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1.
J Physiol Pharmacol ; 72(4)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35072652

RESUMO

Participation of anti-inflammatory interleukin-13 (IL-13) in the process of carcinogenesis was well studied. Angiogenesis plays a key role in the process of tumour growth and metastasis. Higher expression of angiogenin (ANG) have been proven in many types of cancers. The aim of the study was to more fully understand the significance of plasma IL-13 as an immunomodulator and ANG as a stimulator of the angiogenesis process in patients with bladder cancer (BC) and to investigate the relationship between parameters. These parameters were examined in the group of BC patients and in subgroups of BC depending on clinical stage: non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC), histopathologic malignancy low grade (LG), high grade (HG) and in primary and recurrent BC. The level of IL-13 and ANG in the plasma of BC patients and controls were measured by enzyme-linked immunosorbent assay. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.). Plasma levels of IL-13 and ANG were significantly higher in BC patients and in all patient subgroups examined than in the controls (p < 0.001). A negative significant correlation was found between ANG and IL-13 levels in BC-patients. Based on the receiver operating characteristic curves (ROC), IL-13 had good diagnostic value in BC. The presented results may suggest a relationship between angiogenesis and inflammation in the pathogenesis of bladder cancer and the development of this disease. With the increase of IL-13 level in BC-patients plasma, the ANG level decreased.


Assuntos
Interleucina-13 , Neoplasias da Bexiga Urinária , Humanos , Neovascularização Patológica , Curva ROC , Ribonuclease Pancreático
2.
Biomed Res Int ; 2018: 8315410, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30069482

RESUMO

BACKGROUND: Uroplakins are glycoproteins investigated as potential markers of urothelial carcinoma. However, their role in chemical carcinogenesis is uncertain. In this study the diagnostic value of plasma and urine uroplakin IIIa (UPIIIa) levels in bladder cancer (BC) was investigated, particularly in the aspect of environmental exposure to chemical carcinogens, measured by DNA damage and detoxification ability in the BC smoking group. The correlation between uroplakin, 8-OHdG, and GSTπ was investigated. MATERIAL AND METHODS: This study included 61 BC patients and 33 healthy controls. UPIIIa, 8-OHdG, and GSTπ levels were estimated by the immunoenzymatic method (ELISA). RESULTS: UPIIIa levels were elevated in BC patients in plasma (p≤0.001) and in urine (p≤0.001), as were 8-OHdG and GSTπ levels in urine. Moreover, the 8-OHdG level was higher in invasive or high grade tumors. A positive correlation between UPIIIa/GSTπ and 8-OHdG/GSTπ was observed, but no UPIIIa/8-OHdG correlation was noted. CONCLUSION: The study showed the diagnostic value of urine and plasma UPIIIa in BC (good sensitivity, specificity, and predictive value). The lack of UPIIIa correlation with 8-OHdG and smoking suggests that UPIIIa does not reflect the environmental exposure. The increased levels of 8-OHdG and GSTπ in the invasive tumor stage indicate their value in BC monitoring.


Assuntos
Carcinogênese , Neoplasias da Bexiga Urinária , Uroplaquina III , 8-Hidroxi-2'-Desoxiguanosina , Estudos de Casos e Controles , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Desoxiguanosina/urina , Feminino , Glutationa S-Transferase pi/sangue , Glutationa S-Transferase pi/urina , Humanos , Masculino , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/urina , Uroplaquina III/sangue , Uroplaquina III/urina
3.
Transplant Proc ; 50(6): 1904-1909, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30056926

