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  • 1
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1x105 units/m2. The dose was escalated up to 16x105 units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16x105 units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12x105 units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5x105 units/m2.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The usefulness of LMS in postoperative immunochemotherapy of gastric cancer was investigated. In compliance with the protocol, MMC was given at a dose of 20 mg on the day of gastrectomy, and an additional 10 mg on the next day IV. The patients receiving 600 mg Tegafur daily were then divided into two groups according to whether LMS was also given or not. LMS was administered for 3 days before the operation in a daily dose of 150 mg and for 1 year or more after operation according to a schedule of 3 days' administration followed by an 11-day interval. The 2-year follow-up demonstrated that in stage III patients, the LMS (+) regimen was superior to the LMS (−) regimen, since the former prolonged the relapse-free interval significantly. The survival rate for stage III disease was also significantly higher in the LMS (+) than in the LMS (−) group. There was no significant difference in the incidence of subjective or objective side-effects between two groups. The incidence of agranulocytosis was comparable in the two groups.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Keywords: Key words Metastatic breast cancer ; Chemotherapy ; Anthracyclines ; KRN8602 (MX2) ; Phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: KRN8602 (3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 · HCl) is a newly developed anthracycline that has been found to be effective against multidrug-resistant tumor cells in vitro and in vivo. In order to clinically confirm these promising preclinical observations, we performed a phase II trial of KRN8602 in patients with anthracycline-resistant metastatic breast cancer. Methods: Of 41 patients registered with metastatic breast cancer, 37 were eligible and were given at least two cycles of KRN8602 15 mg/m2 per day at 3–4 week intervals by intravenous bolus injection on days 1, 2, and 3. Results: Of the 37 patients, 6 (16.2%, with a 95% confidence interval of 4.3–28.1%) had a partial response (PR). No complete responses (CRs) were observed. The difference between response rates according to prior history of anthracycline administration was not significant. Myelosuppression was moderately severe, with grade 3 or 4 leukopenia occurring in 65%. Severe nausea/vomiting was observed in 44% of the patients. Conclusions: The results indicate that KRN8602 has modest activity in refractory metastatic breast cancer and is associated with relatively severe toxicity. Furthermore, the preclinical finding that KRN8602 overcomes anthracycline resistance was not reliably reproduced in this clinical phase II trial.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Cette étude a été élaborée pour identifier 11 antigènes différents, y compris la calcitonine (CT), la peptide codée par le gène calcitonine (PCGC), la peptide de stimulation de la gastrine (PSG), et ACE dans les tumeurs de 36 patients ayant un cancer médullaire de la thyroïde (CMT) avec la technique de coloration immunopéroxidase. La clinique des patients ayant un CMT a été comparée aux données immunohistochimiques pour établir des facteurs influençant le pronostic. Les CMT contenaient de nombreuse substances chimiques chez la plupart des patients. La CT et ACE étaient positifs chez tous les patients. La PCGC et la PSG se coloraient positivement chez 96.6 et 82.9% des patients à CMT, respectivement, suggérant que la PCGC et la PSG sont des marqueurs tumoraux potentiels pour le CMT. Dans les cellules tumorales, CT, PSGC., et PSG ont été souvent identifiées dans les mêmes cellules. En général on a trouvé plus d'antigènes chez les patients à CMT familiaux que chez les patients à CMT sporadiques. Chez les 2 patients inopérables chez qui l'évolution était extrêmement agressive, ces tumeurs étaient histologiquement indifférenciéés et la coloration pour ces hormones, pauvres, suggèrant une perte des caractères spécifiques neurendocrines de la tumeur. Chez ces 2 patients, la distribution de CT et d'ACE était inversement proportionnelle l'une par rapport à l'autre: la quantité de CT était réduite dans les cellules alors que la coloration pour l'ACE était homogène. Les résultats de cette étude suggèrent que la PCGC et la PSG, comme le sont déjà la CT et l'ACE, sont peut-être des marqueurs tumoraux pour le CMT. Il est possible que la CT et l'ACE puissent être utilisés pour différencier les patients à haut degré de malignité.
    Abstract: Resumen Este estudio fue diseñado con el fín de identificar 11 antígenos diferentes, incluyendo calcitonina (CT), péptido calcitonina gen-relacionada (PCGR), péptido liberador de gastrina (PLG), y antígeno carcinoembriónico (ACE), en los tumores de 36 pacientes con carcinoma medular de tiroides (CMT) utilizando técnicas de coloración con inmunoperoxidasa. Además, se compararon las características clínicas del CMT con los hallazgos inmunohistoqufmicos para definir factores que tengan influencia sobre el pronóstico. Se encontró que el CMT contiene una variedad de productos en muchos de los pacientes y que la CT y el ACE fueron positivos en la totalidad de los pacientes. El PCGR y PLG mostraron coloración positiva en 96.6% y 82.9% de los pacientes, respectivamente, lo cual sugiere que el PCGR y el PLG son noveles marcadores tumorales del CMT. En las células tumorales comparadas en secciones adyacentes apareadas, las 3 hormonas, CT, PCGR, y PLG fueron frecuentemente demostrados en células idénticas. Los pacientes con enfermedad de tipo familiar exhibieron mayor número de sustancias múltiples que los pacientes con enfermedad esporádica. En los 2 pacientes inoperables con progresión tumoral de extrema agresividad, los tumores mostraron indiferenciación en la histología y pobre coloración para las hormonas péptidos, lo cual sugiere que se habían perdido sus cualidades específicas como tumores neuroendocrinos. Estos 2 pacientes, en particular, revelaron una relación inversa entre la distribución de CT y de ACE, tal que pequeñas cantidades de CT estaban presentes en células que exhibían coloración homogénica para ACE. Este estudio sugiere que el PCGR y el PLG, además de la CT y el ACE, pueden ser potenciales marcadores tumorales para CMT. La CT y el ACE pueden ser posibles marcadores para diferenciar los pacientes con severo grado de malignidad de aquellos con malignidad ordinaria.
