tbuckley/cabot-search huggingface dataset:
Multicentric study with neoadjuvant endocrine therapy for breast conserving surgery. Experience in Mexico.
Authors: JG De la Garza, E Bargallo, C Solorio, T Ramirez, F Salazar, J Sanchez
Journal: Cancer Research (2009)

Abstract Abstract #5119 Background: In patients with large, operable breast tumors who are ineligible for Breast-conserving surgery (BCS), neoadjuvant therapy is a useful option for reducing tumor size and for increasing the proportion of candidates to BCS. Neoadjuvant chemotherapy has been widely studied, but little has been published on neoadjuvant endocrine therapy. This study analyzes the use of neoadjuvant endocrine therapy with aromatase inhibitors in postmenopausal women with hormone receptor-positive locally advanced breast cancer (LABC).&amp;#x2028; Material and Methods: The study was designed as a multicenter study and was conducted in four centers in Mexico between July 2005 and August 2006. Thirty six patients were assigned to receive letrozole 2.5 mg, daily, for 4 months prior to schedule surgery. This group was compared with a group of 36 patients who received conventional chemotherapy as neodjuvant treatment. At baseline none of these patients were considered to be candidates for BCS. Primary end points were response rate (ORR) defined as the percentage of patients with a complete response (CR) or partial response (PR) as determined by breast palpation and the percentage of patients who underwent BCS. Standard descriptive statistics were performed.&amp;#x2028; Results: All patients were postmenopausal, median age was similar in both groups (64 (50 86) years vs. 59 (50 – 77) years; P = 0.1). At baseline 75% of tumors in endrocrine group were T2 (median (range) 4 (2 – 5) cm) while 25% were T3 (median (range) 7.6 (5.5 – 10) cm) and in chemotherapy group 83% were T2 (median (range) 3.9 (2 - 5) cm) and 17% T3 (median (range) 6.8 (5.5 – 9.5) cm). Clinical response was similar between groups. The ORR was 70% for endocrine group versus 80% for chemotherapy group (P = 0.3). In terms of clinical progression, 8% of patients in the endocrine group progressed vs. none in the chemotherapy group, while 22% of endocrine- and 19% of chemotherapy-treated patients had stable disease. The proportion of patients able to undergo BCS was significantly higher in the endocrine group than in the chemotherapy group (36% vs. 19%, respectively; P = 0.0008).&amp;#x2028; Discussion: Over third of patients become BCS-eligible within 4 months of preoperative endocrine therapy. Neoadjuvant therapy with aromatase inhibitors could be an effective treatment option for highly selected postmenopausal women who are unwilling or unable to undergo BCS or preoperative chemotherapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5119.
Abstract 1235: p120ctn is a key effector of Ras-PKC∈-mediated oncogenic signaling
Authors: Stephen G. Dann, Jonathon Golas, Miriam Miranda, Celine Shi, Eric Upeslacis, Edward Rosfjord, Guixian Jin, Jiang Wu, Anke Klippel
Journal: Cancer Research (2012)

Abstract Within the family of protein kinase C (PKC) molecules only the novel isoform member PRKCE (PKC∈) acts as a bona fide oncogene in in-vitro and in-vivo models of tumorigenesis. Previous studies have reported cancer-specific misexpression of PKC∈ at levels well above that of normal adjacent tissue in breast, prostate and lung tumors. We find that oncogenic Ras signaling promotes PKC∈ expression and results in hyperphosphorylation of CTNND1/p120-catenin (p120ctn). In this context, loss of PKC∈ by genetic or pharmacological means results in normalization of morphology and signaling responses. In a KRasD13-dependent breast cancer model loss of PKC∈ function results in growth inhibition in 2-dimensional (2D) and 3-dimensional (3D) culture systems as well as in orthotopic xenografts concomitant with the normalization of a subset of Ras-induced signaling responses. Using phospho-proteomic profiling analysis we observe that CTNND1 (p120ctn) phosphorylation at serine 268 (S268) occurs in a strictly PKC∈ dependent manner. Treatment with a specific PKC∈ inhibitor, PF-5263555, recapitulates the genetic loss of function phenotype and interferes with breast cancer cell growth in-vitro and in-vivo. We also show that PKC∈-mediated phosphorylation at S268 further stabilizes additional p120ctn phosphorylation sites and total protein levels of β-catenin. We demonstrate that p120ctn phosphorylation at S268 represents a specific readout for PKC∈ activity and as such can serve as a suitable biomarker for PKC∈ dysregulation in human cancer and for monitoring therapeutic response. 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 1235. doi:1538-7445.AM2012-1235
Case 20-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Jeremy D. Schmahmann, Jean-Paul Vonsattel
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 16-year-old boy was admitted to the hospital because of repeated seizures.The patient was well until 26 1/2 months earlier, when he had a generalized tonic—clonic seizure, which recurred four or five times later on the same day. He was admitted to another hospital, where phenytoin sodium was administered by vein. No abnormalities were detected on examination, and the results of routine laboratory tests were reported to be normal. An x-ray film of the chest was normal. An electroencephalogram showed left frontal intermittent slowing, spikes, and semirhythmic runs of spike and wave. A cranial computed tomographic . . .
