tbuckley/cabot-search huggingface dataset:
Abstract LB-151: Tumor VEGF-C promotes immune suppression and tolerance
Authors: Amanda W. Lund, Vidya Raghavan, Sachiko Hirosue, Fernanda Duraes, Stephanie Hugues, Melody Swartz
Journal: Cancer Research (2011)

Abstract The expression of the vascular endothelial growth factor, VEGF-C, is correlated with tumor invasion and hypothesized to induce metastasis through enhanced lymphangiogenesis and the creation of an “escape route”. However, new evidence suggests that VEGF-C can induce invasion in the absence of obvious tumor lymphangiogenesis, and furthermore, that lymphatic transport may play a role in modulating immunity. Still however, the role of the lymphatics as players in anti-tumor immunity and tumor invasion remains unexplored. Here we present a new model for VEGF-C induced tumor-invasion in which VEGF-C and lymphatic endothelial cells play a direct role in the suppression of anti-tumor immunity. Using a B16 F10 mouse melanoma that overexpresses VEGF-C, we demonstrated that VEGF-C induces the expression of the lymphoid homing cytokine, CCL21, within the stroma of the tumor and drives lymphocyte trafficking, fluid drainage and metastasis to the sentinel draining lymph node. Within the tumor stroma VEGF-C recruited a more regulatory immune cell infiltrate including increased regulatory T cells (CD25+FoxP3+) and M2 macrophages (CD11b+CD80-CD206+) and decreased antigen specific cytotoxic T cells (CD8+Trp2+). To test the ability of this mediated VEGF-C response to overcome host immunity we engineered a B16 F10 line to express ovalbumin (OVA) as a model tumor antigen. When we preimmunized the mice against OVA we observed that VEGF-C provided protection against vaccine (OVA/LPS) induced anti-tumor immunity. Growth of OVA bearing tumors was inhibited with vaccination and correlated with an increase in CD8+ antigen specific cytotoxic T cells. However, neither the growth nor the infiltration of cytotoxic T cells was affected by vaccination when the tumors also overexpressing VEGF-C. Additionally, to determine the fate of antigen specific CD8+ we adoptively transferred OT-I T cells by tail vein injection and observed their homing to the draining lymph nodes and tumor. In these microenvironments, when exposed to VEGF-C, adoptively transferred cells lost function over time as shown by the detection of Annexin V and decreased IFNγ expression. These results suggest that the expression of VEGF-C by a primary tumor not only promotes metastasis through the expansion of the lymphatic network but also through an immunological switch within the tumor and draining lymph node. We therefore present one of the first studies to identify an active, rather than passive, role for the lymphangiogenic growth factor, VEGF-C, and local lymphatic endothelial cells in the regulation of tumor immunity. 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 LB-151. doi:10.1158/1538-7445.AM2011-LB-151
The Ventilatory Lung Scan in the Diagnosis of Pulmonary Embolism
Authors: Gerald L. DeNardo, David A. Goodwin, Ruggero Ravasini, Peter A. Dietrich
Journal: New England Journal of Medicine (1970)

Regional pulmonary blood flow and ventilation in 15 patients were assessed by a dual radioisotopic technic. In 10 patients with documented pulmonary embolism, the embolic lung was underperfused but well ventilated, whereas in five patients with other pulmonary diseases, abnormalities of ventilation equaled or exceeded abnormalities of perfusion. The method is simple to perform, is associated with a low radiation exposure to the patient, and therefore may be repeated to assess the course of disease or the efficacy of treatment.
