tbuckley/cabot-search huggingface dataset:
Selective HDAC3 Inhibition Induces Apoptosis in B Cell Lymphoma through Protein Acetylation
Authors: Hiroyuki Matsui, Kotaro Shirakawa, Hsin-Yi Chang, Anamaria Daniela Sarca, Yasuhiro Kazuma, Hirofumi Fukuda, Hiroyuki Yamazaki, Tadahiko Matsumoto, Yasushi Ishihama, Akifumi Takaori-Kondo
Journal: Blood (2018)
The molecular characterization of two novel antibodies to HE4 and their utility in detecting early stage ovarian cancer
Authors: Robert Cheek, Lorraine King, Malena Sansbury, Qin He, Timothy Fischer, Douglas Malinowski, Clark Whitehead
Journal: Cancer Research (2007)

2669  The 5 year survival rate for epithelial ovarian cancer (EOC) depends greatly on the stage of the disease at the time of diagnosis; increased survival is associated with early detection (i.e. Stage 1 or 2). However, the vast majority of ovarian cancer is not diagnosed until stage 3 or 4. Therefore, there is a need to identify more ovarian cancers at an earlier stage. The characterization of biomarkers that exhibit such utility have the potential to improve the clinical outcome for many patients. One such candidate EOC biomarker is HE4 (human epididymisprotein 4). HE4 is a secreted and glycosylated protein that is overexpressed in many ovarian cancers. We have generated monoclonal antibodies to recombinant HE4 and selected two clones (90.1.6 and 71.1.1.13) that recognize HE4 in a sandwich ELISA assay format. Epitope mapping of these two clones reveal that they recognize adjacent epitopes within the COOH terminus of HE4. Specifically, the epitopes for 90.1.6 and 71.1.1.13 correspond to the amino acids, V83 to R94 and C93 to K116, respectively. The utility of these antibodies to identify early stage ovarian cancer was investigated by testing a cohort of 200 ovarian cancer sera (67 stage 1, 66 stage 2 and 67 stage 3) and 396 normal sera. A cutoff threshold of 2x standard deviation was obtained from a second independent cohort of 104 normal postmenopausal sera. Within the test cohort, HE4 demonstrated a specificity of 96% and a sensitivity of 66.5% in identifying ovarian cancer from normal sera samples. Specifically within each stage, HE4 displayed sensitivities of 63% (42/67) within the Stage 1, 62% (41/66) within stage 2 and 74% (50/67) within the stage 3 subpopulations. Thus, antibodies specific to the COOH terminus of HE4 demonstrate the ability to identify significant numbers of early stage ovarian cancer using a sandwich ELISA assay format. These antibodies may also be useful in additional experimental systems such as multiplexed bead-based immunoassays.
MicroRNA gene regulation in mantle cell lymphoma
Authors: Robert Chen, Sapna Patel, Lynne Bemis, William Robinson, Han Myint
Journal: Cancer Research (2007)

4522  Mantle Cell Lymphoma (MCL) represents only 5-10% of all non-Hodgkins lymphomas, making it an uncommon but difficult form of lymphoma to treat. It has the worst prognosis among the B cell lymphomas with median survival of three years.  The genetic hallmark of MCL is a t(11;14) q32 translocation which results in ectopic and dysregulated expression of cyclin D1. Recent comparative genomic hybridization studies have identied Syk as another gene important in the pathogenesis of MCL. Previous studies have Suggested that post transcriptional regulation of Cyclin D1 and Syk may be important the pathogenesis of in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the post transcriptional level by binding to the 3’ untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. There have been numerous reports of misregulation of microRNAs and their targets in human cancers. We hypothesized that altered microRNA regulation of cyclin D and/or Syk may be present in MCL. Based on bioinformatics, we identified 8 microRNAs and putative docking sites in either Cyclin D1 and Syk and then examined their integrity in MCL cell lines, We identified a mutation in the 3’UTR of Syk at docking site of 1 microRNA and a SNP in another microRNA. Using a GFP Reporter construct with the mutated Syk 3’UTR we demonstrated that this mutation resulted in altered miRNA function. This data suggests that microRNA regulation of important genes in MCL may be compromised and play a role in the development and progression of this disease.
The metabolic regulator small heterodimer partner contributes to the glucose and lipid homeostasis abnormalities induced by hepatitis C virus infection
Authors: Jizheng Chen, Yue Zhou, Yuan Zhuang, Tian Qin, Min Guo, Jing Jiang, Junqi Niu, John Zhong Li, Xinwen Chen, Qian Wang
Journal: Metabolism (2019)
Personality disorders as a result of symptom of chemotherapy-related cognitive impairment (CRCI) antiangiogenic treatment for metastatic renal cancer: A case report of 71-year-old women.
Authors: Ewa Wachula, Jolanta Zok, Marzenna Ziomek, Piotr Jan Wysocki, Wojciech Rogowski
Journal: Journal of Clinical Oncology (2013)