AB0957 Computer Assisted Osteosclerosis Detection A Useful Tool for Doctor
Authors: D. Nemes, D. Surducan, L. Catan, D. Popa, E. Amaricai, G. Puenea, D. Andrei
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteosclerosis is widely known as a radiological sign of osteoarthritis. Nowadays the classical film radiography is more often replaced by the digital medical imaging. <h3>Objectives</h3> To find out if the osteosclerosis is present within hand and knee from the doctor9s point of view and by using a program of digital medical imaging along with classic X-ray and to establish a correlation between results. <h3>Methods</h3> 103 patients were assessed by doctor and special designed software. As for the program the medical X-ray was segmented and subsequently the bone sections histogram along with several metadata of the image were analyzed by a fuzzy inference system. 206 bone sections called anatomical areas were assessed by the program. The metadata contains the technical characteristics of the image. <h3>Results</h3> Following the assessment there were discrepancies only in 24 anatomical areas (11.65%), in 15 (7.28%) of them the osteosclerosis was emphasized by the program. As it is pointed out below, the osteosclerosis was found especially within the 1st phalanx of finger 1 along with distal extremity of ulna, 2 areas involved in osteoarthritis. There were standing out linear correlations between the assessment carried out by doctor and the assessment achieved by using the program regarding the whole hand (0.949) and the whole knee (0.924). <h3>Conclusions</h3> By using a special program the osteosclerosis could be emphasized as of the first symptoms of osteoarthritis, therefore the patient undergoes a proper treatment with regard to the patient and its quality of life along with positive impact on medical system. Moreover the use of further investigation based on X-rays is prevented. Owing to this fact this program could turn out to be useful in order to help the doctor9s assessment. <h3>References</h3> WE Brant, C Helms. Fundamentals of Diagnostic Radiology. Lippincott Williams &amp; Wilkins Publishers. 2012. JA DeLisa. Physical Medicine &amp; Rehabilitation – Principles and Practice. 4th edition. Lippincott Williams &amp; Wilkins Publishers. 2005. MCJ Christ, RMS Parvathi. Fuzzy c-means algorithm for medical image segmentation. Electronics Computer Technology (ICECT), 2011 3rd International Conference on, vol. 4, no., pp.33-36, 8-10 April 2011. N Gal, V Stoicu-Tivadar. XML as a Cross-Platform Representation for Medical Imaging with Fuzzy Algorithms. EFMI Special Topic Conference, EFMI STC, Lasko, Slovenia, April:2011,83-86 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5792
Abstract 1237: TGF-β signaling pathway analysis using MILLIPLEX MAP TGF-β multiplex panel
Authors: Randy Johnston, Tim Warmke, Rick Wiese, David Hayes, Joseph Hwang
Journal: Cancer Research (2012)

Abstract Transforming growth factor beta (TGF-β) is a secreted protein that controls cellular proliferation, differentiation, apoptosis, migration, adhesion, immune response, and other functions in most cells. The binding of TGF-β to its receptor, TGFβRII, can lead to activation of both the SMAD-dependent canonical pathway as well as the SMAD-independent non-canonical pathways (such as PI3K/Akt, ERK, JNK, and p38). The TGF-β signaling pathway is coordinately regulated by phosphorylation and understanding the role of this pathway in normal physiological processes and in diseases such as cancer and diabetes requires the ability to simultaneously measure phosphorylation status of multiple protein targets. In recent years, bead-based assays, such as those using Luminex xMAP technology, have enabled the measurement of phosphorylation levels of up to 12 proteins simultaneously. Using the TGF-β Signaling Pathway multiplex panel, we observed increased levels of phosphorylated Smad2 and Smad3, but not phosphorylated ERK or Akt in TGF-β treated cells when compared to their unstimulated counterparts. Modifications in phosphorylation levels were confirmed by the treatment of cells with specific inhibitors against TGFβRI, which blocked phosphorylation of Smad2 and Smad3 in TGF-β treated HepG2 cells. Furthermore, significant increase in phosphorylated Smad3 was observed in human breast cancer versus matched breast normal tissues. The TGF-β Signaling Pathway multiplex panel allowed for simultaneous detection of multiple analytes in both the SMAD-dependent canonical pathway as well as the SMAD-independent non-canonical pathways in a specific, sensitive, and reproducible manner. 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 1237. doi:1538-7445.AM2012-1237
