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1.
Dis Esophagus ; 29(8): 1090-1099, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26541471

RESUMEN

Patients with thoracic esophageal cancer are often treated by minimally invasive esophagectomy. However, the long-term survival benefits of minimally invasive esophagectomy remain unclear. Two approaches are available for thoracoscopic surgery: one with the patient in the left lateral decubitus position (LLDP), and the other with the patient in the prone position (PP). We investigated the survival benefit of thoracoscopic esophagectomy according to the tumor stage and patient position during the thoracoscopic procedure. We reviewed the records of 220 consecutive patients with esophageal cancer treated from 1998 to 2012. In total, 146 and 74 patients were treated with thoracoscopic esophagectomy in the LLDP and PP, respectively. No patients were initially proposed to be candidates for esophagectomy by thoracotomy during the study period. Data collection was performed with a focus on survival and recurrent disease. Among all the 220 patients, the overall 5-year survival rates were 83.7%, 74.1%, 45.5%, 78.6%, 44.2%, 29.4% and 24.3% in the patients with pStage IA, IB, IIA, IIB, IIIA, IIIB and IIIC disease, respectively. Despite the greater number of dissected mediastinal lymph nodes in the PP procedure, there were no significant differences in the survival curves between the LLDP and PP procedures. The long-term results of thoracoscopic esophagectomy are comparable and acceptable. The PP procedure was not confirmed to offer a superior survival benefit to the LLDP procedure in this retrospective study.


Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagectomía/mortalidad , Toracoscopía/mortalidad , Anciano , Neoplasias Esofágicas/mortalidad , Esofagectomía/métodos , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/estadística & datos numéricos , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente/métodos , Posición Prona , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Toracoscopía/métodos , Resultado del Tratamiento
2.
J Int Med Res ; 37(6): 1904-12, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20146890

RESUMEN

This study investigated the effects of mitiglinide in 16 patients with type 2 diabetes mellitus treated with 30 mg/day mitiglinide, divided into three doses given just before each meal, for approximately 12 months. A 450 kcal meal tolerance test was performed at baseline and after 3, 6 and 12 months, and levels of plasma glucose and immunoreactive insulin were measured. Various parameters of glucose metabolism and lipid metabolism, urinary albumin and markers of atherosclerosis, coagulation and fibrinolysis were also determined. Mitiglinide showed a rapid stimulatory effect on insulin secretion and reduced the levels of plasma glucose. The free fatty acid level significantly decreased at 60 min after the meal tolerance test. Mitiglinide also significantly lowered glycosylated haemoglobin and raised 1,5-anhydroglucitol after 6 months, and significantly decreased urinary albumin after 12 months. These data indicate that mitiglinide may have beneficial effects not only on glycaemic control but also on lipid metabolism and urinary albumin excretion, and may have a role in the prevention of the vascular complications of diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Isoindoles/uso terapéutico , Albuminuria/complicaciones , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Desoxiglucosa/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Ayuno/sangre , Ácidos Grasos/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/farmacología , Isoindoles/farmacología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Periodo Posprandial/efectos de los fármacos , Análisis de Regresión
3.
Cancer Gene Ther ; 13(5): 520-9, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16341142

