tbuckley/cabot-search huggingface dataset:
SAT0171 FDG PET-CT in Polymyalgia Reumatica and Giant Cell Arteritis
Authors: R. A. Gildberg-Mortensen, E. Øster-Jørgensen, J. P. Weihe, I. M. J. Hansen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory conditions of unknown etiology. They are by some authors considered as manifestations of the same disease and are both treated with corticosteroids. However, a specific diagnosis is important because of different steroid requirements, as well as the risk of vascular complications associated with GCA. Temporal artery biopsy is the gold standard for the diagnosis of GCA, although the presence of skip lesions may render the test negative. PMR is a clinical diagnosis. FDG PET-CT is a non-invasive diagnostic tool that, by using radioactive labeled fluoro-18-deoxyglucose (FDG), visualizes increased metabolic activity in both malign and inflammatory tissue including large vessel inflammation. <h3>Objectives</h3> To evaluate the contribution of PET-CT in the diagnosis of PMR and GCA. <h3>Methods</h3> Patients registered in our department in 2011-2012, who were diagnosed with PMR or GCA and at the time of diagnosis underwent PET-CT scan as well as biopsy of the temporal artery within a time span of one month were included. Biopsy was performed prior to or within a week after initiation of steroid therapy. We used kappa statistics. <h3>Results</h3> 22 patients were included (8 males,14 females). 8 had a clinical diagnosis of PMR, 10 presented with symptoms of GCA and 4 had non-specific symptoms (NSS) including fatigue, fever and high sedimentation rate, where GCA was suspected. Increased FDG-uptake in the large vessels (aorta and its main branches) was found in 10 patients. 5 of them presented with symptoms of GCA, 1 with PMR and 4 with NSS. 4 patients with symptoms of GCA had a positive biopsy, and all showed increased vascular FDG uptake. 2 patients with PMR had a positive biopsy as had 2 patients with NSS. In this agreement and reliability study the kappa coefficient was 0,63, corresponding to a substantial agreement between the biopsy and the PET findings. 1 patient had a positive biopsy and no vascular FDG uptake, whereas 3 patients showed increased vascular uptake and had a negative biopsy. We found inter-observer agreement in 82 % between PET-CT and temporal artery biopsy. <h3>Conclusions</h3> FDG PET-CT definitely has a role in the diagnosis of GCA and should be considered in patients with negative temporal artery biopsy, for the diagnosis of GCA and to rule out differential diagnosis that may mimic PMR such as malignancy. Our findings support the theory that PMR and GCA are different manifestations of the same disease. <h3>References</h3> Tanaz A Kermani et al. Polymyalgia rheumatica, Lancet 2013;381:63-72 D. Blockmans et al. New arguments for a vasculitic nature of polymyalgia rheumatica using positron emission tomography. Rheumatology 1999;38:444-447 <h3>Disclosure of Interest</h3> None Declared
Abstract 1104: Insulin-like growth factor-1 is elevated in viscerally obese oesophageal adenocarcinoma patients and expression of its receptor correlates with tumor invasiveness
Authors: Suzanne L. Doyle, Claire L. Donohoe, Fiona E. Lithander, John V. Reynolds, Graham P. Pidgeon, Joanne Lysaght
Journal: Cancer Research (2011)

Abstract The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer development. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and squamous cell carcinoma (SCC) progression. IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE410, OE21) and adenocarcinoma (OE19, OE33) cell lines by Western Blotting. Tumor cell proliferation in response to IGF-1 was assessed by BrdU incorporation assay. Circulating levels of IGF-1 were measured in 99 serum samples by ELISA and IGF-1R expression was assessed in 50 resected tumor specimens by immunohistochemistry. Results were related to tumor type, gender and visceral adiposity. Higher IGF-1R mRNA and protein expression were observed in SCC cells, however only adenocarcinoma cell lines showed significantly increased cell proliferation in response to IGF-1 (p&amp;lt;0.01). Significantly higher circulating levels of IGF-1 were detected in patients who had adenocarcinoma (p&amp;lt;0.05) and who were viscerally obese (p&amp;lt;0.05). In resected esophageal adenocarcinoma, IGF-1R expression significantly increased as the tissue progressed along the malignant sequence, with the highest expression observed at the invasive leading edge of the tumor. Uniform IGF-1R expression was observed in SCC tumors. This novel study is the first of its kind to examine both the differential role of the IGF system in esophageal adenocarcinoma and SCC, and also its association with visceral obesity. These data indicate that in esophageal adenocarcinoma, the IGF-1 axis plays a key role in malignant progression and represents a plausible mechanism by which visceral obesity increases esophageal adenocarcinoma risk. 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 1104. doi:10.1158/1538-7445.AM2011-1104
