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1.
Cureus ; 13(5): e15243, 2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34178549

RESUMEN

Superior mesenteric artery syndrome (SMAS) is an intermittent or persistent passage obstruction that occurs in the third portion of the duodenum between the aorta and the superior mesenteric artery. After symptoms stabilize, the nutritional intake is started by ingesting a small amount. Recently, an energy-dense, low-volume nutritional food, Terumeal uplead® (Terumo Corporation, Tokyo, Japan) with an energy density of 4.0 kcal/mL, was launched. We report a case of a postoperative SMAS patient who was successfully treated using Terumeal uplead® through gastrostomy. An 83-year-old man who developed adhesive intestinal obstruction underwent right hemicolectomy, lysis of adhesion, and partial small bowel resection. Gastric distension persisted after surgery; thus, gastrostomy was performed for decompression and enteral nutrition on the 21st postoperative day, and enteral feeding was started on the 23rd postoperative day. However, fluoroscopy showed obstruction in the third portion of the duodenum, which was considered to be SMAS. To reduce the administration volume, enteral nutrition was replaced with Terumeal uplead® from the 28th postoperative day (intermittent administration thrice a day, 300 mL, 1,200 kcal per day). From the 34th postoperative day, the gastrostomy tube was clamped for two hours after administration, and no drainage was observed. Oral intake was resumed from the 36th postoperative day, and it was used in combination with enteral nutrition. Three months later, the patient was discharged home and continued oral ingestion with occasional decompression from the gastrostomy tube. Thus, Terumeal uplead® may be useful during the conservative treatment of SMAS by initiation with small amounts.

2.
ESMO Open ; 2(1): e000151, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28761731

RESUMEN

OBJECTIVE: This study was performed to compare health-related quality of life (HRQOL) of gemcitabine plus S-1 (GS), S-1 alone and gemcitabine alone as first-line chemotherapy for locally advanced or metastatic pancreatic cancer in the GEST (Gemcitabine and TS-1 Trial) study and to assess the impacts of adverse events and tumour response on HRQOL. METHODS: Patients were randomly assigned to receive gemcitabine alone (1000 mg/m2 weekly for 3 of 4 weeks), S-1 alone (80, 100 or 120 mg/day twice daily for 4 of 6 weeks) or GS (gemcitabine at 1000 mg/m2 weekly plus S-1 at 60, 80 or 100 mg/day twice daily for 2 of 3 weeks). HRQOL was assessed using the EuroQoL-5D (EQ-5D) questionnaire at baseline and weeks 6, 12, 24, 48 and 72. EQ-5D scores, quality-adjusted life months (QALMs), quality-adjusted progression-free months (QAPFMs) and time until definitive HRQOL deterioration (TUDD) were compared among the three groups. The impacts of adverse events and tumour response on EQ-5D scores were analysed. RESULTS: Including EQ-5D scores after death as 0, the mean profile was significantly better in the GS than gemcitabine group (difference, 0.069; p=0.003), but not the S-1 group (difference, -0.011; p=0.613). The mean profiles until death were similar in the three groups. QALMs, QAPFMs and TUDD were significantly longer in the GS than gemcitabine group (p<0.001, p<0.001 and p=0.004, respectively), but not the S-1 group (p=0.563, p=0.741 and p=0.701, respectively). Fatigue, anorexia and tumour response were significantly associated with changes in EQ-5D scores. CONCLUSIONS: GS achieved better HRQOL than gemcitabine alone, resulting a good balance between overall survival and HRQOL benefits. S-1 alone provides HRQOL similar to that provided by gemcitabine alone. Preventing fatigue and anorexia and maintaining better response would improve HRQOL.

