tbuckley/cabot-search huggingface dataset:
Ethnicity, Insulin Resistance, and Inflammatory Adipokines in Women at High and Low Risk for Vascular Disease
Authors: Josef V. Silha, B.L. Grégoire Nyomba, William D. Leslie, Liam J. Murphy
Journal: Diabetes Care (2007)

We sought to compare the relationship between body composition, insulin resistance, and inflammatory adipokines in Aboriginal Canadian women, who are at high risk of vascular disease, with white women.A subgroup of the First Nations Bone Health Study population, consisting of 131 Aboriginal women and 132 matched white women, was utilized. Body composition was determined by whole-body dual X-ray absorptiometry, and blood analytes were measured after an overnight fast.After excluding individuals with diabetes, A1C, BMI, percent trunk fat, and homeostasis model assessment of insulin resistance (HOMA-IR) were greater in First Nation women compared with white women, whereas adiponectin, retinol binding protein (RBP)4, and insulin-like growth factor binding protein-1 (IGFBP-1) were lower. First Nation women had more trunk fat for any given level of total fat than white women. There were no differences in resistin, leptin, tumor necrosis factor (TNF)-alpha, or C-reactive protein (CRP) levels between First Nation and white women. Insulin resistance correlated with leptin and inversely with adiponectin levels in both First Nation and white women. There were weak correlations between insulin resistance and TNF-alpha, interleukin-6, and CRP, but these were not significant after correction for body fat. No correlation was found between RBP4 and insulin resistance. ANCOVA revealed a higher HOMA-IR adjusted for total body fat in First Nation women than in white women (P = 0.015) but not HOMA-IR adjusted for trunk fat (P > 0.2).First Nation women are more insulin resistant than white women, and this is explained by trunk fat but not total fat. Despite the increased insulin resistance, inflammatory adipokines are not significantly increased in First Nation women compared with white women.
On the heritability of psoriatic arthritis. Disease concordance among monozygotic and dizygotic twins
Authors: O B Pedersen, A J Svendsen, L Ejstrup, A Skytthe, P Junker
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> A nationwide unselected twin population to estimate the relative importance of genetic and environmental effectors in the aetiopathogenesis of psoriatic arthritis (PsA). <h3>Methods:</h3> The study comprised three Danish nationwide twin cohorts. In 1994 and 2002 a total of 37 388 and 46 418 Danish twin individuals respectively were asked by questionnaire if they had PsA. Twins reporting PsA were invited to participate in a clinical examination. Patients were classified according to the Moll and Wright and the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria. Heritability was estimated by probandwise concordance rates and variance component analysis. <h3>Results:</h3> 228 twin individuals reported PsA. Following diagnostic validation in 164 (70%), 50 probands were diagnosed with PsA according to the Moll and Wright criteria. Five of their co-twins were either dead, had emigrated, or did not participate in the twin study and nine did not respond, resulting in 36 complete pairs. A total of one of 10 monozygotic pairs and one of 26 dizygotic pairs were concordant for PsA, yielding a 6.2% difference in proportions (95% CI: −11%, 37%). Five of 10 monozygotic pairs and four of 26 dizygotic pairs were concordant for psoriatic skin disease implying a 35% difference (95% CI: 2%, 60%, p&lt;0.05). <h3>Conclusions:</h3> This first twin study on PsA confirms that genes are important in the causation of psoriatic skin disease. Despite the limited statistical power, the almost identical concordance rates for PsA in monozygotic and dizygotic twins stresses the importance of the continued search for non-genetic effectors in PsA.
Decreased Expression of Retinoid Receptors in Melanoma: Entailment in Tumorigenesis and Prognosis
Authors: Nitin Chakravarti, Reuben Lotan, Abdul H. Diwan, Carla L. Warneke, Marcella M. Johnson, Victor G. Prieto
Journal: Clinical Cancer Research (2007)

