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.

Origin and characterization of cyclodepsipeptides: Comprehensive structural approaches with focus on mass spectrometry analysis of alkali-cationized molecular species.

Cyclodepsipeptides (CDPs) represent a huge family of chemically and structurally diverse molecules with a wide ability for molecular interactions. CDPs are cyclic peptide-related natural products made up of both proteinogenic and nonproteinogenic amino acids linked by amide and ester bonds. The combined use of different analytical methods is required to accurately determine their integral structures including stereochemistry, thus allowing deeper insights into their often-intriguing bioactivities and their possible usefulness.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with Pneumocystis jirovecii pneumonia.

Objectives: Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection.

Methods: We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL).

Precision Medicine in Pancreatic Ductal Adenocarcinoma: The Impact of Targeted Therapies on Survival of Patients Harboring Actionable Mutations.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes.

Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments.

Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, with a 5-year survival rate not exceeding 10%. Only first- and second-line treatments are well codified with the combination of cisplatin-gemcitabine chemotherapy and immunotherapy followed by 5-FU and oxaliplatin chemotherapy, respectively. Many studies have shown that BTC, and more particularly intrahepatic cholangiocarcinoma (iCCA), have a high rate of targetable somatic alteration.

Immunosuppressant mycophenolate mofetil for patients with steroid-refractory immune-related hepatitis induced by checkpoint inhibitors in oncology.

Background: Immune-checkpoint inhibitor (ICI) hepatitis, which does not improve with steroids and requires additional immunosuppressant, is defined as steroid-refractory ICI hepatitis. The outcome of patients with steroid-refractory ICI hepatitis remains poorly determined. Herein, we investigated the incidence, clinical features, and outcome of patients treated with second-line immunosuppressant for steroid-refractory ICI hepatitis.

Chemotherapy-induced ileitis associated or not with colitis in digestive oncology patients: An AGEO multicentre study.

Background: The characteristics and management of ileitis induced by chemotherapy in cancer patients are poorly described in the literature.

Methods: This retrospective multicentre study enroled patients hospitalized in a digestive oncology unit for a symptomatic chemotherapy-induced ileitis.

Results: Forty-three patients were included, with a regimen based on fluoropyrimidine and/or irinotecan in 95% of cases.

FOLFIRI plus BEvacizumab or aFLIbercept after FOLFOX-bevacizumab failure for COlorectal cancer (BEFLICO): An AGEO multicenter study.

After failure of first line FOLFOX-bevacizumab for metastatic colorectal cancer (mCRC), adding either bevacizumab or aflibercept to second-line FOLFIRI increases survival compared to FOLFIRI alone. In this French retrospective multicentre cohort, we included patients with a mCRC treated with either FOLFIRI-aflibercept or FOLFIRI-bevacizumab. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), disease control rate (DCR: CR + PR + SD) and safety.

Characterization of a novel β-alanine biosynthetic pathway consisting of promiscuous metabolic enzymes.

Bacteria adapt to utilize the nutrients available in their environment through a sophisticated metabolic system composed of highly specialized enzymes. Although these enzymes can metabolize molecules other than those for which they evolved, their efficiency toward promiscuous substrates is considered too low to be of physiological relevance. Herein, we investigated the possibility that these promiscuous enzymes are actually efficient enough at metabolizing secondary substrates to modify the phenotype of the cell.

Encorafenib plus cetuximab treatment in BRAF V600E-mutated metastatic colorectal cancer patients pre-treated with an anti-EGFR: An AGEO-GONO case series.

Background: Encorafenib plus cetuximab is efficient in anti-EGFR-naïve patients with BRAF mutated (BRAFm) metastatic colorectal cancer (mCRC). No data are available concerning the efficacy of BRAF inhibitors associated with anti-EGFRs (B + E) in patients previously treated with an anti-EGFR agent.

Methods: We retrospectively collected a series of patients with BRAFm mCRC treated with B + E after previous anti-EGFR treatment, in 14 centers.

Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication.

