ABSTRACT
En vista de la alta prevalencia del cáncer de próstata en la población venezolana y la ausencia de un patrón genético conocido en relación a la expresión de las enzimas Glutatión S-transferasas, se estudió la relación entre la expresión de un polimorfismo nulo de estas enzimas y la presencia de cáncer de adenocarcinoma prostática Métodos: Se incluyen 100 individuos para el muestreo no probabilístico, 50 pacientes con diagnóstico de adenocarcinoma de próstata comprobado mediante biopsia y 50 controles con hiperplasia prostática benigna demostrada mediante tacto y corroborada por ultrasonido transrectal, provenientes de los principales hospitales del país, se procedió a tomar muestra de sangre y mediante reacción de cadena de polimerasa, se determinó la presencia o ausencia de los genes para las enzimas Glutatión S-transferasa Mu 1 (GST M) y glutatión S-transferasa theta 1 (GST T1). Resultados: se logró evidenciar que el genotipo nulo se encontró en 40 y 24% de los pacientes mientras que para los controles fue de 38% y 22% respectivamente, demostrando que en la población venezolana estudiada no existen diferencias significativas entre casos y controles. Conclusiones: No se pudo demostrar una diferencia significativa entre los dos grupos estudiados. Recomendaciones: A pesar de nuestros hallazgos, se necesitan estudios futuros con muestras de mayor tamaño para dilucidar la posible asociación entre este patrón enzimático con el riesgo de presentar cáncer de próstata(AU)
Prostate cancer presents with a high incidence in the Venezuelan population. there is no known genetic pattern related to the expression of drug metabolizing enzymes Glutathione S-transferases. Methods: We proceeded to study the possible correlation between null polymorphism for these enzymes and prostate adenocarcinoma. the sample included 100 patients recruited from the Urology Department of three University Hospitals in Caracas, Venezuela, 50 cancer patients and 50 cancer free controls. Blood samples were drawn from each patient and polymorphisms for Glutathione S-transferase Mu 1 (GST M1) and Glutathione-sS-transferase theta 1(GST T1) were determined by polymerase chain reaction from lymphocytes. Results: Null genotype was found in 40% and 24% of cancer patients whereas the percentage in controls was 38 and 22% respectively, showing no statistically significant differences between the two groups. Conclusions: It was not possible to show a significant difference between the two groups. Recommendations: Due to the small size of the sample, it would be necessary to explore further in a larger population sample to determine whether there is an association between the expression of these enzymes and prostate cancer(AU)
Subject(s)
Humans , Male , Prostatic Hyperplasia/diagnosis , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/pathology , Prostate-Specific Antigen , Ultrasound, High-Intensity Focused, Transrectal/methods , Glutathione TransferaseABSTRACT
ABSTRACT CONTEXT: Inflammatory myofibroblastic tumors are a rare type of soft-tissue tumor. Inflammatory myofibroblastic tumors are characterized by rearrangements involving the anaplastic lymphoma kinase gene locus on 2p23. Case Report: We report the case of a 67-year-old Chinese male who presented with dysuria and fever. Magnetic resonance imaging showed an irregular prostatic mass with an isointense signal and obscure boundary. Histopathological evaluation showed that the mass consisted mainly of spindle-shaped cells. Immunohistochemical evaluation showed that the tumor cells were negative for anaplastic lymphoma kinase. CONCLUSIONS: Inflammatory myofibroblastic prostate tumors are rare lesions with unclear etiology. The pathological diagnosis is very important.
Subject(s)
Humans , Male , Aged , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/pathology , Soft Tissue Neoplasms/enzymology , Soft Tissue Neoplasms/pathology , Anaplastic Lymphoma Kinase/analysis , Prostatic Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Biopsy , Immunohistochemistry , Magnetic Resonance Imaging , Transurethral Resection of ProstateABSTRACT
Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose-6-phosphate amidotransferase), providing UDP-GlcNAc substrates for O-linked beta-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator PA28gamma and overexpression of PA28gamma rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated PA28gamma suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of PA28gamma and inhibition of proteasomal activity via O-GlcNAc modification.
