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1.
Kaohsiung J Med Sci ; 34(3): 125-133, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29475459

RESUMO

The aim of the present work was to study the immune profiling of prostate epithelial cells by the expression of ASK-1/p38 and Raf-1/ERK MAP Kinases signaling pathways mediated by TRAF-6. Immunohistochemical and Western blot analyses for TRAF-6, ASK-1, MEK-6, p38, Raf-1, MEK-1, ERK-1, ERK-2 and PSA were carried out in 5 samples of normal prostate gland, 24 samples of BPH and 19 samples of PC. Immunoreaction to TRAF-6 was found in the cytoplasm of epithelial cells of BPH and tumor cells of PC samples. For patients with the profile (TRAF-6+), optical densities revealed a weak immunoexpression of ASK-1 in PC compared to BPH patients. Whereas, immunoexpression to Raf-1 was higher in PC than in BPH. According to the expression of ASK-1 and Raf-1, two main profiles were identified: (TRAF-6+, ASK-1+, Raf-1+) and (TRAF-6+, ASK-1+, RAF-1-) in both BPH and PC. In addition, ASK-1/p38 axis expression was increased in BPH. Raf-1/ERK signaling pathway was increased in PC samples. On the other hand, representing of individual signaling protein expression enclosing each of p38 and ERK MAP Kinases according to TRAF-6+ showed a qualitative behavior of ASK61/p38 and Raf-1/ERK signaling pathways and a dynamic expression of PSA associated with immune and inflammatory process. These findings suggest that prostate epithelial cell could able an immune and inflammatory setting.


Assuntos
Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Fator 6 Associado a Receptor de TNF/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Células Epiteliais/imunologia , Células Epiteliais/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , MAP Quinase Quinase 6/genética , MAP Quinase Quinase 6/imunologia , MAP Quinase Quinase Quinase 5/genética , MAP Quinase Quinase Quinase 5/imunologia , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/imunologia , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Próstata/imunologia , Próstata/patologia , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/imunologia , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
2.
Immunobiology ; 221(12): 1424-1431, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27451139

RESUMO

BACKGROUND: Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. AIM: We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. MATERIALS AND METHODS: 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. RESULTS: In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. CONCLUSION: Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones.


Assuntos
Células Epiteliais/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-6/metabolismo , Próstata/imunologia , Hiperplasia Prostática/imunologia , Neoplasias da Próstata/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/metabolismo , Carcinogênese , Células Clonais , Células Epiteliais/patologia , Perfilação da Expressão Gênica , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Antígeno Prostático Específico/metabolismo , Células Tumorais Cultivadas , Microambiente Tumoral
3.
Tunis Med ; 93(8-9): 556-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26815524

RESUMO

BACKGROUND: (PSMA+,PSA+) and (PSMA+,PSA-) are the two most individual clones that we have previously identified during prostate cancer (PC) progression. However, molecular signatures associated with these distinct PSMA-PSA prostate clones and their specific correlation with disease outcome is yet to be defined. AIM: Since Akt is a major pathway involved in the critical activating events that leads to malignant form of the disease, we studied the involvement of full Akt activation (T308+,S473+) connected with serum PSA levels, tissue PSMA expression and angiogenic activity on the emergence of (PSMA+,PSA+) and (PSMA+,PSA-) PC clones. METHODS: The study was carried out in 6 normal prostate, 25 benign prostate hyperplasia (BPH) and 23 (PC). Immunohistochemical analysis was performed to study the expression of PSMA, PSA, pAkt(T308), pAkt(S473) and CD34 in prostate tissues. The evaluation of angiogenesis was made by CD34 immune marker. Serum levels of PSA were assayed by Immulite autoanalyser. RESULTS: The most relevant result showed that, among PC patients with pAkt (T308+,S473+) profile, patients that exhibit the (PSMA+,PSA+) clone have .higher serum PSA levels, tissue PSMA expression and angiogenic activity than those with (PSMA+,PSA-) clone. Although have the same (PSMA+,PSA+) prostate clone, BPH patients have distinct molecular-biological features compared to PC patients among pAkt (T308+,S473+) profile. In fact, among patients with maximal Akt activation, the (PSMA+,PSA+) PC clone is characterized by higher serum PSA levels, tissue PSMA production and intensive angiogenic activity than (PSMA+,PSA+) BPH clone. CONCLUSION: These findings emphasize the potential role of the full Akt activation (T308+,S473+) in expansion of several PSMA-PSA prostate clones capable of driving both human PC initiation as well as progression to a metastatic phenotype. Pinpoint patients according to PSMA-PSA clones could recapitulate the histological and molecular features of human PC and may offer a novel approach for controlling metastasis.


