Search

Your search keyword '"Cerisano V"' showing total 3 results
Start Over Author "Cerisano V" Topic doxorubicin
3 results on '"Cerisano V"'

1. Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing's sarcoma cells.

Author

Benini S, Manara MC, Baldini N, Cerisano V, Massimo Serra, Mercuri M, Lollini PL, Nanni P, Picci P, and Scotlandi K

Subjects
Antibodies, Monoclonal metabolism, Apoptosis, Bromodeoxyuridine metabolism, Cell Cycle, Cell Division, Cell Nucleus drug effects, Dose-Response Relationship, Drug, Humans, Suramin pharmacology, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Bone Neoplasms drug therapy, Doxorubicin pharmacology, Receptor, IGF Type 1 antagonists & inhibitors, Sarcoma, Ewing drug therapy, Vincristine pharmacology
Abstract

Innovative treatment modalities are needed for Ewing's sarcoma (ES), a neoplasm with a disappointingly low survival rate despite the use of aggressive multimodal therapeutic approaches. We and others (D. Yee et al., J. Clin. Investig., 86: 1806-1814, 1990; K. Scotlandi et al., Cancer Res., 56: 4570-4574, 1996) have previously shown the existence and the pathogenetic relevance of an autocrine loop, mediated by the insulin-like growth factor-I receptor (IGF-IR), which is crucial for survival and proliferation of ES cells in vitro. Moreover, we reported that the IGF-IR-blocking monoclonal antibody (MAb), alphaIR3, as well as suramin, a drug that can interfere with growth factor by binding to the receptors, inhibited both the tumorigenic and the metastatic ability of ES cells in athymic mice. In this study, we analyzed whether agents that can block the IGF-IR-mediated loop are of value in association with conventional cytotoxic drugs for the design of more effective therapeutic regimens. Both alphaIR3 MAb and suramin treatment significantly increased the antitumor in vitro effects of doxorubicin and vincristine, two drugs with a leader action on ES. These findings were obtained by both simultaneous and sequential treatments. Analysis of the proliferation rate and of apoptosis revealed that alphaIR3 MAb and suramin significantly enhanced the G(1)-phase rate induced by doxorubicin, without substantially affecting doxorubicin-G(2)-M-blockage of cell cycle, and significantly increased the induction of apoptosis, which confirmed that the specific blockage of IGF-IR deprives ES cells of an important tool for the prevention of drug-induced apoptosis. Moreover, combination treatments of doxorubicin plus alphaIR3 MAb significantly increase the doxorubicin-induced impairment of the ability of ES cells to form colonies in soft agar. In conclusion, we showed that, in ES, the blockage of IGF-IR by a neutralizing MAb or by suramin may greatly potentiate the antitumor activity of conventional chemotherapeutic drugs.

Published
2001

2. Expression of an IGF-I receptor dominant negative mutant induces apoptosis, inhibits tumorigenesis and enhances chemosensitivity in Ewing's sarcoma cells

Author

Scotlandi K., Avnet S., Benini S., Manara M. C., Serra M., Cerisano V., Perdichizzi S., Lollini P. -L., De Giovanni C., Landuzzi L., Picci P., Scotlandi K., Avnet S., Benini S., Manara M.C., Serra M., Cerisano V., Perdichizzi S., Lollini P.-L., De Giovanni C., Landuzzi L., and Picci P.

Subjects
Time Factors, Time Factor, Cell Survival, Blotting, Western, Mice, Nude, Apoptosis, Sarcoma, Ewing, Transfection, Receptor, IGF Type 1, Mice, Tumor Cells, Cultured, Animals, Insulin-like growth factor-I, Chemosensitivity, Tumorigenesi, Animal, Apoptosi, Ewing's sarcoma, Gene Expression Regulation, Neoplastic, Survival Rate, Doxorubicin, Dominant negative mutant, Mutation, Nude mice, Cell Division, Neoplasm Transplantation
Abstract

IGF-IR plays an essential role in the establishment and maintenance of the transformed phenotype of ES cells and interference with the IGF-IR pathways causes reversal of the malignant potential of this neoplasm. In this report, we stably transfected a dominant negative IGF-IR expression plasmid in an ES cell line to determine the effectiveness of this strategy against the in vitro and in vivo growth of ES cells. DXR sensitivity of TC-71 cells expressing dominant negative mutants of IGF-IR was also examined. The mutated IGF-IR that we used carries a mutation in the ATP-binding domain of the intracellular β subunit, while the extracellular, ligand-binding α subunit remains unchanged. Cells carrying the dominant mutant IGF-IR had a marked decrease in proliferation, a significant increase in anoikis-induced apoptosis and a severely reduced ability to form colonies in soft agar. In vivo, when cells carrying dominant negative IGF-IR were injected into nude mice, the tumor formation and metastatic abilities of ES cells were reduced and survival increased. Furthermore, transfected clones showed significantly higher sensitivity to DXR, a major drug in the treatment of ES. These results indicate that the IGF/IGF-IR stimulation of ES cells may be inhibited by expression of mutated IGF-IR on their surfaces and that this strategy may be considered a possible alternative to impair this important target of ES cells, whose therapeutic potential was further confirmed. © 2002 Wiley-Liss, Inc.

Published
2002

3. CD99 engagement: An effective therapeutic strategy for Ewing tumors

Author

Scotlandi K, Baldini N, Cerisano V, Mc, Manara, Benini S, Serra M, Pier Luigi Lollini, Nanni P, Nicoletti G, Bernard G, Bernard A, and Picci P

Subjects
Osteosarcoma, Antibodies, Monoclonal, Mice, Nude, Apoptosis, Bone Neoplasms, Sarcoma, Ewing, 12E7 Antigen, Jurkat Cells, Mice, Antigens, CD, Doxorubicin, Vincristine, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, Animals, Humans, Female, Cell Adhesion Molecules, Cell Division, Cell Aggregation
Abstract

CD99 is a Mr 32,000 transmembrane molecule that shows a high level of expression on cells of the hemopoietic system as well as on Ewing tumor cells. Within the hematopoietic system, CD99 has been implicated in cell adhesion and cell death, participating in this way in the differentiation of T-cell precursors. In this study, we demonstrate that engagement of CD99 significantly inhibits the in vitro and in vivo growth ability of Ewing tumor cells by delivering an apoptotic stimulus and reducing the malignant potential of these cells. Moreover, we show that anti-CD99 monoclonal antibodies may be advantageously used in association with conventional anticancer agents. These results provide a novel entry site for therapeutic intervention, which may have application in the care of patients with Ewing tumor, and warrant additional studies to clarify the molecular mechanisms activated by CD99 engagement.

Catalog

Books, media, physical & digital resources
See catalog results