tbuckley/cabot-search huggingface dataset:
Abstract 5762: Fast screening of CD40 agonistic antibodies for cancer immunotherapy
Authors: James Jin, Yanan Guo, Yuelei Shen, Benny Yang
Journal: Cancer Research (2018)

Abstract CD40, Cluster of Differentiation 40, is a member of the TNF-receptor superfamily. CD40 is a co-stimulatory protein found primarily on antigen presenting cells, including B cells, macrophages and dendritic cells. Its ligand, CD40L (CD154) is predominantly expressed on T helper cells, whose engagement activates antigen presenting cells and induces a variety of downstream effects. Whereas most immune checkpoint receptors are expressed on the surface of T cells, CD40 stands out as it is expressed by antigen presenting cells and controls the proper activation of these cells. In turn, CD40 activation exerts a significant impact on T cell-mediated activity against cancer cells. Several pharmaceutical companies are pursuinganti-CD40 therapiesfor treating hematological and solid cancers. Having an access to Biocytogen's antibody discovery and in vivo efficacy screening platform for immune checkpoints, we asked whether we could find suitable anti-CD40 reagents which can successfullycombat developed tumors in preclinical settings. We designed a powerful screening strategy using Biocytogen's humanized CD40 mouse (B-hCD40). Candidate antibodies were generated by immunizing wild-type mice with recombinant hCD40 protein. Then the hybridomas were screened by high-throughput flow cytometry. Instead of examining the immune modulating activity in cell culture, we applied these antibodies to B-hCD40 mice bearing MC38 tumors. Through this straightforwardscreening, several clones stood out by their unparallelingbenefits. These clones were further selected for humanization. Again, the cohort of recombinant humanized CD40 antibodies was screened in B-hCD40 mice. In the end, we discovered the leads with the most potent anti-tumor activity. In conclusion, our work successfully identified several CD40 antibodies that are highly effective for cancer treatment in the preclinical setting. Citation Format: James Jin, Yanan Guo, Yuelei Shen, Benny Yang. Fast screening of CD40 agonistic antibodies for cancer immunotherapy [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 5762.
Transmyocardial Laser Revascularization
Authors: NikolausGassler, Hanns-OlofWintzer, Hans-MartinStubbe, AndreasWullbrand, UdoHelmchen
Journal: Circulation (1997)

Background The creation of transmyocardial channels from the epicardium to the left ventricular cavity with the use of a CO2 laser is a modern approach in the treatment of patients with chronic ischemic cardiac disease. The histological features of human myocardium at different times after transmyocardial laser therapy have not been previously described. We had the opportunity to examine hearts from patients who died without clinical evidence of a persistent therapeutic effect at 3, 16, and 150 days after transmyocardial laser revascularization (TMR), respectively. Methods and Results We grossly localized the laser-created channels in unfixed and formalin-fixed tissue. Three ventricular levels were defined for cutting the hearts into four segments. Then, transmural blocks were excised and cut crosswise and lengthwise for histological investigation through the use of established staining methods. On day 3, laser-induced channels were filled with abundant granulocytes and thrombocytes, fibrinous network, an...
Methylenetetrahydrofolate Reductase Genotypes and Early-Onset Coronary Artery Disease
Authors: AvivMager, ShadanLalezari, TamarShohat, YochaiBirnbaum, YehudaAdler, NuritMagal, MordechaiShohat
Journal: Circulation (1999)

Background—Homozygosity for the common (677C→T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with hyperhomocysteinemia, but there is uncertainty as to the association between this mutation and coronary artery disease (CAD). This study examined the association between MTHFR genotypes and age at onset of CAD. Methods and Results—Patients (n=169) with documented myocardial infarction or angiographically documented CAD who were aged ≤55 years at onset of CAD symptoms and DNA samples from control subjects (n=313) were studied. The prevalence of homozygosity among patients with early CAD onset (aged ≤45 years) was 28%, which was significantly higher than that in patients with later onset (13%) and in control subjects (14%) (odds ratio 2.4, 95% CI 1.24 to 4.69, P=0.006, and odds ratio 2.7, 95% CI 1.15 to 6.42, P=0.01, respectively). Plasma folate was lower in TT homozygotes who had early CAD onset than in those with later onset (P=0.005). Among patients with plasma folate in the...
Abstract 2988: Loss of Rbm38 cooperates with mutant p53 to promote lymphomagenesis through downregulation of Pten
Authors: Jin Zhang, Heejung yang, Yanhong Zhang, Mingyi Chen, Xinbin Chen
Journal: Cancer Research (2018)

