We identified a 5-gene signature (KIF20A, KLF4, KRT6A, LIFR and RGS13). Risk Score (RS) based on 5-gene signature was significantly associated with overall survival (OS). Nomogram combining RS with clinical pathology parameters could potently predict the prognosis of patients with LUAD. Moreover, gliclazide was identified as a candidate drug for the treatment of high-RS LUAD. Finally, gliclazide was shown to induce cell cycle arrest and apoptosis in LUAD cells possibly by targeting CCNB1, CCNB2, CDK1 and AURKA.

This study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.

This study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.Cutaneous T-cell lymphomas (CTCLs) comprise a group of heterogeneous diseases involving malignant T cells. The pathogenesis and etiology of CTCL are still unclear, although a large number of genetic and epidemiological studies on CTCL have been conducted. Most CTCLs have an indolent course, making early diagnosis difficult. Once large-cell transformation occurs, CTCL progresses to more aggressive types, resulting in an overall survival of less than five years. Epigenetic drugs, which have shown certain curative effects, have been selected as third-line drugs in patients with relapsing and refractory CTCL. Many studies have also identified epigenetic biomarkers from tissues and peripheral blood of patients with CTCL and suggested that epigenetic changes play a role in malignant transformation and histone deacetylase inhibitor (HDACi) resistance in CTCL. Single-cell sequencing has been applied in CTCL studies, revealing heterogeneity in CTCL malignant T cells. The mechanisms of HDACi resistance have also been described, further facilitating the discovery of novel HDACi targets. Despite the heterogeneity of CTCL disease and its obscure pathogenesis, more epigenetic abnormalities have been gradually discovered recently, which not only enables us to understand CTCL disease further but also improves our understanding of the specific role of epigenetics in the pathogenesis and treatment. In this review, we discuss the recent discoveries concerning the pathological roles of epigenetics and epigenetic therapy in CTCL.

Angiotropism is the process by which cancer cells attach to and migrate along blood vessels to acquire vasculature, disseminate, and metastasize. However, the molecular basis for such vessel-tumor interactions has not been fully elucidated, partly due to limited experimental models. In this study, we aimed to observe and explore the molecular mechanism underlying angiotropism in melanoma.

To monitor the interactions of human melanoma cells with the vasculature

, a murine coxenograft model was employed by co-injecting highly and poorly invasive melanoma cells subcutaneously. To identify key pathways and genes involved in the angiotropic phenotype of melanoma, analysis of differentially expressed genes (DEGs) and gene set enrichment analysis (GSEA) were performed. The role of tissue factor pathway inhibitor 2 (TFPI2) in angiotropism was evaluated by immunostaining, adhesion assay, shRNA, and

tumorigenicity. Angiotropism and TFPI2 expression were examined in surgical specimens of melanoma by immunohistobservation of angiotropism and suggest that TFPI2 could inhibit the angiotropic phenotype of melanoma.Prehabilitation has shown its potential for most intra-cavity surgery patients on enhancing preoperative functional capacity and postoperative outcomes. However, its large-scale implementation is limited by several constrictions, such as i) unsolved practicalities of the service workflow, ii) challenges associated to change management in collaborative care; iii) insufficient access to prehabilitation; iv) relevant percentage of program drop-outs; v) need for program personalization; and, vi) economical sustainability. Dubs-IN-1 Transferability of prehabilitation programs from the hospital setting to the community would potentially provide a new scenario with greater accessibility, as well as offer an opportunity to effectively address the aforementioned issues and, thus, optimize healthcare value generation. A core aspect to take into account for an optimal management of prehabilitation programs is to use proper technological tools enabling i) customizable and interoperable integrated care pathways facilitating personalization of the service and effective engagement among stakeholders; ii) remote monitoring (i.e. physical activity, physiological signs and patient-reported outcomes and experience measures) to support patient adherence to the program and empowerment for self-management; and, iii) use of health risk assessment supporting decision making for personalized service selection. The current manuscript details a proposal to bring digital innovation to community-based prehabilitation programs. Moreover, this approach has the potential to be adopted by programs supporting long-term management of cancer patients, chronic patients and prevention of multimorbidity in subjects at risk.The treatment sequence of immunotherapy (IO) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is of great importance for the survival of non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. Here, we reported an advanced lung adenocarcinoma case concurrent with EGFR sensitive mutation and high PD-L1 expression (>50%) that was administrated with gefitinib firstly, and then became resistant to EGFR-TKI. He received the strategy of immunity-combined chemo-radiotherapy and responded significantly. However, the disease re-progressed after 10 months. Surprisingly, the tumor re-sensitized to gefitinib for 13 months. At final, following the treatment pressure of TKI-IO combination therapy-TKI strategy, tumor clone eventually transformed into small cell lung carcinoma (SCLC). For one thing, our study provided novel approach and extended the treatment spectra of overcoming immunotherapy resistance after EGFR resistance in driver oncogene-mutated NSCLC. For another thing, our case is the first time to report that SCLC transformation can be achieved after gefitinib-pembrolizumab-gefitinib resistance in EGFR sensitive mutation NSCLC, providing a new condition for SCLC transformation.