tbuckley/cabot-search huggingface dataset:
Abstract 4196: Identification and investigation of ethnic specific gene expression differences in non-cancerous breast tissue
Authors: Lisa L. Baumbach-Reardon, Carmen Gomez, Mary Ellen Ahearn, Ashley Green, Kevin Ellison, Kemal O. Yariz, Biju Issac, Jennifer Clarke, Stefan Ambs, Mark Pegram
Journal: Cancer Research (2012)

Abstract Disparities in breast cancer (BC) stage of presentation and survival are well documented in patients of different ethnicities. These differences are undoubtedly due to a combination of extrinsic and intrinsic factors. Our group is focused on the genetic contributions to these disparities. Recent observations by our group and others suggest not only the involvement of specific genes contributing to BC risk in African-American (AA) women, but that multiple distinct ethnic-specific gene expression patterns exist in both matched cancerous and normal breast tissue samples. We report the first results of a parallel study which is addressing an unanswered question: are there ethnic-specific differences in the transcriptome of normal breast tissue? We are completing gene expression profiling studies in normal breast FFPE samples from 25 AA and 25 Caucasian (Cauc) women with no history of breast cancer. Laser capture micro-dissection (LCM) is used to further identify and extract epithelial vs stromal cells from each FFPE slide for use in RNA expression profiling. RNA isolation and hybridization occurs in collaboration with Almac Diagnostics (Dx) using their proprietary Breast Cancer DSA array. Gene expression data analyses involves multiple statistical packages developed for DNA microarray studies, and is focusing on comparison of gene expression profiles across four study groups- AA vs Cauc samples and epithelial vs stroma cells. For baseline comparison, a subset of this study group (10 AA and 10 Cauc samples non-LCM dissected) has also been analyzed. Results from these non-LCM dissected samples displayed expression differences between AA and Cauc in 333 known genes. Applying the stringency criteria of a fold change of two or greater and a statistical p-value of 0.01, reduced the significant gene list to 61 genes. Initial pathway analyses indicate these genes are involved in cell adhesion, G-protein signaling, apoptosis and survival pathways, and cytoskeleton remodeling - all critical pathways for cell survival. These initial results are being validated in the LCM-dissected samples, and our latest results will be presented. Results from analyses of these normal samples will be compared to our previous results obtained in matched tumor-normal triple negative AA and Cauc breast cancer samples (as well as publicly available data sets). Combined analysis of tumor and normal breast expression (transcriptome) data will help to better understand the possible significance of gene expression differences in breast tissue between ethnic groups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4196. doi:1538-7445.AM2012-4196
Analysis of Probability as an Aid in the Clinical Diagnosis of Coronary-Artery Disease
Authors: George A. Diamond, James S. Forrester
Journal: New England Journal of Medicine (1979)

The diagnosis of coronary-artery disease has become increasingly complex. Many different results, obtained from tests with substantial imperfections, must be integrated into a diagnostic conclusion about the probability of disease in a given patient. To approach this problem in a practical manner, we reviewed the literature to estimate the pretest likelihood of disease (defined by age, sex and symptoms) and the sensitivity and specificity of four diagnostic tests: stress electrocardiography, cardiokymography, thallium scintigraphy and cardiac fluoroscopy. With this information, test results can be analyzed by use of Bayes' theorem of conditional probability. This approach has several advantages. It pools the diagnostic experience of many physicians ans integrates fundamental pretest clinical descriptors with many varying test results to summarize reproducibly and meaningfully the probability of angiographic coronary-artery disease. This approach also aids, but does not replace, the physician's judgment and may assit in decisions on cost effectiveness of tests.
Abstract 1160: Inactivated hippo-pathway as a prognostic biomarker in hepatocellular carcinoma.
