RESUMO
Objective: To evaluate the efficacy and safety of anti-programmed cell death 1 (PD-1) receptor monoclonal antibody (MoAb) in patients with advanced hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitor (TKI). Methods: From February 2019 to February 2020, 56 HCC patients who relapsed after TACE-TKI treatment in Department of Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University were enrolled. All patients received anti-PD-1 MoAb (sintilimab injection) and followed up every 6 weeks. According to mRECIST, the curative effect was evaluated as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Objective response rate (ORR) and disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs) were recorded. Univariate analysis by Chi-square test and binary logistic regression model was used to determine the influencing factors of DCR. The Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the survival data. Results: A total of 48 patients were enrolled in this study including 42 males and 6 females, with a median age of 55 years (29-71 years). ECOG scores comprised of 0 in 24 cases, 1-2 in 24 cases. Thirty-six patients were in Child-Pugh grade A of liver function and 12 cases were grade B. The median follow-up time was 4.5 months. There were 2 patients achieved CR, 12 patients with PR and 16 with SD. ORR was 29.2%, DCR was 62.5%. The independent influencing factors of DCR was ECOG score and AFP level (P=0.031, P=0.012). Median PFS was 4.1 months (95%CI 2.7-5.4 months), and ECOG score was the independent influencing factor of PFS (P=0.042). Treatment-related adverse events were reported in 70.8% (34/48) patients. Incidence of grade â ¢-â £ TRAEs was 22.9% (11/48). Conclusion: In patients with HCC who relapse from TACE and TKI treatment, anti-PD-1 monoclonal antibody is efficacious safe especially in those with ECOG 0 score.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Inibidores Enzimáticos/uso terapêutico , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
Interferon regulatory factors (IRFs) are a family of transcription factors essential to the control of antiviral immune response, cell growth, differentiation and apoptosis. IRF10 was originally found in chicken, which was induced by the v-Rel oncoprotein in lymphoid cell lines and involved in the upregulation of major histocompatibility complex (MHC) class I and guanylate-binding protein. In fish, IRF10 plays negative roles in regulation of the interferon (IFN) response. Here, we identified a splice variant of IRF10, named as EcIRF10-SF in orange spotted grouper, which shares the first three exons with the long form (EcIRF10-LF) and retains part of intron 3, creating a premature termination codon. Furthermore, we observed that the EcIRF10-SF exhibits similar expression pattern compared to its native counterparts. Functional studies demonstrate that the two EcIRF10 isoforms repress DrIFNÏ1 and DrIFNÏ3 promoter activity and negatively regulate fish antiviral gene expression. Subcellular localization analysis shows that the amino acids from 57 to 86 within DBD are required for IRF10 nuclear import. Overall, our description of transcript diversification of IRF10 in the grouper provides a coherent framework to further dissect its roles in immune response.
Assuntos
Bass/genética , Bass/imunologia , Proteínas de Peixes/genética , Imunidade Inata/genética , Fatores Reguladores de Interferon/genética , Regiões Promotoras Genéticas , Transporte Ativo do Núcleo Celular , Animais , Clonagem Molecular , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Fatores Reguladores de Interferon/imunologia , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologiaRESUMO
Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.
Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Reação em Cadeia da Polimerase/métodos , Infecções Respiratórias/etiologia , Viroses/diagnóstico , Viroses/virologia , Vírus/isolamento & purificação , Bactérias/genética , Infecções Bacterianas/epidemiologia , Humanos , Lactente , Pacientes Internados , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Vírus/genéticaRESUMO
BACKGROUND: To establish quicker cardiac arrest and less myocardial distension injury during heart procurement, we combined St. Thomas and histidine-tryptophan-ketoglutarate (HTK) solutions for donor heart preservation since June 2008. METHODS: From June 2008 to March 2010, we enrolled 31 heart transplantation (HT) patients in this study. During heart procurement we initially infused 1,000 mL cold St Thomas cardioplegic solution to achieve cardiac arrest. After procurement, a further 2,000 mL of cold HTK solution was infused at low perfusion pressure. Another 1,000 mL cold HTK solution was perfused before donor heart implantation. We examined donor age, recipient preoperative characteristics, ischemia time, hospital stay, postoperative graft function, major cardiac events, and transplant vasculopathy (TCAD). RESULTS: Twenty-two patients (71.0%) presented with dilated cardiomyopathy and 7 (23.3%) with ischemia cardiomyopathy. There were 23 (76.7%) male donors, and the mean donor age was 38.4 ± 13.8 years. Six patients underwent a redo sternotomy, 1 patient needed a third-do sternotomy, and 1 a seventh sternotomy (third HT) for repeated endocarditis and graft failure. The average ischemia time was 224.9 ± 71.0 minutes and the postoperative hospital stay was 57.7 ± 47.7 days. The surgical mortality (3.2%) was not accompanied by hospital or follow-up mortality. Patient left ventricular ejection fraction postoperative was 59.6 ± 2.3% with good functional status. Major cardiac events occurred in 8 patients (26.7%) without major complications. There were two subjects with TCAD but normal graft function. The correlation between ischemia time and hospital stay was insignificant (r = 0.21; P = .26). CONCLUSIONS: Donor heart preservation combining St Thomas cardioplegic arest and low-pressure perfusion with HTK solution seemed to be safe with. short-term survival similar to other approaches.
Assuntos
Cardiomiopatias/cirurgia , Soluções Cardioplégicas/uso terapêutico , Parada Cardíaca Induzida/métodos , Transplante de Coração , Preservação de Órgãos/métodos , Adolescente , Adulto , Fatores Etários , Bicarbonatos/efeitos adversos , Bicarbonatos/uso terapêutico , Cloreto de Cálcio/efeitos adversos , Cloreto de Cálcio/uso terapêutico , Cardiomiopatias/mortalidade , Soluções Cardioplégicas/efeitos adversos , Isquemia Fria , Feminino , Glucose/efeitos adversos , Glucose/uso terapêutico , Sobrevivência de Enxerto , Parada Cardíaca Induzida/efeitos adversos , Parada Cardíaca Induzida/mortalidade , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Mortalidade Hospitalar , Humanos , Tempo de Internação , Magnésio/efeitos adversos , Magnésio/uso terapêutico , Masculino , Manitol/efeitos adversos , Manitol/uso terapêutico , Pessoa de Meia-Idade , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Cloreto de Potássio/efeitos adversos , Cloreto de Potássio/uso terapêutico , Procaína/efeitos adversos , Procaína/uso terapêutico , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/uso terapêutico , Taiwan , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The JC virus (JCV) may infect human oligodendrocytes and consequently cause progressive multifocal leukoencephalopathy (PML) in patients with immune deficiency. In addition, the virus has also been detected in other human tissues, including kidney, B lymphocytes, and gastrointestinal tissue. The recombinant major structural protein, VP1, of JCV is able to self-assemble to form a virus-like particle (VLP). It has been shown that the VLP is capable of packaging and delivering exogenous DNA into human cells for gene expression. However, gene transfer is not efficient when using in vitro DNA packaging methods with VLPs. In this study, a novel in vivo DNA packaging method using the JCV VLP was used to obtain high efficiency gene transfer. A reporter gene, the green fluorescence protein, and a suicide gene, the herpes simplex virus thymidine kinase (tk), were encapsidated into VLPs in Escherichia coli. The VLP was used to specifically target human colon carcinoma (COLO-320 HSR) cells in a nude mouse model. Intraperitoneal administration of ganciclovir in the tk-VLP-treated mice greatly reduced tumor volume. These findings suggest that it will be possible to develop the JCV VLP as a gene delivery vector for human colon cancer therapy in the future.
