bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term follow-up of pediatric MS patients starting treatment with injectable first-line agents: A multicentre, Italian, retrospective, observational study
Authors: Baroncini Damiano , Zaffaroni Mauro , Moiola Lucia , Lorefice Lorena , Fenu Giuseppe , Iaffaldano Pietro , Simone Marta , Fanelli Fulvia , Patti Francesco , D’Amico Emanuele , Capobianco Marco , Bertolotto Antonio , Gallo Paolo , Margoni Monica , Miante Silvia , Milani Nicoletta , Amato Maria Pia , Righini Isabella , Bellantonio Paolo , Scandellari Cinzia , Costantino Gianfranco , Scarpini Elio , Bergamaschi Roberto , Mallucci Giulia , Comi Giancarlo , Ghezzi Angelo 
Published: January 2018

Background: Few data are available on very long-term follow-up of pediatric multiple sclerosis (MS) patients treated with disease modifying treatments (DMTs). Objectives: To present a long-term follow-up of a cohort of Pediatric-MS patients starting injectable first-line agents. Methods: Data regarding treatments, annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and serious adverse event were collected. Baseline characteristics were tested in multivariate analysis to identify predictors of disease evolution. Results: In total, 97 patients were followed for 12.5 ± 3.3 years. They started therapy at 13.9 ± 2.1 years, 88 with interferons and 9 with copaxone. During the whole follow-up, 82 patients changed therapy, switching to immunosuppressors/second-line treatment in 58% of cases. Compared to pre-treatment phase, the ARR was significantly reduced during the first treatment (from 3.2 ± 2.6 to 0.7 ± 1.5, p < 0.001), and it remained low during the whole follow-up (0.3 ± 0.2, p < 0.001). At last observation, 40% had disability worsening, but EDSS score remained <4 in 89%. One patient died at age of 23 years due to MS. One case of natalizumab-related progressive multifocal encephalopathy (PML) was recorded. Starting therapy before 12 years of age resulted in a better course of disease in multivariate analysis. Conclusion: Pediatric-MS patients benefited from interferons/copaxone, but the majority had to switch to more powerful drugs. Starting therapy before 12 years of age could lead to a more favorable outcome.
Cross-linguistic influence in the child third language acquisition of grammar: Sentence comprehension and production among Turkish-German and German learners of English
Authors: Hopp Holger 
Published: January 2018

Aims and Objectives/Purpose/Research Questions: This paper investigates the extent to which current formal models of third language (L3) grammatical acquisition extend to sequential child L3 acquisition. We examine whether heritage speakers learning a foreign language as an early L3 transfer grammatical properties from the heritage language or the dominant second language (L2). Design/Methodology/Approach: We used a sentence repetition task and a picture story retelling task. The tasks focussed on grammatical phenomena that were either different between English and German, that is, verb-second and adverb order, or between English and German, on the one hand, and Turkish, on the other, that is, verb-complement order as well as subject and article realization. Data and Analysis: We tested matched groups of 31 Turkish-German and 31 monolingual German children learning English in grades 3 and 4, and we compared sentence repetitions as well as oral sentence production across different grammatical phenomena using parametric statistics. Findings/Conclusions: In both tasks, the two groups perform indistinguishably from each other, and both groups show selective transfer of grammatical properties from German. These findings suggest L2 transfer from a typologically related language in sequential child L3 acquisition. Originality: This paper breaks new ground by testing the applicability of formal models of adult L3 acquisition of grammar to sequential child L3 learners. It uses aural comprehension and oral production tasks with carefully matched groups of L2 and L3 learners of English to isolate the source of grammatical transfer in L3 acquisition. Significance/Implications: The research advances our understanding of cross-linguistic influence and unravels the dynamics of grammatical transfer in early child multilingualism. It adjudicates between current models of transfer in L3 acquisition in a multiple-methods design, it shows that these models apply to early L3 acquisition of heritage speakers, and it highlights that these models need to be expanded to include factors such as dominance and proficiency in prior languages.
Could be serum uric acid a risk factor for thrombosis and/or uveitis in Behcet’s disease?
Authors: Atıl Avcı , Deniz Avcı 
Published: January 2018

