Biomedical subjects

W Pastori

Publications and source records attributed to W Pastori.

6 recordsLinked to original sources

PubMed1995

Decreased tyrosine phosphorylation in tumour cells resistant to FCE 24517 (tallimustine).

Resistance to FCE 24517 is not related to the emergence of any of the most frequently observed phenotypes. We have found that two resistant cell lines (L1210/24517 murine leukaemia and LoVo/24517 human colon adenocarcinoma) present congenital modifications in tyrosyl phosphatase and kinase activities. Moreover, the cytotoxic activity of FCE 24517 is increased in combination with a tyrosine phosphatase inhibitor and decreased in combination with protein kinase inhibitors, this being in agreement with the hypothesis that the activity of this drug is strictly dependent on the presence of tyrosine phosphorylated protein(s).

Adenocarcinoma↗

PubMed1994

New sulfonated distamycin A derivatives with bFGF complexing activity.

Tumor-induced neoangiogenesis is an essential event for solid tumor growth. Therefore, a compound able to block angiogenesis-promoting factors could have antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to have this mode of action. A series of sulfonated distamycin A derivatives have been synthesized with the objective of identifying novel compounds able to complex basic fibroblastic growth factor (bFGF) and other factors involved in tumour angiogenesis, and consequently to block the angiogenic process. These new compounds have been characterized for their ability to inhibit bFGF binding, in vivo bFGF-induced angiogenesis and neovascularization of the chorioallantoic membrane, in comparison with suramin. The two most active compounds, FCE 26644 [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole)carbonylimino))-bis(1,3-naphthalenedisulfonic acid)] and FCE 27164 [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole) carbonylimino)-bis (1,3,5-naphthalenetrisulfonic acid)] have been selected for extended evaluation. Both compounds are active in inhibiting platelet-derived growth factor beta (PDGF beta) and interleukin-1 beta binding. Two different assays have been performed to study their mode of action: the sequential binding assay on bFGF and PDGF receptors and the bFGF-induced tyrosine phosphorylation assay. The results of the two assays are in agreement and indicate that no activity is observed if FCE 26644, FCE 27164 and suramin are administered as pretreatment, when a direct interaction of the compounds with bFGF and PDGF receptors is required. Conversely, inhibitory activity is observed when the compounds are allowed to form complexes with the growth factors themselves.

3T3 Cells↗

PubMed1992

In vitro activity of novel sulphonic derivatives of distamycin A.

The successful growth of tumors is dependent on the process of vascularization elicited by the tumor itself. As confirmed by many authors, there is a correlation between the presence of factors that stimulate tumor growth and angiogenesis. One of the approaches we have explored to control angiogenesis has been to synthesize compounds able to complex growth factors. A number of sulphonated derivatives of distamycin A were found active in inhibiting the binding of bFGF and PDGF beta on Swiss 3T3 cells with ID50 values ranging between 142-587 microM for bFGF and 28-79 microM for PDGF beta. The effect of these new derivatives in inhibiting angiogenesis was initially explored in the chorioallantoic membrane assay. It was observed that the selected compounds were active in this model system at the concentration of 350 nm/pellet. These new molecules present low or no cytotoxic activity on M5076 murine reticulosarcoma cells, the ID50 values being higher than 60 microM after 72 h continuous exposure in vitro.

3T3 Cells↗

PubMed1986

The influence of amphotericin B on differentiation induced by dimethylsulfoxide and actinomycin D in HL60 and Friend cell lines.

We use murine erythroid Friend cells and human promyelocytic HL60 cells to investigate the influence of a transmembrane signal in triggering myeloid or erythroid cell differentiation. Combined treatments were given with dimethylsulfoxide, actinomycin D and amphotericin B, a substance which resembles a deviant membrane lipid and which seems to influence exclusively membrane activity. Our results suggest that a membrane modification alone is sufficient for in vitro HL60 cell differentiation, whereas both a transmembrane and a nuclear signal are necessary for Friend cell differentiation.

Amphotericin B↗

PubMed1984

Interaction of calcium ions and cAMP on the cytotoxic effect of doxorubicin.

Doxorubicin tested at the concentration of 1-2 X 10(-7)M inhibited the cloning efficiency of MS2T cells following 22 and 48 h exposure in complete medium. In the same experimental conditions the [3H]thymidine incorporation was practically unaffected. The inhibitory effect of doxorubicin on cloning efficiency appeared to be directly related with the serum concentration. In fact, this effect became more marked when the cloning efficiency was stimulated by increasing serum concentration in the cultural medium. However, this effect did not seem to be Ca2+ dependent. Similarly doxorubicin displayed a strong inhibitory effect, when the proliferative activity was stimulated by an optimal combination of cAMP and low Ca2+. On the contrary the inhibitory effect of doxorubicin was markedly reduced when the Ca2+ concentration reached the physiological value. These results confirm the direct correlation of the killing effect of doxorubicin with proliferative activity of the cells.

Animals↗

PubMedDate not supplied

In vitro and in vivo activity of alkylating bombesin receptor antagonists on small cell lung carcinoma.

Bombesin (BN) and bombesin-like peptides are autocrine growth factors for small cell lung carcinoma (SCLC). BN receptor antagonists can therefore find clinical application in the treatment of this highly malignant disease. Six peptides belonging to a new class of alkylating BN analogues have been selected according to their characteristics evidenced on Swiss 3T3 fibroblasts: high binding affinity to BN receptor, relevant inhibition (> 60%) of the proliferative stimulus induced by BN, long-lasting effect and specificity for BN receptor. The six peptides were able to bind BN receptors on SCLC cells and to inhibit the growth of two SCLC cell lines: NCI-H69 and NCI-N592. Conversely, they did not inhibit the growth of tumor cell lines devoid of BN receptors. Two of them were tested in vivo on N592 cells transplanted into nude mice. The peptide carrying a Cab [p-bis(2 chloroethyl)aminobenzoyl] moiety proved to be completely inactive. The second peptide, with a Melphalan moiety (Mel), showed a moderate activity (33-45% of tumor growth inhibition) without any toxicity. The low solubility of this compound prevented the use of the higher doses in vivo.

3T3 Cells↗