RESUMEN
A high seroprevalence of human herpesvirus type 8 (HHV-8) in mild cirrhotics is significantly associated with hepatitis activity. Cirrhosis is always derived from chronic hepatitis. We aimed to evaluate the prevalence of HHV-8 infection in patients with chronic hepatitis. Blood samples collected from 129 patients with chronic hepatitis and 129 age- and sex-matched healthy controls were analysed for monocyte and platelet counts, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), HHV-8 antibody and DNA, and alanine aminotransferase (ALT). Mean monocyte and platelet counts were significantly higher and lower in patients than in healthy controls (p = 0.02 and < 0.0001, respectively). Seropositive rate for HHV-8 antibodies was significantly greater in patients (32.6%) than in controls (20.9%, p = 0.04), particularly in patients with HCV infection, or higher plasma ALT levels, or both (p = 0.004, 0.01, and 0.0009, respectively). Antibody titres for HHV-8 in patients also exceeded those in controls (p = 0.02). The mean age of HHV-8 seropositive patients (60.3 years) was significantly older than that of seronegatives (52.3 years) (p = 0.0007). Patients aged 55 or older had higher seropositive rate and titres for HHV-8 antibodies than those younger (p = 0.005 and 0.007, respectively). A significantly high HHV-8 seroprevalence is already present in patients with chronic hepatitis before the development of cirrhosis, particularly in patients with HCV infection and/or higher plasma ALT levels. Advancing age seems to play an important role in HHV-8 seroprevalence in patients with chronic hepatitis.
Asunto(s)
Anticuerpos Antivirales/sangre , Hepatitis Crónica/virología , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 8/inmunología , Cirrosis Hepática/virología , Adulto , Anciano , Femenino , Hepatitis Crónica/sangre , Infecciones por Herpesviridae/sangre , Humanos , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Estudios SeroepidemiológicosRESUMEN
The high seroprevalence of human herpesvirus type 8 (HHV-8) in moderate or severe cirrhotics appears to be associated with male sex, hepatitis B virus (HBV) infection, alcoholism, and disease severity. The status of HHV-8 infection in mild cirrhotics remains unclear. Plasma samples collected from 93 mild cirrhotics and 93 age- and sex-matched healthy controls were analyzed for HHV-8 antibody and HHV-8 DNA. Mild cirrhotics had higher seropositivity for HHV-8 antibodies than healthy controls (P=0.0001). Univariate logistic regression analysis revealed that an age ≥55 years (odds ratio (OR) 2.88, P=0.02), hepatitis C virus (HCV) infection (OR 3.42, P=0.01), and hepatitis activity (OR 4.10, P=0.004) were associated with HHV-8 seropositivity in cirrhotics. Stepwise multivariate logistic regression analysis confirmed that age ≥55 years (adjusted OR (aOR) 1.92, P=0.04) and hepatitis activity (aOR 3.55, P=0.005) were independent factors. The rate of hepatitis activity was higher in HCV-infected than in HBV-infected patients (P<0.0001) and in women than in men (P=0.0001). Cirrhotics who were seropositive for HHV-8 or HCV or had hepatitis activity were significantly older (P=0.02, <0.0001 and <0.0001, respectively). Plasma samples from all participants were negative for HHV-8 DNA. HHV-8 antibody titers in mild cirrhotics also markedly exceeded those in controls (P<0.0001), as did those in patients ≥55 years old vs. younger patients (P=0.01), those in patients with vs. without HCV infection (P=0.0008), and those in patients with vs. without hepatitis activity (P=0.0005). Mild cirrhotics had high HHV-8 seroprevalence and HCV infection, and, in particular, old age and hepatitis activity were predictors.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 8/inmunología , Cirrosis Hepática/complicaciones , Estudios Seroepidemiológicos , Adulto , Factores de Edad , Anciano , Alcoholes , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis B/sangre , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Hepatitis B/inmunología , Hepatitis C/sangre , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Hepatitis C/inmunología , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/genética , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/inmunología , Cirrosis Hepática/virología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVES: The aim of this study was to investigate the expression of estrogen receptor α (ERα) and progesterone receptor B (PRB) in the stroma and carcinoma tissues of cervical cancer and their relationship to clinical characteristics and the status of human papillomavirus (HPV) infection. METHODS: Expressional levels of ERα and PRB in tissue blocks of 95 cervical carcinomas were independently scored by 2 pathologists. Human papillomavirus DNA, viral load, and genotypes were determined by polymerase