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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Inc
    The @breast journal 10 (2004), S. 0 
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les résultats du traitement du cancer gastrique chez 54 patients âgés de 80 ans ou plus, opérés entre 1967 à 1989 ont été analysés. La durée moyenne de la période d'observation postopératoire était de 24 jours. Dans la plupart des cas, les examens préopératoires avaient montré des anomalies pulmonaires, rénales ou cardiaques. Le taux de morbidité globale postopératoire, due essentiellement à des complications pulmonaires, était de 40.7%. Chez les deux patients ayant une insuffisance pluriviscérale, l'un est décédé d'un infarctus du myocarde le lendemain de l'intervention, l'autre d'une pneumopathie au 12è jour post-opératoire. Dans la période postopératoire immédiate, un certain nombre de ces patients âgés a nécessité des soins intensifs. Le taux de morbidité était corrélé avec le caractère total de la gastrectomie, la durée de l'opération (〉3 heures) et une perte sanguine peropératoire de plus de 300 ml (p〈0.05). Après analyse multifactorielle, le type de chirurgie s'est avéré être le facteur indépendant majeur de la survenue des complications postopératoires. La plupart des tumeurs (92.6%) pouvaient être enlevées par les techniques conventionelles et une intervention à visée curative était réalisée chez 36 patients (66.7%). Vingt-quatre patients sont décédés en rapport avec l'évolution de leur maladie. Le taux de survie actuarielle à 5 ans était de 23.8%. Après ajustement en fonction de l'âge et du sexe, ce taux est passé à 36.9%. La probabilité de survie à long terme pour les patients à un stade précoce (T1-2, N0-1) était statistiquement meilleure que pour ceux dont la maladie était avancée (T3-4, N2, ou M1). Même pour un patient de 80 ans ou plus, une chirurgie gastrique large pour cancer peut être envisagée dans certaines conditions bien précises.
    Abstract: Resumen Informamos en este artículo el resultado del tratamiento quirúrgico de cáncer gástrico en 54 pacientes mayores de 80 años, en el período 1967 a 1989. El período de seguimiento postoperatorio fue de 24 días en promedio. En la mayoría de los casos los exámenes preoperatorios demostraron alteraciones pulmonares, renales o cardiacas. La tasa de morbilidad postoperatoria fue 40.7% y la causa mas frecuente fue la complicación pulmonar. De dos pacientes con múltiples alteraciones orgánicas, uno murió un día después de la operación como consecuencia de infarto miocárdico y uno murió de neumonía 12 días después de la operación. Se requiere cuidado intensivo en el período postoperatorio temprano. La incrementada morbilidad apareció relacionada con resecciones amplias, tales como gastrectomía total, con operaciones más de 3 horas de duración y con pérdida intraoperatoria de sangre superior a 300 ml (p〈0.05). En el análisis de variables, el tipo de cirugía apareció como un factor independiente mayor relacionado con complicaciones postoperatorias. La mayoría de los tumores (92.6%) pudo ser resecado mediante procedimientos estándar de resección y la operación curativa fue posible en 36 pacientes (66.7%). Se presentaron 24 muertos debidas a progresión del cáncer. La tasa cruda global de sobrevida a 5 años fue 23.8%, y de 36.9% al efectuar la correctión para sexo y edad. La probabilidad de sobrevida a largo plazo de pacientes con enfermedad en estadios tempranos (Tl-2, No-1) resultó estradísticamente superior que la de los pacientes con enfermedad avanzada (T3-4, N2, M1). Por lo tanto, aun en pacientes en la octava década de la vida, se puede considerar cirugía gástrica en pacientes cuidadosamente seleccionados.