RESUMEN

NK4 or adenovirus vector expressing NK4 (Ad-NK4) can act bifunctionally as a hepatocyte growth factor antagonist and angiogenesis inhibitor and has potential value in cancer therapy. The aim of this study was to evaluate the therapeutic efficacy of Ad-NK4 in combination with gemcitabine (GEM) against pancreatic cancer. In vitro study showed a strong antiproliferative effect of GEM and a potent anti-invasive effect of Ad-NK4 against pancreatic cancer cells. In in vivo experiments, SUIT-2 human pancreatic cancer cells were implanted into the pancreas of nude mice. Mice were treated with Ad-NK4 by injection into the peritumoral region of the pancreas on day 5 after implantation followed by weekly i.p. injections of GEM. On day 28 after implantation, pancreatic tumor volume was significantly smaller than that in mice treated with Ad-LacZ, Ad-NK4 alone, or GEM alone. Furthermore, combination therapy completely suppressed peritoneal dissemination and liver metastases, leading to significantly increased survival. Histologic and immunohistochemical assays of primary tumors indicated that combination therapy prohibited both cell proliferation and angiogenesis, resulting in high levels of apoptosis. These results suggest that peritumoral injection of Ad-NK4 plus GEM is a potent combination therapy for pancreatic cancer.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma/prevención & control , Desoxicitidina/análogos & derivados , Terapia Genética , Factor de Crecimiento de Hepatocito/genética , Neoplasias Hepáticas/prevención & control , Neoplasias Pancreáticas/terapia , Adenoviridae/genética , Animales , Carcinoma/secundario , Terapia Combinada , Desoxicitidina/uso terapéutico , Vectores Genéticos/administración & dosificación , Humanos , Inyecciones , Neoplasias Hepáticas/secundario , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas c-met/genética , ARN Mensajero/análisis , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina
4.
Cancer Chemother Pharmacol ; 58(4): 494-503, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16437251

RESUMEN

PURPOSE: An antitumor camptothecin derivative CPT-11 has proven a broad spectrum of solid tumor malignancy, but its severe diarrhea has often limited its more widespread use. We have demonstrated from a rat model that intestinal beta-glucuronidase may play a key role in the development of CPT-11-induced delayed diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a protective effect. In the present study, we assessed the efficacy of several potential treatments in our rat model to clarify which is the most promising treatment for CPT-11-induced delayed diarrhea. METHODS AND RESULTS: Oral dosing (twice daily from days -1 to 4) of streptomycin 20 mg/kg and penicillin 10 mg/kg (Str/Pen), neomycin 20 mg/kg and bacitracin 10 mg/kg (Neo/Bac), both of which inhibited almost completely the fecal beta-glucuronidase activity, or TJ-14 1,000 mg/kg improved the decrease in body weight and the delayed diarrhea symptoms induced by CPT-11 (60 mg/kg i.v. from days 1 to 4) to a similar extent. The efficacy was less but significant in activated charcoal (1,000 mg/kg p.o. twice daily from days -1 to 4). In a separate experiment using rats bearing breast cancer (Walker 256-TC), TJ-14, Neo/Bac, and charcoal at the same dose regimen improved CPT-11-induced intestinal toxicity without reducing CPT-11's antitumor activity. In contrast, oral dosing (twice a day) of cyclosporin A (50 mg/kg), a P-glycoprotein and cMOAT/MRP2 inhibitor or valproic acid (200 mg/kg), a UDP-glucuronosyltranferase inhibitor, exacerbated the intestinal toxicity without modifying CPT-11's antitumor activity. CONCLUSIONS: The result clearly demonstrated the ability of Neo/Bac, Str/Pen, and TJ-14, less but significant ability of activated charcoal, to ameliorate CPT-11-induced delayed-onset diarrhea, suggesting the treatments decreasing the exposure of the intestines to the luminal SN-38 are valuable for improvement of CPT-11-induced intestinal toxicity. In contrast, the treatments affecting the biliary excretion of CPT-11 and its metabolites might have undesirable results.


Asunto(s)
Antidiarreicos/uso terapéutico , Antineoplásicos Fitogénicos/toxicidad , Camptotecina/análogos & derivados , Diarrea/inducido químicamente , Inhibidores Enzimáticos/farmacología , Glucuronidasa/antagonistas & inhibidores , Intestinos/enzimología , Animales , Camptotecina/toxicidad , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Flavonoides/uso terapéutico , Glucuronidasa/metabolismo , Irinotecán , Masculino , Medicina Kampo , Penicilinas/uso terapéutico , Ratas , Ratas Wistar , Estreptomicina/uso terapéutico
5.
Cancer Res ; 56(16): 3752-7, 1996 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-8706020

