Radiation responses of cancer and normal cells to split dose fractions with uniform and grid fields: increasing the therapeutic ratio.

PURPOSE: Radiation treatment of cancer is usually delivered in a prescribed sequence of dose fractions within which the dependence of dose on time is determined by the treatment plan. New techniques, such as stereotactic body radiation therapy (SBRT) and image guided radiation therapy (IGRT) have been introduced with the motivation of improving therapeutic outcomes, with the consequence that the time dependence of the dose within a fraction is modified. Here, we test whether an increased toxicity to cancer cells arises when a radiation treatment fraction is delivered in two equal parts, allowing time for the expression of factors, for example, RONS and cytokines, in response to the first dose which may sensitize cells to the second dose. A medium time delay between 15 and 60 minutes is proposed to allow factors to be expressed before repair takes place. A grid field is used to enhance diffusion of the factors. MATERIALS AND METHODS: The cell lines used in the study were two prostate cancers (LNCaP and DU 145), a normal prostate (PNT1A), a non-small cell lung cancer (NCI-H460), and a glioma (Hs 683). Uniform or spatially modulated grid fields, delivering the same mean dose, were used. The results for the clonogenic survival fractions were grouped into a 'short' delay (under 10 minutes) and a 'medium' delay (between 15 and 60 minutes). RESULTS: The medium delay with a grid field yielded a significant increase in toxicity for the four cancer cell lines. The medium delay with a uniform field gave a significant increase in toxicity for the two prostate cancer cell lines. A highly significant increase was found in the therapeutic ratio, defined as the ratio of the survival of prostate normal to prostate cancer cells. CONCLUSIONS: The findings show that the intra-fractional dose schedule with medium time delay offers an opportunity to increase the toxicity of radiation to cancer cells, relative to a single radiation delivery. For all cancer cell lines, a grid field gives a greater toxic effect than a uniform field. The split dose treatment offers an increase in cancer toxicity while preserving normal cells, improving the outcomes of a treatment.

Oral efficacy of Δ(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model.

The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have synergistic analgesic efficacy in animal models of neuropathic pain when injected systemically. However, the relevance of this preclinical synergy to clinical neuropathic pain studies is unclear because many of the latter use oral administration. We therefore examined the oral effectiveness of these phytocannabinoids and their interactions in a mouse chronic constriction injury (CCI) model of neuropathic pain. THC produced a dose-dependent reduction in mechanical and cold allodynia, but also induced side-effects with similar potency. CBD also reduced allodynia, albeit with lower potency than THC, but did not produce cannabinoid-like side-effects at any dose tested. Combination THC:CBD produced a dose-dependent reduction in allodynia, however, it displayed little to no synergy. Combination THC:CBD produced substantial, synergistic side-effects which increased with the proportion of CBD. These findings demonstrate that oral THC and CBD, alone and in combination, have analgesic efficacy in an animal neuropathic pain model. Unlike prior systemic injection studies, combination THC:CBD lacks analgesic synergy when delivered orally. Furthermore, both THC and combination THC:CBD display a relatively poor therapeutic window when delivered orally. This suggests that CBD provides a safer, albeit lower efficacy, oral treatment for nerve injury induced neuropathic pain than THC-containing preparations. This article is part of the special issue on 'Cannabinoids'.

Cancer treatment with gas plasma and with gas plasma-activated liquid: positives, potentials and problems of clinical translation.

Gas plasmas, created in atmospheric pressure conditions, both thermal (hot) and non-thermal (cold) are emerging as useful tools in medicine. During surgery, hot gas plasmas are useful to reduce thermal damage and seal blood vessels. Gas plasma pens use cold gas plasma to produce reactive chemical species with selective action against cancers, which can be readily exposed in surgery or treated from outside of the body. Solutions activated by cold gas plasma have potential as a novel treatment modality for treatment of less readily accessible tumours, or those with high metastatic potential. This review summarises the preclinical and clinical trial evidence currently available, as well as the challenges for translation of direct gas plasma and gas plasma-activated solution treatment into regular practice.