Nitrogen isotopic composition as a gauge of tumor cell anabolism-to-catabolism ratio.

Studies have suggested that cancerous tissue has a lower N/N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the N/N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution.

Antitumor Effect by Either FLASH or Conventional Dose Rate Irradiation Involves Equivalent Immune Responses.

Purpose: The capability of ultrahigh dose rate FLASH radiation therapy to generate the FLASH effect has opened the possibility to enhance the therapeutic index of radiation therapy. The contribution of the immune response has frequently been hypothesized to account for a certain fraction of the antitumor efficacy and tumor kill of FLASH but has yet to be rigorously evaluated.

Methods And Materials: To investigate the immune response as a potentially important mechanism of the antitumor effect of FLASH, various murine tumor models were grafted either subcutaneously or orthotopically into immunocompetent mice or in moderately and severely immunocompromised mice.

FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.

Background And Purpose: The impact of radiotherapy (RT) at ultra high vs conventional dose rate (FLASH vs CONV) on the generation and repair of DNA double strand breaks (DSBs) is an important question that remains to be investigated. Here, we tested the hypothesis as to whether FLASH-RT generates decreased chromosomal translocations compared to CONV-RT.

Materials And Methods: We used two FLASH validated electron beams and high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), employing S.

Comparing radiolytic production of HO and development of Zebrafish embryos after ultra high dose rate exposure with electron and transmission proton beams.

The physico-chemical and biological response to conventional and UHDR electron and proton beams was investigated, along with conventional photons. The temporal structure and nature of the beam affected both, with electron beam at ≥1400 Gy/s and proton beam at 0.1 and 1260 Gy/s found to be isoefficient at sparing zebrafish embryos.

Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female wild-type (WT) mice were treated with paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation.

Extracellular Vesicles for the Treatment of Radiation-Induced Normal Tissue Toxicity in the Lung.

Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we sought to determine whether human embryonic stem cell (hESC)-derived EV could resolve in part, the adverse late normal tissue complications associated with exposure of the lung to ionizing radiation. The hESC-derived EV were systemically administered to the mice the retro-orbital sinus to explore the potential therapeutic benefits following exposure to high thoracic doses of radiation (14 Gy).

Anti-Ly6G binding and trafficking mediate positive neutrophil selection to unleash the anti-tumor efficacy of radiation therapy.

The anti-Ly6G antibody is used to deplete Ly6G neutrophils and study their role in diverse pathologies. However, depletion is never absolute, as Ly6G neutrophils resistant to depletion rapidly emerge. Studying the functionality of these residual neutrophils is necessary to interpret anti-Ly6G-based experimental designs.

Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.

Purpose: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses.

Experimental Design: Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model.

Clinical translation of FLASH radiotherapy: Why and how?

Over the past decades, technological advances have transformed radiation therapy (RT) into a precise and powerful treatment for cancer patients. Nevertheless, the treatment of radiation-resistant tumors is still restricted by the dose-limiting normal tissue complications. In this context, FLASH-RT is emerging in the field.

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s). Compared with conventional dose-rate (CONV; 0.07-0.

TAT-RasGAP Enhances Radiosensitivity of Human Carcinoma Cell Lines In Vitro and In Vivo through Promotion of Delayed Mitotic Cell Death.

The synthetic peptide TAT-RasGAP has been shown to potentiate the efficacy of anti-cancer drugs. In this study, we explored the action of TAT-RasGAP when combined with radiation by investigating its radiosensitizing activity in vitro and in vivo. To investigate the modulation of intrinsic radiosensitivity induced by TAT-RasGAP, clonogenic assays were performed using four human cancer cell lines, HCT116 p53 (ATCC: CCL-247), HCT116 p53, PANC-1 (ATCC: CRL-1469) and HeLa (ATCC: CCL-2), as well as one nontumor cell line, HaCaT (CLS: 300493).