chain reaction. Clinical characteristics were reviewed from chart and cancer registry. RESULTS: Estrogen receptor α and PRB were mainly expressed in the stroma but not in the carcinoma tissues of the cervical cancer, and their expressions were highly correlated. More stromal ERαs were found in early-stage tumors than in advanced-stage tumors. Greater stromal expressions of ERα and PRB were associated with a more favorable prognosis (P = 0.018 and P = 0.004, respectively). The expressions were not related to the differentiation of cancer, the status of HPV infection, the HPV load, or the genotype. In multivariate analysis, stromal ERα and PRB expressions were independently associated with a lower risk of mortality. The adjusted hazard ratios of mortality for low and high expressions of ERα were 0.19 (95% confidential interval [95% CI], 0.04-0.87) and 0.15 (95% CI, 0.03-0.81), respectively, whereas for low and high expressions of PRB hazard ratios were 0.46 (95% CI, 0.19-1.16) and 0.24 (95% CI, 0.06-0.96), respectively. CONCLUSIONS: This study showed that stromal ERα and PRB expressions are independent prognostic indicators of cervical squamous cell carcinoma.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Receptor alfa de Estrógeno/biosíntesis , Receptores de Progesterona/biosíntesis , Neoplasias del Cuello Uterino/metabolismo , Factores de Edad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Regulación hacia Abajo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Pronóstico , Células del Estroma/metabolismo , Células del Estroma/patología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
BACKGROUND: Many patients with tuberculosis (TB) are seropositive for human herpesvirus type 8 (HHV-8), and many patients with primary effusion lymphoma have high levels of HHV-8 DNA in their effusions. However, the status of HHV-8 in the effusions of patients with TB remains unclear. METHODS: Blood samples were collected from 129 patients with pulmonary TB and 129 age- and sex-matched healthy controls. Forty of the TB patients had pleural or peritoneal effusions, and 38 of these effusions were available. Both blood and effusion samples were analyzed for lymphocyte and monocyte counts and/or HHV-8 antibodies and DNA. RESULTS: TB patients with or without effusions had significantly greater HHV-8 seropositivity (p = 0.009) and titers of HHV-8 antibodies (p = 0.005) than healthy controls. The seropositivity and blood titers of HHV-8 antibodies were similar in TB patients with and without effusions. Among TB patients with effusions, similar percentages had seropositive plasma and seropositive effusions. Plasma samples of 6 TB patients, but none of the healthy controls, were positive for HHV-8 DNA (p = 0.03). TB patients with or without effusions had lower blood lymphocyte counts and higher blood monocyte counts than healthy controls (p < 0.0001 for both). TB patients with effusions had significantly lower blood lymphocyte counts than those without effusions (p = 0.035). CONCLUSIONS: HHV-8 had similar seroprevalence in TB patients with and without effusions. However, TB patients with effusions had lower blood lymphocyte counts than those without effusions.
Asunto(s)
Herpesvirus Humano 8/aislamiento & purificación , Tuberculosis Pulmonar/virología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Líquido Ascítico/virología , Estudios de Casos y Controles , Femenino , Herpesvirus Humano 8/genética , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Derrame Pleural/virología , Estudios Seroepidemiológicos , TaiwánRESUMEN
Acute bacterial meningitis causes high morbidity and mortality; the associated clinical symptoms often are insensitive or non-specific; and the pathogenic bacteria are geographically diverse. Clinical diagnosis requires a rapid and accurate methodology. This study aimed to develop a new multiplex polymerase chain reaction (mPCR) assay to detect simultaneously six major bacteria that cause adult bacterial meningitis in Taiwan: Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii. Species-specific primers for the six bacteria were developed using reference strains. The specificities of the mPCRs for these bacteria were validated, and the sensitivities were evaluated via serial dilutions. The mPCR assay specifically detected all of the six pathogens, particularly with sensitivities of 12 colony forming units (CFU)/mL, 90 CFU/mL, and 390 CFU/mL for E. coli, S. pneumoniae, and K. pneumoniae, respectively. This mPCR assay is a rapid and specific tool to detect the six major bacterial pathogens that cause acute adult meningitis in Taiwan, particularly sensitive for detecting E. coli, S. pneumoniae, and K. pneumoniae. The assay may facilitate early diagnosis and guidance for antimicrobial therapy for adult patients with this deadly disease in Taiwan.
