Learn More About Hyaluronic Acid

Hyaluronic acid (also called Hyaluronan) is a component of connective tissue whose function is to cushion and lubricate.  Hyaluronan occurs throughout the body in abundant amounts in many of the places people with hereditary connective tissue disorders have problems such as joints, heart valves and eyes.  Hyaluronic acid abnormalities are a common thread in connective tissue disorders.  Interestingly, they are also common biochemical anomalies in most of the individual features of connective tissue disorders such as mitral valve prolapse, TMJ, osteoarthritis, and keratoconus. 

Hyaluronic acid has been nicknamed by the press as the “key to the fountain of youth” because it has been noted that at least some people who ingest a lot of it in their diets tend to live to ripe old ages. ABC News had a show on a village in Japan and hyaluronic acid entitled, “The Village of Long Life: Could Hyaluronic Acid Be an Anti-Aging Remedy?”. (It should be noted that the people in the ABC news show were thought to get high amounts of HA from starchy root vegetables their natural diets. They were not taking supplements.)

While a number of studies have linked abnormal levels of hyaluronic acid to either connective tissue disorders (CTDs) or conditions common in CTDs, such as premature aging, there are also a number of studies on Pubmed noting associations of high levels of hyaluronic acid to some forms of cancer. With HA as with other substances in the human body, such as estrogen and cholesterol, there are most likely optimal levels, and disease often occurs when these levels become out of range in either direction. Low estrogen levels have been linked to bone loss, while high estrogen levels have been associated with breast cancer. High cholesterol levels have been linked to heart attacks and stroke, while low levels have been linked to bleeding problems and depression. HA has been studied less than either cholesterol or estrogen, but the prudent path would be to assume that the body has optimal levels of HA, as it does for cholesterol, estrogen and many other substances.

Hyaluronic acid (HA) is a glycosaminoglycan (GAG), which is a substance that attaches to collagen and elastin to form cartilage. HA not only helps keep the cartilage that cushions joints strong and flexible, but also helps increase supplies of joint-lubricating synovial fluid.

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Mesothelioma and Epithelial Differentiation

One interesting study is called, “Effects of glycosaminoglycans on proliferation of epithelial and fibroblast human malignant mesothelioma cells: a structure–function relationship” by Christopher Potten, Zbigniew Darzynkiewicz, Kohsuke Sasaki, A. Syrokou, G. Tzanakakis, T. Tsegenidis, A. Hjerpe, N. K. Karamanos – Cell Proliferation Volume 32, Issue 2-3, pages 85–99, April 1999.  Here is an excerpt: “Abstract. Proteoglycans interact with other effective macromolecules regulating a variety of cellular events via their glycosaminoglycan (GAG) chains. The effects of all known glycosaminoglycans (GAGs) produced by normal cells and tissues on the proliferation of two human malignant mesothelioma cell lines, one with fibroblast-like morphology and the other with epithelial differentiation – both able to produce hyaluronan (HA), galactosaminoglycans (GalAGs) and heparan sulphate (HS) containing proteoglycans – have been studied. Cell proliferation was assessed by measuring [3H]thymidine incorporation and cell number. GalAGs, i.e. chondroitin sulphates (CSs) and dermatan sulphate (DS), strongly stimulate the proliferation of fibroblast-like cells in a dose-dependent manner (170–250% at 100 ?g/ml), independently of their sulphation pattern. In epithelial cells, however, only DS stimulates cell proliferation. The effects of CSs on proliferation of epithelial cells are not depended on their sulphation pattern. Thus, CSs either with -[GlcA-GalNAc-(-6-O-SO3?)]- or -[GlcA-GalNAc-(-4-O-SO3?]- as the commonest unit, had no significant effect. l-Iduronic acid (IdoA)-rich heparin and fast-moving HS (fm-HS), a HS fraction with a heparin-like structure, had significant antiproliferative effects on mesothelioma cells of both types (30–70% at 1.0 ?g/ml and 85–90% at 100 ?g/ml, respectively). GlcA-rich HS, however, had no significant effects. HA inhibits only the proliferation of fibroblast-like cells by 25% at 50 and 100 ?g/ml. Keratan sulphate suppresses cell proliferation (10–30%) in both cell lines. In the view of these findings, a structure–function relationship of GAGs on cell proliferation of the two human malignant mesothelioma cell lines is discussed. Other factors, such as chain conformation and geometry, as well as interactions of growth factors with GAGs, possibly involved in the regulation of cell proliferation, are also discussed.”

