tbuckley/cabot-search huggingface dataset:
ACTIVATION PATTERN OF M.GLUTEUS MEDIUS IN PRE-PUBESCENT FEMALE AND MALE ATHLETES DURING DROP-JUMP AND CUTTING MANEUVERS
Authors: U Sædís Jónsdóttir, Á Árnason, K Briem, T Sveinsson
Journal: British Journal of Sports Medicine (2014)

Background One of many risk factors for ACL injury may involve neuromuscular activation patterns of muscles in the lower extremities. These have been studied for some muscles in pre- and post-pubescent female and male athletes. Although m.gluteus medius (GM) activity may be important during dynamic activities, its activation patterns have not been extensively studied. Objective To identify gender differences in neuromuscular activation of GM in young athletes. Design Cross-sectional controlled laboratory trial. Setting Measurements took place in the Research Centre of Movement Science at the University of Iceland. Participants 11–12 years old football and handball players were recruited from local sports clubs, 9 boys and 36 girls. Risk factor assessment Surface electrodes were used to collect EMG activity from GM during two dynamic tasks (drop-jumps (DJ) and cutting maneuvers (CM)), before and after a fatigue protocol. Main outcome measurements Timing of peak muscle activation and activation levels at initial contact (IC), normalized to peak activation, were analyzed pre- and post-fatigue between genders for each task. Results Girls demonstrated greater activation at IC than boys (P=.02) and peak activation occurred earlier in girls than boys (P&lt;.01) during the DJ. Moreover, GM activation levels at IC were overall significantly greater after a fatigue protocol than before (P&lt;.01) and peaked earlier (P&lt;.01). During CM the only significant finding was a main effect of fatigue for activation levels at IC (P&lt;.01). Conclusions Gender differences in activation patterns of GM were identified during DJ in young athletes. This may, in part, reflect different kinematic strategies during this dynamic task or gender biased training. As girls go into puberty earlier than boys, this may have influenced movement patterns of some of the female participants. Further investigation into GM activation in relation to lower extremity kinematics within the context of injury prevention is warranted.
The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product.
Authors: S Vijayasaradhi, B Bouchard, A N Houghton
Journal: The Journal of Experimental Medicine (1990)

The gp75 antigen is an abundant intracellular glycoprotein expressed in melanosomes of human pigmented melanocytes and melanomas. IgG antibodies in sera of a patient with metastatic melanoma have been shown to immunoprecipitate gp75, suggesting that immunological tolerance against gp75 can be broken. The mouse mAb TA99, which specifically recognizes gp75, was used to isolate and purify the antigen. Amino acid sequences of three internal peptides were determined from the purified gp75 polypeptide. cDNA clones were isolated by screening with oligonucleotides based on these peptide sequences. The gp75 peptides and cDNA had approximately 90% identity with, respectively, the derived amino acid and nucleotide sequences of a mouse gene that maps to the b (brown) locus. The brown locus determines coat color in the mouse, suggesting that gp75 regulates or influences the type of melanin synthesized.
Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth
Authors: Christina Stache, Annett Hölsken, Rudolf Fahlbusch, Jörg Flitsch, Sven-Martin Schlaffer, Michael Buchfelder, Rolf Buslei
Journal: Neuro-Oncology (2013)

Claudins are tight junction proteins expressed in epithelial tissues that play important roles in cell polarity and adhesion. Altered distribution of claudin-1(CLDN1) affects cell mobility and tumor invasiveness. Craniopharyngiomas (CPs) represent epithelial tumors of the sellar region, consisting of adamantinomatous (adaCP) and papillary (papCP) variants. Their tendency to infiltrate surrounding brain structures complicates successful surgery. Reliable markers are required to predict tumor behavior and to establish individualized treatment protocols. We describe the distribution pattern of CLDN1 in a large cohort of 66 adaCPs, 21 papCPs, and 24 Rathke`s cleft cyst (RCC) cases using immunohistochemistry. CLDN1 mRNA levels were analyzed with qRT-PCR in 33 CP samples. The impact on the migration potential was studied in primary adaCP cell cultures (n = 11) treated with small interfering RNA (siRNA) for CLDN1. Furthermore, CLDN1 distribution patterns and expression levels were compared between invasive (n = 16) and noninvasive (n = 17) tumor groups. PapCPs and RCCs exhibited a distinct homogenous and membranous expression pattern, whereas CLDN1 immunoreactivity appeared weaker and more heterogeneous in adaCPs. In the latter cases, whirl-like cell clusters showed complete absence of CLDN1. mRNA analysis confirmed reduced CLDN1 levels in adaCPs versus papCPs. Interestingly, invasive tumors exhibited significantly lower CLDN1 expression compared with noninvasive counterparts regardless of CP subtype. Accordingly, siRNA treatment for CLDN1 altered tumor cell migration in vitro. CLDN1 represents a novel marker in the differential diagnosis of CP variants and RCCs. Low CLDN1 expression levels correlate with an invasive CP growth pattern and may serve as a prognostic marker.
Helper cells in the autologous mixed lymphocyte reaction. III. Production of helper factor(s) distinct from interleukin 2.
Authors: J A Wolos, J B Smith
Journal: The Journal of Experimental Medicine (1982)

