tbuckley/cabot-search huggingface dataset:
Breast Cancer Treatment of Older Women in Integrated Health Care Settings
Authors: Shelley M. Enger, Soe Soe Thwin, Diana S.M. Buist, Terry Field, Floyd Frost, Ann M. Geiger, Timothy L. Lash, Marianne Prout, Marianne Ulcickas Yood, Feifei Wei, Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2006)

A substantial literature describes age-dependent variations in breast cancer treatment, showing that older women are less likely to receive standard treatment than younger women. We sought to identify patient and tumor characteristics associated with the nonreceipt of standard primary tumor and systemic adjuvant therapies.We studied 1,859 women age 65 years or older with stage I and II breast cancer diagnosed between 1990 and 1994 who were cared for in six geographically dispersed community-based health care systems. We collected demographic, tumor, treatment, and comorbidity data from electronic data sources, including cancer registry, administrative, and clinical databases, and from subjects' medical records.Women 75 years of age or older and women with higher comorbidity indices were more likely to receive nonstandard primary tumor therapy, to not receive axillary lymph node dissection, and to not receive radiation therapy after breast-conserving surgery (BCS). Asian women were less likely to receive BCS, and African American women were less likely to be prescribed tamoxifen. Although nonreceipt of most therapies was associated with a lower baseline risk of recurrence, an important minority of high-risk women (16% to 30%) did not receive guideline therapies.Age is an independent risk factor for nonreceipt of effective cancer therapies, even when comorbidity and risk of recurrence are taken into account. Information regarding treatment effectiveness in this age group and tools that allow physicians and patients to estimate the benefits versus the risks of therapies, taking into account age and comorbidity burden, are critically needed.
Vitamin E in Humans: Demand and Delivery
Authors: M G Traber, H Sies
Journal: Annual Review of Nutrition (1996)

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption—a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic α-tocopherol transfer protein also cause vitamin E deficiency—defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of α-tocopherol is recommended to obtain “optimal plasma alpha-tocopherol concentrations” (30 μM or greater).
Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared
Authors: Olivia Keiser, Catherine Orrell, Matthias Egger, Robin Wood, Martin W. G Brinkhof, Hansjakob Furrer, Gilles van Cutsem, Bruno Ledergerber, Andrew Boulle
Journal: PLoS Medicine (2008)

Background The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. Methods and Findings We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24. Conclusions Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
Triage by methylation-marker testing versus cytology in women who test HPV-positive on self-collected cervicovaginal specimens (PROHTECT-3): a randomised controlled non-inferiority trial
Authors: Viola M J Verhoef, Remko P Bosgraaf, Folkert J van Kemenade, Lawrence Rozendaal, Daniëlle A M Heideman, Albertus T Hesselink, Ruud L M Bekkers, Renske D M Steenbergen, Leon F A G Massuger, Willem J G Melchers, Johan Bulten, Lucy I H Overbeek, Johannes Berkhof, Peter J F Snijders, Chris J L M Meijer
Journal: The Lancet Oncology (2014)
Ontogeny of fasting small intestinal motor activity in the human infant.
Authors: W M Bisset, J B Watt, R P Rivers, P J Milla
Journal: Gut (1988)

A clearly defined progression of fasting small intestinal motor development is seen in the human infant from disorganised low amplitude motor activity before 31 weeks gestation through an intermediate phase of increasing motor organisation and amplitude to the development of a normal cyclical pattern of motor activity with clearly defined phase I, II, and III activity between 37 weeks gestation and term. With increasing maturity smooth muscle contractility [gastric antral pressure (5-30 mmHg), average duodenal pressure (2-12 mmHg)], propagation and slow wave frequency (10.5-12.5 cpm) all increased in a significant fashion (p less than 0.01). The stage of development of fasting motor activity in the small intestine of the preterm infant can now be readily predicted from the gestational age of the infant.
Late-breaking abstract: Immediate effects of cigar smoking on control of breathing among young smokers
Authors: Efstathia Konstantinidi, Panagiotis Behrakis, Andreas Lappas, Anna Tzortzi, Charikleia Stathopoulou, Miltiades Vssiliou
Journal: European Respiratory Journal (2014)

