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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1996-1-29
|
| pubmed:abstractText |
Our laboratory, in collaboration with Oxigene Inc, has been involved in identifying commercially feasible clinical applications of measurement or modulation of ADP-ribosylation as a core technology. For this purpose a pivotal regulatory role for ADP-ribosylation in the repair of DNA lesions leading to cytotoxic as well as mutagenic events has been hypothesized. A new class of DNA repair inhibitors, the N-substituted benzamides, has been identified which can react with radiation to produce reactive intermediates that oxidize thiol amino acids. Their proposed mechanisms of action are two-fold: ie they can interact with radiation: i) to directly enhance DNA damage; and ii) to react with thiols in the zinc finger DNA binding domain of poly ADP-ribosyl transferase to inhibit DNA repair and thereby increase DNA damage. Sensamide, a clinically relevant formulation of metoclopramide which is an N-substituted benzamide, has indicated enhancement of tumor response and survival in patients with inoperable squamous cell carcinoma of the lung when it was administered as a radiosensitizer in a phase I/II trial and compared to historical controls. A mechanism of endogenous regulation of human mononuclear leucocyte ADP-ribosylation has been identified to be HOCl/N-chloramine production via the oxidative burst of phagocytes. HOCl/N-chloramines are potent oxidants of thiol-containing proteins. Quantitative estimation of N-chloramine sensitive plasma thiols has been identified as an effective surrogate measure of leucocyte poly ADPRT.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Metoclopramide,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Poly Adenosine Diphosphate Ribose,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Sensitizing Agents
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0300-9084
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
77
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
385-93
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8527494-Animals,
pubmed-meshheading:8527494-Antineoplastic Agents,
pubmed-meshheading:8527494-Carcinoma, Squamous Cell,
pubmed-meshheading:8527494-Clinical Trials, Phase I as Topic,
pubmed-meshheading:8527494-Clinical Trials, Phase II as Topic,
pubmed-meshheading:8527494-DNA,
pubmed-meshheading:8527494-DNA Damage,
pubmed-meshheading:8527494-DNA Repair,
pubmed-meshheading:8527494-Humans,
pubmed-meshheading:8527494-Leukocytes, Mononuclear,
pubmed-meshheading:8527494-Lung Neoplasms,
pubmed-meshheading:8527494-Metoclopramide,
pubmed-meshheading:8527494-Mutagens,
pubmed-meshheading:8527494-Oxidative Stress,
pubmed-meshheading:8527494-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:8527494-Poly Adenosine Diphosphate Ribose,
pubmed-meshheading:8527494-Radiation-Sensitizing Agents,
pubmed-meshheading:8527494-Zinc Fingers
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Progress in identifying clinical relevance of inhibition, stimulation and measurements of poly ADP-ribosylation.
|
| pubmed:affiliation |
Department of Molecular Ecogenetics, University of Lund, Sweden.
|
| pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
|