Anti-RET monoclonal antibody, clone 4B7

Cannabis appears to have vascular effects that may have implications for cerebrovascular function, but no studies have directly visualized the microvasculature in living cannabis users. The current study used retinal imaging, a tool taken from ophthalmology, to visualize the small retinal microvessels in cannabis users. We compared ret- inal arteriolar (small arteries) and venular (small veins) diameters in 55 frequent cannabis users and 51 compar- ison individuals with a mean age of 19.25 years ( SD = 2.43). Results indicated that mean arteriolar diameter was statistically signi ficantly wider for cannabis users ( M =157.98, SE = 1.42) than for comparison individuals ( M = 153.56, SE = 1.46; F (1,103) = 4.67, p = .033), even after controlling for a variety of covariates and after excluding from analyses cannabis users who had used cannabis in the past 24 h. There was no statistically signi ficant differ- ence in retinal venular diameter between cannabis users and comparison individuals. Findings suggest that fre- quent cannabis use is associated with wider retinal arterioles, which might represent a residual vasodilatory effect of recent cannabis use or impaired autoregulation resulting from chronic cannabis use. Retinal imaging is a non-invasive, cost-effective tool for visualizing the microvasculature in living individuals and can be com- bined, in future research, with neuroimaging and other measures of retinal vascular function to better under- stand the acute and longer -term effects of cannabis use on the microvasculature.

Since patients with medullary thyroid cancer (MTC) often have metastatic disease at the time of diagnosis, the development of efficient systemic treatment options for MTC is important. Vandetanib and cabozantinib are two tyrosine kinase inhibitors (TKIs) that were recently approved by FDA and EMA for systemic treatment of metastatic MTC. Additionally, since MTC is of a neuroendocrine tumour type, treatment with radiolabelled somatostatin analogues (e.g. Lu-177-octreotate) is a valid option for patients with MTC. The aim of this study was to investigate the potentially increased therapeutic effect of combining radiation therapy with these TKIs for treatment of MTC in a mouse model. Nude mice carrying patient-derived MTC tumours (GOT2) were treated with external beam radiotherapy (EBRT) and/or one of the two TKIs vandetanib or cabozantinib. The tumour volume was determined and compared with that of mock-treated controls. The treatment doses were chosen to give a moderate effect as monotherapy to be able to detect any increased therapeutic effect from the combination therapy. At the end of follow-up, tumours were processed for immunohistochemical (IHC) analyses. The animals in the combination therapy groups showed the largest reduction in tumour volume and the longest time to tumour progression. Two weeks after start of treatment, the tumour volume for these mice was reduced by about 70-75% compared with controls. Furthermore, also EBRT and TKI monotherapy resulted in a clear anti-tumour effect with a reduced tumour growth compared with controls. The results show that an increased therapeutic effect could be achieved when irradiation is combined with TKIs for treatment of MTC. Future studies should evaluate the potential of using Lu-177-octreotate therapy in combination with TKIs in patients.