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Biomedical subjects

G Atassi

Publications and source records attributed to G Atassi.

133 records · Page 8Linked to original sources
PubMedDate not supplied

Phenotypic change of the transplantable MXT mammary adenocarcinoma into mixed bone producing sarcoma-like tumors.

The B6D2F1 mouse mammary adenocarcinoma was adapted to grow in vitro as monolayer. After in vitro passaging of tumor cells, phenotypic changes occurred that were expressed in vivo. Following intraperitoneal inoculation of tumor cells, bone-forming tumors developed. These tumors consisted of undifferentiated adenocarcinoma mixed with large amount of cartilagenous and osseous tissue. The etiology of these phenotypic changes was not yet determined. However, hypothesis of the possible origin of the cartilage and bone forming tissue was formulated. The biologic characterization of the intraperitoneally bone-forming tumor was achieved and the experimental conditions to preserve and induce the reproducible sarcoma-like bone forming tumors were defined. Our data support the usefulness of this new original model for fundamental research as well as for screening of anticancer drugs.

Adenocarcinoma↗
PubMedDate not supplied

Influence of inoculation sites and tumor cell culture techniques on the phenotype of a mixed cartilage- and bone-producing mouse mammary tumor.

We have previously reported the characterization of an intraperitoneally (IP) transplantable bone-forming MXT tumor. However, the question was unresolved as whether the bone-forming cells originated from either the host animal or from the neoplasm itself. The present work attempts to answer this question by studying the influences of inoculation sites (subcutaneously, SC; intraperitoneally, IP; in the brain, IB; intracranially, ICR) on both the cartilage- and bone-forming tumor phenotypes. Furthermore the influence of cell culture procedures (two- and three- dimensional cultures) on these phenotypes was investigated. SC administered MXT cancer cells never produce bone-forming tumors, suggesting the existence in the dermis of substance(s) inhibitory to the formation of cartilage or bone. On the contrary, our data clearly demonstrate that bone-forming tumors can be obtained by either IP route, in a way which mimics endochondral ossification, or in the brain (IB), a region usually devoid of connective tissue. This observation substantiates the hypothesis according to which the tumor itself is able to produce osseous tissue. Another main finding is the increasing occurrence of skeletal tissues produced by cells proceeding from three-dimensional culture. Finally, ICR and IB tumors exerted a bone-lytic action against the host skull suggesting that tumor cells either produce osteolytic substances (prostaglandins, enzymes) and/or that they contain various cell types exhibiting different properties toward osteogenesis. This model offers new perspectives for studying the mechanisms of both normal and pathologic osteogenesis.

Animals↗
PubMedDate not supplied

Effect of duration of exposure to S9788, cyclosporin A or verapamil on sensitivity of multidrug resistant cells to vincristine or doxorubicin.

In order to explain the high potency of S9788, a new multidrug resistance modifier currently in clinical development, we investigated its accumulation and retention in sensitive and resistant cells. Our results show that S9788 is 13-fold more accumulated and 23-fold more retained than VRP in the resistant S1/tMDR cell line. We also studied the effect of duration of incubation on the ability of S9788, verapamil and cyclosporin A to overcome the resistance of S1/tMDR and KB-A1 cells to a short exposure of doxorubicin or vincristine. Compared to a single co-incubation of 4 h, a 24 h post-incubation with 5 microM S9788 markedly increased the reversal of S1/tMDR resistance to VCR (fold reversal 4 h = 123; fold reversal 24 h = 4739), while it moderately increased S1/tMDR sensitivity to DOX (fold reversal 4 h = 1.9; fold reversal 24 h = 2.9). Similar results were obtained on KB-A1 resistance to VCR (fold reversal 4 h = 41, fold reversal 24 h = 21819) and KB-A1 resistance to DOX (fold reversal 4 h = 89; fold reversal 24 h = 160). This phenomenon also occurred with verapamil and cyclosporin A. These results clearly show that the effect of duration of exposure on the modulating activity of S9788 and of the 2 other modulators depends on the cytotoxic drug. Although the direct transposition of these results to a clinical situation is difficult, they suggest that a continuous infusion of S9788, starting simultaneously with the administration of the cytotoxic drug and ending 24 h later, might be a more effective schedule for clinical administration than a bolus administration.

Antineoplastic Agents↗