RESUMO
AIMS: To evaluate the effect of IM administration of three sedative drugs, acepromazine, alfaxalone and dexmedetomidine, in combination with morphine, on the size of the feline spleen using ultrasonography. METHODS: Twenty-four client-owned cats undergoing elective de-sexing or minor procedures were recruited for a focused ultrasonographic examination of the spleen prior to and at 10, 20 and 30â minutes following administration of one of three randomly assigned IM sedation protocols: 0.05â mg/kg acepromazine (ACE group), 3â mg/kg alfaxalone (ALF group), or 10 µg/kg dexmedetomidine (DEX group), in combination with 0.5â mg/kg morphine. B-mode images of the spleen were collected and measured following a standardised protocol. Cardiorespiratory parameters and sedation score were also recorded. Mean thickness of the head, body and tail of the spleen for each group at 10, 20 and 30â minutes after drug administration was compared to baseline. RESULTS: Mean splenic thickness increased over time in the ACE group (thickness of body at T0 = 8.9 (SE 2.1) mm and at T30 = 10.5 (SE 2.0) mm; p = 0.001) and the ALF group (thickness of body at T0 = 8.8 (SE 1.0) mm and at T30 = 10.3 (SE 1.7) mm; p = 0.022) but not in the DEX group (thickness of body at T0 = 8.6â mm (1.2) and at T30 = 8.9â mm (0.6); p = 0.67). Mean arterial blood pressure in the DEX group was significantly higher than in the other groups (p = 0.002). Sedation scores in the DEX group were consistently high for the entire period. However, the sedation score in the ACE group increased over 30â minutes (p = 0.007). Sedation score in the ALF group was highest at 10â minutes but gradually decreased over the following 20â minutes (p = 0.003). CONCLUSIONS: Sedation with IM dexmedetomidine and morphine did not change splenic size, whereas acepromazine or alfaxalone and morphine increased it regardless of the degree of sedation. CLINICAL RELEVANCE: Where splenomegaly is identified in a cat sedated with acepromazine or alfaxalone, the effects of the sedation protocol could be considered as a possible cause.
Assuntos
Dexmedetomidina , Gatos , Animais , Dexmedetomidina/farmacologia , Acepromazina/farmacologia , Baço/diagnóstico por imagem , Hipnóticos e Sedativos/farmacologia , Morfina , UltrassonografiaRESUMO
BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagoscopia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Progressão da Doença , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Esofagoscopia/efeitos adversos , Esofagoscopia/mortalidade , Feminino , Hospitais Universitários , Humanos , Japão , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell carcinoma (SESCC) limited to the epithelium or lamina propria mucosae (EP/LPM). We aimed to compare the efficacy of endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) for predicting the tumor invasion depth in patients with SESCC. Specifically, we evaluated the ability of these examinations to distinguish EP/LPM from SESCC invading the muscularis mucosae or superficial submucosa (MM/SM1) and more deeply invasive lesions before ESD.We retrospectively analyzed a database of all patients with SESCC who had undergone both EUS and ME-NBI for pretreatment staging and ESD resection at Hiroshima University Hospital between September 2007 and June 2015. The clinicopathologic characteristics of SESCCs were classified according to the Japanese Classification of Esophageal Cancer.A total of 174 lesions in 174 patients were included: 124 (71%) EP/LPMs, 35 (20%) MM/SM1s, and 15 (9%) SESCCs invading the mid submucosae (SM2). The sensitivity of EUS and of ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 72% and 83%, respectively. The accuracy of EUS and ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 70% and 82%, respectively. Sensitivity and accuracy of ME-NBI in distinguishing EP/LPM from MM/SM1 and more deeply invasive SESCCs is significantly higher than those of EUS (P = 0.048 and P = 0.017, respectively).ME-NBI may be more useful than EUS for the determination of SESCC invasion depth before ESD.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Esofagoscopia , Imagem de Banda Estreita , Idoso , Carcinoma de Células Escamosas/cirurgia , Ressecção Endoscópica de Mucosa , Endossonografia/métodos , Mucosa Esofágica/diagnóstico por imagem , Mucosa Esofágica/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Esofagoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Banda Estreita/métodos , Invasividade Neoplásica/diagnóstico por imagem , Período Pré-Operatório , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The first-line combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and platinum-based doublet chemotherapy has not been sufficiently evaluated for patients with EGFR-mutant non-small cell lung cancer (NSCLC). This randomized phase II study was designed to select a combination regimen for phase III evaluation. PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced non-squamous, EGFR-mutant NSCLC were randomly assigned to receive either a concurrent or a sequential alternating regimen with gefitinib (250 mg) and carboplatin/pemetrexed [area under the curve (AUC) = 6 and 500 mg/m(2); 3-weekly]. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), response, and safety. RESULTS: All 80 patients enrolled were eligible and assessable for efficacy (41 and 39 patients in the concurrent and sequential alternating regimen groups, respectively). Median PFS was 18.3 months for the concurrent regimen and 15.3 months for the sequential alternating regimen [hazard ratio (HR) 0.71 (0.42-1.20), P = 0.20]. Although OS data are immature (16 and 24 death events), median survival times were 41.9 and 30.7 months in the concurrent and sequential alternating regimen groups, respectively [HR 0.51 (0.26-0.99); P = 0.042]. Response rates were similar in both groups (87.8% and 84.6%). Hematological and non-hematological adverse events were common and reversible; interstitial lung disease was neither frequent nor fatal (two cases in each group; 5% of all patients). CONCLUSION: This is the first randomized study to investigate the efficacy of combinational EGFR-TKI and chemotherapy in the EGFR-mutated setting. Both regimens had promising efficacy with predictable toxicities, although concurrent regimens might provide better OS. The concurrent regimen was chosen to compare with gefitinib monotherapy in our ongoing phase III study. CLINICAL TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN C000002789).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Gefitinibe , Predisposição Genética para Doença , Humanos , Japão , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem , Fenótipo , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). METHODS: MIA2 role was examined by immunohistochemistry of human OSCCs and knockdown studies using human 3 OSCC cell lines with MIA2 expression. RESULTS: MIA2 expression was observed in 62 (66.7%) of 93 OSCCs and was associated with tumour expansion and nodal metastasis. Melanoma inhibitory activity 2 expression was inversely correlated with intratumoral infiltration of lymphocytes. Invasion and anti-apoptotic survival were reduced by MIA2 knockdown in HSC3 cells. MOLT-3 lymphocytes infiltrating the HSC3 cell layer was enhanced by MIA2 knockdown or MIA2 depletion with the antibody. In HSC3 cells, MIA2 knockdown decreased the expressions of vascular endothelial growth factor (VEGF), VEGF-C, and VEGF-D. The downregulation of VEGF-C and -D was caused by inhibition of p38 and extracellular signal-regulated kinase (ERK)1/2, respectively. Melanoma inhibitory activity 2 was co-precipitated with integrin α4 andα5 in HSC3 cells. Integrin α4 knockdown decreased p38 phosphorylation and increased apoptosis, whereas integrin α5 knockdown decreased c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis. Inhibition of JNK decreased apoptosis in the HSC3 cells. CONCLUSION: These findings suggest that the roles of MIA2 might be based on the variety of the integrins and the subtypes of mitogen-activated protein kinase.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Idoso , Antígenos de Neoplasias , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Integrinas/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Proteínas de Neoplasias , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/imunologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator C de Crescimento do Endotélio Vascular/biossíntese , Fator D de Crescimento do Endotélio Vascular/biossínteseRESUMO
BACKGROUND: MicroRNA (miRNA)-126 (miR-126) is an endothelial-specific miRNA located within intron 7 of epidermal growth factor-like domain 7 (EGFL7). However, the role of miR-126 in cancer is controversial. METHODS: We examined the function of miR-126 in oral squamous cell carcinoma (OSCC) cells. Furthermore, a series of 118 cases with OSCC were evaluated for the expression levels of miR-126. RESULTS: MicroRNA-126 (miR-126) was associated with cell growth and regulation of vascular endothelial growth factor-A activity, and demethylation treatment increased expression levels of miR-126 and EGFL7 in OSCC cells. A significant association was found between miR-126 expression and tumour progression, nodal metastasis, vessel density, or poor prognosis in OSCC cases. In the multivariate analysis, decreased miR-126 expression was strongly correlated with disease-free survival. CONCLUSION: The present results suggest that miR-126 might be a useful diagnostic and therapeutic target in OSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Linfangiogênese/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação ao Cálcio , Linhagem Celular Tumoral , Intervalo Livre de Doença , Regulação para Baixo , Família de Proteínas EGF , Fatores de Crescimento Endotelial/genética , Feminino , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Ativação TranscricionalRESUMO
