Studies on fibrotic pulmonary disorders have demonstrated Shh in both human and mouse lung restricted to areas of active disease. Acute lung injury has also shown upregulated expression and together this data is highly suggestive for a functional role for Shh signalling in adult lung injury and disease. We propose that hedgehog signalling may contribute to epithelial injury and repair and act as an intermediary in cross-talk between damaged epithelium and the immune/inflammatory system
Shh has also been shown to upregulate Bcl-2 in T lymphocytes, a step linked with memory T lymphocyte generation, 4 and thus, Shh at sites of injury might also serve to ensure adaptive immunity to damaging antigens, or an exacerbation of autoimmunity. Given that many of the diseases associated with Shh expression contain elements of autoimmunity or immune dysregulation, this crosstalk could have important implications both for the initiation and maintenance of a disease process.

Concluding Comments

The potential for post embryonic recapitulation of developmental signals in injury and disease presents many exciting targets for therapeutic modulation. This is particularly true for the pulmonary system, where the air interface facilitates the direct and rapid delivery of short half life Hh modulating agents to target cells. This will avoid the systemic complications of treatment that might be expected in the treatment of conditions such as multiple sclerosis and Parkinsons disease. Our knowledge of the Hh signalling pathway and its role in development has made great advancements over recent years and has led to the development of many new and exciting ideas which may identify functions for the Hh pathway in post-embryonic systems

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Cancer Lett. 2006 Jan 27;

Activation of the hedgehog pathway in a subset of lung cancers.

Chi S, Huang S, Li C, Zhang X, He N, Bhutani MS, Jones D, Castro CY, Logrono R, Haque A, Zwischenberger J, Tyring SK, Zhang H, Xie J.

School of Life Sciences, Institute of Developmental Biology, Shandong University, Jinan, People's Republic of China.

Activation of the hedgehog pathway is reported in lung cancer, but its frequency remains unknown. We examine activation of this pathway in lung cancers by in situ hybridization and immunohistochemstry, and find that less than 10% of the tumors have elevated hedgehog target gene expression. We further identify a cell line NCI-H209 and two primary tumors with no detectable Su(Fu), a negative regulator of the pathway. Ectopic expression of Su(Fu) in NCI-H209 cells down-regulates hedgehog target gene expression and leads to inhibition of cell proliferation. These data indicate that activation of the hedgehog pathway is activated through Shh over-expression or Su(Fu) inactivation in only a subset of lung cancers.

HH,

Is this the entire article "subset of cancers" or just a summary of it?

Thanks,loaded with info. Good board. Good job!

[quote="Anonymous"]HH,

Is this the entire article "subset of cancers" or just a summary of it?

Thanks,loaded with info. Good board. Good job![/quote]

Most of these articles are abstracts or summary.

There are different types of lung cancers. For example, there are non-small cell lung cancer and small cell lung cancers. Small cell lung cancer (SCLC) is often fatal and has not have a good current treatment. Hh pathway activation has been show in about 50% of human SCLC. Hh inhibitors seem to work well on MOST SCLC that show Hh activation. See possible IND with Genentech and also “Lung Cancer Therapy” in this thread. It talks a little more in detail about SCLC and hedgehog. Beachy also has a patent for SCLC and Hh inhibitors