Subject(s)
Humans , Male , Acetylglucosamine/chemistry , Alloxan/pharmacology , Apoptosis/drug effects , Autoantigens/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic , Glucosamine/pharmacology , Phosphorylation , Prostatic Neoplasms/enzymology , Proteasome Endopeptidase Complex/antagonists & inhibitors , RNA, Small Interfering/genetics , Ubiquitinated Proteins/metabolismABSTRACT
Determinar la presencia de CPCS en pacientes con cáncer prostático, la expresión de p504 S yel efecto de la supresión androgénica. Pacientes, materiales y método: en muestras de sangre venosa de 92 pacientes portadores de cáncer a la prostáta se separaron las células mononucleares por centrifugación diferencial. Las cpcs fueron identificadas utilizando anticuerpos monoclonales contra APE y P504S. Muestras de sangre de 10 mujeres fueron usadas como controles. Resultados: En ninguna de las muestras utilizadas como control y en el 68 por ciento de los hombres estudiados se detectaron CPCS. Todas las células detectadas fueron positivas para la expresión de P504S. Los pacientes con supresión androgénica, DES o después de una orquidectomía, tuvieron un nivel de P504S promedio menor que aquellos sin terapia sistémica p menor que 0,03. Conclusiones: la detección de CPCS P504S positivas en biopsias de prostáta es utilizada para el diagnóstico de cáncer, las celulas benignas no expresan este antígeno. Este estudio pionero demuestra que la expresión de P504S en CPCS es menor eb hombres con tratamiento hormonal sistémico.
Objective To determine the effect of androgen blockage on the expression of P504S en circulating prostate cells (CPCs) in men with prostate cancer. Patients, material and method: mononuclear cells were separated from venous blood using differential centrifugation and identification fied using monoclonal antibodies against PSA and P504S. 10 women were used as controls and 92 men with prostate cancer formesd the study group. Results: 64,8 percent of men were positive for CPCs, all the CPCs detected expressed the antigen P504S. No controls were positive. Conclusions. The detection of P504S postive cells in prostate biopsies is used to determine whether they are malignant or not, benign cells P504S negative. This is pioner study to show that CPCs are P504S positive, with the implication that they are malignant cells.
Subject(s)
Humans , Male , Female , Middle Aged , Aged, 80 and over , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Racemases and Epimerases/analysis , Racemases and Epimerases , Androgen Antagonists/therapeutic use , Diethylstilbestrol/therapeutic use , Immunohistochemistry , Biomarkers, Tumor , Neoplasm Metastasis , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/drug therapy , Prospective Studies , Prostate-Specific AntigenABSTRACT
La metaloproteinasa de matriz-2 (MPM-2) es una gelatinasa implicada en el proceso de metástasis. Las células que expresan MPM-2pueden cruzar la matriz extracelular y diseminarse a los tejidos distantes. Presentamos un estudio de la detección de células prostáticas en la circulación sanguínea y la expresión de MPM-2 en varones con cáncer prostático antes y después de una prostatectomía radical. Método y pacientes: Estudio prospectivo, multicéntrico, de pacientes atendidos en el Hospital de Carabineros de Chile, INRAD y el Instituto de Bío-Oncología, entre los años 2006 y 2008. Después de un consentimiento informado por escrito, 4 ml de sangre venosa fueron obtenidos. Las células mononucleares fueron aisladas por centrifugación diferencial y la CPCs detectadas con anti-PSA e identificadas mediante inmunocitoquímica con un sistema basado en fosfatasa alcalina con neofuscina como cromógeno. Las muestras positivas tuvieron un segundo proceso con anti-MPM-2, un sistema de detección basado en peroxidasa y Vector VIP como cromogen. Detalles de la etapa, la edad y nivel de APE sérico fueron registrados. Resultados: 105 pacientes participaron, 30 pretratamiento y 75 postratamiento, con una edad promedio de 71,3 +/- 8,4 años. Existió una asociación entre la frecuencia de detección de CPCs, la etapa clínica y el índice de Gleason. Todas las CPCs expresaron MPM-2. Conclusiones: Los resultados confirman que la expresión de MPM-2 tiene un papel importante en la 1a y 2a diseminación de células cancerosas y no hay una asociación de los otros factores pronóstico. La presencia de las CPCs no implica la presencia de micrometástasis ni su origen de diseminación en el 2o caso de CPCs, pero implica un riesgo más elevado de la enfermedad micrometastásica. Su detección podría ser útil durante el seguimiento para la detección precoz de estos pacientes.
