Salinomycin and Sulforaphane Exerted Synergistic Antiproliferative and Proapoptotic Effects on Colorectal Cancer Cells by Inhibiting the PI3K/Akt Signaling Pathway in vitro and in vivo.

BACKGROUND: Both salinomycin (SAL) and sulforaphane (SFN) exert their antitumorigenic effects in various types of cancer We investigated whether combining salinomycin (SAL, an antibiotic ionophore) with sulforaphane (SFN, a phytochemical) exerted synergistic antiproliferative and proapoptotic activities in colorectal cancer (CRC) cells in vitro and in vivo by evaluating the proliferative and apoptotic responses of two CRC cell lines. MATERIALS AND METHODS: The combination index (CI) was calculated using the Chou-Talalay method, and the effects of the synergistic combination (CI<1) of lower doses of SAL and SFN were selected for further studies. Anti-tumor effect of the combination of SAL and SFN was tested both in vitro and in vivo. RESULTS: Cotreatment effectively inhibited proliferation, migration and invasion and enhanced apoptosis. The xenograft model also showed similar results. Furthermore, we evaluated the molecular mechanism behind SAL- and SFN-mediated CRC cell apoptosis. The combination treatment induced apoptosis in Caco-2 and CX-1 cells by inhibiting the PI3K/Akt pathway, which increased the expression of the tumor suppressor protein p53. The treatment also decreased the expression of the survival protein Bcl-2 and increased the expression of the proapoptotic protein Bax, which increased the Bax/Bcl-2 ratio, as well as enhanced poly ADP-ribose polymerase (PARP) cleavage. Upon inhibiting the PI3K/Akt pathway with LY294002 prior to cotreatment, we detected enhanced PARP cleavage compared to that in the cotreatment only group. CONCLUSION: We investigated whether the combination of SAL and SFN had antiproliferative and proapoptotic effects in CRC cells both in vitro and in vivo. Cotreatment also significantly decreased migration and invasion compared to that of the control and SAL or SFN monotherapies. This novel combination of SAL and SFN might provide a potential strategy to treat CRC.

Low versus high radioiodine activity for ablation of the thyroid remnant after thyroidectomy in Han Chinese with low-risk differentiated thyroid cancer.

AIM: The aim of this study was to compare the efficacy and adverse effects of radioiodine (131I) therapy between two groups of patients with low-risk differentiated thyroid cancer (DTC) who received 30 mCi or 100 mCi radioiodine for ablation of the thyroid remnant after total thyroidectomy. METHODS: The study cohort was 173 patients, 85 of whom were given 30 mCi of radioiodine and the others were given 100 mCi of radioiodine. Follow-up involved neck ultrasonography, measurement of serum levels of thyroglobulin and whole-body scans to evaluate the response of radioiodine treatment. All patients were assessed for adverse effects. RESULTS: Of the 173 patients, 170 (98.3%) patients finally achieved successful ablation. The prevalence of successful ablation was 77.6% in the low-dose group versus 71.5% in the high-dose group after the first dose administration (P=0.36), 79% in the low-dose group versus 88% in the high-dose group after the second dose administration (P=0.416), and 97.6% in the low-dose group versus 98.9% in the high-dose group after the final ablation (P=0.54). We found no significant differences between the two groups. No patient had an adverse effect with a severity grade ⩾2 and the prevalence of adverse effects in the high-dose group was higher than that in the low-dose group, especially for nausea, neck pain, and sore throat. CONCLUSION: These data suggest that a low dose of radioiodine is as effective as a high dose of radioiodine for ablation of the thyroid remnant after total thyroidectomy for low-risk DTC. Moreover, low-dose radioiodine therapy is associated with a lower prevalence of adverse events.

Comparison of striatal dopamine transporter levels in chronic heroin-dependent and methamphetamine-dependent subjects.

To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by 99m Tc-TRODAT-1 single-photon emission computed tomography (SPECT) brain images in people with heroin and METH dependence. We recruited 21 healthy human controls, 23 heroin-dependent subjects and 25 METH abusers. The heroin- and METH-dependent subjects exhibited negative urine toxicology after undergoing physiological detoxification. All subjects underwent SPECT brain imaging, and specific tracer uptake ratios (SURs) were assessed bilaterally in the regions of interest. A significant SUR reduction in heroin-dependent subjects and METH-dependent subjects compared with healthy controls was found in the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. There were no significant differences in the heroin group and METH group for the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. The scores of craving, HAMA (Hamilton Anxiety Rating Scale), in heroin abusers were lower than in the METH abusers. Our results show that people with heroin and METH dependence who are currently abstinent had lower DAT levels in the striatum than healthy controls. There were no differences in striatal DAT in heroin and METH users. These results suggest that chronic heroin and METH abuse appears to produce similar effects in striatal DAT in humans. METH users may have more serious craving and anxiety symptoms than heroin users with prolonged abstinence.