Remodeling of extracellular matrix by normal and tumor-associated fibroblasts promotes cervical cancer progression

Background: Comparison of tissue microarray results of 29 cervical cancer and 27 normal cervix tissue samples using immunohistochemistry revealed considerable reorganization of the fibrillar stroma of these tumors. Preliminary densitometry analysis of laminin-1, α -smooth muscle actin (SMA) and fibronectin immunostaining demonstrated 3.8-fold upregulation of laminin-1 and 5.2-fold increase of SMA in the interstitial stroma, indicating that these proteins and the activated fibroblasts play important role in the pathogenesis of cervical cancer. In the present work we investigated the role of normal and tumor-associated fibroblasts. Methods: In vitro models were used to throw light on the multifactorial process of tumor-stroma interaction, by means of studying the cooperation between tumor cells and fibroblasts. Fibroblasts from normal cervix and cervical cancers were grown either separately or in co-culture with CSCC7 cervical cancer cell line. Changes manifest in secreted glycoproteins, integrins and matrix metallo-proteases (MMPs) were explored. Results: While normal fibroblasts produced components of interstitial matrix and TGF- β 1 that promoted cell proliferation, cancer-associated fibroblasts (CAFs) synthesized ample amounts of laminin-1. The following results support the significance of laminin-1 in the invasion of CSCC7 cells: 1.) Tumor-associated fibroblasts produced more laminin-1 and less components of fibrillar ECM than normal cells; 2.) The production of laminin chains was further increased when CSCC7 cells were grown in co-culture with fibroblasts; 3.) CSCC7 cells were capable of increasing their laminin production; 4.) Tumor cells predominantly expressed integrin α 6 β 4 laminin receptors and migrated towards laminin. The integrin profile of both normal and tumor-associated fibroblasts was similar, expressing receptors for fibronectin, vitronectin and osteopontin. MMP-7 secreted by CSCC7 cells was upregulated by the presence of normal fibroblasts, whereas MMP-2 produced mainly by fibroblasts was activated in the presence of CSCC7 cells. Conclusions: Our results indicate that in addition to degradation of the basement membrane, invasion of cervical cancer is accomplished by the remodeling of the interstitial stroma, which process includes decrease and partial replacement of fibronectin and collagens by a laminin-rich matrix

Publication bias in animal research presented at the 2008 Society of Critical Care Medicine Conference

Abstract Background To determine a direct measure of publication bias by determining subsequent full-paper publication (P) of studies reported in animal research abstracts presented at an international conference (A). Methods We selected 100 random (using a random-number generator) A from the 2008 Society of Critical Care Medicine Conference. Using a data collection form and study manual, we recorded methodology and result variables from A. We searched PubMed and EMBASE to June 2015, and DOAJ and Google Scholar to May 2017 to screen for subsequent P. Methodology and result variables were recorded from P to determine changes in reporting from A. Predictors of P were examined using Fisher’s Exact Test. Results 62% (95% CI 52–71%) of studies described in A were subsequently P after a median 19 [IQR 9–33.3] months from conference presentation. Reporting of studies in A was of low quality: randomized 27% (the method of randomization and allocation concealment not described), blinded 0%, sample-size calculation stated 0%, specifying the primary outcome 26%, numbers given with denominators 6%, and stating number of animals used 47%. Only being an orally presented (vs. poster presented) A (14/16 vs. 48/84, p = 0.025) predicted P. Reporting of studies in P was of poor quality: randomized 39% (the method of randomization and allocation concealment not described), likely blinded 6%, primary outcome specified 5%, sample size calculation stated 0%, numbers given with denominators 34%, and number of animals used stated 56%. Changes in reporting from A to P occurred: from non-randomized to randomized 19%, from non-blinded to blinded 6%, from negative to positive outcomes 8%, from having to not having a stated primary outcome 16%, and from non-statistically to statistically significant findings 37%. Post-hoc, using publication data, P was predicted by having positive outcomes (published 62/62, unpublished 33/38; p = 0.003), or statistically significant results (published 58/62, unpublished 20/38; p < 0.001). Conclusions Only 62% (95% CI 52–71%) of animal research A are subsequently P; this was predicted by oral presentation of the A, finally having positive outcomes, and finally having statistically significant results. Publication bias is prevalent in critical care animal research

Concurrent agreement between an anthropometric model to predict thigh volume and dual-energy X-Ray absorptiometry assessment in female volleyball players aged 14-18 years

This is an Open Access Article. It is published by BioMed Central under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/ The Erratum to this article has been published in BMC Pediatrics 2017 17:62 http://dx.doi.org/10.1186/s12887-017-0818-8© 2016 The Author(s).Background: A variety of performance outputs are strongly determined by lower limbs volume and composition in children and adolescents. The current study aimed to examine the validity of thigh volume (TV) estimated by anthropometry in late adolescent female volleyball players. Dual-energy X-ray absorptiometry (DXA) measures were used as the reference method. Methods: Total and regional body composition was assessed with a Lunar DPX NT/Pro/MD+/Duo/Bravo scanner in a cross-sectional sample of 42 Portuguese female volleyball players aged 14-18 years (165.2 ± 0.9 cm; 61.1 ± 1.4 kg). TV was estimated with the reference method (TV-DXA) and with the anthropometric method (TV-ANTH). Agreement between procedures was assessed with Deming regression. The analysis also considered a calibration of the anthropometric approach. Results: The equation that best predicted TV-DXA was: -0.899 + 0.876 × log10 (body mass) + 0.113 × log10 (TV-ANTH). This new model (NM) was validated using the predicted residual sum of squares (PRESS) method (R2PRESS = 0.838). Correlation between the reference method and the NM was 0.934 (95%CI: 0.880-0.964, Sy·x = 0.325 L). Conclusions: A new and accurate anthropometric method to estimate TV in adolescent female volleyball players was obtained from the equation of Jones and Pearson alongside with adjustments for body mass