    Notes: Abstract We report here the outcome of surgical treatment for gastric cancer in 54 patients over 80 years of age presenting from 1967 to 1989. The mean observation interval of the postoperative period was 24 days. In most cases, preoperative examinations revealed pulmonary, renal or cardiac disturbances. The postoperative morbidity rate was 40.7%, most commonly as a result of pulmonary complications. In the 2 patients with multiple organ disturbances, 1 died 1 day after operation following myocardial infarction and the other died of pneumonia 12 days postoperatively. Intensive care treatments were needed in the early postoperative period. The increased morbidity rate proved to be related to wide resectional procedures such as total gastrectomy, operative time in excess of 3 hours, and intraoperative blood loss 〉300 ml (p〈0.05). When adjustment for confounding variables was made in the multivariate discriminant analysis, the type of surgery proved to be a major independent risk factor related to postoperative complications. The majority of tumors (92.6%) could be removed by standard resectional procedures and curative operation was feasible for 36 (66.7%) patients. There were 24 deaths due to progression of the cancer. The crude overall 5-year actuarial survival rate was 23.8%, while the rate was 36.9% when correction was made for sex and age. The probability of long-term survival for patients in a relatively early stage of disease (T1-2, N0-1) was statistically better than for those with a more advanced disease (T3-4, N2, M1). Thus, even for patients in the 8th decade of life, gastric surgery can be considered, for carefully selected patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succinate dehydrogenase inhibition (SDI) test. Growth of B16 melanoma that had been subcutaneously implanted into the feet of C57 BL mice was inhibited by treatment with the combinations of 5-FU and HYP, of 5-FU and DP, and of 5-FU, HYP and DP as compared with the administration of 5-FU alone. Treatment with HYP plus DP did not alter the body weight of mice that received 5-FU. The administration of DP plus HYP seemed to render the tumor cells more sensitive to 5-FU. The combination of 5-FU, HYP and DP shows promise for the treatment of patients suffering from malignant disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect on EMT6/KU cells of a newly synthesized hypoxic cell sensitizer, 1-[(4′-hydroxy-2′-butenoxy)methyl]-2-nitroimidazole (RK28), combined with heat was determined in vitro under conditions of hypoxia. As compared with aerobic conditions, hypoxia produced a 1.30-fold increase in the cytotoxicity of the drug for mouse mammary EMT6/KU cells induced by 1 h heat treatment at 43° C in medium with a normal pH. Hypoxia also reduced the surviving fraction of cells treated with both RK28 alone for 2 h and the same concentrations of RK28 and heat (43° C) in combination. Those enhancement ratios corresponded to a 20.3- and 〉345-fold increase, respectively. Moreover, concomitant treatment with RK28 and heat greatly inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia and in all experimental groups; there was a statistically significant difference in the time-response curves (P〈0.05). As hypoxic cells in a solid tumor are resistant to various anticancer drugs, RK28 combined with hyperthermia deserves further study for possible clinical applications.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract cis-1,1-Cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammineplatinum(II) (NK121) andcis-diammine(glycolato)platinum (254-S), analogues ofcis-diamminedichloroplatinum (II) (CDDP) with reduced nephrotoxicity, are under clinical phase trial in Japan. Since CDDP has been shown to be more cytotoxic under conditions of an elevated temperature, we tested the cytotoxicity and cellular uptake of these analogues at 37° and 43°C using EMT6/KU cells in vitro. The cytotoxicity of CDDP was enhanced at 43°C, and that of NK121 and 254-S was also enhanced, in a dose- and time-dependent manner. The 90% cytotoxic concentration (IC90) of each drug was reduced 2.9-fold for CDDP, 2.5-fold for NK121, and 2.2-fold for 254-S. Cytotoxicity was maximal when the two modalities were used simultaneously for all three drugs. The intracellular platinum concentration was assayed using flameless atomic absorption spectrophotometry. When exposed to IC90 drug concentration at 43°C for 2 h simultaneously, the intracellular platinum concentration increased to 0.095±0.007 μg/107 cells (a 1.9-fold increase) for CDDP, to 0.198±0.012 μg/107 cells (a 1.3-fold increase) for NK121, and to 0.090±0.014 μg/107 cells (a 1.3-fold increase) for 254-S; respectively, as compared with the level measured after drug exposure at 37°C (P〈0.05 for all drugs). The elevation in platinum concentration may be one of mechanism related to a synegistic effect of the two treatment modalities. The concomitant use of CDDP analogues and heat shows potential for possible clinical application.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1∶4, were examined in 26 patients with macroscopic State I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28±26.88, 4.41±1.78, and 0.51±0.20 μg h ml−1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0843
