tbuckley/cabot-search huggingface dataset:
Validating innovation: A population-based study of gastrointestinal stromal tumors (GIST) to estimate the survival benefit of imatinib.
Authors: D. Goldstein, C. Lee, E. Tracey, C. Cook-Yarborough, S. Lord
Journal: Journal of Clinical Oncology (2011)

10060 Background: Imatinib [IM] trials reported survival gains for advanced GIST patients compared to historical cohorts. They were not placebo-controlled, limiting evidence about the size of benefit. This information is important to inform patients and to justify funding. Methods: A population-based study before and after IM introduction in 2000. Baseline characteristics of adult cases of GIST (International Classification of Diseases (ICD-O) codes 89361 and 89363) were extracted from the New South Wales Central Cancer Registry (CCR) database for the period 1992-2005. Pathology reports and death registrations were also retrieved. We estimated survival using the Kaplan–Meier method, and we test for the survival difference before and after 2000. Proportional-hazard models were constructed to estimate the survival difference adjusted for known prognostic factors. Results: 511 cases of GIST (28% pre-IM, 72% post-IM) were registered at CCR. Those post-IM were more likely to have spindle histology (p<0.0001) and higher mitotic rate (p=0.02). There was no statistically significant difference in age, gender, primary tumor location and tumor size. Patients diagnosed post-IM had a significantly longer survival (5-year probability of survival 71% vs 52%; hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.41-0.73). Other univariate predictors were younger age, smaller tumor size, lower mitotic rate, spindle histology and localised disease. Diagnosis in the IM era remained the strongest predictor after adjusting for these predictors (HR 0.36; 95%CI 0.24-0.53). Findings were similar for both the subset of patients with ICD-0 89363 (n=211, HR 0.36; 95%CI 0.23-0.56); and those classified in the highest quartile of risk (n=49,HR 0.20; 95%CI 0.08-0.50). Conclusions: This population-based study demonstrates a substantial [64%] improvement in survival after 2000. This finding quantifies the effectiveness of introducing IM, in addition to reflecting any other potential improvements in care. Examining temporal trends in survival can provide valuable evidence to help validate findings about molecular-targeted therapies when randomised controlled trials are not feasible.
Potential Therapeutic Applications of Adenosine A<sub>2A</sub> Receptor Ligands and Opportunities for A<sub>2A</sub> Receptor Imaging
Authors: Aren van Waarde, Rudi A. J. O. Dierckx, Xiaoyun Zhou, Shivashankar Khanapur, Hideo Tsukada, Kiichi Ishiwata, Gert Luurtsema, Erik F. J. de Vries, Philip H. Elsinga
Journal: Medicinal Research Reviews (2017)

Abstract Adenosine A 2A receptors (A 2A Rs) are highly expressed in the human striatum, and at lower densities in the cerebral cortex, the hippocampus, and cells of the immune system. Antagonists of these receptors are potentially useful for the treatment of motor fluctuations, epilepsy, postischemic brain damage, or cognitive impairment, and for the control of an immune checkpoint during immunotherapy of cancer. A 2A R agonists may suppress transplant rejection and graft‐versus‐host disease; be used to treat inflammatory disorders such as asthma, inflammatory bowel disease, and rheumatoid arthritis; be locally applied to promote wound healing and be employed in a strategy for transient opening of the blood–brain barrier (BBB) so that therapeutic drugs and monoclonal antibodies can enter the brain. Increasing A 2A R signaling in adipose tissue is also a potential strategy to combat obesity. Several radioligands for positron emission tomography (PET) imaging of A 2A Rs have been developed in recent years. This review article presents a critical overview of the potential therapeutic applications of A 2A R ligands, the use of A 2A R imaging in drug development, and opportunities and limitations of PET imaging in future research.
Annals Graphic Medicine - The Physiology of Panic, or, All Systems Go
Authors: William J. Doan
Journal: Annals of Internal Medicine (2016)

