tbuckley/cabot-search huggingface dataset:
Abstract P4-04-07: Tartrate-resistant Acid Phosphatase (TRAcP)-Expressed Tumor-Associated Macrophages Promote Breast Cancer Progression
Authors: M-S Dai, C-C Wu, P-Y Chang, C-L Ho, Y-F Hsieh, K-Y Lo, W-Y Kao, T-Y Chao, J-C Yu
Journal: Cancer Research (2012)

Abstract Purpose: Tumor-associated macrophages (TAMs) can promote or dampen breast cancer progression, depending on phenotypic changes within the cancer microenvironment. Two contrasting activation states were described in the literature: the M1 anti-tumoral and M2 pro-tumoral subtype of TAMs. In clinical observation, we analyzed the TRAcP expression in breast cancer TAM and correlated to patient's chemotherapy responses and survival. In animal models, we aim to investigate the tumor-promoting or inhibiting properties among tartrate-resistant acid phosphatase (TRAcP) expressed TAMs. Methods: TRAcP expression, T lymphocytes, and other macrophage relevant markers were determined by immunohistochemical staining in the human breast cancer tissue from the patients before neoadjuvant chemotherapy. The expression of TRAcP within the TAMs were calculated and correlated to the patient's chemotherapy responsiveness and outcome. The polarized M1/M2 macrophages and breast cancer hematogenous metastasis were created in the animal model. Activated macrophages from TRAcP+/+ or TRAcP−/− mice were injected with JC (Balb/c breast cancer) cells in the metastatic model. Results: The presence of Foxp3+ regulatory T cell (Treg) correlates to the tumor proliferation (Ki-67 and Her2 expression) and higher Foxp3+ Treg prevalence and tumor Ki-67 expression inferred poorer chemotherapy response. TRAcP staining within the CD68+ macrophages were observed with better chemotherapy response. In animal model, M2 polarized macrophages have higher TRAcP expression, promote breast cancer metastasis, and attract Treg infiltrating in tumor, consistent with the clinical observation. Conclusion: TRAcP-expressing TAMs, representing M2-polarized macrophage, demonstrat local tumor-promoting and immune-suppressive effects, and chemotherapy resistance. TRAcP expression within TAM can be a potential prognostic marker for breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-07.
Deficiency of a Dystrophin-Associated Glycoprotein (Adhalin) in a Patient with Muscular Dystrophy and Cardiomyopathy
Authors: Ricardo Fadic, Yoshihida Sunada, Andrew J. Waclawik, Scott Buck, Paul J. Lewandoski, Kevin P. Campbell, Barend P. Lotz
Journal: New England Journal of Medicine (1996)

Cardiac muscle is commonly affected in muscular dystrophies.1–4 X-linked Duchenne's muscular dystrophy and Becker's muscular dystrophy are caused by mutations in the gene encoding dystrophin,5,6 a membrane cytoskeletal protein.7 In skeletal and cardiac muscle, dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins.8,9 This dystrophin–glycoprotein complex is composed of five glycoproteins (35, 43 doublet, 50, and 156 kd) and two proteins (25 and 59 kd). It spans the sarcolemma to provide linkage between the subsarcolemmal cytoskeleton and laminin, a major component of the extracellular matrix.9,10 In Duchenne's and Becker's muscular dystrophies, the primary deficiency . . .
Partial Normalization by Dietary Cod-Liver Oil of Increased Microvascular Albumin Leakage in Patients with Insulin-Dependent Diabetes and Albuminuria
Authors: Tonny Jensen, Steen Stender, Karin Goldstein, Gunhild Hølmer, Torsten Deckert
Journal: New England Journal of Medicine (1989)

