RESUMO
Resveratrol oligomers, ranging from dimers to octamers, are formed through regioselective synthesis involving the phenoxy radical coupling of resveratrol building blocks, exhibiting remarkable therapeutic potential, including antidiabetic properties. In this study, we elucidate the mechanistic insights into the insulin secretion potential of a resveratrol dimer, (-)-Ampelopsin F (AmF), isolated from the acetone extract of Vatica chinensis L. stem bark in Pancreatic Beta-TC-6 cell lines. The AmF (50 µM) treated cells exhibited a 3.5-fold increase in insulin secretion potential as compared to unstimulated cells, which was achieved through the enhancement of mitochondrial membrane hyperpolarization, elevation of intracellular calcium concentration, and upregulation of GLUT2 and glucokinase expression in pancreatic Beta-TC-6 cell lines. Furthermore, AmF effectively inhibited the activity of DPP4, showcasing a 2.5-fold decrease compared to the control and a significant 6.5-fold reduction compared to the positive control. These findings emphasize AmF as a potential lead for the management of diabetes mellitus and point to its possible application in the next therapeutic initiatives.
Assuntos
Flavonoides , Células Secretoras de Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Resveratrol , Glucoquinase/metabolismo , Glucose/metabolismoRESUMO
Covid or Corona Virus, a term ruling the world from past two years and causes a huge destruction in all countries. One of the most important Covid disease identification method is Lung based Computed Tomography (CT) image scanning, in which it provides an effective disease identification means in clear manner. However, this Lung CT image based disease detection principles are complex to health care representatives and doctors to predict the Covid disease accurately. Several manual errors and medical flaws are raised day-by-day, so that a new systematic methodology is required to identify the Covid disease effectively with respect to machine learning principles. The machine learning principles are most popular to identify the respective disease efficiently as well as classify the disease in accurate manner without any time consumption. The infected portions of the chest are identified accurately and report to the respective person without any delay. In this paper, a new machine learning strategy is introduced called Hybrid Disease Detection Principle (HDDP), in which it is derived from the two classical machine learning algorithms called Convolutional Neural Network (CNN) and the AdaBoost Classifier. Both these algorithms are integrated together to produce a new strategy called HDDP, in which it process the lung CT image based on the machine learning factors such as pre-processing, feature extraction and classification. Based on these effective image processing strategies the proposed algorithm handles the CT images to predict the Covid disease and report to the respective user with proper accuracy ratio. This paper intends to provide effcient disease predictions as well as provide a sufficient support to medical people and patients in fine manner to assist them with modern classification algorithms.
RESUMO
Phytochemical investigation of the stem bark of Hopea parviflora resulted in the isolation of 9 compounds; which includes friedelin (1), friedelin-3ß-ol (2), (-)-ampelopsin A (3), (-)-É-viniferin (4), (-)-hopeaphenol (5), vaticaphenol A (6), 2,4,8-trihydroxyphenanthrene-2-O-glucoside (7), ellagic acid-3,3',4-trimethoxy-4'-O-α-L-rhamnopyranoside (8) and ß-sitosterol-ß-D-glucoside (9). Among them, compounds 1, 2, 6, 7, 8 and 9 are isolated for the first time from this species. Further, we evaluated the anti-inflammatory activity of compounds 4, 5, 6, 7 and 8. In this study, compound 8 inhibited the activity of proinflammatory mediators like NO, TNF-α, IL-6, 5-LOX and COX-2, also promoted the action of anti-inflammatory mediator like IL-10 via inhibition of the NF-κB pathway in LPS-stimulated RAW 264.7 macrophages.