RESUMEN

Irinotecan hydrochloride (CPT-11), an antitumor camptothecin derivative, causes severe forms of diarrhea clinically. We characterized CPT-11-induced diarrhea histologically and enzymologically and assessed the relationships between intestinal toxicity and the activity of the enzymes that play a key role in the major metabolic pathway of CPT-11 in rats. CPT-11 (60 mg/kg i.v. for 4 days) induced intestinal toxicity characterized by severe chronic diarrhea, loss of body weight, and anorexia. Histological damage was most severe in the cecum. The segmental difference in the degree of the damage showed good correlation with the beta-glucuronidase activity in the contents of the lumen in each case, but not with the intestinal tissue carboxylesterase activity, which converts CPT-11 to its active form (7-ethyl-10-hydroxycamptothecin). Inhibition of the beta-glucuronidase activity in the intestinal microflora by antibiotics (1 mg penicillin and 2 mg streptomycin per ml of drinking water) markedly ameliorated the diarrhea and reduced cecal damage. Analysis of CPT-11 and its metabolites in the feces indicated that antibiotics completely inhibited the deconjugation of the glucuronic conjugate of 7-ethyl-10-hydroxycamptothecin by beta-glucuronidase. It is suggested that CPT-11-induced diarrhea would be attributable to the damage to the cecum, and that the inhibition of the beta-glucuronidase activity in the intestinal microflora is a major protective effect of antibiotics.


Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Bacterias/enzimología , Camptotecina/análogos & derivados , Glucuronidasa/fisiología , Intestinos/efectos de los fármacos , Animales , Antibacterianos/farmacología , Camptotecina/metabolismo , Camptotecina/farmacocinética , Camptotecina/toxicidad , Diarrea/inducido químicamente , Intestinos/microbiología , Irinotecán , Masculino , Ratas , Ratas Wistar
6.
Surg Endosc ; 19(12): 1592-6, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16247578

RESUMEN

BACKGROUND: Laparoscopically assisted distal gastrectomy (LADG) with limited lymph node dissection (D1+alpha) has been used to treat a subset of patients with early gastric cancer. Technical advances have expanded indications for LADG to more advanced gastric cancers. However, little data are available on the feasibility or advantages of LADG with standard radical D2 lymph node dissection for patients with gastric cancer. METHODS: This study reviewed the clinical features of 37 patients who underwent LADG with D2 lymph node dissection for preoperatively diagnosed gastric carcinoma, then compared the results with the features of 31 patients who underwent conventional open distal gastrectomy (ODG) with D2 lymph node dissection. RESULTS: The laparoscopic procedure was not converted to laparotomy in any patient. There was no operative mortality and no serious morbidity among the patients who underwent LADG with D2 lymph node dissection. As compared with the ODG group, the LADG group had less operative blood loss (p < 0.001), earlier recovery of bowel activity (p = 0.012), and a shorter duration of fever after surgery (p = 0.015), despite the longer operation time (p = 0.007). CONCLUSIONS: According to this study, LADG with D2 lymph node dissection is feasible and provides several advantages similar to those of limited lymph node dissection (D1+alpha). Depending on surgeons' technical proficiency, LADG can be used with standard radical lymph node dissection for patients with gastric cancers.


Asunto(s)
Carcinoma/cirugía , Gastrectomía/métodos , Laparoscopía , Escisión del Ganglio Linfático/métodos , Neoplasias Gástricas/cirugía , Carcinoma/secundario , Estudios de Factibilidad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología
7.
Dentomaxillofac Radiol ; 44(6): 20150011, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25785821

