tbuckley/cabot-search huggingface dataset:
Differential Gene Expression Analysis Reveals Activation of Growth Promoting Signaling Pathways by Tenascin-C
Authors: Christian Ruiz, Wentao Huang, Monika E. Hegi, Katrin Lange, Marie-France Hamou, Erika Fluri, Edward J. Oakeley, Ruth Chiquet-Ehrismann, Gertraud Orend
Journal: Cancer Research (2004)

Abstract Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C. To address the mechanism of action, we performed a RNA expression analysis of T89G cells grown in the presence or absence of tenascin-C and found that tenascin-C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell spreading on a fibronectin/tenascin-C substratum was restored, indicating that tenascin-C destabilizes actin stress fibers through down-regulation of tropomyosin-1. Tenascin-C also increased the expression of the endothelin receptor type A and stimulated the corresponding mitogen-activated protein kinase signaling pathway, which triggers extracellular signal-regulated kinase 1/2 phosphorylation and c-Fos expression. Tenascin-C additionally caused down-regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was enhanced through stabilization of β-catenin and stimulated the expression of the β-catenin target Id2. Finally, our in vivo data derived from astrocytoma tissue arrays link increased tenascin-C and Id2 expression with high malignancy. Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1 expression, are closely linked to transformation and tumorigenesis, we suggest that tenascin-C specifically modulates these signaling pathways to enhance proliferation of glioma cells.
Enhancement of Human Cancer Cell Motility and Invasiveness by Anaphylatoxin C5a via Aberrantly Expressed C5a Receptor (CD88)
Authors: Hidetoshi Nitta, Yoshihiro Wada, Yoshiaki Kawano, Yoji Murakami, Atsushi Irie, Keisuke Taniguchi, Ken Kikuchi, Gen Yamada, Kentaro Suzuki, Jiro Honda, Masayo Wilson-Morifuji, Norie Araki, Masatoshi Eto, Hideo Baba, Takahisa Imamura
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. We therefore sought C5aR expression and a direct influence of the C5a–C5aR axis on cancer cells. Experimental Design: C5aR expression was investigated in human cancer tissues and cell lines. Effects of C5a stimulation on cancer cells were studied by cytoskeletal rearrangement, time-lapse analysis, Matrigel chamber assay, and invasion in nude mouse in a comparison of C5aR-expressing cancer cells with control cells. Results: C5aR was aberrantly expressed in various human cancers. Several cancer cell lines also expressed C5aR. C5a triggered cytoskeletal rearrangement and enhanced cell motility three-fold and invasiveness 13-fold of C5aR-expressing cancer cells. Such enhancement by C5a was not observed in control cells. Cancer cell invasion was still enhanced in the absence of C5a concentration gradient and even after the removal of C5a stimulation, suggesting that random cell locomotion plays an important role in C5a-triggered cancer cell invasion. C5a increased the release of matrix metalloproteinases (MMP) from cancer cells by two- to 11-fold, and inhibition of MMP activity abolished the C5a-enhancing effect on cancer cell invasion. Compared with control cells, C5aR-expressing cells spread 1.8-fold more broadly at implanted nude mouse skin sites only when stimulated with C5a. Conclusions: These results illustrate a novel activity of the C5a–C5aR axis that promotes cancer cell invasion through motility activation and MMP release. Targeting this signaling pathway may provide a useful therapeutic option for cancer treatment. Clin Cancer Res; 19(8); 2004–13. ©2013 AACR.
Management of knee osteoarthritis
Authors: B F LEEB
Journal: Annals of the Rheumatic Diseases (2001)

I read with great interest Dr Jawad's letter and the authors' reply about the EULAR recommendations for the management of knee osteoarthritis (OA).1 2 

As a member of the ESCISIT task force I feel free to discuss some of the issues raised by Dr Jawad and to give further arguments for the accuracy of the recommendations developed by the group of European experts.3 

Although most points of criticism were answered by M Dougados and M Doherty it seems to me that treatment of knee OA with symptomatic slow acting drugs in osteoarthritis (SYSADOA) and cyclo-oxygenase-2 (COX-2) inhibitors needs to be discussed in a different way in the light of recent publications.

