tbuckley/cabot-search huggingface dataset:
Mast cell activation syndrome (MCAS) diagnosed using double-balloon enteroscopy
Authors: K. Mönkemüller, M. Kassalik, D. Baraksei, L. Fry, J. Moege
Journal: Endoscopy (2012)

A 69-year-old woman was referred for small-bowel endoscopy because of abdominal pain and diarrhea of 1-year's duration. She complained of bloating and fullness of her abdomen, accompanied by headaches, occasional palpitations, and anxiety. Her past medical history was positive for coronary artery disease, hypertension, and hyperlipidemia. An outpatient colonoscopy revealed diverticula.
99mTc-Tektrotyd SPECT/MRI in the Diagnosis of a Gastroenteropancreatic Neuroendocrine Tumor
Authors: Shahin Zandieh, Juan Pablo Gambini, Jörg Haller, Margarida Rodrigues
Journal: Clinical Nuclear Medicine (2012)

99mTc-tektrotyd is a recently developed tracer for imaging neuroendocrine tumors. We report the case of a patient with a history of prostate cancer and chronic lymphocytic leukemia, who presented with a liver biopsy showing leukemic infiltration associated with chromogranin and CDX2 positivity, suggestive of metastases from an intestinal neuroendocrine tumor. While diagnostic CT did not detect the primary tumor and showed only some liver metastases, 99mTc-tektrotyd SPECT/MRI fusion identified a pancreatic head tumor and several liver metastases. This case illustrates the feasibility and clinical value of SPECT/MRI fusion using 99mTc-tektrotyd in neuroendocrine tumor patients.
P17.18 * IMMUNOFLUORESCENCE OBSERVATION OF VASCULOGENIC MIMICRY CHANNELS IN HUMAN GLIOBLASTOMA SAMPLES
Authors: X. Mei, Y. Chen, Z. Chen
Journal: Neuro-Oncology (2014)

BACKGROUND: Vasculogenic mimicry(VM) has been reported in many malignant human tumors, including gliomas. In the present study, we have found four types of microcirculation vessels in human glioblastomas. Method and material: Thirty-seven human glioblastoma samples were examined for VM by CD34 and PAS dual staining,as well as immunofluorescence dual staining for CD34 and GFAP. The GFAP positive (GFAP+) cells were considered as glioma cells. Even though CD34 positive (CD34+) was endothelial cells, but both CD34 + / GFAP+ should be also considered as glioma cells. Result: CD34 and PAS dual staining revealed 4 types of microcirculation vessels in human glioblastoma samples: endothelium dependent vessels, tumor cell dependent vessels, extracellular matrix (ECM) dependent vessels, and mosaic vessels. While immunofluorescence study confirmed VM should be vessels lined with GFAP+ cells (could be CD34- or co-express CD34). Twelve samples were found VM by CD34 and PAS dual staining (32%), while 20 samples were revealed VM by immunofluorescence dual staining (57%). CONCLUSION: Our results suggest that glioblastoma cells have potential to express endothelial cell marker CD34. And immunofluorescence dual staining is a more sensitive as well accurate technique revealing VM vessels in glioblastoma.
