bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study
Authors: Lee Seok Ki , Kwon Min Su , Lee Yoon Se , Choi Seung-Ho , Kim Sang Yoon , Cho Kyoung Ja , Nam Soon Yuhl 
Published: December 2012

Abstract

Background
Adenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated.

Methods
The medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed.

Results
Positive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate.

Conclusions
The expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.
u-PA inhibitor amiloride suppresses peritoneal metastasis in gastric cancer
Authors: Ding Youcheng , Zhang Hui , Zhou Zhuqing , Zhong Mingan , Chen Qiliang , Wang Xujing , Zhu Zhenggang 
Published: December 2012

Abstract

Background
Peritoneal metastasis in gastric cancer represents a ubiquitous human health problem but effective therapies with limited side effects are still lacking. Although previous research suggested that u-PA was involved in some tumor metastasis such as lung-specific metastasis, the role of u-PA for peritoneal metastasis in gastric cancer is still unclear. The aim of this study was to explore whether selective pharmacological blockade of u-PA is able to affect the peritoneal metastasis of gastric cancer both in vivo and in vitro.

Methods
In the present study, we evaluated the effects and explored the anti-tumor mechanisms of amiloride, a selective u-PA inhibitor, on a panel of gastric cancer cell lines and in a murine model of human gastric cancer MKN45.

Results
The study showed that amiloride significantly inhibited the tumor growth and prolonged the survival of the tumor-bearing mice. In vitro, compared with controls, amiloride could not only significantly down-regulate the mRNA expression and protein level of u-PA from MKN45 cells with dose dependence but also inhibit the adhesion of HMrSV5 cells, migration and invasion of MKN45 cells.

Conclusions
The findings in our current report provide evidence that selective u-PA inhibitor amiloride has potent effects against peritoneal metastasis in gastric cancer, suggesting its possible therapeutic value for the treatment of gastric cancer.
Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma
Authors: Bonanno Giuseppina , Mariotti Andrea , Procoli Annabella , Folgiero Valentina , Natale Daniela , De Rosa Luca , Majolino Ignazio , Novarese Linda , Rocci Alberto , Gambella Manuela , Ciciarello Marilena , Scambia Giovanni , Palumbo Antonio , Locatelli Franco , De Cristofaro Raimondo , Rutella Sergio 
Published: December 2012

Abstract

Background
Multiple myeloma (MM) is a plasma cell malignancy with a multifaceted immune dysfunction. Indoleamine 2,3-dioxygenase 1 (IDO1) degrades tryptophan into kynurenine (KYN), which inhibits effector T cells and promote regulatory T-cell (Treg) differentiation. It is presently unknown whether MM cells express IDO1 and whether IDO1 activity correlates with immune system impairment.

Methods
We investigated IDO1 expression in 25 consecutive patients with symptomatic MM and in 7 patients with either monoclonal gammopathy of unknown significance (MGUS; n=3) or smoldering MM (SMM; n=4). IDO1-driven tryptophan breakdown was correlated with the release of hepatocyte growth factor (HGF) and with the frequency of Treg cells and NY-ESO-1-specific CD8+ T cells.

Results
KYN was increased in 75% of patients with symptomatic MM and correlated with the expansion of CD4+CD25+FoxP3+ Treg cells and the contraction of NY-ESO-1-specific CD8+ T cells. In vitro, primary MM cells promoted the differentiation of allogeneic CD4+ T cells into bona fide CD4+CD25hiFoxP3hi Treg cells and suppressed IFN-γ/IL-2 secretion, while preserving IL-4 and IL-10 production. Both Treg expansion and inhibition of Th1 differentiation by MM cells were reverted, at least in part, by d,l-1-methyl-tryptophan, a chemical inhibitor of IDO. Notably, HGF levels were higher within the BM microenvironment of patients with IDO+ myeloma disease compared with patients having IDO- MM. Mechanistically, the antagonism of MET receptor for HGF with SU11274, a MET inhibitor, prevented HGF-induced AKT phosphorylation in MM cells and translated into reduced IDO protein levels and functional activity.