Assuntos
Anti-Inflamatórios/farmacologia , Dipterocarpaceae , Ácido Elágico/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Dipterocarpaceae/química , Ácido Elágico/isolamento & purificação , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Células RAW 264.7RESUMO
Promalabaricone B (PMB), an acylphenol was isolated from dichloromethane-soluble extract of the seeds of Myrisitica fatua Houtt. PMB exhibited significant inhibitory activity on α-glucosidase enzyme. The molecular docking and dynamics studies of PMB with human maltase-glucoamylase were performed. PMB exhibited an enhanced glucose uptake in L6 myotubes with 46.3% in 2.5 µM. Encouraged with these results; we investigated the molecular mechanism of PMB through the upregulation of AMPK. The results revealed that PMB promoted the glucose uptake in myocytes by stimulating the translocation and expression of GLUT4. From this, it is clear that PMB can acts as a potential therapeutic option for diabetes treatment, and its hypoglycaemic effect may be mediated by AMPK upregulation and induction of GLUT4 translocation.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Myristica/química , Fenóis/farmacologia , Sementes/química , Regulação para Cima/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Glicosilação/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fenóis/química , Fenóis/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Transdução de Sinais/efeitos dos fármacos , Suínos , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hopea ponga (Dennst.) Mabb. Is used in traditional herbal formulations for diabetes complications. The aim of this study is to evaluate the antidiabetic effect of extracts and compounds from H. ponga. MATERIALS AND METHODS: Silica gel column chromatography was performed to identify various chemical components of the plant extract. Different extracts of H. ponga and isolated compounds were screened for their antidiabetic effect by modulation of digestive enzymes and protein glycation. The effect of glucose uptake by the compounds and the pathways through which the compounds mediate the glucose uptake potential were confirmed by fluorescent microscopy, flow cytometry and western blot analysis. RESULTS: Acetone and ethanol extracts of the stem bark of Hopea ponga (Dennst.) Mabb. Afforded six resveratrol oligomers namely, E-resveratrol (1), (-)-ε-viniferin (2), (-)-α-viniferin (3), trihydroxyphenanthrene glucoside (THPG) (4), vaticaphenol A (5), (-)-hopeaphenol (6), along with four phytosterols. The structures were determined on the basis of spectroscopic analyses including nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) data. Compounds 1-5 and 7-10 were tested for their α-glucosidase, α-amylase and glycation inhibitiory activities. All the resveratrol oligomers (1-5) showed prominent α-glucosidase inhibition with IC50 values, 12.56⯱â¯1.00, 23.98⯱â¯1.11, 7.17⯱â¯1.10, 31.74⯱â¯0.42 and 16.95⯱â¯0.39⯵M, respectively. Molecular docking studies also supported the observed α-glucosidase inhibition. Compound 3 displayed IC50 values of 4.85⯱â¯0.06 and 27.10⯱â¯0.04⯵M in α-amylase and glycation inhibitory assays activity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the compounds 3 and 4 were found to be less toxic at a concentration of 100⯵M (<10%) and 25⯵M (<20%), respectively. The effect of glucose uptake performed by 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in L6 myoblast were measured by fluorescent microscopy and flow cytometry. The compounds 3 and 4 showed 2-NBDG uptake of 49.6% and 38.8% respectively. By examining the molecular pathway through which the compounds elicit their glucose uptake potential, it was observed that both the compounds mainly act via AMPK pathway. CONCLUSION: This is the first report on the isolation of compounds from H. ponga. Altogether, the results of this study reveal the antidiabetic effects of H. ponga extracts and isolated compounds promoting traditional use of this plant in the treatment of diabetes.
Assuntos
Dipterocarpaceae/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Resveratrol/farmacologia , Acetona/química , Animais , Linhagem Celular , Diabetes Mellitus/tratamento farmacológico , Ensaios Enzimáticos , Etanol/química , Glicosilação/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Concentração Inibidora 50 , Medicina Tradicional/métodos , Simulação de Acoplamento Molecular , Estrutura Molecular , Mioblastos , Casca de Planta/química , Extratos Vegetais/química , Caules de Planta/química , Ratos , Resveratrol/química , Resveratrol/isolamento & purificação , Testes de Toxicidade , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Amilases/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismoRESUMO
Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2-7). All the compounds displayed moderate inhibitory activity on α-amylase and significant activity on α-glucosidase; however malabaricone B (6) and C (7) were identified as potent α-glucosidase inhibitors with IC50 values of 63.70⯱â¯0.546, and 43.61⯱â¯0.620⯵M respectively. Acylphenols (compounds 3-7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus.
