A 51-year-old woman presented with metachronous tumor development in bilateral breasts, thyroid, and endometrium. Additional signs and symptoms fulfilled the National Comprehensive Cancer Network criteria for Cowden syndrome. Immunohistochemistry showed loss of PTEN expression in all tumors. Single nucleotide variants, 647 germline variants (including one each in PTEN and MSH3), and 21 somatic mutations within exons were detected in all tumors after whole-exome sequencing. There were 0, 11, and 46 specific somatic mutations in bilateral breasts, thyroid, and endometrial cancers, respectively.Although PTEN mutation is key to the development of Cowden syndrome, DNA repair dysfunction might be the initial driver of mutations. Fewer mutations were required to induce initial bilateral breast carcinomas, with subsequent thyroid and endometrial carcinomas requiring more mutations for induction. When genetic screening is unavailable, breast cancer patients with clinical manifestations of Cowden syndrome must be carefully assessed for secondary malignancies, such as thyroid and endometrial carcinomas.

Background: Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates. Methods: This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records. Results: Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001). Conclusions PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making.

OBJECTIVETo identify protein markers for the early diagnosis of pancreatic cancer by a comparative proteomic method.

METHODSComparative analysis on the pancreatic peripheral blood protein profiling from 20 pancreatic cancer patients, 10 chronic pancreatitis patients and 20 cancer-free controls from May 2007 to September 2008 was carried out by two-dimensional fluorescence electrophoresis (2D-DIGE). Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The significance difference proteins were confirmed by Western-blot.

RESULTSA differentially expressed proteins: complement 3 (C3) was identified. The gray level of C3 in pancreatic cancer tissue, chronic pancreatitis, and normal control group were 1.63 ± 0.28, 0.65 ± 0.13 (t = 11.81, P = 0.00) and 0.88 ± 0.19 (t = 9.93, P = 0.00), respectively. C3 was high expression in pancreatic cancer group compared with normal control group. The expression of C3 was higher in pancreatic cancer group than in chronic pancreatitis group. The high expression of C3 in pancreatic carcinoma was confirmed by Western blot.

CONCLUSIONS2D-DIGE and MALDI-TOF-MS technology is a quick, easy and practical method to screen for specific biomarkers in serum of patients with pancreatic carcinoma. The identified protein C3 in this study may be as specific serum biomarkers of pancreatic carcinoma.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Case-Control Studies ; Complement C3 ; analysis ; Early Diagnosis ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; blood ; diagnosis ; Pancreatitis, Chronic ; blood ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Two-Dimensional Difference Gel Electrophoresis

PURPOSE: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma. METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro. RESULTS: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells. CONCLUSIONS: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.
Animals ; Asthma* ; Bronchoalveolar Lavage Fluid ; Cell Adhesion Molecules ; Chemokines ; Cholesterol ; Cytokines ; Eosinophils ; Epithelial Cells ; Female ; Gene Expression ; Goblet Cells ; HL-60 Cells ; Humans ; Hyperplasia ; Immunoglobulin E ; Inflammation* ; Injections, Intraperitoneal ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Lovastatin* ; Lung ; Mice ; Mucin 5AC ; Mucus* ; Ovalbumin ; Ovum ; Real-Time Polymerase Chain Reaction