MR-05 * GLIOMA STEM CELL SPECIFIC microRNA-mRNA INTERACTION NETWORK
Authors: S. Singh, K. Burrell, A. Alamsahebpour, E. Koch, S. Agnihotri, J. Gumin, E. Sulman, F. Lang, B. Wouters, K. Aldape, G. Zadeh
Journal: Neuro-Oncology (2014)

microRNAs have been shown to have oncogenic or tumor suppressor function in glioblastoma (GBM). It has been postulated that there exists an extensive microRNA-mediated RNA-RNA interaction network in GBMs utilizing systems biology approach supporting a competitive endogenous RNA (ce-RNA). MicroRNAs have functional relevance in the regulation of critical genes and pathways implicated in the maintenance of glioma stem cell (GSC) properties. To address this, we have applied biochemical methods to establish direct miRNA-mRNA interaction network relevant and specific to GSCs. To avoid inclusion of the inherent bias of miRNA-target prediction algorithms, we have generated an unbiased global miRNA mediated RNA-RNA interactome by performing RNA-sequencing all RNA species (small and large RNAs) isolated from AGO2-microRNA-induced silencing complex (miRISC) of GSCs and normal human neural stem cells (hNSCs). Additionally, we have also established this interactome after exposure of GSCs and normal hNSCs to hypoxia, a key tumor micro-environmental factor that is known to be pivotal in generating GBM heterogeneity. In all, three independent GSC lines and one NSC line were profiled, and results compared with each other. miRNA-mRNA interaction nodes were determined by RNA read counts from RNA-seq data and combinations of miRNA target prediction softwares. The rank order list of miRNA-mRNA interaction nodes generated from RNA sequence reads reveals that enrichment of specific RNAs in functional AGO2-miRISC is not a direct function of their relative abundance in cells, thus this biochemically generated interactome is distinct from that generated by bioinformatics tools. Our data shows that MYC as one of the key networks targetted by microRNAs specifically in GSCs under hypoxic conditions. We demonstrate that scope and influence of GSC specific miRNA-mRNA network and specific nodes of this interactome varies with hypoxia and tumor region in GBMs
Abstract 3456: Nicotine and the alpha-7 nicotinic acetylcholine receptor in the regulation of response to radiotherapy
Authors: Samantha L. Sobus, Michelle A. Romano, Janelle Mackowiak, Graham W. Warren
Journal: Cancer Research (2012)

Abstract Purpose: Nicotine is a systemically available component of tobacco known to decrease the effectiveness of chemotherapy and/or radiotherapy (RT) however, the mechanisms of decreased RT response are not well characterized. The purpose of this study is to evaluate the effects of nicotine and activation of the alpha-7 nicotinic acetylcholine receptor (a7-nAChR) on regulating cell survival following RT and to identify potential mechanisms of regulation. Methods: Human lung cancer (A549, H460) and oropharyngeal cancer (FaDu) cell lines were treated with nicotine alone or in combination with nAChR inhibitors, MEK inhibitors, PI3K inhibitors, or mTOR inhibitors followed by treatment with RT to evaluate cell survival using clonogenic assays. The effects of a7-nAChR agonists on RT were also evaluated. Western blots were performed to evaluate nAChR subunit expression profiles in a broad spectrum of cancer cell lines and to evaluate the effects of nicotine (alone or with inhibitors listed above) or agonists on downstream signal transduction. Results: Nicotine administration 2 hours prior to RT increased survival in all cell lines. nAChR expression was confirmed in several cell lines including A549 and H460 cells. Inhibition of specific nAChRs in A549 and H460 cells demonstrated that the a7-nAChR prevented the effects of nicotine on RT in both cell lines. Nicotine administration increased p-ERK 1/2, p-Akt (Ser-473), mTOR (S2448), activated matrix metalloproteinase 2 (MMP2), and hypoxia inducible factor 1-alpha (HIF-1a). Inhibition of MEK prevented ERK 1/2 phosphorylation, but did not prevent the effects of nicotine on