tbuckley/cabot-search huggingface dataset:
Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.
Authors: A S Sarkis, D F Bajorin, V E Reuter, H W Herr, G Netto, Z F Zhang, P K Schultz, C Cordon-Cardo, H I Scher
Journal: Journal of Clinical Oncology (1995)

This study sought to examine the prognostic role of p53 nuclear overexpression in muscle-invasive bladder cancer because of its correlation with progression of superficial bladder cancer.Ninety of 111 patients treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with a median follow-up duration of 5.8 years were evaluated. p53 nuclear overexpression was determined by immunohistochemistry on deparaffinized tissue sections. Patients were stratified into two groups according to the percent of tumor cells with positive nuclear reactivity. Overexpression was defined as tumors with > or = 20% cells with positive nuclear reactivity and nonoverexpression as tumors with less than 20% reactivity.Nuclear overexpression was observed in 47 patients and nonoverexpression in 43 patients. Patients whose tumors had p53 overexpression had a significantly higher proportion of cancer deaths. A multivariate analysis that evaluated the pretreatment variables p53 nuclear overexpression, age, sex, palpable mass, prechemotherapy tumor stage, performance status, ureteral obstruction, tumor size, multifocality, and grade showed that p53 overexpression had independent significance for survival (P = .001; relative risk ratio, 3.1). The impact of p53 overexpression on survival was predominantly in T2 and T3a tumors. Long-term survival was evident in seven of 17 patients (41%) with p53 overexpression versus 20 of 26 (77%) in whom p53 was not overexpressed (P = .007).p53 nuclear overexpression has independent prognostic value for survival in patients with invasive bladder cancer treated with neoadjuvant chemotherapy.
P450BM-3 and other Inducible Bacterial P450 Cytochromes: Biochemistry and Regulation
Authors: A J Fulco
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Abstract 4628: Analysis of melanoma GWAS data suggests specific risk loci influencing age of onset of melanoma
Authors: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski
Journal: Cancer Research (2015)

Abstract Introduction/Purpose: The average age of diagnosis of melanoma is younger than that of other major cancers. In addition, melanoma is the second most common cancer among individuals in their 20s. Analyzing GWAS data by ‘wide-locus region’ (i.e. analyzing multiple nearby single nucleotide polymorphisms (SNPs) together) increases statistical power compared to single-SNP analyses. This approach has uncovered new associations in GWAS data for diseases other than melanoma. By applying wide-locus analysis to GWAS data from melanoma cases, we aimed to discover common genetic risk variants related to age of melanoma onset. Procedures: We re-analyzed data from the 1977 melanoma cases of European ancestry made available by the MD Anderson Cancer Center study (accession: phs000187.v1.p1). Patients were genotyped on the Illumina OMNI1-Quad chip. Biostatistical analysis was performed from a window moving across the whole genome using u-statistics for multivariate, genetically structured wide-locus data to derive genetic risk scores to determine if any gene regions were associated with age of onset in melanoma patients. This statistical approach resulted in a genome-wide significance level of p&amp;lt;10−5.64. Results: Common variants in several genes were associated with melanoma age-of-onset at the level of genome-wide significance. The most significant functional risk loci were located at DLEU1 (p&amp;lt;10−6.75), NRP1 (p&amp;lt;10−6.66), PTPN11P (p&amp;lt;10−6.49) and BAT1/ATP6/NFKBIL (p&amp;lt;10−6.41). Of note, none of these risk loci have been shown to be associated with risk of developing melanoma overall, or longevity in prior GWAS. The NRP1 and PTPN11P genes have been linked to the RAS pathway, an important driver of melanoma pathogenesis. Conclusions: Our analysis revealed novel associations between several common genetic variants and earlier age of melanoma diagnosis. Some of these loci interact with the RAS pathway. Additional studies of common genetic variants and age of cancer diagnosis using this approach may reveal similar findings in other melanoma cohorts and possibly other cancer types. Citation Format: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski. Analysis of melanoma GWAS data suggests specific risk loci influencing age of onset of melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4628. doi:10.1158/1538-7445.AM2015-4628
4th International Kyoto Liver Cancer Symposium: Emerging Strategies to HCC. Kyoto, Japan, June 7-8, 2014: Abstracts
Journal: Liver Cancer (2014)

