Long-term organoid culture of a small intestinal neuroendocrine tumor.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has markedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3 NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly malignant.

LAMC2 Regulates Key Transcriptional and Targetable Effectors to Support Pancreatic Cancer Growth.

Purpose: The identification of pancreatic ductal adenocarcinoma (PDAC) dysregulated genes may unveil novel molecular targets entering inhibitory strategies. Laminins are emerging as potential targets in PDAC given their role as diagnostic and prognostic markers. Here, we investigated the cellular, functional, and clinical relevance of LAMC2 and its regulated network, with the ultimate goal of identifying potential therapies.

Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited therapeutic options. However, metabolic adaptation to the harsh PDAC environment can expose liabilities useful for therapy. Targeting the key metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) and its downstream pathway shows efficacy only in subsets of patients but gene modifiers maximising response remain to be identified.

Circulating IgG4 Plasmablast Count as a Diagnostic Tool in Autoimmune Pancreatitis.

Background & Aims: Type 1 autoimmune pancreatitis (AIP) is an IgG4-related disease whose diagnosis is challenging. The aim of this study was to investigate the diagnostic value of circulating total and IgG4 plasmablasts in differentiating this condition from the other main pancreatic diseases.

Methods: Patients with type 1 AIP (n = 19) were prospectively enrolled in a tertiary center together with patients suffering from type 2 or not otherwise specified (NOS) AIP (n = 10), pancreatic adenocarcinoma (n = 17), chronic pancreatitis (n = 20), and intraductal papillary mucinous neoplasia or chronic asymptomatic pancreatic hyperenzymemia (n = 21) as control groups.

Molecular alterations in basal cell carcinoma subtypes.

A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.

Harnessing the epigenome to boost immunotherapy response in non-small cell lung cancer patients.

The introduction of immune checkpoint inhibitor (ICI)-based therapy for non-oncogene addicted non-small cell lung cancer (NSCLC) has significantly transformed the treatment landscape of the disease. Inhibitors of the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint axis, which were initially considered as a late-line treatment option, gradually became the standard of care as first-line treatment for subgroups of NSCLC patients. However, a significant fraction of patients either fails to respond or progresses after a partial response to ICI treatment.

HS-5 and HS-27A Stromal Cell Lines to Study Bone Marrow Mesenchymal Stromal Cell-Mediated Support to Cancer Development.

In this study, we compared the overall gene and pathway expression profiles of HS-5 and HS-27A stromal cell lines with those of primary bone marrow MSCs to verify if they can be considered a reliable alternative tool for evaluating the contribution of MSCs in tumor development and immunomodulation. Indeed, due to their easier manipulation as compared to primary MSC cultures, several published studies took advantage of stromal cell lines to assess the biological mechanisms mediated by stromal cells in influencing tumor biology and immune responses. However, the process carried out to obtain immortalized cell lines could profoundly alter gene expression profile, and consequently their biological characteristics, leading to debatable results.

Small Molecule Inhibitors of Microenvironmental Wnt/β-Catenin Signaling Enhance the Chemosensitivity of Acute Myeloid Leukemia.

Wnt/β-catenin signaling has been reported in Acute Myeloid leukemia, but little is known about its significance as a prognostic biomarker and drug target. In this study, we first evaluated the correlation between expression levels of Wnt molecules and clinical outcome. Then, we studied-in vitro and in vivo-the anti-leukemic value of combinatorial treatment between Wnt inhibitors and classic anti-leukemia drugs.

Organoid-Transplant Model Systems to Study the Effects of Obesity on the Pancreatic Carcinogenesis .

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality among adults in developed countries. The discovery of the most common genetic alterations as well as the development of organoid models of pancreatic cancer have provided insight into the fundamental pathways driving tumor progression from a normal cell to non-invasive precursor lesion and finally to widely metastatic disease, offering new opportunities for identifying the key driver of cancer evolution. Obesity is one of the most serious public health challenges of the 21st century.

