tbuckley/cabot-search huggingface dataset:
Abstract 1511: Macrophage aggressiveness in the lung tumor microenvironment
Authors: Ryan J. Quinton, David R. Griffin, Melissa M. Alegre, Richard A. Robison, Kim L. O'Neill
Journal: Cancer Research (2011)

Abstract Macrophages are highly versatile phagocytes active in multiple roles in the immune system of vertebrates. However, within the tumor microenvironment, macrophages initiate and are exposed to a variety of cell signals. Some of these signals are involved in tumor growth, angiogenesis, and metastasis, and have been shown to alter macrophage function. These tumor associated macrophages display characteristics that indicate polarization from M1 to M2 phenotypes, and have been shown to promote angiogenesis and metastasis in cancer patients. In addition, clinical trials have shown that a high macrophage count in breast cancer patients is associated with a poor prognosis. We hypothesize that the engulfment ability and aggressiveness of macrophages incubated with lung cancer cells will be down regulated. Human mononuclear phagocytotic U937 cells were differentiated to macrophages by exposure to phorbol-12-myristate-13-acetate (PMA). These cells were then marked with APC fluorochrome dye for identification, and phagocytic activity was measured using PE conjugated fluorescent beads. Macrophages were incubated with two lung cancer cell lines (A549, H460) for various times and phagocytic indices were quantified using flow cytometry. Preliminary results indicated no change in phagocytic activity after 1 hour of exposure, and a 15% down regulation of overall engulfment after 24 hours of contact. These results were compared to cells incubated with non-cancerous lymphocytes, where there was no change in overall phagocytic activity. These data also indicated that the majority of normal macrophages were highly aggressive (engulfing 3 or more beads when analyzed by flow cytometry), but macrophages that were incubated with cancer cell lines experienced a statistically significant down regulation in aggressiveness, where the number of macrophages which engulfed 3 or more beads was reduced by 30% (p = 0.044). These findings indicate that exposure of U937-derived macrophages to lung cancer cell lines resulted in a possible shift towards the M2 phenotype. 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 1511. doi:10.1158/1538-7445.AM2011-1511
Abstract 590: Antiproliferative effects and signaling profiles of the novel HSP90 inhibitor NVP-AUY922 in non-small cell lung cancer
Authors: Tsuyoshi Ueno, Shinichi Toyooka, Kazunori Tsukuda, Takaoka Munenori, Junichi Soh, Yuho Maki, Takayuki Muraoka, Norimitsu Tanaka, Hiroaki Asano, Masaomi Yamane, Takahiro Oto, Katsuyuki Kiura, Yoshio Naomoto, Shinichiro Miyoshi
Journal: Cancer Research (2011)

Abstract Background; Gefitinib and erlotinib, which have been designed to inhibit tyrosine kinase of epidermal growth factor receptor (EGFR), showed drastic anti-tumor effect on NSCLCs with common EGFR mutations, but acquired resistance is a major problem to failure this treatment. Heat shock protein (HSP) 90 inhibitors have been developed as promising anti-cancer agents, because HSP90, a molecular chaperone, plays a pivotal role in NSCLC survival as it stabilizes a large set of client proteins, many of which are important for tumor cell survival and proliferation. In this study, we examined “NVP-AUY922,” a new HSP90 inhibitor, and showed its effects against NSCLCs. Methods: We used 24 NSCLC cell lines with specific genetic alterations, which are K-ras mutation, B-raf mutation and EGFR mutation. Cell proliferation was determined by modified MTS assay. The expressions of client proteins were assessed by Western Blotting. Results: NVP-AUY922 exhibited strong antiproliferative effects to most NSCLC cell lines, except H1395 and Calu3. One of resistant cells is a B-raf mutator and another has no specific genetic alterations, but NSCLCs with EGFR mutations were sensitive. The average IC50 of NVP-AUY922 in sensitive cells was 18.7 + 8.32 nM. In most cell lines, higher depletion of both total and phosphorylated client proteins such as MET, HER2, EGFR and AKT, were shown by NVP-AUY922 treatment with higher concentration. But in Calu3, a resistant cell line, they did not decrease in lower concentration. MET, HER2 and EGFR were suppressed for whole duration tested, while the expression of AKT was depleted for 48 hours and then recovered at 72 hours after treatment. The client protein of H1395 decreased in lower concentration and the cause of resistance to NVP-AUY922 has been unknown so far. Conclusions; NVP-AUY922 was effective to most NSCLC cell lines at low concentration and suggested to be a promising new drug of NSCLCs, even those resistant to EGFR-TKIs. 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 590. doi:10.1158/1538-7445.AM2011-590
Direct Cost Analysis About The Three Chelators For The Treatment Of Thalassemia Patients With Chronic Iron Overload: An Italian Perspective From The MIOT Network
Authors: Alessia Pepe, Antonella Meloni, Giuseppe Rossi, Antonella Carollo, Vincenzo Santamaria, Augusto Scaccetti, Gaetano Roccamo, Aurelio Maggio, Massimo Lombardi
Journal: Blood (2013)
A Randomized Trial of Enhanced Therapy for Early Syphilis in Patients with and without Human Immunodeficiency Virus Infection
Authors: Robert T. Rolfs, M. Riduan Joesoef, Edward F. Hendershot, Anne M. Rompalo, Michael H. Augenbraun, Michael Chiu, Gail Bolan, Steven C. Johnson, Pamela French, Eric Steen, Justin D. Radolf, Sandra Larsen, William E. Brady, Kenneth F. Wagner, Debra A. D'Aquilante
Journal: New England Journal of Medicine (1997)

Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis.
Abstract 5242: Pancreatic cancer cell type specific oxygen dependent growth and drug sensitivity
Authors: Arvin M. Gouw, Annie L. Hsieh, Anne Le, Anirban Maitra, Chi V. Dang
Journal: Cancer Research (2012)

Abstract Most cell are cultured at 37°C, in 4% CO2 and 20% O2. Studies have shown that changing the temperature of the cell culture will lead to either cold shock or heat shock. Others have also shown that level of CO2 is crucial for pH balance in cell growth. Although cultured cells are exposed to 20% O2, oxygen tension in vivo is significantly lower in normal tissues ranging from 5 to 8% O2. Furthermore cancer tissues tend to be more hypoxic because of the poorly developed neo-vasculature. Hence, we sought to determine if pancreas cancer cells will grow and/or respond to drugs differently under 20% vs. 6% oxygen tension. Methods: Six pancreatic cancer cell lines were cultured in DMEM media with 10% FBS and 5% Penicillin in 4% CO2, 37°C with variable O2 conditions: 20% and 6%. Cells are plated onto 6-well plates. Triplicates of cells were trypsinized daily for 4 days for cell counts which was done by using hematocytometer. To test drug sensitivity, we used a known Lactate Dehydrogenase A (LDHA) inhibitor, FX11. LDHA inhibition has been shown to suppress tumor growth both in vitro and in vivo. Some cells were treated with an LDHA inhibitor, FX11 in varying concentrations: 5mM, 10mM and 20mM, while the controls were exposed to DMSO. Results: 1. Pancreas cancer cell lines E3, P215 and A6L grow better in 6% than in 20% oxygen level. 2. Pancreas cancer cell line A6L shows higher sensitivity to FX11 in 6% compared to 20% oxygen. 3. Pancreas cell line P215 shows lower sensitivity to FX11 in 6% compared to in 20% oxygen. Conclusion: The artificial nature of standard culture condition does not account for the significantly lower oxygen tension in vivo. Because cancer cell lines are established from tumors which tend to be hypoxic, measurements of cell growth rates and respond to therapeutic agents at 20% O2 may not reflect responses at 6% O2 and specifically not to in vivo conditions. 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 5242. doi:1538-7445.AM2012-5242
Hyperphosphatemia, Hyperphosphaturia and Hypocalcemia in Acute Lymphoblastic Leukemia
Authors: Jaime Zusman, David M. Brown, Mark E. Nesbit
Journal: New England Journal of Medicine (1973)

Four children with acute lymphoblastic leukemia received a controlled dietary intake of protein, calcium and phosphorus to study prospectively the changes in the serum and urinary calcium and phosphorus values, which occur during therapy of the disease. Two 12-hour urine collections were obtained daily for determinations of phosphorus, calcium, uric acid and creatinine. Serum creatinine, urea nitrogen, calcium, phosphorus and uric acid were measured midway through each collection. Hyperphosphatemia (values of 5.7 to 9.4 mg per 100 ml), hypocalcemia (values of 6.6 to 8.3 mg per 100 ml) and marked hyperphosphaturia were observed within 24 to 48 hours of the initiation of chemotherapy. The tubular reabsorption of phosphorus decreased to levels that were 20 to 70 per cent of pretreatment base-line values. Symptomatic hypocalcemia is most common in patients with exceptionally high peripheral lymphoblast counts and some degree of renal insufficiency. These events may be caused by the increased endogenous phosphorus load resulting from the destruction of lymphoblasts, in the same fashion that purine release leads to hyperuricemia. (N Engl J Med 289:1335–1340, 1973)
Abstract A17: Transforming growth factor beta stimulates STAT3 tyrosine phosphorylation and cellular invasion through interleukin-6 in human breast cancer cell lines
Authors: Nicole NT Parker, Mary E. Law, Gerhard Müller-Newen, Pat Corsino, Brad Davis, Stephen Jahn, Brian K. Law
Journal: Cancer Research (2009)

