bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype
Authors: Wiese David A , Thaiwong Tuddow , Yuzbasiyan-Gurkan Vilma , Kiupel Matti 
Published: September 2013

AbstractBackgroundBreast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC.MethodsTwenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs.ResultsIHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis.ConclusionFMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA in the tumorigenesis of triple negative, basal-like FMAs. The strong similarities in clinical behavior, morphology and IHC phenotype suggest that triple negative, basal-like FMAs may be a suitable spontaneous animal model for studying novel therapeutic approaches against human basal-like TNBC.
Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9
Authors: Makawita Shalini , Dimitromanolakis Apostolos , Soosaipillai Antoninus , Soleas Ireena , Chan Alison , Gallinger Steven , Haun Randy S , Blasutig Ivan M , Diamandis Eleftherios P 
Published: September 2013

Abstract

Background
The identification of new serum biomarkers with high sensitivity and specificity is an important priority in pancreatic cancer research. Through an extensive proteomics analysis of pancreatic cancer cell lines and pancreatic juice, we previously generated a list of candidate pancreatic cancer biomarkers. The present study details further validation of four of our previously identified candidates: regenerating islet-derived 1 beta (REG1B), syncollin (SYCN), anterior gradient homolog 2 protein (AGR2), and lysyl oxidase-like 2 (LOXL2).

Methods
The candidate biomarkers were validated using enzyme-linked immunosorbent assays in two sample sets of serum/plasma comprising a total of 432 samples (Sample Set A: pancreatic ductal adenocarcinoma (PDAC, n = 100), healthy (n = 92); Sample Set B: PDAC (n = 82), benign (n = 41), disease-free (n = 47), other cancers (n = 70)). Biomarker performance in distinguishing PDAC from each control group was assessed individually in the two sample sets. Subsequently, multiparametric modeling was applied to assess the ability of all possible two and three marker panels in distinguishing PDAC from disease-free controls. The models were generated using sample set B, and then validated in Sample Set A.

Results
Individually, all markers were significantly elevated in PDAC compared to healthy controls in at least one sample set (p ≤ 0.01). SYCN, REG1B and AGR2 were also significantly elevated in PDAC compared to benign controls (p ≤ 0.01), and AGR2 was significantly elevated in PDAC compared to other cancers (p < 0.01). CA19.9 was also assessed. Individually, CA19.9 showed the greatest area under the curve (AUC) in receiver operating characteristic (ROC) analysis when compared to the tested candidates; however when analyzed in combination, three panels (CA19.9 + REG1B (AUC of 0.88), CA19.9 + SYCN + REG1B (AUC of 0.87) and CA19.9 + AGR2 + REG1B (AUC of 0.87)) showed an AUC that was significantly greater (p < 0.05) than that of CA19.9 alone (AUC of 0.82). In a comparison of early-stage (Stage I-II) PDAC to disease free controls, the combination of SYCN + REG1B + CA19.9 showed the greatest AUC in both sample sets, (AUC of 0.87 and 0.92 in Sets A and B, respectively).

Conclusions
Additional serum biomarkers, particularly SYCN and REG1B, when combined with CA19.9, show promise as improved diagnostic indicators of pancreatic cancer, which therefore warrants further validation.
Simultaneous identification of 36 mutations in KRAS codons 61and 146, BRAF, NRAS, and PIK3CAin a single reaction by multiplex assay kit
Authors: Bando Hideaki , Yoshino Takayuki , Shinozaki Eiji , Nishina Tomohiro , Yamazaki Kentaro , Yamaguchi Kensei , Yuki Satoshi , Kajiura Shinya , Fujii Satoshi , Yamanaka Takeharu , Tsuchihara Katsuya , Ohtsu Atsushi 
Published: September 2013

Abstract

Background
Retrospective analyses in the West suggest that mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA are negative predictive factors for cetuximab treatment in colorectal cancer patients. We developed a novel multiplex kit detecting 36 mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA using Luminex (xMAP) assay in a single reaction.

