tbuckley/cabot-search huggingface dataset:
Prediction of Lymph Node Metastasis in Patients with Endometrioid Endometrial Cancer Using Expression Microarray
Authors: Michael A. Bidus, John I. Risinger, Gadisetti V.R. Chandramouli, Lou A. Dainty, Tracy J. Litzi, Andrew Berchuck, J. Carl Barrett, G. Larry Maxwell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To characterize the gene expression profiles of endometrioid endometrial cancers associated with lymph node metastasis in an effort to identify genes associated with metastatic spread. Experimental Design: Tumors from 41 patients with endometrioid endometrial cancer grossly confined to the uterine cavity were evaluated. Positive lymph nodes were noted in 12 of 41 patients. RNA was analyzed for gene expression using the Affymetrix HG133A and HG133B GeneChip set, representing 45,000 array features covering &amp;gt;28,000 UniGene clusters. Data analysis was done using multidimensional scaling, binary comparison, and hierarchical clustering. Gene expression for several differentially expressed genes was examined using quantitative PCR. Results: Gene expression data was obtained from 30,964 genes that were detected in at least 5% of the cases. Supervised analysis of node-positive versus node-negative cases indicated that 450 genes were significantly differentially expressed between the two classes at P &amp;lt; 0.005, 81 of which were differentially expressed by at least 2-fold at P &amp;lt; 0.005. Overexpressed genes included two cell cycle checkpoint genes, CDC2 and MAD2L1, which have previously been described in association with lymph node metastasis in other cancer types. The ZIC2 zinc finger gene was overexpressed in endometrial cancers with positive nodes versus those with negative nodes. Conclusion: Gene expression profiling of the primary tumors in patients with endometrioid endometrial cancers seems promising for identifying genes associated with lymph node metastasis. Future studies should address whether the status of nodal metastasis can be determined from the expression profiles of preoperative tissue specimens.
The CHRNA5-A3 Region on Chromosome 15q24-25.1 Is a Risk Factor Both for Nicotine Dependence and for Lung Cancer
Authors: Margaret R. Spitz, Christopher I. Amos, Qiong Dong, Jie Lin, Xifeng Wu
Journal: JNCI Journal of the National Cancer Institute (2008)

Common variants in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25.1 were associated with lung cancer risk in three recently published independently conducted genome-wide association studies, with no consensus as to the relative impact of the variants on the propensity to smoke vs a direct carcinogenic effect. To further explore our hypothesis that these variants are indeed associated with both cancer causation and nicotine dependence, we performed a more detailed analysis of the association of these putative risk genotypes with smoking phenotype, as well as in lifetime never smokers, and in other smoking-related cancers. We demonstrate a statistically significant association of the variants with both nicotine dependence, as well as lung cancer phenotypes, including earlier age at lung cancer onset. The variants were associated with higher risks of lung cancer in lower smoking-exposed strata, and in individuals with a strong family history of lung or smoking-related cancers. In contrast, we found no evidence that the variants were associated with elevated risks in 547 lifetime never-smoking lung cancer case subjects, nor in other smoking-related cancers (bladder and renal). Thus, we conclude that the variants are implicated both in smoking behavior and more directly in lung cancer risk.
Activation of β2-Adrenoceptor Prevents Shiga Toxin 2-Induced TNF-α Gene Transcription
Authors: AKIO NAKAMURA, EDWARD J. JOHNS, AKIRA IMAIZUMI, YUKISHIGE YANAGAWA, TAKAO KOHSAKA
Journal: Journal of the American Society of Nephrology (2001)