Assuntos
Antígenos de Superfície/genética , Clonagem Molecular , Glutamato Carboxipeptidase II/genética , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Próstata/metabolismo , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo
4.
Histol Histopathol ; 29(10): 1263-80, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24788382

RESUMO

A major clinical challenge is posed by the current inability to readily distinguish indolent from aggressive tumors in prostate cancer patients. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from normal, benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Combined with the evidence of the phenotypic heterogeneity of benign prostate hyperplasia, primary tumors and metastases, it is conceivable that several prostate clones emerge progressively during tumor progression. We have identified several PSA-PSMA prostate clones during prostate cancer progression. In this paper we focus on the susceptibilities of these PSA-PSMA prostate clones to factors that promote prostate hyperplastic, neoplastic and metastatic development and their consequences in disease outcome.


Assuntos
Antígenos de Superfície/genética , Glutamato Carboxipeptidase II/genética , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Antígenos de Superfície/química , Biomarcadores Tumorais/química , Biomarcadores Tumorais/genética , Clonagem Molecular , Feminino , Glutamato Carboxipeptidase II/química , Humanos , Masculino , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Antígeno Prostático Específico/química , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia
5.
J Immunoassay Immunochem ; 35(1): 48-59, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24063616

RESUMO

Prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) measured in serum are not fully satisfactory as biomarkers of prostate cancer (PC). Results obtained in this article indicated that PSMA/PSA ratio evaluated by immunohistochemistry in normal prostate (NP), benign prostatic hyperplasia (BPH), and PC at the individual level could be a useful tool for diagnosis and prognosis of PC. PSMA and PSA were equally expressed in NP and the PSMA/PSA ratio was 1.22 ± 0.15. Data also indicated that PSMA/PSA ratio fluctuates in BPH and PC compared to NP. In BPH, the PSMA/PSA ratio was around 0.47 ± 0.02, whereas it's significantly increased in PC, about 4.95 ± 0.83. In parallel, the highest PSMA/PSA ratio was associated with high intratumoral angiogenesis in PC patients with (PSMA+,PSA+) profile.


Assuntos
Adenocarcinoma/diagnóstico , Antígenos de Superfície/genética , Glutamato Carboxipeptidase II/genética , Antígeno Prostático Específico/genética , Próstata/metabolismo , Hiperplasia Prostática/genética , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/sangue , Estudos de Casos e Controles , Interpretação Estatística de Dados , Expressão Gênica , Glutamato Carboxipeptidase II/sangue , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Próstata/irrigação sanguínea , Próstata/patologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/patologia , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
6.
Tunis Med ; 91(7): 458-63, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24008878