Methods
Tumor samples and clinical data from Asian colorectal cancer patients treated with cetuximab were collected. We investigated KRAS, BRAF, NRAS, and PIK3CA mutations using both the multiplex kit and direct sequencing methods, and evaluated the concordance between the 2 methods. Objective response, progression-free survival (PFS), and overall survival (OS) were also evaluated according to mutational status.

Results
In total, 82 of 83 samples (78 surgically resected specimens and 5 biopsy specimens) were analyzed using both methods. All multiplex assays were performed using 50 ng of template DNA. The concordance rate between the methods was 100%. Overall, 49 (59.8%) patients had all wild-type tumors, 21 (25.6%) had tumors harboring KRAS codon 12 or 13 mutations, and 12 (14.6%) had tumors harboring KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA mutations. The response rates in these patient groups were 38.8%, 4.8%, and 0%, respectively. Median PFS in these groups was 6.1 months (95% confidence interval (CI): 3.1–9.2), 2.7 months (1.2–4.2), and 1.6 months (1.5–1.7); median OS was 13.8 months (9.2–18.4), 8.2 months (5.7–10.7), and 6.3 months (1.3–11.3), respectively. Statistically significant differences in both PFS and OS were found between patients with all wild-type tumors and those with KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA mutations (PFS: 95% CI, 0.11–0.44; P < 0.0001; OS: 95% CI, 0.15–0.61; P < 0.0001).

Conclusions
Our newly developed multiplex kit is practical and feasible for investigation of a range of sample types. Moreover, mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment, similar to the result obtained in European studies.
An observational study of response heterogeneity in children with attention deficit hyperactivity disorder following treatment switch to modified-release methylphenidate
Authors: Hautmann Christopher , Rothenberger Aribert , Döpfner Manfred 
Published: September 2013

Abstract

Background
Methylphenidate (MPH) has been shown to be effective in the treatment of attention deficit hyperactivity disorder (ADHD) in children. The overall population of children and adolescents with ADHD may comprise distinct clusters of patients that differ in response to MPH. The aim of this analysis was to look for subgroups with different treatment trajectories and to identify their distinctive features.

Methods
OBSEER was a prospective, observational study examining the effectiveness and safety of once-daily modified-release MPH over 3 months in patients (aged 6–17 years) with ADHD under routine care. Assessments were carried out at baseline (Visit 1), after 1–3 weeks (Visit 2) and 6–12 weeks (Visit 3) after first use of once-daily modified-release MPH. Change in ADHD symptoms, as rated by parents and teachers, was examined post hoc in patients of the intent-to-treat-population (N = 822), using growth-mixture modelling to detect response trajectory groups after switching medication. Age, MPH dose at Visit 1 before medication switch, prescribed once-daily modified-release MPH dose at Visits 1 and 2, conduct problems and emotional symptoms were considered predictors of response subgroups.

Results
Assessing formal statistical criteria and usefulness of the models, a 4-class solution best fitted the data: after switching medication two response groups with severe symptoms at study start and subsequent substantial treatment effects, and two showing no or comparatively little treatment effect, one of which had severe and the other less severe symptoms at study start. Patient age, conduct problems and MPH dose at Visit 1 were predictors of inclusion in subgroups.

Conclusions
Older children and children with few conduct problems were more likely to be members of a patient cluster with fewer symptoms at study start. Children with a low MPH dose before medication switch had a higher chance of being in the patient cluster with a strong treatment response after switching medication. The current analyses should assist in identifying children likely to achieve a favourable treatment course with MPH and, additionally, those who are in need of alternative treatment options.
Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel
Authors: Li Xiaoxiao , Qiu Wensheng , Liu Bin , Yao Ruyong , Liu Shihai , Yao Yasai , Liang Jun 
Published: September 2013

