tbuckley/cabot-search huggingface dataset:
Abstract 1718: Exploring temozolomide resistance in glioblastoma using a combinatorial zinc-finger library approach
Authors: Radhakrishnan Narayanan, Benjamin S. Levin, Morgan L. Maeder, J Keith Joung, Catherine L. Nutt, David N. Louis
Journal: Cancer Research (2011)

Abstract Recent therapeutic advances have improved control of glioblastomas, with a significant fraction of tumors responding to initial therapies. Unfortunately, all glioblastomas recur and lead to patient death. In an effort to better understand therapeutic resistance, we have explored high-dimensional profiling studies to understand mechanisms of therapeutic resistance and to identify novel therapeutic targets. Temozolomide (TMZ) is an alkylating chemotherapeutic agent that is used to treat all glioblastomas. Recurrent glioblastomas, however, become resistant to the effects of TMZ through a mechanism associated with inactivation of MSH6, a member of the mismatch repair gene family; MSH6-deficient glioblastomas grow more rapidly during TMZ therapy. To explore pathways of therapeutic resistance, we have designed an unbiased drug resistance selection screen to create TMZ-resistant human glioblastoma cell lines using combinatorial zinc-finger transcription factors (ZTFs). The combinatorial ZTF library enables activation of a gene or a set of genes that will be selected for resistance to TMZ. We have isolated resistant clones in the TMZ-sensitive A172 and Gli36 cell lines and present molecular profile analysis of these clones. By comparative gene expression profile analysis of novel ZTF-induced TMZ resistant glioblastoma cell lines, we expect to identify molecular pathways that confer TMZ resistance. In doing so, we also aim to identify possible biomarkers for TMZ resistance in recurrent glioblastomas. 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 1718. doi:10.1158/1538-7445.AM2011-1718
Case 28-2005
Authors: Myles Wolf, Henry Rose, R. Neal Smith
Journal: New England Journal of Medicine (2005)

A 42-year-old man who had had steroid-dependent asthma for three years, weight loss for eight months, hematuria for two months, and rash, weakness, and hemoptysis for several days was admitted to the hospital. He had pedal edema; palpable purpura on the hands, feet, and lower legs; and motor weakness of the legs with sensory abnormalities.
Bone Imaging in Kohler's Disease
Authors: S Gips, R B Ruchman, D Groshar
Journal: Clinical Nuclear Medicine (1997)

Kohler's disease is a rare self-limited osteochondrosis of the tarsal navicular bone affecting children between the ages of 3 and 7 years. The condition is more frequent in boys than in girls, with a ratio of 4-6:1. The diagnosis may be missed because of the usual mild clinical manifestations and the difficulty in distinguishing the radiographic abnormalities from the normal radiographic changes of bone growth. In this report, bone scintigraphy was useful in detecting an avascular disorder of the tarsal navicular bone characteristic of Kohler's disease.
P16.09 * VALUE OF FET-PET EVALUATION IN PATIENTS TREATED WITH AXITINIB
Authors: J. Duerinck, S. Du Four, S. De Raedt, H. Everaert, A. Van Binst, B. Neyns
Journal: Neuro-Oncology (2014)