GIDEON is a global, prospective, non-interventional study evaluating patients with unresectable hepatocellular carcinoma (uHCC) treated with sorafenib in clinical practice. Completion of GIDEON created a large database of >3000 sorafenib-treated patients across 39 countries and 5 regions, allowing for assessment of regional differences in treatment history, practices, and outcomes.
Reminiscences in Pharmacology: Auld Acquaintance Ne'er Forgot
Authors: Arnold D. Welch
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Oxidized Low Density Lipoproteins in Atherogenesis: Role of Dietary Modification
Authors: Peter D. Reaven, Joseph L. Witztum
Journal: Annual Review of Nutrition (1996)

The development of atherosclerosis is a complex and multistep process. There are many determinants in the pathogenesis of this condition, with different factors presumably playing key roles at different times in the evolution of the atherosclerotic plaque. It has been suggested that oxidation of low density lipoproteins (LDL) by cells in the artery wall leads to a proatherogenic particle that may help initiate early lesion formation. For this reason, understanding the determinants of LDL susceptibility to oxidation is essential for developing therapeutic strategies to inhibit this process. Oxidation of LDL begins with the abstraction of hydrogen from polyunsaturated fatty acids; thus, LDL fatty acid composition undoubtedly contributes to the process of LDL oxidation. Since dietary fatty acids influence the fatty acid composition of LDL and cell membranes, the amount and type of fat in the diet may effect susceptibility of LDL and cells to oxidative damage. Additionally, since cell membrane fatty acid composition also influences cellular formation of reactive oxygen species, dietary fatty acids may help determine the prooxidant activity of artery wall cells. Both cells and lipoproteins contain a variety of antioxidants that provide protection against oxidative stress. A major source of these antioxidants is the diet. Enrichment of the diet with foods high in such antioxidants as vitamin E, β-carotene. or vitamin C, or supplementation of the diet with antioxidant vitamins, may inhibit oxidation and the process of atherosclerosis.
EMMPRIN upregulates the urokinase-type plasminogen activator system promoting tumor cell invasion
Authors: Cathy Quemener, Eric e Gabison, Benyoussef Naimi, Fabien Calvo, Suzanne Menashi, Samia Mourah
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3084 

EMMPRIN (Extracellular Matrix MetalloPRoteinase Inducer) is a membrane glycoprotein overexpressed in many cancer tissues, known for its ability to stimulate MMP expression. In this work, we show that EMMPRIN is also a regulator of the urokinase plasminogen activation system of serine proteases, thus participating to the increase of the overall proteolytic function of the cancer cells. Enhanced EMMPRIN expression in a tumorigenic breast epithelial cell line NS2T2A increased the levels of uPA, uPAR and the uPA inhibitor PAI-1, as measured by qRT-PCR, western blot and plasminogen-casein zymography. This response was down regulated by either EMMPRIN siRNA or a blocking antibody to EMMPRIN. EMMPRIN-containing purified membrane fraction from CHO cells when added exogenously to NS2T2A cells induced a similar activation of the uPA/PAI-1 system. Additionally, overexpression of EMMPRIN in NS2T2A cells increased uPA levels in co-cultured endothelial cells, showing a paracrine regulation loop involving a tumor-stroma interaction. EMMPRIN expressing cells also exhibited enhanced invasive potential in vitro and the use of amiloride (uPA inhibitor) and marimastat (MMP inhibitor) showed that the two proteolytic systems reduced alone and in combination the invasive potential mediated through EMMPRIN. These data demonstrate a novel regulatory pathway for uPA activity and suggest that EMMPRIN is involved in uPA dysregulation observed in cancer.
The effect of Tai Chi on four chronic conditions—cancer, osteoarthritis, heart failure and chronic obstructive pulmonary disease: a systematic review and meta-analyses
Authors: Yi-Wen Chen, Michael A Hunt, Kristin L Campbell, Kortni Peill, W Darlene Reid
Journal: British Journal of Sports Medicine (2015)

