RESUMEN
Squamous cell carcinoma of the esophagus (SCCE) has a poor prognosis compared with other gastrointestinal cancers. Many patients present with locoregional unresectable or metastatic disease at the time of diagnosis. For these patients with metastatic esophageal cancer, chemotherapy is generally indicated. The aim of this phase I/II study was to evaluate the efficacy and safety of the combined use of docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU)(DCF) in patients with recurrent/metastatic SCCE. This study adopted divided doses of docetaxel and CDDP in order to reduce the toxicities of the treatment. The dose of docetaxel was escalated using the following protocol in the phase I stage: level 1, 30 mg/m2; level 2, 35 mg/m2 and level 3, 40 mg/m2, which was intravenously infused for 2 hours on days 1 and 8. CDDP was administered at a dose of 12 mg/m2 infused for 4 hours on days 1-5. The 5-FU was administered at a dose of 600 mg/m2 continuously infused from day 1 to 5. This regimen was repeated every 4 weeks. The study subjects were nine patients (phase I) and 48 patients (phase II). The recommended dose was determined as level 3 in phase I. In the phase II stage, the overall response rate was 62.5%, with a complete response rate of 12.5%. The median progression-free survival was 6 months, and the median overall survival was 13 months. Grade 3/4 toxicities of leukopenia, neutropenia and febrile neutropenia occurred in 64.6%, 68.8% and 14.6% of the patients, while grade 3/4 non-hematological toxicities were relatively rare. No treatment-related death was recorded. This modified DCF regimen with divided doses can be a tolerable and useful regimen of definitive chemotherapy for unresectable SCCE because of its high efficacy, although adequate care for severe neutropenia must be administered.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Taxoides/administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/patología , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Esquema de Medicación , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Esófago/patología , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neutropenia/inducido químicamente , Proyectos de Investigación , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Patients' quality of life (QoL) deteriorates remarkably after gastrectomy. Billroth I reconstruction following distal gastrectomy has the physiological advantage of allowing food to pass through the duodenum. It was hypothesized that Billroth I reconstruction would be superior to Roux-en-Y reconstruction in terms of long-term QoL after distal gastrectomy. This study compared two reconstructions in a multicentre prospective randomized clinical trial to identify the optimal reconstruction procedure. METHODS: Between January 2009 and September 2010, patients who underwent gastrectomy for gastric cancer were randomized during surgery to Billroth I or Roux-en-Y reconstruction. The primary endpoint was assessment of QoL using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) questionnaire 36 months after surgery. RESULTS: A total of 122 patients were enrolled in the study, 60 to Billroth I and 62 to Roux-en-Y reconstruction. There were no differences between the two groups in terms of postoperative complications or mortality, and no significant differences in FACT-Ga total score (P = 0·496). Symptom scales such as epigastric fullness (heaviness), diarrhoea and fatigue were significantly better in the Billroth I group at 36 months after gastrectomy (heaviness, P = 0·040; diarrhoea, P = 0·046; fatigue, P = 0·029). The rate of weight loss in the third year was lower for patients in the Billroth I group (P = 0·046). CONCLUSION: The choice of anastomotic reconstruction after distal gastrectomy resulted in no difference in long-term QoL in patients with gastric cancer. REGISTRATION NUMBER: NCT01065688 (http://www.clinicaltrials.gov).
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Anastomosis en-Y de Roux/métodos , Gastrectomía/métodos , Gastroenterostomía/métodos , Calidad de Vida , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis en-Y de Roux/psicología , Femenino , Estudios de Seguimiento , Gastrectomía/psicología , Gastroenterostomía/psicología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Procedimientos de Cirugía Plástica/métodos , Neoplasias Gástricas/psicología , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
A line or rat hepatoma cells in culture which, in response to serum starvation, become arrested in the early G1 phase of growth, can be stimulated by insulin alone to enter the cell cycle and traverse S phase. A half-maximum response is observed at 30 to 70 picomolar concentrations and the maximum response is essentially identical to that found with optimum serum concentrations.