Retinoids inhibit proliferation and induce differentiation in melanoma cells. Retinoic acid receptors (RAR) and retinoid X receptors (RXR) mediate the various modulatory effects of retinoids in cells. We have studied the in situ expression of each RAR and RXR protein (alpha, beta, gamma) in a large series of melanocytic lesions and correlated the expression with clinicopathologic features and prognosis of the patients.Tissue microarray blocks of 226 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic and nuclear expression of RAR and RXR protein (alpha, beta, gamma).A significant decrease of RARbeta protein (P < 0.0001), nuclear expression of RARgamma (P < 0.0001), and RXRalpha (P < 0.0001) was found in primary and metastatic melanomas as compared with nevi. Loss of nuclear immunoreactivity for RARgamma (P = 0.048) and RXRalpha (P = 0.001) was observed in the lesions showing vertical growth pattern. In addition, in patients with concomitant loss of cytoplasmic staining for RARalpha and RXRalpha, the probability of overall survival (log-rank test, P = 0.002) and disease-specific survival (log-rank test, P = 0.014) was significantly lower.Aberrant expression of retinoid receptors seems to be a frequent event in melanoma and suggests an impairment of the retinoid pathway in this cancer. Our data indicate the loss of retinoid receptor expression with melanoma progression and suggest a possible prognostic significance of the analysis of retinoid receptors in melanoma.
Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation
Authors: Ginna G. Laport, Bruce L. Levine, Edward A. Stadtmauer, Stephen J. Schuster, Selina M. Luger, Stephan Grupp, Nancy Bunin, Frank J. Strobl, Julio Cotte, Zhaohui Zheng, Brian Gregson, Patricia Rivers, Robert H. Vonderheide, David N. Liebowitz, David L. Porter, Carl H. June
Journal: Blood (2003)
Mechanisms of<i>egfr</i>Gene Transcription Modulation: Relationship to Cancer Risk and Therapy Response
Authors: Burkhard Brandt, Sönke Meyer-Staeckling, Hartmut Schmidt, Konstantin Agelopoulos, Horst Buerger
Journal: Clinical Cancer Research (2006)

Abstract The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation, and motility of normal as well as cancer cells. For predictive cancer diagnostics and therapeutic targeting of EGFR, it is important to know how the expression level of EGFR is controlled and related to receptor signaling. A novel transcriptional regulation mechanism has been described that depends on the length of a CA repeat in intron 1 [CA simple sequence repeat 1 (CA SSR I)] of the EGFR gene. Thereby, the number of CA repeats is inversely correlated to pre-mRNA synthesis. Indirect evidence for the importance of this mechanism includes the preferential occurrence of amplifications in cancer tissue harboring short CA repeats in this sequence and the discovery of distinct alleles in young breast cancer patients with a family history of the disease and in Japanese breast cancer patients. It can be postulated that the length of the CA repeat influences DNA bendability and, in consequence, the binding of repressor proteins. In summary, it seems that the CA SSR I represents an inherited variable for response to anti-EGFR therapies that could be determined before therapy. Moreover, the potential for synergistic effects with other polymorphism [e.g., EGFR R497K (HER-1 497K) and CCND1 A870G] leading to a simultaneous increase of EGFR signaling activity and expression should be investigated. From a practical perspective, assessment of the CA SSR I number of CA dinucleotide repeats as a predictor for clinical outcome is very attractive because it is a constant feature that does not change over time and can be easily measured in normal and cancer tissues (blood cells, skin, and tumor biopsies) in an assay that is technically simple, objective, and even quantitative.
Translocation of <i>Helicobacter pylori</i> CagA into Human B Lymphocytes, the Origin of Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Wei-Cheng Lin, Hwei-Fang Tsai, Sung-Hsin Kuo, Ming-Shiang Wu, Chung-Wu Lin, Ping-I Hsu, Ann-Lii Cheng, Ping-Ning Hsu
Journal: Cancer Research (2010)

Abstract Infection by cagA-positive Helicobacter pylori (H. pylori) is strongly associated with gastric carcinomas and gastric mucosa–associated lymphoid tissue (MALT) lymphomas. H. pylori translocates the bacterial protein CagA into gastric epithelial cells, and the translocated CagA deregulates intracellular signaling pathways and thereby initiates pathogenesis. This in turn raised the possibility that H. pylori is associated with the development of MALT lymphomas during persistent infection by direct interaction with B lymphocytes. In this work, we showed that CagA can be directly translocated into human B lymphoid cells by H. pylori, and the translocated CagA undergoes tyrosine phosphorylation and binds to intracellular SH-2. Meanwhile, the translocated CagA induces activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in human B lymphoid cells, and upregulates the expressions of Bcl-2 and Bcl-XL, which prevents apoptosis. These results provide the first direct evidence for the role of CagA as a bacterium-derived oncoprotein that acts in human B cells, and further implies that CagA is directly delivered into B cells by H. pylori and is associated with the development of MALT lymphomas. Cancer Res; 70(14); 5740–8. ©2010 AACR.
Sun Exposure and Mortality From Melanoma
Authors: M. Berwick, B. K. Armstrong, L. Ben-Porat, J. Fine, A. Kricker, C. Eberle, R. Barnhill
Journal: JNCI Journal of the National Cancer Institute (2005)

