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Biomedical subjects

A Sacchi

Publications and source records attributed to A Sacchi.

At least 109 records · Page 6Linked to original sources
PubMed1988

MHC antigens expressed on 3LL metastatic variants: correlation with the expression of a TSP-180 protein.

In attempts to correlate metastatic potential with specific properties of tumor cells, homogeneous subpopulations, which are endowed with low or high metastatic potential, have been selected from Lewis lung carcinoma (3LL). In particular, since cell surface constituents are possibly involved in the metastatic process, changes in antigen expression have been correlated with the metastatic potential of 3LL variants. In this view, we quantitated the expression of MHC (Db,Kb) antigens and of a tumor specific protein (TSP) identified by the monoclonal antibody (MoAb) 135-13C on some "in vitro" and "in vivo" variants of 3LL. The MoAb 135-13C was found to recognize a TSP-180 protein that appears on the cell surface of several murine carcinomas, but is not detected on normal cells in culture. Studies of the MHC expression on these variants, by the use of the indirect immunofluorescent staining or the direct binding of the MoAb to H-2Db (28-14-8) and the MoAb to H-2Kb (28-13-3), demonstrate that "in vivo" and "in vitro" 3LL variants which, are endowed with a higher metastatic potential, express on the cell surface a higher amount of the Db antigen. By contrast, all the 3LL lines have few cells recognized by the MoAb to H-2Kb and express low amounts of this antigen on the cell surface. The direct binding to different tumor lines and the analysis of the immunoprecipitates from the cell lysates by the use of the MoAb 135-13C demonstrate that the TSP-180 protein is highly expressed on 3LL cells which possess high capacity to metastasize to the lung. The variations induced in 3LL metastatic phenotype by the injection of the variant lines in allogeneic mice (Balb/c, C3HeB:H-2d,H-2k, respectively) or after treatment with the specific MoAb 135-13C have, also, been studied. An attempt was made to correlate the changes in 3LL metastatic phenotype with the expression of the TSP-180 protein and of the MHC antigens. We conclude that a high expression on the cell surface of the Db antigen and of the TSP-180 protein, is associated with a high malignant phenotype of 3LL tumor cells.

Animals↗
PubMed1987

Metastatic dissemination of 3LL variants after treatment with monoclonal antibody to a tumor-associated antigen.

Two tumor lines derived from 3LL (Lewis lung carcinoma) endowed with different metastatic potential and stable for their metastatic phenotype during serial in vivo passages, have been analysed for growth and dissemination following treatment with a monoclonal antibody. We have used a recently developed MoAb 135-13C to a tumor-associated antigen of murine lung carcinoma having an apparent molecular weight of 180,000 (TSP-180). The metastatic dissemination of the 3LL variants before and after treatment with the MoAb has been correlated with the expression on the cell surface of the MHC antigens (Db, Kb) and of the TSP-180 protein. The results of this study indicate that cell with high TSP-180 protein expression and MHC antigen expression have the greatest metastatic potential. Administration of MoAb 135-13C to tumor-bearing mice or i.v. injection of cells preincubated with the MoAb 135-13C increase the dissemination capacity of the variant endowed with lower metastatic potential while inducing a reverse effect on the high metastatic one. Studies on the MHC expression demonstrate that MoAb 135-13C treatment induces changes in the Db and Kb expression at level of secondary neoplasms. The results are discussed in view of the importance of the use of the metastatic variants to study therapeutic effect of specific targeting agent.

Animals↗
PubMed1986

Expression of tumor antigen correlated with metastatic potential of Lewis lung carcinoma and B16 melanoma clones in mice.

Expression of a tumor-associated antigen, recognized by a monoclonal antibody (MoAb 135-13C) to lung carcinoma cells, has been studied in cloned Lewis lung carcinoma (3LL) and in B16 melanoma (F1 and F10) tumor lines endowed with different metastatic potentials. MoAb 135-13C recognizes a protein complex (tumor-specific Mr 180,000 protein) that appears on the cell surface of several murine lung carcinomas but is not detected on normal cells in culture. Standard metastatic variants of B16 melanoma (F1 and F10) and two variant sublines of 3LL (M1087 and BM21548) together with the parental line of 3LL have been used for these experiments. The two cloned variant lines derived from 3LL have been shown to retain high (M1087) and low (BM21548) metastatic phenotypes during in vivo passaging. We found that all three cell lines of 3LL bind monoclonal antibody specifically, but one cell variant with higher metastatic potential shows a higher capacity to bind MoAb 135-13C than did the other variant. Similarly we found that B16 F10 cells bind higher amounts of MoAb 135-13C than did B16 F1 cells. In addition the analysis of the amounts of MoAb 135-13C bound to the cell surface of several other in vitro and in vivo tumor lines with different metastatic capacity demonstrates that all tumor lines which express high ability to colonize to the lung also express, on the cell surface, higher amounts of tumor-specific Mr 180,000 protein. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiograms of immunoprecipitates from cell lysates of 3LL and B16 tumor lines demonstrate that MoAb 135-13C specifically precipitated three proteins banding at molecular weights of 204,000, 134,000, and 116,000. We conclude that MoAb 135-13C recognizes a surface protein complex which is present in higher amounts in 3LL and B16 cells which possess higher capacity to metastasize to the lung.