RESUMEN

OBJECTIVES: To assess the safety of different magnetic dental attachments during 3-T MRI according to the American Society for Testing and Materials F2182-09 and F2052-06e1 standard testing methods and to develop a method to determine MRI compatibility by measuring magnetically induced torque. METHODS: The temperature elevations, magnetically induced forces and torques of a ferromagnetic stainless steel keeper, a coping comprising a keeper and a cast magnetic alloy coping were measured on MRI systems. RESULTS: The coping comprising a keeper demonstrated the maximum temperature increase (1.42 °C) for the whole-body-averaged specific absorption rate and was calculated as 2.1 W kg⁻¹ with the saline phantom. All deflection angles exceeded 45°. The cast magnetic alloy coping had the greatest deflection force (0.33 N) during 3-T MRI and torque (1.015 mN m) during 0.3-T MRI. CONCLUSIONS: The tested devices showed minimal radiofrequency (RF)-induced heating in a 3-T MR environment, but the cast magnetic alloy coping showed a magnetically induced deflection force and torque approximately eight times that of the keepers. For safety, magnetic dental attachments should be inspected before and after MRI and large prostheses containing cast magnetic alloy should be removed. Although magnetic dental attachments may pose no great risk of RF-induced heating or magnetically induced torque during 3-T MRI, their magnetically induced deflection forces tended to exceed acceptable limits. Therefore, the inspection of such devices before and after MRI is important for patient safety.


Asunto(s)
Prótesis Dental , Imagen por Resonancia Magnética/métodos , Aleaciones Dentales , Seguridad de Equipos , Fenómenos Magnéticos , Fantasmas de Imagen , Ondas de Radio , Temperatura , Torque
8.
Clin Exp Metastasis ; 17(10): 849-55, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-11089883

RESUMEN

In order to establish a highly metastatic variant of a mouse colon carcinoma cell line (CT26), BALB/c mice were first subcutaneously injected with CT26 cells. Several weeks later, metastatic tumors in lungs were resected, mechanically dispersed into a single cell suspension and cultured in vitro until cells reached confluency. These tumor cells were then subcutaneously injected into new mice. After repeating this procedure five times, a highly lung metastatic cell line, denoted as LM17, has been established. The LM17 cells grow in vitro with or without serum, whereas parental CT26 cells require serum for their growth. The LM17 cells adhere to type I collagen or fibronectin stronger than CT26 cells do. The LM17 cells invade through Matrigel-coated basement membrane in greater number than CT26 cells. By gelatin zymography, LM17 cells showed higher proteinase activity than CT26. Furthermore, subcutaneous injection of irradiated LM17 cells infected with adenovirus harboring mouse GM-CSF gene prevents the growth and lung metastasis of pre-existing subcutaneous tumor. The injection of irradiated GM-CSF-producing LM17 cells after the surgical removal of pre-existing tumor also protected the occurrence of lung metastasis. These results suggest that this highly metastatic LM17 cell line could be useful for analysis of the lung metastatic mechanism and as the mouse GM-CSF gene therapy model.


Asunto(s)
Carcinoma/patología , Carcinoma/terapia , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Terapia Genética/métodos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Células Tumorales Cultivadas , Adenoviridae/genética , Animales , Vacunas contra el Cáncer/farmacología , Pruebas de Carcinogenicidad , Carcinoma/secundario , Adhesión Celular , División Celular , Neoplasias del Colon/secundario , Femenino , Gelatina/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Neoplasias Pulmonares/terapia , Ratones , Ratones Endogámicos BALB C , Invasividad Neoplásica
9.
Am J Surg Pathol ; 17(8): 813-9, 1993 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7687828

RESUMEN

We studied 71 patients with solid-type gastric adenocarcinoma selected from 5,437 surgically resected specimens during the period from 1975 to 1988; six had vimentin-positive adenocarcinomas, and five of these were advanced. One was at an early stage. All six tumors showed the same histologic features and had either a diffuse or alveolar arrangement, with tumor cells having either poor or no cohesiveness. Many tumor cells were round to polygonal, with eosinophilic or clear cytoplasm and large, eccentric vesicular nuclei, as seen in malignant rhabdoid tumors of the kidney. In all cases, the cytoplasm showed coexpression of vimentin and cytokeratin as revealed by double immunostaining. Four of the five cases with advanced carcinoma died of the disease 1 to 6 months after surgery. The cases with vimentin-positive tumors had significantly poorer prognoses than those with vimentin-negative tumors. We also studied adenocarcinomas of various histologic types randomly selected from our file (160 intestinal type and 69 diffuse type of Lauren) but failed to detect any vimentin positive ones. These results indicate that vimentin is expressed in some of the solid-type adenocarcinomas, which have a poor prognosis, and indicating that rhabdoid-like cells may be found in a variety of adenocarcinomas of the stomach.


