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Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods. The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low.Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.
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Anemia Aplástica/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda/metabolismo , Síndromes Mielodisplásicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tirosina Quinase 3 Semelhante a fms/metabolismo , Adolescente , Adulto , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/mortalidade , Trióxido de Arsênio , Arsenicais/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Óxidos/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Sequências de Repetição em Tandem/genética , Tretinoína/administração & dosagem , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
We developed superconducting nanowire single-photon detectors based on tungsten silicide, which show saturated internal detection efficiency up to a wavelength of 10 µm. These detectors are promising for applications in the mid-infrared requiring sub-nanosecond timing, ultra-high gain stability, low dark counts, and high efficiency, such as chemical sensing, LIDAR, dark matter searches, and exoplanet spectroscopy.
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BACKGROUND: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. METHODS: We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). MAIN RESULTS: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. CONCLUSIONS: TSLP variants are associated with asthma in a sex-specific fashion.
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Asma/genética , Citocinas/genética , Predisposição Genética para Doença/genética , Caracteres Sexuais , População Negra/genética , Criança , Estudos de Coortes , Costa Rica , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Hispânico ou Latino/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genética , Linfopoietina do Estroma do TimoRESUMO
Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis in a patient of scleroderma is very rare. Very few cases have been reported in English literature. We report a case of a 58-year-old male with long-standing limited cutaneous scleroderma (Scl-70 positive) presenting with normotensive scleroderma renal crisis. Perinuclear ANCA with antimyeloperoxidase antibody was found to be strongly positive. Renal biopsy showed pauci immune-necrotizing crescentic glomerulonephritis. We believe that this case report will be helpful in understanding clinical features of normotensive ANCA-associated glomerulonephritis in scleroderma patients.
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BACKGROUND: The present study evaluated the clinical significance of BAG-1, an antiapoptotic protein, in leukoplakia and carcinoma of the tongue. METHODS: BAG-1 expression was evaluated by immunohistochemistry in paraffin-embedded tissues of leukoplakia (n=25) and carcinoma of the tongue (n=61). RESULTS: Cytoplasmic expression was predominantly seen in 80% and 70% of patients with leukoplakia and carcinoma, respectively. BAG-1 expression was found to be significantly lower in tobacco users than in non-tobacco users. BAG-1 expression in tobacco-using leukoplakia and carcinoma patients was compared by grouping the carcinoma patients according to lymph node status and disease stage. Carcinoma patients with tumor-positive lymph nodes had significantly lower BAG-1 expression than patients with negative lymph nodes and leukoplakia. Further, a trend towards an inverse correlation was observed with p53 and c-erbB2. In univariate and multivariate survival analysis, patient subgroups with 2+ or 3+ marker positivity (BAG-1 negativity, p53 and c-erbB2 positivity) had a reduced overall survival compared with patient subgroups with 1+ marker positivity or negativity. CONCLUSION: BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype. Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis.
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Proteínas de Ligação a DNA/genética , Leucoplasia Oral/patologia , Proteínas de Neoplasias/genética , Receptor ErbB-2/metabolismo , Neoplasias da Língua/patologia , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/metabolismo , Citoplasma/patologia , Proteínas de Ligação a DNA/metabolismo , Humanos , Imuno-Histoquímica , Metástase Linfática , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Fumar/sangue , Análise de Sobrevida , Tabaco sem Fumaça , Neoplasias da Língua/mortalidade , Fatores de Transcrição/metabolismoRESUMO
There is growing interest in assessing multistep carcinogenesis and predicting its course using different molecular markers. TP53 is a tumor suppressor gene and appears to be one of the molecular targets of tobacco-related carcinogens in oral cancer. The present study evaluated the role of p53 expression in patients with leukoplakia and carcinoma of the tongue. p53 expression was studied by immunohistochemistry. All patients with leukoplakia of the tongue were male tobacco users. Nuclear staining of p53 was observed in 79% of those patients. Fifty percent, 25% and 4% of the patients expressed 1+, 2+ and 3+ nuclear staining, respectively. When leukoplakia patients were graded according to histopathology, 67% had hyperplasia and 33% had dysplasia. Nuclear p53 accumulation was 88% in hyperplasia and 62% in dysplasia. In patients with tongue cancer, nuclear accumulation of p53 was seen in only 19% of the tumors, with a staining intensity of 1+ in 13%, 2+ in 2% and 3+ in 4% of the tumors. The prevalence of nuclear p53 positivity (79%) was significantly higher in patients with leukoplakia than in patients with tongue cancer (19%; chi2 = 34.32, r = -0.45, df = 1, p = 0.0001; odds ratio (OR) = 16.66, 95% CI, 5.25-52.86). Therefore, leukoplakia patients who show p53 expression have a higher risk of developing tongue cancer than those who do not show p53 expression. As the percentage of positivity of nuclear p53 was very low, none of the clinicopathological parameters or disease status showed any significant association with it. The interesting finding is that none of the female cancer patients showed nuclear p53 expression. Therefore, p53 accumulation is believed to be an early event in neoplastic progression of the tongue.