Assuntos
Adenocarcinoma/terapia , Neoplasias do Colo/terapia , Terapia Genética/métodos , Vírus JC/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Animais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Escherichia coli/genética , Ganciclovir/uso terapêutico , Técnicas de Transferência de Genes , Vetores Genéticos , Proteínas de Fluorescência Verde/análise , Humanos , Camundongos , Camundongos Nus , Transdução Genética , Células Tumorais Cultivadas , Vírion/genéticaRESUMO
BACKGROUND: We assessed whether the standard uptake of 18-fluorodeoxyglucose (18-FDG) in non-small cell lung cancers (NSCLC) differed between stage I and non-stage I tumors. METHODS: We reviewed 163 patients with NSCLC who underwent surgical lymph node dissection after tumor resection in 2002-2003. Patients with clinical stage I NSCLC who were investigated with preoperative positron emission tomography integrated computed tomography (PET-CT) scans using 18-FDG uptake were included; those with N2 disease were excluded. We reviewed 55 patients with a mean follow-up of 68 months. RESULTS: We analyzed 36 patients with stage I (Group 1) and 19 patients with non-stage I NSCLC (Group 2; 8 stage II, 7 stage III and 4 stage IV). There were no statistical differences in sex, age, tumor size, histological type, location or tumor differentiation between the groups. Group 1 had lower maximum standard 18-FDG uptake values (SUVmax) than Group 2 (4.9 +/- 2.7 vs. 8.1 +/- 3.8; P = 0.001). Using multiple logistic regression, patients with higher preoperative SUVmax and serum carcinoembryonic antigen (CEA) levels showed advanced tumor stages postoperatively (SUVmax > 4.7, odds ratio 7.65; CEA > 3.5 ng/mL, odds ratio 8.39). High 18-FDG uptake was significantly associated with reduced median survival (62.69 months for SUVmax < 4.7 and 40.89 months for SUVmax > 4.7). CONCLUSIONS: High preoperative 18-FDG uptake of tumors was significantly associated with reduced overall patient survival. The SUVmax of the tumor and serum CEA levels demonstrated aggressive tumors and could be helpful preoperatively when considering patients for induction therapy or resection.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Idoso , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Seleção de Pacientes , Pneumonectomia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
UNLABELLED: The aim of this study was designed to investigate the usefulness of thallium-201 single photon emission computed tomography (SPECT) in predicting response of intensity-modulated radiation therapy (IMRT) for recurrent oral squamous cell carcinoma (OSCC). PATIENTS, METHODS: Thirty-one patients with histologically proven recurrent OSCC were recruited. Before IMRT, all patients underwent SPECT at 15 min and 120 min after intravenous injection 111 MBq of thallous chloride ((201)Tl). Tumour uptake was measured with the semiquantitative early ratio (ER), delayed ratio (DR), and retention index (RI). The patients were classified into responder (complete response and partial response) and non-responder (stable disease and progressive disease) groups according to the tumour response evaluated by the Response Evaluation Criteria in Solid Tumors guidelines. RESULTS: As comparing DR and RI between the two groups, both parameters were significantly higher in the responder group. When a DR of 1.75 was used as a cutoff value for the responders, the receiver operating characteristic (ROC) analyses revealed sensitivity and specificity of 79% and 75%, respectively. At a cutoff value for the responders of a RI of 78.5%, the ROC analyses showed sensitivity and specificity of 95% and 83%, respectively. CONCLUSION: Our results suggest that (201)Tl-SPECT, as measured by the DR or RI has clinical potential in predicting response of IMRT for patients with recurrent OSCC. The ROC curve analyses further suggest that RI may be superior to DR in distinguishing responders from non-responders.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/radioterapia , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , RecidivaRESUMO
UNLABELLED: The AIM of this prospective study was to evaluate the usefulness of the thallium-201 ( (201) Tl) thyroid scan in the detection of malignancy in cold thyroid nodules whose status was equivocal following palpation fine-needle aspiration cytology (FNAC). PATIENTS, METHODS: Fifty-one patients with clinically palpable solitary cold thyroid nodules classified as non-diagnostic or suspicious following biopsy underwent (201) Tl thyroid scans. Each scan was performed 15 min (early scan) and 3 h (delayed scan) after an intravenous administration of 74 MBq (201) Tl. Thallium uptake in the nodules was visually assessed and scored on a three point scale, with a grade of three defining malignancy. All patients underwent surgery and the histopathology of nodule tissues were compared with results of the scans. RESULTS: Fifty-one nodules were examined. Forty were benign and 11 were malignant. For early scans, the diagnostically relevant parameters were: sensitivity (100%), specificity (75%), and accuracy (80%). Corresponding findings for the delayed scan were: 91%, 98%, and 96%. CONCLUSION: The (201) Tl scan is useful for detecting malignancy in cold thyroid nodules classified as nondiagnostic or suspicious lesions by FNAC.