Modulation of IL-17 producing cells in estrogen-mediated inhibition of experimental arthritis
Authors: Annica Andersson, Alexandra Stubelius, Malin Erlandsson, Hans Carlsten, Ulrika Islander
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Endogenous hormones play a role in regulating the development of autoimmune diseases. In rheumatoid arthritis (RA) estrogen treatment alleviates the disease, however due to severe side effects it is not a suitable therapy. It is important to clarify the effects of estrogen on the immune system to be able to take advantage of its beneficial effects in RA. The proinflammatory cytokine IL-17 has emerged as a key player in driving autoimmunity. The aim of this study was to investigate the effects of estrogen on IL-17 producing cells (Th17 and γδTCR<sup>+</sup>IL-17<sup>+</sup>) in experimental arthritis. <h3>Material and methods</h3> Ovariectomised DBA/1 mice with collagen-induced arthritis (CIA) underwent treatment with 17β-estradiol (E2) or placebo. Experiments were terminated at several time points during the disease development and IL-17 producing cells were analysed with flow cytometry. <h3>Results</h3> As expected, E2 treated mice displayed less severe and lower frequency of arthritis compared to the placebo group. Surprisingly, E2 treatment increased the frequency of IL-17 producing cells in draining lymph nodes of mice with CIA. However, E2 had the opposite effect in joints and decreased the number of IL-17-producing cells compared to placebo. Fewer IL-17-producing cells in joints of E2 treated mice were accompanied with a reduction in the number of neutrophils. CCR6 is a chemokine receptor that is important for the migration of cells into the joints. Interestingly, treatment with E2 specifically decreased the frequency of CCR6<sup>+</sup> IL-17 producing cells in joints. <h3>Conclusions</h3> E2 treatment ameliorates arthritis and one mechanism might be by regulating IL-17 producing cells (Th17 and γδTCR<sup>+</sup>IL-17<sup>+</sup>). Mice receiving E2 treatment displayed an increase of IL-17 producing cells in lymph nodes but a decrease of IL-17 producing cells in joints, compared to placebo. A possible explanation for this phenomenon is that E2 affects the ability of the IL-17 producing cells to migrate from lymph nodes to the blood and into the site of inflammation, the joint. This hypothesis is strengthened by the fact that treatment with E2 decreased the frequency of CCR6<sup>+</sup> IL-17 producing cells in the joint, however further investigations are needed to verify this theory.
Abstract 1470: Enhancing radiation therapy by simultaneous inhibition of thioredoxin- and glutathione-dependent metabolism
Authors: Samuel N. Rodman, Yueming Zhu, Tyler J. Ronnfeldt, Werner W. Wilke, Bryan G. Allen, Douglas R. Spitz, Melissa A. Fath
Journal: Cancer Research (2012)

Abstract Cancer cells have been shown to be in a constant state of metabolic oxidative stress, concurrent with an elevated level of reactive oxygen species (ROS). In order to facilitate survival in the face of increased steady-sate levels of ROS, cancer cells rely on glutathione (GSH) and thioredoxin (Trx) dependent metabolism. We have recently demonstrated that the simultaneous inhibition of GSH using Buthionine sulphoximine [(BSO), a GHS synthesis inhibitor] and thioredoxin reductase using auronofin [(Au), a thioredoxin reductase inhibitor] effectively chemo-radio-sensitized lung cancer cells via a mechanism involving oxidative stress. In this work we extend this observation to demonstrate that Au 2 mg/kg and BSO 450 mg/kg, given prior to ionizing radiation (6 Gy x 2 doses) can significantly delay tumor growth rate for mice treated with radiation alone in H292 lung cancer xenografts. In addition, we demonstrate