Nerve growth factor (NGF) is a member of the neurotrophin family and is essential for the differentiation and maintenance of neural cells. Recently, it has been reported that NGF is involved in the growth of breast cancer. On the other hand, two types of NGF receptors have been identified, a low-affinity receptor, p75NGFR, and a high-affinity receptor, TrkA. NGF-p75NGFR interaction is known to play an important role in apoptosis, whereas NGF-TrkA interaction is responsible for the survival of neural cells. We examined the relationship between clinicopathological factors, Ki-67 index, apoptotic index and the immunohistochemical expression of NGF, TrkA and p75NGFR in 71 invasive ductal breast carcinoma (IDBC) specimens. Our data indicate that positive Ki-67 expression (a labeling index exceeding 30%) correlates significantly with the positive expression of NGF (p=0.0091). Moreover, the apoptotic index was found to correlate with a strong expression of p75NGFR. Furthermore, patients who were NGF positive and p75NGFR negative had significantly poorer disease-free survival rates (p=0.0165). In contrast, those who were NGF negative and p75NGFR positive had significantly more favorable outcomes (p=0.0191). These findings suggest that a combined evaluation of NGF and p75NGFR expression is a predictive factor in the prognosis of IDBC patients.

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PubMedDate not supplied

Particle-mediated gene transfer of murine interleukin-12 cDNA suppresses the growth of Lewis lung carcinoma.

We evaluated the effectiveness of the Helios gene gun system, a recently developed, commercially available gene gun device. Following skin transfection with beta-galactosidase or interleukin-12 cDNA using the gene gun, beta-galactosidase expression was detected exclusively in the epidermal cell layer, and transgene expression of IL-12 cDNA was maximal 2 days post-transfection and remained detectable for at least 5 additional days. Furthermore, particle-mediated delivery of IL-12 cDNA into epidermal cells overlying an intradermal tumor resulted in a significant suppression of tumor growth of Lewis lung carcinoma. Appreciable levels of IFN-gamma production were readily detected at the skin transfection site, and were induced from splenocytes and lymph node cells in the IL-12 treated mice. These results show that in vivo delivery of IL-12 cDNA into skin by the Helios gene gun device can have a useful routine application for cancer therapy research.

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