1,387 results match your criteria: "Cancer Center Clínica Universidad de Navarra[Affiliation]"

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach.

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Background: Palliative sedation refers to the proportional use of titrated medication which reduces consciousness with the aim of relieving refractory suffering related to physical and psychological symptoms and/or existential distress near the end of life. Palliative sedation is intended to be an end of life option that enables healthcare professionals to provide good patient care but there remains controversy on how it is used. Little is known about decision-making processes regarding this procedure.

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Enrolling adequate numbers of patients into the control arm of randomized controlled trials (RCTs) often presents barriers. There is interest in leveraging real-world data (RWD) from electronic health records (EHRs) to construct external control (EC) arms to supplement RCT control arms and form hybrid control (HC) arms. This investigation showed the use of an HC arm in second-line metastatic pancreatic ductal adenocarcinoma (PDAC).

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The complement system in clinical oncology: Applications, limitations and challenges.

Semin Immunol

December 2024

Laboratory of Translational Oncology, Program in Solid Tumors, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain; Department of Biochemistry and Genetics, School of Sciences, Universidad de Navarra, Pamplona, Spain; Navarra's Health Research Institute (IDISNA), Pamplona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain. Electronic address:

The complement system, a key component of innate immunity, is involved in seemingly contradictory aspects of tumor progression and cancer therapy. It can act as an immune effector against cancer and modulate the antitumor activity of certain therapeutic antibodies, but it can also contribute to a tumor-promoting microenvironment. Understanding this dual role should lead to the development of better therapeutic tools, strategies for cancer treatment and biomarkers for the clinical management of cancer patients.

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Antiapoptotic Bcl-2 family proteins are involved in myeloma cell survival. To date, their expression in multiple myeloma (MM) patients has mostly been analyzed at the RNA level. In the present study, we quantified for the first time the protein expression of the Bcl2-family members using a capillary electrophoresis immunoassay in 120 newly diagnosed MM patients, aged ≤65 years, treated in the context of the PETHEMA/GEM2012 study.

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The precise mechanisms by which the complement system contributes to the establishment of an immunosuppressive tumor microenvironment (TME) and promotes tumor progression remain unclear. In this study, we investigated the expression and function of complement C5a receptor 1 (C5aR1) in human and mouse cancer-associated dendritic cells (DCs). First, we observed an overexpression of C5aR1 in tumor-infiltrating DCs, compared to DCs from blood or spleen.

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High-risk cytogenetic abnormalities in multiple myeloma: PETHEMA-GEM experience.

Hemasphere

December 2024

Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC) CIBERONC Salamanca Spain.

This study examines the impact of cytogenetic abnormalities and their co-segregation on the prognosis of newly diagnosed multiple myeloma patients. The analysis included 1304 patients from four different GEM-PETHEMA clinical trials. Genetic alterations, such as t(4;14), t(14;16), del(17p), +1q, and del(1p), were investigated using FISH on CD38 purified plasma cells.

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Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

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Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma?

Arch Pathol Lab Med

December 2024

From the Department of Pathology, Université Paris Cité, Faculté de Médecine Paris Cité, APHP, Centre, Hôpital Cochin, Paris, France (Kime, Just).

Context.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.

Objective.

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Article Synopsis
  • The IMvigor210 trial assessed the long-term efficacy and safety of atezolizumab, an anti-PD-L1 therapy, in patients with advanced metastatic urothelial carcinoma (UC), showing manageable toxicity.
  • The trial involved two cohorts: untreated UC patients ineligible for cisplatin-based chemotherapy and those previously treated with platinum-based chemotherapy, with a median follow-up of up to 96.4 months.
  • Results indicated objective response rates of 23.5% in untreated patients and 16.5% in previously treated patients, with median overall survival of 16.3 months and 7.9 months, respectively, along with a notable percentage of patients experiencing grade 3/4 adverse events. *
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Use of individualized starting dose and niraparib hematologic adverse event management costs in ovarian cancer.

