tbuckley/cabot-search huggingface dataset:
Second Allograft for Hematologic Relapse of Acute Leukemia After First Allogeneic Stem-Cell Transplantation From Related and Unrelated Donors: The Role of Donor Change
Authors: Maximilian Christopeit, Oliver Kuss, Jürgen Finke, Ulrike Bacher, Dietrich Wilhelm Beelen, Martin Bornhäuser, Rainer Schwerdtfeger, Wolfgang Andreas Bethge, Nadezda Basara, Martin Gramatzki, Johanna Tischer, Hans-Jochem Kolb, Lutz Uharek, Ralf G. Meyer, Donald Bunjes, Christof Scheid, Hans Martin, Dietger Niederwieser, Nicolaus Kröger, Hartmut Bertz, Hubert Schrezenmeier, Christoph Schmid
Journal: Journal of Clinical Oncology (2013)

To evaluate the role of a second allogeneic hematopoietic stem-cell transplantation (HSCT2) given for relapsed acute leukemia (AL) after related or unrelated first hematopoietic stem-cell transplantation (HSCT1) and to analyze the role of donor change for HSCT2 in both settings.We performed a retrospective registry study on 179 HSCT2s given for relapse after HSCT1 from matched related donors (n = 75) or unrelated donors (n = 104), using identical or alternative donors for HSCT2. Separate analyses were performed according to donor at HSCT1.Independent of donor, 74% of patients achieved complete remission after HSCT2, and half of these patients experienced relapse again. Overall survival (OS) at 2 years was 25% ± 4% (39% ± 7% after related HSCT2; 19% ± 4% after unrelated HSCT2). Long-term survivors were observed even after two unrelated HSCT2s. Multivariate analysis for OS from HSCT2 confirmed established risk factors (remission duration after HSCT1: hazard ratio [HR], 2.37; 95% CI, 1.61 to 3.46; P < .001; stage at HSCT2: HR, 0.53; 95% CI, 0.34 to 0.83; P = .006). Outcome of HSCT2 was better after related HSCT1 than after unrelated HSCT1 (2-year OS: 37% ± 6% v 16% ± 4%, respectively; HR, 0.68; 95% CI, 0.47 to 0.98; P = .042, multivariate Cox regression). After both related and unrelated HSCT1, selecting a new donor for HSCT2 did not result in a relevant improvement in OS compared with HSCT2 from the original donor; however, donor change was not detrimental either.After relapse from allogeneic HSCT1, HSCT2 can induce 2-year OS in approximately 25% of patients. Unrelated HSCT2 is feasible after related and unrelated HSCT1. Donor change for HSCT2 is a valid option. However, a clear advantage in terms of OS could not be demonstrated.
A Homeobox Protein, Prox1, Is Involved in the Differentiation, Proliferation, and Prognosis in Hepatocellular Carcinoma
Authors: Masayuki Shimoda, Meiko Takahashi, Takanobu Yoshimoto, Tomoya Kono, Iwao Ikai, Hajime Kubo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: It has been shown that a lymphatic differentiation master gene, prox1, also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed. Experimental Design: To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1 in HCC cell lines and by knocking down its expression by RNA interference. Results: We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of Prox1 by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1 greatly suppressed the growth. Conclusions: Our results suggest that Prox1 is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.
Adiponectin: a relevant player in obesity-related colorectal cancer?
Authors: Antonio La Cava
Journal: Gut (2012)

Obesity is a condition characterised by an abnormally elevated mass of body fat. The past decades have seen a dramatic rise in the worldwide incidence of obesity due to lifestyle changes that have led to an overall reduced physical activity and an increase in the intake of excessive and/or highly caloric or processed foods. As a consequence, obesity represents nowadays a major global health concern. In particular, several epidemiological studies have linked obesity to a shortened lifespan due primarily to a higher risk for the development of chronic pathologies that include cardiovascular complications such as high blood pressure, coronary heart disease and stroke, in addition to insulin resistance and type 2 diabetes.1 Additionally, obesity has also been shown to increase the risk of developing different types of tumours such as the cancer of the oesophagus, colon, rectum, pancreas, gallbladder, kidney, breast, thyroid and endometrium.2 

In obesity, low …
Adaptation of the cardiac muscle sodium pump to chronic potassium deficiency
Authors: J. P T WARD, I. R CAMERON
Journal: Cardiovascular Research (1984)