RESUMO

BACKGROUND: As promising targets for in vivo diagnostic,prognostic and therapeutic approaches, the distribution and staining pattern of prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA) in tumors are of significant interest. AIMS: To compare the cellular distribution and heterogeneity of PSA and PSMA expression in normal prostate (NP), benign prostatic hyperplasia (BPH) and primary prostatic tumors and to analyze their relation with the angiogenic activity according to Gleason grade (low, medium and high) in primary PC. METHODS: The study was carried out in 6 NP, 44 BPH and 39 PC. Immunohistochemical analysis was performed. Monoclonal antibodies 3E6 and ER-PR8 were used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis was made by CD34 immune marker. RESULTS: In our study we noticed differences in the intracellular localization of the PSMA immunostaining which seem to be related to the normal and pathological context. A significant number of primary tumors presented with apical pattern of PSMA (28/39); whereas a relevant part of NP samples and BPH samples showed cytoplasmic localization (4/6 and 30/44,respectively) in luminal epithelial cells. Compared to PSMA, PSA was preferentially localized in cytoplasmic compartment in all type of prostate. A direct correlation between histological grade, PSMA expression and angiogenic activity could be demonstrated in primary PC. CONCLUSIONS: Simultaneous stains with PSA and PSMA in individual prostate tissue will greatly improve the detection rate and identify a high risk PC that could progress to metastatic phenotype. Our findings clearly support the feasibility but also direct the potential of PSMA-targeted in vivo therapeutic approaches in PC patients rather than PSA especially those with poorly differentiated adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Distribuição Tecidual , Adulto Jovem
7.
Biomed Res Int ; 2013: 409179, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23991415

RESUMO

PURPOSE: To investigate differences in the biological features of the most immunoexpressed prostate cancer (PC) profiles (PSA+, PSMA+) according to the RKIP. METHODS: 19 PC with dominant Gleason grade ≥ 8 were studied. Expression of PSA, PSMA, RKIP, Raf-1, MEK-1, ERK-1, ERK-2, p-Akt (T308), p-Akt (S473), NF- κ B p50, and NF- κ Bp65 were detected immunohistochemically. RESULTS: . Loss of RKIP in the most immunoexpressed PC (PSA+, PSMA+) profile was associated with increased levels of PSA and PSMA expression. Intensities of immunoreactions to PSA and PSMA were higher in cancer cells negative for RKIP (12.51 ± 1.6 and 34.95 ± 1.92) compared to those positive for RKIP (4.68 ± 1.11 and 28.56 ± 0.91). In parallel, missing RKIP expression in PC patients with PSA+, PSMA+ profile was connected with increased components of both Raf-1/MEK/ERK and NF- κ B (p65/p50), whereas Akt is activated independently of RKIP. CONCLUSIONS: Although characterized by the same (PSA+, PSMA+) profile, PC phenotype missing the RKIP related to invasive potential and greater biological aggressiveness reflected in overexpression of components of Raf-1/MEK/ERK and NF- κ B (p65/p50) in which Akt is activated independently of RKIP. Taking into account the PC phenotypes according to RKIP among PSA-PSMA profiles may improve distinguishing them from cancers that will become more aggressive and therefore adapt the therapeutic strategies in those patients.


Assuntos
Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Células Tumorais Cultivadas
8.
Cell Biol Int ; 36(5): 449-54, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22103356

RESUMO

Involvement of NF-κB (nuclear factor κB) mediated by IL-1ß (interleukin-1ß) on cell proliferation and PSA (prostate-specific antigen) production of LNCaP prostate cell lines and the possible cross-talk with Akt (also known as protein kinase B) signalling pathway has been investigated. NF-κB and Akt were analysed by Western blotting from LNCaP cells treated by IL-1ß before proliferation and PSA production were measured. IL-1ß inhibited proliferation and decreased PSA production. The Akt pathway was not sensitive, whereas NF-κB phosphorylation occurred as a result of treatment. PSA production and proliferation of LNCaP cells were down-regulated by NF-κB mediated by IL-1ß promoting anti-apoptotic signalling and co-suppressor factors of PSA expression. IL-1ß through NF-κB activation provides a rationale for therapeutic approaches in the anticancer treatment of prostate.


