PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycle.

Modeling tumor metabolism in vitro remains challenging. Here, we used galactose as an in vitro tool compound to mimic glycolytic limitation. In contrast to the established idea that high glycolytic flux reduces pyruvate kinase isozyme M2 (PKM2) activity to support anabolic processes, we have discovered that glycolytic limitation also affects PKM2 activity.

Formate promotes invasion and metastasis in reliance on lipid metabolism.

Metabolic rewiring is essential for cancer onset and progression. We previously showed that one-carbon metabolism-dependent formate production often exceeds the anabolic demand of cancer cells, resulting in formate overflow. Furthermore, we showed that increased extracellular formate concentrations promote the in vitro invasiveness of glioblastoma cells.

Quantification of 782 Plasma Peptides by Multiplexed Targeted Proteomics.

Blood analysis is one of the foundations of clinical diagnostics. In recent years, the analysis of proteins in blood samples by mass spectrometry has taken a jump forward in terms of sensitivity and the number of identified proteins. The recent development of parallel reaction monitoring with parallel accumulation and serial fragmentation (prm-PASEF) combines ion mobility as an additional separation dimension.

Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions.

Pyruvate dehydrogenase (PDH) is the central enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle. The importance of PDH function in T helper 17 (Th17) cells still remains to be studied. Here, we show that PDH is essential for the generation of a glucose-derived citrate pool needed for Th17 cell proliferation, survival, and effector function.

Cervical Fluids Are a Source of Protein Biomarkers for Early, Non-Invasive Endometrial Cancer Diagnosis.

Background: Abnormal uterine bleeding is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women's health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90-95% of those women who do not have EC.

Methods: This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of protein biomarkers to diagnose EC.

[Prophylaxis and management of cancer-associated thrombosis: Practical issues about anticoagulant use].

Cancer-associated thrombosis (CAT) is a common complication resulting from various vascular mechanisms related to cancer, antitumoral therapy and patient status, and is associated with a poor prognosis. Anticoagulants recommended for CAT treatment or prevention mainly include low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs). Regarding thromboprophylaxis, a situation for which LMWH is a preferred option due to a lower risk of hemorrhage especially in patients with unresected gastro-intestinal and genito-urinary malignancies, the identification of patients at risk is a major issue.

Pan-claudin family interactome analysis reveals shared and specific interactions.

Claudins are a family of transmembrane proteins expressed in epithelial tissues and are the major components of tight junctions (TJs), which define barrier properties in epithelia and maintain cell polarity. How claudins regulate the formation of TJs and which functions they exert outside of them is not entirely understood. Although the long and unstructured C-terminal tail is essential for regulation, it is unclear how it is involved in these functions beyond interacting with TJ-associated proteins such as TJ protein ZO-1 (TJP1).

Proteomic consequences of TDA1 deficiency in Saccharomyces cerevisiae: Protein kinase Tda1 is essential for Hxk1 and Hxk2 serine 15 phosphorylation.

Hexokinase 2 (Hxk2) of Saccharomyces cerevisiae is a dual function hexokinase, acting as a glycolytic enzyme and being involved in the transcriptional regulation of glucose-repressible genes. Relief from glucose repression is accompanied by phosphorylation of Hxk2 at serine 15, which has been attributed to the protein kinase Tda1. To explore the role of Tda1 beyond Hxk2 phosphorylation, the proteomic consequences of TDA1 deficiency were investigated by difference gel electrophoresis (2D-DIGE) comparing a wild type and a Δtda1 deletion mutant.

Monitoring Breast Cancer Care Quality at National and Local Level Using the French National Cancer Cohort.

Purpose: The French National Cancer Institute has developed, in partnership with the French National Authority for Health, breast cancer-specific Care Quality, and Safety Indicators (BC QIs). With regard to the most common form of cancer, our aim is to support local and national quality initiatives, to improve BC pathways and outcomes, reduce heterogeneity of practice and regional inequities. In this study, we measure the BC QIs available in the French National medico-administrative cancer database, the French Cancer Cohort, for 2018.

Association between physical activity and neoadjuvant chemotherapy completion and pathologic complete response in primary breast cancer: the CANTO study.

Background: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear.

Methods: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical activity was assessed using the Global Physical Activity Questionnaire [GPAQ-16], quantified in standardised MET-h/wk.

