tbuckley/cabot-search huggingface dataset:
Abstract 5387: Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer.
Authors: Katrin Panzitt, Ali Shojaie, Nagireddy Putluri, Sumanta Basu, Vasanta Putluri, Susmita Samanta, Michael Ittmann, Ismael Vergara, George Michailidis, Ganesh Palapattu, Arun Sreekumar
Journal: Cancer Research (2013)

Abstract Prostate Cancer is the second most common cause of cancer-related death in men in the US. Like other tumors, prostate cancer development and progression is dictated by multiple molecular events that include changes in levels of genes, transcripts, proteins and metabolites. To better understand the biology of prostate cancer development it is essential to integrate these disparate yet related datasets. Our laboratory has identified matched transcriptomic, proteomic and metabolomic changes in localized prostate cancer relative to adjacent benign tissue as well in metastatic disease compared to organ-confined tumor. To study this using a System's Biology approach we have recently embarked on a pilot study aimed at integrating transcriptomic and metabolomic data to obtain biochemical pathways that key to prostate cancer development. Using an in-house network-based enrichment strategy, amino sugar metabolism was found to be significantly enriched in organ-confined prostate cancer but not in metastatic disease. Amino sugar metabolism describes the utilization of glucose-derived carbon and amino acid (mostly glutamine)-derive nitrogen to produce glucosamines. These amino sugars participate in synthesis of immune modulatory compounds as well as in glycosylation cascades. In this study, we describe the molecular analyses of Glucosamine-6 phosphate-N-acetyl Transferase (GNPNAT1), a key enzyme that converts D-glucosamine 6-phosphate to N-acetyl-D-glucosamine 6-phosphate, in prostate cancer. Our results indicate upregulation of GNPNAT1 in organ-confined prostate cancer as compared to benign adjacent tissue as well as metastatic tissue and regulation of the pathway by androgen. Stable knockdown of GNPNAT1 in androgen dependent LNCap cells leads to diminished cell growth and cell cycle arrest. In contrast, growth and cell cycle are not affected by the knockdown of GNPNAT1 in androgen independent C4-2 cells. Knockdown of GNPNAT1 in C4-2 cells enhances invasiveness which is not observed in LNCap knockdown cells. In this work we show that GNPNAT1 is linked to androgen receptor (AR) action and thus is a critical enzyme for the survival of androgen dependent prostate cancer cells. Citation Format: Katrin Panzitt, Ali Shojaie, Nagireddy Putluri, Sumanta Basu, Vasanta Putluri, Susmita Samanta, Michael Ittmann, Ismael Vergara, George Michailidis, Ganesh Palapattu, Arun Sreekumar. Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer. [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 5387. doi:10.1158/1538-7445.AM2013-5387
Chronic Dissecting Aneurysm of the Aorta Resembling Chronic Rheumatic Heart Disease
Authors: Elliott Levine, Max Stein, George Gordon, Nathan Mitchell
Journal: New England Journal of Medicine (1951)

THE incidence of dissecting aneurysm of the aorta is higher than is usually realized, since it is found at about 1 of 500 autopsies.1 With increased accuracy in diagnosis more cases of acute dissection of the aorta are being recognized before death. In Baer and Goldburgh's2 series of 44 cases, 11 were diagnosed ante mortem.When the characteristic clinical picture of dissecting aneurysm of the aorta occurs, with the development of aortic systolic or aortic diastolic murmurs with a short period of survival, the diagnosis is more obvious than when the patient survives the acute phase and then develops a . . .
Abstract P2-05-10: 64Cu-DOTA-trastuzumab positron emission tomography imaging of HER2 in women with advanced breast cancer
Authors: JE Mortimer, P Conti, T Shan, M Carroll, P Kofi, D Colcher, AA Raubitschek, JR Bading, J Miles
Journal: Cancer Research (2012)

