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Biomedical subjects

G Sava

Publications and source records attributed to G Sava.

At least 73 records · Page 4Linked to original sources
PubMed1984

Chemical xenogenization of murine lymphoma cells with triazene derivatives: immunotoxicological studies.

Equitoxic doses of 5-(3-3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and aryl-triazene derivatives (compounds all capable of inducing a marked increase in murine tumor cell immunogenicity) were studied for their effects on the host immune system. At different times after drug exposure the animals were tested for allograft responses, competence in producing lymphocytes active in lethal graft-versus-host disease, delayed-type hypersensitivity, humoral antibody production, and mitogen responsiveness. While some of the aryl-triazenes tested (DM-COOK DM-NO2) showed a pattern of immunodepression similar to that of DTIC, others were less (MIC, MM-COOK, MM-Cl) or far less (DM-Cl, MM-NO2) active than DTIC in impairing host immunocompetence, although all retained or even augmented their ability to induce chemical xenogenization.

Animals↗
PubMed1984

Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma.

The selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.

Animals↗
PubMed1984

Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison with cis-PDD in mice bearing solid malignant neoplasms.

The antineoplastic activity of an organometallic complex of ruthenium(II), [cis-RuCl2(DMSO)4]o, has been examined in comparison with that of cis-PDD, using three metastasizing tumors of the mouse: Lewis lung carcinoma, B16 melanoma and MCa mammary carcinoma. [cis-RuCl2(DMSO)4]o significantly reduces primary tumor growth in all the tumors tested, and its activity is similarly pronounced at three different dosages in mice bearing Lewis lung carcinoma. On the contrary, the survival time of animals having i.v. or i.m. tumor implants are only moderately increased, and also in the case of combined treatments with surgery. The antineoplastic activity of cis-PDD appears to be less pronounced than that of [cis-RuCl2(DMSO)4]o, and is limited to mice bearing B16 melanoma, which, among the three tumors used, appears to be naturally more responsive to cis-PDD and [cis-RuCl2(DMSO)4]o. The use of [cis-RuCl2(DMSO)4]o appears advantageous over that of cis-PDD since, unlike cis-PDD, its antineoplastic effects have been obtained at dosages with reduced host toxicity, indicated by the absence of significant hematological toxicity and toxicity for normal proliferating tissues.

Animals↗
PubMed1984

Effects of antimetastatic dimethyltriazenes in mice bearing Lewis lung carcinoma lines with different metastatic potential.

The effects of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and its benzenoid analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined in mice bearing two Lewis lung carcinoma lines with different potential to spontaneously metastasize to the lungs. DTIC similarly depresses the growth of intramuscular and pulmonary tumor nodules, and also reduces the development of spontaneous lung metastases for both tumor lines. DM-COOK causes effects similar to those of DTIC on the tumor line with low metastatic potential; on the contrary, although it is highly active in inhibiting lung metastasis formation for the line with high metastatic potential, it is ineffective or marginally cytotoxic on intramuscular or on pulmonary tumor nodules, respectively. These data indicate, at least for the dimethyltriazene DM-COOK, a dissociation between sensitivity to cytotoxic and antimetastatic effects, and that tumor cell populations with a higher potential to spontaneously metastasize have a greater sensitivity to selective antimetastatic effects, concomitant with a reduced cytotoxic response to the effects of this drug.

Animals↗
PubMed1984

[A rare complication of vaginal hysterectomy: vaginal evisceration. Apropos of a case of recurrent evisceration].

A patient developed repeated vaginal eviscerations after vaginal hysterectomy. This is a rare complication, only 21 cases having been reported in the literature. The present case was a 61 year old woman with post-vaginal hysterectomy eviscerations 8 and 21 months after the operation. Reduction of the herniated loop and suturing of the ununited vaginal stump is generally a simple procedure, but the perineal reconstruction necessary to prevent recurrence raises problems that are discussed in detail.

Abdomen↗
PubMed1984

Antimetastatic action and hematological toxicity of p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide used as prophylactic adjuvants to surgical tumor removal in mice bearing B16 melanoma.

The treatment of mice bearing i.m. B16 melanoma with equitoxic dosages of the clinically used 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and of its benzenoid water-soluble analogue p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) prior to surgical tumor removal results in a remarkable proportion of cures, even when the treatment is started on already palpable tumors for which surgery alone is ineffective. The survival time of mice which are not cured is also significantly increased with DM-COOK. At the same time, DM-COOK does not affect artificial metastases or spontaneous metastases in mice undergoing surgery and treated with DM-COOK postoperatively. Inhibition of i.m. tumor growth in surgical experiments, and of s.c. tumors in mice not treated with surgery, is significant, although not as pronounced as is necessary to obtain significant prolongation of the life span of the host; the survival time of mice with s.c. tumors treated with both drugs is indeed not significantly increased. DM-COOK thus appears to exert selective antimetastatic effects, unrelated to cytotoxicity for tumor cells, against B16 melanoma in addition to those reported for Lewis lung carcinoma and M5 ovarian reticular cell sarcoma; its therapeutic usefulness is evidenced in adjuvant surgical experiments. DM-COOK, unlike DTIC, is devoid of hematological toxicity for the host. Since, in leukemic mice, it is at least as active as DTIC in increasing the life span of the treated animals, it appears to be an advantageous substitute for DTIC that could undergo preliminary clinical trial.