Melanoma incidence and survival are positively associated, both geographically and temporally. Solar elastosis, a histologic indicator of cutaneous sun damage, has also been positively associated with melanoma survival. Although these observations raise the possibility that sun exposure increases melanoma survival, they could be explained by an association between incidence and early detection of melanoma. We therefore evaluated the association between measures of skin screening and death from cutaneous melanoma.Case subjects (n = 528) from a population-based study of cutaneous melanoma were followed for an average of more than 5 years. Data, including measures of intermittent sun exposure, perceived awareness of the skin, skin self-screening, and physician screening, were collected during in-person interviews and review of histopathology and histologic parameters (i.e., solar elastosis, Breslow thickness, and mitoses) for all of the lesions. Competing risk models were used to compute risk of death (hazard ratios [HRs], with 95% confidence intervals [CIs]) from melanoma. All statistical tests were two-sided.Sunburn, high intermittent sun exposure, skin awareness histories, and solar elastosis were statistically significantly inversely associated with death from melanoma. Melanoma thickness, mitoses, ulceration, and anatomic location on the head and neck were statistically significantly positively associated with melanoma death. In a multivariable competing risk analysis, skin awareness (with versus without, HR = 0.5, 95% CI = 0.3 to 0.9, P = .022) and solar elastosis (present versus absent, HR = 0.4, 95% CI = 0.2 to 0.8, P = .009) were strongly and independently associated with melanoma death after adjusting for Breslow thickness, mitotic index, and head and neck location, which were also independently associated with death.Sun exposure is associated with increased survival from melanoma.
THE INTERCONVERTIBILITY OF "R" AND "S" FORMS OF PNEUMOCOCCUS
Authors: Martin H. Dawson
Journal: The Journal of Experimental Medicine (1928)

1. Single cell cultures of "R" pneumococci may revert in all respects to the "S" type. 2. In all instances in which reversion has occurred the "R" forms have invariably reverted to the same specific type from which they were originally derived. 3. The transformation "R" to "S" may be effected in vitro by growth in anti-"R" sera, as well as in vivo by the method of animal passage. 4. Reversion from "R" to "S" whether effected in vivo or in vitro, is always accompanied by the acquisition of maximal virulence.
Targeted Disruption of the Leukotriene B4Receptor in Mice Reveals Its Role in Inflammation and Platelet-Activating Factor–Induced Anaphylaxis
Authors: Bodduluri Haribabu, Margrith W. Verghese, Douglas A. Steeber, Dwight D. Sellars, Cheryl B. Bock, Ralph Snyderman
Journal: The Journal of Experimental Medicine (2000)

Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) act through G protein–coupled receptors LTB4 receptor (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR, we produced mice with a targeted disruption of the BLTR gene. Mice deficient for BLTR (BLTR−/−) developed normally and had no apparent hematopoietic abnormalities. Peritoneal neutrophils from BLTR−/− mice displayed normal responses to the inflammatory mediators C5a and platelet-activating factor (PAF) but did not respond to LTB4 for calcium mobilization or chemotaxis. Additionally, LTB4 elicited peritoneal neutrophil influx in control but not in BLTR−/− mice. Thus, BLTR is the sole receptor for LTB4-induced inflammation in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in response to arachidonic acid was significantly reduced in BLTR−/− mice. In mice, intravenous administration of PAF induces immediate lethal anaphylaxis. Surprisingly, female BLTR−/− mice displayed selective survival (6 of 9; P = 0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an unexpected sex-related involvement in PAF-induced anaphylaxis.
Abstract P1-12-10: Tamoxifen treated patients have a better survival than patients treated with aromatase inhibitors - A population based registry study in Sweden
Authors: Håkan Olsson, Rickard Einefors, Per Broberg
Journal: Cancer Research (2015)

