Objectives. Among various cells of tumor immune microenvironment (TIME) macrophages have been shown to play a pivotal role in the prognosis of many malignancies including laryngeal squamous cell carcinoma (LSCC). Laryngopharyngeal reflux (LPR) is associated with LSCC and can impact its prognosis. Local factors, particularly pH, can affect cancer growth by altering TIME and tumor associated macrophages phenotype. However, it is still unknown whether and how LPR affects TIME and macrophages polarization in LSCC. In this study we compared macrophage polarization in LSCC of patients with and without coexisting LPR.Methods. A total of 63 patients with T1-2 LSCC without (the 1st group, 30 patients) and with coexisting LPR (the 2nd group, 33 patients) were enrolled in the study. Only HPV-negative cases of males were included in the study. Immunohistochemistry was performed to visualize CD68 and CD163 macrophages. The number of macrophages was counted at the central tumor clusters (TC), peritumor stroma (TS) and at the intact laryngeal mucosa (IM) taken from the tumor-negative edge. Results. Samples of the 2nd group patients with LSCC and LPR demonstrated significantly (P<0.05) higher inflammatory infiltration of all the evaluated compartments (TC, TS and IM). CD68+ cells count was comparable in TC and IM of the 1st and the 2nd group patients. In contrast, CD163+ cells were more numerous in the 2nd group patients in TC, TS and IM (P<0.001). Moreover, the number of M2 macrophages was significantly higher than M1 macrophages in patients with coexisting LPR. As a result, CD163/CD68 ratio was significantly (P<0.001) higher in LSCC with coexisting LPR.Conclusions. LPR is associated with altered macrophages polarization and increase of M2-type macrophages in LSCC. The shift in macrophage polarization towards the M2 type in patients with LPR could facilitate LSCC development and progression.
Vestibular and acustic dysfunctions in clean up workers of Chornobyl accident (30 years of follow up)Objective. The objective of the work was to study the clinical and electrophysiological disorders in vestibular and acustic dysfunctions in clean up workers of Chornobyl accident depending on the dose and duration of action of ion izing radiation, the peculiarities of determined effects for 30 years after the accident. Materials and methods. The standard clinical and electrophysiological examinations of vestibular and acoustic ana lyzers functions were conducted in 7812 males' clean up workers including 325 persons selected for prolonged stud ies in 1986 2015. The mathematical methods of analysis were carried out using the software package SYSTAT, EPICURE and EGRET. Results. Vestibular dysfunction and acoustic dysfunction according the central type of progressive development of inhibitory processes in the brain stem, subcortical and cortical structures of vestibular and acoustic analyzers were determined. The dependence of changes in these structures on the dose and duration of ionizing radiation effect was defined. The regularities of determined radiation effects in correlation with the formation of organic cerebrovascu lar pathology in the clean up workers in remote post accident years that are consistent with neurophysiological, MRI and other examinations confirmed with correlation analysis were established. Conclusions. It was registered that the vestibular and acoustic dysfunctions in the clean up workers were manifest ed by the clinical and electrophysiological changes at the level of central structures in the studied analyzers, which indicate the parallelism of common mechanism of determined radiation effects already at a dose of 0.20 Gy, and also their dose dependency in dynamics of 30 post accidental years. It was established that vestibular dysfunction in the clean up workers is clinically early manifested, and the electroacoustic and electrophysiological changes in a case of normal hearing are evidence of preclinical inhibitory processes in the brain stem, subcortical and cortical structures of acoustic analyzer in the early post accident years. The features of the clinical course of vestibular and acoustic dysfunctions in long term monitoring of short term effects of ionizing radiation in high doses in the group of the clean up workers who have acute radiation sickness, and the manifestation of change is greater and accelerated in time under long term IR effect, than the relatively short term ones in similar small doses in distant years. Significant increase of hearing disorders by type of presbyacuzis precox in the respective age categories, which is one of the symptoms of their premature their aging was studied in clean up workers. Key words: acoustic and vestibular dysfunctions, static and kinetic equilibrium, spontaneous and experimental nys tagmus, tone and speech audiometry, auditory induced potentials: (short time latent or brain stem, long latent or cortical ones), dynamic impedancemetry, otoac...
Summary. Aim: To evaluate the presence of the aggregated proteins in malignant and benign neoplasms for clarifying the role of impaired protein metabolism in the formation of the altered tissues. Object and Methods: The histological specimens prepared from the operative materials of 196 patients with different forms of malignant and benign neoplasms were stained with Congo red and Thioflavin T and studied under the light and polarization microscope. Results: The various forms of β-stacked protein aggregates (β-SPA) inclusions were detected in amyloids, keloid tissue, benign polyps, and several malignant tumors. Conclusion: The formation of non-functional protein aggregates proves the complex character of the impairment of protein metabolism resulting in local or systemic accumulation of secondary protein toxins results in β-SPA formation as the self-sustaining complex of parametabolic processes. The β-SPA formation is of considerable interest since their properties lead to the impairment of the normal physiological processes in adjacent tissues ensuring the chronic course of the pathology.
Western blots demonstrated decreased levels of ZFP161 protein in Zfp161 knockout and shRNA knockdown cells. Simultaneously, decreased c-MYC protein levels were observed in Zfp161 knockout and shRNA knockdown cells compared with wild type and knockdown control cells. Using qPCR, decreased c-Myc RNA levels were observed in Zfp161 knockout cells compared to wildtype cells and decreased c-Myc RNA levels were observed in shRNA knockdown cells compared to control cells. Our results show that knockout and knowdown of Zfp161 results in a significant decrease in c-Myc expression in human cells. The decrease of c-Myc in Zfp161 knockout and knockdown cells translated into a robust decrease of in vitro cell survival in colony formation assays.Conclusions: Zfp161 is a regulator of the c-Myc oncogene in human cells. Zfp161 knockout and knowdown cells show a robust decrease of cell survival in vitro.
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