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Carcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes p53 , Leucoplasia Oral/metabolismo , Neoplasias da Língua/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Adulto , Núcleo Celular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVES: (1)To assess the nutritional status of chronic renal insufficiency (CRI) and dialysis patients using the subjective global assessment (SGA) method. (2) To validate SGA in assessing the nutritional status of this group of patients. PARTICIPANTS: The nutritional status of 81 patients was evaluated using dietary recall, anthropometry, biochemical parameters and SGA. There were 51 males and 30 females. Their mean +/- SD age was 53.8 +/- 14.3 years. There were 27 patients with (CRI) on conservative management, 38 patients with end stage renal disease (ESRD) on maintenance hemodialysis (HD) and 16 patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD). METHODS: SGA was done using seven variables derived from medical history and physical examination. Each variable was scored from 1-7 depending on the severity. The SGA scores were correlated with the standard methods. RESULTS: Thirteen (48%) patients with CRI, 22 (58%) patients on HD and 8 (50%) patients on CAPD were malnourished. It was seen that the dietary protein & calorie intake and serum albumin level did not correlate well with the SGA scores. The anthropometric measures correlated with the SGA scores (Skinfolds and SGA r = 0.2, MAC and SGA r = 0.5 and MAMC and SGA r = 0.5). CONCLUSION: Malnutrition is an important complication in CRI patients and ESRD patients on dialysis. SGA is a reliable method of assessing nutritional status. Most important is the fact that it can detect the changing trend of nutritional status, which may be missed by one-time anthropometry and biochemical methods.
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Desnutrição/etiologia , Avaliação Nutricional , Estado Nutricional , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Resultado do Tratamento , Adulto , Antropometria , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Flow cytometry is highly sensitive for detection and quantitative analysis of surface and intracellular antigens in malignant hemopoietic cells. Immunophenotyping is a routine practice for classification and lineage assignment of acute leukemia. In the present study, our aim is to identify the role of a single 5 color, CD45, myeloperoxidase (MPO), cCD79a, cCD3, and Tdt, cytoplasmic markers combination as a primary tube. We compared with final diagnosis on the basis of morphology, cytochemistry, and primary and secondary panels of immunophenotyping and also with other study. MATERIALS AND METHODS: We have included 455 new cases of acute leukemias with applied primary and secondary panels of markers for immunophenotyping. We analyzed sensitivity and specificity of different subsets with combination of positive and negative markers. RESULTS: MPO was positive in 61.4% of acute myeloid leukemia (AML) cases. All 184 (100%) cases of the AML were negative for cCD3 and cCD79a co-expression. cCD79a expression was highly sensitive as 98.5% B-acute lymphoblastic leukemia (B-ALL) expressed it. cCD3 expression was detected in 100% cases of T-ALL, and its co-expression was not seen in B-ALL and AML. CONCLUSION: Our study indicates that there was very good correlation of 5-color cytoplasmic tube-based diagnosis versus final diagnosis based on morphology, cytochemistry, and flow cytometry. We can use this 5-color cytoplasmic tube method to make immunophenotyping cost-effective.
