Despite evidence that the ability to taste is weakened by obesity and can be rescued with weight loss intervention, few studies have investigated the molecular effects of obesity on the taste system. ...Taste bud cells undergo continual turnover even in adulthood, exhibiting an average life span of only a few weeks, tightly controlled by a balance of proliferation and cell death. Recent data reveal that an acute inflammation event can alter this balance. We demonstrate that chronic low-grade inflammation brought on by obesity reduces the number of taste buds in gustatory tissues of mice-and is likely the cause of taste dysfunction seen in obese populations-by upsetting this balance of renewal and cell death.
Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of ...the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.5%), colorectal cancer (7.7%), and head and neck cancer (6.7%). FAT1 encodes a cadherin-like protein, which we found is able to potently suppress cancer cell growth in vitro and in vivo by binding β-catenin and antagonizing its nuclear localization. Inactivation of FAT1 via mutation therefore promotes Wnt signaling and tumorigenesis and affects patient survival. Taken together, these data strongly point to FAT1 as a tumor suppressor gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer. Loss of FAT1 function is a frequent event during oncogenesis. These findings address two outstanding issues in cancer biology: the basis of Wnt activation in non-colorectal tumors and the identity of a 4q35 tumor suppressor.
Both genome-wide genetic and epigenetic alterations are fundamentally important for the development of cancers, but the interdependence of these aberrations is poorly understood. Glioblastomas and ...other cancers with the CpG island methylator phenotype (CIMP) constitute a subset of tumours with extensive epigenomic aberrations and a distinct biology. Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathogenicity, but the molecular basis of G-CIMP remains unresolved. Here we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), establishes G-CIMP by remodelling the methylome. This remodelling results in reorganization of the methylome and transcriptome. Examination of the epigenome of a large set of intermediate-grade gliomas demonstrates a distinct G-CIMP phenotype that is highly dependent on the presence of IDH mutation. Introduction of mutant IDH1 into primary human astrocytes alters specific histone marks, induces extensive DNA hypermethylation, and reshapes the methylome in a fashion that mirrors the changes observed in G-CIMP-positive lower-grade gliomas. Furthermore, the epigenomic alterations resulting from mutant IDH1 activate key gene expression programs, characterize G-CIMP-positive proneural glioblastomas but not other glioblastomas, and are predictive of improved survival. Our findings demonstrate that IDH mutation is the molecular basis of CIMP in gliomas, provide a framework for understanding oncogenesis in these gliomas, and highlight the interplay between genomic and epigenomic changes in human cancers.
Single‐stage long‐segment tracheal transplantation Genden, Eric M.; Miles, Brett A.; Harkin, Timothy J. ...
American journal of transplantation,
October 2021, 2021-10-00, 20211001, Letnik:
21, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Tracheal transplantation has been envisioned as a viable option for reconstruction of long‐segment tracheal defects. We report the first human single‐stage long‐segment tracheal transplantation. ...Narrow‐band imaging and bronchoscopic biopsies demonstrate allograft vascularization and viable epithelial lining. The recipient was immunosuppressed with Tacrolimus, Mycophenolate mofetil, and corticosteroids. Six months after transplantation, the trachea is both functional and the patient is breathing without the need of a tracheostomy or stent.
The authors present a case of single‐stage, vascularized, long‐segment tracheal transplantation to reconstruct an extensive tracheal airway defect. Randhawa and Patterson comment on page 3223.
A systematic review of the literature was performed to compare long-term outcomes of thymectomy and medical treatment for generalized myasthenia gravis (MG).
A Medline search through June 2015 ...resulted in 71 studies, 27 of which were selected (10,140 patients: 5,275 thymectomies, 4,865 medication).
The pooled proportion of remission with thymectomy was 0.31 (95% CI, 0.25-0.37), with conservative treatment it was 0.15 (95% CI, 0.12-0.18). The odds ratio (OR) of remission with thymectomy in comparison with medication alone was 2.44 (95% CI, 1.91-3.12) overall and according to medication type and remission definitions.
Thymectomy is superior to conservative treatment with solely medication on remission in MG.
Left untreated, malignant pleural mesothelioma (MPM) is associated with uniformly poor prognosis. Better survival has been reported with surgery-based multimodality therapy, but to date, no trial has ...demonstrated survival benefit of surgery over other therapies. We evaluated whether cancer-directed surgery influenced survival independently from other predictors in a large population-based dataset.