Intractable pneumothorax with interstitial pneumonia (IP) is famous for the disease finally to lead to death in case of persistent air leakage. It is because severe infection, respiratory insufficiency and tissue healing insufficiency by treatments with steroid hormones and immune-suppressants on IP. Pleurodesis is generally performed although the effect of it is questionable. It is important to stop immune-suppressants and reduce steroid hormones before the treatments to succeed in thoracoscopic surgery and thoracographic fibrin glue sealing method (TGF) if possible. Less invasive interventional treatments like TGF are recommendable because intractable pneumothorax with IP is in the high risk group to need to avoid surgery. Hand suturing, looping, covering and putting TachoComb on the air leak point instead of end-stapling should be performed in order to stop air leakage when forced to choose thoracoscopic surgery.
Assuntos
Doenças Pulmonares Intersticiais/complicações , Pneumotórax/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Adesivo Tecidual de Fibrina/administração & dosagem , Humanos , Pessoa de Meia-Idade , Pneumotórax/complicações , ToracoscopiaRESUMO
Reverse osmosis (RO) membrane is one of the most powerful tools for solving the global water crisis, and is used in a variety of water treatment scenes such as drinking water purification, waste-water treatment, boiler feed water production, ultra pure water production for semiconductor industry, etc. The desired performance of RO membrane varies according to quality of feed water being treated, and Toray has been developing RO membranes with suitable characteristic for each operating condition. RO membranes for seawater desalination and wastewater reclamation are especially regarded as most promising targets. Recently, high boron removal and energy saving RO membrane for seawater desalination and low fouling RO membrane for wastewater reclamation have been developed. In this paper, the prospect of attaining these renovative RO membrane, and furthermore, job references will be discussed.
Assuntos
Membranas Artificiais , Osmose , Reciclagem , Água do Mar/química , Cloreto de Sódio/química , Eliminação de Resíduos Líquidos/métodos , Boro/química , Poluentes Químicos da Água/química , Purificação da Água/instrumentação , Purificação da Água/métodosRESUMO
Six plant sources of hydrolyzable tannins (HT) or HT and condensed tannins (CT; designated as HT1, HT2, HT3, HT + CT1, HT + CT2, and HT + CT3) were evaluated to determine their effects in vitro on CH(4) production and on ruminal archaeal and protozoa populations, and to assess potential differences in biological activities between sources containing HT only or HT and CT. Samples HT1, HT2, and HT3 contained only HT, whereas samples HT + CT1, HT + CT2, and HT + CT3 contained HT and CT. In experiment 1, in vitro incubations with samples containing HT or HT + CT resulted in a decrease in CH(4) production of 0.6 and 5.5%, respectively, compared with that produced by incubations containing the added tannin binder polyethylene glycol-6000. Tannin also suppressed the population of methanogenic archaea in all incubations except those with HT2, with an average decrease of 11.6% in HT incubations (15.8, 7.09, and 12.0 in HT1, HT2, and HT3) and 28.6% in incubations containing HT + CT (35.0, 40.1, and 10.8 in HT + CT1, HT + CT2, and HT + CT3) when compared with incubations containing added polyethylene glycol-6000. The mean decrease in protozoal counts was 12.3% in HT and 36.2% in HT + CT incubations. Tannins increased in vitro pH, reduced total VFA concentrations, increased propionate concentrations, and decreased concentrations of iso-acids. In experiment 2, when a basal diet was incubated with graded levels of HT + CT1, HT + CT2, and HT + CT3, the total gas and CH4 production and archaeal and protozoal populations decreased as the concentration of tannins increased. Our results confirm that tannins suppress methanogenesis by reducing methanogenic populations in the rumen either directly or by reducing the protozoal population, thereby reducing methanogens symbiotically associated with the protozoal population. In addition, tannin sources containing both HT and CT were more potent in suppressing methanogenesis than those containing only HT.
