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Biomedical subjects

A Goldin

Publications and source records attributed to A Goldin.

At least 55 records · Page 3Linked to original sources
PubMed1980

Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound.

Because the antigenic changes occurring after in vivo treatment of murine lymphoma cells with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) were suggested to result from DTIC-induced somatic mutation(s), quinacrine dihydrochloride, an antimutagenic compound, was tested for possible antagonistic activity related to this phenomenon. The increased immunogenicity of L1210Ha leukemia occurring at the first transplant generation of DTIC-treated histocompatible (BALB/cCr x DBA/2Cr)F1 male mice or the appearance of strong lymphoma-associated transplantation antigens at transplant generation 6 was prevented by simultaneous administration of quinacrine. However, the compound did not modify the antitumor or immunodepressive activity of DTIC in the mouse. We concluded that the selective antagonistic effect of quinacrine on DTIC-mediated immunogenic changes (DMIC) supported the hypothesis that the molecular mechanism of DMIC could be related to somatic mutation(s).

Animals↗
PubMed1980

Combined chemotherapy.

Combined 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.

Animals↗
PubMed1980

Usefulness and limitations of murine tumor models for the identification of new antitumor agents.

Murine tumor systems that have been employed in the identification of most of the known antitumor agents are reviewed and their usefulness and limitations in the identification of new antitumor agents is discussed. A new antitumor screening program has been initiated by the Division of Cancer Treatment, National Cancer Institute which employs human tumors growing in athymic mice. The questions addressed using this screen and representative data are presented.

Animals↗
PubMed1979

Comparison of accuracy of 99mTc-pyridoxylidene glutamate scanning with oral cholecystography and ultrasonography in diagnosis of acute cholecystitis.

A prospective study of 116 patients admitted as emergencies with a clinical diagnosis of acute cholecystitis or biliary colic has shown that the best investigation for confirming a diagnosis of acute cholecystitis is 99mTc-pyridoxylidene glutamate (PG) scanning. Its sensitivity is 99% and its specificity 86%, whereas those of oral cholecystography are 75% and 82%, respectively, and those of ultrasonography are 54% and 62%, respectively. However, estimation of plasma liver enzymes is essential to exclude acute hepatitis before proceeding to early cholecystectomy.

Acute Disease↗
PubMed1979

Nude mouse models as predictors of chemotherapy in man: thymidine and pyrimidines.

The National Cancer Institute cancer treatment screening program has been reorganized incorporating, as an important feature, a panel of human tumors growing as xenografts in congenitally athymic mice. The new screening program is a prospective experiment in the search for new and more effective agents for the treatment of clinical neoplasia. The new program is described and questions that are being asked prospectively are presented. Data are summarized on the activity against human tumor xenografts for a number of clinically established antitumor drugs and examples are presented in which there is interest in compounds for the clinic on the basis of activity in the new screen. Studies are outlined in which high dose thymidine inhibited the growth of human melanoma and teratocarcinoma transplanted in athymic mice. Studies are discussed employing murine tumors in which marked augmentation of the in vivo antitumor activity of 5-fluorouracil was obtained by combination therapy with the pyrimidine nucleosides thymidine, uridine and cytidine. The desirability of investigating combination chemotherapy with pyrimidine nucleosides and 5-fluorouracil and other pyrimidine antagonists in the treatment of human tumor xenografts is stressed. There is a broad range of investigations that can be conducted in nude mouse models and it is important to conduct such programs in relation to the clinic.

Animals↗
PubMed1979

Effects of adriamycin and cyclophosphamide treatment on induction of macrophage cytotoxic function in mice.

