tbuckley/cabot-search huggingface dataset:
Refractory Thyroid Cancer: A Paradigm Shift in Treatment Is Not Far Off
Authors: David G. Pfister, James A. Fagin
Journal: Journal of Clinical Oncology (2008)

Oncology 1,2 is noteworthy, even without further elaboration. Why has there been limited interest in developmental therapeutics for thyroid malignancies in the past? Much has to do with the natural history of thyroid carcinomas, traditional management paradigms, and the limitations of available chemotherapies. More than 90% of thyroid malignancies are derived from the thyroid follicular cell. The vast majority are differentiated tumors, with the papillary subtype predominating (approximately 80%); most of the remainder are follicular carcinomas and related variants. For these differentiated tumors, standard treatment with primary surgery and thyroidstimulating hormone (TSH) suppression with supraphysiologic thyroid hormone administration often suffices. Depending on disease stage, patient age, and a variety of histopathologic factors, ablation of the thyroid remnant with radioactive iodine 131 (RAI) is added. 3 This collective strategy is associated with an overall survival rate of approximately 90% at 20 years. 4 The prognosis remains relatively favorable even among patients who experience relapse, as the annual mortality rate is far less than the annual rate of recurrence. 5 Indeed, many patients with recurrent disease, even when incurable, will have an indolent course over months to years, with few or no symptoms without active anticancer therapy beyond TSH suppression. At relapse, further surgery, repeat RAI, external-beam radiation, or even observation with continued TSH suppression have all been commonly prioritized before chemotherapy. Drugs such as doxorubicin (the only United States Food and Drug Administration–approved agent), cisplatin, or bleomycin—administered as single agents or as part of some combination regimen— benefit a minority of patients, and related toxicities may be significant. 6-8
Expression and inactivation of glycogen synthase kinase 3 alpha/ beta and their association with the expression of cyclin D1 and p53 in oral squamous cell carcinoma progression
Authors: Rajakishore Mishra, Siddavaram Nagini, Ajay Rana
Journal: Molecular Cancer (2015)

The study aims to evaluate the expression and activity of glycogen synthase kinase 3 isoforms α/β (GSK3α/β) and to assess their oncogenic potential through a correlation with the expression of cyclin D1 and p53 in oral cancer. The expression of total and phosphorylated GSK3α/β as well as cyclin D1 and p53 together with their interaction were assessed in human oral cancer tissue samples, apparently normal adjacent tissues, benign tumor samples, premalignant lesions and healthy normal tissues (total 179) using various methods, such as immunohistochemistry, Western blot assays, immunoprecipitation and RT-PCR analysis. The expression of GSK3β was significantly higher relative to GSK3α indicating the greater role of the β isoform in oral cancer. Among various types of oral cancers, OSCC (of the lip and tongue) showed elevated expression of GSK3α/β, and the expression was correlated with disease progression. The increased expression of pS21GSK3α and pS9GSK3β not only correlated positively with cyclin D1 and p53 expression in tongue cancer progression but a gradual shift of their expression from the cytoplasmic to the nuclear compartment and overall disease severity was also observed. The interaction of GSK3β-cyclin D1 and the positive correlation of pS9GSK3β and the transcription of cyclin D1 were observed. These results demonstrate that the inactivation of GSK3β is an important event in OSCC and can be used as a marker for assessing disease severity and may be exploited for therapeutic intervention.
Active inflammation and structural change in early active axial spondyloarthritis as detected by whole-body MRI
Authors: Christian E Althoff, Joachim Sieper, In-Ho Song, Hildrun Haibel, Anja Weiß, Torsten Diekhoff, Martin Rudwaleit, Bruce Freundlich, Bernd Hamm, Kay-Geert A Hermann
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate active inflammatory lesions (AIL) and structural changes (SC) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) compared with patients with ankylosing spondylitis (AS) on whole-body MRI (wb-MRI).75 patients with active disease and a symptom duration of <5 years (39 with AS and 36 with nr-axSpA) were investigated with a comprehensive wb-MRI protocol and scored for AIL and SC in the spine, sacroiliac joints (SIJs) and non-axial manifestations.92% of patients with AS showed active inflammation in the SIJ, 53% in the spine and 94% and 39%, respectively, in the nr-axSpA group. There was a non-significant trend towards more inflammation in patients with AS compared with patients with nr-axSpA in SIJs and spine. Peripheral enthesitis/osteitis was more common in patients with AS (n=22) than in those with nr-axSpA (n=12) (p=0.05). SC were more common in patients with AS than in those with nr-axSpA, with significantly higher scores for SIJ fatty bone marrow deposition (FMD) in patients with AS (4.8±3.2) compared with those with nr-axSpA (2.4±2.7; p=0.001) and more frequent bone proliferation in the spine and the SIJ (p=0.02 and p=0.005, respectively). SIJ erosions were more common in AS (score 4.2±2.3) than in nr-axSpA (score 3.8±1.8) patients (not significant).Wb-MRI detects active inflammation and SC more frequently in the SIJs than in the spine. Half of the patients showed inflammation in non-axial sites. Active inflammatory and structural lesions were present both in patients with AS and those with nr-axSpA, being only slightly more common in patients with AS.
Transient Exposure to Hydrogen Peroxide Causes an Increase in Mitochondria-Derived Superoxide As a Result of Sustained Alteration in L-Type Ca <sup>2+</sup> Channel Function in the Absence of Apoptosis in Ventricular Myocytes
Authors: Helena M. Viola, Peter G. Arthur, Livia C. Hool
Journal: Circulation Research (2007)

