Saturday, April 8, 2017

BREAST CANCER RESEARCH RIGHT NOW! #53: Lymphedema and Fibrosis

From the first moment my wife discovered she had breast cancer, there was a deafening silence from the men I know. Even ones whose wives, mothers or girlfriends had breast cancer seemed to have received a gag order from some Central Cancer Command and did little more than mumble about the experience. Not one to shut up for any known reason, I started this blog…

Every month, I’ll be highlighting breast cancer research that is going on RIGHT NOW! Harvested from different websites, journals and podcasts, I’ll translate them into understandable English and share them with you. Today:

So, I found out something new: the hardening of the skin due to lymphedema is NOT peculiar to breast cancer!

Last month, the following Keystone Symposium was held: “Injury, Inflammation, and Fibrosis: Fibrosis is a common response of many organs to chronic injury and inflammation. This leads to destruction of organ architecture with loss of function. Until recently, there have been no therapies to slow the progression of fibrosis and to maintain normal organ function. Recent advances have provided new insights into the pathogenesis of fibrosis, new drug targets, and new drugs in clinical studies. This conference will bring together basic biologists and translational and clinical researchers to discuss core mechanisms underlying inflammation and fibrosis, to compare and contrast fibrotic diseases, preclinical models, the potential for regeneration and regression of fibrosis, and potential therapies. The interaction between the host genetics, the environment and the microbiome in the pathogenesis of fibrotic diseases will be addressed. Also, non-invasive methods to assess fibrosis including advanced imaging and intermediate biomarkers will be discussed. This conference will be a unique opportunity for investigators who are focused on organ-specific diseases – i.e., medical subspecialists – to participate in cross-disciplinary, multi-organ discussions in order to gain new insights into their research. ”

A brief reading of the papers presented don’t address fibrosis following the removal of lymph nodes due to radical mastectomy, but it appears to ME (remember, I’m a layman – a biology (and chemistry, physics, astronomy, etc.) teacher with about 30 years of classroom teaching experience) that several of the subjects covered seem to me to have lymphedema applications.

I suppose I SHOULD clarify what they’re talking about above: “Long standing lymphedema causes a condition known as fibrosis. As the fluid continually collects in a limb, it becomes hard and dense. With each stage of lymphedema there is also a change in the tissue texture of a limb. Each stage of lymphedema presents additional difficulties and worsening of fibrosis, if treatment is not received. Initially, there is no fibrosis associated with lymphedema. It is also important to remember that the size of a limb (arm lymphedema, leg lymphedema) is NOT an indication of how much fibrosis there is.  I have seen very slightly swollen legs that were as hard as a rock because of late stage fibrosis.”

Surprisingly, I just realized that I have seen fibrosis – it happened to my mother because of her Congestive Heart Failure (CHF). Her legs were essentially normal in size, but had become so rigidly hard (she refuse to do physical therapy, allow her legs to be wrapped, or even, eventually to walk at all…) that lymphorrea – “the light amber colored fluid that drains from open skin areas (wounds) on a lymphodemous limb. It is not normal plasma, but is a protein-rich substance that can lead to serious complications for the lymphedema patient. The composition of lymphorrhea is approximately 1.0=5.5 g/ml of protein” -- leaked from her legs on a regular basis.

Back to the Symposium: While none of the papers  is currently available, I’ll be looking for them in the coming months and waiting to see if any of the research is being applied. While my area of interest is fibrosis of the limbs, it’s clear that fibrosis can happen to the heart, liver, kidneys, skin (in a condition that an old friend of mine had called scleroderma), and bile ducts.

In particular I’ll be looking to see if any of this new information…leaks…into the field of lymphedema of the extremities: MicroRNAs as Potential Therapeutic Targets in Fibrotic Diseases, Mitochondrial Priming by Matrix Stiffness Sensitizes Myofibroblasts to BH3 Mimetic-Induced Apoptosis in Scleroderma Fibrosis, Multistep Cancer-Associated Fibroblast Activation: A Notch/CSL-Gli Regulatory Axis, Cellular and Molecular Heterogeneity of Fibroblast Responses in Mouse Model of Dermal Fibrosis, Molecular Signatures of Collagen-Producing Cells in Multiple Models of Pathologic Tissue Fibrosis.

We shall see!


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