Chemotherapy resistance of glioblastoma stem cells [2]

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Mek inhibition results in marked antitumor activity against metastatic melanoma patient-derived melanospheres and in melanosphere-generated xenografts

One of the key oncogenic pathways involved in melanoma aggressiveness, development and progression is the RAS/BRAF/MEK pathway, whose alterations are found in most patients. These molecular anomalies are promising targets for more effective anti-cancer therapies. Some Mek inhibitors showed promising antitumor activity, although schedules and doses associated with low systemic toxicity need to be defined. In addition, it is now accepted that cancers can arise from and be maintained by the cancer stem cells (CSC) or tumor-initiating cells (TIC), commonly expanded in vitro as tumorspheres from several solid tumors, including melanoma (melanospheres). Here, we investigated the potential targeting of MEK pathway by exploiting highly reliable in vitro and in vivo pre-clinical models of melanomas based on melanospheres, as melanoma initiating cells (MIC) surrogates. MEK inhibition, through PD0325901, provided a successful strategy to affect survival of mutated-BRAF melanospheres and growth of wild type-BRAF melanospheres. A marked citotoxicity was observed in differentated melanoma cells regardless BRAF mutational status. PD0325901 treatment, dramatically inhibited growth of melanosphere-generated xenografts and determined impaired tumor vascularization of both mutated- and wild type-BRAF tumors, in the absence of mice toxicity. These results suggest that MEK inhibition might represent a valid treatment option for patients with both mutated- or wild type-BRAF melanomas, affecting tumor growth through multiple targets

Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy

Cancer stem cell (SC) chemoresistance may be responsible for the poor clinical outcome of non-small-cell lung cancer (NSCLC) patients. In order to identify the molecular events that contribute to NSCLC chemoresistance, we investigated the DNA damage response in SCs derived from NSCLC patients. We found that after exposure to chemotherapeutic drugs NSCLC-SCs undergo cell cycle arrest, thus allowing DNA damage repair and subsequent cell survival. Activation of the DNA damage checkpoint protein kinase (Chk) 1 was the earliest and most significant event detected in NSCLC-SCs treated with chemotherapy, independently of their p53 status. In contrast, a weak Chk1 activation was found in differentiated NSCLC cells, corresponding to an increased sensitivity to chemotherapeutic drugs as compared with their undifferentiated counterparts. The use of Chk1 inhibitors in combination with chemotherapy dramatically reduced NSCLC-SC survival in vitro by inducing premature cell cycle progression and mitotic catastrophe. Consistently, the co-administration of the Chk1 inhibitor AZD7762 and chemotherapy abrogated tumor growth in vivo, whereas chemotherapy alone was scarcely effective. Such increased efficacy in the combined use of Chk1 inhibitors and chemotherapy was associated with a significant reduction of NSCLC-SCs in mouse xenografts. Taken together, these observations support the clinical evaluation of Chk1 inhibitors in combination with chemotherapy for a more effective treatment of NSCLC. \uc2\ua9 2012 Macmillan Publishers Limited. All rights reserved

Search for charged Higgs bosons in the H± → τ±ν_τ decay channel in proton-proton collisions at √s= 13 TeV

A search is presented for charged Higgs bosons in the H-+/- -> tau(+/-)nu(tau) decay mode in the hadronic final state and in final states with an electron or a muon. The search is based on proton-proton collision data recorded by the CMS experiment in 2016 at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). The results agree with the background expectation from the standard model. Upper limits at 95% confidence level are set on the production cross section times branching fraction to tau(+/-)nu(tau) for an H-+/- in the mass range of 80GeV to 3TeV, including the region near the top quark mass. The observed limit ranges from 6 pb at 80 GeV to 5 fb at 3 TeV. The limits are interpreted in the context of the minimal supersymmetric standard model m(h)(mod-) scenario.Peer reviewe

Study of dijet events with large rapidity separation in proton-proton collisions at s \sqrt{s} = 2.76 TeV