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Sustancias de Crecimiento , Insulina/farmacología , Neoplasias Hepáticas Experimentales/patología , Animales , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular , Mitosis/efectos de los fármacos , Proinsulina/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
Tumor-specific gene delivery is crucial to achieving successful effects in suicide gene therapy. Carcinoembryonic antigen (CEA) promoter has been widely used for this purpose, but the expression level of tumor-specific promoters such as CEA promoter is generally low. In the previous study, we used the Cre/loxP system and showed that LacZ expression by the CEA promoter was remarkably enhanced and maintained its specificity using the Cre/loxP regulation system. In this study, the Cre/loxP system was first applied to augmentation of selective expression of the cytosine deaminase (CD) gene as a suicide gene therapy in CEA-producing cells. The double infection with AxCEANCre expressing Cre recombinase under the control of the CEA promoter and AxCALNLCD expressing the CD gene under the control of the CAG promoter by the Cre switching system rendered CEA-producing tumor cells 13-fold more sensitive to 5-fluorocytosine (5-FC) compared with the single infection with AxCEACD expressing CD gene driven by the CEA promoter. The therapeutic efficacy of the enhanced CD/5-FC suicide gene therapy was evaluated in orthotopic implantation models of human gastric carcinoma. Adenovirus vectors (1 x 10(9) plaque-forming units) were administered i.p. into mice three times, and then 5-FC was administered i.p. for the next 10 days. Tumor volume and weight in mice treated with AxCEANCre and AxCALNLCD/5-FC were significantly reduced as compared with those in mice treated not only with Mock (AxCALacZ) but also with AxCEACD/5-FC (P < 0.0001). This beneficial effect on tumor burden was also reflected in the overall survival. The survival periods of the mice treated with AxCEANCre and AxCALNLCD/5-FC were longer than those of mice treated with Mock or AxCEACD/5-FC (P < 0.01). These results suggested that application of the Cre/loxP system could provide a new approach for enhanced selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.
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Antimetabolitos Antineoplásicos/farmacología , Antígeno Carcinoembrionario/genética , Flucitosina/farmacología , Terapia Genética/métodos , Nucleósido Desaminasas/genética , Neoplasias Gástricas/terapia , Adenoviridae/genética , Animales , Antimetabolitos Antineoplásicos/farmacocinética , Antígeno Carcinoembrionario/biosíntesis , Citosina Desaminasa , Femenino , Flucitosina/farmacocinética , Expresión Génica , Vectores Genéticos/genética , Células HeLa , Humanos , Integrasas/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nucleósido Desaminasas/metabolismo , Regiones Promotoras Genéticas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Células Tumorales Cultivadas , Proteínas Virales/genéticaRESUMEN
We performed aortic valve replacement in 24 patients aged over 70 with small calcified valves. The surgical management of such patients remains controversial as the extensive calcification compromises implantation. Hence, we used an ultrasonic debridement instrument to remove calcium and selected a small prosthesis with the largest possible orifice without enlargement of the aortic annulus. Echocardiography showed significant reductions in left ventricular mass index compared with preoperative values. Early and mid-term prognosis has been relatively good.
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Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Calcinosis/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/fisiopatología , Superficie Corporal , Desbridamiento/métodos , Femenino , Prótesis Valvulares Cardíacas , Humanos , Litotricia/métodos , Masculino , Pronóstico , Ajuste de Prótesis , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Terapia por Ultrasonido , Función Ventricular IzquierdaRESUMEN
Thirteen cases of functional single ventricle who had undergone bidirectional Glenn procedure were divided into 2 groups according to presence (5) or absence (8) of additional pulmonary blood flow. Additional flow was preserved in cases with relatively small pulmonary artery index (PA index), and their sources were antegrade pulmonary blood flow (2), and Blalock-Taussig (BT) shunt (3). In the control group, PA index was reduced to about 70% of the preoperative value, while in the additional group, pulmonary artery growth was recognized without significant elevation of mean pulmonary artery pressure. However, atrioventricular valve regurgitation progressed and systemic ventricular volume did not decrease after Glenn in the additional group. Therefore special consideration for the timing of Fontan procedure is mandatory.