Conclusions
These data suggest that IDO1 expression may contribute to immune suppression in patients with MM and possibly other HGF-producing cancers.
An effective oxidation approach for luminescence enhancement in CdS quantum dots by H2O2
Authors: Lee Woojin , Kim Hoechang , Jung Dae-Ryong , Kim Jongmin , Nahm Changwoo , Lee Junhee , Kang Suji , Lee Byungho , Park Byungwoo 
Published: December 2012

Abstract
The effects of surface passivation on the photoluminescence (PL) properties of CdS nanoparticles oxidized by straightforward H2O2 injection were examined. Compared to pristine cadmium sulfide nanocrystals (quantum efficiency ≅ 0.1%), the surface-passivated CdS nanoparticles showed significantly enhanced luminescence properties (quantum efficiency ≅ 20%). The surface passivation by H2O2 injection was characterized using X-ray photoelectron spectroscopy, X-ray diffraction, and time-resolved PL. The photoluminescence enhancement is due to the two-order increase in the radiative recombination rate by the sulfate passivation layer.
Convergence theorems for mixed type asymptotically nonexpansive mappings
Authors: Guo Weiping , Cho Yeol Je , Guo Wei 
Published: December 2012

Abstract
In this paper, we introduce a new two-step iterative scheme of mixed type for two asymptotically nonexpansive self-mappings and two asymptotically nonexpansive nonself-mappings and prove strong and weak convergence theorems for the new two-step iterative scheme in uniformly convex Banach spaces.
SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+T-lymphocytes cannot be upregulated by interferons
Authors: St Gelais Corine , de Silva Suresh , Amie Sarah M , Coleman Christopher M , Hoy Heather , Hollenbaugh Joseph A , Kim Baek , Wu Li 
Published: December 2012

Abstract

Background
SAMHD1 is an HIV-1 restriction factor in non-dividing monocytes, dendritic cells (DCs), macrophages, and resting CD4+ T-cells. Acting as a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, SAMHD1 hydrolyzes dNTPs and restricts HIV-1 infection in macrophages and resting CD4+ T-cells by decreasing the intracellular dNTP pool. However, the intracellular dNTP pool in DCs and its regulation by SAMHD1 remain unclear. SAMHD1 has been reported as a type I interferon (IFN)-inducible protein, but whether type I IFNs upregulate SAMHD1 expression in primary DCs and CD4+ T-lymphocytes is unknown.

Results
Here, we report that SAMHD1 significantly blocked single-cycle and replication-competent HIV-1 infection of DCs by decreasing the intracellular dNTP pool and thereby limiting the accumulation of HIV-1 late reverse transcription products. Type I IFN treatment did not upregulate endogenous SAMHD1 expression in primary DCs or CD4+ T-lymphocytes, but did in HEK 293T and HeLa cell lines. When SAMHD1 was over-expressed in these two cell lines to achieve higher levels than that in DCs, no HIV-1 restriction was observed despite partially reducing the intracellular dNTP pool.

Conclusions
Our results suggest that SAMHD1-mediated reduction of the intracellular dNTP pool in DCs is a common mechanism of HIV-1 restriction in myeloid cells. Endogenous expression of SAMHD1 in primary DCs or CD4+ T-lymphocytes is not upregulated by type I IFNs.
Fulminant hepatic failure in association with quetiapine: a case report
Authors: Al Mutairi Fawaz , Dwivedi Girish , Al Ameel Turki 
Published: December 2012

Abstract

Introduction
Fulminant hepatic failure is a serious disease with significant mortality and morbidity. Identifying the exact cause of hepatic failure and predicting prognosis is of paramount importance in managing such patients. Drug-induced liver injury is a common but challenging entity to treat. The use of newer drugs and medications with previously unknown hepatotoxicity add to the challenges faced by treating physicians. Quetiapine is an antipsychotic that has rarely been linked to acute liver injury. In the present work we describe a case of fulminant hepatic failure secondary to use of quetiapine.

Case presentation
A 59-year-old Caucasian woman with known Parkinson’s disease was being treated with quetiapine for hallucinations. She was referred to our hospital with yellow discoloration of the sclera and later on developed clinical features suggestive of hepatic encephalopathy. A diagnosis of fulminant hepatic failure was made following her admission to the intensive care unit. Her condition improved after discontinuing the drug and providing the standard supportive treatment.