In normal mice, the autologous mixed lymphocyte reaction (AMLR) can activate helper T cells that, in the presence of hapten-modified syngeneic cells, can induce a hapten-specific cytotoxic response. Supernatants from AMLR cultures contain a factor(s) that will mediate a cytotoxic T cell response to hapten-altered self. The AMLR factor is effective in facilitating the generation of cytotoxicity only in those cultures containing both T cells and hapten-altered, syngeneic, nonstimulatory cells. Factor production requires an interaction between Lyt-1+23- cells and non-T cells (the T cells synthesize it). The AMLR factor does not appear to be interleukin 2 (IL-2) because it does not activate thymocytes in the presence of antigen, nor does it maintain an IL-2-dependent cell line or function in co-stimulator assays. For the AMLR factor to facilitate the generation of cytotoxicity, thymic adherent cells are a necessary intermediate. These data suggest that the factor recoverable from AMLR cultures acts early in the cytotoxic pathway, before IL-1 production.
Zebrafish Models for Cancer
Authors: Shu Liu, Steven D. Leach
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

First established as a valuable vertebrate model system for studying development, zebrafish have emerged as an attractive animal system for modeling human cancers. Major technical advances have been essential for the generation of zebrafish cancer models relevant to human diseases. These models develop tumors in various organ sites that bear striking resemblance to human malignances, both histologically and genetically. Thus, the focus of cancer research in zebrafish has transcended the need to validate zebrafish as a viable model organism to study cancer biology. With the significant advantages of in vivo imaging, the power of forward genetics, well-established high efficiency for transgenesis, and ease of transplantation, further exploration of the zebrafish cancer models not only will generate unique insights into underlying mechanisms of cancer but will also provide platforms useful for drug discovery.
Germline Mutation in <i>BRCA1</i> or <i>BRCA2</i> and Ten-Year Survival for Women Diagnosed with Epithelial Ovarian Cancer
Authors: Francisco J. Candido-dos-Reis, Honglin Song, Ellen L. Goode, Julie M. Cunningham, Brooke L. Fridley, Melissa C. Larson, Kathryn Alsop, Ed Dicks, Patricia Harrington, Susan J. Ramus, Anna de Fazio, Gillian Mitchell, Sian Fereday, Kelly L. Bolton, Charlie Gourley, Caroline Michie, Beth Karlan, Jenny Lester, Christine Walsh, Ilana Cass, Håkan Olsson, Martin Gore, Javier J. Benitez, Maria J. Garcia, Irene Andrulis, Anna Marie Mulligan, Gord Glendon, Ignacio Blanco, Conxi Lazaro, Alice S. Whittemore, Valerie McGuire, Weiva Sieh, Marco Montagna, Elisa Alducci, Siegal Sadetzki, Angela Chetrit, Ava Kwong, Susanne K. Kjaer, Allan Jensen, Estrid Høgdall, Susan Neuhausen, Robert Nussbaum, Mary Daly, Mark H. Greene, Phuong L. Mai, Jennifer T. Loud, Kirsten Moysich, Amanda E. Toland, Diether Lambrechts, Steve Ellis, Debra Frost, James D. Brenton, Marc Tischkowitz, Douglas F. Easton, Antonis Antoniou, Georgia Chenevix-Trench, Simon A. Gayther, David Bowtell, Paul D.P. Pharoah
Journal: Clinical Cancer Research (2014)

To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.
Highly Efficacious Nontoxic Preclinical Treatment for Advanced Metastatic Breast Cancer Using Combination Oral UFT-Cyclophosphamide Metronomic Chemotherapy
Authors: Raquel Munoz, Shan Man, Yuval Shaked, Christina R. Lee, John Wong, Giulio Francia, Robert S. Kerbel
Journal: Cancer Research (2006)