The cross sections for inclusive and Mueller-Navelet dijet production are measured as a function of the rapidity separation between the jets in proton-proton collisions at s√ = 2.76 TeV for jets with transverse momentum pT > 35 GeV and rapidity |y| 20 GeV is introduced to improve the sensitivity to the effects of the Balitsky-Fadin-Kuraev-Lipatov (BFKL) evolution. The measurement is compared with the predictions of various Monte Carlo models based on leading-order and next-to-leading-order calculations including the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi leading-logarithm (LL) parton shower as well as the LL BFKL resummation

Search for W´ bosons decaying to a top and a bottom quark at root s=13 TeV in the hadronic final state

A search is performed for W ' bosons decaying to a top and a bottom quark in the all-hadronic final state, in proton-proton collisions at a center-of-mass energy of 13TeV. The analyzed data were collected by the CMS experiment between 2016 and 2018 and correspond to an integrated luminosity of 137fb(-1). Deep neural network algorithms are used to identify the jet initiated by the bottom quark and the jet containing the decay products of the top quark when the W ' boson from the top quark decays hadronically. No excess above the estimated standard model background is observed. Upper limits on the production cross sections of W ' bosons decaying to a top and a bottom quark are set. Both left- and right-handed W ' bosons with masses below 3.4TeV are excluded at 95% confidence level, and the most stringent limits to date on W ' bosons decaying to a top and a bottom quark in the all-hadronic final state are obtained. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe

Search for Wγ resonances in proton-proton collisions at s\sqrt{s}=13 TeV using hadronic decays of Lorentz-boosted W bosons

A search for Wγ resonances in the mass range between 0.7 and 6.0 TeV is presented. The W boson is reconstructed via its hadronic decays, with the final-state products forming a single large-radius jet, owing to a high Lorentz boost of the W boson. The search is based on proton-proton collision data at $\sqrt{s}$ = 13 TeV, corresponding to an integrated luminosity of 137 fb$^{-1}$, collected with the CMS detector at the LHC in 2016–2018. The Wγ mass spectrum is parameterized with a smoothly falling background function and examined for the presence of resonance-like signals. No significant excess above the predicted background is observed. Model-specific upper limits at 95% confidence level on the product of the cross section and branching fraction to the channel are set. Limits for narrow resonances and for resonances with an intrinsic width equal to 5% of their mass, for spin-0 and spin-1 hypotheses, range between 0.17 fb at 6.0 TeV and 55 fb at 0.7 TeV. These are the most restrictive limits to date on the existence of such resonances over a large range of probed masses. In specific heavy scalar (vector) triplet benchmark models, narrow resonances with masses between 0.75 (1.15) and 1.40 (1.36) TeV are excluded for a range of model parameters. Model-independent limits on the product of the cross section, signal acceptance, and branching fraction to the Wγ channel are set for minimum Wγ mass thresholds between 1.5 and 8.0 TeV

Brazilian Consensus on Photoprotection

Brazil is a country of continental dimensions with a large heterogeneity of climates and massive mixing of the population. Almost the entire national territory is located between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the south certainly makes Brazil one of the countries of the world with greater extent of land in proximity to the sun. The Brazilian coastline, where most of its population lives, is more than 8,500 km long. Due to geographic characteristics and cultural trends, Brazilians are among the peoples with the highest annual exposure to the sun. Epidemiological data show a continuing increase in the incidence of nonmelanoma and melanoma skin cancers. Photoprotection can be understood as a set of measures aimed at reducing sun exposure and at preventing the development of acute and chronic actinic damage. Due to the peculiarities of Brazilian territory and culture, it would not be advisable to replicate the concepts of photoprotection from other developed countries, places with completely different climates and populations. Thus the Brazilian Society of Dermatology has developed the Brazilian Consensus on Photoprotection, the first official document on photoprotection developed in Brazil for Brazilians, with recommendations on matters involving photoprotection