tbuckley/cabot-search huggingface dataset:
Abstract 4071: PAXgene Tissue: A new tissue fixation technology for simultaneous preservation of morphology and nucleic acids
Authors: Daniel Grölz, Nadine Dettmann, Isabell Blassnig, Ralf Wyrich, Lynne Rainen
Journal: Cancer Research (2012)

Abstract Introduction: PAXgene Tissue (PAXgene) is a new, formalin-free fixation technology developed for simultaneous preservation of morphology and biomolecules in tissue samples. PAXgene fixed, paraffin embedded (PFPE) tissue is suitable for conventional histochemical and immunohistochemical staining as well as for extraction of high quality nucleic acids. Material and Methods: Cases of human lung, breast and colorectal cancer were divided and fixed in formalin, PAXgene, or snap frozen in liquid nitrogen (LN2). PAXgene fixed, stabilized specimens were stored for up to four days at room temperature prior to processing. Formalin fixed, paraffin embedded (FFPE) and PFPE tissue morphologies were compared using H&amp;E stain. RNA, miRNA and DNA were isolated from FFPE, PFPE and LN2 tissue. RNA expression was analyzed in 96-well RT-qPCR arrays with pre-designed assays, and miRNA expression profiling was performed with single Sybr-green or primer/probe based assays. DNA was analyzed by agarose gel electrophoresis, long-range, and multiplex PCR. Results: Morphology of PFPE samples was similar to or indistinguishable from FFPE tissue. A high correlation of both RNA and miRNA gene expression results was observed between PFPE and LN2 samples. For all PCR assays, Ct values were within +/− 2 Ct. In contrast, poor correlation was observed between RNA from FFPE compared to RNA from LN2 with differences of up to 10 Cts. Correlation of FFPE to LN2 was higher in the case of miRNA but was still not as high as that of miRNA from PFPE. High molecular weight DNA which performed well in PCR could be isolated from LN2 and PFPE tissue, but DNA from FFPE failed in long-range PCR and showed biased or no amplification in multiplexed PCR. Conclusion: The PAXgene Tissue fixation technology preserves morphology and nucleic acids in tissue samples. It enables morphological and multimodal research biomarker testing with one sample. PAXgene Tissue is for research use only. It is not intended for diagnostic use. 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 4071. doi:1538-7445.AM2012-4071
SAT0265 Ratio of non-radiographic and radiographic axial spondyloarthritis in patients referred because of back pain is dependent on symptom duration
Authors: D. Poddubnyy, H. Brandt, J. Vahldiek, I. Spiller, I.-H. Song, M. Rudwaleit, J. Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axial SpA (=ankylosing spondylitis – AS) are considered currently as two stages of axial SpA. We reported recently that about 12% of the patients with non-radiographic axial SpA progress in AS over 2 years [1]. Although it can be expected that in the first years after back pain onset non-radiographic (without definite sacroiliitis on the x-ray) SpA is more likely to see than established AS, their frequencies and their ratio in relation to back pain duration at the referral time point is not known. <h3>Objectives</h3> To estimate the ratio of nr-axSpA and AS diagnoses in relation to the symptom duration in patients referred to a rheumatologist because of chronic back pain and suspicion of axial SpA. <h3>Methods</h3> In this monocenter study performed in Berlin [2] orthopaedists and primary care physicians were requested to refer patients with chronic low back pain (duration &gt;3 months) and onset of back pain before &lt;45 years of age to a SpA-specialized rheumatology outpatient clinic for further diagnostic investigation if at least one of the following screening parameters was present: 1) inflammatory back pain, 2) positive HLA-B27, and 3) sacroiliitis detected by imaging. The final diagnosis was made according to the opinion of rheumatologist. <h3>Results</h3> In total, 522 patients were referred. A diagnosis of definite axial SpA was made in 43.7% of the cases. Among patients who were referred with chronic back pain axial SpA was diagnosed in a similar percentage of about 50% if symptom (back pain) duration was &lt;9 years and of 36% if symptom duration was &gt;9 years. The ratios of nr-axSpA to AS among patients with definite axial SpA in relation to the duration of back pain at the time-point of referral are presented in figure. Nr-axSpA represented the majority of patient (67.3%) only if duration of back pain was 1 year and less at the time of referral. Between 1 and 6 years of back pain duration the probability of nr-axSpA and AS was nearly equal. In patients with back pain duration of more than 6 years, AS was more likely to be diagnosed than nr-axSpA, and this increased further over time. <h3>Conclusions</h3> Non-radiographic axial SpA is a relevant diagnosis in patients with axial SpA at any time point, however, the probability of non-radiographic form of axial SpA is highest if symptom duration is short. <h3>References</h3> Poddubnyy D, et al. Ann Rheum Dis 2011;70:1369-74. Brandt HC, et al. Ann Rheum Dis 2007;66:1479-84. <h3>Disclosure of Interest</h3> None Declared
