Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT.

PURPOSE: Angiogenesis plays an important role in the growth and metastatic spread of solid tumours and is characterised by the expression of integrins on the cell surface of endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related αvß3 integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we validated the feasibility of 68Ga[Ga]-DOTA-E-[c(RGDfK)]2 (68Ga-RGD) PET/CT to visualise angiogenesis in patients with oral squamous cell carcinoma (OSCC). METHODS: Ten patients with OSCC and scheduled for surgical resection including elective neck dissection received an intravenously administration of 68Ga-RGD (42 ± 8 µg; 214 ± 9 MBq). All patients subsequently underwent dynamic (n = 5) or static PET/CT imaging (n = 5) for 60 min or for 4 min/bed position at 30, 60 and 90 min after injection, respectively. Quantitative tracer uptake in tumour lesions was expressed as standardised uptake values (SUV). Additionally, tumour tissue was immunohistochemically stained for αvß3 integrin to assess the expression pattern. RESULTS: 68Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUVmax ranged between 4.0 and 12.7. Tracer accumulation in tumour tissue plateaued at 10 min after injection. Uptake in background tissue did not change over time, resulting in tumour-to-muscle tissue of 6.4 ± 0.7 at 60 min post injection. CONCLUSIONS: 68Ga-RGD PET/CT of αvß3 integrin expression in OSCC patients is feasible with adequate tumour-to-background ratios. It will provide more insight in angiogenesis as a hallmark of the head and neck squamous cell carcinomas' tumour microenvironment. TRIAL REGISTRATION: https://eudract.ema.europa.eu no. 2015-000917-31.

Process Evaluation and Experience Sharing on Utilizing Information Communication Technologies and Digital Games in a Large Community Family Health Event: Hong Kong Jockey Club SMART Family-Link Project.

Background: Information communication technologies (ICT) are increasingly used in health promotion, but integration is challenging and involves complex processes. Large community health promotion events are often held but the experiences and processes have rarely been evaluated and published. No reports have described and systematically evaluated an ICT-supported health promotion event using digital games. Objective: We evaluated the development and implementation of a large community family health promotion event with ICT integration to promote family happiness with collaboration between academia (The University of Hong Kong) and the social (family) service sector, and collected feedback from participants and social service workers. Methods: We (i) conducted a systematic process evaluation, (ii) administered an on-site questionnaire survey on participant satisfaction and feedback, and (iii) collected post-event qualitative feedback from social workers on using new technologies, digital game design and overall experiences. Results: Fourteen digital games were designed and run in booths at the event by 12 non-governmental social service organizations and academia. Four gaming technologies were utilized: chroma key (green screen), somatosensory (kinect and leap motion techniques), augmented reality and virtual reality. 1,365 participants joined the event, in which 1,257 from 454 families were recruited and pre-registered through 12 NGOs. About 39.3% were male and more than half (53.3%) were aged 18 years and above. About 3,487 game booth headcounts were recorded. Games using virtual reality, kinect motion and green screen technologies were most liked. The average game satisfaction score was high (4.5 out of 5). Social service workers reported positive experiences with using new technologies in health promotion, and interests in future collaborations involving more ICT. Conclusions: Our systematic evaluation showed successful integration of ICT components in the health promotion event. This event, most likely the first of its kind, served as a capacity building and knowledge transfer platform for interdisciplinary co-sharing and co-learning of new technologies. It provided a solid foundation for further academic and social service partnerships and should be a useful model for similar community events and their evaluation. Further development and integration of ICT for health promotion among social service organizations with comprehensive evaluation are warranted.

A role for topoisomerase II alpha in the formation of radiation-induced chromatid breaks.

Chromatid breaks in cells exposed to low dose irradiation are thought to be initiated by DNA double-strand breaks (DSB), and the frequency of chromatid breaks has been shown to increase in DSB rejoining deficient cells. However, the underlying causes of the wide variation in frequencies of G2 chromatid breaks (or chromatid 'radiosensitivity') in irradiated T-lymphocytes from different normal individuals and cancer cases are as yet unclear. Here we report evidence that topoisomerase II alpha expression level is a factor determining chromatid radiosensitivity. We have exposed the promyelocytic leukaemic cell line (HL60) and two derived variant cell lines (MX1 and MX2) that have acquired resistance to mitoxantrone and low expression of topoisomerase II alpha, to low doses of gamma-radiation and scored the induced chromatid breaks. Chromatid break frequencies were found to be significantly lower in the variant cell lines, compared with their parental HL60 cell line. Rejoining of DSB in the variant cell lines was similar to that in the parental HL60 strain. Our results indicate the indirect involvement of topoisomerase II alpha in the formation of radiation-induced chromatid breaks from DSB, and suggest topoisomerase II alpha as a possible factor in the inter-individual variation in chromatid radiosensitivity.

Pharmacological specificity of the caffeine discriminative stimulus in humans: effects of theophylline, methylphenidate and buspirone.

The present study examined further the pharmacological specificity of the methylxanthine CNS stimulant caffeine as a discriminative stimulus in humans. Nine normal healthy volunteers (ages 19-39) were trained to discriminate between caffeine (320mg/70kg, p.o.) and placebo, using monetary reinforcement of correct letter code identification. After four training sessions, subjects were tested with the training conditions until they were >80% correct on four consecutive sessions. Then dose-effect curves were determined for caffeine (56-320mg/70kg), theophylline (56-320mg/70kg), methylphenidate (10-56mg/70kg), and buspirone (1-32mg/70kg). Seven of nine subjects met the discrimination criterion within four to nine sessions. During dose-effect curve determinations, caffeine and methylphenidate each produced dose-related increases in caffeine-appropriate responding. Theophylline produced caffeine-appropriate responding that was not dose related in a consistent manner across subjects, occasioning an average of 50% caffeine-appropriate responding at most doses tested. Buspirone produced predominantly placebo-appropriate responding. Caffeine-appropriate responding tended to be directly related to ARCI LSD scores, self-reported "bad" effects, "high", and stimulant-bad effects and inversely related to ARCI PCAG scores and sedative ratings. These results agree with non-human data and suggest that the caffeine discriminative stimulus has pharmacological specificity, in that caffeine-appropriate responding generalizes to other stimulants such as theophylline or methylphenidate, but not to non-stimulant compounds such as buspirone.

Effects of caffeine on tobacco withdrawal.

Smoking cessation increases caffeine blood levels, and this has been hypothesized to cause some of the symptoms of tobacco withdrawal (e.g., anxiety and insomnia). To test this hypothesis, 10 coffee drinkers who smoked cigarettes were entered into a completely within-subjects experimental design in which the effects of caffeine dose (0, 50, and 100 mg/coffee serving) and smoking status (smoking versus abstinence) were examined over a 4-day period. Self-reported and observed measures of tobacco withdrawal, caffeine withdrawal, and intoxication, as well as psychomotor tasks and vital signs, were completed daily; blood was drawn at the end of each period. Temporary abstinence produced typical withdrawal symptoms but did not significantly increase caffeine blood levels. Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger. These findings suggest that, in the absence of increased blood levels, caffeine does not increase the severity of tobacco withdrawal.