ISSN:0378-584X    

DOI:10.1159/000216809

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000216810

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

Retroviruses first attracted attention as the etiological agents of tumors in various animals, including birds, rodents and primates. The retrovirus-induced tumors comprise above all T- and B-cell leukemias/ lymphomas, chronic myelogenous leukemia and mammary carcinomas, and are characterized by a long latent period between infection and manifestation of the disease. Since their detection, oncogenic retroviruses have been the object of intense study contributing to our knowledge of basic mechanisms and molecular events involved in carcinogenesis in general. An essential step in the retrovirus life cycle is the covalent integration of the double-stranded DNA copy of viral RNA into the cellular genome, forming the provirus. The pro viruses are quite stable and are generally a permanent acquisition for the cellular genome. Therefore, the presence of the provirus can have profound genetic implications for the host cell. There are at least three main routes that are assumed to lead to retroviral oncogenesis: Transduction of cell-derived oncogenes (v-onc) carried by some retroviruses, activation of cellular proto-oncogenes (c-onc) in cís by insertional mutation or activation of cellular genes in trans by virus encoded transcription factors

ISSN:0378-584X    

DOI:10.1159/000216811

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000216812

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

The induction and activation of autologous cytotoxic cells (lym-phokine activated killer cells = LAK) by interleukin-2 (Il –2) is an interesting new approach in cancer treatment. So far, Il –2 alone or in combination with the transfer of in vitro activated LAK (adoptive immunotherapy = AI) was shown to be effective predominantly in renal cell cancer and malignant melanoma with a response rate of 20–35%. The results in colorectal tumors are disappointing. Clinical experiences with Il –2 in other tumor entities are limited and/or mostly lack sufficient responses. To improve therapeutic results and to reduce the serious side effects, present trials focus on combinations of Il–2 with other cytokines, predominantly interferon-α (IFN-α), or chemotherapy. So far, the combination of Il –2 + IFN-α seems to be at least as effective as Il -2 +AI in renal cell cancer. Combinations of chemotherapy and Il –2, especially in gastrointestinal tumors, have not been shown to exceed the moderate results of chemotherapy alone so far. Trials with highly activated or specific cytotoxic cells as tumor-infiltrating lymphocytes (TILs) or adherent-LAK-cells are still more experimental. The value of IL-2 for elimination of minimal residual disease in acute leukemias after autologous bone marrow transplantation or as consolidation of complete response will have to be defined. The present paper reviews clinical studies with Il –2 in malignancies and its significance for ther

ISSN:0378-584X    

DOI:10.1159/000216813

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

Interferon alpha bietet eine neue Therapieoption bei malignen Non-Hodgkin-Lymphomen. Günstige Erfahrungen wurden bei niedriggradig maligner Histologie gesammelt. Noduläre niedriggradig maligne Non-Hodgkin-Lymphome (nach der Kiel-Klassifikation meist zentro-blastisch-zentrozytische Non-Hodgkin-Lymphome) sprechen in 39% mit meist partiellen Remissionen an. Dabei ist eine Dosis-Wirkungs-Beziehung wahrscheinlich. Alpha-Interferon wird in einigen Studien mit Alkylantien kombiniert. Die Kombination ist von der Toxizität her tolerabel und resultiert in hohen Ansprechquoten. Eine Verlängerung der Überlebenszeit ist bisher nicht gesichert. Weitere Studienkonzepte sehen den Einsatz von Alpha-Interferon in der Remissionserhaltung nach Chemotherapie vor. Patienten mit chronisch lymphatischer Leukämie sprechen im fortgeschrittenen Stadium nur mäßig in 16% der Fälle an, während in frühen Stadien (vorwiegend Stadium A nach Binet) bei 73% der Patienten eine Remission eintritt. Da die Prognose der letzteren Patientengruppe ohnehin sehr gut ist, bleibt die Relevanz dieses Ergebnisses jedoch unklar. Die Therapieergebnisse bei kutanen T-Zell-Lymphomen und Mycosis fungoides sind kontrovers. Insgesamt sprechen 44% der Patienten auf die Therapie an. Hochgradig maligne Non-Hodgkin-Lymphome wurden überwiegend mit hochdosierter Gabe von Interferon alpha behandelt. Remissionen wurden in nur 14 % der Fälle mit meist kurzzeitigen partiellen Remissio

