Angiopoietin-2 and the Vascular Endothelial Growth Factor Promote Migration and Invasion in Hepatocellular Carcinoma- and Intrahepatic Cholangiocarcinoma-Derived Spheroids.

Aggressive hepatocellular carcinoma (HCC) overexpressing Angiopoietin-2 (ANG-2) (a protein linked with angiogenesis, proliferation, and epithelial-mesenchymal transition (EMT)), shares 95% of up-regulated genes and a similar poor prognosis with the proliferative subgroup of intrahepatic cholangiocarcinoma (iCCA). We analyzed the pro-invasive effect of ANG-2 and its regulator vascular endothelial growth factor (VEGF) on HCC and CCA spheroids to uncover posUsible common ways of response. Four cell lines were used: Hep3B and HepG2 (HCC), HuCC-T1 (iCCA), and EGI-1 (extrahepatic CCA).

Assessment of bone turnover markers and DXA parameters to predict bone metastasis progression during zoledronate treatment: a single-center experience.

Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover markers (BTM) with dual-energy X-ray absorptiometry (DXA) assessment could identify early BM progression and risk of skeletal-related events (SREs) during zoledronate treatment.

Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic individuals are not achievable due to its relatively low incidence, pancreatic cancer surveillance programs are recommended for patients with germline causative variants in PDAC susceptibility genes or a strong family history. In this study, we sought to determine the prevalence and significance of germline alterations in major genes (, , , , , , , , , , , ) involved in PDAC susceptibility.

Uncoupling p38α nuclear and cytoplasmic functions and identification of two p38α phosphorylation sites on β-catenin: implications for the Wnt signaling pathway in CRC models.

Background: Activation of the Wnt pathway has been linked to colorectal cancer (CRC). Previous reports suggest that Wnt3a can activate p38. Besides, p38α feeds into the canonical Wnt/β-catenin pathway by inhibiting GSK3β through phosphorylation.

SMYD3 Modulates AMPK-mTOR Signaling Balance in Cancer Cell Response to DNA Damage.

Cells respond to DNA damage by activating a complex array of signaling networks, which include the AMPK and mTOR pathways. After DNA double-strand breakage, ATM, a core component of the DNA repair system, activates the AMPK-TSC2 pathway, leading to the inhibition of the mTOR cascade. Recently, we showed that both AMPK and mTOR interact with SMYD3, a methyltransferase involved in DNA damage response.

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease: a multicenter international study.

Background And Aims: Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aimed to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPtical diagnosis Training to Improve dysplasia Characterization in Inflammatory Bowel Disease (OPTIC-IBD).

The chromatin remodeling factors EP300 and TRRAP are novel SMYD3 interactors involved in the emerging 'nonmutational epigenetic reprogramming' cancer hallmark.

SMDY3 is a histone-lysine N-methyltransferase involved in several oncogenic processes and is believed to play a major role in various cancer hallmarks. Recently, we identified ATM, BRCA2, CHK2, MTOR, BLM, MET, AMPK, and p130 as direct SMYD3 interactors by taking advantage of a library of rare tripeptides, which we first tested for their binding affinity to SMYD3 and then used as probes to systematically search the human proteome. Here, we used this innovative approach to identify further SMYD3-interacting proteins involved in crucial cancer pathways and found that the chromatin remodeling factors EP300 and TRRAP interact directly with SMYD3, thus linking SMYD3 to the emerging 'nonmutational epigenetic reprogramming' cancer hallmark.

Tumor Testing and Genetic Analysis to Identify Lynch Syndrome Patients in an Italian Colorectal Cancer Cohort.

Lynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in the gene. LS is associated with an increased lifetime risk of colorectal cancer (CRC) and other malignancies. The screening algorithm for LS patient selection is based on the identification of CRC specimens that have MMR loss/high microsatellite instability (MSI-H) and are wild-type for .

Histone and DNA Methylation as Epigenetic Regulators of DNA Damage Repair in Gastric Cancer and Emerging Therapeutic Opportunities.

Gastric cancer (GC), one of the most common malignancies worldwide, is a heterogeneous disease developing from the accumulation of genetic and epigenetic changes. One of the most critical epigenetic alterations in GC is DNA and histone methylation, which affects multiple processes in the cell nucleus, including gene expression and DNA damage repair (DDR). Indeed, the aberrant expression of histone methyltransferases and demethylases influences chromatin accessibility to the DNA repair machinery; moreover, overexpression of DNA methyltransferases results in promoter hypermethylation, which can suppress the transcription of genes involved in DNA repair.

SMYD3 Modulates the HGF/MET Signaling Pathway in Gastric Cancer.

