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BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
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Neoplasias del Colon , Estudio de Asociación del Genoma Completo , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adyuvante , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Fluorouracilo/uso terapéutico , Humanos , Recurrencia Local de Neoplasia , Oxaliplatino/efectos adversos , Estudios ProspectivosRESUMEN
BACKGROUND: Palliative care (PC) is increasingly recognized as essential for oncology care, and several academic societies strongly recommend integrating oncology and palliative care (IOP) in daily practice. Similarly, the Japanese government encouraged the implementation of IOP through the Cancer Control Act of 2007; however, its detailed progress remains unclear. Therefore, this cross-sectional nationwide survey was conducted to investigate the current status and hospital executive physicians' perception of IOP. METHODS: The questionnaire was developed based on IOP indicators with international consensus. It was distributed to executive physicians at all government-designated cancer hospitals (DCHs, n = 399) and matched non-DCHs (n = 478) in November 2017 and the results were compared. RESULTS: In total, 269 (67.4%) DCHs and 259 (54.2%) non-DCHs responded. The number of PC resources in DCHs was significantly higher than those in non-DCHs (e.g., full-time PC physicians and nurses, 52.8% vs. 14.0%, p < 0.001; availability of outpatient PC service ≥3 days per week, 47.6% vs. 20.7%, p < 0.001). Routine symptom screening was more frequently performed in DCHs than in non-DCHs (65.1% vs. 34.7%, p < 0.001). Automatic trigger for PC referral availability was limited (e.g., referral using time trigger, 14.9% vs. 15.3%, p = 0.700). Education and research opportunities were seriously limited in both types of hospitals. Most executive physicians regarded IOP as beneficial for their patients (95.9% vs. 94.7%, p = 0.163) and were willing to facilitate an early referral to PC services (54.7% vs. 60.0%, p < 0.569); however, the majority faced challenges to increase the number of full-time PC staff, and < 30% were planning to increase the staff members. CONCLUSIONS: This survey highlighted a considerable number of IOP indicators met, particularly in DCHs probably due to the government policy. Further efforts are needed to address the serious research/educational gaps.
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Prestación Integrada de Atención de Salud/tendencias , Servicio de Oncología en Hospital/tendencias , Cuidados Paliativos/métodos , Estudios Transversales , Prestación Integrada de Atención de Salud/métodos , Prestación Integrada de Atención de Salud/normas , Humanos , Japón , Servicio de Oncología en Hospital/normas , Cuidados Paliativos/normas , Cuidados Paliativos/tendencias , Encuestas y CuestionariosRESUMEN
BACKGROUND: Although potato as a crop is commercially grown from seed tubers, plants grown from tissue culture plantlets are often used in physiological studies including freezing tolerance determination. OBJECTIVE: This study aimed to examine the effects of the source of plants on freezing tolerance of potato plants at young developmental stages. MATERIALS AND METHODS: We compared freezing tolerance and contents of soluble proteins and sugars of Solanum tuberosum plants derived from tissue culture with those derived from tubers before and after cold acclimation. RESULTS: Tuber-derived plants showed significantly higher freezing tolerance than tissue-culture-derived plants after cold acclimation, although non-acclimated plants did not show any marked differences. Soluble protein contents were higher in tuber-derived plants regardless of cold acclimation. Sucrose content increased to a higher level in tuber-derived plants after cold acclimation. CONCLUSION: These results suggest that source of plant tissue can have a significant effect on the response of young potato plants to freezing stress and that the use of tissue culture plants in freezing tolerance studies may not accurately reflect the frost tolerance of commercially grown plants.
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Criopreservación , Congelación , Tubérculos de la Planta , Semillas , Solanum tuberosumRESUMEN
BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Doxorrubicina/efectos adversos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). METHODS: FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. KEY RESULTS: Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. CONCLUSIONS & INFERENCES: Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).
