tbuckley/cabot-search huggingface dataset:
Clinical utility of biomarkers of systemic inflammation for patients with metastatic renal cell carcinoma.
Authors: Wayne Harris, Mikhail Y. Akbashev, Omer Kucuk, Yuan Liu, Wayland Hsiao, Adeboya O. Osunkoya, Deborah O. Baumgarten, Viraj A. Master
Journal: Journal of Clinical Oncology (2013)

e15617 Background: The presence or absence of systemic inflammation has been associated with dramatic changes in prognosis for patients with metastatic renal cell carcinoma (mRCC). In this study we define kinetic inflammatory response (KIR) patterns as changes in the intensity of the systemic inflammatory response (SIR) over time as a result of therapeutic intervention or disease progression with the goal of ascertaining whether such patterns have any clinical utility. Methods: A retrospective, single institution study was conducted at the Winship Cancer Institute of Emory University. Inclusion criteria included treatment with a targeted agent for mRCC of any histology and the concurrent assessment of serum CRP and albumin on a minimum of three occasions at least two weeks apart. The modified Glasgow Prognostic Score (mGPS) was used to quantify the intensity of the SIR at each available time point. Results: A cohort of 55 patients was identified from among 635 patients who were evaluated for kidney cancer during the screening period of January 1, 2005 and June 30, 2011. The SIR was assessed a total of 804 times with a median of 14 time points per patient (range 3 to 49). A total of 113 lines of theapy were administered with a median of 2 per patient (range 1 to 5). KIR patterns were categorized as optimal, suboptimal, relapse, refractory and acquired systemic inflamation. Tandem KIR patterns were also observed. The absence or sustained loss of systemic inflammation was associated with responsiveness to therapy and prolonged overall survival (OS) whereas the persistence or acquisition of systemic inflammation was associated with resistance to therapy and shortened OS. In one instance, active surveillance with biomarkers of systemic inflammation led to the discovery of an occult penile metastasis. Conclusions: KIR pattern recognition provides a simple and inexpensive way for clinicians to monitor interactions between the tumor and the innate immune system with the clinical objective of inducing or maintaining an inflammation free state. Biomarkers of systemic inflammation may prove to be particularly useful for active surveillance of patients with fully resected, locally advanced or mRCC.
Modeling and analysis of drug concentration-effect and time course patterns in gene expression data from microarray experiments.
Authors: Yutaka Midorikawa, Shogo Yamamoto, Shumpei Ishikawa, Naoko Kamimura, Kunihiro Nishimura, Haruhiko Sugimura, Masatoshi Makuuchi, Hiroyuki Aburatani
Journal: Cancer Research (2005)

9  Time course and dose-response experiments with multiple time-points and drug concentrations provide far more valuable information than experiments with two design-points (such as before treatment versus after treatment, treated versus untreated) commonly found in the microarray literature. Analysis of the data from such experiments, however, remains a challenge. Methods that have become standard in microarray data analysis such as class comparisons, clustering, and supervised or unsupervised learning techniques have limited use. Clustering provides good visualization and discovery tools but has little quantitative value. Here we present an automated method for fitting parametric models to hundreds of gene expression profiles simultaneously. Models, with expression levels as functions of time or drug concentration, are fitted to either time course or dose response data, and estimated model parameters are further analyzed to extract significant patterns. To demonstrate its ease and usefulness, the method was applied to an Affymetrix HG-U95Av2 dataset consisting of 51 arrays. The specific study focused on the effects of two platinum drugs, cisplatin and oxaliplatin, on A2780 human ovarian carcinoma cells. The time course data consisted of gene expression profiles obtained prior to treatment, and at five time-points up to 24h after treatment with IC90 concentrations for both drugs. Gene expression profiles obtained 16h after treatment with IC10, IC25, IC50, IC75 and IC90 concentrations for cisplatin and oxaliplatin comprised the dose response data. Data from control samples, treated with drug-free medium, was available at four time points. Replicates, including in some cases 4 or 5 replicates, were available at most time points and dose concentrations. The models for the time course included exponential increase and decrease models with meaningful parameters such as initial expression level, maximum level, time lag to change in expression, and rate-constant (or half-time). Dose response was modeled using a four-parameter Hill model. All calculations were performed in SigmaPlot (Systat Software, Inc.). Macros were used to automate the process and obtain fitted curves and model parameters for hundreds of genes simultaneously. Model fitted curves and parameters were obtained for genes that show significant changes as well as genes in several pathways of interest. Comparisons of model parameters between genes in a pathway or between two drug treatments should help improve understanding of drug action and effects. Supported in part by NIH RR10742.
Degradation of splicing factor SRSF3 contributes to progressive liver disease
Authors: Deepak Kumar, Manasi Das, Consuelo Sauceda, Lesley G. Ellies, Karina Kuo, Purva Parwal, Mehak Kaur, Lily Jih, Gautam K. Bandyopadhyay, Douglas Burton, Rohit Loomba, Olivia Osborn, Nicholas J.G. Webster
Journal: Journal of Clinical Investigation (2019)

