tbuckley/cabot-search huggingface dataset:
Regulation of protein phosphatase 2A (PP2A) B subunits by Bcr/Abl: Potential targets for chronic myeloid leukemia.
Authors: Kathryn Roberts, Leonie Ashman, Alistair Sim, Nicole Verrills
Journal: Cancer Research (2007)

4154  Over 90% of chronic myeloid leukemia (CML) cases are associated with constitutive activity of the BCR/ABL oncoprotein, which induces and maintains transformation of hematopoietic stem cells. Inhibition of BCR/ABL with Imatinib mesylate has shown remarkable success in treating CML patients; however resistance to imatinib is emerging as a major barrier to treatment success. To direct the development of improved therapies, signalling pathways activated by BCR/ABL must be identified. A recent study discovered that the activity of the tumour suppressor, protein phosphatase 2A (PP2A), is inhibited in BCR/ABL+ CML. Importantly, pharmacological or molecular re-activation of PP2A reduced BCR/ABL activation and expression, reduced the activity of BCR/ABL regulated signalling pathways, and inhibited the growth of both imatinib-sensitive and resistant BCR/ABL+ CML cells in vitro and in vivo (Neviani et al., 2005 Cancer Cell 8:355). Thus activation of PP2A is an extremely attractive target for the improved treatment of CML. PP2A, a major serine/threonine phosphatase, is a ubiquitous multimeric enzyme composed of a catalytic subunit (Cα and Cβ), a structural subunit (Aα and Aβ), and a variable regulatory subunit (B), of which there are 4 different families (B, B9, B99, B999) each with several isoforms. The association of a particular B subunit with the core AC dimer introduces substrate specificity and subcellular localization of PP2A activity. In this study we show that BCR/ABL expression in FDC-P1 myeloid precursor cells increases tyrosine phosphorylation of PP2A-C, and this correlates with reduced PP2A activity. Imatinib treatment of wildtype BCR/ABL cells, but not imatinib-resistant Y253F-BCR/ABL cells, reduced PP2A-C phosphorylation and restored PP2A activity. In addition, we have shown for the first time that BCR/ABL expression alters the expression and binding of PP2A regulatory subunits. The PP2A Bα, B’α, B’β and B’Δ subunits are increased in BCR/ABL+ cells, and imatinib treatment reduced the expression of these proteins. These results suggest that in myeloid precursor cells increased BCR/ABL activity inhibits PP2A activity, and that this may be regulated by specific B subunit binding. To determine the functional role of each of these B subunits, shRNA studies are being performed. This study confirms that PP2A is an essential component of BCR/ABL leukemogenesis, and suggests that specific inhibition of PP2A regulatory subunits may be a useful strategy for CML therapy.
Use of alternative medicine for cancer and its impact on survival.
Authors: Skyler Bryce Johnson, Cary Philip Gross, Henry S. Park, James B. Yu
Journal: Journal of Clinical Oncology (2017)

e18175 Background: There is limited available information on the patterns of utilization and efficacy of alternative medicine (AM) for patients with cancer. The primary objective was to compare survival between patients with cancer receiving AM and conventional cancer treatment. The secondary objective was to determine cancer patient characteristics associated with selection of AM. Methods: Patients diagnosed with non-metastatic breast, prostate, lung, or colorectal cancer were identified between 2004-2013 using the National Cancer Database (NCDB). Alternative medicine use was defined as ‘Other-Unproven: Cancer treatments administered by nonmedical personnel’ administered as sole anti-cancer treatment among patients who did not receive chemotherapy, radiotherapy, surgery, and/or hormone therapy. Treatment selection was evaluated by the chi-square test, t-test, and logistic regression. Patients were 2:1 matched on age, clinical group stage, Charlson-Deyo comorbidity score, insurance type, race, year of diagnosis, and cancer type. Overall survival was analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. Results: We identified 281 patients who chose AM in lieu of conventional cancer treatment. Approximately 44% of these patients had breast cancer, followed by prostate (25.5%), lung (18.4%) and colorectal cancer (12.1% of patients). Independent covariates associated with increased likelihood of AM use included breast or lung primary site (vs. prostate), higher socioeconomic status, Intermountain West or Pacific location (vs. Northeast), stages II or III (vs. I) and Charlson-Deyo comorbidity score of 0 (vs. 1). Alternative medicine was independently associated with greater risk of death compared to conventional cancer treatment overall (HR: 2.50, 95% confidence interval 1.88-3.27) and in subgroups of patients with breast, lung, and colorectal cancer. Conclusions: Alternative medicine utilization in patients with cancer is rare and varied by geographic, socioeconomic, and disease-related factors. Patients who chose alternative medicine for primary treatment of their curable cancer had greater risk of death compared to those who chose conventional cancer treatment.
Index indicates cholesterol management strategy for statin related muscle pain
Authors: Susan Mayor
Journal: BMJ (2017)