Abstract The tumor suppressor TP53 is the most commonly mutated gene in human cancers and mutant p53 has a gain of function by promoting tumor progression, metastasis, and resistance to anticancer therapy. Interestingly, the RNA binding protein Rbm38, a critical regulator of mutant p53 translation, is frequently lost in tumors with mutant p53. To determine the role of the Rbm38-mutant p53 axis in tumorigenesis, we showed that loss of Rbm38 significantly alters the cancer susceptibility of mutant p53 knockin mice by shortening the lifespan, altering the tumor incidence, and promoting T-cell lymphomagenesis. To understand how Rbm38 deficiency promotes mutant p53 gain of function, we showed that loss of Rbm38 not only enhances mutant p53 expression but also decreases expression of tumor suppressor Pten, a critical regulator of T-cell development. Furthermore, we showed that Rbm38 is required for Pten expression by stabilizing Pten mRNA through an AU-rich element in its 3'UTR. Thus, we have uncovered a novel mechanism by which Pten is regulated by Rbm38 via mRNA stability. Our data also suggest that Rbm38 controls T-cell lymphomagenesis by concomitantly modulating mutant p53 and Pten, which may be explored as a therapeutic strategy for the treatment of T-cell malignancies. Citation Format: Jin Zhang, Heejung yang, Yanhong Zhang, Mingyi Chen, Xinbin Chen. Loss of Rbm38 cooperates with mutant p53 to promote lymphomagenesis through downregulation of Pten [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 2988.
Abstract 3208: Optimal array layouts for tumor treating fields therapy in glioblastoma: Oblique array layouts are superior to standard LR and AP positions
Authors: Nikola Mikic, Anders Korshøj
Journal: Cancer Research (2018)

Abstract Introduction: Tumor treating fields (TTFields) is a new and effective treatment for glioblastoma. Two pairs of transducer arrays are placed on the scalp of the patient to deliver low intensity, alternating electric fields, which inhibit mitosis and cancer growth. In the present study, we investigated systematic variations in electrode array positions to identify optimal layouts, which induce the highest electric fields in the tumor tissue. Method: The electric field distribution was calculated using finite element methods applied to a realistic computational head model. Array positions were rotated systematically in fifteen-degree intervals around a central cranio-caudal axis of the head to obtain thirteen different layouts in the same plane. Tumors were introduced in the computational mesh at nineteen different fronto-parietal positions in the same plane as defined by the electrode positions. Results: Electrode array layout greatly affected the field distribution. For the vast majority of tumors, two optimal and oblique array orientations were identified. At these positions, field intensities were approximately 30-40% higher compared to the standard anterior/posterior and left/right positions. In addition, the two optimal layouts were oriented at ninety-degree interval to each other. Correspondingly, a single optimum layout was identified when analyzing the combination of two pairs of arrays. Each tumor position was associated with only one optimum (combined) layout, which was generally oblique relative to the sagittal plane (15-45 degrees). An oblique layout at forty-five degrees to the sagittal plane was effective for most tumor positions and in all cases it was superior to the default layout combination of anterior-posterior and left-right positions. Conclusion: Our results provide guiding principles for optimal electrode placement, which will be helpful, especially in situations where the placement must be changed due to concurring clinical conditions such as shunts, scars, tissue rash etc. Patient specific models should be for more accurate TTF distributions. Additional research is needed to confirm these current results. Citation Format: Nikola Mikic, Anders Korshøj. Optimal array layouts for tumor treating fields therapy in glioblastoma: Oblique array layouts are superior to standard LR and AP positions [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 3208.
Abstract 5191: Targeting CX3CR1 Impairs the reseeding and colonization of circulating tumor cells and decelerates metastatic progression
Authors: Chen Qian, Asurayya Worrede-Mahdi, Ramanpreet Kaur, Fei Shen, Joseph Salvino, Olimpia Meucci, Alessandro Fatatis
Journal: Cancer Research (2018)

Abstract This study aims to understand the mechanisms and dynamics by which cancer cells, departing from existing metastases as circulating cancer cells (CTCs), further seed and colonize skeleton and soft tissues, expanding metastatic spreading and precipitating the clinical progression to terminal disease. We have previously shown that the chemokine receptor CX3CR1 is implicated in the metastatic seeding of breast cancer cells and that FX-68, a novel small-molecule antagonist for this receptor, effectively contains both number of lesions and total tumor burden in animal models of metastatic disease. Here we established that FX-68 impairs the reseeding of skeleton and soft tissue and that the CTCs unable to reseed and forced to remain in the blood eventually succumb to apoptotic death. The metastatic potential of CTCs was confirmed by reinoculation experiments as well as by forcefully mobilizing cancer cells from metastases back in the blood and assessing the number of additional lesions generated, in the presence and absence of FX-68. Furthermore, we found that prolonging the permanence of CTCs in the blood by targeting CX3CR1 with FX-68 improved exposure of cancer cells to the chemotherapy drugs doxorubicin or docetaxel significantly decreased tumor progression and extended overall survival. Finally, we found evidence that cancer cells seeding the skeleton despite the inhibition of CX3CR1 failed to develop into tumors, suggesting a role of CX3CR1 expression in the metastasis-initiating properties of breast cancer cells. In summary, our results strongly support developing CX3CR1 antagonists and promoting their clinical use, as this approach will provide novel and effective tools to contain the progression of metastatic disease in patients. Citation Format: Chen Qian, Asurayya Worrede-Mahdi, Ramanpreet Kaur, Fei Shen, Joseph Salvino, Olimpia Meucci, Alessandro Fatatis. Targeting CX3CR1 Impairs the reseeding and colonization of circulating tumor cells and decelerates metastatic progression [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 5191.
Abstract 18605: Long-Term Cardiac Follow-up of Patients With Severe Congenital Heart Disease: Are Care Gaps Associaed With an Increased Probability of Mortality
Authors: Eva Goossens, Aihua Liu, Liming Guo, Sarah Cohen, Judith Therrien, Philip Moons, Ariane Marelli
Journal: Circulation (2016)

