678 research outputs found
Reflection as the Core of Supervision
Based on ou practice as supervisors over more than three decades, we have come to see and believe in the incalculable value of what we understand to be the value of reflection on ones practice
EGFR-specific T cell frequencies correlate with EGFR expression in head and neck squamous cell carcinoma
Background\ud
In head and neck squamous cell carcinoma (HNSCC), expression levels of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and decreased survival rates. As the mechanisms responsible for cellular immune response to EGFR in vivo remain unclear, the frequency and function of EGFR-specific cytotoxic T cells (CTL) was determined in HNSCC patients.\ud
\ud
Methods\ud
The frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry. Patients' results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation with dendritic cells pulsed with the peptides.\ud
\ud
Results\ud
Frequency of EGFR-specific CTL correlated significantly with EGFR expression in tumor sections (p = 0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells.\ud
\ud
Conclusion\ud
EGFR expressed on HNSCC cells induces a specific immune response in vivo. Strategies for expansion of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients
Dendritic cell generation and CD4+CD25HIGHFOXP3+ regulatory T cells in human head and neck carcinoma during Radio-chemotherapy
<p>Abstract</p> <p>Background</p> <p>Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown.</p> <p>Methods</p> <p>For DC generation, CD14<sup>+ </sup>monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4<sup>+</sup>CD25<sup>high</sup>F0XP3<sup>+ </sup>Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry.</p> <p>Results</p> <p>In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients.</p> <p>Conclusion</p> <p>The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC.</p
Precision Measurement of the Mass of the h_c(1P1) State of Charmonium
A precision measurement of the mass of the h_c(1P1) state of charmonium has
been made using a sample of 24.5 million psi(2S) events produced in e+e-
annihilation at CESR. The reaction used was psi(2S) -> pi0 h_c, pi0 -> gamma
gamma, h_c -> gamma eta_c, and the reaction products were detected in the
CLEO-c detector.
Data have been analyzed both for the inclusive reaction and for the exclusive
reactions in which eta_c decays are reconstructed in fifteen hadronic decay
channels. Consistent results are obtained in the two analyses. The averaged
results of the present measurements are M(h_c)=3525.28+-0.19 (stat)+-0.12(syst)
MeV, and B(psi(2S) -> pi0 h_c)xB(h_c -> gamma eta_c)= (4.19+-0.32+-0.45)x10^-4.
Using the 3PJ centroid mass, Delta M_hf(1P)= - M(h_c) =
+0.02+-0.19+-0.13 MeV.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS/,
submitted to PR
Precision Measurement of B(D+ -> mu+ nu) and the Pseudoscalar Decay Constant fD+
We measure the branching ratio of the purely leptonic decay of the D+ meson
with unprecedented precision as B(D+ -> mu+ nu) = (3.82 +/- 0.32 +/-
0.09)x10^(-4), using 818/pb of data taken on the psi(3770) resonance with the
CLEO-c detector at the CESR collider. We use this determination to derive a
value for the pseudoscalar decay constant fD+, combining with measurements of
the D+ lifetime and assuming |Vcd| = |Vus|. We find fD+ = (205.8 +/- 8.5 +/-
2.5) MeV. The decay rate asymmetry [B(D+ -> mu+ nu)-B(D- -> mu- nu)]/[B(D+ ->
mu+ nu)+B(D- -> mu- nu)] = 0.08 +/- 0.08, consistent with no CP violation. We
also set 90% confidence level upper limits on B(D+ -> tau+ nu) < 1.2x10^(-3)
and B(D+ -> e+ nu) < 8.8x10^(-6).Comment: 24 pages, 11 figures and 6 tables, v2 replaced some figure vertical
axis scales, v3 corrections from PRD revie
Measurement of the Absolute Branching Fraction of D_s^+ --> tau^+ nu_tau Decay
Using a sample of tagged D_s decays collected near the D^*_s D_s peak
production energy in e+e- collisions with the CLEO-c detector, we study the
leptonic decay D^+_s to tau^+ nu_tau via the decay channel tau^+ to e^+ nu_e
bar{nu}_tau. We measure B(D^+_s to tau^+ nu_tau) = (6.17 +- 0.71 +- 0.34) %,
where the first error is statistical and the second systematic. Combining this
result with our measurements of D^+_s to mu^+ nu_mu and D^+_s to tau^+ nu_tau
(via tau^+ to pi^+ bar{nu}_tau), we determine f_{D_s} = (274 +- 10 +- 5) MeV.Comment: 9 pages, postscript also available through
http://www.lns.cornell.edu/public/CLNS/2007/, revise
J/psi and psi(2S) Radiative Transitions to eta_c
Using 24.5 million psi(2S) decays collected with the CLEO-c detector at CESR
we present the most precise measurements of magnetic dipole transitions in the
charmonium system. We measure B(psi(2S)->gamma eta_c) =
(4.32+/-0.16+/-0.60)x10^-3, B(J/psi->gamma eta_c)/B(psi(2S)->gamma eta_c) =
4.59+/-0.23+/-0.64, and B(J/psi->gamma eta_c) = (1.98+/-0.09+/-0.30)%. We
observe a distortion in the eta_c line shape due to the photon-energy
dependence of the magnetic dipole transition rate. We find that measurements of
the eta_c mass are sensitive to the line shape, suggesting an explanation for
the discrepancy between measurements of the eta_c mass in radiative transitions
and other production mechanisms.Comment: 11 pages, 3 figure
Inclusive chi_bJ(nP) Decays to D0 X
Using Upsilon(2S) and Upsilon(3S) data collected with the CLEO III detector
we have searched for decays of chi_bJ to final states with open charm. We fully
reconstruct D0 mesons with p_D0 > 2.5 GeV/c in three decay modes (K-pi+,
K-pi+pi0, and K-pi-pi+pi+) in coincidence with radiative transition photons
that tag the production of one of the chi_bJ(nP) states. We obtain significant
signals for the two J=1 states. Recent NRQCD calculations of chi_{bJ}(nP) --> c
cbar X depend on one non-perturbative parameter per chi_bJ triplet. The
extrapolation from the observed D0 X rate over a limited momentum range to a
full c cbar X rate also depends on these same parameters. Using our data to fit
for these parameters, we extract results which agree well with NRQCD
predictions, confirming the expectation that charm production is largest for
the J=1 states. In particular, for J=1, our results are consistent with c cbar
g accounting for about one-quarter of all hadronic decays.Comment: Version 2 updates include corrections to important errors in Table V
and VII column headers which summarize results, and additional minor edits.
17 pages, available through http://www.lns.cornell.edu/public/CLNS
In vitro chemosensitivity of head and neck cancer cell lines
BACKGROUND: Systemic treatment of head and neck squamous cell carcinoma (HNSCC) includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. METHODS: Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel) was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. RESULTS: All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. CONCLUSION: Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance
- …