Cancer research papers

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Health and productivity benefits of anti-PD-(L)1 agents for early-stage cancer treatment in Hungary. reports: Anti-PD-(L)1 agents, inhibitors of programmed cell death protein 1 (PD-1) or its ligand (PD-L1), are established therapies that improve cancer management as well as the disease and societal burden of specific metastatic and early-stage cancers. The aim of the study was to determine the impact of adopting anti-PD-(L)1 agents for the treatment of all eligible patients with early-stage cancers versus reserving anti-PD-(L)1 agents for patients with metastatic disease alone in Hungary. This study evaluated two scenarios, one where anti-PD-(L)1 agents were used to treat all eligible early-stage disease case s (ESD scenario) of melanoma (stage IIB-C and III), renal cell carcinoma (RCC), and triple-negative breast cancer (TNBC) versus a reference scenario where anti-PD-(L)1 agents were only used to treat metastatic disease cases in Hungary (2024-2033).

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Digital spatial profiling of α-PD-1 treated breast cancer bone metastases reveals region-specific signaling and enrichment of immune-suppressive markers. reports: Bone is the most common and preferential site for breast cancer metastasis. Upon dissemination to the bone, breast cancer cells engraft into multiple niches, but it is unclear whether there are region-specific differences that may drive breast cancer progression in bone. We used a proteomic digital spatial profiling (DSP) approach to investigate which proliferation, cell death, and immune-related markers and pathways are enriched in immune and cancer cells residing 1) in the bone marrow or 2) along the endosteal surface, in an E0771, α-PD-1 treated pre-clinical model of breast cancer bone metastasis.

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Ultrasound-triggered carrier-free nanoprodrugs activate cGAS-STING pathway to enhance tumor-targeting chemo-immunotherapy. reports: Chemotherapy-induced cell apoptosis results in nuclear damage and the subsequent release of double-stranded DNA (dsDNA) fragments, which can stimulate the cGAS-STING pathway to initiate antitumor immune responses. However, this pathway may be less effective due to nonspecific systemic toxicity caused by chemotherapeutic agents and inefficient dsDNA accumulation. This study aimed to develop an ultrasound (US)-triggered carrier-free nanoprodrug PBSN38-curcumin (PBSN38-CUR), incorporating the sonosensitizer curcumin (CUR) and reactive oxygen species (ROS)-responsive prodrug pinacol boronic ester-conjugated 7-ethyl-10-hydroxycamptothecin (PBSN38).

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Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma. reports: Immune checkpoint inhibitor (ICI) therapy has significantly improved the treatment of solid tumors such as hepatocellular carcinoma (HCC); however, most patients fail to respond. Here, we examined whether co-administration of the tumor-penetrating internalizing (i)RGD peptide, which selectively increases tumor vascular permeability in a neuropilin-1-dependent manner, enhances intratumoral delivery and therapeutic efficacy of αPD-L1 in mouse models of HCC. αPD-L1, with or without iRGD, was administered intravenously to mice bearing endogenous HCCs (TGFα/c-myc and diethylnitrosamine [DEN]/carbon tetrachloride [CCl 4 ] models).

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A multicenter multimodel habitat radiomics model for predicting immunotherapy response in advanced NSCLC. reports: A robust predictive biomarker is critical for identifying patients with NSCLC who may benefit from immunotherapy. This study developed a CT-based habitat model using 590 advanced NSCLC cases. The model was constructed in contrast-enhanced CT images and validated on an independent cohort with non-contrast CT.

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TLR7-mediated inflammation drives PD-L1 upregulation and T cell exhaustion during influenza A virus infection. reports: T cell dysfunction driven by dysregulated programmed cell death-1 (PD-1)/PD-ligand (PD-L) immune checkpoint signaling is associated with severe influenza A virus (IAV) infection. While this pathway limits immunopathology, it can suppress antiviral immunity and promote T cell exhaustion. We investigated the role of toll-like receptor 7 (TLR7), a viral RNA sensor, in regulating PD-1/PD-L-mediated T cell responses during IAV infection.

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Immune Checkpoint Inhibitors for the Treatment of Periorbital Non-Melanoma Skin Cancers. reports: Non-melanoma skin cancers (NMSCs) of the periocular region present significant clinical challenges, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most prevalent. The purpose of this study is to report on the outcomes of anti-programmed death (PD-1)/PD-L1 immunotherapy in patients with locally advanced periorbital NMSCs. We conducted a retrospective study of the patients treated for locally advanced periocular BCC and cutaneous SCC using anti-PD-1/PD-L1 immunotherapy from January 2016 to January 2023.

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Tumor cell-intrinsic PD-1 in malignant ascites drives ovarian cancer progression via MAPK/ERK signaling. reports: Programmed cell death protein 1 (PD-1), an immune checkpoint primarily expressed on T cells, plays a critical role in mediating tumor immune evasion. However, the role of PD-1 in non-immune cells remains poorly understood. Here, we report tumor cell-intrinsic PD-1 expression in malignant ascites from ovarian cancer patients.

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Curcumin enhances GSDME-mediated pyroptosis to potentiate PD-1/PD-L1 immune checkpoint blockade in colorectal cancer. reports: Colorectal cancer (CRC) patients with a microsatellite-stable (MSS) status exhibit poor responsiveness to PD-1/PD-L1 blockade. Pyroptosis induction may resensitize MSS tumors to PD-1/PD-L1 blockade; however, the expression of GSDME, a key executor of pyroptosis, is often downregulated in CRC. Here, curcumin (CUR), a natural polyphenol, was identified as a potentiator of GSDME-dependent pyroptosis in CRC.