Abstract Background: We propose to utilize64Cu-DOTA-trastuzumab with PET imaging to assess the in vivo expression of HER2 in women with advanced breast cancer. We hypothesized that the uptake of HER2 in normal tissues compromises the quality of radiographic images and that the pre-administration of trastuzumab prior to injection of64Cu-DOTA-trastuzumab would improve image quality. Two different doses of cold trastuzumab (5 mg and 50 mg) were tested. Once the dose of cold trastuzumab was established in women with documented HER2 positive metastatic disease, we initiated a second study of64Cu-DOTA-trastuzumab PET imaging in women whose cancers were HER2 1+ and 2+ by immunohistochemical staining. Methods: Patients with biopsy confirmation of recurrent disease located outside the breast and axilla considered for study. Complete staging workup included CT of the chest, abdomen, and pelvis, bone scintigraphy and18F FDG PET. At lease 1 non-hepatic site of metastasis that was &amp;gt; 2 cm separate from the biopsy site was also required. HER2 status was assessed by both IHC and FISH. In the first study all patients were required to have HER2 positive disease and could not have received anti-HER therapy for &amp;gt; 2 months. Immediately prior to injection of64Cu-DOTA-trastuzumab, a cold dose of either 5 mg or 50 mg of trastuzumab was administered.64Cu-DOTA-trastuzumab PET imaging was performed at 24 and 48 hours. Results: Eight women with HER2 positive metastatic breast cancer have undergone64Cu-DOTA-trastuzumab PET imaging: 2 received a pre-64Cu-DOTA-trastuzumab PET dose of 5 mg trastuzumab and 6 received 50 mg.64Cu-DOTA-trastuzumab PET effectively visualized and provided uptake measurements for presumably HER2+ metastatic lesions in bone, liver, lung and, to a lesser degree, lymph nodes. The 50 mg dose resulted in approximately 75% decrease in liver uptake of64Cu and improved the visualization of hepatic metastasis. We have initiated the second phase of the study utilizing the pre-administration of 50 mg trastuzumab in women with HER2 1+ and 2 + disease. To date we have imaged one patient. Conclusion:64Cu-DOTA-trastuzumab PET imaging is feasible and image quality is improved with the pre-administration of 50 mg trastuzumab. Enrollment of women with IHC 1+ and 2+ disease continues. This work was supported by the Department of Defense grant # 1024511. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-10.
Abstract 916: Preclinical responses of the MEK inhibitor AZD6244 in a genetically modified mouse model of prostate cancer.
Authors: Hirotsugu Uemura, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Nishio, Marco A. De Velasco
Journal: Cancer Research (2013)

Abstract The mitogen-activated protein kinase (MAPK) pathway is involved in a broad range of cellular processes that include proliferation, survival, apoptosis, and cellular differentiation. MAPK has also been shown to increase the transcription of androgen-dependent (AR) genes, independently of androgens by phosphorylation of the AR or its cofactors. Thus, MAPK signal inhibition has the potential to be a therapeutic target for prostate cancer. To determine the clinical benefit of MAPK inhibition, we used the highly selective MEK inhibitor, AZD6244, in a prostate-specific PTEN-conditional knockout mouse model of prostate cancer. In this model, prostate tumors from mice exhibit increased levels of p-Erk1/2 expression that correlates with tumor progression. Acute pharmacodynamic responses, after a single dose of AZD6244, showed a strong inhibition of Erk1/2 phosphorylation that was maintained for at least 24 hours after drug administration. Levels of cellular proliferation decreased, and apoptosis was induced shortly after the administration of AZD6244. However, apoptosis was suppressed after 8 hours. To further characterize the responses to MAPK signal inhibition, we examined the activity of downstream molecules of the PI3K/Akt and JAK/STAT3 signaling pathways. While PI3K/Akt activity decreased mildly, activation of JAK/STAT3 was transiently but strongly increased. To determine tumor responses to chronic administration of AZD6244, Pten-mutant mice harboring prostate tumors were treated with AZD6244 for 4 a period of 4 weeks. 2-D morphometric analysis of tumor surface area showed a reduction of 10.9% (P =0.035) in treated mice. Furthermore, inhibition of p-Erk was maintained and tumor cell proliferation was reduced by 25.24% (P =0.005). The apoptotic index increased from 3.9% in controls to 7.2% (P=0.004) in mice receiving AZD6244. Our findings suggest that inhibition of MAPK signaling can contribute to decreased tumor progression and may represent a promising therapeutic alternative. Citation Format: Hirotsugu Uemura, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Nishio, Marco A. De Velasco. Preclinical responses of the MEK inhibitor AZD6244 in a genetically modified mouse model of prostate cancer. [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 916. doi:10.1158/1538-7445.AM2013-916
A1.3 Phenotyping B-cell may have value as RA diagnostic biomarker for patients with &lt;12 months inflammatory arthritis
Authors: A Burska, R Parmar, P Emery, M Melado, S Sacre, F Ponchel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biomarkers for early diagnosis of RA are still needed despite the improvement brought about by the use of the ACR/EUALR-2010 criteria which include the ACPA biomarker. B-cell subset dys-regulation has not been studied in detail in the early RA disease continuum. The aim of this pilot study is to determine whether B-cell subset phenotyping investigating differentiation subset and cell surface expression for TLRs and chemokine receptors can discriminate between patients who clearly are RA from those with other (inflammatory) rheumatic diseases in an early arthritis clinic. <h3>Methods</h3> 46 patients with &lt;12 months IA were enrolled; age, CRP, joint counts, symptom duration, RF and ACPA were recorded. 6-8 colour flowcytometry was performed using standard protocols. <h3>Results</h3> Using newly developed 2010-RA diagnosis criteria 23 of the 46 patients were diagnosed with RA. Not surprisingly, ACPA positivity was associated with RA (P&lt;0.0001) as part of the criteria, as well as higher CRP (P = 0.004) and swollen joint count (P = 0.003). Differentiation subset analysis showed that naïve B-cells (CD19<sup>+</sup> CD27+CD38-) were increased in RA patients (P = 0.028). Furthermore, putative regulatory B-cells (CD19<sup>+</sup> CD38+CD24+) were reduced (P = 0.003). More B-cells expressing TLR4 (P = 0.037) were associated with RA but less B-cells expressed CXCR4 (P = 0.012) and CCR6 (P = 0.002). Clustering analysis was used to further investigate pattern of expression of specific groups of markers or phenotypes. Clustering showed 3 groups of patients, one enriched for RA and the other two with mixed RA and non-RA patients (P = 0.088). ACPA positivity was associated with the first group (P = 0.024). Clustering also highlighted IL-6R as a possible marker associated with subgroup-1 (p = 0.001) and ACPA positivity. <h3>Conclusion</h3> There are clear B-cell related immunological differences in patients with early RA. We will therefore need to evaluate these biomarkers in early inflammatory patients with a high risk of progression towards RA and establish their value in larger number of patients.
Scientists Develop New Interest In Cancer Vaccine Research
Authors: P. A. Newman
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Scientists Develop New Interest In Cancer Vaccine Research Get access Patricia A. Newman Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 20, 16 October 1991, Pages 1439–1441, https://doi.org/10.1093/jnci/83.20.1439 Published: 16 October 1991
99mTc-Methylene Diphosphonate Bone Scintigraphy Findings in Posttransplant Distal Limb Syndrome
Authors: Thorsten Derlin, Jasmin D. Busch, Peter Bannas
Journal: Clinical Nuclear Medicine (2014)