Allergen Content of Therapeutic Preparations for Allergen-Specific Immunotherapy of European Paper Wasp Venom Allergy.

Allergy to (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample.

Dynamics of Long-Term Patient-Reported Quality of Life and Health Behaviors After Adjuvant Breast Cancer Chemotherapy.

Purpose: We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors.

Methods: Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498) were included.

A phase III randomized trial of weight loss to reduce cancer-related fatigue among overweight and obese breast cancer patients: MEDEA Study design.

Background: Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF.

Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration.

Glioblastoma (GBM) is the most aggressive primary brain tumor characterized by infiltrative growth of malignant glioma cells into the surrounding brain parenchyma. In this study, our analysis of GBM patient cohorts revealed a significantly higher expression of 8 () compared to normal brain tissue and could be associated with impaired patient survival. Increased expression of significantly enhanced migration of two different sphere-forming GBM cell lines.

[Survivorship care plan (SCP) : The viewpoints of women with breast cancer and their general practitioners].

Background: The French National Cancer Institute recommends the use of survivorship care plans (SCP) for all cancer survivors. Developing useful SCP's requires understanding of what survivors and their providers need and how SCP's can be implemented in practice. We conducted a study to assess the delivery of SCP comprehensive binders for breast cancer women (BCW) and their general practitioners (GP) in a Cancer center from January 2019.

The clinical potential of prm-PASEF mass spectrometry.

Introduction: The continuous technical improvement in sensitivity and specificity placed mass spectrometry as an alternative method for analyzing clinical samples. In parallel to the rapid development of discovery proteomics, targeted acquisition has been implemented as a complementary option for measuring a small set of proteins with high sensitivity and robustness in a large sample cohort. The combination of trapped ion mobility with a rapid time-of-flight (TOF) mass spectrometer improves the sensitivity even further and triggers the development of prm-PASEF.

Long-term patient reported outcomes and hematologic toxicity among patients who received Granulocyte-Colony Stimulating Factors during chemotherapy for early breast cancer.

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498). Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.

Highly Multiplexed Targeted Proteomics Acquisition on a TIMS-QTOF.

Targeted proteomics allows the highly sensitive detection of specific peptides and proteins in complex biological samples. Here, we describe a methodology for targeted peptide quantification using a trapped ion mobility quadrupole time-of-flight mass spectrometer (timsTOF Pro). The prm-PASEF method exploits the multiplexing capability provided by the trapped ion mobility separation, allowing more than 200 peptides to be monitored over a 30 min liquid chromatography separation.

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection.

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients' survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors.

Serum Detection of Nonadherence to Adjuvant Tamoxifen and Breast Cancer Recurrence Risk.

Purpose: Nonadherence to long-term treatments is often under-recognized by physicians and there is no gold standard for its assessment. In breast cancer, nonadherence to tamoxifen therapy after surgery constitutes a major obstacle to optimal outcomes. We sought to evaluate the rate of biochemical nonadherence to adjuvant tamoxifen using serum assessment and to examine its effects on short-term, distant disease-free survival (DDFS).

Shedding Light on the Venom Proteomes of the Allergy-Relevant Hymenoptera (European Paper Wasp) and spp. (Yellow Jacket).

Allergic reactions to stings of Hymenoptera species can have serious or even fatal consequences. If the identification of the culprit insect is possible, venom-specific immunotherapy effectively cures Hymenoptera venom allergies. Although component-resolved diagnostics has strongly evolved in recent years, the differentiation between allergies to closely related species such as and spp.

Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial.

Purpose: MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen.

Patients And Methods: R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m intravenously plus oral capecitabine 825 mg/m two times per day for 14 days (DC) every 3 weeks for 6 cycles.

[Tolerance of Tamoxifen as an adjuvant therapy and long-term follow up of 55 premenopausal breast cancer women, cared for at the Institut de cancérologie de Lorraine, treated with Tamoxifen].

Introduction: Objectives: the purpose of this study is to assess TAM safety in terms of side effects and hormonal status, the persistence of the treatment over a five years time-frame and to report the remote follow-up data.

Methods: Fifty five patients were included patients between January 2001 and November 2002 at the Institut de cancérologie de Lorraine. The subjects were aged 50 years or less, premenopausal at diagnosis and treated with adjuvant TAM therapy at a daily dose of 20 mg, for an expected duration of 5 years, at a daily.