Detection of Synchronous Carcinomas of the Colon With F-18 Fluorodeoxyglucose
Authors: CARLOS A. C. PIN, MARCUS V. GRIGOLON, ELBA C. S. C. ETCHEBEHERE, ALLAN O. SANTOS, MARIANA C. L. LIMA, CELSO D. RAMOS, EDWALDO E. CAMARGO
Journal: Clinical Nuclear Medicine (2000)

Colon and rectal carcinomas are common in North America and Northwestern Europe. In South America, the risk of this disease is not as great. Adenocarcinomas are the most common types of tumors, and they occur mainly in the descending colon, sigmoid, and rectum. A patient with a possible right colon carcinoma was examined using F-18 FDG.
Abstract 5477: Engineered toxin body demonstrating CD20-specific binding and cell kill in B-cell non-Hodgkin's lymphoma cells.
Authors: Rachel Wirth, Sangeetha Rajagopalan, Erin Willert, William Null, Jennifer Erdman, Jen-Sing Liu, Jack P. Higgins
Journal: Cancer Research (2013)

Abstract Non-Hodgkin's lymphoma (NHL) offers an attractive area for therapeutic biologics. The most successful example of this targeted approach is rituximab, which is approved for front and second line therapy of NHL. Rituximab targets the CD20 antigen expressed on 90% of B-cell NHL cells. However, rituximab has limited direct cell-kill effects, acting instead primarily through indirect immune responses induced by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC). Direct-cell kill approaches to CD20 have been limited to radioimmunotherapy because CD20 does not efficiently internalize. Despite improved clinical efficacy seen over Rituximab with both 131 tositumomab and ibritumomab tiuxetan, challenges around the administration of radioimmunotherapies have severely curtailed therapeutic use. We have developed an engineered toxin body (ETB) comprising a CD20 scFv and a modified Shiga-like Toxin A (3F7) capable of specifically recognizing and killing CD20 expressing cells. Utilizing a flow cytometry based binding affinity assay, 3F7 demonstrated selective binding to CD20 positive Raji cells whereas no significant binding was observed in CD20 negative BC-1 cells. Further, direct competition of 3F7 binding to Raji cells was observed in the presence of rituximab or the parent monoclonal antibody. 3F7 demonstrated CD20-specific direct cell kill of Raji, Daudi and Ramos cells with minimal cell kill of CD20 negative BC-1 or Jurkat cells. Initial dose finding studies in mice found that a therapeutic dosing schedule was well tolerated. Raji xenograft studies in mice are ongoing. 3F7 is a novel therapeutic approach with direct cell-kill activity against CD20-expressing cells which could expand treatment options for B-cell lymphoma. Citation Format: Rachel Wirth, Sangeetha Rajagopalan, Erin Willert, William Null, Jennifer Erdman, Jen-Sing Liu, Jack P. Higgins. Engineered toxin body demonstrating CD20-specific binding and cell kill in B-cell non-Hodgkin's lymphoma cells. [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 5477. doi:10.1158/1538-7445.AM2013-5477
Resting and Acetazolamide-Activated Tc-99m HMPAO Brain SPECT for Congenital Bilateral Absence of the Internal Carotid Arteries
Authors: Takao Sagiuchi, Katsumi Ishii, Shinichi Kan, Tomoko Ohmori, Yuuji Asano, Kazushige Hayakawa
Journal: Clinical Nuclear Medicine (2003)

SAGIUCHI, TAKAO M.D.*†; ISHII, KATSUMI M.D.†; KAN, SHINICHI M.D.†; OHMORI, TOMOKO M.D.†; ASANO, YUUJI M.D.†; HAYAKAWA, KAZUSHIGE M.D.† Author Information
Case 11-2010
Authors: Nagagopal Venna, R. Gilberto Gonzalez, Sandra I. Camelo-Piragua
Journal: New England Journal of Medicine (2010)

A 69-year-old woman presented to this hospital because of a 2-month period of increasing apathy, confusion, and depression. She had a history of connective-tissue disease and idiopathic thrombocytopenic purpura. Ten days before admission, a magnetic resonance image of the brain was obtained, which was abnormal.