AB0979 A clinical and radiographic study comparing hand involvement in idiopathic osteoarthritis and hemochromatosis arthropathy
Authors: J. Zwerina, T. Dallos, E. Sahinbegovic, T. Stamm, E. Aigner, B. Manger, M. Englbrecht, C. Datz, G. Schett
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Hand osteoarthritis (HOA) can result from different conditions. Most known is idiopathic HOA, but there are also secondary forms due to metabolic diseases. Hereditary hemochromatosis (HH) arthropathy is the most common form of secondary HOA. <h3>Objectives</h3> To perform a direct comparison between idiopathic hand OA and hemochromatosis arthropathy to delineate clinical similarities and differences. <h3>Methods</h3> In total 337 patients were assessed, 141 patients with HH arthropathy of the hands and 196 patients with primary HOA. Structured clinical assessment including hand function tests, as well as hand radiographs with scoring according to Kellgren-Lawrence, were done in all patients. <h3>Results</h3> HH arthropathy and HOA differed significantly: Patients with HH arthropathy were younger and predominantly male as compared to HOA. In males but not females, HH arthropathy led to earlier start of symptoms than in HOA. Patients with HOA had more tender joints and worse hand function than patients with HH arthropathy, although subjective measures of joint pain and function were similar. Metacarpophalangeal and wrist joint involvement was more frequent and severe in HH arthropathy, while HOA patients had more frequently degenerative changes in the first carpometacarpal as well as proximal and distal interphalangeal joints. <h3>Conclusions</h3> Secondary HOA in conjunction with HH and primary HOA differ significantly in terms of epidemiology, localization, severity of symptoms and radiographic changes. <h3>Disclosure of Interest</h3> None Declared
Abstract 3322: Phenotypic plasticity in the normal breast
Authors: Candice Anne Marcum Sauder, Jillian E. Koziel, MiRan Choi, Melanie J. Fox, Sunil Badve, Rachel J. Blosser, Theresa Mathieson, Constance A. Rufenbarger, Jill E. Henry, Anna Maria V. Storniolo, Brittney-Shea Herbert, Susan E. Clare
Journal: Cancer Research (2012)

Abstract Metaplasia is observed in almost all epithelial cancers. The origins of metaplasia are obscure although chronic inflammation is thought to be one etiology. We present data that suggests that an origin of metaplasia is the normal resident stem cell population. Methods: Starting from 10 gauge tissue cores of normal breast donated to the Komen Tissue Bank, 28 normal mammary epithelial (HME) and 33 normal stromal (HMS) cell lines were established using an organoid isolation method after digestion with enzymes for 24 hours. The HME cell lines were characterized by immunohistochemistry (IHC). Ploidy was assayed. Cellular morphology was observed both on two-dimensional and in three-dimensional culture systems. The HME cells were subjected to FACS analysis using multiple antibodies. Results: 96.9% of early passage cells are diploid. The HME cells express vimentin, CK 5/6, p63, CD 10, CK 18, and HER-1 when grown on two dimensional plastic surfaces. Cells placed in the center of a sandwich of Matrigel uniformly make spheres 37mm-325mm in diameter. Hematoxylin and eosin staining of the formalin-fixed and paraffin-embedded sections of these spheres reveal keratinized squamous differentiation. When the cells are grown on Laminin, Collagen Type IV, or Fibronectin surfaces multiple cell types are observed including osteoclasts, distinguished by the presence of Tartrate Resistant Acid Phospatase; and chondrocytes, confirmed by staining with Alcian Blue. Other cells with a spindle-shape and cytoplasmic vacuoles turn a dark reddish-brown color when stained with Oil Red O, characteristics of adipocytes. In other areas of the culture, the cells form a syncitium and they express the protein MyoD, a marker of immature muscle. Finally, there are numerous cells with long, dendritic processes. These cells express