FRI0429 Cause-specific mortality in patients with psoriatic arthritis
Authors: A. Ogdie, S. Maliha, T. Love, H. Choi, J. Gelfand
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Data on cause-specific mortality in patients with psoriatic arthritis have been limited. Studies examining cause of death in PsA to date have been clinic- or hospital-based rather than population-based studies and none have included a reference group. <h3>Objectives</h3> To examine cause-specific mortality in patients with psoriatic arthritis compared to the general population. <h3>Methods</h3> A cohort study was performed using The Health Improvement Network, a medical record database within the United Kingdom, among patients aged 18-89. Data from 1994-2010 were included. PsA was defined by a single diagnosis code (positive predictive value 85%) and up to 10 unexposed controls (without psoriasis, PsA, or rheumatoid arthritis) matched on practice and start date within the practice were selected for each patient with PsA. Cause of death was classified using categories from UK death statistics and defined using diagnostic codes specifically labeled as the cause of death, codes on the date of death or codes entered within 60 days of the death date. Patients could have more than one cause of death. Each death was manually reviewed to ensure accurate classification. Causes of death were descriptively compared and then age- and sex- adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. <h3>Results</h3> Among patients with PsA (N=8,709) and controls (N=82,170), 539 and 6,121 deaths were identified. The most common causes of death among patients with PsA and controls were heart disease (17.8% and 16.3% respectively) and cancer (17.3% and 15.1%). Respiratory disease (11.1% and 11.4%), infection (5.9% and 5.8%), gastrointestinal disease (3.5% and 3.6%), and accidents (1.1 and 1.5%) were also similar among the two groups. Cause of death was unknown in 28% and 30% respectively. Hazard ratios were not significant for any specific cause of death: cardiovascular disease (HR 1.18; 95%CI 0.95-1.47), cancer (HR 1.06; 95%CI 0.86-1.32), infection (HR 1.10; 95%CI 0.77-1.58), and respiratory disease (HR 1.02; 95%CI 0.78-1.34). <h3>Conclusions</h3> In this cohort, we have previously reported that mortality risk was not elevated among patients with PsA. Similarly, cause-specific mortality is not significantly different among patients with PsA compared to controls. <h3>References</h3> Ogdie A, Haynes K, Troxel AB, Love TJ, Hennessy S, Choi H, Gelfand JM. Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study. Ann Rheum Dis. 2012 Dec 21. [Epub ahead of print] <h3>Disclosure of Interest</h3> A. Ogdie: None Declared, S. Maliha: None Declared, T. Love: None Declared, H. Choi: None Declared, J. Gelfand Grant/research support from: Amgen, Novartis, Abbott, Pfizer, Genentech, Consultant for: Amgen, Centocor, Abbott, Celgene, Novartis, Pfizer, Paid instructor for: for CME work related to psoriasis
A Preliminary Study of Growth Hormone Therapy for Crohn's Disease
Authors: Alfred E. Slonim, Linda Bulone, Mary B. Damore, Teresia Goldberg, Mark A. Wingertzahn, Matthew J. McKinley
Journal: New England Journal of Medicine (2000)

Crohn's disease is a chronic inflammatory disorder of the bowel. In a preliminary study, we evaluated whether the administration of growth hormone (somatropin) as well as a high-protein diet would ameliorate the symptoms of the disease.
Randomized trial of yoga in women with breast cancer undergoing radiation treatment
Authors: L. Cohen, K. Chandwani, B. Thornton, G. Perkins, E. Rivera, B. Arun, N. Raghuram, H. Nagendra
Journal: Journal of Clinical Oncology (2006)

8505 Background: Yoga, an ancient Indian science, incorporates stress-reduction techniques that include regulated breathing, visual imagery, and meditation, as well as various postures that may be useful for cancer patients. Methods: A yoga program was developed that including loosening and breathing exercises, postures, alternate nostril breathing, a deep relaxation technique, and meditation for patients with breast cancer who were undergoing radiotherapy. Women participated in bi-weekly classes during their 6 weeks of radiation treatment. Sixty-one women with breast cancer were randomly assigned to either the yoga program or to a waitlist control group. Patients completed measures of intrusive thoughts and avoidance behaviors (Impact of Events Scale: IES), depressive symptoms (CES-D), sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (BFI), and quality of life (SF-36) at baseline, 1 week, and 1 and 3 months after the last radiation therapy. We report on the outcomes 1 week after the end of radiotherapy. Results: The average age of the women was 52, 3% stage 0, 28% stage I, 43% stage II, and 26% stage III, 48% had undergone breast-conserving surgery, and 75% had received chemotherapy prior to starting radiotherapy. Analysis of covariance, controlling for baseline, revealed that the yoga group had significantly better SF-36 physical function scores (adjusted means: yoga 81.8 vs. control 68.6, P &lt; 0.01), significantly higher SF-36 general health scores (adjusted means: yoga 78.3 vs. control 67.9, P &lt; 0.03), marginally better SF-36 social functioning scores (adjusted means: yoga 85.3 vs. control 76.0, P &gt; 0.1), significantly lower levels of sleep-related daytime dysfunction (adjusted means: yoga 0.5 vs. control 1.2, P &lt; 0.04), and marginally lower levels of fatigue (adjusted means: yoga 1.9 vs. control 3.1, P &lt; 0.06) than the control group. There were no other group differences on the SF-36 subscales or for the CES-D or IES scores. Conclusions: The results indicated that the yoga program was associated with statistically and clinical significant improvements in aspects of quality of life. No significant financial relationships to disclose.