Asunto(s)
Adenocarcinoma/química , Adenocarcinoma/patología , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , Vimentina/análisis , Adenocarcinoma/ultraestructura , Anciano , Antígeno Carcinoembrionario/análisis , Núcleo Celular/ultraestructura , Femenino , Humanos , Inmunohistoquímica , Queratinas/análisis , Masculino , Glicoproteínas de Membrana/análisis , Persona de Mediana Edad , Mucina-1 , Pronóstico , Neoplasias Gástricas/ultraestructura
10.
Am J Surg Pathol ; 19(9): 1054-60, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7661279

RESUMEN

Pyogenic granuloma is a common disease in the skin, but it is extremely rare in the gastrointestinal tract except for the oral cavity. We have seen three lesions (from three patients) of an intestinal counterpart of pyogenic granuloma and have reviewed their clinicopathologic features. Macroscopically, all three lesions revealed a polypoid growth with either a sessile or pedunculated configuration. All had an ulceration on the top. Microscopically, all these lesions were composed of a lobular proliferation of varying sizes of capillaries with an edematous stroma. Endothelial cells of the capillaries were swollen variously and in one case revealed a few mitotic figures. An inflammatory process was associated with the presence of ulcerations. Immunohistochemically, both Factor VIII-related antigen and QB-end/10(CD34) were positive only for the endothelial cells in all three cases. The characteristic macroscopic and histologic features thus allow for an early diagnosis of pyogenic granuloma in the gastrointestinal tract, which is similar to that observed in the skin.


Asunto(s)
Granuloma Piogénico/patología , Enfermedades Intestinales/patología , Anciano , Capilares/metabolismo , Capilares/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Granuloma Piogénico/metabolismo , Humanos , Inmunohistoquímica , Enfermedades Intestinales/metabolismo , Intestinos/irrigación sanguínea , Intestinos/patología , Masculino , Persona de Mediana Edad
11.
Am J Surg Pathol ; 19(5): 576-89, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7726368

RESUMEN

Twenty-nine patients (20 men, nine women; mean age, 65.9 years; range, 49-77 years) with intraductal papillary mucinous neoplasms associated with so-called "mucinous ductal ectasia" of the pancreas were studied both histochemically and immunohistochemically. These cases included six cases of hyperplasia, 13 adenomas, and 10 adenocarcinomas. The mean sizes of the hyperplasia, adenomas, and adenocarcinomas were 2.0 cm, 3.0 cm, and 4.8 cm in diameter, respectively. Tumor size correlated with the degree of cellular atypia. The proliferative rates were significantly higher in the carcinomatous epithelium with those in the hyperplastic and adenomatous epithelia. The polarity of distribution of carcinoembryonic antigen and carbohydrate antigen 19-9 were better preserved in the hyperplastic epithelia than in the carcinomatous epithelia. On the other hand, the papillary and nonpapillary hyperplastic epithelium contained mainly a neutral periodate-reactive glycoprotein with only trace amounts of sialomucins and sulphomucins. In addition, the adenomatous epithelium contained mostly sialomucins with a small amount of sulphomucins. The carcinomatous epithelium contained predominantly sulphomucin. The results of both the histological and immunohistochemical studies suggested the possibility of a sequential change from nonpapillary and papillary hyperplasia, via adenoma, to carcinoma in intraductal papillary-mucinous neoplasms associated with mucinous ductal ectasia. Moreover, these results, in combination with the histochemical findings, are considered helpful in making an appropriate preoperative diagnosis with endoscopic pancreatic ductal biopsy specimens, thus enabling the surgeon to select the most appropriate surgical procedure.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Adenoma/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma Mucinoso/fisiopatología , Adenoma/fisiopatología , Anciano , Anticuerpos Monoclonales , Femenino , Humanos , Hiperplasia/patología , Hiperplasia/fisiopatología , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/patología , Enfermedades Pancreáticas/fisiopatología , Neoplasias Pancreáticas/fisiopatología , Pronóstico
12.
Cancer Lett ; 170(1): 81-9, 2001 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-11448538