through clonogenic survival assays that the combination of Au (250-500 nM) and BSO (100 μM) radio-sensitizes two breast cancer cell lines in vitro, and more importantly the combination of Au and BSO given by intraperitoneal injection prior to radiation decreases the percent of breast cancer stem/progenitor cells in vivo. The rate limiting substrate for GSH synthesis is cysteine, whose level is controlled by the xc- cystine/glutamate antiporter. Sulfasazine (SSZ) has been shown to be a potent inhibitor of the xc- cystine/glutamate antiporter. We demonstrate that SSZ (0.1-0.5 mM) decreases total GSH (up to 90%) levels in a dose dependent manner in both Mia PaCa-2 and PANC-1 human pancreatic cell lines. The combination of Au (250 nM for 3 hours) with SSZ (0.2 mM for 24 hours) demonstrates an 80% and 30% decrease in clonogenic cell survival in MiaPaCa-2 and PANC-1 pancreatic cells that is inhibited by treatment with the thiol antioxidant, 15 mM N-acetylcysteine. These results indicate that inhibition of hydroperoxide metabolism using pharmacologically relevant agents to simultaneously disrupt GSH and Trx system, can sensitize multiple cancer cell lines to radiation. These results support the hypothesis that standard of care radiotherapy protocols could be enhanced using SSZ, Au, and/or BSO. Supported by The Iowa Center for Research by Undergraduates, R21CA139182, R01CA133114 and a Breast Cancer Research Group Seed Grand from the Holden Comprehensive Cancer Center. 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 1470. doi:1538-7445.AM2012-1470
Abstract S2-6: Aromatase Inhibitors and Risk of Myocardial Infarction, Stroke and Fracture
Authors: JA Ligibel, A O'Malley, M Fisher, G Daniel, EP Winer, NL. Keating
Journal: Cancer Research (2010)

Abstract Randomized trials have demonstrated that aromatase inhibitors (AI's) are more effective than tamoxifen in preventing breast cancer recurrence. Since many women with early stage disease have a modest risk of recurrence, it is important to consider carefully the potential side effects of treatments in this setting. Trials have suggested increased risk of fracture is the only serious side effect of AI's, but study participants are often healthier than the general population, and little is known about toxicities of AI's in nontrial populations. We sought to evaluate the association between use of AI's and the incidence of myocardial infarction (MI), stroke, and fracture in community-based populations. Methods: Using encounter and pharmacy data from WellPoint plans in the HealthCore Integrated Research Database, 44,463 women aged ≥50 years with at least 2 diagnosis codes for breast cancer between 2001 and 2007 were identified and followed through the end of 2008. We used propensity score methods to identify matched controls from a cohort of 88,101 women aged ≥50 years enrolled in WellPoint plans who had no diagnosis codes for breast cancer. We identified receipt of aromatase inhibitors and tamoxifen and used Cox proportional hazards models with time-varying treatment variables to assess whether treatment with aromatase inhibitors or tamoxifen was associated with MI, stroke, and fracture among women with breast cancer and to assess the association of breast cancer with the outcomes of interest. Results: Among 44,049 breast cancer patients and 44,049 matched controls, the average age was 67 and 87% of cases and controls had no baseline comorbidities. After a median follow-up of 899 days for cases and 1004 for controls, 1.3% of women had an MI, 2.9% an ischemic stroke, 1.5% a hip fracture and 9.5% any fracture. Breast cancer patients treated with AI's had a significantly lower adjusted hazard of ischemic stroke and a significantly higher adjusted hazard of fracture compared with breast cancer patients not receiving an AI or tamoxifen. Table. Adjusted hazard ratio (95% CI) associated with breast cancer and hormonal therapy Treatment with AI or tamoxifen was not associated with MI or any fracture. Patients treated with tamoxifen had a significantly lower adjusted hazard of stroke and hip fracture compared with breast cancer patients not receiving hormonal therapy. Conclusion: The side effect profile of AI's in this community-based population was similar to that seen in clinical trials and suggests that these drugs are associated with few serious side effects. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-6.
