hypoxia immunity metabolism and hyperthermia

Hypoxia is common in solid tumors and in many other disease states such as myocardial infarction, stroke, bone fracture, and pneumonitis. Once hypoxia has developed, the undernourished and hypoxic cells trigger signals in order to obtain new blood vessels to satisfy their increasing demands and to resolve hypoxia. The principal signal activated is an ancestral oxygen sensor, the hypoxia inducible factor (HIF). After its nuclear translocation, HIF triggers a series of mediators that recruit, into the hypoxic milieu, several immature myeloid, mesenchymal, and endothelial progenitors cells. Resident and recruited cells participate in the processes of neoangiogenesis, for resolving the hypoxia, while at the same time trigger an inflammatory reaction. The inflammatory reaction has as primary end point, the repair of the damaged area, but if an insufficient production of resolvins is produced, the inflammatory reaction becomes chronic and is unable to repair the damaged tissue. In this brief overview, we will show the differences and the similar events present in cancer, myocardial infarction, and stroke. Furthermore, the metabolic alterations produced in the tumor by hypoxia/HIF axis and the consequences on hyperthermic treatment are also discussed

A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced WT BRAF Melanoma Patients.

ABSTRACT Background Treatment strategies for advanced cutaneous melanoma (CM) patients, resistant or not treatable with novel target and immunotherapeutic drugs, remain a significant challenge, particularly for patients with unresectable stage IIIC/D disease localized to inferior limbs and pelvis, for whom specific outcomes are rarely considered. Materials and methods This is a prospective study of multidisciplinary treatments, including locoregional melphalan chemotherapy, in 62 BRAF wild-type CM patients with locoregional metastases in the inferior limbs and pelvis, including inguinal regions. Patients were either in progression following or ineligible for, or not treatable with novel immunotherapy. For exclusively inferior limb-localised disease, patients received locoregional melphalan chemotherapy performed by hyperthermic isolated limb perfusion (n = 19) or isolated limb infusion (n = 19), and for synchronous lesions localised to inferior limbs and pelvis, received hypoxic pelvic and limb perfusion (n = 24). Additional multidisciplinary therapy included local, locoregional and systemic treatments and the primary endpoint was tumour response. Results The objective response rate following first cycle of locoregional chemotherapy was 37.1% at 3 mo and median progression-free survival was 4-mo, with 12.9% procedure-related complications, 30.6% low-grade haematological toxicity and 11.3% severe limb toxic tissue reactions. Multivariate logistic regression showed that the odds of response were significantly higher for patients ≤ 75 y of age and for patients with locoregional metastases exclusively located in the inferior limbs. Conclusion In this subgroup of CM patients with BRAF wild-type status, locoregional metastases localized to inferior limbs and pelvis, in progression following or ineligible for immunotherapy, melphalan locoregional chemotherapy demonstrated a safe and effective profile. Trial Registration ClinicalTrials.gov Identifier NCT01920516; date of trial registration: August 6, 2013

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, USA. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of $7\times 6\times 7.2$~m$^3$. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, U.S.A. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of 7 × 6 × 7.2 m3. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components

Searching for solar KDAR with DUNE

Abstract: The observation of 236 MeV muon neutrinos from kaon-decay-at-rest (KDAR) originating in the core of the Sun would provide a unique signature of dark matter annihilation. Since excellent angle and energy reconstruction are necessary to detect this monoenergetic, directional neutrino flux, DUNE with its vast volume and reconstruction capabilities, is a promising candidate for a KDAR neutrino search. In this work, we evaluate the proposed KDAR neutrino search strategies by realistically modeling both neutrino-nucleus interactions and the response of DUNE. We find that, although reconstruction of the neutrino energy and direction is difficult with current techniques in the relevant energy range, the superb energy resolution, angular resolution, and particle identification offered by DUNE can still permit great signal/background discrimination. Moreover, there are non-standard scenarios in which searches at DUNE for KDAR in the Sun can probe dark matter interactions

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3σ (5σ) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3σ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Review Article - Hyperthermia today: Electric energy, a new opportunity in cancer treatment

Hyperthermia is an ancient, but nowadays rapidly developing treatment method in tumor-therapy. Its new paradigm applied in the electro-hyperthermia (oncothermia), which provides energy by means of electric-field and produces non-equilibrium thermal situation in the tissue. The temperature gradients formed in stationer conditions, destroy the membrane of the malignant cells and selectively eliminate the cancer tissue. The characteristic control parameter is the absorbed energy-dose, which is partly used to make the distortions, partly to increase the temperature of the target. This type of technique could be applied for some tumor sites, including brain, soft tissues, liver and abdominal masses, pancreatic cancer, head and neck tumors as well