Assuntos
Radioisótopos de Tálio , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Cintilografia , Reprodutibilidade dos TestesRESUMO
Protein phosphorylation has been exploited by Nature in profound ways to control various aspects of cell proliferation, differentiation, metabolism, survival, motility and gene transcription. Cellular signal transduction pathways involve protein kinases, protein phosphatases, and phosphoprotein-interacting domain (e.g., SH2, PTB, WW, FHA, 14-3-3) containing cellular proteins to provide multidimensional, dynamic and reversible regulation of many biological activities. Knowledge of cellular signal transduction pathways has led to the identification of promising therapeutic targets amongst these superfamilies of enzymes and adapter proteins which have been linked to various cancers as well as inflammatory, immune, metabolic and bone diseases. This review focuses on protein kinase, protein phosphatase and phosphoprotein-interacting cellular protein therapeutic targets with an emphasis on small-molecule drug discovery from a chemistry perspective. Noteworthy studies related to molecular genetics, signal transduction pathways, structural biology, and drug design for several of these therapeutic targets are highlighted. Some exemplary proof-of-concept lead compounds, clinical candidates and/or breakthrough medicines are further detailed to illustrate achievements as well as challenges in the generation, optimization and development of small-molecule inhibitors of protein kinases, protein phosphatases or phosphoprotein-interacting domain containing cellular proteins.
Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/química , Fosfoproteínas Fosfatases/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Proteínas Quinases/efeitos dos fármacos , Proteínas/metabolismo , Inibidores Enzimáticos/farmacologia , Fosfoproteínas Fosfatases/química , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/química , Proteínas Quinases/metabolismo , Estrutura Terciária de Proteína , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
AIM: The aim of this study was to evaluate the effectiveness of technetium-99m tetrofosmin (Tc-99m TF) single photon emission computed tomography (SPECT) of the neck and chest to detect metastatic lesions in papillary thyroid carcinoma (PTC) after near total thyroidectomy and radioiodine (I-131) treatment in patients who present with elevated serum human thyroglobulin (hTg) levels but negative I-131 whole body scan (WBS). MATERIALS AND METHODS: Twenty patients with PTC treated by near total thyroidectomy and I-131 treatments were included in this study. All 20 patients had negative I-131 WBS results and elevated hTg levels (hTg 2.0 microIU/ml) under thyroid-stimulating hormone (TSH) stimulation (TSH 30 microIU/ml). Nineteen of the 20 cases were confirmed to have metastases by operation/biopsy histopathological findings or clinical follow-up longer than 1 year by additional morphological imaging techniques. The remaining patient has been followed up closely and has been disease free for 10 months. Tc-99m TF SPECT was performed to detect metastatic lesions. RESULTS: Tc-99m TF SPECT demonstrated lesions in 11/19 patients; a sensitivity of 57.9%. Tc-99m TF SPECT failed to demonstrate lesions in eight patients including smaller lymph nodes and miliary lung metastases. CONCLUSIONS: We conclude that Tc-99m TF SPECT is a useful additional tool to detect metastatic lesions in PTC with elevated hTg but negative I-131 WBS. However, smaller lymph nodes and miliary lung metastases may be missed.
