tbuckley/cabot-search huggingface dataset:
Optical barcoding of PLGA for multispectral analysis of nanoparticle fate in vivo
Authors: David X. Medina, Kyle T. Householder, Ricki Ceton, Tina Kovalik, John M. Heffernan, Rohini V. Shankar, Robert P. Bowser, Robert J. Wechsler-Reya, Rachael W. Sirianni
Journal: Journal of Controlled Release (2017)

Understanding of the mechanisms by which systemically administered nanoparticles achieve delivery across biological barriers remains incomplete, due in part to the challenge of tracking nanoparticle fate in the body. Here, we develop a new approach for "barcoding" nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) with bright, spectrally defined quantum dots (QDs) to enable direct, fluorescent detection of nanoparticle fate with subcellular resolution. We show that QD labeling does not affect major biophysical properties of nanoparticles or their interaction with cells and tissues. Live cell imaging enabled simultaneous visualization of the interaction of control and targeted nanoparticles with bEnd.3 cells in a flow chamber, providing direct evidence that surface modification of nanoparticles with the cell-penetrating peptide TAT increases their biophysical association with cell surfaces over very short time periods under convective current. We next developed this technique for quantitative biodistribution analysis in vivo. These studies demonstrate that nanoparticle surface modification with the cell penetrating peptide TAT facilitates brain-specific delivery that is restricted to brain vasculature. Although nanoparticle entry into the healthy brain parenchyma is minimal, with no evidence for movement of nanoparticles across the blood-brain barrier (BBB), we observed that nanoparticles are able to enter to the central nervous system (CNS) through regions of altered BBB permeability - for example, into circumventricular organs in the brain or leaky vasculature of late-stage intracranial tumors. In sum, these data demonstrate a new, multispectral approach for barcoding PLGA, which enables simultaneous, quantitative analysis of the fate of multiple nanoparticle formulations in vivo.
Diversity in non-repetitive human sequences not found in the reference genome
Authors: Birte Kehr, Anna Helgadottir, Pall Melsted, Hakon Jonsson, Hannes Helgason, Adalbjörg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Arnaldur Gylfason, Gisli H Halldorsson, Snaedis Kristmundsdottir, Gudmundur Thorgeirsson, Isleifur Olafsson, Hilma Holm, Unnur Thorsteinsdottir, Patrick Sulem, Agnar Helgason, Daniel F Gudbjartsson, Bjarni V Halldorsson, Kari Stefansson
Journal: Nature Genetics (2017)
Margaret McCartney: When organ donation isn’t a donation
Authors: Margaret McCartney
Journal: BMJ (2017)

“Soft opt-out boosts donation in Wales,” wrote the BMA.1 “‘Dozens saved’ in six months by Welsh deemed consent organ donation system,” said the Guardian .2 Should the rest of the UK follow what Wales started in December 2015: a system of opt-out organ donation?

The rest of the UK requires consent for organ donation, either by the dead person having pre-empted the decision by joining the donor register or by family consent. Wales uses a “soft” opt-out, meaning that it’s not intended to be legally enforced and that potential situations where doctors remove organs for transplant directly against the surviving …
The Effects of Azacitidine on Quality of Life Measured Longitudinally In MDS Patients Treated at a Tertiary Care Center
Authors: Sarah A. Ingber, Kim Thompson, Adam Lam, Alex Mamedov, Liying Zhang, Alibhai Shabbir, David Good, Alden Chesney, Marciano D. Reis, Matthew Cheung, Vicky Harris, Richard A. Wells, Rena Buckstein
Journal: Blood (2010)
The Erythropoiesis Stimulating Agent Omontys/Peginesatide up-Modulates Erythroid Progenitor Formation, and Cell Surface Erythropoietin Receptor Levels.
Authors: Rakesh Verma, Jennifer M Green, Karen Leu, Richard B Mortensen, Peter R. Young, Peter J Schatz, Don M. Wojchowski
Journal: Blood (2012)
Collagen Type I (CTI) Stimulates Proplatelet Formation (PPF) of Murine Megakaryocytes and Platelet like Particle Formation (PP) of Human Megakaryoblastic Cell Line (MEG) through the Activation of Rac.
Authors: Shugo Kowata, Kazunori Murai, Mamiko Ishiguro, Yoji Ishida
Journal: Blood (2005)
Maternal microbiota and antibodies as advocates of neonatal health
Authors: Stephanie C. Ganal-Vonarburg, Tobias Fuhrer, Mercedes Gomez de Agüero
Journal: Gut Microbes (2017)