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Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/tratamiento farmacológico , Dolor/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Dispepsia/sangre , Femenino , Ghrelina/sangre , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Resultado del Tratamiento , Adulto JovenRESUMEN
Preliminary evidence suggests that the multikinase inhibitor sorafenib has clinical activity in FLT3-ITD-positive (FLT3-ITD) acute myeloid leukemia (AML). However, the quality and sustainability of achievable remissions and clinical variables that influence the outcome of sorafenib monotherapy are largely undefined. To address these questions, we evaluated sorafenib monotherapy in 65 FLT3-ITD AML patients treated at 23 centers. All but two patients had relapsed or were chemotherapy-refractory after a median of three prior chemotherapy cycles. Twenty-nine patients (45%) had undergone prior allogeneic stem cell transplantation (allo-SCT). The documented best responses were: hematological remission in 24 patients (37%), bone marrow remission in 5 patients (8%), complete remission (with and without normalization of peripheral blood counts) in 15 patients (23%) and molecular remission with undetectable FLT3-ITD mRNA in 10 patients (15%), respectively. Seventeen of the patients without prior allo-SCT (47%) developed sorafenib resistance after a median treatment duration of 136 days (range, 56-270 days). In contrast, allo-SCT patients developed sorafenib resistance less frequently (38%) and significantly later (197 days, range 38-225 days; P=0.03). Sustained remissions were seen exclusively in the allo-SCT cohort. Thus, sorafenib monotherapy has significant activity in FLT3-ITD AML and may synergize with allogeneic immune effects to induce durable remissions.
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Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Piridinas/uso terapéutico , Tirosina Quinasa 3 Similar a fms/metabolismo , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Estudios Retrospectivos , SorafenibRESUMEN
Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Unresectable or metastatic HCC has a poor prognosis, and systemic cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. However, there has been increasing interest in developing novel molecularly targeted agents in HCC due to the accumulation of knowledge of cell signaling and molecular carcinogenesis. Furthermore, some of these agents have proven to be efficacious in other traditionally challenging carcinomas, such as renal cell carcinoma. Recently, a phase III, randomized, placebo-controlled trial demonstrated that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor and Ras kinase, improves overall survival (OS) in patients with advanced HCC. This seminal study described the first agent to improve OS in HCC and began a new era of molecule-targeted cancer therapies. Currently, many novel molecularly targeted agents are under evaluation in clinical trials. In this review, we comprehensively summarize the molecular pathogenesis, targets, and signal transduction pathways involved in HCC. We also detail the current status of molecularly targeted agents that are under clinical development in advanced HCC, including the mechanisms of action of these agents.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Receptores de Factores de Crecimiento/antagonistas & inhibidores , Receptores de Factores de Crecimiento/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: We evaluated MRP2 expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines. RESULTS: MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP. CONCLUSION: Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients.
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Carcinoma de Células Escamosas/genética , Resistencia a Antineoplásicos/genética , Neoplasias Esofágicas/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidad , Femenino , Fluorouracilo/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Terapia Neoadyuvante , ARN Interferente Pequeño/farmacología , Análisis de SupervivenciaRESUMEN
BACKGROUND: We reported recently the clinical efficiency of interferon (IFN)-α/5-fluorouracil (5-FU) combination therapy in advanced hepatocellular carcinoma (HCC). However, prediction of the response to the combination therapy remains unsatisfactory. The aim of this study was to investigate the anti-tumour effects of microRNA (miR)-21 on the sensitivity of HCC cells to IFN-α/5-FU and whether miR-21 can be used as a predictor of the response to such therapy in HCC. METHODS: Changes in the sensitivity of HCC cells (PLC/PRF/5 and HepG2) to IFN-α/5-FU were examined after transfection with pre-miR-21 or anti-miR-21. The correlation between miR-21 expression level, evaluated by qRT-PCR, and response to the therapy was also investigated in clinical HCC specimens. RESULTS: Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-α/5-FU. Annexin V assay showed that the percentage of apoptotic cells was significantly lower in cells transfected with pre-miR-21 than control cells. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-α/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4. miR-21 expression in clinical HCC specimens was significantly associated with the clinical response to the IFN-α/5-FU combination therapy and survival rate. CONCLUSIONS: The miR-21 in HCC cell lines and clinical HCC samples is a significant modulator of the anti-tumour effect of IFN-α and 5-FU. This suggests that miR-21 is a potentially suitable marker for the prediction of the clinical response to the IFN-α/5-FU combination therapy.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , MicroARNs/genética , Antineoplásicos/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , División Celular/efectos de los fármacos , Cartilla de ADN , Evaluación Preclínica de Medicamentos , Resistencia a Medicamentos , Resistencia a Antineoplásicos , Fluorouracilo/antagonistas & inhibidores , Fluorouracilo/uso terapéutico , Humanos , Inmunohistoquímica , Interferón-alfa/antagonistas & inhibidores , Interferón-alfa/uso terapéutico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , MicroARNs/farmacología , ARN Mensajero/genética , ARN Neoplásico/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , TransfecciónAsunto(s)
Enfermedad de Hirschsprung/diagnóstico , Seudoobstrucción Intestinal/diagnóstico , Seudoobstrucción Intestinal/etiología , Enfermedades del Recto/complicaciones , Enfermedades del Recto/diagnóstico , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Adulto , Sulfato de Bario/administración & dosificación , Biopsia , Medios de Contraste/administración & dosificación , Enema , Femenino , Glucocorticoides/uso terapéutico , Humanos , Prednisolona/uso terapéutico , Resultado del TratamientoRESUMEN
Traditional Chinese herbal medicines are frequently prescribed in pharmacotherapy in Japan. In the present study, we evaluated the possible interaction of several herbal extracts including Rhei Rhizoma extract with cytochrome P450 (CYP) 3A and efflux transporters such as P-glycoprotein and multidrug resistance-associated protein (MRP) 2. Rhei Rhizoma extract (100 microg/ml) significantly suppressed the CYP3A-mediated 6beta-hydroxylation of testosterone in hepatic microsomes, and increased the extent of bioavailability of midazolam, a typical CYP3A substrate, in rats. Also, Rhei Rhizoma extract (300 microg/ml) significantly suppressed P-glycoprotein-mediated efflux transport of rhodamine 123 (Rho123) in rat everted intestine. In an in-vivo study, Rhei Rhizoma extract added to intestinal perfusate at a concentration of 300 microg/ml significantly suppressed the intestinal exsorption of Rho123, though it exerted no effect on the biliary excretion of Rho123. Furthermore, the in-vitro and in-vivo MRP2-mediated intestinal efflux of 2,4-dinitrophenyl-S-glutathione was significantly suppressed by Rhei Rhizoma extract (1000 microg/ml). In conclusion, Rhei Rhizoma extract, which is taken orally at doses of 0.5-1 g each or 1-3 g daily in clinical practice, may cause pharmacokinetic herb-drug interactions in the process of the intestinal and/or hepatic CYP3A-mediated drug metabolism and P-glycoprotein- and/or MRP2-mediated efflux transport in the intestine.
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Proteínas Portadoras/metabolismo , Citocromo P-450 CYP3A/metabolismo , Rheum/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Ciclosporina/farmacología , Dinitroclorobenceno/metabolismo , Moduladores del GABA/farmacocinética , Glutatión/análogos & derivados , Glutatión/metabolismo , Inmunosupresores/farmacología , Indicadores y Reactivos , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Midazolam/farmacocinética , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Rodamina 123RESUMEN
PURPOSE: To determine the safety and efficacy of weekly high-dose oral calcitriol and docetaxel, given to patients with non-resectable, incurable pancreatic cancer. PATIENTS AND METHODS: Twenty-five patients were enrolled onto this phase II study. Patients were treated with oral calcitriol 0.5 microg/kg on day 1, followed by docetaxel 36 mg/m(2) IV on day 2, administered weekly for three consecutive weeks, followed by 1 week without treatment. Patients followed a low-calcium diet and increased their hydration. The primary end-point of the trial was time-to-progression. RESULTS: Three of 25 patients attained a partial response (12%, 95% CI 3 to 31) and seven (28%) achieved stable disease. Median time-to-progression was 15 weeks, and median overall survival was 24 weeks. Toxicities observed (hyperglycemia, fatigue) were mostly attributable to the docetaxel or its pre-treatment. CONCLUSIONS: This regimen of high-dose calcitriol with docetaxel may have activity in incurable pancreatic cancer, with a modest increase in TTP when compared to historical findings using single-agent docetaxel. However, results do not appear superior to those seen with gemcitabine, with or without erlotinib.