Web Exclusives6 December 2016Annals Graphic Medicine - The Physiology of Panic, or, All Systems GoFREEWilliam J. Doan, BA, MFA, PhDWilliam J. Doan, BA, MFA, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G16-0009 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G16-0009.Author/Artist Information: William J. Doan, BA, MFA, PhD, is a Professor of Theatre at The Pennsylvania State University and a past president of the Association for Theatre in Higher Education, and his whose works include published books and plays. His work may be seen at http://driftingplay.weebly.com/. (E-mail, [email protected]edu.)Author Contributions: Conception and design: W. Doan.Final approval of the article: W. Doan. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Art and Science of Nursing 6 December 2016Volume 165, Issue 11Page: W14-W16KeywordsConflicts of interestDisclosureHealth care ePublished: 6 December 2016 Issue Published: 6 December 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CD154 Blockade Prevents Allosensitization through Inhibiting Both T- and B-Cell Activation and Decreasing Expression of IFN-γ and IL-10 in T-Cells.
Authors: Hong Xu, Jun Yan, Yiming Huang, Paula M. Chilton, Michael K. Tanner, Lala-Rukh Hussain, Suzanne T. Ildstad
Journal: Blood (2007)
A Novel Notch Pathway Inhibitor Blocks Osteoclast Activity and Synergistically Induces Apoptosis with the Proteasome Inhibitor Bortezomib in Multiple Myeloma Cells.
Authors: Franziska Jundt, Rolf Schwarzer, Martin Kaiser, Oezlem Acikgoez, Ulrike Heider, Stephan Mathas, Robert Preissner, Orhan Sezer, Bernd Dorken
Journal: Blood (2007)
Change in patient-reported outomes over time from breast cancer diagnosis.
Authors: C. E. Hill-Kayser, C. Vachani, M. K. Hampshire, G. A. Di Lullo, J. M. Metz
Journal: Journal of Clinical Oncology (2011)

210 Background: Breast cancer survivors may be at risk for significant late effects after treatment. Understanding the patterns of change over time of patient reported outcomes (PRO) is often very challenging. Methods: Patient-reported data was gathered via a convenience sample frame from breast cancer survivors utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLink website, the tool allows survivors to enter data regarding diagnosis, demographics, treatments received, and late effects experienced, and provides them with customized guidelines for future care. All data has been maintained anonymously with IRB approval. Results: 1,145 breast cancer survivors were queried with regard to PRO. Median age at diagnosis (dx) was 49 yrs, and median current age 52 yrs. Of users, 98% reported having had surgery; of these 56% underwent mastectomy and 49% lumpectomy (5% both). Similarly, 59% underwent sentinel LN biopsy, and 47% axilary dissection. Of the same cohort, 88% received chemotherapy and/or hormonal treatment, and 70% radiation therapy. The median time from dx until use of the care plan tool was 2 years (range 0-33 years). Late effects reported by survivors ≤ 2 and &gt; 2 years from diagnosis are shown (see table). Overall, survivors ≤ 2 years from dx were more likely to note changes in skin color or texture; those &gt; 2 years from diagnosis were more likely to note osteopenia, lymphedema, and sexual changes. Patient reported cognitive changes, arm pain/numbness/tingling, and loss of shoulder flexibility did not differ between the two groups. Conclusions: This anonymous tool uses a convenience sample frame to gather PRO after breast cancer diagnosis/ treatment. PRO varied significantly with time since dx, with more late effects reported &gt; 2 years from dx. This information may be of use during patient counseling and survivorship care delivery. [Table: see text]
Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2α Signaling as a Generalizable Mechanism for Dystonia
Authors: Joseph E. Rittiner, Zachary F. Caffall, Ricardo Hernández-Martinez, Sydney M. Sanderson, James L. Pearson, Kaylin K. Tsukayama, Anna Y. Liu, Changrui Xiao, Samantha Tracy, Miranda K. Shipman, Patrick Hickey, Julia Johnson, Burton Scott, Mark Stacy, Rachel Saunders-Pullman, Susan Bressman, Kristina Simonyan, Nutan Sharma, Laurie J. Ozelius, Elizabeth T. Cirulli, Nicole Calakos
Journal: Neuron (2016)
Effect of the Adminstration of Rituximab between Mobilization Chemotherapy and Leukapheresis on Stem Cell Collection Parameters: A Study of Fifty NHL Patients Mobilized Using Intermediate Dose Cyclophosphamide and Sequential GM-CSF and G-CSF.
Authors: Asad Bashey, Lin Liu, Anita Ihasz, Ewa Carrier, Januario Castro, Peter Holman, Mackintosh Ellen, Ball Edward, Lane Thomas
Journal: Blood (2004)
Genome-Wide Aberrant Splicing in Patients with Acute Myelold Leukemia (AML) Is Associated with Altered Expression of Splicing Factors
Authors: Sophia Adamia, Hervé Avet-Loiseau, Jana Jakubikova, Suzan Lazo-Kallanian, John Daley, Laurence Lode, Ilene Galinsky, Richard M. Stone, James D. Griffin
Journal: Blood (2012)
Association of a common genetic variant of the <i>IGF1</i> gene with clinical outcome in patients with HER2-positive breast cancer.
Authors: A. Lang, A. Muendlein, B. L. Hartmann, H. Drexel, T. Decker, H. Fricke, W. Hofmann, E. Mueller-Holzner, C. Marth, M. Hubalek
Journal: Journal of Clinical Oncology (2011)

