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-   -   cox2 inhibitors seem to impeed bone mets (https://her2support.org/vbulletin/showthread.php?t=24220)

Lani 06-15-2006 03:52 PM

cox2 inhibitors seem to impeed bone mets
 
Wish the study was done on other cell lines as well to be more applicable to her2+s:
ABSTRACT: Stimulation of Cyclooxygenase-2 Expression by Bone-Derived Transforming Growth Factor-? Enhances Bone Metastases in Breast Cancer [Cancer Research; Subscribe]
Cyclooxygenase-2 (COX-2), the rate-limiting enzyme of prostaglandin synthesis, has been implicated in invasiveness and distant metastases of cancer. Bone is one of the most common target sites of cancer metastasis. However, the role of COX-2 in bone metastasis is unclear. We examined the surgical specimens of bone metastases from patients with various types of cancers by using immunohistochemistry and observed evident COX-2 expression in these bone metastases. In a nude mouse model of bone metastasis, the MDA-MB-231 human breast cancer cells showed no COX-2 expression at orthotopic sites, whereas these cells, when metastasized to bone, intensely expressed COX-2, suggesting that the bone microenvironment induced COX-2 expression. Consistent with this notion, inhibition of bone resorption by the bisphosphonate ibandronate reduced COX-2 expression in MDA-MB-231 cells in bone. Transforming growth factor-? (TGF?), one of the most abundant growth factors stored in bone, increased COX-2 expression and prostaglandin E2 production in MDA-MB-231 cells in culture. MDA-MB-231 cells overexpressing dominant-negative TGF? type II receptors showed decreased bone metastases and reduced osteoclastic bone resorption with impaired COX-2 expression. The COX-2 inhibitors, NS-398 and nimesulide, significantly suppressed bone metastases with decreased osteoclast number and increased apoptosis in MDA-MB-231 cells. These results suggest that bone-derived TGF? up-regulates COX-2 expression in breast cancer cells, thereby increasing prostaglandin E2 production, which in turn, stimulates osteoclastic bone destruction, leading to the progression of bone metastases. Our results also suggest that COX-2 is a potential therapeutic target for bone metastases in breast cancer.

R.B. 06-16-2006 03:19 AM

In my wanders I have seen several suggestions that the inflamatory and related pathways are related to movement of cancer to the bone.

Also that the same pathways are related to osteoporosis etc.

At the head of these pathways and the raw material for it is omega six. It is recognised that the amount of omega six has increased hugely in the past 100 years, and continues to do so.

RB

Esther 06-16-2006 08:28 AM

I read that there was a study being done in Canada using 100 mg of doxycicline and Celebrex, and were having great results in maintaining stability or achieving some regression in BC bone mets.

Would sure be an inexpensive treatment,with few if any side effects.


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