US researchers have developed an index to evaluate whether muscle symptoms may be due to statin treatment, as well as a strategy to reduce cardiovascular risk in patients affected, after reviewing available evidence.1

Some 10-20% of patients taking statins report muscle related symptoms including aches, pains, and cramps that prevent the use of recommended doses, putting them at increased risk of cardiovascular events.

“Muscle symptoms experienced by patients on statin therapy may or not be related …
Inhaled budesonide does not prevent acute mountain sickness after rapid ascent to 4559 m
Authors: Marc Moritz Berger, Franziska Macholz, Mahdi Sareban, Peter Schmidt, Sebastian Fried, Daniel Dankl, Josef Niebauer, Peter Bärtsch, Heimo Mairbäurl
Journal: European Respiratory Journal (2017)

Recent studies showed that inhaled budesonide (200 µg twice per day) reduced the incidence of acute mountain sickness (AMS) after passive ascent to 3700 and 3900 m [1, 2]. These findings raised the possibility that mediators released from the hypoxic lung transmit signals to the brain which contribute to the cerebral processes leading to AMS [3]. Because neither of these studies reflect alpine-style climbing, the present study was performed to test whether inhalation of budesonide at two different doses (200 and 800 µg twice per day) prior to active and rapid ascent (<20 h) to 4559 m prevents AMS in this high-risk setting. Prophylactic inhalation of budesonide does not prevent acute mountain sickness after rapid ascent to high-altitude <http://ow.ly/Bc9p30dOz46>
ラットにおける梗塞後の心臓リモデリングのための生物還元性デンドリマ重合体により送達されたヒトリラキシン遺伝子発現【Powered by NICT】
Authors: Lee Young Sook, Choi Joung-Woo, Oh Jung-Eun, Yun Chae-Ok, Kim Sung Wan
Journal: Biomaterials (2016)
Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents
Authors: Cosima Locher, Helen Koechlin, Sean R. Zion, Christoph Werner, Daniel S. Pine, Irving Kirsch, Ronald C. Kessler, Joe Kossowsky
Journal: JAMA Psychiatry (2017)

Depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents.To examine the relative efficacy and safety of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents.PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Database from inception through August 7, 2016.Published and unpublished randomized clinical trials of SSRIs or SNRIs in youths with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (eg, tricyclic antidepressants, monoamine oxidase inhibitors) were excluded.Effect sizes, calculated as standardized mean differences (Hedges g) and risk ratios (RRs) for adverse events, were assessed in a random-effects model.Primary outcomes, as defined by authors on preintervention and postintervention data, mean change data, and adverse event data, were extracted independently by multiple observers following PRISMA guidelines.Thirty-six trials were eligible, including 6778 participants (3484 [51.4%] female; mean [SD] age, 12.9 [5.1] years); 17 studies for DD, 10 for AD, 8 for OCD, and 1 for PTSD. Analysis showed that SSRIs and SNRIs were significantly more beneficial compared with placebo, yielding a small effect size (g = 0.32; 95% CI, 0.25-0.40; P < .001). Anxiety disorder (g = 0.56; 95% CI, 0.40-0.72; P < .001) showed significantly larger between-group effect sizes than DD (g = 0.20; 95% CI, 0.13-0.27; P < .001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g = 1.57; 95% CI, 1.36-1.78; P < .001) compared with those with AD (g = 1.03; 95% CI, 0.84-1.21; P < .001). The SSRIs produced a relatively large effect size for ADs (g = 0.71; 95% CI, 0.45-0.97; P < .001). Compared with participants receiving placebo, patients receiving an antidepressant reported significantly more treatment-emergent adverse events (RR, 1.07; 95% CI, 1.01-1.12; P = .01 or RR, 1.49; 95% CI, 1.22-1.82; P < .001, depending on the reporting method), severe adverse events (RR, 1.76; 95% CI, 1.34-2.32; P < .001), and study discontinuation due to adverse events (RR, 1.79; 95% CI, 1.38-2.32; P < .001).Compared with placebo, SSRIs and SNRIs are more beneficial than placebo in children and adolescents; however, the benefit is small and disorder specific, yielding a larger drug-placebo difference for AD than for other conditions. Response to placebo is large, especially in DD. Severe adverse events are significantly more common with SSRIs and SNRIs than placebo.
LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification
Authors: Cong Yu, Lifu Li, Fei Xie, Shichao Guo, Fayuan Liu, Nianguo Dong, Yongjun Wang
Journal: Cardiovascular Research (2017)

Abstract Aims Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a vital role in cardiovascular physiology and pathology. Although the lncRNA TUG1 is implicated in atherosclerosis, its function in calcific aortic valve disease (CAVD) remains unknown. Methods and results In this study, we found that TUG1 was highly expressed in human aortic valves and primary valve interstitial cells (VICs). Moreover, TUG1 knockdown induced inhibition of osteoblast differentiation in CAVD both in vitro and in vivo. Mechanistically, silencing of TUG1 increased the expression of miR-204-5p and subsequently inhibited Runx2 expression at the post-transcriptional level. Importantly, TUG1 directly interacted with miR-204-5p and downregulation of miR-204-5p efficiently reversed the suppression of Runx2 induced by TUG1 short hairpin RNA (shRNA). Thus, TUG1 positively regulated the expression of Runx2, through sponging miR-204-5p, and promoted osteogenic differentiation in CAVD. Conclusion All together, the evidence generated by our study elucidates the role of lncRNA TUG1 as a miRNA sponge in CAVD, and sheds new light on lncRNA-directed diagnostics and therapeutics in CAVD.
Secondary acute lymphoblastic leukemia is a distinct clinical entity with prognostic significance
Authors: A S Rosenberg, A Brunson, J K Paulus, J Tuscano, T Wun, T H M Keegan, B A Jonas
Journal: Blood Cancer Journal (2017)

Abstract The effect of prior malignancy on the risk of developing, and prognosis of, acute lymphoblastic leukemia (ALL) is unknown. This observational study utilized the California Cancer Registry to estimate the risk of developing ALL after a prior malignancy using standardized incidence ratios (SIRs, 95% confidence intervals). ALL occurring after a malignancy with an SIR&gt;1 (increased-risk (IR) malignancies) was considered secondary ALL (s-ALL). Adjusted hazard ratios (aHRs, 95% confidence intervals) compared the effect of s-ALL with de novo ALL on overall survival. A total of 14 481 patients with ALL were identified (1988–2012) and 382 (3%) had a known prior malignancy. Any prior malignancy predisposed patients to developing ALL: SIR 1.62 (1.45–1.79). Hematologic malignancies (SIR 5.57, 4.38–6.98) and IR-solid tumors (SIR 2.11, 1.73–2.54) increased the risk of developing ALL. s-ALL increased the risk of death compared with de novo ALL (aHR 1.38 (1.16–1.63)) and this effect was more pronounced among younger patients (age&lt;40 years: aHR 4.80 (3.15–7.30); age⩾40 years: aHR 1.40 (1.16–1.69)) (interaction P &lt;0.001). This population-based study demonstrates that s-ALL is a distinct entity that occurs after specific malignancies and carries a poor prognosis compared with de novo ALL, particularly among patients &lt;40 years of age.
Soft Tissue Response on 18F-Fluorocholine PET/CT in Metastatic Castrate-Resistant Prostate Cancer Treated With 223Ra-Dichloride
Authors: Sandi A. Kwee, John Lim, Marc N. Coel
Journal: Clinical Nuclear Medicine (2017)

