Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Tonsillar metastasis of gastric cancer

Metastasis from a malignant tumor to the palatine tonsils is rare, with only 100 cases reported in the English-language literature. Tonsillar metastasis from a gastric cancer is very rare. We report here a case of palatine tonsillar metastasis after gastric cancer surgery. The patient was an 88-year-old woman who had gastric cancer with abdominal wall invasion. She had undergone a distal gastrectomy with abdominal wall resection and D2 lymph node dissection. Histologically, the tumor was primarily a moderately differentiated adenocarcinoma. It was stage IV (T4, N1, M0) using TNM clinical classification. The patient developed pharyngeal discomfort and abdominal pain and was hospitalized during the follow-up period, 1 year 9 months post-operatively. Multiple lung metastases, Virchow’s lymph node metastasis, and adrenal metastasis were observed. A mass of 2.5 cm was also observed in the right palatine tonsil. It was diagnosed as a moderately differentiated adenocarcinoma, a metastasis from gastric cancer. There was a concern of asphyxiation due to hemorrhage of the tumor; however, the tumor dislodged approximately 10 days after biopsy and tonsillar recurrence was not observed. The patient died 1 year 10 months post-operatively. In the literature there are cases with tonsillar metastases where surgical treatment, radiotherapy, and chemotherapy were performed and extension of survival was seen. Tonsillar metastasis is a form of systemic metastasis of a malignant tumor, and there is a high risk for asphyxiation from tumor dislodgement or hemorrhage. Thus, it is important to recognize tonsillar metastasis as an oncologic emergency

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS

A measurement is presented of the $t\bar{t}$ inclusive production cross-section in $pp$ collisions at a center-of-mass energy of $\sqrt{s}=8$ TeV using data collected by the ATLAS detector at the CERN Large Hadron Collider. The measurement was performed in the lepton+jets final state using a data set corresponding to an integrated luminosity of 20.3 fb$^{-1}$. The cross-section was obtained using a likelihood discriminant fit and $b$-jet identification was used to improve the signal-to-background ratio. The inclusive $t\bar{t}$ production cross-section was measured to be $260\pm 1{\textrm{(stat.)}} ^{+22}_{-23} {\textrm{(syst.)}}\pm 8{\textrm{(lumi.)}}\pm 4{\mathrm{(beam)}}$ pb assuming a top-quark mass of 172.5 GeV, in good agreement with the theoretical prediction of $253^{+13}_{-15}$ pb. The $t\bar{t}\to (e,\mu)+{\mathrm{jets}}$ production cross-section in the fiducial region determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3 figures, 2 tables, all figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Chronic Myeloid Leukemia Stem Cell Biology

Leukemia progression and relapse is fueled by leukemia stem cells (LSC) that are resistant to current treatments. In the progression of chronic myeloid leukemia (CML), blast crisis progenitors are capable of adopting more primitive but deregulated stem cell features with acquired resistance to targeted therapies. This in turn promotes LSC behavior characterized by aberrant self-renewal, differentiation, and survival capacity. Multiple reports suggest that cell cycle alterations, activation of critical signaling pathways, aberrant microenvironmental cues from the hematopoietic niche, and aberrant epigenetic events and deregulation of RNA processing may facilitate the enhanced survival and malignant transformation of CML progenitors. Here we review the molecular evolution of CML LSC that promotes CML progression and relapse. Recent advances in these areas have identified novel targets that represent important avenues for future therapeutic approaches aimed at selectively eradicating the LSC population while sparing normal hematopoietic progenitors in patients suffering from chronic myeloid malignancies

Measurement of the charge asymmetry in dileptonic Decays of top quark pairs in pp collisions at √ s = 7 TeV using the ATLAS detector

A measurement of the top-antitop (tt) charge asymmetry is presented using data corresponding to an integrated luminosity of 4.6 fb −1 of LHC pp collisions at a centre- of-mass energy of 7 TeV collected by the ATLAS detector. Events with two charged leptons, at least two jets and large missing transverse momentum are selected. Two observables are studied: A tt/C, based on the reconstructed tt final state. The asymmetries are measured to be A ll/C = 0.024 +/- 0.015 (stat.) +/- 0.009 (syst.) Att/C = 0.021 +/- 0.025 (stat.) +/- 0.017 (syst.) The measured values are in agreement with the Standard Model predictions