Assuntos
Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Myristicaceae/química , Compostos Fitoquímicos/química , Sítios de Ligação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Simulação de Dinâmica Molecular , Células Musculares/citologia , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Myristicaceae/metabolismo , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química , Caules de Planta/química , Caules de Planta/metabolismo , Estrutura Terciária de Proteína , Resorcinóis/química , Resorcinóis/metabolismo , Resorcinóis/farmacologia , alfa-Glucosidases/química , alfa-Glucosidases/metabolismoRESUMO
BACKGROUND: Tumors of the head and neck present aggressive pathological behavior in patients due to high expression of CDK/CCND1 proteins. P276-00, a novel CDK inhibitor currently being tested in clinic, inhibits growth of several cancers in vitro and in vivo. The pre clinical activity of P276-00 in head and neck cancer and its potential mechanisms of action at molecular level are the focus of the current studies. METHOD: We have investigated the anti-cancer activity of P276-00 in head and neck tumors in vitro and in vivo. Candidate gene expression profiling and cell based proteomic approaches were taken to understand the pathways affected by P276-00 treatment. RESULTS: It was observed that P276-00 is cytotoxic across various HNSCC cell lines with an IC50 ranging from 1.0-1.5 µmoles/L and culminated in significant cell-cycle arrest in G1/S phase followed by apoptosis. P276-00 treatment suppressed cell proliferation through inhibition of CCND1 expression, reduced phosphorylation of retinoblastoma protein and abrogative transcription of E2F1 gene targets. Further, we observed that apoptosis was mediated through P53 activation leading to higher BAX/BCL-2 ratio and cleaved caspase-3 levels. It was also seen that P276-00 treatment reduced expression of tumor micro-environment proteins such as IL-6, secreted EGFR and HSPA8. Finally, P276-00 treatment resulted in significant tumor growth inhibition in xenograft tumor models via lowered proliferative activity of E2F1 and aggravated P53 mediated apoptosis. CONCLUSION: In summary, we have observed that P276-00 inhibits cyclin-D/CDK4/P16/pRB/E2F axis and induces apoptosis by increased P53 phosphorylation in HNSCC cells. These results suggest a novel indication for P276-00 in head and neck cancer with a potential role for IL-6 and HSPA8 as candidate serum biomarkers.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Flavonas/farmacologia , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D/metabolismo , Ciclina D1/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Fator de Transcrição E2F1/metabolismo , Receptores ErbB/metabolismo , Perfilação da Expressão Gênica , Proteínas de Choque Térmico HSC70/metabolismo , Humanos , Concentração Inibidora 50 , Interleucina-6/metabolismo , Camundongos , Camundongos SCID , Transplante de Neoplasias , Fosforilação , Proteína do Retinoblastoma/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Perhaps the most crucial step in the clinical development of an antimicrobial agent is the selection of a dosing regimen. Such decisions impact not only the success of a program but also the well being of individual patients, the emergence of resistance, and society as a whole. For fusidic acid, the selection of a dosing regimen for the treatment of patients with acute bacterial skin and skin-structure infection (ABSSSI) was based on the integration of knowledge gained from human population pharmacokinetic, in vitro infection, and mathematical models. The overarching goal of these studies was to identify a dosing regimen that would maximize the probabilities of positive clinical outcomes and limit the emergence of bacterial resistance during therapy. Novel dosing regimens identified included 1500 mg twice daily on day 1 followed by 600 mg twice daily for 10-14 days, a regimen that was subsequently found to be effective in a phase 2 clinical study of patients with ABSSSI. Herein, we review the data supporting the use of this novel fusidic acid dosing regimen, which will undergo further clinical evaluation in phase 3 clinical trials.
Assuntos
Antibacterianos , Ácido Fusídico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Modelos Biológicos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Contagem de Colônia Microbiana , Esquema de Medicação , Ácido Fusídico/administração & dosagem , Ácido Fusídico/farmacocinética , Humanos , Método de Monte Carlo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Resultado do TratamentoRESUMO
Microarray technology can be used to study the molecular mechanisms of new chemical entities with the aim to develop effective therapeutics. 7-Hydroxyfrullanolide (7HF) is a sesquiterpene lactone that was found to be efficacious in multiple animal models of inflammation by suppression of pro-inflammatory cytokines; however, its molecular mechanism of action remains unclear. We investigated the effects of 7HF on lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells using microarray-based gene expression studies and explored the molecular targets affected. Gene expression profiles and pathway analysis revealed that 7HF potently suppressed multiple inflammatory pathways induced by LPS. More importantly, 7HF was found to inhibit NF-κB related transcripts. These transcripts were further validated using freshly isolated synovial cells from rheumatoid arthritis patients, thus clinically validating our findings. Cell-based imaging and subsequent Western blot analysis demonstrated that 7HF inhibited the translocation of NF-κB into the nucleus by directly inhibiting the phosphorylation of IKK-ß. Since the transcription of adhesion molecules is regulated by NF-κB, further investigation showed that 7HF dose-dependently suppressed ICAM-1, VCAM-1 and E-selectin expression on LPS-stimulated endothelial cells as well as inhibited the adhesion of monocytes to LPS-stimulated endothelial cells. Taken together, our results reveal that 7HF possesses NF-κB inhibitory potential and suggest a likely molecular mechanism of its anti-inflammatory activity.