e13560 Background: Chemotherapy-related cognitive impairment, known also as chemo brain, is defined as cognitive changes experienced by patients undergoing chemotherapy, especially in aspects of visual and verbal memory, attention and psychomotor functions. Cognitive changes and dysfunction after common cancer chemotherapy and recently appearing after biologic agents are increasing as a disturbing side-effect in cancer survivors. The etiology of this phenomenon is not well understood. Methods: We present the case of 71-year- old female, with metastatic renal cancer who are exposed to anti-angiogenic treatment for years.From 2005 to 2009 the patient was treated by combination therapy which consisted of bevacizumab and INF-alfa.The anti-angiogenic therapy was discontinued prematurely because of cardiac toxicity. Partial response of metastatic lesions was achieved as a result of the treatment. In 2010, new metastases were found, and a second line therapy by m-TOR inhibitor everolimus was commenced. Because of hematological toxicity of CTC grade 3, the patient required a 50% dose reduction. During anti-angiogenic treatment some psychiatric symptoms such as paranoid personality disorders, memory impairment, dementia, emotional coldness and social withdrawal were observed. Results: In laboratory tests any electrolytes and metabolic imbalance were noticed. The CT and the MR imaging of the head excluded any structural damages and focal brain parenchymal lesions. Psychotherapy and pharmacotherapy were suggested.The patient is still on everolimus until now in order to maintain stabilization. Conclusions: The chemotherapy-related cognitive impairment can be problematic for survivors. Better understanding factors that contribute to chemotherapy-related cognitive dysfunction is important because this information could identify patients at risk and inform treatment.
Multifaceted mechanisms of colistin resistance revealed by genomic analysis of multidrug-resistant Klebsiella pneumoniae isolates from individual patients before and after colistin treatment
Authors: Yan Zhu, Irene Galani, Ilias Karaiskos, Jing Lu, Su Mon Aye, Jiayuan Huang, Heidi H. Yu, Tony Velkov, Helen Giamarellou, Jian Li
Journal: Journal of Infection (2019)
ABC of preterm birth: Immediate care of the preterm infant
Authors: Peter W Fowlie, William McGuire
Journal: BMJ (2005)

Preparing appropriately for the delivery and immediate care of the preterm infant is essential when time permits and may impact on the eventual outcome for the infant. This article describes the skills and equipment needed for the care and possible resuscitation of these vulnerable babies. The support and advice needed by parents and families at this time is also explored.

When preterm delivery can be anticipated there may be an opportunity for paediatric staff to discuss intrapartum and postnatal care with prospective parents and colleagues from midwifery and obstetrics. Even if detailed discussion is not possible, relevant historical details should be taken to anticipate problems and prepare appropriately for the arrival of the preterm infant.

Broadly, the level of resuscitation that may be needed is inversely related to the gestation of the preterm infant. Usually, the approach taken in resuscitating preterm infants of > 32 completed weeks' gestation is the same as that taken for term infants. Most need only basic measures such as drying and stimulation. Infants of gestation < 32 weeks (or birth weight < 1500 g) require more active support. For infants of < 28 weeks' gestation, this support will probably include endotracheal intubation and assisted ventilation.

Ideally, two members of staff who are experienced in the early care of preterm infants should be present at the delivery of each anticipated infant. A senior paediatrician with extensive experience in dealing with preterm babies should be at the delivery of infants of < 28 weeks' gestation. Before delivery, the attending staff should recheck essential equipment for resuscitation.



