tbuckley/cabot-search huggingface dataset:
Antitumor effect of biochemical defense modifier Antineoplaston AS2-1 against colon cacer through G1 and G2 cell arrest
Authors: Matono Keiko
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2976 

Introduction: Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine, were first described by Burzynski in 1976. The small peptides reportedly control neoplastic growth and have minimum adverse effects. However, the molecular mechanisms of the antitumor effects are not well known. In the present study, we have investigated antitumor mechanisms of Antineoplaston AS2-1 against colon cancer cells with regard to cell cycle. Methods: We tested Antineoplaston AS2-1 on in vitro and in vivo cell growth activity in human colon cancer cells (KM12SM, SW620, SW1417, Colo205, HCT116). And we analyzed cell cycle by FACS and expression of cell cycle regulators by western blot. Results: Antineoplaston AS2-1 inhibited proliferation of all human colon cancer cells in a dose and a time dependent manner in vitro. Antineoplaston AS2-1 inhibited tumor growth of nude mice implanted by human colon cancer cells KM12SM and HCT116 in a dose and a time dependent manner in vivo. We demonstrated G1 cell arrest in short time treatment with AS2-1. However, by treatment with high dosage (5mg/ml) of AS2-1 for long time(3 days) the cell cycle analysis showed increase of the G2 phase cells. The protein levels of cyclin-dependent kinase (cdk)-2, cyclin E, cdk-4, cyclin D in the colon cancer cells significantly decreased and the level of p16 and p21 increased time and dose dependently with antineoplaston AS2-1 treatment. And antineoplaston AS2-1 decreased the level of phosphorylated retinoblastoma protein. The protein levels of cyclin A, cdc2, cyclinB1 which can control G2 phase were decreased by high dose and long term treatment with AS2-1. We confirmed that these results did not come from glutamine deficiency. We have further investigated influence on methylation status and induction of apoptosis by treatment with AS2-1. Conclusion: Antineoplaston AS2-1 shows antitumor effects against colon cancer through both the G1 and G2 cell arrests and we have applied the antineoplaston AS2-1 as an adjuvant therapy after hepatic resection of colorectal metastases in combination with hepatic arterial infusion chemotherapy.
Abstract 16379: DNA Methylation Profiling Identifies Novel Epigenetic Markers of Cardiovascular Events
Authors: Svati H Shah, Lydia C Kwee, Elizabeth A Grass, William E Kraus, Simon G Gregory
Journal: Circulation (2014)

Objectives: Considerable effort has been made in identifying the genetic underpinnings of cardiovascular disease (CVD), including cardiovascular events. However, DNA variation does not fully account for all heritable factors of CVD risk or early mortality. DNA methylation is a non-DNA sequence-based, heritable form of gene regulation that plays a role in CVD. To identify the role of epigenetic variation in CVD we performed DNA methylation profiling in a CVD cohort (CATHGEN).

Methods: The study population included individuals from the CATHGEN biorepository referred for cardiac catheterization for concern of ischemic heart disease. Cases were defined as individuals who died >580 days (N=62) after index cath. and controls were alive and without any CVD events for >1700 days (N=49) after index cath. We used Illumina’s HumanMethylation450 array to profile the methylation status of 485,000 CpG dinucleotides. After QC, preprocessing, normalization, and removal of cross-reactive probes, we logit-transformed the resulting β-values of the remaining 445,323 probes. We tested for association between methylation and case-control status using a linear model, adjusting for age, race, sex, row and chip. Follow-up was based either on the resulting p-value for association between methylation and case-control status (p>0.001, n=1438 probes), or a threshold for the difference between average methylation status in cases and controls (
Subcutaneous Campath1H instead of thymoglobulin in nonmyeloablative allogeneic transplantation : Reduced acute toxicity, but delayed lymphocyte recovery leading to more mixed chimerism, more fatal infections and impaired long-term survival
Authors: Gunnar Juliusson, K Karlsson, U Frodin, G Backstrom, Claes Malm
Journal: Blood (2002)
Bristol case surgeon claimed to have been on "learning curve"
Authors: Clare Dyer
Journal: BMJ (1999)

One of the two surgeons at the centre of the Bristol heart surgery scandal, in the United Kingdom, told the public inquiry this week that a high death rate was inevitable while surgeons were on a “learning curve” for a new operation.