Asunto(s)
Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/microbiología , Reacción en Cadena de la Polimerasa Multiplex/métodos , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Adulto , Técnicas Bacteriológicas/métodos , Técnicas Bacteriológicas/estadística & datos numéricos , Secuencia de Bases , Cartilla de ADN/genética , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Genes Bacterianos , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Meningitis por Escherichia coli/diagnóstico , Meningitis por Escherichia coli/microbiología , Meningitis Neumocócica/diagnóstico , Meningitis Neumocócica/microbiología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa Multiplex/estadística & datos numéricos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Sensibilidad y Especificidad , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , TaiwánRESUMEN
BACKGROUND: Liver fibrosis and cirrhosis may be reversible in some circumstances. Reliable diagnostic tests are necessary for monitoring hepatic fibrogenesis. Matrix metalloproteinase (MMP)-2 and MMP-9 are two of the major MMPs in the circulation and may be most relevant to hepatic fibrosis. The behaviour of MMPs may be significantly different in men and women and may also differ in cases of cirrhosis of various aetiologies. AIMS: To evaluate the manifestations of MMP-2 and MMP-9 in liver cirrhosis of different aetiologies in men and women and to compare these patterns with those of healthy controls. METHODS: We measured MMP-2 and MMP-9 levels in plasma samples from 112 patients with cirrhosis and 112 age- and gender-matched healthy controls. We then correlated these MMP levels with gender and disease aetiology. RESULTS: Plasma MMP-2 concentrations in patients showed a trend towards increasing values with cirrhosis severity and were markedly increased in patients regardless of gender and aetiology compared with healthy controls (p<0.0001). Plasma mean MMP-9 levels were comparable in patients with cirrhosis and controls, but increased with disease severity. They were significantly lower in patients (130.5 ng/mL), female patients (85.4 ng/mL) and male patients (150.4 ng/mL) with mild cirrhosis than in controls (163.2 ng/mL), female controls (162.5 ng/mL) and male controls (163.3 ng/mL) (p=0.001, 0.041 and 0.009, respectively). MMP-2 and MMP-9 concentrations were not significantly different between genders among controls and among various patient subgroups. CONCLUSIONS: Plasma MMP-2 level may be a useful diagnostic marker for monitoring hepatic fibrogenesis in patients with disease of different aetiologies.
Asunto(s)
Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Human herpesvirus type 8 (HHV-8) DNA is consistently found in all types of Kaposi's sarcoma, which is prevalent in immunocompromised patients. Patients with advanced lung carcinoma often showed immunologic abnormalities, and prevalence of HHV-8 infection is unclear. In this study, blood samples from 109 lung carcinoma patients and 109 age- and sex-matched healthy controls were analyzed for lymphocyte and monocyte counts, and for antibody, DNA, and genotype of HHV-8. Lung carcinoma patients had significantly lower lymphocyte and higher monocyte counts than healthy controls (p < 0.0001, both). HHV-8 seropositivity was more prevalent in lung carcinoma patients (41.3%), particularly in male patients (50.8%), than in controls (24.8%) (p = 0.01 and 0.002, respectively). The seropositivity was also significantly higher in male (50.8%) than female patients (27.3%, p = 0.01). Titers of HHV-8 antibody in patients also significantly exceeded those in controls (p = 0.004). Under a higher threshold (antibody titer ≥1:160) which is equivalent to that of enzyme-linked immunosorbent assay, lung carcinoma patients still had higher HHV-8 seropositivity than controls (p = 0.006). Three patients with stage IV lung carcinoma were positive for HHV-8 DNA with K1 gene subtype C3, D1, and E, respectively; they had much lower lymphocyte counts (658 ± 132 µL) than patients positive for HHV-8 antibodies only (1,449 ± 873 µL). The study indicates that lung carcinoma patients, particularly males, have a high seroprevalence of HHV-8. HHV-8 DNA detected in the patients with advanced lung carcinoma may be a result of virus reactivation in the immunocompromised status.