RESUMO

Mammalian target of rapamycin inhibitors (mTORI) are increasingly used in the treatment of tuberous sclerosis complex (TSC) and as immunosuppressants after organ transplantation. In TSC patients, mTORI are the treatment of choice after kidney transplantation. It is still under debate if benefits from long-term mTORI use will not be limited by side effects. MATERIALS AND METHODS: We report long-term follow-up data of the first TSC patient after kidney transplantation treated with sirolimus de novo. In 2005, a female patient was transplanted with a kidney graft after bilateral nephrectomy due to angiomyolipoma. Initial immunosuppressive treatment consisted of antithymocyte globulin, methylprednisolone, tacrolimus, and, due to TSC diagnosis, sirolimus. Creatinine level at discharge was 1.2 mg/dL. RESULTS: Long-term mTORI use resulted in skin lesion regression (angiofibromas, "confetti" skin lesions, shagreen patch) and disease stabilization in brain, abdominal, and chest magnetic resonance imaging/computed tomography scans. Pulmonary function tests showed improvement in restriction and slow deterioration in obstruction and diffusion parameters. Sirolimus related adverse reactions were hyperlipidemia and hypertriglyceridemia and respiratory and urinary tract infections. No gastrointestinal or hematologic symptoms occurred. Sirolimus concentrations ranged between 1.7 and 8.2 ng/mL (mean 4.01 ± 2.09 ng/mL). Since 2009 proteinuria and slow increase in creatinine level have been observed. No biopsy was performed to establish etiology and potential association with mTORI. In 2017 creatinine level was 2.2 mg/dL. CONCLUSION: The case of the patient confirms clinical effectiveness and acceptable safety of long-term mTORI treatment. Long-term mTORI use requires meticulous patient observation to optimize dosage, achieve immunosuppressive effect, and improve TSC manifestations with minimal side effects.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Sirolimo/uso terapêutico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/tratamento farmacológico , Adulto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade
4.
Mol Cell Biochem ; 447(1-2): 217-224, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29396722

RESUMO

Bladder cancer is a common disease and a significant cause of death worldwide. There is thus great interest in identifying a diagnostic and prognostic biomarker, as well as gaining an understanding of the molecular basis of bladder cancer. Stearoyl-CoA desaturase 1 gene (SCD1) is highly overexpressed in many human cancers. However, the expression of SCD1 has not yet been investigated in patients with bladder cancer. Here, we document that (a) the SCD1 is highly overexpressed in human bladder cancer; (b) high expression of SCD1 is more frequently observed in the late stage of disease and patients with lymph node metastasis; (c) bladder cancer patients with a higher SCD1 mRNA level have a poorer survival rate than those with normal SCD1 expression. Overall, this is the first report to indicate an association between SCD1 mRNA level and clinical indicators of human bladder cancer. Our study has provided evidence supporting the potential role of SCD1 as a biomarker for human bladder cancer prognosis.


Assuntos
Biomarcadores Tumorais/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Estearoil-CoA Dessaturase/biossíntese , Neoplasias da Bexiga Urinária/enzimologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
5.
Biomed Res Int ; 2018: 8693297, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30627578

RESUMO

BACKGROUND: Urothelial carcinoma is the most common type of bladder cancer (BC). It makes up more than 90% of all bladder cancers. Uroplakins are tissue-specific, glycoproteins, playing a role in the construction and function of urothelium. The emergence of uroplakins in the urine and/or plasma may be of potential importance in the early detection of BC. In our study, the diagnostic value of plasma and urine uroplakin 2 (UP2) concentration in bladder cancer was investigated, with an assessment of the antioxidant potential of BC patients. The correlation between UP2, total antioxidant capacity (TAC), and concentration of glutathione (GSH) was also examined. MATERIALS AND METHODS: This study included 61 BC patients and 33 healthy controls. UP2 concentration was estimated by the immunoenzymatic method (ELISA). TAC and GSH were determined in spectrophotometrically methods. RESULTS: UP2 concentration in BC patients was significantly higher (p≤0.001) both in plasma and in urine compared to the control groups (C). TAC concentration in urine (p≤0.001) and GSH concentration in plasma (p=0.047) were significantly lower in BC group compared to the C group. The high specificity and sensitivity for UPK2 in plasma (76%, 80%, respectively) and urine (88%, 84%, respectively) were observed. Positive correlations were observed between concentration of UP2 in plasma and TAC concentration in urine and between UP2 concentration in plasma and GSH concentration in the same material. CONCLUSION: The study showed the early diagnostic value of urine and plasma UP2 in BC. There was a decrease in UP2 concentration in the urine of patients with the development of BC. The decrease of antioxidant systems (TAC, GSH) indicates their relationship with the BC process. Based on the obtained results, it is justified to continue the study in a larger group of patients with BC.