Two patients with castrate-resistant prostate cancer and symptomatic skeletal metastases underwent F-fluorocholine PET/CT prior to treatment with Ra-dichloride to reveal additional active lesions in the prostate gland and lymph nodes. Subsequent scans performed at the midpoint and end of Ra-dichloride therapy showed resolution of this soft tissue activity alongside declining bone lesion activity. Concomitant increases in plasma interleukin 6 were detected, suggesting that immune system activation may have mediated the soft tissue response. Abscopal effects usually encountered with external beam radiotherapy may also be occurring with Ra-dichloride therapy.
rtPAによるフィブリン分解はヌードマウスにおけるナノ治療A549腫瘍への送達を増強する【Powered by NICT】
Authors: Zhang Bo, Jiang Ting, She Xiaojian, Shen Shun, Wang Sheng, Deng Jun, Shi Wei, Mei Heng, Hu Yu, Pang Zhiqing, Jiang Xinguo
Journal: Biomaterials (2016)
Survival in individuals with severe alpha 1-antitrypsin deficiency (PiZZ) in comparison to a general population with known smoking habits
Authors: Hanan A. Tanash, Magnus Ekström, Eva Rönmark, Anne Lindberg, Eeva Piitulainen
Journal: European Respiratory Journal (2017)

Knowledge about the natural history of severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is limited. Our aim was to compare the survival of PiZZ individuals with randomly selected controls from the Swedish general population. The PiZZ subjects (n=1585) were selected from the Swedish National AATD Register. The controls (n=5999) were randomly selected from the Swedish population register. Smoking habits were known for all subjects. Median follow-up times for the PiZZ subjects (731 never-smokers) and controls (3179 never-smokers) were 12 and 17 years, respectively (p&lt;0.001). During follow-up, 473 PiZZ subjects (30%), and 747 controls (12%) died. The PiZZ subjects had a significantly shorter survival time than the controls, p&lt;0.001. After adjustment for gender, age, smoking habits and presence of respiratory symptoms, the risk of death was still significantly higher for the PiZZ individuals than for the controls, hazard ratio (HR) 3.2 (95% CI 2.8–3.6; p&lt;0.001). By contrast, the risk of death was not increased in never-smoking PiZZ individuals identified by screening, compared to never-smoking controls, HR 1.2 (95% CI 0.6–2.2). The never-smoking PiZZ individuals identified by screening had a similar life expectancy to the never-smokers in the Swedish general population. Early diagnosis of AAT deficiency is of utmost importance.
ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease
Authors: John U. Doherty, Smadar Kort, Roxana Mehran, Paul Schoenhagen, Prem Soman
Journal: Journal of the American College of Cardiology (2017)
Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control
Authors: Cristina V. Cardemil, Rebecca M. Dahl, Lisa James, Kathleen Wannemuehler, Howard E. Gary, Minesh Shah, Mona Marin, Jacob Riley, Daniel R. Feikin, Manisha Patel, Patricia Quinlisk
Journal: New England Journal of Medicine (2017)