Asunto(s)
Carcinoma/complicaciones , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/aislamiento & purificación , Neoplasias Pulmonares/complicaciones , Anciano , Anticuerpos Antivirales/sangre , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Genotipo , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/inmunología , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
Our previous study showed that human herpesvirus type 8 (HHV-8) seroprevalence was significantly higher in patients with end-stage renal disease (ESRD) immediately after haemodialysis than in healthy controls based on an immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA). However, other studies indicated that ESRD patients and healthy controls had similar HHV-8 seroprevalence. This study aimed to investigate whether this discrepancy is due to the effect of uraemic status.Plasma samples from 162 ESRD patients, taken immediately before and after haemodialysis, and 162 age and sex matched healthy controls were analysed for HHV-8 antibodies using both IFA and ELISA.HHV-8 seropositivities based on IFA and ELISA, both before and after haemodialysis, were significantly greater in ESRD patients than in healthy controls (pâ<â0.008 for all comparisons). The seropositivities and antibody titres of ESRD patients obtained with IFA were similar before and after haemodialysis. Seropositivities based on ELISA were identical before and after haemodialysis. The seropositivities obtained with the IFA markedly exceeded those with ELISA in each group of subjects (pâ<â0.0001 for all comparisons).Uraemic status did not significantly affect the IFA or ELISA results for HHV-8 antibodies.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Herpesviridae/diagnóstico , Herpesvirus Humano 8/inmunología , Fallo Renal Crónico/complicaciones , Uremia/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/inmunología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/inmunología , Humanos , Huésped Inmunocomprometido , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/virología , Masculino , Persona de Mediana Edad , Diálisis Renal , Estudios Seroepidemiológicos , Uremia/inmunología , Uremia/terapia , Uremia/virología , Adulto JovenRESUMEN
BACKGROUND: Human herpesvirus type 8 (HHV-8) is the aetiologic agent of Kaposi's sarcoma (KS). The incidence of KS in renal transplant patients is much higher than in healthy controls. The risk is even higher among recipients seropositive for HHV-8 before transplantation. Patients with end-stage renal disease (ESRD) are immunocompromised and are candidates for renal transplantation, but HHV-8 seroprevalence in ESRD patients has not been well documented. OBJECTIVES: This study aimed to evaluate HHV-8 seroprevalence in ESRD patients in a cohort in Taiwan. STUDY DESIGN: Blood samples collected from 149 ESRD patients and 149 age- and sex-matched healthy controls were analysed for HHV-8 antibody with immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) and for HHV-8 DNA with polymerase chain reaction. RESULTS: Seropositivity and titres for HHV-8 antibodies with IFA as well as seropositivity with ELISA were significantly greater in ESRD patients than in healthy controls (P=0.006, 0.001 and 0.003, respectively). Patients with a history of taking herbal medicine had significantly greater ELISA positivity than those without such a history (P=0.004). ELISA positives, particularly patients, had much higher IFA antibody titres than ELISA negatives (P<0.0001). Seropositivity in ESRD patients was not related to lymphopaenia, monocytosis, dialysis duration or a history of transfusion. Two diabetic ESRD patients were positive for HHV-8 DNA. CONCLUSIONS: ESRD patients had significantly greater HHV-8 seropositivity than healthy controls in Taiwan. This association seems to be related to the geographic location of the cohort and invites further studies for the early association of HHV-8 infection in ESRD patients and risk for KS.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Herpesviridae/epidemiología , Herpesvirus Humano 8/inmunología , Fallo Renal Crónico/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Fluoroinmunoensayo , Infecciones por Herpesviridae/virología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Seroepidemiológicos , Taiwán/epidemiología , Topografía Médica , Adulto JovenRESUMEN
BACKGROUND: Cytology fails to detect neoplastic cells in approximately 40% to 50% of malignant pleural effusions (PEs), which commonly accompany lung adenocarcinomas. The diagnostic accuracy of various tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions (LAC-CNPEs) has been poor. The current study attempted to maximize diagnostic efforts in distinguishing LAC-CNPEs from benign PEs. METHODS: PE samples were collected from 74 patients with lung adenocarcinoma with associated cytologically positive (41 patients) and negative (33 patients) PEs, and from 99 patients with benign conditions including tuberculosis (26 patients), pneumonia (28 patients), congestive heart failure (25 patients), and cirrhosis (20 patients). The authors evaluated the diagnostic sensitivity and optimal cutoff points for the tumor markers HER2/neu, CYFRA 21-1, and carcinoembryonic antigen (CEA) to distinguish LAC-CNPEs from benign PEs. RESULTS: Mean levels of HER2/neu, CYRFA 21-1, and CEA were found to be significantly higher in LAC-CNPEs compared with benign PEs (P = .0050, P = .0039, and P < .0001, respectively). The cutoff points for HER2/neu, CYFRA 21-1, and CEA were optimally set at 3.6 ng/mL, 60 ng/mL, and 6.0 ng/mL, respectively. Their sensitivities ranged from 12.1%, to 30.3%, to 63.6%, respectively. CEA combined with CYFRA 21-1 increased diagnostic sensitivity to 66.7%. The false-positive rates of these markers in benign PEs were 6.1%, 2.0%, and 0%, respectively. CONCLUSIONS: The combination of CEA with CYFRA 21-1 appears to provide the best differentiation between LAC-CNPEs and benign PEs to date using 2 tumor markers, and allows for the early diagnosis and early treatment of approximately two-thirds of affected patients.
Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Citodiagnóstico , Neoplasias Pulmonares/diagnóstico , Derrame Pleural Maligno/diagnóstico , Adenocarcinoma/metabolismo , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/metabolismo , Antígeno Carcinoembrionario/metabolismo , Detección Precoz del Cáncer , Femenino , Humanos , Inmunoensayo , Queratina-19/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/metabolismo , Pronóstico , Receptor ErbB-2/metabolismoRESUMEN
Hepatocellular carcinoma is a common type of cancer with poor prognosis. This study examines the in vitro and in vivo mechanisms of diosmin on human hepato-cellular carcinoma HA22T cell proliferation inhibition. HA22T cells were treated with different diosmin concentrations and analyzed with Western blot analysis, MTT assay, wound healing, flow cytometry, siRNA transfection assays and co-immuno-precipitation assay. The HA22T-implanted xeno-graft nude mice model was applied to confirm the cellular effects. Diosmin showed strong HA22T cell viability inhibition in a dose dependent manner and significantly reduced the cell proliferative proteins as well as inducing cell cycle arrest in the G2/M phase through p53 activation and PI3K-Akt-MDM2 signaling pathway inhibition. However, protein phosphatase 2A (PP2A) siRNA or PP2A inhibitor totally reversed the diosmin effects. The HA22T-implanted nude mice model further confirmed that diosmin inhibited HA22T tumor cell growth and down regulated the PI3K-Akt-MDM2 signaling and cell cycle regulating proteins, as well as activating PP2A and p53 proteins. Our findings indicate that HA22T cell proliferation inhibition and tumor growth suppression by diosmin are mediated through PP2A activation.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Diosmina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Animales , Secuencia de Bases , Western Blotting , Ciclo Celular/efectos de los fármacos , Línea Celular , Citometría de Flujo , Hepatocitos/efectos de los fármacos , Masculino , Ratones , Ratones Desnudos , Ácido Ocadaico/farmacología , Fosforilación , Proteína Fosfatasa 2 , Ratas , Ratas Sprague-Dawley , Trasplante HeterólogoRESUMEN
The role of protein kinase C (PKC) in the carcinogenesis of human breast tissue has been studied at the molecular level for more than two decades. In this study, we employed Western blotting to determine the presence of PKC isoforms in cancerous and normal breast tissues. The results indicate significant expression of a conventional PKC (PKCα) and two atypical PKCs (PKC ζ and λ/ι) in both breast tumors and adjacent normal breast tissue. For the α,ζ and λ/ι isoforms, the expression of individual isoforms was higher in the breast tumors than in the adjacent normal breast tissue. Although the correlation coefficient was low, significant linear correlation was found among the activities of the isoforms. The data suggest a potential new direction in cancer chemotherapy, namely the blockage of the signal transduction pathway of specific PKC isoforms.