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Imunofenotipagem/métodos , Leucemia/imunologia , Doença Aguda , Citometria de Fluxo , Humanos , Leucemia/patologiaRESUMO
We describe the properties of ultrasensitive graphene photon detectors for use in the far-infrared/terahertz spectral region and present theoretical predictions for their power detection sensitivity. These predictions are based on two graphene contacting schemes with superconducting contacts: contacts with a thin insulating barrier, and direct superconducting contacts. To quantitatively assess these predictions, we perform thermal measurements of graphene at low temperatures and analyse them to extract information on electron-phonon cooling in graphene. These new results for the electron-phonon cooling channel allow reliable prediction of the noise equivalent power (NEP) that can be expected from an optimized graphene detector, using measurement of the Johnson noise emission as the thermometry method. We find that an NEP of 2 × 10(-19) W Hz(-1/2) should be achievable under certain biasing conditions with an ideal device.
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The association of air pollution with the prevalence of chronic lower respiratory tract symptoms among children with a history of asthma or related symptoms was examined in a cross-sectional study. Parents of a total of 3,676 fourth, seventh, and tenth graders from classrooms in 12 communities in Southern California completed questionnaires that characterized the children's histories of respiratory illness and associated risk factors. The prevalences of bronchitis, chronic phlegm, and chronic cough were investigated among children with a history of asthma, wheeze without diagnosed asthma, and neither wheeze nor asthma. Average ambient annual exposure to ozone, particulate matter (PM(10) and PM(2.5); [less than/equal to] 10 microm and < 2.5 microm in aerodynamic diameter, respectively), acid vapor, and nitrogen dioxide (NO(2)) was estimated from monitoring stations in each community. Positive associations between air pollution and bronchitis and phlegm were observed only among children with asthma. As PM(10) increased across communities, there was a corresponding increase in the risk per interquartile range of bronchitis [odds ratio (OR) 1.4/19 microg/m(3); 95% confidence interval (CI), 1.1-1.8). Increased prevalence of phlegm was significantly associated with increasing exposure to all ambient pollutants except ozone. The strongest association was for NO(2), based on relative risk per interquartile range in the 12 communities (OR 2.7/24 ppb; CI, 1.4-5.3). The results suggest that children with a prior diagnosis of asthma are more likely to develop persistent lower respiratory tract symptoms when exposed to air pollution in Southern California.
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Poluição do Ar/efeitos adversos , Asma/complicações , Bronquite/etiologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Dióxido de Nitrogênio/toxicidade , Ozônio/toxicidade , Sons Respiratórios/etiologiaRESUMO
Serum FSH, LH, prolactin and plasma estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were estimated by RIA method in male patients with tongue cancer (N=110) and in healthy age-matched male controls (N=25). In this retrospective study, there was a trend towards higher levels of FSH (P<0.01), LH (P<0.01), prolactin (P<0.001), estradiol (P<0.0001), progesterone (P<0.0001) and DHEA (P<0.01) with concomitant lower levels of testosterone (P<0.001) and DHEA-S (P<0.02) in patients with tongue cancer compared to controls. We did not find significant difference in hormone levels when grouped according to the site of the tumor and stage of the disease. Patients below 40 years of age had significantly higher levels of DHEA and DHEA-S and lower levels of FSH than their counterparts. We observed a decreased ratio of testosterone: estradiol and increased levels of FSH, LH and prolactin in tongue cancer patients. These hormonal abnormalities clearly suggest a disturbance in the pituitary-adrenal-testicular axis. Based on our previous work and from these results, we suggest that prolactin might be playing an important role in the development and progression of tongue cancer.