In a double-blind crossover study, we compared the effects of eight weeks of dietary supplementation with cod-liver oil with the effects of supplementation with olive oil on endothelial permeability, blood pressure, and plasma lipid levels in 18 patients with insulin-dependent diabetes mellitus and albuminuria. When the patients received the cod-liver-oil supplement, the mean (+/- SEM) transcapillary escape rate of albumin (as compared with the base-line rate) decreased from 8.7 +/- 0.5 to 6.9 +/- 0.6 percent per hour (P less than 0.01), and the blood pressure decreased from 146 +/- 4/90 +/- 2 mm Hg to 139 +/- 4/85 +/- 2 mm Hg (P less than 0.05). There was no correlation, however, between cod-liver oil's effect on the transcapillary escape rate of albumin and its effect on blood pressure. There was no change from base line after the patients received the olive-oil supplement. During dietary supplementation with cod-liver oil, the plasma concentration of high-density lipoprotein cholesterol increased and the concentrations of very-low-density lipoprotein cholesterol and triglycerides decreased (P less than 0.05 for all comparisons), but the level of low-density lipoprotein cholesterol did not change. In contrast, during supplementation with olive oil, the concentration of low-density lipoprotein cholesterol decreased and the levels of very-low-density lipoprotein cholesterol and triglyceride increased (P less than 0.05 for all comparisons), but there was no change in the level of high-density lipoprotein. No changes were observed in the glomerular filtration rate, degree of albuminuria, insulin requirement, glycosylated hemoglobin level, or blood glucose level during supplementation with either oil. We conclude that dietary supplementation with cod-liver oil lowers the elevated transcapillary escape rate of albumin characteristic of patients with insulin-dependent diabetes and albuminuria, independently of its effect on blood pressure--perhaps by decreasing vascular permeability. We did not find any effect of cod-liver oil on urinary albumin excretion.
1111 THE LIVER EXHIBITS THERMAL VARIATIONS DEPENDING ON THE FIBROSIS DEGREE: A PROOF OF CONCEPT CONCERNING THE USE OF DIFFERENTIAL SCANNING CALORIMETRY FOR ASSESSING LIVER FIBROSIS
Authors: J.L. Arjona-San Roman, R. Melendez-Perez, G. Gutierrez-Reyes, D. Kershenobich, G. Escobedo
Journal: Journal of Hepatology (2013)
YIELD OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY TO DETECT INVASIVE COMPLICATIONS OF AORTIC PROSTHETIC VALVE ENDOCARDITIS
Authors: Paul Cremer, Ahmed Eltelbany, Nabin Shrestha, Syed Hussain, Wael Jaber, L. Leonardo Rodriguez, Steve Gordon, Brian Griffin, Gosta Pettersson, Venu Menon
Journal: Journal of the American College of Cardiology (2016)
SAT0472 Which strategies adopt patients with early inflammatory arthritis to address their problems with work performance?
Authors: M.-L.B. Lenssinck, A. Burdorf, J.M. Hazes, J.J. Luime
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Employees with inflammatory arthritis (IA) face restrictions in work performance from early onset of the disease, even with the improved medication regimes (1-2). Little is known about the specifics of work adaptations and whether the workers involved experience the adaptations as successful (3). <h3>Objectives</h3> to determine what problems patients with IA encounter at work, what adjustments they made in work task, working hours and workplace and what roles particular stakeholders played to facilitate these adaptations. <h3>Methods</h3> Telephone interviews were conducted among working recent-onset IA patients on work adaptations, self-management of the worker, disclosure, stakeholders involved and combining work with other activities at home or in leisure activities. <h3>Results</h3> Ninetypatients with paid employment were interviewed. Sixty-five patients encountered problems at work, initiated by pain, fatigue, physical limitations and high job demands. Forty-five persons adapted their work. The vast majority discussed their joint complaints and the consequences for their work with their colleagues and/or supervisor. Stakeholders involved in order of importance were: supervisor, rheumatologist, occupational physician and general practitioner. Forty-three persons found it difficult to combine work with other activities at home or in leisure activities and thirty-one of them had to give up or reduce certain activities to continue their work. <h3>Conclusions</h3> A large proportion of patients with early IA already encountered problems at work, sometimes even before the diagnosis was made. Pain, fatigue and physical limitations were the most important problems at work which most patients dealt actively with by adjusting their work tasks or work time. Remaining employed is regarded very important, patients expect their rheumatologist to optimize medication to facilitate this. <h3>References</h3> Geuskens GA, Burdorf A, Hazes JM. Consequences of rheumatoid arthritis for performance of social roles–a literature review. J Rheumatol 2007;34(6):1248-60. Geuskens GA, Hazes JM, Barendregt PJ, Burdorf A. Work and sick leave among patients with early inflammatory joint conditions. Arthritis Rheum 2008;59(10):1458-66. Allaire SH. What work changes do people with arthritis make to preserve employment, and are such changes effective? Arthritis Rheum 2004;51(6):871-3. <h3>Disclosure of Interest</h3> None Declared
Abstract 2051: Inhibitors against CHK1 and WEE1, MK-8776 and MK-1775, strongly synergize in vitro and in vivo to inhibit tumor growth
Authors: Stuart D. Shumway, Amy D. Guertin, Melissa M. Martin, Brian Roberts, Melissa S. Hurd, Xianlu Qu, Nathan R. Miselis, Andrew Bloecher, Carlo Toniatti
Journal: Cancer Research (2012)

