tbuckley/cabot-search huggingface dataset:
Abstract 4302: Targeting the sphingolipid pathway in NK large granular lymphocyte leukemia
Authors: Rebecca J. Watters, Xin Liu, Todd E. Fox, Mark Kester, Thomas P. Loughran
Journal: Cancer Research (2011)

Abstract Large granular lymphocytes (LGL) are a lymphoid subset that consists of 10-15% of peripheral blood mononuclear cells. LGL can be divided into (2) major lineages of CD3- NK cells and CD3+ T Cells. Symptoms may include rheumatoid arthritis and neutropenia which leads to recurrent bacterial infections. The sphingolipid metabolism pathway has been found to be deregulated in NK-LGL leukemia. Glucosylceramide synthase (GCS), a key component of this pathway is an enzyme that catalyzes the conversion of proapoptotic ceramide to inactive glucosylceramide by transferring a glucose residue from UDP-glucose to ceramide. GCS has been found to be upregulated in cancer cells and its overexpression has been associated with multidrug resistance in leukemia cells. Both rat and human leukemic LGL cells have been treated with a combination treatment targeting two key components of the sphingolipid pathway. One of the agents in use is the C6-ceramide (C6) nanoliposome which has led to caspase-dependent apoptosis in a time- and dose-dependent manner. Systemic i.v. delivery of nanoliposomal ceramide led to complete remission in 5/14 syngeneic Fischer F344 rat model of NK-LGL leukemia. However a greater response will be achieved by combination treatment of C6 and through targeting a second key component of ceramide metabolism with DL-threo-1-Phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP). PPMP is a GCS inhibitor that prevents the endogenous ceramide already present in the cell from being glycosylated into its inactive form where it can no longer induce cell death. Overall, this combination treatment shows a synergistic effect with increase of ceramide levels in order to induce apoptosis and therefore death of these persistent LGL cells. Cell flow cytometry examining 7AAD/Annexin V staining has shown ∼80% apoptosis when 6.25 uM C6 ceramide and 15 uM PPMP are used in combination on aggressive rat LGL cells. Whereas, only ∼19% is observed with C6 and ∼17% of PPMP are observed individually in treatment. Overall, apoptosis appeared increased in a dose response manner after treatment with PPMP and C6. This is a significant finding of P&amp;lt;0.005, when compared to DMSO and ghost nanoliposome controls which only induce ∼15% apoptosis. In addition, this combination treatment has been utilized on normal human peripheral blood mononuclear cells where only 11.2% apoptosis was induced and 9% in the normal spleen mononuclear cells in rats. As a result, this combination treatment appears promising in specifically targeting LGL cells while sparing normal cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4302. doi:10.1158/1538-7445.AM2011-4302
TREATMENT OF B-CELL LYMPHOMA WITH I-131 LABELED MURINE MONOCLONAL ANTIBODIES.
Authors: J. F. Eary, C. C. Badger, O. Press, S. Brown, J. Davis, F. Appelbaum, W. Nelp, K. Krohn, D. Fisher, R. Miller, R. Levy, I. Bernstein
Journal: Clinical Nuclear Medicine (1987)

Eary, J. F.; Badger, C. C.; Press, O.; Brown, S.; Davis, J.; Appelbaum, F.; Nelp, W.; Krohn, K.; Fisher, D.; Miller, R.; Levy, R.; Bernstein, I. Author Information
Abstract 5457: FOXO3a transcriptionally regulates pro-apoptotic function of Par-4 and induces apoptosis in prostate cancer cells.
Authors: Trinath P. Das, Chendil Damodaran
Journal: Cancer Research (2013)