Animals↗
PubMed1983

Effects of isomeric aryldimethyltriazenes on Lewis lung carcinoma growth and metastases in mice.

The effects of the ortho and para isomers of aryldimethyltriazeno carboxylic and benzensulfonic acids and amides have been examined in mice bearing subcutaneous Lewis lung carcinoma. The toxicity of these compounds varies widely and does not correlate with the effects on tumor progression. The growth of subcutaneous primary tumor is unaffected or only marginally inhibited by all the tested compounds, while a marked depression in the formation of spontaneous lung metastasis is observed, with the exception of the sodium salt of the ortho benzensulfonic acid. The compounds showing the greatest activity on metastasis are the hydrosoluble salts of the ortho and para carboxylic acid and the para sulfonamido derivative, indicating that, in addition to the activity reported for the potassium salt of the para carboxylic acid, also its ortho isomer and the para sulfonamido derivative possess selective and pronounced antimetastatic effects. No correlation can be found between the reported effects on tumor progression and physicochemical parameters of the triazenes tested.

Animals↗
PubMed1983

Antitumor effects of rhodium(I), iridium(I) and ruthenium(II) complexes in comparison with cis-dichlorodiammino platinum(II) in mice bearing Lewis lung carcinoma.

The effects of square planar rhodium, [RhacacCOD]o and iridium, [IracacCOD]o complexes and of octahedral ruthenium, [cis-RuCl2 (DMSO)4]o complex have been examined in comparison with cis-dichlorodiammino platinum(II) (cis-PDD). The toxicity in BDF1 mice varies widely and decreasing LD50-values, ranging from 0.94 mg/kg to 1000 mg/kg, have been obtained for cis-PDD, [RhacacCOD]o, [IracacCOD]o and [cis-RuCl2(DMSO)4]o, respectively. All the tested complexes similarly inhibit the growth of subcutaneous Lewis lung carcinoma and the development of spontaneous as well as of artificial metastases, with the exception of [IracacCOD]o which is inactive on metastases. The antitumor activity of [RhacacCOD]o and [cis-RuCl2(DMSO)4]o appears interesting, since it is of the same magnitude as that of cis-PDD, considering also that they were found to be only marginally nephrotoxic.

Animals↗
PubMed1983

[Cysts and pseudocysts of the adrenal gland. Apropos of 3 surgically-treated patients].

Three observations including one cyst and two pseudocysts of the adrenals are reported. Such lesions are uncommon and are only detected fortuitously or because of poorly specified pains. Diagnosis, formerly based upon intravenous urography and arteriography, has largely benefited from echotomography and computed tomography. Endothelial cysts and pseudocysts account for most of these lesions. The possibility of malignancies justifies the systematic surgical approach.

Adrenal Gland Diseases↗
PubMed1983

Immunotherapy of Lewis lung carcinoma with hydrosoluble peptidoglycan monomer (PGM).

The water-soluble peptidoglycan monomer (PGM) isolated from the culture fluid of Brevibacterium divaricatum, which has immunostimulating activity, has been examined for its antitumor effects in C57BL mice bearing Lewis lung carcinoma. The formation of spontaneous lung metastases from SC tumor implants is significantly inhibited. The growth of SC primary tumors, including advanced ones, is also significantly inhibited, though to a less pronounced extent than the growth of metastases. The effects on metastases are evident with all treatment schedules used, whereas those on SC primary tumors are treatment schedule-dependent. The treatment with PGM was found to be therapeutically useful when combined with surgical removal of IM implants; in conditions where a single post-operative treatment was ineffective, combined post-operative and immediately pre-operative administration of PGM significantly increased (by 40%) the survival time of treated animals over that of controls undergoing surgery only.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Antitumor effects of GANU and other nitrosourea derivatives against transplantable leukemias and solid tumors in mice.

The antitumor effects of GANU have been examined in a panel of mouse tumors for which data appear to be lacking in the literature. GANU has significant activity against P388 leukemia and TLX5 lymphoma, and also against the solid tumors B16 melanoma and Lewis lung carcinoma; pulmonary metastases of this tumor are particularly sensitive to the effects of GANU. The effects of GANU on TLX5 lymphoma and Lewis lung carcinoma are less pronounced than those of BCNU and CCNU, as already reported for L1210 leukemia. In contrast with other results obtained with this tumor, chlorozotocin has a less pronounced effect than GANU, and virtually none in lung metastases of Lewis lung carcinoma.

Animals↗
PubMed1982

Mechanism of the antileukemic effects of 1-p-carboxamidophenyl-3,3-dimethyltriazene and its in vitro metabolites.