AbstractBackgroundForkhead box transcription factor 1 (FOXM1) has been reported to overexpress and correlate with pathogenesis in a variety of human malignancies. However, little research has been done to investigate its clinical significance in gastric cancer.MethodsWe examined the expression of FOXM1 in 103 postoperational gastric cancer tissues and 5 gastric cell lines by immunohistochemistry and western blot analysis respectively. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed. Moreover, the association of FOXM1 expression and chemosensitivity to docetaxel in gastric cancer cells was further explored.ResultsOur study demonstrated that the level of FOXM1 expression was significantly higher in gastric cancer than in para-cancer tissues (P < 0.001) and normal gastric cell lines (P = 0.026). No significant association was found between FOXM1 expression and any clinical pathological features (P > 0.1). FOXM1 amplification was identified as an independent prognostic factor in gastric cancer (P = 0.001), and its affection is more significant in patients with tumor size larger than 5 cm (P = 0.004), pT3-4 (P = 0.003) or pIII-IV (P = 0.001). Additionally, shown to mediate docetaxel resistance in gastric cancers by our research, FOXM1 was revealed to alter microtubule dynamics in response to the treatment of docetaxel, and the drug resistance could be reversed with FOXM1 inhibitor thiostrepton treatment.ConclusionsFOXM1 can be a useful marker for predicting patients’ prognosis and monitoring docetaxel response, and might be a new therapeutic target in docetaxel resistant gastric cancer.
Femtosecond laser modification of an array of vertically aligned carbon nanotubes intercalated with Fe phase nanoparticles
Authors: Labunov Vladimir , Prudnikava Alena , Bushuk Serguei , Filatov Serguei , Shulitski Boris , Tay Beng Kang , Shaman Yury , Basaev Alexander 
Published: September 2013

Abstract
Femtosecond lasers (FSL) are playing an increasingly important role in materials research, characterization, and modification. Due to an extremely short pulse width, interactions of FSL irradiation with solid surfaces attract special interest, and a number of unusual phenomena resulted in the formation of new materials are expected. Here, we report on a new nanostructure observed after the interaction of FSL irradiation with arrays of vertically aligned carbon nanotubes (CNTs) intercalated with iron phase catalyst nanoparticles. It was revealed that the FSL laser ablation transforms the topmost layer of CNT array into iron phase nanospheres (40 to 680 nm in diameter) located at the tip of the CNT bundles of conical shape. Besides, the smaller nanospheres (10 to 30 nm in diameter) are found to be beaded at the sides of these bundles. Some of the larger nanospheres are encapsulated into carbon shells, which sometime are found to contain CNTs. The mechanism of creation of such nanostructures is proposed.
Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial
Authors: Han Gajin , Park Jae-Woo , Ko Seok-Jae , Son Jihee , Seon Jongki , Kim Juyeon , Kim Seulki , Yeo Inkwon , Ryu Bongha , Kim Jinsung 
Published: September 2013

Abstract

Background
Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’.

Methods/Design
This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks.

Discussion
It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial.

Trial registration
ClinicalTrials.gov Identifier:NCT01579877
FGF10 Signaling differences between type I pleuropulmonary blastoma and congenital cystic adenomatoid malformation
Authors: Lezmi Guillaume , Verkarre Virginie , Khen-Dunlop Naziha , Vibhushan Shamila , Hadchouel Alice , Rambaud Caroline , Copin Marie-Christine , Rittie Jean-Luc , Benachi Alexandra , Fournet Jean-Christophe , Delacourt Christophe 
Published: September 2013

Abstract

Background
Type I pleuropulmonary blastoma (PPB) and congenital cystic adenomatoid malformation of the lung (CCAM) are cystic lung diseases of childhood. Their clinical and radiological presentations are often similar, and pathologic discrimination remains difficult in many cases. As a consequence, type I PPB and CCAM are frequently confused, leading to delayed adequate management for type I PPB. Recent studies have suggested a role for fibroblast growth factor (FGF) 10 signal pathway in CCAM pathogenesis. The objective of our study was to determine whether FGF10 signaling differs between CCAM and type I PPB.

Methods
Immunohistochemical studies were performed for expression of FGF10, its receptor FGFR2b, and its inhibitor sonic hedgehog (SHH) in focal type I PPB (n=6), CCAM type I (n=7), CCAM type II (n=7), and control lungs (n=5).