4.
Histochem Cell Biol ; 143(3): 301-12, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25249350

RESUMEN

Information concerning the cellular localization of cholecystokinin (CCK)-1 receptors has been discrepant and remained scanty at ultrastructural levels. The present immunohistochemical study at light and electron microscopic levels revealed the distinct localization of CCK1 receptors in visceral organs. Immunohistochemistry by use of a purified antibody against mouse CCK1 receptor was applied to fixed tissue sections of the pancreas, gallbladder, stomach, and intestine of mice. A silver-intensified immunogold method revealed the subcellular localization under electron microscope. The immunoreactivity for CCK1 receptors was selectively found in the basolateral membrane of pancreatic acinar cells and gastric chief cells but was absent in pancreatic islets and gastric D cells. Another intense expression in the gut was seen in the myenteric nerve plexus of the antro-duodenal region and some populations of c-Kit-expressing pacemaker cells in the duodenal musculature. The gallbladder contained smooth muscle fibers with an intense immunoreactivity of CCK1 receptors on cell surfaces. The restricted localization of CCK1 receptors on the basolateral membrane of pancreatic acinar cells and gastric chief cells, along with their absence in the islets of Langerhans and gastric D cells, provides definitive information concerning the regulatory mechanism by circulating CCK. Especially, the subcellular localization in the acinar cells completes the investigation for the detection of circulating CCK by the basolateral membrane.


Asunto(s)
Vesícula Biliar/citología , Páncreas/citología , Receptor de Colecistoquinina A/análisis , Receptor de Colecistoquinina A/metabolismo , Estómago/citología , Animales , Vesícula Biliar/ultraestructura , Hibridación Fluorescente in Situ , Masculino , Ratones , Ratones Endogámicos , Microscopía Electrónica , Datos de Secuencia Molecular , Páncreas/ultraestructura , Receptor de Colecistoquinina A/ultraestructura , Estómago/ultraestructura
5.
Nihon Shokakibyo Gakkai Zasshi ; 110(8): 1487-94, 2013 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-23912009

RESUMEN

A 51-year-old man presenting with fever, weight loss and general fatigue was diagnosed with jaundice and liver tumors and admitted to our hospital for further investigation and treatment. We diagnosed multiple pyogenic liver abscesses, obstructive jaundice, and silent syphilis. The patient was successfully treated with endoscopic biliary stenting, endoscopic nasobiliary drainage, percutaneous transhepatic abscess drainage, and, most effectively, transcatheter regional hepatic arterial infusion with antibiotics. We speculated that the decline in neutrophil phagocytic function may concern to occur the pyogenic liver abscess.


Asunto(s)
Absceso Piógeno Hepático/complicaciones , Neutrófilos/fisiología , Fagocitosis/fisiología , Antibacterianos/administración & dosificación , Humanos , Infusiones Intraarteriales , Ictericia Obstructiva/complicaciones , Absceso Piógeno Hepático/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Sífilis/complicaciones
6.
J Clin Oncol ; 31(13): 1640-8, 2013 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-23547081

RESUMEN

PURPOSE: The present phase III study was designed to investigate the noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with gemcitabine alone with respect to overall survival. PATIENTS AND METHODS: The participants were chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer. Patients were randomly assigned to receive only gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle). RESULTS: In the total of 834 enrolled patients, median overall survival was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1 months in the gemcitabine plus S-1 group. The noninferiority of S-1 to gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P < .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were generally well tolerated, although hematologic and GI toxicities were more severe in the gemcitabine plus S-1 group than in the gemcitabine group. CONCLUSION: Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Neoplasias Pancreáticas/patología , Calidad de Vida , Análisis de Supervivencia , Taiwán , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del Tratamiento , Gemcitabina
7.
Biomed Res ; 34(6): 275-80, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24389403

RESUMEN

Several studies on alcohol and gastric emptying using the (13)C breath test showed that alcohol consumption delayed gastric emptying of meals in healthy male subjects. However, they did not employ female subjects, and the retention time of alcoholic beverages in the stomach has not been examined, yet. We examined the retention time (= gastric emptying rate) of alcoholic beverages in the stomach in healthy male and female subjects. We also examined whether the congeners (nonalcoholic components) of red wine have any effect on gastric emptying. The retention time of 60 mL of red wine, vodka, congeners of red wine, or mineral water, was measured using a (13)C labeled acetic acid breath test. In male subjects, the retention time of wine and vodka was significantly longer than that of congeners and mineral water. In female subjects, although the (13)C content in the breath was slightly but significantly decreased by wine and congeners, but not by vodka, and the parameters for gastric emptying did not differ significantly among the 4 drinks. That is, alcohol hardly influenced the retention time in female subjects. In conclusion, there are sex differences in the gastric emptying rate of alcohol.


