bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of Tumoral Sialyltransferase Expression and Circulating E-Selectin Concentrations in Node-Negative Breast Cancer Patients
Authors: Hebbar M. , Krzewinski-Recchi M.-A. , Hornez L. , Verdière A. , Harduin-Lepers A. , Bonneterre J. , Delannoy P. , Peyrat J.-P. 
Published: January 2018

Aims and Background A crucial step in the metastatic process is the interaction between the endothelial molecule E-selectin and its tumoral ligands sialyl-Lewisx and sialyl-Lewisa. Sialyltranferases are involved in the biosynthesis of these ligands. The aim of this study was to assess the prognostic value of tumoral sialyltransferase expression and of circulating soluble E-selectin (sE-selectin) in node-negative breast cancer patients. Methods Using a multiplex RT-PCR method, we measured the expression of five sialyltransferases (ST3Gal III, ST6Gal I, ST3Gal IV, ST3Gal I and ST3Gal II) in tumors of 135 surgically treated node-negative breast cancer patients. Circulating sE-selectin concentrations were measured by an ELISA method prior to surgery. We also analyzed tumor size, histoprognostic grading and steroid hormone receptor status. Results The median follow-up was 7.5 years. Expression of estrogen receptors was associated with a good prognosis for relapse-free survival in univariate analysis. A high ST3Gal III/ST6Gal I ratio and a high sE-selectin concentration were associated with a bad prognosis for relapse-free survival and overall survival in univariate and multivariate analysis. Conclusion In the present study, tumoral sialyltransferase expression and circulating sE-selectin concentrations had prognostic value in patients with node-negative breast cancer. This result provides further evidence for the important role of these agents in the metastatic process.
Quantitative Real-Time RT-PCR Analysis of Eight Novel Estrogen-Regulated Genes in Breast Cancer
Authors: Sorbello V. , Fuso L. , Sfiligoi C. , Scafoglio C. , Ponzone R. , Biglia N. , Weisz A. , Sismondi P. , De Bortoli M. 
Published: January 2018

Background Biological markers capable of predicting the risk of recurrence and the response to treatment in breast cancer are eagerly awaited. Estrogen and progesterone receptors (ER, PgR) in tumor cells mark cancers that are more likely to respond to endocrine treatment, but up to 40% of such patients do not respond. Here, the expression of a group of estrogen-regulated genes, previously identified by microarray analysis of in vitro models, was measured in breast tumors and possible associations with other clinicopathological variables were investigated. Methods The expression of CD24, CD44, HAT-1, BAK-1, G1P3, TIEG, NRP-1 and RXRα was measured by quantitative real-time RT-PCR on RNA from eighteen primary breast tumors. Statistical analyses were used to identify correlations among the eight genes and the available clinicopathological data. Results Variable expression levels of all the genes were observed in all the samples examined. Significant associations of CD24 with tumor size, CD44 with lymph node invasion, and HAT-1 and BAK-1 with ER positivity were found. The possible combinatorial value of these genes was assessed. Unsupervised hierarchical clustering analysis demonstrated that the expression profile of these genes was able to predict ER status with an acceptable approximation. Conclusions Eight novel potential markers for breast cancer have been preliminarily characterized. As expected from in vitro data, their expression is able to discriminate ER- versus ER+ tumors.
Evaluation of Sample Handling in Relation to Levels of Tissue Inhibitor of Metalloproteinases-1 Measured in Blood by Immunoassay
Authors: Holten-Andersen M.N. , Schrohl A.-S. , Brünner N. , Nielsen H.J. , Høgdall C.K. , Høgdall E.V.S. 
Published: January 2018

