Pivotal role of exogenous pyruvate in human natural killer cell metabolism.

Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.

Efficacy and safety of the combination of encorafenib/cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: an AGEO real-world multicenter study.

Background: The combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) after a prior systemic therapy. This study aims to describe the efficacy and safety of encorafenib/cetuximab +/- binimetinib in patients with BRAF V600E-mutated mCRC in a real-world setting.

Patients And Methods: This retrospective study included patients with BRAF V600E-mutated mCRC who received this combination from January 2020 to June 2022 in 30 centers.

Triplet chemotherapy with or without bevacizumab as first line treatment for metastatic colorectal cancer: An AGEO multicenter real-world study.

Background: Prior trials validated triplet chemotherapy (Tri-CT) with bevacizumab as first line treatment for metastatic colorectal cancer (mCRC) but real-world data are scarce and practices remain heterogeneous.

Aims: To evaluate Tri-CT +/- bevacizumab efficacy and safety, and to identify factors influencing treatment decisions.

Methods: The COLOTRIP retrospective study enrolled mCRC patients treated from 2014 to 2019 in 14 French centers.

Addition of trastuzumab to perioperative chemotherapy in HER2-positive gastroesophageal adenocarcinoma patients: A multicenter retrospective observational AGEO study.

Background: Approximately 10-20% of patients with gastroesophageal adenocarcinoma (GE-ADK) have HER2-positive tumors. The addition of trastuzumab to chemotherapy improves OS in patients with advanced disease. We investigated the effect of perioperative trastuzumab on survival outcomes.

Performance of a blood-based RNA signature for gemcitabine-based treatment in metastatic pancreatic adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, and chemotherapy is a key treatment for advanced PDAC. Gemcitabine chemotherapy is still an important component of treatment; however, there is no routine biomarker to predict its efficacy. Predictive tests may help clinicians to decide on the best first-line chemotherapy.

Optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma-a retrospective, international, multicentric AGEO study.

Background: The optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma (OGA) remains challenging.

Methods: Patients treated with trastuzumab (T) plus platinum salts and fluoropyrimidine (F) as first-line chemotherapy between 2010 and 2020 for HER2-positive advanced OGA at 17 academic care centers in France, Italy, and Austria were included. The primary objective was the comparison of F + T vs T alone as maintenance regimen in terms of progression-free survival (PFS) and overall survival (OS) after a platinum-based chemotherapy induction + T.

Glycemic control in people with diabetes treated with cancer chemotherapy: contribution of continuous glucose monitoring.

Aims: The aim of our study was to assess, with Continuous Glucose Monitoring (CGM), exhaustive information on the glucose profile in people with diabetes starting chemotherapy. We also evaluated the adaptation of glucose-lowering drugs following analysis of CGM recordings.

Methods: Eighty-five people with diabetes starting chemotherapy were included in the ONCODIAB study.

Chemotherapy in advanced pancreatic adenosquamous carcinoma: A retrospective multicenter AGEO study.

Pancreatic adenosquamous carcinoma (PASC) account for <5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study.

Novel Potent Selective Orally Active S1P5 Receptor Antagonists.

S1P5 is one of the five sphingosine-1-phosphate (S1P) receptors which play important roles in immune and CNS cell homeostasis, growth, and differentiation. Little is known about the effect of modulation of S1P5 due to the lack of S1P5 specific modulators with suitable druglike properties. Here we describe the discovery and optimization of a novel series of potent selective S1P5 antagonists and the identification of an orally active brain-penetrant tool compound .

Peripheral natural killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion.

Antiviral effectors such as natural killer (NK) cells have impaired functions in chronic hepatitis B (CHB) patients. The molecular mechanism responsible for this dysfunction remains poorly characterised. We show that decreased cytokine production capacity of peripheral NK cells from CHB patients was associated with reduced expression of NKp30 and CD16, and defective mTOR pathway activity.

Inflammasome Deletion Promotes Anti-tumor NK Cell Function in an IL-1/IL-18 Independent Way in Murine Invasive Breast Cancer.

Inflammasomes are molecular complexes that trigger an inflammatory response upon detection of pathogens or danger signals. Recent studies suggest that they are also involved in cancer progression. However, their roles during tumorigenesis remain poorly understood and controversial.

Bilateral vocal cord paralysis after endoscopic placement of fully covered self-expandable metal stent for palliative treatment of malignant proximal esophageal obstruction: two case reports.

Background: Oesophageal stents have several well-known respiratory complications, including aspiration pneumonia, fistula and airway compression. However, bilateral vocal cord paralysis has rarely been described.

Methods: We describe two patients who presented with refractory dysphagia due to malignant proximal oesophageal strictures.

Allogeneic mesenchymal stem cell therapy: A regenerative medicine approach to geroscience.

Extraordinary advances in medicine and public health have contributed to increasing life expectancy worldwide. However, health span-"healthy aging"-has paradoxically lagged to parallel this increase. Consequently, aging-associated illnesses, such as Alzheimer's disease and aging frailty, are having a growing impact on patients, their families, and entire health-care systems.

Net survival in recurrence-free colon cancer patients.

Purpose: Conditional net survival in recurrence-free patients (CNS-RF) provides relevant clinical information and has never been assessed yet in a non-selected colon cancer population. We aimed to estimate conditional 5-year net survival in recurrence-free patients with colon cancer in the population-based Digestive Cancer Registry of Burgundy (France).

Methods: CNS-RF was estimated in the 3736 patients resected for cure for primary colon cancer between 1976 and 2006, using a flexible parametric model of net survival for every additional year survived at diagnosis and from 1 to 5 years thereafter.

Continuation versus discontinuation of first-line chemotherapy in patients with metastatic squamous cell oesophageal cancer: A randomised phase II trial (E-DIS).

Purpose: The role of chemotherapy has not been established in the treatment of metastatic squamous cell oesophageal cancer (mESCC).

Patients And Methods: E-DIS is a discontinuation trial, aimed at estimating efficacy, quality of life and safety of chemotherapy continuation (CT-CONT) in patients with mESCC who are free from progression after a selection phase of chemotherapy. The primary end-point was overall survival.

A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder.

NSI-189 is a novel neurogenic compound independent of monoamine reuptake pathways. This trial evaluated oral NSI-189 as monotherapy in major depressive disorder. To improve signal detection, the sequential-parallel comparison design (SPCD) was chosen.

Patterns of care and outcomes in oesophageal cancer.

Background: The optimal treatment for oesophageal cancer is a matter of debate. The aim of this study was to describe patterns of care and survival in a well-defined population for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus.

Design: Data were provided by the Digestive Cancer Registry of Burgundy (France).

[Epidemiology of pancreatic cancer].

Actually, pancreatic cancer is a major challenge in digestive oncology. Its prognosis remains very poor with a five-year net survival less than 10%. Although if pancreatic cancer incidence was low, data from French digestive cancer registries show a dramatic increase in recent years, more marked in women (annual variation of +3.

Time trends in colorectal cancer early postoperative mortality. A French 25-year population-based study.

Background: Postoperative mortality after resection of colorectal cancer is an important issue. The aim of this study was to assess early postoperative mortality in a well-defined French population.

Methods: Data on 30- and 90-day postoperative mortality after resection for colorectal cancer were extracted from the digestive cancer registry of Burgundy.