Introduction Serum uric acid level increases in many inflammatory conditions. Uric acid triggers the vascular inflammation and artery damage, which causes to an increased risk of endothelial dysfunction and atherosclerosis. It is not clear in the literature whether uric acid contributes to uveitis by similar mechanisms. We investigated whether uric acid level increases in Behcet’s disease patients with thrombosis or anterior uveitis. Patients and methods We reviewed the medical records of 914 Behcet’s disease. After screening for exclusion criteria, there were 50 Behcet’s disease patients with thrombotic complication and as the control group 202 BD patients without any vascular complication were included to the study. In the Anterior uveitis group, there were 53 Behcet’s disease patients. The Control group consisted of 39 Behçet’s disease patients without eye findings. Results Mean uric acid value was 4.96 ± 1.06 mg/dl in Behcet’s disease patients with thrombosis whereas 4.08 ± 0.94 mg/dl in controls, indicating a significant difference ( p < 0.001). There was no significant difference between the mean ages of the patients in both groups. The mean age of the BD group without eye findings was 39.31 ± 10.47 years and that of the Behcet’s disease with Anterior Uveitis group was 37.72 ± 9.65 years ( p = 0.453). The mean serum UA in the BD group without eye findings was 4.21 ± 1.21 mg/dl, while in the BD with Anterior Uveitis group it was 4.57 ± 1.37 mg/dl ( p = 0.201). Conclusion The extent of increase in uric acid level was greater in Behcet’s disease patients that have a thrombotic complication compared to those without thrombotic complication. Uric acid seems to play a role in the pathogenesis of thrombosis. It is concluded that the elevation of serum uric acid level in patients with anterior uveitis with Behcet’s disease is not statistically significant.
Influence of 5-Fluorouracil and Folinic Acid on Interleukin-18 Production in Colorectal Cancer Patients
Authors: Merendino R.A. , Ruello A. , Cascinu S. , Ferlazzo B. , Bene A. , Bonanno D. , Quattrocchi P. , Caristi N. , Gangemi S. 
Published: January 2018

Aims and Background This study was carried out to evaluate the IL-18 blood concentrations of operated colorectal cancer patients and their possible variation in response to combination chemotherapy with 5-fluorouracil (5-FU) and folinic acid. Methods IL-18 levels were assayed in sera of 18 healthy donors and 18 surgical colorectal cancer patients before and after adjuvant chemotherapy with 5-fluorouracil and folinic acid. An ELISA kit for human IL-18 was used for the assay. Results Colorectal cancer patients showed significantly higher baseline levels of IL-18 than healthy donors (p<0.005). Furthermore, serum IL-18 levels increased significantly with respect to baseline in patients receiving adjuvant chemotherapy (p<0.005). Conclusions This study suggests that treatment with 5-fluorouracil and folinic acid may provoke an increase in IL-18 serum levels in colorectal cancer patients. This increase may help to explain the efficacy of adjuvant chemotherapy with 5-FU in colorectal cancer.
Elevated 80K-H Protein in Breast Cancer: A Role for FGF-1 Stimulation of 80K-H
Authors: Forough R. , Lindner L. , Partridge C. , Jones B. , Guy G. , Clark G. 
Published: January 2018