Abstract Metronomic antiangiogenic chemotherapy, the prolonged administration of relatively low drug doses, at close regular intervals with no significant breaks, has been mainly studied at the preclinical level using single chemotherapeutic drugs, frequently in combination with a targeted antiangiogenic drug, and almost always evaluated on primary localized tumors. We tested a “doublet” combination metronomic chemotherapy treatment using two oral drugs, UFT, a 5-fluorouracil (5-FU) prodrug administered by gavage, and cyclophosphamide, for efficacy and toxicity in a new mouse model of advanced, terminal, metastatic human breast cancer. The optimal biological dose of each drug was first determined by effects on levels of circulating endothelial progenitor cells as a surrogate marker for angiogenesis, which was assessed to be 15 mg/kg for UFT and 20 mg/kg for cyclophosphamide. A combination treatment was then evaluated in mice with advanced metastatic disease using a serially selected metastatic variant of the MDA-MB-231 breast cancer-cell line, 231/LM2-4. UFT or cyclophosphamide treatment showed only very modest survival advantages whereas a combination of the two resulted in a remarkable prolongation of survival, with no evidence of overt toxicity despite 140 days of continuous therapy, such that a significant proportion of mice survived for over a year. In contrast, this striking therapeutic effect of the combination treatment was not observed when tested on primary orthotopic tumors. We conclude that combination oral low-dose daily metronomic chemotherapy, using cyclophosphamide and UFT, is superior to monotherapy and seems to be a safe and highly effective experimental antimetastatic therapy, in this case, for advanced metastatic breast cancer. (Cancer Res 2006; 66(7): 3386-91)
Transcriptomic Analysis Identifies Phosphatases as Novel Targets for Adenotonsillar Hypertrophy of Pediatric Obstructive Sleep Apnea
Authors: Abdelnaby Khalyfa, Sina A. Gharib, Jinkwan Kim, Ehab Dayyat, Ayelet B. Snow, Rakesh Bhattacharjee, Leila Kheirandish-Gozal, Julie L. Goldman, David Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Obstructive sleep apnea (OSA) is a highly prevalent disorder in children, in which enlarged adenotonsillar tissues (AT) play a major pathophysiologic role. Mechanisms leading to the proliferation and hypertrophy of AT in children who subsequently develop OSA remain unknown, and surgical extirpation of AT is associated with potential morbidity and mortality.We hypothesized that a computationally based analysis of gene expression in tonsils from children with OSA and children with recurrent tonsillitis without OSA can identify putative mechanistic pathways associated with tonsillar proliferation and hypertrophy in OSA.Palatine tonsils from children with either polysomnographically documented OSA or recurrent infectious tonsillitis were subjected to whole-genome microarray and functional enrichment analyses followed by significance score ranking based on gene interaction networks. The latter enabled identification and confirmation of a candidate list of tonsil-proliferative genes in OSA.In vitro studies using a mixed tonsil cell culture system targeting one of these candidates, phosphoserine phosphatase, revealed that it was more abundantly expressed in tonsils of children with OSA, and that pharmacological inhibition of phosphoserine phosphatase led to marked reductions in T- and B-lymphocyte cell proliferation and increased apoptosis.A systems biology approach revealed a restricted set of candidate genes potentially underlying the heightened proliferative properties of AT in children with OSA. Furthermore, functional studies confirm a novel role for protein phosphatases in AT hypertrophy, and may provide a promising strategy for discovery of novel, nonsurgical therapeutic targets in pediatric OSA.
Measurement of Cyclin E Genomic Copy Number and Strand Length in Cell-Free DNA Distinguish Malignant versus Benign Effusions
Authors: Ritu Salani, Ben Davidson, Michael Fiegl, Christian Marth, Elisabeth Müller-Holzner, Guenther Gastl, Han-Yao Huang, Jui-Chi Hsiao, Her-Sheng Lin, Tian-Li Wang, Bai-Ling Lin, Ie-Ming Shih
Journal: Clinical Cancer Research (2007)