RT. Inhibition of PI3K prevented Akt phosphorylation, MMP2 activation, and HIF-1a induction with concomitant inhibition of the effects of nicotine on RT. Administration of an mTOR inhibitor (rapamycin) significantly sensitized cells to RT, but did not prevent the pro-survival effects of nicotine. Administration of selective a7-nAChR agonists (LY 2087101, PHA 54613, PNU 282987, TC 1698) demonstrated that all increased p-ERK 1/2 and p-Akt; however, only LY 2087101 and PHA 54613 increased cell survival with RT. Further analysis demonstrates that only LY 2087101 and PHA 54613 increased mTOR (S2448) while there was no change in mTOR (S2448) with PNU 282987 or TC 1698. Conclusions: Data demonstrates that activation of the a7-nAChR can decrease the effectiveness of RT. Results suggest that PI3K and mTOR may play a central role in conferring resistance to radiation by nicotine or during a7-nAChR activation. Further analyses of critical mechanisms are required to understand the adverse systemic effects of tobacco on cancer treatment. 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 3456. doi:1538-7445.AM2012-3456
THU0393 The clinical observational study of adult onset still’s disease in a large cohort of korean patients
Authors: J.J. Kim, K.H. Jung, Y.B. Joo, C.B. Choi, Y.K. Sung, J.B. Jun, T.H. Kim, S.C. Bae, D.H. Yoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adult onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology that classified into three patterns. The treatment of AOSD has been empirical and the information predicted outcome is lack. <h3>Objectives</h3> The objective of this study is to evaluate the clinical features and responses to therapy in Korean AOSD patients. <h3>Methods</h3> We retrospectively reviewed medical records of one hundred thirty-seven Korean patients with AOSD satisfied Yamaguchi's criteria at one tertiary hospital from 2005 to 2011. <h3>Results</h3> 83.3% was female, and the average age of diagnosis is 37.1 years old. Median period of follow-up is 59.0 months. Thirty-seven patients (27.0%) are monocyclic, sixty-eight patients (49.6%) are polycyclic and thirty-two patients (23.4%) are chronic articular pattern. Clinical manifestations were: fever 89.8%, arthritis 66.4%,evanescent rash 62.8%, abnormal liver function test 62.8%, leukocytosis 55.3%, hyperferritinemia 43.1%, myalgia 38% and sore throat 35.8 et al. There was no correlation between disease pattern and clinical manifestations except level of serum ferritin between monocyclic and polycyclic pattern. Average of modified Pouchot's score at disease onset was 4.9±1.7 and statistically correlated with monocyclic and polycyclic patterns. Prescriptions were: glucocorticoid (GC) 80.9%, methotrexate (MTX) 73.8%, leflunomide 34%, cyclosporine (CsA) 32.6%, hydroxychloroquine (HCQ) 26.2%, azathioprine (AZA) 5.7%, anti-TNF blockers 7.8% (etanercept 5, adalimumab 2, infliximab 6) and intravenous immunoglobulin 3.5%. Almost patients were treated with combination of GC and/or immune suppressants. Combination of MTX and GC were 18%. The rates of these combination plus additional leflunomide, CsA or HCQ were 20.3%, 17.6% and 9.5% respectively. The rates of combination were GC with CsA 7.2%, GC with HCQ 2.7%, GC with leflunomide 1.8% and GC with AZA 1.4% respectively. The response rates were GC 76.1%, MTX 70.2%, leflunomide 68.8%, CsA 52.3 and anti-TNF blocker 72.7%. Four cases made an attempt to treat with anakinra or tocilizumab. GC response was correlated with disease remission (p-value &lt;0.017). MTX and leflunomide were effective at GC responders in polycylic and chronic articular patterns. CsA was not effective in the presence of arthritis, especially chronic articular pattern (p-value &lt;0.008). <h3>Conclusions</h3> Polycyclic pattern of AOSD is more common in this study. Ferittin and modified Pouchot's score could be considered as predictors of disease pattern but not sufficient. GC and MTX were effective treatments like previous studies. Additionally leflunomide could be used effectively in the presence of arthritis in combination with MTX rather than CsA. <h3>Disclosure of Interest</h3> None Declared