INTRODUCTION: VEGF/VEGFR targeted therapy for recurrent glioblastoma (rGB) normalizes tumour vasculature and restores the blood-brain barrier (BBB), resulting in decreased contrast enhancement and reduced peritumoral oedema. MRI-T2/FLAIR images are useful to document non-contrast-enhancing tumor progression, but its specificity is limited. Since the uptake of Fluoroethyltyrosine in GB reflects tumor metabolism and not BBB-integrity, the extent of (18)F-fluoroethyltyrosine (FET) uptake, as assessed by positron emission tomography (PET), may be of value in assessing the tumor response to treatment with small molecule VEGFR-inhibitors such as axitinib., MATERIAL AND METHODS: We evaluated patients with rGB treated with axitinib with MRI and FET-PET (static images acquired 45 min. after tracer administration) at baseline. In patients demonstrating a response on MRI (using RANO criteria), FET-PET was repeated. For 18F-FET PET, reduction of the metabolically active volume (Sum of tumour associated pixels with target-to-normal brain ratio of ≥1.5) was considered as a metabolic response to treatment. RESULTS: 15 patients treated with axitinib were evaluated with MRI and FET-PET. On MRI, 2 pts had CR and 4 PR. All responses on MRI were also characterized by a decrease in FET-active tumor volume. The extent of reduction of metabolically active volume did not correlated with the extent of tumor regression on Gd- MRI: the 2 patients with CR on MRI had a 65% and 43% decrease on FET-PET, respectively, whereas the decrease on FET-PET ranged between 26 and 100% in the patients with PR on MRI. A trend was observed between a higher baseline FET-active tumor volume and an increased progression-free survival (PFS) and overall survival (OS). A greater reduction of the metabolically active volume did correlate with longer PFS and OS (logrank p > 0,001 and p < 0,025, respectively). CONCLUSION: In patients with rGB treated with the VEGFR-inhibitor axitinib, baseline FET-PET has prognostic value. Response evaluation based on FET-PET is complementary to MRI based assessment and may prove superior in predicting survival on treatment with axitinib. Our preliminary findings deserve further evaluation in a larger series.
RISK FOR DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM AFTER HEART TRANSPLANTATION: CHARACTERIZATION OF AN OLD PROBLEM
Authors: Wanxing Chai, Jignesh Patel, Michelle Kittleson, Lawrence Czer, Matthew Rafiei, Lily Stern, Fardad Esmailian, Jon Kobashigawa
Journal: Journal of the American College of Cardiology (2012)
Case 9-2001
Authors: Kenneth C. Gorson, E. Tessa Hedley-Whyte, Martha M. Skinner
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 64-year-old, right-handed woman was admitted to the hospital because of motor and sensory impairment in her right arm.Two years before admission, generalized lymphadenopathy had been diagnosed. At that time, the levels of urea nitrogen, creatinine, and calcium were normal. The hematocrit was 34.8 percent. Microscopical examination of a bone marrow specimen showed increased iron storage. Immunologic tests were performed (Table 1). Immunoelectrophoresis showed an IgG kappa monoclonal protein (1300 mg per deciliter). No Bence Jones protein was detected. A gallium scan showed no abnormalities. The angiotensin-converting enzyme level was normal. Repeated computed tomographic (CT) scans . . .
BETTER ESTIMATING RADIATION EFFECTIVE DOSE FROM CARDIAC COMPUTED TOMOGRAPHY (CT): A COMPREHENSIVE EXAMINATION OF THE RELATIONSHIP BETWEEN EFFECTIVE DOSE AND DOSE-LENGTH PRODUCT
Authors: Sigal Trattner, Sandra Halliburton, Carla Thompson, Anjali Chelliah, Yanping Xu, Sachin Jambawalikar, M. Robert Peters, Munir Ghesani, James Jang, Udo Hoffmann, David J. Brenner, Andrew Jeffrey Einstein
Journal: Journal of the American College of Cardiology (2016)
Isolated Nasal Tip Metastasis From Esophageal Squamous Cell Carcinoma
Authors: Aisheng Dong, Changjing Zuo, Yang Wang, Zhijun Zhai, Wu Wen
Journal: Clinical Nuclear Medicine (2014)

Cutaneous metastatic tumors to the nasal tip are very rare. A 74-year-old woman presented with progressive dysphagia for 4 months and a painless red violaceous nodule in the nasal tip for the last 6 weeks. Gastroendoscopy showed midesophageal wall thickening, which corresponded to esophageal squamous cell carcinoma confirmed by endoscopic biopsy. F-FDG PET/CT showed intense FDG uptake of the esophageal carcinoma (SUVmax, 19.0) and the nasal tip nodule (SUVmax, 29.1). The patient underwent biopsy of the nasal tip nodule. Nasal tip metastasis from the esophageal squamous cell carcinoma was confirmed by pathologic examination.
Abstract 1640: Combined inhibition of EMMPRIN and EGFR abrogates growth and migration of head and neck squamous cell carcinoma cells.
Authors: Shinsuke Suzuki
Journal: Cancer Research (2013)

