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2.
Clin Chim Acta ; 495: 161-166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30978328

RESUMO

BACKGROUND: According to quality specifications required by international guidelines, the evaluation of the 99th URL value is a very difficult task that is usually beyond the capacity of a single laboratory. The aims of this article are to report and discuss the results of a multicenter study concerning the evaluation of the 99th percentile URL and reference change (RCV) of the ADVIA Centaur High-Sensitivity Troponin I (TNIH), recently distributed to the Italian clinical laboratories. MATERIALS AND METHODS: The reference population evaluated with ADVIA XPT method for the calculation of cTnI reference distribution parameters consisted of 1325 healthy adults subjects (age range from 18 to 86 years), including 653 women (mean age 50.7 years, SD 14.5 years) and 672 men (mean age 50.9 years, SD 13.8 years), well matched for both age (P = .8112) and sex (F/M = 0.97). RESULTS: cTnI distribution values of reference population was highly skewed, while log-transformed cTnI values roughly approximated a log-normal distribution. Men have higher cTnI values than women throughout all the adult lifespan. Moreover, the subjects with age ≤ 55 years had significantly lower cTnI values than those with age > 55 years (p < .0001). Of note, 62% of women and 77% of men had equal or higher than cTnI values than the LoD value of the method (i.e., 2.2 ng/L). CONCLUSIONS: The results of the present study demonstrate that the ADVIA Centaur High-Sensitivity Troponin I using the XPT automated platform fits both the criteria and quality specifications required by the most recent international guidelines for high-sensitivity methods for cTnI assay.


Assuntos
Análise Química do Sangue/normas , Miocárdio/metabolismo , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoensaio/normas , Masculino , Pessoa de Meia-Idade , Valores de Referência , Troponina I/metabolismo , Adulto Jovem
3.
Clin Chim Acta ; 493: 156-161, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826369

RESUMO

BACKGROUND: The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. MATERIALS AND METHODS: Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. RESULTS AND CONCLUSIONS: The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca/normas , Eletrocardiografia/normas , Troponina I/sangue , Troponina T/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
4.
J Autoimmun ; 98: 113-121, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30638709

RESUMO

Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed. Treatment ex vivo with TPC decreased the production of IL-1ß, IL-2, IL-5, IL-6, IL-9, IL-12(p70), IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IFNγ, TNFα, GM-CSF by CD3/CD28 activated PBMCs whereas it negligibly affected cell viability. It reduced Th1 and Th17 differentiation while did not impact Th22 differentiation in PBMCs stimulated by phorbol 12-myristate 13-acetate plus ionomycin. In inflamed TABs, treatment with TPC down-regulated the production of IL-1ß, IL-6, IL-13, IL-17A and CD68 gene expression. The effects of TPC were comparable to the effects of dexamethasone, included as the standard of care, with the exception of a greater reduction of IL-2, IL-18, IFNγ in CD3/CD28 activated PBMCs and CD68 gene in inflamed TABs. In conclusion our results warrant further investigations regarding TPC as an immunotherapeutic agent in GCA and potentially other autoimmune and inflammatory diseases.

5.
Rheumatology (Oxford) ; 57(1): 64-72, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968695

RESUMO

Objectives: GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods: Patients subjected to temporal artery biopsies (TABs) naïve from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated. Results: Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor. Conclusion: IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.


Assuntos
Arterite de Células Gigantes/metabolismo , Interleucinas/metabolismo , Artérias Temporais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos , Ionóforos de Cálcio/farmacologia , Carcinógenos/farmacologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Arterite de Células Gigantes/genética , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Interleucinas/sangue , Interleucinas/genética , Ionomicina/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Acetato de Tetradecanoilforbol/farmacologia
6.
Clin Chem Lab Med ; 56(3): 397-402, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29220884