Assuntos
Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Humanos , Interleucina-1beta/farmacologia , Masculino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
J Exp Clin Cancer Res ; 29: 171, 2010 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-21189143

RESUMO

BACKGROUND: The present study was undertaken to relate the co-expression of prostate-associated antigens, PSMA and PSA, with the degree of vascularization in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression. METHODS: The study was carried out in 6 normal, 44 benign prostatic hyperplastic and 39 cancerous human prostates. Immunohistochemical analysis were performed using the monoclonal antibody CD34 to determine the angiogenic activity, and the monoclonal antibodies 3E6 and ER-PR8 to assess PSMA and PSA expression, respectively. RESULTS: In our study we found that in normal prostate tissue, PSMA and PSA were equally expressed (3.7 ± 0.18 and 3.07 ± 0.11). A significant difference in their expression was see in hyperplastic and neoplastic prostates tissues (16.14 ± 0.17 and 30.72 ± 0.85, respectively) for PSMA and (34.39 ± 0.53 and 17.85 ± 1.21, respectively) for PSA. Study of prostate tumor profiles showed that the profile (PSA+, PSMA-) expression levels decreased between normal prostate, benign prostatic tissue and primary prostate cancer. In the other hand, the profile (PSA-, PSMA+) expression levels increased from normal to prostate tumor tissues. PSMA overexpression was associated with high intratumoral angiogenesis activity. By contrast, high PSA expression was associated with low angiogenesis activity. CONCLUSION: These data suggest that these markers are regulated differentially and the difference in their expression showed a correlation with malignant transformation. With regard to the duality PSMA-PSA, this implies the significance of their investigation together in normal and pathologic prostate tissues.


Assuntos
Antígenos de Superfície/biossíntese , Glutamato Carboxipeptidase II/biossíntese , Antígeno Prostático Específico/biossíntese , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia
10.
Eur Cytokine Netw ; 21(4): 241-50, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21081304

RESUMO

BACKGROUND: There is growing evidence that inflammation is a causal factor in cancer, where pro-inflammatory cytokines such as IL-6, IL-1 or TNF-α could induce cellular proliferation by activation of NF-κB. This study focuses on the IL-6/ERK transduction pathway, its relationship with NF-κB, and the consequences of dysregulation in the development of prostate pathologies such as benign prostate hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate cancer (PC). METHODS: Immunohistochemical and Western blot analyses for IL-6, gp-130, Raf-1, MEK-1, ERK-1, p-MEK, ERK-2, p-ERK, NF-κB/p-50 and NF-κB/p-65 were carried out in 20 samples of normal prostate glands, 35 samples of BPH, 27 samples with a diagnosis of PIN (low-grade PIN or high-grade PIN), and 95 samples of PC (23 with low, 51 with medium and 21 with high Gleason scores). RESULTS: Immunoreaction to IL-6, gp-130, ERK-1, ERK-2, p-ERK and NF-κB/p50 was found in the cytoplasm of epithelial cells in normal prostate samples; p-MEK was found in the nucleus of epithelial cells; but not expression to Raf-1, MEK-1 and NF-κB/p65. In BPH, all of these proteins were immunoexpressed, while there was increased immunoexpression of IL-6, gp-130, p-MEK, ERK-1, ERK-2 and NF-κB/p50 (cytoplasm). In PC, immunoexpression of IL-6 and gp-130 were similar to that found in BPH; while immunoexpression of Raf-1, MEK-1, p-MEK, ERK-1, ERK-2, p-ERK, NF-κB/p50 (nucleus and cytoplasm), and NF-κB/p65 (nucleus and cytoplasm) was higher than in BPH. CONCLUSION: Translocation of NF-κB to the nucleus in PC and high-grade PIN could be stimulated by the IL-6/ERK transduction pathway, but might also be stimulated by other transduction pathways, such as TNF-α/NIK, TNF/p38, IL-1/NIK or IL-1/p38. Activation of NF-κB in PC could regulate IL-6 expression. These transduction pathways are also related to activation of other transcription factors such as Elk-1, ATF-2 or c-myc (also involved in cell proliferation and survival). PC is a heterogeneous disease, where multiple transduction pathways might alter the apoptosis/proliferation balance. Significant attention should be give to the combination of novel agents directed towards inactivation of pro-inflammatory cytokines than can disrupt tumour cell growth.