Abstract Head and neck cancer squamous cell carcinoma (HNSCC) is the most common malignancy of the upper aerodigestive tract. Despite intense efforts to improve different treatment modalities, mortality rates in advanced cases remain high. A deeper understanding of the HNSCC progression mechanisms is needed to improve survival in patients with HNSCC. The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase, which regulates crucial cellular signaling pathways contributing to tumor progression. EGFR is frequently amplified and overexpressed in several human solid tumors including a high percentage of HNSCCs. Evidence accumulated in several studies has shown that EGFR stimulation induces expression of matrix metalloproteinases (MMPs), which degrade extracellular matrix, and its activation process is critical for tumor development. Recently, extracellular matrix metalloproteinase inducer (EMMPRIN), which is known as CD147 and is a member of the immunoglobulin superfamily, has been reported to be highly expressed in malignant tumors including HNSCC. It has been reported that EGFR expression is associated with EMMPRIN in some solid tumors; however, the relationship of EMMPRIN with EGFR in head and neck cancers is not fully understood. To determine the relationship between EMMPRIN and EGFR in HNSCC, HNSCC cells were stimulated with epidermal growth factor (EGF), a ligand of EGFR. Immunoblotting analysis showed that EMMPRIN expression in HNSCC cells was upregulated by EGF in a dose- and time-dependent manner. In addition, gelatin zymography showed that EGF stimulation-induced cell invasion and MMP-9 expression of HNSCC cells. Interestingly, this increase in invasion and MMP-9 expression were abrogated by downmodulation of EMMPRIN expression using the siRNA technique. Furthermore, to determine the effects of combined EMMPRIN and EGFR targeting in the HNSCC cell line, HNSCC cells were investigated in cell proliferation and migration assays. The effects of combined treatment with the EMMPRIN function blocking antibody and the EGFR inhibitor AG1478 were examined on the proliferation and migration of HNSCC cells. This combined treatment resulted in greater inhibition of HNSCC cell proliferation and migration compared with the individual agents alone. These results suggest that EMMPRIN mediates EGFR-induced invasion and MMP-9 expression in cases where combined targeting of EMMPRIN and EGFR may be an efficacious treatment approach. Citation Format: Shinsuke Suzuki. Combined inhibition of EMMPRIN and EGFR abrogates growth and migration of head and neck squamous cell carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1640. doi:10.1158/1538-7445.AM2013-1640
A8.30 Collagen-induced arthritis and imiquimod-induced psoriasis development is unaffected by the absence of interleukin-33
Authors: S Khaleghparast Athari, J Biton, R Hervé, A Raffaillac, D Lemeiter, A Herbelin, L Semerano, JP Girard, F Caux, MC Boissier, N Bessis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Interleukin (IL)-33 is a dual cytokine with both an alarmin role and a Th2-like inducing effect. It is involved in the pathogenesis of rheumatoid arthritis (RA) and its models, and we recently demonstrated that exogenous IL-33 was able to inhibit collagen-induced arthritis (CIA) in C57Bl/6 mice. However, its physiopathological role in RA is unclear. For instance, mice deficient for its receptor ST2 are more susceptible to arthritis, while the disease is not modified in IL-33 deficient mice. We aimed at studying the immune response in wild type mice and IL-33 deficient mice with CIA. To further understand the place of endogenous IL-33 in inflammatory diseases, we also studied its role in a model of skin inflammation. <h3>Material and methods</h3> CIA was induced in IL-33-lacZ gene trap ( <i>IL-33<sup>gt</sup></i>) reporter strain mice (J Immunol, 2012, 188:3488; gift from JP Girard, Toulouse). These mice, generated on a C57BL/6 background, are deficient for IL-33 gene but express lacZ under the IL-33 promoter. IL-33 expression was analysed by X-Gal staining in various mice compartments. CD4<sup>+</sup>FoxP3<sup>+</sup> regulatory T cells (Tregs), Th1 and Th17 frequencies were evaluated by flow cytometry in <i>wt</i> and <i>IL-33<sup>gt</sup></i>mice. Bone resorption was studied by evaluating osteoclasts activity on a synthetic mineral matrix. Psoriasis-like skin inflammation was induced by immiquimod skin application. <h3>Results</h3> We first confirmed that IL-33 <i><sup>gt</sup></i> mice develop CIA with similar severity than wild-type ( <i>wt</i>) littermates mice. IL-33 promotor activity was detected in the joints of IL-33 <i><sup>gt</sup></i> mice after CIA induction. Tregs, Th1 and Th17 frequencies were not modified in the spleen and lymph nodes of both strains. After CIA induction, osteoclast activity was higher in IL-33 <i><sup>gt</sup></i>mice than in <i>wt</i> mice, although differences were not significant. Interestingly, psoriasis development was not impaired in IL-33 <i><sup>gt</sup></i>mice. <h3>Conclusions</h3> Despite its expression in the synovium of arthritic mice, IL-33 is not required for CIA development, any more than in psoriasis. Its absence also doesn't influence T cell shift toward Th1, Th17 or Tregs sub-populations. Altogether, these data and our previous ones, showing that exogenous IL-33 can almost completely inhibit CIA development, suggest that this cytokine is not crucial for chronic inflammation development, but that the development of treatment based on IL-33/ST2 axis targeting should be considered.
Severe Group A Streptococcal Infections Associated with a Toxic Shock-like Syndrome and Scarlet Fever Toxin A
Authors: Dennis L. Stevens, Martha H. Tanner, Jay Winship, Raymond Swarts, Kristen M. Ries, Patrick M. Schlievert, Edward Kaplan
Journal: New England Journal of Medicine (1989)

