Micellar formulations of Crizotinib and Dasatinib in the management of glioblastoma multiforme

Glioblastoma multiforme (GBM) defies the currently practiced management of radiotherapy, chemotherapy and surgery and hence, it is associated with a high fatality rate with a median survival of 14.6 months. In our previous work investigating different tyrosine kinase inhibitors (TKIs), we established that a combination of Crizotinib and Dasatinib exerted the most potent effect on different GBM cell lines. In this work, to improve targeted therapy at the site of the tumour and avoid systemic toxicity, we exploited the enhanced permeability and retention effect by designing micellar formulations of these two TKIs. Crizotinib and Dasatinib were successfully encapsulated in poly(styrene-co-maleic acid) (SMA) micelles which were then evaluated for their physicochemical characteristics, anti-proliferative effect, mode of cell death, efficacy in spheroid models, effect on cell signalling, antiangiogenic potential and in vivo anticancer activity. Our results showed that this combination had induced a potent anti-proliferative effect in four GBM cell lines grown as a monolayer and as a spheroid. The combination was also efficacious in in vitro models of angiogenesis and vascular mimicry. In vivo data showed the enhanced activity of the micellar TKIs compared to free drugs. In conclusion, we proved that micellar formulations of Crizotinib and Dasatinib carry promising in vitro and in vivo efficacy that warrant further investigation.     

A framework for testing the equality between the health concentration curve and the 45‐degree line

The health concentration curve is the standard graphical tool to depict socioeconomic health inequality in the literature on health inequality. This paper shows that testing for the absence of socioeconomic health inequality is equivalent to testing if the conditional expectation of health on income is a constant function that is equal to average health status. In consequence, any test for parametric specification of a regression function can be used to test for the absence of socioeconomic health inequality (subject to regularity conditions). Furthermore, this paper illustrates how to test for this equality using a test for parametric regression functional form and applies it to health‐related behaviors from the National Health Survey 2014.     

Open surgical partial nephrectomy for upper tract urothelial carcinoma

We aimed to determine the ability of partial nephrectomy to prevent end‐stage renal disease and tumor recurrence or progression in patients with upper tract urothelial carcinoma. Retrospectively, eight patients undergoing partial nephrectomy for upper tract urothelial carcinoma were identified and their medical records reviewed. All patients had imperative indications for nephron sparing, and diagnosis of upper tract urothelial carcinoma not adequately amenable to endoscopic management. Although three patients suffered acute tubular necrosis, only one required postoperative hemodialysis. During the follow‐up period 25% (2/8) developed end‐stage renal disease, including the one patient who had received postoperative hemodialysis. Recurrences occurred in five of seven patients with adequate oncological surveillance. Recurrences were successfully treated endoscopically in 80% (4/5) patients, and one patient had metastases. Of the eight patients, four have died. Death occurred 4 months, 1 year, 1.2 years and 3.5 years after partial nephrectomy. Of these patients, one succumbed to metastatic disease; the exact cause of death is unknown in the other three, but there was no documentation of metastatic cancer. The mean duration of follow up in the remaining four patients, all without evidence of metastatic urothelial cancer, is 71 months (range 22–108 months). In summary, partial nephrectomy for upper tract urothelial carcinoma in patients with imperative indications averts end‐stage renal disease in most patients, and appears to be associated with acceptable disease‐specific survival. Partial nephrectomy is a sparingly used option in patients with upper tract urothelial carcinoma refractory to endoscopic management who have imperative indications for nephron sparing.