Assuntos
Interleucina-6/metabolismo , NF-kappa B/metabolismo , Próstata/enzimologia , Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Proteínas Tirosina Fosfatases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasia Prostática Intraepitelial/enzimologia , Neoplasia Prostática Intraepitelial/fisiopatologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Transdução de Sinais , Adulto Jovem
11.
Arch Esp Urol ; 62(5): 359-66, 2009 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-19721171

RESUMO

OBJECTIVES: Cancer is a complex process in which cytokines play an important role. Cytokines are low-molecular weight soluble proteins involved in cellular transmission signals and several disorders. Pro-inflammatory cytokines (IL-1, TNF-alpha and IL-6) are involved in prostate cancer development. The aim of this study was to relate the expression (analyzed by Western blot and immuno-histochemistry) of several pro-inflammatory cytokines (IL-1, TNF-alpha and IL-6) with serum levels of prostate-specific antigen (PSA) in normal (no pathological samples) as pathological samples (hyperplasia and cancer), in order to elucidate their possible role in tumor progression. We are also discussing the possible use of these cytokines as a potential therapeutic target. METHODS: This study was carried out in 5 normal, 25 benign prostatic hyperplastic (BPH) and 17 prostate cancer (PC) human prostates. Immunohistochemical and Western blot analysis were performed. Serum levels of PSA were assayed by a PSA DPC immulite assays (Diagnostics Products Corporation, Los Angeles, CA). RESULTS: In BPH, IL-1alpha, IL-6 and TNF-alpha were only expressed in patients with PSA serum levels of 0-4 ng/ml or 4-20 ng/ml, but not in the group >20 ng/ml. In PC these cytokines were only expressed in patients with PSA serum levels >4 ng/ml, although the expression of these cytokines was elevated when PSA levels were >20 ng/ml. CONCLUSIONS: In PC there might be an association between high expression of pro-inflammatory cytokines (IL-1, TNFalpha and IL-6), elevated serum levels of PSA and cancer progression. A better understanding of the biologic mechanism of this association may improve the finding of new targets for therapy in these patients.


Assuntos
Interleucina-1/biossíntese , Interleucina-6/biossíntese , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Fator de Necrose Tumoral alfa/biossíntese , Idoso , Idoso de 80 Anos ou mais , Humanos , Interleucina-1/análise , Interleucina-6/análise , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/patologia , Neoplasias da Próstata/química , Fator de Necrose Tumoral alfa/análise
12.
Arch. esp. urol. (Ed. impr.) ; 62(5): 359-366, jun. 2009. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-72608

RESUMO

OBJETIVO: El cáncer es un proceso complejo en el cual las citoquinas juegan un importante papel. Las citoquinas son proteínas solubles de bajo peso molecular, que participan en la transmisión celular y en diferentes patologías. Las citoquinas pro-inflamatorias (IL-1, TNF-α e IL-6) están muy relacionadas con el desarrollo del cáncer de próstata. El objetivo de nuestro trabajo consistió en relacionar la expresión (mediante inmunocitoquímica y Western blot) de diferentes citoquinas pro-inflamatorias (IL-1, TNF-α e IL-6) con los niveles de antígeno prostático específico (PSA) en suero, tanto en pacientes normales (sin patología prostática) como en condiciones patológicas (hiperplasia y cáncer), así como su posible papel en la progresión tumoral. Se discutirá el posible uso de estas citoquinas como diana terapéutica.MÉTODOS: Este estudio se ha realizado en 5 pacientes normales, 25 pacientes diagnosticados de hiperplasia benigna de próstata (HBP) y 17 pacientes de cáncer (CP). Se han realizado análisis de Western blot e inmunocitoquímica. Los niveles séricos de PSA se midieron mediante un “PSA DPC immulite assays” (Diagnostics Products Corporation, Los Angeles, CA).RESULTADOS: En HBP, IL-1α, IL-6 y TNF-α, solo se expresan en pacientes con niveles séricos de PSA de 0-4 ng/ml ó 4-20 ng/ml, pero no en el grupo >20 ng/ml. En cáncer, estas citoquinas se expresan en pacientes con niveles séricos de PSA >4 ng/ml, aunque la expresión de estas citoquinas se eleva considerablemente cuando los niveles de PSA son >20 ng/ml.CONCLUSIONES: En cáncer, podría existir una asociación entre elevada expresión de citoquinas pro-inflamatorias (IL-1, TNF-α e IL-6), elevados niveles séricos de PSA y progresión del cáncer. Un mejor conocimiento de los mecanismos biológicos de esta asociación, podrían ayudarnos a encontrar una posible diana terapéutica para los pacientes con patología prostática(AU)


