ISSN:0030-2414    

DOI:10.1159/000225488

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Comined chemotherapy approaches should take into account the complex interrelationships with the host and tumor. Principles of combination drug chemotherapy that may contribute to increased antitumor specificity in the treatment of clinical neoplasia are reviewed and examples provided under the following broad headings; (a) Increased antitumor effectiveness without a proportionate increase in limiting host toxicity. This includes the biochemical concepts of sequential and concurrent blockade, complementary inhibition and error amplification, (b) Decrease in host toxicity without a proportionate loss in antitumor effectiveness, (c) Delay in origin and treatment of resistant mutants, (d) Treatment of metastatic and sequestered tumor cells, (e) Identification of optimal dosages, ratios and schedules for drug combinations, (f) Kinetic considerations such as tumor cell synchronization, choice of drugs that act at different phases of the cell cycle or that stimulate Go cells to divide, (g) Use of drugs that assist active compounds, (h) Employment of combined modalities including surgery, radiation or immunotherapy plus chemotherapy, (i) Loading dose chemotherapy of advanced disseminated tumor, (j) Identification of drugs that may prevent viral or carcinogenic tumor induction, (k) Development of methodology for determination of the effectiveness of polychemotherapy.

ISSN:0030-2414    

DOI:10.1159/000225489

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Serum from DBA/2J mice bearing a syngeneic T1699 mammary adenocarcinoma contains not only a specific antitumor antibody but also another factor(s) which arm normal monocytes in vitro and transform them into specific killer cells. Arming of normal monocytes by the factor(s) was inhibited by cytochalasin B and dactinomycin but not by mitomycin C. The ADCC activity of monocytes was at least partially resistant to the action of dactinomycin but cytotoxicity of armed effectors was totally blocked by the same drug. Effective cytolysis by armed monocytes required at least 5–6 h of continuous contact between the target and effector cells; and cytotoxicity could be reversed by cytochalasin B during this perio

ISSN:0030-2414    

DOI:10.1159/000225391

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The heterogeneity existing among cancer chemotherapeutic agents, even when structurally closely related, in their quantitative and qualitative interaction with the various cellular components of host defence mechanisms involved in cancer control is reviewed. In addition to being a possible determinant of antineoplastic drugs in vivo efficacy, this heterogeneity can be of importance also in the development of less empirical and more effective approaches to the design of combinations to be used in cancer chemoimmunotherapy. Nonspecific immunomodulatory agents are in fact also heterogenous in their mode of action on the various components of the immune complex. Examples of chemoimmunotherapeutic combinations based on drugs acting at complementary levels on host defences are presented and the mechanistic basis for their in vivo synergistic activity discussed.

ISSN:0030-2414    

DOI:10.1159/000225490

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Adult domestic rabbits were found to harbor anaerobic coryneform bacteria and possess serum agglutinins against these bacteria. The isolates from rabbit skin were characterized by morphology, anaerobiosis, catalase test, and gas chromatographic analysis of volatile acid products. Preliminary findings on the effect of anaerobic coryneforms on the regression of Shope papillomas have suggested that the life of such bacteria as normal flora enhances the regression.

ISSN:0030-2414    

DOI:10.1159/000225392

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Secretory IgA-S content was evaluated in vitro in human normal and tumoral bronchial mucosa from 39 cases. In 75% of the cases, IgA-S production by tumoral tissue was higher than the levels found in control populations. On the other hand, IgA-S synthesis by normal bronchial tissue of patients with lung tumors, particularly with squamous cell carcinoma, was increased in comparison with patients free of neoplastic bronchopulmonary disease, in 30% of the cases. Comparing tumorous tissue with normal mucosa from the contralateral bronchus of the same patient, marked differences in IgA-S patterns were observed. Regarding the results obtained, we could consider the measuring of IgA-S in bronchial mucosa as a valuable diagnostic aid in patients with suspect pulmonary masses.

ISSN:0030-2414    

DOI:10.1159/000225393

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Recent advances in the rational design of anticancer chemotherapy in this laboratory have been based on strategic differences between normal and cancer cells. On the basis of our identification of quantitative biochemical markers and characteristic enzymic and metabolic programs of neoplastic cells, we have designed single and combination drug treatments. This chemotherapeutic approach aims at specific enzymic targets in cancer cells that are closely linked with transformation and progression. With the identification of markedly increased concentrations of CTP, dATP, dGTP, dCTP and dTTP in neoplasms, there should be an operational advantage in directing chemotherapy to depress the concentration of these metabolites elevated in cancer cells, because a drug-imposed curtailment of these metabolites might destroy cancer cells that depend more stringently on the increased concentrations of these nucleotides. Experiments in tissue culture and in solid tumors utilizing treatment schedules with pyrazofurin in combination with galactosamine, and the use of adriamycin, succeeded in achieving profound alterations in the nucleotide concentrations of cancer cells.

ISSN:0030-2414    

DOI:10.1159/000225492

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The presence of carcinogens in cell nuclei could be demonstrated by fluorescence microscopy after in vivo administration. This appears to be related to the carcinogenic activity of the compound studied.

ISSN:0030-2414    

DOI:10.1159/000225394

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Three polycyclic hydrocarbons: benzo(a)pyrene; dibenz(a, h)-anthracene and dibenz(a, c)anthracene, differing in their carcinogenicity, were administered to female rats. The comparative intracellular localization of these compounds was studied by fluorescence microscopy. The two carcinogenic molecules were localized both in the cytoplasm and the nucleus of cells and in numerous organs. The noncarcinogenic compound dibenz(a, c)anthracene was undetectable. This work suggests that the differences in carcinogenicity may result in the possibility of the compounds to penetrate the nucleus of target cells.

ISSN:0030-2414    

DOI:10.1159/000225395

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

We studied the chemo-radiotherapy of testicular tumors in clinical stage III. Our study involved 54 patients with lung metastases of seminoma and nonseminoma, treated with a combination of radiotherapy and chemotherapy. The results obtained have not satisfied our expectations. While in the 16 seminoma patients only 43% overall response rate was obtained (probably due to the bad general condition of the patients who had mostly received previous treatment), in the 38 nonseminoma patients a 63% overall response rate was obtained, with 31% complete remission. In previously untreated patients a 73% overall response rate was obtained at 34 % complete remission.

ISSN:0030-2414    

DOI:10.1159/000225493

出版商:S. Karger AG    

年代:1980

数据来源: Karger