Janardan Dhasmana, speaking publicly for the first time since the General Medical Council found him guilty of serious professional misconduct last year, said: “Whenever you start any new operation you are bound to have, unfortunately, high mortality.” There was always a possibility that a child would die who could have survived if sent elsewhere. “Unfortunately, at that time there were no clear guidelines. Every surgeon was doing …
Emotional wellbeing and its relation to health
Authors: S. Stewart-Brown
Journal: BMJ (1998)

In 1947 the World Health Organisation defined health as “a state of complete physical, mental and social wellbeing.”1 Until now the NHS has given precedence to promoting physical wellbeing, but the green paper Our Healthier Nation signals that this may need to change.2 It emphasises the importance of emotional wellbeing for health: indeed, health is defined as “being confident and positive and able to cope with the ups and downs of life.” These statements are supported by an increasing body of epidemiological, social science, and experimental research that is beginning to suggest that initiatives which aim to promote physical wellbeing to the exclusion of mental and social wellbeing may be doomed to failure.

The concept of mental and social wellbeing is less well defined than that of physical wellbeing. Debate still continues about the meaning of the term mental health. A recent study in Scotland showed that lay people were more comfortable with the …
APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral immunity
Authors: Gang Yu, Tom Boone, John Delaney, Nessa Hawkins, Michael Kelley, Meena Ramakrishnan, Susan McCabe, Wan-rong Qiu, Masayo Kornuc, Xing-Zhong Xia, Jane Guo, Marina Stolina, William J. Boyle, Ildiko Sarosi, Hailing Hsu, Giorgio Senaldi, Lars E. Theill
Journal: Nature Immunology (2000)
Highlights in Antiviral Drug Research: Antivirals at the Horizon
Authors: Erik De Clercq
Journal: Medicinal Research Reviews (2012)

Abstract This review highlights ten “hot topics” in current antiviral research: (i) new nucleoside derivatives (i.e., PSI ‐352938) showing high potential as a direct antiviral against hepatitis C virus ( HCV ); (ii) cyclopropavir, which should be further pursued for treatment of human cytomegalovirus ( HCMV ) infections; (iii) North ‐methanocarbathymidine ( N ‐ MCT ), with a N ‐locked conformation, showing promising activity against both α‐ and γ‐herpesviruses; (iv) CMX 001, an orally bioavailable prodrug of cidofovir with broad‐spectrum activity against DNA viruses, including polyoma, adeno, herpes, and pox; (v) favipiravir, which is primarily pursued for the treatment of influenza virus infections, but also inhibits the replication of other RNA viruses, particularly (‐) RNA viruses such as arena, bunya, and hanta; (vi) newly emerging antiarenaviral compounds which should be more effective (and less toxic) than the ubiquitously used ribavirin; (vii) antipicornavirus agents in clinical development (pleconaril, BTA ‐798, and V ‐073); (viii) natural products receiving increased attention as potential antiviral drugs; (ix) antivirals such as U 0126 targeted at specific cellular kinase pathways [i.e., mitogen extracellular kinase ( MEK )], showing activity against influenza and other viruses; and (x) two structurally unrelated compounds (i.e., LJ ‐001 and d UY 11) with broad‐spectrum activity against virtually all enveloped RNA and DNA viruses. © 2012 Wiley Periodicals, Inc. Med. Res. Rev., 00, No. 0, 1–34, 2012
Abstract 12126: Sirt7 Regulates Tgfb Signaling by Modulating Autophagy
Authors: Satoshi Araki, Yasuhiro Izumiya, Shinsuke Hanatani, Yuichi Kimura, Yoshiro Onoue, Thomas Braun, Eva Bober, Hisao Ogawa
Journal: Circulation (2014)