The SEER database was explored from 1973 to 2009 to identify all cases of pathologically-proven MPM. Age, sex, race, year of diagnosis, histology stage, cancer-directed surgery, radiation, and vital status were analyzed. The association between prognostic factors and survival was estimated using Cox regression and propensity matched analysis.
There were 14,228 patients with pathologic diagnosis of MPM. On multivariable analysis, female gender, younger age, early stage, and treatment with surgery were independent predictors of longer survival. In comparison to no treatment, surgery alone was associated with significant improvement in survival adjusted hazard ratio (adj HR) 0.64 (0.61-0.67), but not radiation adj HR 1.15 (1.08-1.23). Surgery and radiation combined had similar survival as surgery alone adj HR 0.69 (0.64-0.76). Results were similar when cases diagnosed between 1973 and 1999 were compared to cases diagnosed between 2000 and 2009.
Despite developments in surgical and radiation techniques, the prognosis for MPM patients has not improved over the past 4 decades. Cancer-directed surgery is independently associated with better survival, suggesting that multimodal surgery-based therapy can benefit these patients. Further research in adjuvant treatment is necessary to improve prognosis in this challenging disease.
To reduce public health hazards, greywater reuse may involve disinfection, which is often performed through chlorination. The formation of toxic disinfection by-products is a negative side-effect of ...chlorine’s reaction with organic matter, of which trihalomethanes (THM) are one of the most dominant (though not most toxic) groups. Greywater treatment in vertical flow constructed wetlands leads to a decrease in dissolved organic matter. We hypothesized that these dissolved organic carbon (DOC) changes would be reflected in differences in THM formation. Greywater samples, at different treatment levels (i.e., decreasing organic matter content), were exposed to 5 mg/L of chlorine for 1 h. THM formation in raw greywater samples was significantly lower than in the more treated (recirculated) samples, despite their significantly higher DO concentrations. This trend was verified in six different systems. Furthermore, this was also shown when greywater was exposed to higher chlorine doses (25 and 50 mg/L). It is suggested that the increase in THM formation for longer recirculated water is the result of two factors: competition between a higher number of reactive sites in the raw water’s organic matter, which leads to smaller THM yields, and changes in the abundance of THM formation moieties in the recirculated water’s DOC. The latter was reflected in the SUVA increase in the treated water. Overall, THM formation, following treated greywater chlorination at the lower chlorine concentration studied, is not expected to pose an environmental health risk when the water is reused for irrigation.
To avoid complications or bad results following reconstruction of skin cancer defects, there are several factors that can be incorporated into the design and execution of repairs. These techniques ...not only decrease the need to correct bad results, they improve the final aesthetic and functional outcome. So although one surgeon might focus on standard corrective treatments, another might use elements of flap design and implementation that will decrease the need for such corrective procedures. We discuss 4 useful reconstructive repairs and delineate the properties of design and execution that help to ensure success and avoid bad results.
The TNM classification for lung cancer, originally designed for NSCLC, is applied to staging of bronchopulmonary carcinoid tumors. The validity of the eighth edition of the staging system for ...carcinoid tumors has not been assessed. In this study, we evaluated its prognostic accuracy by using data from a large national population-based cancer registry.
Patients with typical and atypical bronchopulmonary carcinoids diagnosed between 2000 and 2013 were identified from the National Cancer Institute’s Surveillance, Epidemiology and End Results registry. We used competing risks analysis to compare 10-year disease-specific survival (DSS) across stages.
Overall, 4645 patients with bronchopulmonary carcinoid tumors were identified. Worsening DSS with increasing TNM status and stage was demonstrated across both typical and atypical carcinoids, with overlaps between adjacent subcategories. The combined stages (I versus II, II versus III, and III versus IV) showed greater separation in DSS despite persistent overlaps between groups. For typical carcinoids, we found decreased DSS for stages II, III, and IV, with hazard ratios of 3.8 (95% confidence interval CI: 2.6–5.6), 4.3 (95% CI: 3.0–6.1), and 9.0 (95% CI: 6.1–13.1), respectively, compared with stage I.
The combined stage categories of the eighth edition of the TNM staging system provide useful information on outcomes for typical and atypical carcinoids. However, persistent overlaps in combined stage and subcategories of the staging system limit the usefulness of the TNM staging system, particularly in intermediate stages. These limitations suggest the need for future further study and refinement.
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