could be blocked only by Losartan suggests that AII and AT(1) receptor play a pivotal role in the ZI in maintaining the body water balance.


Assuntos
Angiotensina III/administração & dosagem , Angiotensina II/administração & dosagem , Líquido Extracelular/efeitos dos fármacos , Líquido Intracelular/efeitos dos fármacos , Subtálamo/efeitos dos fármacos , Animais , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Líquido Extracelular/fisiologia , Líquido Intracelular/fisiologia , Masculino , Microinjeções , Ratos , Subtálamo/fisiologia
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