Previous studies have shown that the concentration of cell-free DNA was higher and its strand length longer in body fluids obtained from patients with cancer as compared to patients with benign diseases. We hypothesized that analysis of both DNA copy number and strand length of cell-free DNA from an amplified chromosomal region could improve the diagnosis of malignant diseases in body fluids.To test this hypothesis, we used ovarian cancer effusion as an example and applied a quantitative real-time PCR to measure the relative copy number and strand length of DNA fragments from one of the most frequently amplified genes, cyclin E, in ovarian serous carcinomas.As compared with nonamplified chromosomal loci, including beta-actin, p53, 2p24.1, and 4p15.31, measurement of cyclin E DNA copy number (100 bp) had the best performance in distinguishing malignant (n = 88) from benign (n = 70) effusions after normalization to effusion volume or Line-1 DNA with areas under the receiver operating characteristics curve (AUC) of 0.832 and 0.847, respectively. Different DNA lengths of the cyclin E locus were further analyzed and we found that the AUC was highest by measuring the 400-bp cyclin E locus (AUC = 0.896). The AUC was improved to 0.936 when it was combined with the length integrity index as defined by the relative abundance of 400 bp cyclin E to 100 bp p53 loci. Cyclin E real-time PCR assay had a higher sensitivity (95.6%) than routine cytology examination (73.9%) and was able to diagnose false-negative cytology cases in this study.The above findings indicate that measurement of the DNA copy number and strand length of the cyclin E locus is a useful cancer diagnostic tool.
Detection of a Meal Using Continuous Glucose Monitoring
Authors: Eyal Dassau, B. Wayne Bequette, Bruce A. Buckingham, Francis J. Doyle
Journal: Diabetes Care (2008)

The purpose of this study was to introduce a novel meal detection algorithm (MDA) to be used as part of an artificial beta-cell that uses a continuous glucose monitor (CGM).We developed our MDA on a dataset of 26 meal events using records from 19 children aged 1-6 years who used the MiniMed CGMS Gold. We then applied this algorithm to CGM records from a DirecNet pilot study of the FreeStyle Navigator continuous glucose sensor. During a research center admission, breakfast insulin was withheld for 1 h, and discrete glucose levels were obtained every 10 min after the meal.Based on the Navigator readings, the MDA detected a meal at a mean time of 30 min from the onset of eating, at which time the mean serum glucose was 21 mg/dl above baseline (range 2-36 mg/dl), and >90% of meals were detected before the glucose had risen 40 mg/dl from baseline.The MDA will enable automated insulin dosing in response to meals, facilitating the development of an artificial pancreas.
Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for <i>EGFR</i>-Mutant Lung Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Authors: Melissa L. Johnson, Helena A. Yu, Eric M. Hart, Bing Bing Weitner, Alfred W. Rademaker, Jyoti D. Patel, Mark G. Kris, Gregory J. Riely
Journal: Journal of Clinical Oncology (2015)

Purpose AUY922 is an HSP90 inhibitor that causes degradation of HSP chaperones and their client proteins, including epidermal growth factor receptor. We conducted a phase I/II trial to evaluate AUY922 and erlotinib for patients with EGFR-mutant lung cancer and disease progression during erlotinib treatment. Patients and Methods All patients had developed acquired resistance after treatment with erlotinib and underwent repeat tumor biopsies before study entry to assess for EGFR T790M. In phase I, 18 patients were treated with AUY922 intravenously once per week and erlotinib once per day in 28-day cycles using a 3 + 3 dose-escalation design. In phase II, 19 additional patients were treated at the maximum-tolerated dose. The primary end point of the phase II trial was complete plus partial response rate. Results In phase I (n = 18), three patients were treated in each cohort, except the highest-dose cohort (AUY922 70 mg and erlotinib 150 mg), which expanded to six patients because of a dose-limiting toxicity (ie, junctional cardiac rhythm). Common drug-related adverse events were diarrhea, skin rash, hyperglycemia, and night blindness. All patients treated at maximum-tolerated dose (n = 25) were evaluable for response. The partial response rate was 16% (four of 25 patients; 95% CI, 5% to 36%) and was independent of tumor T790M status. Conclusion Partial responses were observed, but the duration of treatment with AUY922 and erlotinib was limited by toxicities, especially night blindness. This phase II study of AUY922 and erlotinib did not meet its primary end point.
<i>p27kip1</i> in Intestinal Tumorigenesis and Chemoprevention in the Mouse
Authors: WanCai Yang, Laura Bancroft, Jiao Liang, Min Zhuang, Leonard H. Augenlicht
Journal: Cancer Research (2005)