RESUMEN

The tumor microenvironment is one of the key factors affecting the cellular response to radiation; however, the influence of serum concentration on tumor radiosensitivity remains poorly understood. We recently discovered that gamma-irradiation of tumor cells causes centrosome overduplication, which may lead to lethal nuclear fragmentation through the establishment of multipolar mitotic spindles. In the present study, we investigated the effect of serum depletion on radiation-induced cell death in relation to the centrosome dynamics in human pancreatic cancer cells. Exposure of Capan-1 cells to gamma-irradiation resulted in a time-dependent increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death. Treatment of irradiated cells with serum depletion drastically accelerated centrosome overduplication and the formation of multipolar spindles, resulting in increased nuclear fragmentation and cell death. Cell cycle analysis of irradiated cultures revealed that the reduced serum level increased the population of cells arrested in the G2/M phase, which might be responsible for the abnormal centrosome accumulation. These findings suggest that serum concentration can influence radiation-induced cell killing through modulating cell cycle progression and possibly centrosome overduplication.


Asunto(s)
Centrosoma/efectos de la radiación , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Muerte Celular/efectos de la radiación , Medio de Cultivo Libre de Suero , Humanos , Mitosis/efectos de la radiación , Células Tumorales Cultivadas
13.
J Cancer Res Clin Oncol ; 126(2): 79-84, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10664246

RESUMEN

Inactivation of the TSG101 gene has been shown to induce cellular transformation of NIH3T3 fibroblasts, and aberrant TSG101 transcripts have been observed not only in various human solid tumors but also in hematopoietic malignant disorders. In the present study, we performed nested reverse transcription/polymerase chain reaction (RT-PCR) analysis to identify aberrant TSG101 transcripts in 43 human leukemia and lymphoma cell lines. We could detect only a single band of the wild-type transcript with the expected size in virtually all cell lines after the first round of PCR. As in the case with various human solid tumors, the smaller TSG101 transcripts appeared in most of these cell lines after the second round of PCR. Thus, the expression level of the variant transcripts was extremely low as compared with that of the wild-type transcript, and this finding was also confirmed by Northern blot analysis. Identification of various truncated transcripts with extensive deletions in the TSG101 coding region was confirmed by means of sequencing analysis, and expression of these transcripts did not appear to be associated with a specific type of hematopoietic malignant disorder. Southern blot analysis did not indicate any gross TSG101 gene rearrangement. The truncated transcripts were also detected in normal peripheral blood leukocytes. Our results suggest that the truncated TSG101 transcripts are definitely detectable in various human leukemia and lymphoma cell lines, but do not support the notion that the variant transcripts may have a major functional relevance in the pathogenesis of human hematopoietic malignant disorder.


Asunto(s)
Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor/genética , Leucemia/genética , Linfoma/genética , Factores de Transcripción/genética , Transcripción Genética , Secuencia de Aminoácidos , Northern Blotting , Cartilla de ADN , Complejos de Clasificación Endosomal Requeridos para el Transporte , Humanos , Leucocitos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas/efectos de los fármacos
14.
Surgery ; 116(3): 544-9, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7915857

RESUMEN

BACKGROUND: The difference in liver regeneration rate in relation to proliferating cell nuclear antigen (PCNA) and plasma fibronectin level in the cirrhotic and control liver after 70% hepatectomy were examined in the rat. METHODS: Liver cirrhosis was induced by intraperitoneal injection of thioacetamide for 12 weeks; rats without thioacetamide administration served as controls. On the day before and days 1, 2, 3, and 7 after 70% hepatectomy, PCNA labeling index of hepatocyte, plasma fibronectin level, and percentage of the initial liver weight were determined. RESULTS: Liver regeneration rate as expressed by percent of initial liver weight was impaired in the cirrhotic liver, and significantly lower regeneration rate was observed on days 3 and 7 after hepatectomy in the cirrhotic rats as compared with controls. PCNA labeling index was higher in the cirrhotic liver before hepatectomy. Little change of PNA labeling index was observed in the cirrhotic liver, although the index increased significantly in the control liver; significantly higher values were observed on days 1, 2, and 3, with the maximal value on day 2 after hepatectomy. The plasma fibronectin level was significantly lower in the cirrhotic rat before and after hepatectomy. CONCLUSIONS: The results show that liver regeneration is impaired in the cirrhotic liver associated with little activation of PCNA and with lower plasma fibronectin level.