Assuntos
Antioxidantes/metabolismo , Biomarcadores Tumorais , Proteínas de Neoplasias , Neoplasias da Bexiga Urinária , Uroplaquina II , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/urina , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Uroplaquina II/sangue , Uroplaquina II/urina
6.
J Pharm Biomed Anal ; 132: 173-183, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-27744176

RESUMO

Fluoroquinolones are the drugs of choice in the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. In order to improve assessment of antibacterial efficacy in the target tissue a simple, selective, rapid and robust HPLC-ESI-MS/MS method for the determination of levofloxacin and ciprofloxacin concentrations in human prostate bioptates was developed and validated. Preparation procedure for prostate samples (10mg) was carried out using homogenization and filtration steps. Analyses were performed within 3.5min using RP C18 column in the isocratic elution mode with mobile phase composed of a mixture of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution (v/v; 79:21). The method was linear between 0.3µg/g and 15µg/g for levofloxacin and ciprofloxacin with coefficient of correlation (r) ≥0.999. The limit of detection and the limit of quantification for levofloxacin were 0.06µg/g and 0.2µg/g and for ciprofloxacin were 0.04µg/g and 0.13µg/g, respectively. Average concentrations (±SD) of levofloxacin and ciprofloxacin obtained from patients tissue were 5.4±2.2µg/g and 3.9±1.5µg/g, respectively. Additionally, during validation procedure a novel, experimental design approach was applied for the robustness study. For evaluation of analytical method robustness, Plackett-Burman design was employed and for sample preparation method robustness Fractional Factorial design was used. The developed and validated method was successfully applied to examine prostate tissue samples obtained from patients enrolled into a clinical study. Up to now, there has been no other HPLC-ESI-MS/MS method reported for the simultaneous determination of levofloxacin and ciprofloxacin in human prostatic tissue.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ciprofloxacina/análise , Ciprofloxacina/farmacocinética , Levofloxacino/análise , Levofloxacino/farmacocinética , Próstata/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos , Antibacterianos/análise , Calibragem , Fluoroquinolonas/análise , Humanos , Limite de Detecção , Masculino , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Temperatura
7.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1029-1030: 48-59, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27423043

RESUMO

Fluoroquinolones are considered as gold standard for the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. However, recent studies reported that fluoroquinolone- resistant bacterial strains are responsible for gradually increasing number of infections after transrectal prostate biopsy. In daily clinical practice, antibacterial efficacy is evaluated only in vitro, by measuring the reaction of bacteria with an antimicrobial agent in culture media (i.e. calculation of minimal inhibitory concentration). Such approach, however, has no relation to the treated tissue characteristics and might be highly misleading. Thus, the objective of this study was to develop, with the use of Design of Experiments approach, a reliable, specific and sensitive ultra-high performance liquid chromatography- diode array detection method for the quantitative analysis of levofloxacin in plasma and prostate tissue samples obtained from patients undergoing prostate biopsy. Moreover, correlation study between concentrations observed in plasma samples vs prostatic tissue samples was performed, resulting in better understanding, evaluation and optimization of the fluoroquinolone-based antimicrobial prophylaxis during transrectal ultrasound guided prostate biopsy. Box-Behnken design was employed to optimize chromatographic conditions of the isocratic elution program in order to obtain desirable retention time, peak symmetry and resolution of levofloxacine and ciprofloxacine (internal standard) peaks. Fractional Factorial design 2(4-1) with four center points was used for screening of significant factors affecting levofloxacin extraction from the prostatic tissue. Due to the limited number of tissue samples the prostatic sample preparation procedure was further optimized using Central Composite design. Design of Experiments approach was also utilized for evaluation of parameter robustness. The method was found linear over the range of 0.030-10µg/mL for human plasma and 0.300-30µg/g for human prostate tissue samples. The intra-day and inter-day variability for levofloxacine from both plasma and prostate samples were less than 10%, with accuracies between 93 and 108% of the nominal values. The limit of detection and the limit of quantification for human plasma were 0.01µg/mL and 0.03µg/mL, respectively. For the prostate tissue, the limit of detection and the limit of quantification were 0.1µg/g and 0.3µg/g, respectively. The average recoveries of levofloxacin were in the range from 99 to 106%. Also, the method fulfills requirements of robustness what was determined and proved by Design of Experiments. The developed method was successfully applied to examine prostate tissue and plasma samples from 140 hospitalized patients enrolled into the clinical study, 12h after oral administration of LVF at a dose of 500mg. The mean (±SD) LVF concentration in prostate was 6.22±3.52µg/g and in plasma 2.54±1.14µg/mL. Due to simplicity of the method and relative small amount of sample needed for the assay, the method can be applied in clinical practice for monitoring of LVF concentrations in plasma and prostate gland.


