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We studied the gene-expression patterns in specimens of tumor and peritumor tissue biopsies of 26 patients with head and neck carcinomas depending on smoking status. Histological and immunohistochemical examinations verified that all tumors belonged to the "classical" subgroup of head and neck carcinomas, and the HPV-negative tumor status was confirmed. The expression of 28 tumor-associated genes determined by RT-PCR was independent of patients' sex or age, TNM status, degree of differentiation, or tissue localization. Moreover, in peritumor tissue, none of the 28 genes were differentially expressed between the groups of smoking and nonsmoking patients. During oncotransformation in both studied groups, there were similar processes typical for HNSCC progression: the expression levels of paired keratins 4 and 13 were reduced, while the expression levels of keratin 17 and CD44 were significantly increased. However, further investigation revealed some distinctive features: the expression of the genes EGFR and TP63 increased significantly only in the nonsmoking group, and the expression of IL6, CDKN2A, EGF, and PITX1 genes changed only in the smoking group. In addition, correlation analysis identified several clusters within which genes displayed correlations in their expression levels. The largest group included 10 genes: TIMP1, TIMP2, WEE1, YAP, HIF1A, PI3KCA, UTP14A, APIP, PTEN, and SLC26A6. The genetic signatures associated with smoking habits that we have found may serve as a prerequisite for the development of diagnostic panels/tests predicting responses to different therapeutic strategies for HNSCC. [ABSTRACT FROM AUTHOR]

The current understanding of the effects of radiation is gradually becoming broader. However, it still remains unclear why some patients respond to radiation with a pronounced positive response, while in some cases the disease progresses. This is the motivation for studying the effects of radiation therapy not only on tumor cells, but also on the tumor microenvironment, as well as studying the systemic effects of radiation. In this framework, we review the biological effects of two types of radiotherapy: photon and proton irradiations. Photon therapy is a commonly used type of radiation therapy due to its wide availability and long-term history, with understandable and predictable outcomes. Proton therapy is an emerging technology, already regarded as the method of choice for many cancers in adults and children, both dosimetrically and biologically. This review, written after the analysis of more than 100 relevant literary sources, describes the local effects of photon and proton therapy and shows the mechanisms of tumor cell damage, interaction with tumor microenvironment cells and effects on angiogenesis. After systematic analysis of the literature, we can conclude that proton therapy has potentially favorable toxicological profiles compared to photon irradiation, explained mainly by physical but also biological properties of protons. Despite the fact that radiobiological effects of protons and photons are generally similar, protons inflict reduced damage to healthy tissues surrounding the tumor and hence promote fewer adverse events, not only local, but also systemic. [ABSTRACT FROM AUTHOR]