193 Background: Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Circulating IGF1 levels may be linked with an increased risk of colorectal and breast cancer. Further, IGF1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, recently have been associated with a poor clinical outcome in patients with colorectal cancer. However, the influence of IGF1 SNPs on the prognosis of patients with breast cancer is unknown. Therefore, we aimed at investigating the influence of IGF1 tagging polymorphisms associated with IGF1 levels on event-free survival in patients with HER2-positive breast cancer. Methods: The present study included 161 consecutive white patients with HER2-positive breast cancer treated between 2000 and 2010 at the Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria. Event-free survival was calculated as the time from cancer diagnosis to either relapse or death from any cause. Genomic DNA was extracted from archived formalin-fixed paraffin embedded tumor tissue samples; five IGF1 tagging polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678) were genotyped by SNaPshot assays. Results: Mean follow up period was 4.3 (± 2.5) years. Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.029). Concordantly, in univariate Cox regression analyses the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 2.87 [1.07 –7.70]; p = 0.036). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 2.86 [1.06 –7.71]; p = 0.038). Thus, our results are in concordance with a recent report that the same SNP is associated with poorer clinical outcome in colorectal cancer patients. Other investigated genetic variants of the IGF1 gene were not significantly associated with event-free survival (all p-values &gt; 0.05). Conclusions: For the first time, our study investigates the influence of IGF1 tagging polymorphisms on the clinical outcome of HER2-positive breast cancer patients suggesting SNP rs2946834 as a predictor for reduced event-free survival.
The influence of iPS-inducing factors NANOG and KLF4 in the prognosis of patients with breast cancer.
Authors: T. Nagata
Journal: Journal of Clinical Oncology (2011)