Assuntos
Archaea/fisiologia , Bovinos , Cilióforos/fisiologia , Ácidos Graxos Voláteis/metabolismo , Metano/metabolismo , Rúmen , Taninos/metabolismo , Animais , Archaea/efeitos dos fármacos , Archaea/genética , Cilióforos/efeitos dos fármacos , Feminino , Polietilenoglicóis/farmacologia , RNA Ribossômico 16S/genética , Rúmen/metabolismo , Rúmen/microbiologia , Rúmen/parasitologia , Tensoativos/farmacologiaRESUMO
A study of 783 patients with stomach cancer and 1,566 hospital controls in Hiroshima and Miyagi prefectures of Japan showed that farmers, representing mostly the lowest socioeconomic class, had higher risk of developing stomach cancer. The usual inverse gradient in risk by social class was in the urban population of Miyagi, but not Hiroshima, prefecture. The study in Japan did not reproduce the association of stomach cancer with consumption of salted/dried fish and salt-pickled vegetables described for the Hawaiian Japanese. Salted/dried fish and pickled vegetables were more widely used by farmers than by nonfarmers in Japan or by Japanese migrants to Hawaii. The ability to detect associations for these typical Japanese foods in Hawaii stemmed from the fact that these reduced levels of use were more completely expressed by the Hawaiian-Japanese controls than by patients. The lower risk of developing stomach cancer for lettuce and celery users agreed with the Hawaiian-Japanese findings, and the combined results supported conjectures on possible protective food effects. Lettuce, in particular, warranted attention from this viewpoint, since similar findings have been consistently reported.
Assuntos
Neoplasias Gástricas/epidemiologia , Fatores Etários , Agricultura , Dieta , Feminino , Humanos , Japão , Masculino , Menarca , Risco , Fatores Sexuais , Fatores Socioeconômicos , Neoplasias Gástricas/mortalidade , Abastecimento de ÁguaRESUMO
We investigated primary human lung cancers resected surgically or obtained at autopsy. Included were squamous cell carcinoma (SQC) (five cases), adenocarcinoma (ADC) (six cases), large cell carcinoma (LCC) (four cases), and small cell carcinoma (SCC) (two cases). The objective of the study was to search for the presence of insulin-like growth factor I (IGF-I)-like immunoreactivity using immunohistochemical staining and for the localization of IGF-I binding sites, using in vitro quantitative receptor autoradiographic techniques. IGF-I-like immunostaining was present in all cases of SQC, ADC, and LCC, but not in cases of SCC. Strong immunostaining was observed in cases of SQC. On the other hand, ADC and LCC tissues showed a moderate or weak staining. Specific binding sites for IGF-I were present in all cases of SQC, ADC, LCC, and SCC examined. High densities of 125I-IGF-I binding sites were localized in cases of SQC and SCC. Low to high densities of the binding sites were found in LCC. Cases of ADC showed low densities of 125I-IGF-I binding sites. Specific binding obtained at a concentration of 80 pM 125I-IGF-I was competitively displaced by unlabeled IGF-I, with a 50% inhibitory concentration value of 1.84 +/- 0.31 x 10(-10) mol, whereas human insulin was much less potent in displacing the binding. This specificity profile is consistent with characteristics of IGF-I receptors. Scatchard analysis showed the presence of a single class of high affinity binding sites for IGF-I, with a Kd of approximately 1 nmol. Thus, the possibility that IGF-I may play a role in the growth of human lung cancers would have to be considered.