Background Many middle-aged and older persons have more than one chronic condition. Thus, it is important to synthesise the effectiveness of interventions across several comorbidities. The aim of this systematic review was to summarise current evidence regarding the effectiveness of Tai Chi in individuals with four common chronic conditions—cancer, osteoarthritis (OA), heart failure (HF) and chronic obstructive pulmonary disease (COPD). Methods 4 databases (MEDLINE, EMBASE, CINAHL and SPORTDiscus) were searched for original articles. Two reviewers independently screened the titles and abstracts and then conducted full-text reviews, quality assessment and finally data abstraction. 33 studies met the inclusion criteria. Meta-analyses were performed on disease-specific symptoms, physiological outcomes and physical performance of each chronic condition. Subgroup analyses on disease-specific symptoms were conducted by categorising studies into subsets based on the type of comparison groups. Results Meta-analyses showed that Tai Chi improved or showed a tendency to improve physical performance outcomes, including 6-min walking distance (6MWD) and knee extensor strength, in most or all four chronic conditions. Tai Chi also improved disease-specific symptoms of pain and stiffness in OA. Conclusions The results demonstrated a favourable effect or tendency of Tai Chi to improve physical performance and showed that this type of exercise could be performed by individuals with different chronic conditions, including COPD, HF and OA.
The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials
Authors: C. Groot, A.M. Hooghiemstra, P.G.H.M. Raijmakers, B.N.M. van Berckel, P. Scheltens, E.J.A. Scherder, W.M. van der Flier, R. Ossenkoppele
Journal: Ageing Research Reviews (2015)
Mutations in <i>EXPH5</i> underlie a rare subtype of autosomal recessive epidermolysis bullosa simplex
Authors: E. Rashidghamat, L. Ozoemena, L. Liu, J.A. McGrath, A.E. Martinez, J.E. Mellerio
Journal: British Journal of Dermatology (2015)

Funding sources: This study received funding/support from the National Institute for Health Research Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Conflicts of interest: none declared. Dear Editor, Epidermolysis bullosa simplex (EBS) is a heterogeneous disorder with mutations in at least nine different genes underlying various autosomal dominant and recessive subtypes thereof.1 Making an accurate clinical and laboratory diagnosis in some of the less common forms of EBS can be challenging. A 9‐year‐old boy with first‐cousin Pakistani parents presented with skin fragility from birth. He had scattered vesicles and bullae up to 1–2 cm in size on the limbs and trunk (Fig. 1a, b). Blistering was made worse by hot weather. Individual blisters healed within 1–2 weeks, leaving postinflammatory hypopigmentation. His blistering tendency persisted but ameliorated with age. Hair, teeth, nails and mucosae were normal. His 2‐year‐old brother had similar symptoms and signs from birth. Of note, the father of both children, whose parents were also first cousins, had similar skin fragility as a child that resolved completely by 10 years of age. The pattern of inheritance was consistent with autosomal recessive transmission, with possible pseudodominant inheritance, given the father's history of blistering. Unfortunately, the father declined to participate in the study and was not available for further evaluation.
Short Stature and Access to Lung Transplantation in the United States. A Cohort Study
Authors: Jessica L. Sell, Matthew Bacchetta, Samuel B. Goldfarb, Hanyoung Park, Priscilla V. Heffernan, Hilary A. Robbins, Lori Shah, Kashif Raza, Frank D’Ovidio, Joshua R. Sonett, Selim M. Arcasoy, David J. Lederer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates.Objectives: To examine the relationship between lung transplant candidate height and waiting list outcomes.Methods: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year.Measurements and Main Results: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170–176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29–39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24–96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10–85%) higher rate of respiratory failure while awaiting lung transplantation.Conclusions: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height.
Data Collection and Complication Rates in Clinical Audit
Authors: Ian Eardley, Patrick T Doyle, K Nigel Bullock
Journal: Journal of the Royal Society of Medicine (1993)

Audit data were collected continuously between February 1988 and July 1991. For the initial period (February 1988–June 1990) data were collected by monitoring of ward admission and discharge records and by collecting data from operating theatre records whilst complications were noted in a ‘complications book’ which was kept on the notes trolley. In July 1991, when a computerized system for storing and processing audit data was introduced into the department, the methods of data collection changed. For each patient a proforma was attached to the clinical notes which was filled in at each stage of the hospital stay. On this proforma was a list of possible complications which were ticked, as appropriate, at the time of discharge from hospital. We have reviewed the results of clinical audit during these two periods. The number of operations performed per month fell slightly in the latter period ( p=0.005). However, there was a significant increase in both the number of complications ( p&lt;0.0001) and in the complication rate ( p&lt;0.0001). Further analysis showed that there was a similar increase in the number of recorded major and minor complications, and that this increase was also seen even when changes in medical personnel were accounted for. We suggest that the increased complication rate recorded in the latter period reflects the change in the method of data collection. This has important implications when comparing outcome measures for clinical departments.
No transformation without reconciliation
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