Authors: Hiromitsu Hayashi, Hideyuki Kuroki, Naomi Yokoyama, Shigeki Nakagawa, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Yoshiaki Ikuta, Akira Chikamoto, Toru Beppu, Hideo Baba
Journal: Cancer Research (2013)

Abstract The contact inhibition of proliferation and cell movement is crucially important in embryonic development, tissue regeneration, and wound healing for the well-controlled organogenesis. The disruption of contact inhibition results in sustained cell proliferation and uncontrolled cell movement, which is a hallmark of solid tumors. Loss of contact inhibition allows cancer cells to facilitate the invasion of neighboring tissues and metastasis to remote organs. The recently identified Hippo signaling pathway has been implicated in contact inhibition of proliferation as well as organ size control. Indeed, the conditional inactivation of hippo-pathway in liver leads to enlarged liver (massive hepatomegaly) and tumorigenesis (Cell, 2007). Clinically, HCC often shows the huge tumor more than size in 10cm, strongly speculating that inactivation of hippo-pathway plays an important role in HCC progression. However, clinical significance of hippo-pathway in HCC is largely unknown. Here, we investigated the clinical significance of inactivated hippo-pathway, which induce overexpressed oncogenes (YAP/TAZ), using resected 80 HCC samples, and suggested the tumoral-high TAZmRNA expression was a worse prognostic biomarker for HCC patients represented by high proliferative activity. The tumor size in High TAZmRNA expression group (n =24) was significantly larger than that in low expression group (n = 56) (P &amp;lt; 0.05). YAP/TAZ protein over-expression in HCC was associated with high proliferative activity by Ki-67 positive cells. The high TAZmRNA expression group showed significantly worsen disease free survival and overall survival compared with that in low expression group (P = 0.01 and 0.02, respectively). Thus, inactivation of Hippo-pathway plays a crucial role in tumor progression by accelerating proliferative activity, and tumoral TAZmRNA expression level may be a useful prognostic biomarker in HCC. Citation Format: Hiromitsu Hayashi, Hideyuki Kuroki, Naomi Yokoyama, Shigeki Nakagawa, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Yoshiaki Ikuta, Akira Chikamoto, Toru Beppu, Hideo Baba. Inactivated hippo-pathway as a prognostic biomarker in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1160. doi:10.1158/1538-7445.AM2013-1160
Abstract ES9-1: Long-Term Management of Pain Due to, and after, Primary Treatment of Breast Cancer
Authors: MW Rabow
Journal: Cancer Research (2010)

Abstract As more women are living longer after treatment for breast cancer, survivorship issues take on even greater importance. As a result of effective breast cancer treatment, approximately one-half of survivors experience chronic pain due to the lasting sequelae of surgery, radiation, chemotherapy, and/or endocrine treatment. Research also suggests that these pain symptoms are under-reported and under-treated. The sources of chronic pain after breast cancer surgical treatment include nerve injury, scarring, lymphedema, and post-breast cancer treatment syndrome. After radiation, scarring, neuropathy, and lymphedema are possible. Multiple cytotoxic chemotherapy agents, including Paclitaxel, can cause a chronic painful peripheral neuropathy. Endocrine treatments, including Aromatase Inhibitors and bisphosphonates, are associated with bone, muscle and joint pain. Treatment for these pain syndromes should be guided by basic principles of analgesia and directed by an understanding of the type of pain involved (nociceptive or neuropathic). Evidence-based treatment modalities include pharmacologic agents, including NSAIDS, acetaminophen, opioids and co-analgesics including neuropathic agents and antispasm medications. Non-pharmacologic treatments include exercise, physical therapy, heat, and cold. Integrative practices may be effective as well, including acupuncture, guided imagery, and massage. Diet and weight loss also have a role. Finally, emotional support for patients facing chronic pain, as will as the attendant concerns about the meaning of that pain, is key in helping ameliorate the distressing experience and disability of chronic pain. Support groups, cognitive behavioral therapy, and psychodynamic therapy all may be helpful to the survivor facing chronic pain after breast cancer treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES9-1.
The antineoplasic effect of molecular iodine on human mammary cancer involves the activation of apoptotic pathways and the inhibition of angiogenesis.