Assuntos
Antibacterianos/farmacocinética , Infecções Bacterianas/prevenção & controle , Cromatografia Líquida de Alta Pressão/métodos , Levofloxacino/farmacocinética , Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Infecções Bacterianas/etiologia , Endossonografia/efeitos adversos , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Levofloxacino/sangue , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Próstata/metabolismo , Próstata/microbiologia
8.
Eur Rev Med Pharmacol Sci ; 20(1): 166-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26813470

RESUMO

OBJECTIVE: Sunitinib is a multiple tyrosine kinase inhibitor (TKI) that exerts anti-tumor and antiangiogenic activity. It is used for the treatment of metastatic gastrointestinal stromal tumours, renal cell carcinoma and pancreatic neuroendocrine tumours. A few studies confirm the anti-tumour activity of sunitinib in brain tumours and uveal melanoma, as well as its efficacy in the reduction of brain metastases of some primary cancers. Therefore, the penetration of sunitinib through the blood-brain barrier (BBB) and blood-aqueous humour barrier (BAB) is an issue of growing interest. The aim of the study was to investigate the influence of the time-of-day administration on the penetration of sunitinib into the cerebrospinal fluid (CSF) and aqueous humour (AH). MATERIALS AND METHODS: The rabbits were divided into two groups: I (control group)--receiving sunitinib at 8 a.m., and II--receiving sunitinib at 8 p.m. Sunitinib was administered p.o. at a single dose of 25 mg. The concentrations of sunitinib and its active metabolite (SU12662) in the plasma, CSF, AH were measured with the validated HPLC-UV method. RESULTS: The plasma AUC0-t for sunitinib in group I was 2051.8 ng × h/mL, whereas in group II it was 3069.3 ng × h/mL. The aqueous humour AUC0-t for sunitinib in thr groups were 43.2 and 76.3 ng × h/mL, respectively. The cerebrospinal AUC0-t for sunitinib in groups I and II were 55.5 and 66.3 ng × h/mL, respectively. CONCLUSIONS: After the evening administration (8 p.m.) the exposure to sunitinib in the rabbits' plasma, AH and CSF was higher than after the morning administration (8 a.m.), but the degree of sunitinib penetration through the BAB and BBB was very low (< 5%) and comparable in both groups.


Assuntos
Barreira Hematoaquosa/metabolismo , Barreira Hematoencefálica/metabolismo , Indóis/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirróis/administração & dosagem , Animais , Humor Aquoso/química , Líquido Cefalorraquidiano/química , Relógios Circadianos/fisiologia , Indóis/análise , Indóis/farmacocinética , Masculino , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/farmacocinética , Pirróis/análise , Pirróis/farmacocinética , Coelhos , Sunitinibe , Fatores de Tempo
9.
Eur J Clin Microbiol Infect Dis ; 34(9): 1815-21, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26048634

RESUMO

The aim of this study was to establish the prevalence of resistance to fluoroquinolones in Escherichia coli strains isolated from patients undergoing transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and to evaluate the incidence of possible infectious complications associated with this procedure. One hundred and four patients undergoing a TRUS-Bx in a single medical centre were prospectively enrolled in this study. In all patients, pre-biopsy rectal swabs were obtained. The analysis determined the antimicrobial susceptibility of E. coli strains to levofloxacin, ciprofloxacin and a panel of other antibiotics. Before biopsy, each of the men received a levofloxacin-based prophylaxis. Telephone follow-up was used to identify patients who had complications after TRUS-Bx. Fluoroquinolone-resistant strains were isolated from 9.62 % of the patients. In all cases, there were related to E. coli and all those strains were resistant to both levofloxacin and ciprofloxacin. Fluoroquinolones showed greater antimicrobial activity against E. coli (p < 0.05) than ampicillin, amoxicillin/clavulanate and cephalothin. Minor infectious complications occurred in three patients (2.91 %). The relation between the resistance of E. coli to fluoroquinolones and the risk of readmission, as well as infectious complications, was statistically significant (p < 0.05). Despite recent reports of increasing prevalence of fluoroquinolone-resistant E. coli and the associated increase of severe infectious complications, the presented results have not confirmed this phenomenon. Resistance to fluoroquinolones of E. coli strains isolated from rectal swab cultures prior to TRUS-Bx is the risk factor for readmission and infectious complications after this procedure.


