tbuckley/cabot-search huggingface dataset:
Change of TS, DPD and OPRT levels in gastric carcinoma and normal gastric mucosa after S-1-based neoadjuvant chemotherapy
Authors: Yoichi Sakurai, Shingo Kamoshida, Shinpei Furuta, Risaburo Sunagawa, Kazuki Inaba, Yoshinori Ishida, Yoshihide Nagasako, Yoshihiro Hiramatsu, Jun Isogaki, Ichiro Uyama, Yoshiyuki Komori, Yutaka Tsutsumi
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3623 

Background : S-1, a most effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine derivative, used as adjuvant chemotherapy has recently been shown to improve clinical outcome in patients with stage II and III gastric carcinoma (N Engl J Med 2007; 357:1810-1820). Furthermore, S-1 associated with cisplatin has recently been shown to be more effective than S-1 alone and we have therefore adopted S-1 plus cisplatin as a primary regimen of neoadjuvant chemotherapy (NAC) for patients with advanced-stage gastric carcinoma. Thymidylate synthase (TS) and DPD are the 5-FU metabolism related enzymes that have been shown to be associated with anticancer responses and long-term clinical outcomes. Orotate phosphoribosyltransferase (OPRT) on the other hand is a primary enzyme involved in the first-step activation process of 5-fluorouracil and we have shown that OPRT levels in gastric carcinoma can predict sensitivity to 5-fluorouracil (Cancer Sci 2006; 97:492-498). We have hypothesized that response and resistance to S-1-based NAC is associated with the changes of these enzyme levels involved in 5-FU metabolism. Aims: The primary aim of the present study was to examine the changes of TS, DPD and OPRT levels in gastric carcinoma and normal gastric mucosa after S-1-based NAC. Materials and Methods: A total of 38 patients with advanced-stage gastric carcinoma who underwent surgical resection were subjected to the study. A total of 25 patients (NAC group) received NAC with the combination of S-1 (80 to 120 mg/m2 per day for 4 weeks) and cisplatin (35 to 60 mg/m2 on day 8) and 13 patients underwent surgery without NAC (NonNAC group). At least 2 cycles of this regimen were performed. TS, DPD and OPRT levels in gastric carcinoma and normal gastric mucosa were determined by enzyme-linked immunosorbent assays that specifically established. Results: While the TS levels in gastric carcinoma were significantly higher than those in normal gastric mucosa (46 ± 74 vs. 10 ± 9 ng/mg protein), there was no difference of DPD and OPRT between carcinoma and normal gastric mucosa. The TS levels of carcinoma in NAC group were significantly higher than those in NonNAC group (61 ± 88 vs. 18 ± 8 ng/mg protein). There was no difference of DPD levels in carcinoma between NAC group and NonNAC group (159 ± 68 vs. 175 ± 63 ng/mg protein). There was no difference of OPRT levels in carcinoma between NAC group and NonNAC group (5.1 ± 3.3 vs. 6.0 ± 3.8 ng/mg protein). Conclusion: The results that enhanced TS levels in gastric carcinoma tissue after S-1-based neoadjuvant chemotherapy may provide some insight into resistance appears after further anticancer chemotherapy with fluoropyrimidine derivatives.
Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells
Authors: Zongyong Ai, Zheng Xiang, Yuemin Li, Guoku Liu, Hong Wang, Yun Zheng, Xiaoyan Qiu, Shumei Zhao, Xiaoqing Zhu, Yanhua Li, Weizhi Ji, Tianqing Li
Journal: Biomaterials (2015)
Allele-Specific Loss Of The Mir-15a/16-1 Cluster Correlates With ZAP70 Expression In CLL Patients With 13q Deletion
Authors: Angelo Veronese, Felice Pepe, Jessica Chiacchia, Sara Pagotto, Serena Veschi, Mirco Di marco, Andrea D'Argenio, Marco Russo, Barbara Vannata, Idana Innocenti, Giuseppe Leone, Francesco Autore, Dorothee Wernicke-Jameson, Fabio Verginelli, Laura Rassenti, Thomas J. Kipps, Renato Mariani-Costantini, Luca Laurenti, Carlo M. Croce, Rosa Visone
Journal: Blood (2013)
Pathogenesis of Virus-Induced Myeloid Leukemia in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Richard Siegler, Marvin A. Rich
Journal: JNCI Journal of the National Cancer Institute (1967)