Authors: L Vega-Riveroll, P Mondragón, J Rojas-Aguirre, J Romero-Romo, G Delgado, C Aceves
Journal: Cancer Research (2009)

Abstract Abstract #3082 Breast cancer is the most frequent malignant neoplasia in women. One factor thought to influence the incidence of breast cancer is diet. Japanese women, who have a high dietary intake of iodine (5280 vs 209 µg/day in western population) due to ingestion of seaweed, have the lowest incidence of breast cancer in the world. In normal mammary gland, iodine deficiency is involved in dysplasias, which are reversible with I2 but not with iodide administration. Recent data generated in our laboratory showed that continuous treatment with I2, but not iodide, has a potent antineoplastic effect on tumoral progression in N-methyl-N-nitrosourea-treated virgin rats (50-70%). Also I2 treatment in MCF-7 human breast cancer cells, but not in normal mammary cells (MCF-12F), shows a significant apoptotic effect induced by activation of Bax-caspases and AIF-PARP-1 pathways. Based on these findings, a study of women diagnosed with cancer (mammography and tru-cut biopsy) was initiated. Patients were divided into placebo or I2 (5 mg/day) groups for 2 to 5 weeks before surgery. One day before beginning the I2 treatment and the day of the surgery, urine and blood samples were collected. The day before surgery, a second mammography was obtained. In the tumor samples proliferation (PCNA), apoptosis (TUNEL), and vasculature area (CD-31) were analyzed by immunohistochemistry. Bax, Bcl2, p53, and VEGF proteins were analyzed by Western blot. Circulating TSH and T3 levels were measured by RIA and urinary iodide by HPLC. The results showed that although tumor size did not differ between groups, a significantly lower proliferation and increased apoptotic rate were observed in tumors from women supplemented with iodine. In these tumors the ratio Bax/Bcl2 increased, p53 levels were unchanged, and VEGF levels and vasculature area diminished significantly. Serum TSH and T3 showed no changes in any group, indicating that I2 treatment had not compromised the thyroid status. We propose that I2 supplements should be considered for use in clinical trials of breast cancer therapies. We thank Dr. Jorge Álvarez-Aguirre2,3, Dr. Alonso Gallegos-Corona2, Lic. Concepción Correa-Tinajero3, Alejandro Núñez-Nolasco2,3, and Silvia Serrato-Águila2. This work was partially supported by: PAPIIT-UNAM IN201207, and CONACyT 44976-M and 85952. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3082.
PTU-089 Audit on Factors that Predict Bone Disease in Cirrhosis
Authors: A Sugumaran, E Mohamed, S Walsh, T Mathialahan
Journal: Gut (2013)

<h3>Introduction</h3> Osteodystrophy is a recognised complication with cirrhosis. Female sex, cholestasis, low BMI are proven to increase risk of bone disease in cirrhotics<sup>1,2</sup>. Our aim is to audit our current practise of diagnosis and management of osteoporosis in liver patients and to identify other associated risk factors. <h3>Methods</h3> Retrospective audit was done on 73 cirrhotic patients enrolled in the Hepatocellular Carcinoma (HCC) surveillance programme in our hospital. Our practise was compared with British Society of Gastroenterology (BSG) recommendations2. Data on demographics, aetiology of cirrhosis, alcohol or steroid intake, post menopausal state, presence of varices, investigations for osteoporosis done and treatment given were collected and analysed. <h3>Results</h3> Only 34 patients had DEXA scan performed at any point, with average duration between cirrhosis diagnosis and first scan being 2.41 years. 14 had osteoporosis (T score &lt; –2.5) at hip or lumbar spine and 11 were osteopenic (T of –1.5 to –2.5), showing a prevalence of bone disease at 73.5%. On analysis, except for female sex, no other variable increased risk of bone disease. Few patients were tested for Vitamin D (6.8%) or hormonal studies (8.1%) but 78% had thyroid tests and 100% had bone profile. Treatment for osteoporosis was given, as recommended in all subjects; however 2-yearly follow up scans happened only in 19.2%. Though 6/11 patients had varices, association was not statistically significant by Pearson chi-square test (p value of 0.058). Similarly, longer duration of cirrhosis did not increase risk as analysed by t-test. <h3>Conclusion</h3> Our audit showed high prevalence of bone disease (osteoporosis and osteopenia) in chronic liver disease patients, however there is bias as DEXA scans were requested only in symptomatic patients. There was poor compliance with BSG guideline especially with surveillance intervals. Female sex increases risk but the association of bone disease with duration of cirrhosis and presence of varices are not statistically significant. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Wariaghli G, Mounach A, Achemlal M, <i>et al.</i> Osteoporosis in chronic liver disease: a case control study. Rheumatology International 2010 May; 30(7):893–92. Collier JD, Ninkovic M, Compston JE. Guidelines on the management of osteoporosis associated with chronic liver disease. Gut 2002; 50 (Suppl 1):i1-i9
SAT0549 Osteoclast Precursors Are Reugulated by Proinflammatory Cytokines and Arise before Clinical Onset of Arthritis
Authors: A. Puchner, S. Blüml, V. Saferding, E. Goncalves-Alves, H. Leiss, S. Hayer, J. Smolen, K. Redlich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Bone erosions and systemic bone loss in rheumatoid arthritis patients results from an increased activity of osteoclast, which are derived from precursor cells of the myeloid lineage. Although there is much known about the mechanisms regulating the formation and activation of mature osteoclasts, the identity of an osteoclast precursor population in and its regulation by inflammatory cytokines during arthritis is poorly understood. <h3>Methods</h3> HTNFtg mice were clinically scored once per week for grip strength and swelling. In addition, blood was collected every other week starting on week 4. Mice were sacrificed at week 10 - blood, spleen and bone marrow were collected for flow cytometry analysis. IL1/IL6<sup>–/–</sup> were crossed into hTNFtg mice and blood was also analyzed. K/BxN Arthritis was induced in wild type mice, blood and spleen were collected 14 days after disease induction. Different monocyte subsets were Facs-sorted and cultured in the presence of RANKL and MCSF to induce osteoclasts <h3>Results</h3> We show that during TNF-driven arthritis CD11b<sup>+</sup> cells are elevated in blood spleen and bone marrow even before the onset of clinical symptoms and remain elevated throughout. In particular, a certain subset of myeloid cells, characterized by the expression of CD11b and LY6C as well as LY6G, increases in blood, spleen and bone marrow during arthritis. After sorting, these cells are particularly able to form mature osteoclasts <i>in vitro</i>. The increase of this myeloid population is not only observed in TNF-driven arthritis, but can also in K/BxN serum transfer arthritis. We furthermore demonstrate that IL-1 and/or IL-6 importantly regulate the expansion of these cells as in IL1/IL-6 double deficient hTNFtg we did not detect an elevation of this subset. <h3>Conclusions</h3> Osteoclast precursors arise from a monocyte subpopulation that is specifically increased during inflammatory arthritis. Elevated numbers of these cells can be detected before clinical onset of disease and therefore may provide a biomarker for inflammatory arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5638
FRI0244 Assessing organ involvement and current symptoms as indicators for disease progression in 3047 patient cohort
Authors: P. Moinzadeh, N. Hunzelmann, T. Krieg, N. Blank, G. Fierlbeck, E. Genth, I. Kötter, A. Kreuter, I. Melchers, C. Pfeiffer, U. Müller-Ladner, G. Riemekasten, C. Sunderkötter