Gastric cancer (GC) is the third most deadly cancer worldwide. Considerable efforts have been made to find targetable drivers in order to improve patient outcomes. MET is one of the most important factors involved in GC initiation and progression as it plays a major role in GC invasiveness and is related to cancer stemness.

Development of potent isoflavone-based formyl peptide receptor 1 (FPR1) antagonists and their effects in gastric cancer cell models.

Formyl peptide receptor-1 (FPR1) is a G protein-coupled chemoattractant receptor that plays a crucial role in the trafficking of leukocytes into the sites of bacterial infection and inflammation. Recently, FPR1 was shown to be expressed in different types of tumor cells and could play a significant role in tumor growth and invasiveness. Starting from the previously reported FPR1 antagonist 4, we have designed a new series of 4H-chromen-2-one derivatives that exhibited a substantial increase in FPR1 antagonist potency.

Repeated endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions after previous nondiagnostic or inconclusive sampling.

Objectives: Repeated endoscopic ultrasound (EUS)-guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine-needle biopsy (rEUS-FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes.

PD-L1 Downregulation and DNA Methylation Inhibition for Molecular Therapy against Cancer Stem Cells in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous cancer characterized by various cellular subtypes. This study investigates the potential of a combination strategy using immunotherapy and epigenetic reprogramming against HCC. We used a transgenic HCC mouse C57BL/6J-TG(ALB1HBV)44BRI/J to assess the dynamics of the programmed death receptor and its ligand (PD-1/PD-L1) and DNA methylation markers.

Passive tau-based immunotherapy for tauopathies.

Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. In secondary tauopathies, i.e.

Nutritional patterns as machine learning predictors of liver health in a population of elderly subjects.

Background And Aims: Non-alcoholic hepatic steatosis affects 25% of adults worldwide and its prevalence increases with age. There is currently no definitive treatment for NAFLD but international guidelines recommend a lifestyle-based approach, including a healthy diet. The aim of this study was to investigate the interactions between eating habits and the risk of steatosis and/or hepatic fibrosis, using a machine learning approach, in a non-institutionalized elderly population.

Dissecting the role of the NADPH oxidase NOX4 in TGF-beta signaling in hepatocellular carcinoma.

The NADPH oxidase NOX4 has been proposed as necessary for the apoptosis induced by the Transforming Growth Factor-beta (TGF-β) in hepatocytes and hepatocellular carcinoma (HCC) cells. However, whether NOX4 is required for TGF-β-induced canonical (SMADs) or non-canonical signals is not fully understood yet, neither its potential involvement in other parallel actions induced by TGF-β. In this work we have used CRISPR Cas9 technology to stable attenuate NOX4 expression in HCC cells.

Clinical development of passive tau-based immunotherapeutics for treating primary and secondary tauopathies.

Introduction: Tauopathies are clinicopathological entities with increased and pathological deposition in glia and/or neurons of hyperphosphorylated aggregates of the microtubule-binding protein tau. In secondary tauopathies, i.e.

Pharmacological interventions and hormonal therapies for depressive symptoms in peri- and post-menopausal women: a network meta-analysis of randomized controlled trials.

Although significant portion of women experience depressive symptoms during or after menopausal transition, there has been considerable controversy over the benefits of hormone replacement therapy (HRT) and antidepressants due to insufficient evidence supporting the superiority of either treatment. This frequentist model based network meta-analysis (NMA) included randomized controlled trials (RCTs) of menopausal depression symptoms management in menopausal women. Seventy RCTs involving a total of 18,530 women (mean age 62.

Exploring the Association of Burning Mouth Syndrome with Depressive and Anxiety Disorders in Middle-Aged and Older Adults: A Systematic Review.

Background: Burning Mouth Syndrome (BMS) is an idiopathic condition mainly affecting middle-aged and older individuals with hormonal disturbances or psychiatric disorders and is characterized by chronic pain. The etiopathogenesis of this multifactorial syndrome is largely unknown. The objective of the present systematic review was therefore to evaluate the relationship of BMS with depressive and anxiety disorders in middle-aged and older individuals.

Depressive and Biopsychosocial Frailty Phenotypes: Impact on Late-life Cognitive Disorders.

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links.

The Potential Role of Adjuvant Chemoradiotherapy in Patients with Microscopically Positive (R1) Surgical Margins after Resection of Cholangiocarcinoma.

(1) Background: Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms with dismal prognosis and the role of adjuvant chemoradiotherapy in high-risk resected patients is unclear. (2) Methods: We retrospectively analyzed the outcomes of BTC patients who received curative intent surgery with microscopically positive resection margins (R1) and adjuvant chemoradioradiotherapy (CCRT) or chemotherapy (CHT) from January 2001 to December 201. (3) Results: Out of 65 patients who underwent R1 resection, 26 received adjuvant CHT and 39 adjuvant CCRT.