Abstract Inhibitors of the checkpoint kinases CHK1 and WEE1 are under development as sensitizers to chemotherapy or radiation therapy. Disruption of either CHK1 or WEE1 activity compromises the cell cycle arrest that normally accompanies the DNA damage response, forcing cells to prematurely divide before repairing damaged DNA. However, inhibition of either CHK1 or WEE1 alone also disrupts DNA replication, resulting in DNA double strand breaks (DSBs) primarily in S-phase cells. Here we describe the ability of inhibitors against CHK1 and WEE1 to synergize both in vitro and in vivo. MK-8776 and MK-1775 are advancing through early clinical trials as potent and selective inhibitors of CHK1 and WEE1, respectively. MK-8776 increases the cell-based potency of MK-1775 in multiple cancer cell lines by as much as a 10-fold EC50 shift in proliferation assays. Staining for the DSB marker γH2AX at low concentrations of each drug demonstrates that MK-8776 and MK-1775 in combination induce up to 50-fold more DNA damage than either MK-8776 or MK-1775 alone. The ability of the combination to drive premature mitosis, determined by pHH3 quantitation, was variable, suggesting that generation of DSBs rather than G2/M checkpoint abrogation is the mechanism underlying combination cytotoxicity. Induction of DSBs requires cyclin-dependent kinase activity and takes place largely in S-phase cells, implying deregulation of DNA replication. Furthermore, staining for DNA damage response markers γH2AX and pCHK1-ser345 was both more intense and more durable in a LoVo xenograft model of cancer when MK-8776 and MK-1775 were dosed together compared to either compound alone. At tolerated doses, the combination demonstrated significantly greater anti-tumor efficacy than either MK-8776 or MK-1775 alone in LoVo xenografts (91% tumor growth inhibition for the combination versus 28% and 41% for MK-8776 and MK-1775, respectively). Similar observations were made in additional xenograft models. These results demonstrate in vitro and in vivo synergy between MK-8776 and MK-1775, indicating unique and complimentary anti-tumor effects of CHK1 and WEE1 inhibition. Our studies provide preclinical rationale for combining WEE1 and CHK1 inhibitors as a novel cancer treatment regimen. 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 2051. doi:1538-7445.AM2012-2051
FRI0372 Clinical Response to Belimumab in Academic Clincal Practices
Authors: A. Askanase
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Belimumab is a human monoclonal antibody that inhibits soluble B-Lymphocyte Stimulator and improves systemic lupus erythematosus (SLE) disease activity. <h3>Objectives</h3> This study was initiated to evaluate the use and efficacy of belimumab in academic SLE clinical practices. <h3>Methods</h3> An invitation to participate was sent to 16 physicians experienced in SLE Phase III clinical trials. All agreeing to participate completed a one-page questionnaire for each patient prescribed belimumab that includes demographic and SLE characteristics, and information about belimumab administration. The questionnaire completed every three months by the physicians also captured clinical responses and belimumab safety. Clinical response was defined as a ≥50% improvement in the initial clinical manifestation being treated without worsening in other organ systems. <h3>Results</h3> Of 16 invitations sent, nine investigators participated. Questionnaires on 150 patients treated with belimumab for at least 3 months were available for analysis. The mean age was 41.9±12.6 years. 92.0% were female, 67.1% White, 24.7% Black, 5.7% Asian, and 5.3% Hispanic. The average SLE disease duration was 12.2±8.2 years. Concomitant medications included: prednisone in 73.3% (mean dose of 12.2±10.9, 41.7% on ≥10 mg), antimalarials in 71.7%, and immunosuppressants in 66.3% (mycophenolate mofetil 34.2%, azathioprine 20.3%, methotrexate 11.8%). Only 3.7% of patients were not on any background SLE medications, 8.0% were on antimalarials alone. The dominant clinical manifestations driving treatment were arthritis in 69.5%, rash in 44.4%, and inability to taper steroids in 27.3%. Other SLE manifestations were serositis 16.0%, hematological 13.9%, and renal 10.7%. 65.2% of patients had ≥2 active manifestations. Of the 150 patients on belimumab for at least 3 months, 69 (46.0%) clinically responded by 3 months with marked improvement in arthritis and/or rash. Similarly, of the 112 patients on belimumab for at least 6 months for whom follow-up data were available, 54 (48.2%) clinically responded with improvements in arthritis, rash and/or nephritis. While the numbers are limited, black patients showed improvement at 6 months, with 19/26, 73% of patients responding, p=0.05. <h3>Conclusions</h3> These observational data support the use of belimumab across all racial/ethnic groups and efficacy similar to that reported in the Phase III trials. Relevant to physician and patient decision-making, improvement was seen as early as 3 months. <h3>Disclosure of Interest</h3> A. Askanase Consultant for: GlaxoSmithKline <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4343
Reflux and Barrett's disease: revival of endoscopic antireflux procedures?
Authors: R. Bisschops
Journal: Endoscopy (2013)