    Notes: Abstract This study was designed to identify 11 different antigens including calcitonin (CT), calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), and carcinoembryonic antigen (CEA), in the tumors of 36 patients with medullary thyroid carcinoma (MTC) using immunoperoxidase staining techniques. In addition, clinical features of MTC patients were compared with the immunohistochemical findings to establish factors influencing prognosis. MTC was found to contain various products in many patients and CT and CEA were positive in all patients. CGRP and GRP showed positive staining in 96.6% and 82.9% of MTC patients, respectively, suggesting that CGRP and GRP are novel tumor markers for MTC. In tumor cells, CT, CGRP, and GRP were often revealed in identical cells. Familial patients showed more multiple substances than sporadic patients. In the 2 inoperable patients with extremely aggressive progression, tumors showed undifferentiated histology and poor staining for peptide hormones, suggesting that specific qualities such as neuroendocrine tumor had been lost. These 2 patients particularly revealed an inverse relationship between CT and CEA distribution such that small amounts of CT were present in cells which have homogenous staining for CEA. This study suggests that CGRP and GRP, in addition to CT and CEA, may be a histologically potential tumor marker for MTC. CT and CEA may be possible markers for differentiating patients with high malignancy from those with ordinary malignancy.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 19 (1995), S. 455-455 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1436-2813
    Keywords: gastric cancer ; adjuvant chemotherapy ; futraful
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus futraful (N1-(2′-tetrahydrofuryl)-5-fluorouracil), as an adjunct to surgery for gastric cancer was investigated in a prospective randomized controlled study. Three thousand and thirty-three Japanese patients in 344 hospitals were entered and 2873 could be followed for 5 years. All patients had undergone gastrectomy from April 1977 to May 1979 and were assigned, at random, to either Groups A, B or C. In Group A, bolus MMC was administered with no further treatment. In Group C, oral futraful was given for one year, without MMC induction. In Group B, both a bolus MMC injection and oral futraful were prescribed. This randomized study showed no statistical difference in the 5 year survival rate among the three groups. However, in patients given MMC and put on oral futraful for one year, the 5 year survival rate for those with stage III gastric cancer or for those with positive lymphnode metastasis plus obvious serosal invasion seemed to be improved.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1436-2813
    Keywords: estrogen receptor ; breast cancer ; nude mouse ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomasin vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1×1×1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1436-2813
    Keywords: gastric cancer ; mitomycin-C ; tegafur ; PSK ; OK-432
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+)·n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1436-2813
    Keywords: human breast carcinoma ; nude mice ; hormone dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tumor cells (0.5 ml, 1×107) of MCF-7 line were inoculated into the subcutaneous tissue or intraperitoneum of female BALB/c nude mice. Primarily tansplanted mice were treated with 17β-estradiol dipropionate (E2) in a dose of 5 mg/kg and 17α-hydroxy progesterone caproate (Pg) in a dose of 250 mg/kg once a week. After the transferable strain was established, tumors were transplanted into female and male mice treated with E2, Pg, and E2+Pg. The tumors treated with E2 or E2+Pg grew exponentially while tumors in the other group regressed. Pg was assumed to play some role in the growth of MCF-7, in the presence of estrogen. Although cytosol estrogen receptors (ERc), nuclear estrogen receptors (ERn), and progesterone receptors (PgR) were detected by dextran coatedcharcoal method and exchange assay in the growing tumors, ERn and PgR of regressing tumors was usually negative. This MCF-7 strain in nude mice may be a promising animal model for studying chemo-hormone therapy for human breast carcinomas.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1436-2813
    Keywords: human breast carcinoma ; nude mice ; cancer chemotherapy ; endocrine therapy ; hormone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytotoxic and endocrine therapy on a human breast carcinoma (Br-10) serially transplanted into nude mice was given with reference to the sequence of drug administration. Mitomycin C (MMC) was combined with 2.5 mg/kg of tamoxifen (TAM). MMC was dissolved in 0.2 ml of physiological saline and administered intraperitoneally once weekly. TAM was dissolved in 0.1 ml of sesame oil and administered intramuscularly twice weekly. Both drugs were administered in the reverse sequence for 2 or 3 weeks. Cytosol estrogen receptor (ERc), nuclear estrogen receptor (ERn) and progesterone receptor (PgR), and3H-thymidine uptake labeling index (L.I.) were assayed after the treatment. When 1.5 mg/kg of MMC was combined with TAM, statistically significant differences were nil between the different sequential administrations. When the MMC administration was reduced to 0.75 mg/kg and 2 weeks, respectively, the MMC→TAM sequence was more effective than the reversed sequential administration. MMC preserved ERc and depressed L.I. to almost half of that of the control tumor. TAM generated the ER systems and slightly depressed L.I. These different modes of action between MMC and TAM on ER systems and L.I. may explain the antitumor effects of different sequential administrations.
    Type of Medium: Electronic Resource
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