Abstract Deletion and mutation of tumor suppressor genes (PTEN and p53) may play an important role in the carcinogenesis of prostate cancer (CaP). Constitutive activation of Akt promotes cell proliferation and survival by regulating a number of transcription factors/genes in many cancer cells including CaP. Activation of AKT negatively regulates the pro-apoptotic functions of Fork head transcription factor (FOXO3a) and prostate apoptosis response-4 (Par-4) in CaP cells. In our studies, we found a molecular interplay between FOXO3a and Par-4 in CaP cells and more precisely, how, FOXO3a regulates Par-4 function in CaP cells. Knockin and knockout assays in CaP cells suggest that FOXO3a is upstream of Par-4 and FOXO3a may responsible for the transactivation of Par-4 and its pro-apoptotic function in CaP cells. Further, Immunofluorescence assays suggest during apoptotic stimuli, Par-4 and FOXO3A colocalization in nucleus, which in turn initiates pro-apoptotic signaling and induction of apoptosis. These results were further confirmed by pull down assays, which supports the physical interaction of these two proteins. These findings encouraged us to explore the FOXO3a binding sites in the promoter region of Par-4. We identified four FOXO3a binding sites at -2075 to -2069, -1810 to -1804, -1561 to -1555, and -1340 to -1334 in the promoter region of Par-4 gene. Luciferase reporter constructs of Par-4 promoter (2.1 kb) spanning the FOXO3a binding sites and sequentially deleted constructs were utilized to identify the crucial FOXO3a binding site for the regulation of Par-4. Sequential deletion of FOXO3a binding sites in Par-4 promoter resulted in inhibition of Par-4 function and induction of apoptosis in CaP cells. Further, confirm the role of FOXO3a, we specifically activated Par-4 function by small molecules and simultaneously co-transfect with dominant-negative FOXO3a constructs. As expected dominant negative FOXO3a abrogates Par-4 function in CaP cells, confirming FOXO3a is an upstream of Par-4 signaling and it is required for Par-4 induced apoptosis in CaP cells. We believe, these results decipher the mechanisms associated with FOXO3a induced Par-4 gene activation and apoptosis in CaP cells and activating of FOXO3a may result Par-4 mediated apoptosis in CaP cells. Citation Format: Trinath P. Das, Chendil Damodaran. FOXO3a transcriptionally regulates pro-apoptotic function of Par-4 and induces apoptosis in prostate cancer 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 5457. doi:10.1158/1538-7445.AM2013-5457 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract B48: Germline mutations in BRCA1 and BRCA2 as predictive biomarkers of therapy response
Authors: Mary Lynn Tassotto, Lindsay Sutherland, John Th'ng
Journal: Cancer Research (2009)

Abstract The results of in vitro chemosensitivity studies have shown some consistency with response to chemotherapy in patients, indicating that this approach may be used to identify patients that are resistant to conventional chemotherapy regimens. However, this approach is not routinely used in an adjuvant or neoadjuvant setting as a treatment strategy. Treatment selection for breast and ovarian cancer is currently based on pathological classification of the tumour, without assessment of in vitro chemosensitivity. BRCA1 and BRCA2 germline mutations are considered to be both prognostic cancer biomarkers and predictive biomarkers of breast and ovarian cancer susceptibility; however, their utilization as predictive biomarkers of therapy response has not been investigated. Expression levels of BRCA1 modulate chemosensitivity in breast cancer cell lines, and epigenetic regulation of BRCA1 leading to decreased BRCA1 expression is often observed in sporadic breast cancer. We have hypothesized that cells with mutations in BRCA1 or BRCA2 may be differentially sensitive to DNA damaging agents used in cancer therapy due to decreased levels of BRCA1 or BRCA2 gene expression in these cells. Using lymphocytes isolated from individuals with germline mutations in BRCA1 and BRCA2, we will present results showing the in vitro response to ionizing radiation and chemosensitivity to Paclitaxel and Doxorubicin, two chemotherapeutic agents commonly used in the adjuvant systemic treatment of breast cancer. Citation Information: Cancer Res 2009;69(23 Suppl):B48.
Occult Crossed Renal Ectopia Detected on a VQ Scan
Authors: Aadil A. Gutta, Trevor Mdaka, Ouma E. Ramafi
Journal: Clinical Nuclear Medicine (2011)

An association exists between congenital heart disease and urinary tract anomalies.1,2 We present the case of a 15-year-old female patient with a known VSD (ventricular septal defect) and Eisenmenger syndrome. Pulmonary embolism was clinically suspected and the patient underwent a ventilation/perfusion (VQ) scan. As expected in a right-to-left shunt, some of the injected Tc-99m macro-aggregated albumin particles bypassed the pulmonary vessels and lodged in highly perfused areas of the systemic circulation, specifically the brain and the kidneys. Unsuspected crossed renal ectopia was discovered on lung perfusion images, which was subsequently confirmed by a Tc-99m dimercaptosuccinic acid study.
ClearPath: a new method for fast and simple drainage of a perianastomotic abscess
Authors: Antonino Granata, Gabriele Curcio, Neville Azzopardi, Luca Barresi, Ilaria Tarantino, Mario Traina
Journal: Endoscopy (2014)

