945 research outputs found
Heated IntraPEritoneal Chemotherapy (HIPEC) for Patients With Recurrent Ovarian Cancer A Systematic Literature Review
Integrin αvβ6-specific therapy for pancreatic cancer developed from foot-and-mouth-disease virus
GOALS OF INVESTIGATION: The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) has remained at <5% for decades because no effective therapies have been identified. Integrin αvβ6 is overexpressed in most PDAC and represents a promising therapeutic target. Thus, we attempted to develop an αvβ6-specific peptide-drug conjugate (PDC) for therapy of PDAC. METHODOLOGY: We conjugated the DNA-binding pyrrolobenzodiazepine (PBD)-based payload SG3249 (tesirine) to an αvβ6-specific 20mer peptide from the VP1 coat protein of foot-and-mouth-disease virus (FMDV) (forming conjugate SG3299) or to a non-targeting peptide (forming conjugate SG3511). PDCs were tested for specificity and toxicity on αvβ6-negative versus-positive PDAC cells, patient-derived cell lines from tumor xenografts, and on two different in vivo models of PDAC. Immunohistochemical analyses were performed to establish therapeutic mechanism. RESULTS: The αvβ6-targeted PDC SG3299 was significantly more toxic (up to 78-fold) for αvβ6-expressing versus αvβ6-negative PDAC cell lines in vitro, and achieved significantly higher toxicity at equal dose than the non-targeted PDC SG3511 (up to 15-fold better). Moreover, SG3299 eliminated established (100mm3) Capan-1 PDAC human xenografts, extending the lifespan of mice significantly (P=0.005). Immunohistochemistry revealed SG3299 induced DNA damage and apoptosis (increased γH2AX and cleaved caspase 3, respectively) associated with significant reductions in proliferation (Ki67), β6 expression and PDAC tumour growth. CONCLUSION: The FMDV-peptide drug conjugate SG3299 showed αvβ6-selectivity in vitro and in vivo and can specifically eliminate αvβ6-positive cancers, providing a promising new molecular- specific therapy for pancreatic cancer
Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications
Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems
Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients with metastatic renal carcinoma
Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals
Measurement of the top quark mass using the matrix element technique in dilepton final states
We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7 fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84 GeV
Two-zero Textures of the Majorana Neutrino Mass Matrix and Current Experimental Tests
In view of the latest T2K and MINOS neutrino oscillation data which hint at a
relatively large theta_13, we perform a systematic study of the Majorana
neutrino mass matrix M_nu with two independent texture zeros. We show that
three neutrino masses (m_1, m_2, m_3) and three CP-violating phases (delta,
rho, sigma) can fully be determined from two neutrino mass-squared differences
(delta m^2, Delta m^2) and three flavor mixing angles (theta_12, theta_23,
theta_13). We find that seven patterns of M_nu (i.e., A_{1,2}, B_{1,2,3,4} and
C) are compatible with current experimental data at the 3-sigma level, but the
parameter space of each pattern is more strictly constrained than before. We
demonstrate that the texture zeros of M_nu are stable against the one-loop
quantum corrections, and there exists a permutation symmetry between Patterns
A_1 and A_2, B_1 and B_2 or B_3 and B_4. Phenomenological implications of M_nu
on the neutrinoless double-beta decay and leptonic CP violation are discussed,
and a realization of those texture zeros by means of the Z_n flavor symmetries
is illustrated.Comment: 41 pages, including 4 tables and 14 figures, more discussions added,
to appear in JHE
Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV
We present a search for the production of neutral Higgs bosons decaying into
tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The
data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by
the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the
95% C.L. on the product of production cross section and branching ratio for a
scalar resonance decaying into tautau pairs, and we then interpret these limits
as limits on the production of Higgs bosons in the minimal supersymmetric
standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL
Journal Staff
We present the first measurements of the differential cross section d sigma/dp(T)(gamma) for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities vertical bar y(gamma)vertical bar < 1.0 and transverse momenta 30 < p(T)(gamma) < 200 GeV. The b-quark jets are required to have p(T)(jet) > 15 GeVand vertical bar y(jet)vertical bar < 1.5. The ratio of differential production cross sections for gamma + 2 b-jets to gamma + b-jet as a function of p(T)(gamma) is also presented. The results are based on the proton-antiproton collision data at root s = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next- to- leading order perturbative QCD calculations as well as predictions based on the k(T)- factorization approach and those from the sherpa and pythia Monte Carlo event generators
Measurement of the photon-jet production differential cross section in collisions at \sqrt{s}=1.96~\TeV
We present measurements of the differential cross section dsigma/dpT_gamma
for the inclusive production of a photon in association with a b-quark jet for
photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for
photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is
the photon transverse momentum. The b-quark jets are required to have pT>15 GeV
and rapidity |y_jet| < 1.5. The results are based on data corresponding to an
integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the
Fermilab Tevatron Collider at sqrt(s)=1.96 TeV. The measured cross
sections are compared with next-to-leading order perturbative QCD calculations
using different sets of parton distribution functions as well as to predictions
based on the kT-factorization QCD approach, and those from the Sherpa and
Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.
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