Results
FGF10, FGFR2b, and SHH expressions differed markedly between type I PPB and both types of CCAM. Type I and type II CCAM cystic walls expressed FGF10, FGFR2b, and SHH, whereas staining was absent or poor in type I PBB cystic walls. Expression of FGF10, FGFR2b, and SHH did not differ between CCAM cystic walls and control airway walls.

Conclusions
These findings show that immunohistochemistry with FGF10, FGFR2b, or SHH could be useful in differentiating CCAM from type I PPB, when a child presents with a focal cystic lung lesion. The absence of strong expression of FGF10, FGFR2b, and/or SHH makes the diagnosis of CCAM very doubtful.
Glanders: an overview of infection in humans
Authors: Van Zandt Kristopher E , Greer Marek T , Gelhaus H Carl 
Published: September 2013

Abstract
Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection.
Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia
Authors: Ronchetti Domenica , Mosca Laura , Cutrona Giovanna , Tuana Giacomo , Gentile Massimo , Fabris Sonia , Agnelli Luca , Ciceri Gabriella , Matis Serena , Massucco Carlotta , Colombo Monica , Reverberi Daniele , Recchia Anna Grazia , Bossio Sabrina , Negrini Massimo , Tassone Pierfrancesco , Morabito Fortunato , Ferrarini Manlio , Neri Antonino 
Published: September 2013

Abstract

Background
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets.

Methods
The patterns of sno/scaRNA expression in highly purified CD19+ B-cells of 211 CLL patients and in 18 normal B-cell samples - 6 from peripheral blood, and 12 from tonsils (4 germinal center, 2 marginal zone, 3 switched memory and 3 naïve B-cells) - were analyzed on the Affymetrix GeneChip® Human Gene 1.0 ST array.

Results
CLLs display a sno/scaRNAs expression profile similar to normal memory, naïve and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups.

Conclusions
These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.
Erythropoietin is a JAK2 and ERK1/2 effector that can promote renal tumor cell proliferation under hypoxic conditions
Authors: Miyake Makito , Goodison Steve , Lawton Adrienne , Zhang Ge , Gomes-Giacoia Evan , Rosser Charles J 
Published: September 2013

Abstract

Background
Erythropoietin (EPO) provides an alternative to transfusion for increasing red blood cell mass and treating anemia in cancer patients. However, recent studies have reported increased adverse events and/or reduced survival in patients receiving both EPO and chemotherapy, potentially related to EPO-induced cancer progression. Additional preclinical studies that elucidate the possible mechanism underlying EPO cellular growth stimulation are needed.

Methods
Using commercial tissue microarray (TMA) of a variety of cancers and benign tissues, EPO and EPO receptor immunohistochemical staining was performed. Furthermore using a panel of human renal cells (Caki-1, 786-O, 769-P, RPTEC), in vitro and in vivo experiments were performed with the addition of EPO in normoxic and hypoxic states to note phenotypic and genotypic changes.

Results
EPO expression score was significantly elevated in lung cancer and lymphoma (compared to benign tissues), while EPOR expression score was significantly elevated in lymphoma, thyroid, uterine, lung and prostate cancers (compared to benign tissues). EPO and EPOR expression scores in RCC and benign renal tissue were not significantly different. Experimentally, we show that exposure of human renal cells to recombinant EPO (rhEPO) induces cellular proliferation, which we report for the first time, is further enhanced in a hypoxic state. Mechanistic investigations revealed that EPO stimulates the expression of cyclin D1 while inhibiting the expression of p21cip1 and p27kip1 through the phosphorylation of JAK2 and ERK1/2, leading to a more rapid progression through the cell cycle. We also demonstrate an increase in the growth of renal cell carcinoma xenograft tumors when systemic rhEPO is administered.

Conclusions
In summary, we elucidated a previously unidentified mechanism by which EPO administration regulates progression through the cell cycle, and show that EPO effects are significantly enhanced under hypoxic conditions.