Role of B7-H3 in predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

Background: Neoadjuvant platinum-based chemotherapy offers a modest survival advantage in muscle-invasive bladder cancer (MIBC) for patients with pathologic response. B7-H3 (), an immune checkpoint overexpressed in various cancers, including urothelial-cell carcinoma (UCC), has been associated with chemoresistance and poor oncologic outcomes. We aimed to explore if B7H3 expression on bladder biopsy samples was a predictive biomarker for pathologic response to neoadjuvant platinum-based chemotherapy.

Synthesis and evaluation of anti-PD-L1-B11 antibody fragments for PET imaging of PD-L1 in breast cancer and melanoma tumor models.

There is a critical need to non-invasively assess the PD-L1 expression in tumors as a predictive biomarker for determining the efficacy of anti-PD-1/PD-L1 immunotherapies. Non-invasive imaging modality like positron emission tomography (PET) can be a powerful tool to assess the PD-L1 expression in the whole body including multiple metastases as a patient selection criterion for the anti-PD-1/PD-L1 immunotherapy. In this study, we synthesized B11-nanobody, B11-scFv and B11-diabody fragments from the full-length anti-PD-L1 B11 IgG.

A multicriteria vulnerability index for equitable resource allocation in public health funding.

Setting: This paper describes an action research project with the Centre universitaire intégré de santé et de services sociaux - Capitale Nationale (CIUSSS-CN) who identified a need to assess vulnerability in their territories in order to ensure equitable distribution of the Integrated Perinatal and Early Childhood Services (SIPPE) program funds. The objective was to design and validate a multicriteria model to provide a more accurate portrait of vulnerability based on recent social realities.

Intervention: Our multidisciplinary research team of 7 members included experts in analytics, decision aiding, and community and public health.

The anti-B7-H3 blocking antibody MJ18 does not recognize B7-H3 in murine tumor models.

The immune checkpoint molecule B7-H3 is regarded as one of the most promising therapeutic targets for the treatment of human cancers. B7-H3 is highly expressed in many cancers and its expression has been associated to impaired antitumor immunity and poor patient prognosis. In immunocompetent mouse tumor models, genetic deletion of B7-H3 in tumor cells enhances antitumor immune response leading to tumor shrinkage.

A case-based reasoning tool to recommend drinking water source protection actions.

In response to a need expressed by water actors to support them in identifying appropriate actions for protecting drinking water sources, we modelled, designed, implemented, tested, and validated a prototype case-based reasoning (CBR) system. This required an intensive knowledge acquisition and structuring process which we conducted in collaboration with 102 water management and governance actors in Quebec, Canada. Knowledge was organized in a case base containing nearly 200 past experiences implementing water protection actions at different decision-making scales (local, regional, provincial), by various organizations (government, municipalities, water-related associations), over the last two decades.

Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer.

Introduction And Objectives: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy.

NKG7 Is a T-cell-Intrinsic Therapeutic Target for Improving Antitumor Cytotoxicity and Cancer Immunotherapy.

Cytotoxic CD8 T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. By evaluating human CD8 T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function.

Targeting the immune checkpoint B7-H3 for next-generation cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) for programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have become preferred treatment strategies for several advanced cancers. However, response rates for these treatments are limited, which encourages the search for new ICI candidates. Recent reports have underscored significant roles of B7 homolog 3 protein (B7-H3) in tumor immunity and disease progression.

Surfaceome Profiling of Rhabdomyosarcoma Reveals B7-H3 as a Mediator of Immune Evasion.

Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins enriched in RMS tumors. Among the top candidates, we identified B7-H3 as the major immunoregulatory molecule expressed by RMS tumors.

Targeting endosomal pH for cancer chemotherapy.

Altered pH homeostasis in cancer cells has been linked with essentially all classical hallmarks of cancer, including chemoresistance. We recently identified a conceptually novel mechanism for how dysregulated pH in hypoxic cells causes chemoresistance which is based on the aberrant cellular distribution of the endosomal pH regulator, the sodium/hydrogen exchanger 6 (NHE6).

Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance.

The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification.

Platelet-Derived Growth Factor Receptor Activation Promotes the Prodestructive Invadosome-Forming Phenotype of Synoviocytes from Patients with Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLS) play a major role in invasive joint destruction in rheumatoid arthritis (RA). This prodestructive phenotype has been shown to involve autocrine TGF-β that triggers formation of matrix-degrading invadosomes through molecular mechanisms that are not fully elucidated. The platelet-derived growth factor (PDGF) receptor (PDGFR) family of receptor tyrosine kinases (RTK) has been shown to cooperate with TGF-β in various pathological conditions.

Snail Is a Critical Mediator of Invadosome Formation and Joint Degradation in Arthritis.

Progressive cartilage destruction, mediated by invasive fibroblast-like synoviocytes, is a central feature in the pathogenesis of rheumatoid arthritis (RA). Members of the Snail family of transcription factors are required for cell migration and invasion, but their role in joint destruction remains unknown. Herein, we demonstrate that Snail is essential for the formation of extracellular matrix-degrading invadosomal structures by synovial cells from collagen-induced arthritis (CIA) rats and RA patients.

Integrating groundwater into land planning: a risk assessment methodology.

Generally, groundwater is naturally of good quality for human consumption and represents an essential source of drinking water. In Canada, small municipalities and individuals are particularly reliant on groundwater, since they cannot afford complex water treatment installations. However, groundwater is a vulnerable resource that, depending on its characteristics, can be contaminated by almost any land use.

Integration of groundwater information into decision making for regional planning: a portrait for North America.

Groundwater is widely used as a source of drinking water in North America. However, it can be contaminated by microbial or chemical agents potentially hazardous to human health. In recent decades, governments have developed better knowledge of groundwater and established measures to protect and preserve the resource.