tbuckley/cabot-search huggingface dataset:
Abstract SY40-02: Interplay between microenvironment and cancers
Authors: Nina Bhardwaj, Emmanuelle Godefroy, Francine Jotereau, Olivier Manches, Anne Gallois, Judith Goldberg
Journal: Cancer Research (2012)

Abstract Tumors are highly adept at evading the immune system through a multitude of mechanisms, including the secretion of factors that modulate both innate and adaptive immunity. Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme that degrades the extracellular matrix and is over expressed by many tumors, including melanoma. We recently documented the presence of MMP-2-specific CD4(+) T cells in tumor-infiltrating lymphocytes (TILs) in several melanoma patients (Cancer Cell 19:333, 2011). Strikingly, MMP-2-specific CD4(+) T cells displayed an inflammatory T(H)2 profile, mainly TNF-α, IL-4, and IL-13 and expressing GATA-3. When exposed to MMP-2, immature human dendritic cells (DCs) primed naïve CD4(+) T cells to differentiate into an inflammatory T(H)2 phenotype through OX40L expression and inhibition of IL-12p70 production. MMP-2 was subsequently found to degrade the type I IFN receptor, thereby preventing STAT1 phosphorylation, which is necessary for IL-12p35 production, and the subsequent formation of bioactive IL-12. More recently we have explored the mechanisms underlying the up regulation of OX40L and have identified signaling pathways and potential receptors that lead to this modulation. Active MMP-2, therefore, acts as an endogenous type 2 “conditioner” providing an explanation for the observed prevalence of detrimental type 2 responses in melanoma. Novel properties of MMP-2 on other components of the immune system, and on tumor progression, will be discussed along with DC-based strategies to alleviate immune suppression. 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 SY40-02. doi:1538-7445.AM2012-SY40-02
SAT0167 Vascular Standardized Uptake Value of FDG-PET/CT Correlates with Indices of LVV Activity.
Authors: P. Giulia, F. Muratore, M. Casali, L. Boiardi, P. Macchioni, N. Pipitone, A. Versari, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography [PET/CT] is a useful tool to diagnose large vessel vasculitis (LVV) but its role in distinguishing between active and inactive disease is still debated. <h3>Objectives</h3> To evaluate the utility of vascular standardized uptake value (SUV) assessment in differentiating between patients with clinical active and inactive LVV. <h3>Methods</h3> All patients with LVV seen in our center undergo clinical, laboratory (ESR, CRP) and imaging assessment with PET/CT scans. We retrospectively compared 14 consecutive evaluations of 12 patients with active disease according to clinical indices ITAS (Indian Takayasu activity score) and Kerr/National Institute of Health (Kerr/NIH) with 15 evaluations of 10 patients with inactive disease. ITAS, Kerr/NIH scores, ESR and CRP values were obtained within 20 days from PET/CT scans. PET/CT scans were reviewed by two nuclear medicine physicians without any clinical information. Vascular uptake was assessed using visual 4-point semiquantitative scale, vascular max SUV and vascular max SUV/liver max SUV ratio (SUV ratio) in 12 vessel segments. The highest max SUV among the different vessel segments was used for the analysis. <h3>Results</h3> Patients with active disease according to ITAS and Kerr/NIH indices compared to patients with inactive disease had higher vascular max SUV (mean ± SD 4.31 ± 1.63 vs 2.89 ± 0.99 p= 0.008) and higher SUV ratio (1.71 ± 0,74 vs 1.1 ± 0.54 p=0.016). Patients with visual grade &gt;2 (high vascular uptake) compared to patients with visual grade &lt;1 (low vascular uptake) had higher vascular max SUV (mean ± SD 4.62 ± 1.50 vs 2.6 ± 0.52 p&lt; 0.0001) and SUV ratio (1.78 ± 0.78 vs 1.05 ± 0.41 p=0.004). Correlations between max SUV and ESR or CRP (r = 0.551 p = 0.002 vs. ESR; r = 0.565 p = 0.001 vs. CRP) and between SUV ratio and ESR or CRP (r = 0.522 p = 0.004 vs. ESR; r = 0.586 p = 0.001 vs. CRP) were significant. <h3>Conclusions</h3> Our results show higher values of max SUV and SUV ratio in active than in inactive LVV patients. Both max SUV and SUV ratio correlates significantly with ESR and CRP. The assessment of max SUV and SUV ratio is a promising tool in differentiating between active and inactive disease during follow-up of patients wit LVV. <h3>Disclosure of Interest</h3> None Declared
Chlorothiazide-Induced Hypercalcemia in Juvenile Osteoporosis and Hyperparathyroidism
Authors: A. M. Parfitt
Journal: New England Journal of Medicine (1969)

Thiazide diuretic administration was followed within three to four days by symptomatic hypercalcemia (calcium level of 12.6 mg per 100 ml) and elevation of blood urea nitrogen in a patient with idiopathic juvenile osteoporosis treated with calciferol. Pre-existing hypercalcemia was exacerbated in two patients with primary hyperparathyroidism. Restoration of previous plasma calcium levels and disappearance of symptoms rapidly followed discontinuation of the drug. There was little change in plasma calcium (corrected for change in plasma protein) in eight other patients. The change in plasma level did not correlate with the magnitude of the fall in urine calcium, so that effects of thiazides other than hypocalciuria may contribute to the hypercalcemia. Thiazide diuretics should be given with caution to actually or potentially hypercalcemic patients, and those with diseases causing accelerated bone resorption, in whom increased excretion of calcium by the kidney may be preventing or delaying the onset of hypercalcemia.
