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  • 1
    Language: English
    In: Medicinal Research Reviews, July 2005, Vol.25(4), pp.383-397
    Description: The short chain fatty acid valproic acid (VPA) and VPA‐analogs modulate the biology of diverse tumor cell entities by inducing differentiation, inhibiting proliferation, increasing apoptosis, and immunogenicity and by decreasing metastatic and angiogenetic potential. This review updates an earlier one in 2002, reflecting the interest in VPA as a potent anticancer drug. A number of studies show that the types of known tumor cells susceptible to VPA is steadily increasing. Of special note is the strong antineoplastic activity of VPA in chemoresistant cancer cells. A novel and promising approach is combining VPA with other drugs to achieve a broad therapeutic index. Clinical studies are underway and the preliminary results indicate that VPA alone or in combination offers a promising avenue of treatment, both in solid and hematopoetic malignancies. © 2005 Wiley Periodicals, Inc.
    Keywords: Valproic Acid ; Hdac ; Differentiation ; Angiogenesis ; Combination Therapy ; Clinical Studies
    ISSN: 0198-6325
    E-ISSN: 1098-1128
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  • 2
    Language: English
    In: Medicinal research reviews, July 2005, Vol.25(4), pp.383-97
    Description: The short chain fatty acid valproic acid (VPA) and VPA-analogs modulate the biology of diverse tumor cell entities by inducing differentiation, inhibiting proliferation, increasing apoptosis, and immunogenicity and by decreasing metastatic and angiogenetic potential. This review updates an earlier one in 2002, reflecting the interest in VPA as a potent anticancer drug. A number of in vitro studies show that the types of known tumor cells susceptible to VPA is steadily increasing. Of special note is the strong antineoplastic activity of VPA in chemoresistant cancer cells. A novel and promising approach is combining VPA with other drugs to achieve a broad therapeutic index. Clinical studies are underway and the preliminary results indicate that VPA alone or in combination offers a promising avenue of treatment, both in solid and hematopoetic malignancies.
    Keywords: Antineoplastic Agents -- Pharmacology ; Valproic Acid -- Pharmacology
    ISSN: 0198-6325
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 3
    In: Anti-Cancer Drugs, 1997, Vol.8(10), pp.958-963
    Description: Sodium valproate (VPA) belongs to the group of simple branched-chain fatty acids and due its anticonvulsive activity is broadly applied in the treatment of epilepsy. We previously showed that VPA is able to induce cellular differentiation, to enhance immunogenicity and to inhibit proliferation of human neuroblastoma (NB) cells in vitro. Furthermore, we demonstrated that VPA inhibits proliferation, enhances neural cell adhesion molecule expression and decreases CD44 expression of human and rat glioma cells in vitro. In the present study we investigated the anttitumoral effects of VPA on established human NB xenografts from UKF-NB-3 human NB cells in athymic (nude) mice. When the animals developed s.c. tumors of about 100 mm volume they were treated with 400 or 200 mg/kg/day VPA i.p. At the end of the treatment period (40 days) tumor volumes in animals treated with 400 and 200 mg/kg VPA were about 4− (p〈 0.0001) and 2-fold (p〈 0.0005) smaller than in the saline-treated control group, respectively. Histological examination of the remnant tumors of treated animals revealed induction of differentiation by induction of stroma-rich tumors and nodules that contained elongated NB cells. Pyknotic nuclei and apoptotic bodies indicated induction of apoptosis. We conclude that VPA is able to abrogate NB growth in vivo and may therefore be useful in the treatment of NB patients.
    Keywords: Antineoplastic Agents -- Pharmacology ; Neuroblastoma -- Drug Therapy ; Valproic Acid -- Pharmacology;
    ISSN: 0959-4973
    E-ISSN: 14735741
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