tbuckley/cabot-search huggingface dataset:
Development of a gene expression companion diagnostic assay on the COBAS® TaqMan 48 Analyzer using RNA extracted from FFPE tissue
Authors: Kiran Malhotra, Jocelyn Lee, Howard Lan, Janine Cooc, Kathleen Danenberg, Helen Wu
Journal: Clinical Cancer Research (2007)

A28  Roche Molecular Systems has developed a real-time RT-PCR gene expression test to select patients for treatment with a cancer immunotherapeutic developed by an external pharmaceutical company. This test will be used for patient selection during a Phase III clinical trial. In collaboration with Response Genetics Incorporated, and the external pharmaceutical company, we have developed a potential IVD companion diagnostic test to be used for the measurement of relative gene expression of the biomarker of interest in RNA extracted from formalin-fixed paraffin embedded tumor tissues. Extraction of quality RNA (genomic DNA free) from FFPE tissue has proven to be challenging due to cross-linking of proteins and nucleotides during the formalin fixation process. In order to address the challenge of RNA specific expression, we report here the development of an improved protocol for total RNA extraction using RNeasy® FFPE Kit (Qiagen) along with a method to measure genomic DNA on the COBAS® TaqMan 48 Analyzer.  Analytical performance of this RT-PCR assay was established by linearity, exclusivity, limit of detection, reproducibility and method correlation studies. Linearity studies using 2-fold serial dilutions (100 -0.39 ng) of total RNA extracted from FFPE Xenograft demonstrated R² values of ≥ 0.95 for both biomarker of interest and housekeeping gene. Exclusive amplification of biomarker of interest was shown by testing plasmids from 9 highly homologous gene family members. Limit of detection for RNA was established as 50 ng, where gene expression was measured greater than 95% of time in a mixture of 1% RNA expressing the biomarker of interest in a background of non-expressing RNA. Assay reproducibility was assessed by comparing the correlation of gene expression between 2 runs using 12 manually micro dissected FFPE lung specimens, different operators, instruments, and reagents lots. There was 100% correlation between all specimens for all replicates tested within run and run to run. Pearson Correlation comparing gene expression between the 2 different runs was R= 0.987. Method correlation with a prototype assay demonstrated percent agreement of 91.6%.  The current results indicate that we have developed a total RNA extraction method from FFPE tissue and a robust multiplex real time RT-PCR assay for the measurement of a specific biomarker on the COBAS® TaqMan 48 Analyzer to meet the needs of a Phase III clinical trial and for possible Companion Diagnostics IVD applications.
Community Practice Implementation of a Self-administered Version of PREMM1,2,6 to Assess Risk for Lynch Syndrome
Authors: Daniel G. Luba, James A. DiSario, Colleen Rock, Devki Saraiya, Kelsey Moyes, Krystal Brown, Kristen Rushton, Maydeen M. Ogara, Mona Raphael, Dayna Zimmerman, Kimmie Garrido, Evelyn Silguero, Jonathan Nelson, Matthew B. Yurgelun, Fay Kastrinos, Richard J. Wenstrup, Sapna Syngal
Journal: Clinical Gastroenterology and Hepatology (2017)
Global Dosage Compensation Is Ubiquitous in Lepidoptera, but Counteracted by the Masculinization of the Z Chromosome
Authors: Ann Kathrin Huylmans, Ariana Macon, Beatriz Vicoso
Journal: Molecular Biology and Evolution (2017)

While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera.
Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin Nephropathy
Authors: Nao Uchida, Yoshihiro Kushida, Masaaki Kitada, Shohei Wakao, Naonori Kumagai, Yasumasa Kuroda, Yoshiaki Kondo, Yukari Hirohara, Shigeo Kure, Gregorio Chazenbalk, Mari Dezawa
Journal: Journal of the American Society of Nephrology (2017)

Multilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow–derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively). In FSGS-SCID mice, human Muse cells preferentially integrated into the damaged glomeruli and spontaneously differentiated into cells expressing markers of podocytes (podocin; 31%), mesangial cells (megsin; 13%), and endothelial cells (CD31; 41%) without fusing to the host cells; attenuated glomerular sclerosis and interstitial fibrosis; and induced the recovery of creatinine clearance at 7 weeks. Human Muse cells induced similar effects in FSGS-BALB/c mice at 5 weeks, despite xenotransplant without concurrent immunosuppressant administration, and led to improvement in urine protein, creatinine clearance, and plasma creatinine levels more impressive than that in the FSGS-SCID mice at 5 weeks. However, functional recovery in FSGS-BALB/c mice was impaired at 7 weeks due to immunorejection, suggesting the importance of Muse cell survival as glomerular cells in the FSGS kidney for tissue repair and functional recovery. In conclusion, Muse cells are unique reparative stem cells that preferentially home to damaged glomeruli and spontaneously differentiate into glomerular cells after systemic administration. Introduction of genes to induce differentiation is not required before Muse cell administration; thus, Muse cells may be a feasible therapeutic strategy in FSGS.
Results of an Early Access Treatment Protocol (EAP) of Daratumumab in United States Patients with Relapsed or Refractory Multiple Myeloma
Authors: Ajai Chari, Tomer M Mark, Amrita Krishnan, Keith Stockerl-Goldstein, Saad Z Usmani, Anil Londhe, Delores Etheredge, Hollee Parros, Sarah Fleming, Baolian Liu, Scott Freeman, Jon Ukropec, Thomas Lin, Sagar Lonial
Journal: Blood (2016)
Consensus conference. Perioperative red blood cell transfusion
Journal: JAMA (1988)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inhibition of RNA polymerase II allows controlled mobilisation of retrotransposons for plant breeding
Authors: Michael Thieme, Sophie Lanciano, Sandrine Balzergue, Nicolas Daccord, Marie Mirouze, Etienne Bucher
Journal: Genome biology (2017)

Retrotransposons play a central role in plant evolution and could be a powerful endogenous source of genetic and epigenetic variability for crop breeding. To ensure genome integrity several silencing mechanisms have evolved to repress retrotransposon mobility. Even though retrotransposons fully depend on transcriptional activity of the host RNA polymerase II (Pol II) for their mobility, it was so far unclear whether Pol II is directly involved in repressing their activity. Here we show that plants defective in Pol II activity lose DNA methylation at repeat sequences and produce more extrachromosomal retrotransposon DNA upon stress in Arabidopsis and rice. We demonstrate that combined inhibition of both DNA methylation and Pol II activity leads to a strong stress-dependent mobilization of the heat responsive ONSEN retrotransposon in Arabidopsis seedlings. The progenies of these treated plants contain up to 75 new ONSEN insertions in their genome which are stably inherited over three generations of selfing. Repeated application of heat stress in progeny plants containing increased numbers of ONSEN copies does not result in increased activation of this transposon compared to control lines. Progenies with additional ONSEN copies show a broad panel of environment-dependent phenotypic diversity. We demonstrate that Pol II acts at the root of transposon silencing. This is important because it suggests that Pol II can regulate the speed of plant evolution by fine-tuning the amplitude of transposon mobility. Our findings show that it is now possible to study induced transposon bursts in plants and unlock their use to induce epigenetic and genetic diversity for crop breeding.
Effect of roflumilast in patients with severe COPD and a history of hospitalisation
Authors: Klaus F. Rabe, Peter M.A. Calverley, Fernando J. Martinez, Leonardo M. Fabbri
Journal: European Respiratory Journal (2017)

Exacerbations of chronic obstructive pulmonary disease (COPD) are acute events characterised by a worsening of respiratory symptoms that necessitates a change in medication and/or hospital admission [1]. Severe exacerbations (those resulting in hospitalisation and/or death) are associated with a poor prognosis [2], decreased quality of life [3] and higher mortality [2, 4]. Roflumilast is a once-daily, oral, selective phosphodiesterase-4 inhibitor that targets both the systemic and pulmonary inflammation associated with COPD [5]. Previous studies have shown that roflumilast as an add-on to inhaled therapies reduces COPD exacerbations in patients with severe COPD who have chronic bronchitis and a history of exacerbations [6–9]. However, the adverse events associated with systemic therapies such as roflumilast necessitate that these therapies are used to treat specific patient populations in whom they are likely to have the greatest clinical benefit [10]. Roflumilast provides greater therapeutic benefit in severe COPD patients with a hospitalisation in the prior year <http://ow.ly/lzWy30bNBd4> We thank Alexis Pashiardis (Synergy Vision, London, UK; supported by AstraZeneca) for writing and editorial assistance with the preparation of this research letter. These results were presented at the European Respiratory Society International Congress in 2015.
EMILIN2, extracellular matrix protein, as a regulator of the myeloid response in a model of inflammation-induced colon carcinogenesis
Authors: Renato Cannizzaro, Eva Andreuzzi, Giulia Tarticchio, Alice Paulitti, Stefano Marastoni, Rosanna Pellicani, Emma Di Carlo, Raffaella Magris, Stefania Maiero, Mara Fornasarig, Alfonso Colombatti, Maurizio Mongiat
Journal: Annals of Oncology (2017)
Successful ERCP through an endoscopic ultrasound-guided gastrojejunostomy
Authors: Olaya Brewer Gutierrez, Majidah Bukhari, Yen Chen, Omid Sanaei, Mouen Khashab
Journal: Endoscopy (2017)

