tbuckley/cabot-search huggingface dataset:
Multiple Mechanisms of Telomere Maintenance Exist in Liposarcomas
Authors: Jay E. Johnson, Robert J. Varkonyi, Jaclyn Schwalm, Ryan Cragle, Andres Klein-Szanto, Arthur Patchefsky, Edna Cukierman, Margaret von Mehren, Dominique Broccoli
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Telomeres are specialized nucleoprotein complexes that protect and confer stability upon chromosome ends. Loss of telomere function as a consequence of proliferation-associated sequence attrition results in genome instability, which may facilitate carcinogenesis by generating growth-promoting mutations. However, unlimited cellular proliferation requires the maintenance of telomeric DNA; thus, the majority of tumor cells maintain their telomeres either through the activity of telomerase or via a mechanism known as alternative lengthening of telomeres (ALT). Recent data suggest that constitutive telomere maintenance may not be required in all tumor types. Here we assess the role and requirement of telomere maintenance in liposarcoma. Experimental Design: Tumor samples were analyzed with respect to telomerase activity, telomere length, and the presence of ALT-specific subcellular structures, ALT-associated promyelocytic leukemia nuclear bodies. This multiassay assessment improved the accuracy of categorization. Results: Our data reveal a significant incidence (24%) of ALT-positive liposarcomas, whereas telomerase is used at a similar frequency (27%). A large number of tumors (49%) do not show characteristics of telomerase or ALT. In addition, telomere length was always shorter in recurrent disease, regardless of the telomere maintenance mechanism. Conclusions: These results suggest that approximately one half of liposarcomas either employ a novel constitutively active telomere maintenance mechanism or lack such a mechanism. Analysis of recurrent tumors suggests that liposarcomas can develop despite limiting or undetectable activity of a constitutively active telomere maintenance mechanism.
Bone lesions in primary amyloidosis
Authors: Ali Khojasteh, Lowry K. Arnold, Mehdi Farhangi
Journal: American Journal of Hematology (1979)

Abstract Amyloidosis primarily involving bone is described in a 59‐year‐old male patient. Well circumscribed lytic lesions of the skeleton raised the possibility of myelomatosis. The prolonged insidious course of the disease was uncomplicated by hypercalcemia, pathological fracture, or hematologic abnormalities. The clinical course, together with histological findings and strongly positive bone scan, were the distinguishing features. The osseous manifestation without plasma cell tumor appears to be a rare occurrence in amyloidosis.
Neighborhood Socioeconomic Status, Race, and Mortality in Young Adult Dialysis Patients
Authors: Tanya S Johns, Michelle M Estrella, Deidra C Crews, Lawrence J Appel, Cheryl A M Anderson, Patti L Ephraim, Courtney Cook, L Ebony Boulware
Journal: Journal of the American Society of Nephrology (2014)

Young blacks receiving dialysis have an increased risk of death compared with whites in the United States. Factors influencing this disparity among the young adult dialysis population have not been well explored. Our study examined the relation of neighborhood socioeconomic status (SES) and racial differences in mortality in United States young adults receiving dialysis. We merged US Renal Data System patient-level data from 11,027 black and white patients ages 18-30 years old initiating dialysis between 2006 and 2009 with US Census data to obtain neighborhood poverty information for each patient. We defined low SES neighborhoods as those neighborhoods in U.S. Census zip codes with ≥20% of residents living below the federal poverty level and quantified race differences in mortality risk by level of neighborhood SES. Among patients residing in low SES neighborhoods, blacks had greater mortality than whites after adjusting for baseline demographics, clinical characteristics, rurality, and access to care factors. This difference in mortality between blacks and whites was significantly attenuated in higher SES neighborhoods. In the United States, survival between young adult blacks and whites receiving dialysis differs by neighborhood SES. Additional studies are needed to identify modifiable factors contributing to the greater mortality among young adult black dialysis patients residing in low SES neighborhoods.
Head actinomycetoma with a double aetiology, caused by<i>Nocardia brasiliensis</i>and<i>N. asteroides</i>
Authors: N. Soto-Mendoza, A. Bonifaz
Journal: British Journal of Dermatology (2000)

We describe a 64‐year‐old man with an actinomycetoma of the frontal region of the head caused simultaneously by two aetiological agents, Nocardia brasiliensis and N. asteroides. This case is presented due to the unusual body site affected and, above all, because two aetiological agents were isolated.
Single center outcomes of laparoscopic transperitoneal lateral adrenalectomy – Lessons learned after 500 cases: A retrospective cohort study
Authors: Michał Pędziwiatr, Mateusz Wierdak, Mateusz Ostachowski, Michał Natkaniec, Magdalena Białas, Alicja Hubalewska-Dydejczyk, Maciej Matłok, Piotr Major, Piotr Budzyński, Marcin Migaczewski, Andrzej Budzyński
Journal: International Journal of Surgery (2015)