We sought to understand the effect of a transient exposure of cardiac myocytes to H(2)O(2) at a concentration that did not induce apoptosis. Myocytes were exposed to 30 micromol/L H(2)O(2) for 5 minutes followed by 10 U/mL catalase for 5 minutes to degrade the H(2)O(2). Cellular superoxide was measured using dihydroethidium. Transient exposure to H(2)O(2) caused a 66.4% increase in dihydroethidium signal compared with controls exposed to only catalase, without activation of caspase 3 or evidence of necrosis. The increase in dihydroethidium signal was attenuated by the mitochondrial inhibitors myxothiazol or carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone and when calcium uptake by the mitochondria was inhibited with Ru360. We investigated the L-type Ca(2+) channel (I(Ca-L)) as a source of calcium influx. Nisoldipine, an inhibitor of I(Ca-L), attenuated the increase in superoxide. Basal channel activity increased from 5.4 to 8.9 pA/pF. Diastolic calcium was significantly increased in quiescent and contracting myocytes after H(2)O(2). The response of I(Ca-L) to beta-adrenergic receptor stimulation was used as a functional reporter because decreasing intracellular H(2)O(2) alters the sensitivity of I(Ca-L) to isoproterenol. H(2)O(2) increased the K(0.5) required for activation of I(Ca-L) by isoproterenol from 5.8 to 27.8 nmol/L. This effect and the increase in basal current density persisted for several hours after H(2)O(2). We propose that extracellular H(2)O(2) is associated with an increase in superoxide from the mitochondria caused by an increase in Ca(2+) influx from I(Ca-L). The effect persists because a positive feedback exists among increased basal channel activity, elevated intracellular calcium, and superoxide production by the mitochondria.
Phylum-Wide Analysis of SSU rDNA Reveals Deep Phylogenetic Relationships among Nematodes and Accelerated Evolution toward Crown Clades
Authors: Martijn Holterman, Andre van der Wurff, Sven van den Elsen, Hanny van Megen, Tom Bongers, Oleksandr Holovachov, Jaap Bakker, Johannes Helder
Journal: Molecular Biology and Evolution (2006)