An increase in fibroblast growth factor-1 (FGF-1) is established as part of the cause of several important cancers including breast cancer, but the mechanisms by which it induces malignant behavior are not known. We now report that the protein 80K-H, a substrate for PKC, appears to be part of this mechanism and that it is increased in breast cancer and localizes to the nucleus as part of the mechanism. Our conclusion is based on an examination of a total of 58 biopsy specimens from human breast cancer patients for the presence of relationships between the 80K-H protein and the following: fibroblast growth factor receptor-1 (FGFR-1), tumor grade, microvessel counts (MVC), estrogen receptor (ER) and progesterone receptor (PgR) status. Based on histological grading and immunohistochemical (IHC) assays, we found strong direct relationships between 80K-H and FGFR-1 (r=0.49, p=0.003) and tumor grade (r=0.42, p=0.006). A trend for a direct relationship was observed with PgR (r=0.27, p=0.087). Notably, 80K-H immunostaining was largely limited to the epithelial cells of the mammary ducts. Subsequently, we studied the effects of FGF-1 on 80K-H in cultured human mammary carcinoma epithelial cells in order to establish a more direct relationship between these two molecules. We observed that FGF-1 treatment of MCF-7 cells stimulated translocation of 80K-H protein to the cell nucleus, as demonstrated by subcellular fractionation studies. Maximal intranuclear 80K-H was observed approximately 30 minutes following FGF-1 treatment. In addition, FGF-1 treatment of MCF-7 cells increased growth and invasion of MCF-7 cells, as demonstrated by cell proliferation and a modified Boyden chamber assay, respectively. Further support for 80K-H nuclearization was provided by the immunostaining of human breast cancer specimens and computer-assisted identification of a putative nuclear localization signal (NLS) near the amino terminus of 80K-H protein structure. These data support the existence of a previously unrecognized FGF-1/80K-H nuclear pathway in progression of human breast cancer and suggest that 80K-H may be useful for the assessment of breast tumor progression.
TP53 Codon 72 Polymorphism does not Affect Risk of Cervical Cancer in Patients from the Gambia
Authors: Tanara G. , Falugi C. , Cesario A. , Margaritora S. , Russo P. , Cosimi A. 
Published: January 2018

Aims A case-control study was performed to investigate the relationship between cervical cancer and TP53 polymorphism at codon 72 in young black African women from The Gambia. Materials and Methods The TP53 polymorphism at codon 72 was examined by PCR amplification and SSCP analysis in 40 patients with primary cervical cancer and in 20 healthy women of the same age and from the same geographical area. The occurrence of TP53 polymorphism in combination with the HPV-16 E6 genotype (assayed by PCR) was evaluated. Results The distribution of TP53 genotypes in cervical cancer patients and in the control group was not statistically different (p=0.45) and homozygosity for argine at residue 72 was not associated with cervical cancer (odds ratio: 1.24; 95% confidence interval 0.21-9.16). Similarly, a different genotype distribution, cervical cancer and presence of HPV-16 E6 were not observed. Conclusions These results cannot rule out an association between TP53 polymorphism at codon 72, HPV infection and the etiology of cervical cancer in this population sample.
Levels of Tissue Inhibitor of Metalloproteinases 1 in Plasma and Urine from Patients with Bladder Cancer
Authors: Holten-Andersen M.N. , Brünner N. , Nielsen H.J. , Christensen I.J. , Møller Sørensen N. , Schrohl Rasmussen A.-S. , Primdahl H. , Ørntoft T. 
Published: January 2018

Aim To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer. Methods TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma (n=3) or adenocarcinoma (n=7). Results Free and total TIMP-1 in plasma were weakly but significantly correlated with age; urinary TIMP-1 was not. A strong correlation between free and total TIMP-1 in plasma was observed, with an average ratio of 0.85. No correlation between total TIMP-1 in urine and plasma was found (p=0.55). No significant differences in free or total TIMP-1 in plasma were found between healthy individuals, patients with cystitis or bladder cancer (p=0.4). Urinary TIMP-1 levels were significantly increased in patients with cystitis (p=0.001). No apparent differences in TIMP-1 levels were found in patients with bladder cancer at different stages. Conclusion Our previous observation of a weak but significant correlation between plasma TIMP-1 and age was confirmed. Likewise, an association between free and total TIMP-1 in plasma with a ratio of 0.85 was established. No correlation between plasma and urine TIMP-1 was found. Measurement of TIMP-1 in plasma and/or urine is apparently not useful for the identification of bladder cancer.
Influence of Bicalutamide with or without Tamoxifen or Anastrozole on Insulin-like Growth Factor 1 and Binding Proteins in Prostate Cancer Patients
Authors: Boccardo F. , Rubagotti A. , Battaglia M. , Zattoni F. , Bertaccini A. , Romagnoli A. , Conti G. 
Published: January 2018

Background There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression. Patients and methods IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia. Results Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5). Conclusions The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.
Clinical Utility of Determination of HER-2/neu and EGFR Fragments in Serum of Patients with Metastatic Breast Cancer
Authors: Witzel I. , Thomssen C. , Krenkel S. , Wilczak W. , Bubenheim M. , Pantel K. , Neumann R. , Jänicke F. , Müller V. 
Published: January 2018

