tbuckley/cabot-search huggingface dataset:
Abstract LB-252: Enzymology of the mechanism of action for MDX-1203 antibody drug conjugate
Authors: Daniel W. Derwin, David Passmore, Qian Zhang, Bilal Sufi, Chin Pan, Chetana Rao, Mary Huber, Sanjeev Gangwar, Pina Cardarelli, Shrikant Deshpande, Vangipuram Rangan
Journal: Cancer Research (2012)

Abstract MDX-1203 is an antibody drug conjugate under clinical evaluation by Bristol-Myers Squibb. The antibody portion is MDX-1115, a fully human anti-CD70 IgG. The drug portion is MED-2460, a small molecule which itself is composed of the releasable prodrug MED-2284, a cleavable di-peptide linker, and a maleimide reactive group intended to facilitate protein attachment. The mechanism of action of MDX-1203 involves tumor specific delivery and cellular uptake of ADC, followed by the intervention of two different enzymatic pathways. Release of prodrug is accomplished through proteolysis of a citruline-valine di-peptide linker, presumably by Cathepsin B activity in the acidic environment of the lysosome. Activation of released prodrug, MED-2284, occurs in the endoplasmic reticulum via esterase cleavage in the of the piperazine protecting group by the enzyme human Carboxylesterase 2. Michaelis Menten methodologies are used to probe activity of each enzymatic pathway and their relative role in the activity of the drug. Proteolysis is investigated through the use of Human Liver Cathepsin B protease. A kinetic model is constructed for a cysteine modified analogue MED-2460, and then applied to the more complex system involving antibody conjugated drug. Enzymatic activation of released prodrug MED-2284 is investigated with recombinant Human Carboxylesterase 2. For each pathway, the kinetic parameters Km, kcat, and enzymatic efficiency are measured and reported. Parameters are compared in an effort to define the enzymatic rate limiting step in the activation MDX-1203, and define their respective roles in the overall activity of the drug. 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 LB-252. doi:1538-7445.AM2012-LB-252
DISTAL DICROTIC NOTCH IN THE CORONARY ARTERY PRESSURE WAVEFORM PREDICTS SIGNIFICANT STENOSIS, AS VALIDATED BY FRACTIONAL FLOW RESERVE, BUT PERFORMS INFERIORLY AS COMPARED TO PD/PA
Authors: Mirza Mujadil Ahmad, Rafath Ullah, Mirza Nubair Ahmad, Zoya Ammar, Saagar Shah, Arsalan Riaz, Syed Shahab Kazmi, Anjan Gupta, Khawaja Afzal Ammar
Journal: Journal of the American College of Cardiology (2016)
Abstract 4112: Prognostic impact of autophagic markers LC3, Beclin 1 and p62/sequestosome 1 in colon carcinomas from patients treated in 5-FU-based adjuvant therapy trials
Authors: Frank A. Sinicrope, Tsung-Teh Wu, Nathan R. Foster, Daniel J. Sargent, Shengbing Huang, Jae Myung Park
Journal: Cancer Research (2012)

Abstract Background. Autophagy maintains energy metabolism and enables tumor cell survival during cellular stress. Beclin 1 is involved in autophagosome formation during which membrane-bound LC3 binds to p62/sequestosome 1. We reported that ectopic p62 can promote 5-fluorouracil-induced cell death (JBC 286:40002-12, 2011). It is unknown whether these autophagy markers can predict clinical outcome. Materials &amp; Methods. Beclin 1, LC3B, and p62 proteins were analyzed by immunohistochemistry in tissue microarrays containing stage II and III colon carcinomas (N=151) from patients receiving 5-FU or surgery alone. The mean weighted score (intensity x extent) was dichotomized for survival analysis using Cox models. Results. Increased levels of cytoplasmic LC3, Beclin 1, and p62 expression were detected in 21%, 14%, and 68% of cancers, respectively, and were not associated with tumor site, stage or grade. By multivariable analysis, increased LC3 was significantly associated with worse disease-free survival (DFS) (p=0.022), but not overall survival (OS) [p=0.069](Table). Beclin 1 was not prognostic, but increased p62 was significantly associated with improved DFS (p=0.038), but not OS (p= 0.176)[Table]. When restricted to 5-FU-treated patients, increased LC3 was associated with worse DFS [HR= 2.38 (1.19, 4.75, p=0.020), elevated Beclin 1 predicted worse OS [HR=2.83 (1.27, 6.34), p = 0.019], and p62 was not prognostic. Conclusion. LC3 and Beclin 1 overexpression were independently associated with adverse outcome. Increased p62 was associated with better outcome consistent with its ability to promote cell death. These data support strategies to inhibit autophagy for therapeutic advantage. 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 4112. doi:1538-7445.AM2012-4112
Some diminutive colorectal polyps can be removed and discarded without pathological examination
Authors: B. Denis, J. Bottlaender, A. Weiss, A. Peter, G. Breysacher, P. Chiappa, P. Perrin
Journal: Endoscopy (2010)