A Trial of Three Regimens to Prevent Tuberculosis in Ugandan Adults Infected with the Human Immunodeficiency Virus
Authors: Christopher C. Whalen, John L. Johnson, Alphonse Okwera, David L. Hom, Robin Huebner, Peter Mugyenyi, Roy D. Mugerwa, Jerrold J. Ellner, Peter Nsubuga, Michael Vjecha, Harriet Myanja, Cissy Kityo, Anita Loughlin, John Milberg, Vukosava Pekovic
Journal: New England Journal of Medicine (1997)

Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common.
Abstract 5509: Natural occurring leelamine inhibits melanoma development by targeting multiple signaling pathways.
Authors: Raghavendra Gowda, SubbaRao V. Madhunapantula, Omer F. Kuzu, Arati Sharma, Robertson P. Gavin
Journal: Cancer Research (2013)

Abstract Melanoma remains a highly drug resistant tumor type. Melanoma cells rapidly progress resistance to drugs targeting single proteins by circumventing the point of inhibition. To overcome this problem, one approach has been to develop drugs targeting multiple proteins or pathways deregulated in the growth of the disease, such as the PI3 kinase, MAP kinase, and STAT3 signaling cascades. Agents simultaneously inhibiting several key pathways aiding melanoma development would be a first in class type of new drug for treating melanoma. To identify a drug that might target the PI3K, MAPK and STAT3 cascades, a natural product library was screened identifying leelamine as a potential inhibitor. Leelamine had the greatest inhibitory efficacy selectively killed melanoma cells by decreasing levels of cellular proliferation and increasing apoptosis rates. Leelamine inhibited the growth of preexisting xenografted tumors by ∼60%, by targeting PI3K, MAPK and STAT3 pathways without affecting animal body weight or blood markers of major organ function. The most prominent tumor inhibitory mechanisms of actions of leelamine occurred through by decreasing of Akt, Erk and Stat3 activity, which reduced cellular proliferation and consequently decreased tumor vascularization as well as increasing apoptosis. Collectively, these discoveries demonstrate the development of a naturally occurring pharmacological agent that targets multiple pathways and thereby more effectively treat melanoma. Citation Format: Raghavendra Gowda, SubbaRao V. Madhunapantula, Omer F. Kuzu, Arati Sharma, Robertson P. Gavin. Natural occurring leelamine inhibits melanoma development by targeting multiple signaling pathways. [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 5509. doi:10.1158/1538-7445.AM2013-5509
Disseminated Mycobacterium avium disease with nodular infiltration in the small intestine, detected by capsule endoscopy
Authors: E. Yamada, H. Endo, A. Nakajima, S. Yamanaka
Journal: Endoscopy (2011)

A 42-year-old man with human immunodeficiency virus (HIV) infection presented with abdominal pain and diarrhea, and was admitted to our hospital. His CD4 count was 10 cells/mm3, and he was under highly active antiretroviral therapy (HAART). A chest radiograph revealed cavitary disease, and sputum examination by polymerase chain reaction (PCR) was positive for Mycobacterium avium.