Nestin, glial fibrillary acidic protein (GFAP), and beta-III tubulin. Using FACS, the HME cells were found to be CD49f positive and EpCAM negative. Multiple nucleoli were confirmed using anti-Nucleostemin IHC. Conclusions: Phenotypic plasticity is common to all the HME cell lines characterized to date. Differentiation into cells of mesodermal and ectodermal origin, CD49+/EpCAM- by FACS, and the presence of multiple nucleoli suggest that the isolated cells are a multipotent/stem cell residing in the normal adult breast. These cells, through a series of yet to be elucidated events, may be the cells of origin of both benign and malignant metaplasia observed in breast lesions. 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 3322. doi:1538-7445.AM2012-3322
P129 HEPATITIS C VIRUS MEK1- AND TC-PTP-DEPENDENTLY CONVERTS EPIDERMAL GROWTH FACTOR (EGF) INTO A POTENT INDUCTOR OF CXCR2 LIGAND EXPRESSION
Authors: C. Gröpper, N. Triller, S. Eisenbürger, R. Bartenschlager, D. Häussinger, J.G. Bode
Journal: Journal of Hepatology (2014)
The First Documented Case of High-Grade Synovial Cell Sarcoma of the Rectum
Authors: Richard B. Hostetter, Min Yan, Houman Vaghefi, Kenneth Pennington, Gary Cornette
Journal: Journal of the National Comprehensive Cancer Network (2012)

A patient presented with signs and symptoms of tenesmus, urgency, and rectal bleeding that she had been experiencing over the course of several months. Full endoscopic evaluation showed a 6-cm submucosal mass approximately 10 cm from the dente line projecting as an endoluminal mass with a large broad base. An initial endoscopic resection was attempted but aborted because of significant hemorrhage, and surgical oncology was consulted. After stabilization, the patient underwent a transanal resection of the mass the following day. An endoscopic gastrointestinal anastomosis stapler resulted in a margin-negative complete resection of what was later determined to be a high-grade synovial cell sarcoma. This case report presents the first known documented case of synovial cell sarcoma of the rectum.
[Comments on Ïs Sperm Motility Maturation Affected by Static Magnetic Fields?"]: Response
Authors: Francisco Perez-Sanchez
Journal: Environmental Health Perspectives (1997)

In the paper titled "Is Sperm Motility Maturation Affected by Static Magnetic Fields?" (1), the authors conclude that "sperm production is unaffected because no changes were observed in testicular or epididymal weights after exposure to static magnetic fields."This conclusion, however, is not sup- ported by the data presented.With five animals per group and the standard deviations (SD) given (Table 2 of their paper), a calculation of the power of such comparisons is possible.With values of a = 0.05 and a = 0.80, the minimal detectable dif- ference (DD) is larger than the maximal observed difference (OD), for each parameter (see Table 1).The results of the study are therefore unable to prove the nonexistence of an effect of static magnetic fields, at least with respect to the weight data.
A5.17 Comparison of adipose mesenchymal stem cells derived from rheumatoid arthritis and osteoarthritis patients. The influence of adipocytokines
Authors: U Skalska, W Maslinski, E Kontny
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Adipose-derived stem cells (ASCs) have immunomodulatory properties and are intensively studied as a potential therapeutical method to treat rheumatoid arthritis (RA). ASCs immunosuppressive function may be affected by adipocytokines released by intra-articular adipose tissue. Knowing that inflammatory conditions may alter immunoregulatory properties of ASCs, we aimed to verify if there are any differences between ASCs derived from RA and osteoarthritis (OA) patients regarding their influence on synovial fibroblasts (FLS) and peripheral blood mononuclear cells (PBMC). The effect of selected adipocytokines were also analysed. <h3>Materials and Methods</h3> Infrapatellar fat pad and synovial membrane were obtained from RA and OA patients during total knee joint replacement surgery. PBMC were obtained from buffy coats of healthy donors. ASCs were isolated and cultured with/without: medium/high molecular weight adiponectin (MMW/HMW), TNFα or IFNγ. The influence of ASCs on FLS and PBMC was assesed in co-cultures. PBMC, RA-FLS and OA-FLS were co-cultured with RA- or OA-ASCs. 24h after ASCs stimulation, PBMC/RA-FLS/OA-FLS were added to ASCs and cultured 72h. FLS proliferation was assessed by BrdU incorporation test, MMP-3 and IL-6 concentration was measured in FLS culture supernatants (SNs). Concentration of IL-10, TGFβ and RANTES was measured in PBMC culture SNs. <h3>Results</h3> We did not observe any differences in proliferation rate and cytokines secretion between variants of FLS co-cultures (RA-FLS + RA-ASCs <i>vs.