Background The possible effect of preanalytical conditions such as blood sample preparation and handling on TIMP-1 levels in blood needs thorough investigation. Materials and Methods Blood was collected in dry tubes and tubes containing EDTA and kept at 4°C or 20°C for 1, 3, 8, 24 or 72 hours before processing into serum or EDTA plasma. In addition, serum and EDTA plasma samples were frozen and thawed 1–8 times. TIMP-1 was measured by ELISA. Results Time to processing for up to 72 hours did not significantly affect TIMP-1 levels in serum. In EDTA plasma, TIMP-1 levels were stable for up to eight hours; however, if samples were kept for 24 hours or longer the TIMP-1 levels increased (p<0.0001). Repeated freezing and thawing had a significant effect on TIMP-1 levels in serum (p=0.04). In plasma, repeated freezing and thawing for up to six times did not influence TIMP-1. However, in plasma samples exposed to seven or eight freeze/thaw cycles TIMP-1 levels decreased, although not significantly (p=0.23). Conclusions Handling and processing of blood samples is crucial for TIMP-1 measurement by immunoassay. In serum, TIMP-1 levels are unaffected by time to processing. Plasma samples should be processed within eight hours to avoid a TIMP-1 increase. For the measurement of TIMP-1 in archival material, serum should not be used because TIMP-1 levels are significantly affected by repeated freezing and thawing; archival plasma can readily be used provided that samples have not been frozen and thawed more than six times.
Serum Tumor Markers may Precede Instrumental Response to Chemotherapy in Patients with Metastatic Cancer
Authors: Massacesi C. , Rocchi M.B.L. , Marcucci F. , Pilone A. , Galeazzi M. , Bonsignori M. 
Published: January 2018

Purpose Although serum tumor markers (STMs) are widely used in clinical practice, their predictive role for the response to anticancer treatment is still controversial. The correlation of CEA, CA 15.3, CA 19.9, CA 125 (only with peritoneal involvement) and NSE levels with imaging response and clinical benefit was investigated in 60 non-selected patients with metastatic epithelial cancers treated by single-agent docetaxel chemotherapy. Methods STM measurement was performed at baseline and subsequently every three to four weeks. We applied the WHO criteria to evaluate both STM and instrumental responses. Concordance analysis was performed by the Cohen Kw index, and the significance of the results was established using the Fleiss, Cohen & Everitt test. Qualitative interpretation of data was obtained with the Landis & Koch scale. Correlations of STM response with clinical benefit (PS or pain improvement) were evaluated by the chi-square test. Results The primary tumors included breast cancers (38 patients), gastrointestinal non-colorectal cancers (12 patients), and lung cancers (10 patients). An overall significant good degree of agreement was observed between STM and instrumental response (p<0.0005). The degree of agreement for each marker was as follows: excellent for CEA (p<0.0005) and CA 125 (p=0.006), good for CA 15.3 (p<0.0005) and CA 19.9 (p=0.011). Restricted analysis for the correlation of each marker with primary tumor origin showed good prediction of radiological response for CA 15.3 and CEA in breast cancer patients (p<0.0005 for both), for CEA and CA 19.9 in gastrointestinal cancer patients (p=0.01 and 0.04, respectively), and for CEA+NSE in lung cancer patients (p=0.01). Conversely, STM response did not correlate significantly with the clinical benefit for the patients, both in terms of PS and pain improvement (p=0.24 and p=0.42, respectively). Conclusion This study showed STMs to be good predictors of tumor response. Although STMs cannot replace diagnostic imaging, in metastatic cancer they might be useful to optimize the timing of radiological re-evaluation in the palliative setting.
Sequential Adjuvant Hormone Therapy in Postmenopausal Breast Cancer: Rationale and Clinical Results
Authors: Longo R. , D'Andrea M.R. , Gasparini G. 
Published: January 2018

For the past 15 years tamoxifen has been the standard adjuvant hormone therapy for women with early-stage breast cancer and estrogen receptor (ER)-positive tumors, irrespective of nodal status and other clinicopathological parameters. Recent studies provided evidence that the optimal duration of tamoxifen treatment is 5 years. Based on the positive clinical results obtained with the administration of aromatase inhibitors (AIs) in the metastatic setting, several controlled clinical trials have evaluated the efficacy and side effects of AIs versus standard tamoxifen also as adjuvant therapy in postmenopausal breast cancer patients. The results of the above studies, suggest a therapeutic advantage of AIs over tamoxifen with regard to relapse-free survival and the risk of metachronous contralateral breast cancer. We review the rationale and the available clinical data on initial or sequential hormone treatment with AIs and we propose a novel scenario for possible therapeutic strategies based on the clinicopathological characteristics of the patients and on the biology of each single tumor.
Is the Urokinase-type Plasminogen Activator System a Reliable Prognostic Factor in Gastric Cancer?
Authors: Luebke T. , Baldus S.E. , Spieker D. , Grass G. , Bollschweiler E. , Schneider P.M. , Thiele J. , Dienes H.P. , Hoelscher A.H. , Monig S.P. 
Published: January 2018

