During the past decade considerable evidence has mounted concerning the importance of growth factors in the wound healing process both for cell replication and for stimulating reparative cells to synthesize and secrete extracellular matrix components. During normal wound healing the growth factor concentration has to be maintained at a certain level. If the growth factor concentration is too low, normal healing fails to occur. Whereas if the growth factor concentration is too high due to either over-expression of the growth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between the beneficial therapeutic effect and toxic effects with increasing gene dosage, an agent may be necessary to give in combination with gene therapy to regulate the over-expression of growth factor. In addition to genetic approaches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound healing. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a particular collagen gene. This exogenous oligodeoxynucleotide will compete with the cis element in the collagen gene for the trans-acting factor which regulates promoter activity. These epigenetic approaches afford the opportunity to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approaches for regulating the wound healing process, either normal or aberrant wound healing, have certain advantages and disadvantages which are discussed in the present article.

Evaluation Studies as Topic↗

PubMedDate not supplied

Female lung cancer and petrochemical air pollution in Taiwan.

To investigate the relationship between petrochemical air pollution and female lung cancer, we conducted a matched case-control study among women who had died in Taiwan from 1990 through 1994. Data about all eligible female lung cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group included women who died from nonneoplasms and diseases that were not associated with respiratory problems. We pair-matched the controls to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. We used the proportion of a municipality's total population employed in the petrochemical manufacturing industry as an indicator of a resident's exposure to air emissions from the petrochemical manufacturing industry. The subjects were divided into tertiles according to the above indicator. Women who lived in the 2 groups of municipalities characterized by higher levels of petrochemical pollution had a statistically significant higher risk of developing lung cancer than the group that lived in municipalities with the lowest petrochemical air pollution levels (after controlling for possible confounders). The linear trend was also statistically significant (p < .05). The results of this study shed important light on the relationship between the Taiwan petrochemical industry and the resulting risk to human health.

Age Factors↗

PubMedDate not supplied

A sense phosphorothioate oligodeoxynucleotide containing the transforming growth factor beta regulatory element acts as a novel local nonsteroidal antifibrotic drug.

Fibrosis is a potential response to tissue injury. At present, glucocorticoids with their numerous toxic side effects are the only effective treatment for fibrotic diseases. Granulomas induced by sponge implantation were treated with single-stranded phosphorothioate oligodeoxynucleotides containing the wild type or mutated transforming growth factor-beta response element designed to inhibit the rat proalpha1(I) promoter activity. Single-stranded phosphorothioate oligonucleotides resulted in antifibrotic activity based on their ability to reduce granuloma tissue formation and selectively inhibit collagen synthesis. The mutated single-standed phosphorothioate oligonucleotides or dexamethasone given at an equivalent dose to single-standed phosphorothioate oligonucleotides failed to do so. These data suggest that the phosphorothioate oligodeoxynucleotide containing the transforming growth factor-beta regulatory element has an antifibrotic effect and may be used to inhibit the development of fibrosis.

Animals↗