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Biomedical subjects

G Sava

Publications and source records attributed to G Sava.

At least 55 records · Page 3Linked to original sources
PubMed1991

Synthesis and antitumor activity of hydrosoluble analogs of p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt.

The hydrosoluble triazene derivatives of phenylacetic, phenylbutyric and cinnamic acid have been synthesized and their logP and pKa values were simultaneously determined according to a multiparametric fitting of potentiometric data. The antitumor activity caused by the synthesized compounds in mice bearing either Lewis lung carcinoma or TLX5 lymphoma was evaluated and discussed in comparison with the parent compound (p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK, CAS 70055-49-1). The tested compounds were at least as active as DM-COOK, the cinnamic and the phenylacetic derivatives being the more active compounds in mice bearing TLX5 lymphoma and Lewis lung carcinoma, respectively.

Animals↗
PubMed1990

Metal complexes of ruthenium: antineoplastic properties and perspectives.

Octahedral ruthenium(III) and ruthenium(II) complexes show antineoplastic properties on a number of experimental tumors. Tetraammine-, pentaammine-, heterocycle-, and dimethylsulfoxide-coordinated ruthenium complexes have shown high affinity for nitrogen donor ligands in vitro and as a result exhibit various degrees of biological activities including antitumor action in vivo. The chemical behavior of ruthenium(III) complexes indicates the possibility of opening a window of selective toxicity, in practice lacking in the chemotherapeutic approach to neoplastic diseases. Ruthenium ions may accumulate in tumor tissues via a mechanism mediated by transferrin transport. Moreover, binding of ruthenium to DNA is several times higher in its reduced ruthenium(II) form and the reduction from ruthenium(III) prodrugs to the more toxic ruthenium(II) compounds is particularly efficient in tumor hypoxic environments. Correspondingly, solid tumors appear to be more susceptible than those of the lymphoproliferative type. In particular, tumors of the colorectal region and lung tumors (primary or metastatic), which are generally associated with a bad prognosis, have given interesting responses in experimental models, indicating these tumors as preferential targets for the development of ruthenium anticancer drugs.

Animals↗
PubMed1990

Kinetic investigation of the aqueous stability and antitumor activity of a hydrosoluble diaryltriazene, AVIS, related to the antimetastatic agent DM-COOK.

The aim of this study is to investigate the hydrolysis of 1,3-di(p-carboxyphenyl)triazene dipotassium salt, AVIS (1), over a pH range of 2.60-8.50. This compound decomposes into p-aminobenzoic acid and the corresponding diazonium cation with no formation of alkylcarbo cations; the same compounds are formed from hydrolyses of DM-COOK (2), an antimetastatic agent, and of its possible demethylated metabolite, MM-COOK (3), a chemical xenogenization inducer. In these latter cases, however, a methylcarbo cation is formed. The pH dependence of the pseudo-first-order rate constants is intermediate between 2 and 3. Preliminary data on its toxicity and antitumor activity on both Lewis lung carcinoma and TLX5 lymphoma seem to indicate the essential role of alkylcarbo cation in mediating the antitumor action of aryldimethyltriazenes.

Animals↗
PubMed1989

Effects of two pyridinalalkyliminerhodium(I) complexes in mice bearing MCa mammary carcinoma.

The examination of the differential effects of two square-planar rhodium(I) complexes on primary tumor growth and on the formation of spontaneous and artificially (i.v. tumor injection) induced lung metastases of MCa mammary carcinoma suggests different mechanisms of action, depending on the chemical characteristics of the compound used. Of the two complexes used, cyclooctadiene(2-pyridinalmethylimine)Rh(I) chloride and cyclooctadiene(2-pyridinalisopropylimine)Rh(I) chloride, the former compound confirmed the antineoplastic action previously shown in the Lewis lung carcinoma model. The activity of this derivative on lung metastasis formation seems to be unrelated to a cytotoxic action for tumor cells localized in the lungs. More likely, it appears that modifications occurring at the primary tumor level, probably different from a tumor-cell-directed lethality, are responsible for the reduction of spontaneous lung metastasis formation observed in treated animals. The hyperplasia of the spleen induced in treated animals seems to suggest that this compound is endowed with properties typical for biological response modifiers.

Animals↗
PubMed1989

Reduction of B16 melanoma metastases by oral administration of egg-white lysozyme.

The oral administration of hen egg-white lysozyme to mice bearing B16 melanoma significantly reduces the formation of spontaneous lung metastases and, when combined with surgical removal of the primary tumor, prolongs the survival of the treated hosts. The antimetastatic effect, comparable with that found in the Lewis lung carcinoma and MCa mammary carcinoma systems, is independent of the direct interaction of lysozyme with tumor cells and tends to indicate the suggested intervention of an indirect action mediated by the induction of host responses.

Administration, Oral↗
PubMed1989

Antineoplastic action of egg-white lysozyme on the growth of MCa mammary carcinoma and TLX5 lymphoma in the CBA mouse.