A8.28 Depletion of autoantibody-secreting plasma cells based on the specificity of the secreted antibody
Authors: A Taddeo, BF Hoyer, V Gerl, HD Chang, A Pelz, S Kohler, A Radbruch, F Hiepe
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Long-lived plasma cells (LLPCs) producing pathogenic antibodies are an important factor in autoimmune diseases maintenance and relapse. The therapeutic options available so far for targeting these cells (e.g. autologous stem cell transplantation, bortezomib) have the major disadvantage of eliminating the protective humoral immunity with the obvious caveats regarding a higher risk of infection. Therefore the development of new therapeutic tools for the selective depletion of LLPCs secreting pathogenic antibodies would be a great step forward. <h3>Material and methods</h3> We synthetized an antigen affinity matrix (AM) conjugating a plasma cell specific antibody (i.e. anti-CD138) with the antigen/autoantigen-of-interest (i.e. Ovalbumin or Acetylcholine-Receptor, AChR). We performed proof-of-concept experiments using the anti-CD138-ovalbumin using: 1) anti-ovalbumin secreting hybridoma cells and 2) spleen cells from ovalbumin-immunised mice. Moreover, we used the anti-CD138-AChR AM for the ex-vivo depletion of splenic pathogenic plasma cells isolated from mice with experimental autoimmune myasthenia gravis (EAMG). <h3>Results</h3> Antibodies secreted by ovalbumin-specific plasma cells could bind the ovalbumin delivered at surface of the plasma cell by the AM. In this way, anti-ovalbumin-specific hybridoma cells and splenic plasma cells were induced to commit suicide in presence of complement. Conversely, unrelated plasma cells (i.e. secreting antibodies against other antigens) were not lysed confirming the specificity of the method. Importantly, pathogenic plasma cells secreting anti-AChR-autoantibodies from the spleen of mice with EAMG can be eliminated using an anti-CD138-AChR-construct, suggesting that the AM technology can be used for the specific depletion of autoantibodies secreting plasma cells. <h3>Conclusion</h3> Here we show that the AM technology could represent the first available tool for the depletion of (auto)antigen-specific plasma cells without affecting the protective plasma cells. We are currently testing the therapeutic efficacy of this AM in murine models of autoimmune disease.
SAT0239 Predictors of end-stage renal disease and recurrence of lupus activity after initiation of dialysis in patients with lupus nephritis
Authors: S.-J. Moon, S.-K. Kwok, J.H. Ju, J.-K. Min, H.-Y. Kim, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lupus nephritis (LN) accounts for most of the morbidity and mortality of patients with systemic lupus erythematosus (SLE). The prevalence of renal involvement in SLE patients was various up to 60%, depending on the ethnicity and geographic origin of those studied. Despite advances in the management strategies, 5 to 22% of LN patients eventually progress to end-stage renal disease (ESRD), requiring either dialysis or transplantation <h3>Objectives</h3> To identify the predictors of ESRD and determine the long-term outcome of ESRD patients according to renal replacement modality in Korean patients with LN. <h3>Methods</h3> Between 1985 and 2010, 321 Korean patients with LN were enrolled in this study. We analyzed the clinical and laboratory indices, the treatment responses and the biopsy findings. The events of interest were estimated by the Kaplan-Meier method and the risk factors were assessed by univariate and multivariate Cox proportional hazards regression analyses. <h3>Results</h3> The median follow-up time after the diagnosis of LN was 84 months. During follow-up, twenty nine patients evolved to ESRD. Renal survival rate at 5 and 10 years after LN onset was 95.9% and 91.1%, respectively. Deteriorated renal function (estimated glomerular filtration rate &lt;60 ml/min/1.73m<sup>2</sup>) at LN onset (hazard ratio: 9.223) was found to be an independent risk factor for the development of ESRD. Recurrence of lupus nephritis in renal allograft and flare-ups of lupus activity were not observed among the patients undergoing kidney transplantation (KT) (<i>n</i>=11). In contrast, those with maintenance dialysis (<i>n</i> =18) developed thirteen episodes of lupus flare in ten patients and five died of either infection (<i>n</i> =2) or lupus flare (<i>n</i>=3). <h3>Conclusions</h3> The impaired renal function at baseline is an independent predictor of ESRD in Korean patients with LN. The benefits of KT on the control of lupus activity and survival should be emphasized. <h3>References</h3> Cheigh JS, et al. Systemic lupus erythematosus in patients with end-stage renal disease: long-term follow-up on the prognosis of patients and the evolution of lupus activity. Am J Kidney Dis 1990; 16: 189-95. Croca SC, et al. Assessment of a lupus nephritis cohort over a 30-year period. Rheumatology (Oxford)2011; 50: 1424-30. <h3>Disclosure of Interest</h3> None Declared