RESUMO

It is well known that the results of immunoassay methods can be affected by specific or non-specific interferences, ranging from 0.4% to 4.0%. The presence of interference may greatly compromise the accuracy of immunoassay analyses causing an error in the measurement, producing false-positive or false-negative results. From a clinical point of view, these analytical errors may have serious implications for patient care because they can cause misdiagnosis or inappropriate treatment. Unfortunately, it is a very difficult task to identify the irregular analytical errors related to immunoassay methods because they are not detectable by normal laboratory quality control procedures, are reproducible within the test system, may be clinically plausible and are relatively rare. The first line of defense against erroneous results is to use in laboratory practice only immunoassay systems with the highest level of robustness against interference. The second line of defense is always taking into account the possibility of interference in immunoassay results. A correct approach should be addressed on identification of samples at high risk of interference. The attainment of this goal requires a critical review of the test result in relation to patient's clinical conditions and literature data, taking into account the analytical characteristics of the immunoassay system. The experts in immunoassay systems should make every effort to find some specific and reliable quality indicators for irregular analytical errors in order to better detect and monitor erroneous immunoassay results due to specific or non-specific interferences.


Assuntos
Técnicas de Laboratório Clínico , Erros de Diagnóstico , Imunoensaio , Humanos , Controle de Qualidade
8.
Semin Arthritis Rheum ; 47(2): 235-240, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28274481

RESUMO

OBJECTIVE: Data on the presence of varicella-zoster virus (VZV) in temporal arteries of patients with giant cell arteritis (GCA) are controversial. We analyzed VZV infection in temporal arteries from Italian patients with temporal artery biopsy (TAB)-positive GCA, TAB-negative GCA, and controls. METHODS: A total of 79 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 at a single institution from 34 TAB-positive GCA patients, 15 TAB-negative GCA patients, and 30 controls were retrieved. Six 5-µm sections of all FFPE TABs were cut. The first section was analyzed by immunohistochemistry using mouse monoclonal anti-VZVgE IgG1 antibody. DNA was extracted from the remaining five sections and analyzed by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. For 10 of the 34 TAB-positive GCA patients, an additional 2-mm piece of frozen TAB was available. DNA was extracted from the entire 2-mm length frozen specimen and analyzed by PCR for the presence of VZV DNA. Thirty additional 5-µm sections were cut from the FFPE TABs of these 10 patients and analyzed by immunohistochemistry for the presence of VZV antigen. RESULTS: Immunohistochemical analysis detected VZV antigen in 1/34 (3%) TAB-positive GCA, 0/15 TAB-negative GCA, and 0/30 controls, and in none of the 300 sections cut from the 10 FFPE TABs positive for GCA for which the frozen specimens were available. DNA obtained from all TABs was amplifiable. VZV DNA was neither found in any of the FFPE TABs nor found in frozen TABs. CONCLUSION: Our data do not support in Italian patients a possible role for VZV infection in the etiopathogenesis of GCA.


Assuntos
Arterite de Células Gigantes/virologia , Herpesvirus Humano 3/isolamento & purificação , Artérias Temporais/virologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Graefes Arch Clin Exp Ophthalmol ; 251(6): 1607-12, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23456172

RESUMO

BACKGROUND: To characterise the polyspecific intraocular antibody synthesis in aqueous humor of patients with Fuchs uveitis and other types of non-infectious uveitis. METHODS: Aqueous and serum samples collected from 24 patients with Fuchs uveitis, 21 patients with non-infectious uveitis, and 27 healthy subjects undergoing elective cataract surgery (control group) were analysed. In addition, vitreous samples, collected from seven uveitis patients (five Fuchs and two panuveitis) during retinal surgery, were examined. Specific immunoglobulin G antibodies against cytomegalovirus (CMV), rubella virus, herpes simplex virus (HSV), and varicella zoster virus (VZV) were investigated, and Goldmann-Witmer coefficients (GWCs) were calculated. Real-time PCR was performed to detect viral genome for HSV, VZV, and CMV, while nested PCR was conducted to detect rubella RNA. RESULTS: None of the control samples tested positive for any of the viral antibodies investigated. Intraocular antibody production was found in eight samples of patients affected by Fuchs uveitis (6/8 positive for rubella virus and 2/8 positive for herpes virus). Among patients with non-infectious uveitis, three tested positive for intraocular antibody production (one RV, one HSV and one for VZV). PCR was positive for RV in two patients with Fuchs uveitis, in three patients with non-infectious uveitis (one for RV and two for HSV), and in three control subjects (one for CMV and one for HSV). CONCLUSIONS: Our series confirmed the presence of specific viral antibodies, especially against rubella virus, in the subgroup of patients affected by Fuchs uveitis, suggesting that this virus may be responsible for this chronic inflammatory condition. Rubella virus is probably the main causative agent of Fuchs uveitis, but other viruses may also be involved in the pathogenesis of this disease.