Asunto(s)
Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Proteína Quinasa C/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Isoenzimas/metabolismo , Persona de Mediana Edad , Adulto JovenRESUMEN
Currently, there are no diagnostic or metastatic markers that can be used in early diagnosis and treatment of human hepatocellular carcinoma (HCC). The aim of this study was to find a molecular marker that regulated migration and metastasis in HCC. We analyzed the gene expression of ß-catenin, c-Myc and IL-8 in human HCC tissue by RT-PCR and immunohistochemistry and analyzed five variously differentiated HCC cell lines by Western blotting and migration and invasion assays to find markers for HCC diagnosis and HCC metastasis. mRNA expression of ß-catenin was significantly higher in the tumor area compared to the non-tumor area and was more abundant in specimens of late-stage HCC. Immunohistochemistry revealed that the translocation of ß-catenin into the nucleus was closely correlated with IL-8 protein levels and tumor stage. Similarly, the level of expression and nuclear translocation of ß-catenin was greater in HA22T cells with high proliferative activity than in HCC cell lines with low proliferative activity (PLC, Hep3B, HepG2). Knockdown of the ß-catenin gene with ß-catenin antisense oligonucleotides resulted in inhibition of cell migration and invasion of HA22T cells. Taken together, these results suggest that ß-catenin may be a suitable diagnostic marker of metastasis in human HCC.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , beta Catenina/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Invasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor-κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule-1 (ICAM-1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion-dependent cell-to-cell interactions. The effects of RANKL on cell migration and ICAM-1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM-1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL-mediated migration and ICAM-1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In addition, an NF-κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL-mediated cell migration and ICAM-1 up-regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF-κB, resulting in the activation of ICAM-1 and contributing to the migration of human lung cancer cells.
Asunto(s)
Molécula 1 de Adhesión Intercelular/biosíntesis , Neoplasias Pulmonares/patología , Ligando RANK/fisiología , Línea Celular Tumoral , Movimiento Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Genes Reporteros , Humanos , Molécula 1 de Adhesión Intercelular/genética , Luciferasas/metabolismo , Neoplasias Pulmonares/metabolismo , MAP Quinasa Quinasa 1/metabolismo , MAP Quinasa Quinasa 2/metabolismo , FN-kappa B/metabolismo , Fosforilación , Ligando RANK/genética , Ligando RANK/farmacología , Interferencia de ARN , Transducción de Señal , Regulación hacia ArribaRESUMEN
Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Leptin, an adipocyte-derived cytokine that is closely associated with obesity, has recently been shown to be involved in carcinogenesis and cancer progression. The aim of this study was to investigate whether leptin is associated with the motility of prostate cancer cells. We found that leptin increased the migration of human prostate cancer cells and expression of αvß3 integrin on these cells. Leptin-mediated migration and increased integrin expression were attenuated by OBRl receptor antisense oligonucleotide (ODN). Activation of insulin receptor substrate (IRS-1), phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB pathways after leptin treatment was demonstrated. Furthermore, leptin-induced integrin expression and migration activity were inhibited by specific inhibitors; small interfering RNAs (siRNAs); and mutants of the IRS-1, PI3K, Akt, and NF-κB cascades. Therefore, this study shows that leptin stimulates the migration of human prostate cancer cells, one of the mechanisms underlying leptin-directed migration was transcriptional up-regulation of αvß3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-κB signal transduction pathway.
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Movimiento Celular , Integrina alfaVbeta3/metabolismo , Leptina/metabolismo , Neoplasias de la Próstata/metabolismo , Línea Celular Tumoral , Genes Reporteros , Humanos , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Integrina alfaVbeta3/genética , Masculino , Mutación , FN-kappa B/genética , FN-kappa B/metabolismo , Invasividad Neoplásica , Oligonucleótidos Antisentido/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Transducción de Señal , Factores de Tiempo , Transcripción Genética , Transfección , Regulación hacia ArribaRESUMEN
AIMS: Cytology fails to detect neoplastic cells in 40-50% of cases of malignant pleural effusion, a condition that frequently accompanies lung adenocarcinoma. Published reports of diagnostic sensitivity of various tumour markers are inconsistent, and optimal cut-off points have not been determined. This study aimed to evaluate the ability of three markers to discriminate lung adenocarcinoma-associated malignant pleural effusion (LAC-MPE) from benign effusion. METHODS: Pleural effusion samples were collected from 41 patients with LAC-MPE, and from 93 with various benign conditions. The diagnostic sensitivity and specificity for Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen (CEA) were evaluated. Cut-off points for these markers are optimally set at 3.6 microg/L, 60 microg/L, and 6.0 microg/L, respectively. RESULTS: Her-2/neu, Cyfra 21-1, and CEA vary in their diagnostic accuracy to differentiate LAC-MPE from benign pleural effusion: 79.85%, 88.81%, and 94.03%, respectively. CEA combined with Cyfra 21-1 increases diagnostic sensitivity to 97.6%, with a specificity of 91.4%. CONCLUSIONS: With appropriate cut-off points, CEA currently provides the best diagnostic accuracy. Combining CEA with Cyfra 21-1 increases diagnostic sensitivity to nearly 100%. The results of the present study may help clinicians decide whether to obtain a cytological/histological specimen by invasive means to investigate a possible diagnosis of malignancy.