230 Background: iPS cell-inducing factors (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) are reported that they appears not only in ES cells (embryonic stem cell), but also in normal cell or carcinoma cell, including breast carcinoma. We evaluated the expression of iPS inducing factors in the human breast cancer specimen with immunohistochemistry, and analyze the relativity of the relapse and the prognosis after the operation. Methods: 66 cases of breast cancer that were performed the surgical operation in this department were examined. Expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 were determined by immunohistochemistry of tissue microarray. Results: The average of the patient’s age was 56.4 years old (36-87), and the advanced breast cancers in stage 2 or more were 44 cases (66%). About the hormone receptor and the HER2 appearance, hormone receptor-positive (HR+) types were 53 cases (80%), 6 cases (9%) were HER2-positive (HER2+) type, and 7 cases (11%) were triple-negative (TN) type. During the following period from operation, the relapse was found in 16 cases (24%), and six cases (9%) died. The average of survival time after the operation was 80.7 months (4-162). Patients with high expression group of NANOG had poor disease-free survival (p = 0.045) and overall survival (p &lt; 0.0001) than those with low expression group. On the other hand, patients with high expression group of KLF4 had better disease-free survival (p = 0.028) than low expression group. Conclusions: High expression of NANOG was prognostic factor, but KLF4 was inversely related to prognosis in breast cancer patients. It was suggested that NANOG increased the growth and metastatic activities of breast cancer cells, while KLF4 decreased these activities.
Donor Cell-Derived Hematologic Malignancy: A Survey of Complication Working Group of the Japan Society for Hematopoietic Cell Transplantation
Authors: Motohiro Kato, Takuya Yamashita, Ritsuro Suzuki, Kimikazu Matsumoto, Hisakazu Nishimori, Satoshi Takahashi, Koji Iwato, Chiaki Nakaseko, Tadakazu Kondo, Kazunori Imada, Fumihiko Kimura, Tatsuo Ichinohe, Yoshiko Hashii, Koji Kato, Yoshiko Atsuta, Shuichi Taniguchi, Takahiro Fukuda
Journal: Blood (2015)
Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis
Authors: James D. Chalmers, Kelly L. Moffitt, Guillermo Suarez-Cuartin, Oriol Sibila, Simon Finch, Elizabeth Furrie, Alison Dicker, Karolina Wrobel, J. Stuart Elborn, Brian Walker, S. Lorraine Martin, Sara E. Marshall, Jeffrey T.-J. Huang, Thomas C. Fardon
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis.Methods: This was a single-center prospective cohort study using the TAYBRIDGE (Tayside Bronchiectasis Registry Integrating Datasets, Genomics, and Enrolment into Clinical Trials) registry in Dundee, UK. A total of 433 patients with high-resolution computed tomography–confirmed bronchiectasis provided blood samples for desmosine measurement, and 381 provided sputum for baseline elastase activity measurements using an activity-based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3 years.Measurement and Main Results: Elastase activity in sputum was associated with the bronchiectasis severity index (r = 0.49; P < 0.0001) and was also correlated with the Medical Research Council dyspnea score (r = 0.34; P < 0.0001), FEV1% predicted (r = −0.33; P < 0.0001), and the radiological extent of bronchiectasis (r = 0.29; P < 0.0001). During a 3-year follow-up, elevated sputum elastase activity was associated with a higher frequency of exacerbations (P < 0.0001) but was not independently associated with mortality. Sputum elastase activity was independently associated with FEV1 decline (β coefficient, −0.139; P = 0.001). Elastase showed good discrimination for severe exacerbations with an area under the curve of 0.75 (95% confidence interval [CI], 0.72–0.79) and all-cause mortality (area under the curve, 0.70; 95% CI, 0.67–0.73). Sputum elastase activity increased at exacerbations (P = 0.001) and was responsive to treatment with antibiotics. Desmosine was correlated with sputum elastase (r = 0.42; P < 0.0001) and was associated with risk of severe exacerbations (hazard ratio 2.7; 95% CI, 1.42–5.29; P = 0.003) but not lung function decline.Conclusions: Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with bronchiectasis.
Human consciousness is fundamental for perception and highest emotions
Authors: Leonid Perlovsky
Journal: Behavioral and Brain Sciences (2016)

Have Morsella et al. examined the fundamentals of consciousness? An experiment by Bar et al. (2006) has demonstrated the fundamental aspects of conscious and unconscious mechanisms of perception. The mental representations are not crisp and conscious like the perceived objects are, but vague and unconscious. This experiment points to the fundamental function of the neural mechanisms of consciousness in perception. Consciousness is also fundamental for the highest emotions.
A vaccine approach for breast cancer immunotherapy by targeting HER2/neu antigen to B cells via CD19 molecule.
Authors: D. Xiang, Y. Ma, C. Ding, G. H. Kloecker, J. Yan
Journal: Journal of Clinical Oncology (2011)

287 Background: Trastuzumab has been proven to be effective in the immunotherapy for Her-2/neu-positive breast cancer. However, this adoptively transferred therapeutic Ab must be continuously given to the patient with huge financial cost. Thus, it would be desirable if tumor vaccines could elicit long-lasting trastuzumab-like Ab. Methods: Constructing fusion protein of anti-mouse CD19 single chain variable fragment (anti-CD19-scFv) with human Her-2/neu extracellular domain P3-4 (P3-4) by extracting total RNA from Rat anti-mouse CD19 hybridoma (1D3) and first strand cDNA was synthesized accordingly. VH and VL were amplified using designed primers. Single chain Fv (VL-VH) was then synthesized by overlapping PCR. Then constructs were sequenced and cloned into pET-20b(+) vectors. Fragments P3-4 of extracellular domains of human Her-2/neu was cloned from pcDNA3.1-Her2 and then cloned into pET-20b(+)-scFv. Series of constructs were expressed and purified according to standard protocol and verified by Western Blot. Results: Both in vitro and in vivo studies demonstrated that fusion proteins anti-CD19-scFv and anti-CD19-scFv-P3-4 but not P3-4 could specifically bind to B cells with high affinity. Mice immunized with anti-CD19-scFv-P3-4 secreted higher titers of IgG and IgM than those from controls (p&lt;0.05). Studies also demonstrated that sera from anti-CD19-scFv-P3-4 but not anti-CD19-scFv or P3-4 immunized mice stained with Her-2/neu expressing SKOV-3 tumor cells. These Abs also competitively inhibited trastuzumab-mediated Ag binding, suggesting that trastuzumab-like Ab responses were elicited. WT mice immunized with anti-CD19-scFv-P3-4 fusion protein then challenged with D2/F2-Her-2 mammary tumor cells showed significantly reduced tumor burden compared to those immunized with control fusion proteins (p&lt;0.05) and had enhanced median overall survival to 45 days versus 34 days in WT mice immunized with either anti-CD19-scFv or P3-4. Conclusions: Targeting of Her-2/neu antigens to B cells stimulates Th-dependent humoral immune responses with anti tumor effect in mouse model. These findings provide a novel avenue for successful development of breast cancer vaccination strategy and help to fight for cancer.
Health care cost in hormone-naive and hormonally pretreated patients with prostate cancer treated with degarelix.
Authors: Johannes Wolff, Alexander Tolle, Michael Gedamke
Journal: Journal of Clinical Oncology (2012)