Assuntos
Fator de Crescimento Insulin-Like I/análise , Neoplasias Pulmonares/patologia , Somatomedinas/análise , Adenocarcinoma/patologia , Autorradiografia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Imuno-Histoquímica , Radioisótopos do Iodo , Receptores de Superfície Celular/metabolismo , Receptores de SomatomedinaRESUMO
Three alkaline RNases were purified from human pancreatic juice to near homogeneity as judged by sodium dodecyl sulfate and native polyacrylamide gel electrophoreses. The molecular weights of these RNases determined by sodium dodecyl sulfate electrophoresis were 27,000, 19,000, and 13,000. The activities of these three RNases were increased by addition of Mg2+, Ca2+, Co2+, K+, Na+, spermine, and spermidine and decreased by the addition of heparin, Cu2+, and Zn2+. These RNases showed higher hydrolytic activity toward polycytidylic acid than toward polyguanylic acid, polyuridylic acid, or polyadenylic acid. The three human pancreatic RNases were immunologically identical but differed from human liver RNase, as shown by Ouchterlony double-diffusion test. Radioimmunoassay of human pancreatic RNase showed that immunologically similar RNases are present in human saliva, and serum.
Assuntos
Suco Pancreático/enzimologia , Ribonucleases/isolamento & purificação , Animais , Bovinos , Cromatografia em Gel , Cromatografia por Troca Iônica , Reações Cruzadas , Humanos , Imunodifusão , Cinética , Peso Molecular , Radioimunoensaio , Ribonucleases/metabolismoRESUMO
Clonal chromosome abnormalities were found in 89 (97%) of 92 patients with non-Hodgkin's malignant lymphoma including immunologically determined 34 B- and 25 T-lymphomas; only 3 of 19 T-lymphoma patients examined had serum adult T-cell leukemia/lymphoma-associated antigen antibody. Association of 8q24 translocations with small non-cleaved cell (P less than 0.01) and that of t(14;18) (q32;q21) with follicular histology (P = 0.03) were significant. Several other abnormalities were also found to be correlated with histological or immunological phenotypes: trisomy 5 with diffuse, mixed cell lymphoma (P = 0.03); a break at 3q21 with diffuse, large cell lymphoma (P = 0.04); gain of chromosome 18 or X and rearrangements of 13q with immunoblastic lymphoma (P = 0.02, 0.03, and 0.03, respectively); and rearrangements of 7q with diffuse large cell histology (P = 0.02) and T-cell phenotype (P = 0.02). Multiple clones were more frequently seen in T-cell lymphoma than in B-cell lymphoma (P = 0.01). Structural changes of the long arm of chromosome 4 or 15 and a break in 6p21 were also associated with T-lymphoma (P = 0.03, respectively). Since the frequency of T-lymphoma is significantly higher and that of t(14;18) is significantly lower in the adult T-cell leukemia/lymphoma nonendemic area of Saitama in Japan than in Minnesota in the United States (P less than 0.01), factors affecting the lymphoma-genesis may be different or operating in different intensities in different areas.
Assuntos
Aberrações Cromossômicas , Linfoma não Hodgkin/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Japão , Cariotipagem , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
A method for radioimmunoassay of human pancreatic RNase was developed. The method is sensitive, reproducible, and specific. Almost no cross-reactivity exists between human pancreatic and liver RNases. A good correlation was observed between the serum concentration of pancreatic RNase as measured by radioimmunoassay and its enzymatic activity using polycytidylic acid as substrate. The concentration of serum pancreatic RNase correlates well with age, blood urea nitrogen, and albumin contents but does not correlate with serum amylase activity. Using the data of 52 patients with malignant tumors except pancreatic cancer, serum RNase level could be expressed by a multiple regression equation: Immunoreactive RNase content in pancreatic cancer was elevated in patients with complications from renal failure. Serum pancreatic RNase contents in patients with pancreatic cancer measured by radioimmunoassay agreed well with the values calculated using the equation derived from the data of patients with other malignant tumors.
