Targeted agents have improved the efficacy of chemotherapy for cancer patients, however, there remains a lack of understanding of how these therapies affect the unsuspecting bystanders of the stromal microenvironment. Cetuximab, a monoclonal antibody therapy targeting the epidermal growth factor receptor (EGFR), is given in combination with chemotherapy as the standard of care for a subset of metastatic colorectal cancer patients. The overall response to this treatment is underwhelming and, while genetic mutations that confer resistance have been identified, it is still not known why this drug is ineffective for some patients. We discovered that cancer-associated fibroblasts (CAFs), a major cellular subset of the tumor stroma, can provide a source of cancer cell resistance. Specifically, we observed that upon treatment with cetuximab, CAFs increased their secretion of EGF, which was sufficient to render neighboring cancer cells resistant to cetuximab treatment through sustained mitogen-activated protein kinases (MAPK) signaling. Furthermore, we show the cetuximab-induced EGF secretion to be specific to CAFs and not to cancer cells or normal fibroblasts. Altogether, this work emphasizes the importance of the tumor microenvironment and considering the potential unintended consequences of therapeutically targeting cancer-driving proteins on non-tumorigenic cell types.

were more likely to have intermediate (44.6%) and inadequate (18.9%) prenatal care (P5.04). Adolescents also had higher antepartum admissions (P5.006) and a higher access ratio (P5.01). Outcomes were similar except for higher rates of preterm contractions (P5.03). CONCLUSION:The pattern of resource utilization demonstrates an overall favoring of inpatient services among adolescent mothers with inadequate access to outpatient resources. Strategies to improve access to prenatal outpatient visits are essential.

Fucus spiralis L. is a broadly distributed monoecious intertidal seaweed. The specific status of F. spiralis however is debatable. Here, we contribute to the bioinformatics and systematics of F. spiralis by analysing the complete mitochondrial and plastid genomes of a specimen from California, U.S.A. The F. spiralis mitogenome is 36,396 base pairs (bp) in length and contains 67 genes, and the plastid genome is 125,066 bp in length and contains 171 genes. The F. spiralis genomes are 99.7% and 99.8% similar in nucleotide sequence to F. vesiculosus , and support the revised classification of F. spiralis to Fucus vesiculosus var. spiralis .

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