Mammalian body surfaces are inhabited by vast numbers of microbes, the commensal microbiota, which help the host to digest food, provide nutrients, and mature its immune system. For a long time, postnatal colonization was believed to be the main stimulus for microbial-induced immune development. Using a model of reversible colonization of germ-free mice during gestation, we recently showed that the microbial shaping of the neonatal immune system begins even before birth through molecular signals derived from the microbiota of the mother. Maternal microbiota was important to mature intestinal innate immune cells and to alter intestinal gene expression profiles in the offspring. These changes prepare the newborn for postnatal colonization. The majority of the gestational colonization-dependent effects required maternal antibodies. Here, we discuss and provide further evidence how maternal antibodies are important players in transferring a signal originating from the maternal intestinal microbiota to the offspring.
Treatment Outcome of Localized Extranodal NK/T Cell Lymphoma in Nasal and Upper Aerodigestive Tract: A Single Institue Experience in Korea.
Authors: Seok Jin Kim, Hwa Jung Sung, In Keun Choi, Byung Soo Kim, Chul Won Choi, Jun Suk Kim, In Sun Kim, Soo-Young Yoon, Chul Yong Kim
Journal: Blood (2005)
Cancer/Testis Antigen Profiling in Multiple Myeloma Define a Cohort of Patients with Poor Prognosis Regardless of Genetic Subtypes.
Authors: Wee-Joo Chng, Natalia Gonzalez-Paz, Shaji Kumar, Scott Van Wier, Gregory Ahmann, Tammy Price-Troska, Kim Henderson, Marta Chesi, Morie Gertz, S. Vincent Rajkumar, Martha Lacy, Angela Dispenzieri, Robert Kyle, Philip Greipp, Rafael Fonseca, Peter Leif Bergsagel
Journal: Blood (2005)
Expression of the Smad3 Transgene Restores Radiosensitivity and Migratory Capacity to a Smad3−/− Clonal Bone Marrow Stromal Cell Line.
Authors: Michael W. Epperly, Shaonan Cao, Xichen Zhang, Emily E. Greenberger, Julie Goff, Hong Wang, Al Bahnson, Donna Shields, Darcy Franicola, Joel S. Greenberger
Journal: Blood (2005)
Dissecting the role of AMP-activated protein kinase in human diseases
Authors: Jin Li, Liping Zhong, Fengzhong Wang, Haibo Zhu
Journal: Acta Pharmaceutica Sinica B (2017)

AMP-activated protein kinase (AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes. Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type 2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.
Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?
Authors: Soisungwan Satarug, David A. Vesey, Glenda C. Gobe
Journal: Environmental Health Perspectives (2017)

Background:Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer's disease.Objective:We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection.Discussion:Staple foods constitute 40–60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70–1.85 μg/g creatinine in men and 0.95–3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16–31.5 μg/day was associated with 25–94% increase in risk of estrogen receptor–positive breast cancer.Conclusion:Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal.Citation:Satarug S, Vesey DA, Gobe GC. 2017. Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environ Health Perspect 125:284–288; http://dx.doi.org/10.1289/EHP108
Weight gain after adjuvant treatment in breast cancer patients in Istanbul, Turkey
Authors: N. S. Turhal, N. Yurt, G. Yurtseven, D. Cabuk, M. Teomete, M. Gumus
Journal: Journal of Clinical Oncology (2009)

