Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents

The Target Silicon Detector for the FOCUS Spectrometer

We describe a silicon microstrip detector interleaved with segments of a beryllium oxide target which was used in the FOCUS photoproduction experiment at Fermilab. The detector was designed to improve the vertex resolution and to enhance the reconstruction efficiency of short-lived charm particles.Comment: 18 pages, 14 figure

Measurement of the relative branching ratio BR(\Xi_c^+ \to p^+ K^-\pi^+)\BR(\Xi_c^+ \to \Xi^- \pi^+ \pi^+)

We report the observation of the Cabibbo suppressed decay \Xi_c^+ \to p K^-\pi^+ using data collected with the FOCUS spectrometer during the 1996--97 Fermilab fixed target run. We find a \Xi_c^+ signal peak of 202\pm35 events. We have measured the relative branching ratios BR(\Xi^+_c\to p K^-\pi^+)/BR(\Xi^+_c\to\Xi^-\pi^+\pi^+)= 0.234 \pm 0.047 \pm 0.022 and BR(\Xi^+_c\to p \bar{K}^*(892)^0)/BR(\Xi^+_c\to p K^-\pi^+)= 0.54 \pm 0.09 \pm 0.05 .Comment: 9 pages, 4 figure

Observation of a 1750 MeV/c^2 Enhancement in the Diffractive Photoproduction of K^+K^-

Using the FOCUS spectrometer with photon beam energies between 20 and 160 \gev, we confirm the existence of a diffractively photoproduced enhancement in $K^+K^-$ at 1750 \mevcc with nearly 100 times the statistics of previous experiments. Assuming this enhancement to be a single resonance with a Breit-Wigner mass shape, we determine its mass to be $1753.5\pm 1.5\pm 2.3$ \mevcc and its width to be $122.2\pm 6.2\pm 8.0$ \mevcc. We find no corresponding enhancement at 1750 \mevcc in $K^*K$, and again neglecting any possible interference effects we place limits on the ratio $\Gamma (X(1750) \to K^*K)/\Gamma (X(1750) \to K^+K^-)$. Our results are consistent with previous photoproduction experiments, but, because of the much greater statistics, challenge the common interpretation of this enhancement as the $\phi (1680)$ seen in $e^+e^-$ annihilation experiments.Comment: 10 pages, 5 figure

A measurement of lifetime differences in the neutral D-meson system

Using a high statistics sample of photoproduced charm particles from the FOCUS experiment at Fermilab, we compare the lifetimes of neutral D mesons decaying via D0 to K- pi+ and K- K+ to measure the lifetime differences between CP even and CP odd final states. These measurements bear on the phenomenology of D0 - D0bar mixing. If the D0 to K-pi+ is an equal mixture of CP even and CP odd eigenstates, we measure yCP = 0.0342 \pm 0.0139 \pm 0.0074.Comment: 15 pages, 5 figure

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Evidence for a narrow dip structure at 1.9 GeV/c2^2 in 3π+3π−3\pi^+ 3\pi^- diffractive photoproduction

A narrow dip structure has been observed at 1.9 GeV/c$^2$ in a study of diffractive photoproduction of the $~3\pi^+3\pi^-$ final state performed by the Fermilab experiment E687.Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reade

Measurements of the Sigma_c^0 and Sigma_c^{++} Mass Splittings

Using a high statistics sample of photoproduced charmed particles from the FOCUS experiment at Fermilab (FNAL-E831), we measure the mass splittings of the charmed baryons Sigma_c^0 and Sigma_c^{++}. We find M(Sigma_c^0 - Lambda_c^+) = 167.38 +/- 0.21 +/- 0.13 MeV/c^2 and M(Sigma_c^++ - Lambda_c^+) = 167.35 +/- 0.19 +/- 0.12 MeV/c^2 with samples of 362 +/- 36 and 461 +/- 39 events, respectively. We measure the isospin mass splitting M(Sigma_c^++ - Sigma_c^0) to be -0.03 +/- 0.28 +/- 0.11 Mev/c^2. The first errors are statistical and the second are systematic.Comment: 10 pages, 2 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types