With respect to SYSADOA, the statement that these substances may modify structure has been strengthened by the publication of Reginster et al , in which glucosamine sulphate (GS) treatment was proved to exert a significant decrease in joint space narrowing compared with placebo during a three year period, indicating the disease modifying effect of GS for …
Neoadjuvant Chemotherapy Shows Similar Response in Patients With Inflammatory or Locally Advanced Breast Cancer When Compared With Operable Breast Cancer: A Secondary Analysis of the GeparTrio Trial Data
Authors: Serban Dan Costa, Sibylle Loibl, Manfred Kaufmann, Dirk-Michael Zahm, Jörn Hilfrich, Jens Huober, Holger Eidtmann, Andreas du Bois, Jens-Uwe Blohmer, Beyhan Ataseven, Erich Weiss, Hans Tesch, Bernd Gerber, Klaus H. Baumann, Christoph Thomssen, Georg Peter Breitbach, Shaip Ibishi, Christian Jackisch, Keyur Mehta, Gunter von Minckwitz
Journal: Journal of Clinical Oncology (2009)

PURPOSE Neoadjuvant chemotherapy followed by mastectomy is the treatment of choice in patients with inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC), but it is considered less effective in these diseases than in operable breast cancer (OBC). We report a prospective comparison of the GeparTrio trial of patients with IBC (cT4 days) or LABC (cT4a-c or cN3; stage IIIB or IIIC) and patients with OBC (cT2-3). PATIENTS AND METHODS Participants were stratified by stage and were randomly assigned to six or eight cycles of docetaxel/doxorubicin/cyclophosphamide (TAC) or to two cycles of TAC followed by four cycles of vinorelbine/capecitabine. We present results of a secondary aim of the study, which was to compare pathologic complete response (pCR; ie, no remaining invasive/noninvasive tumor in breast and lymph nodes) in different stage groups. Results A total of 287 patients with IBC (n = 93) or LABC (n = 194) and 1,777 patients with OBC were entered onto the trial. At baseline, parameters were as follows for the three types of cancer, respectively: median tumor sizes: 8.0 cm, 7.0 cm, and 4.0 cm (P < .001); multiple lesions: 31.2%, 27.3%, and 19.6% (P < .001); nodal involvement: 86.6%, 71.2%, and 51.6% (P < .001); grade 3: 44.4%, 30.4%, and 39.9% (P = .178); lobular-invasive type: 7.5%, 17.5%, and 13.3% (P = .673); negative hormone receptor status: 38.0%, 20.0%, and 36.4% (P = .008); and positive human growth factor receptor 2 status: 45.1%, 38.9%, and 35.7% (P = .158). Response rates for IBC, LABC, and OBC, respectively, were 8.6%, 11.3%, and 17.7% for pCR (P = .002); 71.0%, 69.6%, and 83.4% for overall response by physical or sonographic examination (P < .001); and 12.9%, 33.0%, and 69.9% for breast conservation (P < .001). All P values were for IBC and LABC versus OBC. However, tumor stage itself was not an independent predictor for pCR in multivariable analysis (odds ratio, 1.51; 95% CI, 0.88 to 2.59; P = .13). CONCLUSION No evidence of a difference in response to neoadjuvant chemotherapy was found by tumor stage when analysis was adjusted for baseline characteristics.
A novel monilethrix mutation in coil 2A of KRT86 causing autosomal dominant monilethrix with incomplete penetrance
Authors: R. De Cruz, L. Horev, J. Green, S. Babay, M. Sladden, A. Zlotogorski, R. Sinclair
Journal: British Journal of Dermatology (2012)