Introduction: The ACC/AHA 2008 guidelines for adults with congenital heart disease (CHD) recommend follow-up in patients with severe CHD at specialized centers every 6-12 months. Care gaps, however...
ADHD: methylphenidate should be first line drug treatment in children, review confirms
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Methylphenidate is the most effective and safest short term drug treatment for children with attention-deficit hyperactivity disorder (ADHD), while amphetamines are most effective in adults, a major analysis has found.1

The findings should help clinicians navigate the current inconsistency in guidelines. While the findings match recommendations on first line drugs from the UK’s National Institute for Health and Care Excellence, other protocols in Europe recommend psychostimulants as first line treatment without any distinction between methylphenidate and amphetamines.

The network meta-analysis and systematic review, published in the Lancet Psychiatry ,1 compared the effectiveness and side effects of seven medicines with each other or with placebo over 12 weeks of treatment. It examined amphetamines (including lisdexamfetamine), atomoxetine, bupropion, …
Glutamine addiction activates polyglutamine-based nanocarriers delivering therapeutic siRNAs to orthotopic lung tumor mediated by glutamine transporter SLC1A5
Authors: Cuifeng Wang, Jiamin Wu, Zhongjuan Wang, Zeping Yang, Zhi Li, Huihui Deng, Long Li, Xiao Peng, Min Feng
Journal: Biomaterials (2018)
Calpastatin Counteracts Pathological Angiogenesis by Inhibiting Suppressor of Cytokine Signaling 3 Degradation in Vascular Endothelial Cells
Authors: TakuroMiyazaki, YoshitakaTaketomi, YutaSaito, TomohikoHosono, Xiao-FengLei, Joo-riKim-Kaneyama, SatoruArata, HaruoTakahashi, MakotoMurakami, AkiraMiyazaki
Journal: Circulation Research (2015)

Rationale:Janus kinase/signal transducer and activator of transcription (JAK/STAT) signals and their endogenous inhibitor, suppressor of cytokine signaling 3 (SOCS3), in vascular endothelial cells (ECs) reportedly dominate the pathological angiogenesis. However, how these inflammatory signals are potentiated during pathological angiogenesis has not been fully elucidated. We suspected that an intracellular protease calpain, which composes the multifunctional proteolytic systems together with its endogenous inhibitor calpastatin (CAST), contributes to the JAK/STAT regulations. Objective:To specify the effect of EC calpain/CAST systems on JAK/STAT signals and their relationship with pathological angiogenesis. Methods and Results:The loss of CAST, which is ensured by several growth factor classes, was detectable in neovessels in murine allograft tumors, some human malignant tissues, and oxygen-induced retinopathy lesions in mice. EC-specific transgenic introduction of CAST caused downregulation of JAK/STAT si...
Abstract 14151: Improved Electrocardiographic Monitoring Practices in the Practical Use of the Latest Standards of Electrocardiography (PULSE) Trial
Authors: Marjorie Funk, Kristopher P Fennie, Jeanine L May, Kimberly Stephens, Shelli L Feder, Pei-Shiun Chang, Barbara J Drew, Pulse Site Investigators
Journal: Circulation (2013)