Assuntos
Neoplasias/enzimologia , Pâncreas/enzimologia , Ribonucleases/sangue , Humanos , Radioisótopos do Iodo , Cinética , Radioimunoensaio/métodos , Análise de Regressão , Albumina Sérica/análiseRESUMO
BACKGROUND: The secosteroid 1 alpha,25-dihydroxyvitamin D(3) (1) has a wide variety of biological activities, which makes it a promising therapeutic agent for the treatment of cancer, psoriasis and osteoporosis. Insight into the structure-activity relationships of the A-ring of 1 is still needed to assist the development of more potent and selective analogues as candidate chemotherapeutic agents, as well as to define the molecular mode of action. RESULTS: All possible A-ring stereoisomers of 5,6-trans-2-methyl-1,25-dihydroxyvitamin D(3) (6a-h) and their 20-epimers (7a-h) were designed and efficiently synthesized. The dependence of the affinities for vitamin D receptor (VDR) and vitamin D binding protein (DBP), as well as the HL-60 cell differentiation-inducing activity, upon the stereochemistry of the A-ring and at C20 in the side chain was evaluated. CONCLUSIONS: The binding affinities and potency of the 5,6-trans and 5,6-cis analogues were enhanced by a 2-methyl substituent in a certain orientation. Molecular docking studies based upon the X-ray crystal structure of VDR suggested that the axial 2-methyl group would be accommodated in a pocket surrounded by hydrophobic amino acid residues in the ligand binding domain, resulting in enhanced interaction.
Assuntos
Vitamina D/análogos & derivados , Vitamina D/química , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Bovinos , Diferenciação Celular/efeitos dos fármacos , Células HL-60 , Humanos , Ligação Proteica , Conformação Proteica , Receptores de Calcitriol/química , Receptores de Calcitriol/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Timo , Vitamina D/metabolismo , Vitamina D/farmacologia , Proteína de Ligação a Vitamina D/química , Proteína de Ligação a Vitamina D/metabolismoRESUMO
A multi-institutional cooperative study comparing lithium carbonate with chlorpromazine was conducted, using a controlled double-blind design in a series of 80 cases of endogenous manic psychosis, to evaluate the drugs' clinical utility and efficacy, characteristics of therapeutic effect, and side-effects. Dosages employed were consistently at an equipotent ratio of 4:1 (lithium carbonate:chlorpromazine). Physicians' overall ratings showed lithium carbonate as significantly superior to chlorpromazine in efficacy for manic psychosis. Improvements of basic mood and of disturbance in speech and voice were prominent with lithium carbonate. Onset of the therapeutic effect of lithium carbonate was within ten days of medication in 65% of the patients, significantly faster than with chlorpromazine. Side-effects encountered with lithium carbonate therapy at dose levels not higher than 1,800 mg/day were milder and less frequent compared with those seen with chlorpromazine.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Clorpromazina/uso terapêutico , Lítio/uso terapêutico , Adolescente , Adulto , Clorpromazina/administração & dosagem , Clorpromazina/efeitos adversos , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Feminino , Humanos , Japão , Lítio/administração & dosagem , Lítio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Organizações de Normalização ProfissionalRESUMO
OBJECTIVES: To conduct a phase I/II study of irinotecan with cisplatin to establish a recommended dose, and assess the safety, efficacy and feasibility of this regimen in unresectable advanced or recurrent gastric cancer. PATIENTS AND METHODS: In the phase I portion of the study, patients received a fixed dose of cisplatin (30 mg/m2) with escalating doses of irinotecan, ranging from 30 mg/m2 to 70 mg/m2, on days 1 and 15. In the phase II portion of the study, 40 patients were evaluated for response and safety at the recommended dose. RESULTS: Eighteen patients were enrolled in the phase I study. Dose-limiting toxicity (diarrhea and neutropenia) appeared at the irinotecan dose of 70 mg/m2. Therefore, the recommended irinotecan dose was 60 mg/m2. In the phase II study, 40 patients received cisplatin (30 mg/m2) plus irinotecan (60 mg/m2). Twenty-five out of 40 patients had received prior chemotherapy. The median number of cycles was 3.5. The response rate was 32.5% (13/40) overall, and 53.3% (8/15) in patients without prior chemotherapy. The median time to tumor progression (TTP) was 162 days. The median survival time was 288 days. Four patients (10%) developed grade 4 neutropenia and 3 patients (7.5%) developed grade 4 anemia. The only observed non-hematological toxicity at grade 3 or higher was diarrhea, seen in 2.5% (1/40) of the patients. CONCLUSION: Bi-weekly administration of irinotecan and cisplatin is safe and active for the management of unresectable advanced or recurrent gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Camptotecina/efeitos adversos , Cisplatino/efeitos adversos , Diarreia/induzido quimicamente , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