Exposure of renal tubular epithelial cells to shiga toxin 2 (Stx-2) causes cytotoxicity, and the potency of this toxin is enhanced in the presence of tumor necrosis factor—α (TNF-α). It has been shown that Stx-2 induces TNF-α production and that activation of β2-adrenoceptors downregulates TNF-α. However, little is known about the signaling pathway by which β2-adrenoceptor agonists suppress the Stx-2—induced TNF-α gene transcription. The possible signaling components involved in this pathway were investigated. Human adenocarcinoma—derived renal tubular epithelial cells (ACHN) were exposed to Stx-2 in the presence or absence of a β2-adrenoceptor agonist. Mitogen-activated protein kinase (MAPK), activating protein—1 (AP-1), and nuclear factor—κB (NF-κB) were measured to evaluate the regulatory mechanisms involved in TNF-α gene transcription. Stx-2 (4 pg/ml) stimulated MAPK (p42/p44, p38) and AP-1 and increased TNF-α promoter activity by 2.4-fold. The increase in TNF-α was attenuated by both a p42/p44 inhibitor, PD098059 (10-6 M), and a p38 inhibitor, SB203580 (10-6 M), and AP-1—binding activity was inhibited by PD098059. Terbutaline (10-6 M to 10-8 M) suppressed MAPK (p42/p44, p38), NF-κB (p50, p65), and TNF-α promoter activity in a dose-dependent way that was prevented by the β2-adrenoceptor antagonist, ICI118,551. However, inhibition of MAPK (p42/p44) and TNF-α promoter activity was partially prevented by the cAMP-protein kinase (PKA) inhibitors, H-89 (5 × 10-6 M) and KT5720 (10-5 M), whereas the suppression of p38 MAPK or NF-κB (p50) was not blocked by these inhibitors. The suppression of NF-κB (p65) was completely overcome by H-89 or KT5720. In summary, the downregulation of TNF-α transcription by terbutaline was mediated by an inhibitory effect of β2-adrenoceptor activation on MAPK (p42/p44, p38) and NF-κB (p50/p65), which were exerted through a cAMP-PKA pathway and a cAMP-independent mechanism. It is likely that cAMP-PKA and MAPK (p42/p44, p38) may play a critical role in the regulation of the Stx-2—induced TNF-α transcription via β2-adrenoceptor activation.
A Specific Role for AKT3 in the Genesis of Ovarian Cancer through Modulation of G2-M Phase Transition
Authors: Briony E. Cristiano, Joanna C. Chan, Katherine M. Hannan, Nicole A. Lundie, Nelly J. Marmy-Conus, Ian G. Campbell, Wayne A. Phillips, Melissa Robbie, Ross D. Hannan, Richard B. Pearson
Journal: Cancer Research (2006)

Abstract Ovarian cancer is the major cause of death from gynecological malignancy, and there is an urgent need for new therapeutic targets. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been strongly implicated in the genesis of ovarian cancer. However, to identify and evaluate potential targets for therapeutic intervention, it is critical to understand the mechanism by which the PI3K/AKT pathway facilitates ovarian carcinogenesis. Here, we show that AKT3 is highly expressed in 19 of 92 primary ovarian tumors. Strikingly, purified AKT3 exhibited up to 10-fold higher specific activity than AKT1, potentially amplifying the effects of AKT3 overexpression. Consistent with this finding, AKT3 levels in a range of ovarian cancer cell lines correlated with total AKT activity and proliferation rates, implicating AKT3 as a key mediator of ovarian oncogenesis. Specific silencing of AKT3 using short hairpin RNA markedly inhibited proliferation of the two cell lines with highest AKT3 expression and total AKT activity, OVCA429 and DOV13, by slowing G2-M phase transition. These findings are consistent with AKT3 playing a key role in the genesis of at least one subset of ovarian cancers. (Cancer Res 2006; 66(24): 11718-25)
The differential effects of oestrogens and progestins on vascular tone
Authors: P. Sarrel
Journal: Human Reproduction Update (1999)