OBJECTIVES: Cancer is a complex pro-cess in which cytokines play an important role. Cytoki-nes are low-molecular weight soluble proteins involved in cellular transmission signals and several disorders. Pro-inflammatory cytokines (IL-1, TNF-α and IL-6) are involved in prostate cancer development. The aim of this study was to relate the expression (analyzed by Western blot and immuno-histochemistry) of several pro-inflammatory cytokines (IL-1, TNF-α and IL-6) with serum levels of prostate-specific antigen (PSA) in normal (no pathological samples) as pathological samples (hyperplasia and cancer), in order to elucidate their possible role in tumor progression. We are also discussing the possible use of these cytokines as a potential therapeutic target.METHODS: This study was carried out in 5 normal, 25 benign prostatic hyperplastic (BPH) and 17 prostate cancer (PC) human prostates. Immunohistochemical and Western blot analysis were performed. Serum levels of PSA were assayed by a PSA DPC immulite assays (Diag-nostics Products Corporation, Los Angeles, CA)RESULTS: In BPH, IL-1α, IL-6 and TNF-α were only ex-pressed in patients with PSA serum levels of 0-4 ng/ml or 4-20 ng/ml, but not in the group >20 ng/ml. In PC these cytokines were only expressed in patients with PSA serum levels >4 ng/ml, although the expression of these cytokines was elevated when PSA levels were >20 ng/ml.CONCLUSIONS: In PC there might be an association between high expression of pro-inflammatory cytokines (IL-1, TNFα and IL-6), elevated serum levels of PSA and cancer progression. A better understanding of the biologic mechanism of this association may improve the finding of new targets for therapy in these patients(AU)


Assuntos
Humanos , Masculino , Feminino , Fator de Necrose Tumoral alfa , Interleucina-6 , Interleucina-1 , Antígeno Prostático Específico , Neoplasias da Próstata , Imuno-Histoquímica , Western Blotting
13.
Cancer Detect Prev ; 32(1): 23-32, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18400418

RESUMO

BACKGROUND: The aim of this study was to relate the expression, analyzed by Western blot and immunohistochemistry, of several pro-inflammatory cytokines, including IL-1, IL-6 and TNF-alpha, with serum levels of prostate-specific antigen (PSA) in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression. We are also discussing the possible use of these cytokines as a potential therapeutic target. METHODS: The study was carried out in 5 normal, 25 benign prostatic hyperplastic (BPH) and 17 cancerous human prostates (PC). Immunohistochemical and Western blot analysis were performed. Serum levels of PSA were assayed by an immulite autoanalyzer. RESULTS: The most relevant results showed that in BPH, IL-1alpha, IL-6 and tumor necrosis factor (TNF) were only expressed in patients with PSA serum levels of 0-4 or 4-20 ng/ml, but not in the group >20 ng/ml. In PC these cytokines were only expressed in patients with PSA serum levels >4 ng/ml. CONCLUSIONS: In PC there was an association between the high expression of pro-inflammatory cytokines (TNFalpha, IL-6, IL-1), elevated serum levels of PSA and cancer progression. A better understanding of the biologic mechanism of this association may provide new targets for therapy in these patients.


Assuntos
Citocinas/metabolismo , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade
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