Introduction: Sirt7 is a NAD-dependent histon deacetylase. Recent study shows Sirt7 modulates cancer progression by modulating oncogenic gene expression. However, the role of Sirt7 remains unclear in wound healing processes. Hypothesis: Sirt7 contributes to proper wound healing processes after myocardial infarction (MI) by modulating fibrosis. Methods: MI were created in Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Sirt7 knockdown experiments by using siRNA were performed with rat neonatal cardiac fibroblast. Results: Sirt7 mRNA expression was increased at 1, 3 and 14 days after MI in the myocardium of border zone (BZ). Histological analysis revealed that Sirt7 protein increased in the fibrosis area of BZ at 3 days after MI. Sirt7-/- mice were susceptibility to cardiac rupture within 1 week after MI despite no change of cardiac function between WT and Sirt7-/- mice. Interstitial fibrosis and α-SMA positive myofibroblast in BZ was decreased in Sirt7-/- mice at 3 days after MI. In cardiac fibroblast,...
Abstract 3035: Cripto/GRP78 signaling promotes the stem cell phenotype in normal and neoplastic mammary epithelial cells
Authors: Benjamin T. Spike, Jonathan A. Kelber, Evan Booker, Madhuri Kalathur, Rose Rodewald, Julia Lipianskaya, Justin La, Marielle He, Tracy Wright, Richard Klemke, Geoffrey Wahl, Peter C. Gray
Journal: Cancer Research (2014)

Abstract Microenvironmental factors are critical regulators of stem cell and tumor cell behavior. However, few stem cell factors have been identified and targeted in breast and other cancers. Using a highly enriched stem cell pool isolated from fetal mammary rudiments and single cell analyses, we have identified the onco-fetal protein Cripto as a potent soluble factor that regulates the mammary stem cell state. Cripto is a GPI-anchored/secreted signaling protein and a known regulator of PI3K/AKT and TGF-beta pathways. Here, we develop a novel Cripto antagonist, ALK4L75A-Fc, which selectively blocks the growth factor-like effects of soluble Cripto. We show that this antagonist promotes the differentiation of mammary stem cells cultured ex vivo while Cripto treatment maintains the stem cell phenotype and yields colonies with enhanced mammary gland reconstitution capacity. We previously discovered that Cripto signaling requires binding to cell surface Glucose Response Protein 78kDa (GRP78). GRP78 is an HSP70 family member that is induced by stresses including hypoxia and glucose deprivation and it is highly expressed in tumors where these conditions prevail. We show here that cell surface GRP78 marks fetal mouse mammary stem cells and a population of bipotent adult mammary epithelial cells that are selectively responsive to soluble Cripto in vitro. GRP78high mammary epithelial cells also harbor substantially higher stem cell activity upon transplantation than GRP78low cells. Consistently, we further show that deletion of GRP78 from adult mammary epithelial cells ex vivo blocks mammary gland reconstitution. Finally, we find that Cripto antagonism with ALK4L75A-Fc inhibits the proliferation of triple negative breast cancer cell lines in vitro and that this antagonist can also inhibit tumor growth in vivo. Since Cripto and GRP78 are both induced by hypoxia and other stressful conditions found in tumors, our data raise the possibility that Cripto/GRP78 signaling may exacerbate breast and other cancers by increasing the number of stem cell-like tumor cells in tumor microenvironments where these conditions predominate. Citation Format: Benjamin T. Spike, Jonathan A. Kelber, Evan Booker, Madhuri Kalathur, Rose Rodewald, Julia Lipianskaya, Justin La, Marielle He, Tracy Wright, Richard Klemke, Geoffrey Wahl, Peter C. Gray. Cripto/GRP78 signaling promotes the stem cell phenotype in normal and neoplastic mammary epithelial cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3035. doi:10.1158/1538-7445.AM2014-3035
Abstract 3658: 90K attenuates the development of colitis-associated colorectal tumors through negative regulation of intestinal epithelial Toll-like receptor 4
Authors: Ik-Joo Chung, Jun-Eul Hwang, Ji-Hee Lee
Journal: Cancer Research (2014)