Myeloid leukemia was induced in thymectomized mice with murine leukemia virus (Rich) and the pathogenesis of the ensuing neoplasia studied. Two types of lesions resulted: a noninflammatory accumulation of mature neutrophils in the medullary cords of peripheral nodes and a massive proliferation of myeloblasts in the red pulp of the spleen. Once these myeloblasfs entered the splenic sinuses, they flooded through the liver and eventually appeared in the peripheral blood, constituting the “leukemic” phase of the disease. The bone marrows of animals with spleens that showed evolving neoplasia were always free of tumor. Tumor was never found in the bone marrow unless it was also present in the spleen, whereas it was often far-advanced in the spleen of animals with normal bone marrows. These observations suggested that the spleen, rather than the bone marrow, is the site of tumor origin.
31-year-old female runner with 5-week history of hip pain
Authors: J O'Brien, J Taunton, J Larsen, B B Forster
Journal: British Journal of Sports Medicine (2010)

A 31-year-old woman presented to her primary physician with right groin pain of 5 weeks duration. There was no definite precipitating injury; however, before developing the pain, she ran recreationally, approximately 10 km, three times per week.

Initially she experienced discomfort after exercise; however, after 2 weeks she began to develop pain after 6 or 7 km, which was relieved by rest.

The pain gradually became more severe, often occurring when she began to exercise and sometimes the symptoms recurred at night. Throughout this time, the pain was localised to the right groin, without radiation to her back or down her leg.

She had no significant past medical or surgical history and was not taking any medications. She admitted that she was careful about her diet to maintain her weight and had a regular menstrual cycle.

Her physical examination was unremarkable, with full range of movement only limited by patient discomfort.

A radiograph of her hip was performed (figure 1).



Figure 1 
What is the diagnosis?



She was referred for physiotherapy; however, the pain persisted and she returned to her primary physician 2 months after her initial presentation.

On this occasion, there was some weakness and discomfort on right hip adduction, otherwise her examination was unremarkable.

She was referred for a magnetic resonance imaging (MRI) examination of her pelvis (figure 2).



Figure 2 
What is the diagnosis?



Following these investigations, the patient continued to exercise as before, limited by discomfort despite the advice of her physician. Six weeks later she re-presented to the physician with an exacerbation of the right groin pain.

On this occasion, she demonstrated an anthalgic gait and significantly limited hip flexion as well as abduction and adduction of the right hip.

### Diagnosis

Femoral neck stress fracture (FNSF), with subsequent progression to a complete fracture of the right femoral neck. …
Remote Ischemic Conditioning Reduces Myocardial Infarct Size in STEMI Patients Treated by Thrombolysis
Authors: Derek M. Yellon, Akbar K. Ackbarkhan, Vinod Balgobin, Heerajnarain Bulluck, Anil Deelchand, Mohammad R. Dhuny, Nizam Domah, Dhunujnaye Gaoneadry, Rabindranath K. Jagessur, Noorjehan Joonas, Sudhir Kowlessur, Jairajsing Lutchoo, Jennifer M. Nicholas, Keyvoobalan Pauvaday, Oomesh Shamloll, John M. Walker, Derek J. Hausenloy
Journal: Journal of the American College of Cardiology (2015)
Inhibition of Proto-Oncogene c-Src Tyrosine Kinase
Authors: Luisa Mestroni, Duy Thai Nguyen
Journal: Journal of the American College of Cardiology (2014)

Cellular-Src (c-Src) encodes a plasma membrane–associated tyrosine protein kinase, which plays a vital role in signaling pathways related to cellular development and carcinogenesis [(1,2)][1]. It was the first proto-oncogene to be described and is the cellular homologue in humans of the viral
Towards real-time visualization of a juggler’s brain
Authors: Giuseppina Schiavone, Ulf Großekathöfer, Simon à Campo, Vojkan Mihajlović
Journal: Brain-Computer Interfaces (2015)