Animals↗
PubMed1985

Etoposide prior to cis-diamminedichloroplatinum in combination chemotherapy: in vitro and in vivo studies.

Antitumor effect and toxicity of etoposide (VP 16) in combination with cis-diamminedichloroplatinum (DDP) were studied on the in vitro C108 line and its in vivo counterpart, the M1087 line, both deriving from Lewis lung carcinoma. A colony-forming assay was used to assess the in vitro cytotoxicity of each drug and, on the basis of survival curve shape indications, different drug sequences were analyzed in order to find the optimal combination. Tumor growth inhibition, growth delay, metastasis reduction and percentage increase in lifespan were considered as parameters of therapeutic effect. From the present work it can be derived that the VP 16-DDP combination produces a poor antitumour effect against the Lewis lung carcinoma lines, otherwise associated with a highly acute toxicity. The sequence in which VP 16 is given before DDP induces a significant antimetastatic effect together with acceptable toxicity.

Animals↗
PubMed1985

Treatment with monoclonal antibody to a Lewis lung carcinoma-associated antigen: different effects on primary tumor and its metastases.

The growth and dissemination of Lewis lung carcinoma have been analyzed following treatment of isolated tumor cells or of tumor-bearing animals with monoclonal antibody (MoAb) 135-13C, which recognizes a cell surface tumor-associated protein of 180,000 daltons. The results of this study indicate that MoAb 135-13C binds with high affinity to Lewis lung tumor cells and induces different effects on the primary tumor (20%-25% reduction of tumor weight) and its metastasis (twofold increase of lung nodule formation). Different schedules of MoAb 135-13C administration have shown that these effects are dose- and time-dependent. In particular, the maximum increase in metastasis formation is observed when the MoAb 135-13C is administered at time of systemic tumor dissemination. In vitro preincubation of tumor cells with MoAb prior to their iv injection into normal animals results in a significant increase of pulmonary metastatic nodules.

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

Effects of dimethyltriazenes on in vitro Lewis lung carcinoma tumor lines with different metastatic capacity.

The effects of a selective antimetastatic agent: the aryldimethyltriazene derivative 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined on two in vitro tumor cell lines derived from lung metastases of Lewis lung carcinoma. These stabilized in vitro tumor cell lines named C108 and BC215 have been reported to differ in their metastatic potential evaluated as lung colony forming ability and as the number of spontaneous metastases produced after intramuscular implant of tumor cells. The cytotoxic effect of DM-COOK in vitro was also compared with the one demonstrated by the structure-related compound 4-(3,3-dimethyl-1-triazeno)imidazole-5- carboxamide (DTIC) on the same variant lines. Survival curves show a different chemosensitivity of the two in vitro lines to the DM-COOK treatment, whereas no differences were detected between C108 and BC215 after exposure to DTIC. Moreover, DM-COOK and DTIC exhibit different trends of cell killing, implying different mechanisms of action for the two drugs. Results are discussed in view of the selective in vitro action of the aryldimethyltriazene derivative DM-COOK on cells which express a high metastatic potential.

Animals↗
PubMed1983

Research on heterocyclic compounds. XIV - Imidazothiazole and imidazobenzothiazole derivatives: synthesis and antiinflammatory activity.

A group of ethyl 6-methylimidazo[2,1-b]thiazole-5-carboxylates and 2-methylimidazo[2,1-b]benzothiazole-3-carboxylates was prepared by reaction of ethyl 2-chloroacetoacetate with some 2-aminothiazoles and 2-aminobenzothiazoles, respectively. Such reactions may sometimes afford a side product which was isolated and characterized. The ethyl esters were then converted into the corresponding acids by hydrolysis. Three of these acids were evaluated for antiinflammatory, analgesic, and antipyretic activities, as well as for ulcerogenic potential.

Animals↗
PubMed1983

Association of elongation factor 2 with ribosomes during growth of a murine ascitic tumor.