Another study is called, “The value of Wilms tumor susceptibility gene 1 in cytologic preparations as a marker for malignant Mesothelioma” by Jonathan L. Hecht M.D., Ph.D., Benjamin H. Lee M.D., Ph.D., Jack L. Pinkus Ph.D., Geraldine S. Pinkus M.D., – Cancer Cytopathology Volume 96, Issue 2, pages 105–109, 25 April 2002.  Here is an excerpt: “Abstract – It has been shown that detection of the Wilms tumor susceptibility gene 1 protein (WT1) has diagnostic utility in the distinction of mesothelioma from adenocarcinoma in tissue sections of pleural tumors. This immunohistochemical study evaluates the effectiveness of WT1 as a marker for malignant mesothelioma in paraffin sections of cell block preparations derived from effusion specimens.  METHODS The authors evaluated 111 cell blocks for WT1 immunoreactivity, including 14 mesotheliomas and 97 metastatic adenocarcinomas from various sites.  RESULTS Nuclear reactivity for WT1 was observed in all samples of mesothelioma. However, only 22 of 97 samples (23%) of metastatic adenocarcinoma, nearly all of which were of ovarian origin (91%), exhibited nuclear reactivity for WT1. In 14 other samples (most of pulmonary derivation), WT1 staining restricted to the cytoplasm was observed for some tumor cells and was regarded as nonspecific.  CONCLUSIONS – Based on this staining profile, WT1 represents an effective marker for mesotheliomas in cell block preparations and can aid in its distinction from pulmonary adenocarcinoma. In assessment of effusion specimens with metastatic carcinoma, nuclear reactivity for WT1 is highly suggestive of an ovary primary tumor.

Wilms tumor susceptibility gene 1 is a tumor suppressor gene that initially was identified due to its deletion or mutation in Wilms tumors. Monoclonal antibodies to its protein product, WT1, were developed subsequently, and it was found that they had diagnostic utility not only in the identification of Wilms tumors and desmoplastic small round cell tumors1, 2 but also in the distinction of mesothelioma from adenocarcinoma in pleural tumors.3, 4 This immunohistochemical study evaluates the diagnostic utility of WT1 as a marker for malignant mesothelioma in paraffin sections of cell block preparations derived from effusion specimens.  Cancer (Cancer Cytopathol) 2002;96:000–000.

Another study is called, “Value of E-cadherin and N-cadherin immunostaining in the diagnosis of Mesothelioma” by ORDONEZ Nelson G. 2, Allée du Parc de Brabois F-54514 Vandoeuvre-lès-Nancy – Cedex France.  Here is an excerpt: “Abstract – Distinguishing between epithelioid mesothelioma and pulmonary adenocarcinoma involving the pleura can be difficult on routine histological preparations. This differential diagnosis can be greatly facilitated by using immunohistochemical markers. E-cadherin and N-cadherin are among the newly described markers that have been proposed as potentially useful in the diagnosis of mesothelioma. E-cadherin and N-cadherin are members of the cadherin family of calcium-dependent cell adhesion molecules that play an important role in the embryogenic development and maintenance of normal tissue. Although several investigations have indicated that immunostaining for these markers can be useful in discriminating between mesotheliomas and adenocarcinomas, others have not confirmed this observation. In an attempt to resolve this controversy, the present study investigated 31 epithelioid mesotheliomas and 29 pulmonary adenocarcinomas for E-cadherin and N-cadherin expression using the 5H9, HECD-1, and clone 36 anti-Ewadherin antibodies, and the 3B9 and clone 32 anti-N-cadherin antibodies. Among the mesotheliomas, 68% reacted with the clone 36, 52% reacted with the HECD-1, and 19% reacted with the 5H9 anti-Ecadherin antibodies, and 74% reacted with the 3B9 and 71% reacted with the clone 32 anti-N-cadherin antibodies. Of the adenocarcinomas, 93% stained with the done 36, 90% reacted with the HELD-1, and 90% reacted with the 5H9 anti-Ecadherin antibodies, 45% reacted with the clone 32 and 34% reacted with the 3B9 anti-N-cadherin antibodies. Based on the frequent strong reactivity with adenocarcinomas but not with mesotheliomas, it is concluded that only the 5H9 anti-Ecadherin antibody may have some utility in discriminating between epithelioid pleural mesotheliomas and pulmonary adenocarcinomas. The causes of the disparate results reported in the literature on the value of E-cadherin and N-cadherin immunostaining in distinguishing between mesotheliomas and pulmonary adenocarcinomas are unclear, but a significant factor appears to be differences in the reactivity of the antibodies used.”

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.

By: Montwrobleski77

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Monty Wrobleski is the author of this article.  For more information please click on the following links
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