tbuckley/cabot-search huggingface dataset:
Abstract 14775: Intracoronary and Systemic Microparticle Expression is Associated with Activated Platelet Monocyte Aggregate Formation, Platelet Activation, Myocardial Necrosis and Inflammation in St Elevation Myocardial Infarction
Authors: Chrysostomos Mavroudis, Despina Eleftheriou, Bikash Majumder, Ray Sapsford, Lowdell Mark, Paul Brogan, Roby Rakhit
Journal: Circulation (2012)

Background: In acute coronary syndrome (ACS) activated platelets bind to monocytes forming platelet monocyte aggregates (PMA), a sensitive marker of platelet activation. Microparticles (MP) are submicron membrane vesicles derived from many cell types in response to cell activation. Recent data suggests that MP are implicated in the pathogenesis of ACS. Aim: To investigate the relationship between intracoronary and systemic MP expression, PMA, markers of myocardial necrosis, platelet activation and inflammation in ST elevation myocardial infarction (STEMI). Methods: Patients undergoing primary angioplasty for STEMI were recruited. Blood samples from the infarct related artery [intracoronary (IC)] and arterial sheath [systemic arterial (SA)] were collected. PMA and MP levels were estimated using fluorescent monoclonal antibodies (MonAb) and flow cytometry. PMA were identified as CD14+CD61+CD62P+ events. All MP were AnV+ events. We used CD62P MonAb for platelet derived MP (PMP); CD105 and CD31 MonAb for endo...
Abstract 596: Impact of histologic type on survival in primary thyroid lymphomas
Authors: Taha Al-Juhaishi, Victor Yazbeck
Journal: Cancer Research (2018)

Abstract Background: Primary Thyroid Lymphoma (PTL) is a rare disease constituting less than 2% of all extranodal lymphomas; and approximately 2-8% of all thyroid malignancies. In this study, we sought to describe the impact of histologic types on survival. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients (≥18 years) diagnosed with PTL between 1973 and 2014. B-cell and T-cell lymphomas of all stages were included. Overall survival (OS) was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: Total of 2397 patients were included. Median age was 65 years (56-77); majority were female (n=1734, 72%) and caucasian (n=2178, 91%). Diffuse large B cell lymphoma was the most common histology (DLBCL, N=1351, 56%), followed by marginal zone (MZL, N=334, 14%), follicular (FL, N= 214, 8.9%), Burkitt (BL, N=43, 1.8%), chronic/small lymphocytic leukemia/lymphoma (CLL/SLL, N=41, 1.7%), Hodgkin lymphoma (HL, N=33, 1.4%), T cell lymphomas (TCL, N=14, 0.6%), Lymphoplasmocytic lymphoma (LPL, N=11, 0.4%), and Mantle cell (MCL, N=8, 0.3%). 349 patients (14.6 %) were reported with unclear histology. Total of 1502 (63%) had surgery, 1417 (59%) had chemotherapy and 1153 (48%) had radiation. At a median follow-up of 10.5 years, 1187 (50%) patients died. Median overall survival was 11.4 [10.6-12.3; 95% CI] years. Survival was different by histology type (table, P&amp;lt;0.001). Compared with DLBCL, follicular lymphoma (HR 0.72 [0.57-0.92], P=0.008) and MZL (HR 0.62 [0.48-0.78], P&amp;lt;0.001) were associated with lower mortality, independently of age, sex, race, surgery, chemotherapy, radiation and year of diagnosis. Adjusted mortality decreased by a relative 1% annually (HR 0.99 [0.98-0.99], P&amp;lt;0.001). Conclusion: PTL is a rare disease mostly affecting elderly caucasian women. Outcomes vary depending on histologic type. Follicular, MZL and Hodgkin's lymphoma seem to have a favorable prognosis. Overall Survival by HistologyHistologyNumber (%)Mean Survival in Years (95% CI)1-year survival5-year survivalDLBCL1351 (66%)12.6 [11.7-13.4]80%66%Burkitt43 (2.1%)15.9 [13.5-18.3]79%79%CLL/SLL41 (2%)13 [9.5-16.5]78%67%Follicular214 (10.4%)17.8 [15.1-20.6]97%83%Hodgkin33 (1.6%)25 [20-30]94%84%LPL10 (0.5%)14.2 [7.4-21]100%76%MZL334 (16.3%)13 [11.9-14.1]95%83%Mantel-Cell8 (0.4%)8.7 [3.9-13.5]87%56%T-cell14 (0.7%)10.7 [3.9-17.5]70%53% Citation Format: Taha Al-Juhaishi, Victor Yazbeck. Impact of histologic type on survival in primary thyroid lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 596.
Abstract 5879: Effect of Minnelide, a prodrug, on cervical cancer growth
Authors: Vivek Ramakrishnan, Bhuwan Giri, Urvashi Hooda, Peter Wilkinson, Christopher deHaydu, Janneth Oleas, Sabita Roy, Sundaram Ramakrishnan, Ashok Saluja
Journal: Cancer Research (2018)

