Because of its pivotal role in the recycling pathway allowing NAD generation from nicotinamide, NAMPT occupies a central position in controlling the activity of several NAD-dependent enzymes. NAD, a universal energy-and signal-carrying molecule and its phosphorylated form, NADP, are required in several intracellular processes such as redox reactions, DNA repair, G-protein coupled receptor signaling, intra-cellular calcium-mobilizing molecules, transcriptional regulation, mono-adenosine diphosphate (ADP)-ribosylation in immune response, and activity of poly-ADP ribosyltransferases and deacetylases (sirtuins) with roles in regulating cell survival and cytokine responses. Under the influence of NAMPT, adequate levels of NAD control SIRT-6 (sirtuin) activity, which in turn positively regulates TNF-α mRNA translation favoring cell survival. NAMPT activity enhances cellular proliferation, tips the balance toward cellular survival following a genotoxic insult and controls the circadian clock machinery of some key transcriptions factors.

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.

OBJECTIVE: Previous studies have shown that visfatin is significantly elevated in patients with gastric carcinoma and postmenopausal breast cancer (PBC). We thus explored whether serum visfatin could be used as a potential diagnostic and prognostic tool for PBC, taking into account clinicopathological features, serum tumor markers, anthropometric and metabolic parameters. METHODS: Serum visfatin, tumor marker CA 15-3, carcinoembryonic antigen, metabolic and anthropometric parameters were determined in 103 postmenopausal women with pathologically confirmed, incident invasive breast cancer, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum visfatin was significantly higher in cases than in controls and patients with BBL (p<0.001). In cases, visfatin was significantly associated with CA 15-3 (p=0.03), hormone-receptor status (p<0.001), lymph node invasion (p=0.06) but not with metabolic and anthropometric variables (p>0.05). Multivariable regression analysis revealed that absence of estrogen and progesterone receptors (ER-PR-) was the strongest significant determinant of serum visfatin (p<0.001) in cases adjusting for demographic, metabolic and clinicopathological features. Based upon receiver operator characteristic analysis, serum visfatin outperformed CA 15-3 only in discriminating between PBC cases with early cancer stage than those with late stage, and in differentiating particularly patients with ER-PR- breast tumors. CONCLUSION: Further prospective and longitudinal studies are needed to determine whether serum visfatin could be used as a prognostic tool in the armamentarium of PBC monitoring and management in conjunction with other biomarkers.

BACKGROUND: Lobomycosis, also known as Jorge Lobo's disease, represents a rare chronic subcutaneous mycosis caused by the fungus Lacazia loboi, an organism that is found within lesions but has not been cultured to date. The natural reservoir of L. loboi is unknown but it is believed to be aquatic, or associated with soil and vegetation. More than 550 human cases have been reported, especially in patients with a history of travel or residence in endemic areas (Central and South America, particularly Brazil) or in communities along rivers. MAIN OBSERVATIONS: We describe a 64-year-old Greek female farmer living in a coastal region, who presented with an erythematous plaque on her left inner thigh resembling a keloid. The diagnosis was based on the triad: 1) absence of fungal growth in cultures, 2) positive direct microscopic examination of the lesion and 3) histopathology, all consistent with lobomycosis. Particularly, skin biopsy showed deep cutaneous fungal infection with granulomatous reaction. Fungal cells were found inside giant cells. The fungi were thick-walled with some budding, isolated or in short chains. Dermal fibrosis was present. Our patient had a medical history of common variable immunodeficiency but no history of travel to South or Central America. She probably acquired this rare infection by injury during her agricultural works. CONCLUSION: Our case represents probably the first documented case of human lobomycosis in Southeastern Europe. This case is unusual due to the rarity of lobomycosis in Mediterranean countries, particularly in Southeastern Europe.

Worldwide breast cancer (BC) constitutes a significant public health concern. Excess body weight is associated with postmenopausal BC (PBC) risk. Recent studies have shown that the constellation of obesity, insulin resistance and serum adipokine levels are associated with the risk and prognosis of PBC. Nicotinamide phosphoribosyl-transferase (Nampt), also known as visfatin and pre-B-cell-colony-enhancing factor, found in the visceral fat, represents a novel pleiotropic adipokine acting as a cytokine, a growth factor and an enzyme. It plays an important role in a variety of metabolic and stress responses as well as in the cellular energy metabolism, particularly NAD biosynthesis. Nampt exhibits proliferative, anti-apoptotic, pro-inflammatory and pro-angiogenic properties. Nampt's insulin-mimetic function remains a controversial issue. Circulating Nampt levels are increased in obese women. Also, Nampt levels are significantly elevated in women suffering from PBC than in healthy controls independently from known risk factors of BC, anthropometric and metabolic parameters as well as serum concentrations of well known adipokines. High expression of Nampt in BC tissues was reported to be associated with more malignant cancer behavior as well as adverse prognosis. Taking into account the mitogenicity of Nampt as well as its proliferative, anti-apoptotic and pro-angiogenic properties, a novel hypothesis is proposed whereas Nampt may be involved in the etiopathogenesis of PBC and may represent a missing link between overweight/obesity and PBC. Nampt could exert its effects on the normal and neoplastic mammary tissue by endocrine and paracrine mechanisms; Nampt could also be secreted by tumor epithelial cells in an autocrine manner. It could stimulate mammary epithelial cell proliferation, invasion, metastasis, and angiogenesis, which is essential for BC development and progression. Serum Nampt might be a novel risk factor as well as a potential diagnostic and prognostic biomarker in PBC. In addition, pharmacologic agents that neutralize biochemically Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer agents. The potential harmful effect on PBC risk due to vitamin B3 (nicotinic acid, a natural NAD precursor in the biosynthetic route leading to NAD) intake is speculated for the first time. In this hypothesis, the role of Nampt in BC carcinogenesis and progression is explored as well as the pathophysiological mechanisms that underlie the association between Nampt and PBC in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against PBC.