No abstract

The aim of this study is to report on the oral lesions detected in 123 patients diagnosed at the University Hospital of Bari from October 2020 to December 2020, focusing on the correlation of clinical and pathological features in order to purpose a new classification. Methods. General and specialistic anamnesis were achieved and oral examination was performed. The following data were collected: age/gender, general symptoms and form of Covid-19, presence and features of taste disorders, day of appearance of the oral lesions, type and features of oral lesions and day of beginning of therapies. If ulcerative lesions did not heal, biopsy was performed. Results. Many types of oral lesions were found and classified into four groups considering the timing of appearance and the start of the therapies. Early lesions in the initial stages of Covid-19 before the start of therapies was observed in 65.9% of the patients. In the histopathological analysis of four early lesions, thrombosis of small and middle size vessels was always noticed with necrosis of superficial tissues. Conclusion. The presence of oral lesions in early stages of Covid-19 could represent an initial sign of peripheral thrombosis, a warning sign of possible evolution to severe illness. This suggests that anticoagulant therapies should start as soon as possible.

Gastric cancer (GC) is one of the leading types of cancer worldwide, particularly in East Asian populations. Helicobacter pylori (HP) infection has been established as a major risk factor for GC. Although more than 50% of the world population is infected with this bacterium, less than 2% develop GC. Therefore, further risk factors (such as host genetic polymorphisms and lifestyle, as well as environmental and epigenetic factors) may also play a role in its occurrence. The correlation between HP infection and GC represents a typical model of a multi‑step process, characterized by some pre-neoplastic lesions with a high risk of progression (atrophic gastritis, intestinal metaplasia and dysplasia). In addition, HP also plays an oncogenic role in the development of mucosa‑associated lymphoid tissue (MALT) lymphoma, that accounts for approximately 3% of all gastric tumors. Hyperplastic polyps often arise in patients with atrophic gastric mucosa and HP‑associated gastritis (25% of cases); however, their malignant transformation is rare (<3% of cases). A number of trials have demonstrated the possibility of cancer prevention through HP screening and eradication, particularly in high‑risk populations, whereas it may not be cost‑effective in areas of low risk. In this review, we discuss i) the complex pathogenetic mechanisms of gastric carcinogenesis in which HP is involved; ii) the main approaches to the diagnosis, prevention, surveillance and treatment of pre-malignant lesions associated with HP infection; iii) the most effective way to detect GC in its earlier stages; and iv) the most important contribution to reducing the burden of GC.

Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38a/b kinases. We report that p38a is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38a activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38a as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38a pathway in the treatment of colorectal cancer. Colorectal cancer is a major health concern, with more than 1 000 000 new cases and 500 000 deaths expected worldwide per year.1 Prognostic evaluation is currently based on histological appearance, and there are no molecular markers internationally recognized as standard predictor factors. The conventional therapy involving surgery and adjuvant therapy seems to give rise to improvements in progression-free and overall survival. Nevertheless about 50% of patients die within 5 years owing to metastasis or recurrent disease.2 The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of cell cycle and cell death regulatory pathways in tumor cells in order to identify differential cellular effects of agents that may have a direct impact on cancer therapy.During the last decade, a number of deacetylase inhibitors (DI) have been identified. These DI induce tumor cells to undergo growth arrest, differentiation, and/or apoptosis in culture and in animal models, at doses that seem to be nontoxic and appear to be selective. Butyrate, a DI that is naturally formed in the human colon, is able to reduce the size and the number of tumors in rat models of bowel cancer.3 In vitro, sodium butyrate (NaB) is a potent differentiating agent for several colorectal cancer cell lines (CRCs).4-6 NaB-mediated cell cycle withdrawal of CRCs appears to be dependent on acetylation of histones and consequent changes in transcription, requiring continuous protein synthesis and the expression of p21. 7 It has recently been shown that 1 mM NaB is the best working concentration to activate the differentiation program in CRCs without triggering apoptosis, whereas 5 mM NaB is sufficient to induce a p53-independent...

Colorectal cancer cell (CRC) fate is governed by an intricate network of signaling pathways, some of which are the direct target of DNA mutations, whereas others are functionally deregulated. As a consequence, cells acquire the ability to grow under nutrients and oxygen shortage conditions. We earlier reported that p38a activity is necessary for proliferation and survival of CRCs in a cell type-specific manner and regardless of their phenotype and genotype. Here, we show that p38a sustains the expression of HIF1a target genes encoding for glycolytic rate-limiting enzymes, and that its inhibition causes a drastic decrease in ATP intracellular levels in CRCs. Prolonged inactivation of p38a triggers AMPK-dependent nuclear localization of FoxO3A and subsequent activation of its target genes, leading to autophagy, cell cycle arrest and cell death. In vivo, pharmacological blockade of p38a inhibits CRC growth in xenografted nude mice and azoxymethane-treated Apc Min mice, achieving both a cytostatic and cytotoxic effect, associated with high nuclear expression of FoxO3A and increased expression of its target genes p21 and PTEN. Hence, inhibition of p38a affects the aerobic glycolytic metabolism specific of cancer cells and might be taken advantage of as a therapeutic strategy targeted against CRCs. Colorectal cancer is the second leading cause of death for tumors in the western world because of a high percentage of metastatic disease, which shows a 5-year survival rate of approximately 10%.