The purpose of this paper is to present reported findings of the effects of ovarian steroids on vascular tone. The medical literature was reviewed for relevant contributions. Oestrogen replacement therapy in postmenopausal women is associated with a reduction in mortality from coronary artery disease. Many different cellular actions have been described which help explain the cardioprotective effects of oestrogens, and among these are effects on vascular tone. Oestrogens induce vasodilation through mechanisms involving the arterial endothelium and through endothelial-independent actions. Progestins have varying effects on arterial tone, including induction of vascular smooth muscle relaxation as well as induction of smooth muscle constriction. The effects of oestrogens and progestins on vascular tone are clinically meaningful. Pathophysiological arterial conditions, including angina pectoris and migraine headaches, have been associated with oestradiol deficiency and improvement has been associated with oestradiol replacement. Women with coronary artery disease show improved arterial vasodilator responses after oestradiol treatment which can be reduced by the addition of progestin treatment. Androgens are also vasoactive. Study of the effects of ovarian hormones on vascular tone has become an important area for basic and clinical research. Keywords:arterial tone/cardioprotection/nitric oxide/oestradiol/progestins
A Self-Regulation Program for Maintenance of Weight Loss
Authors: Rena R. Wing, Deborah F. Tate, Amy A. Gorin, Hollie A. Raynor, Joseph L. Fava
Journal: New England Journal of Medicine (2006)

Since many successful dieters regain the weight they lose, programs that teach maintenance skills are needed. We developed a maintenance program based on self-regulation theory and tested the efficacy of delivering the program face to face or over the Internet.We randomly assigned 314 participants who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of three groups: a control group, which received quarterly newsletters (105 participants), a group that received face-to-face intervention (105), and a group that received Internet-based intervention (104). The content of the programs in the two intervention groups was the same, emphasizing daily self-weighing and self-regulation, as was the frequency of contact with the groups. The primary outcome was weight gain over a period of 18 months.The mean (+/-SD) weight gain was 2.5+/-6.7 kg in the face-to-face group, 4.7+/-8.6 kg in the Internet group, and 4.9+/-6.5 kg in the control group, with a significant difference between the face-to-face group and the control group (2.4 kg; 95% confidence interval [CI], 0.002 to 10.8; P=0.05). The proportion of participants who regained 2.3 kg or more over the 18-month period was significantly higher in the control group (72.4%) than in the face-to-face group (45.7%; absolute difference, 27%; 95% CI, 14 to 39; P<0.001) or the Internet group (54.8%; absolute difference, 18%; 95% CI, 5 to 30; P=0.008). Daily self-weighing increased in both intervention groups and was associated with a decreased risk of regaining 2.3 kg or more (P<0.001).As compared with receiving quarterly newsletters, a self-regulation program based on daily weighing improved maintenance of weight loss, particularly when delivered face to face. (ClinicalTrials.gov number, NCT00067145 [ClinicalTrials.gov].)
Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension.
Authors: S Morelli, C Ferri, L Di Francesco, R Baldoncini, M Carlesimo, U Bottoni, G Properzi, A Santucci
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVES--To investigate the behaviour of circulating endothelin-1 (ET-1) in patients affected by systemic sclerosis and to elucidate the relationship between systemic and pulmonary plasma peptide and arterial pressure levels. METHODS--Plasma ET-1 concentrations were determined in 48 patients affected by systemic sclerosis (41 women, seven men; mean age 47.2 (SD 5.5) years) with or without systemic or pulmonary hypertension (or both). A group of 18 normal volunteers served as controls (15 women, three men; mean age 45.0 (10.1) years). RESULTS--Plasma ET-1 levels were significantly greater in patients affected by systemic sclerosis (1.65 (0.29) pg/ml) than in controls (0.63 (0.19) pg/ml) (p &lt; 0.0001). Pulmonary artery systolic hypertension alone was present in 14 patients with systemic sclerosis (50.5 (8.49) mm Hg, range 37-67 mm Hg), and systemic hypertension alone (160.7 (5.9)/100.6 (3.2) mm Hg) was present in 11 patients. Both conditions were present in 12 patients, while 11 patients had systemic hypertension. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension alone (1.62 (0.21) pg/ml) and those with systemic hypertension alone (1.65 (0.43) pg/ml). In particular, patients with normal pulmonary artery and systemic pressures (n = 11) had plasma ET-1 concentrations identical to those found in patients (n = 12) with both pulmonary and systemic hypertension (1.70 (0.15) v 1.64 (0.35) pg/ml, respectively). No correlations were observed between plasma ET-1 and either pulmonary or systemic pressures. CONCLUSION--Systemic sclerosis is characterised by increased plasma ET-1 levels, but neither pulmonary nor systemic hypertension are accompanied by further increase in plasma peptide levels.
Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease
Authors: Takashi Maehara, Masafumi Moriyama, Hitoshi Nakashima, Katsuhisa Miyake, Jun-Nosuke Hayashida, Akihiko Tanaka, Shouichi Shinozaki, Yoshiaki Kubo, Seiji Nakamura
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Interleukin (IL)-21 is mainly produced by CD4 T helper (Th) cells including Th2, Th17 and follicular helper T (Tfh) cells. Recent studies have reported that IL-21 is involved in the formation of germinal centres (GCs) and class switching of IgG4. It has been suggested that IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz9s disease (MD), is distinct from Sjögren9s syndrome (SS) and shows a high frequency of GC formation in salivary glands. In this study the expression of IL-21 in IgG4-DS and SS patients was examined. <h3>Methods</h3> Twelve patients with IgG4-DS, 15 with SS and 15 healthy subjects were screened for (1) ectopic GC formation in formalin-fixed labial salivary gland (LSG) biopsy samples; (2) expression of IL-21, Th2-, Th17- and Tfh-related molecules (cytokines, chemokine receptors and transcription factors) in LSGs; (3) relationship between IgG4/IgG ratio and mRNA expression of IL-21 in LSGs. <h3>Results</h3> mRNA expression of IL-21 and Bcl-6 in LSGs from patients with IgG4-DS was significantly higher than in patients with SS and controls. IL-21 and CXCR5 were detected by immunohistochemistry in or around GC in patients with SS and those with IgG4-DS. IL-21 was detected in infiltrating lymphocytes outside GC only in patients with IgG4-DS. Expression of IL-21 was consistent with that of Th2-related molecules while IL-17 was rarely seen in IgG4-DS. Furthermore, the expression of IL-21 in LSGs was correlated with the number of GC formations and the IgG4/IgG ratio in patients with IgG4-DS. <h3>Conclusions</h3> These results suggest that overexpression of IL-21 by Th2 cells might play a key role in GC formation and IgG4 production in IgG4-DS.
Prophylactic Antibiotic Therapy in Chronic Obstructive Pulmonary Disease
Authors: Samantha C. Herath, Phillippa Poole
Journal: JAMA (2014)

