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1.
Cancer Res Commun ; 4(7): 1702-1714, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38904264

ABSTRACT

Phosphatase of regenerating liver 2 (also known as PTP4A2) has been linked to cancer progression. Still, its exact role in glioblastoma (GBM), the most aggressive type of primary brain tumor, remains elusive. In this study, we report that pharmacologic treatment using JMS-053, a pan-phosphatase of regenerating liver inhibitor, inhibits GBM cell viability and spheroid growth. We also show that PTP4A2 is associated with a poor prognosis in gliomas, and its expression correlates with GBM aggressiveness. Using a GBM orthotopic xenograft model, we show that PTP4A2 overexpression promotes tumor growth and reduces mouse survival. Furthermore, PTP4A2 deletion leads to increased apoptosis and proinflammatory signals. Using a syngeneic GBM model, we show that depletion of PTP4A2 reduces tumor growth and induces a shift in the tumor microenvironment (TME) toward an immunosuppressive state. In vitro assays show that cell proliferation is not affected in PTP4A2-deficient or -overexpressing cells, highlighting the importance of the microenvironment in PTP4A2 functions. Collectively, our results indicate that PTP4A2 promotes GBM growth in response to microenvironmental pressure and support the rationale for targeting PTP4A2 as a therapeutic strategy against GBM. SIGNIFICANCE: High levels of PTP4A2 are associated with poor outcomes in patients with glioma and in mouse models. PTP4A2 depletion increases apoptosis and proinflammatory signals in GBM xenograft models, significantly impacts tumor growth, and rewires the TME in an immunocompetent host. PTP4A2 effects in GBM are dependent on the presence of the TME.


Subject(s)
Brain Neoplasms , Disease Progression , Glioblastoma , Tumor Microenvironment , Glioblastoma/pathology , Glioblastoma/genetics , Animals , Humans , Mice , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Apoptosis , Macrophages/metabolism , Xenograft Model Antitumor Assays
2.
Eur Eat Disord Rev ; 32(4): 784-794, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38520705

ABSTRACT

BACKGROUND & AIMS: Changes in stomach size may impact eating behaviour. A recent study showed gastric dilatation in restrictive eating disorders using computed tomography scans. This study aimed to describe stomach size in the standing position in women with anorexia nervosa (AN). METHODS: Women treated for AN at our institution were retrospectively included if they had undergone upper gastrointestinal radiography (UGR) after the diagnosis of AN. Two control groups (CG1 and CG2) were included, both comprising female patients: CG1 patients were not obese and underwent UGR for digestive symptoms of other aetiologies, and CG2 comprised obese individuals who had UGR before bariatric surgery. A UGR-based Stomach Size Index (SSI), calculated as the ratio of the length of the stomach to the distance between the upper end of the stomach and the top of the iliac crests, was measured in all three groups. Gastromegaly was defined as SSI >1.00. RESULTS: 45 patients suffering from AN (28 with restrictive and 17 with binge/purge subtype), 10 CG1 and 20 CG2 subjects were included in this study. Stomach Size Index was significantly higher in AN (1.27 ± 0.24) than in CG1 (0.80 ± 0.11) and CG2 (0.68 ± 0.09); p < 0.001, but was not significantly different between patients with the restrictive and binge/purge subtypes. Gastromegaly was present in 82.2% of patients with AN and not present in the control groups. In patients with AN, gastromegaly was present in 12/15 patients without digestive symptoms (80.0%) and in 25/30 patients with digestive complaints (83.3%) at time of UGR (p = 0.99). In the AN group, no significant relationship was found between SSI and body mass index. CONCLUSION: Gastromegaly is frequent in AN and could influence AN recovery. This anatomical modification could partially explain the alterations of gastric motility previously reported in AN.