After the initial enthusiasm at the end of the previous century, interest in endoscopic anti-reflux procedures decreased due to inefficiency or complications with devices, a lack of good clinical trials, or financial problems of the manufacturers. In 2012 some interesting results on new and old devices have been published.
Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease
Authors: Gilbert S. Omenn, Gary E. Goodman, Mark D. Thornquist, John Balmes, Mark R. Cullen, Andrew Glass, James P. Keogh, Frank L. Meyskens, Barbara Valanis, James H. Williams, Scott Barnhart, Samuel Hammar
Journal: New England Journal of Medicine (1996)

Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.
Colonic adenoma detection and differentiation – does technology improve efficacy?
Authors: Thomas Rösch
Journal: Endoscopy (2014)

One of my teachers outside of my own teaching hospital, while I was still a fellow and later on, was Mike Sivak, one of the former editors of Gastrointestinal Endoscopy, and a truly intellectual endoscopist. He kept telling me that the most influential endoscopic technique is polypectomy. It is polypectomy of precancerous lesions which makes sense of screening colonoscopy, although final proof or disproof of this assumption by a randomized trial will not be available before 2020 [1]. Nationwide screening programs have mostly involved primary stool tests, but a few countries have also included colonoscopy as a primary screening examination in their armamentarium. Based on the main purpose of screening colonoscopy, namely to detect and remove polyps as precursor lesions, there are two main challenges with regard to diagnostic colonoscopy: the detection of colonic adenomas, as represented by the so-called adenoma detection rate (ADR) [2], and more recently the differential diagnosis of colonic polyps into adenomas and hyperplastic polyps. The latter could pave the way to reducing the need for histopathologic analysis of removed polyps. The endoscopic differential diagnosis between adenomas (requiring follow-up earlier than 10 years) and hyperplastic polyps (requiring no specific follow-up) would then finally determine follow-up intervals after polypectomy. This so-called DISCARD strategy (Detect InSpect ChAracterise Resect, and Discard; [3]) would save on histopathology costs associated with screening. High standards have been set by both ASGE and ESGE with regard to this issue [4] [5].
TWO-YEAR CLINICAL OUTCOMES WITH BIODEGRADABLE POLYMER BIOLIMUS-ELUTING STENT IN PATIENTS WITH CHRONIC KIDNEY DISEASE: COMPARISON WITH DURABLE POLYMER EVEROLIMUS-ELUTING STENT
Authors: Takashi Morinaga, Takashi Hiromasa, Yohei Kobayashi, Hiroyuki Jinnouchi, Shoichi Kuramitsu, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2015)
Targeting DNA Replication before It Starts: Cdc7 as a Therapeutic Target in p53 Mutant Her2 and Triple Negative Breast Ca.
Authors: R. Sainsbury, I. Proctor, S. Rodriguez, M. Loddo, S. Tudzarova, K. Stoeber, G. Williams
Journal: Cancer Research (2009)