We report a case of posttransplant distal limb syndrome (PTDLS) representing a rare complication in kidney transplant recipients characterized by a pain syndrome of the distal extremities. A 68-year-old man with a history of kidney transplantation presented with symmetrical and incapacitating pain in the feet and knees and underwent whole-body Tc-methylene diphosphonate (MDP) scintigraphy for further evaluation. Planar scintigraphy demonstrated marked tracer uptake in the distal femoral and tibial epiphyses, and magnetic resonance imaging showed corresponding osteoedema. Tc-MDP scintigraphy is a valuable tool for evaluation of the etiology of musculoskeletal pain and may demonstrate typical findings in case of PTDLS.
AB0011 Impact of HLA-DRB1 shared epitope alleles according the new classification on the susceptibility and structural severity in rheumatoid arthritis
Authors: D. Acheli, H. Amroun, S. Salah, M. Aiche, S. Metatla, M.-C. Abbadi, H. Djoudi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> rheumatoid arthritis (RA) is a complex polygenic disease. HLA-DRB1 alleles encoding the shared epitope (SE) are associated with RA susceptibility and severity. Recently HLA-DRB1 SE alleles has been reclassified into S1, S2, S3P and S3D groups. <h3>Objectives</h3> assessed the impact of this new classification of the HLA-DRB1 SE<sup>+</sup> in RA susceptibility and structural severity. <h3>Methods</h3> serum and genomic DNA samples of 154 RA patients and 95 healthy controls were obtained. HLA-DRB1 genotyping and sub typing was performed by PCR- sequence specific probes (PCR-SSP). Rheumatoid factor (RF) and C-reactive protein (CRP) were quantified by nephelometry. ACPAs were detected by ELISA. Disease activity was assessed using the DAS28-VS and radiographic damage by Sharp Vander Heidje method <h3>Results</h3> we found a positive association between RA susceptibility and S3P alleles (OR=2.94, 95% CI 1.82 to 4.84; p&lt;7.10<sup>-5</sup>) and S2 alleles (OR=2.71, 95%CI 1.047 to 8.17; p&lt;0.04). In opposite, a negative association was found for S1 alleles (OR =0.58, 95% CI 0.37 to 0.89, p&lt;0.01) and X alleles (OR=0.59, 95% CI 0.40 to 0.86; p&lt;5.10<sup>-3</sup>). No significant association was observed for the S3D class of alleles (13.9% vs 14.2%, p&lt;0.93). Finally we didn’t observe any association between the HLA-DRB1 alleles and structural severity. <h3>Conclusions</h3> According to the revised classification, RA susceptibility alleles in Algerian patients were S2 and S3P groups alleles but the protective alleles were S1 and X alleles. Our results support the hypothesis of a differential role played by different HLA-DRB1 allele groups in RA susceptibility and structural severity. <h3>Disclosure of Interest</h3> None Declared
Abstract 1021: Use of functional tumor cell line mitochondria to explore the mechanisms of BH3 peptides and ABT-737-induced mitochondrial membrane permeabilization
Authors: Nelly Buron, Mathieu Porceddu, Pierre Rustin, Etienne Jacotot, Annie Borgne-Sanchez
Journal: Cancer Research (2010)