ASSESSMENT OF BIORESORBABLE SCAFFOLD STRUTS WITH A NOVEL HIGH-DEFINITION 60MHZ IVUS IMAGING SYSTEM: COMPARISON WITH 40MHZ IVUS AND OPTICAL COHERENCE TOMOGRAPHY
Authors: Kozo Okada, Hideki Kitahara, Yoshiaki Mitsutake, Takumi Kimura, Kojiro Miki, Fumiaki Ikeno, Paul Yock, Peter Fitzgerald, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2016)
AB1477-HPR The risk of developing avascular necrosis of the hip differs greatly among collagen vascular diseases requiring treatment with high-dose glucocorticoids
Authors: Y. Takizawa, K. Setoguchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Avascular necrosis (AVN) of the hip is still one of the most serious complications associated with high-dose glucocorticoids (HDGC) treatment [1]; however, it has yet to be sufficiently appreciated among patients with collagen vascular diseases (CVD) other than lupus [2]. <h3>Objectives</h3> To clarify the frequency of AVN in each age and disease group of CVD, and risk factors for its development. <h3>Methods</h3> Patients with CVD hospitalized in 2002-2009 were subjected to analysis. <h3>Results</h3> Twenty-nine of the total 892 patients who had been hospitalized developed AVN of the hip afterwards. Since 28 (96.6%) of them had been treated with HDGC, i.e., prednisolone ≥30 mg/day for longer than 2 weeks or pulsed methylprednisolone (p-MPSL), only those with selected diseases who had received treatment with HDGC (n=268) were chosen and subjected to analysis. AVN occurred most frequently in miscellaneous small-vessel vasculitides (SV, n=2, 28.6%), followed by adult-onset Still disease (AOSD, n=3, 15.8%), systemic lupus erythematosus (SLE, n=16, 13.1%), microscopic polyangiitis (MPA, n=3, 7.3%), inflammatory muscle diseases (IMD, n=3), and Behcet disease (n=1, 6.3%).Although not significant, more than one HDGC treatment (odds ratio (OR): 2.04 (0.9289-4.4906), p=0.07), younger age (mean±standard deviation (SD): 43.3±18.1 years versus 49.6±19.5 years, p=0.1), p-MPSL (OR 1.74 (0.8-3.81), p=0.16) raised the risk of developing AVN. As for age, the risk of AVN was highest in those who received the first HDGC treatment in the teens (15.8%) and lowest (0%) in those who did in the eighties. The time to the development of AVN from the first treatment was significantly longer (6.91±3.55 years) in those who received more than one HDGC treatment than in those who received only one (3.80±2.67 years, p=0.02). It was observed that the patients with SLE (68.8%) and MPA (66.7%) tended to develop AVN late after several treatments, whereas all of the patients with AOSD and SV developed it earlier after only one treatment. <h3>Conclusions</h3> Not only patients with lupus but also those with AOSD, IMD, and certain diseases of vasculitis syndromes who had been on treatment with HDGC were at risk for developing AVN of the hip. The way it developed was highly variable, mainly dependent on the underlying disease. <h3>References</h3> Migliaresi S, Picillo U, Ambrosone L, et al. Avascular osteonecrosis in patients with SLE: relation to corticosteroid therapy and anticardiolipin antibodies. Lupus 1994;3:37-41. Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine 2011 (in press) <h3>Disclosure of Interest</h3> None Declared
Abstract 3230: Targeted sequencing of 16 archived ovary cancers.
