5,051 results match your criteria: "Paoli Calmettes Institute; INSERM UMR599 232 Bd[Affiliation]"

Protective role of macrophages from maternal-fetal interface in unvaccinated coronavirus disease 2019 pregnant women.

J Med Virol

July 2024

Institut Recherche Développement, Assistance Publique-Hôpitaux de Marseille, Microbe, Evolution, Phylogeny and Infection, Aix-Marseille University, Marseille, France.

Pregnant women represent a high-risk population for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The presence of SARS-CoV-2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal-fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID-19) during their pregnancy.

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Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study.

J Clin Oncol

September 2024

Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.

Purpose: quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of multilineage involvement questions the significance of MRD. We aimed to define the prognostic role of MRD as assessed by or lymphoid-specific immunoglobulin/T-cell receptor () gene markers.

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Background And Objective: Building on previous research demonstrating better prostate cancer (PC) diagnostics via a biomarker-enhanced approach, this study focuses on cost analysis of PC care using the Stockholm3 test. We assessed the economic impact in European health care systems using real-world evidence for diagnostic outcomes and relevant costs.

Methods: We evaluated two PC diagnostic strategies: (1) the conventional prostate-specific antigen (PSA) strategy with magnetic resonance imaging (MRI) and (2) PSA testing with a reflex to biomarkers at PSA ≥1.

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Patients with Core-Binding Factor (CBF) and NPM1-mutated acute myeloid leukemia (AML) can be monitored by quantitative PCR after having achieved first complete remission (CR) to detect morphologic relapse and drive preemptive therapy. How to best manage these patients is unknown. We retrospectively analyzed 303 patients with CBF and NPM1-mutated AML, aged 18-60 years, without allogeneic hematopoietic cell transplantation (HCT) in first CR, with molecular monitoring after first-line intensive therapy.

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Article Synopsis
  • A phase II trial (OSAD93) tested the effectiveness of combining ifosfamide (IFO) and cisplatin (CDDP) without doxorubicin as a neoadjuvant treatment for adult osteosarcoma, focusing on patients with localized high-grade tumors.
  • The study included 60 patients who received four courses of chemotherapy, with the primary goal being a Good Histological Response (GHR) of 10% or fewer residual tumor cells in over 30% of patients, and secondary outcomes of disease-free survival (DFS), overall survival (OS), and toxicity.
  • Although the GHR target was not achieved, the study showed promising long-term survival rates (5-year DFS 51.
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  • A study examined the mortality and factors affecting outcomes for 1,164 patients who underwent allogeneic hematopoietic stem-cell transplantation and were admitted to ICUs in France from 2015 to 2020.
  • The findings revealed a 90-day mortality rate of 48%, with higher risks linked to age, time from transplant to ICU admission, and the need for invasive treatments like vasopressors and mechanical ventilation.
  • Despite high mortality rates, many critically ill patients who received intensive care did survive their ICU stays, prompting the need for a careful evaluation of treatment options for those with multiple risk factors.
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  • The study focused on cytomegalovirus end-organ disease (CMV-EOD) in critically ill, immunocompromised patients across 18 ICUs in France, Israel, and Spain, analyzing clinical characteristics and patient outcomes from January 2010 to December 2021.
  • A total of 185 patients were examined, with pneumonia being the most common form of CMV-EOD, affecting 62.2%, followed by gastrointestinal disease; the overall hospital mortality rate was strikingly high at 61.4%.
  • Key factors linked to increased mortality included having hematologic malignancies, particularly with active graft-versus-host disease, experiencing CMV pneumonia, and low lymphocyte counts
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Heterotopic ovarian transplantation instead hormonal replacement therapy after radical hysterectomy for cervical cancer: case report and review of literature.

J Assist Reprod Genet

September 2024

Department of Gynecology-Obstetric and Reproductive Medicine - CECOS, AP-HM, Hôpital La Conception, Marseille, France.

Purpose: Only a few case reports have described heterotopic ovarian tissue transplantation (OTT) with the only objective of restoring ovarian function.

Methods: Case report and review of the literature for reporting cases of heterotopic OTT with the only aim of restoring ovarian endocrine function. In a cancer survivor woman with a history of hysterectomy and bilateral oophorectomy for cervical cancer and because she poorly tolerated hormone replacement therapy (HRT), we performed a heterotopic OTT in a pelvic subcutaneous "pocket" after an OT cryostorage of 17 years.

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Upregulation of diverse self-antigens that constitute components of the inflammatory response overlaps spatially and temporally with the emergence of pathogen-derived foreign antigens. Therefore, discrimination between these inflammation-associated self-antigens and pathogen-derived molecules represents a unique challenge for the adaptive immune system. Here, we demonstrate that CD8 T cell tolerance to T cell-derived inflammation-associated self-antigens is efficiently induced in the thymus and supported by redundancy in cell types expressing these molecules.

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Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018.

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Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality.

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DOK1 and DOK2 regulate CD8 T cell signaling and memory formation without affecting tumor cell killing.

Sci Rep

July 2024

Centre de Recherche en Cancérologie de Marseille, CRCM, Immunity and Cancer Team, Institut Paoli-Calmettes, Inserm, CNRS, Aix Marseille University, Marseille, France.

Targeting intracellular inhibiting proteins has been revealed to be a promising strategy to improve CD8 T cell anti-tumor efficacy. Here, we are focusing on intracellular inhibiting proteins specific to TCR signaling: DOK1 and DOK2 expressed in T cells. We hypothesized that depletion of intracellular inhibition checkpoint DOK1 and DOK2 could improve CD8 T-cell based cancer therapies.