Introduction The growth factor receptors EGFR and HER-2/neu are targets for new treatment strategies and are of potential use as prognostic and predictive factors. However, the optimal method of determination in order to obtain clinically relevant information remains a source of controversy. Methods HER-2/neu and EGFR expression was examined by immunohistochemistry in primary tumors of patients with breast cancer. In addition, serum was tested for the extracellular domains of HER-2/neu (HER-2/neu ECD) and EGFR (sEGFR) before initiation of therapy for metastatic disease (n=76). The course of disease from the time of metastasis with regard to these parameters was evaluated by univariate and multivariate analyses. Results HER-2/neu ECD levels at the time of metastatic disease were correlated with HER-2/neu expression determined by immunohistochemistry from primary tumors (p=0.001). No correlation was observed between expression of EGFR in primary tumors and sEGFR serum levels. HER-2/neu ECD and sEGFR levels at the onset of metastatic disease did not show a significant impact on overall survival. Conclusions Determination of HER-2/neu ECD levels in the serum measured by ELISA at the onset of metastatic disease could offer an alternative to immunohistochemistry of the primary tumor since serum levels are correlated with protein expression in primary tumors. In contrast, no such correlation was observed for EGFR.
Pre-Treatment Prediction of Chemoresistance in Second-Line Chemotherapy of Ovarian Carcinoma: Value of Serological Tumor Marker Determination (Tetranectin, YKL-40, CASA, CA 125)
Authors: Gronlund B. , Høgdall E.V.S. , Christensen I.J. , Johansen J.S. , Nørgaard-Pedersen B. , Engelholm S.A. , Høgdall C. 
Published: January 2018

Objective To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. Methods From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed. Results At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2–0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0–3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2–2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66–0.91; p=0.001). Conclusion Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.
The Effect of Venous Thromboembolism on Survival of Cancer Patients and its Relationship with Serum Levels of Factor VIII and Vascular Endothelial Growth Factor: A Prospective Matched-Paired Study
Authors: Dogan M. , Demirkazik A. , Konuk N. , Yalcin B. , Buyukcelik A. , Utkan G. , Tek I. , Akbulut H. , Sencan O. , Icli F. 
Published: January 2018

Background Venous thromboembolism (VT) increases mortality and morbidity in cancer patients. The primary aim of this study was to evaluate the effect of VT on the survival of cancer patients and its relationship with serum vascular endothelial growth factor (VEGF) and plasma factor VIII levels. Patients and methods Eighty-two patients with locally advanced or metastatic cancer were included in this study between September 2001 and March 2004, and 31 of them had VT. Fifty-one matched-paired cancer patients without VT were prospectively selected as a control group in the same period. Criteria for the selection of control group patients were having the same malignancy, stage, metastatic site, performance status and age (±5 years) as patients in the VT group. Results Plasma factor VIII and serum D-dimer levels in the VT group were significantly higher than those in the control group (p=0.030 and p=0.016, respectively). However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT group, the median survival of patients who had higher serum VEGF levels (>150 pg/mL) was significantly shorter than that of patients in the same group with lower serum VEGF levels (p=0.005). The median survival of the VT group was 14 months, whereas it was 25 months in the control group (p=0.199). Conclusion There was a worse prognostic trend for cancer patients with VT. Nevertheless, the difference in survival was not statistically significant between the groups. Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer patients with VT. Cancer patients with VT and higher serum VEGF levels had a significantly poorer prognosis.
Evidence for Cell Adhesion-Mediated Drug Resistance of Multiple Myeloma Cells in Vivo
Authors: Schmidmaier R. , Mörsdorf K. , Baumann P. , Emmerich B. , Meinhardt G. 
Published: January 2018

Background/Aims Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients. To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry. Methods A 3-color stain with CD38, CD138 and antibodies against VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the response to the next chemotherapy of chemo-naive patients was correlated with the expression levels of adhesion molecules. Results ICAM-1, VLA-4, and VCAM expression was higher in pre-treated patients than in chemo-naive patients and the expression levels increased with the number of chemotherapy regimens. Primarily multidrug-resistant patients had significantly higher expression levels of VLA-4 and ICAM-1 than responders. Conclusion This study suggests that multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug resistant and that such a subpopulation of cells is selected by chemotherapy.