Serine-rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes. Hepatic SRSF3 expression was similarly decreased and RNA splicing dysregulated in mouse models of NAFLD and NASH. We showed that palmitic acid–induced oxidative stress caused conjugation of the ubiquitin-like NEDD8 protein to SRSF3 and proteasome-mediated degradation. SRSF3 was selectively neddylated at lysine 11 and mutation of this residue (SRSF3-K11R) was sufficient to prevent both SRSF3 degradation and alterations in RNA splicing. Lastly, prevention of SRSF3 degradation in vivo partially protected mice from hepatic steatosis, fibrosis, and inflammation. These results highlight a neddylation-dependent mechanism regulating gene expression in the liver that is disrupted in early metabolic liver disease and may contribute to the progression to NASH, cirrhosis, and ultimately hepatocellular carcinoma.
Profiling of Oncogenic Signaling in Multiple Myeloma — Association with Biology, Disease Progression and Prognosis
Authors: Nicola Lehners, Jing Xu, Thomas Hielscher, Leo Rasche, Elena Ellert, Albrecht Stenzinger, Peter Schirmacher, Carsten Müller-Tidow, Hartmut Goldschmidt, Mindaugas Andrulis, Niels Weinhold, Marc S Raab
Journal: Blood (2018)
Sixty seconds on . . . ice lollies
Authors: Abi Rimmer
Journal: BMJ (2019)

These lollies aren’t designed to cool you down on a hot day: they’re for postoperative patients.

No, although some evidence shows that those patients should have ice lollies too.1 These are high risk patients recovering from major surgery, in a nine bed intensive care unit at the University College London Hospitals foundation trust.

More like SNAP-1 (Sprint National Anaesthesia Project), whose data on …
Dedicator of cytokinesis protein 2 couples with lymphoid enhancer–binding factor 1 to regulate expression of CD21 and B-cell differentiation
Authors: Yukai Jing, Danqing Kang, Luyao Liu, Huang Huang, Anwei Chen, Lu Yang, Panpan Jiang, Na Li, Heather Miller, Zheng Liu, Xiaofei Zhu, Jun Yang, Xiaochuan Wang, Jinqiao Sun, Zhiping Liu, Wanli Liu, Xinyuan Zhou, Chaohong Liu
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 19850: Pilot Study About A New Parameter For Vasodilation In Coronary Artery -An Alternative Use Of Pressure Wire-
Authors: Hidekiimi Nomura, Kentaro Jujo, Kensuke Shimazaki, Tetsu Moriyama, Mayui Nakazawa, Issei Ishida, Katsumi Saito
Journal: Circulation (2017)