Asunto(s)
Autoantígenos/metabolismo , Fibronectinas/sangre , Hepatectomía , Regeneración Hepática/fisiología , Hígado/fisiología , Proteínas Nucleares/metabolismo , Animales , Hígado/metabolismo , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/fisiopatología , Masculino , Tamaño de los Órganos , Antígeno Nuclear de Célula en Proliferación , Ratas , Ratas Endogámicas F344 , Tioacetamida
15.
Cancer Genet Cytogenet ; 126(1): 13-9, 2001 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-11343773

RESUMEN

Chromosomal instability, characterized by abnormal numbers or structures of chromosomes, is a common feature of human cancers, but the mechanisms behind these changes are still unclear. Since centrosomes play a pivotal role in balanced chromosomal segregation during mitosis, we attempted to investigate the association between centrosome abnormalities and chromosomal instability in a large number of human pancreatic cancer cell lines. Immunofluorescence microscopy revealed centrosomes that were highly atypical with respect to their size, shape, and number in most cell lines. These abnormal centrosomes contributed to the assembly of multipolar spindles, resulting in defective mitosis and chromosome mis-segregation. Interestingly, a high frequency of centrosome defects inversely correlated with the growth rate of cells in culture. Fluorescence in situ hybridization revealed a dramatic variation of chromosome numbers in cell lines with the defective centrosome phenotype. Furthermore, a significant positive correlation existed between the level of centrosome defects and the level of chromosomal imbalances. These results indicate that centrosome abnormalities can lead to spindle disorganization and chromosome segregation errors, which may drive the accumulation of chromosomal alterations. Thus, defects in centrosome function may be an underlying cause of genetic instability in human pancreatic cancers.


Asunto(s)
Centrosoma , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Neoplasias Pancreáticas/genética , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pancreáticas/patología , Células Tumorales Cultivadas
16.
Cancer Chemother Pharmacol ; 42(4): 280-6, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9744772

RESUMEN

PURPOSE: SN-38, a metabolite of irinotecan hydrochloride (CPT-11), is considered to play a key role in the development of diarrhea as well as in the antitumor activity of CPT-11. We have previously found that the inhibition of beta-glucuronidase, which hydrolyzes detoxified SN-38 (SN-38 glucuronide) to reform SN-38, in the lumen by eliminating the intestinal microflora with antibiotics, markedly ameliorates the intestinal toxicity of CPT-11 in rats. In this study we compared the disposition of CPT-11 and its metabolites in rats treated with and without antibiotics. METHODS: Rats were given drinking water containing 1 mg/ml penicillin and 2 mg/ml streptomycin from 5 days before the administration of CPT-11 (60 mg/kg i.v.) and throughout the experiment. CPT-11, SN-38 glucuronide and SN-38 concentrations in the blood, intestinal tissues and intestinal luminal contents were determined by HPLC. RESULTS: Antibiotics had little or no effect on the pharmacokinetics of CPT-11, SN-38 glucuronide or SN-38 in the blood, or in the tissues or contents of the small intestine, which has less beta-glucuronidase activity in its luminal contents. In contrast, antibiotics markedly reduced the AUC1-24 h of SN-38 (by about 85%) in the large intestine tissue without changing that of CPT-11, and this was accompanied by a complete inhibition of the deconjugation of SN-38 glucuronide in the luminal contents. CONCLUSIONS: These results suggest that SN-38, which results from the hydrolysis of SN-38 glucuronide by beta-glucuronidase in the intestinal microflora, contributes considerably to the distribution of SN-38 in the large intestine tissue, and that inhibition of the beta-glucuronidase activity by antibiotics results in decreased accumulation of SN-38 in the large intestine.