Abstract Current limitations of chemotherapy include toxicity on healthy tissues and multidrug resistance on malignant cells. A number of recent anti-cancer strategies are targeting the mitochondrial apoptotic machinery to induce tumor cell death. In this study, we set up protocols to isolate mitochondria from various origins with high purity, quality and functionality. We analyzed the effect of putative Bcl-2 inhibitors on both healthy and tumor isolated mitochondria. We measured mitochondrial membrane permeabilization (swelling), mitochondrial transmembrane potential (ΔΨm) and mitochondrial outer membrane permeabilization (MOMP) in both isolated healthy and tumoral cell mitochondria. Like t-Bid and some BH3 peptides, the molecule ABT-737 was found to present a tumor-specific mitochondrio-toxicity, while compounds like HA-14.1, YC-137, Chelerythrine, Gossypol, TW-37 or EM20-25 did not. We thus demonstrated that ABT-737 can induce a relatively large and targeted MOMP triggering the release of apoptotic proteins from tumoral cell mitochondria (Cytochrome c, Smac/Diablo and Omi/HtrA2 but not AIF) however without any mitochondrial swelling. Furthermore, ABT-737 addition to isolated tumoral cell mitochondria induced specific Bax/Bak channel formation by oligomerizing monomeric Bax and/or Bak already inserted in the mitochondrial membrane. We also provided evidence that tumoral cell mitochondria can be either resistant or sensitive to ABT-737-induced MOMP, depending on their origin and interactions between pro- and anti-apoptotic proteins. Finally, this method based on MOMP is an interesting screening tool, tailored for identifying Bcl-2 antagonists with selective toxicity profile against tumoral cell mitochondria but devoid of toxicity against healthy mitochondria. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1021.
INCIDENCE OF PERMANENT PACEMAKER IMPLANTATIONS AND NEW-ONSET INTRAVENTRICULAR CONDUCTION ABNORMALITIES AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: A COMPARISON OF THE NOVEL SAPIEN 3 WITH THE SAPIEN XT PROSTHESIS
Authors: Oliver Husser, Thorsten Kessler, Christof Burgdorf, Markus Kasel, Adnan Kastrati, Heribert Schunkert, Christian Hengstenberg
Journal: Journal of the American College of Cardiology (2015)
Removal of a migrated covered metallic stent through an esophageal stricture, with multiple endoloops
Authors: J. Molina-Infante, M. Fernandez-Bermejo, B. Perez-Gallardo
Journal: Endoscopy (2010)

Migration is a common delayed complication (3 % – 14 %) following deployment of an esophageal self-expandable metallic stent (SEMS) [1]. Although removal of migrated SEMS in the stomach is recommended to avoid gastrointestinal complications such as bleeding, obstruction, and perforation, this can be technically challenging.
FRI0461-HPR Trunk stabilizing exercise and strengthening exercises in patients with non-specific chronic low back pain: A pilot blinded randomized trial
Authors: C.M. Carmo, M.F.A. Jacob, K.S. Takara, F.G. Santos, F.A. Caromano, C. Tanaka
Journal: Annals of the Rheumatic Diseases (2013)