Introductions: Fractional flow reserve (FFR) that was tested by the pressure wire has been recently a reliable physiological evaluation of ischemic status on coronary artery stenosis. However, micr...
Interactions of breast cancer cells with the microenvironment of the human bone marrow
Authors: T. Kaiser, G. Klein, E. Solomayer, D. Wallwiener, T. Fehm
Journal: Journal of Clinical Oncology (2009)

e22097 Background: Bone is one of the most favored sites for metastasis of breast cancer cells (BrCa) resulting in the formation of osteolytic and/or osteoblastic lesions. There is increasing evidence that the bone marrow (BM) microenvironment plays a pivotal role in modulating tumor cell homing to the bone, metastasis and progression. However, the molecular crosstalk between BrCa cells and the cellular and extracellular components of the bone marrow leading to osteotropism still remains a poorly characterized step in the metastatic process. Methods: Cell adhesion and migration assays using the invasive MDA-MB-231 and the noninvasive MCF7 BrCa cell lines were performed to investigate the impact of BM components on cellular functions of tumor cells. Results: Cell-matrix adhesion assays showed a strong and concentration-dependent attachment of BrCa cells to several extracellular matrix components present in the human bone marrow such as fibronectin, different laminin isoforms, collagens type I and IV or tenascin-C. Moreover, the BrCa cells attached avidly to the BM-derived primary osteoblasts, whereas the binding to stromal cells was significantly weaker. Notably, cell-cell adhesion experiments with primary osteoclasts revealed an anti-adhesive effect on tumor cell binding leading to no attachment activity of BrCa cells with the cell surface of primary osteoclasts. The influence of cellular components of the BM on tumor cell migration was analyzed by cell migration assays using conditioned media of osteoblasts, osteoclasts and stromal cells or a modified Transwell chamber technique. The migration assays with invasive MDA-MB-231 cells clearly showed that osteoblasts, but not osteoclasts or stromal cells released factors which led to a faster wound closure, suggesting an enhanced migratory ability of the metastatic tumor cells, whereas the migration of nonmetastatic MCF7 cells was unaffected. Conclusions: These data indicate that the crosstalk with osteoblasts affects both the adhesive and the migratory ability of BrCa cells favoring the bone colonization process. Furthermore, the presented experimental conditions may provide useful tools to study effects of antiresorptive drugs like bisphosphonates to improve therapeutic strategies for treatment metastatic bone disease. No significant financial relationships to disclose.
Case 25-2019: A 41-Year-Old Pregnant Woman with Abdominal Pain
Authors: Noelle N. Saillant, Aoife Kilcoyne, Peter J. Fagenholz, Raymond Lui, Melissa Krystel-Whittemore
Journal: New England Journal of Medicine (2019)

A 41-year-old pregnant woman presented to the hospital at 36 weeks 3 days of gestation with abdominal pain of 15 hours' duration. The pain was in the right lower quadrant and was described as sharp and constant. Management decisions were made.
The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration
Authors: Masaki Uchida, Bernhard Maier, Hitesh Kumar Waghwani, Ekaterina Selivanovitch, S. Louise Pay, John Avera, EJun Yun, Ruben M. Sandoval, Bruce A. Molitoris, Amy Zollman, Trevor Douglas, Takashi Hato
Journal: Journal of Clinical Investigation (2019)

Nature exploits cage-like proteins for a variety of biological purposes, from molecular packaging and cargo delivery to catalysis. These cage-like proteins are of immense importance in nanomedicine due to their propensity to self-assemble from simple identical building blocks to highly ordered architecture and the design flexibility afforded by protein engineering. However, delivery of protein nanocages to the renal tubules remains a major challenge because of the glomerular filtration barrier, which effectively excludes conventional size nanocages. Here, we show that DNA-binding protein from starved cells (Dps) - the extremely small archaeal antioxidant nanocage - is able to cross the glomerular filtration barrier and is endocytosed by the renal proximal tubules. Using a model of endotoxemia, we present an example of the way in which proximal tubule-selective Dps nanocages can limit the degree of endotoxin-induced kidney injury. This was accomplished by amplifying the endogenous antioxidant property of Dps with addition of a dinuclear manganese cluster. Dps is the first-in-class protein cage nanoparticle that can be targeted to renal proximal tubules through glomerular filtration. In addition to its therapeutic potential, chemical and genetic engineering of Dps will offer a nanoplatform to advance our understanding of the physiology and pathophysiology of glomerular filtration and tubular endocytosis.
Immunolocalization of sperm protein 17 (Sp17) in normal and malignant cells
Authors: Jasmine P. Gaines, Zhana E. Muminova, Mandy Phillippi, Bradley K. Yoder, Denise R. Shaw, Theresa V. Strong
Journal: Cancer Research (2005)