Background Monilethrix is a genetic hair shaft disorder that causes a dystrophic alopecia. Mutations causing autosomal dominant monilethrix have been found in the helix initiation and helix termination motifs of the type II hair keratins KRT81, KRT83 and KRT86. Mutations in DSG4 are linked to recessive transmission. Objectives We investigated a large Tasmanian family demonstrating autosomal dominant monilethrix with incomplete penetrance in order to identify the responsible genetic mutation. As only some affected hairs were moniliform, analysis was undertaken to demonstrate a deficit in the tensile strength of nonmoniliform hairs. Methods One hundred and twenty family members were examined. Light microscopy of hair samples was used to support clinical diagnoses. Linkage and gene sequencing studies were then undertaken. Nonbeaded fibres were analysed using the Single Fibre Analyser 3 (SIFAN 3™). Results We identified a novel A280V (c.839C > T substitution) mutation in the coil 2A region of KRT86. This is the first mutation located in a region other than the helix initiation or termination motifs. The A280V mutation was identified in both affected and clinically unaffected family members. Nonmoniliform hairs demonstrated reduced elasticity among both affected and unaffected individuals carrying the A280V mutation. Conclusions This is the first mutation located in a region other than the helix initiation or termination motifs, thus expanding the spectrum of mutations and highlighting the importance of molecular diagnosis in monilethrix.
Correlation between isokinetic profile and knee injuries in male volleyball athletes
Authors: L D Mendonça, N F N Bittencourt, R A Barreto, T F Paiva, R F Porto, A A Silva, S T Fonseca
Journal: British Journal of Sports Medicine (2011)

Background Knee injuries are prevalent in elite volleyball and their preventive management is still discussed. Isokinetic assessment is largely use in sports injury prevention; however few studies investigate the differences in the isokinetic profile of injured knees. These studies analyses the agonist/antagonist ratio and do not consider other parameters as fatigue index. Objective to investigate the differences between injured and non injured knee in the hamstring/quadriceps ratio and fatigue index in volleyball male athletes. Setting all testing took place in the Sports Injury Prevention and Rehabilitation Laboratory- LAPREV in elite volleyball. Participants 49 male (mean+SD age, 21.96+4.1; height, 196.5+0.06; body mass, 89.1+9.03) athletes were evaluated in this study, being 20 at injured group. Participants with lower-extremity surgery in the previous 6 months and pain during the isokinetic test were excluded. Assessment of risk factor: hamstring/quadriceps ratio at 60°/s and 300°/s and fatigue at 300°/s at the dominant knee with 90° of hip flexion. Main outcome measurements trauma and overuse knee injuries provided by questionnaire. Results Differences between groups were found just in hamstring fatigue (p=0.002). The means of this parameter were 63.1 and 55.6 for injured and non-injured group respectively. For quadriceps fatigue the means were 48.4 and 47.3 respectively. No differences were found in the ratio analysis between groups (p=0.403 for 60°/s and p=0.289 for 360°/s). The means were 199.4 and 203.5 for injured and non-injured groups at 60°/s and 157.4 and 168.6 respectively at 300°/s. Conclusion The results showed that the injured group has more hamstring fatigue compared to non-injured group. The ratio analysis does not reveal differences between groups. The fatigue analysis must be incorporated in the athlete's assessment, because seems to be more informative about injury risk.
Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent’sJapan disease
Authors: Takashi Igarashi, Willy Günther, Takashi Sekine, Jun Inatomi, Hiroshi Shiraga, Shouri Takahashi, Junzou Suzuki, Noboru Tsuru, Toshio Yanagihara, Mitsunobu Shimazu, Thomas J. Jentsch, Rajesh V. Thakker
Journal: Kidney International (1998)
Pathogenesis of Attic Cholesteatomas
Authors: Jacob Sadé
Journal: Journal of the Royal Society of Medicine (1978)

