Loss of H3K9 trimethylation leads to premature aging.

Aging is the major risk factor for most human diseases and represents a major socioeconomical challenge for modern societies. Despite its importance, the process of aging remains poorly understood. Epigenetic dysregulation has been proposed as a key driver of the aging process.

[Triple negative breast cancer: Current status and perspectives].

Triple negative breast cancer (TNBC) is defined by the absence of expression of estrogen and progesterone receptors, as well as the absence of overexpression of HER2. Accounting for 10 to 15% of breast cancers, it remains characterized by an aggressive phenotype with an increased risk of early recurrence and overall survival less favorable compared to other subtypes. The challenges in management and therapeutic evolution are likely related to the demonstrated high biological heterogeneity of this subtype.

Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by status in patients with advanced ovarian carcinomas.

Objective: Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that mutations are associated with platinum sensitivity, the relationship between status and KELIM score has yet to be elucidated.

Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study.

Background: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection.

Methods: Time to deterioration in QoL was analyzed for the primary study population.

Gradual ER calcium depletion induces a progressive and reversible UPR signaling.

The unfolded protein response (UPR) is a widespread signal transduction pathway triggered by endoplasmic reticulum (ER) stress. Because calcium (Ca) is a key factor in the maintenance of ER homeostasis, massive Ca depletion of the ER is a potent inducer of ER stress. Although moderate changes in ER Ca drive the ubiquitous Ca signaling pathways, a possible incremental relationship between UPR activation and Ca changes has yet to be described.

The hepatocyte epidermal growth factor receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche.

Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of pro-fibrotic factors are not well characterized. Epidermal growth factor receptor (EGFR) signaling in hepatocytes is essential for the regenerative processes of the liver; however, its potential role in regulating the fibrotic niche is not yet clear.

ER stress signaling at the interphase between MASH and HCC.

HCC is the most frequent primary liver cancer with an extremely poor prognosis and often develops on preset of chronic liver diseases. Major risk factors for HCC include metabolic dysfunction-associated steatohepatitis, a complex multifactorial condition associated with abnormal endoplasmic reticulum (ER) proteostasis. To cope with ER stress, the unfolded protein response engages adaptive reactions to restore the secretory capacity of the cell.

Exploring the IRE1 interactome: From canonical signaling functions to unexpected roles.

The unfolded protein response is a mechanism aiming at restoring endoplasmic reticulum (ER) homeostasis and is likely involved in other adaptive pathways. The unfolded protein response is transduced by three proteins acting as sensors and triggering downstream signaling pathways. Among them, inositol-requiring enzyme 1 alpha (IRE1α) (referred to as IRE1 hereafter), an endoplasmic reticulum-resident type I transmembrane protein, exerts its function through both kinase and endoribonuclease activities, resulting in both X-box binding protein 1 mRNA splicing and RNA degradation (regulated ire1 dependent decay).

Protein homeostasis imprinting across evolution.

Protein homeostasis (a.k.a.

Modulation of Protein Disulfide Isomerase Functions by Localization: The Example of the Anterior Gradient Family.

Oxidative folding within the endoplasmic reticulum (ER) introduces disulfide bonds into nascent polypeptides, ensuring proteins' stability and proper functioning. Consequently, this process is critical for maintaining proteome integrity and overall health. The productive folding of thousands of secretory proteins requires stringent quality control measures, such as the unfolded protein response (UPR) and ER-Associated Degradation (ERAD), which contribute significantly to maintaining ER homeostasis.

IRE1 RNase controls CD95-mediated cell death.

Signalling by the Unfolded Protein Response (UPR) or by the Death Receptors (DR) are frequently activated towards pro-tumoral outputs in cancer. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of the DR CD95/Fas, and its cell death-inducing ability. Both genetic and pharmacologic blunting of IRE1 activity increased CD95 expression and exacerbated CD95L-induced cell death in glioblastoma (GB) and Triple-Negative Breast Cancer (TNBC) cell lines.

TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma.

Cholangiocarcinoma is a devastating liver cancer characterized by high aggressiveness and therapy resistance, resulting in poor prognosis. Long non-coding RNAs and signals imposed by oncogenic pathways, such as transforming growth factor β (TGFβ), frequently contribute to cholangiocarcinogenesis. Here, we explore novel effectors of TGFβ signalling in cholangiocarcinoma.

Intraperitoneal insufflation of carbon dioxide rescues intestinal damage in an experimental murine model of colitis.

Objectives: Necrotizing enterocolitis (NEC) is a severe neonatal surgical condition, associated with a prolonged pro-inflammatory state, leading to high mortality and morbidity rates. Carbon dioxide (CO ) insufflation during laparoscopy may have an anti-inflammatory effect. We aimed to evaluate the effects of CO -insufflation on experimental colitis.

Different binding modalities of quercetin to inositol-requiring enzyme 1 of S. cerevisiae and human lead to opposite regulation.

The flavonoid Quercetin (Qe) was identified as an activator of Inositol-requiring enzyme 1 (IRE1) in S. cerevisiae (scIre1p), but its impact on human IRE1 (hIRE1) remains controversial due to the absence of a conserved Qe binding site. We have explored the binding modes and effect of Qe on both scIre1p and hIRE1 dimers using in silico and in vitro approaches.

A deep learning model to generate synthetic CT for prostate MR-only radiotherapy dose planning: a multicenter study.

Introduction: For radiotherapy based solely on magnetic resonance imaging (MRI), generating synthetic computed tomography scans (sCT) from MRI is essential for dose calculation. The use of deep learning (DL) methods to generate sCT from MRI has shown encouraging results if the MRI images used for training the deep learning network and the MRI images for sCT generation come from the same MRI device. The objective of this study was to create and evaluate a generic DL model capable of generating sCTs from various MRI devices for prostate radiotherapy.

TGFβ-induced circLTBP2 predicts a poor prognosis in intrahepatic cholangiocarcinoma and mediates gemcitabine resistance by sponging miR-338-3p.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circular RNA (circRNA) circLTBP2 in iCCA.

Chemotherapy-Related Amenorrhea and Quality of Life Among Premenopausal Women With Breast Cancer.

Importance: Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition.

Objective: To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL).

Design, Setting, And Participants: The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis.

UFMylation: a ubiquitin-like modification.

Post-translational modifications (PTMs) add a major degree of complexity to the proteome and are essential controllers of protein homeostasis. Amongst the hundreds of PTMs identified, ubiquitin and ubiquitin-like (UBL) modifications are recognized as key regulators of cellular processes through their ability to affect protein-protein interactions, protein stability, and thus the functions of their protein targets. Here, we focus on the most recently identified UBL, ubiquitin-fold modifier 1 (UFM1), and the machinery responsible for its transfer to substrates (UFMylation) or its removal (deUFMylation).

The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGFβ signaling and cancer cell invasion.

Background: Long non-coding RNAs (lncRNAs) regulate cellular processes by interacting with RNAs or proteins. Transforming growth factor β (TGFβ) signaling via Smad proteins regulates gene networks that control diverse biological processes, including cancer cell migration. LncRNAs have emerged as TGFβ targets, yet, their mechanism of action and biological role in cancer remain poorly understood.

The Molecular Mechanisms Underlying Onset and Progression of Liver Cancers.

Liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are deadly cancers that have risen in frequency globally and have limited curative therapeutic options [...

Impact of First Line Antiangiogenic Therapy Duration on Nivolumab Outcome in Metastatic Renal Cell Carcinoma Patients Treated in the GETUG-AFU 26 NIVOREN.

Background: In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC.

Methods: Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included.