Conclusions
Our findings in the present report emphasize the importance of keeping an open mind in cases of fulminant hepatic failure. As drug-induced hepatotoxicity is the most common cause of fulminant hepatic failure in many parts of the world, consideration should be given to the medication(s) patients receive as the potential cause and a review of this list should be part of the clinical care given.
New species of Ehrlichia isolated from Rhipicephalus (Boophilus) microplus shows an ortholog of the E. canis major immunogenic glycoprotein gp36 with a new sequence of tandem repeats
Authors: Cruz Alejandro Cabezas , Zweygarth Erich , Ribeiro Mucio Flavio Barbosa , da Silveira Julia Angelica Gonçalves , de la Fuente Jose , Grubhoffer Libor , Valdés James J , Passos Lygia Maria Friche 
Published: December 2012

Abstract

Background

Ehrlichia species are the etiological agents of emerging and life-threatening tick-borne human zoonoses that inflict serious and fatal infections in companion animals and livestock. The aim of this paper was to phylogeneticaly characterise a new species of Ehrlichia isolated from Rhipicephalus (Boophilus) microplus from Minas Gerais, Brazil.

Methods
The agent was isolated from the hemolymph of Rhipicephalus (B.) microplus engorged females that had been collected from naturally infested cattle in a farm in the state of Minas Gerais, Brazil. This agent was then established and cultured in IDE8 tick cells. The molecular and phylogenetic analysis was based on 16S rRNA, groEL, dsb, gltA and gp36 genes. We used the maximum likelihood method to construct the phylogenetic trees.

Results
The phylogenetic trees based on 16S rRNA, groEL, dsb and gltA showed that the Ehrlichia spp isolated in this study falls in a clade separated from any previously reported Ehrlichia spp. The molecular analysis of the ortholog of gp36, the major immunoreactive glycoproteins in E. canis and ortholog of the E. chaffeensis gp47, showed a unique tandem repeat of 9 amino acids (VPAASGDAQ) when compared with those reported for E. canis, E. chaffeensis and the related mucin-like protein in E. ruminantium.

Conclusions
Based on the molecular and phylogenetic analysis of the 16S rRNA, groEL, dsb and gltA genes we concluded that this tick-derived microorganism isolated in Brazil is a new species, named E. mineirensis (UFMG-EV), with predicted novel antigenic properties in the gp36 ortholog glycoprotein. Further studies on this new Ehrlichia spp should address questions about its transmissibility by ticks and its pathogenicity for mammalian hosts.
Familial gastric cancer: detection of a hereditary cause helps to understand its etiology
Authors: Vogelaar Ingrid P , van der Post Rachel S , Bisseling Tanya M , van Krieken J Han JM , Ligtenberg Marjolijn JL , Hoogerbrugge Nicoline 
Published: December 2012

Abstract
Worldwide, gastric cancer is one of the most common forms of cancer, with a high morbidity and mortality. Several environmental factors predispose to the development of gastric cancer, such as Helicobacter pylori infection, diet and smoking. Familial clustering of gastric cancer is seen in 10% of cases, and approximately 3% of gastric cancer cases arise in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at relatively young age. Germline mutations in the CDH1 gene are the major cause of HDGC and are identified in approximately 25-50% of families which fulfill strict criteria. Prophylactic gastrectomy is the only option to prevent gastric cancer in individuals with a CDH1 mutation. However, in the majority of families with multiple cases of gastric cancer no germline genetic abnormality can be identified and therefore preventive measures are not available, except for general lifestyle advice. Future research should focus on identifying new genetic predisposing factors for all types of familial gastric cancer.
Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents
Authors: Azerang Parisa , Rezayan Ali Hossein , Sardari Soroush , Kobarfard Farzad , Bayat Mitra , Tabib Kimia 
Published: December 2012

Abstract

Background
The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest.

Methods
This study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides.

Results
All the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity.

Conclusions
Inhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.
Multiple essential roles for primary cilia in heart development
Authors: Willaredt Marc August , Gorgas Karin , Gardner Humphrey A R , Tucker Kerry L 
Published: December 2012

Abstract

Background
The primary cilium is a microtubule-based, plasma membrane-ensheathed protrusion projecting from the basal bodies of almost all cell types in the mammalian body. In the past several years a plethora of papers has indicated a crucial role for primary cilia in the development of a wide variety of organs. We have investigated heart development in cobblestone, a hypomorphic allele of the gene encoding the intraflagellar transport protein Ift88, and uncovered a number of the most common congenital heart defects seen in newborn humans.