There is concern that group A streptococci, which have caused less serious infections in developed countries in recent decades, may be acquiring greater virulence. We describe 20 patients from the Rocky Mountain region who had group A streptococcal infections from 1986 to 1988 that were remarkable for the severity of local tissue destruction and life-threatening systemic toxicity. Among the 20 patients (median age, 36), necrotizing fasciitis with or without myositis was the most common soft-tissue infection (55 percent). Nineteen patients (95 percent) had shock, 16 (80 percent) had renal impairment, and 11 (55 percent) had acute respiratory distress syndrome. The mortality rate was 30 percent. All patients but 1 had positive tissue cultures for Streptococcus pyogenes; 12 had positive blood cultures. Most of the patients had no underlying disease; 2 used intravenous drugs. Strains of group A beta-hemolytic streptococci isolated from 10 patients were not of a single M or T type; however, 8 of the 10 strains produced pyrogenic exotoxin A (scarlet fever toxin A, a classic erythrogenic toxin), which has rarely been observed in recent years. From our study of this cluster of severe streptococcal infections with a toxic shock-like syndrome, we conclude that in our region, more virulent group A streptococci have reappeared that produce the pyrogenic toxin A associated with scarlet fever. (N Engl J Med 1989; 321:1–7.)
P4-10-08: Risk Factor Profiles of Women with DCIS and Invasive Ductal Breast Cancers.
Authors: F Schnabel, Kim J Chun, J Billig, A Cimeno, P Mehta, A Guth, T Hochman, R Shapiro, K Hiotis, B Siegel, D Axelrod
Journal: Cancer Research (2011)

Abstract Background There are well established risk factors for breast cancer, including elements of personal and family history. Ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) have long been viewed as representing two points on the spectrum of one disease. There is limited and conflicting information in the literature regarding risk factor profiles for DCIS as compared with IDC. The purpose of this study was to investigate the relationship of established risk factors in a population of women newly diagnosed with pure DCIS and IDC. Methods The Breast Cancer Database at NYU Langone Medical Center was queried for women who were diagnosed with pure DCIS and IDC from 1/2010-3/2011. Variables of interest included: age, family history of breast cancer (FHBC), BRCA1/2 status, age at menarche and menopause, parity, age at first birth, breast feeding, body mass index (BMI), history of atypical hyperplasia or lobular carcinoma in situ (ADH, ALH, LCIS), stage, ER/PR status, and method of presentation. Wilcoxon non-parametric tests, Chi-Square tests, and Fisher's Exact Tests were used to evaluate differences among DCIS and IDC patients. Results Of the 593 women identified in this study, 140 (24%) had pure DCIS and 453 (76%) had IDC. The median age at diagnosis was 59 years. There were 9 (1.5%) BRCA1/2 mutation carriers. Of these, 7 had IDC and 2 had DCIS. The majority of patients with IDC were stage I (67%) and ER/PR+ (73%). The majority of patients with DCIS were also ER/PR+ (71%). In our cohort, the majority of DCIS (83%) was mammographically detected versus 47% of IDC cases. There were no statistically significant differences in breast cancer risk factors between the two groups. Conclusions In contrast to some previously published work, the risk factor profile in our cohort was similar for patients with IDC and DCIS. In this population, the majority of cases of DCIS were detected mammographically, underscoring the importance of mammography in early detection of breast cancer. There is increasing interest in identifying a population of women with DCIS who might never progress to invasive disease. Our data suggests that this population is unlikely to be distinguished by its risk factor profile. Genetic and molecular characteristics are more likely to provide the criteria by which this subgroup of patients is identified. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-08.
Abstract 5181: Forced hemidesmosome assembly blocks pancreatic cancer cell invasiveness
Authors: Séverine Laval, Hanane Laklai, Marjorie FanJul, Mélanie Pucelle, Christiane Susini, Stéphane Pyronnet, Corinne Bousquet
Journal: Cancer Research (2010)