e11620 Background: Weight gain is a common and unwanted result of chemotherapy. We wanted to find out how much weight Turkish beast cancer patients gains after chemotherapy and whether it lasts afterwards. Methods: 183 breast cancer patients who underwent a curative resection and received adjuvant chemotherapy afterwards in a private clinic between 1998 and 2007 are studied. Their weight before and after chemotherapy as well as their weight more than a year after chemotherapy is recorded together with their educational level, menopausal status, the type of chemotherapy or hormonal treatment, stage of disease, marital status, occupation and the underlying diseases. Results: Median age of patients is 53 and 72% is in menopause. Educational level is equally distributed for primary education (26%), High school (30%) and University and above (32%). Majority is (76%) married with two children (43%) and house wife (50%). Family history of any cancer is high (33%). Most of the patients had stage II cancer (57%), received anthracycline± taxane based chemotherapy (97%) and has no underlying disease (67%). The majority also does not smoke (72%) or drink alcohol (93%). Mean weight before the chemotherapy was 69.1 and increased to 70.8 upon completion of chemotherapy (p= 0.000) and 72 kg. more than a year after completion of chemotherapy (p=0.000). The other parameters including hormonal treatment, menopause, educational level and smoking do not have any effect on this weight increase. The all groups had similar weight gain with chemotherapy. Conclusions: Although upon starting the study we expected more, we confirmed some amount of weight gain with chemotherapy in Turkish patients and that gain is seen all across various social groups. The doctors should inform their patients of this change and precaution them toward this unwanted consequence. No significant financial relationships to disclose.
Abstract P3-01-02: Trends in positive predictive values following transition from screen film to digital mammography
Authors: DA Motiuk, P Dahl, E Roy, B-J Docktor, P Burrowes
Journal: Cancer Research (2017)

Abstract Purpose Our health region converted from screen-film mammography (SFM) to digital mammography (DM) in 2005. DM has several advantages over SFM, including superior contrast resolution, less noise, and opportunities for image optimization through post-acquisition processing; although, the spatial resolution of DM is inferior to SFM. We sought to determine what effect this transition may have had on positive predictive values (PPVs) for malignant and premalignant lesions. Methods From our institution's breast biopsy database, we retrospectively reviewed core biopsy results for mammographic calcifications performed in the years 2001-2004 (SFM years) and 2009-2012 (DM years). We subsequently determined the PPV3 (detection of malignancy after biopsy) for each group of years (SFM and DM). We then performed subgroup analysis to calculate PPVs for each of ductal carcinoma in-situ (DCIS) without invasion, DCIS with invasion, and premalignant lesions. Premalignant lesions included atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in-situ. Results A total of 4787 biopsies in 4633 patients were reviewed. The comparative detection of cancer after biopsy performed for mammographic calcification between SFM and DM was not statistically significant (PPV3 = 23.5% and 24.0%, respectively; P=.71). Upon further analysis, however, PPV for premalignant lesions increased (SFM=6.6% and DM=8.9%; P&amp;lt;.01) and PPV for DCIS without invasion increased (SFM=15.5% and DM=18.2%; P=.015), while PPV for DCIS with invasion decreased (SFM=8.0% and DM=5.8%; P&amp;lt;.01). Conclusion We observed no significant impact on PPV3 for calcifications following the transition from SFM to DM; however, our subgroup analysis suggests that with digital mammography we are now detecting a statistically significantly lower proportion of DCIS with invasion but greater proportions of DCIS without invasion and premalignant lesions. As the natural history of these lower-grade lesions, particularly in the premalignant category, is still not entirely understood, the significance of potentially detecting more of these earlier cancers/precancers is uncertain. Citation Format: Motiuk DA, Dahl P, Roy E, Docktor B-J, Burrowes P. Trends in positive predictive values following transition from screen film to digital mammography [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-01-02.
Genetic Evidence for a Role of Src Kinases in Mobilization, Homing and Engraftment of Hematopoietic Stem Cells: Deficiency of Src Kinases Results in Enhanced G-CSF Induced Mobilization.
Authors: Jovencio Borneo, Christie M. Orschell, Veerendra Munugalavadla, Reuben Kapur
Journal: Blood (2004)
Patterns of use of tamoxifen and aromatase inhibitors: A population-based observational study
Authors: L. Huiart, S. Dell'Aniello, S. Suissa
Journal: Journal of Clinical Oncology (2009)