DM-CONH2, a dimethyltriazene active in prolonging the survival time of mice bearing TLX5 lymphoma, requires metabolic activation by liver homogenate supernatant and cofactors in order to exert in vitro cytotoxic effects on the same tumor cells, as determined by in vivo bioassay of their viability. From the examination of the metabolites produced during these in vitro experiments, it is found that in vitro cytotoxicity is attributable to the generation of MM-CONH2 by oxidative N-demethylation of DM-CONH2. Also the generation of DM-COO is observed, although this compound is not cytotoxic in vitro. The in vivo effects of DM-CONH2 and CM-COOK on TLX5 lymphoma are not caused exclusively by cytotoxic effects of the drugs, since they are evident also when no reduction in the number or viability of peritoneal tumor cells is evident, whereas these parameters are significantly reduced by MM-CONH2. The increase in survival time of mice bearing TLX5 lymphoma caused by the dimethyltriazenes used appears to be caused by the drugs without being subjected to metabolic activation, with a mechanism different from cytotoxicity for tumor cells.

Animals↗
PubMed1982

Methodologic problems encountered in the assay of proteinases in Lewis lung carcinoma, a mouse metastasizing tumor.

The proteolytic activity in homogenates and extracts of subcellular fractions prepared from subcutaneous Lewis lung carcinoma was determined using proteins and synthetic peptides as substrates. The presence of cathepsin D, plasminogen activator, cathepsin B-, cathepsin G- and elastase-like enzymes was observed. No difference was revealed between the proteolytic activity in homogenates of Lewis lung carcinoma, at the growth stage examined, and in homogenates of normal lung. High specific activities were found in the lysosomal extract, whereas decreasing activities were found in the nuclear extract, the homogenate and the postlysosomal mitochondrial supernatant; no active or trypsin-activatable collagenase activity was detected. The presence in the tumor tissue of these enzymatic activities is in agreement with their proposed role in the process of metastasis. The lack of differences between homogenates of tumor and normal lung tissue suggests that the use of whole cells is required to selectively study tumor proteinases specifically involved in tumor malignancy.

Animals↗
PubMed1982

Biochemical and biological characteristics of leucocyte proteinase inhibitors.

Pig leucocytes contain inhibitors of neutral and thiol proteinases. These proteins could be isolated from post-granule supernatant fraction as well as from nuclear extract using ion exchange chromatography, gel chromatography and affinity chromatography. Inhibitors differ in molecular weight, isoelectric point, immunologically and their inhibition ability against tested enzymes.

Animals↗
PubMed1982

Antitumor activity of N-diazoacetyl derivatives of glycine and phenylalanine against P388 leukemia and B16 melanoma in mice.

N-Diazoacetyl derivatives of glycine and phenylalanine show antitumor activity in mice bearing P388 leukemia or B16 melanoma. The presented data indicate that antitumor activity is shown by diazomethylamide derivatives of glycine and phenylalanine, in addition to that already established for the amino acid derivatives having an O-diazoacetyl group (azaserine) or a diazoketone structure (DON and azotomycin) and for 1,2-bis-diazoacetyl ethane.

Animals↗
PubMed1982

Some further characteristics of endogenous proteinase inhibitors.

Leucocytes and spleen contain four different types of protein proteinase inhibitors. Two of them can be inactivated by cathepsin D. In this work biochemical and immunological studies of the inactivation of I-2 by cathepsin D are presented. Polyacrylamide gel electrophoretic examinations indicate that cathepsin D inactivates I-2 by hydrolysis of the inhibitor molecule. The conversion of the active inhibitor into inactive protein proceeds catalytically. The studies on the inhibitor mechanism of the isoinhibitors of I-1 type explain the unusual inhibitor property of this type of inhibitor to inhibit two different types of proteinases, cysteine and serine. The evidence suggests that the inhibitory mechanism is based on an active sulfhydryl group of the inhibitor which may interact with the disulfide bridge of the inhibited proteinase.

Animals↗
PubMed1982

Prophylactic antimetastatic treatment with aryldimethyltriazenes as adjuvants to surgical tumor removal in mice bearing Lewis lung carcinoma.

The effects of two benzenoid dimethyltriazenes (1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt [DM-COOK] and 1-p-tolyl-3,3-dimethyltriazene), which have been previously shown to reduce the formation of spontaneous lung metastases in mice bearing subcutaneous Lewis lung carcinoma, have been investigated in mice implanted im with the same tumor in the calf of the hind leg. Primary tumor was removed surgically by amputation in mice treated with the tested compounds preoperatively, and the survival time of the animals was then determined. A high rate of cures, ranging from 23% to 43%, has been observed when the treatment consisted of eight or three daily doses prior to tumor removal; a single immediately preoperative dose was less effective and caused a 10% cure rate. Survival time of uncured mice was also significantly increased, particularly by DM-COOK. The division of the dose into two daily injections did not modify the activity of the triazenes, thus indicating that the antimetastatic coverage between two subsequent doses is not limited by fast pharmacokinetics or decomposition of the drugs. These results show that, at least in one animal system, aryldimethyltriazenes can be used also on palpable tumors as prophylactic adjuvants to surgery in order to reduce preoperative and intraoperative tumor spread.

Animals↗