Assuntos
Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Biópsia Guiada por Imagem/métodos , Levofloxacino/uso terapêutico , Profilaxia Pré-Exposição/métodos , Idoso , Idoso de 80 Anos ou mais , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Ultrassonografia
10.
Eur Rev Med Pharmacol Sci ; 18(16): 2393-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25219843

RESUMO

OBJECTIVES: At present it is known that the adjustment of the anticancer therapy to the circadian rhythms in tissues reduces the toxicity of the treatment. Chronotherapy also increases the efficacy of the anticancer treatment, which has been proved for many drugs. Sunitinib is a tyrosine kinase inhibitor, which is broadly used for the treatment of numerous cancers. The aim of the study was a comparison of the concentrations and pharmacokinetics of sunitinib after a single administration to rabbits at 08:00 (control group) and 20:00. Additionally, the effect of sunitinib on glucose levels was investigated. MATERIALS AND METHODS: The research was carried out on two groups of rabbits: I08:00, a group with the drug administered at 08:00 (n=8) and II20:00, a group with the drug administered at 20:00 (n=8). The rabbits were treated with sunitinib at an oral dose of 25 mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with a validated HPLC method with UV detection. RESULTS: The comparison of the sunitinib Cmax and AUC0-t in the group with sunitinib administered at 20:00 with the control group gave the ratios of 2.20 (90% confidence interval (CI) (2.17; 2.22) and 1.64 (1.61; 1.68), respectively. Statistically significant differences between the groups under analysis were revealed for Cmax (p < 0.0001), AUC0-t (p = 0.0079), AUC0-∞ (p = 0.0149), and tmax (p = 0.0085). The mean glycemia drop was higher in group I08:00. than in group II20:00 (22.7% vs. 14.3%; p = 0.0622). The glycemia values returned to the initial values in 24 h after the administration of the drug in both groups. CONCLUSIONS: The research proved a significant influence of the time-of-day administration on the pharmacokinetics of sunitinib.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Indóis/administração & dosagem , Indóis/farmacocinética , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Pirróis/administração & dosagem , Pirróis/farmacocinética , Animais , Antineoplásicos/sangue , Área Sob a Curva , Glicemia/análise , Esquema de Medicação , Indóis/sangue , Masculino , Inibidores de Proteínas Quinases/sangue , Pirróis/sangue , Coelhos , Sunitinibe
11.
Int Urol Nephrol ; 44(4): 1045-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22160729

RESUMO

Large cell calcifying sertoli cell tumor (LCCSCT) is an exceptionally rare neoplasm originating from sperm cord cells. The tumors have relatively low malignant potential and unlikely proceed to metastasis formation. The lesions may occur in an isolated form or in ca. 40% of cases may be associated with genetic abnormalities, by and large Peutz-Jeghers syndrome and Carney complex. At presentation, 20% of LCCSCT cases are bilateral and/or multifocal. Owning to characteristic skin lesions and particular hyperechoic ultrasound image of the tumor, preliminary diagnosis of the syndromic LCCSCT is possible in the preoperative period. Consequently, testicle organ-sparing procedure can be attempted, which is especially justified in bilateral lesions. Here, we report a case of a bilateral LCCSCT in a 20-year-old man with atypical Peutz-Jeghers syndrome due to amplification of the exon 1 of STK11 gene who was successfully treated with bilateral testicle-sparing tumorectomies.


Assuntos
Calcinose/cirurgia , Orquiectomia/métodos , Síndrome de Peutz-Jeghers/complicações , Tumor de Células de Sertoli/cirurgia , Neoplasias Testiculares/cirurgia , Quinases Proteína-Quinases Ativadas por AMP , Calcinose/complicações , Calcinose/patologia , Diagnóstico Diferencial , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Tumor de Células de Sertoli/complicações , Tumor de Células de Sertoli/patologia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologia , Adulto Jovem
12.
Br J Cancer ; 100(9): 1508-12, 2009 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-19401704

RESUMO

It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1-6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2-8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4-7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer.