Abstract Human Papilloma Virus (HPV) infection is associated with the development of Cervical cancer. Therapeutic resistance and recurrence remain the major obstacle to successful treatment of cervical cancer patients. Recently, a novel pro-drug Minnelide, derived from the diterpenoid triepoxide, triptolide, was found to be very effective against several human cancers in experimental animal models. The goal of the present study is to determine the effect of triptolide (in vitro) or Minnelide (in vivo) on HPV positive cervical cancer cells. Triptolide inhibited the proliferation of human cervical cancer cell lines, Ca Ski, SiHa, Me-180, and C-33a with an IC50 of 50 - 100 nM. Furthermore, triptolide inhibited the expression of viral oncoproteins E6 and E7 transcripts significantly. Consequently, p53, tumor suppressor protein levels were increased in the treated cells which led to increased apoptosis and reduced proliferation. Subsequently, we determined the effect of Minnelide on cervical cancer growth in athymic, nude mice. Tumor (SiHa and CaSki) bearing mice were treated with either 0.2 or 0.4 ug/kg doses of Minnelide. These studies showed that Minnelide inhibited tumor growth by about 70 % when compared to control group of mice and improved survival significantly. In a parallel study, combination treatment with carboplatin and Minnelide showed more than additive inhibition of tumor growth. In summary, Minnelide treatment reduced the transcript levels of HPV oncoproteins and inhibited cellular proliferation by upregulating p53. Our studies further demonstrate that Minnelide can be used either as a monotherapy or in combination with platinum drugs to inhibit the growth of cervical cancers. Citation Format: Vivek Ramakrishnan, Bhuwan Giri, Urvashi Hooda, Peter Wilkinson, Christopher deHaydu, Janneth Oleas, Sabita Roy, Sundaram Ramakrishnan, Ashok Saluja. Effect of Minnelide, a prodrug, on cervical cancer growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5879.
Previous Cytomegalovirus Infection and Restenosis After Coronary Stent Placement
Authors: Franz-JosefNeumann, AdnanKastrati, ThomasMiethke, JulindaMehilli, GiselaPogatsa-Murray, WernerKoch, MelchiorSeyfarth, AlbertSchömig
Journal: Circulation (2001)

Background— Reactivated cytomegalovirus may promote neointima formation after percutaneous coronary interventions by facilitating cell cycle progression through inhibition of the eukariotic tumor suppressor protein p53. This prospective study sought to investigate the effect of previous cytomegalovirus infection on restenosis after coronary stenting. Methods and Results— In 551 consecutive patients with successful stent placement, we determined cytomegalovirus IgG titers. Primary and secondary end points were the rate of angiographic restenosis at 6 months and the rate of target vessel reintervention at 1 year, respectively. Three hundred forty patients (62%) had a positive cytomegalovirus IgG titer. We obtained angiographic follow-up in 82% of all patients. Angiographic restenosis rate was 28.7% in patients with positive cytomegalovirus titers and 34.6% in patients with negative titers (P=0.18). Between the groups with and without positive cytomegalovirus titers, there were no significant differences in ...
Abstract 5740: PD-L1 overexpression induced by oncogenic <i>KRAS</i> and <i>BRAF</i> mutations through MAPK pathway activation in non-small cell lung cancer
Authors: Yosuke Miura, Noriaki Sunaga, Pinjie Bao, Luc Girard, Yusuke Tsukagoshi, Tomomi Masuda, Norimitsu Kasahara, Reiko Sakurai, Kyoichi Kaira, Takeshi Hisada, John Minna, Masanobu Yamada
Journal: Cancer Research (2018)

