Keloids and hypertrophic scars are sequelae of abnormal healing after orofacial injury. These conditions represent debilitating derangements in remodeling and are associated with impaired function and significant dysmorphea. They are defined largely by an abnormal accumulation of extracellular matrix. Recently, remarkable similarities have been found between the generation of tumor stroma and the healing of wounds.
The aim of this pilot study is to investigate whether keloids are the result of a trauma-induced neoplastic process or simply an inflammatory response to injury; this will be accomplished by studying expression by abnormal scar tissues of CD44 variant isoforms, known markers for neoplastic tissue.
The specific aims are: 1. To survey tissues derived from normal skin (NSk), normal scar (NSc), hypertrophic scar (HSc) and keloid for variant CD44 isoforms known to be markers for neoplastic lesions. 2. To synthesize cDNA probes for the different CD44 variant isoforms found in neoplastic lesions and to use them to assess variant isoform gene expression. Briefly tissues obtained from human NSk, NSc, HSc and keloids will be screened by immunohistochemistry techniques for CD44 variant isoforms using specific antibodies against these molecules. Also, cDNA probes for the various CD44 isoforms will be synthesized, in order to study their gene expression by these tissues using Northern blot analysis and in situ hybridization. These findings will aid in understanding the pathogenesis of keloid formation and whether it is a trauma-induced neoplastic process or a reactive response to injury. In either case, if CD44 variant isoforms are present and expressed differentially in cases of normal versus abnormal scar tissues, these results are expected to lead to additional studies using variant-specific CD44 monoclonal antibodies as tools in developing new strategies for diagnosis and, perhaps, treatment of hypertrophic scars and keloids. Most importantly, this work as potential for offering new insight into the basic biology of abnormal scar formation in minorities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
5P50DE010598-08
Application #
6201790
Study Section
Project Start
1999-08-01
Project End
2002-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Spolsky, Vladimir W; Marcus, Marvin; Der-Martirosian, Claudia et al. (2012) Oral health status and the epidemiologic paradox within Latino immigrant groups. BMC Oral Health 12:39
Glynn, Shirley M (2010) The psychosocial characteristics and needs of patients presenting with orofacial injury. Oral Maxillofac Surg Clin North Am 22:209-15
Glynn, Shirley M; Shetty, Vivek (2010) The long-term psychological sequelae of orofacial injury. Oral Maxillofac Surg Clin North Am 22:217-24
Lui, Anna; Glynn, Shirley; Shetty, Vivek (2009) The interplay of perceived social support and posttraumatic psychological distress following orofacial injury. J Nerv Ment Dis 197:639-45
Shetty, Vivek; Atchison, Kathryn; Leathers, Richard et al. (2008) Do the benefits of rigid internal fixation of mandible fractures justify the added costs? Results from a randomized controlled trial. J Oral Maxillofac Surg 66:2203-12
Marshall, Grant N; Schell, Terry L; Glynn, Shirley M et al. (2006) The role of hyperarousal in the manifestation of posttraumatic psychological distress following injury. J Abnorm Psychol 115:624-8
Shetty, Vivek; Atchison, Kathryn; Der-Martirosian, Claudia et al. (2003) Determinants of surgical decisions about mandible fractures. J Oral Maxillofac Surg 61:808-13
Shetty, Vivek; Dent, Dr Med; Glynn, Shirley et al. (2003) Psychosocial sequelae and correlates of orofacial injury. Dent Clin North Am 47:141-57, xi
Leathers, Richard; Le, Anh D; Black, Edward et al. (2003) Orofacial injury in underserved minority populations. Dent Clin North Am 47:127-39
Atchison, Kathryn A; Dubin, Linda Fagan (2003) Understanding health behavior and perceptions. Dent Clin North Am 47:21-39

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