Assuntos
Carcinoma Papilar/diagnóstico por imagem , Metástase Neoplásica/diagnóstico por imagem , Compostos Organofosforados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Tireoglobulina/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Carcinoma Papilar/sangue , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/sangue , Irradiação Corporal Total/normasRESUMO
99mTc ethyl cysteinate dimer (99mTc-ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in patients with acute carbon monoxide (CO) poisoning. Ten patients with acute CO poisoning and no past histories of psychoneurological disorders were enrolled in this study. After oxygen treatment, all of the 10 patients were investigated using 99mTc-ECD brain SPECT and brain computed tomography (CT) scan. Brain CT scan findings were normal in all of the 10 patients. 99mTc-ECD brain SPECT showed the hypoperfusion lesions of the basal ganglia and brain cortex in five and seven patients, respectively. Only three of the 10 patients had normal 99mTc-ECD brain SPECT findings. This study suggests that, in comparison with brain CT scan, 99mTc-ECD brain SPECT is a better tool for the early detection of hypoperfusion brain lesions in acute CO poisoning in patients with normal brain CT findings.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Cisteína/análogos & derivados , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adolescente , Adulto , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Intoxicação por Monóxido de Carbono/complicações , Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Masculino , Radiografia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 32 female patients with primary Sjögren's syndrome (PSS) showing definite neuropsychiatric symptoms/signs and normal brain magnetic resonance imaging (MRI) findings. It demonstrated hypoperfusion brain lesions in 18 (56.3%) of the patients, most frequently in the parietal lobes, and appears to be a sensitive tool for this clinical application.
Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Cisteína/análogos & derivados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Síndrome de Sjogren/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Encéfalo/irrigação sanguínea , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnósticoRESUMO
Methylprednisolone pulse therapy (MPT) was introduced to avoid life-threatening complications in systemic lupus erythematosus (SLE) with brain manifestations. However, its efficacy in SLE patients remains uncertain and needs to be objectively evaluated. In this study, technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect regional cerebral blood flow (rCBF) in SLE patients with normal brain magnetic resonance imaging (MRI) findings. Twelve female SLE patients with neuropsychiatric symptoms were enrolled in this study. All patients had normal brain MRI and abnormal Tc-99m ECD brain SPECT findings. The Tc-99m ECD brain SPECT studies were performed 2 weeks after MPT. Pre- and post-MPT serum levels of anticardiolipin antibodies (ACA) and antiribosomal P antibodies (anti-P) were also measured. Before MPT, four patients had positive ACA and seven had positive anti-P. After MPT, all 12 patients demonstrated negative serologic findings and no neuropsychiatric symptoms. After MPT, ten patients showed complete recovery and two showed partial recovery of rCBF in the follow-up Tc-99m ECD brain SPECT images. This imaging is a logical and objective tool for measuring the effects of MPT in SLE patients with brain involvement by the determination of rCBF changes.
Assuntos
Anti-Inflamatórios/administração & dosagem , Circulação Cerebrovascular/imunologia , Cisteína/análogos & derivados , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Metilprednisolona/administração & dosagem , Compostos de Organotecnécio , Proteínas de Protozoários , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Anticorpos Anticardiolipina/sangue , Autoanticorpos/sangue , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/imunologia , Feminino , Humanos , Pulsoterapia , Proteínas Ribossômicas/imunologiaRESUMO
Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 78 SLE patients with neuropsychiatric manifestations. These patients were separated into two subgroups: group 1 including 48 cases with definite neuropsychiatric symptoms/signs and group 2 with 30 cases having no neuropsychiatric symptoms/signs. Tc-99m ECD brain SPECT demonstrated hypoperfusion brain lesions in 90% and 20% of patients in groups 1 and 2, respectively. In both groups, parietal lobe and cerebellum are the most and least common areas with hypoperfusion lesions, respectively. This study suggests that Tc-99m ECD brain SPECT may provide objective information for detection of hypoperfusion brain lesions in SLE patients.