Assuntos
Neoplasias da Mama/epidemiologia , Portador Sadio/epidemiologia , Triagem de Portadores Genéticos/instrumentação , Mutação , Neoplasias/epidemiologia , Neoplasias da Próstata/epidemiologia , Proteínas Serina-Treonina Quinases/genética , Quinase do Ponto de Checagem 2 , Neoplasias do Colo/epidemiologia , Família , Feminino , Humanos , Masculino , Neoplasias/genética
15.
Cancer Lett ; 222(1): 83-8, 2005 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-15837544

RESUMO

Telomerase is extensively investigated as potential diagnostic and prognostic marker in human tumors. In this study, we determined telomerase activity in histological specimens and voided urine of 52 human bladder cancers. Using the PCR-ELISA method telomerase activity was found in 21 (88%) of the 24 tumor tissues and in the corresponding sediments from voided urine of patients with superficial bladder carcinoma (Ta/T1). In case of muscle-invasive tumors (T2-T4), telomerase activity was found in 27 (96%) of the 28 tumor tissues and in 26 (93%) of the 28 urine sediments. Enzyme activity was not detected in 13 control urine sediments. Telomerase activity was not significantly associated with clinicopathological parameters supporting the diagnostic rather than prognostic value of this marker in bladder cancer. The present study demonstrates that telomerase activity detection in voided urine has high potential for noninvasive diagnosis of superficial bladder tumors.


Assuntos
Biomarcadores Tumorais/urina , Telomerase/urina , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Sensibilidade e Especificidade , Telomerase/análise , Telomerase/metabolismo , Urinálise , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/urina
16.
Horm Metab Res ; 35(10): 565-9, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14605988

RESUMO

Common molecular changes in cancer cells are high carbon flux through the glycolytic pathway and overexpression of fatty acid synthase, a key lipogenic enzyme. Since glycerol 3-phosphate dehydrogenase creates a link between carbohydrates and the lipid metabolism, we have investigated the activity of glycerol 3-phosphate dehydrogenase and various lipogenic enzymes in human bladder cancer. The data presented in this paper indicate that glycerol 3-phosphate dehydrogenase activity in human bladder cancer is significantly higher compared to adjacent non-neoplastic tissue, serving as normal control bladder tissue. Increased glycerol 3-phosphate dehydrogenase activity is accompanied by increased enzyme activity, either directly (fatty acid synthase) or indirectly (through ATP-citrate lyase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and citrate synthase) involved in fatty acid synthesis. Coordinated upregulation of glycerol 3-phosphate dehydrogenase and lipogenic enzymes activities in human bladder cancer suggests that glycerol 3-phosphate dehydrogenase supplies glycerol 3-phosphate for lipid biosynthesis.


Assuntos
Glicerolfosfato Desidrogenase/metabolismo , Lipídeos/biossíntese , Neoplasias da Bexiga Urinária/enzimologia , ATP Citrato (pro-S)-Liase/metabolismo , Citrato (si)-Sintase/metabolismo , Ácido Graxo Sintases/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Glicerol-3-Fosfato Desidrogenase (NAD+) , Humanos , Fosfogluconato Desidrogenase/metabolismo
17.
Neoplasma ; 49(5): 346-8, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12458336

RESUMO

Metastatic tumors of the penis are rare. They are usually secondary to primaries of the genitourinary and gastrointestinal tracts. This entity is usually accompanied by distressing symptoms like dysuria, pain, induration, swelling of the penis and priapism, making immediate intervention necessary. Different methods of treatment are used to achieve the palliative effect: local surgical excision, penis amputation, radiotherapy or chemotherapy. Nevertheless, the prognosis is poor, because the disease is already disseminated and in most cases other metastases will occur soon.