Inference of evolutionary relationships between nematodes is severely hampered by their conserved morphology, the high frequency of homoplasy, and the scarcity of phylum-wide molecular data. To study the origin of nematode radiation and to unravel the phylogenetic relationships between distantly related species, 339 nearly full-length small-subunit rDNA sequences were analyzed from a diverse range of nematodes. Bayesian inference revealed a backbone comprising 12 consecutive dichotomies that subdivided the phylum Nematoda into 12 clades. The most basal clade is dominated by the subclass Enoplia, and members of the order Triplonchida occupy positions most close to the common ancestor of the nematodes. Crown Clades 8–12, a group formerly indicated as “Secernentea” that includes Caenorhabditis elegans and virtually all major plant and animal parasites, show significantly higher nucleotide substitution rates than the more basal Clades 1–7. Accelerated substitution rates are associated with parasitic lifestyles (Clades 8 and 12) or short generation times (Clades 9–11). The relatively high substitution rates in the distal clades resulted in numerous autapomorphies that allow in most cases DNA barcode–based species identification. Teratocephalus, a genus comprising terrestrial bacterivores, was shown to be most close to the starting point of Secernentean radiation. Notably, fungal feeding nematodes were exclusively found basal to or as sister taxon next to the 3 groups of plant parasitic nematodes, namely, Trichodoridae, Longidoridae, and Tylenchomorpha. The exclusive common presence of fungivorous and plant parasitic nematodes supports a long-standing hypothesis that states that plant parasitic nematodes arose from fungivorous ancestors.
Rapamycin Markedly Slows Disease Progression in a Rat Model of Polycystic Kidney Disease
Authors: Yunxia Tao, Jun Kim, Robert W. Schrier, Charles L. Edelstein
Journal: Journal of the American Society of Nephrology (2004)

Increased tubular epithelial cell proliferation is a prerequisite for cyst formation and expansion in polycystic kidney disease (PKD). Rapamycin is a potent antiproliferative agent. The aim of the present study was to determine the effect of rapamycin on tubular cell proliferation, cyst formation, and renal failure in the Han:SPRD rat model of PKD. Heterozygous (Cy/+) and littermate control (+/+) male rats were weaned at 3 wk of age and then treated with rapamycin 0.2 mg/kg per d intraperitoneally or vehicle (ethanol) for 5 wk. Vehicle-treated Cy/+ rats had a more than doubling of kidney size compared with +/+ rats. Rapamycin reduced the kidney enlargement by 65%. Rapamycin significantly reduced the cyst volume density in Cy/+ rats by >40%. Blood urea nitrogen was 59% increased in vehicle-treated Cy/+ rats compared with +/+ rats. Rapamycin reduced the blood urea nitrogen to normal in Cy/+ rats. The number of proliferating cell nuclear antigen (PCNA)-positive cells per noncystic tubule was eightfold increased in vehicle-treated Cy/+ compared with +/+ rats. Rapamycin significantly reduced the number of PCNA-positive cells in noncystic tubules of Cy/+ rats. In addition, the number of PCNA-positive cells per cyst in Cy/+ rats was significantly reduced by rapamycin. In summary, in a rat model of PKD, rapamycin treatment (1) decreases proliferation in cystic and noncystic tubules, (2) markedly inhibits renal enlargement and cystogenesis, and (3) prevents the loss of kidney function.
EFFECTIVE RECRUITMENT AND RETENTION OF MINORITY RESEARCH PARTICIPANTS
Authors: Antronette K. Yancey, Alexander N. Ortega, Shiriki K. Kumanyika
Journal: Annual Review of Public Health (2005)

Our ability, as leaders in public health scholarship and practice, to achieve and measure progress in addressing racial/ethnic disparities in health status and health care is severely constrained by low levels of participation of racial/ethnic minority populations in health-related research. Confining our review to those minority groups federally defined as underrepresented (African Americans/blacks, Latinos/Hispanics, and Native Americans/American Indians), we identified 95 studies published between January 1999 and April 2005 describing methods of increasing minority enrollment and retention in research studies, more than three times the average annual output of scholarly work in this area during the prior 15-year period. Ten themes emerged from the 75 studies that were primarily descriptive. The remaining 20 studies, which directly analyzed the efficacy or effectiveness of recruitment/retention strategies, were examined in detail and provided useful insights related to four of the ten factors: sampling approach/identification of targeted participants, community involvement/nature and timing of contact with prospective participants, incentives and logistical issues, and cultural adaptations. We then characterized the current state of this literature, discussing implications for future research needs and directions.
Frequency of NFKBIA deletions is low in glioblastomas and skewed in glioblastoma neurospheres
Authors: Monica Patanè, Paola Porrati, Elisa Bottega, Sara Morosini, Gabriele Cantini, Vita Girgenti, Ambra Rizzo, Marica Eoli, Bianca Pollo, Francesca L Sciacca, Serena Pellegatta, Gaetano Finocchiaro
Journal: Molecular Cancer (2013)