Abstract Mutant KRAS and BRAF are important oncogenic drivers in non-small cell lung cancer (NSCLC), however, effective treatment strategies for most of these mutants have not been established. Immuno-oncology clinical trials have shown promising results of anti-programmed death 1 (PD-1) antibodies for a subset of NSCLC patients and tumor expression of programmed-death ligand 1 (PD-L1) is regarded as a predictive marker for anti-PD-1 therapy. We found that CD274 mRNA and PD-L1 protein expression were reduced in NSCLC lines by small interfering RNAs (siRNAs) targeting mutant KRAS, but not wild-type KRAS, and also by pharmacologic inhibitors of MEK and ERK. In addition, there was a positive correlation between CD274 expression and KRAS expression in NSCLC lines, and analyses of The Cancer Genome Atlas (TCGA) database revealed that NSCLCs with high KRAS expression exhibited higher levels of CD274 compared to the tumors with low KRAS expression among KRAS-mutant NSCLCs. Similarly, siRNA-mediated BRAF knockdown and inhibitors of BRAF and MEK reduced PD-L1 expression in BRAF-mutant NSCLC cells, suggesting that PD-L1 expression was also upregulated by oncogenic BRAF. Mechanistically, these results suggest that oncogenic KRAS and BRAF induce PD-L1 overexpression in NSCLCs by activation of the MEK-ERK pathway. For clinical translation, our results suggest that: 1. in NSCLCs the combination of KRAS and PD-L1 overexpression could be a surrogate predictive marker for anti-PD-1 treatment; and 2. that since the goal of checkpoint inhibitor immuno-oncology therapy is to inhibit the PD-L1 axis, that a combination of anti-PD-1 and targeted therapy to inhibit the MEK-ERK pathway could be beneficial. Citation Format: Yosuke Miura, Noriaki Sunaga, Pinjie Bao, Luc Girard, Yusuke Tsukagoshi, Tomomi Masuda, Norimitsu Kasahara, Reiko Sakurai, Kyoichi Kaira, Takeshi Hisada, John Minna, Masanobu Yamada. PD-L1 overexpression induced by oncogenic KRAS and BRAF mutations through MAPK pathway activation in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5740.
The effect of early growth patterns and lung function on the development of childhood asthma: a population based study
Authors: Maribel Casas, Herman T den Dekker, Claudia J Kruithof, Irwin K Reiss, Martine Vrijheid, Jordi Sunyer, Johan C de Jongste, Vincent W V Jaddoe, Liesbeth Duijts
Journal: Thorax (2018)

Background Infant weight gain is associated with lower lung function and a higher risk of childhood asthma. Detailed individual childhood growth patterns might be better predictors of childhood respiratory morbidity than the difference between two weight and height measurements. We assessed the associations of early childhood growth patterns with lung function and asthma at the age of 10 years and whether the child’s current body mass index (BMI) influenced any association. Methods We derived peak height and weight growth velocity, BMI at adiposity peak, and age at adiposity peak from longitudinally measured weight and height data in the first 3 years of life of 4435 children enrolled in a population-based prospective cohort study. At 10 years of age, spirometry was performed and current asthma was assessed by questionnaire. Spirometry outcomes included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), FEV 1 /FVC ratio, and forced expiratory flow after exhaling 75% of vital capacity (FEF 75 ). Results Greater peak weight velocity was associated with higher FVC but lower FEV 1 /FVC and FEF 75 . Greater BMI at adiposity peak was associated with higher FVC and FEV 1 but lower FEV 1 /FVC and FEF 75 . Greater age at adiposity peak was associated with higher FVC, FEV 1 , FEV 1 /FVC and FEF 75 , particularly in children with a small size at birth, and lower odds of current asthma in boys. The child’s current BMI only explained the associations of peak weight velocity and BMI at adiposity peak with FVC and FEV 1 . Peak height velocity was not consistently associated with impaired lung function or asthma. Conclusion Peak weight velocity and BMI at adiposity peak were associated with reduced airway patency in relation to lung volume, whereas age at adiposity peak was associated with higher lung function parameters and lower risk of asthma at 10 years, particularly in boys.
Myocardial Injection With GSK-3β–Overexpressing Bone Marrow–Derived Mesenchymal Stem Cells Attenuates Cardiac Dysfunction After Myocardial Infarction
Authors: JaeyeaonCho, PeiyongZhai, YasuhiroMaejima, JunichiSadoshima
Journal: Circulation Research (2011)