The “inverted triangle” shows how commonly certain interventions are needed



Preterm infants get cold quickly because of their relatively large surface area. Resulting hypothermia reduces surfactant production, may hasten hypoglycaemia and acidaemia, and is associated with increased mortality. Preterm infants should …
MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21
Authors: Anna E. Vilgelm, Nabil Saleh, Rebecca Shattuck-Brandt, Kelsie Riemenschneider, Lauren Slesur, Sheau-Chiann Chen, C. Andrew Johnson, Jinming Yang, Ashlyn Blevins, Chi Yan, Douglas B. Johnson, Rami N. Al-Rohil, Ensar Halilovic, Rondi M. Kauffmann, Mark Kelley, Gregory D. Ayers, Ann Richmond
Journal: Science Translational Medicine (2019)

CDK4/6 inhibition becomes effective in preclinical models of melanoma when combined with MDM2 antagonism.
Utilization of EPA databases for cancer research
Authors: Myra Karstadt
Journal: Cancer Research (2004)

4868A  Currently clinical trials of anticancer drugs are based on the principle that Phase I estimates the maximum tolerated dose (MTD), and the dose for subsequent Phase II and Phase III studies is then based on the MTD. The MTD is also used as guidance for patient treatment following drug approval because undesirable toxicity can be readily observed in patients being treated, whereas an early determination of an effective dose [e.g., the minimally effective dose (MED)] in an individual patient has until now been more difficult to measure. It is questionable whether desirable cytotoxicity (therapeutic efficacy) and undesirable toxicity are necessarily parallel. Indeed, studies have shown that the effective dose may be much lower than the dose that is toxic to non-target sites, and efficacy of antitumor action at such higher doses may even be decreased. There are now a growing number of noninvasive methods that can perform functional measurements: DCE-MRI (Dynamic Contrast Enhanced MRI), Multinuclear NMR Spectroscopy (MRS), PET (Positron Emission Tomography), SPECT (Single Photon Emission Computerized Tomography), Dynamic CT, and others. Of those, DCE-MRI can be used to measure directly whether a given agent changes the perfusion of tumors. We will present our updated data showing that DCE-MRI is highly predictive of tumor response to docetaxel (p
Associations of Combined Exposures to Surrounding Green, Air Pollution, and Road Traffic Noise with Cardiometabolic Diseases
Authors: Jochem O. Klompmaker, Nicole A. H. Janssen, Lizan D. Bloemsma, Ulrike Gehring, Alet H. Wijga, Carolien van den Brink, Erik Lebret, Bert Brunekreef, Gerard Hoek
Journal: Environmental Health Perspectives (2019)

Background: Surrounding green, air pollution, and noise have been associated with cardiometabolic diseases, but most studies have assessed only one of these correlated exposures. Objectives: We aimed to evaluate associations of combined exposures to green, air pollution, and road traffic noise with cardiometabolic diseases. Methods: In this cross-sectional study, we studied associations between self-reported physician-diagnosed diabetes, hypertension, heart attack, and stroke from a Dutch national health survey of 387,195 adults and residential surrounding green, annual average air pollutant concentrations [including particulate matter with aerodynamic diameter ≤10μm (PM10), PM with aerodynamic diameter ≤2.5μm (PM2.5), nitrogen dioxide (NO2), and oxidative potential (OP) with the dithiothreitol (DTT) assay (OPDTT)] and road traffic noise. Logistic regression models were used to analyze confounding and interaction of surrounding green, air pollution, and noise exposure. Results: In single-exposure models, surrounding green was inversely associated with diabetes, while air pollutants (NO2, OPDTT) and road traffic noise were positively associated with diabetes. In two-exposure analyses, associations with green and air pollution were attenuated but remained. The association between road traffic noise and diabetes was reduced to unity when adjusted for surrounding green or air pollution. Air pollution and surrounding green, but not road traffic noise, were associated with hypertension in single-exposure models. The weak inverse association of surrounding green with hypertension attenuated and lost significance when adjusted for air pollution. Only PM2.5 was associated with stroke and heart attack. Conclusions: Studies including only one of the correlated exposures surrounding green, air pollution, and road traffic noise may overestimate the association of diabetes and hypertension attributed to the studied exposure. https://doi.org/10.1289/EHP3857
Estrogen induces Matrix Metalloproteinase (MMP)-26 expression in endometrial carcinoma.
Authors: Hirotaka Nishi, Yumi Osakabe, Osamu Akutagawa, Atsuya Fujito, Keiichi Isaka
Journal: Cancer Research (2005)