The antitumor effects of egg-white lysozyme, at dosages between 25 and 100 mg/kg/day given for 5 to 14 days, was examined in CBA mice bearing MCa mammary carcinoma or TLX5 lymphoma. At early stages of tumor growth the antitumor action of lysozyme is statistically significant, independently from the route of administration (e.g., i.v. and oral admixed with food). With larger tumor masses, oral administration of lysozyme is effective on s.c. tumor growth but not on i.m. tumors. The effects of lysozyme in mice bearing TLX5 lymphoma consist of reduction of the capacity of tumor cells to form brain metastases: the effect is mediated by spleen cells. Dietary intake of lysozyme is also active in prolonging the survival time of animals treated with surgery and postsurgical cisplatin treatment. These effects indicate lysozyme to be an active substance, effective on the growth of malignant tumors and capable of synergizing with conventional therapies such as surgery plus cisplatin for the control of disseminated tumors in mice.

Administration, Oral↗
PubMed1988

Effects of an inducer and an inhibitor of hepatic metabolism on the antitumor action of dimethyltriazenes.

To investigate the role of monomethyltriazenes as the active metabolites of antitumor dimethyltriazenes, the in vivo simultaneous treatment with an inducer (phenobarbital, PB) or an inhibitor (carbon tetrachloride, CCl4) of hepatic drug metabolism was examined in mice bearing Lewis lung carcinoma. Treatment with PB or CCl4 with the dosage and schedules employed proved to be effective in markedly modifying the N-demethylation of the three dimethyltriazenes tested, as had been determined in vitro. No unambiguous increase by PB, or decrease by CCl4, which might theoretically be expected if metabolic conversion to monomethyltriazenes was involved, was observed for the antitumor and antimetastatic activity of dimethyltriazenes. At the same time, a difference was noted between the effects on primary tumors and those on metastases. These data support the view that generalizations on the relevance of monomethyltriazenes as the active metabolites responsible for the antitumor and antimetastatic activity of dimethyltriazenes may not be valid.

Animals↗
PubMed1988

Evidence for host-mediated antitumor effects of lysozyme in mice bearing the MCa mammary carcinoma.

The host-mediated effects of lysozyme on primary tumor growth and on the formation of pulmonary metastases were investigated in mice bearing the MCa mammary carcinoma. The oral administration of lysozyme to CBA mice for 7 consecutive days before i.v. inoculation of MCa mammary carcinoma cells causes a significant reduction in the formation of lung tumors. The growth of s.c. tumors and the development of lung metastases is also significantly lowered in mice inoculated with tumor cells previously kept at 37 degrees C for 30 min in the presence of peritoneal resident cells or whole plasma samples obtained from normal mice treated with 25-100 mg/kg/day lysozyme for 7 consecutive days. The lysozyme concentration in plasma samples of the treated mice remains undetectable even at daily dosages up to 400 mg/kg, ruling out the hypothesis of a direct effect of the ingested lysozyme. These data seem to suggest a role for host immune reactivity in the antineoplastic effects of lysozyme. The results are consistent with previously reported data and further stress the interesting antitumor properties of the oral administration of lysozyme in mice bearing solid metastasizing tumors.

Animals↗
PubMed1988

[Limy bile syndrome. Study of a case with double localization in the gallbladder and common bile duct].

We report the case of a patient with limy bile located in both the gallbladder and common bile duct, and disappearing spontaneously. Since the first description of this syndrome in 1911, approximately 300 cases have been reported in the literature, including 20 cases with double localization. The male/female ratio was 1/3. All patients were more than 40 year old. Conventional radiogram was sufficient to establish diagnosis. Spontaneous disappearance of limy bile is rare. The etiopathogenesis remains unclear; cholecystectomy is appropriate.

Adult↗
PubMed1987

[Role of protective colostomy in colorectal surgery. Apropos of 68 cases].

A retrospective study was made from the records of 68 patients who had temporary loop colostomy with left colectomy between 1975 and 1985. Six fecal fistula occurred. Two of these patients died in spite of the colostomy. The colostomy closure was complicated by six leakages and four wound infections. The results are compared with those from literature. Finally loop colostomy for protecting an anastomosis keeps good indications with sub-obstructions and acute obstructions without large colectasia, infections without abscess, bowels no or bad prepared, and some low colo-rectal anastomosis. Large bowel obstruction with megacolon, and peritonitis avoid all kind of anastomosis. The colostomy closure is a high colonic surgery procedure. It must occur three months after its formation. A barium enema is necessary before loop colostomy closure.

Adult↗
PubMed1986

Mutagenic activity of the dacarbazine analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt in bacterial cells.

The mutagenic activity of the antimetastatic agent p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) was studied in procaryotic cells and compared with that of dacarbazine (DTIC) which is clinically used in the management of human neoplasms. The results indicated that DM-COOK has a very low mutagenic activity on the Salmonella typhimurium strains tested, while it is more effective in inducing trp+ revertants in E. coli B strains. The magnitude of these effects was always less pronounced than that displayed by DTIC. The mutagenic activity of DM-COOK appeared to be independent from the addition of a metabolic activating system and had a different pattern from that displayed by MM-COOK. It is therefore unlikely that DM-COOK acts through conversion into the monomethyl derivative.