Surpassing the initial 'wow' effect of a complex juggling trick and producing long-lasting engaging performances are the main goals of any juggling act. Conveying to the audience the skill and the effort required for a performance is often difficult. In this paper, we use a wearable EEG headset to investigate how juggling skills can be inferred from a juggler's brain. We observed characteristic brain activity and synchronization while juggling in both an expert and an intermediate juggler. We also found that processing of visuomotor skills and memory retention can be distinguished during motor imagery and simulated juggling conditions. For the first time, we were able to monitor a juggler's brain in action. We have shown that using EEG while juggling could both improve our understanding of neuronal mechanisms governing visuomotor control and, importantly, represent a potential to enrich artistic performance and increase audience engagement.
Trends of survival in patients with multiple myeloma in Japan: a multicenter retrospective collaborative study of the Japanese Society of Myeloma
Authors: S Ozaki, H Handa, T Saitoh, H Murakami, M Itagaki, H Asaoku, K Suzuki, A Isoda, M Matsumoto, M Sawamura, J Konishi, K Sunami, N Takezako, S Hagiwara, Y Kuroda, T Chou, E Nagura, K Shimizu
Journal: Blood Cancer Journal (2015)

Trends of survival in patients with multiple myeloma in Japan: a multicenter retrospective collaborative study of the Japanese Society of Myeloma
The Pursuit of Clinically Relevant Measures of Platelet Function After Antiplatelet Drug Therapy⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: John A. Cairns, John Eikelboom
Journal: Journal of the American College of Cardiology (2008)
Loss of PTEN Promotes Resistance to T Cell–Mediated Immunotherapy
Authors: Weiyi Peng, Jie Qing Chen, Chengwen Liu, Shruti Malu, Caitlin Creasy, Michael T. Tetzlaff, Chunyu Xu, Jodi A. McKenzie, Chunlei Zhang, Xiaoxuan Liang, Leila J. Williams, Wanleng Deng, Guo Chen, Rina Mbofung, Alexander J. Lazar, Carlos A. Torres-Cabala, Zachary A. Cooper, Pei-Ling Chen, Trang N. Tieu, Stefani Spranger, Xiaoxing Yu, Chantale Bernatchez, Marie-Andree Forget, Cara Haymaker, Rodabe Amaria, Jennifer L. McQuade, Isabella C. Glitza, Tina Cascone, Haiyan S. Li, Lawrence N. Kwong, Timothy P. Heffernan, Jianhua Hu, Roland L. Bassett, Marcus W. Bosenberg, Scott E. Woodman, Willem W. Overwijk, Gregory Lizée, Jason Roszik, Thomas F. Gajewski, Jennifer A. Wargo, Jeffrey E. Gershenwald, Laszlo Radvanyi, Michael A. Davies, Patrick Hwu
Journal: Cancer Discovery (2015)

T cell-mediated immunotherapies are promising cancer treatments. However, most patients still fail to respond to these therapies. The molecular determinants of immune resistance are poorly understood. We show that loss of PTEN in tumor cells in preclinical models of melanoma inhibits T cell-mediated tumor killing and decreases T-cell trafficking into tumors. In patients, PTEN loss correlates with decreased T-cell infiltration at tumor sites, reduced likelihood of successful T-cell expansion from resected tumors, and inferior outcomes with PD-1 inhibitor therapy. PTEN loss in tumor cells increased the expression of immunosuppressive cytokines, resulting in decreased T-cell infiltration in tumors, and inhibited autophagy, which decreased T cell-mediated cell death. Treatment with a selective PI3Kβ inhibitor improved the efficacy of both anti-PD-1 and anti-CTLA-4 antibodies in murine models. Together, these findings demonstrate that PTEN loss promotes immune resistance and support the rationale to explore combinations of immunotherapies and PI3K-AKT pathway inhibitors.This study adds to the growing evidence that oncogenic pathways in tumors can promote resistance to the antitumor immune response. As PTEN loss and PI3K-AKT pathway activation occur in multiple tumor types, the results support the rationale to further evaluate combinatorial strategies targeting the PI3K-AKT pathway to increase the efficacy of immunotherapy.
Finding the Right Price for Improving Care
Authors: Blake Charlton
Journal: JAMA Internal Medicine (2015)