Authors: Shihong Li, Narisra Jongkam, Wei Xia, Hong Tran, K. Stephen Suh
Journal: Cancer Research (2013)

Abstract We developed a method to extract up to 22 μg DNA from a single 10 μm FFPE slide. Although FFPE DNA is notoriously fragmented, our extraction method enabled us to consistently generate 150-250 bp amplicons. This DNA enables whole genome sequencing and targeted sequencing using various platforms. This poster will present targeted amplicon sequencing on the Ion Torrent PGM™ . Single FFPE pathology slides from 16 ovary cancer specimens (5 cured with first line chemotherapy and 11 relapsed within 5 years), archived from 1999-2005, were processed. Amplicons targeting selected exons and hotspots of 54 cancer genes were sequenced using both traditional Sanger sequencing (28 amplicons covering 8 genes) and by Next Generation sequencing (190 amplicons covering 46 genes using Ion AmpliSeq™ Cancer Panel). 5 ng FFPE DNA (based on Qubit measurement) from each patient was subjected to 190-plex PCR. The resulting amplicon libraries were ligated with indexed adaptors. Each eight libraries were pooled and sequenced on one 318 Chip. Average read depth ranged from 1521 to 3138, with 87.3% to 99.6% targets covered at least 20 times. Quality scores were above 30 for the first 80 bps, above 25 for 100 bps, and above 19 for 200 bps. 12 to 76 genetic variants were detected from each patient at frequency ranges from 0.7% to 100%. Both the genomic variation that occurred only in cured or relapsed group, and the genetic variations that were common to both groups will be presented. Citation Format: Shihong Li, Narisra Jongkam, Wei Xia, Hong Tran, K. Stephen Suh. Targeted sequencing of 16 archived ovary cancers. [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 3230. doi:10.1158/1538-7445.AM2013-3230
Single-channel endoscopic closure of ERCP-related large duodenal perforations
Authors: Chun-Yan Zeng, Yong Zhu, Gui-Hai Guo, You-Xiang Chen
Journal: Endoscopy (2014)

Duodenal perforation is a rare but potentially lethal complication of endoscopic retrograde cholangiopancreatography (ERCP) [1] [2] [3]. Large duodenal perforations, which may occur during ERCP and which cannot be closed using titanium clips, require immediate surgery or are treated with two-channel endoscopic closure using nylon loops and endoclips [4] [5] [6] [7]. Here, using a single-channel endoscope, we describe the successful closure of one ERCP-related large duodenal perforation using nylon loop sutures and titanium clips.