Pathological examination of colorectal polyps is useful if clinical management is affected (i. e. when invasive carcinoma is detected or postpolypectomy surveillance interval is guided). Our aim was to assess whether the pathological examination of some diminutive (measuring ≤ 5 mm) polyps can be omitted.Consecutive patients undergoing a colonoscopy at Pasteur Hospital (Colmar, France) between January and August 2008 were included in this prospective study. Six senior gastroenterologists predicted the future surveillance interval without referring to the result of pathological examination.In all, 350 polyps from 175 patients were removed and analyzed. The endoscopist was able to predict the correct surveillance interval without referring to the result of pathological examination in 118 patients (67.4 %; 95 % confidence interval [CI] 60.5 - 74.4). The pathological examination of 18.4 % (95 % CI 13.7 - 23.1) of diminutive polyps either associated with a cancer or a polyp measuring ≥ 10 mm or removed in very old or frail patients could be omitted without any consequence for the patient. If diminutive polyps one or two in number were discarded without pathological examination in patients with a personal history of colorectal neoplasm, three patients out of 43 would have a 5-year instead of a 3-year surveillance interval. As a whole, if 44.1 % (95 % CI 38.0 - 50.1) of diminutive polyps were discarded, the surveillance interval would remain identical in 98.3 % (95 % CI 96.4 - 100) of patients.The pathological examination of up to 44 % of diminutive polyps (i. e. 33 % of all polyps), can be safely omitted. The pathological examination would be required only for those with suspicious gross appearance, those three or more in number, and those isolated one or two in number that are removed from people without personal history of colorectal neoplasm.
Abstract 5380: Detection of OvCa1 in human malignancies.
Authors: Jessica L. Jackson, Kristen A. Grothaus, Connie J. Temm, Lindsey D. Mayo, George E. Sanduksy
Journal: Cancer Research (2013)

Abstract Immunohistochemistry biomarkers are currently being developed to target specific proteins found in cancer cells, which could contribute to a better understanding of specific types of cancers and provide information to develop better treatments for cancer patients. The biomarker and putative tumor suppressor, OvCa1, has a function that is not well characterized. Due to a lack of staining reagents, we developed monoclonal antibodies of OvCa1 to examine multiple human malignancies. The goal of this project was to gain a better understanding of OvCa1 and its role in cancer. Primary cancers with different histological grades as well as metastatic lesions were examined with the monoclonal antibodies. Ovarian cancer tissue samples from the Indiana University Simon Cancer Center Tissue Bank were used for this study. The samples were fixed in neutral buffered formalin and processed into paraffin blocks. The tissues were cut using a microtome and placed on slides. Staining of the OvCa1 antibody was completed using immunohistochemistry (IHC) techniques. Thirty-one samples were evaluated including low grade tumors, medium grade tumors, high grade tumors, and metastatic ovarian carcinomas. All cases revealed a range of staining intensity with the OvCa1 antibody. The results indicated that OvCa1 for the high grade, stage 3/4, ovarian carcinomas had the highest staining intensity. Medium grade tumors had less OvCa1 expression. The metastatic tumors had less staining than any of the other three grades. Immunostaining was observed primarily in the cytoplasm and nucleus of the tumor cells. In addition, we evaluated approximately 20 tumors from various different organs. These included prostate, breast, spleen, lung, colon, stomach, and kidney tumors, which were positive for immunostaining with the OvCa1 antibody. In summary, the results indicated that all histological grades expressed the biomarker, OvCa1, and the staining intensity was highest in the high grade, stage 3/4, tumors. Our preliminary studies demonstrated a further need to delineate OvCa1 as a potential biomarker, which could be used for early detection and diagnosis of ovarian cancer. Citation Format: Jessica L. Jackson, Kristen A. Grothaus, Connie J. Temm, Lindsey D. Mayo, George E. Sanduksy. Detection of OvCa1 in human malignancies. [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 5380. doi:10.1158/1538-7445.AM2013-5380
Abstract 4954: Comparison of miR expression patterns in plasma, serum, and cell line cMV
Authors: Traci L. Pawlowski, Kimberly Yeatts, Meredith Millis, Katrina Radebach, Yuka Kojima, Jason Zhong, Adam Stark, Christine Kuslich
Journal: Cancer Research (2011)