High Burden of Obstructive Sleep Apnea in Subgroups of Chronic Rhinosinusitis: Importance of Phenotyping Chronic Rhinosinusitis Patients for Stratifying Risk Factors for This Major Comorbidity
Authors: Jessica W. Hui, Mohamed Benhammuda, Vahid Kalantari, Arpita Mehta, Raj Kota, Pete Batra, Phillip LoSavio, Mary C. Tobin, Mahboobeh Mahdavinia
Journal: Journal of Allergy and Clinical Immunology (2016)
THU0482-HPR Comparison of agreement and responsiveness to treatment effects of 100 mm visual analog scale and 11 point numerical rating scale to assess wrist pain in patients with rheumatoid arthritis
Authors: E. Taal, M.M. Veehof, M.A. van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Visual analog scales (VAS) and Numerical Rating Scales (NRS) are commonly used to measure pain in rheumatoid arthritis. <h3>Objectives</h3> To examine agreement between measurement of wrist pain by 100mm VAS and 11-point NRS and comparibility of responsiveness to treatment effects on wrist pain of both types of scales in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Data were used from a previously reported four–week randomized clinical trial on the efficacy of wrist working splints among 33 patients with RA suffering from wrist arthritis [1]. Patients were randomly allocated to the splinting group (n=17) and the control group (n=16). The study demonstrated that wrist splints were highly effective in reducing wrist pain, assessed with 100 mm VAS, after four weeks of splint wearing. Average wrist pain during the past week was measured with a 100mm VAS (0-100) and a 11-point NRS (0-10). The scales were included on different places in a questionnaire, and the order of the scales was randomly varied between patients and between baseline and four-week measurement. Agreement between VAS and NRS to measure wrist pain was examined at baseline by Bland-Altman analysis. Preceding this analysis VAS pain scores were divided by 10 and rounded to the nearest integer to make them comparable to NRS pain scores. Differences in change scores on VAS and NRS between the splinting and the control group were analysed with analysis of covariance, and effect sizes (Hedges <i>g</i>) with corresponding 95% confidence intervals were calculated. <h3>Results</h3> At baseline VAS and NRS pain scores were highly correlated (Pearson r=0.82). Mean difference between the VAS and NRS pain scores at baseline was -0.24 (SD=1.15). Bland-Altman analysis showed high individual variability between VAS and NRS pain scores with wide limits of agreement (- 2.49 to 2.01). Highly significant treatment effects were found on wrist pain measured by VAS (F(1,30)=11.1; P=0.002) and NRS (F(1,30)=9.1; P=0.005), and effect sizes for VAS (Hedges <i>g</i>= -1.24; 95%CI: -1.98 to -0.49) and NRS (Hedges <i>g</i>=-1.05; 95%CI: -1.78 to -0.33) were of similar magnitude and not significantly different as shown by the overlapping 95% confidence intervals. <h3>Conclusions</h3> The high intra-individual variability in wrist pain measured by 100 mm VAS or 11 point NRS indicates that individual scores on VAS and NRS are not comparable. However, on a group level, VAS and NRS showed similar responsiveness to treatment effects of splint wearing on wrist pain in patients with RA. <h3>References</h3> Veehof MM, Taal E, Heijnsdijk-Rouwenhorst, van de Laar MAFJ. Efficacy of wrist working splints in rheumatoid arthritis: a randomized controlled study. Arthritis Care Res 2008; 59:1698-1704 <h3>Disclosure of Interest</h3> None Declared
Abstract 1601: Hsp90 inhibition results in a significant delay in tumor progression in a model of emerging EGFR TKI resistance in non-small cell lung cancer
Authors: Kelly L. Slocum, Hana Sheikh, Kip West, Emmanuel Normant, Keith Robison, John MacDougall, Christian Fritz
Journal: Cancer Research (2011)