ISSN:0378-584X    

DOI:10.1159/000216814

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

In der vorliegenden klinischen Phase-I-Studie wurde zum ersten Mai natürliches IL-2 in Form einer kontinuierlichen Infusion über 5 Tage verabreicht. Das n IL-2 unterscheidet sich in der biologischen Aktivi-tät und in immunmodulatorischen Funktionen vom rekombinanten IL-2. 14 Patienten (9 männlich, 5 weiblich), davon 4 Kinder, mit einem Altersmedian von 40 Jahren (4–65) wurden in 16 Zyklen behandelt. Die kontinuierliche i.v. n IL-2-Gabe über 5 Tage erfolgte nach einem Dosiseskalationsschema, beginnend mit 1 × 106U bis zu 6 × 106 U n IL-2. Bei 2 von 16 Zyklen mußte die Dosis reduziert und bei 6 die Therapie abgebrochen werden. Gründe für eine Dosisreduk-tion waren Thrombozytopenie und Hypotonie, Gründe für einen Abbruch waren Kreatininanstieg, pulmonale Insuffizienz, Thrombozytopenie, Bewußtseinstrübung und Bilirubinanstieg. Die 4 Kinder zeigten ein anderes Nebenwirkungsspektrum wie Bauchschmerzen, Gesichtsödem und Thrombozytopenie. Es war keine intensivmedizinische Behandlung notwendig. Die häufigsten klinischen Nebenwirkungen waren Erythem, Fieber, Übelkeit/Erbrechen, Dyspnoe und Hypotonie. Die Bewertung der Ansprechrate ergab eine partielle Remission bei 21,5%, ein «no change» bei 7% und eine Progression bei 71,5%. Die Ergebnisse mit n IL-2 sind nach Abbruchrate, Toxizität und Remissionen ähnlich denen

ISSN:0378-584X    

DOI:10.1159/000216815

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

We studied the influence of recombinant human (rh) interleukin-3 (IL-3) and rh granulocyte-macrophage colony-stimulating factor (GM-CSF) on the clonal growth of a human colorectal adenocarcinoma cell line in a methylcellulose assay for colony growth of solid tumor cell lines (HTCAMC) and a capillary modification of a human tumor cloning assay in agar (HTCAcap). Both growth factors stimulated the clonal growth of this cell line in a dose-dependent fashion. Neutralizing the monoclonal antibody abolished the effect of rhGM-CSF. There was an inverse correlation between the spontaneous plating efficacy (PE) of the cells and their susceptibility to the stimulation by the growth factors. From day 4 to 7 we found conditions in which clusters and colonies occurred preferentially in the growth factor-stimulated cultures. Single colonies taken from these cultures grew rapidly into macroscopically visible tumors in liquid cultures and had a high secondary PE (PE2) in the HTCAcap, both presenting an argument against a differentiating effect of the growth factors on this tumor cell line. Furthermore, we were able to define conditions in which rhGM-CSF significantly increased the cytotoxicity of 5-fluorouracil (5-FU). However, this effect was dependent on spontaneous PE of the cells, degree of stimulation by the factor, degree of cytotoxicity of 5-FU in the controls, as well as the therapeutic regimen. Since there were only narrow margins for a beneficial effect of rhGM-CSF in this setting when absolute numbers of surviving colonies were counted, it remains doubtful whether this approach will be exploitable in the clinical situation.

ISSN:0378-584X    

DOI:10.1159/000216816

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

In a phase II study, the efficacy and toxicity of human recombinant tumor necrosis factor (rh TNF-alpha) were evaluated in patients with advanced colorectal carcinoma. Rh TNF-alpha was given as short term infusion at a dose of 3 × 105 U/m2 on three successive days. Treatment was repeated after a two week interval. The response was evaluated after four treatment cycles. In 15 patients entering the study, we found one partial response, one stable disease, 9 progressive diseases, and four patients who where not evaluable for tumorremission. There were numerous side effects of the treatment, mainly fever, chills, loss of appetite, leukopenia, and hepatotoxicity. In this regimen, rh TNF-alpha does not suggest a therapeutic advantage for treatment of advanced colorectal carcinoma

ISSN:0378-584X    

DOI:10.1159/000216817

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger

摘要:

Between 1982 and 1986, 38 patients with soft tissue sarcomas were treated with a combination of ADM/DTIC (group A), another 45 (group B) received ADM/IFO between 1986 and 1990. Clinical characteristics were comparable in both groups. Remission rate was 34 % in group A and 43 % in group B. Duration of remission was 10 months and median survival 13 months in both groups. Toxicity, especially myelotoxicity, was severe without marked differences between both groups. We conclude that adriamycin/DTIC and adriamycin/ifosfamide are both active regimens in metastatic soft tissue sarcomas, nevertheless, overall prognosis remains poor.

ISSN:0378-584X    

DOI:10.1159/000216818

出版商:S. Karger GmbH    

年代:1990

数据来源: Karger