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Erythropoietin-producing hepatocellular (Eph) receptors comprise the largest group of surface receptors and are responsible for cellular signals. Eph/ephrin signaling has been identified to play a role in key cancer development and progression processes, especially in the upper gastrointestinal tract. The Eph/ephrin system has been described as a tumor suppressor in duodenal cancer, while in esophageal, gastric, hepatic, and pancreatic cancer, the system has been related to tumor progression. For their significant role in developing a wide range of malignancies, Eph receptors and their ligands have proven to be an important target for new anticancer therapies. In this review, we present an overview of the literature and highlight evidence supporting the role of the Eph/ephrin system in upper digestive tract cancers. In addition, we discuss molecular findings that represent promising therapeutic targets for these cancers.

Human papillomavirus (HPV) infection has recently been linked to a subset of cancers affecting the oral cavity. However, the molecular mechanisms underlying HPV-driven oral squamous cell carcinoma (OSCC) onset and progression are poorly understood. Methods: We performed MS-based proteomics profiling based on HPV status in OSCC in young patients, following biological characterization and cell assays to explore the proteome functional landscape. Results: Thirty-nine proteins are differentially abundant between HPV (+) and HPV (−) OSCC. Among them, COPS3, DYHC1, and S100A8 are unfavorable for tumor recurrence and survival, in contrast to A2M and Serpine1, low levels of which show an association with better DFS. Remarkably, S100A8 is considered an independent prognostic factor for lower survival rates, and at high levels, it alters tumor-associated immune profiling, showing a lower proportion of M1 macrophages and dendritic cells. HPV (+) OSCC also displayed the pathogen-associated patterns receptor that, when activated, triggered the S100A8 and NFκB inflammatory responses. Conclusion: HPV (+) OSCC has a peculiar microenvironment pattern distinctive from HPV (−), involving the expression of pathogen-associated pattern receptors, S100A8 overexpression, and NFκB activation and responses, which has important consequences in prognosis and may guide therapeutic decisions.

Background: Oral tongue squamous cell carcinoma (OTSCC) causes over 350,000 cases annually and particularly impacts populations in developing countries. Smoking and alcohol consumption are major risk factors. Determining the role of the tumor immune microenvironment (TIME) in OTSCC outcomes can elucidate immune mechanisms behind disease progression, and can potentially identify prognostic biomarkers.Methods: We performed a retrospective study of 48 OTSCC surgical specimens from patients with tobacco and alcohol exposures. A panel of immunoregulatory cell subpopulations including T (CD3, CD4, CD8) and B (CD20) lymphocytes, dendritic cells (CD1a, CD83), macrophages (CD68), and immune checkpoint molecules programmed cell death protein 1 (PD-1) and ligand 1 (PD-L1) were analyzed using immunohistochemistry. The levels of immune effector cell subpopulations and markers were analyzed in relation to overall survival.Results: Pathological characteristics of the tumor microenvironment included inflammatory infiltrates (83.3%), desmoplasia (41.6%), and perineural invasion (50.0%). The TIME contained high levels of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+), as well as immature (CD1a) and mature (CD83) dendritic cells, PD-1, and PD-L1. Higher numbers of TIME infiltrating CD3+ T cells and CD20+ B cells were predictive of better survival, while higher levels of CD83+ mature dendritic cells predicted better survival. CD3+ T cells were identified as an independent prognostic marker for OTSCC. Lastly, CD3+ T cells were strongly correlated with the number of CD8+ cells and PD-L1 expression.Conclusion: Our findings provide evidence that the TIME profile of OTSSC impacted prognosis. The high expression of CD3+ T cells and B cells are predictive of better overall survival and indicative of an immunologically active, inflammatory TIME in patients with better survival. The number of CD3+ T cells was an independent prognostic marker.

Panoramic radiographs are complementary exams to evaluate oral alterations in an early manner, these changes can be dental developmental anomalies, and post-eruption dental disorder. Aim: This study evaluated the findings in panoramic radiographs and correlated the variables of gender and dental location. Methods: A retrospective study was through the observation of 1.111 panoramic radiographs from the Radiology Department in Brazil. It was included patients from 5 to 79 years of age of both gender, and it classified the anomalies in shape, size, and number and post-eruption dental changes in and correlated with gender and location. Patients with syndromes were excluded from the sample. Results: The majority of the sample was composed of fameles 752 (67.7%), as to the frequency of dental developmental anomalies related lesions 684 cases (61.6%) and post-eruption dental disorder 567 (51.8%), in the radiographs. The most prevalent change was endodontic treatment (32.6%), followed by root dilaceration (25.9%), and included tooth (19.5%). The most prevailing alteration when correlated with the gender variables was the cyst root (p