A3.10 Characterisation of CD4<sup>+</sup>T cell response and effects of regulatory T cells in pristane induced lupus (PIL)
Authors: H Leiss, B Schwarzecker, I Gessl, B Niederreiter, JS Smolen, GH Stummvoll
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> CD4+ T cells and the Th1 subset in particular play a pivotal role in SLE. Regulatory T cells (Treg) are essential for maintaining peripheral tolerance, but their number and function in SLE is decreased. We herein characterise CD4+ T cell and Treg homeostasis as well as the effects of intravenous administration of exogenous Treg on disease severity in a model of induced systemic lupus. <h3>Methods</h3> Mice were injected ip. with 0.5ml of pristane or PBS as control and killed after 8 months. Cell suspensions with CD4+ FoxP3+ cells (iTreg) were injected intravenously: when PIL was induced (5 x 10e6, iTreg-boost) or every 4 weeks (1 x 10e6, iTreg-repeated). Animals were monitored for clinical signs of arthritis and in order to analyse and compare disease severity, histological features of arthritis and pneumonitis were quantified by an image analysis system (Osteomeasure®). Lymphocytes were isolated from granulomas (ectopic lymphoid tissue within the peritoneum), lymphnodes (LN) and spleens and were analysed separately for each mouse by FACS. <h3>Results</h3> Clinically, PIL presented involvement of inner organs; most frequently affected were the lungs (100% pneumonitis) and the joints, whereas 52% out of the PIL group and 36% of the Treg-treated groups developed clinical arthritis. Monthly iTreg significantly decreased clinical signs of arthritis and histological lung and joint parameters. Out of 6 mice treated, 4 (66%) did not show any signs of arthritis at all. One-shot iTreg did not prevent joint manifestations or pneumonitis, but seemed to have a retarding effect indicated by a delayed onset of clinical symptoms and by a significantly decreased erosive area. Intraperitoneal granuloma typical for PIL appeared to be the hotspots of inflammation showing a significantly elevated Teff/Treg ratio of 1.3. Upon re-stimulation, CD4+ cells showed a pronounced Th1 response (27% IFNγ producers) compared to LN and spleens from both PIL and HC (with Th1 percentages ranging from 9-16%), but also frequencies of Th2 and Th17 cells were elevated in PIL, again with the highest yield in granuloma. iTreg reduced the Teff/Treg ratio in PIL granuloma to 0.7. <h3>Conclusion</h3> Repeated injections of exogenously induced Tregs reduce the T<sub>eff</sub>/T<sub>reg</sub> ratio as well as the severity of pneumonitis and arthritis. A single boost of Tregs even when applied before the clinical onset cannot decrease all parameters, but appears to retard onset of symptoms and progression. Thus, iTreg have significant effects on lupus symptoms when applied repeatedly, which may have consequence for future therapeutic considerations.
Dose-dense (DD) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2/neu-positive breast cancer is not feasible due to excessive diarrhea: updated results.
Authors: C Dang, N Lin, B Moy, S Come, D Lake, M Theodoulou, T Troso-Sandoval, M Dickler, M Gorsky, G D'Andrea, S Modi, A Seidman, P Drullinsky, A Partridge, L Schapira, G Wulf, T Gilewski, D Atieh, E Mayer, S Isakoff, S Sugarman, M Fornier, T Traina, J Bromberg, V Currie, M Robson, H Burstein, B Overmoyer, P Ryan, I Kuter, J Younger, S Schumer, N Tung, C Zarwan, L Schnipper, C Chen, E Winer, L Norton, C Hudis
Journal: Cancer Research (2009)

Abstract Abstract #2108 Background: DD q 2 weekly (w) AC → P + T x 1 year (y) has an acceptable safely profile w/ congestive heart failure (CHF) rate of 1/70 pts (Dang, JCO 2008). Lapatinib (L) is effective in HER2 (+) BC. We conducted a pilot study of dd AC → w P + T + L to determine its feasibility and cardiac safety.&amp;#x2028; Methods: Enrolled pts had HER2 (+) BC; LVEF &amp;gt; 50%. Rx consisted of AC at 60/600 mg/m2 x 4 q 2 w (w/ pegfilgrastim 6 mg day 2) → P at 80 mg/m2 x 12 q w + T x 1 y; L (1000 mg daily beginning w/ P + T and continued x 1 y). MUGA is obtained at baseline and at months (mo) 2, 6, 9, and 18. Rx is considered feasible if 1) &amp;gt; 80% pts can complete the PTL phase without a dose delay or reduction and 2) the cardiac event rate (CHF or cardiac death) is &amp;lt; 4%. Pts can remain on-Rx w/ one dose reduction of L (1000 mg → 750 mg) for a G 3 event or &amp;lt; G 3 toxicity (unacceptable).