AT-15 * A PHASE II STUDY OF ANTINEOPLASTONS A10 AND AS2-1 IN PATIENTS WITH BRAINSTEM GLIOMAS FINAL REPORT (PROTOCOL BT-11)
Authors: S. Burzynski, T. Janicki, A. Marszalek, G. Burzynski
Journal: Neuro-Oncology (2014)

PURPOSE: To evaluate the efficacy and safety of antineoplastons A10 and AS2-1 (ANP) in patients with brainstem glioma (BSG). METHODS: In the intent to treat (ITT) population forty patients (median age 11.2 years) were enrolled, and all were included in safety analysis, but only 39 patients were evaluated for efficacy. ANP was administered intravenously daily. Efficacy analyses were conducted in all BSG patients and in two subgroups: recurrent pediatric diffuse intrinsic pontine glioma (RPDIPG) and non-DIPG (NDIPG). RESULTS: In BSG, complete responses (CR) were observed in 13% of patients, partial responses (PR) 10%, and stable disease (SD) 20.5%. Overall survival (OS) at 1, 2, 5, 10 and 15 years was 38.5%, 28%, 23%, 20%, and 17% correspondingly. Six patients are presently alive 7.6 years to over 18 years. In the RPDIPG group, CR was 6%, PR 23.5%, and SD 17.5%. One year OS was 29%, 2 years 12%, and 5, 10 and 15 years 6%. In the NDIPG group, there were 36% CR and 27% SD. OS at 1, 2, 5, 10, and 15 years was 82%, 73%, 73%, 62%, and 50% correspondingly. Grade 3 and higher sodium and potassium abnormalities occurred in 15%, fatigue and somnolence in 12.5%, skin allergy and urinary incontinence occurred in 2.5% (all toxicities in ITT). No chronic adverse events occurred. Responding patients experienced improved quality of life. CONCLUSION: The results suggest that ANP shows efficacy and acceptable tolerability profile in patients with BSG, RPDIPG, and NDIPG.
Re: A Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Adjuvant Radiation Therapy and Chemotherapy for Resectable Rectal Cancer
Authors: J. J. DECOSSE, W. J. CENNERAZZO
Journal: JNCI Journal of the National Cancer Institute (1996)

To our knowledge, Gelber et al. (7) have provided the first quantitative scrutiny of quality-of-life management of patients treated for locally advanced rectal cancer. The authors conclude, Use of combined chemotherapy and radiation therapy as an adjuvant to surgery for patients with poor-prognosis resectable rectal cancer is justified. To which may be added—in comparison with postoperative adjuvant radiation therapy alone. There also appears to be an assumption, which generally conforms with the literature, that adjuvant postoperative radiation therapy alone does not improve survival. However, the usual treatment decision confronting the patient is combined treatment versus no treatment. In the absence of a comparison, have the authors examined their data by deleting the impact of those toxic events or delayed reactions attributable to radiation therapy in the control group? Such complications, including death, were cited in the published manuscript from which the current study is derived (2). Reasonably predictive estimates of quality of life after various treatment options are valuable in helping the patient with rectal cancer to make difficult choices. By embracing the side effects of treatment alternatives, Gelber et al. are to be congratulated for their accomplishment in this difficult field. However, quality of life has many elements. Some dimensions, such as performance status and economic considerations, can be quantified. Other elements, such as pain, psychological factors, and genitourinary function, are more difficult to integrate. We have a long way to go before reliable clinical utility can be achieved.
Familial Prevalence and Genetic Transmission of Idiopathic Hypertrophic Subaortic Stenosis
Authors: Chester E. Clark, Walter L. Henry, Stephen E. Epstein
Journal: New England Journal of Medicine (1973)

The pattern of inheritance of asymmetric septal hypertrophy, the characteristic anatomic abnormality in idiopathic hypertrophic subaortic stenosis, was studied by echocardiography in 30 families, in 28 of which at least one first-degree relative of the proband also had asymmetric septal hypertrophy. Forty-six per cent of 105 first-degree relatives studied had the disorder; an equal percentage of males and females were affected. Penetrance was complete in nine of the 10 parental pairs available for analysis. Clinical features were unreliable for detection of asymmetric septal hypertrophy since only 16 per cent had findings of classic idiopathic hypertrophic subaortic stenosis. The history was negative in 60 per cent, and the physical examination in 65 per cent. The electrocardiogram was normal in 50 per cent of those with asymmetric septal hypertrophy on echocardiography. Most cases of the disorder appear to be due to a genetic defect that is transmitted as an autosomal dominant trait with a high degree of penetrance. (N Engl J Med 289:709–714, 1973)