Animals↗
PubMed1985

Tumor cell metastasis and surface neutral proteinase: effects of antimetastatic and antitumor drugs.

The levels of a trypsin-like neutral proteinase present on tumor cell surface (SNP) have been determined in P388, L1210, TLX5 leukemias, and in two lines of Lewis lung carcinoma having different metastatic potential. No correlation between metastatic potential and SNP levels of the tumor lines examined has been observed, and metastasis depression by antimetastatic and antineoplastic drugs was not accompanied by SNP inhibition. These data seem to support the view that metastatic potential is not necessarily related to tumor proteinase levels.

Animals↗
PubMed1985

Effects of postsurgical immunotherapy with PGM in mice bearing Lewis lung carcinoma treated with p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt.

The effects of preoperative treatment with dimethyltriazene p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt (DM-COOK) followed by surgery and non-specific immunotherapy with the peptidoglycan monomer PGM have been evaluated using the Lewis lung carcinoma implanted i.m. in BD2F1 female mice. The survival time of mice treated with this combination is prolonged and the percentage of animals cured is markedly increased as compared with untreated controls or with mice treated with DM-COOK or PGM alone. The synergism between DM-COOK and PGM could be attributed to the capacity of the triazene to render the treated tumor cells more antigenic, combined with the favourable effects of PGM to restore host defense mechanisms. In this combined treatment, the use of cyclophosphamide at dosages having the same activity displayed by PGM alone does not ameliorate the results obtained with DM-COOK alone.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Infiltration of liver and brain by tumor cells in leukemic mice: prevention by dimethyltriazenes and cyclophosphamide.

The dimethyltriazenes p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) increase, unlike cyclophosphamide (Cy), the survival time of mice bearing L1210 lymphoid leukemia, P388 lymphocytic leukemia and TLX5 lymphoma with a mechanism unrelated to cytotoxicity for tumor cells. The in vivo bioassays of brains, and the histologic examinations of the livers of leukemic mice show that DM-COOK and DTIC prevent leukemic infiltration in these organs at dosages devoid of cytotoxic effects for peritoneal tumor cells. At a dosage equitoxic with that of dimethyltriazenes, cyclophosphamide causes the absence of tumor cells in the peritoneal cavity and in the brains and livers of mice bearing P388 and L1210 leukemias. DM-COOK and DTIC thus possess a mild or insignificant cytotoxic action together with antimetastatic properties also on mouse transplantable leukemias. The use of DM-COOK appears advantageous over that of cyclophosphamide and DTIC because of a reduced host toxicity, which is particularly evident for cyclophosphamide and DTIC on liver parenchyma and bone marrow.

Animals↗
PubMed1984

Antitumor and antimetastatic activity of the immunoadjuvant peptidoglycan monomer PGM in mice bearing MCa mammary carcinoma.

The antitumor and antimetastatic activities of the water-soluble peptidoglycan monomer GlnNAc-Mur-NAc-L-Ala-D-iso-Gln-meso-diamminopimelic acid (omega-NH2)-D-Ala-D-Ala (PGM), which has immunostimulant effects, have been evaluated in CBA mice bearing MCa mammary carcinoma. The antineoplastic effects of PGM depend strictly on the dosage and treatment schedule used. Though a significant inhibition of the primary tumor growth is observed over a wide range of dosage, only the IV administration of daily doses of 50 mg/kg/day on days 1, 5, 10, 15 inhibits spontaneous lung metastasis formation and in parallel prolongs the survival time of the treated mice. The magnitude of the antimetastatic effects of PGM depends on the degree of dissemination of the tumor, and is greater when the number of metastatic foci is low. Examination of the therapeutic potential of PGM in combination with surgery has further indicated that the timing of administration plays an important role in the overall effectiveness of this substance. A 5-day interval is necessary between two consecutive injections for the induction of significant increases of the survival times.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Immunogenic changes of murine lymphoma cells following in vitro treatment with aryl-triazene derivatives.

A series of dimethyl aryl-triazene derivatives and related monomethyl compounds were studied for their efficacy in mediating a strong increase in immunogenicity (i.e., chemical xenogenization, CX) of murine leukemic cells following in vitro treatment. It was found that all compounds under investigation were able to induce CX. The dimethyl derivatives were able to induce CX only after metabolic activation, whereas related monomethyl compounds were active per se. The antigenicity acquired by triazene-treated leukemic cells was very marked; intact hosts histocompatible with the parental line were able to reject up to 10(7) cells. Antigenic tumor cells retained their immunogenic properties even after a large number of transplant generations in the absence of the drug. This means that marked immunogenicity of triazene-treated cells is a stable and heritable characteristic.

Animals↗