A Novel Approach for Hepatitis Delta Virus Viremia Quantification by Droplet Digital PCR Assay
Authors: A. Olivero, M.L. Abate, G. Niro, G.P. Caviglia, C. Rosso, A. Ciancio, R. Fontana, A. Smedile, M. Rizzetto, G.M. Saracco
Journal: Journal of Hepatology (2016)
Prognostic role of prior cytokine immunotherapy in outcome of treatment with tremelimumab (CP-675,206) in patients with metastatic melanoma
Authors: C. A. Bulanhagui, J. Gomez-Navarro, S. Antonia, J. A. Sosman, J. M. Kirkwood, B. G. Redman, T. F. Gajewski, A. Ribas, L. H. Camacho, D. Pavlov
Journal: Journal of Clinical Oncology (2008)

3057 Background: A recent report has suggested that prior therapy with interferon (IFN), but not interleukin-2 (IL-2), may be a negative prognostic factor for survival of patients treated with an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody (mAb). The results of a phase I/II trial were analyzed to evaluate this hypothesis and guide future studies on the potential role of prior treatment with cytokines in relation to the outcome of immunotherapy with the fully human anti-CTLA4 mAb tremelimumab (CP-675,206). Methods: Data for this analysis were derived from a phase I/II, open-label, randomized clinical trial in adult patients (N = 119) with stage III/IV melanoma who were intravenously administered 3 to 15 mg/kg tremelimumab every 30 to 90 days. Patient outcomes were retrospectively analyzed with regard to exposure to prior immunotherapy. Results: Compared with patients who had not received prior immunotherapy (n = 25, 21%), patients who received prior treatment with any immunotherapy (n = 94, 79%) had similar median survival and median time to progression. Although no significant differences were observed with or without prior IFN, prior treatment with IL-2 was associated with significantly reduced TTP and survival (Table). Conclusions: These data suggest patients previously treated with IL-2 therapy may derive less clinical benefit from tremelimumab than patients not treated with IL-2. However, a variety of confounding factors may have introduced bias, and further analyses of larger databases are planned. n ECOG > 0 (N = 117) Objective response rate (N = 112) Median TTP (N = 119) Median survival (N = 119) Prior IL-2 46 41% 5% 1.8 months 9.7 months No prior IL-2 73 45% 15% 2.0 months 13.5 months P value 0.707 0.121 0.011 0.041 ECOG = Eastern Cooperative Oncology Group; TTP = Time to progression; IL-2 = Interleukin-2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Bristol-Myers Squibb, Pfizer Pfizer Pfizer Bristol-Myers Squibb, Pfizer
THU0471 Tocilizumab in Refractory Adult-Onset Still’s Disease: Multicenter Study of 27 Patients
Authors: F. Ortiz-Sanjuán, R. Blanco, F. Narváez, E. Rubio-Romero, S. Castañeda, M. Hernández, W. Sifuentes-Giraldo, I. Ros Vilamajó, A. Mas, A. Gallego Flores, S. Manrique-Arija, C. Gómez Arango, R. Roselló, C. Marras, C. Plasencia-Rodriguez, J. Llobet, M. Velloso-Feijoo, M. Freire, M. Caracuel, M. Moll Tudurí, P. Lluch, J. Loricera, V. Calvo-Río, M. González-Gay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adult-onset Still’s disease (AOSD) is often refractory to standard immunosuppressive therapy. Tocilizumab (TCZ) has shown efficacy in isolated cases or in small series. <h3>Objectives</h3> We assess the efficacy of TCZ in AOSD. <h3>Methods</h3> Multicenter study of 27 patients with AOSD of 18 hospitals diagnosed according to Yamagouchi’s criteria (J Rheumatol 1992;19:424). TCZ was used due to lack of good response to standard therapy or to other biologic agents. <h3>Results</h3> The 27 patients (20 women/ 7 men), had a mean age of 37.2±15.9 (range 16-71) and an average duration of AOSD of 5.9±4.6 years (range 0.1-17) to onset of TCZ. Prior to the onset of TCZ and besides corticosteroids, patients had recived the following drugs: Metotrexate (26 patients), Anakinra (12), Etanercept (6), Adalimumab (5) and Infliximab (3). TCZ standard dose was 8 mg/k/iv/4 weeks. At TCZ onset, the most frequent clinical manifestations were joint (27 cases), cutaneous (14) and fever (18), along with analytical abnomalities, increase of ESR or CRP (20 cases), anemia (11) or leukocytosis (15). Clinical and analytical improvement was observed soon, 1<sup>st</sup> month after the onset of TCZ therapy <b>(TABLE).