Therapeutic renaissance of thalidomide in the treatment of haematological malignancies

Ribatti, Doménico; Vacca, Angelo

doi:10.1038/sj.leu.2403852

Cited by 56 publications

(30 citation statements)

References 101 publications

(91 reference statements)

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“…The pathways to block both cell populations in terms of receptors, growth factors and intracellular signaling proteins, are circled. them, and alters the secretion and bioactivity of cytokines they release into the bone marrow milieu (Ribatti and Vacca, 2005). Treatment with two classes of thalidomide analogs, namely selected cytokine inhibitory drugs and immunomodulatory drugs, may alter MM adhesion to BMSC and fibronectin, and abrogate the upregulation of IL-6 and VEGF induced by tumor cell binding.…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

2006

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Tumor microenvironment is essential for tumor cell proliferation, angiogenesis, invasion and metastasis through its provision of survival signals, secretion of growth and pro-angiogenic factors, and direct adhesion molecule interactions. This review examines its importance in the induction of an angiogenic response in multiple myeloma (MM). The encouraging results of preclinical and clinical trials in which MM has been treated by targeting the tumor microenvironment are also discussed.

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Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

2006

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“…La talidomide agisce come costimolatore, aumentando la risposta dei linfociti T alla stimolazione mediata dal recettore per i linfociti T, determinando un aumento della produzione di IL-2, IL-10 e interferon-γ (INFγ) (10,(18)(19)(20). Infine, la talidomide inibisce l'angiogenesi mediata dal vascular endothelial growth factor (VEGF) e dal fibroblast growth factor-2 (FGF-2) (21).…”

Section: Thalidomide Is An Immunomodulatory Anti-inflammatory and Anunclassified

Thalidomide in treatment of connective diseases and vasculities

Maruotti¹,

Cantatore²,

Ribatti³

2011

Reumatismo

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MECCANISMO D'AZIONEI meccanismi attraverso cui si esplicano le attività immunomodulatoria, antinfiammatoria e antiangiogenica della talidomide appaiono interconnessi, anche se non ancora completamente chiariti. La talidomide è capace di ridurre la quota circolante dei linfociti T CD4+ e quindi il rapporto CD4/CD8 (7-9). Favorisce l'aumento del numero delle cellule Natural Killer (NK) (10) e dei linfociti T helper 2 rispetto ai linfociti T helper 1. Inoltre, la talidomide inibisce la proliferazione di linfociti T attivati e la chemiotassi leucocitaria (9, 11, 12) ed è responsabile di modificazioni nella espressione delle integrine e del CD44 e dell'Intercellular Cell Adhesion Molecule-1 (ICAM-1). La talidomide può inoltre bloccare il ciclo cellulare in G1 nelle cellule tumorali per l'induzione di p21, favorendo l'apoptosi (11, 13). Molti studi dimostrano che la talidomide inibisce la produzione del tumor necrosis factor α (TNFα) attraverso un'aumentata degradazione del mRNA del TNFα e il legame dell'α-1glicoproteina acida (9,14). La talidomide inoltre blocca l'attività del fattore di trascrizione L a talidomide, introdotta sul mercato nel 1956 come farmaco sedativo-ipnotico usato anche come antiemetico e per il trattamento della nausea in gravidanza, fu successivamente ritirata dal commercio nel 1962 a causa dei seri effetti teratogeni come sordità, difetti facciali e del palato, focomelia in bambini nati da donne che avevano assunto anche una sola dose di talidomide durante la gestazione (1, 2). Tuttavia, a partire dal 1965 è stata riutilizzata, talvolta con discreto successo, in molte patologie, tra cui l'eritema nodoso associato alla lebbra, il morbo di Crohn, l'insufficienza cardiaca congestizia avanzata, sarcoidosi cutanee, ulcere orali e cachessia associate ad infezione da HIV e svariati tipi di tumori solidi ed ematologici. In questa sede verrà descritto in modo più approfondito l'utilizzo della talidomide nel trattamento del lupus eritematoso sistemico e della sindrome di Behçet (3-6). Reumatismo, 2006; 58(3):187-190 TNFα, SUMMARY Thalidomide is an immunomodulatory, anti-inflammatory and anti-angiogenic drug. Thalidomide exerts its effects by decreasing circulating CD4 positive T-cells and stimulating CD8 positive T-cells, by increasing the number of Natural Killer cells and T-helper 2 cells. Thalidomide also inhibits proliferation of stimulated T-cells and leukocyte chemotaxis. It modifies a number of integrin receptors and other leukocytic surface receptors and down-modulates cell-adhesion molecules involved in leukocyte migration. It has been demonstrated that thalidomide inhibits

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“…Thalidomide is being increasingly used in the treatment of various malignant and nonmalignant hematologic disorders [1,2]. It has immuno-and cytokine-modulatory properties and antiangiogenic activity [3].…”

Section: Introductionmentioning

confidence: 99%

Isolated thrombocytopenia induced by thalidomide in a patient with multiple myeloma: Case report and review of literature

Prasad¹,

Kaushal²,

Mehta³

2007

American J Hematol

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Thalidomide is being increasingly used in hematology and oncology. Its use is associated with neuropathy, sedation, edema, fatigue, constipation, and deep venous thrombosis. Cytopenias are unusual, but there are case reports. However, there are no reports of isolated thrombocytopenia. We describe here a case of prolonged isolated thrombocytopenia most likely caused by thalidomide. The patient's in platelet count decreased promptly after an increase in the dose and improved after discontinuation of the drug. The relevant literature is reviewed. Am. J. Hematol. 82:855-857, 2007. V

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Therapeutic renaissance of thalidomide in the treatment of haematological malignancies

Cited by 56 publications

References 101 publications

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

Thalidomide in treatment of connective diseases and vasculities

Isolated thrombocytopenia induced by thalidomide in a patient with multiple myeloma: Case report and review of literature

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