462 research outputs found
SOX9 Maintains Reserve Stem Cells and Preserves Radioresistance in Mouse Small Intestine
Reserve intestinal stem cells (rISCs) are quiescent/slowly cycling under homeostatic conditions, allowing for their identification with label-retention assays. rISCs mediate epithelial regeneration after tissue damage by converting to actively proliferating stem cells (aISCs) that self renew and demonstrate multipotency, which are defining properties of stem cells. Little is known about the genetic mechanisms that regulate the production and maintenance of rISCs. High expression levels of the transcription factor Sox9 (Sox9high) are associated with rISCs. This study investigates the role of SOX9 in regulating the rISC state
CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α
Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle-drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared to standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demonstrated that the addition of CRLX101 to standard chemoradiotherapy significantly increased therapeutic efficacy by inhibiting DNA repair and HIF-1α pathway activation in tumor cells. Notably, CRLX101 was more effective than oxaliplatin at enhancing the efficacy of chemoradiotherapy, with CRLX101 and 5-fluorouracil (5-FU) producing the highest therapeutic efficacy. Gastrointestinal toxicity was also significantly lower for CRLX101 compared to CPT when combined with radiotherapy. Our results offer a preclinical proof of concept for CRLX101 as a modality to improve the outcome of neoadjuvant chemoradiotherapy for rectal cancer treatment, in support of ongoing clinical evaluation of this agent (LCC1315 {"type":"clinical-trial","attrs":{"text":"NCT02010567","term_id":"NCT02010567"}}NCT02010567)
Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy
Immunotherapy holds tremendous promise for improving cancer treatment1. Administering radiotherapy with immunotherapy has been shown to improve immune responses and can elicit an “abscopal effect”2. Unfortunately, response rates for this strategy remain low3. Herein, we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NPs formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent upon NP surface properties. We showed that AC-NPs deliver tumor specific proteins to antigen-presenting cells and significantly improve the efficacy of αPD-1 treatment using the B16F10 melanoma model, generating up to 20% cure rate as compared to 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+/Treg and CD8+/Treg ratios. Our work presents a novel strategy for improving cancer immunotherapy with nanotechnology
Deuteron and antideuteron production in Au+Au collisions at sqrt(s_NN)=200 GeV
The production of deuterons and antideuterons in the transverse momentum
range 1.1 < p_T < 4.3 GeV/c at mid-rapidity in Au + Au collisions at
sqrt(s_NN)=200 GeV has been studied by the PHENIX experiment at RHIC. A
coalescence analysis comparing the deuteron and antideuteron spectra with those
of protons and antiprotons, has been performed. The coalescence probability is
equal for both deuterons and antideuterons and increases as a function of p_T,
which is consistent with an expanding collision zone. Comparing (anti)proton
yields p_bar/p = 0.73 +/- 0.01, with (anti)deuteron yields: d_bar/d = 0.47 +/-
0.03, we estimate that n_bar/n = 0.64 +/- 0.04.Comment: 326 authors, 6 pages text, 5 figures, 1 Table. Submitted to PRL.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Centrality dependence of charged hadron production in deuteron+gold and nucleon+gold collisions at sqrt(s_NN)=200 GeV
We present transverse momentum (p_T) spectra of charged hadrons measured in
deuteron-gold and nucleon-gold collisions at \sqrts = 200 GeV for four
centrality classes. Nucleon-gold collisions were selected by tagging events in
which a spectator nucleon was observed in one of two forward rapidity
detectors. The spectra and yields were investigated as a function of the number
of binary nucleon-nucleon collisions, \nu, suffered by deuteron nucleons. A
comparison of charged particle yields to those in p+p collisions show that the
yield per nucleon-nucleon collision saturates with \nu for high momentum
particles. We also present the charged hadron to neutral pion ratios as a
function of p_T.Comment: 330 authors, 15 pages text, 16 figures, 3 tables. Submitted to Phys.