726 EVALUATION OF THE IMPACT OF BARE-METAL STENT TIPS ON OVERALL SURVIVAL IN PATIENTS WITH HEPATOCELLULAR CARINOMA (HCC)
Authors: E. Knüppel, M. Schultheiss, W. Euringer, E. Panther, D. Bettinger, R. Thimme, H.E. Blum, H.C. Spangenberg
Journal: Journal of Hepatology (2012)
Effect of Intrathoracic Pressure on Left Ventricular Performance
Authors: Andrew J. Buda, Michael R. Pinsky, Neil B. Ingels, George T. Daughters, Edward B. Stinson, Edwin L. Alderman
Journal: New England Journal of Medicine (1979)

Left ventricular dysfunction is common in respiratory-distress syndrome, asthma and obstructive lung disease. To understand the contribution of intrathoracic pressure to this problem, we studied the effects of Valsalva and Müller maneuvers on left ventricular function in eight patients. Implantation of intramyocardial markers permitted beat-by-beat measurement of the velocity of fiber shortening (VCF) and left ventricular volume. During the Müller maneuver, VCF and ejection fraction decreased despite an increase in left ventricular volume and a decline in arterial pressure. In addition, when arterial pressure was corrected for changes in intrapleural pressure during either maneuver it correlated better with left ventricular end-systolic volumes than did uncorrected arterial pressures. These findings suggest that negative intrathoracic pressure affects left ventricular function by increasing left ventricular transmural pressures and thus afterload. We conclude that large intrathoracic-pressure changes, such as those that occur in acute pulmonary disease, can influence cardiac performance. (N Engl J Med 301:453–459, 1979)
Abstract 4778: Computer-assisted molecular design use for the discovery and optimization of rationally-designed anticancer natural products. Discovery of olive oil-derived oleocanthal as a c-Met inhibitor and optimization of Veratrum alkaloids as Hedgehog signaling inhibitors
Authors: Khalid A. El Sayed, Ahmed Y. Elnagar, Mohammad Khanfar
Journal: Cancer Research (2012)

Abstract Dysregulation of the proto-oncogene receptor tyrosine kinase c-Met, which encodes the high-affinity receptor for hepatocyte growth factor (HGF) and the Hedgehog (Hh) pathway aberrantly associated with numerous malignancies including basal cell carcinoma, medulloblastoma, prostate, pancreatic and breast cancers. The Mediterranean diet is associated with lower incidences of cardiovascular disease, age-related cognitive disease and cancer. (-)-Oleocanthal is a naturally occurring minor secoiridoid from extra-virgin olive oil with potent anti-inflammatory activity via its ability to inhibit COX-1 and COX-2 and anti-Alzheimer's activity. Cyclopamine and its 11-oxo derivative jervine are C-nor-D-homosteroidal alkaloids with known potent teratogenic effects that induce cyclopic malformations in sheep. The jervane Veratrum alkaloids cyclopamine and jervine and the veratrane alkaloid veratramine were among the early known natural products that blocked the expression of the Hh pathway targets PTCH1 and GLI1, lowering Bcl2 levels and inducing apoptosis in many tumors. Computer-assisted molecular design (CAMD) identified oleocanthal as a potential virtual c-Met inhibitor hit. Oleocanthal inhibited the proliferation, migration, and invasion of the epithelial human breast and prostate cancer cell lines MCF7, MDA-MB-231, and PC-3, respectively. Oleocanthal demonstrated anti-angiogenic activity and inhibited the phosphorylation of c-Met kinase in vitro. CAMD study of our library of natural, biocatalytic, and semisynthetic jervane and veratrane alkaloids suggested that compounds with C-3-keto functionality with α4,5 or β1,2 and γ4,5 exhibited high virtual Hh binding affinity scores and possible Hh pathway activity. These compounds showed significant ability to inhibit the growth, proliferation, and migration of the prostate metastatic cancer cell line PC-3, which aided the establishment of a preliminary structure-activity relationship. (-)-Oleocanthal and Veratrum alkaloids can have potential therapeutic application for the control of c-Met- and Hh-dependent malignancies. 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 4778. doi:1538-7445.AM2012-4778
239 BRAIN REGION SELECTIVE MECHANISMS CONTRIBUTE TO THE PROGRESSION OF CEREBRAL ALTERATIONS IN ACUTE LIVER FAILURE IN RATS
Authors: O. Cauli, P. Lopez-Larrubia, R. Rodrigo, A. Agusti, J. Boix, L. Nieto-Charques, S. Cerdan, V. Felipo
Journal: Journal of Hepatology (2012)