Abstract Background: Inflammation is a risk factor for colon cancer. TLR4 expression is upregulated in almost all colitis-associated cancer and dysplasia. The molecular mechanisms linking inflammation and colon carcinogenesis are incompletely understood. We found that tumor associated antigen 90K antagonized TLR4/NF-kB signaling pathway in colon cancer cells. We hypothesized that 90K is involved in TLR4 expression in colitis-induced colon carcinogenesis. Methods: The effect of 90K against TLR4 was analysed by cell cultures, NF-kB reporter assay, and immunoprecipitation. C57BL/6 mice were treated with 3% dextran sodium sulfate (DSS) for acute colitis model. Colitis was assessed by disease activity index (DAI) including weight loss, stool consistency and rectal bleeding, and histopathology. Results: 90K interacts with TLR4, suppresses the NF-kB signal in the MYD88-dependent pathway that is major adaptor molecules in TLRs/NF-kB signal. Adenoviral 90K administration attenuated the severity of acute DSS-induced colitis as assessed by DAI and histopathologic scoring compared with the control group. 90K restored body weight loss and the severity of acute DSS colitis through the suppression of TLR4/MYD88/NF-kB signal. Conclusions: Tumor associated antigen 90K is involved in negative regulation of inflammatory signaling triggered by TLR4-induced NF-kB activation. The data suggest that 90K might thereby suppress proliferation and progression of colon cancers. Citation Format: Ik-Joo Chung, Jun-Eul Hwang, Ji-Hee Lee. 90K attenuates the development of colitis-associated colorectal tumors through negative regulation of intestinal epithelial Toll-like receptor 4. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3658. doi:10.1158/1538-7445.AM2014-3658
Abstract 19883: Use of Digoxin and Risk of Death or Readmission for Heart Failure: A Nationwide Propensity-score Matched Study
Authors: Christian Madelaire, Morten Schou, Christian Torp-Pedersen, Finn Gustafsson, Lars Køber, Gunnar H Gislason
Journal: Circulation (2014)

Background:  Digoxin is widely used as symptomatic treatment of patients with chronic heart failure (HF) to prevent readmissions and reduce symptoms in patients with severe HF. However, its role in modern treatment of HF with sinus rhythm is debatable. We investigated risk of death and a hospital readmission in a nationwide cohort of patients with chronic HF and sinus rhythm according to use of digoxin.   Methods:  From the Danish National Patient Registry, we identified all patients with HF 1996-2011 alive 30 days after discharge and subsequent use of digoxin after discharge. Patients with atrial fibrillation were excluded. Patients were classified into 4 severity groups according to loop-diuretic dosage. Propensity-score matched Cox regression models were used to analyze risk of death or readmission for HF.   Results:  The study population comprised 10,403 HF patients using digoxin and 20,806 propensity-score matched controls without use of digoxin. During 5 year follow-up 21,572 patients died and 27,879 were readmitted for HF. Use of digoxin was associated with an increased risk of death, Hazard Ratio (HR) 1.26 (95% CI 1.23-1.30, P   Conclusion:  In chronic HF with sinus rhythm, treatment with digoxin was associated with an increased risk of death and use of digoxin only prevented a readmission for HF in patients requiring high doses of loop diuretics.
5-Hydroxytryptophan-induced cortisol response and CSF 5-HIAA in depressed patients
Authors: Koyama T, Lowy Mt, Meltzer Hy
Journal: American Journal of Psychiatry (1987)

To determine if the enhanced cortisol response to oral administration of the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) that has been reported in unmedicated depressed and manic patients might be related to brain monoaminergic metabolism, the authors assessed correlations between 5-HTP-induced cortisol response and CSF in nine depressed patients. They found a significant negative correlation with CSF levels of 5-hydroxyindoleacetic acid, a 5-HT metabolite, but not with CSF levels of other monoamine metabolites. This finding is consistent with the hypothesis that low presynaptic brain serotonergic activity may be related to enhanced cortisol response to 5-HTP in depressed patients.
Elder abuse
Authors: A. Tonks, G. Bennett
Journal: BMJ (1999)

Two incidents last week brought elder abuse into the public eye: a community trust in London reported that three staff had been sacked (and others disciplined) for physically abusing the elderly people in one of their homes, Beech House, and Lucille McLauchlan, the nurse imprisoned in Saudi Arabia for murder, was convicted of stealing money from a 79 year old patient when she was a nurse in Dundee. The mistreatment at Beech House included slapping, cold baths, verbal threats, intimidation, withholding drinks, and tying patients up. No one doubts that elderly people can be abused by their carers, but despite a series of high profile cases over the past 30 years, 1 2 elder abuse is not widely accepted as a social or medical problem.