CLINICAL QUESTION Is prophylactic antibiotic treatment associated with fewer exacerbations or improved health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD)? BOTTOM LINE Continuous macrolide antibiotic use for prophylaxis was associated with a clinically significant reduction in COPD exacerbations. Pulsed antibiotic use was not associated with benefit. Continuous and pulsed antibiotics were associated with improved HRQOL, but this was not clinically significant.
Cardiovascular disease and the risk of lung cancer, the HUNT study
Authors: Tore Amundsen, Peter Hatlen, Sven Carlsen, Oyvind Salvesen, Arnulf Langhammer
Journal: European Respiratory Journal (2013)

Background:  Inflammation is involved in both lung cancer (LC) and cardio-vascular disease (CVD).   Aims:  We hypothesize that CVD is an independent risk factor for LC.   Methods:  Data from the Nord-Trondelag Health Study linked to the Norwegian Cancer and Death Cause Registry, analyses stratified by smoking. 97,087 persons (1,634,967 person years), never smokers n=38,656, former smokers n=20,914, current smokers n=26,894, follow-up 15 years. The proportional hazard model (HR CI 95%) for CVD on LC incidence, adjusted for age, sex, BMI, burden of smoking and chronic cough.    Results:  LC = 1,080, cases (1.1%), CVD = 5,981 (6.9%). CVD vs LC in former smokers = HR 1.74 (CI95% 1.11-273), current smokers = HR 1.38 (CI95% 1.04-1.83), never smokers = HR 0.87 (CI95% 03.4-2.23).   Conclusion:  CVD was an independent risk factor for lung cancer in former and current smokers. CVD may be a novel risk factor for lung cancer screening.
Near-Identical Segregation of mtDNA Heteroplasmy in Blood, Muscle, Urinary Epithelium, and Hair Follicles in Twins With Optic Atrophy, Ptosis, and Intractable Epilepsy
Authors: Achilles Spyropoulos, Mark Manford, Rita Horvath, Charlotte L. Alston, Patrick Yu-Wai-Man, Langping He, Robert W. Taylor, Patrick F. Chinnery
Journal: JAMA Neurology (2013)