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Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/análisis , Antígeno Carcinoembrionario/análisis , Queratina-19/análisis , Neoplasias Pulmonares/diagnóstico , Derrame Pleural/metabolismo , Receptor ErbB-2/análisis , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/análisis , Antígeno Carcinoembrionario/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Queratina-19/metabolismo , Masculino , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Chronic ectopic pregnancy is an enigma. The clinical presentation can be mild, with absent or subtle symptoms. Ovarian pregnancy usually ends with rupture. We report the first case of unruptured chronic ovarian pregnancy that was initially diagnosed by peritoneal washing cytology. CASE: A 35-year-old woman suffered from low abdominal pain during the presumed menstrual period for 6 months. Abdominal computed tomography revealed a huge cystic mass with intralesional hematoma and soft tissue components located in the pelvic cavity. Mild right hydronephrosis caused by tumor obstruction of the right ureter were noted. Right ovarian cancer was suspected. Peritoneal washing cytology revealed both cytotrophoblasts and syncytiotrophoblasts. Patient received enucleation of the right ovary. Microscopically, the ovarian mass exhibited extensive hemorrhage and necrosis, embedding degenerated chorionic villi. CONCLUSION: When a patient experiences low abdominal pain during a menstrual period, the possibility of ectopic pregnancy should be considered in addition to possible endometriosis. Ovarian or other abdominal pregnancies, even untruptured, may be discriminated from other lesions in cases of abdominal pain by peritoneal washing cytology.
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Líquido Ascítico/citología , Neoplasias Ováricas/patología , Ovario/patología , Embarazo Ectópico/diagnóstico , Embarazo , Dolor Abdominal/etiología , Adulto , Enfermedad Crónica , Técnicas Citológicas , Diagnóstico Diferencial , Femenino , Humanos , Tomografía Computarizada por Rayos X , Obstrucción Ureteral/etiologíaRESUMEN
Immunologic abnormalities in patients with cirrhosis strongly correlate with severity of liver cirrhosis. The association between cirrhosis and human herpesvirus type 8 (HHV-8) infection is unclear. Plasma samples were obtained from 74 healthy control subjects and 59 patients with cirrhosis. The seropositive rates for HHV-8 antibodies in patients with cirrhosis (25/59 [42%]) were significantly higher than that in healthy control subjects (18/74 [24%]; P = .027), particularly in men (P = .027), patients with alcohol-related cirrhosis (P = .032), and patients with thrombocytopenia (P = .019) or Child-Pugh class C cirrhosis (P = .018) or both (P = .015), or hepatitis B virus (HBV) infection (P = .003). Antibody titers in seropositive patients also significantly exceeded those in healthy control subjects (P = .008). All subjects were negative for anti-HIV. In Taiwan, cirrhosis is associated with HHV-8 infection, particularly in men, patients with Child-Pugh class C cirrhosis and/or thrombocytopenia, and patients with alcohol- or HBV-related cirrhosis.
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Alcoholismo/complicaciones , Hepatitis B/complicaciones , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 8 , Cirrosis Hepática/complicaciones , Trombocitopenia/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Infecciones por VIH/complicaciones , Hepatitis B/epidemiología , Infecciones por Herpesviridae/epidemiología , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Factores Sexuales , Trombocitopenia/epidemiologíaRESUMEN
Fine-needle aspiration cytology (FNAC) is a highly accurate tool for the diagnosis of pleomorphic adenomas; however, this common salivary gland neoplasm can be diagnostically challenging, causing pitfalls in cytodiagnosis. A 50-year-old woman suffered from a painless, slowly-growing mass in the right posterior upper neck for 5 months. FNAC from this mass revealed many discohesive parakeratotic cells and keratin flakes, and a few stromal elements. Under the impression of metastatic well-differentiated squamous cell carcinoma, the tumor mass was totally excised. Histology confirmed a pleomorphic adenoma with marked squamous metaplasia and frequent keratin pearl formations without the evidence of malignancy. Pleomorphic adenoma occasionally reveals focal squamous metaplastic changes, when extensive, it may be misdiagnosed as metastatic well-differentiated squamous cell carcinoma in FNAC, particularly in the neck region.