Abstract Circulating microvesicles (cMV) isolated from either blood plasma or serum can yield genetic material sufficient for informative microRNA (miR) expression analysis. The ability to purify RNA from cMV isolated from several sources was compared, and the miR expression patterns were determined. cMV were isolated from the blood plasma and serum of men with and without prostate cancer, as well as from healthy and prostate tumor tissue and prostate cancer cell lines. Total RNA was extracted from the plasma and cell line cMV using the Qiagen miReasy kit and from the serum cMV using the ExoMir extraction method. The miR expression was determined for each source using Agilent V3 miRNA microarrays. Each sample (300 ng) was hybridized to the microarrays, and the acquired data were analyzed with the GeneSpring software package. Expression patterns for miR from cMV isolated from the plasma and serum of men with and without prostate cancer were evaluated for significant differences. Hierarchical clustering on both samples and genes demonstrated a distinct expression pattern for miR from plasma cMV compared with miR from cell line and tumor tissue cMV. These findings demonstrate that cMV isolated from the peripheral blood offer a unique and potentially clinically relevant source of miR for blood-based analysis. 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 4954. doi:10.1158/1538-7445.AM2011-4954
AB1061 Comparing four imaging techniques of visualzing gouty tophi using one single patient
Authors: H. Su, X. Li, N. Zhao, D. Yu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gouty arthritis-causing uric acid is persistently in excess in the form of tophi. The ultimate therapeutic ideal should be to completely eliminate all tophi. So far, clinicians have relied on physical examination and plain radiographs to assess the locations and sizes of Gouty tophi. The dual energy computerized tomography (DECT), magnetic resonance imaging (MRI), 2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) each offers a different perspective of gouty tophi. None of the papers have used all four techniques concomitantly, no guidelines are available concerning their applications. <h3>Objectives</h3> To visualize in a gout patient,using four different imaging techniques,the locations, sizes, compactness of tophi. <h3>Methods</h3> The feet and knees were imaged by X-ray, MRI, DECT and PET. <h3>Results</h3> DECT uncovered deposits in unexpected locations. The combination of DECT, MRI and PET showed that tophi were much larger and more inflammatory than clinically suspected. <h3>Conclusions</h3> The locations and sizes of tophi in chronic gout patients can far exceed those accessible by physical examination and X-ray. These can be critical when making decisions concerning the initiation and aggressiveness of serum uric acid- lowering therapies. <h3>References</h3> Neogi T. Clinical practice. Gout. N Engl J Med. 2011 Feb 3;364(5):443-52. Dalbeth N, McQueen FM. Use of imaging to evaluate gout and other crystal deposition disorders. Curr Opin Rheumatol. 2009 Mar;21(2):124-31. Choi HK, Al-Arfaj AM, Eftekhari A, Munk PL, Shojania K, Reid G, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis. 2009 Oct;68(10):1609-12. Nicolaou S, Yong-Hing CJ, Galea-Soler S, Hou DJ, Louis L, Munk P. Dual-energy CT as a potential new diagnostic tool in the management of gout in the acute setting. AJR Am J Roentgenol. 2010 Apr;194(4):1072-8. Ko KH, Hsu YC, Lee HS, Lee CH, Huang GS. Tophaceous gout of the knee: revisiting MRI patterns in 30 patients. J Clin Rheumatol. 2010 Aug;16(5):209-14. <h3>Disclosure of Interest</h3> None Declared
Diagnosis of pancreatic plasmacytoma by endoscopic ultrasound-guided fine-needle aspiration
Authors: E. Artifon, L. Okawa, E. Baba, S. Siqueira, E. Moura, P. Sakai, T. Savides
Journal: Endoscopy (2011)

