Giorgio Olivetti

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Bone Marrow-Derived Stem Cells:A Mixed Blessing in the Multifaceted World of Diabetic Complications

Diabetes is one of the main economic burdens in health care, which threatens to worsen dramatically if prevalence forecasts are correct. What makes diabetes harmful is the multi-organ distribution of its microvascular and macrovascular complications. Regenerative medicine with cellular therapy could be the dam against life-threatening or life-altering complications. Bone marrow-derived stem cells are putative candidates to achieve this goal. Unfortunately, the bone marrow itself is affected by diabetes, as it can develop a microangiopathy and neuropathy similar to other body tissues. Neuropathy leads to impaired stem cell mobilization from marrow, the so-called mobilopathy. Here, we review the role of bone marrow-derived stem cells in diabetes: how they are affected by compromised bone marrow integrity, how they contribute to other diabetic complications, and how they can be used as a treatment for these. Eventually, we suggest new tactics to optimize stem cell therapy

Inflammation and Ovarian Cancer

Epithelial ovarian cancer (EOC) is a highly lethal gynecological cancer for which overall prognosis has remained poor over the past few decades. A number of theories have been postulated in an effort to explain the etiology of EOC. Noteworthy, these theories likely are not mutually exclusive, as they all converge more or less on the role of inflammation in promoting ovarian tumorigenesis and cancer progression. The tumor milieu in which ovarian carcinoma develops has been described as one enriched with a broad spectrum of pro-inflammatory cytokines and chemokines. In particular, several of these cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, produced by tumor itself or/and activated immune cells, besides stimulating cancer cell growth, have been shown to influence clinical disease status and prognosis, by reducing responsiveness to chemotherapy and inducing symptoms such as anorexia, altered energy metabolism, anemia, weight loss, depression and fatigue. Recent data show that cytokine antagonists may have a role to play in the treatment of ovarian cancer. Their action by inhibiting both production and activity of inflammatory cytokines seems to obtain the control of angiogenetic and apoptotic events, the reversal of chemoresistance, the improvement of systemic symptoms and prognosis. In the light of our scientific research and the most recent experimental and clinical advances, our review will discuss the most relevant and recent findings on the role of proinflammatory cytokines in the pathogenesis and prognosis of ovarian cancer and the possible therapeutic implications

Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications

Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Although early diagnosis has contributed to therapeutic success, breast cancer remains a major health issue. In the last few year the hormone therapy for estrogen-dependent breast cancer has evolved achieving significant clinical results; at the same time, it has enabled us to better define the role of estrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. Specific obesity-associated factors, including leptin, insulin and inflammatory mediators, seem to influence breast cancer growth and prognosis independently of estrogens and at least in part by interacting with estrogen signalling at a cellular level. Therefore, a careful assessment of the nutritional status and body composition is paramount for a proper therapeutic approach for postmenopausal breast carcinoma. The use of antidiabetic and anti-inflammatory drugs associated with conventional hormone therapies and dietary/physical interventions could offer a new therapeutic approach for breast carcinoma that develops in the context of adiposity