Introduction  Immediate effects of cigar smoking on control of breathing have not been comprehensively investigated yet.  Materials and methods  50 young smokers (average age=23±4, 32 males, mean pack-years=3.6) using cigarettes and occasionally cigars voluntarily participated in this study. 25 had mild respiratory symptoms (atopic history, mild cough and exercise induced chest tightness) and mild peripheral airways obstruction (FEF25%-75%=74.15% pred., MRS-subgroup). The other 25 had normal dynamic flows and no respiratory complaints (NRS-subgroup). Mouth occlusion pressure at 0.1 s (P0.1), tidal volume(VT), inspiratory time(Ti), expiratory time(TE), period of the respiratory cycle(TTOT), duty cycle(Ti/TTOT) and mean inspiratory and expiratory flow (VT/Ti and VT/TE) were measured before and immediately after 30 minutes of cigar smoking or equal session in the smoking area without smoking (control group). Wilcoxon signed rank and U-Mann-Whitney rank sum tests were performed for the statistical analysis.  Results   Immediately after 30 minutes of cigar smoking TE and TTOT significantly decreased (-9.27%, p=0.009 and -5.85%, p=0.049) whereas Ti/TE and Ti/TTOT significantly increased (+8.06%, p=0.018 and +4.02%, p=0.021) in the NRS-subgroup. In the MRS-subgroup, only Ti/TTOT was significantly altered (+2.88%, p=0.034). In the whole population (n=50) significant increase of Ti/TE, Ti/TTOT and VT/TE (+6.4%, p=0.006, +3.4%, p=0.002 and +5.8%, p=0.026) and significant decrease of TE and TE/TTOT (-7.5%, p=0.017 and -2.56%, p=0.015) were detected.  Conclusions  Cigar smoking has immediate effects on respiratory timing but not on P0.1 regardless of respiratory complaints and mild peripheral airways obstruction presence.
Interest in physician-assisted suicide (PAS) among Oregon cancer patients
Authors: M. C. Brouns, T. M. Beer, L. K. Ganzini
Journal: Journal of Clinical Oncology (2004)

8070 Background: Oregon remains the only U.S. state where PAS is legal. We sought to determine the level of interest in PAS among cancer patients in OR, how views changed over the course of their illness, psychosocial and medical correlates of interest in PAS, and the relationship between expressing an interest and actually requesting PAS from a physician. Methods: Patients with advanced cancer were recruited from oncology clinics at OHSU and PVAMC. Baseline medical and psychological factors were assessed using standardized instruments; patients were questioned about their attitudes towards and interest in PAS. Patients who expressed an interest in PAS at the initial survey were asked to participate in a longitudinal study. Results: 417 potential subjects were identified and 161 agreed to participate. 57% supported legalization of PAS, 38% might consider PAS for themselves, and 9% indicated a serious interest in obtaining a lethal prescription. Among 42 participants followed longitudinally for 3 to 27 months, 8 expressed interest in a lethal prescription at first evaluation but never subsequently, while 11 expressed interest at some point after the first evaluation. Interest in obtaining a lethal prescription was predicted by increasing hopelessness (p=0.03), decreasing satisfaction with medical care (p=0.002), and increasing suffering (p=0.01). Only 2 patients (1%) made an explicit request for a lethal prescription. 7% of subjects with an interest in PAS at first evaluation had discussed this with their physician, while 42% had on longitudinal follow-up. Conclusions: Interest in PAS among Oregon cancer patients is similar to that previously reported from areas where PAS is not legally sanctioned. Interest is highly variable over time, and few patients make a formal request for a lethal prescription. Less than half discussed this issue with their oncologist. Expressing an interest in PAS on a survey appears to be a marker of psychological and symptom distress, but may be neither sensitive nor specific for identifying patients who actually request PAS under legalized conditions. No significant financial relationships to disclose.
Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
Authors: Arkaitz Carracedo, Li Ma, Julie Teruya-Feldstein, Federico Rojo, Leonardo Salmena, Andrea Alimonti, Ainara Egia, Atsuo T. Sasaki, George Thomas, Sara C. Kozma, Antonella Papa, Caterina Nardella, Lewis C. Cantley, Jose Baselga, Pier Paolo Pandolfi
Journal: Journal of Clinical Investigation (2008)

Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may have therapeutic potential. In this study, we show that rapamycin and its analogs activate the MAPK pathway in human cancer, in what represents a novel mTORC1-MAPK feedback loop. We found that tumor samples from patients with biopsy-accessible solid tumors of advanced disease treated with RAD001, a rapamycin derivative, showed an administration schedule–dependent increase in activation of the MAPK pathway. RAD001 treatment also led to MAPK activation in a mouse model of prostate cancer. We further show that rapamycin-induced MAPK activation occurs in both normal cells and cancer cells lines and that this feedback loop depends on an S6K-PI3K-Ras pathway. Significantly, pharmacological inhibition of the MAPK pathway enhanced the antitumoral effect of mTORC1 inhibition by rapamycin in cancer cells in vitro and in a xenograft mouse model. Taken together, our findings identify MAPK activation as a consequence of mTORC1 inhibition and underscore the potential of a combined therapeutic approach with mTORC1 and MAPK inhibitors, currently employed as single agents in the clinic, for the treatment of human cancers.
Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma
Authors: Roshan Mahabir, Mishie Tanino, Aiman Elmansuri, Lei Wang, Taichi Kimura, Tamio Itoh, Yusuke Ohba, Hiroshi Nishihara, Hiroki Shirato, Masumi Tsuda, Shinya Tanaka
Journal: Neuro-Oncology (2013)