Rationale:Glycogen synthase kinase (GSK)-3β upregulates cardiac genes in bone marrow–derived mesenchymal stem cells (MSCs) in vitro. Ex vivo modification of signaling mechanisms in MSCs may improve the efficiency of cardiac cell-based therapy (CBT). Objective:To test the effect of GSK-3β on the efficiency of CBT with MSCs after myocardial infarction (MI). Methods and Results:MSCs overexpressing either GSK-3β (GSK-3β–MSCs), LacZ (LacZ-MSCs), or saline was injected into the heart after coronary ligation. A significant improvement in the mortality and left ventricular (LV) function was observed at 12 weeks in GSK-3β–MSC–injected mice compared with in LacZ-MSC– or saline-injected mice. MI size and LV remodeling were reduced in GSK-3β–MSC–injected mice compared with in LacZ-MSC– or saline-injected ones. GSK-3β increased survival and increased cardiomyocyte differentiation of MSCs, as evidenced by activation of an Nkx2.5-LacZ reporter and upregulation of troponin T. Injection of GSK-3β–MSCs induced Ki67-positiv...
Abstract 5312: The effect of <i>Dnmt1</i> overexpression on intestinal tumorigenesis
Authors: Nicole A. Vander Schaaf, JinA Park, Oluwasei Dina, KwangHo Lee, Peter W. Laird
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Strong genetic drivers of tumorigenesis, such as loss of function of the APC tumor-suppressor gene, have been well characterized, but the role of epigenetic alterations remains poorly understood. Upregulation of DNA methyltransferases (DNMTs), including DNMT1, has been reported in various human cancers, but its functional significance to cancer is unclear. Here we report a novel mouse model of inducible Dnmt1 upregulation, bypassing the embryonic lethality of Dnmt1 overexpression. We accomplish inducible control of Dnmt1 expression by targeting the tet transcriptional activator to the endogenous Dnmt1 promoter. We combine this model with the ApcMin allele to investigate the effect of Dnmt1 upregulation on intestinal tumorigenesis. Our preliminary data suggests that Dnmt1 overexpression increases the size and multiplicity of intestinal polyps in ApcMin/+ mice. Previous work in our lab showed that DNA methylation is critical for tumor formation, but it is not known which DNA methylation alterations have functional relevance. To investigate this, we will use the Dnmt1 overexpression model to identify DNA methylation events that are responsible for the observed phenotype in ApcMin/+ mice. In summary, we describe a novel mouse model of Dnmt1 overexpression and provide preliminary evidence to suggest that such upregulation exacerbates intestinal tumorigenesis. Our investigation may yield new insights into the role of epigenetics in CRC initiation and progression and into potential epigenetic therapies. Citation Format: Nicole A. Vander Schaaf, JinA Park, Oluwasei Dina, KwangHo Lee, Peter W. Laird. The effect of Dnmt1 overexpression on intestinal tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5312.
Abstract 138: The Use of β-1.3/1.6-D-Glucan as Complementary Therapy for Cardiovascular Diseases
Authors: PeterSugita
Journal: Circulation Research (2014)

Cardiovascular disease nowadays is still the one silent killer over the world.So far, current standard therapies for cardiovascular diseases do not reach expected results such as the improving heart function by rehabilitating the damaged cardiomyocytes For thousands of years Ganoderma lucidum extract has been used as herbal therapy for various types of diseases, including cardiovascular diseases. An International Publication No. WO 2005/084692 A2 with the title Effect of Glucan on Stem Cell Recruitment and Tissue Repair mentions that “the orally administered glucan enhances proliferation, activation and differentiation of committed stem progenitor cells by functioning with the complement system by providing a second signal for CR3 activation.” Furthermore, it is also discussed that “the committed stem cells are selected from the group consisting of committed stem cells from the liver, heart, muscle, kidney and neural tissue.” In 1995 we began a research on β-D-Glucan derived from the purified extract of E...
Synchronized Ratiometric Codelivery of Metformin and Topotecan through Engineered Nanocarrier Facilitates In Vivo Synergistic Precision Levels at Tumor Site
Authors: Venkatesh Teja Banala, Shweta Sharma, Puja Barnwal, Sandeep Urandur, Ravi P. Shukla, Naseer Ahmad, Naresh Mittapelly, Gitu Pandey, Monika Dwivedi, Navodayam Kalleti, Kalyan Mitra, Srikanta Kumar Rath, Ritu Trivedi, Prabhat Ranjan Mishra
Journal: Advanced Healthcare Materials (2018)