Introduction: Although ECG monitoring is ubiquitous in hospitals, evidence suggests that monitoring practices are inconsistent and often inadequate. Hypothesis: An intervention consisting of an online ECG monitoring education program and strategies to implement and sustain change will result in improved practices related to ECG monitoring. Methods: The PULSE Trial is a 5-year, 3-phase, multi-site randomized clinical trial to evaluate the effect of the implementation of AHA practice standards for ECG monitoring on nurses’ knowledge, quality of care, and patient outcomes. We are reporting quality of care results from baseline and after the intervention in experimental group hospitals. Over 5 consecutive days at each time point, 3 research nurses observed monitors and electrode placement, reviewed current medical records, and compared arrhythmias stored in the monitor’s memory with documentation by unit nurses. The sample contained 2,872 patients on cardiac units in 14 hospitals in the US, Canada, and China....
Homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita–like phenotypes
Authors: Hemanth Tummala, Laura C. Collopy, Amanda J. Walne, Alicia Ellison, Shirleny Cardoso, Tekin Aksu, Nese Yarali, Deniz Aslan, Rüştü Fikret Akata, Juliana Teo, Zhou Songyang, Nikolas Pontikos, Jude Fitzgibbon, Kazunori Tomita, Tom Vulliamy, Inderjeet Dokal
Journal: Blood (2018)
Abstract 1412: Comprehensive characterization of clock genes in human cancers
Authors: Youqiong Ye, Yu Xiang, Joseph Takahashi, Gordon Mills, Seung-Hee Yoo, Leng Han
Journal: Cancer Research (2018)

Abstract Cancer chronotherapy has been considered to optimize the balance of anti-tumor effects and toxicity. To develop cancer chronotherapy, the first crucial step is to understand the significant roles of clock genes in cancer. Circadian machinery is controlled by two main transcription auto-regulatory feedback loops, which including 14 core circadian genes. Core clock genes have at least one paralog gene may be functionally redundant in circadian regulation. Dysregulation of circadian genes promotes tumorigenesis through mechanisms that include the cell cycle, DNA damage and metabolism. However, there has been no comprehensive analysis to characterize the roles of circadian genes and circadian rhythms in tumorigenesis and to assess their potential utility in cancer chronotherapy. We determined genetic and epigenetic alterations of clock genes in human cancer, and explore clock gene clinical effect through integrative analysis, based on The Cancer Genome Atlas (TCGA) profiles contained DNA, RNA, protein, epigenetic levels and clinical data. Our results suggested several clock genes may function as oncogene, such as ARNTL2, NR1D1, and NPAS2, while several other clock genes may function as tumor suppressors, such as PERs, CRYs, RORs. We revealed disruption and reprogramming of circadian rhythms across patient samples by showing significantly reduced number of genes correlated to clock genes. We further showed that transcriptional dysregulation of clock genes is strongly associated with patient survival, tumor stage and subtype. Taken together, our results provide the comprehensive analysis of clock system across different cancer types and expected outcomes will lay the groundwork for the future development of cancer chronotherapy. Citation Format: Youqiong Ye, Yu Xiang, Joseph Takahashi, Gordon Mills, Seung-Hee Yoo, Leng Han. Comprehensive characterization of clock genes in human cancers [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 1412.
Use of microRNA (miR) expression profiling to identify distinct subclasses of triple-negative breast cancers (TNBC).
Authors: Charles L. Shapiro, Luciano Cascione, Pierluigi Gasparini, Francesca Lovat, Stefania Carasi, Alfredo Pulvirenti, Alfredo Ferro, Kay Huebner
Journal: Journal of Clinical Oncology (2012)

1007 Background: TNBC is divided into basal and non-basal subclasses. To further subclassify TNBC we performed microRNA (miR) expression profiles and linked them to patient overall survival. Methods: During 1996-2005, 365 consecutive TNBC (phenotypically estrogen, progesterone and HER2 negative by immunohistochemistry [IHC]) were identified from the NCCN Breast Cancer Data Base/Tumor Registry at OSU Medical Center. One hundred fifty-eight (43%) formalin-fixed paraffin embedded (FFPE) breast cancer and 40 normal breast tissue blocks were available and tissue cores were obtained for RNA. RNA was isolated using the Ambion recoverall total nucleic acid isolation kit and the expression of ~700 miRs was assessed for each sample using the nanoString nCounter method. A consensus-clustering algorithm (ConsensusClusterPlus, Bioconductor www.bioconductor.org) was used to identify subclasses of TNBC and Kaplan-Meier overall survival curves were compared using the log-rank test. Censoring occurred at the date of death from causes other than breast cancer or at time of the last known follow-up, whichever occurred first. The median follow-up was 67 mo. (range 4-171 mo.). Results: The median age was 52 yrs. (range 20-84 yrs.); 81% white and 9% African-American; stages I, II, and III were 31%, 54% and 15%, respectively; and most patients received adjuvant anthracycline-based regimens with (25%) or without taxanes (75%). The algorithm identified 5 distinct subclasses; 1 clustering with normal breast miR expression whereas the other 4 each had a unique pattern of deregulated miRs. The median overall survivals were significantly different across the 5 cancer subclasses (log-rank p=0.028) (Table). Conclusions: miR expression profiling identifies and discriminates 5 TNBC subclasses, which do not coincide with those identified as basal and non-basal by IHC. Molecular analyses are ongoing to associate the miR-based subclasses with specific clinical features or the expression of specific pathways. [Table: see text]