Assuntos
Cisteína/análogos & derivados , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/fisiopatologia , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Estudos de Casos e Controles , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Antibodies to hepatitis C virus (HCV) may decrease or disappear after viral clearance in treated or spontaneously resolved infection. We evaluated the usefulness of serial antibody assays in predicting the antiviral treatment responses. One hundred and four chronic hepatitis C patients who received 24 weeks of interferon and ribavirin combination therapy were assayed with a third generation enzyme immunoassay anti-HCV. The mean titre of anti-HCV decreased by more than 50% (from 89.5 +/- 10.8 to 43.6 +/- 17.5) at 48 weeks post-treatment in patients with a sustained virological response, while in nonsustained virological responders and nonresponders, the titres remained over 85% of the pretreatment level at 48 weeks post-treatment. There was a divergence of anti-HCV titres between sustained and nonsustained virological responders during 6-9 months. By using the ratio of 9-month to 6-month titres as an index and receiver operator characteristic curve analysis with the cut-off point set at 90%, we could differentiate sustained virological responders from nonsustained virological responders with a sensitivity and specificity of 91.7% and 90.9%, respectively, 3 months after treatment. The titre of this third generation anti-HCV decreased progressively in sustained virological responders and this assay may be used to monitor and predict antiviral treatment responses.
Assuntos
Antivirais/uso terapêutico , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , Combinação de Medicamentos , Feminino , Hepatite C Crônica/sangue , Humanos , Técnicas Imunoenzimáticas , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico , Proteínas Recombinantes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: This study was undertaken to investigate the effects of temperature on preserving the radiochemical purity and immunoreactivity of 125I- and 131I-labeled monoclonal antibody (MAb) 1H10--an antibody against human cervical carcinoma cell-surface antigen. METHODS: An antibody-irrelevant human melanoma cell line, H2269, served as the control group. Iodine-125 and 131I radiolabeling of MAbs 1H10 and H2669 was performed by the chloramine-T method. All the prepared MAbs were divided into aliquots and stored at 4, -20, and -70 degrees C for 2-14 d. The radiochemical purity and immunoreactivity of the labeled antibodies in set conditions were measured by thin-layer chromatography and a modified index, respectively, after a single freeze-and-thaw cycle. RESULTS: Reduced release of free radioiodide and better preservation of immunoreactivity were observed in the radiolabeled MAbs stored at -70 degrees C than in those stored at -20 degrees C or 4 degrees C. The extent of free iodide dissociation and immunologic binding degradation of 125I-labeled MAb 1H10 appeared milder than that of 131I-labeled MAb under the same conditions. However, both 125I- and 131I-labeled MAb stored at -70 degrees C or -20 degrees C retained more than 90% radiochemical purity for at least 3d. CONCLUSION: Freezing provides an appropriate alternative for reducing radiolysis and preserving immunoreactivity of radioiodinated MAbs. MAb 1H10, labeled with either 125I or 131I and stored at temperatures of -20 degrees C or below for 3 d after labeling, appeared stable in both radiolabeling and binding studies in vitro and was still acceptable for in vivo use.
Assuntos
Anticorpos Monoclonais/química , Antígenos de Neoplasias/imunologia , Antígenos de Superfície/imunologia , Carcinoma/imunologia , Radioisótopos do Iodo/química , Anticorpos Monoclonais/imunologia , Cromatografia em Camada Fina , Temperatura Baixa , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Feminino , Congelamento , Humanos , Melanoma/imunologia , Temperatura , Fatores de Tempo , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/imunologiaRESUMO
BACKGROUND: To determine the incidence, causes, and associated risk factors of adult intussusception. METHODS: Forty-five cases of adult intussusception proven by surgery were collected from 58,000 surgeries performed from December 1986 through December 1998. The condition leading to intussusception, imaging studies, and clinical risk factors were analyzed. RESULTS: Nineteen men and 26 women, 18 to 83 years of age (mean, 52.6 years), experienced intussusception. The incidence of adult intussusception was 0.08% of abdominal surgeries and 3.0% of intestinal obstructions. A benign process was diagnosed in 25 cases (55.6%), malignancy in 16 cases (35.6%), surgery-related intussusception in 1 case (2.2%), and an idiopathic condition existed in 3 cases (6.6%). The major cause of adult intussusception due to benign lesions was polyps (12/25) and for malignancy, it was colonic adenocarcinoma (14/16). The diagnostic imaging rates were 52% for computed tomography, 41% for barium studies and 32% for abdominal ultrasound. There was no mortality due to intussusception; 4 patients (8.9%) died of colon cancer with liver metastasis. No definite risk factor was identified, but leukocytosis and a shorter preoperative duration tended to increase the risk of complications (p = 0.084, 0.082 respectively). CONCLUSION: Malignancy was the major cause of colonic intussusception, as was a benign process the primary cause of intestinal intussusception. These adult patients with intussusception received adequate surgical care and had a good prognosis except for those with colon cancer and liver metastasis.