A-75-year-old man with rectal adenocarcinoma underwent laparoscopic anterior resection with the creation of a protective ileostomy.
Molecules involved in cerebellar long-term depression (LTD) and mutant mice defective in it
Authors: Tomoo Hirano
Journal: Behavioral and Brain Sciences (1996)

Recent studies have demonstrated that a Purkinje cell specific ionotropic glutamate receptor δ2 subunit is involved in long-term depression (LTD). Identification of molecules involved in LTD has led to the production of mutant mice defective in LTD, motor control, and motor learning. There are disagreements about whether or not and how nitric oxide (NO) is involved in LTD. [CRÉPEL et al.; LINDEN; VINCENT]
FRI0353 Incidence of giant cell arteritis in the current era of advanced diagnostic imaging
Authors: P. D. Udayakumar, C. S. Crowson, K. J. Warrington, E. L. Matteson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Giant cell arteritis (GCA) is the most common type of vasculitis which occurs especially in women who are older than 70 years of age and of northern European origin. Magnetic resonance angiogram (MRA), computed tomography angiogram (CTA) and positron emission tomography (PET) are being increasingly used as non-invasive tools to diagnose extracranial involvement of the large vessels in patients with suspected GCA. <h3>Objectives</h3> We aimed at updating the incidence of GCA in the current era of advanced diagnostic imaging, 2005-2009 compared to 2000-2004. <h3>Methods</h3> Using the resources of Rochester Epidemiology Project (REP), incident cases of GCA in Olmsted County, Minnesota, USA between January 1, 2005 and December 31, 2009 was identified and compared to the incident cases between January 1, 2000 and December 31, 2004 in the same population. GCA was defined according to the 1990 American College of Rheumatology (ACR) classification criteria and a physician diagnosis. Patients greater than 50 years of age with elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) and CTA, MRA or PET scan evidence of large vessel vasculitis involving the ascending aorta and/or its branches were also included. Asymptomatic patients with incidental finding of aortitis in pathology status-post aortic aneurysm repair or aortic valve replacement were not included. Incidence of GCA per 100,000 population was calculated after adjusting for age and sex to the 1980 US white population aged greater than or equal to 50 years. <h3>Results</h3> We identified 39 patients with GCA in 2005-2009 and 35 patients in 2000-2004. Mean age of patients was 77.1 years [standard deviation (SD) 8.8] in 2005-2009 cohort and 79.3 years (SD 7.4) in 2000-2004 (p=0.28). Majority of the patients were women: 77% in 2005-2009 and 83% in 2000-2004 (p=0.53). Temporal artery biopsy was positive in 28 of 39 patients (76%) in 2005-2009 and in 28 of 35 (82%) in 2000-2004 (p=0.49). 5 of 11 patients in 2005-2009 cohort and 1 of 7 patients in 2000-2004 cohort with negative temporal artery biopsies were included based on the radiological criteria. Among these 5 patients in 2005-2009 cohort, CTA was used in 2; MRA in 1; PET scan in 2 patients; and MRA was used in the patient in 2000-2004 cohort. The overall age- and sex- adjusted incidence rate in 2005-2009 was 19.5 per 100,000 population [95% confidence interval (CI): 13.2, 25.8]. This is nearly identical to the estimated incidence of GCA in 2000-2004, which was 18.9 per 100,000 (95% CI: 12.4, 25.5). <h3>Conclusions</h3> Imaging techniques such as CTA, MRA and PET are more commonly used in the recent years for diagnosing GCA involving the ascending aorta and/or its major branches in suspected patients with negative temporal artery biopsy. The overall incidence of GCA has not changed significantly in the recent years. <b>Disclosure of Interest</b>: None Declared
Criterion and predictive validity of the diagnosis of adjustment disorder: a prospective study of youths with new-onset insulin- dependent diabetes mellitus
Authors: M Kovacs, V Ho, M H Pollock
Journal: American Journal of Psychiatry (1995)

