| Bronchioalveolar
lung carcinoma (BAC) is a subset of adenocarcinoma
for which precise etiology is not known. Although
a majority of adenocarcinoma is etiologically
associated with tobacco smoke and other pollutants,
a large portion of BAC occurs without tobacco
smoking history. Most characteristic genetic predisposition
associated with BAC is k-ras gene mutation. Despite
early surveillance and development of new therapeutic
agents, incidence of BAC is increasing and its
prognosis is still poor. BAC is resistant to chemotherapy
and radiation therapy. Gene therapy for lung cancer
has been hopeful, yet clinically unsuccessful
because of an insufficient cancer tissue-specific
gene delivery. We recently demonstrated successful
cancer tissue-targeted interferon (IFN)-ß
gene delivery using adult mesenchymal stem cell
prepared from human umbilical cord matrix (hUCMSC).
Our preliminary data indicate that this stem cell-expressed
IFN-ß substantially attenuated lung metastasized
breast cancer xenografts in vivo. In this study,
we will test our hypothesis that 1) genetically
engineered adult stem cells which express cancer
cell toxic IFN-ß are specifically delivered
to BAC sites; 2) the engineered stem cell significantly
attenuates BAC cancer growth in mouse model with
k-ras mutation; 3) this stem cell-based therapy
does not damage any normal tissue. Our treatment
strategy is significantly better than existing
therapeutic strategies, including surgical therapy
followed by radiation and chemotherapies, since
we anticipate far fewer side effects. If our hypothesis
is proven correct, although this study will be
conducted using the mouse model, this procedure
will be applied to human patients in the future.
Therefore, this study is feasible, scientifically
valuable and has high potential for future human
application.
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