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Deer antler stem cell-derived exosomes: a regenerative medicine powerhouse from nature's own repair kit. reports: Exosomes are essential mediators of intercellular communication and, as such, have attracted considerable interest in regenerative medicine. Aantler stem cells (ASCs) have become the central candidate in the field of the periodic regeneration of the deer antlers-the only mammalian organ that can entirely regenerate; they have been found to inherit regenerative characteristics of their parent cells, combined with a low immunogenicity. This is a systematic review of the research advancements on ASC-Exos, including the following main aspects: At the technical level, it describes the isolation techniques (ultracentrifugation, size exclusion chromatography, immunoaffinity capture) and their principles, advantages and disadvantages and their identification methods: TEM (cup-shaped/spherical morphology), DLS (size distribution), Western blot (markers: CD63, CD81, TSG101); In the functional and mechanistic levels, through cargos (proteins, mRNAs, let-7a/let-7b), ASC-Exos enhance fibroblast proliferation/migration (CCK-8, Transwell), osteogenic genes expression (Runx2, Osterix) to differentiate into osteoblasts as well as controlling macrophage polarization (reduce TNF-α, IL-6; enhance IL-10); At the translational application level, ASC-Exos have been shown to be effective in bone repair (rat femoral defect, micro-CT/histology), cartilage protection (alleviate osteoarthritis), wound healing (mouse full-thickness wounds, angiogenesis), pulmonary fibrosis (inhibit CCL7-mediated monocyte-macrophage recruitment), tumor immunotherapy (engineered M2Pep/poly (I: C) ASC-Exos + PD-L1 antibodies suppress tumor growth/metastasis), treatment of neurodegenerative diseases, anti-aging and intervention in age-related diseases and treatment of metabolic disorders.

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Evaluating the Relationship Between Programmed Death Ligand-1 (Clone: 22C3), Anaplastic Lymphoma Kinase (D5F3), and C-ros Oncogene 1 (OT11A1) Expression in Lung Adenocarcinoma. reports: Objective This study investigates the relationship between programmed death ligand-1 (PD-L1), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) expression in lung adenocarcinoma (ADC). Methods Sixty-two cases were analyzed for ALK, ROS1, and PD-L1 expression using immunohistochemistry. Statistical evaluations were performed using chi-square and Fisher's exact tests.

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Soluble immune checkpoint proteins as predictive biomarkers for lymph node metastases in penile cancer. reports: Penile cancer (PeCa) is a rare but aggressive disease where lymph node metastases (LNM) represent the most significant prognostic factor. Accurate identification of LNM remains a clinical priority, but traditional imaging and clinical parameters often fail to detect occult LNM. Soluble immune checkpoint proteins (sICs) have recently emerged as potential non-invasive biomarkers in various malignancies, although unexplored in PeCa.

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Distinct tumor-immune ecologies in NSCLC patients predict progression and define a clinical biomarker of therapy response reports: We investigated multiplexed histological images from nine patients (both pre- and on-treatment) with immunotherapy-refractory Non-Small Cell Lung Cancer (NSCLC) treated with an oral HDAC inhibitor (vorinostat) combined with a PD-1 inhibitor (pembrolizumab). Patient responses comprised of either stable disease (SD) or progressive disease (PD). We built an extensive multiplexed-image analysis pipeline involving both cell segmentation and quadrats, coupled with spatial statistics, machine learning, and deep learning to analyze the spatial and temporal features that predict disease progression and identify potential clinical biomarkers. This is a preprint and not peer reviewed.

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BRAF/MEK Inhibition Induces Cell State Transitions Boosting Immune CheckpointSensitivity in BRAFV600E-mutant Glioma reports: Resistance to BRAF plus MEK inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poorly understood. This study addresses the urgent need to develop treatments for BRAFi+MEKi-resistant glioma in novel mouse models and patient-derived materials. BRAFi+MEKi reveals glioma plasticity by heightening cell state transitions along glial differentiation trajectories, giving rise to astrocyte- and immunomodulatory oligodendrocyte (OL)-like states. This is a preprint and not peer reviewed.

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Attenuation of malignant phenotype of glioblastoma following a short course of the pro-oxidant combination of Resveratrol and Copper reports: BackgroundWe investigated a novel therapeutic approach to glioblastoma (GBM) that targets cell-free chromatin particles (cfChPs) that are released from dying GBM cells and aggravate the oncogenic phenotype of living GBM cells. cfChPs can be deactivated by oxygen radicals (OR) generated upon admixing the nutraceuticals Resveratrol (R) and Copper (Cu). Oral administration of R-Cu leads to generation of OR which are readily absorbed to deactivate cfChPs. This is a preprint and not peer reviewed.

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VNAR: shark single-domain antibodies for the new era of medical biotechnology. reports: Shark-derived single-domain antibodies, known as VNARs, represent unique and advanced tools in medical biotechnology. Recognized for their small size, simple structure, and exceptional stability, VNARs can access cryptic epitopes that are inaccessible to traditional antibodies, making them valuable tools for next-generation diagnostic and therapeutic applications. Additionally, their evolutionary origin and structural diversity provide resistance to extreme pH, temperature, and proteolytic environments, making them especially suitable for demanding biomedical settings such as ocular and intestinal applications.

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