Subject(s)
Anorexia Nervosa , Stomach , Humans , Anorexia Nervosa/diagnostic imaging , Female , Adult , Stomach/diagnostic imaging , Stomach/pathology , Retrospective Studies , Young Adult , Organ Size , Adolescent
3.
Alcohol Alcohol ; 59(2)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38366913

ABSTRACT

AIMS: up to 80% of patients with alcohol use disorder display cognitive impairments. Some studies have suggested that alcohol-related cognitive impairments could be worsened by hepatic damage. The primary objective of this study was to compare mean scores on the Brief Evaluation of Alcohol-Related Neurocognitive Impairments measure between alcohol use disorder patients with (CIR+) or without cirrhosis (CIR-). METHODS: we conducted a prospective case-control study in a hepatology department of a university hospital. All patients were assessed using the Evaluation of Alcohol-Related Neuropsychological Impairments test. RESULTS: a total of 82 patients (50 CIR+, 32 CIR-) were included in this study. CIR- patients were significantly younger than CIR+ patients (respectively, 45.5 ± 6.8 vs 60.1 ± 9.0; P < .0001). After adjusting for age and educational level, the mean Evaluation of Alcohol-Related Neuropsychological Impairments total scores in the CIR+ group were significantly lower than in the group of CIR- patients (14.1 ± 0.7 vs 7.8 ± 0.4, respectively, P < .0001). The mean subscores on delayed verbal memory, alphabetical ordination, alternating verbal fluency, visuospatial abilities, and ataxia subtests were also significantly lower in the CIR+ than in the CIR- group (respectively, 1.9 ± 0.2 vs 2.8 ± 0.2; 1.8 ± 0.2 vs 2.7 ± 0.2; 2.2 ± 0.2 vs 3.6 ± 0.2; 0.7 ± 0.2 vs 1.6 ± 0.2; 0.7 ± 0.2 vs 3.1 ± 0.2; P < .0001 for all comparisons). CONCLUSIONS: in the present study, alcohol use disorder patients with cirrhosis presented more severe cognitive impairments than those without cirrhosis. Longitudinal studies are needed to investigate how cirrhosis can influence cognitive impairments.


Subject(s)
Alcoholism , Cognitive Dysfunction , Humans , Alcoholism/complications , Alcoholism/psychology , Case-Control Studies , Neuropsychological Tests , Cognitive Dysfunction/complications , Liver Cirrhosis/complications , Cognition
4.
Front Psychiatry ; 15: 1260138, 2024.
Article in English | MEDLINE | ID: mdl-38384590

ABSTRACT

Emotion dysregulation (ED) has primarily been described in patients suffering from borderline personality disorder (BPD) and is an integral part of this diagnosis, but it is also a transdiagnostic construct that can be found in several other psychiatric disorders. The strong relationships between ED and BPD may lead clinicians to underestimate ED associated to other clinical contexts. This can lead to difficulties in diagnostic and treatment orientation, especially in the context of comorbidities. In this article, after reviewing the literature on the development and functioning of emotion dysregulation, and on the evidence for emotion dysregulation in eight disorders (borderline personality disorder, pathological narcissism with/without narcissistic personality disorder, obsessive-compulsive personality disorder, antisocial personality disorder, bipolar disorder, autism spectrum disorder, complex post-traumatic stress disorder, and adult attention deficit hyperactivity disorder), we present a transdiagnostic processual model of emotion dysregulation based on core triggers and interpersonal styles to try to address this issue and to provide a simple but technical tool to help clinicians in their diagnostic assessment and treatment orientation. By focusing more on typical patterns and interpersonal dynamics than only on categories, we believe that this model may contribute to the actual need for improvement of our current psychiatric classifications, alongside other well-studied and under-used dimensional models of psychopathology (e.g., HiTOP, AMPD), and may be useful to build more specific treatment frameworks for patients suffering from ED.

5.
Cell Rep ; 43(2): 113773, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38350444

ABSTRACT

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral or non-viral etiologies including steatotic liver diseases (SLDs). Expansion of immunosuppressive myeloid cells is a hallmark of inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance. Here, we present a high-resolution atlas of innate immune cells from patients with HCC that unravels an SLD-associated contexture characterized by influx of inflammatory and immunosuppressive myeloid cells, including a discrete population of THBS1+ regulatory myeloid (Mreg) cells expressing monocyte- and neutrophil-affiliated genes. THBS1+ Mreg cells expand in SLD-associated HCC, populate fibrotic lesions, and are associated with poor prognosis. THBS1+ Mreg cells are CD163+ but distinguished from macrophages by high expression of triggering receptor expressed on myeloid cells 1 (TREM1), which contributes to their immunosuppressive activity and promotes HCC tumor growth in vivo. Our data support myeloid subset-targeted immunotherapies to treat HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Triggering Receptor Expressed on Myeloid Cells-1 , Immunosuppression Therapy , Myeloid Cells , Immunosuppressive Agents , Inflammation
6.
J Telemed Telecare ; : 1357633X241229462, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38327172