Assuntos
Neoplasias Penianas/secundário , Neoplasias Penianas/terapia , Neoplasias Urogenitais/patologia , Idoso , Carcinoma/diagnóstico , Carcinoma/secundário , Carcinoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Penianas/diagnóstico , Prognóstico
18.
Eur Urol ; 36(5): 418-20, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10516453

RESUMO

We are reporting the case of a parapubic hernia that occurred after radical prostatectomy. This kind of the hernia is caused by the weakening of the attachments of rectus muscles to the pubic bone. Because of its location, it may be misdiagnosed as a far more common direct inguinal hernia. A laparoscopic approach made it possible to precisely diagnose and repair the defect in the abdominal wall.


Assuntos
Hérnia Ventral/cirurgia , Laparoscopia/métodos , Prostatectomia/efeitos adversos , Seguimentos , Hérnia Ventral/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Osso Púbico , Resultado do Tratamento
19.
Wiad Lek ; 51 Suppl 3: 20-4, 1998.
Artigo em Polonês | MEDLINE | ID: mdl-9814100

RESUMO

We present laparoscopic method of treatment of parapubic hernia that may occur after radical prostatectomy performed due to prostatic cancer. This kind of hernia is closely related to the weakening of the rectus muscle of abdomen insertions to the pubic bone that takes place during the operations using lower midline incision in order to reach organs in the small pelvis. Because of its localization it may be misdiagnosed as a commoner direct inquinal hernia. In this case the traditional anterior approach would not be curative. Using laparoscopy as it is suggested by authors will make the proper diagnosis much more easy and thus will enable effective treatment of the patient.


Assuntos
Hérnia/diagnóstico , Herniorrafia , Laparoscopia/métodos , Prostatectomia/efeitos adversos , Diagnóstico Diferencial , Hérnia/etiologia , Hérnia Inguinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/cirurgia
20.
Eur J Cardiothorac Surg ; 14 Suppl 1: S38-42, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9814790

RESUMO

This study was undertaken to assess our experience with the first 50 patients who underwent CABG without cardiopulmonary bypass. In seven patients left internal mammary artery to left anterior descending artery (LIMA-LAD) grafting was performed through a short left anterior thoracotomy. In 43 other patients median sternotomy was used. Primary CABG was performed in 48 patients; there were two reoperations. Eleven patients had unstable angina. Three patients had left ventricular ejection fraction (LVEF) equal to or lower than 25%. One patient had carcinoma of the right lung coexisting with unstable angina and underwent also right lower lobectomy. In each patient the clinical course, 12-lead ECG, transthoracic echocardiography and the serum levels of creatine kinase (CPK), alanine aminotransferase (ALAT), aspartate aminotransferase (AspAT) were assessed. The need for inotropic or intraaortic balloon counterpulsation (IABP) support and blood transfusion was also recorded. There were three deaths, all in the sternotomy group (6%). A patient with systemic lupus erythemetodes (SLE) died of postoperative MI due to graft thrombosis. Another patient who was found to have porcelain aorta and had LIMA-LAD grafting as a rescue procedure died of MI with low cardiac output. The third patient with unstable angina and ejection fraction of 30% developed postoperative MI with ventricular arrhythmia. One patient with LIMA-LAD graft in whom percutaneous translaminal coronary angioplasty (PTCA) had been abandoned because of coronary spasm developed acute myocardial ischaemia 5 h postoperatively. He had a vein graft placed to LAD in cardiopulmonary bypass, his further course was uneventful. Six patients had IABP support. Nine patients needed inotropic support. Ten patients received blood transfusion. Twelve-lead ECG did not show acute ischaemia or MI, apart from the above described cases. Echocardiographic check showed improved IVS contractility in three patients and better apex motion in one case. In the other survivors the echocardiographic findings were the same as before the procedure. ALAT and AspAT serum levels were normal in all the survivors, and the CPK levels did not exceed 200 IU/ml. One patient from the mini-thoracotomy group had recurrent angina 2 months after the procedure. His left internal mammary artery (LIMA) graft was occluded; we replaced it with a vein graft. All 47 survivors remain asymptomatic, with the mean follow-up time of 6 months. Coronary surgery without cardiopulmonary bypass seems a valuable alternative for high-risk patients.


Assuntos
Ponte Cardiopulmonar , Anastomose de Artéria Torácica Interna-Coronária/métodos , Feminino , Humanos , Anastomose de Artéria Torácica Interna-Coronária/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Esterno/cirurgia , Toracotomia/métodos , Resultado do Tratamento
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