Abstract Heat shock protein 90 (Hsp90) plays a role in regulating the stability of key cancer-causing proteins through its role as a protein chaperone. Proteins chaperoned by Hsp90, known as client proteins, include cancer-causing forms of ALK, BCR-ABL, EGFR, FLT3 and HER2. Infinity is developing two drug candidates in its Hsp90 chaperone inhibitor program: IPI-504 (retaspimycin hydrochloride), an intravenously-administered small molecule, and IPI-493, which is administered orally. EGFR tyrosine kinase inhibitors (TKIs) are an effective treatment for lung cancer patients with activating mutations in EGFR. After a dramatic initial response, however, most patients become resistant to drug treatment and progress. In about half of these cases, resistance is due to a second point mutation in EGFR (T790M). It is believed that in at least some of these cases, the TKI resistance mutations are pre-existing and that treatment with TKIs selects for the resistant cells. In an effort to model the emergence of resistance to TKIs from pre-existing mutations, we developed a novel in vivo model, where gefitinib treatment initially leads to tumor regression followed by rebound of tumor growth and outgrowth of drug resistant clones containing the T790M mutation. We show that in this model, treatment with IPI-493 alone and IPI-493 following gefitinib resulted in tumor growth inhibition of 61 and 77%, respectively, when compared with gefitinib treatment alone. Treatment with IPI-493 alone also resulted in a significant delay in time to tumor progression with ∼40% of animals still on study 45 days following tumor implant; all animals treated with either vehicle or gefitinib had been removed due to tumor progression. Interestingly, treatment with IPI-493 following gefitinib resulted in an even more impressive delay in time to progression, with &amp;gt;50% of animals still on study on day 65 post-implant. These results suggest that further studies with Hsp90 inhibitors in EGFR mutant NSCLC patients who have been pre-treated with a TKI may be warranted. 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 1601. doi:10.1158/1538-7445.AM2011-1601
Abstract 2039: Hyaluronan-CD44 interaction with PKCε promotes oncogenic signaling by the stem cell marker, Nanog and the production of microRNA-21 leading to downregulation of the tumor suppressor protein, PDCD4, anti-apoptosis and chemotherapy resistance in breast tumor cells
Authors: Lilly Y. W Bourguignon, Christina C. Spevak, Gabriel Wong
Journal: Cancer Research (2010)

Abstract Multidrug resistance and disease relapse is a challenging clinical problem in the treatment of breast cancer. In this study we investigated the hyaluronan (HA)-induced interaction between CD44 (a primary HA receptor) and protein kinase Cε (PKCε) which regulates a number of human breast tumor cell functions. Our results indicate that HA binding to CD44 promotes PKCε activation which, in turn, increases the phosphorylation of the stem cell marker, Nanog, in the breast tumor cell line, MCF-7. Phosphorylated Nanog is then translocated from the cytosol to the nucleus and becomes associated with RNase III DROSHA and the RNA helicase, p68. This process leads to microRNA-21 (miR-21) production, and a tumor suppressor protein [e.g., the Program Cell Death 4 (PDCD4)] reduction. All of these events contribute to upregulation of inhibitors of apoptosis proteins (IAPs, e.g., XIAP and survivin) and the multidrug resistant protein (MDR1)/P-glycoprotein (P-gp) resulting in anti-apoptosis and chemotherapy resistance. Transfection of MCF-7 cells with PKCε or Nanog-specific small interfering RNAs (siRNAs) effectively blocks HA-mediated PKCε/Nanog signaling events, abrogates miR-21 production and increases PDCD4 expression/eIF4A binding. Subsequently, this PKCε/Nanog signaling inhibition causes IAP/MDR1 (P-gp) downregulation, apoptosis and chemosensitivity. To further evaluate the role of miR-21 in oncogenesis and chemoresistance, MCF-7 cells were also transfected with a specific anti-miR-21 inhibitor in order to silence miR-21 expression and inhibit its target functions. Our results indicate that anti-miR-21 inhibitor not only enhances PDCD4 expression/eIF4A binding, but also blocks HA/CD44-mediated tumor cell behaviors [e.g., IAP/MDR1 (P-gp) upregulation, anti-apoptosis and chemotherapy resistance] in MCF-7 cells. Taken together, these findings suggest that the HA-induced CD44 interaction with PKCε plays a pivotal role in Nanog signaling and miR-21 production leading to the tumor suppressor protein (PDCD4) downregulation, anti-apoptosis/survival and chemoresistance. Thus, this newly-discovered HA/CD44 signaling pathway should provide important drug targets for sensitizing tumor cell apoptosis and overcoming chemotherapy resistance in breast cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2039.