The authors examined the criterion and predictive validity of the diagnosis of adjustment disorder in a pediatric study group.Ninety-two school-age children with new-onset insulin-dependent diabetes mellitus were evaluated repeatedly and were diagnosed by using DSM-III. The criteria for adjustment disorder were further operationalized by requiring four clinically significant symptoms or signs; the time frame for its onset was extended to 6 months after the diagnosis of insulin-dependent diabetes. Predictive validity was assessed in terms of new psychiatric disorders other than adjustment disorder during the next 5 years.Of the 92 children, 33 developed adjustment disorder and five developed other psychiatric disorders in response to the diagnosis of insulin-dependent diabetes mellitus. Mean time from diabetes diagnosis to onset of adjustment disorder was 29 days, the average episode length was 3 months, and the recovery rate was 100%. Among youths with adjustment disorder in response to the medical diagnosis, the 5-year cumulative probability of a new psychiatric disorder was 0.48, compared to 0.16 among the other youths.The findings generally support the criterion validity of the diagnosis of adjustment disorder. However, episode duration and the predictive validity of the diagnosis appear to be functions of the study group being examined. In nonpsychiatrically referred pediatric patients, early problems in adaptation to the stress of changed health status, as evidenced by adjustment disorder, appear to signal vulnerability to later psychopathology.
THU0171 Therapeutic response of lupus nephritis based on pathological findings in yokohama city university hospital:
Authors: D. Kishimoto, A. Ihata, R. Watanabe, T. Watanabe, K. Terauchi, K. Kobayashi, T. Uehara, K. Takase, M. Hama, R. Yoshimi, A. Ueda, M. Takeno, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> ISN/RPS classification of lupus nephritis was popular and reliable classification because of its semi-quantitativity of glomerular changes. However, tubulointerstitial involvement and the grade of glomerular sclerosis and of hyaline thrombi which could be poor prognostic factors, were not fully evaluated in this classification. <h3>Objectives</h3> To clarify the relationship between pathological evaluation and therapeutic response in lupus nephritis (LN). <h3>Methods</h3> According to ISN/RPS classification, samples of renal biopsy (RBx) from 51 patients with LN (35.1 y.o, 46 females) were evaluated. Tubulointerstitial involvement (TII), thorombi and glomerular sclerosis were also assessed. Treatment response at 6 months, 1, 2 and 5 years were evaluated by SLICC renal activity and response index score. <h3>Results</h3> Biopsy specimens included 19.5 glomeruli at average, though less than 10 glomeruli were found in 17.6%. The RBx samples were classified into ClassI/II/III/IV/V/VI (1/5/10/26/9/0). TII, thrombi and glomerular sclerosis were found in 60.8%, 21.6% and 58.8% of the specimens, respectively. These findings were negatively correlated with complete response (CR) rate. The existence of TII and glomerular sclerosis significantly influenced the CR rate at 6 onths. The finding of thrombi was a significant poor prognostic factor identified at 2 years. Corticosteroids (CS) and cyclophosphamide (CY) was chosen as the first line agents as the induction therapy. Initial dose of CS was increased with higher frequency of pulse therapy against Class III and IV after 2004. Similarly, intravenous infusion with CY was more frequently used for Class III, IV and V after 2004 than before. Complete response rate at 2 years was 70.0% and 46.2% in class III and IV, respectively. <h3>Conclusions</h3> Tubulointerstitial involvement and glomerular sclerosis might reflect the response of an induction therapy. Thrombi might influence long-term treatment outcome. <h3>References</h3> Petri M, et al. Arthritis Rheum 2008;58(6):1784-1788 <h3>Disclosure of Interest</h3> None Declared
AB0973 The Novel Photo Optical Imaging (LIGHTSCAN) is More Sensitive than Musculoskeletal Ultrasound and Clinical Examination in Patients with Rheumatoid Arthritis and Osteoarthritis
Authors: I. Amitai, S. Ohrndorf, S. Werner, B. Schicke, G.-R. Burmester, O. Minet, U. Zabaryło, M. Backhaus
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The Lightscan, a novel imaging technology, is detecting inflammatory activity in proximal interphalangeal (PIP) joints. <h3>Objectives</h3> This study aimed at the comparison of Lightscan (LS) to musculoskeletal ultrasonography (US) and clinical examination (CE) in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and in healthy controls. <h3>Methods</h3> A total of 87 subjects (70 female, mean age 49±19 years, range 22-86) were examined. The total cohort included 30 patients with active RA (DAS28&gt;2.6), 8 RA patients in clinical remission (DAS28≤2.6), 21 patients with OA, and 28 individuals as a healthy control group. All patients received clinical joint examination (tender/swollen joints). US in grey-scale (GSUS) and power Doppler mode (PDUS) of the PIPs 2-5 (palmar/dorsal view) were performed. All patients were examined by LS. LS was transilluminating the PIPs of both hands using laser diodes with three different wavelengths (670, 820, and 904 nm), one joint after the other. A CCD camera was recording the scattered-light in a 2-dimensional light pattern. Those black/white bitmaps with a depth of 8 bits were transformed into a false colour image [1] and analysed with a non-local image segmentation method [2]. In order to compare LS with US, a sum-score was defined and calculated for GSUS, PDUS and LS individually. The means of the sum-score were compared to each other. ROC-analysis was done for LS and US. <h3>Results</h3> In the statistical analysis the results of LS and CE agreed in 52% on average (agreement was calculated for each PIP joint individually; agreement range was 32-66%). Disagreement in 40% (range 28-55%) of the results was due to the high rate of positive findings in LS. In 8% (range 2-12.5%) positive findings were only found in CE. In the ROC-analysis, LS showed better sensitivity and specificity for the detection of inflammation in RA and OA (AUC=0.88) than GSUS (AUC=0.8) and PDUS (AUC=0.67). By using this analysis, the cut-off for LS was defined at the score of 1.3. <h3>Conclusions</h3> It is known that US is more sensitive than the CE [3,4]. Thus, while showing better results in the ROC-analysis, we conclude LS to be more sensitive than US and CE in assessing inflammatory activity in patients with RA and OA. <h3>References</h3> Minet O et al. J Biophotonics. 2010;3:130-7 Minet O et al. Las. Phys. Lett. 2007;4:604-10 Backhaus, M et al. Arthritis Rheum. 1999;42:1232-45 Backhaus, M et al. Ann Rheum Dis. 2002;6:895-904 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3338
Minimal residual disease detection in peripheral blood of primary breast cancer patients – translational research in the SUCCESS-study.
Authors: C Jenderek, J Jückstock, C Schindlbeck, B Rack, R Fuchs, S Noeding, P Krabisch, F Ebner, W Lichtenegger, MW Beckmann, K Friese, H Sommer, W Janni
Journal: Cancer Research (2009)

