925 research outputs found
HER2 testing in breast cancer: Opportunities and challenges
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results
Transverse-target-spin asymmetry in exclusive -meson electroproduction
Hard exclusive electroproduction of mesons is studied with the
HERMES spectrometer at the DESY laboratory by scattering 27.6 GeV positron and
electron beams off a transversely polarized hydrogen target. The amplitudes of
five azimuthal modulations of the single-spin asymmetry of the cross section
with respect to the transverse proton polarization are measured. They are
determined in the entire kinematic region as well as for two bins in photon
virtuality and momentum transfer to the nucleon. Also, a separation of
asymmetry amplitudes into longitudinal and transverse components is done. These
results are compared to a phenomenological model that includes the pion pole
contribution. Within this model, the data favor a positive
transition form factor.Comment: DESY Report 15-14
Longitudinal double-spin asymmetries in semi-inclusive deep-inelastic scattering of electrons and positrons by protons and deuterons
A comprehensive collection of results on longitudinal double-spin asymmetries is presented for charged pions and kaons produced in semi-inclusive deep-inelastic scattering of electrons and positrons on the proton and deuteron, based on the full HERMES data set. The dependence of the asymmetries on hadron transverse momentum and azimuthal angle extends the sensitivity to the flavor structure of the nucleon beyond the distribution functions accessible in the collinear framework. No strong dependence on those variables is observed. In addition, the hadron charge-difference asymmetry is presented, which under certain model assumptions provides access to the helicity distributions of valence quarks
Measurement of single-spin azimuthal asymmetries in semi-inclusive electroproduction of pions and kaons on a longitudinally polarised deuterium target
Single-spin asymmetries have been measured for semi-inclusive
electroproduction of , , and mesons in
deep-inelastic scattering off a longitudinally polarised deuterium target. The
asymmetries appear in the distribution of the hadrons in the azimuthal angle
around the virtual photon direction, relative to the lepton scattering
plane. The corresponding analysing powers in the moment of the
cross section are for ,
for ,
for and for . The moments are
compatible with zero for all particles.Comment: Revised version shortened 9 pages, 3 tables, 7 figure
Bose-Einstein correlations in hadron-pairs from lepto-production on nuclei ranging from hydrogen to xenon
Bose-Einstein correlations of like-sign charged hadrons produced in
deep-inelastic electron and positron scattering are studied in the HERMES
experiment using nuclear targets of H, H, He, He, N, Ne, Kr,
and Xe. A Gaussian approach is used to parametrize a two-particle correlation
function determined from events with at least two charged hadrons of the same
sign charge. This correlation function is compared to two different empirical
distributions that do not include the Bose-Einstein correlations. One
distribution is derived from unlike-sign hadron pairs, and the second is
derived from mixing like-sign pairs from different events. The extraction
procedure used simulations incorporating the experimental setup in order to
correct the results for spectrometer acceptance effects, and was tested using
the distribution of unlike-sign hadron pairs. Clear signals of Bose-Einstein
correlations for all target nuclei without a significant variation with the
nuclear target mass are found. Also, no evidence for a dependence on the
invariant mass W of the photon-nucleon system is found when the results are
compared to those of previous experiments
Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts
<p>Abstract</p> <p>Background</p> <p>Amplification of the <it>ERBB2 </it>(<it>Her-2/neu</it>) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for <it>topoisomerase II alpha </it>(<it>TOP2A</it>), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy.</p> <p>Methods and patients</p> <p>Archival tissue samples from 63 breast cancer patients with <it>ERBB2 </it>amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near <it>ERBB2</it>. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available.</p> <p>Results</p> <p>Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted <it>TOP2A </it>had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. <it>TOP2A </it>deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between <it>TOP2A </it>deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06).</p> <p>Conclusion</p> <p><it>TOP2A </it>deletion is associated with poor prognosis in <it>ERBB2</it>-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.</p
Subleading-twist effects in single-spin asymmetries in semi-inclusive deep-inelastic scattering on a longitudinally polarized hydrogen target
Single-spin asymmetries in the semi-inclusive production of charged pions in
deep-inelastic scattering from transversely and longitudinally polarized proton
targets are combined to evaluate the subleading-twist contribution to the
longitudinal case. This contribution is significantly positive for (\pi^+)
mesons and dominates the asymmetries on a longitudinally polarized target
previously measured by \hermes. The subleading-twist contribution for (\pi^-)
mesons is found to be small
Double hadron leptoproduction in the nuclear medium
First measurement of double-hadron production in deep-inelastic scattering
has been measured with the HERMES spectrometer at HERA using a 27.6 GeV
positron beam with deuterium, nitrogen, krypton and xenon targets. The
influence of the nuclear medium on the ratio of double-hadron to single-hadron
yields has been investigated. Nuclear effects are clearly observed but with
substantially smaller magnitude and reduced -dependence compared to
previously measured single-hadron multiplicity ratios. The data are in fair
agreement with models based on partonic or pre-hadronic energy loss, while they
seem to rule out a pure absorptive treatment of the final state interactions.
Thus, the double-hadron ratio provides an additional tool for studying
modifications of hadronization in nuclear matter
Single-spin asymmetries in semi-inclusive deep-inelastic scattering on a transversely polarized hydrogen target
Single-spin asymmetries for semi-inclusive electroproduction of charged pions
in deep-inelastic scattering of positrons are measured for the first time with
transverse target polarization. The asymmetry depends on the azimuthal angles
of both the pion () and the target spin axis () about the virtual
photon direction and relative to the lepton scattering plane. The extracted
Fourier component \cmpi is a signal of the previously unmeasured quark
transversity distribution, in conjunction with the so-called Collins
fragmentation function, also unknown. The Fourier component \smpi of the
asymmetry arises from a correlation between the transverse polarization of the
target nucleon and the intrinsic transverse momentum of quarks, as represented
by the previously unmeasured Sivers distribution function. Evidence for both
signals is observed, but the Sivers asymmetry may be affected by exclusive
vector meson productio
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