Assuntos
Intussuscepção/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Intussuscepção/diagnóstico , Intussuscepção/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoAssuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Feminino , Hiperplasia Nodular Focal do Fígado/diagnóstico , Humanos , Compostos Radiofarmacêuticos , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The linear peptide dolastatin 15 (1), a potent antineoplastic constituent from the shell-less mollusk Dolabella auricularia, has been selected as the lead compound for developing novel antitumor drugs. Recently LU103793 (2), a synthetic and structure-simplified analog of dolastatin 15, has been demonstrated to be highly cytotoxic [IC50 = 0.1 nM; M. De Arruda, C.A. Cocchiaro, C.M. Nelson, C. M. Grinnel, B. Janssen, A. Haupt & T. Barlozzari (1995) Cancer Res. 55, 3085-3092]. Both compounds have been undergoing human cancer clinical trials in Europe and North America. Based on the novel structure of LU103793, a series of analogs modified at the N-terminal dolavalyl moiety and -Pro-Pro-benzylamide unit was developed. These synthesized analogs were tested using a sulforhodamine B (SRB) assay for the drug-screening program at NCI on a variety of human cancer cell lines. As expected, most analogs exhibited potent and selective growth inhibition against leukemia. Analog 18 was specifically active against HL-60 and K-562 cell lines (GI50s: 0.05 microM and 0.07 microM, respectively) while analogs 14 and 17 were selectively potent against prostate and breast cancer cell lines (GI50s at micromolar levels). However, all analogs were less potent than 2 as growth inhibitors of some breast and colon cancer cell lines (e.g. MDA-MB-435 and HT-29). We believe that modification of novel marine natural products as synthetic analogs might show particular promise for developing novel anticancer candidates with moderate specificity.
Assuntos
Antineoplásicos/química , Divisão Celular/efeitos dos fármacos , Oligopeptídeos/química , Sequência de Aminoácidos , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Células Tumorais CultivadasRESUMO
In a previous study we observed increased serum levels of a 3,3'-diiodothyronine sulfate (T2S)-like material (compound W) in women who received human chorionic gonadotropin (hCG) treatment. In the present study we assessed serum compound W values in 113 women (total serum sample: 190) with trophoblastic disease, in 7 normal nonpregnant women during the menstrual cycle and 7 women given hCG treatment in the course of in vitro fertilization. Fifty-three women with trophoblastic disease had serum free thyroxine (FT4) concentrations greater than 3.0 ng/dL with suppressed serum thyrotropin (TSH) levels; 61 had FT4 values less than 3.0 ng/dL with a mean TSH of 0.83 mU/L. Mean (+/- SE) compound W concentrations in the high FT4 group were significantly higher than in the low FT4 group (76 +/- 8.1 vs. 21 +/- 1.7 ng T2S equivalent, p < 0.001) There were significant correlations between serum hCG and compound W concentrations (r = 0.472, p < 0.001), serum FT4 and hCG (r = 0.503, p < 0.0001) and serum FT4 and compound W (r = 0.585, p < 0.0001). In nonpregnant women serum compound W levels increased from 7.5 +/- 8 ng/dL at the end of the menstrual period to 15 +/- 1.7 ng/dL 21 days after the last menstrual period. Finally, a single dose of hCG (10,000 USP units, intramuscularly) increased mean (+/- SE) serum compound W levels from 12.8 +/- 2.3 to 64 +/- 9.7 ng/dL and 54 +/- 12 ng/dL at 9 and 16 days, respectively. These results indicate that hCG and perhaps luteinizing hormone (LH) increase serum compound W concentrations in women. The mechanism and significance presently are unclear.