Journal Article Adaptation of the cardiac muscle sodium pump to chronic potassium deficiency Get access JEREMY P T WARD, JEREMY P T WARD * From the Department of Medicine, St Thomas' s Hospital Medical School, Lambeth Palace Road, London SE1 *Present address and address for reprint requests: Dr J P T Ward, Department of Physiology, St George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 ORE Search for other works by this author on: Oxford Academic PubMed Google Scholar IAN R CAMERON IAN R CAMERON From the Department of Medicine, St Thomas' s Hospital Medical School, Lambeth Palace Road, London SE1 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 18, Issue 5, May 1984, Pages 257–263, https://doi.org/10.1093/cvr/18.5.257 Published: 01 May 1984
The significance of the peer review process against the background of bias: priority ratings of reviewers and editors and the prediction of citation, the role of geographical bias
Authors: T Opthof
Journal: Cardiovascular Research (2002)

Editors are facing larger numbers of submitted manuscripts than they can publish [1]. In their selection process of papers they depend on the advice of one or more peer reviewers [1]. It is thus important that the process is fair and as unbiased as possible.

The origin of ‘peer review’ dates back to 1752, when the Royal Society of London obtained the fiscal responsibility for the Philosophical Transactions [2]. There are few historical accounts of the evolution of editorial peer review [3]. Today, specialized research on the peer review system is only just starting to emerge and has been the topic of four world congresses [4–7]. This type of research focuses—amongst many other issues—on themes as whether or not masking the identity of authors to reviewers influences the reports of reviewers and whether or not anonymity of reviewers is a relevant topic [4–7].

Previous reports on the editorial process of Radiology [8] and the Journal of Clinical Investigation [9], have indicated that reviewers set markedly different standards in their appreciation of manuscripts. The concordance between reviewers on identical manuscripts is limited [9]. The fact that in the social sciences published papers have an almost 90% chance to be rejected when resubmitted to other journals casts doubt on the validity of the peer review system [10]. Such data are to our knowledge not available for the biomedical sciences. However, there is circumstantial evidence that peer review can successfully discriminate between manuscripts that have a greater chance to be cited in the future. Thus, Wilson showed that papers rejected by the Journal of Clinical Investigation were cited at lower frequency if published by other journals [11]. Manuscripts rejected by Cardiovascular Research were also cited at significantly lower frequency, even if published by … 

* Corresponding author. Tel.: +31-30-253-8900; fax: +31-30-253-9036
Chronic Hypoxia Decreases Synthesis of Homologous Recombination Proteins to Offset Chemoresistance and Radioresistance
Authors: Norman Chan, Marianne Koritzinsky, Helen Zhao, Ranjit Bindra, Peter M. Glazer, Simon Powell, Abdellah Belmaaza, Brad Wouters, Robert G. Bristow
Journal: Cancer Research (2008)

Abstract Hypoxic and/or anoxic tumor cells can have increased rates of mutagenesis and altered DNA repair protein expression. Yet very little is known regarding the functional consequences of any hypoxia-induced changes in the expression of proteins involved in DNA double-strand break repair. We have developed a unique hypoxic model system using H1299 cells expressing an integrated direct repeat green fluorescent protein (DR-GFP) homologous recombination (HR) reporter system to study HR under prolonged chronic hypoxia (up to 72 h under 0.2% O2) without bias from altered proliferation, cell cycle checkpoint activation, or severe cell toxicity. We observed decreased expression of HR proteins due to a novel mechanism involving decreased HR protein synthesis. Error-free HR was suppressed 3-fold under 0.2% O2 as measured by the DR-GFP reporter system. This decrease in functional HR resulted in increased sensitivity to the DNA cross-linking agents mitomycin C and cisplatin but not to the microtubule-interfering agent, paclitaxel. Chronically hypoxic H1299 cells that had decreased functional HR were relatively radiosensitive [oxygen enhancement ratio (OER), 1.37] when compared with acutely hypoxic or anoxic cells (OER, 1.96–2.61). Using CAPAN1 cells isogenic for BRCA2 and siRNA to RAD51, we confirmed that the hypoxia-induced radiosensitivity was due to decreased HR capacity. Persistent down-regulation of HR function by the tumor microenvironment could result in low-fidelity DNA repair and have significant implications for response to therapy and genetic instability in human cancers. [Cancer Res 2008;68(2):605–14]
Competing-Risk Analysis of Leukemia and Nonleukemia Mortality in X-Irradiated, Male RF Mice
Authors: Charles V. Robinson, Arthur C. Upton
Journal: JNCI Journal of the National Cancer Institute (1978)