51  BACKGROUND: The human matrix metalloproteinase (MMP)-26, also called matrilysin-2 or endometase, has been isolated as a matrilysin (MMP-7) homolog. Several reports describe that MMP-26 may be related to the development of endometrial carcinomas. METHODS: Total RNAs were isolated from 51 normal endometrial tissue samples, 4 endometrial hyperplasia tissue samples, and 30 endometrial carcinomas. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the MMP-26 mRNA expression level. To identify MMP-26 protein localization, we performed immunohistochemical analysis. We examined the effect of estrogen and its receptor (ER) on MMP-26 expression in endometrial carcinoma cell lines by realtime-time RT-PCR, western blot and luciferase assays. To examine protein-DNA binding between ER and MMP-26 promoter, we performed electrophoretic mobility shift assays (EMSA). RESULTS: Real-time RT-PCR analysis revealed that MMP-26 mRNA expression was significantly higher in the normal human endometria and hyperplasias, compared with that in the endometrial carcinomas. Estrogen and ER not only transactivated the MMP-26 promoter activity but also enhanced endogenous MMP-26 expression. The MMP-26 promoter region contains one ER consensus motif (ERE), and luciferase assays showed that this is essential for MMP-26 transactivation by ER. Recombinant ER interacted with ERE on the MMP-26 promoter by EMSA. CONCLUSIONS: We found a significant difference in MMP-26 expression in normal and malignant endometrial tissue samples and ER induced MMP-26 expression. ER may induce endometrial hyperplasia but not endometrial carcinoma. Our results provide evidence that regulation of MMP-26 promoter activity by estrogen may represent a mechanism for endometrial carcinogensis.
Exploratory modeling and simulation to support development of motesanib in Asian patients with non-small cell lung cancer (NSCLC) based on MONET1 study results.
Authors: Rene Bruno, Cheng-Pang Hsu, Laurent Claret, Jianfeng Lu, Yu-Nien Sun
Journal: Journal of Clinical Oncology (2013)

e19103 Background: Motesanib failed to improve overall survival (OS) in the MONET1 phase III study when combined to carboplatin/paclitaxel (CP) vs. CP in first-line NSCLC cancer patients (JCO 30:2829-2836, 2011). However, outcome of the study was favorable in a sub-population of Asian patients. We performed exploratory modeling and simulations based on the MONET1 data in order to support further development of motesanib in Asians. Methods: We developed 1) a longitudinal tumor growth inhibition model to estimate time to tumor regrowth (TTG)) using data from 934 out of 1,090 (86%) included in MONET1 and 2) a multivariate parametric model for OS including baseline prognostic factors and tumor size metrics to capture treatment effect. OS model was assessed in simulating OS distribution and hazard ratios (HR) in multiple replicates of MONET1 and comparing 95% predictive distribution (PI) with observed data. Multiple replicates of virtual phase III studies in Asian patients were simulated to assess probability of success of alternative designs. Results: Baseline tumor size (TS) and smoking history (former and current smokers vs. never smokers) were significant independent prognostic factors for OS with Asian ethnicity and log (TTG). Logarithm of OS (in days) was defined by a linear model. Parameter estimates of the OS model are given below (Table). The model successfully predicted OS distributions and HR in the full populations and in Asian patients. Simulations suggested that a 500 patient phase III study would exceed 80% power to demonstrate motesanib combination OS superiority in Asian with an expected HR of 0.74. Conclusions: A model-based estimate of TTG captured treatment effect in Asian and simulations suggested superiority of motesanib combination in these patients. The OS model could be used to simulate expected OS based on longitudinal NSCLC tumor size data with new investigational agents and support development decisions and study design. [Table: see text]
Contribution of the transcriptional factor GATA-6 overexpression to the 15-lipoxygenase-1 transcriptional silencing maintenance in cancer cells
Authors: Xiangsheng Zuo, Russell Broaddus, Yuanqing Wu, Baoxiang Guan, Jeffrey S Morris, Scott M Lippman, Imad Shureiqi
Journal: Cancer Research (2007)

