Linked Life Data

16178003

Source:http://linkedlifedata.com/resource/pubmed/id/16178003

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-10-24
pubmed:abstractText
The proteasome is responsible for the degradation of intracellular proteins, including several involved in cell cycle control and the regulation of apoptosis. Preclinical studies have shown that the proteasome inhibitor bortezomib decreases proliferation, induces apoptosis, enhances the activity of chemotherapy and radiation, and reverses chemoresistance in a variety of hematologic and solid malignancy models in vitro and in vivo. Proteasome inhibition with bortezomib has specifically promoted apoptosis of tumor cells through the stabilization of p53, p21, p27, Bax, and IkappaBalpha, resulting in nuclear factor kappaB inhibition. Bortezomib was the first proteasome inhibitor to enter clinical trials. In two Phase II trials, SUMMIT and CREST, it was found that treatment with bortezomib, alone or in combination with dexamethasone, produced durable responses with meaningful survival benefits in patients with recurrent and/or refractory multiple myeloma. In the APEX Phase III trial, bortezomib produced significant survival benefits and improved response rates over high-dose dexamethasone at first recurrence and beyond in patients with multiple myeloma. Clinical trials evaluating the safety and activity of bortezomib alone or in combination regimens with dexamethasone, doxorubicin, melphalan, prednisone, and/or thalidomide in the treatment of patients with newly diagnosed multiple myeloma have shown encouraging results. Preliminary studies suggest that bortezomib may serve as induction therapy before stem cell transplantation. Proteasome inhibition with bortezomib also has shown activity with manageable toxicity in mantle cell and other lymphomas, leukemias, and solid malignancies, including nonsmall cell lung carcinoma. Further studies with bortezomib as monotherapy and in combination regimens in the treatment of solid and hematologic malignancies are warranted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-543X
pubmed:author
pubmed:copyrightInfo
(c) 2005 American Cancer Society.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1794-807
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies.
pubmed:affiliation
First Department of Medicine and Medical Oncology, Wilhelminenspital, Vienna, Austria. heinz.ludwig@wienkav.at
pubmed:publicationType
Journal Article, Review