http://elea.unisa.it/xmlui/handle/10556/4464 2026-04-20T10:55:34Z 2026-04-20T10:55:34Z Mastantuono, Teresa Di Maro, Martina Chiurazzi, Martina Battiloro, Laura Starita, Noemy Nasti, Gilda Lapi, Dominga Iuppariello, Luigi Cesarelli, Mario D’Addio, Gianni Colantuoni, Antonio http://elea.unisa.it/xmlui/handle/10556/4483 2025-04-30T15:26:24Z 2016-01-01T00:00:00Z

Microvascular blood flow improvement in hyperglycemic obese adult patients by hypocaloric diet Mastantuono, Teresa; Di Maro, Martina; Chiurazzi, Martina; Battiloro, Laura; Starita, Noemy; Nasti, Gilda; Lapi, Dominga; Iuppariello, Luigi; Cesarelli, Mario; D’Addio, Gianni; Colantuoni, Antonio The present study was aimed to assess the changes in skin microvascular blood flow (SBF) in newly diagnosed hyperglycemic obese subjects, administered with hypocaloric diet. Adult patients were recruited and divided in three groups: NW group (n=54), NG (n=54) and HG (n=54) groups were constituted by normal weight, normoglycemic and hyperglycemic obese subjects, respectively. SBF was measured by laser Doppler perfusion monitoring technique and oscillations in blood flow were analyzed by spectral methods under baseline conditions, at 3 and 6 months of dietary treatment. Under resting conditions, SBF was lower in HG group than in NG and NW ones. Moreover, all subjects showed blood flow oscillations with several frequency components. In particular, hyperglycemic obese patients revealed lower spectral density in myogenic-related component than normoglycemic obese and normal weight ones. Moreover, postocclusive reactive hyperemia (PORH) was impaired in hyperglycemic obese compared to normoglycemic and normal weigh subjects. After hypocaloric diet, in hyperglycemic obese patients there was an improvement in SBF accompanied by recovery in myogenic-related oscillations and arteriolar responses during PORH. In conclusion, hyperglycemia markedly affected peripheral microvascular function; hypocaloric diet ameliorated tissue blood flow.

2016-01-01T00:00:00Z Montuori, Nunzia Pesapane, Ada Giudice, Valentina Serio, Bianca Rossi, Francesca Wanda De Paulis, Amato Selleri, Carmine http://elea.unisa.it/xmlui/handle/10556/4482 2025-04-30T15:27:54Z 2016-01-01T00:00:00Z

67 kDa laminin receptor (67LR) in normal and neoplastic hematopoietic cells: is its targeting a feasible approach? Montuori, Nunzia; Pesapane, Ada; Giudice, Valentina; Serio, Bianca; Rossi, Francesca Wanda; De Paulis, Amato; Selleri, Carmine The 67 kDa laminin receptor (67LR) is a non-integrin cell surface receptor for laminin (LM) that derives from a 37 kDa precursor (37LRP). 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potentialin many human solid tumors, recommending this receptor as a new promising target for cancer therapy. This is supported by in vivo studies showing that 67LR downregulation reduces tumour cell proliferation and tumour formation by inducing apoptosis. 67LR association with the anti-apoptotic protein PED/PEA-15 activates a signal transduction pathway, leading to cell proliferation and resistance to apoptosis. However, the main function of 67LR is to enhance tumor cell adhesion to the LM of basement membranes and cell migration, two crucial events in the metastasis cascade.Thus, inhibition of 67LR binding to LM has been proved to be a feasible approach to block metastatic cancer cell spread. Despite accumulating evidences on 67LR overexpression in hematologic malignancies, 67LR role in these diseases has not been clearly defined. Here, we review 67LR expression and function in normal and malignant hematopoietic cells, 67LR role and prognostic impact in hematological malignancies and first attempts in targeting its activity.

2016-01-01T00:00:00Z Montuori, Nunzia Pesapane, Ada Rossi, Francesca Wanda Giudice, Valentina De Paulis, Amato Selleri, Carmine Ragno, Pia http://elea.unisa.it/xmlui/handle/10556/4481 2025-04-30T15:24:49Z 2016-01-01T00:00:00Z

Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer Montuori, Nunzia; Pesapane, Ada; Rossi, Francesca Wanda; Giudice, Valentina; De Paulis, Amato; Selleri, Carmine; Ragno, Pia The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPIanchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLFRs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials.

2016-01-01T00:00:00Z Giudice, Valentina Ricci, Pier Carlo Marino, Luigi Rocco, Mattia Villani, Gaetano Langella, Monica Manente, Lisa Seneca, Elisa Ferrara, Idalucia Pezzullo, Luca Serio, Bianca Selleri, Carmine http://elea.unisa.it/xmlui/handle/10556/4480 2025-04-30T15:27:52Z 2016-01-01T00:00:00Z

In vitro apoptotic effects of farnesyltransferase blockade in acute myeloid leukemia cells Giudice, Valentina; Ricci, Pier Carlo; Marino, Luigi; Rocco, Mattia; Villani, Gaetano; Langella, Monica; Manente, Lisa; Seneca, Elisa; Ferrara, Idalucia; Pezzullo, Luca; Serio, Bianca; Selleri, Carmine Farnesyltransferase inhibitors (FTIs) are a class of oral anti-cancer drugs currently tested in phase I-II clinical trials for treatment of hematological malignancies. The in vitro effects of various FTIs (alpha-hydroxyfarnesylphosphonic acid, manumycin-A and SCH66336) were tested on CD34+ KG1a cell line and in primary acute myeloid leukemia (AML) cells from 64 patients. By cell viability and clonogeneic methylcellulose assays, FTIs showed a significant inhibitory activity in CD34+ KG1a and primary bone marrow (BM) leukemic cells from 56% of AML patients. FTIs also induced activation of caspase-3 and Fas-independent apoptosis, confirmed by the finding that inhibition of caspase-8 was not associated with the rescue of FTItreated cells. We concluded that other cellular events induced by FTIs may trigger activation of caspase-3 and subsequent apoptosis, but the expression of proapoptotic molecules, as Bcl-2 and Bcl-XL, and antiapoptotic, as Bcl-X(s), were not modified by FTIs. By contrast, expression of inducible nitric oxide synthase (iNOS) was increased in FTI-treated AML cells. Our results suggest a very complex mechanism of action of FTIs that require more studies for a better clinical use of the drugs alone or in combination in the treatment of hematological malignancies.

2016-01-01T00:00:00Z