The theory of competing risks, extended by the addition of several newly defined estimators, was applied to the analysis of mortality data for acutely X-irradiated, male RF mice, in which the cause of each death was assigned to one of four categories: myeloid leukemia (M), thymic lymphoma (T), lymphosarcoma and reticulum cell sarcoma (L), and all remaining causes (R), Doses from 0 to 450 rads were delivered within two age ranges: A) 5-6 weeks and B) 9-10 weeks, to give 11 treatment groups totaling 2,073 mice. The data were analyzed in terms of: 1) the nonparametric, Kaplan-Meier (K-M) adjusted survival function; 2) its logarithmic transform, the cumulative force of mortality (cumFM) function; 3) a disease model called "early terminating," applied to causes M and T; and 4) a "late-terminating" model, applied to causes L and R. For any given cause and group, two estimators were used, which measured, respectively: a) the relative lateness of the corrected (or adjusted) time course and b) the relative corrected incidence. For causes M and T, these were: a) the mean age of the force of mortality distribution (MAF), or corrected mean latent period; and b) the final cumFM. For causes L and R, the estimators were: a) the adjusted mean age at death (adjMAD), given an upper limit (as %) of adjusted mortality (adjMAD, 50% for L; adjMAD, 100%--the K-M estimator--for R) and b) the cumFM at a cutoff time of 640 days. For causes M and T, the MAF values showed highly significant decreases of the latent periods with dose, through 300 rads. The final cumFM data showed a marked increase of corrected incidence with dose, for both M and T. In addition, the data for cause M were consistent with a three-parameter, leukemogenic cell model that incorporated two opposing radiation effects: leukemogenic cell potentiation and cell killing. For cause R, the adjMAD, 100% data showed a general decrease with dose and considerable scatter. For cause L, the adjMAD, 50% values showed: for treatment A, a gradual decrease with dose through 300 rads; for treatment B, a highly significant drop for 150 rads, with little change for higher doses. The cumFM, 640-day values for both L and R showed a general increase of corrected incidence with dose. The mortality curves for all causes combined showed the expected life shortening, i.e., decreases of the mean age at death with dose, in the 0- to 300-rad range. In addition, the standard deviations of the mortality curves were significantly less for animals irradiated at age range B than at age range A, for each of the doses--150, 300, and 450 rads.
Increases in airway eosinophils and interleukin-5 with minimal bronchoconstriction during repeated low-dose allergen challenge in atopic asthmatics
Authors: I Sulakvelidze, MD Inman, T Rerecich, PM O'Byrne
Journal: European Respiratory Journal (1998)

Repeated low-dose allergen challenge increases airway hyperresponsiveness in atopic asthmatics. However, it is not known whether low-dose allergen challenge increases airway inflammation. Eight atopic asthmatics were enrolled in a controlled, cross-over study to evaluate the effect and time course of repeated low-dose allergen challenge on airway inflammation and hyperresponsiveness. The dose of allergen to reduce forced expiratory volume in one second (FEV1) by approximately 5% was selected in a screening allergen challenge. The subjects then were challenged for five consecutive days with either diluent or the selected low-dose of allergen. Methacholine airway hyperresponsiveness (PC20,meth) was measured and sputum induced on days 1, 3 and 5 of the repeated challenge, and then 1 day and 3 days after the last challenge. Repeated low-dose allergen challenge caused small reductions in FEV1, but increased airway eosinophils and interleukin (IL)-5, airway hyperresponsiveness, asthma symptoms and beta2-agonist use, all of which peaked on days 3 or 5 of the challenge. The mean (SEM) percentage sputum eosinophils was 21.2 (0.7)% after allergen versus 3.9 (0.1)% after diluent (p&lt;0.001); percentage EG2+ cells were 13.4 (03)% after allergen versus 1.1 (0.04)% after diluent (p&lt;0.01) and geometric mean (GSEM) eosinophil cationic protein (ECP) was 1061.8 (1.6) microg x L(-1) after allergen versus 447.03 (1.2) microg x L(-1) after diluent (p&lt;0.05). Geometric mean (GSEM) IL-5 was 71.4 (1.4) pg x mL(-1) after allergen versus 18.4 (1.04) pg x mL(-1) after diluent (p&lt;0.01). All the changes had resolved by 3 days after the last challenges. The study demonstrated that repeated inhalation of a low-dose of allergen causes airway eosinophilia and increases in interleukin-5, associated with airway hyperresponsiveness, and mild worsening of asthma control, without the development of marked acute bronchoconstriction or the development of late responses.
Drug points: Allergy associated with ciprofloxacin
Authors: P Burke
Journal: BMJ (2000)