Assuntos
Anticorpos Antivirais/sangue , Humor Aquoso/virologia , Infecções Oculares Virais/virologia , Distrofia Endotelial de Fuchs/virologia , Genoma Viral , Vírus da Rubéola , Rubéola (Sarampo Alemão)/virologia , Uveíte Anterior/virologia , Adulto , Citomegalovirus/genética , Citomegalovirus/imunologia , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Virais/diagnóstico , Feminino , Distrofia Endotelial de Fuchs/diagnóstico , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/imunologia , Humanos , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Rubéola (Sarampo Alemão)/diagnóstico , Vírus da Rubéola/genética , Vírus da Rubéola/imunologia , Sensibilidade e Especificidade , Simplexvirus/genética , Simplexvirus/imunologia , Uveíte Anterior/diagnóstico , Corpo Vítreo/virologia
10.
Am J Hypertens ; 24(12): 1280-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21850058

RESUMO

BACKGROUND: Adrenal venous sampling (AVS) is the gold standard for the identification of unilateral primary aldosteronism (PA), but is technically difficult. The aim of our study was to assess whether intraprocedural cortisol measurement (IPCM) increases AVS success rate. METHODS: Twenty-five consecutive PA patients underwent cosyntropin-stimulated AVS. Cortisol was measured immediately in a first set of samples drawn from adrenal veins and inferior vena cava. The selectivity criterion was an adrenal vein-to-inferior vena cava cortisol ratio ≥5. If bilateral selectivity was not achieved in a first set of samples, a second set was obtained during the same radiological session. PA was judged as unilateral if the gradient of cortisol-corrected aldosterone between dominant and nondominant side was >3.5. Twenty-five consecutive PA patients who had previously been submitted to AVS without IPCM served as historical controls. Lateralizing patients who underwent unilateral adrenalectomy were followed for 2 years after surgery. RESULTS: Bilateral selectivity using IPCM was achieved in 19/25 patients in the first set of samples, and in an additional four cases in the second set (92% vs. 76%; P = 0.06). The final rate of bilateral selectivity was higher than that obtained in the historical series (23/25 vs. 16/25, P = 0.04), whereas bilateral selectivity in the first set of samples was not different from that achieved in the historical series. Nineteen lateralizing patients (13 of the present series, six of the historical series) were submitted to adrenalectomy, resulting in reversal of PA. CONCLUSIONS: IPCM increases the success rate of AVS.


Assuntos
Hidrocortisona/sangue , Hiperaldosteronismo/sangue , Glândulas Suprarrenais/irrigação sanguínea , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/cirurgia , Aldosterona/sangue , Angiotensina I/sangue , Feminino , Humanos , Hiperaldosteronismo/diagnóstico por imagem , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Flebografia , Renina/sangue , Veia Cava Inferior/diagnóstico por imagem
11.
J Cell Physiol ; 219(2): 314-23, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19137541