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Antineoplásicos/farmacología , Calcitriol/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Taxoides/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Calcitriol/administración & dosificación , Calcitriol/efectos adversos , Agonistas de los Canales de Calcio/administración & dosificación , Agonistas de los Canales de Calcio/efectos adversos , Agonistas de los Canales de Calcio/farmacología , Calcio de la Dieta , Progresión de la Enfermedad , Docetaxel , Quimioterapia Combinada , Fatiga/inducido químicamente , Femenino , Humanos , Hiperglucemia/inducido químicamente , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Tasa de Supervivencia , Taxoides/administración & dosificación , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
RESULTS: For over five years, we have been using a new ultraviolet B ray source, a Xenon-Chloride lamp emitting non-coherent, monochromatic 308-nm light that represents the natural evolution of the excimer laser. A source of monochromatic excimer light (MEL) produces 50 mW/cm(2) power density at a distance of 15 cm from the source and has a maximum irradiating area of 504 cm(2), this feature representing the greatest therapeutic advantage offered by 308 nm sources. On the other hand, the benefits offered by the MEL compared to traditional phototherapies are essentially correlated to the fact that there is no need to administer oral psoralens (PUVA therapy) and that sessions need to be repeated only every 7-15 days, an important condition for the improvement of the patient's quality of life (since at least 2-3 weekly sessions are required with the traditional UVB therapy). Using MEL, UV B light can be applied on the entire body, with partial subintrant skin irradiations, or on one or just a few individual patches, taking care to accurately protect the healthy surrounding skin and allowing for a phototherapy exclusively targeted onto the lesion to be treated. Clinical indications and the reasons for choosing MEL for the treatment of photosensitive skin disorders are virtually identical to those stated for PUVA therapy or narrowband UV B light. Due to the absence of photosensitizing substances and drug-induced toxicity, patients who work in the open air, pregnant women and patients suffering from liver or kidney failure can also be treated. Furthermore, the short time required for sessions, the duration of cycles and the selective exposure of the skin areas to be treated undoubtedly represent significant benefits for patients in terms of safety and efficacy. In addition to psoriasis, the use of MEL can also be extended to other pathologies such as vitiligo, alopecia areata, atopic dermatitis and patch-stage IA mycosis fungoides with encouraging
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Láseres de Excímeros/uso terapéutico , Enfermedades de la Piel/radioterapia , HumanosRESUMEN
Overlapped in the tuberal hypothalamic area (THA), melanin-concentrating hormone (MCH) and hypocretin (Hcrt) neurons contribute to the integrated regulation of food intake, energy regulation and sleep. Recently, physiological role in appetite suppression has been defined for a novel hypothalamic molecule, nesfatin-1. Acute i.c.v. infusion of nesfatin-1 (nesf-1) promotes anorexia whereas chronic treatment reduces body weight in rats. This satiety molecule is expressed in neurons from areas prominently involved in appetite regulation including THA. We therefore sought functionally relevant to determine whether nesf-1 might be a reliable signaling marker for a new cell contingent within THA, in addition to MCH and Hcrt neurons. Thus, we completed a detailed topographical mapping of neurons immunostained for nesf-1 (nesf-1+) together with cell quantification in each discrete nucleus from THA in the rat. We further combined the immunodetection of nesf-1 with that of MCH or Hcrt to assess possible co-expression. More than three quarters of the nesf-1+ neurons were encountered in nuclei from the lateral half of THA. By double immunofluorescent staining, we showed that all neurons immunoreactive for melanin concentrating hormone (MCH+) neurons depicted nesf-1 immunoreactivity and approximately 80% of the nesf-1+ neurons were labeled for MCH. Maximal co-expression rates were observed in the lateral THA containing approximately 86% of the double-labeled neurons plotted in THA. The present data suggest that nesf-1 co-expressed in MCH neurons may play a complex role not only in food intake regulation but also in other essential integrative brain functions involving MCH signaling, ranging from autonomic regulation, stress, mood, cognition to sleep.
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Hipotálamo/citología , Melaninas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Animales , Mapeo Encefálico , Proteínas de Unión al Calcio , Recuento de Células , Proteínas de Unión al ADN , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Neuropéptidos/metabolismo , Nucleobindinas , Orexinas , Ratas , Ratas Sprague-DawleyRESUMEN
Adding pectin to an elemental formula increases its viscosity through gelatinization, thus presumably preventing gastro-oesophageal reflux and aspiration pneumonia. We investigated the influence of the viscosity of an elemental formula on gastric emptying. Eleven healthy volunteers underwent three tests at intervals of >1 week. After fasting for >8 h, each subject received a test meal (enteral nutrition solution, enteral solution plus pectin, or water). Then gastric emptying (continuous (13)C breath test), gastro-oesophageal intraluminal pressures, oesophageal pH, and blood levels of glucose, insulin and gastrin were all measured simultaneously. The gastric emptying coefficient was significantly increased by adding pectin to enteral nutrition (3.01 +/- 0.10 vs 2.78 +/- 0.10, mean +/- SE, P < 0.05). The antral motility index was also significantly higher with pectin than without at 45-60 min and 60-75 min after the test meal (526 +/- 237 vs 6.5 +/- 4.6 mmHg s(-1) and 448 +/- 173 vs 2.3 +/- 2.3 mmHg s(-1) respectively; P < 0.05). Plasma glucose was significantly higher with pectin than without it at 60 min after ingestion (141.5 +/- 6.03 vs 125.8 +/- 4.69 microM mL(-1), P < 0.05). In healthy individuals, pectin increased the viscosity of enteral nutrition and accelerated gastric emptying.
