Source:http://linkedlifedata.com/resource/pubmed/id/15585416
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
2004-12-8
|
| pubmed:abstractText |
The melanoma differentiation-associated gene-7 (mda-7; approved gene symbol IL24) is a tumor suppressor gene whose expression induces selective apoptosis in tumor cells. To characterize the safety and biologic activity of mda-7 gene transfer, we conducted a phase I trial using intratumoral injections of an adenovirus containing the mda-7 construct (Ad-mda7; INGN 241; 2 x 10(10) to 2 x 10(12) vp) in 28 patients with resectable solid tumors. One hundred percent of injected lesions demonstrated INGN 241 vector transduction, transgenic mRNA, elevated MDA-7 protein, and apoptosis induction, with the highest levels near the injection site. Apoptosis of cells in injected tumors was consistently observed even in heavily pretreated patients. INGN 241 vector DNA and mRNA were detected more than 1 cm from the injection site, whereas MDA-7 protein and bioactivity were more widely distributed. Toxicity attributable to the injections was self-limiting and generally mild; however, one patient experienced a grade 3 SAE possibly related to the study drug. Evidence of clinical activity was found in 44% of lesions with the repeat injection schedule, including complete and partial responses in two melanoma patients. Thus intratumoral administration of INGN 241 is well tolerated, induces apoptosis in a large percentage of tumor cells, and demonstrates evidence of clinically significant activity.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
1525-0016
|
| pubmed:author |
pubmed-author:ChadaSunilS,
pubmed-author:CoffeeKeithK,
pubmed-author:CunninghamC CaseyCC,
pubmed-author:HoodJillJ,
pubmed-author:MerrittJames AJA,
pubmed-author:MhashilkarAbnerA,
pubmed-author:NemunaitisJohnJ,
pubmed-author:ParkerKarenK,
pubmed-author:RichardsDonD,
pubmed-author:SenzerNeilN,
pubmed-author:TongAlexA,
pubmed-author:VukeljaSashaS,
pubmed-author:ZhangYuanY
|
| pubmed:issnType |
Print
|
| pubmed:volume |
11
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
149-59
|
| pubmed:dateRevised |
2006-4-21
|
| pubmed:meshHeading |
pubmed-meshheading:15585416-Adenoviridae,
pubmed-meshheading:15585416-Adult,
pubmed-meshheading:15585416-Aged,
pubmed-meshheading:15585416-Aged, 80 and over,
pubmed-meshheading:15585416-Biopsy,
pubmed-meshheading:15585416-Female,
pubmed-meshheading:15585416-Gene Expression,
pubmed-meshheading:15585416-Gene Therapy,
pubmed-meshheading:15585416-Genes, Tumor Suppressor,
pubmed-meshheading:15585416-Genetic Vectors,
pubmed-meshheading:15585416-Humans,
pubmed-meshheading:15585416-Injections,
pubmed-meshheading:15585416-Interleukins,
pubmed-meshheading:15585416-Kinetics,
pubmed-meshheading:15585416-Male,
pubmed-meshheading:15585416-Melanoma,
pubmed-meshheading:15585416-Middle Aged,
pubmed-meshheading:15585416-Neoplasm Staging,
pubmed-meshheading:15585416-Neoplasms,
pubmed-meshheading:15585416-RNA, Messenger,
pubmed-meshheading:15585416-Transgenes,
pubmed-meshheading:15585416-Treatment Outcome
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Clinical and local biological effects of an intratumoral injection of mda-7 (IL24; INGN 241) in patients with advanced carcinoma: a phase I study.
|
| pubmed:affiliation |
Mary Crowley Medical Research Center, Dallas, TX 75246, USA. casey.cunningham@usoncology.com
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Clinical Trial, Phase I
|