Objective: Matrix metalloproteinase-2 is a gelatinase implicated in the metastatic process. Cells expressing MMP-2 can cross the extracellular matrix and disseminate to other tissues. We present a study of MMP-2 express of circulating prostate cells in men with prostate cancer. Methods and Patients: A prospective, multicenter study of men with prostate cancer attending the Hospital de Carabineros de Chile, INRAD and the Instituto de BioOncología between 2006 and 2008. After written informed consent a 4 ml blood sample was taken, mononuclear cells were obtained using differential centrifugation and CPCs identified using immunocytochemistry. Positive samples with PSA staining cells underwent a second process with anti-MPM-2. Age, clinical stage, serum PSA were noted for each patient. Results: 105 patients entered the study, 30 pre-treatment and 75 post treatment, with an average age of 71.3 +/- 8.4 years. There was an association with CPC detection frequency with clinical stage and Gleason score. All CPCs expressed MMP-2. Conclusions: The results indicate that MMP-2 expression is important in the dissemination of primary and secondary prostate cancer cells, that there is no association between prognostic factors and MMP-2 expression in CPCs. The presence of CPCs does not imply the presence of micrometastasis nor origin of dissemination in the case of 2nd CPCs but the presence implies a higher risk of micrometastasis. The detection of these cells could be a useful tool in the follow up of patients with prostate cancer.
Subject(s)
Humans , Male , Middle Aged , /metabolism , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/blood , Neoplastic Cells, Circulating/metabolism , Enzyme Activation , Immunohistochemistry , Multicenter Studies as Topic , Prostatic Neoplasms/pathology , Prospective StudiesABSTRACT
Determinar la presencia de células prostáticas en la circulación sanguínea (CPCs) en pacientes con cáncer prostático y la expresión de P504S. Método: Las células mononucleares fueron separadas de la sangre venosa por centrifugación diferencial, e identificadas utilizando anticuerpos monoclonales contra APE y P504S. Diez mujeres fueron usadas como controles. 66 hombres con cáncer prostático formaron el grupo de estudio. Resultados: 69,7 por ciento tuvieron células prostáticas en la sangre venosa, todas las células detectadas fueron positivas para la expresión de P504S. Conclusiones: La detección de células prostáticas P504S positivas en biopsias de la próstata esutilizando para el diagnóstico de cáncer, células benignas no se expresan el antígeno. Este es el primer estudio que demuestra la expresión de P504S en CPCs, con la inferencia que estas células son malignas.
To determine the expression of P504S en circulating prostate cells (CPCs) in men with prostate cancer. Method: Mononuclear cells were separated from venous blood using differential centrifugation andidentified using monoclonal antibodies against PSA and P504S. 10 women were used as controls and 66 men with prostate cancer formed the study group. Results: 69.7 percent of men were positive for CPCs, all the CPCs detected expressed the antigen P504S. Conclusions: The detection of P504S positive cells in prostate biopsies is used to determine whether they are malignant or not, benign cells are P504S negative. This is the first study to show that CPCsare P504S with the implication that they are malignant cells.
Subject(s)
Humans , Male , Female , Middle Aged , Aged, 80 and over , Biomarkers, Tumor , Prostatic Neoplasms/diagnosis , Racemases and Epimerases , Antibodies, Monoclonal , Neoplastic Cells, Circulating , Prospective Studies , Immunohistochemistry , Prostatic Neoplasms/enzymology , Racemases and Epimerases/metabolismABSTRACT
Reactive oxygen species (ROS) are involved in a diversity of important phenomena in the process of tumor development. To investigate the alterations of oxidative stress and their related systems in tumor progression, a variety of components in the antioxidative stress defense system were examined in prostate cancer cell lines, PC3 and LNCaP. Cell surface molecules involved in metastasis were expressed highly in PC3 cells compared with LNCaP cells, and strong invasion ability was shown in PC3 cells only. ROS level in LNCaP cells was twice higher than that in PC3 cells, although nitric oxide (NO) level was similar between the two cell lines. The content of GSH increased up to about 2-fold in PC3 compared with LNCaP. Activities of glutathione reductase, thioredoxin reductase, and glutathione S-transferase except catalase are significantly higher in PC3 cells than in LNCaP cells. Furthermore, oxidative stress-inducing agents caused down-regulation of GSH and glutathione S-transferase much more significantly in LNCaP cells than in PC3 cells. These results imply that malignant tumor cells may maintain low ROS content by preserving relatively high anti-oxidative capacity, even in the presence of stressful agents.