Abstract The NF-kB family of transcription factors is up-regulated in inflammation and different cancers. Recent data described heterozygous deletions of the NF-kB Inhibitor alpha gene ( NFKBIA ) in about 20% of glioblastomas (GBM): deletions were mutually exclusive with epidermal growth factor receptor ( EGFR ) amplification, a frequent event in GBM. We assessed the status of NFKBIA and EGFR in 69 primary GBMs and in corresponding neurospheres (NS). NFKBIA deletion was investigated by the copy number variation assay (CNV); EGFR amplification by CNV ratio with HGF ; expression of EGFR and EGFRvIII by quantitative PCR or ReverseTranscriptase PCR. Heterozygous deletions of NFKBIA were present in 3 of 69 primary GBMs and, surprisingly, in 30 of 69 NS. EGFR amplification was detected in 36 GBMs: in corresponding NS, amplification was lost in 13 cases and reduced in 23 (10 vs 47 folds in NS vs primary tumors; p &lt; 0.001). The CNV assay was validated investigating HPRT1 on chromosome X in females and males. Results of array-CGH performed on 3 primary GBMs and 1 NS line were compatible with the CNV assay. NS cells with NFKBIA deletion had increased nuclear activity of p65 (RelA) and increased expression of the NF-kB target IL-6. In absence of EGF in the medium, EGFR amplification was more conserved and NFKBIA deletion less frequent point to a low frequency of NFKBIA deletions in GBM and suggest that EGF in the culture medium of NS may affect frequency not only of EGFR amplifications but also of NFKBIA deletions.
Retinoic acid regulation of renal tubular epithelial and vascular smooth muscle cell function.
Authors: R J Anderson, C J Ray, B G Hattler
Journal: Journal of the American Society of Nephrology (1998)

Vitamin A and its derivatives have been postulated to play an important role in renal tubulogenesis and compensatory hypertrophy. This study examined the effects of two carboxylic derivatives of vitamin A on Lewis lung carcinoma-porcine kidney-1 (LLC-PK1) renal tubular epithelial cell mito- and motogenesis and cell size. It was found that all-trans and 13-cis retinoic acids exerted modest, dose-dependent effects to stimulate incorporation of 3H-thymidine into acid-precipitable material of LLC-PK1 cells. The effects of all-trans retinoic acid to promote 3H-thymidine uptake in LLC-PK1 cells modestly enhanced that seen with acidic fibroblastic growth factor. Similar findings of these two retinoic acid derivatives to promote 3H-thymidine uptake and to enhance 3H-thymidine uptake stimulated by another growth factor (platelet-derived growth factor BB) were also observed in cultured bovine aortic smooth muscle cells. Both retinoic acids promoted healing of denuded areas made within confluent monolayers of serum-starved LLC-PK1 cells. All-trans retinoic acid also stimulated recovery of mechanically denuded areas within bovine aortic smooth muscle monolayers. Neither all-trans nor 13-cis retinoic acids s affected cell size as assessed by forward light scatter with flow cytometry, suggesting lack of effect to induce hypertrophy. These results demonstrate that two carboxylic acid derivatives of vitamin A are capable of stimulation of basal and growth factor-induced incorporation of 3H-thymidine uptake into acid-precipitable material and healing of denuded areas in disparate cell types. These findings are compatible with a role for vitamin A and its analogues in the tissue repair process.
Bridging the Gap: Moving Predictive and Prognostic Assays from Research to Clinical Use
Authors: P. Michael Williams, Tracy G. Lively, J. Milburn Jessup, Barbara A. Conley
Journal: Clinical Cancer Research (2012)