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Procedimientos Quirúrgicos Cardíacos/métodos , Cardiopatías Congénitas/cirugía , Ventrículos Cardíacos/anomalías , Arteria Pulmonar/cirugía , Circulación Pulmonar , Vena Cava Superior/cirugía , Anastomosis Quirúrgica , Procedimiento de Fontan , Cardiopatías Congénitas/fisiopatología , Ventrículos Cardíacos/cirugía , HumanosRESUMEN
We experienced 2 infants in whom octreotide acetate was effective on intractable chylothorax after surgery for congenital heart diseases. They were 8- and 5-month-old. They were diagnosed as having corrected transposition of the great arteries (TGA) and tetralogy of Fallot respectively, and underwent bidirectional Glenn anastomosis and right modified Blalock Taussig shunt. Chylothorax was revealed on the 11th and the 1st postoperative day, and was not improved by any conventional therapy in either case. Then octreotide acetate was infused continuously with 0.1-0.6 micorg/kg/hour for 24 and 7 days. Chylothorax disappeared completely without any complications such as disturbance of blood sugar level or growth retardation. Octreotide acetate was effective and safe even in infants in intractable chylothorax after surgery for congenital heart diseases, as long as used for short period.
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Quilotórax/tratamiento farmacológico , Cardiopatías Congénitas/cirugía , Octreótido/uso terapéutico , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Cardíacos/métodos , Humanos , Lactante , Masculino , Tetralogía de Fallot/cirugía , Transposición de los Grandes Vasos/cirugíaRESUMEN
Peripheral stimulation is known to influence the state of cortical excitability. The purpose of this study is to investigate whether peripheral magnetic stimulation has similar effects on cortical excitability to transcranial magnetic stimulation (TMS). A magnetic stimulator with a flat figure-of-eight coil was used for both TMS, and peripheral magnetic stimulation applied to the bilateral forearms. TMS was performed on the left primary motor cortex to evaluate influence of the peripheral magnetic stimulation, and motor evoked potential (MEP) was measured from the right first dorsal interosseous. Peripheral magnetic stimulation was performed at a stimulus frequency of 1 Hz or 10 Hz, to the stimulus sites on the right and left supination of the forearm. The effects of peripheral magnetic stimulation were evaluated by comparing the mean MEP amplitude elicited by TMS before and after peripheral magnetic stimulation. We found that cortical excitability varied according to the stimulation site and frequency of the peripheral magnetic stimulation. The inhibition of cortical excitability was observed following 1 Hz peripheral magnetic stimulation over the right forearm (p<;0.001). In contrast, increased cortical excitability was observed using 1 Hz peripheral magnetic stimulation over the left forearm and 10 Hz stimulation over either the right or left forearms. We suggest that peripheral magnetic stimulation has a similar effect to TMS, and can induce both facilitation and inhibition of cortical excitability.
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Corteza Motora/fisiología , Estimulación Magnética Transcraneal/métodos , Adulto , Electromiografía , Potenciales Evocados Motores/fisiología , Femenino , Antebrazo/fisiología , Humanos , MasculinoRESUMEN
One of the major obstacles in the successful clinical application of monoclonal antibodies has been the development of host immune responses to murine Ig constant and variable regions. While the CDR grafting of MAbs may alleviate many of these problems, the potential remains that one or more murine CDRs on the human Ig backbone of a "humanized" MAb may still be immunogenic. Studies were undertaken employing a MAb of potential clinical utility, CC49, to define those CDRs that are essential for antigen binding and those that may be immunogenic in humans. We previously developed a humanized CC49 (HuCC49) by grafting the MAb CC49 hypervariable regions onto frameworks of human MAbs. To identify those CDRs essential for binding, a panel of variant HuCC49 MAbs was generated here by systematically replacing each of the murine CDRs with their human counterparts. The relative affinity constant of each variant was determined. Serum from a patient who received murine CC49 was used to determine the potential immunogenicity of each CDR in humans. The serum was shown to react with the anti-CC49 variable region. Results showed that patients' anti-idiotypic responses are directed mainly against LCDR3 and moderately against LCDR1 and HCDR2. These studies demonstrate for the first time that variants containing individual CDR substitutions of a humanized MAb can be constructed, and each CDR can be defined for the two most important properties for potential clinical utility: antigen binding and immunogenicity.
