RESUMO
An FDA-approved kinase inhibitor called sorafenib (SOR) is used to treat primary kidney and liver cancer as well as to stop the spread of advanced breast cancer. Side effects from SOR, such as palmar-plantar erythrodysesthesia syndrome, can negatively impact an individual's quality of life. There are a lot of data supporting the importance of lycopene (LYC) in preventing cancer. The antitumor properties of the combination of sorafenib and lycopene were examined in this study. A viability test against MDA-MB-231 was used to assess the anticancer efficacy of sorafenib, lycopene, and their combination in vitro. Moreover, a cell cycle analysis and Annexin-V/PI double staining were performed by using flow cytometry. In addition, the protein level of JNK-1, ERK-1, Beclin-1, P38, and P53 of the MDA-MB-231 cell line was estimated using ELISA kits. In addition, mice with SEC were divided into four equal groups at random (n = 10) to investigate the possible processes underlying the in vivo antitumor effect. Group IV (SEC-SOR-LYC) received SOR (30 mg/kg/day, p.o.) and LYC (20 mg/kg/day, p.o.); Group I received the SEC control; Group II received SEC-SOR (30 mg/kg/day, p.o.); and Group III received SEC-LYC (20 mg/kg/day, p.o.). The findings demonstrated that the combination of sorafenib and lycopene was superior to sorafenib and lycopene alone in causing early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis and autophagy. Likewise, the combination of sorafenib and lycopene demonstrated inhibition of the levels of Bcl-2, Ki-67, VEGF, IL-1ß, and TNF-α protein. Otherwise, the quantities of the proteins BAX, P53, and caspase 3 were amplified. Furthermore, the combined treatment led to a substantial increase in TNF-α, caspase 3, and VEGF gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor's decreased weight and volume, hence demonstrating its potential anticancer effect.
RESUMO
BACKGROUND: Cognitive-behavioral therapy (CBT) is first choice of treatment for depressive symptoms and disorders in adolescents, however improvements are necessary because overall efficacy is low. Insights on CBT components and contextual and structural characteristics might increase the efficacy. The aim of our approach is to evaluate the efficacy of CBT for youth with depression and investigate the influence of specific components, contextual and structural factors that could improve effects. METHODS: A systematic review of randomized controlled trials was conducted, searches were undertaken in CINAHL, CENTRAL, EMBASE, MEDLINE/PubMed and PsycINFO. Outcomes were meta-analyzed and confidence in results was assessed using the GRADE-method. Meta-regression was used to pinpoint components or other factors that were associated with an in- or decrease of effects of CBT. RESULTS: We included 31 trials with 4335 participants. Moderate-quality evidence was found for CBT reducing depressive symptoms at the end of treatment and at follow-up, and CBT as indicated prevention resulted in 63% less risk of being depressed at follow-up. CBT containing a combination of behavioral activation and challenging thoughts component (as part of cognitive restructuring) or the involvement of caregiver(s) in intervention were associated with better outcomes for youth on the long term. CONCLUSIONS: There is evidence that CBT is effective for youth with a (subclinical) depression. Our analyses show that effects might improve when CBT contains the components behavioral activation and challenging thoughts and also when the caregiver(s) are involved. However, the influential effects of these three moderators should be further tested in RCTs.