The US Food and Drug Administration (FDA) recently approved alirocumab and evolocumab, 2 monoclonal antibody PCSK9 inhibitors that reduce low-density lipoprotein cholesterol.In this edition of JAMA Internal Medicine, Tice et al 1 of the Institute for Clinical and Economic Review (ICER) provide a systematic review of the efficacy, safety, and costs of these therapies.These drugs seem to be effective and safe; however, most included trials lasted fewer than 6 months, and none used cardiovascular events as a primary outcome.A metaanalysis of these trials estimates a 50% relative risk reduction of cardiovascular mortality; however, because of the metaanalysis's limitations, the actual effect on mortality will not be characterized until ongoing trials conclude in 2017.What is novel about this review is the inclusion of cost, the third rail of American medicine.Tice et al 1 estimate that treat-
New Insights on Endothelial Progenitor Cell Subpopulations and Their Angiogenic Properties⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Eduard Shantsila, Timothy Watson, Hung-Fat Tse, Gregory Y.H. Lip
Journal: Journal of the American College of Cardiology (2008)
Abstract 9439: Incidence of New Coronary Calcification: What is the Warranty Period of CAC = 0 in the Multi-Ethnic Study of Atherosclerosis?
Authors: Dhaval Desai, Khurram Nasir, Zeina Dardari, Joel Kaufman, Ron Blankstein, J. Jeffrey Carr, Arthur Agatston, Joao Lima, Moyses Szklo, Roger Blumenthal, Matthew Budoff, Michael Blaha
Journal: Circulation (2014)

Background: While CAC=0 is associated with excellent prognosis, progression to CAC&gt;0 has been shown to confer increased risk. The time interval at which a repeat CAC scan would be reasonable - the “warranty period” of CAC=0 - is currently poorly defined. Methods: We studied 3116 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline CAC=0 and at least 1 follow-up CAC scan per MESA protocol (up to 10 years after baseline). Cumulative incidence of incident CAC was calculated yearly. Cumulative survival fee of CAC was calculated using Kaplan-Meier statistics and additionally modeled using a parametric survival model with Weibull distribution. The warranty period of CAC=0 was defined distribution as the time needed for 15%, 20%, or 25% (number needed to scan [NNS] 6, 5, or 4) to progress to detectable CAC. Results: The mean age of the subjects was 58 ± 9 years with 63% women and mean FRS of 8 ± 6%. Cumulative prevalence of CAC&gt;0 increased with time, from 11% at 2 years to nearly 50% at 10 years. The cumulative incidence rate of CAC&gt;0 was non-linear, increasing from approximately 2.5 per 100 person-years at 2 years to 5-6 per 100 person-years from years 4 to 10. The table shows the estimated warranty period of CAC=0 by gender and baseline FRS CHD risk. Among men, using an acceptable detection rate of 25% (NNS=4 to detect CAC&gt;0), the estimated warranty period of a low, intermediate, and high risk man was 6, 5, and 3 years. For women, the equivalent warranty period was 7, 5, and 4 years. In general, rescanning at 5 years will enable selection of 50% of the individuals with baseline CAC=0 who will go on to have CHD events following their repeat scan over 10-year follow-up. Conclusions: Although limited by lack of yearly CAC scanning, modeling in MESA allows estimation of the warranty period of CAC=0. A general rule would be to rescan low risk CAC=0 patients at 6-7 years and intermediate risk at 4-5 years, although exact warranty periods vary by gender and desired yield of repeat testing.
Accelerating stem cell trials for Alzheimer's disease
Authors: Joshua G Hunsberger, Mahendra Rao, Joanne Kurtzberg, Jeff W M Bulte, Anthony Atala, Frank M LaFerla, Henry T Greely, Akira Sawa, Sam Gandy, Lon S Schneider, P Murali Doraiswamy
Journal: The Lancet Neurology (2015)
Gastroesophageal Reflux Disease
Authors: Glen D. Solomon
Journal: Annals of Internal Medicine (2015)

Letters15 December 2015Gastroesophageal Reflux DiseaseGlen D. Solomon, MDGlen D. Solomon, MDFrom Wright State University, Dayton, Ohio.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5180 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Harnik's table of medical therapy for gastroesophageal reflux disease lists the surface barrier sodium alginate (with antacid) as a treatment option (1). This combination was sold for many years as Gaviscon (GlaxoSmithKline). In the United States, the over-the-counter product Gaviscon has been reformulated and no longer contains sodium alginate. In Europe, Gaviscon Double Action Liquid (Reckitt Benckiser) continues to contain sodium alginate plus an antacid. No over-the-counter products in the United States contain sodium alginate.Reference1. Harnik IG. In the Clinic. Gastroesophageal reflux disease. Ann Intern Med. 2015;163:ITC1-16. [PMID: 26148292]. doi:10.7326/AITC201507070 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Wright State University, Dayton, Ohio.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0470. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGastroesophageal Reflux Disease Ian G. Harnik Metrics 15 December 2015Volume 163, Issue 12Page: 959KeywordsConflicts of interestDisclosureGastroesophageal reflux diseaseSodium ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives
Authors: S Lonial, B Durie, A Palumbo, J San-Miguel
Journal: Leukemia (2015)