Assuntos
Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Sesquiterpenos/farmacologia , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Quinase I-kappa B/metabolismo , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologia , Monócitos/citologia , Monócitos/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismoRESUMO
Several studies have characterized drug-induced toxicity in liver and kidney. However, the majority of these studies have been performed with 'individual' organs in isolation. Separately, little is known about the role of whole blood as a surrogate tissue in drug-induced toxicity. Accordingly, we investigated the 'concurrent' response of liver, kidney and whole blood during a toxic assault. Rats were acutely treated with therapeutics (acetaminophen, rosiglitazone, fluconazole, isoniazid, cyclophosphamide, amphotericin B, gentamicin and cisplatin) reported for their liver and/or kidney toxicity. Changes in clinical chemistry parameters (e.g. AST, urea) and/or observed microscopic tissue damage confirmed induced hepatotoxicity and/or nephrotoxicity by all drugs. Drug-induced toxicity was not confined to an 'individual' organ. Not all drugs elicited significant alterations in phenotypic parameters of toxicity (e.g. ALT, creatinine). Accordingly, the transcriptional profile of the organs was studied using a toxicity panel of 30 genes derived from literature. Each of the test drugs generated specific gene expression patterns which were unique for all three organs. Hierarchical cluster analyses of purported hepatotoxicants and nephrotoxicants each led to characteristic 'fingerprints' (e.g. decrease in Cyp3a1 indicative of hepatotoxicity; increase in Spp1 and decrease in Gstp1 indicative of nephrotoxicity). In whole blood cells, a set of genes was derived which closely correlated with individual drug-induced concomitant changes in liver or kidney. Collectively, these data demonstrate drug-induced multi-organ toxicity. Furthermore, our findings underscore the importance of transcriptional profiling during inadequate phenotypic anchorage and suggest that whole blood may be judiciously used as a surrogate for drug-induced extra-hematological organ toxicity.
Assuntos
Células Sanguíneas/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Rim/efeitos dos fármacos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Células Sanguíneas/metabolismo , Células Sanguíneas/patologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Especificidade de Órgãos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testes de Toxicidade Aguda/métodosRESUMO
Studying peripheral blood transcriptome in the quest for translational markers of toxicity is considered to be an attractive offshoot in the field of toxicogenomics. Moreover, it is acknowledged that, xenobiotics which cause a toxic response through similar mechanisms lead to distinctive gene expression patterns. The current study was undertaken to gauge the response of an accessible surrogate tissue, such as blood, to drug-induced perturbations aimed at deriving gene expression patterns. Human peripheral blood mononuclear cells (hPBMC) were exposed to conventional drugs, with reported kidney and/or liver injury, in order to determine their transcriptomic response. Test drugs were divided into two classes viz., drugs affecting kidney (cyclophosphamide, amphotericin B, gentamicin and cisplatin) and liver (acetaminophen, rosiglitazone, fluconazole and isoniazid). After performing gene expression analysis and hierarchical clustering, signature patterns for the two classes were obtained, with a set of 365 genes that can discriminate the two classes of drugs. Our results imply that transcriptional profile of hPBMC get altered as a consequence of drug exposure and unique patterns indicative of specific organ toxicity can hence be deduced. These signature patterns obtained for drugs could be studied for their qualification to identify drug-induced toxicity.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Perfilação da Expressão Gênica , Rim/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Fígado/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Masculino , Análise de Sequência com Séries de OligonucleotídeosRESUMO
The incidence of nonsentinel (NSN) lymph node metastases in patients with a tumor-positive sentinel (SN) lymph node varies greatly from 20% to 70% in the published literature. Current practice is that most patients with a positive SN (micro- and macrometastases) undergo a complete axillary dissection. However, it has been shown by other investigators that a large number of patients with a positive SN do not necessarily need a complete axillary dissection. In this analysis, we reviewed the pathology slides from 58 patients who had undergone SN and axillary node dissection. The tumor size, histologic parameters, receptor (estrogen and progesterone), and HER-2neu oncoprotein expression were noted. Student t test and Fisher exact test were used for statistical analysis. Of 58 patients, 19 (32.7%) had NSN metastases. Primary tumor size (P < .002), size of SN metastatic tumor (P < .03), and the presence of extracapsular tumor extension (P < .0001) were associated significantly with NSN metastases. We have shown in this study that it would be possible to predict the NSN status based on primary tumor size, size of SN metastatic tumor, and presence of SN extracapsular tumor extension.
Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico , Biópsia de Linfonodo Sentinela/métodos , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Metástase Linfática/patologia , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de RiscoRESUMO
CONTEXT: Axillary lymph node status is the most important prognostic factor in patients with breast cancer. Tumor size and lymph node status, the most reliable pathologic bases of the tumor staging system, are practical parameters for estimating survival status. With the advent of lymphatic mapping and sentinel node (SN) identification, there is potential for a more efficient and sensitive evaluation of the axillary lymph node status. OBJECTIVE: To correlate SN status with tumor size, grade, and lymphovascular invasion. DESIGN: We examined 234 patients with unifocal breast carcinomas measuring 25 mm or less as detected by preoperative ultrasound during the period May 1998 through December 2002. Sentinel nodes were examined by frozen section and paraffin section as per protocol. RESULTS: Of the 234 patients, SN was identified in 221 (94.5%). An average of 1.38 SNs were examined per patient. Seventy-seven of 221 patients were SN positive on paraffin section. Sixty-six (85.7%) of these 77 cases could be correctly diagnosed as positive for metastatic carcinoma on frozen section. Two cases reported as positive on paraffin section were reported as suspicious on frozen section. Logistic regression indicated that tumor size, grade, and lymphovascular invasion were all significantly associated with SN status (P < .001). CONCLUSIONS: Tumor size, grade, and lymphovascular invasion were significantly associated with SN status in unifocal invasive breast carcinoma.
Assuntos
Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Carcinoma/secundário , Linfonodos/patologia , Metástase Linfática/diagnóstico , Biópsia de Linfonodo Sentinela/métodos , Axila/patologia , Secções Congeladas/métodos , Humanos , Estadiamento de Neoplasias/métodos , Inclusão em Parafina/métodos , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
CONTEXT: Angiogenesis and the cell proliferation index can predict the prognosis of invasive breast carcinoma; however, little is known of their roles in noninvasive tumor. OBJECTIVE: To investigate the correlation of microvessel density and cell proliferation index with other histologic parameters (histologic type, nuclear grade, and mitotic count) in 65 cases of noninvasive carcinoma of the breast. DESIGN: Formalin-fixed, paraffin-embedded tissues from 65 cases of carcinoma in situ of the breast were immunostained with antibody against factor VIII antigen and proliferation-associated nuclear antigen MIB-1. The microvessel density was measured by counting the total number of microvessels around the carcinoma in situ per 10 low-power microscopic fields. The cell proliferation index was calculated by counting MIB-1-positive nuclei in 100 tumor cells. A chi2 test and Spearman rank correlation test were used for statistical analysis. RESULTS: The microvessel density and cell proliferation index of comedo-type, high-nuclear-grade ductal carcinomas in situ are significantly higher than those of either noncomedo type ductal carcinomas in situ or lobular carcinoma in situ (P <.001). CONCLUSIONS: Angiogenesis and the cell proliferation index are active biological processes and may be considered as markers to separate low- and high-risk patients with noninvasive breast carcinomas.
Assuntos
Neoplasias da Mama/irrigação sanguínea , Carcinoma in Situ/irrigação sanguínea , Carcinoma Intraductal não Infiltrante/irrigação sanguínea , Carcinoma Lobular/irrigação sanguínea , Neovascularização Patológica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/patologia , Divisão Celular , Núcleo Celular/química , Núcleo Celular/ultraestrutura , Feminino , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Índice Mitótico , Invasividade Neoplásica , Proteínas de Neoplasias/análise , Coloração e RotulagemRESUMO
Complete hydatidiform moles (CHM), a post-conceptual pathologic condition of the placenta, have a high prevalence rate (12/1,000 deliveries) in Kerala, India. This study addresses the expression of IL-1 alpha and beta by immunohistochemistry in relation to persistence and invasion of the disease. Mild to moderate expression of IL-1 alpha in the villous cytotrophoblasts, syncytiotrophoblasts and decidua of the first trimester in the normal placenta and all gestational ages in the molar placenta were observed. IL-1 beta expression was observed in the extravillous trophoblasts, syncytiotrophoblasts and decidua in both the normal and molar placentae and also in the villous cytotrophoblasts and the stromal Haufbaur cells in molar placentae. Strong expression of IL-1 beta in the placenta suggests its involvement in placental physiology supporting earlier reports. Higher expression of IL-1 beta correlated well with the invasive and persistent nature of the tumour and holds potential as a marker of persistence and invasion in CHM.