ABSTRACT

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, the Gustave Roussy Cancer Center introduced teleconsultation via telephone, as an alternative to face-to-face consultation to reduce patient hospital visits. This study was designed to assess patient and doctor satisfaction with this modality of care in oncology patient care during the period of the pandemic and beyond. METHODS: We designed two questionnaires based on validated scores to assess satisfaction from teleconsultation in patients (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) and doctors (Telehealth Usability Questionnaire [TUQ]), and anxiety levels in both groups (anxiety section of the Hospital Anxiety and Depression Scale [HADS], HADS-A). These were electronically sent to patients and doctors with experience of at least one remote consultation during the first wave of the COVID-19 pandemic. RESULTS: 239 patients and 32 doctors were eligible for the analyses. In the patient group, the mean satisfaction scores were 79.5 (SD 18.1) and 74.92 (SD 15.3) for EORTC OUT-PATSAT 35 and TSQ, respectively. In the doctor group, the mean satisfaction scores were 67.1 (SD 12.7) and 64.9 (SD 13.9) for TUQ and TUQ for Skype for Business, respectively. 65.7% of patients and 81.2% of doctors had no/low anxiety. Univariable analyses in patients showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores with anxiety and gender, with lower mean scores in women compared to men. Multivariable analysis showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores to anxiety in both patients and doctors. CONCLUSIONS: Teleconsultation via telephone is an acceptable modality of care for oncology patients, with high satisfaction from its implementation during the pandemic reported by patients and doctors. This was consistent across responder groups with different characteristics. An individualized approach to patients should be implemented for the safe and effective use of teleconsultation in oncology beyond the pandemic.

7.
J Oncol Pharm Pract ; 30(2): 278-285, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37254519

ABSTRACT

INTRODUCTION: During administration of chemotherapies, disconnection presents risks for nurses. Thus, it is recommended to flush the infusion line with solvent to reduce this risk and ensure that the entire dose is administered. Objectives of this study were to evaluate flushing practices and to investigate the efficiency of flushing, according to the type of hospitalization, in hospitalization (HU) or day-care unit (DCU), for three drugs. METHODS: Twenty secondary infusion lines were collected in five HU and 20 in two DCU. Flushing volumes were estimated by weighing solvent bags. The amount of residual drug was measured for secondary lines by mass spectrometry coupled with high-performance liquid chromatography. RESULTS: Chemotherapies were administered by 26 nurses. All of infusion lines contained chemotherapy after flushing. Flushing volumes, residual concentrations and flushing efficiencies were significantly different between these two types of units. In contrast, flushing volumes administrated did not differ between chemotherapy drugs. CONCLUSIONS: Local recommendations are fully implemented in HU and partially in DCU. The use of small volumes in DCU is related to the patient length of stay, it may, also, be due to omitting the average tubing volume. All infusion lines still contained chemotherapy, including those with a flush volume much higher than recommended, showing that the risk of exposure persists. To achieve a rinse volume greater than 50 mL, it is necessary to use at least 100 mL. It is also important to insist on personal protective equipment and to consider closed safety system for administration.


