EA_25 Column End Assembly
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- EA_25 Column End Assembly
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- 1293622
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- Ato
- Gene target:
- EA_25 Column End Assembly
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Related articles to: EA_25 Column End Assembly
- Oncolytic viruses (OVs) are designed to selectively infect, proliferate within, and destroy cancer cells while concurrently eliciting robust antitumor immune responses. Notwithstanding their significant potential, inadequate tumor selectivity and restricted treatment efficacy persist as substantial barriers to wider clinical utilization. This review rigorously evaluates current advancements in OV engineering designed to address these issues. Transcriptional targeting, which employs tumor-specific promoters like hTERT, E2F1, and hypoxia-inducible elements, microRNA detargeting, and the redirection of viral entry towards tumor-associated antigens such as EGFR, HER2, and EpCAM, alongside multi-layered logic-gated regulatory systems, represent strategies to augment tumor specificity. To bolster anticancer efficacy, OVs have been modified with immunomodulatory agents, including cytokines (GM-CSF, IL-12), immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4), chemokines, and stroma-degrading enzymes (hyaluronidase, relaxin). Subsequent advancements encompass nanoparticle encapsulation, carrier-cell transport mechanisms, metabolic reprogramming strategies, and synergistic combinations with immunotherapy, chemotherapy, or radiotherapy. Furthermore, systems and synthetic biology techniques are enabling the development of advanced "smart" OVs, which possess the capacity for real-time detection and adaptation within the tumor microenvironment. These combined methodologies present considerable promise for enhancing the safety profile, intratumoral distribution, and overall therapeutic efficacy of oncolytic virotherapy. - Source: PubMed
Publication date: 2026/04/16
Murod KhakimovSaodat YarmukhamedovaAvazmetova IntizorZokir RaximovKhalbayeva ZarinaNozima KhamdamovaYo'ldashevich Jumaniyozov KuvondikAlkhawaja Ali SameerSiahmansouri Homayoon - This study aims to establish an efficient Circulating tumor cells (CTCs) multi-targeted magnetic combined sorting system for Gastric cancer (GC), while comparing it with tissue and circulating tumor DNA (ctDNA) samples to evaluate its feasibility and consistency for genomic profiling analysis. Establish an efficient CTCs sorting system for GC targeting epithelial cell adhesion molecule, cell surface vimentin, and protein tyrosine kinase 7, and evaluate its physicochemical properties and cell capture efficiency. Assess the feasibility of tumor cell detection through animal experiments. Sixty-eight GC patients underwent CTCs detection. Clinical information was analyzed to evaluate the clinical utility of CTCs in the auxiliary diagnosis of GC. Next-generation sequencing was performed on GC tissue, CTCs, and ctDNA samples to assess the consistency of genetic mutations across different sample types. The constructed CTCs sorting system exhibits excellent physicochemical properties, achieving a capture rate of 94.68%. Animal studies confirm a positive correlation between tumor cells count and tumor volume. The number of CTCs in the blood of GC patients is significantly correlated with tumor size, stage, and metastasis. The CTCs count in GC patients is significantly higher than in healthy individuals and high-risk groups for cancer, with diagnostic sensitivity and specificity of 97.29% and 97.73%, respectively. The mutation detection rate in CTCs samples was significantly higher than that in tissue and ctDNA samples. The concordance rate between CTCs and tissue mutations was 24.32%, while the concordance rate between CTCs and ctDNA mutations was 19.05%. This study successfully established a multi-target combined CTCs multi-targeted magnetic combined sorting system for GC. CTCs detection based on this system can be used for the auxiliary diagnosis of GC patients. Furthermore, compared to GC tissue and ctDNA samples, CTCs detection enables more comprehensive genomic profiling analysis and serves as an important supplement to GC genomic analysis. - Source: PubMed
Publication date: 2026/04/17