556 Background: Few data are available outside clinical trials on the use of aromatase inhibitors (AI) as adjuvant treatment for early breast cancer (BC). We therefore used a large population-based database to describe patterns of use of AI over time, in comparison with tamoxifen, as well as switches between these regimens. Methods: We identified 13,479 women treated for BC with tamoxifen, anastrazole, letrozole, or exemestane between 1998 and June 2008 in the UK General Practice Research Database (GPRD). Patients were followed from their first prescription for 5 years or until recurrence, death, switch to another treatment or occurrence of a major thromboembolic or uterine event. Results: Mean age at cohort entry was 62 years (SD=14.0) in the tamoxifen group (n=10,806) and 70.8 (SD = 12.4) in the AI group (n=2,673). Overall, in the first year of treatment 88.8% of patients had prescriptions covering more than 80% of the year (88.3% and 90.8% in tamoxifen and in AI group respectively). Table 1 describes prescriptions covering less than 80% of the days for each year of treatment in 3 subgroups. Among women started on AI therapy diagnosed with BC after 2006, 9.6% switched treatment. Half of them switched from one AI to another AI, the other half switched from AI to tamoxifen. Switches occurred within the first year of treatment in 76% of cases. Among women over 50 years of age who started a tamoxifen therapy after 2000, 31% of women switched to AI in the course of the study, of which 12% within the first year of treatment (11.1% and 13.7% for women diagnosed in 2000–2004 and after 2005 respectively). Conclusions: The real-life patterns of use of tamoxifen and AI therapy demonstrate high rates of adherence. However, the relatively high percentage of switchers among AI users is suggestive of an association with side-effects. [Table: see text] No significant financial relationships to disclose.
MCL1 Targeting Agent Homoharringtonine Exerts Strong Cytotoxicity Towards Diffuse Large B-Cell Lymphoma (DLBCL) Cells and Synergizes with BCL2 Targeting Agent ABT199 in Eliminating BCL2-Positive DLBCL Cells
Authors: Magdalena Klanova, Ladislav Andera, Jan Soukup, Brazina Jan, Jan Svadlenka, Simona Benesova, Dana Prukova, Dana Vejmelkova, Radek Jaksa, Karel Helman, Petra Vockova, Lucie Lateckova, Jan Molinsky, Bokang Maswabi, Mahmudul Alam, Roman Kodet, Marek Trneny, Pavel Klener
Journal: Blood (2014)
Abstract 350: Atorvastatin Attenuates Pressure Overload-induced Cardiac Hypertrophy and Dysfunction Through Enhanced Autophagy
Authors: Zhuo Zhao, Wei Wang, Hua-Ting Wang, Qing-Xin Geng, Di Zhao, Guohai Su
Journal: Circulation Research (2015)

Aims: Cardiac hypertrophy is a maladaptive change in response to pressure overload and is also an important risk for developing heart failure. We previously demonstrated that atorvastatin inhibits cardiac hypertrophy and remodeling in a mouse model of transverse aorta constriction (TAC). This study was designed to determine the regulation of atorvastatin on cardiac autophagy and its association with the development of cardiac hypertrophy and dysfunction in the mice TAC model. Methods and results: TAC or sham operations were performed in male C57/L6 mice at 8 weeks of age. Atorvastatin (50 mg/kg/day) or vehicle (normal saline) were administered daily by oral gavage to TAC mice (n=10 per group). Echocardiography and real-time PCR data showed that chronic atorvastatin treatment for four weeks significantly attenuated pressure overload-induced cardiac hypertrophy and dysfunction, as well as cardiac mRNA level of atrial natriuretic factor (ANF), a biomarker of cardiac hypertrophy and heart failure. After 4 weeks of TAC, results from electron microscopy and Western blot showed that cardiac autophagy was activated, evidenced by the increased expression of microtubule-associated protein-1 light chain 3-II (LC3-II), Beclin-1, caspase-3, and the formation of autophagosomes. Interestingly, cardiac autophagy was further increased by the treatment of atorvastatin for 4 weeks. Western blot analysis showed phosphorylated Akt and mammalian target of rapamycin (p-mTor) decreased in the heart of TAC versus sham mice, which were further decreased by atorvastatin treatment. Conclusions: These findings suggest that atorvastatin attenuates cardiac hypertrophy and dysfunction in TAC mice probably through its regulation on cardiac autophagy via Akt/mTor pathways.
Expression of Cancer Testis (CT) Antigens NY-ESO-1 and LAGE-1 in Multiple Myeloma (MM): Could a Vaccine against the Former Antigen Be Effective against the Latter?
Authors: Bruno Karia, Fabricio de Carvalho, Valéria C.C. Andrade, Achim A. Jungbluth, André L. Vettore, Gisele W.B. Colleoni
Journal: Blood (2009)
Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3
Authors: Masahiro Hiasa, Tatsuo Okui, Yohance M. Allette, Matthew S. Ripsch, Ge-Hong Sun-Wada, Hiroki Wakabayashi, G. David Roodman, Fletcher A. White, Toshiyuki Yoneda
Journal: Cancer Research (2017)