Although laparoscopic adrenalectomy is considered relatively safe, the results of treatment vary depending on the profile of the hospital. We would like to present our experience with laparoscopic surgery of the adrenals.We conducted a retrospective cohort study of consecutive patients operated for adrenal tumours in the years 2003-2014. The study group included 175 (35%) men and 325 (65%) women. The entire group was divided into 4 cohorts of 125 consecutively operated patients. Primary outcomes were operative measures (operative time, its correlation with tumour size, blood loss, conversion rate, use of peritoneal drainage). Secondary outcomes were the intra- and postoperative complications (using the Clavien-Dindo classification), histological type of the tumours and length of hospital stay.There were no differences between groups in terms of the size and location of the tumour. The mean operative time in each group was 85.7; 83.7; 89.6; 104.6 min (p < 0.001). The operative time correlated to the size of the tumour. There were no differences in the conversion rates as well as in the blood loss. However, it was observed that the complication rate was declining in subsequent subgroups (14.4%, 11.2%, 8% and 5.6%, respectively, p = 0.013). Length of hospital stay was 4.9 days, 3.9 days, 2.9 days, 2.4 days, respectively (p < 0.001).The results of laparoscopic adrenalectomy depend not only on the experience of the single surgeon, but on the whole team involved in perioperative care. In high volume centers with extensive experience in surgery of adrenals, this technique may provide an alternative to open surgery, also in selected cases of malignant tumours.
The NBPF1 Promoter Has Been Recruited from the Unrelated EVI5 Gene Before Simian Radiation
Authors: K. Vandepoele, V. Andries, F. van Roy
Journal: Molecular Biology and Evolution (2009)

Most new genes arise through the duplication of existing genes. In most cases, the duplication is not limited to the coding sequence but encompasses the regulatory region as well. The NBPF gene family has expanded during recent primate evolution, and it has no known mouse ortholog. One of its members, NBPF1, was found to be disrupted by a constitutional translocation in a neuroblastoma patient. Here, we show that the ancestral NBPF gene copied the regulatory region from an unrelated gene, EVI5, after the split between simians and prosimians but before simian radiation. Phylogenetic analysis points to the possible involvement of positive selection acting on the NBPF1 promoter in the simian lineage. We previously showed decreased NBPF1 expression in certain neuroblastoma cell lines. Here, we show that this expression pattern is mimicked by the EVI5 gene, but partly by different mechanisms. Epigenetic regulation of the EVI5 promoter is common in neuroblastoma cell lines, but it is not for the NBPF promoters. Here, we describe the recent acquisition of the NBPF1 promoter from an unrelated gene, and remarkably, both the donor (EVI5) and acceptor (NBPF1) genes are disrupted by constitutional translocations in patients with neuroblastoma, suggesting a functional link between these genes and the disease.
Kaposi's Sarcoma–Associated Herpesvirus: A New DNA Tumor Virus
Authors: C. Boshoff, Y. Chang
Journal: Annual Review of Medicine (2001)

▪ Abstract Kaposi's sarcoma–associated herpesvirus (KSHV) is a newly identified gammaherpesvirus associated with all clinical forms of Kaposi's sarcoma (KS), body-cavity–based, primary effusion lymphomas (PELs), and a subset of Castleman's disease (CD). Sequence analysis of the KSHV genome demonstrates an extensive array of genes with homology to cellular genes involved in cell cycle regulation, cell proliferation, apoptosis, and immune modulation. Functional studies indicate that these genes may modify the host cell environment, contributing to the pathogenesis of KSHV-associated disorders. Several KSHV genes have been found to cause dysregulated cell proliferation or to interfere with established tumor suppressor pathways. The epidemiologic association of KSHV with malignancies and the coding features of its genome suggest that it is a new DNA tumor virus.
Second-Line Chemotherapy in Patients With Relapsed Extragonadal Nonseminomatous Germ Cell Tumors: Results of an International Multicenter Analysis
Authors: Jörg T. Hartmann, Lawrence Einhorn, Craig R. Nichols, Jean-P. Droz, Alan Horwich, Arthur Gerl, Sophie D. Fossa, Jörg Beyer, Jörg Pont, Hans-J. Schmoll, Lothar Kanz, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2001)

Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival.We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment.Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P =.003), sensitivity to cisplatin (P =.003), elevated beta-HCG at relapse (P: =.04), and normal LDH at diagnosis (P =.01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis.Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.
Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
Authors: G. Orozco, S. Eyre, A. Hinks, X. Ke, A. G. Wilson, D. E. Bax, A. W. Morgan, P. Emery, S. Steer, L. Hocking, D. M. Reid, P. Wordsworth, P. Harrison, W. Thomson, A. Barton, J. Worthington
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the <i>CD40</i>, <i>CCL21</i> and <i>CDK6</i> genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the <i>CD244</i> gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. <h3>Methods</h3> A total of 4 SNPs (rs4810485 in <i>CD40</i>, rs2812378 in <i>CCL21</i>, rs42041 in <i>CDK6</i> and rs6682654 in <i>CD244</i>) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the χ<sup>2</sup> test using Stata. <h3>Results</h3> Association to the <i>CD40</i> gene was robustly replicated (p=2×10<sup>−4</sup>, OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the <i>CCL21</i> locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (<i>CDK6</i>) and rs6682654 (<i>CD244</i>) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to <i>CD40</i> was confirmed (p=7.8×10<sup>−8</sup>, OR 0.87 (95% CI 0.83 to 0.92). <h3>Conclusion</h3> In this large UK cohort, strong association of the <i>CD40</i> gene with susceptibility to RA was found, and weaker evidence for association with RA in the <i>CCL21</i> locus.
Adrenomedullin Infusion Attenuates Myocardial Ischemia/Reperfusion Injury Through the Phosphatidylinositol 3-Kinase/Akt-Dependent Pathway
Authors: Hiroyuki Okumura, Noritoshi Nagaya, Takefumi Itoh, Ichiro Okano, Jun Hino, Kenji Mori, Yoshitane Tsukamoto, Hatsue Ishibashi-Ueda, Senri Miwa, Keiichi Tambara, Shinya Toyokuni, Chikao Yutani, Kenji Kangawa
Journal: Circulation (2003)

Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in patients with heart failure. However, the effect of AM on myocardial ischemia/reperfusion remains unknown.Male Sprague-Dawley rats were exposed to a 30-minute period of ischemia induced by ligation of the left coronary artery. They were randomized to receive AM, AM plus wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), or saline for 60 minutes after coronary ligation. Hemodynamics and infarct size were examined 24 hours after reperfusion. Myocardial apoptosis was also examined 6 hours after reperfusion. The effect of AM on Akt phosphorylation in cardiac tissues was examined by Western blotting. Intravenous administration of AM significantly reduced myocardial infarct size (28+/-4% to 16+/-1%, P<0.01), left ventricular end-diastolic pressure (19+/-2 to 8+/-2 mm Hg, P<0.05), and myocardial apoptotic death (19+/-2% to 9+/-4%, P<0.05). Western blot analysis showed that AM infusion accelerated Akt phosphorylation in cardiac tissues and that pretreatment with wortmannin significantly attenuated AM-induced Akt phosphorylation. Moreover, pretreatment with wortmannin abolished the beneficial effects of AM: a reduction of infarct size, a decrease in left ventricular end-diastolic pressure, and inhibition of myocardial apoptosis after ischemia/reperfusion.Short-term infusion of AM significantly attenuated myocardial ischemia/reperfusion injury. These cardioprotective effects are attributed mainly to antiapoptotic effects of AM via a PI3K/Akt-dependent pathway.
Is This Right? (… or Is It Left?)
Authors: Peter G. Danias, Warren J. Manning
Journal: Circulation (1999)

A n asymptomatic 57-year-old woman presented with dextrocardia and situs inversus.The surface ECG (Figure, panel A) reveals a rightward QRS axis.Poor R-wave progression is present in the standard precordial leads, whereas the right chest leads (rV 1 through rV 6 ), conversely, demonstrate progression of the R wave.The repolarization abnormality seen in leads rV 4 through rV 6 is secondary to left ventricular hypertrophy related to long-standing systemic hypertension.The posteroanterior chest radiograph (B) is a mirror image of the normal radiograph, with the heart located at the right hemithorax, the ascending aorta (arrows) and aortic knuckle forming the left heart border, and the left hemidiaphragm positioned higher than the right hemidiaphragm.The letters L and R indicate the patient's left and right side, respectively.The coronal MRI (C) of the chest and upper abdomen demonstrates the relationship of the thoracic and abdominal organs.AAo indicates ascending aorta; LV, left ventricle; PA, pulmonary artery; and RA, right atrium.
The molecular portrait of in vitro growth by meta-analysis of gene-expression profiles.
Authors: Rickard Sandberg, Ingemar Ernberg
Journal: Genome biology (2005)