The effect of a third dose of the measles–mumps–rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity.
すい癌の改善されたSPECT/CTイメージングのためのカテプシンS開裂可能な,多ブロックH PMA共重合体【Powered by NICT】
Authors: Fan Wei, Shi Wen, Zhang Wenting, Jia Yinnong, Zhou Zhengyuan, K Brusnahan Susan, C Garrison Jered
Journal: Biomaterials (2016)
High-Sensitivity Troponin Levels, Ischemia, and Mortality—Reply
Authors: P. J. Devereaux, Bruce M. Biccard, Matthew T. V. Chan
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
ヒト間葉系幹細胞の軟骨形成に同調した時間分解性コラーゲン模倣ヒドロゲル【Powered by NICT】
Authors: A Parmar Paresh, C Skaalure Stacey, W Chow Lesley, St-Pierre Jean-Philippe, Stoichevska Violet, Y Peng Yong, A Werkmeister Jerome, A M Ramshaw John, M Stevens Molly
Journal: Biomaterials (2016)
Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition
Authors: Philip C. Calder, Nabil Bosco, Raphaëlle Bourdet-Sicard, Lucile Capuron, Nathalie Delzenne, Joel Doré, Claudio Franceschi, Markus J. Lehtinen, Tobias Recker, Stefano Salvioli, Francesco Visioli
Journal: Ageing Research Reviews (2017)

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted.
Enzymatic Activity of Normal Adult, Regenerating, Fetal, and Neoplastic Hepatic Tissues of the Rat
Authors: Jesse P. Greenstein, J. W. Thompson
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Enzymatic Activity of Normal Adult, Regenerating, Fetal, and Neoplastic Hepatic Tissues of the Rat Get access Jesse P. Greenstein, Jesse P. Greenstein senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Thompson J. W. Thompson pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 3, December 1943, Pages 271–274, https://doi.org/10.1093/jnci/4.3.271 Published: 01 December 1943
Resistance of brain tumor cells to gamma knife radiosurgery
Authors: Ryan Smith, Kris Smith, Christopher Biggs, Adrienne Scheck
Journal: Cancer Research (2008)

1461  Patients diagnosed with Glioblastoma Multiforme (GBM) are typically treated with surgery, radiation, and chemotherapy. Unfortunately, glioblastoma cells are some of the most radioresistant known, and these tumors typically recur. Hypofractionation with gamma knife radiosurgery is widely used as treatment for recurrent GBM. We wished to develop a biologic dosimeter to model the response of cells from primary and recurrent GBM to single fraction high dose radiation. Paired cell lines from primary and recurrent GBMs were treated with 12 or 24Gy in single fractions at 80% confluence in gas-permeable cassettes. The Gamma Knife planning system was used to map isodose lines on the cassettes, and cell cultures were morphologically assessed for response. Cell survival increased at greater distances from the maximum dose point, as expected. Overall cell survival at different isodose lines varied between cell lines from different patients. Primary cell lines were generally more radiosensitive as demonstrated by the overall area of cell death surrounding the center of the treatment area. In addition, these cell lines produced fewer surviving colonies in the central high dose region, while their recurrent pairs were generally more radioresistant and produced more viable colonies within comparable dose regions. This suggests that cells from recurrent tumors are generally more radioresistant and may have a larger subpopulation of cells capable of withstanding high doses of radiation. Surviving colonies were isolated, grown, and retreated with the same radiation dose (12 or 24 Gy). These cells showed an overall lower level of resistance after being retreated, and fewer surviving colonies in the central high dose area. This suggested the absence of a subpopulation of highly resistant cells. In summary, a viable biologic dosimeter for assessment of radioresponse has been successfully created for the Gamma Knife. Radioresistance was different among GBM cells from different patients. Cells from tumors that recurred following standard radiation and chemotherapy showed increased radioresistance at the time of recurrence when compared to cells from the same patient’s primary, untreated tumor. However the finding that hypofractionated single high dose radiation treatment appears to re-sensitize the cells to repeat radiation is surprising, and is currently being analyzed. These studies may suggest new strategies in the treatment and management of GBM in vivo with radiosurgery. Molecular and genetic characterization of these cells is underway to characterize this interesting response. This work was funded by the Barrow Neurological Foundation Women9s Board.