University of Florence

About: University of Florence is a education organization based out in Florence, Toscana, Italy. It is known for research contribution in the topics: Population & Carbonic anhydrase. The organization has 27292 authors who have published 79599 publications receiving 2341684 citations. The organization is also known as: Università degli studi di Firenze & Universita degli studi di Firenze.

Charged-particle nuclear modification factors in PbPb and pPb collisions at √sNN=5.02 TeV

Abstract: we acknowledge the enduring support for the construction and operation of the LHC and the CMS detector provided by the following funding agencies: BMWFW and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES and CSF (Croatia); RPF (Cyprus); SENESCYT (Ecuador); MoER, ERC IUT and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NIH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MBIE (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS and RFBR (Russia); MESTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU and SFFR (Ukraine); STFC (United Kingdom); DOE and NSF (U.S.A.).

PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis.

Abstract: Background Despite the success of immunotherapy directed at inhibiting of programmed death-1 (PD-1)/PD-ligand (L)1 signaling, it is not established whether PD-L1 expression correlates with the clinical response and outcome in different tumors. The present meta-analysis investigates whether the PD-L1 status, detected by immunohistochemistry, is associated with clinical response and mortality in patients treated with anti-PD-1/PD-L1 therapy. Methods A systematic literature search and quantitative analysis were planned, conducted and reported following CONSORT and QUORUM checklists, up to December 2015, to identify clinical trials with information on cancer outcome by PD-L1 immunohistochemical expression in tumor tissues. We used random effects models to estimate Summary Objective Response Rates (SORRs) and Summary Odd Ratio (SOR) for the comparison of PD-L1 positive and negative patients. Results We summarized 20 trials carried out in metastatic melanoma (MM), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) patients receiving anti-PD-1/PD-L1 antibodies (4230 MM, 1417 NSCLC and 312 RCC patients). Positive PD-L1 MM patients showed a significant decrease (53%) in the risk of mortality vs. negative cases with no heterogeneity. Furthermore, SORRs were 45% and 27% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference in term of responses: 2.14 (95% CI: 1.65, 2.77), with low between-study heterogeneity (I 2 = 35%). Furthermore, results from randomized clinical trials on MM showed that PD-L1 expression is significantly associated with greater clinical response rates to anti-PD1 treatments (SOR 1.89; 95%CI: 1.35, 2.64) but not to other treatments (SOR 0.96; 95%CI: 0.5, 1.87). In non-squamous NSCLC SORRs were 29% and 11% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference between responses: 3.78 (1.54, 9.24), with no between-study heterogeneity. Squamous NSCLC and RCC did not show any significant difference in response according to the PD-L1 status. Conclusion PD-L1 expression is significantly associated with mortality and clinical response to anti-PD-1/PD-L1 antibodies in MM patients and with clinical response in patients with non-squamous NSCLC.

Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche.

Abstract: The sub-population of tumor cells termed 'cancer stem cells' (CSCs) possess the capability to generate tumors, undergo epithelial-mesenchymal transition (EMT) and are implicated in metastasis, making treatments to specifically target CSCs an attractive therapeutic strategy. Tumor hypoxia plays a key role in regulating EMT and cancer stem cell function. Carbonic anhydrase IX (CAIX) is a hypoxia-inducible protein that regulates cellular pH to promote cancer cell survival and invasion in hypoxic microenvironments and is a biomarker of poor prognosis for breast cancer metastasis and survival. Here, we demonstrate that inhibition of CAIX expression or activity with novel small-molecule inhibitors in breast cancer cell lines, or in primary metastatic breast cancer cells, results in the inhibition of breast CSC expansion in hypoxia. We identify the mTORC1 axis as a critical pathway downstream of CAIX in the regulation of cancer stem cell function. CAIX is also required for expression of EMT markers and regulators, as well as drivers of 'stemness', such as Notch1 and Jagged1 in isolated CSCs. In addition, treatment of mice bearing orthotopic breast tumors with CAIX-specific small-molecule inhibitors results in significant depletion of CSCs within these tumors. Furthermore, combination treatment with paclitaxel results in enhanced tumor growth delay and eradication of lung metastases. These data demonstrate that CAIX is a critical mediator of the expansion of breast CSCs in hypoxic niches by sustaining the mesenchymal and 'stemness' phenotypes of these cells, making CAIX an important therapeutic target for selectively depleting breast CSCs.

Primitive Variable Solvers for Conservative General Relativistic Magnetohydrodynamics

Abstract: Conservative numerical schemes for general relativistic magnetohydrodynamics (GRMHD) require a method for transforming between "conserved" variables such as momentum and energy density and "primitive" variables such as rest-mass density, internal energy, and components of the four-velocity. The forward transformation (primitive to conserved) has a closed-form solution, but the inverse transformation (conserved to primitive) requires the solution of a set of five nonlinear equations. Here we discuss the mathematical properties of the inverse transformation and present six numerical methods for performing the inversion. The first method solves the full set of five nonlinear equations directly using a Newton-Raphson scheme and a guess from the previous time step. The other methods reduce the five nonlinear equations to either one or two nonlinear equations that are solved numerically. Comparisons between the methods are made using a survey over phase space, a two-dimensional explosion problem, and a general relativistic MHD accretion disk simulation. The run time of the methods is also examined. Code implementing the schemes is available with the electronic edition of the article.