Publications by authors named "Rad R"

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines.

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B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.

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In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

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Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. However, detailed assessment of neoTCR-characteristics affecting therapeutic efficacy is mostly missing. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient.

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Article Synopsis
  • Natural killer (NK) cells are vital for fighting metastasis, but disseminated tumor cells (DTCs) in the lungs release prostaglandin E2 (PGE), which leads to NK cell dysfunction.
  • This dysfunction is triggered by PGE binding to specific receptors (EP2 and EP4), altering NK cell gene expression and reducing the production of important anti-metastatic signals.
  • Targeting the PGE-EP2/EP4 pathway may provide a new therapeutic strategy to enhance NK cell activity against metastatic tumors in distant organs.
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CDK4/6 inhibitors are standard of care in the treatment of metastatic breast cancer. Treatment regimen consists of a combination with endocrine therapy, since their therapeutic efficacy as monotherapy in most clinical trials was rather limited. Thus, understanding the molecular mechanisms that underlie response to therapy might allow for the development of an improved therapy design.

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Coronary artery disease (CAD) is the most common cardiovascular disease and the main cause of mortality in developing countries. Since physical activity and nutritional behaviors are modifiable risk factors in people at risk of CAD, the present study aims to explore the effect of an intervention based on the social cognitive theory (SCT) on physical activity and nutritional behaviors in middle-aged population at risk of CAD in the city of Bandar Abbas. The present cross-sectional study was conducted on 519 middle-aged subjects who visited the healthcare centers in Bandar Abbas, southern Iran, in 2023.

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In a patient with permanent neonatal syndromic diabetes clinically similar to cases with ONECUT1 biallelic mutations, we identified a disease-causing deletion located upstream of ONECUT1. Through genetic, genomic, and functional studies, we identified a crucial regulatory region acting as an enhancer of ONECUT1 specifically during pancreatic development. This enhancer region contains a low-frequency variant showing a strong association with type 2 diabetes and other glycemic traits, thus extending the contribution of this region to common forms of diabetes.

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Background & Aims: Although most hepatocellular carcinoma (HCC) cases are driven by hepatitis and cirrhosis, a subset of patients with chronic hepatitis B develop HCC in the absence of advanced liver disease, indicating the oncogenic potential of hepatitis B virus (HBV). We investigated the role of HBV transcripts and proteins on HCC development in the absence of inflammation in HBV-transgenic mice.

Methods: HBV-transgenic mice replicating HBV and expressing all HBV proteins from a single integrated 1.

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B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality.

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Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases.

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Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay.

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Article Synopsis
  • - Chronic hepatitis B virus (HBV) infection affects 300 million people globally, leading to dysfunction in virus-specific CD8 T cells that struggle to eliminate HBV-infected liver cells due to mechanisms that aren't fully understood.
  • - Research indicates a liver immune rheostat inhibits the activation of these CD8 T cells, particularly the CXCR6 subtype, leading to loss of their functionality, as shown by increased activity of the transcription factor cAMP-responsive element modulator (CREM) in both experimental models and chronic HBV patients.
  • - Enhanced signaling pathways related to cAMP and protein kinase A (PKA) in these T cells contribute to their dysfunction, as they establish prolonged contacts with liver cells, impairing essential activation
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Article Synopsis
  • Cancer cells adapt to various stresses, including those from treatments, through metabolic adaptability, focusing on the energy sensor AMP-activated protein kinase (AMPK).
  • In pancreatic ductal adenocarcinoma (PDAC), high levels of AMPK expression and activity were observed, leading to the identification of PF-3758309 as a potential AMPK inhibitor through drug repurposing.
  • PF-3758309 not only demonstrates pre-clinical effectiveness in PDAC models but also helps sensitizes cancer cells to ferroptosis inducers, paving the way for AMPK-targeted therapies in combination treatments for this type of cancer.
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Mushrooms have been used as medicine by humans for more than 5000 years. They have had a successful role in treating immune deficiencies. Nowadays, some extracts and compounds obtained from medicinal mushrooms have increased a great prospect of treating many disorders by having a great role in modulation of immune system, cancer inhibiting, cardio-vascular health, antiviral, antibacterial, antioxidant and protective effects against hepatitis and diabetes.

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Article Synopsis
  • - Mitochondria respond to infections with signals that can trigger inflammation, but the full understanding of how this works is still being explored.
  • - The study reveals that the enzyme caspase-activated DNase (CAD) plays a key role in activating mitochondrial pro-inflammatory responses, aiding the body's defense against viral infections.
  • - In experiments, cells and mice lacking CAD showed weakened immune responses to viral infections, indicating that CAD is crucial for linking mitochondrial activity to inflammation and overall immune defense.
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Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell-dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection.

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  • PARP inhibitors have shown effectiveness in treating ovarian cancer, particularly benefiting patients with homologous recombination deficiency (HRD), and various assays can be used to assess these biomarkers.
  • The study compares the performance of multiple molecular assays for genomic instability (GI) against the standard Myriad myChoice assay using DNA from high-grade serous ovarian cancer (HGSOC) samples.
  • Results indicate high concordance between different assays for assessing GI, supporting their use in clinical settings for HRD evaluation, which aligns with European Medicines Agency guidelines for PARP inhibitor treatment.
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  • Long noncoding RNAs (lncRNAs) are prevalent in the genome, but their functions are not well understood, partly due to their overlap with other genetic sequences.
  • The researchers developed a new genome-scale screening method using Cas13d/CasRx to explore lncRNAs more effectively, overcoming limitations of previous methods.
  • They created a targeted library called Albarossa, focusing on 24,171 lncRNA genes, which improves the ability to discover important lncRNAs across various cancers while addressing challenges like transcriptome size and tissue specificity.
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Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which the water-channel protein AQP4 is the target antigen. The immunopathology in neuromyelitis optica is largely driven by autoantibodies to AQP4. However, the T cell response that is required for the generation of these anti-AQP4 antibodies is not well understood.

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Serine/threonine-protein kinase B-raf (BRAF) mutations are found in 8-15% of colorectal cancer patients and identify a subset of tumors with poor outcome in the metastatic setting. We have previously reported that BRAF-mutant human cells display a high rate of protein production, causing proteotoxic stress, and are selectively sensitive to the proteasome inhibitors bortezomib and carfilzomib. In this work, we tested whether carfilzomib could restrain the growth of BRAF-mutant colorectal tumors not only by targeting cancer cells directly, but also by promoting an immune-mediated antitumor response.

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Background: Coronary artery disease (CAD) is the most common cardiovascular disease (CVD) and the main cause of mortality in developed and developing countries. Physical activity and nutritional behaviors are modifiable factors in people at the risk of CAD and its risk factors; thus, the present study aimed to design, implement, and evaluate an intervention based on the social cognitive theory for physical activity and nutritional behaviors in the middle-aged population at the risk of CAD residing in Bandar Abbas city.

Materials And Methods: The present study will be conducted in three phases: qualitative, cross-sectional, and community-based intervention.

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