2918  Transcriptional suppression of 15-lipoxygenase-1 (15-LOX-1) helps enable human colorectal cancer cells escape apoptosis, a critical mechanism for colonic tumorigenesis. GATA-6 is strongly expressed in vitro in cancer cells; its downregulation by pharmaceuticals is associated with reversal of 15-LOX-1 transcriptional suppression. The mechanistic contribution of GATA-6 overexpression to colonic tumorigenesis, especially concerning 15-LOX-1 transcriptional suppression, remains unknown. We tested whether GATA-6 is differentially overexpressed in human colorectal cancers and whether reversing GATA-6 overexpression in colon cancer cells is sufficient to restore 15-LOX-1 expression and influence cell proliferation or apoptosis. The expression of GATA-6 RNA and protein was measured in paired human colorectal cancer and normal tissues from two separate patient groups. We used GATA-6 small interfering RNA transfection to downregulate GATA-6 expression and examine the effects of this downregulation on 15-LOX-1 expression, cell proliferation and apoptosis in Caco-2 and HCT-116 colon cancer cells with and without the nonsteroidal anti-inflammatory drug NS-398 or the histone deacetylase inhibitor sodium butyrate. GATA-6 expression was higher in the cancer than in the normal epithelia at the mRNA and protein levels; GATA-6 knockdown was insufficient by itself but contributed significantly to restoring 15-LOX-1 expression and inducing apoptosis by NS-398 or sodium butyrate. Maintaining 15-LOX-1 transcriptional silencing in cancer cells is multifactorial and requires other regulatory suppressive events besides GATA-6.
Thermal ablation versus parathyroidectomy for secondary hyperparathyroidism: A meta-analysis
Authors: Lifeng Gong, Weigang Tang, Jingkui Lu, Wei Xu
Journal: International Journal of Surgery (2019)

Thermal ablation and parathyroidectomy (PTX) have been recommended for patients with secondary hyperparathyroidism (SHPT). However, it is uncertain which is the better method. The aim of the present meta-analysis was to evaluate the efficacy and surgical complications of the two treatment methods. The following databases were searched from inception to December 31, 2018: PubMed, EMBASE, the Cochrane Library, CNKI, and Wanfang. Eligible studies comparing thermal ablation and PTX for SHPT were included. Data were analysed using Review Manager Version 5.3. Six studies were included in the meta-analysis. Four cohort studies and two randomized controlled trials involving 326 patients with SHPT were identified. There was no difference concerning parathyroid hormone (PTH) levels (MD 58.04, 95% CI -17.60–133.68, P = 0.13), calcium levels (MD -0.07, 95% CI -0.17–0.04, P = 0.21), phosphorus levels (MD 0.21, 95% CI -0.18–0.61, P = 0.29), or hoarseness (OR 0.53, 95% CI 0.24–1.16, P = 0.11) between the two surgical methods. Compared with PTX, thermal ablation reduced the risk of hypocalcaemia (OR 0.23, 95% CI 0.11–0.47, P < 0.01). However, thermal ablation increased the risk of SHPT persistence and/or recurrence compared with PTX (OR 4.24, 95% CI 1.44–15.76, P = 0.03). Thermal ablation and PTX were effective surgical approaches for SHTP. Thermal ablation reduced the risk of hypocalcaemia and increased the risk of SHPT persistence and recurrence. More large multicentre randomized controlled trials are necessary to confirm the conclusions.
A novel phenoxazine derivative suppresses proliferation of human endometrial carcinoma
Authors: Daiei Nakayama, Hirotaka Nishi, Yumi Osakabe, Atsuya Fujito, Toshihide Nakada, Akio Tomoda, Keiichi Isaka
Journal: Cancer Research (2005)

1095  We examined the effects of a novel phenoxazine, 2-amino-4, 4alpha-dihydro-4alpha7-dimethyl-3H-phenoxazine-3-one (Phx), which was produced by the reaction of 2-amino-5methyl-phenol with bovine hemoglobin on the proliferation of human endometrial adenocarcinoma cell lines, EI, EN and KLE cells, and on induction of apoptosis and G1 arrest in these cells. Phx inhibited proliferation of these cell lines in a dose- and time-dependent manner, i.e., the inhibition rate of proliferation of EN and KLE cells was 43% and 40%, respectively, in the presence of 50 microM Phx, and 75% and nearly 100%, in the presence of 100 microM Phx, after 2 days. When these endometrial adenocarcinoma cells were incubated with a medium containing 100 microM Phx for 24 h, accumulation of EN and KLE cells in the G1 phase and that of apoptotic cells were demonstrated by flow cytometry and TUNEL assays. Apoptosis of these cells caused by Phx was unlikely to be associated with p53, Bax, and Bcl-2, because the levels of these proteins were not altered regardless of the presence or absence of Phx. We also examined the therapeutic efficacy of Phx in xenografted tumor. Human endometrial carcinoma xenografts (EN and KLE) were transplanted into nude mice. We observed significant growth inhibition of these tumors by Phx injection. The present results suggest that Phx demonstrates antitumor activity against human endometrial carcinoma by inducing both cell cycle accumulation at G1 and apoptosis associated with p53 insensitive pathways.