A 68-year-old man with a history of primary sclerosing cholangitis and hilar cholangiocarcinoma had presented with biliary obstruction and had undergone endoscopic retrograde cholangiopancreatography (ERCP) with stricture dilation and main right/left intrahepatic duct stent placement (7-Fr × 12-cm). Some months after diagnosis, the patient had developed gastric outlet obstruction due to proximal duodenal infiltration by the primary tumor, and a gastrojejunostomy with a 15 × 10-mm lumen-apposing metal stent (LAMS) had been successfully created using endoscopic ultrasound (EUS) guidance.
Children as Partners for Health: A Critical Review of the Child-to-Child Approach
Authors: Haroon Saloojee
Journal: BMJ (2001)

Pat Pridmore, David Stephens 

Zed Books, £14.95, pp 194

ISBN 1 85649 636 8

Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] 

“Children should be seen and not heard” is an old adage, probably first uttered as an exasperated last stand by an adult frustrated by the unbridled exuberance of a child. Now like-minded adults have to grudgingly acknowledge that the battle may be lost forever as children triumphantly raise Article 12 of the Convention on the Rights of the Child as their victory flag, with its proclamation that children must be given a voice and their views and opinions …

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Use of PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Sarcomas
Authors: Maud Toulmonde, Nicolas Penel, Julien Adam, Christine Chevreau, Jean-Yves Blay, Axel Le Cesne, Emmanuelle Bompas, Sophie Piperno-Neumann, Sophie Cousin, Thomas Grellety, Thomas Ryckewaert, Alban Bessede, François Ghiringhelli, Marina Pulido, Antoine Italiano
Journal: JAMA Oncology (2017)

There is a strong rationale for treating sarcomas with immunotherapy.
Impact of Self-Reported Pre-Transplant Quality of Life (QOL) on Long-Term Survival after Allogeneic or Autologous Hematopoietic Cell Transplantation (HCT)
Authors: F. Lennie Wong, Jennifer Berano-Teh, Liton F. Francisco, Aida Siyahian, Liezl Atencio, Alicia Gonzales, Saro Armenian, Stephen J. Forman, Smita Bhatia
Journal: Blood (2016)
Circulating tumor cells (CTCs) in patients (pts) with small cell lung cancer (SCLC) as a marker of disease burden and therapeutic response, and predictor of disease relapse.
Authors: Anjana Ranganathan, Daniel Schwed-Lustgarten, Charu Aggarwal, Lynn Werner, Drew A. Torigian, Andrea B. Troxel, Tracey L. Evans, James Stevenson, Roger B. Cohen, Bhavesh Vaidya, Chandra Rao, Mark C. Connelly, Steven Albelda, Corey J. Langer
Journal: Journal of Clinical Oncology (2012)

7092 Background: Currently there are no validated biomarkers for assessment or prediction of disease burden or activity in SCLC. Enumeration of CTCs by CellSearch is FDA approved, highly reproducible and validated in other malignancies. Application as a prognostic and predictive marker in SCLC is limited due to a lack of studies documenting serial monitoring in pts on therapy. Methods: We are conducting a prospective study serially enumerating CTCs in pts with newly diagnosed SCLC. CTC number (per 7.5 ml peripheral blood) and percentage of CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining respectively, are being assessed prior to initiation of chemotherapy, during each cycle and at relapse. We are correlating CTC number with disease stage, number of metastatic sites, response to therapy, and time to progression (TTP). Results: 21 SCLC pts are evaluable. 9 pts with limited disease (LD) had median baseline CTC value of 1 (0-8); only 2 of 9 pts had &gt;5 CTCs. 12 pts with extensive disease (ED) had median baseline CTC value of 80.5 (0-37780); 8 of 12 pts had &gt;5 detectable CTCs (p value 0.02). Amongst the 12 pts with ED, median baseline CTC count was higher in pts with ≥3 (n=3) compared to 1-2 sites of metastatic disease (n=9) (2668 vs 71; p value 0.52). Median percentage of CTCs positive for γH2AX and M30 was also higher for pts with ≥3 compared to 1-2 metastatic sites (83, 164.5 vs. 2, 7.5) (p-value 0.40, 0.69). Serial CTC data are available on 3 pts with ED; all had responsive disease and reduction in CTC number to 0-1 after 2 cycles of chemotherapy. As this protocol is ongoing, correlation of CTCs with updated response status and TTP will be presented at the ASCO meeting. Conclusions: CTCs can be isolated and serially enumerated in pts with SCLC. Baseline CTCs correlate directly with disease stage. In pts with ≥ 3 metastatic sites, baseline CTCs tend to be greater and show higher levels of DNA damage and apoptosis compared to those with 1-2 metastatic sites. Reduction in CTCs is associated with radiographic response to therapy. Correlation between absolute number at baseline and TTP is not yet known.
Parallel Gene and Protein Expression Analysis of the Immune Response to Major Surgery in Oesophageal Cancer Patients Treated with Surgery Alone or a Multimodality Regimen
Authors: JO Murphy, N Miller, A Ryan, A Murphy, N Ravi, JV Reynolds
Journal: Endoscopy (2006)