The effects of i.p. and s.c. Adriamycin and cyclophosphamide treatment of BALB/c x DBA/2F1 mice were studied alone and in combination with immunotherapeutic agents, pyran copolymer and Bacillus Calmette-Guérin, on macrophage cytotoxic ability, As assessed by direct viable cell counts of MBL-2 leukemia cells, both Adriamycin and cyclophosphamide produced growth-inhibitory macrophages. This function after s.c. cytostatic treatment peaked at Day 1 and decreased progressively, attaining normal control values by Day 6. When adjuvants, such as pyran and B. Calmette-Guérin, were administered i.p. simultaneously with s.c. Adriamycin or cyclophosphamide, adjuvant-induced cytotoxic function was not markedly affected. A better knowledge of the influence of cytostatic agents alone or combined with immunoadjuvants on macrophage cytotoxic ability may be useful in designing more effective chemoimmunotherapy protocols.

Animals↗
PubMed1979

International activities of the Division of Cancer Treatment, National Cancer Institute.

International collaborative activities of the Division of Cancer Treatment, National Cancer Institute, U.S.A., have a long-standing history, and in recent years have expanded to such an extent that an Office of International Treatment Research has been created. The scope of these activities encompasses three areas: 1) participation in International Collaborative Agreements with official national research entities, 2)direct NCI-supported projects, and 3) miscellaneous, less formalized programs. These are described and specific recent contributions are summarized. Emphasis is placed on the importance of international collaboration and exchange of information in searching for new drugs and in maximizing progress in cancer treatment.

France↗
PubMed1978

Adoptive immunochemotherapy of a transplantable AKR leukemia (K36).

Adoptive immunotherapy of a transplantable AKR leukemia (K36) was carried out as an adjunct to cytoxan chemotherapy using normal allogeneic H-2-incompatible spleen cells as well as sensitized H-2-matched allogeneic spleen cells. A significant therapeutic effect was obtained with cytoxan and allogeneic C57BL/6 splenocytes, demonstrating the potential use of the graft-versus-host reaction. Utilizing specific adoptive immunochemotherapy, a maximum effect was found with splenocytes from allogeneic but H-2-compatible CBA/J mice immunized against an allogeneic Gross-virus-induced lymphoma (E female G2). This therapeutic effect was most likely the result of prior sensitization of donor lymphocytes to common virus-associated tumor antigens.

Animals↗
PubMed1978

Criteria for selection of new analogs of antitumor antibiotics.

If a new analog of a known antitumor antibiotic is to justify interest, it must be demonstrated to possess either quantitative or qualitative superiority over the parent compound in pharmacologic, toxicologic, immunologic, tumor cytotoxic, or other biologic properties that are therapeutically favorable. The most commonly used criterion is in vivo activity in are therapeutically favorable. The most commonly used criterion is in vivo activity in experimental tumor systems. This may be demonstrated in primary screening systems or in secondary screening systems, or in refractory tumor systems, or in one or more tumors of a human xenograft panel. Data on adriamycin and bleomycin analogs give evidence of some of these approaches. An additional criterion for selection of analogs involves the demonstration of a broader spectrum of effectiveness against a panel of experimental systems. Actinomycin D is used as an exampled. There are a variety of factors that may be employed in determining further clinical interest for analogs of known antitumor antibiotics. It is important to delineate the limiting characteristics in the clinical application of the parent antitumor antibiotic and to the choose the appropriate systems to identify and characterize new analogs and investigate them in depth in order to determine whether they may provide some advantage either in antitumor selectivity or in the diminution of host toxicity with retention of antitumor effectiveness.

Animals↗
PubMed1978

Intra-arterial streptokinase and renal artery embolization.

An animal experiment was constructed to simulate the clinical entity of renal artery embolization. Because of the high morbidity and mortality rates associated with the current methods of treatment, percutaneous infusion of the renal artery with streptokinase was evaluated as a new method of therapy. Results were analyzed by the following criteria: (1) arteriography, (2) gross pathology, and (3) differential renal function studies. In 12 dogs whose left kidney was embolized without treatment, renal function was 38 per cent of the contralateral normal kidney twenty-one days later. Seven dogs were embolized but treated immediately with intra-arterial streptokinase for six hours; renal function was increased to 58 per cent of the contralateral normal kidney. Various fibrinolytic agents and their possible clinical application in embolism are discussed.

Animals↗