C.A. Labarrere

Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells

A dried powder from basidiomycetous fungi, Ganoderma lucidum, has been used in East Asia in therapies for several different diseases, including cancer. However, the molecular mechanisms involved in the biological actions of Ganoderma are not well understood. We have recently demonstrated that phosphatidylinositol 3-kinase (PI 3-kinase) and nuclear factor-kappaB (NF-kappaB) regulate motility of highly invasive human breast cancer cells by the secretion of urokinase-type plasminogen activator (uPA). In this study, we investigated the effect of G. lucidum on highly invasive breast and prostate cancer cells. Here we show that spores or dried fruiting body of G. lucidum inhibit constitutively active transcription factors AP-1 and NF-kappaB in breast MDA-MB-231 and prostate PC-3 cancer cells. Furthermore, Ganoderma inhibition of expression of uPA and uPA receptor (uPAR), as well secretion of uPA, resulted in the suppression of the migration of MDA-MB-231 and PC-3 cells. Our data suggest that spores and unpurified fruiting body of G. lucidum inhibit invasion of breast and prostate cancer cells by a common mechanism and could have potential therapeutic use for cancer treatment.

Precision of biomarkers to define chronic inflammation in CKD.

Background/Aims: Several inflammatory biomarkers have been found to be associated with cardiovascular disease or all-cause mortality in dialysis patients, but their usefulness in clinical practice or as surrogate endpoints is not certain. The purpose of the present study was to determine the intrapatient variation of C-reactive protein, IL-6, fetuin-A and albumin in a population of dialysis patients. Methods: Apparently healthy dialysis patients with either a tunneled dialysis catheter or fistula had monthly assessments of these biomarkers for a total of four determinations, and the intraclass correlation coefficients were calculated as measures of intersubject variance. Results: Our results showed large within-subject variation relative to the total variation in the measurements (31–46%). Having a tunneled catheter as opposed to a fistula was not significantly associated with mean levels, suggesting that chronic subclinical catheter infection does not explain the variation seen in the biomarkers. In contrast, there was a rapid change in these biomarkers with a clinically apparent acute infection. Conclusion: These results suggest that these biomarkers have limitations for use as surrogate endpoints in clinical trials due to wide fluctuations, even in apparently clinically healthy individuals.

Microvascular prothrombogenicity and transplant coronary artery disease

A major impediment for the long-term success of heart transplantation is the development of transplant coronary artery disease (CAD). Several risk factors for the development of transplant CAD are associated with the transformation of a normal thromboresistant microvasculature into a prothrombogenic microvasculature. Prothrombogenicity is characterized by loss of anticoagulation (i.e. loss of antithrombin), loss of fibrinolytic activity (i.e., loss of tissue plasminogen activator) and presence of endothelial activation (i.e. upregulation of endothelial intercellular adhesion molecule-1 and major histocompatibility class II antigen human leukocyte antigen-DR) in the arterial allograft microvasculature. Microvascular prothrombogenicity during the first trimester after transplantation is directly associated with subsequent development of transplant CAD. Although the mechanisms responsible for the loss of thromboresistant endothelium are unclear, the fact that changes in the anticoagulant, fibrinolytic, and activational status of endothelial cells may occur early after transplantation suggests a peritransplant phenomenon as an initiating event. Reducing prothrombogenicity of the cardiac microvasculature early after transplantation could slow the development of transplant CAD and significantly improve allograft survival.

Interleukin-6 and risk of coronary artery disease and graft failure in heart transplant recipients

The difference in the COP and EP between the borderline donor subgroup and all others was not statistically significant. Post-transplant survival was not significantly different from recipients of normal cardiac allograft (p 0.43). Likewise for the high-risk recipient group, the COP and EP were at 72 and 203 days respectively. Although post-op survival was shorter than the normal risk group, both groups achieve a survival benefit. Conclusion: Heart transplantation has survival benefit in both these risk groups of recipients and donors in our population reflecting our rigorous donor and recipient selection and management.