Subject(s)
Infusions, Intravenous , Humans , Solvents
8.
Clin Cancer Res ; 30(3): 629-637, 2024 02 01.
Article in English | MEDLINE | ID: mdl-37982819

ABSTRACT

PURPOSE: Patients with advanced soft-tissue sarcomas (STS) exhibit a poor prognosis and have few therapeutic options. DNA-dependent protein kinase (DNA-PK) catalytic subunit is a multifunctional serine-threonine protein kinase that plays a crucial role in DNA double-strand damage repair via nonhomologous end joining. EXPERIMENTAL DESIGN: To investigate the therapeutic potential of DNA-PK targeting in STS, we first evaluated the prognostic value of DNA-PK expression in two large cohorts of patients with STS. We then used the potent and selective DNA-PK inhibitor AZD7648 compound to investigate the antitumor effect of the pharmacologic inhibition of DNA-PK in vitro via MTT, apoptosis, cell cycle, and proliferation assays. In vivo studies were performed with patient-derived xenograft models to evaluate the effects of AZD7648 in combination with chemotherapy or ionizing radiation on tumor growth. The mechanisms of sensitivity and resistance to DNA-PK inhibition were investigated by using a genome-wide CRISPR-Cas9 positive screen. RESULTS: DNA-PK overexpression is significantly associated with poor prognosis in patients with sarcomas. Selective pharmacologic inhibition of DNA-PK strongly synergizes with radiation- and doxorubicin-based regimen in sarcoma models. By using a genome-wide CRISPR-Cas9 positive screen, we identified genes involved in sensitivity to DNA-PK inhibition. CONCLUSIONS: DNA-PK inhibition deserves clinical investigation to improve response to current therapies in patients with sarcoma.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Protein Kinases/genetics , Protein Serine-Threonine Kinases/genetics , DNA-Activated Protein Kinase , Sarcoma/drug therapy , Sarcoma/genetics , Sarcoma/radiotherapy , DNA Repair , DNA , Radiation, Ionizing , Cell Line, Tumor
9.
Rev Infirm ; 72(292): 29-31, 2023.
Article in French | MEDLINE | ID: mdl-37364973

ABSTRACT

The development of alternatives to seclusion and restraint is a priority for psychiatric care services. Among them, the implementation of soothing spaces is currently experiencing considerable growth.


Subject(s)
Mental Disorders , Psychiatry , Humans , Patient Isolation/methods , Patient Isolation/psychology , Restraint, Physical/psychology , Psychotherapy , Hospitals, Psychiatric , Mental Disorders/therapy , Mental Disorders/psychology
10.
Exp Hematol Oncol ; 12(1): 51, 2023 May 31.
Article in English | MEDLINE | ID: mdl-37259134

ABSTRACT

Soft-tissue sarcoma (STS) are a heterogeneous group of rare tumors with different biological behavior that are fatal in more than 40% of cases, due to their metastatic evolution and inadequate treatment options. ATR inhibition already showed an activity, even if modest, in broad pre-clinical models of STS. By using genome-wide CRISPR/Cas9 library screening, we identified ATM signaling network genes as critical drivers for resistance to the specific ATR inhibitor AZD6738. The role of such genes in resistance to AZD6738 was confirmed by using CRISPR/Cas9 knockout models. More strikingly, the ATM inhibitor AZD0156 works synergistically with AZD6738 in vitro and abolishes STS growth in vivo in our models of most frequent histotypes (such as dedifferentiated liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma among others). Moreover, the combination of AZD6738 and AZD0156 induced significantly higher levels of DNA damage than either drug used as single agent alone. In summary, our results demonstrate that targeting ATM is an effective approach to overcome resistance to ATR inhibition in different STS subtypes, including the most frequent histologies.

11.
Healthcare (Basel) ; 12(1)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38200974

ABSTRACT

The pathway to parenthood constitutes a fundamental and transformative stage in every individual's life. While postpartum depression in mothers has been increasingly studied and acknowledged, paternal postpartum depression (PPD) has garnered only moderate research attention. This study aims to delve into the comprehension and knowledge of healthcare professionals who may encounter men suffering from postpartum depression. Within the framework of this qualitative research, we conducted six semi-structured interviews with various healthcare professionals. The data were subjected to interpretative phenomenological analysis, revealing the following themes: (1) the professionals' uncertainty in the face of paternal PPD; (2) the context and timing of healthcare professionals' involvement appeared unsuited for detecting paternal PPD; (3) the experiences of fathers were found not to be shared with healthcare professionals due to their inhibitions and avoidance reactions; (4) the social representation of the role of fathers influenced professionals in their considerations of this aspect. Strengthening the training and confidence of healthcare professionals in France would lead to an enhancement in the screening and management of paternal PPD. Additionally, the healthcare system should better organize postnatal support to enable caregivers to be more available during the peak of depression occurrence.