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Hormones are believed to play a dominant role as promoters in the growth and development of hormone-dependent cancers. Much less is known about the circulating hormones in male patients with oesophageal cancer. This lack of attention led us to evaluate the role of peptide and steroid hormones (by RIA) in male patients with oesophageal cancer (n=49). Blood samples of patients were collected pretherapeutically and data was compared with age matched controls (n=25). In this retrospective study, significantly high levels of FSH (P<0.02), LH (P<0.001) and prolactin (P<0.001) were observed with concomitant low levels of estradiol (P<0.001), DHEA-S (P<0.02) and testosterone (P<0.001) in patients when compared with respective controls. The patients when grouped according to anatomical site and histological type of the tumor, intergroup variation was not observed in these hormones. From our, study, it seems that hormonal imbalance or altered ratio of peptide and steroid hormones might be playing a significant role in the development and/or progression of oesophageal carcinoma in men.
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The value of plasma prolactin (PRL), estrogen-receptor (ER) and progesterone-receptor (PR) determinations in predicting overall survival was evaluated in a group of 151 breast cancer patients. The patients were enrolled at The Gujarat Cancer and Research Institute, Ahmedabad and were followed for a period of three years. As 85% patients had node-positive disease (N=129), the results were analyzed only for this group of patients. Of the 129 node-positive breast cancer patients, 61% had hyperprolactinemia (PRL >20.0 ng/ml plasma), and ER+ tumors. 67% of the tumors were PR+. Significant correlation was not observed between age, menopausal status and clinicopathological features and ER and PR content. When the patients were subgrouped according to the cut-off levels for the three prognostic indicators i.e. PRL, ER and PR, the difference between the two subgroups of PRL was statistically significant for overall survival (P<0.02). ER+ and PR+ patients had better overall survival than their counterparts. However, the differences were statistically non-significant for both the subgroups. Moreover, ER- hyperprolactinemic patients had unfavourable prognosis (P<0.02) compared to their counterparts. This study suggest that hyperprolactinemia is an important indicator of unfavourable prognosis in node-positive breast cancer patients, both when evaluated singly and in conjunction with steroid receptors, ER-hyperprolactinemic patients had poor prognosis.
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Pre-therapeutic circulating prolactin levels and tumoral prolactin receptors (PRLR) were determined in 25 male patients with tongue cancer. The patients were divided into PRLR positive (PRLR+) and PRLR negative (PRLR-) groups. The overall survival was statistically non-significant between these two groups of PRLR as well as when considering 2% as the cut-off level. Moreover, no correlation was observed between PRLR status and clinicopathologic prognosticators. Furthermore, patients with < 2% PRLR had significantly higher levels of circulating prolactin than their counterparts (P < 0.05). Patients with PRLR- tumors having hyperprolactinemia (prolactin > 15.0 ng/ml) had unfavourable overall survival (chi 2 = 4.08, df = 1, P < 0.04) than those with normoprolactin (prolactin < 15.0 ng/ml). From this pilot study, it seems that PRLR negativity with hyperprolactinemia could be used as an independent predictor of short-term prognosis in cancer tongue patients.
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Carcinoma de Células Escamosas/metabolismo , Prolactina/sangue , Receptores da Prolactina/metabolismo , Neoplasias da Língua/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Humanos , Masculino , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Neoplasias da Língua/sangue , Neoplasias da Língua/mortalidadeRESUMO
AIMS: The aim of this study was to evaluate the prognostic value of pre-operative prolactin (PRL) in conjunction with established prognosticators, and the risk of disease relapse in patients with early and advanced breast cancer. To confirm the hypothesis that PRL is produced by breast tumours molecular analysis of PRL, using immunohistochemistry, mRNA by RT-PCR and direct sequencing, was performed. Furthermore, presence of prolactin receptors (PRLR) was evaluated by immunohistochemical localization in these patients. METHODS: In 111 breast cancer patients, pre-operative PRL was determined by an immunoradiometric assay (IRMA) method. Immunohistochemical localization of PRL (IHL-PRL) and PRLR was performed on formalin-fixed, paraffin-embedded tissue sections. Expression of PRL mRNA was carried out by reverse transcriptase polymerase chain reaction (RT-PCR). RT-PCR PRL amplimer was sequenced and compared with human pituitary PRL amplimer. RESULTS: Fifty-eight per cent (64/111) of the patients had hyperprolactinaemia (PRL520.0 ng/ml). With increasing tumour