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Nutrición Enteral , Alimentos Formulados , Vaciamiento Gástrico/efectos de los fármacos , Pectinas/farmacología , Adulto , Glucemia/metabolismo , Pruebas Respiratorias , Femenino , Vaciamiento Gástrico/fisiología , Gastrinas/sangre , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/prevención & control , Motilidad Gastrointestinal/fisiología , Humanos , Concentración de Iones de Hidrógeno , Insulina/sangre , Masculino , Pectinas/administración & dosificación , ViscosidadAsunto(s)
Psoriasis/radioterapia , Terapia Ultravioleta/métodos , Adolescente , Adulto , Anciano , Axila , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
BACKGROUND/AIMS: Hyperbaric oxygen therapy (HBOT) has been reported to augment oxygen delivery to ischemic tissues and improve the liver dysfunction in clinical cases. HBOT was performed after 90% hepatectomy in rats to determine its effect on the regeneration of remnant liver. METHODS: After 90% hepatectomy was performed in 8-week-old male Wistar rats, the animals were subdivided into an HBOT (2 atm abs., 80% O2, 1 h/day, 3 days) group and a non-HBOT group. Members of both groups were sacrificed, usually every 4 h until a maximum of 50 h after hepatectomy, and the liver regeneration rate, the proportion of PCNA-positive cells and the ATP volume in the remnant tissues were examined. RESULTS: In the HBOT group, the liver regeneration rate at 36 h and 50 h after operation and the proportion of PCNA positive cells at 8 h was significantly increased compared with the non-HBOT group. The ATP volume in the remnant livers in the HBOT group was also significantly increased at 12 h. CONCLUSION: HBOT augmented liver regeneration after hepatectomy by stabilization of energy metabolism induced by oxygen delivery in rats.
Asunto(s)
Hepatectomía , Oxigenoterapia Hiperbárica , Regeneración Hepática/fisiología , Animales , Metabolismo Energético/fisiología , Masculino , Modelos Animales , Oxígeno/metabolismo , Ratas , Ratas WistarRESUMEN
The rats treated with a single i.p. injection of diethylnitrosoamine (DEN) and percial hepatectomy were fed for 11 weeks with a high fat diet mixed with 10% lard, eicosapentaenoic-acid-rich oil (EPA-oil) or arachidonic-acid-rich oil (AA-oil) and the emergence of glutathione S-transferase placental form (GST-P) in the liver was evaluated. There were no significant differences in the serum aminotransferase activities. The molar ratio of n-6 and n-3 fatty acid in the liver phospholipids was significantly low in the EPA-oil group compared with the other groups. In the EPA-oil group, the area percent and the unit area of GST-P positive foci were significantly smaller than the other groups. In the AA-oil group, no significant differences were recognized in the quantitative values for GST-P positive foci compared with the control and lard groups. In conclusion, a hepatic neoplasmic lesion induced by DEN was suppressed with EPA-rich fish oil, and arachidonic-acid-rich oil showed no effect of suppression or acceleration.
Asunto(s)
Carcinógenos/farmacología , Grasas de la Dieta/farmacología , Ácidos Grasos/química , Ácidos Grasos/farmacología , Glutatión Transferasa/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Administración Oral , Alanina Transaminasa/sangre , Animales , Ácido Araquidónico/farmacología , Proteínas Sanguíneas/análisis , Ácido Eicosapentaenoico , Ácidos Grasos Insaturados/farmacología , Hígado/química , Masculino , Tamaño de los Órganos/efectos de los fármacos , Fosfolípidos/química , Ratas , Aumento de Peso/efectos de los fármacosRESUMEN
Human Toll-like receptor 4 (TLR4) has recently been identified and has been shown to be the main protein involved in recognizing Gram-negative bacteria. We examined the regulation of TLR4 surface expression in a human monocytic cell line (THP-1 cells) by two traditional Chinese herbal medicines. Bu-Zhong-Yi-Qi-Tang (TJ-41) and Shi-Quan-Da-Bu-Tang (TJ-48). TJ-41 and TJ-48 upregulated TLR4 surface expression in THP-1 cells, as well as enhanced TLR4 surface expression in these cells both dose- and time-dependently. These findings suggest that TJ-41 and TJ-48 increase the receptor involved in the response to Gram-negative bacteria and may enhance defenses against these pathogens.
Asunto(s)
Proteínas de Drosophila , Medicamentos Herbarios Chinos/farmacología , Glicoproteínas de Membrana/biosíntesis , Monocitos/metabolismo , Receptores de Superficie Celular/biosíntesis , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Monocitos/citología , Factores de Tiempo , Receptor Toll-Like 4 , Receptores Toll-Like , Regulación hacia ArribaRESUMEN
To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.