Aim The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohisto-chemically assessed uPA and PAI-1 in patients with gastric cancer. Methods This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. Results Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). Conclusions Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.
Mutations in Exons 6 and 7 of TP53 Gene Correlate Positively with Serum Tumor Necrosis Factor Alpha Independent of Microsatellite Instability in BAT26 Gene in Egyptian Patients with Endometrial Carcinoma
Authors: Diab A.M. , Tawfeek T.A.S. , Moeity F. , Elsammak M. 
Published: January 2018

Abnormalities in the TP53 gene are the most frequent genetic alterations in human cancers. The role and mechanism of TP53 mutations have been well studied in many types of human cancer. Similarly, the presence of microsatellite instability (MSI) in the DNA mismatch repair system (hMSH2) may provide evidence of faulty DNA mismatch repair. One of the most important locations of MSI is the BAT26 gene. In addition, deranged serum cytokines, especially elevated levels of the tumor necrosis factor (TNF) alpha, have been found in many gynecological conditions. Aims The current study aimed at evaluating mutations in exons 6 and 7 of TP53 and the presence of microsatellite instability in BAT26 of the hMSH2 system in Egyptian patients with endometrial carcinoma. The study also evaluated whether there was a correlation between any of these genetic mutations/instability and the tissue expression of estrogen and progesterone receptors and the serum TNF-alpha level. Patients and methods The current study included 2 groups: a control group comprising 20 healthy women aged 52.21 ± 5.80 years attending the clinic for routine checkups and 40 patients with endometrial cancer aged 55.30 ± 6.21 years. Mutations in TP53 and BAT26 were evaluated using polymerase chain reaction–single-strand conformational polymorphism (PCR-SSCP) and automated sequencing while serum TNF-alpha was measured using an ELISA technique. Estrogen and progesterone receptor expression in biopsy tissue was evaluated using immunohistochemical staining. Results Seven of the 40 patients (17.5%) were positive for TP53 gene alterations in exon 6, while 9 patients (22.5%) were positive for TP53 alterations in exon 7. Cases positive for TP53 mutations had higher tumor stages. Ten patients (25%) showed MSI in BAT26. Nearly all patients with mutations in BAT26 had a strong family history for endometrial cancer (χ2=13.33, p<0.05). There was no positive correlation between the presence of MSI in the BAT26 gene and mutations in the TP53 gene or high serum TNF-alpha levels. Cases positive for TP53 mutations had a significantly higher level of TNF-alpha than cases negative for TP53 mutations (p<0.05). Cases showing mutations in exon 6 or 7 of TP53 showed a significantly higher intensity of immunohistochemical staining for estrogen and progesterone receptor expression in biopsy tissue than cases negative for mutations. (χ2=8.11, p<0.05). Conclusion Our results suggest that the development of endometrial carcinoma is probably mediated through a multi-step carcinogenesis pathway and mutation of TP53 does not necessarily result from the presence of microsatellite instability in BAT26. The high serum TNF-alpha levels detected in our patients may represent an immunological antitumor response that was particularly evident in cases positive for TP53 mutations.
Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials
Authors: Cooper Cindy L , Whitehead Amy , Pottrill Edward , Julious Steven A , Walters Stephen J 
Published: January 2018

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.
Patient satisfaction and healthcare services in specialized multiple sclerosis centres in Germany
Authors: Becker Veit , Heeschen Volker , Schuh Katrin , Schieb Heinke , Ziemssen Tjalf 
Published: January 2018

