306 research outputs found
Lenalidomide normalizes tumor vessels in colorectal cancer improving chemotherapy activity
BACKGROUND: Angiogenesis inhibition is a promising approach for treating metastatic colorectal cancer (mCRC). Recent evidences support the seemingly counterintuitive ability of certain antiangiogenic drugs to promote normalization of residual tumor vessels with important clinical implications. Lenalidomide is an oral drug with immune-modulatory and anti-angiogenic activity against selected hematologic malignancies but as yet little is known regarding its effectiveness for solid tumors. The aim of this study was to determine whether lenalidomide can normalize colorectal cancer neo-vessels in vivo, thus reducing tumor hypoxia and improving the benefit of chemotherapy. METHODS: We set up a tumorgraft model with NOD/SCID mice implanted with a patient-derived colorectal cancer liver metastasis. The mice were treated with oral lenalidomide (50 mg/Kg/day for 28 days), intraperitoneal 5-fluorouracil (5FU) (20 mg/Kg twice weekly for 3 weeks), combination (combo) of lenalidomide and 5FU or irrelevant vehicle. We assessed tumor vessel density (CD146), pericyte coverage (NG2; alphaSMA), in vivo perfusion capability of residual vessels (lectin distribution essay), hypoxic areas (HP2-100 Hypoxyprobe) and antitumor activity in vivo and in vitro. RESULTS: Treatment with lenalidomide reduced tumor vessel density (p = 0.0001) and enhanced mature pericyte coverage of residual vessels (p = 0.002). Perfusion capability of tumor vessels was enhanced in mice treated with lenalidomide compared to controls (p = 0.004). Accordingly, lenalidomide reduced hypoxic tumor areas (p = 0.002) and enhanced the antitumor activity of 5FU in vivo. The combo treatment delayed tumor growth (p = 0.01) and significantly reduced the Ki67 index (p = 0.0002). Lenalidomide alone did not demonstrate antitumor activity compared to untreated controls in vivo or against 4 different mCRC cell lines in vitro. CONCLUSIONS: We provide the first evidence of tumor vessel normalization and hypoxia reduction induced by lenalidomide in mCRC in vivo. This effect, seemingly counterintuitive for an antiangiogenic compound, translates into indirect antitumor activity thus enhancing the therapeutic index of chemotherapy. Our findings suggest that further research should be carried out on synergism between lenalidomide and conventional therapies for treating solid tumors that might benefit from tumor vasculature normalization
The DLV System for Knowledge Representation and Reasoning
This paper presents the DLV system, which is widely considered the
state-of-the-art implementation of disjunctive logic programming, and addresses
several aspects. As for problem solving, we provide a formal definition of its
kernel language, function-free disjunctive logic programs (also known as
disjunctive datalog), extended by weak constraints, which are a powerful tool
to express optimization problems. We then illustrate the usage of DLV as a tool
for knowledge representation and reasoning, describing a new declarative
programming methodology which allows one to encode complex problems (up to
-complete problems) in a declarative fashion. On the foundational
side, we provide a detailed analysis of the computational complexity of the
language of DLV, and by deriving new complexity results we chart a complete
picture of the complexity of this language and important fragments thereof.
Furthermore, we illustrate the general architecture of the DLV system which
has been influenced by these results. As for applications, we overview
application front-ends which have been developed on top of DLV to solve
specific knowledge representation tasks, and we briefly describe the main
international projects investigating the potential of the system for industrial
exploitation. Finally, we report about thorough experimentation and
benchmarking, which has been carried out to assess the efficiency of the
system. The experimental results confirm the solidity of DLV and highlight its
potential for emerging application areas like knowledge management and
information integration.Comment: 56 pages, 9 figures, 6 table
Wavelength-shifting fibers for calorimetric measurements in a long base line neutrino oscillation experiment
Abstract The NOE Collaboration has proposed a calorimeter to measure the energy of the final states of ν interaction events. The properties of long scintillator bars with wavelength-shifting fiber readout have been studied to develop a calorimeter design option. Various prototypes have been exposed to a cosmic rays stand. The total measured light yield in the middle of a 6 m -long fiber is about 15 photoelectrons. With this photon collection performance, it has been simulated that the calorimeter can achieve 17%/ E and 50%/ E resolutions for electrons and pions, respectively
The hadronic cross section measurement at KLOE
KLOE uses the radiative return to measure cross section σ(e+e-->π+π-γ) at the electron-positron collider DAΦNE. Divinding by a theoretical radiator function, we obtain the cross section σ(e+e-->π+π-γ) for the mass range 0.35π<0.95GeV2. We calculate the hadronic contribution to the muon anomaly for the given mass range: aμ=388.7+/-0.8stat+/-3.5syst+/-3.5t
Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register
Introduction Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were >= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications
Determination of from radiative processes at DANE
We have measured the cross section with
the KLOE detector at DANE, at an energy GeV. From the
dependence of the cross section on , where
is the energy of the photon radiated from the initial state, we
extract for the mass range
GeV. From our result we extract the pion form
factor and the hadronic contribution to the muon anomaly, .Comment: Contributed paper to EPS 2003 and LP 200
Anti-cancer effect and gene modulation of ET-743 in human biliary tract carcinoma preclinical models
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