Introduction: A multimodality treatment approach is increasingly utilised in gastrointestinal cancer, however its impact on the immune response to surgery is unclear. This study examined postoperative protein production and gene expression of inflammatory cytokines in oesophageal cancer patients receiving neoadjuvant chemoradiotherapy or surgery alone.
Sport-related concussion physician’s chart review – 2011–2016
Authors: James D Carson, Sari A Kraft, Nariko Kuwahara, Lovisa Cheung, Qurat-ul-Ain Mansoora, Aliya Safwan, Vijitha Jegatheesan, Mariam Mubarik, Mena Kirloss, Julie Chiu, Rahim Moineddin, Pierre Fremont
Journal: British Journal of Sports Medicine (2017)

Objective To determine what proportion of patients experience an exacerbation of their symptoms as a result of premature return to play (RTP) and return to learn (RTL) following a sport-related concussion (SRC). Design Retrospective longitudinal chart review. Setting A sport medicine physician’s office in Ontario, Canada. Participants 266 cases related to 251 students with an SRC. Interventions A review of 266 electronic medical records (charts) of patients seen for SRC over a five-year period (2011–2016). Two blinded authors independently reviewed each chart and SCAT2 or SCAT3/Child SCAT3 symptom self report form. In situations where there was discrepancy between the two reviewers’ results, a third author reviewed the charts. Outcome measures remature RTP and RTL were defined as chart records documenting the recurrence or worsening of symptoms that accompanied the patients’ RTP or RTL. Main Results 403 cases were identified as concussion patients assessed. 266 were included as these cases were related to 251 students involved in a sport activity. Premature return to sport and to school were observed in 67 (25.19%) and 107 (40.23%) of the cases, respectively. Conclusions In our comparable study ending 5 years prior, premature return to sport and to school were observed in 43.5% and 44.7% of the cases, respectively. Despite changing our medical advice, based upon evolving expert recommendations on return to learn (RTL) after an SRC, premature RTL is still quite common. Efforts are needed to find the best method of implementing a coordinated plan for the post-concussion athlete who is returning to school. Competing interests None.
Antiangiogenic effects of a novel HIV-1 nef cytotoxic peptide on the growth of primary and metastatic colorectal cancer
Authors: Harvey L. Bumpers, Ming-Bo Huang, William Grizzle, Joel Okoli, Michael Powell, James Lillard, Vincent C. Bond
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

52 

Introduction: The chemokine receptor, CXCR-4 and its ligand, SDF-1 α, have been shown to be involved in angiogenesis and metastasis, and have been suggested to be a potential target for cancer therapeutics. HIV-1 Nef peptides have been shown to have a significant inhibitory effect on vascular endothelium. The SCID mouse serves as an excellent vessel to propagate human colorectal cancer and evaluate the effects of this cytotoxic viral protein, Nef, on its in vivo growth. Methods: Fresh surgical specimens of colorectal cancer were implanted in the subcutaneous tissue or gonad fat pad of SCID mice. The mice were injected intraperitoneally with the standard Nef at doses of 2 mcg biweekly. Injections were started at the time of tumor implantation or one week after implantation. Volumetric measurements and weights were taken weekly. Controls were injected with buffer, Nef (with a scrambled amino acid sequence), or no treatment at all. All experimental groups consisted of 5 mice. Xenografts were taken from each group of mice, treated with CD 31 monoclonal antibody, and stained with dapi to identify vascular endothelium. Similar specimens were also stained with hematoxylin and eosin for light microscopic assessment of vascularity. Results: All mice were sacrificed one month after tumor implantation. Tumor growth was significantly inhibited, by 50-65%, in those mice receiving standard Nef peptide. Vessel density as demonstrated by anti-CD 31 monoclonal antibodies was found to be significantly decreased in the Nef-treated group as compared to the controls. The differences in staining intensity was quantitated and found to be greater in all 3 control groups when compared to the Nef-treated groups. Conclusions: HIV-1 Nef cytotoxic peptide inhibits neovascularization as one of it’s mechanism in the cytotoxicity of human colorectal cancer xenografts in SCID mice. Nef demonstrated an ability to inhibit colorectal cancer angiogenesis even when the tumors were allowed implant and invade for a week prior to treatment.