MET Gene Dysregulation as a Promising Therapeutic Target in Lung Cancer-A Review.

Several molecular abnormalities in the MET gene have been identified, including overexpression, amplification, point mutations, and "skipping mutation" in exon 14. Even though deregulated MET signaling occurs rarely in non-small cell lung cancer (NSCLC), it possesses tumorigenic activity. Since the discovery of the significant role played by MET dysregulations in resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI), many clinical trials have been focused on mechanisms underlying this acquired resistance. Therefore, new therapeutic strategies are being considered in the personalized therapy of NSCLC patients carrying MET abnormalities. First, MET kinase inhibitors (tepotinib and capmatinib) have been shown to be effective in the first and subsequent lines of treatment in NSCLC patients with "skipping mutations" in exon 14 of MET gene. In this article, the authors show the role of MET signaling pathway alterations and describe the results of clinical trials with MET inhibitors in NSCLC patients.

Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement.

In patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy. The aim of the study was to assess the usefulness of the reverse transcriptase (RT-PCR) method in the diagnosis of gene rearrangements, the effectiveness of EGFR, ALK, ROS1, and PD-L1 inhibitors in first-line treatment in NSCLC patients. We enrolled 95 non-squamous NSCLC patients with known status of EGFR, ALK, ROS1, MET and RET genes and PD-L1 protein expression. We used the real time PCR, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and RT-PCR techniques for determination of predictive factors. In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056). The risk of death was lower in patients treated with molecularly targeted therapies or immunotherapy compared to patients with predictive factors without personalized treatment (HR = 0.265, 95% CI 0.116-0.606) and to patient without predictive factors who received chemotherapy (HR = 0.42, 95% CI 0.162-1.09). Diagnosis of predictive factors and implementation of personalized treatment are key to prolonging the survival in advanced NSCLC patients.

Recent Studies on Anti-Depressant Bioactive Substances in Selected Species from the Genera Hemerocallis and Gladiolus: A Systematic Review.

Herbal therapy is a potential alternative applied to pharmacological alleviation of depression symptoms and treatment of this disorder, which is predicted by the World Health Organization (WHO) to be the most serious health problem worldwide over the next several years. It has been well documented that many herbs with psychotropic effects have far fewer side effects than a variety of pharmaceutical agents used by psychiatrists for the treatment of depression. This systematic review presents literature data on the antidepressant activity of representatives of the genera Hemerocallis (H. fulva and H. citrina Baroni, family Xanthorrhoeaceae) and Gladiolus (G. dalenii, family Iridaceae) and on biologically active compounds and their mechanisms of action to consider the application of herbal preparations supporting the treatment of depression.

Presence of kynurenic acid in alcoholic beverages - Is this good news, or bad news?

Kynurenic acid (KYNA) is a metabolite of tryptophan formed enzymatically along kynurenine pathway in bacteria, fungi, plants and animals. It was suggested that yeast may produce KYNA during the fermentation process. Since KYNA was found to interact with alcohol metabolism by inhibition of aldehyde dehydrogenase activity the aim of this study was to measure the content of KYNA in selected alcoholic beverages of various type, beer, wine, mead and spirits. Moreover, the absorption and elimination rate of KYNA administered as a beverage was investigated in humans. Twelve healthy volunteers (6 female and 6 male) were studied. Fifty six samples of alcoholic beverages were of commercial origin. KYNA was determined by means of high-performance liquid chromatography method with fluorometric detection. KYNA was identified in all studied beverages. The amounts of KYNA found in various types of beverages differed significantly: mead 9.4-38.1 µg/100 ml, wine 1.4-10.9 µg/100 ml, beer 0.1-5.2 µg/100 ml, spirits 0.01-0.1 µg/100 ml. In human, it was found that KYNA is rapidly absorbed from digestive tract reaching its maximal concentration in blood 30 min after administration. Thus, the potential interaction between KYNA and alcohol occurring in human body after ingestion of alcoholic beverages was proven.