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Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/metabolismo , Región Variable de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/metabolismo , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Anticuerpos Antiidiotipos/biosíntesis , Anticuerpos Monoclonales/inmunología , Afinidad de Anticuerpos , Reacciones Antígeno-Anticuerpo , Baculoviridae/genética , Sitios de Unión/genética , Unión Competitiva , Línea Celular , Humanos , Región Variable de Inmunoglobulina/inmunología , Cinética , Ratones , Datos de Secuencia Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , SpodopteraRESUMEN
To investigate the characteristic structure of hydatidiform mole, various types of collagen expression were determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type I, III, and VI collagen with specific monoclonal antibodies. Collagens were also extracted from the villous tissues obtained from normal pregnancy and hydatidiform mole by the salt precipitation method. Immunohistochemical staining for type I, III, and VI collagen revealed weak staining of the villous stroma in hydatidiform mole compared with that in normal pregnancy. Both the ratios of type III to type I collagen and the ratios of type V to type I collagen in the villous tissues were significantly decreased (P < 0.05) in molar pregnancy compared with those in normal pregnancy. These results suggest that alterations in the distribution and composition of collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.
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Vellosidades Coriónicas/química , Colágeno/análisis , Mola Hidatiforme/química , Neoplasias Uterinas/química , Adulto , Anticuerpos Monoclonales , Electroforesis en Gel de Poliacrilamida , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Pepsina A/metabolismo , EmbarazoRESUMEN
To investigate the characteristic structure of hydatidiform mole, type IV collagen expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect type IV collagen with specific monoclonal antibody, and Northern blot analysis was performed to assess expression of messenger ribonucleic acid for the alpha1(IV) chain. In addition, serum levels of type I, III, and IV collagen were measured by RIA. Immunohistochemical staining for type IV collagen revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that the villous expression of messenger ribonucleic acid for the alpha1(IV) chain was significantly increased in hydatidiform moles compared with normal pregnancy (P < 0.01). Although there were no differences in the serum type I and III collagen levels between hydatidiform mole and normal pregnancy, the type IV collagen level was significantly higher in patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that type IV collagen might play an important role in determining the pathophysiology and structure of hydatidiform mole.
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Vellosidades Coriónicas/metabolismo , Colágeno/metabolismo , Mola Hidatiforme/metabolismo , Adulto , Northern Blotting , Colágeno/sangre , Colágeno/genética , Femenino , Humanos , Inmunohistoquímica , Concentración Osmolar , Embarazo , ARN Mensajero/metabolismo , RadioinmunoensayoRESUMEN
To provide some insight into the etiology of spontaneous abortion, the expression of type IV collagen was investigated in human decidual tissues obtained after spontaneous abortion (n = 17) and normal pregnancy (n = 22). Indirect immunofluorescent staining was performed for type I, III, and IV collagen as well as laminin, and Northern blot analysis was conducted to assess the expression of messenger ribonucleic acid for the alpha 1(IV) chain. Immunohistochemical analysis did not reveal any significant differences between normal pregnancy and spontaneous abortion with respect to interstitial collagens (type I and III collagen) and laminin in the decidual tissue. However, although pericellular immunostaining for type IV collagen was recognized around the decidual cells in normal pregnancy, very weak or no staining was observed in spontaneous abortion. Northern blot analysis revealed that the decidual expression of messenger ribonucleic acid for the alpha 1(IV) chain was significantly reduced in spontaneous abortion compared to that in normal pregnancy (P < 0.001). These results suggest that type IV collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with spontaneous abortion.