Rev. Lett. v2 has minor changes to reflect revisions during review process.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Mid-Rapidity Direct-Photon Production in p+p Collisions at sqrt(s) = 200 GeV
A measurement of direct photons in p+p collisions at sqrt(s)=200 GeV is
presented. A photon excess above background from pi^0 --> gamma+gamma, eta -->
gamma+gamma, and other decays is observed in the transverse momentum range 5.5
< p_T < 7 GeV/c. The result is compared to a next-to-leading-order perturbative
QCD calculation. Within errors, good agreement is found between the QCD
calculation and the measured result.Comment: 330 authors, 7 pages text, RevTeX, 2 figures, 2 tables. Submitted to
Physical Review D. Plain text data tables for the points plotted in figures
for this and previous PHENIX publications are (or will be) publicly available
at http://www.phenix.bnl.gov/papers.htm
Azimuthal Angle Correlations for Rapidity Separated Hadron Pairs in d+Au Collisions at sqrt(s_NN) = 200 GeV
We report on two-particle azimuthal angle correlations between charged
hadrons at forward/backward (deuteron/gold going direction) rapidity and
charged hadrons at mid-rapidity in deuteron-gold (d+Au) and proton-proton (p+p)
collisions at sqrt(s_NN) = 200 GeV. Jet structures are observed in the
correlations which we quantify in terms of the conditional yield and angular
width of away side partners. The kinematic region studied here samples partons
in the gold nucleus carrying nucleon momentum fraction x~0.1 to x~0.01. Within
this range, we find no x dependence of the jet structure in d+Au collisions.Comment: 330 authors, 6 pages text, 4 figures, no tables. Submitted to Phys.
Rev. Lett. Plain text data tables for the points plotted in figures for this
and previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Suppressed pi^0 Production at Large Transverse Momentum in Central Au+Au Collisions at sqrt(s_NN) = 200 GeV
Transverse momentum spectra of neutral pions in the range 1 < p_T < 10 GeV/c
have been measured at mid-rapidity by the PHENIX experiment at RHIC in Au+Au
collisions at sqrt(s_NN) = 200 GeV. The pi^0 multiplicity in central reactions
is significantly below the yields measured at the same sqrt(s_NN) in peripheral
Au+Au and p+p reactions scaled by the number of nucleon-nucleon collisions. For
the most central bin, the suppression factor is ~2.5 at p_T = 2 GeV/c and
increases to ~4-5 at p_T ~= 4 GeV/c. At larger p_T, the suppression remains
constant within errors. The deficit is already apparent in semi-peripheral
reactions and increases smoothly with centrality.Comment: 326 authors, 6 pages text, RevTeX, 3 figures, 2 tables. Submitted to
PRL. Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Transverse-energy distributions at midrapidity in , Au, and AuAu collisions at --200~GeV and implications for particle-production models
Measurements of the midrapidity transverse energy distribution, d\Et/d\eta,
are presented for , Au, and AuAu collisions at
GeV and additionally for AuAu collisions at
and 130 GeV. The d\Et/d\eta distributions are first
compared with the number of nucleon participants , number of
binary collisions , and number of constituent-quark participants
calculated from a Glauber model based on the nuclear geometry. For
AuAu, \mean{d\Et/d\eta}/N_{\rm part} increases with , while
\mean{d\Et/d\eta}/N_{qp} is approximately constant for all three energies.
This indicates that the two component ansatz, , which has been used to represent
distributions, is simply a proxy for , and that the term
does not represent a hard-scattering component in distributions. The
distributions of AuAu and Au are then calculated from
the measured distribution using two models that both reproduce
the AuAu data. However, while the number-of-constituent-quark-participant
model agrees well with the Au data, the additive-quark model does not.Comment: 391 authors, 24 pages, 19 figures, and 15 Tables. Submitted to Phys.
Rev. C. Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are publicly available at
http://www.phenix.bnl.gov/papers.htm
- …