Asunto(s)
Etanol/farmacocinética , Vaciamiento Gástrico/fisiología , Aguas Minerales/administración & dosificación , Estómago/fisiología , Pruebas Respiratorias , Isótopos de Carbono , Estudios Cruzados , Etanol/metabolismo , Femenino , Humanos , Masculino , Factores Sexuales , Vino/análisis , Adulto Joven
8.
Diabetes ; 61(4): 897-907, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22357963

RESUMEN

Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R(-/-),-2R(-/-)) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R(-/-) mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R(-/-),-2R(-/-) mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R(-/-) bone marrow-derived cells developed more albuminuria than diabetic CCK-1R(-/-) mice with WT bone marrow-derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-α and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy.


Asunto(s)
Colecistoquinina/metabolismo , Diabetes Mellitus/metabolismo , Inflamación/metabolismo , Riñón/metabolismo , Macrófagos/fisiología , Animales , Quimiocinas CC , Quimiotaxis/efectos de los fármacos , Colecistoquinina/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/fisiología , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Ratones , Ratones Noqueados , FN-kappa B/genética , FN-kappa B/metabolismo , Receptor de Colecistoquinina B/genética , Receptor de Colecistoquinina B/metabolismo , Receptores de Colecistoquinina/genética , Receptores de Colecistoquinina/metabolismo , Sincalida/análogos & derivados , Sincalida/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
9.
Oncol Rep ; 27(3): 867-72, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22200743

RESUMEN

Pancreatic cancer is a disease with a dismal prognosis and treatment options are limited. This study investigated the interaction of gemcitabine with R1507 and/or metformin and the induction of an inhibitor of apoptosis protein by this com-bination. Pancreatic cancer cells were treated with gemcitabine, R1507 and metformin alone or in combination. The effects of treatments were evaluated for cell proliferation, apoptosis, and the expression of genes related to inhibition of apoptosis and chemotherapy resistance. Combination of gemcitabine with R1507 and/or metformin additively interacted with the inhibition of cell proliferation in human pancreatic ductal adenocarcinoma cell lines, SUIT-2 and MIAPaCa-2 with differential gemcitabine resistance, and assessment of apoptosis demonstrated that drug associations increased the apoptotic index in both cell lines. Treatment with gemcitabine induced the expression of survivin and XIAP in both cell lines, indicating the induction of chemoresistance. In conclusion, these data demonstrate that the combination of gemcitabine with R1507 and/or metformin has an additive effect in pancreatic cancer cell lines with differential sensitivity to gemcitabine; however, gemcitabine may induce chemotherapy resistance.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Metformina/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Carcinoma Ductal Pancreático/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Metformina/administración & dosificación , Neoplasias Pancreáticas/metabolismo , Receptor IGF Tipo 1/inmunología , Survivin , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Gemcitabina
10.
Biomed Res ; 32(6): 401-6, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22199131

RESUMEN

Gallstone disease is one of the most prevalent digestive diseases. The frequency of gallstone disease is about 10% in middle-age persons and 20% in aged persons. Gallbladder dysmotility and stasis of bile flow promote sludge and/or gallstone formation. Gallbladder contraction depends on cholecystokinin (CCK) via CCK-1 receptors (R)s. Previously, we raised CCK-1R deficient (-/-) mice and observed sludge and/or gallstone formation in more than 30% at 12-24 months of age. As ursodeoxycholate (UDCA) is commonly used for patients with gallstone disease, we expected that continuous administration of UDCA could prevent sludge and/or gallstone formation in CCK- 1R(-/-) mice. A diet containing 0.1% UDCA was administered in age-matched CCK-1R(-/-) and wild-type male and female mice for 8 months. Administration of UDCA decreased the frequency of sludge and/or gallstone formation compared with the control (CRF-1) diet (39%→26% in male, 35%→25% in female mice); however, these effects did not attain a level of statistical significance. Although the body weight was significantly higher in UDCA-fed than CRF-1-fed male mice regardless of genotypes, the plasma lipid concentrations did not differ between the two diets. In conclusion, administration of UDCA was less effective than expected at preventing sludge and/or gallstone formation in CCK-1R(-/-) mice.