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Aborto Espontáneo/metabolismo , Colágeno/metabolismo , Decidua/metabolismo , Adulto , Northern Blotting , Colágeno/genética , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Embarazo , ARN Mensajero/metabolismo , Valores de Referencia , Coloración y EtiquetadoRESUMEN
Monoclonal antibody (MAb) CC49 reacts with a pancarcinoma antigen, tumor associated glycoprotein (TAG)-72. To circumvent human anti-murine antibody (HAMA) responses in patients, we earlier developed a humanized CC49 (HuCC49) by grafting the complementarity-determining regions (CDRs) of MAb CC49 onto variable light (VL) and variable heavy (VH) frameworks of the human MAbs LEN and 21/28'CL, respectively. With the aim of minimizing its immunogenicity further, we have now generated a variant HuCC49 MAb by grafting the specificity-determining residues (SDRs) of MAb CC49 onto the frameworks of the human MAbs. Based on the evaluation of its binding affinity for TAG-72 and its reactivity with anti-idiotypic antibodies present in sera from patients who have been treated with murine CC49, this variant retains its antigen-binding activity and shows minimal reactivity with anti-idiotypic antibodies in patients' sera. Development of this variant, which is a potentially useful clinical reagent for diagnosis and therapy of human carcinomas, demonstrates that for humanization of a xenogeneic antibody grafting of the potential SDRs should be sufficient to retain its antigen-binding properties.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Anticuerpos Heterófilos/genética , Anticuerpos Monoclonales/inmunología , Anticuerpos Antineoplásicos/inmunología , Anticuerpos Antineoplásicos/uso terapéutico , Antineoplásicos/inmunología , Antineoplásicos/uso terapéutico , Regiones Determinantes de Complementariedad/análisis , Regiones Determinantes de Complementariedad/genética , Diseño de Fármacos , Ingeniería Genética , Variación Genética , HumanosRESUMEN
While in vivo gene inoculation is being increasingly exploited to express genes of choice and elicit specific immune responses in animal models, the utility of this method has not been explored extensively for the expression of antibody genes. The primary constraint of this method is the need to deliver to, and express in, a single cell two functional genes, i.e., those encoding heavy and light chains of an antibody molecule. Several single-gene constructs encoding variants of the monoclonal antibody (MAb) CC49 have been developed, MAb CC49 recognizes a tumor-associated glycoprotein, TAG-72. SP2/O myeloma cells, transfected with the CC49 single gene, express a single-chain protein which is secreted by the transfectoma as a homodimer. Following intramuscular injection of mice with the expression plasmids of the single-gene constructs, the encoded CC49 antibody (AB1) was detected in the plasma of the host. In addition, cellular and humoral immune responses to AB1 have been demonstrated. Antibodies (AB2) to the in vivo-produced variable region of AB1 have been detected and persisted for at least 70 days post-inoculation of the recombinant plasmid. Thus, in vivo gene inoculation of single-chain immunoglobulins may be an alternative or complimentary approach to the induction of anti-idiotypic responses in immunotherapy protocols.
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Anticuerpos Antineoplásicos/genética , Técnicas de Transferencia de Gen , Terapia Genética , Inmunoglobulinas/inmunología , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Anticuerpos Antineoplásicos/inmunología , Expresión Génica , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunologíaRESUMEN
5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are representative of the chemotherapeutic agents for colorectal adenocarcinomas. Pyrimidine nucleoside phosphorylase (PyNPase) catalyses the conversion of 5'-DFUR to 5-FU, the activated form. Murine adenocarcinoma CT26 cells were transfected with human PyNPase cDNA. The engineered transfectants producing PyNPase augmented the response to 5'-DFUR in vitro and in vivo. Animals were administered by means of intraperitoneal (i.p.) injection, and not orally, in order to obtain a better efficiency of absorption. The tumours of the transfected cells nearly all disappeared, even following treatment with quite a small amount of the anticancer agent. The animals injected with the tranfected cells were protected against subsequent challenge with the parental tumour cell line. These findings demonstrate that PyNPase gene transfection increases the sensitivity to 5'-DFUR, and thereby decreases the toxicity of the agent.