The Beech House inquiry exposed ignorance, denial, poor management, low morale, and inadequate training—a litany that defines any poor quality enterprise. These failures still occur because the messages from repeated institutional …
Abstract 1519: Targeted enrichment and next generation sequencing of non-small cell lung carcinoma FFPE samples
Authors: Rusla du Breuil, Tatiana Shvetsova, Kruti Patel, Troy Moore, Gwen Fewell
Journal: Cancer Research (2014)

Abstract Targeted enrichment is a powerful tool used for identifying genetic variations that underlie cancer and complex diseases. Current methodologies utilize hybridization probes or PCR to enrich for protein coding regions of a genome followed by deep sequencing. Most of these targeting methods fail to achieve the specificity, coverage and uniformity that are critical for accurate detection and analysis of genetic variability. Nested Patch PCR™ was developed to overcome these pitfalls with highly specific on-target sequence interrogation across hundreds of genomic regions in a single-tube format. This novel technology enables rapid detection of various genetic variations (i.e. SNPs, indels) across a large number of samples, including FFPE (formalin-fixed paraffin embedded) samples which are typically difficult to analyze due to low yield and quality of DNA. To show the utility of TargetRich technology, an enrichment panel was designed targeting NRAS, PTEN, KRAS, ALK, PIK3CA, KIT, BRAF and EGFR to interrogate 250 non-small cell lung carcinoma FFPE samples. The panel was designed against 19.8kb, 134 exons, with 99.9% coverage. A minimum of 50ng FFPE DNA were run for each sample on an Illumina Miseq and the resulting data was comparable to high molecular weight DNA in uniformity and performance; supporting TargetRich® as a sensitive and robust platform to analyze FFPE samples. Citation Format: Rusla du Breuil, Tatiana Shvetsova, Kruti Patel, Troy Moore, Gwen Fewell. Targeted enrichment and next generation sequencing of non-small cell lung carcinoma FFPE samples. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1519. doi:10.1158/1538-7445.AM2014-1519
Mutually exclusive expression of odorant receptor transgenes
Authors: Shou Serizawa, Tomohiro Ishii, Hiroko Nakatani, Akio Tsuboi, Fumikiyo Nagawa, Masahide Asano, Katsuko Sudo, Junko Sakagami, Hitomi Sakano, Takashi Ijiri, Yoichi Matsuda, Misao Suzuki, Tetsuo Yamamori, Yoichiro Iwakura, Hitoshi Sakano
Journal: Nature Neuroscience (2000)
Creating value: The power of molecular diagnostic tests
Authors: Deborah J. Neff
Journal: Clinical Cancer Research (2010)

Abstract The talk will review the real world example of how Pathwork Diagnostics approached both technical and commercial challenges during the development and launch of a new molecular diagnostic. Our technical challenges were to create a mechanism for handling large sets of gene expression data, to accurately answer complex clinical questions and to maintain robust performance levels appropriate for a clinical diagnostic test. Our commercial challenges were centered around the appropriate selection of our regulatory path and market channels, and how to drive adoption and reimbursement. We will discuss the resulting successful launch of the Pathwork ®Tissue of Origin Test and the clinical utility evidence that demonstrates the positive impact of this molecular diagnostic test on patient care and outcome.
A valuable lesson: Always check the x ray film
Authors: R. N Siddiqui
Journal: BMJ (1999)

tion.Most of these deaths are by hanging, indicating the need for the removal of structures that make hanging easier such as non-collapsible curtain rails.A quarter of inpatient suicides occur in wards with difficulties in observing patients; this implies that some wards are unsuitable for the care of acutely ill patients.Suicides after discharge from hospital suggest the need for early-in some cases, immediate-follow up after discharge.Most psychiatric patients who commit suicide are not regarded as being at high immediate risk at their final contact with mental health services.Better suicide prevention may therefore need changes to services for all patients rather than specific initiatives for those known to be at highest risk.A series of recommendations is to be published by the Department of Health 10 ; these are based on the above findings and are intended to improve the safety of mental health services as a whole.We acknowledge the help of district directors of public health; health authority and trust contacts; consultant psychiatrists for completing the questionnaires; Professor Graham Dunn, professor of biostatistics, University of Manchester, for comments on the presentation of the statistical analysis.
<i>Afternoon in the Cluny Garden, Paris</i>
Authors: Jeanette M. Smith
Journal: JAMA (2015)

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