THU0006 Predictors of Low Ankle-Brachial Index in Patients with Antiphospholipid Syndrome
Authors: S. Caraiola, C. Jurcut, D. Nitescu, C. Badea, R. Jurcut, A. Baicus, C. Baicus, C. Tanasescu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Large studies validated the ankle-brachial index (ABI) as an important clinical marker of peripheral atherosclerosis in general population. However there are few studies regarding ABI in patients with antiphospholipid syndrome (APLS), a clinical condition associated with an increased cardiovascular risk. <h3>Objectives</h3> The aim of this study was to evaluate the predictors of an abnormal ABI in patients with APLS. <h3>Methods</h3> In 106 patients with APLS (primary and secondary) we performed the evaluation of the ABI according to standard recommendations. Traditional cardiovascular risk factors, along with a large spectrum of antiphospholipid antibodies (including the antiphosphatidylserine, antiphosphatidylethanolamine and antiprothrombine antibodies) and lupus anticoagulant were assessed. We calculated the pulse pressure as the difference between systolic and diastolic blood pressure – as a marker of arterial stiffness. We divided the study group in two subgroups: A- patients with an abnormal ABI (defined by a value below 0.9); and B - patients with normal ABI. <h3>Results</h3> In our study, 30 pts (28.3%) were found to have a low ABI. Mean age (51.1±13.2 in subgroup A vs 42.1±11.0 yo in subgroup B, p=0.001), mean age at diagnostic (42.9±13.4 vs 36.1±10.6 yo, p=0.007), prevalence of arterial hypertension (63.3 vs 32.8%, p=0.008), diabetes (23.3 vs 6.5%, p=0.02), pulse pressure (53.8±12.3 vs 48.6±9.8 mmHg, p=0.02), fasting glucose (95.2±17.5 vs 84.6±15.9 mg/dl, p=0.004) and values of HDL-cholesterol in men (43.1±7.9 vs 58.4±10.1, p=0.01) were associated with an abnormal ABI. Anti-beta 2-glycoprotein I IgG antibodies [median values (interval): 4.00 (1.00-79.00) vs 3.00 (0.00-29.00), p=0.02] and anti-prothrombin IgM antibodies [4.50 (0.00-82.00) vs 3.00 (0.00-14.00), p=0.05] were found to have higher values in patients with abnormal ABI. The anti-beta 2-glycoprotein IgG antibodies has had the higher AUC (area under the curve) for the prediction of low ABI (AUC=0.660). In multivariate analysis, only the titer of anti-beta 2-glycoprotein I IgG were significantly associated with an abnormal ABI (p=0.04). <h3>Conclusions</h3> In our study group of APLS patients we found a high prevalence of an abnormal ABI. As expected, the traditional cardiovascular risk factors are associated with more important vascular changes in these patients. However, only the titer of anti-beta 2-glycoprotein I IgG was independently associated with a low ABI in patients with APLS reflecting the role of disease itself in the pathogenesis of atherosclerosis. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4529
A5.05 Prediction of persistent inflammatory arthritis with ultrasound: A data-driven method
Authors: I Sahbudin, P de Pablo, L Pickup, Z Cader, G Allen, P Nightingale, CD Buckley, K Raza, A Filer
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Prediction of disease persistence in early inflammatory arthritis is important to enable timely initiation of appropriate therapy. Currently available predictive algorithms for persistent arthritis do not include US variables. We used a data-driven method to identify the minimal core set of US, clinical and serological variables predicting persistent inflammatory arthritis in a cohort of patients with early arthritis. <h3>Methods</h3> 107 patients [female n = 60, median age 51] with ≥1 clinically apparent synovitis and symptom duration ≤3 months underwent clinical, laboratory and US assessments. Final diagnosis was determined at 18-months follow-up. US assessment determined the presence of Grey scale (GS) and Power Doppler (PD) synovitis at 38 joints (bilateral MCPs 1–5, PIPs 1–5, wrists, shoulders, elbows, ankles and MTPs 2–5). First, univariate analysis was performed to identify clinical, serological and US variables significantly associated with persistent disease at 18-months. Second, principal component analysis (PCA) was performed on 1) clinical and serological variables (age, gender, symptom duration, ESR, CRP, RF, ACPA, duration of early morning stiffness, tender joint and swollen joint count), 2) US GS variables and 3) US PD variables to identify variables that reflected similar themes. Finally, one variable from each component was extracted and made available in a forward step-wise multivariate logistic regression analysis. <h3>Results</h3> 63 patients developed persistent inflammatory arthritis and 44 patients had resolving disease. On PCA, three components were identified within the clinical and serological variables, four components were identified within the GS US variables and four components within the PD US variables. The final multivariate logistic regression model included RF positivity (OR = 5.83, p = 0.01), MCP2 PD positivity (OR = 4.33, p = 0.002) and MTP2 PD positivity (OR =&nbsp;10.72, p = 0.030). In seronegative patients, the final multivariate logistic regression included early morning stiffness &gt;60mins (OR=3.62, p = 0.017) and PIP 2 PD (OR&nbsp;= 8.44, p = 0.003). <h3>Conclusion</h3> This is the first study using a data-driven method to show that US provides independent data beyond clinical and serological variables in the prediction of persistent arthritis, even in RF and ACPA-negative patients. Bilateral MCP2 and MTP2 is the minimal joint sub-set that provides independent predictive data in this cohort.