12.
Theranostics ; 12(17): 7624-7639, 2022.
Article in English | MEDLINE | ID: mdl-36438498

ABSTRACT

Rationale: Patients with colorectal cancer die mainly due to liver metastases (CRC-LM). Although the tumor microenvironment (TME) plays an important role in tumor development and therapeutic response, our understanding of the individual TME components, especially cancer-associated fibroblasts (CAFs), remains limited. Methods: We analyzed CRC-LM CAFs and cancer cells by single-cell transcriptomics and used bioinformatics for data analysis and integration with related available single-cell and bulk transcriptomic datasets. We validated key findings by RT-qPCR, western blotting, and immunofluorescence. Results: By single-cell transcriptomic analysis of 4,397 CAFs from six CRC-LM samples, we identified two main CAF populations, contractile CAFs and extracellular matrix (ECM)-remodeling/pro-angiogenic CAFs, and four subpopulations with distinct phenotypes. We found that ECM-remodeling/pro-angiogenic CAFs derive from portal resident fibroblasts. They associate with areas of strong desmoplastic reaction and Wnt signaling in low-proliferating tumor cells engulfed in a stiff extracellular matrix. By integrating public single-cell primary liver tumor data, we propose a model to explain how different liver malignancies recruit CAFs of different origins to this organ. Lastly, we found that LTBP2 plays an important role in modulating collagen biosynthesis, ECM organization, and adhesion pathways. We developed fully human antibodies against LTBP2 that depleted LTBP2+ CAFs in vitro. Conclusion: This study complements recent reports on CRC-LM CAF heterogeneity at the single-cell resolution. The number of sequenced CAFs was more than one order of magnitude larger compared to existing data. LTBP2 targeting by antibodies might create opportunities to deplete ECM-remodeling CAFs in CRC-LMs. This might be combined with other therapies, e.g., anti-angiogenic compounds as already done in CRC. Moreover, we showed that in intrahepatic cholangiocarcinoma, in which ECM-remodeling CAF proportion is similar to that of CRC-LM, several genes expressed by ECM-remodeling CAFs, such as LTBP2, were associated with survival.


Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Liver Neoplasms , Humans , Cancer-Associated Fibroblasts/metabolism , Liver Neoplasms/pathology , Tumor Microenvironment/physiology , Fibroblasts/metabolism , Colorectal Neoplasms/pathology , Latent TGF-beta Binding Proteins/metabolism
13.
EMBO Mol Med ; 14(12): e15343, 2022 12 07.
Article in English | MEDLINE | ID: mdl-36278433

ABSTRACT

Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy.


Subject(s)
Brain Neoplasms , Glioblastoma , Lactate Dehydrogenases , Animals , Mice , Lactic Acid , Metabolomics , Glioblastoma/enzymology , Glioblastoma/pathology , Brain Neoplasms/enzymology , Brain Neoplasms/pathology
14.
Front Bioinform ; 2: 999700, 2022.
Article in English | MEDLINE | ID: mdl-36304332