Abstract Based on protein expression profiles of core regulatory proteins involved in the G1–S and G2–M phase transitions, we have identified three distinct cell cycle phenotypes in a series of 200 breast cancers: (I) a G0 “out-of-cycle” state (18% of cases); (II) a G1 arrested/delayed state (24% cases); and (III) accelerated S-G2-M phase progression (58% of cases). The accelerated cell cycle progression phenotype had a higher risk of relapse when compared with G0 and G1-delayed/arrested phenotypes (HR=3.90 (1.81-8.4, p&amp;lt;0.001) and was associated with Her2 and triple negative subtypes (p&amp;lt;0.001). High-grade tumours with the G1 delayed/arrested phenotype showed an identical low risk of relapse compared with well-differentiated G0 tumours. In addition to its prognostic significance, the cell cycle phenotype also impacts on individualised therapeutic decisions. It is only patients showing the actively cycling, aggressive cell cycle phenotype that are likely to benefit from conventional chemotherapeutic S- or M-phase-directed agents or from the new generation of targeted cell cycle inhibitors that are now entering clinical trials.The DNA replication initiation factor Cdc7 is an emerging anti-cancer target. Cdc7 inhibition results in an abortive S phase and potent cancer cell killing. Specificity is based on normal cells undergoing a reversible G1 arrest following Cdc7 inhibition due to activation of a novel cell cycle checkpoint that is lost or impaired in cancer cells. Our analysis of the molecular circuitry underlying this replication origin activation checkpoint reveals that G1 arrest is dependent on three non-redundant checkpoint axes coordinated through the Forkhead transcription factor FoxO3a and p53. We show that only breast cancers displaying the accelerated cell cycle phenotype express elevated Cdc7 levels and are therefore highly represented in p53 mutant Her2-subtype and triple negative tumours. Breast cancers of the luminal subtype expressing low levels of Cdc7 undergo a cytostatic G1 arrest after Cdc7 inhibition due to their p53 wild type status, a checkpoint response mimicking untransformed cells. In contrast Her2 and triple negative tumours show a marked response to Cdc7 inhibitors with potent cancer-cell-specific killing as a result of (i) overexpression of the target protein and (ii) impairment of the origin activation checkpoint due to p53 lesions. Thus integrating cancer cell cycle phenotypic data with a molecular analysis of the origin activation checkpoint serves as a predictor of response to pharmacological Cdc7 inhibitors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2148.
MINDIIZING OCCUPATIONAL AND PATIENT RADIATION EXPOSURE IN THE NUCLEAR MEDICINE LABORATORY USING AN OPTIMIZED INJECTION TECHNIQUE
Authors: Anne S. Holly, Kathryn D. Stunof, Douglas A. Ortendahl, Robert S. Eattner
Journal: Clinical Nuclear Medicine (1987)

Holly, Anne S.; Stunof, Kathryn D.; Ortendahl, Douglas A.; Eattner, Robert S. Author Information
TRANSTHYRETIN CARDIAC AMYLOIDOSIS IS PREVALENT AMONG MEN WITH SEVERE AORTIC STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Adam Castano, David Narotsky, Susheel Kodali, Tamim Nazif, Isaac George, Torsten Vahl, Nadira Hamid, Rebecca Hahn, Rachelle Morgenstern, Sabahat Bokhari, Mathew Maurer
Journal: Journal of the American College of Cardiology (2016)
Treatment strategies will need to be changed because of drug resistance
Authors: J. S Friedland, G. Simoes
Journal: BMJ (1996)

EDITOR,—Dale I Morse notes that the emergence of multidrug resistant Mycobacterium tuberculosis has been one of the spurs to supervised chemotherapy.1 Other aspects of treatment protocols are equally important in controlling the emergence of drug resistance. Currently, the British National Formulary recommends that standard treatment for tuberculosis should be with three drugs (isoniazid, rifampicin, and pyrazinamide). Indications for adding a fourth drug include previous default from treatment and immigration from areas of the world with a high prevalence …
Donor-Cell Leukemia after Bone Marrow Transplantation for Severe Aplastic Anemia
Authors: Paul V. Browne, Mark Lawler, Peter Humphries, Shaun R. McCann
Journal: New England Journal of Medicine (1991)

ACUTE leukemia after bone marrow transplantation for severe aplastic anemia is a rare event.1 , 2 In previous reports, such leukemia has been shown to originate in host cells.2 We report the development of acute monoblastic leukemia in donor cells nine months after transplantation in a patient with aplastic anemia. We used cytogenetic analysis and a novel application of the polymerase chain reaction (PCR) to show that the leukemia was of donor-cell origin. The donor was hematologically normal at the time of transplantation and has remained so to the time of this writing 18 months later. Case Report A 19-year-old man presented . . .
P362 THE BILE ACID RECEPTOR TGR5 CONTROLS BILE ACID POOL HYDROPHOBICITY THROUGH REGULATION OF GALLBLADDER MOTOR FUNCTION
Authors: N. Péan, I. Doignon, R. Boisgard, I. Garcin, B. Julien, L. Humbert, K. Schoonjans, D. Rainteau, T. Tordjmann
Journal: Journal of Hepatology (2014)