Complete neural stem cell (NSC) neuronal differentiation requires a branched chain amino acids-induced persistent metabolic shift towards energy metabolism.

Neural stem cell (NSC) neuronal differentiation requires a metabolic shift towards oxidative phosphorylation. We now show that a branched-chain amino acids-driven, persistent metabolic shift toward energy metabolism is required for full neuronal maturation. We increased energy metabolism of differentiating neurons derived both from murine NSCs and human induced pluripotent stem cells (iPSCs) by supplementing the cell culture medium with a mixture composed of branched-chain amino acids, essential amino acids, TCA cycle precursors and co-factors.

Notch Signaling Molecules as Prognostic Biomarkers for Acute Myeloid Leukemia.

The role of Notch signaling in acute myeloid leukemia (AML) is still under investigation. We have previously shown that high levels of Notch receptors and ligands could interfere with drug response. In this study, the protein expression of 79 AML blast samples collected from newly diagnosed patients was examined through flow cytometry.

Comparative Lesions Analysis Through a Targeted Sequencing Approach.

Assessing intra-tumoral heterogeneity (ITH) is of paramount importance to anticipate failure of targeted therapies and design accordingly effective anti-tumor strategies. Although concerns are frequently raised due to differences in sample processing and depth of coverage, next-generation sequencing of solid tumors have unraveled a highly variable degree of ITH across tumor types. Capturing the genetic relatedness between primary and metastatic lesions through the identification of clonal and subclonal populations is critical to the design of therapies for advance-stage diseases.

Selection of candidate genes controlling veraison time in grapevine through integration of meta-QTL and transcriptomic data.

Background: High temperature during grape berry ripening impairs the quality of fruits and wines. Veraison time, which marks ripening onset, is a key factor for determining climatic conditions during berry ripening. Understanding its genetic control is crucial to successfully breed varieties more adapted to a changing climate.

Takotsubo cardiomyopathy associated with Kounis syndrome: A clinical case of the "ATAK complex".

A 60-year-old female developed cardiac arrest after experiencing an anaphylactic shock during administration of plasma-expanders. An electrocardiogram registered after restoration of sinus rhythm showed mild ST-elevation in the anterior precordial leads and T waves changes followed by appearance of echocardiographic alterations of left ventricular apex kinesis. Coronary angiography revealed normal coronary arteries, and cardiovascular magnetic resonance confirmed apical ballooning with late gadolinium enhancement in the segments with abnormal contractility.

Immunoevolution of mouse pancreatic organoid isografts from preinvasive to metastatic disease.

Pancreatic ductal adenocarcinoma (PDA) has a highly immunosuppressive microenvironment, which is contributed by the complex interaction between cancer cells and a heterogeneous population of stromal cells. Therefore, facile and trackable models are needed for integrative and dynamic interrogation of cancer-stroma interaction. Here, we tracked the immunoevolution of PDA in a genetically-defined transplantable model of mouse pancreatic tumour organoids that recapitulates the progression of the disease from early preinvasive lesions to metastatic carcinomas.

Genotyping-by-sequencing in an orphan plant species Physocarpus opulifolius helps identify the evolutionary origins of the genus Prunus.

Background: The Rosaceae family encompasses numerous genera exhibiting morphological diversification in fruit types and plant habit as well as a wide variety of chromosome numbers. Comparative genomics between various Rosaceous genera has led to the hypothesis that the ancestral genome of the family contained nine chromosomes, however, the synteny studies performed in the Rosaceae to date encompass species with base chromosome numbers x = 7 (Fragaria), x = 8 (Prunus), and x = 17 (Malus), and no study has included species from one of the many Rosaceous genera containing a base chromosome number of x = 9.

Results: A genetic linkage map of the species Physocarpus opulifolius (x = 9) was populated with sequence characterised SNP markers using genotyping by sequencing.