Assuntos
Mola Hidatiforme Invasiva/metabolismo , Interleucina-1/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Neoplasias Uterinas/metabolismo , Biomarcadores Tumorais , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Mola Hidatiforme Invasiva/patologia , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Gravidez , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: An increased level of plasma homocysteine is being recognized as a new risk factor for coronary artery disease. Since there are not enough data about its importance in Indians with coronary artery disease, we aimed to assess the significance of plasma homocysteine as a coronary risk factor in South Indian patients. METHODS AND RESULTS: In a case-control study, fasting plasma homocysteine levels were estimated in 565 subjects, of whom 221 were cases and 344 were controls. Of the 221 clinically defined cases, 112 underwent coronary angiography while 107 of the 344 controls had angiographically proven normal coronary arteries. Ninety healthy volunteers from the community were also included as controls. Fluorescent polarization immunosorbent assay was used to measure plasma homocysteine levels. In 12 patients, this method was compared to high pressure liquid chromatography and was found to give comparable results. The mean plasma homocysteine level was 18.30 +/- 10.08 micromol/L in clinically defined cases and 18.04 +/- 10.69 micromol/L in controls. Similarly, in angiographicallyproven coronary arterydisease patients, the mean plasma homocysteine levelwas 18.49 +/- 10.04 micromol/L and in individuals with angiographically normal coronary arteries, it was 19.16 +/- 11.38 micromol/L. CONCLUSIONS: There is no statistically significant difference in plasma homocysteine levels between controls and cases with coronary artery disease. The mean plasma homocysteine levels in controls as assessed by fluorescent polarization immunosorbent assay in the present study population are higher as compared to other published reports.
Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etnologia , Homocisteína/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Radiografia , Fatores de Risco , Estatísticas não ParamétricasRESUMO
The association between human immunodeficiency virus (HIV) infection and syphilis infection as an etiological factor in Gestational Trophoblastic Disease (GTD) was investigated by means of micro-enzyme linked immunosorbent assay (Micro-ELISA) and Treposcreen-Rapid Plasma Reagin Card Test in 138 sera from patients with Gestational Trophoblastic Disease. We have found only one sample to be positive for HIV infection and one for VDRL. These findings suggest a lack of an etiologic role for the HIV and Syphilis infection in GTD.
Assuntos
Coriocarcinoma/epidemiologia , Infecções por HIV/epidemiologia , Mola Hidatiforme/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Sífilis/epidemiologia , Neoplasias Uterinas/epidemiologia , Coriocarcinoma/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Humanos , Mola Hidatiforme/complicações , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Sífilis/complicações , Sífilis/diagnóstico , Neoplasias Uterinas/complicaçõesRESUMO
Excretory Secretory (ES) material isolated from the culture fluid of S. digitata was highly antigenic. Neither oesophagus nor excretory cells and excretory pore of the parasite showed reasonable fluorescence with ES antisera. However, the uterine tissue and the egg showed strong fluorescence. The egg showed fluorescence mainly in the space between embryo and egg membrane (amniotic fluid). The amniotic fluid was highly antigenic and appears to be the most important source of ES material released by the filarial parasites.
Assuntos
Antígenos de Helmintos/análise , Filarioidea/imunologia , Animais , Feminino , Imuno-Histoquímica , SetaríaseRESUMO
Antitumor immunity to oral cancer was assessed in 46 patients suffering from squamous cell carcinoma of the oral cavity using a leucocyte adherence inhibition assay (LAI). The response shown by the leucocytes of oral cancer patients to the oral cancer antigen was compared to that shown by the leucocytes from 10 normal age- and sex-matched healthy controls and 43 patients suffering from other types of cancers. Seventy-six percent of the oral cancer patients showed a high degree of leucocyte adherence inhibition in the presence of the antigen. The specificity of this test was further assessed using combinations of the leucocytes from oral cancer patients with extracts from seven cancers occurring at various other sites and extracts of normal oral tissue. The test was highly specific and the leucocytes of oral cancer patients showed significant inhibition only in the presence of oral cancer extract. The inhibition was between 0 and 30% with most other cancer extracts except in the case of extract from cancer of the cervix, where 4/10 patients showed above 30% inhibition. Specific blocking of the LAI response was observed on addition of sera from oral cancer patients to leucocyte-antigen mixtures from oral cancer patients. This effect was not observed on addition of these sera to specific leucocyte-antigen mixtures from other cancer patients. These observations point towards the usefulness of this test in monitoring antitumor immunity in oral cancer patients.