32 research outputs found

    The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma

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    Background The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma. Methods Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed. Results A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS. Conclusions Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type

    Early detection of subclinical ventricular deterioration in aortic stenosis with cardiovascular magnetic resonance and echocardiography

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Severe aortic stenosis (AS) patients with late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) or left ventricular (LV) systolic dysfunction are known to have worse outcome. We aimed to investigate whether LGE on CMR would be useful in early detection of subclinical LV structural and functional derangements in AS patients. Methods: 118 patients with moderate to severe AS were prospectively enrolled. Echocardiography and CMR images were taken and the patients were divided into groups according to the presence/absence of LGE and of LV systolic dysfunction (LV ejection fraction (EF) <50%). The stiffness of LV was calculated based on Doppler and CMR measurements. Results: Patients were grouped into either group 1, no LGE and normal LVEF, group 2, LGE but normal LVEF and group 3, LGE with depressed LVEF. There was a significant trend towards increasing LV volumes, worsening of LV diastolic function (E/e, diastolic elastance), systolic function (end-systolic elastance) and LV hypertrophy between the three groups, which coincided with worsening functional capacity (all p-value < 0.001 for trend). Also, significant differences in the above parameters were noted between group 1 and 2 (E/e, 14.6 ± 4.3 (mean ± standard deviation) in group 1 vs. 18.2 ± 9.4 in group 2; end-systolic elastance, 3.24 ± 2.31 in group 1 vs. 2.38 ± 1.16 in group 2, all p-value < 0.05). The amount of myocardial fibrosis on CMR correlated with parameters of diastolic (diastolic elastance, Spearmans ρ = 0.256, p-value = 0.005) and systolic function (end-systolic elastance, Spearmans ρ = −0.359, p-value < 0.001). Conclusions: These findings demonstrate the usefulness of CMR for early detection of subclinical LV structural and functional deterioration in AS patients.Peer Reviewe

    Correction: Demographic and Clinico-Epidemiological Features of Dengue Fever in Faisalabad, Pakistan.

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    [This corrects the article DOI: 10.1371/journal.pone.0267652.]

    Characterization of a Thermoacidophilic l-Arabinose Isomerase from Alicyclobacillus acidocaldarius: Role of Lys-269 in pH Optimum

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    The araA gene encoding l-arabinose isomerase (AI) from the thermoacidophilic bacterium Alicyclobacillus acidocaldarius was cloned, sequenced, and expressed in Escherichia coli. Analysis of the sequence revealed that the open reading frame of the araA gene consists of 1,491 bp that encodes a protein of 497 amino acid residues with a calculated molecular mass of 56,043 Da. Comparison of the deduced amino acid sequence of A. acidocaldarius AI (AAAI) with other AIs demonstrated that AAAI has 97% and 66% identities (99% and 83% similarities) to Geobacillus stearothermophilus AI (GSAI) and Bacillus halodurans AI (BHAI), respectively. The recombinant AAAI was purified to homogeneity by heat treatment, ion-exchange chromatography, and gel filtration. The purified enzyme showed maximal activity at pH 6.0 to 6.5 and 65°C under the assay conditions used, and it required divalent cations such as Mn(2+), Co(2+), and Mg(2+) for its activity. The isoelectric point (pI) of the enzyme was about 5.0 (calculated pI of 5.5). The apparent K(m) values of the recombinant AAAI for l-arabinose and d-galactose were 48.0 mM (V(max), 35.5 U/mg) and 129 mM (V(max), 7.5 U/mg), respectively, at pH 6 and 65°C. Interestingly, although the biochemical properties of AAAI are quite similar to those of GSAI and BHAI, the three AIs from A. acidocaldarius (pH 6), G. stearothermophilus (pH 7), and B. halodurans (pH 8) exhibited different pH activity profiles. Based on alignment of the amino acid sequences of these homologous AIs, we propose that the Lys-269 residue of AAAI may be responsible for the ability of the enzyme to act at low pH. To verify the role of Lys-269, we prepared the mutants AAAI-K269E and BHAI-E268K by site-directed mutagenesis and compared their kinetic parameters with those of wild-type AIs at various pHs. The pH optima of both AAAI-K269E and BHAI-E268K were rendered by 1.0 units (pH 6 to 7 and 8 to 7, respectively) compared to the wild-type enzymes. In addition, the catalytic efficiency (k(cat)/K(m)) of each mutant at different pHs was significantly affected by an increase or decrease in V(max). From these results, we propose that the position corresponding to the Lys-269 residue of AAAI could play an important role in the determination of the pH optima of homologous AIs

    Proposal of a Provisional Classification of Sebaceous Carcinoma Based on Hormone Receptor Expression and HER2 Status