Abstract The signaling mechanisms involving Transforming Growth Factor β (TGFβ) and Signal Transducer and Activator of Transcription 3 (STAT3) are characterized in breast cancer, but the mechanism of crosstalk between these two pathways is poorly understood. In this study we addressed the question of TGFβ-STAT3 cross-signaling in nontransformed epithelial cells and in human breast cancer cell lines. Breast cancer continues to be a serious disease in the United States. A large component of novel chemotherapeutics specifically target overexpressed or overactivated proteins in cancers. Two examples of these oncogenic molecules are the cytokine TGFβ and the transcription factor STAT3. Although these proteins have each been implicated in early and late stages of cancer and invasion, the mechanism of cross-talk between the TGFβ and STAT3 pathways has not been well characterized. We have observed that TGFβ treatment is sufficient to induce phosphorylation of STAT3 on its activating Tyr (705) site in nontransformed mouse mammary NMuMG epithelial cells. The time dependence of this relationship implies de novo expression of an intermediate factor that data suggest is Interleukin-6 (IL-6). TGFβ treatment induces gene upregulation of IL-in a time-dependent manner similar to that of TGFβ stimulated STAT3 tyrosine phosphorylation. Inhibition of IL-6 with the mIL-6 Receptor Fusion Protein Inhibitor (mIL-6.RFPI) abrogated TGFβ stimulation of STAT3 tyrosine phosphorylation. Further, TGFβ treatment is sufficient to induce cellular invasion in NMuMG cells. This effect was recapitulated by IL-6 treatment, while IL-6 inhibition markedly reduced TGFβ stimulated invasion. The human breast cancer cell lines MDA-MB-231 and MDA-MB-361, which are basal-like and luminal breast cancer models, respectively, display varying levels of constitutive STAT3 tyrosine phosphorylation. The MDA-MB-361 cell line exhibits no endogenous STAT3 phosphorylation but responds to TGFβ treatment in the same manner as nontransformed NMuMG mammary epithelial cells. Conversely, the MDA-MB-231 cell line displays high levels of constitutive STAT3 tyrosine phosphorylation, which data suggest is dependent in part on TGFβ signaling and is completely dependent on IL-6 signaling. Taken together, interruption of the TGFβ-IL-6-STAT3 signaling loop in MDA-MB-231 cells is sufficient to abrogate this signaling and dramatically reduce endogenous cellular invasiveness, while induction of the TGFβ-IL-6-STAT3 pathway in MDA-MB-361 cells confers an invasive phenotype on this otherwise noninvasive cell line. Citation Information: Cancer Res 2009;69(23 Suppl):A17.
P264 The prevalence of -blocker prescription in COPD patients
Authors: A. R. C. Patel, G. C. Donaldson, A. J. Mackay, J. A. Wedzicha, J. R. Hurst
Journal: Thorax (2011)

<h3>Introduction</h3> Ischaemic heart disease (IHD) is a major cause of morbidity and mortality in COPD patients. Effective cardiovascular therapies may have significant impact in COPD populations. In particular, β-blockers have been shown to be safe and effective in COPD. We aimed to quantify the changing prevalence of emerging cardiovascular medications in this group over the last decade. <h3>Methods</h3> We analysed the recruitment records of well-characterised patients enrolled into the London COPD Cohort from 1995 to 2010. Date of enrolment, comorbidities, medications, demographics, smoking history and spirometry results were analysed. Prescribing data reflects that of the patients9 primary physicians. <h3>Results</h3> The mean±SD age of 386 COPD patients was 68.4±8.7 years, FEV<sub>1</sub> was 1.22±0.55 l or 49.5±19.6% predicted. 57% were male, 24% were current smokers with a median (IQR) pack year history of 45 (25–65). 64 (17%) patients had IHD of whom half had a previous myocardial infarction, 4% had heart failure, 6% had a previous stroke, 5% had peripheral vascular disease (PVD), 9% had a tachyarrhythmia. The overall prevalence of at least one cardiovascular disease was 30%. 36% had hypertension, 8% had hypercholesterolaemia and 7% had diabetes. Common cardiovascular medications included statins (28%), aspirin (23%), calcium-channel blockers (21%), ACE-inhibitors (18%), loop diuretics (15%), thiazides (14%) and angiotensin receptor blockers (7%). β-blockers were indicated in 25% of patients (IHD ± heart failure ± tachyarrhythmia; 22% when those with the contraindication of PVD are excluded). The prevalence of β-blockers was only 5% overall and prescribed to only 8/84 (10%) in those with a clinical indication and no PVD (χ<sup>2</sup> test, p=0.020). In the 64 patients with IHD, statins and angiotensin pathway drugs became more prevalent in the last decade of the study period (Abstract P264 figure 1) in keeping with emerging evidence of benefit. β-blockers did rise in prevalence as evidence of safety emerged, although to a much smaller extent than statins and angiotensin pathway drugs. <h3>Conclusions</h3> Emerging cardiovascular medications have become more common in COPD patients reflecting greater recognition of cardiovascular risk. However, β-blockers were underused despite clear indications and evidence of safety and benefit in COPD. Measures are required to improve evidence-based prescribing to overcome historical beliefs.
Late-Onset Adrenal Hyperplasia in Hirsutism
Authors: Frederique Kuttenn, Philippe Couillin, François Girard, Line Billaud, Monique Vincens, Chafika Boucekkine, Jean-Christophe Thalabard, Thierry Maudelonde, Poli Spritzer, Irene Mowszowicz, Andre Boue, Pierre Mauvais-Jarvis
Journal: New England Journal of Medicine (1985)