A 42-year-old male was diagnosed with a solitary plasmacytoma in the right shoulder in 2002, which was treated with local radiotherapy. In December 2004, new plasmacytomas in the knee and ankle were diagnosed and treated with radiotherapy and chemotherapy, with good clinical response. In November 2007, a new plasmacytoma in the right thigh was diagnosed and systemic treatment was chosen.
FRI0155 Patient reported outcomes in early arthritis patients
Authors: L. Heimans, K. V. Wevers-de Boer, K. K. Koudijs, H. K. Ronday, M. van Oosterhout, A. J. Peeters, T. W. Huizinga, C. F. Allaart
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Besides suppression of inflammation and prevention of radiographic damage, improvement of functional ability and Health Related Quality Of Life (HRQOL) is one of the main goals of treatment in patients with RA. <h3>Objectives</h3> To investigate patient reported outcomes (PROs) of functioning and HRQOL after 1 year remission-steered treatment. <h3>Methods</h3> 610 patients with early RA or undifferentiated arthritis (UA) were included in the IMPROVED-study. All started with methotrexate (MTX) and tapered high dose prednisone. Patients in early remission (Disease Activity Score (DAS)&lt;1.6 after 4 months) tapered prednisone to 0 and when in remission after 8 months, also tapered MTX. Patients not in early remission were randomized to MTX plus hydroxychloroquine, sulphasalazine and prednisone (arm 1) or to MTX+adalimumab (arm 2). Every 4 months, patients filled out the McMaster-Toronto Arthritis Patients Preference Questionnaire (MACTAR) and the Health Assessment Questionnaire (HAQ) to measure functional ability, the Short Form 36 (SF-36) for mental en physical HRQOL and visual analogue scales (VAS). Scores were analyzed separately for all treatment arms and compared between arm 1 and 2. Predictors of HRQOL were identified using linear mixed models. <h3>Results</h3> 387 patients achieved early remission and 221 patients did not; 83 patients were randomized to arm 1 and 78 to arm 2, 50 did not follow the protocol. After 1 year, remission was most often achieved by patients who were in early remission. Patients in arm 2 more often achieved remission (40%) than patients in arm 1 (25%). Except mental HRQOL, which was stable over 1 year and close to the population mean of 50 in all patients, all PROs and VAS results improved over 1 year, the most during the first 4 months (table). Only VAS disease activity improved significantly more in arm 2 (mean difference 13, 95%CI 2;23), other VAS scores were similar in both arms. The strongest independent predictor for HRQOL was baseline HAQ (beta for mental HRQOL:-1.8, 95%CI -2.8;-0.8, for physical HRQOL:-9.1, 95%CI -9.8;-8.4). <h3>Conclusions</h3> In early arthritis patients functional ability and HRQOL improve after 1 year of remission targeted treatment, with the largest change in the first 4 months. Patients who achieve early remission improve the most, achieving functional ability and HRQOL in the normal range. In patients who did not achieve early remission, there was no difference in improvement after treatment with DMARD+prednisone or adalimumab+MTX although more patients achieved remission after 1 year in the latter group. <h3>Disclosure of Interest</h3> None Declared
Acute Myocardial Infarction in 258 Cases of Diabetes
Authors: Jean O. Partamian, Robert F. Bradley
Journal: New England Journal of Medicine (1965)