Ionizing irradiation is an effective treatment for malignant glioma (MG); however, a higher rate of recurrence with more aggressive phenotypes is a vital issue. Although epithelial-mesenchymal transition (EMT) is involved in irradiation-induced cancer progression, the role for such phenotypic transition in MG remains unknown. To investigate the mechanism of irradiation-dependent tumor progression in MG, we performed immunohistochemistry (IHC) and qRT-PCR using primary and recurrent MG specimens, MG cell lines, and primary culture cells of MG. siRNA technique was used for MG cell lines. In 22 cases of clinically recurrent MG, the expression of the mesenchymal markers vimentin and CD44 was found to be increased by IHC. In paired identical MG of 7 patients, the expression of collagen, MMPs, and YKL-40 were also elevated in the recurrent MGs, suggesting the The Cancer Genome Atlas-based mesenchymal subtype. Among EMT regulators, sustained elevation of Snail was observed in MG cells at 21 days after irradiation. Cells exhibited an upregulation of migration, invasion, numbers of focal adhesion, and MMP-2 production, and all of these mesenchymal features were abrogated by Snail knockdown. Intriguingly, phosphorylation of ERK1/2 and GSK-3β were increased after irradiation in a Snail-dependent manner, and TGF-β was elevated in both fibroblasts and macrophages but not in MG cells after irradiation. It was noteworthy that irradiated cells also expressed stemness features such as SOX2 expression and tumor-forming potential in vivo. We here propose a novel concept of glial-mesenchymal transition after irradiation in which the sustained Snail expression plays an essential role.
Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel
Authors: Lucas C Duits, K Nadine Phoa, Wouter L Curvers, Fiebo J W ten Kate, Gerrit A Meijer, Cees A Seldenrijk, G Johan Offerhaus, Mike Visser, Sybren L Meijer, Kausilia K Krishnadath, Jan G P Tijssen, Rosalie C Mallant-Hent, Jacques J G H M Bergman
Journal: Gut (2014)

Reported malignant progression rates for low-grade dysplasia (LGD) in Barrett's oesophagus (BO) vary widely. Expert histological review of LGD is advised, but limited data are available on its clinical value. This retrospective cohort study aimed to determine the value of an expert pathology panel organised in the Dutch Barrett's Advisory Committee (BAC) by investigating the incidence rates of high-grade dysplasia (HGD) and oesophageal adenocarcinoma (OAC) after expert histological review of LGD.We included all BO cases referred to the BAC for histological review of LGD diagnosed between 2000 and 2011. The diagnosis of the expert panel was related to the histological outcome during endoscopic follow-up. Primary endpoint was development of HGD or OAC.293 LGD patients (76% men; mean 63 years±11.9) were included. Following histological review, 73% was downstaged to non-dysplastic BO (NDBO) or indefinite for dysplasia (IND). In 27% the initial LGD diagnosis was confirmed. Endoscopic follow-up was performed in 264 patients (90%) with a median follow-up of 39 months (IQR 16-72). For confirmed LGD, the risk of HGD/OAC was 9.1% per patient-year. Patients downstaged to NDBO or IND had a malignant progression risk of 0.6% and 0.9% per patient-year, respectively.Confirmed LGD in BO has a markedly increased risk of malignant progression. However, the vast majority of patients with community LGD will be downstaged after expert review and have a low progression risk. Therefore, all BO patients with LGD should undergo expert histological review of the diagnosis for adequate risk stratification.
Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling
Authors: Moritz Felcht, Robert Luck, Alexander Schering, Philipp Seidel, Kshitij Srivastava, Junhao Hu, Arne Bartol, Yvonne Kienast, Christiane Vettel, Elias K. Loos, Simone Kutschera, Susanne Bartels, Sila Appak, Eva Besemfelder, Dorothee Terhardt, Emmanouil Chavakis, Thomas Wieland, Christian Klein, Markus Thomas, Akiyoshi Uemura, Sergij Goerdt, Hellmut G. Augustin
Journal: Journal of Clinical Investigation (2012)

