Biology subjects

Diab, M.

Publications and source records attributed to Diab, M..

4 recordsLinked to original sources

bioRxiv2026

The Lifespan Architecture of Human EEG

Human brain maturation and aging are highly nonlinear, yet their organization at the level of large-scale electrophysiological activity remains poorly understood. We analyzed resting-state electroencephalography (EEG) recordings from 1,763 healthy individuals aged 5-85 years to map lifespan trajectories across spectral, complexity, and morphological features. Age-sensitive features clustered into distinct nonlinear trajectories, most commonly showing rapid change during childhood and adolescence followed by stabilization in adulthood, while a smaller subset exhibited turning points in midlife. These trajectories also differed in their spatial expression, ranging from highly conserved scalp-wide patterns to heterogeneous profiles in which the same feature followed distinct trajectories across scalp regions. Transition ages revealed recurring regional sequences, suggesting that diverse EEG features share common reorganization chronologies. Together, these results show that lifespan EEG variation is structured through complementary temporal trajectories, spatial architectures, and regional transition sequences. This normative framework provides a basis for investigating brain development and aging and for identifying atypical patterns associated with neurological and psychiatric disorders.

neuroscience↗

bioRxiv2025

High-Dimensional Protein Analysis Uncovers Distinct Immunological and Stromal Signatures Between Primary and Metastatic Pancreatic Ductal Adenocarcinoma

Our understanding of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) primarily stems from murine models or primary patient tumors. While metastatic tumors have generally less immune infiltration compared to primary tumors, the specific cellular features of metastatic PDAC remain understudied. This knowledge gap is impactful as most patients present with metastatic disease and are most often enrolled in clinical trials. We hypothesized PDAC tumors harbor distinct immunologic and stromal features depending on their anatomical site. Using multiplex immunohistochemistry (mIHC), spatial analysis, and single-cell mass cytometry (CyTOF), we uncover dominant immune and stromal cell populations in tumors derived from 27 primary and 26 liver metastases. Metastatic liver tumors from PDAC patients contained fewer T cells and alpha-smooth muscle actin (-SMA+) activated fibroblasts than primary lesions, while CD68+ cells were more abundant. Spatial analyses revealed distinct immune cell communities in primary and metastatic PDAC, whereby CK19+ cells clustered differentially with -SMA+, CD3+, and CD68+ cells, depending on tumor site. When comparing tumor-associated regions, the proportion of peritumoral CK19- cells remained consistent, but their composition varied by disease site. CD8+ T cells were significantly less frequent in metastatic tumors, while both CD4+ and CD8+ T cells present in primary tumors expressed more transcription factors (TFs) associated with suppressive properties, including FoxP3 and ROR{gamma}t. CyTOF revealed that T cells co-expressed multiple inhibitory checkpoint receptors, with LAG-3 and PD-1 predominating. This report reveals that primary and metastatic tumors from PDAC patients harbor vastly distinct immunologic and stromal features at the protein level. Statement of SignificanceProtein level analysis reveals distinct immunological and stromal features between primary and metastatic PDAC tumors, offering a rationale for immunotherapies that target myeloid cells and increase T cell abundance in metastatic disease.

cancer biology↗

bioRxiv2024

Advantage of the F(ab)'2 fragment over IgG for RIT and PRIT

Radioimmunotherapy (RIT) has proved clinically effective in the treatment of relapsed or consolidating NHL after chemotherapy. However, it is still at the clinical trial stage for the treatment of solid tumors. The efficacy of the treatment on this type of tumor is limited by hematological toxicity, which restricts the activities injected. Pre-targeted radioimmunotherapy (PRIT) enables radiolabeling to be carried out in vivo at a time when the quantities of antigen-targeted vector reach a maximum level in the tumor, but have largely decayed in the bloodstream, thus limiting hematological toxicity. This therapeutic approach would make it possible to use higher radiopharmaceutical activities than those used in RIT, thereby increasing the doses deposited in the tumor and the therapeutic response. Despite encouraging preclinical trials, this approach has failed to live up to expectations in terms of clinical applications. In the context of PRIT using the Inverse Electron Demand Diels Alder (IEDDA) reaction as a method for radiolabeling tumor-targeted vectors, a major research effort has been made to improve the quality of in vivo radiolabeling using tetrazine (Tz) and transcycloctene (TCO) variants whose stability and reactivity have been optimized. Most trials in this field have been carried out using antibodies which, thanks to their long biological half-life, enable prolonged irradiation of tumors. Low-molecular-weight vectors such as affinity proteins or antigen-specific antibody fragments (VHH,scFv, F(ab)) have the advantage of being rapidly eliminated from circulation by renal filtration, but on the other hand, the quantities and residence times of these vectors in the tumor are reduced compared with IgG. F(ab)2 antibody fragments have properties intermediate between those of IgG and low-molecular-weight vectors that could be suitable for PRIT approaches, but they have not yet been evaluated in PRIT using IEDDA. In preparation for a preclinical trial of radioimmunotherapy of triple-negative breast cancer in spontaneously affected dogs, we compared the biodistribution of IgG and its F(ab)2 fragment targeting canine CD138 in a xenogeneic model of canine breast cancer and in a mouse model of colon cancer expressing human ACE antigen. This analysis shows that the use of F(ab)2 fragments improves the therapeutic index compared with IgG. F(ab)2 fragments seem particularly well suited to tumor targeting in PRIT using short-lived isotopes such as 211At.

cancer biology↗

bioRxiv2019

The EO771 mammary cancer cell line displays a luminal B phenotype and it is sensitive to anti-estrogen treatments

Despite decades of therapeutic trials, detection, many drugs available and numerous studies on breast cancer, it remains the most deadly cancer in women. In order to choose the most appropriate treatment and to know the prognosis of the patients, the breast cancer is divided into different subtypes using a molecular classification. Thus, the need to discover new effective therapy is necessary, requiring to have models to test them. The EO771 (also named E0771 or EO 771) murine mammary cancer cell line is originally isolated from a spontaneous tumor in C57BL/6 mouse. Although frequently used, this cell line remains poorly characterized. Therefore, the EO771 phenotype was investigated. Transcriptomic and protein analysis allowed to classify the EO771 as luminal B subtype and more precisely estrogen receptor negative, estrogen receptor {beta} positive, progesterone receptor positive and ErbB2 positive. This phenotype was associated to a sensitivity to anti-estrogen treatments such as tamoxifen, 4-hydroxy-tamoxifen, endoxifen and fulvestrant.

cancer biology↗