A 51-year-old-man presented with symptoms and baseline investigations suggestive of an infective process. Most strikingly, there was a pronounced neutrophil predominant leucocytosis. Lack of a clinical and biochemical response to empirical antibiotic therapy, prompted imaging for a deep-seated infective process, incidentally uncovering a gastro-oesophageal junction tumour. Resection of the tumour was followed by rapid resolution of the leucocytosis. He remains in clinical remission since tumour resection and adjuvant chemotherapy. Cancer-associated leukemoid reactions in non-disseminated tumours are rare. The role of polymorphonuclear (PMN) leucocytes both in the peripheral blood and the tumour itself is discussed herein. There is increasing recognition of the importance of the non-cancer cellular components of the tumour microenvironment. Myeloid suppressor cells are a subset of PMN leucocytes which play a role in tumour progression.The role of these cells and granulocyte colony-stimulating factor is highlighted in this case.
AB1046 Combination of digital X-ray radiogrammetry and frax® in evaluation of structural-functional state of bone in postmenopausal women
Authors: V. Povoroznyuk, N. Grygorieva, V. Povorozniuk
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Aim</h3> The aim of the study was to estimate the informative value of digital X-ray radiogrammetry and its combination with FRAX® in evaluation of structural-functional state of bone in Ukrainaian postmenopausal women. <h3>Methods</h3> 247 postmenopausal women aged 45-87 years were examined, average age 65±0.6 years, duration of postmenopausal period 16±1.6 years. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometer (DXA) and digital X-ray radiogrammetry (DXR) of the II-IV metacarpal bones. The ten years probability of major osteoporotic fracture calculated with FRAX®. <h3>Results</h3> There is difference in distribution of bone indexes in depending of used methods. Among women which had osteoporosis of femoral neck by DXA, 73% had osteoporosis, 24% - osteopenia, 3% - norma data by DXR. Sensitivity of DXR indexes ranging was from moderate to high, but specificity was low (with femoral neck – 73% and 38%, total hip – 78% and 22%, lumbar spine – 56% and 18%, total body – 68% and 24% accordingly). Such sensitivity and specificity increased when combining DXR with the ten years probability of major osteoporotic fracture without BMD (FRAX®) (with femoral neck – 82% and 75%, total hip – 89% and 72%, lumbar spine – 64% and 58%, total body – 79% and 69% accordingly). <h3>Conclusions</h3> DXR of is informative method in evaluation of structural-functional state of bone in postmenopausal women. Sensitivity and specificity increased when combining DXR with FRAX® from 56% and 18% up to 89% and 75% accordingly. <h3>Disclosure of Interest</h3> None Declared.
Feasibility trial of electro-acupuncture for aromatase inhibitor related arthralgia in breast cancer survivors.
Authors: JJ Mao, CT Stricker, JT Farrar, SX Xie, MA Bowman, DW Bruner, D Pucci, X Han, A DeMichele
Journal: Cancer Research (2009)

Abstract Abstract #3105 Background: Arthralgia affects postmenopausal women receiving aromatase inhibitors (AI) for breast cancer. Given the existing evidence for electro-acupuncture (EA) for treatment of osteoarthritis in the general population, this study aims to establish the feasibility of studying EA for treating AI-related arthralgia.&amp;#x2028; Patients and Methods: Postmenopausal women with stage I-III breast cancer with joint pain related to AIs were enrolled in a pilot single arm trial of acupuncture. Acupuncture was provided twice a week for 2 weeks followed by 6 weekly treatments (total of 10 treatments over 8 weeks). Manualized protocol was based on Chinese medicine diagnosis of “Bi” syndrome with eletro-stimulation of needles around the painful joint(s). Pain severity of the modified Brief Pain Inventory was used as the primary outcome. Joint stiffness and Joint interference were secondary outcomes. Patient Global Impression of Change (PGIC) was used to assess clinical relevance. Fatigue and anxiety were also evaluated. Paired-t tests were used for analysis.&amp;#x2028; Results: Twelve women were enrolled and all provided data for analysis. From baseline to the end of intervention, patients reported improvement in pain severity (5.3 to 1.9), stiffness (6.9 to 2.4), and joint symptom interference (4.7 to 0.8), all P&amp;lt;0.001; 11/12 reported joint symptoms “very much improved” based on PGIC . Subjects also reported significant decrease in fatigue (4.4 to 1.9, p=0.005) and anxiety (7.1 to 4.8, p=0.01). One subject withdrew from interventions due to an adverse event (herpes zoster) thought to be unrelated to acupuncture. Two subjects reported grade 1 self-limiting pain associated with acupuncture. No infection or development or worsening of lymphedema was observed.&amp;#x2028; Conclusion: EA is a potentially safe and effective treatment for AI-related arthralgia; thus, a randomized controlled trial is warranted to establish the short term and long term efficacy and safety of EA in breast cancer survivors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3105.