Methods
We generated serial sections of mutant cobblestone and wild type embryos in the region encompassing the heart and the cardiac outflow tract. The sections were further processed to generate three-dimensional reconstructions of these structures, and immunofluorescence confocal microscopy, transmission electron microscopy, and in situ hybridization were used to examine signal transduction pathways in the relevant areas. Whole mount in situ hybridization was also employed for certain developmental markers.

Results
In addition to an enlarged pericardium and failure of both ventricular and atrial septum formation, the cobblestone mutants displayed manifold defects in outflow tract formation, including persistent truncus arteriosus, an overriding aorta, and abnormal transformation of the aortic arches. To discern the basis of these anomalies we examined both the maintenance of primary cilia as well as endogenous and migratory embryonic cell populations that contribute to the outflow tract and atrioventricular septa. The colonization of the embryonic heart by cardiac neural crest occurred normally in the cobblestone mutant, as did the expression of Sonic hedgehog. However, with the loss of primary cilia in the mutant hearts, there was a loss of both downstream Sonic hedgehog signaling and of Islet 1 expression in the second heart field, a derivative of the pharyngeal mesoderm. In addition, defects were recorded in development of atrial laterality and ventricular myocardiogenesis. Finally, we observed a reduction in expression of Bmp4 in the outflow tract, and complete loss of expression of both Bmp2 and Bmp4 in the atrioventricular endocardial cushions. Loss of BMP2/4 signaling may result in the observed proliferative defect in the endocardial cushions, which give rise to both the atrioventricular septa as well as to the septation of the outflow tract.

Conclusions
Taken together, our results potentially identify a novel link between Sonic hedgehog signaling at the primary cilium and BMP-dependent effects upon cardiogenesis. Our data further point to a potential linkage of atrioventricular septal defects, the most common congenital heart defects, to genes of the transport machinery or basal body of the cilia.
Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data
Authors: Parker Matthew , Chen Xiang , Bahrami Armita , Dalton James , Rusch Michael , Wu Gang , Easton John , Cheung Nai-Kong , Dyer Michael , Mardis Elaine R , Wilson Richard K , Mullighan Charles , Gilbertson Richard , Baker Suzanne J , Zambetti Gerard , Ellison David W , Downing James R , Zhang Jinghui ,   Pediatric Cancer Genome Project
Published: December 2012

Abstract
Background
Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers.

Results
To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations.

Conclusions
Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.
Impact of Age on Outcomes After Initial Therapy With Chemotherapy and Different Chemoimmunotherapy Regimens in Patients With Chronic Lymphocytic Leukemia: Results of Sequential Cancer and Leukemia Group B Studies
Authors: Woyach Jennifer A. , Ruppert Amy S. , Rai Kanti , Lin Thomas S. , Geyer Susan , Kolitz Jonathan , Appelbaum Frederick R. , Tallman Martin S. , Belch Andrew R. , Morrison Vicki A. , Larson Richard A. , Byrd John C. 
Published: December 2012

Purpose Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age. Patients and Methods We examined patients enrolled onto successive first-line CALGB CLL trials to determine whether efficacy of regimens varied by age, focusing on ideal chemotherapy choice and benefit of immunotherapy addition to chemotherapy in older patients. Regimens included chlorambucil, fludarabine, fludarabine plus rituximab (FR), fludarabine with consolidation alemtuzumab, and FR with consolidation alemtuzumab. Results A total of 663 patients were evaluated for response, progression-free survival (PFS), and overall survival (OS) by age group. Interaction effects of fludarabine versus chlorambucil by age group (PFS, P = .046; OS, P = .006) showed that among patients younger than 70 years, PFS and OS was improved with fludarabine over chlorambucil (PFS: hazard ratio [HR] = 0.6, 95% CI, 0.5 to 0.8; OS: HR = 0.7, 95% CI, 0.5 to 0.9), but not in older adults (PFS, HR = 1.0, 95% CI, 0.6 to 1.7; OS: HR = 1.5, 95% CI, 0.9 to 2.3). In contrast, FR improved outcomes relative to fludarabine, irrespective of age (PFS: HR = 0.6, 95% CI, 0.4 to 0.7; OS: HR = 0.7, 95% CI, 0.5 to 0.9). Alemtuzumab consolidation did not provide benefit over similar regimens without alemtuzumab (P > .20), irrespective of age. Conclusion These data support the use of chlorambucil as an acceptable treatment for many older patients with CLL and suggest rituximab is beneficial regardless of age. These findings bear relevance to both routine care of CLL patients 70 years and older and also future clinical trials in this population.