14 research outputs found

    Trends in outcomes from endovascular aortic repair over two decades

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    Endovascular therapy for aortic pathology has changed over the past two decades with the newer stent technologies. We examine the outcomes of endovascular aortic repair in a small subset of patients

    Vegetable twig causing obstructive parotid sialadenitis

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    We report the case of a 4-year-old boy with obstructive parotid sialadenitis in whom the classic clinical presentation clinched the diagnosis which highlights the importance of applied anatomy and clinical examination even in the present age of novel imaging techniques

    Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment

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    Objective The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery. Materials and methods A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality. Results The study analyzed the patients who were treated between January 2012 and June 2015. Among 705 patients with carcinoma of the tongue treated primarily with wide local excision and neck dissection, 383 received adjuvant treatment. A total of 215 patients received radiation, and 168 received concurrent radio-chemotherapy. Of 378 patients, 78 developed hypothyroidism during follow-up: 27 patients received concurrent radio-chemotherapy, and the remaining 51 received only radiation. Lower neck received 40–48 Gy in 2 patients, 50 Gy in 74 patients, and 60–70 Gy and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months. Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the oral tongue. The minimum period to develop hypothyroidism was 3 months in this study. Gender and adjuvant treatment were not found to be significant for the incidence of hypothyroidism. Conclusions A significant number of patients with carcinoma of the tongue who receive adjuvant treatment will develop hypothyroidism, hence frequent monitoring of thyroid function is advised during follow-up

    Tissue-Specific Oncogenic Activity of KRASA146T

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    KRAS is the most frequently mutated oncogene. The incidence of specific KRAS alleles varies between cancers from different sites, but it is unclear whether allelic selection results from biological selection for specific mutant KRAS proteins. We used a cross-disciplinary approach to compare KRASG12D, a common mutant form, and KRASA146T, a mutant that occurs only in selected cancers. Biochemical and structural studies demonstrated that KRASA146T exhibits a marked extension of switch 1 away from the protein body and nucleotide binding site, which activates KRAS by promoting a high rate of intrinsic and guanine nucleotide exchange factor– induced nucleotide exchange. Using mice genetically engineered to express either allele, we found that KRASG12D and KRASA146T exhibit distinct tissue-specific effects on homeostasis that mirror mutational frequencies in human cancers. These tissue-specific phenotypes result from allele-specific signaling properties, demonstrating that context-dependent variations in signaling downstream of different KRAS mutants drive the KRAS mutational pattern seen in cancer. SIGNIFICANCE: Although epidemiologic and clinical studies have suggested allele-specific behaviors for KRAS, experimental evidence for allele-specific biological properties is limited. We combined structural biology, mass spectrometry, and mouse modeling to demonstrate that the selection for specific KRAS mutants in human cancers from different tissues is due to their distinct signaling properties.National Institutes of Health (Grant U01CA215798
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