Background: As patients with multiple sclerosis (MS) require lifelong treatment, optimization of therapy with respect to efficacy and safety is needed to limit long-term disease progression. Patients with MS also need a range of health-related services. Satisfaction with these as well as treatment is clinically relevant because satisfied patients are more likely to adhere to therapy. The aim of this study was to determine the status of patient satisfaction and of healthcare services in 70 specialized MS centres in Germany. Methods: In 2011, patients with MS responded to a questionnaire, which solicited clinical and demographic information, as well as patients’ perceptions of their overall situation and their satisfaction with treatment. Results: Of 2791 patients surveyed, 81.9% had relapsing-remitting MS with mild disability [mean (standard deviation) Expanded Disability Status Scale score: 2.6 (1.8)]. Disease activity data were collected from 2205 patients, of whom 57.6% had remained relapse-free during the preceding 12 months. However, 38.9% had experienced one or more relapses, most of whom (67.3%) while receiving immunomodulatory treatment. About one-third of the patients indicated that they were more dissatisfied with their overall situation compared with the time before diagnosis. However, many patients (58.3%) were satisfied with their existing medication. Overall, 72.8% of patients would prefer oral to injectable treatments, assuming there was no difference in their efficacy. Conclusions: A substantial proportion of patients experienced breakthrough disease on treatment and may potentially benefit from a change of therapy. Although largely satisfied with treatment, most patients with MS would choose oral over injectable treatments.
An epidemiological study on the course of disease and therapeutic considerations in relapsing–remitting multiple sclerosis patients receiving injectable first-line disease-modifying therapies in Germany (EPIDEM)
Authors: Schmidt Stephan , Koehler Jürgen , Winterstein Christine , Schicklmaier Petra , Kallmann Boris 
Published: January 2018

Background: In relapsing–remitting multiple sclerosis (RRMS), ‘no evidence of disease activity’ (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management. Methods: EPIDEM was a multicenter non-interventional retrospective study in a large cohort of RRMS patients receiving injectable DMTs for at least 2 years in outpatient centers throughout Germany. It documented measures and ratings of disease activity on DMTs to characterize the factors that made the treating neurologists consider to switch therapy towards potentially more effective or better-tolerated drugs. Results: The cohort included predominantly female patients with a mean age of 45 years and a mean disease duration of 9.6 years, who had been continuously treated with an injectable DMT for a median duration of 54 months. Overall, 34.0% of the patients had experienced ⩾1 relapse on any DMT in the previous 2 years; 21.0% exhibited magnetic resonance imaging (MRI) activity, and the Kurtzke Expanded Disability Status Scale (EDSS) score increased by at least 0.5 points in 20.1%. Overall, 50.3% of the patients with EDSS progression and 70.6% of the patients with relapses were assessed as clinically stable by the neurologists. A change of treatment was considered in a fraction of patients with disease activity: in 22.8% of those with relapse activity, in 37.8% of those with MRI activity and in 20.1% of those with EDSS progression. Conclusion: The results of EPIDEM underline the importance of standardized evaluation and documentation of ongoing disease activity and disability deterioration. Judged from the present data, the current paradigm of low tolerance for disease activity and recommendations for early treatment optimization have not been turned fully into action as yet. More widespread implementation of current guideline recommendations may allow patients to more benefit from the growing panel of effective treatment options.
Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing–remitting multiple sclerosis: the CLARITY Extension study
Authors: Comi Giancarlo , Cook Stuart , Rammohan Kottil , Soelberg Sorensen Per , Vermersch Patrick , Adeniji Abidemi K. , Dangond Fernando , Giovannoni Gavin 
Published: January 2018

Background The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing–remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. Results At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference −0.33, 97.5% confidence interval −0.33–0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. Conclusion A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment. ClinicalTrials.gov identifier: NCT00641537
Normative values of isometric elbow strength in healthy adults: a systematic review
Authors: Kotte Shamala H. P. , Viveen Jetske , Koenraadt Koen L. M. , The Bertram , Eygendaal Denise 
Published: January 2018

Background Post-traumatic deformities such as biceps tendon rupture or (peri-)articular fractures of the elbow are often related to a decrease in muscle strength. Postoperative evaluation of these deformities requires normative values of elbow strength. The purpose of this systematic review was to determine these normative values of isometric elbow strength in healthy adults resulting from studies evaluating this strength (i.e. flexion, extension, pronation and supination strength). Methods The databases of PubMed, EMBASE and Web of Sciences were searched and screened for studies involving the isometric elbow strength as measured in asymptomatic volunteers. The quality of the studies was assessed and studies of low quality were excluded. Results Nineteen studies met the inclusion criteria and were of sufficiently high quality to be included in the present review. In these studies, elbow strength was measured in a total of 1880 healthy volunteers. The experimental set-up and devices used to measure elbow strength varied between studies. Using some assumptions, a normative values table was assembled. Conclusions Large standard deviations of normative values in combination with different measurement devices used, as well as the different measurement positions of the subjects, demonstrated that there is no consensus about measuring the isometric elbow strength and therefore the normative values have to be interpreted with caution.