Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups.

Background/objectives: Patients with relapsed/refractory (R/R) AML with mutation () have a dismal prognosis. offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials.

Atlas of gray matter volume differences across psychiatric conditions: A systematic review with a novel meta-analysis that considers co-occurring disorders.

Background: Regional gray matter volume (GMV) differences between individuals with mental disorders and comparison subjects may be confounded by co-occurring disorders. To disentangle the disorder-specific GMV correlates, we conducted a large-scale multi-disorder meta-analysis using a novel approach that explicitly models co-occurring disorders.

Methods: We systematically reviewed voxel-based morphometry studies indexed in PubMed and Scopus up to January 2023 comparing adults with major mental disorders (anorexia nervosa, schizophrenia-spectrum, anxiety, bipolar, major depressive, obsessive-compulsive, and post-traumatic stress disorders, plus attention-deficit/hyperactivity, autism spectrum, and borderline personality disorders) to comparison subjects.

Diet Impacts on Gene Expression in Healthy Colon Tissue: Insights from the BarcUVa-Seq Study.

(1) Introduction: The global rise of gastrointestinal diseases, including colorectal cancer and inflammatory bowel diseases, highlights the need to understand their causes. Diet is a common risk factor and a crucial regulator of gene expression, with alterations observed in both conditions. This study aims to elucidate the specific biological mechanisms through which diet influences the risk of bowel diseases.

Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival.

Objective: Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways.

Design And Methods: Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control).

An eHealth ecosystem for stepped and early psychosocial care in advanced lung cancer: Rationale and protocol for a randomized control trial.

Background: Receiving a diagnosis of lung cancer is an emotional event, not least because it is usually diagnosed at advanced stages with limited life expectancy. Although evidence-based educational, emotional, and social interventions exist, they reach few patients and usually when it is too late.

Objective: This project will be carried out in a comprehensive center for cancer care and health research, aiming to study the efficacy, costs, and utility of an eHealth ecosystem to meet the psychosocial needs of patients with advanced lung cancer.

A Digital Cancer Ecosystem to Deliver Health and Psychosocial Education as Preventive Intervention.

Health education and psychosocial interventions prevent emotional distress, and the latter has been shown to have an impact on survival. In turn, digital health education interventions may help promote equity by reaching a higher number of cancer patients, both because they avoid journeys to the hospital, by and having a better efficiency. A total of 234 women recently diagnosed with breast cancer in a comprehensive cancer center used the digital ecosystem ICOnnecta’t from March 2019 to March 2021.

Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease.

Advanced endometrial cancer (EC) lacks therapy, thus, there is a need for novel treatment targets. CXCR4 overexpression is associated with a poor prognosis in several cancers, whereas its inhibition prevents metastases. We assessed CXCR4 expression in EC in women by using IHC.

Generation of two heterozygous GATA2 CRISPR/Cas9-edited iPSC lines, R398W and R396Q, for modeling GATA2 deficiency.

Germline heterozygous GATA2 mutations underlie a complex disorder characterized by bone marrow failure, immunodeficiency and high risk to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Our understanding about GATA2 deficiency is limited due to the lack of relevant disease models. Here we generated high quality human induced pluripotent stem cell (iPSC) lines carrying two of the most recurrent germline GATA2 mutations (R389W and R396Q) associated with MDS, using CRISPR/Cas9.

Extramedullary multiple myeloma patient-derived orthotopic xenograft with a highly altered genome: combined molecular and therapeutic studies.

Extramedullary multiple myeloma (EMM) has an overall survival of 6 months and occurs in 20% of multiple myeloma (MM) patients. Genetic and epigenetic mechanisms involved in EMM and the therapeutic role of new agents for MM are not well established. Besides, well-characterized preclinical models for EMM are not available.

Engineering and Assessing Cardiac Tissue Complexity.

Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. However, reproducing tissue-like properties is still a pending issue, as constructs generated to date remain immature relative to native adult heart.

Macrophage-Derived Iron-Bound Lipocalin-2 Correlates with Renal Recovery Markers Following Sepsis-Induced Kidney Damage.

During the course of sepsis in critically ill patients, kidney dysfunction and damage are among the first events of a complex scenario toward multi-organ failure and patient death. Acute kidney injury triggers the release of lipocalin-2 (Lcn-2), which is involved in both renal injury and recovery. Taking into account that Lcn-2 binds and transports iron with high affinity, we aimed at clarifying if Lcn-2 fulfills different biological functions according to its iron-loading status and its cellular source during sepsis-induced kidney failure.

Tumor Expression of Cyclin-Dependent Kinase 5 (Cdk5) Is a Prognostic Biomarker and Predicts Outcome of Oxaliplatin-Treated Metastatic Colorectal Cancer Patients.

In recent years, an increasing number of studies have shown that elevated expression of cyclin dependent kinase (Cdk5) contributes to the oncogenic initiation and progression of many types of cancers. In this study, we investigated the expression pattern of Cdk5 in colorectal cancer (CRC) cell lines and in a large number of tumor samples in order to evaluate its relevance in this pathogenesis and possible use as a prognostic marker. We found that Cdk5 is highly expressed and activated in CRC cell lines and that silencing of the kinase decreases their migration ability.

Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary.

Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients.

Evaluation of tobacco specific nitrosamines exposure by quantification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human hair of non-smokers.

Chronic exposure to specific carcinogens present in secondhand smoke has been associated with different types of cancers. Hair is an ideal matrix to develop a proper biomarker as it absorbs substances in circulation and allows measuring their average concentration over long periods of time. A method was developed for the simultaneous quantification of nicotine, cotinine, NNN, NNK and NNAL in 20 mg human hair samples.

The impact of KRAS mutations on VEGF-A production and tumour vascular network.

Background: The malignant potential of tumour cells may be influenced by the molecular nature of KRAS mutations being codon 13 mutations less aggressive than codon 12 ones. Their metabolic profile is also different, with an increased anaerobic glycolytic metabolism in cells harbouring codon 12 KRAS mutations compared with cells containing codon 13 mutations. We hypothesized that this distinct metabolic behaviour could be associated with different HIF-1α expression and a distinct angiogenic profile.