Downregulation of ORP3 Correlates with Reduced Survival of Colon Cancer Patients with Advanced Nodal Metastasis and of Female Patients with Grade 3 Colon Cancer.

Genome instability is an essential hallmark in tumor development, including colorectal cancer. We have recently identified the oxysterol binding protein-related protein 3 (ORP3), also known as oxysterol binding protein-like 3 (OSBPL3), as a novel ploidy-control gene, whose knock-out leads to aneuploidy induction and promotes tumor formation, indicating that ORP3 is a bona fide tumor suppressor protein. Here we analyzed expression of ORP3 in a cohort (n = 206) of colon cancer patients in relation to patient survival. We show that low ORP3 mRNA levels correlate with reduced survival of patients with advanced nodal metastasis (N2). While patient survival does not associate with grading when the whole cohort is evaluated, importantly, low ORP3 mRNA levels associate with worse survival of female patients with grade 3 colon cancer. Similarly, low ORP3 mRNA levels associate with worse survival of grade 3 colon cancer patients 70 years of age and younger while low ORP3 mRNA levels seem to be beneficial for colon cancer patients with a T2 tumor size. Together, the data show that ORP3 expression is downregulated during colon cancer progression, which correlates with reduced patient survival. Thus, ORP3 mRNA levels may be a prognostic marker for better stratification of colon cancer patients.

In Vitro Hypoglycemic and Antioxidant Activities of Dichloromethane Extract of Xerophyta spekei.

Diabetes mellitus is a chronic metabolic disorder which has greatly led to an increase in morbidity and mortality globally. Although Xerophyta spekei is widely used for the management of diabetes among the Embu and Mbeere communities in Kenya, it has never been empirically evaluated for its hypoglycemic activity. This study was carried out to verify the hypoglycemic activity of dichloromethane (DCM) extract of Xerophyta spekei as well as its antioxidant activity using various in vitro techniques. Phytochemicals associated with its antioxidant activity were identified through GC-MS. Data were subjected to descriptive statistics and expressed as mean ± standard error of the mean (X̄ ± SEM). Comparison between various variables was performed by using unpaired Student's t-test and one-way analysis of variance (ANOVA), followed by Tukey's post-hoc test. The confidence interval was set at 95%. The obtained results were presented in tables and graphs. Results showed that there was no difference in α-amylase inhibition activity between the plant extract and the standard (IC50 525.9 ± 12.34 and 475.1 ± 9.115, respectively; p > 0.05). Besides, the glucose adsorption activity of the extract increased with an increase in glucose concentration (from 5.89 to 32.64 mg/dl at 5 mmol and 30 mmol of glucose, respectively; p < 0.05). The extract also limited the diffusion of glucose more than the negative control (7.49 and 17.63 mg/dl, respectively; p < 0.05). It also enhanced glucose uptake by yeast cells. In addition, the studied plant extract showed notable antioxidant activities. The therapeutic effects exhibited by this plant in managing diabetes mellitus and other ailments could be due to its antioxidant as well as its hypoglycemic activity. The study recommends the evaluation of X. spekei for in vivo hypoglycemic and antioxidant activities. Besides, the isolation of bioactive phytochemicals from the plant may lead to the development of new hypoglycaemic agents.