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).

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study.

Background: Axitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified.

Patients And Methods: Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs.

Physician-perceived utility of the EORTC QLQ-GINET21 questionnaire in the treatment of patients with gastrointestinal neuroendocrine tumours: a multicentre, cross-sectional survey (QUALINETS).

Background And Objective: Patient-reported outcome measures can provide clinicians with valuable information to improve doctor-patient communication and inform clinical decision-making. The aim of this study was to evaluate the physician-perceived utility of the QLQ-GINET21 in routine clinical practice in patients with gastrointestinal neuroendocrine tumours (GI-NETs). Secondary aims were to explore the patient, clinician, and/or centre-related variables potentially associated with perceived clinical utility.

LONG-TERM EFFECT OF LU-DOTATATE ON SEVERE AND REFRACTORY HYPOGLYCEMIA ASSOCIATED WITH MALIGNANT INSULINOMA.

Objective: Malignant insulinoma is an extremely uncommon tumor that is usually accompanied by severe hypoglycemia that is difficult to manage. At this time, the long-term effect of Lu-DOTATATE (lutetium [Lu-177]-DOTA-Tyr3-octreotate) on this tumor is not well known.

Methods: We report a case of severe, life-threatening, and refractory hypoglycemia associated with malignant insulinoma treated with Lu-DOTATATE.

Trabectedin for reversing platinum resistance and resensitization to platinum in patients with recurrent ovarian cancer.

Aims: We evaluated trabectedin in patients with platinum-resistant/refractory and partially platinum-sensitive recurrent ovarian cancer and the outcomes after reintroduction of platinum.

Methods: Twenty-seven patients (platinum-resistant/refractory n = 24/PPS; n = 3) treated with trabectedin were retrospectively analyzed.

Results: Trabectedin resulted in an objective response rate (ORR) of 18.

GCAT|Genomes for life: a prospective cohort study of the genomes of Catalonia.

Purpose: The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiological, genomic and epigenomic factors in the development of major chronic diseases in Catalonia, a north-east region of Spain.

Huge recurrent gastric neuroendocrine tumor: a second-line chemotherapeutic dilemma.

Chemotherapy is considered "state of the art" for the treatment of poorly differentiated neuroendocrine neoplasms. Unfortunately, there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms. We report the case of a patient with a gastric neuroendocrine carcinoma stage IV, with massive gastrointestinal bleeding at diagnosis.

Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE).

Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification.

Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening.

The mitochondrial calcium uniporter complex is essential for calcium (Ca) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens.

Activity and safety of sunitinib in patients with advanced radioactive iodine-refractory differentiated thyroid carcinoma in clinical practice.

Our aim was to evaluate the effectiveness of off-label use of sunitinib in patients with advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAI) therapy. We performed a retrospective analysis of patients treated in the setting of clinical practice in a University General Hospital. Eleven consecutive patients (5 women, 6 men, mean age 63.

Pediatric primary follicular mucinosis: further evidence of its relationship with mycosis fungoides.

Follicular mucinosis (FM) is an uncommon reaction pattern in which the accumulation of mucin in the follicular epithelium is the main pathologic finding. FM may be idiopathic (primary follicular mucinosis [PFM]), in association with mycosis fungoides or cutaneous T-cell lymphoma, or in association with other neoplastic and inflammatory conditions. Herein we report a case of PFM with identical T-cell clone rearrangement at anatomically distinct sites, supporting the idea that some authors have proposed, that FM may represent a low-grade lymphoproliferative disease related to mycoses fungoides with favorable prognosis.

Influence of KRAS p.G13D mutation in patients with metastatic colorectal cancer treated with cetuximab.

Background: Patients with metastatic colorectal cancer (mCRC) with activating mutations at codon 12 or 13 of the KRAS gene are currently excluded from treatment with monoclonal antibodies against the epidermal growth factor receptor (EGFR), for example, cetuximab. Occasionally, some of these patients benefit from treatment with cetuximab, especially patients with a mutation at codon 13. We conducted an analysis to study the influence of the KRAS p.

Modifications in the C terminus of the synaptosome-associated protein of 25 kDa (SNAP-25) and in the complementary region of synaptobrevin affect the final steps of exocytosis.

Fusion proteins made of green fluorescent protein coupled to SNAP-25 or synaptobrevin were overexpressed in bovine chromaffin cells in order to study the role of critical protein domains in exocytosis. Point mutations in the C-terminal domain of SNAP-25 (K201E and L203E) produced a marked inhibition of secretion, whereas single (Q174K, Q53K) and double mutants (Q174K/Q53K) of amino acids from the so-called zero layer only produced a moderate alteration in secretion. The importance of the SNAP-25 C-terminal domain in exocytosis was also confirmed by the similar effect on secretion of mutations in analogous residues of synaptobrevin (A82D, L84E).