Asunto(s)
Bilis , Cálculos Biliares/prevención & control , Receptor de Colecistoquinina A/genética , Ácido Ursodesoxicólico/administración & dosificación , Animales , Cálculos Biliares/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
11.
Jpn J Clin Oncol ; 41(8): 953-8, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21715364

RESUMEN

OBJECTIVE: The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer. METHODS: Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks. RESULTS: A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3. CONCLUSIONS: Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Adenoescamoso/tratamiento farmacológico , Carcinoma Adenoescamoso/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Adulto , Anciano , Anorexia/etiología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Combinación de Medicamentos , Erupciones por Medicamentos/etiología , Femenino , Humanos , Estimación de Kaplan-Meier , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Ácido Oxónico/administración & dosificación , Tegafur/administración & dosificación , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Gemcitabina
12.
Gan To Kagaku Ryoho ; 38(6): 1043-7, 2011 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-21677505

RESUMEN

The case was a 58-year-old woman who visited our hospital for a thorough examination after multiple liver tumors were found in her at a nearby hospital. By liver tumor biopsy, we diagnosed them as carcinoid. Bone scintigraphy showed an abnormal accumulation in the external left scapula and in both of her hip joints, but the primary lesion was unclear. She died 8 years and 5 months after disease onset from deterioration of liver lesions, inspite of our treatments, such as gemcitabine administration of systemic chemotherapy, transcatheter arterial chemoembolization for liver lesions, and radiation therapy for bone lesions. Pathological anatomy suggested a pancreatic, well-differentiated neuroendocrine carcinoma.


Asunto(s)
Tumor Carcinoide/patología , Neoplasias Hepáticas/secundario , Neoplasias Pancreáticas/patología , Antineoplásicos/uso terapéutico , Tumor Carcinoide/tratamiento farmacológico , Tumor Carcinoide/radioterapia , Diferenciación Celular , Terapia Combinada , Resultado Fatal , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia
13.
Lancet Oncol ; 12(3): 256-62, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21306953

RESUMEN

BACKGROUND: Axitinib is a potent, selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. A randomised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients. On the basis of these results, we aimed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial. METHODS: In this double-blind, placebo-controlled, phase 3 study, eligible patients had metastatic or locally advanced pancreatic adenocarcinoma, no uncontrolled hypertension or venous thrombosis, and Eastern Cooperative Oncology Group performance status 0 or 1. Patients, stratified by disease extent (metastatic vs locally advanced), were randomly assigned (1:1) to receive gemcitabine 1000 mg/m(2) intravenously on days 1, 8, and 15 every 28 days plus either axitinib or placebo. Axitinib or placebo were administered orally with food at a starting dose of 5 mg twice a day, which could be dose-titrated up to 10 mg twice daily if well tolerated. A centralised randomisation procedure was used to assign patients to each treatment group, with randomised permuted blocks within strata. Patients, investigators, and the trial sponsor were masked to treatment assignments. The primary endpoint was overall survival. All efficacy analyses were done in all patients assigned to treatment groups for whom data were available; safety and treatment administration and compliance assessments were based on treatment received. This study is registered at ClinicalTrials.gov, number NCT00471146. FINDINGS: Between July 27, 2007, and Oct 31, 2008, 632 patients were enrolled and assigned to treatment groups (316 axitinib, 316 placebo). At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8·5 months (95% CI 6·9-9·5) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8·3 months (6·9-10·3) for gemcitabine plus placebo (n=316; hazard ratio 1·014, 95% CI 0·786-1·309; one-sided p=0·5436). The most common grade 3 or higher adverse events for gemcitabine plus axitinib and gemcitabine plus placebo were hypertension (20 [7%] and 5 [2%] events, respectively), abdominal pain (20 [7%] and 17 [6%]), fatigue (27 [9%] and 21 [7%]), and anorexia (19 [6%] and 11 [4%]). INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. These results add to increasing evidence that targeting of VEGF signalling is an ineffective strategy in this disease. FUNDING: Pfizer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Imidazoles/uso terapéutico , Indazoles/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Axitinib , Desoxicitidina/análogos & derivados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Análisis de Supervivencia , Gemcitabina
14.
Pancreas ; 40(1): 79-83, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21160370