Multiple myeloma patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model that employs JJN3 human multiple myeloma cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP+) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation. We found that JJN3 cells expressed a vacuolar proton pump (V-ATPase) that induced an acidic bone microenvironment. Inhibition of JJN3-colonized bone acidification by a single injection of the selective V-ATPase inhibitor, bafilomycin A1, decreased MMBP, CGRP+ sensory neuron sprouting, and pERK1/2 and pCREB expression in DRG. CGRP+ sensory nerves also expressed increased levels of the acid-sensing nociceptor ASIC3. Notably, a single injection of the selective ASIC3 antagonist APETx2 dramatically reduced MMBP in the model. Mechanistic investigations in primary DRG neurons cocultured with JJN3 cells showed increased neurite outgrowth and excitation inhibited by bafilomycin A1 or APETx2. Furthermore, combining APETx2 with bafilomycin A1 reduced MMBP to a greater extent than either agent alone. Finally, combining bafilomycin A1 with the osteoclast inhibitor zoledronic acid was sufficient to ameliorate MMBP, which was refractory to zoledronic acid. Overall, our results show that osteoclasts and multiple myeloma cooperate to induce an acidic bone microenvironment that evokes MMBP as a result of the excitation of ASIC3-activated sensory neurons. Furthermore, they present a mechanistic rationale for targeting ASIC3 on neurons along with the multiple myeloma-induced acidic bone microenvironment as a strategy to relieve MMBP in patients. Cancer Res; 77(6); 1283-95. ©2017 AACR.
PP76. DO LEVELS OF MGMT PROMOTER METHYLATION CORRELATE WITH SURVIVAL AND SENSITIVITY TO TEMOLOZOMIDE? THE NHS TAYSIDE EXPERIENCE
Authors: Mr Zhong Wei Khor, Dr Hannah Lord
Journal: Neuro-Oncology (2017)

BACKGROUND: Previous studies have identified that the silencing of O6-methylguanine-DNA methyltransferase (MGMT) via methylation of its promoter region renders Glioblastoma Multiforme (GBM) more sensitive to Temozolomide, improving patients’ prognoses. In this study, we seek to explore and confirm this relationship in the patient population of NHS Tayside, as well as determine whether the level of MGMT methylation has a correlation with overall and progression free survival. PROCEDURE: A retrospective study involving 27 patients with GBM treated at NHS Tayside between 2012 and 2016 was carried out. Data regarding patient overall survival, progression free survival, treatment received, methylation status and percentage methylation was obtained through the patients’ case files. The relationship between MGMT status/percentage and patient outcomes was examined. RESULTS:14 patients out of 27 patients were MGMT methylation positive (defined as MGMT methylation status of 8.7% and above). Irrespective of MGMT methylation status, all patients were commenced on TMZ chemotherapy with the exception of 3 in the MGMT methylation negative arm and 1 in the MGMT methylation positive arm due to palliative reasons. The average overall survival time for patients with positive MGMT methylation was 17 months 24 days, as compared to 8 months 23 days for the 13 patients who were un-methylated. Average progression free survival was also significantly longer for MGMT methylation positive patients (15 months 13 days) compared to methylation negative patients (7 months and 6 days). Above the threshold for positive MGMT methylation (8.7%), there was no correlation between MGMT levels with patient overall survival and progression free survival. CONCLUSIONS: In this study, there is a clear benefit shown between MGMT methylation status and patient outcome, with no correlation between methylation levels and positive outcomes above the accepted threshold. These data further confirm the validity of MGMT methylation as a prognostic factor for survival in patients with GBM in a non-trial population. This study also further validates the current threshold set (8.7%) for positive methylation status to be significant for patient prognostication.