<h3>Importance</h3> Mitochondrial DNA (mtDNA) disorders have emerged as major causes of inherited neurologic disease. Despite being well recognized for more than 2 decades, the clinical presentation continues to broaden. The phenotypic heterogeneity is partly owing to different percentage levels of mutant mtDNA heteroplasmy in different tissues, but the factors influencing this are poorly understood. <h3>Observations</h3> This case report describes monozygotic male twins with ptosis, optic atrophy, and recent-onset intractable myoclonic epilepsy. The assessment of respiratory chain enzyme activities in the muscle from 1 twin revealed a severe and isolated defect involving mitochondrial complex I. Mitochondrial DNA sequencing revealed a pathogenic m.14487T&gt;C<i>MTND6</i>mutation, which was present at very high levels of heteroplasmy in muscle (84%) and lower levels in blood (15%), urinary epithelium (75%), and buccal mucosa (58%). Of particular interest, his identical twin was found to harbor very similar levels of the m.14487T&gt;C mutation in his blood, urine, buccal mucosa, and hair follicle DNA samples, while the presence of low levels in the mother’s tissues confirmed maternal transmission. <h3>Conclusions and Relevance</h3> It was shown that m14487T&gt;C can also cause the unusual combination of optic atrophy, ptosis, and encephalomyopathy leading to intractable seizures. Near-identical heteroplasmy levels in different tissues in both siblings support a nuclear genetic mechanism controlling the tissue segregation of mtDNA mutations.
Prognostic Significance of E-Cadherin Protein Expression in Pathological Stage I-III Endometrial Cancer
Authors: Loren K. Mell, Jeffrey J. Meyer, Maria Tretiakova, Andrey Khramtsov, Can Gong, S. Diane Yamada, Anthony G. Montag, Arno J. Mundt
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endometrial cancer. Experimental Design: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as “3” if &amp;gt;75%, “2” if 25–75%, “1” if 5–25%, and “0” if &amp;lt;5% of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. Results: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4%, 18.6%, 26.5%, 25.5% of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall τ: 0.30, P &amp;lt; 0.01), and negatively correlated with grade (Kendall τ: −0.13, P = 0.15) and papillary serous or clear cell histology (Kendall τ: −0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1–2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0% (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5% (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2% (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0% (P = 0.17). On multivariate Cox regression, a higher E-cadherin expression score was associated with decreased overall mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.34–1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95% CI, 0.055–0.94; P = 0.040), disease progression (HR, 0.28; 95% CI, 0.10–0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95% CI, 0.062–0.97; P = 0.045). Conclusions: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.
Neurotensin-like immunoreactivity after intestinal resection in the rat.
Authors: P S Olsen, J H Pedersen, S S Poulsen, Y Yamashita, P Kirkegaard
Journal: Gut (1987)

Neurotensin is a tridecapeptide located mainly in the distal small intestine. The present study was carried out in order to investigate the neurotensin response after proximal small intestinal resection in the rat. After resection, the median plasma concentration of neurotensin like immunoreactivity (NTLI) was unchanged compared with sham operated rats. Intragastric instillation of fat increased the plasma concentration of NTLI from 45 pmol/l (34-63) in sham operated rats to 92 pmol/l (46-121) in resected rats. No significant increase in the plasma concentration of NTLI was found after intragastric instillation of amino acids or glucose. The tissue concentration of NTLI increased significantly in the jejunum and ileum after proximal small intestinal resection, while the number of immunoreactive neurotensin cells was unchanged. This study shows that the adaptive responses in the distal small intestine after proximal small intestinal resection also involve the neurotensin producing cells.