RESUMEN

OBJECTIVES: Pancreatic functions were determined in a Ki-ras-induced actin-interacting protein (KRAP)-deficient (-/-) mouse mutant. METHODS: Pancreatic enzyme, protein, and DNA contents were measured, and histological examinations were conducted. The mixture of bile-pancreatic juice was collected, and amylase and bile acid outputs were determined. Oral glucose tolerance test was determined. Moreover, the gene expression of KRAP was determined in cholecystokinin (CCK)-A(1) receptor (-/-) mice. RESULTS: The body weight was smaller, and the ratio of pancreatic wet weight/body weight was higher in KRAP(-/-) mice compared with wild-type mice. The enzyme contents, but not DNA content, in the pancreas of KRAP(-/-) mice were higher than those of wild-type mice. Histological examination revealed the increase in the number of zymogen granules in the pancreatic acinar cells of KRAP(-/-) mice. Amylase secretions in response to CCK-octapeptide sulfate were significantly higher in KRAP(-/-) than wild-type mice, whereas the basal secretion did not differ between the 2 genotypes. A normal glucose tolerance was observed in KRAP(-/-) mice. The gene expression of KRAP in CCK-A(1) receptor (-/-) mice was significantly lower than in wild-type mice. CONCLUSIONS: The lack and/or decrease in KRAP level in the pancreas may promote the pancreatic growth and hypertrophy.


Asunto(s)
Proteínas de Microfilamentos/fisiología , Páncreas/patología , Amilasas/metabolismo , Animales , Ácidos y Sales Biliares/metabolismo , Genes ras/fisiología , Prueba de Tolerancia a la Glucosa , Hipertrofia , Ratones , Ratones Noqueados , Receptores de Colecistoquinina/fisiología
16.
Cancer Sci ; 102(2): 425-31, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21175992

RESUMEN

Erlotinib combined with gemcitabine has not been evaluated in Japanese patients with unresectable pancreatic cancer. This two-step phase II study assessed the safety and pharmacokinetics of erlotinib 100 mg/day (oral) plus gemcitabine 1000 mg/m(2) (i.v. days 1, 8, 15) in a 28-day cycle in the first step, and efficacy and safety in the second step. The primary end-point was safety. One hundred and seven patients were enrolled (first step, n = 6; second step, n = 101). The most common adverse event was RASH (compiled using the preferred terms rash, acne, exfoliative rash, dermatitis acneiform, erythema, eczema, dermatitis and pustular rash) in 93.4% of patients. One treatment-related death occurred. While interstitial lung disease-like events were reported in nine patients (8.5%; grade 1/2/3, 3.8/2.8/1.9%), all patients recovered or improved. The median overall survival, the 1-year survival rate and median progression-free survival were 9.23 months, 33.0% and 3.48 months, respectively. The overall response and disease control rates were 20.3% and 50.0%, respectively. In Japanese patients with unresectable pancreatic cancer, erlotinib plus gemcitabine had acceptable toxicity and efficacy that was not inferior to that seen in Western patients.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Adenoescamoso/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Pueblo Asiatico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Clorhidrato de Erlotinib , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Quinazolinas/farmacocinética , Gemcitabina
17.
Gan To Kagaku Ryoho ; 37(13): 2875-9, 2010 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-21160263

RESUMEN

There is no agreement on the standard chemotherapeutic regimen for biliary tract cancer(BTC), although multi-drug regimens such as gemcitabine and/or S-1 have been tested in clinical trials. This study retrospectively reviewed data from patients with BTC who were seen at hospitals in the Kitakyushu and Fukuoka areas between 2005 and 2006, and examined the effect of systemic chemotherapy regimen on survival benefits in patients with unresectable BTC. Chemotherapy may benefit patients with BTC any age group, regardless of the primary site.