ABSTRACT

Lungs are the most frequent site of metastases growth. The amount and size of pulmonary metastases acquired from MRI imaging data are the important criteria to assess the efficacy of new drugs in preclinical models. While efficient solutions both for MR imaging and the downstream automatic segmentation have been proposed for human patients, both MRI lung imaging and segmentation in preclinical animal models remains challenging due to the physiological motion (respiratory and cardiac movements), to the low amount of protons in this organ and to the particular challenge of precise segmentation of metastases. As a consequence post-mortem analysis is currently required to obtain information on metastatic volume. In this work, we have developed a complete methodological pipeline for automated analysis of lungs and metastases in mice, consisting of an MR sequence for image acquisition and a deep learning method for automatic segmentation of both lungs and metastases. On one hand, we optimized an MR sequence for mouse lung imaging with high contrast for high detection sensitivity. On the other hand we developed DeepMeta, a multiclass U-Net 3+ deep learning model to automatically segment the images. To assess if the proposed deep learning pipeline is able to provide an accurate segmentation of both lungs and pulmonary metastases, we have longitudinally imaged mice with fast- and slow-growing metastasis. Fifty-five balb/c mice were injected with two different derivatives of renal carcinoma cells. Mice were imaged with a SG-bSSFP (self-gated balanced steady state free precession) sequence at different time points after the injection of cancer cells. Both lung and metastases segmentations were manually performed by experts. DeepMeta was trained to perform lung and metastases segmentation based on the resulting ground truth annotations. Volumes of lungs and of pulmonary metastases as well as the number of metastases per mouse were measured on a separate test dataset of MR images. Thanks to the SG method, the 3D bSSFP images of lungs were artifact-free, enabling the downstream detection and serial follow-up of metastases. Moreover, both lungs and metastases segmentation was accurately performed by DeepMeta as soon as they reached the volume of ∼ 0.02 m m 3 . Thus we were able to distinguish two groups of mice in terms of number and volume of pulmonary metastases as well as in terms of the slow versus fast patterns of growth of metastases. We have shown that our methodology combining SG-bSSFP with deep learning, enables processing of the whole animal lungs and is thus a viable alternative to histology alone.

15.
Cancers (Basel) ; 14(17)2022 Aug 31.
Article in English | MEDLINE | ID: mdl-36077783

ABSTRACT

Radiosensitization of glioblastoma is a major ambition to increase the survival of this incurable cancer. The 5-aminolevulinic acid (5-ALA) is metabolized by the heme biosynthesis pathway. 5-ALA overload leads to the accumulation of the intermediate fluorescent metabolite protoporphyrin IX (PpIX) with a radiosensitization potential, never tested in a relevant model of glioblastoma. We used a patient-derived tumor cell line grafted orthotopically to create a brain tumor model. We evaluated tumor growth and tumor burden after different regimens of encephalic multifractionated radiation therapy with or without 5-ALA. A fractionation scheme of 5 × 2 Gy three times a week resulted in intermediate survival [48-62 days] compared to 0 Gy (15-24 days), 3 × 2 Gy (41-47 days) and, 5 × 3 Gy (73-83 days). Survival was correlated to tumor growth. Tumor growth and survival were similar after 5 × 2 Gy irradiations, regardless of 5-ALA treatment (RT group (53-67 days), RT+5-ALA group (40-74 days), HR = 1.57, p = 0.24). Spheroid growth and survival were diminished by radiotherapy in vitro, unchanged by 5-ALA pre-treatment, confirming the in vivo results. The analysis of two additional stem-like patient-derived cell lines confirmed the absence of radiosensitization by 5-ALA. Our study shows for the first time that in a preclinical tumor model relevant to human glioblastoma, treated as in clinical routine, 5-ALA administration, although leading to important accumulation of PpIX, does not potentiate radiotherapy.

16.
Immunity ; 55(10): 1872-1890.e9, 2022 10 11.
Article in English | MEDLINE | ID: mdl-36130603

ABSTRACT

Memory B cells (MBCs) can persist for a lifetime, but the mechanisms that allow their long-term survival remain poorly understood. Here, we isolated and analyzed human splenic smallpox/vaccinia protein B5-specific MBCs in individuals who were vaccinated more than 40 years ago. Only a handful of clones persisted over such an extended period, and they displayed limited intra-clonal diversity with signs of extensive affinity-based selection. These long-lived MBCs appeared enriched in a CD21hiCD20hi IgG+ splenic B cell subset displaying a marginal-zone-like NOTCH/MYC-driven signature, but they did not harbor a unique longevity-associated transcriptional or metabolic profile. Finally, the telomeres of B5-specific, long-lived MBCs were longer than those in patient-paired naive B cells in all the samples analyzed. Overall, these results imply that separate mechanisms such as early telomere elongation, affinity selection during the contraction phase, and access to a specific niche contribute to ensuring the functional longevity of MBCs.