Abstract Targeted inactivation of p27kip1 was sufficient for intestinal tumor formation in mice, but this was strictly a function of diet: tumors formed in p27+/− or p27−/− mice fed control AIN-76A diet and were increased by a western-style diet but did not develop in mice fed standard chow diet. When crossed with the Apc1638N+/− mouse, Apc+/−,p27+/− or Apc+/−,p27−/− mice not only formed twice as many tumors than the sum of the tumors from mutation at either locus alone, but on AIN76A diet also developed intestinal intussusception, a tumor-associated pathology in patients leading to intestinal blockage that has not been reported for intestinal cancer in mouse models. Moreover, the frequency of intussusception was increased when the compound mutant mice were maintained on the western diet, leading to early death. Despite this more aggressive tumor phenotype generated by inactivation of p27 than by inactivation of another cyclin-dependent kinase inhibitor, p21WAF1/cip1, the nonsteroidal anti-inflammatory drug sulindac was still effective in inhibiting intestinal tumor formation in Apc+/−,p27+/− or Apc+/−,p27−/− mice, which contrasts with the abrogation of the effects of sulindac in Apc+/−,p21+/− or Apc+/−,p21−/− mice, indicating that p27 is not necessary for tumor inhibition by sulindac. Furthermore, tumor inhibition by sulindac was linked to the induction of p21 expression by the drug, regardless of p27 status, leading to suppression of cell proliferation and promotion of cell differentiation and apoptosis in the intestinal mucosa.
HAND DERMATITIS IN HOUSEWIVES
Authors: C. D. CALNAN, H. J. BANDMANN, E. CRONIN, S. FREGERT, N. HJORTH, B. MAGNUSSON, K. MALTEN, C. L. MENEGHINI, V. PIRILA, D. S. WILKINSON
Journal: British Journal of Dermatology (1970)

SUMMARY.— In a series of 4000 patients patch tested in 5 European clinics, 1000 were engaged in domestic work only; they included 281 women with contact dermatitis of the hands. There were no significant differences between the 2 groups as regards age, duration of dermatitis and patch test results. Half of the 281 women had a positive patch test, the responsible allergens in order of rank being balsams, nickel, medicaments, cobalt, rubber, chromate, benzocaine and paraphenylenediamine. But 78% of them were diagnosed as contact dermatitis, 5% atopic and 13% were unclassified. An allergic cause (42%) was as frequent as an irritant (45%) among those with contact dermatitis.
Close and Stable Relationship between Proliferation and a Hypoxia Metagene in Aromatase Inhibitor–Treated ER-Positive Breast Cancer
Authors: Zara Ghazoui, Francesca M. Buffa, Anita K. Dunbier, Helen Anderson, Tim Dexter, Simone Detre, Janine Salter, Ian E. Smith, Adrian L. Harris, Mitchell Dowsett
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The majority of breast cancer patients who have estrogen receptor positive (ER+) tumors whose proliferation is reduced after estrogen deprivation by aromatase inhibitors (AI). This study investigates any link between proliferation and hypoxia, a major determinant of tumor biology, and defines the effect of estrogen deprivation on hypoxia-associated genes. Methods: Genome-wide expression profiles were obtained from tumor biopsies from 81 ER+ postmenopausal patients, before and after 2 weeks' anastrozole treatment. A hypoxia metagene was developed by identifying genes clustered with classical hypoxia-regulated genes, excluding those associated with proliferation. Proliferation was measured by Ki67 and a proliferation metagene derived from two published breast cancer data sets. Results: Hypoxia and proliferation metagenes were associated at baseline (Pearson correlation coefficient, r = 0.67, P &amp;lt; 10−4) and after 2 weeks (r = 0.71, P &amp;lt; 10−4). Hypoxia metagene at baseline was associated with 2-week Ki67 (r = 0.43, P = 0.0002) and more weakly with poor 2-week Ki67 change consistent with a weak association with AI resistance. Hypoxia metagene was significantly downregulated with AI. This downregulation was significantly associated with change in the proliferation metagene and with Ki67 but, importantly, not with the substantial change in expression of classical estrogen-dependent genes. Conclusions: Hypoxia metagene is closely associated with proliferation before and after AI treatment. The downregulation of hypoxia metagene after AI therapy is most likely the result of changes in proliferation. There may be a weak effect of hypoxia metagene on de novo resistance to AIs. These findings are important to consider in coapplication of antiproliferative agents with antiangiogenic or antihypoxia agents. Clin Cancer Res; 17(9); 3005–12. ©2011 AACR.