Most read

This list of most read articles is created by calculating article views for the previous 15 days. It is refreshed daily.

Showing: 1–25 of 50

  1. A prescription for cancer diagnostics

    Cancer research has made great strides in identifying effective therapies for treating advanced-stage tumors. The next challenge is moving the battle to earlier stages of disease.
  2. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention

    Skip authorsShow fewer authors

    Composition of gut bacteria and serum metabolites in young, obese individuals is partially restored following weight loss surgery, including Bacteroides thetaiotaomicron, which decreases serum glutamate levels and fat mass gain in mice.

  3. Elimination of large tumors in mice by mRNA-encoded bispecific antibodies

    Skip authorsShow fewer authors

    Bispecific antibodies that connect T cells with tumor cells can be delivered in the form of in vitro–transcribed pharmacologically optimized mRNA; when injected into mice, these mRNA-encoded antibodies reject large established tumors as efficiently as the corresponding recombinant antibody protein.

  4. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing

    Skip authorsShow fewer authors

    A protocol based on chemical modulation of WNT activity is used to efficiently generate colonic organoids that recapitulate the molecular features of human colon tissue. Colonic organoids generated from induced pluripotent stem cells from patients with familial adenomatous polyposis provide an in vitro platform for disease modeling and preclinical drug testing.

  5. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug

    Skip authorsShow fewer authors

    A randomized clinical trial reveals that the antidiabetic effects of metformin are at least partially due to beneficial changes in the microbiota.

  6. An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer

    Skip authorsShow fewer authors

    Resistance to ERK signaling inhibitors in BRAFV600E-mutant melanomas and lung cancers is achieved by parallel convergent mechanisms, including amplification of the mutant allele in extrachromosomal elements, that allow tumors to adapt while maintaining their intratumor heterogeneity. Intermittent treatment with a combination of RAF, MEK and ERK inhibitors imposes a higher selective pressure than sequential therapy and produces the strongest antitumor effects while minimizing toxicity. These findings warrant evaluating the effectiveness of this combinatorial regimen in patients, to improve treatment responses and delay the emergence of drug resistance.

  7. Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis

    Skip authorsShow fewer authors

    During cold stimulation, cholesterol is converted to bile acids in an alternative pathway. The bile acids then alter the microbiota, which in turn promotes more heat generation.

  8. Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin–N-cadherin pathway after spinal cord injury

    Skip authorsShow fewer authors

    In a mouse model of spinal cord injury, reactive astrogliosis is found to be context dependent and reversible. Blockade of type I collagen–reactive astrocyte interactions prevents astrocyte scar formation and facilitates functional recovery after injury.

  9. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

    Skip authorsShow fewer authors

    MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inform patient enrollment in genomically matched clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Sequencing results of tumor and matched normal tissue from a cohort of >10,000 patients with detailed clinical annotation provide an overview of the genomic landscape of advanced solid cancers and bring new insights into molecularly guided cancer therapy.

  10. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

    Skip authorsShow fewer authors

    Repair of defects in the common bile duct is hampered by a lack of healthy donor tissue. Developing human extrahepatic cholangiocyte organoids and testing them in mouse models may provide a way to overcome this limitation.

  11. Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism

    Skip authorsShow fewer authors

    An HDR-independent therapeutic genome-editing approach corrected the splice-site mutation in Lama2 in a mouse model of congenital muscular dystrophy type 1A, and may be applied more broadly to correct splice-site mutations associated with other diseases.

  12. Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis

    Skip authorsShow fewer authors

    The kinase Plk1 has been studied primarily as a mitotic regulator in dividing cells, but de Cárcer et al. find that Plk1 deficiency or inhibition in mice causes nonmitotic defects in the vasculature, including aortic aneurysm and rupture, as well as defective vascular smooth muscle contractility. These results recommend a note of caution in the clinical use of PLK1 inhibitors as anticancer agents.

  13. Combined mutation in Vhl, Trp53 and Rb1 causes clear cell renal cell carcinoma in mice

    Skip authorsShow fewer authors

    Through combined deletion of Vhl, Trp53 and Rb1 in renal epithelial cells, the authors develop a new mouse model of renal cell carcinoma that recapitulates the cellular and molecular features of a large proportion of human tumors. This model uncovers a role for primary-cilium-related genes in the development of the disease and provides a reliable platform for preclinical therapeutic studies.

  14. Battling the biology of opioid addiction

    Deaths from drug overdose are rising worldwide, in part owing to the growing epidemic of opioid addiction. Efforts to combat opioid addiction will benefit from stronger collaboration between preclinical researchers who are studying addiction and those studying chronic pain.
  15. Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling

    Skip authorsShow fewer authors

    Current mouse models of nonalcoholic steatohepatitis are limited, making identification and preclinical testing of new treatments challenging. Housing mice at thermoneutrality leads to less stress, a stronger immune response and better modeling of this condition.

  16. Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells

    Skip authorsShow fewer authors

    Number of IL-9-expressing ILC2s are elevated in patients with inflammatory arthritis during remission, and these cells are critical in mice for the resolution of inflammatory arthritis via regulatory T cell induction. Delivery of DNA minicircles encoding IL-9 into inflamed joints ameliorates mouse experimental arthritis, suggesting possible therapeutic applications.

  17. Brown and beige fat: development, function and therapeutic potential

    Skip authorsShow fewer authors

    There is much interest in brown and beige adipocytes, as their thermogenic activities can suppress weight gain and metabolic disease in rodent models. The authors review recent data that have provided new insights into the development and biology of brown and beige adipocytes and critically assess the possibilities for manipulating these cells to combat obesity and its associated diseases.

  18. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus

    Skip authorsShow fewer authors

    In a rat model of hydrocephalus triggered by intraventricular hemorrhage, Kristopher Kahle and colleagues show that TLR4–NF-κB-dependent inflammatory signaling in the choroid plexus causes hypersecretion of cerebrospinal fluid that drives hydrocephalus. Targeting TLR4–NF-κB-mediated signaling or the NKCC1–SPAK complex ameliorates hydrocephalus.

  19. ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix

    Skip authorsShow fewer authors

    By surgically directing the vascular delivery of decellularization reagents, the in situ decellularization of desired organs or tissues in mice can be achieved, enabling detailed imaging and characterization of the intact extracellular matrix, including in the cancer metastatic niche.

  20. A mouse model of renal cell carcinoma

    Skip authorsShow fewer authors
    A mouse model with combined renal epithelium-specific deletion of Vhl, Trp53 and Rb1 that develops clear-cell renal cell carcinoma provides a research tool for investigating the mechanisms that drive this cancer, and for evaluating the efficacy of novel therapeutic agents.