THIS is a study of 258 hospitalized diabetic patients who sustained acute myocardial infarction. The data deal with the immediate mortality of the acute attack and the five-year survival among those who recovered from it, as well as with various associated and prognostic factors. The findings are compared with previously reported similar studies of diabetic patients and the general population.Materials and MethodsAll 258 patients had diabetes mellitus and were admitted with acute myocardial infarction to the Joslin Clinic Service of the New England Deaconess Hospital in Boston during a five-year period from 1954 to 1958. The criteria for . . .
Evaluation of Brain Perfusion Using Tc-99m HMPAO in a Patient with a Persistent Vegetative Neurologic State and a Left Ventricular Thrombus
Authors: MICHAEL D. WIRT, NERIS M. NIEVES, MORAKINYO O. TONEY
Journal: Clinical Nuclear Medicine (2002)

WIRT, MICHAEL D. M.D., Ph.D.; NIEVES, NERIS M. M.D.; TONEY, MORAKINYO O. M.D. Author Information
Pain Palliation With Rhenium-186 HEDP in Breast Cancer Patients With Disseminated Bone Metastases
Authors: HOLGER PALMEDO, HANS BENDER, CHRISTIAN DIERKE-DZIERZON, UWE MICHAEL CARL, JÖRN RISSE, DIETER KREBS, HANS JÜRGEN BIERSACK
Journal: Clinical Nuclear Medicine (1999)

For patients with metastatic prostate cancer, first results have shown that rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) is efficient in pain palliation of disseminated bone metastases. The aim of this study was to determine whether significant pain reduction can also be achieved in breast cancer patients with Re-186 HEDP.Thirty patients with breast cancer who had multifocal painful bone metastases received a total of 38 intravenous Re-186 HEDP injections. Pain relief was assessed through daily documentation of the visual analog scale and analgesic consumption. A significant response to treatment was determined if the visual analog scale or analgesic consumption decreased significantly for at least 2 weeks. Blood counts were controlled at baseline and at weeks 4 and 8.A response to pain therapy was observed in 60% (18 of 30) of the patients. A reversible thrombocytopenia and leukopenia of grade 2 (according to World Health Organization criteria) was found in 4 and 2 patients, respectively.Patients with disseminated osseous metastases resulting from breast cancer can benefit from therapy with Re-186 HEDP.
Abstract LB-64: Selective estrogen receptor modulators (SERMs) act as breast cancer chemopreventive agents by attenuating oxidative estrogen metabolism
Authors: L P Madhubhani P. Hemachandra, Jaewoo Choi, Judy Bolotn, Gregory Thatcher
Journal: Cancer Research (2012)

Abstract Possibility of developing hormone dependent cancer in women will increase with long term exposure to endogenous estrogens. Estrogen induced, estrogen receptor (ER) mediated cell proliferation (hormonal pathway) and formation of reactive estrogen metabolites (chemical pathway) are believed to contribute to estrogen carcinogenesis. Estrogens are oxidized to the catechols, 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) by P450 1A1/1A2 and P450 1B1 respectively. Both catechols are further oxidized to form electrophilic o-quinones which can react with DNA and proteins, while 4 hydroxyestradiol O-quinone (4-OHE2-Q) is considered as the ultimate carcinogen. Selective Estrogen Receptor Modulators (SERMs) are used in cancer chemoprevention and in the treatment of post menopausal osteoporosis. The current study focuses on elucidating the influence of clinical and pre clinical benzothiophene SERMs on oxidative estrogen metabolism in ER negative non tumerigenic human breast epithelial cells (MCF-10A). Upon exposure to 17β-estradiol (E2), MCF-10A cells transformed into a malignant phenotype and showed anchorage independent colony growth in soft agar. After treatment of MCF-10A cells with E2 and SERMs, estrogen metabolites were analyzed using a sensitive LC-MS/MS method. Among the SERMs tested, raloxifene and desmethylarzoxifen (DMA) showed a significant reduction in catechol estrogen formation whereas 4′F-DMA had little effect. Furthermore, raloxifene and DMA significantly inhibited E2 induced malignant transformation and reactive oxygen species formation in MCF-10A cells. These data suggest that raloxifene and DMA possess chemopreventive activity through inhibition of genotoxic estrogen quinone formation, in addition to their action via estrogen receptors. 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 LB-64. doi:1538-7445.AM2012-LB-64