</b> After a mean follow-up of 20.8±12 months, cutaneous manifestations disappeared in 13 of 14 patients (92,9%), fever in 17 of 18 (94.4%) and joint manifestation in 22 of 27 (81,5%). Improvement of analytical abnormalities was observed in most cases with normalization of the blood cell count in 9 of 15 (60%) patients, anemia in 11 of 11 (100%), ESR in 15 of 19 (78.9 % ), CRP in 17 of 20 (85%), hepatic enzymes (AST/ALT) in 3 of 4 (50 %) and ferritin seric levels in 11 of 13 (84,6%). The median [IQR] dose of steroids was reduced from 15 [8.8-25] to 5 [1.3-7.5]. <h3>Conclusions</h3> In refractory AOSD, TCZ yields early and maintained clinical-analytical response, even in refractory cases to other biological agents. Although TCZ showed global efficacy, joint are more refractory than other systemic manifestations. <h3>Disclosure of Interest</h3> None Declared
Pregnancy Related Breast Carcinoma: Comparison of Receptor Status with Age-Matched Controls.
Authors: R. Bhargava, P. Sukumvanich, S. Beriwal
Journal: Cancer Research (2009)

Abstract Pregnancy related breast cancer (PRBC) is defined as breast cancer that is diagnosed during a pregnancy or within 1 year post-partum. These are generally considered as biologically aggressive tumors but the recent data suggests their prognosis to be similar to that of non-pregnant patients matched for age and stage. In the last few years, gene-expression profiling has been used to define breast cancer molecular classes with prognostic significance. The determination of tumor molecular class by immunohistochemistry is a reasonable alternative to molecular profiling. Therefore, we used immunohistochemical surrogate markers, estrogen receptors (ER), progesterone receptors (PR) and HER2 to determine breast cancer molecular classes in PRBC and compared them to age matched controls. ER and PR were scored using a semi-quantitative H-score like method that take into account both intensity and percentage cellular staining, and the score has a dynamic range of 0-300. An ER and PR score &amp;gt;10 was considered a positive result. An ER/PR score of 200 or higher in a tumor was considered as strongly positive for the hormone receptor. HER2 was considered positive only if 3+ by IHC or unequivocally amplified by FISH. The tumors were classified as luminal A (LUMA), Luminal B (LUMB), Triple Negative (TN), ERBB2, Luminal A-HER2 Hybrid (LAHH), and Luminal B-HER2 Hybrid (LBHH). The immunohistochemical criteria, prevalence of molecular subtypes in PRBC and age matched controls (age less than 40 years) is shown in the table below. Statistical analysis was performed using SPSS software version 16.0. Chi-square test was performed to compare the differences in percentages between PRBC and the non-pregnant control group. A p-value &amp;lt;0.05 was considered as significant.Tumor ClassCriteriaPregnancy related breast cancerAge matched controls (less than or equal to 40 years of age)LUMAStrong ER+; any PR; HER2 negative10/45 (22%)31/99 (31%)LUMBWeak to moderate ER+ or PR+; HER2 negative9/45 (20%)11/99 (11%)TNNegative for ER, PR and HER220/45 (25%)34/99 (34%)ERBB2Negative for ER and PR; HER2+4/45 (9%)3/99 (3%)LAHHStrong ER+; any PR; HER2+1/45 (2%)7/99 (8%)LBHHWeak to moderate ER+ or PR+; HER2 positive1/45 (2%)13/99 (13%) Comparison of tumor molecular classes using semi-quantitative ER, PR and HER2 results between PRBC and age matched controls shows no statistical difference between the 2 groups (p value of 0.06).The results suggest that PRBCs are not unique and rather represents aggressive biologic tumor types (i.e. triple negative tumors) that are characteristic for young age of the patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6012.
P2-05-08: Expression of VE-Statin/egfl7 in Breast Cancer.