Asunto(s)
Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Conductos Biliares/tratamiento farmacológico , Enfermedades de los Conductos Biliares/mortalidad , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Cancer Sci ; 101(11): 2351-60, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20726858

RESUMEN

Pancreatic cancer is one of the most lethal malignancies. Epidermal growth factor receptor (EGFR), HER3, Akt, and amphiregulin have been recognized as targets for pancreatic cancer therapy. Although gemcitabine + erlotinib has been the recommended chemotherapy for pancreatic cancer, the prognosis is extremely poor. The development of molecularly targeted therapies has been required for patients with pancreatic cancer. To assess the validation of amphiregulin as a target for pancreatic cancer therapy, we examined its expression in pancreatic cancer using real-time PCR analyses and ELISA. We also measured the apoptotic cell rate using TUNEL assays. In addition, alterations in signaling pathways were detected by immunoblotting analyses. Treatment with gemcitabine, which reduced the cell viability and augmented the cell apoptotic rate, activated and subsequently attenuated ERK and EGFR signals. However, gemcitabine, paclitaxel, or cisplatin treatment enhanced the Akt activation, heterodimer formation of EGFR with HER3, and secretion of amphiregulin, indicating that the presence of gemcitabine promoted the activity of targeted molecules including amphiregulin, Akt, and HER3 for pancreatic cancer therapy. Combined treatment with an inhibitor for amphiregulin and gemcitabine, paclitaxel, or cisplatin induced synergistic antitumor effects, accompanied by the suppression of Akt and ERK activation. Blockade of amphiregulin suppressed the activities of EGFR, HER3, and Akt and the expression of amphiregulin itself. According to this evidence, combination chemotherapy of conventional anticancer drugs plus an inhibitor for amphiregulin would allow us to provide more favorable clinical outcomes for patients with pancreatic cancer.


Asunto(s)
Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glicoproteínas/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor ErbB-3/metabolismo , Anfirregulina , Anticuerpos/inmunología , Anticuerpos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Familia de Proteínas EGF , Activación Enzimática , Ensayo de Inmunoadsorción Enzimática , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Glicoproteínas/genética , Glicoproteínas/inmunología , Humanos , Immunoblotting , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/inmunología , Paclitaxel/farmacología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas c-akt/genética , Receptor ErbB-3/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Gemcitabina
19.
Geriatr Gerontol Int ; 10 Suppl 1: S120-6, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20590827

RESUMEN

AIMS: Most of the acetaldehyde, a recognized animal carcinogen, generated during alcohol metabolism is eliminated by liver mitochondrial aldehyde dehydrogenase 2 (ALDH2). More than 40% of Japanese people have the inactive form of ALDH2, and inactive ALDH2 is a risk factor for multiple cancer of the esophagus, as well as head and neck cancer. Possible associations between pancreatic cancer and ALDH2 gene polymorphism, as well as between colon cancer and ALDH2 gene polymorphism, in conjunction with smoking and/or drinking habits, were examined in a Japanese population. METHODS: Patients with pancreatic cancer (n = 187) and with colon cancer (n = 49) were examined. The drinking (5 g ethanol consumption/day) and/or smoking habits as well as ALDH2 gene polymorphism were examined. The age-matched control subjects were recruited in the NILS Longitudinal Study of Aging (LSA). RESULTS: Aging, smoking and inactive ALDH2, but not alcohol, are independent risk factors for pancreatic cancer. The frequency of smoking habits tended to be higher in patients with colon cancer compared with the patients without cancer. However, age, body mass index or the distribution of ALDH2 genotypes did not differ significantly among the patients with colon cancer, colon polyps and others. CONCLUSIONS: Inactive ALDH2 is an independent risk factor for pancreatic cancer, but inactive ALDH2 might not be a risk for colon cancer.


Asunto(s)
Aldehído Deshidrogenasa/genética , Neoplasias del Colon/genética , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/epidemiología , Aldehído Deshidrogenasa Mitocondrial , Pueblo Asiatico/genética , Genotipo , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/epidemiología , Factores de Riesgo , Fumar/epidemiología
20.
Phys Rev Lett ; 104(15): 156401, 2010 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-20482000

RESUMEN

The electronic structure of rubrene single crystals was studied by angle-resolved ultraviolet photoelectron spectroscopy. A clear energy dispersion of the highest occupied molecular orbital-derived band was observed, and the dispersion width was found to be 0.4 eV along the well-stacked direction. The effective mass of the holes was estimated to be 0.65(+/-0.1)m0. The present results suggest that the carrier conduction mechanism in rubrene single crystals can be described within the framework of band transport.

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