Lack of a Specific Urethral Lesion in Exertional Urinary Incontinence
Authors: S. Richard Muellner
Journal: New England Journal of Medicine (1946)

IT IS generally believed that exertional urinary incontinence is due to trauma of childbirth. Although there is no agreement on the precise structure that has been injured, prevailing opinion ascribes this symptom to tears or fixations of the urethral sphincters or to attenuations of the bladder and urethral supports. The signs of obstetric trauma, however, are often not discernible on pelvic examination or at operation, and even when present they frequently cannot be correlated with the degree of urinary incontinence. Thus, marked urinary leakage may occur in patients with intact pelvic structures, whereas women who on exertion lose only a . . .
P2-10-06: Prospective Ultrasonographic Prediction of Sentinel Lymph Node Metastasis by Real-Time Virtual Sonography Constructed with Three-Dimensional Computed Tomography-Lymphography in Breast Cancer Patients.
Authors: S Yamamoto, N Maeda, K Yoshimura, M Oka
Journal: Cancer Research (2011)

Abstract Background: Real-time virtual sonography (RVS) systems display virtual multiplanar reconstruction (MPR) images obtained from three-dimensional (3D) computed tomography (CT)-lymphography (LG), significantly improving preoperative detection of sentinel lymph nodes (SLNs). The purpose of this study was to prospectively evaluate SLN metastasis using an RVS system. Methods: We identified SLNs in 73 clinically node-negative breast cancer patients using an RVS system to display in real time a virtual MPR obtained from CT volume data corresponding to the same cross-sectional image from ultrasonography (US). CT volume data were obtained using our original 3DCT-LG, which accurately detects SLNs in breast cancer. We then prospectively attempted to predict metastasis to SLNs. SLN metastases were assessed by measuring the cortex thickness in the presence of a visible hilum. We defined suspected SLN metastases as SLNs with a cortex thickness of at least 2.5 mm on the basis of our preliminary data. All patients underwent SLN biopsy and SLN metastases were examined pathologically with serial 2.0-mm-thick multiple slices. Results: Suspected SLN metastases were identified in 24 of 73 patients, and 13 of these 24 patients were pathologically positive. The remaining 49 patients displayed no suspected SLNs, and 46 of these 49 were pathologically negative. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of measuring cortical thickness for predicting metastatic involvement of SLNs were 81, 81, 54, 94, and 81%, respectively. Conclusion: If cortical thickness of the SLN is less than 2.5 mm, SLN metastasis is unlikely to be present. If cortical thickness of the SLN is at least 2.5 mm, preoperative fine-needle aspiration cytology may be recommended to verify the possibility of SLN metastasis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-06.