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Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Floxuridina/uso terapéutico , Terapia Genética/métodos , Pentosiltransferasa/biosíntesis , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Animales , Antimetabolitos Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Terapia Combinada , ADN Complementario/genética , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Floxuridina/farmacología , Fluorouracilo/farmacología , Humanos , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Pentosiltransferasa/genética , Profármacos/farmacología , Profármacos/uso terapéutico , Pirimidina Fosforilasas , Transfección , Células Tumorales CultivadasRESUMEN
A major problem associated with the succinate dehydrogenase inhibition (SDI) test using tetrazolium dye (MTT) as a cancer chemosensitivity testing is the contamination of non-malignant cells in the tumour tissues. Highly purified fresh human tumour cells from 44 solid tumours and 24 malignant ascites were used for the MTT assay. The purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients. The OD570 obtained from tumour cells alone was higher than that from non-malignant cells. The chemosensitivity of tumour cells was distinct from that of non-malignant cells. Moreover, the chemosensitivity of highly purified tumour cells was also distinct from that of non-purified cells just separated from tumour tissues. 31 of the 68 patients had evaluable lesions, and received cancer chemotherapy according to the results of MTT assay using highly purified tumour cells. A clinical response was obtained in 10 of the 31 patients (response rate = 32.3%, 5 complete responses, 5 partial responses).
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Antineoplásicos/uso terapéutico , Células Tumorales Cultivadas/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Separación Celular/métodos , Colorimetría , Colorantes , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Succinato Deshidrogenasa/antagonistas & inhibidores , Sales de Tetrazolio , TiazolesRESUMEN
BACKGROUND: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. METHODS AND RESULTS: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18-20 years (mean+/-S.D. body mass index: 21.9+/-3.7 kg/m2, total cholesterol: 180+/-29 mg/dl, triglyceride: 62+/-34 mg/dl, HDL cholesterol: 58+/-12 mg/dl). Men with small LDL (PPD < 25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD < 26.9 nm) had higher serum levels of LDL cholesterol (120+/-31 vs 104+/-24 mg/dl), triglyceride (72+/-39 vs 49+/-16 mg/dl) and apolipoprotein (apo) B (84+/-21 vs 68+/-14 mg/dl), and lower HDL cholesterol (54+/-10 vs 60+/-12 mg/dl). They also had greater body mass index (23.2+/-4.6 vs 20.9+/-3.1 kg/m2) and percent body fat (21.5+/-7.7 vs 17.5+/-4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002) and was negatively correlated with apoB (R=0.34, P < 0.001), triglyceride (R=0.32, P < 0.001). percent body fat (R=0.26, P < 0.001), body mass index (R=0.24, P < 0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. CONCLUSION: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.
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Peso Corporal , Lípidos/sangre , Lipoproteínas LDL/sangre , Adolescente , Adulto , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Japón , Masculino , Obesidad/sangre , Tamaño de la Partícula , Valores de ReferenciaRESUMEN
PURPOSE: The effect of local injection of anticancer drugs by balloon catheter, i.e., balloon occluded arterial infusion (BOAI), on the prognosis of cervical cancer treated with radiotherapy were retrospectively estimated. METHODS AND MATERIALS: Sixty-five patients with cervical cancer (Stage I-IV) treated by irradiation were included in the study. Among the 65 cases, 2 were in Stage I, 13 in Stage II, 40 in Stage III, and 10 in Stage IV. Patients who received surgical resection were excluded. Thirty-nine patients received BOAI and 44 received brachytherapy. Twenty-six patients were not indicated for BOAI because of insufficient renal function, hepatic complications, hematological complications, and refusal from the patients. Cisplatin (0.9-1.7 mg/kg), Adriamycin (0.7-0.9 mg/kg), and Pepleomycin (0.4-0.6 mg/kg) were administered simultaneously into the bilateral internal iliac arteries by BOAI. External irradiation was given by 10 MV x-ray. Total dose administered to the regional lymph nodes by the external irradiation was 48.3 +/- 8.7 Gy. Radium was used at brachytherapy. The dose delivered by the brachytherapy at point A was 45.3 +/- 14.9 Gy. Patients without brachytherapy received 26.1 +/- 19.1 Gy of boost irradiation by the external photon beam. The survival probabilities of the patients were calculated by Kaplan-Meier method. RESULTS: The 5-year survival rates of the Stage III patients with and without BOAI were 53 +/- 13% and 24 +/- 18%, respectively (p = 0.036). By multivariate analyses using Cox's proportional hazard model, stage and BOAI were selected as significant predictors of the prognosis. Transient bone marrow suppression was observed in about half of the patients with BOAI. No significant increase of the incidence of the late radiation damage by BOAI in rectum or in urinary bladder was observed. CONCLUSION: Balloon occluded arterial infusion of anticancer drugs may improve the prognosis of the patients with cervical cancer without increasing the incidence of the late radiation damage. A larger scale prospective randomized study is desired.