Authors: G Lauridant-Philippin, M-C Baranzelli, C Fournier, C Samson, F Soncin, J Bonneterre
Journal: Cancer Research (2011)

Abstract Patients and methods: Specimens of breast cancer (174 invasive and 37 in situ) were obtained from 205 patients (pts) treated in our institution in 2005.Their median age was 57 years (39-92). VE-statin expression was studied by immunohistochemistry (IHC) using anti-hVE-statin/egfl7 (AF3638, R&amp;D) and by RT-qPCR on formalin-fixed paraffin sections. 174 invasive carcinomas (141 ductular and 30 lobular) and 37 DCIS were studied. Determination was done twice by two different observers. Statistics used Chi2 and Fisher's exact tests for categorical data and Kruskall-Wallis test for continuous variables. Results: Pathological characteristics of the patients with invasive tumors were as follows: 81% ductular, 17% lobular; median tumor size 18 mm (2-100); SBR grade 1 in 27%, 2 in 58% and 3 in 15% of the tumors; estradiol receptor (ER) + in 90%, progesterone receptor (PR) + in 66%; 6,5% HER2 positive. In 105 cases there was DCIS together with invasive tumors. For invasive tumors and DCIS, progression-free survival (PFS) at 5 years were 85% and 100% and overall survival (OS) 96% and 95%, respectively. Characteristics of the DCIS were median tumor size 18 mm (2-60), ER+ in 88%, PR+ in 62%. IHC results were obtained in 159 invasive carcinoma and 34 DCIS, RT-qPCR results in 96 samples. In the group of invasive tumors, a cytoplasmic VE-statin/egfl7 signal was obtained in 80% of invasive cells, more frequently than in normal glandular cells (71% vs 41%, p=0,003) but significantly less than in peritumoral DCIS (71% vs 89%, p=0,001). The signal was higher in ductular than in lobular carcinoma (85% vs 54%, p=0,003). In RT-qPCR analyses, RNA levels were higher in SBR1 grade tumors (p=0,008), in ER+ invasive tumors (p=0,02) and in pN- tumors (p=0,003). In the group of DCIS, a cytoplasmic signal was obtained in 82% of the cells. It was more frequently observed in tumor than in normal glandular cells (82% vs 52%, p=0,02). A 3+ cytoplasmic signal was more frequent in DCIS alone than in DCIS associated with invasive carcinoma (23% vs 6%, p=0,02). No prognostic significance differences were observed on PFS or on OS. Discussion: This work is the first expression study of VE-statin/egfl7 in breast cancer. The results were reproduced by two different observers. IHC signal was cytoplasmic and higher in DCIS than in invasive carcinomas. Furthermore the signal was even higher when there was only DCIS than when it was associated with invasive lesion. The signal was higher in ductular than lobular carcinoma, consistent with previous publications on other angiogenesis mediators. Similarly, the signal was higher in low SBR grade, as well in ER positive tumors. Phase 1 studies are ongoing in order to evaluate the effects of inhibition of VE-statin/egfl7. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-05-08.
Serum Dopamine-β-Hydroxylase Activity in Neuroblastoma
Authors: Menek Goldstein, Lewis S. Freedman, Agrege C. Bohuon, Françoise Guerinot
Journal: New England Journal of Medicine (1972)

Abstract The activity of dopamine-β-hydroxylase, the enzyme that catalyzes the conversion of dopamine to norepinephrine, was measured in the serum of 22 patients with neuroblastoma and of 27 control subjects. Twelve patients with neuroblastoma had serum values in the range of the control subjects, whereas 10 had extremely high values. Patients with high serum dopamine-β-hydroxylase activity also excreted large amounts of the norepinephrine metabolite, vanillymandelic acid. There was no correlation between the serum dopamine-β-hydroxylase activity and the urinary excretion levels of dopamine and its metabolite, homovanillic acid. The assay of serum levels of the enzyme may be useful for diagnosis of neuroblastomas.