5144  Sperm protein 17 (Sp17, gene SPA17) is a highly conserved, immunogenic protein expressed at low levels in normal somatic tissues and highly expressed in testis and a variety of malignant cells. Sp17 has been studied extensively in the context of mammalian sperm function. However, the function of Sp17 in normal somatic and malignant cells is poorly understood. We developed monoclonal antibodies specific for Sp17 and examined subcellular localization of the protein by immunocytochemistry and immunofluorescence. In normal tissues, immunofluorescent staining of mature sperm showed strong staining of Sp17 in the flagella. Sp17 staining was also strong in other normal ciliated cells, including ciliated epithelia cells of the fallopian tube and bronchus, suggesting a normal role for this protein in the function of motile cilia. Immunofluorescent analysis of Sp17 expression in an in vitro model of primary ciliogenesis, the renal tubule cell line mCCD, demonstrated localization of the protein in the basal bodies, suggesting a role for Sp17 in the function of primary, nonmotile cilia as well. Immunofluorescent studies of immortalized tumor cell lines demonstrated Sp17 localization to centrosomes. Tissue microarray analysis of breast and ovarian tumors demonstrated overexpression of Sp17 protein in the majority of tumor samples. Sp17 localized to the nucleus in most samples, with some samples exhibiting predominantly cytoplasmic staining. Localization of Sp17 to the centrosome has not been previously reported, and suggests a new role for this protein in normal somatic and malignant cells.
Comprehensive analysis of genetic alterations associated with androgen-resistant prostate cancer transformation using SKY, CGH and cDNA microarray
Authors: See-Tong Pang, Wen-Hui Weng, Björn Johansson, Mohammad R. Pourian, Amilcar Flores-Morales, Peter Nilsson, Birgitta Byström, Åke Pousette, Catharina Larsson, Gunnar Norstedt
Journal: Cancer Research (2004)

1703  Here, we characterized genetic alterations associated with transformation of the androgen sensitive prostate cancer cell line LNCaP-FGC into androgen resistant (LNCaP-r) using SKY, CGH and cDNA microarray. Karyotypically, several additional chromosomal aberrations were seen in LNCaP-r as compared to the parental line. CGH revealed unique net chromosomal alterations in LNCaP-r compared to LNCaP-FGC, including gain of 2p13-23, 2q21-32 and 13q; and loss of 6p22-pter. cDNA microarray anlaysis identified 2,534 transcripts that were differentially expressed in LNCaP-r compared to LNCaP-FGC, 1338 (53%) of which were upregulated and 1,196 (47%) that were downregulated in the androgen-resistant line, In silico analysis the gene expression data by comparative genomic microarray analysis (CGMA) predicted common cytogenetic changes as detected by CGH. Functional classification of the differentially expressed genes revealed a subset of apoptosis related genes such as TP53, BIN2, BIN3, BINL3 and PDCD4 were downregulation in LNCaP-r. Altered expression of apoptotic-regulatory genes may render prostate cancer cells the capability to withstand the detrimental effect caused by androgen ablation. In addition, genes involved in DNA methylation including DNMT2, DNMT3a, methyl-CpG binding domain protein 4 and 2 were upregulated in LNCaP-r. These deregulated genes may contribute to the epigenetic mechanisms that maybe responsible for the progression of prostate cancers. In conclusion, our findings have serves as a basis for molecular dissection of the mechanisms involved in androgen resistance transformation of prostate cancer.
Damp mouldy housing and early childhood hospital admissions for acute respiratory infection: a case control study
Authors: Tristram Ingham, Michael Keall, Bernadette Jones, Daniel R T Aldridge, Anthony C Dowell, Cheryl Davies, Julian Crane, Jessica Barbara Draper, Lauren Olivia Bailey, Helen Viggers, Thorsten Villiers Stanley, Philip Leadbitter, Mereana Latimer, Philippa Howden-Chapman
Journal: Thorax (2019)

