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Mashup Score: 69The intrinsic substrate specificity of the human tyrosine kinome - 19 hour(s) ago
Nature – An atlas of the substrate specificities for the human tyrosine kinome reveals diversity of motif specificities and enables identification of kinase–substrate relationships and kinase…
Source: www.nature.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 21
Abstract. First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic “cycling” of KRAS between its GDP- and GTP-bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report D3S-001, a next generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as EGF and HGF, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust anti-tumor activity preclinically and translated into promising clinical activity
Source: aacrjournals.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker | NEJM - 1 day(s) ago
A highly pathogenic avian influenza A(H5N1) virus infection was identified in a dairy farm worker in Texas. This pathogen has been reported in multiple dairy herds in several states.
Source: www.nejm.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 35
Most platforms used for the molecular reconstruction of the tumor–immune microenvironment (TIME) of a solid tumor fail to explore the spatial context of the three-dimensional (3D) space of the tumor at a single-cell resolution, and thus lack information about cell–cell or cell–extracellular matrix (ECM) interactions. To address this issue, a pipeline which integrated multiplex spatially resolved multi-omics platforms was developed to identify crosstalk signaling networks among various cell types and the ECM in the 3D TIME of two FFPE (formalin-fixed paraffin embedded) gynecologic tumor samples. These platforms include non-targeted mass spectrometry imaging (glycans, metabolites, and peptides) and Stereo-seq (spatial transcriptomics) and targeted seqIF (IHC proteomics). The spatially resolved imaging data in a two- and three-dimensional space demonstrated various cellular neighborhoods in both samples. The collection of spatially resolved analytes in a voxel (3D pixel) across serial sec
Source: www.mdpi.comCategories: General Medicine News, Hem/OncsTweet-
Impressive talk by Sammy Ferri-Borgogno on multi modality spatial profiling at PreCancer Atlas symposium @MDAndersonNews Exemplar study in #OvarianCancer: https://t.co/GjlwDV16D7 Excited about potential of @ST_Omics Stereo-seq: Sub cellular resolution ✅ Coding & non coding RNA… https://t.co/rWIK92EeFB https://t.co/HH7a3KrKuY
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Mashup Score: 17Cellformatica - Augmented Intelligence for Genetic Screens - 2 day(s) ago
Harness the knowledge of AI custom trained on complete corpus of scientific data and literature to de-noise the functional screen data and understand the connections between the candidate compounds or genes and the integrative effects they cause.
Source: www.cellformatica.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 88Tumor-selective treatment of metastatic pancreatic cancer with an engineered, probiotic living drug - 3 day(s) ago
Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges for effective treatment, with systemic chemotherapy often proving inadequate due to poor drug delivery and the tumor’s immunosuppressive microenvironment. Engineered bacteria present a novel approach to target PDAC, leveraging their ability to colonize tumors and deliver therapeutic payloads. Here, we engineered probiotic Escherichia coli Nissle 1917 (EcN) to produce the pore-forming Theta toxin (Nis-Theta) and evaluated its efficacy in a preclinical model of PDAC. Probiotic administration resulted in selective colonization of tumor tissue, leading to improved overall survival compared to standard chemotherapy. Moreover, this strain exhibited cytotoxic effects on both primary and distant tumor lesions while sparing normal tissues. Importantly, treatment also modulated the tumor microenvironment by increasing anti-tumor immune cell populations and reducing immunosuppressive markers. These findings demonstrate the poten
Source: www.biorxiv.orgCategories: General Medicine News, Hem/OncsTweet-
Cool “bugs as drugs” preprint from @KenOliveLab to start off your Monday. Really great stuff Ken (who is on a roll!) Tumor-selective treatment of metastatic #PancreaticCancer with an engineered, probiotic living drug https://t.co/tnt4uh36wg Photomicrograph showing acylhomoserine… https://t.co/IujYBQicjn https://t.co/djCWyW7P2n
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Mashup Score: 8Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma - 4 day(s) ago
Identifying metabolic abnormalities that occur before pancreatic ductal adenocarcinoma (PDAC) diagnosis could increase chances for early detection. We collected data on changes in metabolic parameters (glucose, serum lipids, triglycerides; total, low-density, and high-density cholesterol; and total body weight) and soft tissues (abdominal subcutaneous fat [SAT], adipose tissue, visceral adipose tissue [VAT], and muscle) from patients 5 years before the received a diagnosis of PDAC.
Source: www.gastrojournal.orgCategories: General Medicine News, Hem/OncsTweet-
Prior study summary graphic below: Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of #PancreaticCancer https://t.co/EU1QycMkKl Body composition changes especially VAT/SAT changes and biochemical metabolic perturbations (serum lipids and glucose) can… https://t.co/25SA31UDGH https://t.co/ube18aKjx9
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Mashup Score: 2Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker | NEJM - 5 day(s) ago
A highly pathogenic avian influenza A(H5N1) virus infection was identified in a dairy farm worker in Texas. This pathogen has been reported in multiple dairy herds in several states.
Source: www.nejm.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker | NEJM - 6 day(s) ago
A highly pathogenic avian influenza A(H5N1) virus infection was identified in a dairy farm worker in Texas. This pathogen has been reported in multiple dairy herds in several states.
Source: www.nejm.orgCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 2Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in a Dairy Farm Worker | NEJM - 6 day(s) ago
A highly pathogenic avian influenza A(H5N1) virus infection was identified in a dairy farm worker in Texas. This pathogen has been reported in multiple dairy herds in several states.
Source: www.nejm.orgCategories: General Medicine News, Hem/OncsTweet
RT @CantleyLab: We are delighted to share the #tyrosine @KinaseLibrary, now in @Nature: https://t.co/ZSwnymrBtb Tyrosine predictions and e…