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Article Synopsis
  • The LSC-17 score, based on a gene expression profile related to stemness, indicates poor outcomes in acute myeloid leukemia (AML), but how leukemic stem cell anchoring affects disease progression is unclear.
  • Conditional inactivation of the adhesion molecule JAM-C in a mouse model of AML showed that its deletion affected HSC expansion but not disease initiation or progression, revealing insights into leukemic cell behavior in the bone marrow niche.
  • Findings suggest that the AP-1/TNF-α gene signature, which correlated with different prognosis in AML, provides additional prognostic information alongside the LSC-17 score, highlighting the importance of niche interactions in leukemia.
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Article Synopsis
  • The Euchromatic Histone Methyl Transferase Protein 2 (EHMT2/G9a) is important for regulating gene expression related to organ health, influencing inflammation and potentially cancer development.
  • Recent studies indicate that deactivating EHMT2 in mouse pancreatic cells changes gene expression linked to damage and inflammation, which may enhance susceptibility to injury.
  • The research uses advanced techniques to analyze how the pancreas responds to damage, revealing that loss of EHMT2 leads to an escalated inflammatory response by altering the local cell environment, suggesting its role in both cancer suppression and inflammatory diseases.
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In vivo organoid growth monitoring by stimulated Raman histology.

Npj Imaging

June 2024

Aix Marseille Univ, CNRS, Centrale Med, Institut Fresnel, Marseille, France.

Patient-derived tumor organoids have emerged as a crucial tool for assessing the efficacy of chemotherapy and conducting preclinical drug screenings. However, the conventional histological investigation of these organoids necessitates their devitalization through fixation and slicing, limiting their utility to a single-time analysis. Here, we use stimulated Raman histology (SRH) to demonstrate non-destructive, label-free virtual staining of 3D organoids, while preserving their viability and growth.

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Patient-derived tumor organoids: a new avenue for preclinical research and precision medicine in oncology.

Exp Mol Med

July 2024

INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen Normandie, Caen, France.

Over the past decade, the emergence of patient-derived tumor organoids (PDTOs) has broadened the repertoire of preclinical models and progressively revolutionized three-dimensional cell culture in oncology. PDTO can be grown from patient tumor samples with high efficiency and faithfully recapitulates the histological and molecular characteristics of the original tumor. Therefore, PDTOs can serve as invaluable tools in oncology research, and their translation to clinical practice is exciting for the future of precision medicine in oncology.

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Objective: To report the results of a multicenter cohort of preoperative brachytherapy (PBT) for treatment of early-stage cervical cancer (ESCC).

Methods: A retrospective analysis was conducted among five French comprehensive cancer centers on behalf of the SFRO Brachytherapy Group to examine the outcome of patients with ESCC who received PBT between 2001 and 2019 because of adverse prognostic factors (tumor size >2 cm, presence of lymphovascular invasion, adenocarcinoma).Brachytherapy was followed 4-8 weeks later by surgery.

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Although intensive induction chemotherapy (IC) remains the standard of care for younger patients with acute myeloid leukemia (AML), hypomethylating agents + venetoclax (HMA/VEN) can lead to durable remission among older patients with nucleophosmin 1 (NPM1) mutations. Whether IC or HMA/VEN is superior in patients aged ≥60 years with NPM1-mutant AML is unknown. We performed an international, multicenter retrospective cohort study of 221 patients (147 IC and 74 HMA/VEN) with previously untreated NPM1-mutant AML.

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Background And Objective: A hilar location for a renal tumour is sometimes viewed as a limiting factor for safe partial nephrectomy. Our aim was to evaluate perioperative, oncological, and functional outcomes of robot-assisted partial nephrectomy (RAPN) for hilar tumours (RAPN-H) in comparison to RAPN for nonhilar tumours (RAPN-NH).

Methods: We conducted an observational, multicentre cohort study using prospectively collected data from the French Research Network on Kidney Cancer (UroCCR).

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Background And Objective: Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC.

Methods: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide.

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Endometrioid ovarian carcinoma landscape: pathological and molecular characterization.

Mol Oncol

October 2024

Department of Medical Oncology, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France.

Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers.

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Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer.

Br J Cancer

September 2024

Department of Medical Oncology, Oncopole Claudius Regaud, IUCT-O, Toulouse, France.

Background: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody-drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown.

Methods: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC.

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Nuclear pore complexes (NPCs) have emerged as genome organizers, defining a particular nuclear compartment enriched for SUMO protease and proteasome activities, and act as docking sites for the repair of DNA damage. In fission yeast, the anchorage of perturbed replication forks to NPCs is an integral part of the recombination-dependent replication restart mechanism (RDR) that resumes DNA synthesis at terminally dysfunctional forks. By mapping DNA polymerase usage, we report that SUMO protease Ulp1-associated NPCs ensure efficient initiation of restarted DNA synthesis, whereas proteasome-associated NPCs sustain the progression of restarted DNA polymerase.

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Empirical antifungal therapy for health care-associated intra-abdominal infection: a retrospective, multicentre and comparative study.

Ann Intensive Care

June 2024

Department of Anesthesiology and Intensive Care Unit, Nord Hospital, Assistance Publique Hôpitaux Universitaires De Marseille, Aix Marseille University, Marseille, France.

Background: Current guidelines recommend using antifungals for selected patients with health care-associated intra-abdominal infection (HC-IAI), but this recommendation is based on a weak evidence. This study aimed to assess the association between early empirical use of antifungals and outcomes in intensive care unit (ICU) adult patients requiring re-intervention after abdominal surgery.

Methods: A retrospective, multicentre cohort study with overlap propensity score weighting was conducted in three ICUs located in three medical institutions in France.

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