Asunto(s)
Antineoplásicos Fitogénicos/farmacocinética , Camptotecina/análogos & derivados , Inhibidores Enzimáticos/farmacocinética , Glucuronidasa/antagonistas & inhibidores , Intestino Grueso/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Administración Oral , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/toxicidad , Área Bajo la Curva , Bacterias/enzimología , Camptotecina/administración & dosificación , Camptotecina/sangre , Camptotecina/farmacocinética , Camptotecina/toxicidad , Diarrea/microbiología , Diarrea/prevención & control , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/toxicidad , Inyecciones Intravenosas , Intestino Grueso/microbiología , Intestino Delgado/microbiología , Irinotecán , Masculino , Penicilinas/farmacología , Ratas , Ratas Wistar , Estreptomicina/farmacología
17.
J Am Coll Surg ; 192(5): 600-7, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11333097

RESUMEN

BACKGROUND: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables. STUDY DESIGN: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model. RESULTS: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p = 0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%. CONCLUSIONS: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.


Asunto(s)
Carcinoma/patología , Carcinoma/cirugía , Colecistectomía/métodos , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Hepatectomía/métodos , Estadificación de Neoplasias , Antineoplásicos/uso terapéutico , Carcinoma/mortalidad , Quimioterapia Adyuvante , Colecistectomía/efectos adversos , Femenino , Neoplasias de la Vesícula Biliar/mortalidad , Hepatectomía/efectos adversos , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pancreaticoduodenectomía , Selección de Paciente , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
18.
J Gastroenterol ; 36(7): 504-7, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11480797

RESUMEN

We describe a rare case of a benign pseudotumorous lesion (fibroangiomyomatous hyperplasia with elastosis) in the gallbladder in a 44-year-old Japanese woman, and discuss the rarity of elastosis in the gallbladder. To our knowledge, this case may be the first report of a pseudotumorous lesion of the gallbladder with elastosis in Japan.


Asunto(s)
Angiomioma/diagnóstico , Tejido Elástico/patología , Neoplasias de la Vesícula Biliar/diagnóstico , Adulto , Angiomioma/patología , Angiomioma/cirugía , Diagnóstico Diferencial , Tejido Elástico/cirugía , Femenino , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Hiperplasia/diagnóstico
19.
Eur J Surg Oncol ; 21(4): 427-8, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7664913

RESUMEN

We report two cases of carcinoma of the ampulla of Vater synchronously associated with early gastric cancers. The gastric lesions were diagnosed pre-operatively in one patient and at the time of examination of the resected specimen following pancreatoduodenectomy in the other. Specific problems in the diagnosis and management of these multiple primary carcinomas are discussed. Careful evaluation of the stomach prior to the surgical treatment for ampullary carcinoma is recommended.


Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Neoplasias Primarias Múltiples , Neoplasias Gástricas , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad
20.
Br J Radiol ; 71(845): 492-6, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9691893

RESUMEN

The aim of this study was to evaluate the usefulness of and problems associated with endoscopic ultrasonography (EUS) in the diagnosis and pre-operative staging of pancreatic cancer. 96 patients suspected of having pancreatic cancer were pre-operatively examined with EUS. 37 of these 96 patients had pancreatic cancer. Results of the EUS imaging were compared with findings of histology and/or surgery, and the patient's clinical course. The sensitivity and specificity of EUS for diagnosing pancreatic cancer were 89% and 97%, respectively. EUS had excellent sensitivity regardless of tumour size or location. EUS was accurate (90%) in determining tumour size in pancreatic cancers less than 3 cm in maximum diameter, but not for tumours greater than 3 cm (30%). The accuracy of tumour (T) and nodal (N) staging were 64% and 50%, respectively. EUS is a promising method for the early diagnosis and pre-operative staging of pancreatic cancers, but requires further refinement.


Asunto(s)
Endosonografía , Neoplasias Pancreáticas/diagnóstico por imagen , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
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