Subject(s)
Immunologic Memory , Memory B Cells , B-Lymphocytes/metabolism , Germinal Center , Humans , Immunoglobulin G/metabolism
17.
Cancers (Basel) ; 14(15)2022 Aug 02.
Article in English | MEDLINE | ID: mdl-35954433

ABSTRACT

Glioblastoma (GB) are the most frequent brain cancers. Aggressive growth and limited treatment options induce a median survival of 12-15 months. In addition to highly proliferative and invasive properties, GB cells show cancer-associated metabolic characteristics such as increased aerobic glycolysis. Pyruvate dehydrogenase (PDH) is a key enzyme complex at the crossroads between lactic fermentation and oxidative pathways, finely regulated by PDH kinases (PDHKs). PDHKs are often overexpressed in cancer cells to facilitate high glycolytic flux. We hypothesized that targeting PDHKs, by disturbing cancer metabolic homeostasis, would alter GB progression and render cells vulnerable to additional cancer treatment. Using patient databases, distinct expression patterns of PDHK1 and PDHK2 in GB tissues were obvious. To disturb protumoral glycolysis, we modulated PDH activity through the genetic or pharmacological inhibition of PDHK in patient-derived stem-like spheroids. Striking effects of PDHKs inhibition using dichloroacetate were observed in vitro on cell morphology and metabolism, resulting in increased intracellular ROS levels and decreased proliferation and invasion. In vivo findings confirmed a reduction in tumor size and better survival of mice implanted with PDHK1 and PDHK2 knockout cells. Adding a radiotherapeutic protocol further resulted in a reduction in tumor size and improved mouse survival in our model.

19.
Data Brief ; 42: 108191, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35515991

ABSTRACT

Due to the rising amount of plastic waste generated each year, multiple questions are emerging about their harmful long-term effects on the environment, the eco-systems and human health. One possible strategy to mitigate these issues is to substitute conventional plastics by materials fully biodegradable in natural conditions, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). In order to decrease the overall cost and environmental impact of PHBV-based materials while modulating their technical performance, PHBV can be combined with lignocellulosic fillers. In this article, a total of 88 formulations of PHBV-based biocomposites has been collected, distributed over 5 interdisciplinary projects involving computer scientists, data scientists and biomass processing experts for food and bio-based material production. Available data concern the technical process descriptions, including the description of each step and the different observations measured. These data are stored in a knowledge base that can be queried on the Web.

20.
Int Dent J ; 72(5): 667-673, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35422317

ABSTRACT

AIM: In many countries, periodontal surgery is mainly provided by periodontists. This specialty is not recognised in France, where periodontal care and treatment are principally the responsibility of general dentists (GDs). The objective of this study was to investigate the periodontal care provided and factors associated with the treatment of periodontal diseases, including periodontal surgery, by GDs in France. METHODS: A national cross-sectional survey of GDs practicing in the French metropolitan area was conducted in 2019. A self-administered questionnaire was sent by mail to the GDs selected by stratified simple random sampling. It included questions on respondents' sociodemographic characteristics and their periodontal practice. A multivariate logistic regression model was employed to identify the factors associated with the practice of periodontal surgery by GDs. RESULTS: Three hundred eighty-five GDs responded (response rate, 23.4%). Their mean age was 45.2 years; 51.2% were male and 83.6% were in private practice. They reported performing selective periodontal examinations such as pocket probing on average for 34.2% of their patients, but only 5.5% of them performed them systematically. Several variables were significantly associated with the provision of periodontal surgical procedures such as the gender of the GDs, full mouth periodontal probing, implantology practice, insufficient fees, or uncertainty about treatment procedure. This survey confirmed the referral of patients for periodontal surgery by a minority of practitioners. It also highlighted insufficient screening and diagnostic procedures for periodontal diseases by GDs. CONCLUSIONS: There is a need to improve French GDs' periodontal skills and knowledge and to address other barriers that currently limit their ability to deliver comprehensive periodontal care.


Subject(s)
General Practice, Dental , Periodontal Diseases , Cross-Sectional Studies , Dentists , Female , France , Humans , Male , Middle Aged , Periodontal Diseases/diagnosis , Periodontal Diseases/therapy , Practice Patterns, Dentists' , Surveys and Questionnaires
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