&amp;#x2028; Results: From March 2007 to April 2008, we enrolled 95 pts. Median (med) age was 45 years (range, 28-73). At a med follow-up of 7 months, 90 are evaluable. Of the 90 pts, 34 (37%) withdrew from study during the PTL phase; 29 for a 2nd event of G 3 or unacceptable &amp;lt; G 3 toxicities (15 G 3 diarrhea, 4 G 1/2 diarrhea, 1 G 3 rash, 2 G 2 rash, 1 G 3 dyspnea and also had G 3 diarrhea, 1 G 3 ↑QTc also had G 3 diarrhea, 1 G 3 ↑ALT also had G 3 diarrhea, 1 G 3 paronychia, 1 G 3 pneumonitis, 1 asymptomatic LVEF ↓, 1 myocarditis) and 5 for other reasons (2 personal reason, 1 PCP pneumonia, 1 progression, 1 P hypersensitivity). Overall, 25/90 (27%) pts had G 3 diarrhea and 31/90 (34%) pts required a dose reduction of lapatinib. Med LVEF at baseline is 67% (N=95), at mo 2 is 68% (N=90), at mo 6 is 65% (N=53), and mo 9 is 65% (N=28). To date there are no patient drop-outs due to significant LVEF declines after dd AC; one patient dropped during PTL out due to an asymptomatic LVEF decline.&amp;#x2028; Discussion: L at 1000 mg/day is not feasible combined w/ weekly P and T by protocol stipulation (&amp;gt; 20% pts required L dose reduction) primarily due to excessive G 3 diarrhea. These results have led to the modification of Design 2 (Arm D) of ALTTO. We will report updated results. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2108.
Abstract 344: Subpopulations of lung neuroendocrine cells mirror neuronal development.
Authors: Florent Suau, Ilona Linnoila, Xu Naizhen
Journal: Cancer Research (2013)

Abstract Pulmonary neuroendocrine cells (PNECs) which comprise less than 1% of airway epithelium were recently shown to be the cell of origin for small cell lung cancer (SCLC). SCLC is the most aggressive form of human lung cancers and characterized by early dissemination or metastases and neuroendocrine features. We used immunohistochemistry (IHC) and animal models in order to delineate the cellular hierarchy of PNEC potentially leading to cancer. PNECs were first identified in the early lung development (E12.5) as positive for the proneural basic helix-loop-helix transcription factor Achaete-scute homolog-1 (Ascl1) which is pivotal for PNEC differentiation and highly expressed in SCLC. Later in the development (E16.5) and in adulthood, PNECs coexpressed Ascl1 and calcitonin gene-related peptide (CGRP), a primary neuropeptide in mouse lung. Interestingly, we showed that doublecortin (DCX), a marker of immature migrating neurons, is transiently expressed in PNECs during the early development. Later in the development (E16.5), we observed a subpopulation expressing the neural-specific β3-tubulin (TUBB3), a neuronal marker. We also observed that neural cell adhesion molecule (NCAM), a marker of SCLC, is transiently expressed in a low number of PNECs in the late embryonic period. In parallel, using the transgenic CC10-hASH1 mouse model, where Ascl1 is overexpressed in non-neuroendocrine airway epithelial cells, we determined that it is not sufficient to induce neuroendocrine differentiation or expression of DCX, TUBB3 and NCAM. We conclude that Ascl1, DCX and TUBB3 are consecutively expressed in PNECs during development, similarly to the pattern observed during neuronal development. However, Ascl1 expression seems to be maintained even in the mature PNECs unlike in the mature neurons where it is turned off. On the other hand, NCAM expression in PNECs is transient and maybe reactivated during the instance of SCLC. To establish the relationships between the different PNEC populations and Ascl1 expression, we are currently evaluating Cre-dependent conditional Ascl1 deletion in mouse lung. Further work will be necessary to address the functional potential of the PNEC subpopulations in tumorigenesis. Citation Format: Florent Suau, Ilona Linnoila, Xu Naizhen. Subpopulations of lung neuroendocrine cells mirror neuronal development. [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 344. doi:10.1158/1538-7445.AM2013-344