size, a higher incidence of hyperprolactinaemia was noted which was statistically significant (r=0.34, P=0.0001). In stage III patients, and in node positive patients, the incidence of hyperprolactinaemia was significantly higher compared to their respective counterparts (stage II vs stage III, r=0.37, P=0.00006; node negative vs node positive, r=0.30, P=0.001). Hyperprolactinaemic patients had a significantly higher risk of developing recurrent/metastatic disease and a higher mortality risk as compared to patients with PRL <20.0 ng/ml. The multivariate survival analysis indicated that apart from disease stage, prognosis of patients with pre-operative hyperprolactinaemia was poorer than that of patients with PRL <20.0 ng/ml. Seventy-eight per cent (87/111) of the tumours showed positive immunoreactivity with PRL antibody indicating that PRL, or a similar molecule, is produced ectopically by breast tumours. PRL mRNA expression using RT-PCR confirmed the de novo synthesis of PRL. PRL mRNA expression was seen in 52% (33/63) of tumours. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to the sequence of exon 5 of human pituitary PRL mRNA. Furthermore, PRLR were present in 80% of tumours detected by immunohistochemical localization. A significant positive correlation was noted between IHL-PRL and PRLR (r=0.26, P=0.006). CONCLUSIONS: This multifaceted study of PRL suggests that breast cancer cells produce PRL and that this ectopically produced PRL may act as a major local growth promoter via autocrine and paracrine mechanisms. It may provide new insights into endocrine treatment of breast cancer.
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Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/metabolismo , Substâncias de Crescimento/biossíntese , Prolactina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Substâncias de Crescimento/sangue , Substâncias de Crescimento/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Prolactina/sangue , Prolactina/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores da Prolactina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
Prognostic value of IGF-1 receptors (IGF-1R) was evaluated and compared with circulating prolactin (PRL) in 59 patients with Dukes B or C colon/rectal cancer. IGF-1R was estimated by radioligand binding assay and PRL was estimated by immunoradiometric assay. Eighty-five percent (50/59) of patients had IGF-1R- tumours while IGF-1R positivity was observed in only 15% (9/59) of patients. None of the clinicopathological parameters showed any association with IGF-1R status. No significant difference was observed in overall survival period between patients with IGF-1R+ tumours and those with IGF-1R- tumours. However, a significant difference in overall survival time was observed between patients with PRL < 20.0 and > 20.0 ng/ml plasma (X2 = 4.70, df = 1, P < 0.05). In bivariate analysis, patients with IGF-1R- tumours and concomitant hyperprolactinemia had unfavourable prognosis compared to their counterpart (X2 = 4.21, df = 1, P < 0.05). We conclude that there was a trend of better overall survival in patients with IGF-1R+ tumours, and PRL < 20.0 ng/ml plasma when compared to patients with IGF-1R- tumours, and PRL > 20.0 ng/ml plasma. Further, IGF-1R negativity in conjunction with hyperprolactinemia could be used as an indicator of unfavourable prognosis in patients with Dukes B or C colon/rectal cancer.
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Neoplasias Colorretais/metabolismo , Prolactina/sangue , Receptor IGF Tipo 1/análise , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Análise de SobrevidaRESUMO
The antiestrogen tamoxifen (TAM) is an effective therapy for advanced breast cancer. However, its use is limited by the eventual development of acquired TAM resistance in many patients. There is now strong evidence to suggest that prolactin plays an important role in advanced breast cancer. We have measured plasma prolactin (PRL) and estrogen-receptor (ER) and progesterone-receptor (PR) in post-menopausal patients with breast cancer (Stage III, n = 44). The blood samples were collected pre-operatively and sequentially thereafter for a minimum period of 3 years or until the death of the patients. The ER and PR were estimated in breast tumor samples by dextran-coated charcoal (DCC) method. The patients were treated with surgery and radiotherapy followed by TAM (10 mg, 1 BD). Based on the response to treatments, the patients were divided into two groups: (1) TAM sensitive (n = 19) and (2) TAM resistant (n = 25). In the TAM sensitive group, patients responded to the treatment and did not develop progressive disease within a period of 3 years. On the contrary, in the group of TAM resistant, patients developed progressive disease within a period of 3 years. The development of progressive disease clearly indicated TAM resistance. Plasma PRL correlated well with the disease progression. This study clearly demonstrated that plasma prolactin accurately indicated the response and development of resistance to TAM in patients with advanced breast cancer.