RESUMO

The Clusterin (CLU) gene produces different forms of protein products, which vary in their biological properties and distribution within the cell. Both the extra- and intracellular CLU forms regulate cell proliferation and apoptosis. Dis-regulation of CLU expression occurs in many cancer types, including prostate cancer. The role that CLU plays in tumorigenesis is still unclear. We found that CLU over-expression inhibited cell proliferation and induced apoptosis in prostate cancer cells. Here we show that depletion of CLU affects the growth of PC-3 prostate cancer cells. Following siRNA targeting all CLU mRNA variants, all protein products quickly disappeared, inducing cell cycle progression and higher expression of specific proliferation markers (i.e., H3 mRNA, PCNA, and cyclins A, B1, and D) as detected by RT-qPCR and Western blot. Quite surprisingly, we also found that the turnover of CLU protein is very rapid and tightly regulated by ubiquitin-proteasome mediated degradation. Inhibition of protein synthesis by cycloheximide showed that CLU half-life is less than 2 h. CLU protein products were found poly-ubiquitinated by co-immuniprecipitation. Proteasome inhibition by MG132 caused stabilization and accumulation of all CLU protein products, including the nuclear form of CLU (nCLU), and committing cells to caspase-dependent death. In conclusion, proteasome inhibition may induce prostate cancer cell death through accumulation of nCLU, a potential tumor suppressor factor.


Assuntos
Clusterina/metabolismo , Poliubiquitina/metabolismo , Neoplasias da Próstata/metabolismo , Isoformas de Proteínas/metabolismo , Estabilidade Proteica , Animais , Apoptose/fisiologia , Ciclo Celular/fisiologia , Proliferação de Células , Clusterina/genética , Inibidores de Cisteína Proteinase/metabolismo , Inativação Gênica , Humanos , Leupeptinas/metabolismo , Masculino , Neoplasias da Próstata/fisiopatologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Isoformas de Proteínas/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Células Tumorais Cultivadas
12.
PLoS One ; 3(10): e3617, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18974881

RESUMO

BACKGROUND: Prostate cancer (CaP) is one of the most relevant causes of cancer death in Western Countries. Although detection of CaP at early curable stage is highly desirable, actual screening methods present limitations and new molecular approaches are needed. Gene expression analysis increases our knowledge about the biology of CaP and may render novel molecular tools, but the identification of accurate biomarkers for reliable molecular diagnosis is a real challenge. We describe here the diagnostic power of a novel 8-genes signature: ornithine decarboxylase (ODC), ornithine decarboxylase antizyme (OAZ), adenosylmethionine decarboxylase (AdoMetDC), spermidine/spermine N(1)-acetyltransferase (SSAT), histone H3 (H3), growth arrest specific gene (GAS1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and Clusterin (CLU) in tumour detection/classification of human CaP. METHODOLOGY/PRINCIPAL FINDINGS: The 8-gene signature was detected by retrotranscription real-time quantitative PCR (RT-qPCR) in frozen prostate surgical specimens obtained from 41 patients diagnosed with CaP and recommended to undergo radical prostatectomy (RP). No therapy was given to patients at any time before RP. The bio-bank used for the study consisted of 66 specimens: 44 were benign-CaP paired from the same patient. Thirty-five were classified as benign and 31 as CaP after final pathological examination. Only molecular data were used for classification of specimens. The Nearest Neighbour (NN) classifier was used in order to discriminate CaP from benign tissue. Validation of final results was obtained with 10-fold cross-validation procedure. CaP versus benign specimens were discriminated with (80+/-5)% accuracy, (81+/-6)% sensitivity and (78+/-7)% specificity. The method also correctly classified 71% of patients with Gleason score<7 versus > or =7, an important predictor of final outcome. CONCLUSIONS/SIGNIFICANCE: The method showed high sensitivity in a collection of specimens in which a significant portion of the total (13/31, equal to 42%) was considered CaP on the basis of having less than 15% of cancer cells. This result supports the notion of the "cancer field effect", in which transformed cells extend beyond morphologically evident tumour. The molecular diagnosis method here described is objective and less subjected to human error. Although further confirmations are needed, this method poses the potential to enhance conventional diagnosis.