Abstract Background Cell lines as model systems of tumors and tissues are essential in molecular biology, although they only approximate the properties of in vivo cells in tissues. Cell lines have been selected under in vitro conditions for a long period of time, affecting many specific cellular pathways and processes. Results To identify the transcriptional changes caused by long term in vitro selection, we performed a gene-expression meta-analysis and compared 60 tumor cell lines (of nine tissue origins) to 135 human tissue and 176 tumor tissue samples. Using significance analysis of microarrays we demonstrated that cell lines showed statistically significant differential expression of approximately 30% of the approximately 7,000 genes investigated compared to the tissues. Most of the differences were associated with the higher proliferation rate and the disrupted tissue organization in vitro . Thus, genes involved in cell-cycle progression, macromolecule processing and turnover, and energy metabolism were upregulated in cell lines, whereas cell adhesion molecules and membrane signaling proteins were downregulated. Conclusion Detailed molecular understanding of how cells adapt to the in vitro environment is important, as it will both increase our understanding of tissue organization and result in a refined molecular portrait of proliferation. It will further indicate when to use immortalized cell lines, or when it is necessary to instead use three-dimensional cultures, primary cell cultures or tissue biopsies.
Antibodies to -fodrin derived peptide in Sjogren's syndrome
Authors: J He, Q L Chen, Z G Li
Journal: Annals of the Rheumatic Diseases (2006)

Sjogren’s syndrome (SS) is a chronic autoimmune disorder of unknown cause. Haneji et al identified a 120 kDa fragment of the ubiquitous cytoskeletal protein α-fodrin as an autoantigen in an NFS/sld mouse model of human SS.1 More recently, the sensitivity and specificity of α-fodrin antibodies in SS in several studies suggested that it might be of value in the diagnosis of SS.1–3 In the present study, a conserved motif, rather than the whole protein, in α-fodrin was used as antigenic peptide to define further the role of anti-α-fodrin antibodies in SS. This is the first study so far to evaluate the prevalence of anti-α-fodrin peptide antibodies (α-FPA) in a cohort of Chinese patients with SS.

Serum samples from 89 patients with SS (85 female, 4 male; 74 with primary SS (pSS) and 15 with …
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer
Authors: Christopher J. Sweeney, Yu-Hui Chen, Michael Carducci, Glenn Liu, David F. Jarrard, Mario Eisenberger, Yu-Ning Wong, Noah Hahn, Manish Kohli, Matthew M. Cooney, Robert Dreicer, Nicholas J. Vogelzang, Joel Picus, Daniel Shevrin, Maha Hussain, Jorge A. Garcia, Robert S. DiPaola
Journal: New England Journal of Medicine (2015)

Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone.
Anti-oxidant effects of gold compounds
Authors: Y. MIYACHI, A. YOSHIOKA, S. IMAMURA, Y. NIWA
Journal: British Journal of Dermatology (1987)

The anti-oxidant efficacy, in vitro, of the gold compounds auranofin (AF) and gold sodium thiomalate (GST) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNs) and a cell-free, xanthine-xanthine oxidase system. The oxygen species investigated were the superoxide radical anion (O2-), hydrogen peroxide (H2O2) and the hydroxyl radical (OH.). AF had an inhibitory effect on ROS production by PMNs. In particular, OH. generation was significantly suppressed in a dose-dependent fashion. AF did not inhibit ROS production in the cell-free system. GST produced only a small degree of inhibition at higher concentrations. These findings suggest that AF may play an important role in the inhibition of respiratory bursts and the generation of inflammatory reaction products. Since the products of the respiratory burst, especially potent oxidants such as OH. and H2O2, are thought to be important inflammatory mediators, it is postulated that the blockade of toxic ROS generation by AF affects rheumatoid as well as dermatological inflammation and tissue damage.
RIN1 Is a Breast Tumor Suppressor Gene
Authors: Marc Milstein, Chelsea K. Mooser, Hailiang Hu, Marlena Fejzo, Dennis Slamon, Lee Goodglick, Sarah Dry, John Colicelli
Journal: Cancer Research (2007)

Abstract Breast cancer progression is driven by altered gene expression. We show that the RIN1 gene, which encodes a RAS effector regulating epithelial cell properties, is silenced in breast tumor cell lines compared with cultured human mammary epithelial cells. We also report that RIN1 is often reduced in human breast tumor cells compared with morphologically normal breast glandular cells. At least two silencing mechanisms seem to be involved. Overexpression of the transcription repressor SNAI1 (Snail) was observed in ZR75-1 cells, and SNAI1 knockdown restored RIN1 expression. In addition, DNA methylation within the RIN1 promoter and the first exon in KPL-1 cells suggested that epigenetic modifications may contribute to silencing, and demethylation was shown to restore RIN1 expression. Reexpression of RIN1 was shown to inhibit anchorage-independent growth in soft agar. In addition, RIN1 expression inhibited both the initiation and progression of tumorigenesis for two breast tumor cell lines in a mouse model, consistent with a tumor suppressor function. We also show that RIN1 acts as a negative regulator of tumor cell invasive growth and that this requires the ABL kinase–signaling function of RIN1, suggesting a mechanism through which RIN1 silencing may contribute to breast cancer progression. [Cancer Res 2007;67(24):11510–6]