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    Despite recent progress in comprehensive genetic analysis, little is known about the molecular pathogenesis of sebaceous carcinoma. On the basis of the ontogenic proximity of sebaceous and mammary glands, we designed an intrinsic classification for sebaceous carcinoma adapted from that of breast cancer and evaluated its clinical significance. We investigated 42 cases of sebaceous carcinoma, including 32 ocular and 10 extraocular cases. Immunohistochemical analyses for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, Ki67, and CK5/6 and fluorescence in situ hybridization for the HER2 gene were performed. The immunohistochemistry for ER, PR, and AR showed positivity in 18 (42.9%), 11 (26.2%), and 34 (81.0%) cases, respectively. Expression of the HER2 protein was found in 10 (33.8%) cases, whereas extra copies were found in 3 (7.1%). According to our system, there were 16 (38.1%) cases of the luminal 1 subtype, 4 (9.5%) of the luminal 2 subtype, and 7 (16.7%) of the HER2 subtype, respectively. Fifteen cases (35.7%) belonged to the triple-negative group. In univariable analysis, loss of AR was significantly associated with shorter disease-free survival (P = 0.020), whereas the expression of HER2 was associated with a better outcome with borderline significance (P = 0.060). The luminal 2 subtype showed the best survival, and the all-negative subtype showed the worst (P = 0.001). In multivariable analysis, negativity of PR or AR, low CK5/6, and female sex were independent poor prognostic factors (all P &lt; 0.05). This is the first study to categorize sebaceous carcinoma on the basis of the possible link between its molecular pathogenesis and future therapeutic applications.N

    Cellular Prion Protein Is Closely Associated with Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma

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    The cellular prion protein (PrPC) is known to play a role in cancer proliferation and metastasis. However, the role of PrPC expression in hepatocellular carcinoma (HCC) is unknown. This study investigated whether overexpression of PrPC affects recurrence after surgical resection and survival in HCC. A total of 110 HCC patients who underwent hepatic resection were included. They were followed up for a median of 42 months (range 1–213 months) after hepatectomy. The relationships between PrPC expression and the HCC histologic features, recurrence of HCC following surgical resection, and survival of the patients were examined. Seventy-one cases (64.5%) of HCC demonstrated higher expression of PrPC. The expression of PrPC was only correlated with diabetes mellitus. There was no association between PrPC expression and age, sex, hypertension, hepatitis B virus positivity, alcohol consumption, Child–Pugh class, major portal vein invasion, serum alpha-fetoprotein, and HCC size or number. The 1-year recurrence rates in patients with higher PrPC expression were higher than those with lower PrPC expression. The cumulative survival rates of patients with higher PrPC expression were significantly shorter than those of patients with lower PrPC expression. In conclusion, PrPC expression is closely associated with early recurrence and poor survival of HCC patients following surgical resection

    Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

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    Aberrant expression of CD5 has been reported in 5-10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an extremely unfavorable prognosis with frequent treatment failure. We retrospectively investigated 405 DLBCLs recruited from three university hospitals in Korea from 1997 to 2013. The clinical profile, immunophenotype, and chromosomal structural alterations of the BCL2 and MYC genes were compared according to CD5 expression. A total of 29 cases of de novo CD5+ DLBCL were identified out of 405 in our series (7.4%). Clinicopathologic correlation was performed in all 29 CD5+ DLBCLs and 166 CD5- DLBCLs which were eligible for full clinical review and further pathologic examination. Compared with CD5- counterparts, CD5+ DLBCLs showed female preponderance, frequent bone marrow involvement, higher lactate dehydrogenase level, advanced Ann Arbor stages and poorer prognosis (all p<0.05). Pathologically, the expression of CD5 positively correlated with that of BCL2, MYC and Ki-67 (all p<0.05). Coexpression of BCL2 and MYC, which is referred to as a double-expressor, was relatively more common in CD5+ DLBCL, whereas translocation or amplification of these genes was very rare. in conclusion, the expression of CD5 is an independent poor prognostic factor of DLBCLs, and this subgroup displays unique clinicopathologic features. Although the exact mechanism remains uncertain, consistent activation of BCL2 and MYC by alternative pathways other than chromosomal translocation may contribute to the pathogenesis

    Evaluation of Strain-Rate Sensitivity of Selective Laser Melted H13 Tool Steel Using Nanoindentation Tests

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    This paper demonstrates the successful printing of H13 tool steel by a selective laser melting (SLM) method at a scan laser speed of 200 mm/s for the best microstructure and mechanical behavior. Specifically, the nanoindentation strain-rate sensitivity values were 0.022, 0.019, 0.027, 0.028, and 0.035 for SLM H13 at laser scan speeds of 100, 200, 400, 800, and 1600 mm/s, respectively. This showed that the hardness increases as the strain rate increases and, practically, the hardness values of the SLM H13 at the 200 mm/s laser scan speed are the highest and least sensitive to the strain rate as compared to H13 samples at other scan speeds. The SLM processing of this material at 200 mm/s laser scan speed therefore shows the highest potential for advanced tool design. Residual stress is expected to affect the hardness and shall be investigated in future research
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