Assuntos
Carcinoma/diagnóstico , Perfilação da Expressão Gênica , Técnicas de Diagnóstico Molecular/métodos , Neoplasias da Próstata/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Idoso , Bancos de Espécimes Biológicos , Carcinoma/genética , Humanos , Laboratórios Hospitalares , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Reprodutibilidade dos Testes
13.
Carcinogenesis ; 27(5): 1047-53, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16314398

RESUMO

We previously found that human prostate cancer (CaP) progression is accompanied by differential expression of a panel of 8 informative genes, some of which are metabolically related. Gene profiling focused on this 8-gene pack by northern blot analysis in combination with standard clinical information provided reliable prognostic prediction of human CaP. For a better insight into the potential of this 8-gene signature in tumor detection/classification and therapeutic response, we determined, by qPCR, the expression of these informative genes in the TRAMP mice model of CaP progression. The 8-genes signature resulted effective in discriminating, by linear discriminant analysis (LDA), the prostate of wild type mice from transgenic TRAMP mice developing CaP (P < 0.0002). Since it is known that Green Tea Catechin (GTC) administration to TRAMP mice results in a substantial delay of CaP progression in 80% of the animals, while 20% remain unresponsive, we determined the 8-gene signature in the prostates of GTC-sensitive and GTC-resistant mice. LDA discriminated benign tissue from CaP (i.e. wild-type + chemoprevented, GTC-sensitive TRAMP mice, in which CaP progression was delayed, was discriminated from TRAMP mice + GTC-resistant TRAMP mice, in which CaP developed irrespective of GTC administration; P < 0.01). Moreover, GTC-sensitive TRAMP mice bearing CaP were discriminated from GTCs-resistant ones, (P = 0.0001). These results show that qPCR gene profiling, based on the signature of the 8-genes selected by us, could represent an appropriate means for studying the biological behavior of CaP, which may lead to identifying new tools of potential prognostic value, in that a molecular classification for the presence/absence of cancer and for discriminating GTCs-responsive from GTC-resistant CaP is provided.


Assuntos
Catequina/metabolismo , Perfilação da Expressão Gênica/métodos , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Anticarcinógenos/farmacologia , Primers do DNA/química , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Prognóstico , Chá
14.
J Cell Physiol ; 207(1): 208-19, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16331665

RESUMO

Clusterin (CLU), whose role is still debated, is differentially regulated in several patho-physiological processes and invariably induced during apoptosis. In heat shock response, CLU is considered a stress-inducible, pro-survival/cyto-protective factor via an HSE element present in his promoter. In both human prostate PNT1A and PC-3 epithelial cells we found that apoptotic stimuli induced nuclear localization of CLU (nCLU), and that overexpression of nCLU is pro-apoptotic. We show here that CLU time-course accumulation kinetic is different from that of HSP70 in these cells, thus other factor(s) might mediate HSF-1 activation and CLU expression. Sub-lethal heat shock inhibited the secretion of CLU (sCLU), leading to increased cytoplasm accumulation of CLU (cCLU) in association to cell survival. At difference, lethal heat stress caused massive accumulation of pro-apoptotic nCLU in cells dying by caspase-3-dependent apoptosis. Double heat stress (sub-lethal heat shock followed by recovery and lethal stress) induced HSP70 and thermo-tolerance in PNT1A cells, but not in PC-3 cells. In PNT1A cells, CLU secretion was inhibited and cCLU was accumulated, suggesting that cCLU might be pro-survival, while in PC-3 cells accumulation of nCLU was concomitant to caspase-3 induction and PARP activation instead. Thus, CLU expression/sub-cellular localization is strictly related to cell fate. In particular, nCLU and physiological levels of HSP70 affected cell survival in an antagonistic fashion. Prevalence of heat-induced nCLU, not allowing PC-3 cells to cope with heat shock, could be the rational explaining why malignant cells are more sensitive to heat when delivered by minimally invasive procedures for ablation of localized prostate cancer.


Assuntos
Núcleo Celular/metabolismo , Clusterina/metabolismo , Temperatura Alta , Neoplasias da Próstata/metabolismo , Apoptose/fisiologia , Caspase 3 , Caspases/metabolismo , Linhagem Celular Transformada , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/fisiologia , Clusterina/genética , Meios de Cultivo Condicionados/química , Citoplasma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Fatores de Transcrição de Choque Térmico , Resposta ao Choque Térmico , Humanos , Masculino , Poli(ADP-Ribose) Polimerases/metabolismo , Transporte Proteico , Fatores de Tempo , Fatores de Transcrição/metabolismo
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