Background: In all living organisms, DNA replication is exquisitely regulated in a wide range of growth conditions to achieve timely and accurate genome duplication prior to cell division. Failures in this regulation cause DNA damage with potentially disastrous consequences for cell viability and human health, including cancer. To cope with these threats, cells tightly control replication initiation using well-known mechanisms.

Diaphragm dysfunction and peripheral muscle wasting in septic shock patients: Exploring their relationship over time using ultrasound technology (the MUSiShock protocol).

Background: Intensive Care Unit (ICU) patients are known to lose muscle mass and function during ICU stay. Ultrasonography (US) application for the assessment of the skeletal muscle is a promising tool and might help detecting muscle changes and thus several dysfunctions during early stages of ICU stay. MUSiShock is a research project aiming to investigate structure and function of diaphragm and peripheral muscles using ultrasound techniques in septic shock patients, and to assess their relevance in several clinical outcomes such as the weaning process.

Genetic and biocatalytic basis of formate dependent growth of Escherichia coli strains evolved in continuous culture.

The reductive glycine pathway was described as the most energetically favorable synthetic route of aerobic formate assimilation. Here we report the successful implementation of formatotrophy in Escherichia coli by means of a stepwise adaptive evolution strategy. Medium swap and turbidostat regimes of continuous culture were applied to force the channeling of carbon flux through the synthetic pathway to pyruvate establishing growth on formate and CO as sole carbon sources.

Deprivation of direct adult contact during development affects social representation in a songbird.

Social cognition involves a wide array of skills that are built largely through interactions with conspecifics and therefore depend upon early social experience. Motivation for social stimuli is a key feature of social behavior and an operant conditioning task showed that isolated wild-caught adult starlings (Sturnus vulgaris) are highly motivated to access pictures of other starlings. Here, we show that hand-raised adult starlings maintained in groups of peers throughout development but without any contact with adult models were not or only poorly motivated to access pictures of conspecifics.

First-line chemotherapy with raltitrexed in metastatic colorectal cancer: an Association des Gastro-entérologues Oncologues (AGEO) multicentre study.

Background: In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies.

Methods: This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy.

Change in Cofactor Specificity of Oxidoreductases by Adaptive Evolution of an Escherichia coli NADPH-Auxotrophic Strain.

The nicotinamide cofactor specificity of enzymes plays a key role in regulating metabolic processes and attaining cellular homeostasis. Multiple studies have used enzyme engineering tools or a directed evolution approach to switch the cofactor preference of specific oxidoreductases. However, whole-cell adaptation toward the emergence of novel cofactor regeneration routes has not been previously explored.

First Direct Evidence of Interpartner Hydride/Deuteride Exchanges for Stored Sodiated Arginine/Fructose-6-phosphate Complex Anions within Salt-Solvated Structures.

Mass spectrometric investigations of noncovalent binding between low molecular weight compounds revealed the existence of gas-phase (GP) noncovalent complex (NCC) ions involving zwitterionic structures. ESI MS is used to prove the formation of stable sodiated NCC anions between fructose (F6P) and arginine (R) moieties. Theoretical calculations indicate a folded solvated salt (i.

Efficacy and safety of oral metronomic etoposide in adult patients with metastatic osteosarcoma.

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France).

An appraisal of emerging second line therapies for metastatic colorectal cancer.

Introduction: Despite a significant improvement in overall survival over the last 15 years, colorectal cancer remains a major public health problem worldwide. Much effort has been made to develop an optimal choice of first-line treatments, but after progression the therapeutic possibilities and the criteria for choice are different.

Areas Covered: The purpose of this literature review is to discuss the different possibilities of second-line treatment and to specify the criteria for choice.

Is intra-arterial hepatic chemotherapy painful?

Background: Liver metastases are mainly supplied by the hepatic artery, allowing the administration of intra-arterial hepatic chemotherapy (IAHC) while preserving normal parenchyma. The progression-free survival and response rate are prolonged by IAHC which can improve the rate of secondary resectability. Severe abdominal pain requiring high-dose opioids can appear during HIAC administration.