Subject(s)
Humans , Male , Antioxidants/metabolism , Cell Line, Tumor , Enzyme Induction , Gene Expression Regulation, Neoplastic , Oxidative Stress , Prostatic Neoplasms/enzymology , Reactive Oxygen Species/metabolism , Thioredoxin-Disulfide Reductase/metabolism , Up-Regulation/geneticsABSTRACT
BACKGROUND: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 genes have been studied earlier to evaluate the relative risk of various cancers. AIM, SETTING AND DESIGN: In the present study, we examined the association of the GSTM1 and GSTT1 gene polymorphisms with sporadic prostate cancer patients in north Indian population. MATERIAL AND METHODS: This case control study was undertaken over a period of 24 months and included 103 prostate cancer patients and 117 controls; both patients and controls originated from northern part of India. The GSTT1 and GSTM1 genotypes were identified by multiplex PCR in peripheral blood DNA samples. STATISTICAL ANALYSIS: Difference in genotype prevalence and association between case and control group were assessed by the Chi square and Fisher Exact tests. RESULTS: Frequencies of null genotypes in GSTT1 and GSTM1, was 11% (13/117) and 30% (35/117) respectively in control individuals. The frequencies of GSTT1 and GSTM1 null genotypes in prostate cancer patients were 34% (35/103) and 53% (55/103) respectively. CONCLUSION: Our study demonstrates that the null genotypes of GSTT1 and GSTM1 are substantially at higher risk for prostate carcinoma as compared to the normal healthy controls. The GSTT1 and GSTM1 null genotypes did not show significant association with tobacco usage in prostate cancer patients. However, the null genotypes were significantly stratified in 50-60 year-old patients when incidence of prostate cancer is high.
Subject(s)
Aged , Case-Control Studies , Gene Frequency , Genetic Predisposition to Disease , Genotype , Glutathione Transferase/genetics , Humans , India , Male , Middle Aged , Neoplasm Staging , Polymorphism, Genetic/genetics , Prevalence , Prostatic Neoplasms/enzymology , Risk Factors , SmokingABSTRACT
Tumour markers viz carcinoembryonic antigen (CEA), human chorionic gonadotrophin (HCG) in 30 cases of carcinoma breast and prostatic specific acid phosphatase (PSAP) in 30 cases of carcinoma prostate were studied by peroxidase antiperoxidase technique in paraffin blocks of tissue. Twenty three (76.7%) and 20 (66.7%) cases were positive for CEA and HCG respectively. No correlation was observed between CEA and HCG status, and histological differentiation of the tumours. All the 29 cases (100%) of adenocarcinoma prostate were PSAP positive while a single case, negative for PSAP, was of transitional cell carcinoma.
Subject(s)
Acid Phosphatase/analysis , Adenocarcinoma/enzymology , Breast Neoplasms/chemistry , Carcinoembryonic Antigen/analysis , Carcinoma/chemistry , Carcinoma, Intraductal, Noninfiltrating/chemistry , Carcinoma, Transitional Cell/enzymology , Chorionic Gonadotropin/analysis , Female , Humans , Male , Prostatic Neoplasms/enzymologyABSTRACT
The enzyme activities of Lactate dehydrogenase (LDH). prostate fluid LDH isoenzymes phosphohexose isomerase (PHI), Aldolase (ALD) and Hexokinase (HK) were determined in the sera of 77 samples of males. There were 12 cases of carcinoma prostate with metastases, 15 without metastases, 25 with benign prostatic hypertrophy and 25 nontumor. The enzyme activities of nontumor and benign group were statistically similar. The prostatic fluid LDH5/LDH1 ratio and PHI has been found to be the most sensitive parameter for detecting carcinoma prostate. Serial determinations of LDH, PHI, ALD and HK were found valuable for following the course of the disease during therapy.