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Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Análisis Actuarial , Factores de Edad , Anciano , Braquiterapia/métodos , Cateterismo , Femenino , Humanos , Infusiones Intraarteriales/instrumentación , Infusiones Intraarteriales/métodos , Estadificación de Neoplasias , Aceleradores de Partículas , Pronóstico , Radioterapia/métodos , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: To examine the relationship between leptin and insulin serum levels and systolic and diastolic blood pressure in young men. SETTING: Kobe University of Mercantile Marine, Kobe, Japan. PARTICIPANTS: One hundred and ninety-eight male students aged 18-20 years (comprising 100% of those eligible). DESIGN AND MEASUREMENTS: A cross-sectional survey of a sample of male college students was performed, with measurements to include anthropometry, blood pressure and blood tests after overnight fasting. RESULTS: Compared with 90 men with an optimal blood pressure, 56 men with high-normal and high blood pressure had an increase in body mass index (23.7 +/- 5.2 versus 20.4 +/- 2.2 kg/m2), percentage body fat (21.7 +/- 8.0 versus 16.3 +/- 4.2%) and serum leptin (3.7 +/- 4.7 versus 1.5 +/- 0.8 ng/ml). In addition, they had greater serum insulin (59 +/- 31 versus 43 +/- 12 pmol/l) despite there being no differences in plasma glucose, resulting in a reduction of the ratio of glucose to insulin (x 10(6)) (107 +/- 43 versus 126 +/-, which is an estimate of insulin sensitivity in a nondiabetic population. Furthermore, the 56 men had higher serum triglyceride levels, although there was no difference in low density lipoprotein-cholesterol and high density lipoprotein-cholesterol between men with optimal and high-normal plus high blood pressure. Similar differences were found between men in a top versus low tertile of systolic and diastolic blood pressure. In multiple regression analysis, both log leptin and log insulin emerged as determinants for systolic blood pressure independent of body mass index and percentage body fat, but an association with diastolic blood pressure was only shown for log leptin. CONCLUSION: Hyperleptinemia and hyperinsulinemia may be regulators of arterial pressure, independent of body mass index or percentage body fat.
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Presión Sanguínea , Índice de Masa Corporal , Ayuno/sangre , Insulina/sangre , Leptina/sangre , Tejido Adiposo , Adulto , Peso Corporal , Estudios Transversales , Humanos , MasculinoRESUMEN
We examined the synergistic effects of tamoxifen (TAM) and cepharanthine (CEP) for doxorubicin (DOX) sensitivity using MTT assay. The augmentation of DOX sensitivity by TAM and CEP was significantly correlated with the P-glycoprotein expression. The cytotoxic effect of DOX with TAM and CEP was significantly higher than that of DOX alone, or DOX with TAM, and this synergistic effect was dominant in cell lines with high expression of P-glycoprotein. It was also examined that the intracellular concentration of DOX was increased in combined exposure of TAM and CEP, compared with the exposure of TAM, because TAM and CEP promoted the influx and inhibited the efflux of DOX. Thus, TAM and CEP might be able to circumvent DOX-resistance for treatment in cancer patients.