The amount of elongation factor 2 (EF-2) associated with different ribosomal fractions (mono- and polyribosomes) isolated from a methylcholanthrene-induced sarcoma is estimated during tumor growth (exponential and plateau phase of growth). Direct EF-2 quantification is obtained by a modification of the method of the diphtheria toxin-catalyzed transfer of (14C)ADP-ribose from (14C)NAD+ to the enzyme. Data reported show that the amount of EF-2 associated with the monoribosomal fraction changes during tumor growth, and particularly, that this amount increases when the tumor cells enter into the plateau phase. In contrast, the EF-2 content of the polyribosomal fraction does not change during the different phases of tumor growth. Data also show that the amount of EF-2 bound to the monoribosomal fraction isolated from tumor cells is significantly and constantly lower than that of the corresponding fraction isolated from reticulocytes or hepatocytes. Moreover the tumor monoribosomes generated by the polyribosome breakdown induced by the "starvation" procedure did not show significant changes in their EF-2 content with respect to monoribosomes isolated from tumor cells maintained in physiological conditions. Besides, tumor monoribosomes generated by the polyribosome breakdown induced by puromycin or by running-off treatment exhibit a relevant increase of the EF-2 content. In these conditions the amount of EF-2 associated with the monoribosomes is similar to that associated with the monoribosomes of control cells (hepatocytes and reticulocytes). Results are discussed in view of a possible regulative role of the EF-2 enzyme in the ribosomal cycle of eukaryotic cells.

Animals↗
PubMed1982

DNA content distribution of in vivo and in vitro lines of Lewis lung carcinoma.

The kinetic features of Lewis lung carcinoma (3LL) and of two in vitro and two in vivo derivative lines were studied by flow cytometry. The in vitro lines C108 and BC215 show the same tetraploid DNA content and a very similar cell cycle structure, characterized by a prevalent S fraction. Also, the in vivo lines, the original 3LL and M1087, show a tetraploid DNA content, while the BM21548 is characterized by a hyperdiploid DNA mode and a broader distribution of DNA values. No difference in the modal DNA value is found between each primary tumor and the corresponding lung metastases for all the in vivo lines. In addition, an increase in the G1 component corresponding to a decrease in the S fraction is observed during the tumor growth. These kinetic features were related to some malignant properties of 3LL lines, such as growth pattern and metastatic potential. Our findings indicate that a direct correlation is not always possible to establish.

Animals↗
PubMed1982

[Lumbosciatica and nerve root anomalies].

The authors report 3 cases of lumbar pain and sciatica where operation revealed the existence of abnormalities in the distribution of L5 and S1 roots. In one case, the L5 root was not recognised within fibrous tissue also surrounding S1 and S2 and histological examination of this "fibrosis" led to the identification of nerve structures. Development of postoperative L5 paralysis showed that the L5 root was contained within the tissue non-individualised, consisting of multiple rootlets. In the other two cases the L5 and S1 roots arose from a common trunk. There was an associated herniated disc in all three cases. A review of the literature revealed the rarity of such abnormalities, as well as the fact that they were not recognised before surgery. They are difficult to recognise, even at the time of operation. The prognosis is less good than in typical lumbar pain and sciatica, essentially because of surgical difficulties of the disc curettage.

Adult↗
PubMed1982

Characterization of the steady-state population of the poly(adenylic acid) sequences in a rat hepatoma and in normal liver.

In steady state conditions, the content and size distribution of the poly(A) segments obtained by nuclease digestion of the total RNA from normal liver and a fast growing hepatoma (H 3924 A) are different. Evidence is presented for: an increase of the amount of poly(A) in the hepatoma; a more heterogeneous sedimentation profile of the poly(A) extracted from hepatoma, for the presence of segments of larger size; a different distribution pattern of the poly(A) associated to messengers of various size in the two tissues. These findings suggest an enhanced stability of the poly(A) sequences in the hepatoma, probably correlated to a reduced utilization of its messengers.

Animals↗
PubMed1981

Different metastatic potential of in vitro and in vivo lines selected from Lewis lung carcinoma: correlation with response to different bleomycin schedulings.

In vitro and in vivo variant cell lines selected from Lewis lung carcinoma are described. In vitro tumor lines are shown to differ in their metastatic potential, evaluated as lung colony-forming ability. Moreover, corresponding in vivo sublines, derived from intramuscular implant of cultured tumor cells, exhibit the same behavior for metastases formation as their in vitro counterpart. The metastatic potential of the in vivo lines has been evaluated both as lung colony-forming ability and as spontaneous metastasis formation. Response to bleomycin (BLM) treatment has been studied on the in vitro and the in vivo lines. Results reported show that the most metastatic lines, in vitro and in vivo, appear to be more resistant to a BLM treatment and that appropriate fractionation regimens can improve both the percentage of cell kill and the percentage of metastases reduction.

Animals↗