Abstract Hemidesmosomes (HDs) play a critical role in epithelia integrity by anchoring epithelial cells to the basement membrane (BM). These structures, present at the basal cell surface, link the intracellular intermediate filament network with the extracellular laminins of the BM. Interestingly, HDs are frequently lost in cancer cells, thereby facilitating epithelial tumor cell detachment from the BM. Surprisingly, we here provide evidence that a strong immunoreactivity for the integrin α6β4 and BP180, two specific hemidesmosomal proteins, is observed in human pancreatic ductal adenocarcinoma cells, where their function served paradoxically to stimulate migration and invasion. Using human pancreatic cancer cells in culture, we described molecular events explaining why these proteins are hijacked from their primary function and, importantly, how to force back the reassembly of HDs, thereby decreasing cancer cell migration and invasion. This is achieved by introducing in these cells the somatostatin receptor sst2, whose expression is lost in 90% of pancreatic cancers, and which we have shown to have oncosuppressive functions including inhibition of tumor progression and metastasis. Cell treatment with somatostatin forced HDs reassembly by stimulating two separate critical events, as demonstrated in pancreatic cancer cells and in migrating keratinocytes: 1- the dephosphorylation of the α6β4 integrin which drives its relocalization from lamellipodia, where it is delocalised upon its phosphorylation by growth factors in migrating cells, to HDs; 2- the inhibition of the cleavage of BP180 into its pro-migratory BP120 form, which is here shown to account for the strong BP180 immunoreactivity observed in human pancreatic tumor samples as compared to normal pancreas where the full-length BP180 form is mostly expressed. BP180 cleavage into BP120 is here shown to rely at least on the activity of the MMP-9 metalloprotease whose activity is inhibited by sst2. Strikingly, knocking-down BP180 expression (siRNA) impairs somatostatin-induced HDs assembly in sst2-expressing cells. Interestingly, BP180 siRNA partially revert sst2 inhibitory role on in vitro and in vivo cell migration and invasion, as demonstrated using the chick chorioallatoic membrane model whereby tumor progression of pancreatic cancer cell xenografts is monitored. We have identified novel and original mechanisms for somatostatin-activated sst2 to revert cancer cell pro-migratory phenotype by facilitating HD assembly and cancer cell anchorage to the BM. 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 5181.
SP0003 The Role of Imaging Modalities in the Diagnosis and Followup of GIANT Cell Arteritis
Authors: N. Pipitone
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> iant cell arteritis (GCA) is a primary systemic vasculitis involving the large- and medium-sized arteries, particularly the temporal arteries. Imaging studies have proved useful to detect inflammatory changes in the temporal arteries, and are invaluable in demonstrating inflammation in large arteries, which are not easily accessible to biopsy. Color-Doppler sonography (CDS), magnetic resonance (MR) angiography (MRA) and contrast-enhanced computerized tomography (CT) angiography (CTA) can visualize both the arterial wall and the lumen. All these techniques can aid in diagnosing early arteritis by demonstrating inflammation of the arterial wall even before vascular complications such as stenoses and aneurysms develop. Precocious inflammatory signs of arteritis include vessel wall thickening and transmural edema, which shows as a hypoechoic "halo" surrounding the lumen of an inflamed artery on CDS and as contrast enhancement on MRA and CTA. CDS is particularly suited to investigate the superficial arteries (including the temporal arteries), while CT and MR are able to depict well deep, large vessels such as the thoracic and abdominal aorta, which can hardly or not be visualized by CDS. Alternatively, large-vessel inflammation can be assessed by 18F-Fluorodeoxyglucose positron emission tomography (PET). However, PET cannot demonstrate changes in the temporal or renal arteries. Moreover, PET is unable to delineate the anatomical details of the arterial wall, and is thus not helpful in detecting stenoses or aneurysms. For monitoring purposes, CDS, MRI/MRA, and CT/CTA are helpful in that they can demonstrate both arterial wall and lumen changes. PET can also be used to monitor the extent and intensity of vascular inflammation in large vessels. Digital subtraction angiography has now been largely superseded by CTA or MRA, but may still have a role in guiding interventional procedures. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6168