The treatment landscape for patients with multiple myeloma (MM) is constantly evolving. Over the past decade, the introduction of novel agents such as proteasome inhibitors and immunomodulatory drugs has led to notable changes in therapeutic strategy, and improvements in survival, yet MM remains incurable in the vast majority of cases. More recently, a targeted approach to MM treatment has emerged, using monoclonal antibodies (mAbs) to target antigens expressed on the surface of MM cells. MAbs tested to date kill MM cells via the host's immune system and/or by promoting apoptosis, and appear to have generally improved tolerability compared with currently available treatments. Due to their distinct mode of action, mAbs are promising both for patients who have exhausted current regimens, and as part of first-line treatments in newly diagnosed patients. This review examines the recent developments in mAb-based therapy for MM, primarily focused on those agents in ongoing clinical testing.
Heparanase expression and angiogenesis in endometrial cancer: Analyses of RT-PCR and immunohistochemistry
Authors: Y. Aoki, M. Inamine, M. Hirakawa, W. Kudaka, Y. Nagai
Journal: Journal of Clinical Oncology (2009)

5535 Background: The human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors.Methods: Fifty-two endometrial cancers were obtained from previously untreated patients (median age, 56 years; range, 35–80 years). The expression of heparanase mRNA was evaluated using a semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining (IHC) with anti-heparanase polyclonal antibody. This antibody was raised by immunizing a rabbit with a peptide containing the amino acid residues from 238 to 250 of the Heparanase. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one factor ANOVA test, and Spearman's test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. Results: The expression of heparanase mRNA was detected in 26 of 52 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p = 0.0075), the presence of lymph-vascular space involvement (LVSI) (p = 0.0041), lymph node metastasis (LNM) (p = 0.0049), and histological tumor grade (p = 0.003). IHC showed that the heparanase was expressed in 23 of 52 (44.2%) endometrial cancers, which was significantly related to LVSI (p = 0.0028), depth of myometrial invasion (p = 0.0026), and histological tumor grade (p = 0.0135). Microvessel density was also associated with FIGO stage IIIc (p = 0.027), LVSI (p = 0.001), LNM (p = 0.038), ovarian metastasis (p = 0.03) and histological tumor grade (p = 0.003). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r 2 = 0.475, p = 0.0001). Conclusions: These results suggest that the expression of heparanase can promote tumor angiogenesis and develop metastasis in endometrial cancer. No significant financial relationships to disclose.
Adjusting for Risk Associated With Pediatric and Congenital Cardiac Catheterization
Authors: Natalie Jayaram, Robert H. Beekman, Lee Benson, Ralf Holzer, Kathy Jenkins, Kevin F. Kennedy, Gerard R. Martin, John W. Moore, Richard Ringel, Jonathan Rome, John A. Spertus, Robert Vincent, Lisa Bergersen
Journal: Circulation (2015)

As US health care increasingly focuses on outcomes as a means for quantifying quality, there is a growing demand for risk models that can account for the variability of patients treated at different hospitals so that equitable comparisons between institutions can be made. We sought to apply aspects of prior risk-standardization methodology to begin development of a risk-standardization tool for the National Cardiovascular Data Registry (NCDR) IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry.Using IMPACT, we identified all patients undergoing diagnostic or interventional cardiac catheterization between January 2011 and March 2013. Multivariable hierarchical logistic regression was used to identify patient and procedural characteristics predictive of experiencing a major adverse event after cardiac catheterization. A total of 19,608 cardiac catheterizations were performed between January 2011 and March 2013. Among all cases, a major adverse event occurred in 378 of all cases (1.9%). After multivariable adjustment, 8 variables were identified as critical for risk standardization: patient age, renal insufficiency, single-ventricle physiology, procedure-type risk group, low systemic saturation, low mixed venous saturation, elevated systemic ventricular end-diastolic pressure, and elevated main pulmonary artery pressures. The model had good discrimination (C statistic, 0.70), confirmed by bootstrap validation (validation C statistic, 0.69).Using prior risk-standardization efforts as a foundation, we developed and internally validated a model to predict the occurrence of a major adverse event after cardiac catheterization for congenital heart disease. Future efforts should be directed toward further refinement of the model variables within this large, multicenter data set.