Background. Randomised trials suggest that therapy with aromatase inhibitors improves survival in breast cancer compared with tamoxifen therapy in postmenopausal cases with hormone receptor positive breast cancer. Whether these results from randomized studies transform into the general population is unknown. We have therefore compared survival for all breast cancer cases in Sweden diagnosed 2000-2008 (n=54406) who received adjuvant antihormonal therapy.Material and methods. The study includes all women with BC diagnosed in Sweden between 2000 through 2008 (n=54406). The women had no previous cancer diagnosis during the period of 1958-1999. Dates of birth, BC diagnosis and TNM-stage where directly extracted from the cancer registry. The women’s antihormonal therapy was gathered from the Swedish Prescription Registry (22213 women were on antihormonal therapy). Information regarding the cause of death and date of death was obtained from the Cause of Death Registry and tbe Swedish Population Register up until the 31st of December 2012 and 31st of December 2013 respectively. The breast cancer death and overall death have been calculated and the survival was compared between tamoxifen and aromatase inhibitor treated breast cancer patients. Analyses were adjusted for TNM-stage and age at diagnosis and restricted to women aged 50 and above.Results. Patients being treated with tamoxifen had a better breast cancer prognosis compared with aromatase inhibitor treated patients (HR 0.54, 95%CI 0.48-0.61). Restricting the analysis to stage 1 disease confirmed a better prognosis for tamoxifen treated women (HR 0.48, 95%CI 0.34-0.66). A better prognosis could be seen in all age strata studies, 50-60.61-70.71-90. The findings for overall survival gave similar results.Conclusion .This population based observational study show that women treated with aromatase inhibitors have a worse overall and breast cancer specific survival compared with tamoxifen treated women regardless of age and tumor stage.Citation Format: Håkan Olsson, Rickard Einefors, Per Broberg. Tamoxifen treated patients have a better survival than patients treated with aromatase inhibitors - A population based registry study in Sweden [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-10.
Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry
Authors: Jens Koopmann, Zhen Zhang, Nicole White, Jason Rosenzweig, Neal Fedarko, Sanjay Jagannath, Marcia I. Canto, Charles J. Yeo, Daniel W. Chan, Michael Goggins
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Each year in the United States, ∼ 30,000 people die from pancreatic cancer. Fewer than 5% of patients survive &amp;gt;5 years after diagnosis, because most patients present with advanced disease. Early diagnosis may improve the prognosis of patients with pancreatic cancer. Experimental Design: In an attempt to improve on current approaches to the serological diagnosis of pancreatic cancer, we analyzed serum samples from patients with and without pancreatic cancer using surface-enhanced laser desorption and ionization (SELDI) protein chip mass spectrometry. Using a case-control study design, serum samples from 60 patients with resectable pancreatic adenocarcinoma were compared with samples from 60 age- and sex-matched patients with nonmalignant pancreatic diseases, as well as 60 age- and sex-matched healthy controls. To increase the number of proteins potentially identifiable, serum was fractionated using anion exchange and profiled on two ProteinChip surfaces (metal affinity capture and weak cation exchange). Results: We determined a minimum set of protein peaks able to discriminate between patient groups and used the unified maximum separability algorithm to compare the performance of the individual marker panels alone or in conjunction with CA19–9. Among the peaks identified by SELDI profiling that had the ability to distinguish between patient groups, the 2 most discriminating protein peaks could differentiate patients with pancreatic cancer from healthy controls with a sensitivity of 78% and specificity of 97%. These 2 markers performed significantly better than the current standard serum marker, CA19–9 (P &amp;lt; 0.05). The diagnostic accuracy of the 2 markers was improved by using them in combination with CA 19-9. Similarly, a combination of 3 SELDI markers and CA19–9 was superior to CA19–9 alone in distinguishing individuals with pancreatic cancer from the combined pancreatic disease controls and healthy subject groups (P = 0.078). SELDI markers were also better than CA19–9 in distinguishing patients with pancreatic cancer from those with pancreatitis. Conclusion: SELDI profiling of serum can be used to accurately differentiate patients with pancreatic cancer from those with other pancreatic diseases and from healthy controls.
SOX4 Induces Epithelial–Mesenchymal Transition and Contributes to Breast Cancer Progression
Authors: Jianchao Zhang, Qian Liang, Yang Lei, Min Yao, Lili Li, Xiaoge Gao, Jingxin Feng, Yu Zhang, Hongwen Gao, Dong-Xu Liu, Jun Lu, Baiqu Huang
Journal: Cancer Research (2012)

