Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics.

Background: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. Results: The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. Conclusions: Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings. Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00228-0.

Understanding radiation response and cell cycle variation in brain tumour cells using Raman spectroscopy.

Radiation therapy is currently utilised in the treatment of approximately 50% of cancer patients. A move towards patient tailored radiation therapy would help to improve the treatment outcome for patients as the inter-patient and intra-patient heterogeneity of cancer leads to large differences in treatment responses. In radiation therapy, a typical treatment outcome is cell cycle arrest which leads to cell cycle synchronisation. As treatment is typically given over multiple fractions it is important to understand how variation in the cell cycle can affect treatment response. Raman spectroscopy has previously been assessed as a method for monitoring radiation response in cancer cells and has shown promise in detecting the subtle biochemical changes following radiation exposure. This study evaluated Raman spectroscopy as a potential tool for monitoring cellular response to radiation in synchronised versus unsynchronised UVW human glioma cells in vitro. Specifically, it was hypothesised that the UVW cells would demonstrate a greater radiation resistance if the cell cycle phase of the cells was synchronised to the G1/S boundary prior to radiation exposure. Here we evaluated whether Raman spectroscopy, combined with cell cycle analysis and DNA damage and repair analysis (γ-H2AX assay), could discriminate the subtle cellular changes associated with radiation response. Raman spectroscopy combined with principal component analysis (PCA) was able to show the changes in radiation response over 24 hours following radiation exposure. Spectral changes were assigned to variations in protein, specifically changes in protein signals from amides as well as changes in lipid expression. A different response was observed between cells synchronised in the cell cycle and unsynchronised cells. After 24 hours following irradiation, the unsynchronised cells showed greater spectral changes compared to the synchronised cells demonstrating that the cell cycle plays an important role in the radiation resistance or sensitivity of the UVW cells, and that radiation resistance could be induced by controlling the cell cycle. One of the main aims of cancer treatment is to stop the proliferation of cells by controlling or halting progression through the cell cycle, thereby highlighting the importance of controlling the cell cycle when studying the effects of cancer treatments such as radiation therapy. Raman spectroscopy has been shown to be a useful tool for evaluating the changes in radiation response when the cell cycle phase is controlled and therefore highlighting its potential for assessing radiation response and resistance.

Towards a fair and transparent research participant compensation and reimbursement framework in Vietnam.

BACKGROUND: Providing compensation for participants in clinical research is well established and while international guidelines exist, defining a context-specific and fair compensation for participants in low-resource settings is challenging due to ethical concerns and the lack of practical, national compensation and reimbursement frameworks. METHODS: We reviewed Oxford University Clinical Research Unit (OUCRU) internal reimbursement documentation over a 10-y period and conducted a scoping literature review to expand our knowledge of compensation and reimbursement practices including ethical concerns. We developed a preliminary reimbursement framework that was presented to community advisory boards (CAB) and clinical investigators to assess its applicability, fairness and transparency. RESULTS: The main topics discussed at the workshops centered on fairness and whether the reimbursements could be perceived as financial incentives. Other decisive factors in the decision-making process were altruism and the loss of caregivers' earnings. Investigators raised the issue of additional burdens, whereas the CAB members were focused on non-monetary elements such as the healthcare quality the patients would receive. All elements discussed were reviewed and, where possible, incorporated into the final framework. CONCLUSION: Our new reimbursement framework provides a consistent, fair and transparent decision-making process and will be implemented across all future OUCRU clinical research in Vietnam.

The inferior frontal gyrus and phonological processing: an investigation using rTMS.

Repetitive transcranial magnetic stimulation (rTMS) offers a powerful new technique for investigating the distinct contributions of the cortical language areas. We have used this method to examine the role of the left inferior frontal gyrus (IFG) in phonological processing and verbal working memory. Functional neuroimaging studies have implicated the posterior part of the left IFG in both phonological decision making and subvocal rehearsal mechanisms, but imaging is a correlational method and it is therefore necessary to determine whether this region is essential for such processes. In this paper we present the results of two experiments in which rTMS was applied over the frontal operculum while subjects performed a delayed phonological matching task. We compared the effects of disrupting this area either during the delay (memory) phase or at the response (decision) phase of the task. Delivered at a time when subjects were required to remember the sound of a visually presented word, rTMS impaired the accuracy with which they subsequently performed the task. However, when delivered later in the trial, as the subjects compared the remembered word with a given pseudoword, rTMS did not impair accuracy. Performance by the same subjects on a control task that required the processing of nonverbal visual stimuli was unaffected by the rTMS. Similarly, performance on both tasks was unaffected by rTMS delivered over a more anterior site (pars triangularis). We conclude that the opercular region of the IFG is necessary for the normal operation of phonologically based working memory mechanisms. Furthermore, this study shows that rTMS can shed further light on the precise role of cortical language areas in humans.

Chromatic priming in hemianopic visual fields.

In three monkeys made hemianopic by unilateral striate cortical ablation, in one normal monkey and in a human hemianope (GY), we measured reaction times to chromatic targets presented in the normal hemifield as a function of prior chromatic primes in the blind field. The first of our three tasks showed an unspecific priming effect in that the colour of the here unpredictive prime was irrelevant. However, when contingencies were changed in the second task so that the prime was usually valid, its colour did significantly influence reaction times in two of the hemianopic monkeys as well as in the human subject. Even when the primes lost their predictive value again in the third task, this chromatically specific effect persisted. We conclude that chromatic processing in the cortically blind field can be revealed with indirect approaches that measure residual processing by its influence on the reaction to stimuli in the normal field, and that the validity of the prime (whether it predicts the colour of the target) is especially important.

Auditory chronostasis: hanging on the telephone.

The perception of time can be illusory: we have all waited anxiously for important seconds to tick away slowly at the end of a football game and have experienced the truth of the adage "time flies when you're having fun." One illusion of time experience that has recently been investigated, the apparent slowing of the movement of the second hand on the clock when one first looks at it, has been termed "chronostasis," and it has been suggested that the effect is unique to vision and is dependent on eye movements. We sought to test whether the effect is really unique to vision or whether it can also be produced with auditory stimuli. Subjects were asked to judge the length of a silent gap between two tones presented through headphones. When the tones were presented to one ear, subjects judged the duration of the gap veridically. When subjects were required to shift concentration from one ear to the other, however, the judgement of time showed that the auditory system is also susceptible to chronostasis. We suggest that this generalization of chronostasis to another sensory system is consistent with theories of time perception that emphasize a single, multimodal clock for duration estimation rather than a mechanism that is dependent on motor acts.

Prime-sight in a blindsight subject.

A subject (D.B.) who had no experience of visual stimuli in a field defect caused by visual cortex damage but could discriminate them ('blindsight') nevertheless reported visible after-images of the stimuli when they were turned off ('prime-sight'). This was investigated using projected visual stimuli of varying colors, contrasts, shapes and spatial frequencies, and by measuring the properties of the after-images, including their duration, size scaling, color and interocular transfer, comparing the capacity of the blindsight and prime-sight modes. These phenomena offer a unique opportunity to compare conscious and unconscious neural events in response to the same visual events.