MB-36 * WIP1 AUGMENTS SONIC HEDGEHOG (SHH) SIGNALING AND IS A TARGET IN SHH MEDULLOBLASTOMAS
Authors: J. Lee, M. Buss, J. Wen, M. Remke, M. Taylor, R. Castellino
Journal: Neuro-Oncology (2015)

Sonic Hedgehog (SHH) signaling is active in 30% of childhood medulloblastomas. Dysregulation of p53 signaling is especially prognostic for poor survival in SHH medulloblastoma. But, p53 is mutated in <10% of medulloblastomas. Genomic analyses have demonstrated high-level amplification of PPM1D (WIP1) in p53 wild-type SHH medulloblastomas. WIP1 functions as an oncogene, in part by inactivating p53. We hypothesized that, in the absence of p53 mutation, WIP1 overexpression augments SHH-driven medulloblastoma tumorigenesis and is an important target in the treatment of SHH-active medulloblastomas. WIP1 overexpression in murine granule neuron precursor (GNP) cells enhanced expression of Shh target genes, increased the percentage of cells in S phase, and increased cell viability in response to Shh stimulation. Although WIP1 is known to primarily act through p53 pathways, we found that the interaction between WIP1 and Shh was partially p53-independent. To further understand WIP1 mechanisms in vivo, we developed a mouse in which WIP1 is expressed in the developing brain under control of the Neurod2 promoter (ND2:WIP1). The external granule layer in early post-natal ND2:WIP1 mice exhibited increased proliferation and expression of Shh downstream targets. When ND2:WIP1 transgenic mice were crossed with SmoA1/SmoA1 medulloblastoma-prone mice, medulloblastoma incidence increased and double transgenic SmoA1/SmoA1; ND2:WIP1+ mice demonstrated reduced survival. Conversely, Wip1 knock out significantly suppressed medulloblastoma formation in SmoA1/SmoA1 as well as Tamoxifen-treated Math1-creER; Ptc1 fl/fl mice. Treatment with a lentivirus that knocks down Wip1 or with the WIP1 inhibitor CCT007093 inhibits the effects of Shh stimulation and potentiates the effects of the SHH pathway-inhibiting drugs SANT-1, cyclopamine, or the clinically-relevant LDE225 on the growth of either SmoA1/SmoA1 or Math1-creER + ; Ptc1 fl/fl medulloblastoma cells in vitro. This suggests an important cross-talk between SHH and WIP1 that accelerates tumorigenesis. Our findings also suggest an important role for WIP1 inhibition in the treatment of SHH-active medulloblastomas.
FRI0508 Correlation of power doppler ultrasonographic findings with site-matched histopathology of the synovial tissue
Authors: H. Motomura, I. Matsushita, E. Seki, T. Kimura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasonography (US) has been recently established as an imaging modality to evaluate inflamed joints of patients with rheumatoid arthritis (RA). It is reported that power doppler ultrasonography (PDUS) is capable of directly visualizing and quantifying synovial inflammation [1]. However, detailed correlation between the PDUS findings and histopathological findings of RA synovial tissues, such as accumulation of various inflammatory cells, neovasculogenesis, and synovial hyperplasia, still remains unclear. <h3>Objectives</h3> To assess the significance of PDUS in the evaluation of synovial lesion of the knee joint by comparing the PDUS findings with site-matched histopathological findings. <h3>Methods</h3> We studied 23 patients who were undergoing arthroplasty of the knee joint because of RA or osteoarthritis (OA). Predetermined sites of the knee joint were examined with US before arthroplasty. Synovitis was classified semiquantitatively with grey scale (GS) and PDUS findings. PD signal was graded as 0 (normal), 1 (minor), 2 (moderate), and 3 (major) [2]. Synovial tissues were obtained during arthroplasty from the corresponding sites evaluated by the US. Histopathology of the synovial tissue was evaluated by haematoxylin and eosin staining and immunohistochemical staining with factor VIII. The degree of inflammatory cell infiltrates, synovial lining layer thickness and vascularity was graded as 0 (normal), 1 (mild change), 2 (moderate change), and 3 (severe change) [3]. <h3>Results</h3> Positive PDUS (grade 2 or 3) was found in 11 of 19 knee joints in patients with RA, but was not observed in all patients with OA. We compared imaging findings of preoperative PDUS with histopathological findings of the synovial specimens. We found that the PDUS findings were mostly correlated with each histopathological grade of synovitis and the vascularity showed the highest correlation with the PDUS findings (r=0.541, <i>P</i>&lt;0.01) as expected. However, the site-matched comparison indicated that the blood vessels, possibly low-velocity blood flow, were not apparently detected by the PDUS. Thus, the sensitivity and specificity of PDUS findings for histopathological vascularity were 91% and 58%, respectively. <h3>Conclusions</h3> We showed that positive findings of PDUS were closely associated with histopathological findings of active synovitis. However, our results suggest that PDUS is not sufficiently powerful in evaluating blood vessels with low-velocity blood flow in the synovial tissue. <h3>References</h3> Naredo E, et al. Ann Rheum Dis. 2008; 67:1017-22. Hammer HB, et al. Ann Rheum Dis. 2011; 70:1995-8. Takase K, Clin Exp Rheumatol. 2012; 30: 85-92. <h3>Disclosure of Interest</h3> None Declared