J Comp Eff Res

January 2025

Medical Oncology Department, Program in Solid Tumours, CIMA, Cancer Center Clínica Universidad de Navarra, Madrid, and Grupo Español de Investigación en Cancer ginecológicO (GEICO), Madrid, 28027, Spain.

Article Synopsis
  • The study analyzes the cost differences in managing hematologic adverse events (AEs) for the individualized starting dose (ISD) versus the fixed starting dose (FSD) of niraparib from a US payer perspective.
  • Data from a phase III trial provided AE occurrence rates, and costs were calculated based on 2020 adjustments from a healthcare database.
  • Results showed that managing AEs was significantly cheaper with ISD ($6744.93) compared to FSD ($12,987.71), suggesting ISD not only cuts costs but also improves patient safety.
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Article Synopsis
  • This study examines the combined effects of the PARP inhibitor niraparib and statins on progression-free survival in ovarian cancer patients.
  • The analysis of clinical trials showed that patients taking niraparib experienced better progression-free survival compared to those on placebo (13.8 months vs 8.2 months).
  • Notably, patients using both niraparib and statins had significantly better outcomes than those on placebo with statins, highlighting potential benefits of combining these treatments and the need for more research in this area.
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RANK drives structured intestinal epithelial expansion during pregnancy.

Nature

December 2024

Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.

Article Synopsis
  • - During pregnancy and lactation, mammals experience significant changes in their intestinal epithelium, leading to an increase in intestinal surface area through the expansion of villi.
  • - The RANK-RANKL molecular pathway is crucial for this process, protecting gut cells from death and promoting intestinal stem cell activity, which results in villous elongation.
  • - Mice lacking RANK in their intestinal epithelium have offspring that are heavier and more prone to glucose intolerance, highlighting the importance of RANK-RANKL in both immediate and long-term health outcomes for offspring.
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Article Synopsis
  • Glypican-3 (GPC3) is a potential target for T-cell therapy in hepatocellular carcinoma (HCC), but current CAR T-cell approaches face issues like low persistence and GPC3 shedding.
  • Researchers immunized HLA-A2 transgenic mice to find GPC3-specific T-cell receptors (TCRs) and engineered human T cells (TCR-Ts) that effectively recognize GPC3-positive HCC cells.
  • TCR-B-T cells showed superior effectiveness compared to traditional CAR T-cells, and combining CAR-T and TCR-B-T cells may enhance therapeutic results in treating HCC.
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DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd.

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Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of plasma cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess circulating tumor DNA (ctDNA) fraction. This meta-analysis aims to summarize the current findings and comprehensively investigate the prognostic value of baseline ctDNA detected by ULP-WGS in solid tumors.

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The impact of measurable residual disease (MRD) in relapse/refractory multiple myeloma (RRMM) patients treated with T-cell redirecting immunotherapy is uncertain. We analyzed MRD dynamics using next-generation flow in 201 patients treated in clinical trials with chimeric antigen receptor (CAR) T cells and T-cell engagers (TCE). Achieving MRD negativity at 10 was associated with 89% reduction in the risk of progression and/or death.

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Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.

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Chimeric antigen receptor (CAR)-T cell products, classified as Advanced Therapy Medicinal Products (ATMPs), have shown promising outcomes in cancer immunotherapy. The quality of raw and starting materials used in manufacturing is critical to ensure the efficacy and safety of CAR-T cell products and depends primarily on the selection of the right materials and the right suppliers. It is essential to consider a long-term strategy when selecting raw and starting materials to prevent delays in the supply of innovative, high-quality, and safe therapies to patients.

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Uncovering functional lncRNAs by scRNA-seq with ELATUS.

Nat Commun

November 2024

Center for Applied Medical Research, University of Navarra, PIO XII 55 Ave, Pamplona, Spain.

Long non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level is challenging due to their less accurate annotation and low expression compared to protein-coding genes. Here, we systematically benchmark different preprocessing methods and develop a computational framework, named ELATUS, based on the combination of the pseudoaligner Kallisto with selective functional filtering.

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