The synergistic mechanism of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear, despite its substantial antitumor activity, which has been demonstrated clinically. To clarify the mechanism(s), we determined the sensitivity or resistance factors to either drug in seven gastrointestinal cancer cell lines and then analyzed the altered gene expression after different exposures to CDDP and 5-FU. At the basal gene expression level, glutathione S-transferase pi (GSTpi) expression correlated with the observed resistance to CDDP, whereas dihydropyrimidine dehydrogenase (DPD) and multidrug resistance-associated protein (MRP) expression was related to 5-FU resistance. GSTpi, DPD, and MRP expression increased in response to the respective drug, but they also increased in response to the other drug as well. Additionally, 5-FU revealed a drastically increased thymidylate synthase (TS) gene expression in 5-FU-resistant cells. However, the increasing actions of CDDP and 5-FU on GSTpi, DPD, MRP, and TS expression varied according to the exposure time, concentration, and schedule. A low concentration of CDDP (1 microg/ml, 30 min) followed by 5-FU (0.5 microg/ml, 72 h) was found to cause a less increased expression of DPD, MRP, GSTpi, and TS than either drug alone, thus resulting in synergistic cytotoxicity in 5-FU-resistant COLO201 and CDDP-resistant HCC-48 cells. The sequential combination of CDDP and 5-FU inhibited the growth of human normal renal proximal tubule cells by less than 20%. Low concentrations of CDDP followed by continuous exposure to 5-FU can repress increased gene expression related to both drug resistances, thereby being synergistically cytotoxic in human gastrointestinal cancer cells.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Resistência a Múltiplos Medicamentos/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Transportadores de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Cisplatino/administração & dosagem , Di-Hidrouracila Desidrogenase (NADP) , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Fluoruracila/administração & dosagem , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Glutationa S-Transferase pi , Glutationa Transferase/biossíntese , Glutationa Transferase/genética , Humanos , Isoenzimas/biossíntese , Isoenzimas/genética , Células K562/efeitos dos fármacos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Oxirredutases/biossíntese , Oxirredutases/genética , Timidilato Sintase/genética , Timidilato Sintase/metabolismo , Células Tumorais CultivadasRESUMO
Antagonism of some amino acids (AA) to the inhibitory effects of other AA (Ile, Phe, and Thr) on the growth rate of mixed ruminal bacteria was investigated. In vitro growth rate of the mixed ruminal bacteria was inhibited when the 3 inhibitory AA (1 mM each) were each added to individual control treatments in which an ammonium salt was included as a sole N source. The inhibitory effect caused by Ile was relieved by addition of Leu or Val (equimolar to Ile), and no significant inhibition was shown when both Leu and Val were added together with Ile. The growth inhibition caused by Phe was also alleviated by supplementing with Trp, and was completely negated by adding Tyr. The inhibitory effect of Thr, on the other hand, was not affected by addition of Lys or Met (which are synthesized using a common pathway with Thr), but was mitigated by supplementation with Glu, Ser, Val, Ala, or Gln. Among the antagonistic AA, Leu, Val, Trp, Tyr, and Glu were indispensable for the maximum growth rate of the ruminal bacteria under the experimental condition of supplementation of amino-N, the removal of which from a mixture of 20 protein AA caused the growth rate to decline. Removals of Ile along with Leu or Val or both, of Phe along with Trp or Tyr, and of Thr along with Glu recovered the promotion of bacterial growth rate. It was concluded that inhibitions of the bacterial growth rate caused by Ile, Phe, or Thr could be antagonized by some other AA (Leu, Val, Tyr, Trp, or Glu), and the role of these latter AA as relievers of the inhibitory effects could explain why they are indispensable for maximum growth rate of ruminal bacteria.