An attic cholesteatoma is defined as an epidermoid cyst found in the attic. Stratified squamous epithelium may also be present in the middle ear as other clinical or pathological entities, such as metaplastic islands of the mucosa in chronic ears with central perforations or as a collapse of an atelectatic drum. Histological examination of 22 temporal bones with attic cholesteatomas has shown them to reside mainly medial to the ossicular chain. This explains the difficulty they have in self-cleansing, as well as the ensuing secondary infection. When a similar process occurs lateral to the ossicles, a self-cleansing nature's atticotomy may be formed. The aetiology ofan attic epidermoid cyst, i.e. an attic cholesteatoma, is usually considered to be an invasive retraction from the external ear. However, it is difficult to accept invasion ofexternal canal skin into the upper medial attic (often through the scutum). This is especially so in the face ofsucb biological phenomena as epithelial contact inhibition, or the invariable outward migration of stratified squamous epithelium from the edges of retraction pockets as well as from cholesteatoma perforations. Also, large cholesteatomas usually present themselves from the ‘beginning’ simultaneously with their perforations; no documentation of an evolving process from a pre-existing perforation exists at present. Marginal perforations which have later cvolved into attic cholesteatomas have so far not been documented. Therefore, the possibility that an attic cholesteatoma often arises primarily in the attic and presents itself secondarily in the external canal as a ‘perforated’ epidermoid cyst, is to be considered. The possibility that a congenital rest is responsible for the epidermoid cyst has often been put forward, but evidence that such rests actually exist has not yet been presented. The frequency with which cholesteatoma sacs (including the congenital type) show mucosal cells as part of their lining, suggests a metaplastic phenomenon, This means that the epithelial cells in question may have changed from mucosal into keratinizing cells or vice versa. Metaplastic changes of mucosas into keratinizing epithelium occur very frequently in the bronchi, nose, ears and genitourinary system. Epidermoid cysts may, therefore, be seen as an analogous formation to glandular cysts in the attic - the latter being very frequently found in the attic in chronically infected ears. Such ‘organ’ formations (glands or epidermoid cysts) may arise when their respective cells (forming mucus or keratin) grow in the midst ofconnective tissue rather than on the surface. Budding of cells, giving rise to epidermoid cysts, is occasionally found in chronically-infected ears adjacent to cholesteatomas.
Relationship Between Cancer Patients' Predictions of Prognosis and Their Treatment Preferences
Authors: Jane C. Weeks
Journal: JAMA (1998)

Context.—Previous studies have documented that cancer patients tend to overestimate the probability of long-term survival. If patient preferences about the trade-offs between the risks and benefits associated with alternative treatment strategies are based on inaccurate perceptions of prognosis, then treatment choices may not reflect each patient's true values.Objective.—To test the hypothesis that among terminally ill cancer patients an accurate understanding of prognosis is associated with a preference for therapy that focuses on comfort over attempts at life extension.Design.—Prospective cohort study.Setting.—Five teaching hospitals in the United States.Patients.—A total of 917 adults hospitalized with stage III or IV non–small cell lung cancer or colon cancer metastatic to liver in phases 1 and 2 of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT).Main Outcome Measures.—Proportion of patients favoring life-extending therapy over therapy focusing on relief of pain and discomfort, patient and physician estimates of the probability of 6-month survival, and actual 6-month survival.Results.—Patients who thought they were going to live for at least 6 months were more likely (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.7) to favor life-extending therapy over comfort care compared with patients who thought there was at least a 10% chance that they would not live 6 months. This OR was highest (8.5; 95% CI, 3.0-24.0) among patients who estimated their 6-month survival probability at greater than 90% but whose physicians estimated it at 10% or less. Patients overestimated their chances of surviving 6 months, while physicians estimated prognosis quite accurately. Patients who preferred life-extending therapy were more likely to undergo aggressive treatment, but controlling for known prognostic factors, their 6-month survival was no better.Conclusions.—Patients with metastatic colon and lung cancer overestimate their survival probabilities and these estimates may influence their preferences about medical therapies.
Effect of Lymphokine-Containing Sera on Adenocarcinoma BW10232 and Melanoma B16 in C57BL/6 Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. G. Moulton, J. C. Daniels
Journal: JNCI Journal of the National Cancer Institute (1980)