Epithelial-mesenchymal transition (EMT) is a developmental program, which is associated with breast cancer progression and metastasis. Here, we report that ectopic overexpression of SOX4 in immortalized human mammary epithelial cells is sufficient for acquisition of mesenchymal traits, enhanced cell migration, and invasion, along with epithelial stem cell properties defined by the presence of a CD44(high)/CD24(low) cell subpopulation. SOX4 positively regulated expression of known EMT inducers, also activating the TGF-β pathway to contribute to EMT. SOX4 itself was induced by TGF-β in mammary epithelial cells and was required for TGF-β-induced EMT. Murine xenograft experiments showed that SOX4 cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in clinical specimens of human breast cancer, we found that SOX4 was abnormally overexpressed and correlated with the triple-negative breast cancer subtype (ER(-)/PR(-)/HER2(-)). Our findings define an important function for SOX4 in the progression of breast cancer by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.
White Blood Cells Telomere Length Is Shorter in Males With Type 2 Diabetes and Microalbuminuria
Authors: Nicholas Tentolouris, Rosine Nzietchueng, Valerie Cattan, Gaël Poitevin, Patrick Lacolley, Athanasia Papazafiropoulou, Despoina Perrea, Nicholas Katsilambros, Athanase Benetos
Journal: Diabetes Care (2007)

To examine differences in telomere (terminal restriction fragment [TRF]) length and pulse wave velocity (PWV)--an index of arterial stiffness--in patients with type 2 diabetes with and without microalbuminuria (MA).A total of 84 men with type 2 diabetes, 40 with MA and 44 without MA (aged 63.5 +/- 9.0 vs. 61.2 +/- 9.8 years), were studied. TRF length was determined in white blood cells. MA was defined as albumin excretion rate (AER) in the range of 30-300 mg/24 h in at least two of three 24-h urine collections. PWV was assessed using applanation tonometry. Markers of oxidative stress were also measured.TRF length was shorter in patients with MA than in those without MA (6.64 +/- 0.74 vs. 7.23 +/- 1.01 kb, respectively, P = 0.004). PWV was significantly higher in the patients with MA. Multivariate linear regression analysis in the total sample demonstrated an independent association between TRF length and age (P = 0.02), MA status (P = 0.04) or AER (P = 0.002), and plasma nitrotyrosine levels (P = 0.02). AER was associated significantly with PWV (P < 0.01).Subjects with type 2 diabetes and MA have shorter TRF length and increased arterial stiffness than those without MA. Additionally, TRF length is associated with age, AER, and nitrosative stress. As shorter TRF length indicates older biological age, the increased arterial stiffness in patients with type 2 diabetes who have MA may be due to the more pronounced "aging " of these subjects.
Hemodynamic Patterns during Desynchronized Sleep in Intact Cats and in Cats with Sinoaortic Deafferentation
Authors: TOKAO KUMAZAWA, GIORGIO BACCELLI, MAURIZIO GUAZZI, GIUSEPPE MANCIA, ALBERTO ZANCHETTI
Journal: Circulation Research (1969)

In unanesthetized, unrestrained cats, placed in a sound-attenuated cage, stroke volume and cardiac output were continuously monitored by an electromagnetic flow transducer chronically implanted around the ascending aorta, arterial pressure was measured by means of a femoral catheter connected to a strain-gauge transducer, and heart rate by a cardiotachograph. Total resistance was computed by dividing arterial pressure by cardiac output. Electroencephalograms, cervical electromyogram, and ocular movements were also monitored to obtain evidence of naturally occurring sleep. In animals with intact sinoaortic reflexes the fall in arterial pressure occurring during desynchronized sleep was associated with a small decrease in cardiac output and a relatively greater reduction in total resistance. After sinoaortic deafferentation, the conspicuously exaggerated fall in arterial pressure occurring during the same type of sleep was almost entirely due to a parallel exaggeration of the reduction in total resistance; changes in cardiac output were only slightly greater than before deafferentation. Only in the few episodes of desynchronized sleep in which extreme hypotension was accompanied by signs of cerebral anoxia, did cardiac output greatly decrease; in these cases, calculated resistance was found to increase. Both small and large changes in cardiac output were independent of heart innervation.