Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma.

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Abstract Text:

Vaani Garg,Wendong Zhang,Pooja Gidwani,Mimi Kim,E Anders Kolb,Vaani Garg,Wendong Zhang,Pooja Gidwani,Mimi Kim,E Anders Kolb,

PURPOSE: Dolastatins are a group of structurally unique peptides originally isolated from a sea hare, Dolabella auricularia, which seem to inhibit tubulin polymerization and mitosis. Tasidotin hydrochloride (tasidotin), a novel synthetic analogue of dolastatin 15, is evaluated in preclinical models of pediatric tumors. EXPERIMENTAL DESIGN: The cytotoxicity of tasidotin was evaluated in a panel of pediatric sarcoma cell lines in vitro and in vivo. RESULTS: The IC(50) in Ewing's sarcoma, rhabdomyosarcoma, osteosarcoma, and synovial sarcoma lines ranged from 0.002 micro to 0.32 micromol/L. In the SK-ES1 and RH30 cell lines, tasidotin induced a G(2)-M arrest that persisted for 48 h after the drug was washed from the cells. In vitro, more than half the cells were in the early or late phase of apoptosis 48 h after treatment with tasidotin. In vivo, a significant increase in apoptotic nuclei was apparent in xenograft tumors harvested within 24 h after a 5-day course of tasidotin. In vivo response was determined in severe combined immunodeficient xenograft models of pediatric sarcomas implanted heterotopically. Significant antitumor activity was observed in all tumor lines tested. A complete response was observed in 2 synovial sarcoma lines, 1 osteosarcoma line, 1 rhabdomyosarcoma line, and 1 Ewing's sarcoma line. A partial response was observed in 1 rhabdomyosarcoma and 1 Ewing's sarcoma. CONCLUSIONS: Tasidotin induces a G(2)-M block in treated cells ultimately resulting in apoptosis. Antitumor activity is confirmed in vivo in preclinical xenograft models of pediatric sarcomas.

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Publishing Authors By Initials

V Garg,W Zhang,P Gidwani,M Kim,EA Kolb,V Garg,W Zhang,P Gidwani,M Kim,EA Kolb,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 5446-54

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: Sep

YEAR: 2007

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502500

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma.

AFFILIATION: Tufts University School of Medicine, Boston, Massachusetts, USA.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Clin Cancer Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma Related Publications

• A golgi analysis of cortical pyramidal cells in the unilateral parkinson rat: absence of change in the affected hemisphere vs hypertrophy in the intact hemisphere.
• Allogeneic bone marrow transplantation in leukemia.
• An evaluation of lobotomy and its potentialities for future research in psychiatry and the basic sciences.
• Animal models of pulmonary fibrosis: how far from effective reality?
• Chronic phencyclidine treatment increases dendritic spine density in prefrontal cortex and nucleus accumbens neurons.
• Classically conditioned withdrawal reflex in cerebellar patients. 1. Impaired conditioned responses.
• Comparison of the electrically evoked leg withdrawal reflex in cerebellar patients and healthy controls.
• Detection of changes in grip forces on a sliding object.
• ELECTROPHYSIOLOGICAL INVESTIGATIONS IN RETINAL METABOLIC DISEASE: THEIR RANGE AND APPLICATION.
• Eyeblink conditioning in patients with hereditary ataxia: a one-year follow-up study.
• Grouped comparisons of sleep quality for new and personal bedding systems.
• Neurophysiological properties of cells filling the neonatal medial prefrontal cortex lesion cavity.
• Potential-induced structure changes of oligopyridine adlayers on Au(111) electrodes.
• Preclinical analysis of tasidotin HCl in Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma.
• Progressive pulmonary fibrosis is mediated by TGF-beta isoform 1 but not TGF-beta3.
• Responses of cerebellar units to a passive movement in the decerebrate cat.
• Secondary hyperparathyroidism and brown tumors in a patient with gluten enteropathy.
• Social instability blocks functional restitution following motor cortex stroke in rats.
• The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?
• The posterior interosseous nerve syndrome.
• Three-dimensional computed tomography imaging in an animal model of emphysema.
• Use of soy protein isolate in slimming food.
• [Chances and risks of prevention in elderly people for the three major cancers: breast-, prostate- and colorectal cancers]
• [Diagnostic and treatment goals in elderly patients.]
• [Obliteration of the cervical canal following curettage.]
• [Perforation of the uterus with injury of the bladder during curettage for climacteric hemorrhage.]
• [Some characteristic moments from the work of the medical service of the partisan units in the southern Morava river basin during 1941-1943]
• [Some observations on taking the examination for captain and major in the medical service.]
• [Strategies for the avoidance and treatment of complications during pacemaker implantation.]
• [Various observations on the medical service in the army.]