Abstract The development of clinically useful molecular diagnostics requires validation of clinical assay performance and achievement of clinical qualification in clinical trials. As discussed elsewhere in this Focus section on molecular diagnostics, validation of assay performance must be rigorous, especially when the assay will be used to guide treatment decisions. Here we review some of the problems associated with assay development, especially for academic investigators. These include lack of expertise and resources for analytical validation, lack of experience in designing projects for a specific clinical use, lack of specimens from appropriate patient groups, and lack of access to Clinical Laboratory Improvement Amendments–certified laboratories. In addition, financial support for assay validation has lagged behind financial support for marker discovery or drug development, even though the molecular diagnostic may be considered necessary for the successful use of the companion therapeutic. The National Cancer Institute supports a large number of clinical trials and a significant effort in drug development. In order to address some of these barriers for predictive and prognostic assays that will be used in clinical trials to select patients for a particular treatment, stratify patients into molecularly defined subgroups, or choose between treatments for molecularly defined tumors, the National Cancer Institute has begun a pilot program designed to lessen barriers to the development of validated prognostic and predictive assays. Clin Cancer Res; 18(6); 1531–9. ©2012 AACR.
IMMOBILIZATION OF TREPONEMA PALLIDUM IN VITRO BY ANTIBODY PRODUCED IN SYPHILITIC INFECTION
Authors: Robert A. Nelson, Manfred M. Mayer
Journal: The Journal of Experimental Medicine (1949)

Treponema pallida were extracted from rabbit testicular syphilomas and suspended in a special medium in which the organisms remain motile and infectious for several days. On incubation of such suspensions with syphilitic rabbit or human sera and guinea pig complement, the treponemes became non-motile and lost their capacity to infect rabbits. Various factors affecting this immobilization have been investigated. In a preliminary survey of individual sera, immobilizing antibody could be detected in the majority of sera from syphilitic animals and human beings, but was absent in almost all the normal sera examined. It could be demonstrated that the immobilizing and reagin activities of syphilis sera are due to separate antibodies.
Type 2 Diabetes and Cognitive Function in Community-Dwelling Elderly Women
Authors: Francine Grodstein, Jennifer Chen, Robert S. Wilson, JoAnn E. Manson
Journal: Diabetes Care (2001)

OBJECTIVE—To examine the relationship of type 2 diabetes to cognitive function in community-dwelling women. RESEARCH DESIGN AND METHODS—From 1995 to 1999, we administered four tests of cognitive function (Telephone Interview of Cognitive Status [TICS], immediate and delayed recall of the East Boston Memory Test, and verbal fluency) by telephone to 2,374 participants (70–78 years of age) of the Nurses’ Health Study. Information on diabetes was collected biennially beginning in 1976; 82 women reported type 2 diabetes before their cognitive testing. We used linear and logistic regression models to calculate multivariate-adjusted mean differences in scores and relative risks of a low score (bottom 10% of the distribution) for diabetic women compared with nondiabetic women. RESULTS—After multivariate adjustment, women with type 2 diabetes scored lower on all our cognitive tests than women without diabetes. On the general test of cognition (TICS), the mean difference in score between women with and without diabetes was −0.60 (95% CI −1.18 to –0.03, P = 0.04) and the relative risk of a low TICS score was 1.98 (95% CI 1.06 to 3.69). On a global score combining results of the four tests, the mean for diabetic women was lower than that among women without diabetes (adjusted difference in score −0.73, 95% CI −1.42 to −0.04, P = 0.04), and the relative risk of a low global score was 2.16 (95% CI 1.10 to 4.21). Relative to women without diabetes, longer duration of diabetes was associated with lower scores. Few diabetic women were pharmacologically treated (n = 31), but those taking medication had scores similar to those of women without diabetes. CONCLUSIONS—In these women, diabetes was related to lower scores on several aspects of cognitive function. Longer duration of diabetes may be associated with poorer scores, but hypoglycemic therapy may ameliorate scores.
Diagnosis of Stable Ischemic Heart Disease: Summary of a Clinical Practice Guideline From the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons
Authors: Amir Qaseem
Journal: Annals of Internal Medicine (2012)

Description: The American College of Physicians (ACP) developed this guideline in collaboration with the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, and Society of Thoracic Surgeons to help clinicians diagnose known or suspected stable ischemic heart disease. Methods: Literature on this topic published before November 2011 was identified by using MEDLINE, Embase, Cochrane CENTRAL, PsychINFO, AMED, and SCOPUS. Searches were limited to human studies published in English. This guideline grades the evidence and recommendations according to a translation of the ACCF/AHA grading system into ACP's clinical practice guidelines grading system. Recommendations: This guideline includes 28 recommendations that address the following issues: the initial diagnosis of the patient who might have stable ischemic heart disease, cardiac stress testing to assess the risk for death or myocardial infarction in patients diagnosed with stable ischemic heart disease, and coronary angiography for risk assessment.