Disseminated renal cell carcinoma is an immunogenic tumor in which cytokine immunotherapy is usually used as the second-line treatment. It is associated with a low frequency of objective responses and short progression-free survival. Modern studies resulted in more effective treatment regimens based on new high-affinity TKI multikinases (cabozantinib, lenvatinib), as well as immuno-oncological drugs that can specifically block intercellular transmission of anti-immunogenic signal (PD-1 inhibitors) (nivolumab, pembrolizumab) or its ligand type 1 (PD-L1) (avelumab), antigen type 4 associated with anticytotoxic T-lymphocyte (ipilimumab)). Cabozantinib is a 2nd generation multikinase inhibitor that blocks the receptors of growth factors MET, AXL, and VEGFR-2, which are involved in tumorigenesis and responsible for resistance to traditional antiangiogenic therapy in renal cell carcinoma. Registration studies have shown that cabozantinib together with combined targeted therapy is more effective in patients with favorable and intermediate prognosis, while the PD-1 inhibitor (nivolumab) – in patients with poor and intermediate prognosis.Objective: to analyze the results of cabozantinib studies and its possible use in the sequential treatment of disseminated renal cell carcinoma.
Туберозный склероз, или болезнь Бурневилля -Прингла, -наследственное нейроокулокожное заболевание с аутосомно-доминантным типом наследования, характеризующееся системным по-ражением внутренних органов, костей, глаз, кожи, центральной нервной системы, костной ткани. Впервые вовлечение глаз при туберозном скле-розе (ТС) было описано в 1921 г. офтальмологом J. van der Hoeva [1]. Все изменения при ТС имеют единую патоморфологическую основу -гамартоз-
<b><i>Background:</i></b> Very little is known about receptor tyrosine kinase (RTK) expression on peripheral blood mononuclear cells (PBMC) in humans including renal cell carcinoma (RCC) patients. <b><i>Objectives:</i></b> The primary objective of this study was to evaluate expression levels of major RTKs on PBMC and tumor-infiltrating lymphocytes (TIL) isolated from RCC patients. The secondary aim was to compare levels of RTK expression in RCC patients before surgery and on the 180th day after surgery (lymphocyte lifetime) and to compare them with the expression in healthy donors. In addition, we compared RTK and PD-L1 expression in TIL. <b><i>Methods:</i></b> Tumor and blood samples were obtained from 20 patients with primary RCC immediately after surgical resection. Blood samples were collected from 20 healthy donors. Tumors were harvested into RPMI 1640 medium (Gibco) and processed within 4 h. TIL isolation was performed using a modified protocol [Baldan et al. Br J Cancer. 2015;112:1510–18]. Expression of RTKs was evaluated with NovoExpress Software. Twenty tumors from the same patients were stained with PD-L1 IHC assay (clone SP142; Ventana). <b><i>Results:</i></b> PBMC and TIL express RTKs in humans. The RTK expression level was significantly lower on peripheral blood cells in patients with RCC (mean 41%, range 27.1–62.6%) as compared with healthy donor PBMC (mean 77.1%, range 72.1–80.1%, all <i>p</i> < 0.05). Furthermore, RTK expression was significantly downregulated on intratumoral cells (mean 40%, range 23.2–52.3%) in comparison with healthy donor PBMC. There was no significant recovery of RTK expression on the 180th day except for VEGFR2. Five of 20 (25%) patients were PD-L1 positive. PD-L1 expression on TIL was strongly associated with downregulated expression of PDGFRα (<i>p</i> = 0.017) and PDGFRβ (<i>p</i> = 0.024). <b><i>Conclusions:</i></b> PBMC and TIL had similar low RTK expression levels in RCC patients. PBMC of healthy humans had a significantly higher expression of RTK. PD-L1 and PDGFRα-β expression could correlate. Comprehensive basic and clinical studies will be needed to define a biological role of RTKs on different lymphocyte subsets and correlations between clinical outcomes and expression levels.
Линейный невус сальных желез-редкое спорадическое нейроокулокожное заболевание, характеризующееся триадой симптомов: линейным невусом сальных желез, поражением центральной нервной системы и поражением органов зрения. Авторами представлен краткий обзор отечественной и зарубежной литературы и собственное клиническое наблюдение пациентки со специфическим поражением кожи на фоне врожденного синдрома Шиммельпеннинга-Фейерштейна-Мимса. Проанализированы проблемы дифференциальной диагностики невуса Ядассона с синдромом Шиммельпеннинга-Фейерштейна-Мимса.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.