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> To improve detection and follow-up of patients with systemic sclerosis, the German Network for Systemic Scleroderma (DNSS) was founded and initiated a registry gathering information on diagnosis, clinical symptoms and therapy of SSc patients. <h3>Methods</h3> Up to date, more than 3000 patients have been grouped into four descriptive disease subsets, i.e. limited cutaneous disease (lcSSc), diffuse cutaneous disease (dcSSc), overlap-syndrome and undifferentiated connective tissue disease (UCTD) with scleroderma features. Disease progress between initial patient registration (year 0) and fourth follow-up (year 4) was measured using organ involvement and present symptoms as indicators. <h3>Results</h3> Recent analyses revealed that 49% of patients suffer from limited SSc (lSSc), 31% from diffuse SSc (dSSc) and 10% of patients were diagnosed with an overlap-syndrome. 8% had an undifferentiated form while Scleroderma sine scleroderma was present in 0.7% of patients. Follow-up data are available from 1595 patients after one year, from 901 patients followed for two years, 573 patients followed for three years and 386 followed for at least four years. After four years a significant increase was detected in the frequency of pulmonary hypertension (PAH) (14.4% to 24.2%, p=0.001), lung fibrosis (38.8% to 47.6%, p=0.006), oesophagus involvement (58.5% to 74.8%, p=0.0001), bowel involvement (13.6% to 19.9%, p=0.03), Kidney (10.7% to 15.8%, p=0.03) and Heart (13.4% to 24.0%, p&lt;0.0001) involvement. Disease subsets were associated with different organs being more frequently involved, i.e. lcSSc with PAH (13.5% to 25.0%, p=0.007), oesophagus (60.7% to 77.0%, p=0.0001) and colon involvement (7.3% to 11.6%, p=0.002); dcSSc with PAH (19.0% vs. 25.9%, p=0.035), lung fibrosis (63.5% vs. 71.4%, p=0.02) and heart involvement (19.1% vs. 27.7%, p=0.007). Interestingly, patients with overlap syndrome showed no significant change in organ involvement over time. <h3>Conclusions</h3> After four years of follow-up in a large well defined SSc cohort, a significant increase in frequency of organ involvement was observed, particularly with respect to the lung, GI-tract and heart. Patients with SSc should be followed at least annually for organ involvement, the frequency of follow-ups being increased depending on the disease activity. <h3>Disclosure of Interest</h3> None Declared
GE-16 * JAPANESE PEDIATRIC MOLECULAR NEURO-ONCOLOGY GROUP (JPMNG): ESTABLISHMENT OF A NATIONWIDE MOLECULAR DIAGNOSTIC NETWORK FOR PEDIATRIC MALIGNANT BRAIN TUMORS IN JAPAN
Authors: Y. Kanemura, K. Ichimura, T. Shofuda, R. Nishikawa, M. Yamasaki, M. D. Taylor, H. Arai, S. Shibui
Journal: Neuro-Oncology (2014)

Recent intensive molecular biological analyses revealed that pediatric brain tumors can be subclassified into multiple distinct molecular subgroups. The current consensus is that medulloblastomas consist of four core subgroups, and the sub-grouping of ependymomas is being proposed. This molecular sub-grouping system will not only improve our understanding of the biology of these tumors, but may also contribute for the development of novel therapeutic targets and strategies in the future. We have formed the Japanese Pediatric Molecular Neuro-oncology Group (JPMNG) and initiated a new clinical research project to establish a nationwide network of a molecular diagnosis system for pediatric brain tumors in Japan with the aim to provide a standardized molecular diagnosis according to the international consensus. We initially focus on medulloblastomas and ependymomas. Fresh, fresh-frozen and/or formalin-fixed paraffin-embedded archived tissue specimens are collected. Optimal diagnostic methods are being set up to reliably and reproducibly classify them into molecular subgroups according to the consensus criteria. These include gene expression analysis using the NanoString nCounter system, immunohistochemistry, RT-PCR, DNA sequencing, fluorescence in situ hybridization, and DNA methylation analysis. We have so far collected a total of 85 tissue samples including 30 medulloblastomas and 55 ependymomas. Preliminary study using 17 meduloblastomas indicated that proportions of four core subgroups were WNT (12%), SHH (35%), Group 3 (0%) and Group 4 (53%), respectively. Driver gene analysis showed that two WNT medulloblastomas had CTNNB1 mutations and TP53 mutations were found in one WNT and one SHH tumors. Mutation of TERT promoter was also found in one adult SHH tumors. We expect that this research will provide a highly accurate molecular diagnosis of medulloblastoma and ependymoma comparable to the international standard, leading to form a basis for better clinical management and outcomes and to develop new therapeutic strategies of the pediatric brain tumors in Japan.