Angiopoietin-2 (ANG-2) is a key regulator of angiogenesis that exerts context-dependent effects on ECs. ANG-2 binds the endothelial-specific receptor tyrosine kinase 2 (TIE2) and acts as a negative regulator of ANG-1/TIE2 signaling during angiogenesis, thereby controlling the responsiveness of ECs to exogenous cytokines. Recent data from tumors indicate that under certain conditions ANG-2 can also promote angiogenesis. However, the molecular mechanisms of dual ANG-2 functions are poorly understood. Here, we identify a model for the opposing roles of ANG-2 in angiogenesis. We found that angiogenesis-activated endothelium harbored a subpopulation of TIE2-negative ECs (TIE2lo). TIE2 expression was downregulated in angiogenic ECs, which abundantly expressed several integrins. ANG-2 bound to these integrins in TIE2lo ECs, subsequently inducing, in a TIE2-independent manner, phosphorylation of the integrin adaptor protein FAK, resulting in RAC1 activation, migration, and sprouting angiogenesis. Correspondingly, in vivo ANG-2 blockade interfered with integrin signaling and inhibited FAK phosphorylation and sprouting angiogenesis of TIE2lo ECs. These data establish a contextual model whereby differential TIE2 and integrin expression, binding, and activation control the role of ANG-2 in angiogenesis. The results of this study have immediate translational implications for the therapeutic exploitation of angiopoietin signaling.
Androgen Deprivation Increases p300 Expression in Prostate Cancer Cells
Authors: Hannelore V. Heemers, Thomas J. Sebo, Jose D. Debes, Kevin M. Regan, Kristin A. Raclaw, Linda M. Murphy, Alfred Hobisch, Zoran Culig, Donald J. Tindall
Journal: Cancer Research (2007)

Abstract Standard therapy for nonorgan confined prostate cancer aims to block the production or action of androgens. Although initially successful, antiandrogen therapy eventually fails and androgen depletion independent (ADI) disease emerges. Remarkably, ADI prostate cancers still rely on a functional androgen receptor (AR). Aberrant expression of coregulatory proteins required for the formation of productive AR transcriptional complexes is critical for ADI AR activation. Previously, we have shown that the transcriptional coactivator p300 is required for ADI activation of the AR and is up-regulated in prostate cancer, in which its expression is associated with cell proliferation and predicts aggressive tumor features. The mechanism responsible for the deregulated expression of p300, however, remains elusive. Here, we show that p300 expression in prostate cancer cells is subject to androgen regulation. In several prostate cancer model systems, addition of synthetic and natural androgens led to decreased expression of p300 in a time-dependent and dose-dependent manner. Experiments using AR antagonists or small interfering RNA targeting the AR revealed that down-regulation of p300 depends entirely on the presence of a functional AR. It is noteworthy that androgens down-regulated p300 protein expression while leaving messenger levels unaltered. Conversely, both short-term and long-term androgen deprivation resulted in marked up-regulation of p300 expression. The androgen deprivation–induced increase in p300 expression was not affected by the addition of cytokines or growth factors or by cotreatment with antiandrogens. Moreover, increased p300 expression upon androgen starvation is crucial for prostate cancer cell proliferation, as loss of p300 expression severely reduces expression of cyclins governing G1-S and G2-M cell cycle transition and decreases 5-bromo-2′-deoxyuridine incorporation. [Cancer Res 2007;67(7):3422–30]
<i>Psychiatrie,</i> für Aerzte und Studirende, bearbeitet von Dr. Med. Th. Ziehen, o-Professor an der Universität Utrecht. Zweite vollstän-dig umgearbeitete Auflage. Mit 14 Abbildungen in Holzschnitt u. 8. Tafeln in Lichtdruck. Leipzig, Verlag von S. Hirzel, 1902
Authors: A. Meyer
Journal: American Journal of Psychiatry (1902)

353 whereas the latter comes more often from migraine than from epilepsy.(2) Sufferers from migraine often have brothers and sisters who are also afflicted in the same way.(3) Sufferers from migraine often have epileptic seizures, and still more often epileptics have attacks of migraine.Sensory epilepsy often is the equivalent of a genuine migraine.(4) Migraine and epilepsy begin in infancy, tend to become periodic and
CATERPILLER: A Novel Gene Family Important in Immunity, Cell Death, and Diseases
Authors: Jenny P-Y. Ting, Beckley K. Davis
Journal: Annual Review of Immunology (2004)

▪ Abstract The newly discovered CATERPILLER (CLR) gene family encodes proteins with a variable but limited number of N-terminal domains, followed by a nucleotide-binding domain (NBD) and leucine-rich repeats (LRR). The N-terminal domain consists of transactivation, CARD, Pyrin, or BIR domains, with a minority containing undefined domains. These proteins are remarkably similar in structure to the TIR-NBD-LRR and CC-NBD-LRR disease resistance (R) proteins that mediate immune responses in plants. The NBD-LRR architecture is conserved in plants and vertebrates, but only remnants are found in worms and flies. The CLRs regulate inflammatory and apoptotic responses, and some act as sensors that detect pathogen products. Several CLR genes have been genetically linked to susceptibility to immunologic disorders. We describe prominent family members, including CIITA, CARD4/NOD1, NOD2/CARD15, CIAS1, CARD7/NALP1, and NAIP, in more detail. We also discuss implied roles of these proteins in diversifying immune detection and in providing a check-and-balance during inflammation.