Effects of oleuropein on tumor cell growth and bone remodelling: Potential clinical implications for the prevention and treatment of malignant bone diseases.

Oleuropein (Ole) is the main bioactive phenolic compound present in olive leaves, fruits and olive oil. This molecule has been shown to exert beneficial effects on several human pathological conditions. In particular, recent preclinical and observational studies have provided evidence that Ole exhibits chemo-preventive effects on different types of human tumors.

On the role of cystatin C in cancer progression.

Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases, which has been shown to play a role in several normal and pathological processes. Interestingly, a growing number of experimental and clinical studies suggest that this inhibitor also appears to be implicated in the malignant progression of various human tumors. However, the role of Cyst C in malignant diseases is still controversial as these studies have highlighted that this protein may function either as tumor suppressor or tumor promoter.

Clinical Impact of Cystatin C/Cathepsin L and Follistatin/Activin A Systems in Breast Cancer Progression: A Preliminary Report.

This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively.

Vitamin D in cancer chemoprevention.

Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo.

Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy.

Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar.

Flavonols and flavan-3-ols as modulators of xanthine oxidase and manganese superoxide dismutase activity.

Experiments were performed to assess the dose-dependent effects of quercetin, kaempferol, (+) catechin, and (-) epicatechin on superoxide radical production through the modulation of manganese superoxide dismutase and xanthine oxidase activities. The experiments were carried out at flavanoid concentrations ranging from 1 µM to 100 µM. This investigation highlighted that flavonols induced opposite effects on superoxide radical production at different doses, i.

Follistatin as potential therapeutic target in prostate cancer.

Follistatin is a single-chain glycosylated protein whose primary function consists in binding and neutralizing some members of the transforming growth factor-β superfamily such as activin and bone morphogenic proteins. Emerging evidence indicates that this molecule may also play a role in the malignant progression of several human tumors including prostate cancer. In particular, recent findings suggest that, in this tumor, follistatin may also contribute to the formation of bone metastasis through multiple mechanisms, some of which are not related to its specific activin or bone morphogenic proteins' inhibitory activity.

Serum follistatin in patients with prostate cancer metastatic to the bone.

The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional cytokine activin A (Act A), was investigated in patients with prostate cancer (PCa). The serum concentrations of this molecule were determined by an enzyme-linked immunosorbent assay (ELISA) in PCa patients with (M+) or without (M0) bone metastases, in patients with benign prostate hyperplasia (BPH) and in healthy subjects (HS). The effectiveness of FLST in detecting PCa patients with skeletal metastases was determined by the receiver operating characteristic (ROC) curve analysis.

Cathepsin L in metastatic bone disease: therapeutic implications.

Cathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests that this endopeptidase might also be implicated in the regulation of other important biological functions, including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodeling processes, could contribute to facilitate bone metastasis formation.

Circulating cathepsin K and cystatin C in patients with cancer related bone disease: clinical and therapeutic implications.

The clinical significance of serum cathepsin K and cystatin C was assessed in patients with breast cancer (BCa) or prostate cancer (PCa) with confined disease (M0) or bone metastasis (BM). Cathepsin K and cystatin C circulating levels were determined by ELISAs in 63 cancer patients, in 35 patients with nonmalignant diseases and in 42 healthy blood donors (control group). In BCa patients, cathepsin K serum levels were significantly lower than in sex matched control group (HS; p=0.

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer.

Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male).

Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases.

Background: The effects of the bisphosphonate derivative zoledronic acid (ZA) on the circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in patients with bone metastasis (BMTS) and the possible correlation with the symptomatic response induced by this drug in these patients were evaluated.

Patients And Methods: Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the plasma of 30 patients with painful bone metastases from breast or prostate cancer undergoing multiple treatment with ZA (4 mg i.v.

Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications.

Cathepsin D is a lysosomal acid proteinase which is involved in the malignant progression of breast cancer and other gynecological tumors. Clinical investigations have shown that in breast cancer patients cathepsin D overexpression was significantly correlated with a shorter free-time disease and overall survival, whereas in patients with ovarian or endometrial cancer this phenomenon was associated with tumor aggressiveness and a degree of chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate the role and the prognostic value of cathepsin D also in other solid neoplasms.