Introduction A gap exists in the literature regarding dose–response associations of objectively assessed housing quality measures, particularly dampness and mould, with hospitalisation for acute respiratory infection (ARI) among children. Methods A prospective, unmatched case–control study was conducted in two paediatric wards and five general practice clinics in Wellington, New Zealand, over winter/spring 2011–2013. Children aged &lt;2 years who were hospitalised for ARI (cases), and either seen in general practice with ARI not requiring admission or for routine immunisation (controls) were included in the study. Objective housing quality was assessed by independent building assessors, with the assessors blinded to outcome status, using the Respiratory Hazard Index (RHI), a 13-item scale of household quality factors, including an 8-item damp–mould subscale. The main outcome was case–control status. Adjusted ORs (aORs) of the association of housing quality measures with case–control status were estimated, along with the population attributable risk of eliminating dampness–mould on hospitalisation for ARI among New Zealand children. Results 188 cases and 454 controls were studied. Higher levels of RHI were associated with elevated odds of hospitalisation (OR 1.11/unit increase (95% CI 1.01 to 1.21)), which weakened after adjustment for season, housing tenure, socioeconomic status and crowding (aOR 1.04/unit increase (95% CI 0.94 to 1.15)). The damp–mould index had a significant, adjusted dose–response relationship with ARI admission (aOR 1.15/unit increase (95% CI 1.02 to 1.30)). By addressing these harmful housing exposures, the rate of admission for ARI would be reduced by 19% or 1700 fewer admissions annually. Conclusions A dose–response relationship exists between housing quality measures, particularly dampness–mould, and young children’s ARI hospitalisation rates. Initiatives to improve housing quality and to reduce dampness–mould would have a large impact on ARI hospitalisation.
Quantitative RT-PCR analysing expression of gefitinib resistance related genes predicts clinical outcome of non-small cell lung cancer patients treated with gefitinib
Authors: S. Kakiuchi, S. Yano, H. Ogino, Y. Nakamura, T. Tsuruo, S. Sone
Journal: Journal of Clinical Oncology (2006)

7181 Background: Gefitinib, an inhibitor of epidermal growth factor receptor-tyrosine kinase, has shown favorable anti-tumor activity to a subset of patients with advanced non-small cell lung cancer (NSCLC). However, gefitinib failed to significantly prolong survival in comparison to placebo in unselected population. Consequently, selection of patients who will benefit from this treatment is clinically important. In the previous study, we identified gefitinib-resistance related genes (GRRGs) by cDNA microarray analyses and reported that the responsiveness of individual patients with NSCLC to gefitinib could be predicted by expression of GRRGs. The goal of this study is to establish clinically adoptive prediction system of clinical outcome of NSCLC patients treated by gefitinib. Methods: Tumors from 30 NSCLC patients treated daily with 250mg of gefitinib were evaluated for the expression of GRRGs by quantitative RT-PCR. Gefitinib response score (GRS) reflecting gene expression was calculated based on weighted vote method and this numerical scoring system was validated by leave-one-out approach and independent test cases. Results: The sensitivity of 15 learning cases (five partial response (PR) cases and 10 progressive disease (PD) cases) were predicted by leave-one-out cross validation with 93.3% (14/15) accuracy. This numerical scoring system correctly predicted responses to the drug in all of nine additional test cases (three PR cases and six PD cases). Notably, this system also could predict two stable disease (SD) cases who successfully controlled by gefitinib more than four months as responder. On the other hand, four patients who had been judged as SD but showed progression of the disease within three months were judged as non-responders. Moreover, gefitinib-treated patients with good signature had a statistically significant improvement in time to progression, and survival compared with patients with bad signature (13.0 vs 1.7 months, P &lt; .0001; 27.7 vs 6.6 months, P = .0007, respectively). Conclusions: Our results suggest that clinical outcome of NSCLC patients treated with gefitinib could be predicted by expression levels of GRRGs determined by quantitative RT-PCR analyses. No significant financial relationships to disclose.
Big Data, Big Tech, and Protecting Patient Privacy
Authors: I. Glenn Cohen, Michelle M. Mello
Journal: JAMA (2019)

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