Abstract Abstract #5019 Background: The detection of occult tumor cells in the bone marrow of patients with breast cancer has been shown to be an independent predictive and prognostic factor for early disease recurrence and decreased overall survival. However, it is more feasible to monitor treatment efficacy by sampling peripheral blood. The translational research program of the German SUCCESS-trial evaluates Minimal Residual Disease (MRD) in peripheral blood during adjuvant treatment of breast cancer patients. Follow-up results of the detection of MRD at primary diagnosis and after adjuvant chemotherapy (CT) are presented.&amp;#x2028; Patients and Methods: Cells were separated by Oncoquick® (Greiner-bio one, Frickenhausen, Germany) followed by labeling of epithelial cells with an anti-cytokeratine-antibody (directed against cytokeratins 8, 18 and 19) and immunocytochemical staining. Every preparation was screened by two independent persons. MRD was defined as one or more cytokeratine-positive cell.&amp;#x2028; Results: 1237 breast cancer patients were analyzed at primary diagnosis. After completion of adjuvant CT 655 patients returned for a second blood sampling. The majority of the tumors was small (40.1% pT1, 52.7% pT2, 5.9% pT3, 1.1% pT4) but mostly of intermediate or unfavorable grade, (G1 4.6%, G2 48.9%, G3 46.2%). 65% of the patients were node-positive (35% pN0, 45.6% pN1, 13.8% pN2, 5.7% pN3) and a positive hormone receptor status was seen in 69.1%. In 25.4% the Her2 status was positive. In 20.3% of all patients MRD was found at primary diagnosis. After CT MRD was observed in 15,7%. The mean number of detected cells was 2.3 (range: 1-25) before and 2.1 (range 1-23) after chemotherapy. Neither tumor size (p=0.48, p=0.47), lymph node metastases (p=0.34, p=0.81), histopathological grading (p=0.83, p=0.85) nor hormone receptor status (p=0.72, p=0.65) of the primary tumor correlated with the presence of MRD before or after CT respectively. The Her2/neu status of the primary tumor did not correlate before, but after CT with the presence of the MRD (p=0.63, p=0.08).&amp;#x2028; Conclusion: The detection of MRD in peripheral blood can be widely used and is suitable for repeated measurements. Further follow-up of the SUCCESS trial will show this method´s validity for risk stratification and monitoring of treatment efficacy in breast cancer patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5019.