Two months ago I asked you for advice for new medical students.1 I’m still seeking it. Are these bright-eyed recruits being sold a career that has lost its magic? Is professionalism as we knew it dead, replaced by miserable clock watching? Medicine has much to be proud of in its evolving embrace of shared decision-making, acceptance of new technologies and willingness to tackle complex challenges posed by our ageing population and multimorbidity.2,3 Yet, when I speak with doctors of all ranks, from professors to junior doctors, whether in hospital specialties or primary care, there isn’t much that feels good. Reports are everywhere of low morale and disillusionment. The reports ring true with each conversation and anecdote. The NHS faces unprecedented financial challenges and spiralling demand for services, the implications of which are an impetus for spending cuts and service innovation. Following the discontent caused by the Health and Social Care Act, a restructuring that the profession largely opposed, instability has become established. People yearn stability. Financial considerations dominate minds that wish to be preoccupied with the health and welfare of patients. Until recent months, these unwelcome priorities primarily affected senior doctors. Now, with a government push for an ‘extended’ 24/7 service, junior doctors feel victimised, bullied into accepting a new contract and threatened with longer working hours for no more pay.4 There are two central issues. First, whether or not the government is steering the NHS in a sensible direction? It is a complex debate. Is the government responding pragmatically to a crisis in service delivery? Or is there a grand design to dismantle the NHS? Whichever side you choose, the second issue is more straightforward. Any change is difficult, well-nigh impossible to introduce with an unwilling and demoralised workforce. If the government pits itself against consultants, general practitioners and junior doctors, how can the health service deliver satisfactory care to patients on a day-to-day basis, let alone contemplate fundamental reform? There can be no transformation with reconciliation.
The Central Role of Voltage-Activated and Receptor-Operated Calcium Channels in Neuronal Cells
Authors: M Bertolino, R R Llinás
Journal: The Annual Review of Pharmacology and Toxicology (1992)

It has been known for more than three decades that calcium ions play a fundamental role in the regulation of many cellular processes, including vesicular exocytosis and synaptic transmission (1), muscle contraction (2), and even neurotoxicity and neuronal death. The role of calcium in these macroscopic cellular functions is one of a second messenger, serving to regulate, for example, enzymes, ion channels, the expression of immediate­ early genes, and thereby the induction of specific genetic programs that are responsible for such long-term cellular responses as long-term potentiation. Under normal conditions, the calcium concentration of the extracellular fluid is in the millimolar range, whereas the intracellular free calcium concen­ tration is less than 10-7 M (3). Transient increases in the cytosolic calcium concentration can result from the entry of calcium from the external milieu
People with learning disabilities also need help in bereavement
Authors: S. Huline-Dickens
Journal: BMJ (1996)

benefit individual patients.24They need to be large enough to allow sufficient statistical power to answer the research questions posed.It is also known that only a small proportion of eligible patients are entered into such trials (for example, only 3-5% of patients with cancer in Britain are included in clinical trials4).Among the many reasons for this lack of accrual is a belief that multicentre trials do not officially recognise the considerable time and effort required by clinicians to identify suitable patients, obtain informed consent, and complete the necessary forms.Incentives to recruit patients into trials are required.We suggest that clinicians' vital contribution to randomised controlled trials should be acknowledged separately at the end of published papers.In large multicentre trials it is often not practical or desirable for all collaborating clinicians to be mentioned as authors of papers.Thus many people's efforts in recruiting patients to trials go unrewarded: they do not have publications to their name, and their research is denied the recognition that, since the publication of the Culyer report,' is now necessary to gain funding.Benefits could be gained if it became standard practice for all published papers to incorporate a list of clinicians who enrolled more than a (trial specific) number of patients into the trial.Not only would this acknowledge the important work of these clinicians in the trial but it would also provide evidence of their participation in research for academic assessment and for their curriculum vitae and provide kudos for the clinicians and their department.
Marked intrafamilial phenotypic heterogeneity in dystrophic epidermolysis bullosa caused by inheritance of a mild dominant glycine substitution and a novel deep intronic recessive<i>COL7A1</i>mutation
Authors: S. Turczynski, M. Titeux, N. Pironon, H.I. Cohn, D.F. Murrell, A. Hovnanian
Journal: British Journal of Dermatology (2015)