Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

BACKGROUND: Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient outcomes.METHODS: We analyzed single nucleotide polymorphism (SNP) array-based genotyping data on 532 SOC specimens from The Cancer Genome Atlas database to identify aUPD regions. Cox univariate regression and Cox multivariate proportional hazards analyses were performed for survival analysis.RESULTS: We found that 94.7% of SOC samples harbored aUPD; the most common aUPD regions were in chromosomes 17q (76.7%), 17p (39.7%), and 13q (38.3%). In Cox univariate regression analysis, two independent regions of aUPD on chromosome 17q (A and C), and whole-chromosome aUPD were associated with shorter overall survival (OS), and five regions on chromosome 17q (A, D-G) and BRCA1 were associated with recurrence-free survival time. In Cox multivariable proportional hazards analysis, whole-chromosome aUPD was associated with shorter OS. One region of aUPD on chromosome 22q (B) was associated with unilateral disease. A statistically significant association was found between aUPD at TP53 loci and homozygous mutation of TP53 (p < 0.0001).CONCLUSIONS: aUPD is a common event and some recurrent loci are associated with a poor outcome for patients with serous ovarian cancer

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

<p>Abstract</p> <p>Background</p> <p>High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment.</p> <p>Methods</p> <p>Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. <it>In vivo </it>dendritic cell activity was assessed along with the host's response to challenge tumor growth.</p> <p>Results</p> <p>Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio.</p> <p>Conclusion</p> <p>These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.</p

Analysis of Yarrowia lipolytica Growth, Catabolism, and Terpenoid Biosynthesis during Utilization of Lipid-derived Feedstock

This study employs biomass growth analyses and 13C-isotope tracing to investigate lipid feedstock utilization by Yarrowia lipolytica. Compared to glucose, oil-feedstock in the minimal medium increases the yeast\u27s biomass yields and cell sizes, but decreases its protein content (\u3c20% of total biomass) and enzyme abundances for product synthesis. Labeling results indicate a segregated metabolic network (the glycolysis vs. the TCA cycle) during co-catabolism of sugars (glucose or glycerol) with fatty acid substrates, which facilitates resource allocations for biosynthesis without catabolite repressions. This study has also examined the performance of a β-carotene producing strain in different growth mediums. Canola oil-containing yeast-peptone (YP) has resulted in the best β-carotene titer (121 ± 13 mg/L), two-fold higher than the glucose based YP medium. These results highlight the potential of Y. lipolytica for the valorization of waste-derived lipid feedstock

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype

The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior

First Observation of the Doubly Charmed Baryon Xi_cc^+

We observe a signal for the doubly charmed baryon Xi_cc^+ in the charged decay mode Xi_cc^+ --> Lambda_c^+ K- pi+ in data from SELEX, the charm hadro-production experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1 +/- 0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is (3519 +/- 1) MeV/c^2. The Gaussian mass width of this state is 3MeV/c^2, consistent with resolution; its lifetime is less than 33fsec at 90% confidence.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter

First observation of a narrow charm-strange meson DsJ(2632) -> Ds eta and D0 K+

We report the first observation of a charm-strange meson DsJ(2632) at a mass of 2632.6+/-1.6 MeV/c^2 in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, Ds eta and D0 K+. In the Ds eta decay mode we observe an excess of 49.3 events with a significance of 7.2sigma at a mass of 2635.9+/-2.9 MeV/c^2. There is a corresponding peak of 14 events with a significance of 5.3sigma at 2631.5+/-1.9 MeV/c^2 in the decay mode D0 K+. The decay width of this state is <17 MeV/c^2 at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(Dseta) is 0.16+/-0.06. The mechanism which keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the Ds eta decay mode.Comment: 5 pages, 3 included eps figures. v2 as accepted for publication by PR

Observation of the Cabibbo-suppressed decay Xi_c+ -> p K- pi+

We report the first observation of the Cabibbo-suppressed charm baryon decay Xi_c+ -> p K- pi+. We observe 150 +- 22 events for the signal. The data were accumulated using the SELEX spectrometer during the 1996-1997 fixed target run at Fermilab, chiefly from a 600 GeV/c Sigma- beam. The branching fractions of the decay relative to the Cabibbo-favored Xi_c+ -> Sigma+ K- pi+ and Xi_c+ -> X- pi+ pi+ are measured to be B(Xi_c+ -> p K- pi+)/B(Xi_c+ -> Sigma+ K- pi+) = 0.22 +- 0.06 +- 0.03 and B(Xi_c+ -> p K- pi+)/B(Xi_c+ -> X- pi+ pi+) = 0.20 +- 0.04 +- 0.02, respectively.Comment: 5 pages, RevTeX, 3 figures (postscript), Submitted to Phys. Rev. Let