We studied the incidence of late-onset adrenal hyperplasia as a cause of hirsutism, its association with the major histocompatibility complex, and its clinical expression. Twenty-four of 400 women seen because of hirsutism were found to have late-onset adrenal hyperplasia, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, and its marked increase after ACTH stimulation. The degree of hirsutism varied widely. Plasma antigen levels were high, especially the level of androstenedione, whereas 5 alpha-reductase activity, considered to be a good index of peripheral androgen utilization, showed frequent normal or low values. The 24 patients were genotyped, along with 84 family members, and plasma hormones were measured in the family members. We found a high correlation between late-onset adrenal hyperplasia and HLA antigens B14 and Aw33. Similar biologic profiles were observed in the patients and those of their siblings who were HLA identical (n = 9), confirming that late-onset adrenal hyperplasia is linked to the histocompatibility complex. These nine siblings had no hirsutism. We therefore conclude that the role of skin sensitivity to androgens is important in determining the clinical expression of this disorder.
Abstract 2999: Gene expression signature of differential response to chemotherapy in sporadic pediatric osteosarcoma
Authors: Jeff W. Martin, Madhuri Koti, Susan Chilton-MacNeill, Andre J. van Wijnen, Jeremy A. Squire, Maria Zielenska
Journal: Cancer Research (2012)

Abstract Osteosarcoma is the most common pediatric bone malignancy. Genomic instability, karyotypic heterogeneity and dysregulated gene expression are typical of osteosarcoma tumors, for which treatment is often multimodal and aggressive. Tumor necrosis in response to neoadjuvant chemotherapy is used to estimate outcome and survival, because reliable clinical diagnostic and prognostic biomarkers have not yet been described for this tumor. Our objective in the current study was to identify new molecular biomarkers for osteosarcoma based on differential mRNA expression levels of genes found to be consistently involved in the pathogenesis of osteosarcoma. The NanoString nCounter System utilizes color-coded probe pairs, which allow multiplexed expression analysis of specific genes in solution-phase hybridization with digital output. Advantages of the system are a higher sensitivity than microarrays and the utilization of small amounts of total RNA without requiring cDNA synthesis. We first determined the efficacy and consistency of the system using total RNA extracted from snap-frozen and formalin-fixed, paraffin-embedded osteosarcoma tissue specimens. We then verified that the NanoString assay was consistent with RT-PCR analysis of our samples, after which we subjected a cohort of osteosarcoma tumors to the expression assay. Seventeen genes, including many with well-described functions in osteosarcoma, were analyzed for expression in a cohort of tumors as well as normal human osteoblasts. Expression values of normal human osteoblasts were compared with those of tumors with more than 90% necrosis post-chemotherapy (an indicator of good prognosis) and of tumors with less than 90% necrosis post-chemotherapy (an indicator of poor prognosis). Of note, we found that tumors with poor response to chemotherapy had statistically significant up-regulation of CDKN1C, FOS, and RUNX2. The RUNX2 gene is located at chromosome 6p21.1, which frequently undergoes genetic amplification in osteosarcoma. Amplification-related overexpression of RUNX2 has been previously reported (Martin et al 2010, Sadikovic et al 2010) as a poor prognosticator for chemotherapy response, and the involvement of bone morphogenetic pathways downstream of RUNX2 are being addressed by multiplex analyses of differential gene expression. 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 2999. doi:1538-7445.AM2012-2999
S103 A decrease in elafin due to proteolytic cleavage may contribute to alveolar inflammation in patients with ALI
Authors: A. Kerrin, C. O'Kane, M. Shyamsundar, T. Craig, C. C. Taggart, D. F. McAuley
Journal: Thorax (2010)