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Neoplasias da Mama/sangue , Prolactina/sangue , Tamoxifeno/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Resistência a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Resultado do TratamentoRESUMO
Having established prolactin to be an indicator of disease progression and hyperprolactinemia as an independent predictor of short term prognostication, we have in this report compared plasma prolactin with the expression of c erb B-2 oncoprotein, ER and PR. c erb B-2 oncoprotein, ER and PR are determinants of breast cancer biology. This is a retrospective study of 47 breast cancer patients. When patients were grouped according to the stage of the disease, plasma prolactin was higher in patients with advanced disease than those with stage II disease. The patients were sub-grouped according to prolactin < 20.0 ng/ml and > 20.0 ng/ml. The expression of c erb B-2, ER and PR did not differ in these two sub-groups. The overall survival differed significantly between the two sub-groups of prolactin. The patients were sub-grouped according to c erb B-2 positivity or negativity, there was no significant difference in survival. c erb B-2 expression did not differ between the three grades of the tumor, nodal and receptor positivity or negativity. Hence, the present study reinforces the positive association between hyperprolactinemia and unfavourable prognosis and finds c erb B-2 expression as a weak prognosticator in advanced breast cancer patients.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Receptores ErbB/análise , Prolactina/sangue , Proteínas Proto-Oncogênicas/análise , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Neoplasias da Mama/fisiopatologia , Feminino , Expressão Gênica , Humanos , Hiperprolactinemia/etiologia , Pós-Menopausa , Pré-Menopausa , Prognóstico , Receptor ErbB-2 , Estudos RetrospectivosRESUMO
Serum prolactin and tissue polypeptide specific antigen (TPS) were assayed pretherapeutically and sequentially thereafter in 20 male patients with advanced (stages III and IV) tongue cancer. The markers were correlated with disease stage, histologic grade and an attempt was also made to compare the predictive value of these markers and two year survival. Prolactin and TPS levels were significantly higher at diagnosis when compared to controls (a = 0.005). Prolactin and TPS levels did not correlate with stage and histologic grade of the tumor. We found that the positive predictive value for prolactin and TPS was 100% and 75% respectively. The two year survival of patients with prolactin > 15.0 ng/ml was 7.88 +/- 1.48 months, compared to 16.98 +/- 1.47 months of those with prolactin less than 15.0 ng/ml (P < 0.001), whereas such a trend was not observed for TPS. This analysis showed an excellent correlation between serial serum prolactin changes and the response to treatment or progression of disease in patients with advanced tongue carcinoma.
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Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Peptídeos/sangue , Prolactina/sangue , Neoplasias da Língua/sangue , Neoplasias da Língua/secundário , Epitopos/análise , Humanos , Masculino , Estadiamento de Neoplasias , Peptídeos/imunologia , Valor Preditivo dos Testes , Prognóstico , Prolactina/fisiologia , Antígeno Polipeptídico Tecidual , Neoplasias da Língua/imunologiaRESUMO
Serum squamous cell carcinoma antigen (SCCAg) and protein-bound sialic acid (PBSA) were measured in 43 head and neck cancer patients and 50 controls. SCCAg and PBSA were correlated with clinical stage, histological grade, presence/absence of keratin and disease course. Patients with advanced cancer (stage III and IV) and grade III tumors had higher PBSA levels but no such difference was observed for SCCAg. Head and neck cancer patients were grouped according to the disease status i.e. a) patients who developed recurrence and b) who responded to the adjuvant therapies. There was an excellent correlation between serial serum PBSA changes and the progression of disease or the response to therapy in patients with advanced head and neck cancer.