</i> RA-FLS + OA-ASCs <i>vs.</i> OA-FLS + OA-ASCs <i>vs.</i> OA-FLS + RA-ASCs). FLS proliferation as well as MMP-3 and IL-6 secretion seemed to be not affected by co-culture with unstimulated/stimulated ASCs. By contrast, PBMC co-cultured with ASCs responded by significant up-regulation of RANTES and IL-10 production (p &lt; 0.05). ASCs themeselves secreted negligible amounts of these cytokines, except for TNF-stimulated ASCs, which increased considerably RANTES release (23 ng/ml <i>vs.</i> 530 ng/ml in RA-ASCs and 18 ng/ml <i>vs.</i> 780 ng/ml in OA-ASCs). TGFβ secretion by co-cultured cells didn9t increase considerably comparing to ASCs cultured alone (600-700 ng/ml <i>vs.</i> 700-800 ng/ml), which may indicate that PBMC and ASCs cutlured together decrease TGFβ production. <h3>Conclusions</h3> Analysis of ASCs influence on FLS and PBMC did not show any differences between cells derived from RA and OA. We didn9t observe any strong differences regarding adipocytokines role in ASCs activity. Neverthless, we showed that ASCs from both diseases have the impact on cytokines secretion by PBMC. <h3>Funding</h3> Grant No. 2011/01/N/NZ5/00932, National Science Center, Poland.
THU0139 Impacts of Immediate Changes in Dmards on Outcomes in Rheumatoid Arthritis with Moderate-to-Severe Activity
Authors: D. Kim, C.-B. Choi, Y.-K. Sung, S.-K. Cho, S.-Y. Park, J.-Y. Choi, D.-H. Yoo, S.-S. Lee, J. Lee, J. Kim, H.-S. Lee, T.-H. Kim, B. Y. Yoon, W.-H. Yoo, J.-Y. Choe, S.-H. Lee, S.-C. Shim, W. T. Chung, S.-J. Hong, C. K. Lee, E. Koh, J.-B. Jun, S.-Y. Bang, S.-K. Kim, H.-S. Cha, J. Lee, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The importance of tight control is supported by solid clinical evidence. While treating RA with the aim of achieving remission or a low disease activity-as determined by disease activity score employing 28 joints count (DAS28) or the simplified and the clinical disease activity index (SDAI, CDAI) -is reasonable and important, this approach is not widely accepted in the clinical situation. <h3>Objectives</h3> To identify the effects of tight control of rheumatoid arthritis (RA) on various disease outcomes in a large observational study. <h3>Methods</h3> We selected 1900 RA patients with a baseline DAS28-ESR of more than 3.2 and who had 1 year of follow-up data. The patients were divided into two groups: (1) disease-modifying antirheumatic drugs (DMARDs)-changed group (patients who changed the types or amounts of their DMARDs) and (2) DMARDs-unchanged group (patients who maintained their DMARDs). We measured various disease outcomes, including the Health Assessment Questionnaire–Disability Index (HAQ-DI), DAS28-ESR, C-reactive protein (CRP), ESR, and global health assessments by both physicians and patients. The <i>t</i>-test was used to identify the effects of tight control of RA on various disease outcomes. <h3>Results</h3> Patients in the DMARDs-changed group were younger, had a shorter disease duration, used less leflunomide, used more biologic agents. At baseline, they had higher DAS28-ESR (4.62±0.96 in DMARDs-changed group versus 4.42±0.90 in DMARDs-unchanged group, p&lt;0.001), CRP (1.15±1.62 versus 0.81±1.14, p&lt;0.001), global health assessment by both physician (34.05±20.00 versus 26.94±18.16, p&lt;0.001) and patient (48.96±25.34 versus 46.18±24.74, p=0.016). In the comparison between baseline and the 1-year follow-up, the DMARDs-changed group showed greater improvements in HAQ-DI (–0.76±1.43 versus –0.59±1.22, <i>p</i>=0.006), CRP (–0.39±1.71 versus –0.11±1.37 mg/dl, <i>p</i>=0.001), and the global health assessment by a physician (–11.21±24.18 versus –8.10±19.20, <i>p</i>=0.002). <h3>Image/graph</h3> <h3>Conclusions</h3> Immediate changes in DMARDs according to disease activity can improve disease outcomes, especially DAS28-ESR, CRP, and the global health assessment by a physician. <h3>Disclosure of Interest</h3> None Declared