240 Background: Degarelix, is a GnRH-antagonist, which is used in the treatment of prostate cancer since 2009. We performed a non-interventional study (NIS) with prostate cancer (PCA) patients treated routinely with degarelix. This NIS focused on pharmaco-economical data, quality of life as well as efficacy and safety in patients receiving degarelix as first or second line therapy. Methods: In the interims analysis of this ongoing NIS, data from 279 out of 670 PCA-patients treated with degarelix were included. The included cohort reflects advanced PCA patients (age: 72 years, PSA: 15.8 ng/ml (median values)).Testosterone and PSA values, quality of life and pharmaco-economical data were collected at baseline, 1, 3, 6, 9 and 12 months. Quality of life was assessed by EQ-5D. Pharmaco-economical data included direct costs for physicians, drugs, hospital, emergency treatment and others. Results: Treatment costs in hormon-naïve patients treated with degarelix were lower than in the hormonally pre-treated patients. Direct costs for six month were 498,- € for hormone naïve patients treated with degarelix in contrast to 1436,- € for hormonally pre-treated patients. As expected there was a marked difference in the PSA-decline between hormone-naïve patients and hormonally pre-treated patients. Hormone-naïve patients experienced a sharp median decrease in PSA by 80.7% (n=116) at month 1. This decline remained stable in 98.7% of the patients after one year. Median PSA reduction was significantly different (p=0.013) between hormone-naïve and pre-treated patients. Furthermore treatment of degarelix improved quality of life by 14% at one year compared to baseline. Testosterone was suppressed to a median of 0.2 ng/ml from month 1 to 12. Safety results mirrored the results of clinical trials. Conclusions: First-line treatment with degarelix was supported by a marked difference in health care costs between hormone naïve and pre-treated prostate cancer patients, who received degarelix. As expected a pronounced difference in the PSA-decrease in hormone naïve and pre-treated patients was seen. However a distinct quality of life improvement was noted in all patients.
Comparative Analysis of Tyrosine Kinase Inhibitors-Related Pulmonary Hypertension in the Patients Treated By Imatinib, Dasatinib and Nilotinib
Authors: Mariko Minami, Toshihiro Miyamoto, Takeshi Arita, Tomohiko Kamimura, Junichiro Yuda, Yoshikane Kikushige, Yasuo Mori, Goichi Yoshimoto, Kenjiro Kamezaki, Koji Kato, Motoaki Shiratsuchi, Katsuto Takenaka, Hiromi Iwasaki, Satoshi Yamasaki, Tsuyoshi Muta, Kazuki Tanimoto, Ryosuke Ogawa, Tetsuya Eto, Koichi Akashi
Journal: Blood (2015)
MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks
Authors: Giordano Lippi, Catarina C. Fernandes, Laura A. Ewell, Danielle John, Benedetto Romoli, Giulia Curia, Seth R. Taylor, E. Paxon Frady, Anne B. Jensen, Jerry C. Liu, Melanie M. Chaabane, Cherine Belal, Jason L. Nathanson, Michele Zoli, Jill K. Leutgeb, Giuseppe Biagini, Gene W. Yeo, Darwin K. Berg
Journal: Neuron (2016)