Lymphokine-containing sera (LKS) inhibited the growth of adenocarcinoma BW10232 and melanoma B16 in C57BL/L mice. Resistance to tumor growth was conferred by daily injections into the challenge site. The injection of LKS did not provide long-term resistance, inasmuch as termination of treatment permitted resumption of tumor growth at the primary tumor site. Whether LKS exerted a direct or indirect effect on the tumor cells to retard their was not certain.
Predicting the duration of antiviral treatment needed to suppress plasma HIV-1 RNA
Authors: G. Paolo Rizzardi, Rob J. De Boer, Shelley Hoover, Giuseppe Tambussi, Aude Chapuis, Nermin Halkic, Pierre-Alexandre Bart, Veronica Miller, Schlomo Staszewski, Daan W. Notermans, Luc Perrin, Cecil H. Fox, Joep M.A. Lange, Adriano Lazzarin, Giuseppe Pantaleo
Journal: Journal of Clinical Investigation (2000)

Effective therapeutic interventions and clinical care of adults infected with HIV-1 require an understanding of factors that influence time of response to antiretroviral therapy. We have studied a cohort of 118 HIV-1–infected subjects naive to antiretroviral therapy and have correlated the time of response to treatment with a series of virological and immunological measures, including levels of viral load in blood and lymph node, percent of CD4 T cells in lymph nodes, and CD4 T-cell count in blood at study entry. Suppression of viremia below the limit of detection, 50 HIV-1 RNA copies/mL of plasma, served as a benchmark for a successful virological response. We employed these correlations to predict the length of treatment required to attain a virological response in each patient. Baseline plasma viremia emerged as the factor most tightly correlated with the duration of treatment required, allowing us to estimate the required time as a function of this one measure.
Cardiac Vagal Reflex Modulates Intestinal Vascular Capacitance and Ventricular Preload in Anesthetized Dogs With Acute Myocardial Infarction
Authors: Steven Y. Wang, Dante E. Manyari, John V. Tyberg
Journal: Circulation (1996)

Background The purpose of the present study was to examine the effects of the cardiac vagal reflex on intestinal vascular capacitance and cardiac filling pressure during experimental acute myocardial infarction (AMI). Methods and Results AMI was induced in anesthetized dogs through injection of microspheres into the left main coronary artery. Intestinal blood volume was measured with blood-pool scintigraphy. Portal venous pressure was varied through graded inflation of a portal venous constrictor to determine the intestinal vascular pressure-volume relation. Induction of AMI decreased intestinal blood volume to 88±3% of the control value ( P &lt;.01) and shifted the pressure-volume relation toward the pressure axis. This change was associated with increased left ventricular (LV) end-diastolic pressure (LVEDP) (from 6±1 to 17±2 mm Hg, P &lt;.01) and LV segment length (to 112±4% of the control value, P &lt;.01). During AMI, blockade of the cardiac vagal reflex by intrapericardial application of 2% lidocaine further decreased intestinal blood volume (to 83±3% of the control value, P &lt;.05, versus AMI without lidocaine), increased LVEDP (to 22±2 mm Hg, P &lt;.05, versus AMI without lidocaine), and tended to increase LV segment length (to 115±5%, P &lt;.10). Lidocaine had no effect in dogs with AMI that had been vagotomized. Conclusions These results suggest that the cardiac vagal reflex modulates the decrease in the intestinal vascular capacitance induced by AMI and modulates ventricular preload through pooling of blood in the intestinal circulation.
An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells
Authors: Yusuke Yamamoto, Yusuke Yoshioka, Kaho Minoura, Ryou-u Takahashi, Fumitaka Takeshita, Toshiki Taya, Reiko Horii, Yayoi Fukuoka, Takashi Kato, Nobuyoshi Kosaka, Takahiro Ochiya
Journal: Molecular Cancer (2011)

Abstract Background Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance. Results Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR. Conclusion These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.