Hepatocellular carcinoma is a common type of liver malignancy and one of the leading causes of cancer death worldwide. In the Russian Federation, according to statistical reports, there is also an increase in the incidence. For over 10 years, the tyrosine kinase inhibitor sorafenib has been the only approved treatment for advanced hepatocellular carcinoma. Lenvatinib was registered as the second drug for the treatment of advanced hepatocellular carcinoma in the first line. In the era of checkpoint inhibitors, the possibility of such therapy in the first and subsequent lines of advanced hepatocellular carcinoma remains relevant. The combination of atezolizumab with bevacizumab in a phase III study (IMbrave150) improved treatment outcomes such as overall survival and progression-free survival. The results of the phase III randomized trial IMbrave 150 showed undoubtedly better efficacy of the atezolizumab + bevacizumab combination compared to sorafenib in terms of a median progression-free survival of 6.8 vs 4.3 months. The above clinical observation demonstrates the result of treatment of a patient with advanced hepatocellular carcinoma with a combination of atezolizumab and bevacizumab. After verification of the diagnosis, since January 2021, therapy with a combination of atezolizumab 1200 mg, bevacizumab 15 mg/kg was started with an interval of 21 days.At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs. In the above clinical observation, a patient with severe comorbidity achieved stabilization of the disease in the first three months of therapy. Combination therapy showed a favorable tolerability profile.
Aim. Characterize the intensity of bone remodeling, balance of hormones and local cytokines regulating bone remodeling and bone metabolism, at chronic intake of copper-zinc sulfide ores elements. Methods. A total of 101 miner, producing copper-zinc sulfide ore by underground mining, and 30 employees of ground services of OAO «Uchaly Mining and Processing Plant», were examined. Experimental studies were performed on 60 white adult male rats, distributed to control and experimental groups. The experimental animals of the study group got copper-zinc sulfide ore powder in a 2% starch solution daily for 3 months as a suspension at the dose of 60 mg per 100 g of body weight. The serum levels of testosterone, parathyroid hormone, total thyroxine and triiodothyronine, cortisol, 25-hydroxyvitamin D, soluble Receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, sclerostin and C-terminal telopeptide of collagen type I, as well as bone alkaline phosphatase activity were determined. Results. Miners who were diagnosed with decreased bone density had increased level of C-terminal telopeptide of collagen type I, with bone alkaline phosphatase activity similar to the control group. In miners with physiological level of bone density, there was no statistically significant decrease in blood testosterone level, in the groups with low and very low bone mineral density there was a statistically significant decrease in testosterone level and increased level of parathyroid hormone. Experimental animals exposed to sulfide ore had serum levels of testosterone, 25-hydroxyvitamin D, thyroxine and triiodothyronine decreased, and increased level of parathyroid hormone and cortisol. Together with that, blood concentration of sclerostin was increased, level of osteoprotegerin - decreased, and soluble Receptor activator of nuclear factor kappa-B ligand was not changed. Conclusion. Long-term intake of copper-zinc sulfide ore leads to an imbalance of bone remodeling with a predominance of resorption. It is associated with the reduction of testosterone, calcidiol and thyroid hormones levels providing anabolic and anti-catabolic effect on bone metabolism, and overproduction of parathyroid hormone and cortisol, stimulating osteolysis. Receptor activator of nuclear factor kappa-B ligand / osteoprotegerin ratio and sclerostin level increases.
Bladder cancer is globally considered as one of the most aggressive neoplasms. Traditionally, first-line therapy for metastatic urothelial carcinoma has remained unchanged over the past decades and has been based on combinations of cisplatin. Unfortunately, almost all patients eventually progress and die from bladder cancer, despite the initial response associated with cisplatin-based combinations. Immune checkpoint inhibitors are becoming an increasingly widely used therapeutic option in many solid tumors. In bladder cancer, a high level of programmed death-ligand is determined by rapidly progressive and aggressive tumors and unsatisfactory survival rates. Although checkpoint inhibitors are effective in metastatic urothelial bladder cancer, only a small proportion of treated patients receive a clear benefit, while a large number of patients experience significant side effects and toxicity without improving quality of life or surviving. None of the available biomarkers at this point was associated with response rates. There is evidence of an correlation between PD-L1 expression, the efficacy of immune checkpoint inhibitors, and treatment outcomes in patients with bladder cancer. A major paradigm shift in bladder cancer medicine has followed the FDA approval of avelumab, pembrolizumab, durvalumab, atezolizumab, and nivolumab for the treatment of patients with metastatic urothelial carcinoma previously treated with chemotherapy. Combining classical clinicopathological parameters with data obtained via information technology, together with genomic profiling, could be the future of personalized therapy for bladder cancer.
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