    Keywords: Key words Apoptosis ; Gastrointestinal cancer ; Cell cycle ; Chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the chemosensitivity of these lines was determined. Methods: Twelve gastrointestinal cancer cell lines were examined for the presence of either a wild-type or mutant p53 gene by direct sequencing. We also determined whether or not cell killing would occur when the cell lines were exposed to anticancer drugs. The sensitivity to the anticancer agents was determined based on colony formation. Results: All 12 gastrointestinal cancer cell lines carried either a wild-type or mutant p53 gene. Three lines, MKN45, MKN74 and COLO320, carried the wild-type p53 gene, and nine carried the mutant p53 gene. When three lines were exposed to the anticancer agents etoposide, doxorubicin (DXR) or 5-fluorouracil (5-FU), cell death ensued. In these cells, the population of cells in G1 phase increased after exposure to high-dose anticancer agents, but cells in G2 phase increased when exposed to low-dose anticancer agents. Our observations support the concept that cells carrying the wild-type p53 gene tend to be sensitive to etoposide and DXR and, in particular, deletion of the p53 function results in a greater resistance to anticancer agents. Conclusion: Based on our findings, human gastrointestinal cancer-related cell death apparently occurs via a p53-dependent pathway. A relationship was observed between the induction of cell death and chemosensitivity.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We studied the effects on survival time of postoperative immuno-chemotherapy, including the streptococcal preparation OK-432, in patients with gastric cancer and synchronous peritoneal dissemination. The patients were prospectively randomized and a valid statistical assessment could be made for 109. Patients randomized to group B received therapy that is widely used in Japan to treat patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1 : 4, for 1 year. Patients randomized to group A received the same drugs as were given to group B patients plus OK-432 i. p. for 7 days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1 year, at 2-week intervals. There were no differences between the two groups in any known prognostic factor or in the dose of any drug administered except for OK-432. There was no difference in the toxicity rate between the groups. In this negative trial, there was no improvement in survival time with the addition of OK-432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0843
    Keywords: Key words Flavone acetic acid ; Mitomycin C ; Hyperthermia ; Tumor blood flow ; Hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Flavone acetic acid (FAA, NSC 347512) is known to selectively reduce tumor blood flow. Taking advantage of this pharmacodynamic effect, we have previously shown that FAA in combination with hyperthermia (HT) can produce a marked improvement in antitumor response in mice. In the present study, we investigated whether FAA could increase the cytotoxicity of mitomycin C (MMC), a bioreductive drug with selective cytotoxicity against hypoxic cells, under either normothermic or hyperthermic conditions. In vitro, the cytotoxicity of MMC against B16 melanoma cells was not enhanced with exposure to FAA at concentrations less than 100 μg/ml, even when combined with HT (43°C, 60 min). The cytotoxicity of MMC (1 μg/ml) at pH 6.5, however, was enhanced by exposure of cells to hypoxia in combination with HT. In vivo, the tumor growth time, calculated as the time required to double the initial tumor volume, was 5.2, 6.8, 8.5, and 15.0 days with FAA (150 mg/kg) alone, MMC (4 mg/kg) alone, FAA+MMC, or FAA+MMC+HT (43°C, 15 min) treatment groups, respectively. Antitumor response obtained in animals treated with FAA plus MMC with HT was clearly better than that obtained in any of the other groups. Scheduling of FAA, MMC, and HT was found to be important in producing optimal antitumor response. Administration of MMC (4 mg/kg) prior to FAA (150 mg/kg) and subsequent HT treatment was superior to administration of FAA before MMC. In an attempt to explain these findings, the influence of FAA on blood flow in skeletal muscle and in tumor was examined using a laser blood flowmeter. FAA administration to mice produced a 75% reduction in blood flow to the tumor for up to 2 h but had no detectable effect on normal skeletal blood flow. Our current explanation of the increased antitumor response achieved with the combination of MMC, FAA, and HT is as follows. The FAA-mediated decrease in blood flow to the tumor, when combined with HT, may produce sufficiently hypoxic conditions to significantly increase the antitumor efficacy of the bioreductive drug, MMC. We believe that clinical testing of this combined drug treatment with hyperthermia is warranted.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effects of chemotherapy given postoperatively with and without immunodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i. e. an individualized combination of various agents given or without the immunomodulators PSK, a protein extract of the fungusCoriolus versicolor, and/or OK-432, a preparation of an attenuated strain ofStreptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.
    Type of Medium: Electronic Resource
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