Although the pharmacology and clinical application of water extracts of Ganoderma lucidum have been extensively documented, little is known regarding its alcohol extract. In the present study, the anti-tumor effect of an alcohol extract of Ganoderma lucidum was investigated using MCF-7 cells. We found that the alcohol extract of Ganoderma lucidum inhibited cell proliferation in a dose-and time-dependent manner, which might be mediated through up-regulation of p21/Waf1 and down-regulation of cyclin D1. Furthermore, this compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and not by the immune system. Our findings suggest that there are multiple mechanisms underlying the anti-tumor effects of Ganoderma lucidum. © 2002 Wiley-Liss, Inc. Key words: ganoderma lucidum; breast cancer; cell cycle; apoptosis An increasing number of natural occurring chemical compounds have been identified to be potent in the treatment of various human diseases including cancer. 1-4 Many of these substances are found in oriental herbs or plants. Recently, some chemopreventive extracts of herbs or plants have been shown to be anti-tumorigenic. [5][6][7][8] Carcinogenesis is a multistage or multimechanism process, involving the irreversible alteration of a stem cell (the "initiation" phase), followed by the clonal proliferation of the initiated stem cell (the "promotion" phase), from which the acquisition of the invasive and metastatic phenotypes are generated (the "progression" phase). 9 Cancer prevention or therapy may be accomplished at different steps of this process by different mechanisms. Mixed extract of herbs or plants might contain different chemopreventive chemotherapeutic compounds with more than one mechanism of action, thus possessing a combination of different chemopreventive or chemotherapeutic effects. It is therefore very attractive and important to identify combination effects of mixed extract of herbs or plants.Ganoderma lucidum, an oriental fungus, has been widely used as a medical drug or health-promotion product in China and other Asian countries. The fruiting bodies and cultured mycelia of Ganoderma lucidum have been demonstrated to possess anti-tumor activities, 10 -18 immunomodulatory activities, 19 -20 and neuroactive effects. 21 Although numerous studies on the effects of water extracts of GL have been reported, 10 -16 little is known regarding its alcohol extracts. It has been reported that the alcohol extract of Ganoderma lucidum can induce cell cycle arrest at transition from G1 to S phase in HeLa-cells 17 This study was designed to further investigate the anti-tumor effects of alcohol extracts of Ganoderma lucidum and elucidate the potential mechanisms using an in vitro system. We found that the alcohol extract of Ganoderma lucidum was able to induce cell cycle arrest at G1 phase and induce apoptosis in MCF-7 cells in a time-dependent manner. The mechanisms might be mediated through up-regulation of the expression of p21/Waf1-a...

In a world where increasing joint arthroplasties are being performed on increasingly younger patients, osteolysis as the leading cause of failure after total joint arthroplasty (TJA) has gained considerable attention. Ultra-high molecular weight polyethylene wear-induced osteolysis is the process by which prosthetic debris mechanically released from the surface of prosthetic joints induces an immune response that favors bone catabolism, resulting in loosening of prostheses with eventual failure or fracture. The immune response initiated is innate in that it is nonspecific and self-propagating, with monocytic cells and osteoclasts being the main effectors. To date, detecting disease early enough to implement effective intervention without unwanted systemic side effects has been a major barrier. These barriers can be overcome using newer in vivo imaging techniques and modules linked with fluorescence and/or chemotherapies. We discuss the pathogenesis of osteolysis, and provide discussion of the challenges with imaging and therapeutics. We describe a positron emission tomography imaging cinnamoyl-Phe-(D)-Leu-Phe-(D)-Leu-Phe-Lys module, specific to macrophages, which holds promise in early detection of disease and localization of treatment. Further research and increased collaboration among therapeutic and three-dimensional imaging researchers are essential in realizing a solution to clinical osteolysis in TJA.

Symptomatic intervertebral disc degeneration is associated with several spinal diseases, which cause losses of life quality and money. Tissue engineering provides a promising approach to recover the functionality of the degenerative intervertebral disc. Most studies are directed toward nucleus pulposus (NP) tissue engineering because disc degeneration is believed to originate in NP region, and considerable progress has been made in the past decade. Before this important technique is utilized for clinical treatment of disc degeneration, many challenges need to address including in all three principal components of tissue engineering, i.e., seed cells, signals and biomaterial scaffolds. This article briefly gives certain aspects of state of the art in this field, as well as pays a little more attention to our work published in the past 5 years, on growth and differentiation factor-5 (GDF-5), adipose-derived stem cells (ADSCs) and heparin functionalization of scaffold. We suggest that combinatorial application of ADSCs, GDF-5, heparin functionalization and injectable hydrogels will be advantageous in NP tissue engineering.

Anulus fibrosus cells isolated from nondegenerative intervertebral discs can differentiate into adipocytes, osteoblasts, chondrocytes, neurons, and endothelial cells in vitro.