<h3>Introduction</h3> Unregulated protease activity is implicated in the pathogenesis of acute lung injury (ALI). Elafin is a potent serine protease inhibitor produced by epithelial and inflammatory cells with anti-inflammatory actions. <h3>Aim</h3> To assess the temporal changes in elafin concentration in patients with ALI and test the hypothesis that a decrease in elafin levels due to proteolytic degradation may drive pulmonary inflammation. <h3>Methods</h3> Patients with ALI within 48 h of onset of ALI (n=37), day 3 (n=19) and day 7 (n=9) as well as five healthy volunteers underwent bronchoalveolar lavage (BAL). Elafin was measured by ELISA. To determine whether elafin was susceptible to proteolytic cleavage, western blot analysis of recombinant elafin was incubated with BAL±protease inhibitors. Alveolar macrophages from healthy volunteers were isolated and pre-treated with 10 μg/ml elafin for 1 h, followed by 24 h stimulation with 100 ng/ml LPS. IL-8 was measured in supernatants by ELISA. <h3>Results</h3> Elafin was significantly increased at the onset of ALI compared to healthy volunteers (39±5 ng/ml vs 0.5±0.1 ng/ml; p&lt;0.0004). Elafin levels fell significantly by day seven compared to baseline (16±4 ng/ml vs 39±5 ng/ml; p=0.02). Incubation of exogenous elafin with day 7 ALI BAL revealed that elafin underwent proteolytic cleavage (Abstract S103 Figure 1A). In contrast, proteolytic cleavage was not observed following incubation of exogenous elafin with day 0 ALI or healthy volunteer BAL. Pre-incubation of Day 7 ALI BAL with TLCK and Pefabloc abrogated this degradation suggesting that a trypsin-like protease may be responsible for the cleavage of elafin (Abstract S103 Figure 1A). Pretreatment of alveolar macrophages with elafin decreased LPS induced IL-8 production (Abstract S103 Figure 1B). <h3>Conclusion</h3> Elafin concentrations fall in the pulmonary compartment over the course of ALI. This decrease was found to be due to proteolytic degradation. Furthermore elafin decreases LPS stimulated IL-8 release from alveolar macrophages. Together these data suggest loss of elafin in the alveolar airspace may result in dysregulated inflammation in ALI. Elafin augmentation may be a potential therapeutic strategy in ALI.
Clinical Correlates of the Kimmelstiel–Wilson Lesion
Authors: Franklin H. Epstein, Vito Joseph Zupa
Journal: New England Journal of Medicine (1956)

THE clinical and pathological features of intercapillary glomerulosclerosis have received considerable attention since this entity was described in 1936 by Kimmelstiel and Wilson.1 Numerous reports attest to the occurrence of profuse albuminuria, hypoalbuminemia and edema, usually in association with hypertension and a distinctive retinopathy, in diabetic patients in whom glomerulosclerosis is demonstrated at autopsy.1 2 3 4 5 6 7 8 9 10 Many features of the disease, however, remain unclear. There is disagreement about the relative frequency or importance of associated conditions such as pyelonephritis and congestive heart failure. It is held, on the one hand, that the disease has a predilection for elderly women with mild diabetes . . .
F-18 FDG PET/CT in an Adult Case of Group B Streptococcal Sacroiliitis
Authors: Chi-Lai Ho, Wing Cheung Wu, Sirong Chen, Yim Lung Leung, Thomas Kam Chau Cheng
Journal: Clinical Nuclear Medicine (2010)

An adult patient presented with acute severe pelvic and low-back pain. Evaluations with CT and MRI were negative/inconclusive. F-18 FDG PET/CT localized the site of pathology in right sacroiliac-joint by demonstrating hypermetabolic activities conformal with the joint's outline, signifying infectious/inflammatory sacroiliitis. Blood culture was positive for Group B streptococcus (GBS). Antibiotic treatment was started within 24 hours from onset of symptoms, and there was almost immediate partial pain relief. GBS sacroiliitis is a rare form of septic sacroiliitis requiring prompt diagnosis and urgent treatment. This is the first report of F-18 FDG PET/CT for diagnosing GBS sacroiliitis in adults with no predisposing factors.