Objective To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted The NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for the Bethesda System for Reporting Thyroid Cytopathology. Design Participants of the Atlas Project were selected from among the committee members of the NCI FNA State of the Science Conference and other participants at the live conference. The terminology framework was based on a literature search of English language publications dating back to 1995 using PubMed as the search engine; online forum discussions ( http://thyroidfna.cancer.gov/forums/default.aspx ); and formal interdisciplinary discussions held on October 22 and 23, 2007, in Bethesda, MD. Main outcome For clarity of communication, the Bethesda System for Reporting Thyroid Cytopathology recommends that each report begin with one of the six general diagnostic categories. Each of the categories has an implied cancer risk that links it to an appropriate clinical management guideline. Conclusions The project participants hope that the adoption of this framework will facilitate communication among cytopathologists, endocrinologists, surgeons, and radiologists; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the understanding of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.

The Bethesda System for Reporting Thyroid Cytopathology.

Over the last several decades, it has become clear that epigenetic abnormalities may be one of the hallmarks of cancer. Posttranslational modifications of histones, for example, may play a crucial role in cancer development and progression by modulating gene transcription, chromatin remodeling, and nuclear architecture. Histone acetylation, a well-studied posttranslational histone modification, is controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). By removing acetyl groups, HDACs reverse chromatin acetylation and alter transcription of oncogenes and tumor suppressor genes. In addition, HDACs deacetylate numerous nonhistone cellular substrates that govern a wide array of biological processes including cancer initiation and progression. This review will discuss the role of HDACs in cancer and the therapeutic potential of HDAC inhibitors (HDACi) as emerging drugs in cancer treatment.

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HDACs and HDAC Inhibitors in Cancer Development and Therapy

Luteolin, a flavonoid, as an anticancer agent: A review.

Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab). These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-κB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE) lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (P<0.05). The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC. Thus inducing miR-146a might be a therapeutic strategy for NSCLC.

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miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.

BACKGROUND Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer-specific, all-cause mortality and recurrence outcomes. METHODS Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer-specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided. RESULTS Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (<±5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01, I(2) = 55.0%). Higher risk of mortality was apparent for weight gain ≥10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not associated with all-cause mortality (P = .40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of 25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of 10.0% or more was not associated with hazard of breast cancer-specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, P = .05). CONCLUSIONS Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher.

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Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis.

Systemic inflammatory markers derived from peripheral blood cell, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), have been demonstrated as prognostic markers in several types of malignancy. Here, we investigated and compared the association between systemic inflammatory markers and survival and developed a prognostic nomogram in breast cancer patients. We reviewed the clinical and pathological records of 661 patients diagnosed with invasive breast carcinoma between 1993 and 2011. The NLR, dNLR, PLR and LMR in the immediate preoperative period were assessed. We analyzed the relationship between these inflammatory markers and clinicopathologic variables, disease-specific survival (DSS), and disease-free survival (DFS) in patients. A nomogram was developed to predict 3- and 5-year DSS for breast cancer. In the univariate analysis, high NLR, dNLR, PLR and low LMR were all significantly associated with poor DSS and DFS. In the multivariate analysis, only the PLR (HR 3.226, 95% CI 1.768-5.885 for DSS and HR 1.824, 95% CI 1.824-6.321 for DFS) was still identified as an independent predictor of outcomes. A subgroup analysis revealed that the PLR was the sole independent marker predicting poor DSS in patients with lymph node metastasis (HR 2.294, 95% CI 1.102-4.777) and with luminal subtype (HR 4.039, 95% CI 1.905-8.562). The proposed nomogram, which includes the PLR, shows good accuracy in predicting DSS with a concordance index of 0.82. PLR is an indicator of systemic inflammation as a part of the host immune response. As an independent prognostic factor, an elevated preoperative PLR is superior to the NLR, dNLR, and LMR in predicting clinical outcomes in patients with breast cancer. Moreover, the nomogram incorporating the PLR could accurately predict individualized survival probability in breast cancer.

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Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer

Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma.

Emphysematous gastritis is a rare form of phlegmonous gastritis, characterized by air in the wall of the stomach due to invasion by gas-forming microorganisms. The most commonly involved microorganisms are streptococci, Escherichia coli, Pseudomonas aeruginosa, Clostrodium perfrigens and Staphylococcus aureus. Gastrointestinal mucormycosis is another rare condition, which is most frequently occurs in the stomach. Because emphysematous gastritis associated with invasive gastric mucormycosis is an extremely rare clinical condition and both are life-threatening diseases, early precise diagnosis and early treatment should be done to avoid mortality. Herein we present an extremely rare case of emphysematous gastritis associated with invasive gastric mucormycosis. A 43-yr-old man, suffering from alcoholism and diabetes, has experienced diffuse abdominal pain for 4 days. Abdominal computed tomography scan demonstrated gas within the stomach wall. A histologic examination of the total gastrectomy specimen showed several gas-filled bubbles in the wall, along with numerous fungal hyphae throughout the necrotic stomach wall. He died of multiorgan failure secondary to disseminated mucormycosis, despite the intensive medical therapy.

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Emphysematous Gastritis Associated with Invasive Gastric Mucormycosis: A Case Report

Objectives: The trefoil factor family (TFF) is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3, and plays a role in gastrointestinal mucosal defence and repair. Recently, TFFs have been found to be related to the development of various types of cancer. This study assessed the relationship between the expression of TFF1 and TFF3 and the clinicopathological parameters in gastric carcinoma (GC). Materials and Methods: The expression of TFF1 and TFF3 was analyzed by immunohistochemistry in 292 GCs and 20 normal gastric tissues. Results: All normal gastric tissues expressed TFF1, but 53.8% of GCs showed reduced TFF1 expression. However, TFF3 was not detected in normal gastric tissues and 44.2% of GCs showed a high level of expression. Highly expressed TFF3 was significantly correlated with lymph node metastasis, lymphatic invasion, vein invasion, and advanced stage. The overall survival was shorter in patients with high expression of TFF3 than in those with low expression of TFF3 in 292 GCs and in 125 early GCs (EGCs). Moreover, in patients with EGCs, high expression of TFF3, associated with reduced expression of TFF1, was determined as an independent poor prognostic marker. Conclusions: Reduced expression of TFF1 and increased expression of TFF3 may play a role in the carcinogenesis of gastric cancer. Furthermore, high expression of TFF3 with reduced expression of TFF1 may be a marker of poor prognosis for patients with EGC.

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Hyun Joo Choi

Papers

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer

Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma.

Emphysematous Gastritis Associated with Invasive Gastric Mucormycosis: A Case Report

Reduced Expression of TFF1 and Increased Expression of TFF3 in Gastric Cancer: Correlation with Clinicopathological Parameters and Prognosis

Expression of claudin-7 and loss of claudin-18 correlate with poor prognosis in gastric cancer.