Huang LinfeiRuan YueluZhu LeiXu Jing - Circulating tumor cells (CTCs) are cancer cells found in the bloodstream that serve as biomarkers for early cancer detection, prognostication, and disease monitoring. However, CTC detection remains challenging due to low cell abundance and heterogeneity. Digital holographic microscopy (DHM) offers a promising, label-free method for high-throughput CTC identification by capturing superior morphological information compared to traditional imaging methods, while remaining compatible with in-flow data acquisition. We present a streamlined DHM-based system that integrates microfluidic enrichment with deep learning-driven image analysis, supplemented by immunofluorescent profiling, to improve sensitivity and specificity of CTC enumeration. Specifically, our platform combines inertial microfluidic preprocessing with dual-modality imaging, integrating holography with fluorescence sensing of up to two markers. A deep learning model, trained on a diverse set of healthy blood samples and cancer cell lines, and executed in real-time, provides a morphological confidence on a cell-by-cell basis that may then be combined with immunofluorescence criteria for enumeration. In a pilot study, we demonstrate higher CTC counts in patients with late-stage prostate cancer ( = 13) compared to healthy controls ( = 8), with a patient-level false positive rate of 1 cell/mL. Notably, nearly two-thirds of identified CTCs were EpCAM-negative but PSMA positive (a prostate specific epithelial marker), suggesting that traditional use of EpCAM as an epithelial marker for CTCs may lead to false negatives. These findings highlight the potential of DHM for applications including but not limited to screening, diagnostics, and precision oncology. - Source: PubMed
Publication date: 2026/04/14
Mallery KevinBristow Nathaniel RHeller NicholasTravadi YashArafa AliKamalanathan KayleeGaleano-Garces CatalinaAhmadi MahdiSchaap GrantHesch AlexaHedeen OliviaIzuora ZikoraHapke JoelMiller JeffreyViswanathan ArjunBabris IvoBae SongyiBhattacharya BaisaliLe TuanClacko TonyAntonarakis Emmanuel SKonety Badrinath RDrake Justin MHong Jiarong - We report a multicystic intrahepatic neoplasm in a 54-year-old Japanese woman, representing a previously unrecognized subtype. Grossly, the lesion was a well-demarcated multicystic tumor with focal papillary projections. Histologically, the cysts were lined by columnar to cuboidal neoplastic cells with brush border-like luminal microvilli, abundant granular eosinophilic cytoplasm, and small round nuclei. The cystic lumina contained colloid-like secretion, and bile-filled glands were occasionally observed. The septa were composed of thin hepatocellular parenchyma. Immunohistochemically, the tumor cells were positive for CD10, CK7, CK19, EpCAM, and SPINK1 and negative for HepPar1, MUC1, MUC2, MUC5AC, and MUC6. Whole-exome sequencing identified a pathogenic somatic KRAS p.G12V variant. RNA sequencing detected no PRKACA/B fusions. Single-cell spatial transcriptomics demonstrated that tumor cells clustered most closely with septal and medium-sized interlobular bile ducts. Gene set activity analysis showed significant suppression of gene sets downregulated by KRAS activation and upregulation of KRAS dependency signature gene sets in tumor cells. These findings distinguish this lesion from established entities of intrahepatic biliary cystic neoplasms, including intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, intraductal oncocytic papillary neoplasm, and mucinous cystic neoplasm. We propose the designation "eosinophilic biliary cystic neoplasm of the liver" for this distinct intrahepatic biliary neoplasm. - Source: PubMed
Tanaka MarikoKoinuma DaizoHinata MunetoshiTakeshita KimikoYasunaga YoichiSakuma KeiTakamoto TakeshiNishioka YujiroHasegawa KiyoshiNakai YudaiUshiku Tetsuo - Tumor-targeted CD40 agonists have emerged as one of the novel strategies to activate intratumoral antigen-presenting cells (APCs), subsequently inducing T-cell-specific antitumor responses. However, their clinical efficacy as monotherapy has been limited, highlighting the need for effective combination therapies. We developed KK2269, a bispecific antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD40 on APCs, designed to selectively activate APCs in the presence of EpCAM-positive tumors. Our studies demonstrated that KK2269 activates APCs only in the presence of EpCAM-expressing cells. Using the immunologically cold B16F10-mouse EpCAM subcutaneously transplanted model, the antitumor effects of KK2269 in combination with clinically approved drugs, including anti-programmed cell death 1 (PD-1) antibody, docetaxel, doxorubicin, oxaliplatin, and gemcitabine were evaluated. KK2269 showed significant antitumor activity in combination with an anti-PD-1 antibody, docetaxel, doxorubicin, or oxaliplatin, but not gemcitabine, with docetaxel showing the most significant antitumor effect(s). Intratumoral immune analysis showed that KK2269 was associated with increased expression of APC activation markers, whereas docetaxel was associated with increased expression of dendritic cell (DC)-related genes. Moreover, expression of APC and T-cell activation markers was higher with docetaxel+KK2269 than with either monotherapy. The antitumor and immune activation effects of docetaxel+KK2269 were also observed in the immunosuppressive intrahepatic transplantation model. This study provides a rationale for combining a tumor-targeting CD40 agonist, KK2269, with docetaxel for the treatment of PD-1 blockade resistant tumors, including intrahepatic tumors, and supports exploration of this combination strategy in the clinic. - Source: PubMed
Publication date: 2026/04/16
Tezuka YutaKawasaki KyokoSumitomo YoshikiSaito MasatoYao AkariAndo Munetoshi