Abstract The combination of metabolic modulators with chemotherapy holds vast promise for effective inhibition of tumor progression and invasion. Herein, a ratiometric codelivery platform is developed for metformin (MET), a known metabolic modulator and topotecan (TPT), a chemotherapeutic drug, by engineering lipid bilayer–camouflaged mesoporous silica nanoparticles (LB‐MSNs). In an attempt to deliver and maintain high tumor site concentrations of MET and TPT, a novel ion pairing–assisted loading procedure is developed using pamoic acid (PA) as an in situ trapping agent. PA, a hydrophobic counterion, increases the hydrophobicity of MET and TPT and facilitates MSNs with exceptionally high payload capacity (&gt;40 and 32 wt%, respectively) and controlled release profile. Further, the synergy between MET and TPT determined by a modeling approach helps to afford synchronized delivery of both the drugs. Coloaded MET and TPT LB‐MSNs present synergistic cytotoxicity against MDA‐MB‐231/4T1 cells and effectively promote apoptosis via mitochondrial membrane depolarization and cell cycle arrest. Extended pharmacokinetic profiles in preclinical models with fourfold to sevenfold longer circulation half‐life and 7.5–100 times higher tumor site concentrations correspond to a significant increase in pharmacodynamic efficacy. Taken together, the developed codelivery approach effectively addresses the challenges in the chemotherapeutic efficacy of MET and TPT collectively.
Abstract 5408: Elevated level of serum miR-1290 is correlated with high-grade serous ovarian epithelial ovarian cancer and might be a potential biomarker
Authors: Masaki Kobayashi, Sawada Kenjiro, Yoshimura Akihiko, Miyamoto Mayuko, Nakatsuka Erika, Kodama Michiko, Hashimoto Kae, Mabuchi Seiji, Kimura Tadashi
Journal: Cancer Research (2018)

Abstract Objective: There is a critical need for improved diagnostic markers to detect ovarian high grade serous ovarian cancer (HGSOC). MicroRNAs (miRNAs) stably exist in circulating blood, reflecting tissue or organ conditions and present in circulating microvesicles such as exosomes. Recent studies have confirmed the potential use of miRNAs profiling as a novel non-invasive biomarker for diagnosis of HGSOCs. The aim of this study is to identify which miRNAs are highly produced from HGSOCs and analyze whether serum miRNA can discriminate patients with HGSOC from healthy controls. Methods: Secreted exosomes from ovarian cancer cell lines were collected and exosomal miRNAs extracted. miRNA microarray was performed and several elevated miRNAs specific to HGSOCs were picked up. Among these, we focused on miR-1290. Serum from 71 pre-operative, 46 post-operative ovarian cancer patients and 13 healthy controls were gathered and its expression levels were detected by quantitative Real Time PCR. Results: In HGSOC patients, miR-1290 emerged overexpressed compared to healthy controls (3.52-fold). ROC analysis showed that at the cut-off of 1.61(healthy controls ; 1), the sensitivity and specificity were 63 % and 85 % respectively for detecting HGSOC (AUC = 0.71). The AUC of CA125 + miR-1290 combination was 1.00. Its expression singnificantly decreased after operation(5.87 → 1.17 ; P &amp;lt; 0.01). In advanced stage HGSOC patients, moreover, it expressed marginally higher than early stage ones(4.23 VS 1.58 ; P = 0.23). Conclusions: Serum miR-1290 can be a potential diagnostic biomarker for HGSOC. Citation Format: Masaki Kobayashi, Sawada Kenjiro, Yoshimura Akihiko, Miyamoto Mayuko, Nakatsuka Erika, Kodama Michiko, Hashimoto Kae, Mabuchi Seiji, Kimura Tadashi. Elevated level of serum miR-1290 is correlated with high-grade serous ovarian epithelial ovarian cancer and might be a potential biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5408.
Renal Tubular‐ and Vascular Basement Membranes and their Mimicry in Engineering Vascularized Kidney Tubules
Authors: Anne Metje van Genderen, Jitske Jansen, Caroline Cheng, Tina Vermonden, Rosalinde Masereeuw
Journal: Advanced Healthcare Materials (2018)

The high prevalence of chronic kidney disease leads to an increased need for renal replacement therapies. While there are simply not enough donor organs available for transplantation, there is a need to seek other therapeutic avenues as current dialysis modalities are insufficient. The field of regenerative medicine and whole organ engineering is emerging, and researchers are looking for innovative ways to create (part of) a functional new organ. To biofabricate a kidney or its functional units, it is necessary to understand and learn from physiology to be able to mimic the specific tissue properties. Herein is provided an overview of the knowledge on tubular and vascular basement membranes' biochemical components and biophysical properties, and the major differences between the two basement membranes are highlighted. Furthermore, an overview of current trends in membrane technology for developing renal replacement therapies and to stimulate kidney regeneration is provided.
Sixty seconds on . . . life expectancy
Authors: Nigel Hawkes
Journal: BMJ (2018)

No, but it’s not growing as quickly as it was. And the UK’s slowdown in growth is greater than in any comparable country except the US.

The Office for National Statistics has taken figures from the Human Mortality Database and standardised them for population size and age structure in different countries to allow a fair comparison.1

Comparing 2006-11 …