since this article was accepted for publication, suggests no difference in relative risk reduction in subjects older or younger than 65 years.The conclusion from this analysis may not necessarily apply across the wider age range commonly encountered by those running primary prevention clinics; nevertheless, at this stage more data are required to establish whether the benefits of lipid lowering therapy are age related.
A simple and portable paced step test for reproducible measurements of ventilation and oxygen consumption during exercise.
Authors: P W Jones, J M Wakefield, E Kontaki
Journal: Thorax (1987)

A single work rate paced step test is described. It was designed to allow the measurement of minute ventilation (VI) and oxygen consumption (VO2), under standardised conditions, during exercise in the clinic and lung function laboratory and in field work. The subjects and the operator found the test simple to perform. The values for ventilation at a given oxygen consumption were similar to those from more complex and stressful tests and had a high degree of reproducibility. The ergometer was a 12 inch (30 cm) step with hand rails. The subjects stepped down, once every four seconds in response to a buzzer for 10 minutes. VI and VO2 were measured with a small portable device. In 53 normal subjects of mean weight 69 (range 49-107) kg, mean VO2 measured during the last 5 minutes of the test was 0.89 (range 0.53-1.52) 1/min. Weight and height were independent contributors to the oxygen cost of stepping. The ventilatory equivalent for oxygen (VIO2, which equals VI divided by VO2) increased with age, and was similar to normal values for ventilation at 1.01/min VO2 obtained by workers who used multiple work rate tests on more complex equipment. The within subject variation in VIO2, expressed as the coefficient of variation (cv) and calculated for each age decade, was 14%. This again compared very favourably with the cv for values of ventilation at 1.01/min VO2 from other studies. In 20 normal subjects daily testing showed significant falls in VO2 and V1 over three days of 4% and 5.9% respectively; VIO2 fell by 2%. Testing over four consecutive weeks showed small significant differences between weeks but no clear trend; the within subject weekly variation accounted for less than 3.5% of the total variance for each of the variables. Testing at least four months apart showed a 3.3% fall in the oxygen cost of stepping. No significant diurnal effects on the exercise responses were found.
Senescence-Associated Oxidative DNA Damage Promotes the Generation of Neoplastic Cells
Authors: Karo Gosselin, Sébastien Martien, Albin Pourtier, Chantal Vercamer, Peter Ostoich, Luc Morat, Laure Sabatier, Laurence Duprez, Claire T'Kint de Roodenbeke, Eric Gilson, Nicolas Malaquin, Nicolas Wernert, Predrag Slijepcevic, Marjan Ashtari, Fazia Chelli, Emeric Deruy, Bernard Vandenbunder, Yvan De Launoit, Corinne Abbadie
Journal: Cancer Research (2009)

Abstract Studies on human fibroblasts have led to viewing senescence as a barrier against tumorigenesis. Using keratinocytes, we show here that partially transformed and tumorigenic cells systematically and spontaneously emerge from senescent cultures. We show that these emerging cells are generated from senescent cells, which are still competent for replication, by an unusual budding-mitosis mechanism. We further present data implicating reactive oxygen species that accumulate during senescence as a potential mutagenic motor of this post-senescence emergence. We conclude that senescence and its associated oxidative stress could be a tumor-promoting state for epithelial cells, potentially explaining why the incidence of carcinogenesis dramatically increases with advanced age. [Cancer Res 2009;69(20):7917–24]
Phase I-II Trial of Bortezomib Plus Oral Cyclophosphamide and Prednisone in Relapsed and Refractory Multiple Myeloma
Authors: Donna E. Reece, Giovanni Piza Rodriguez, Christine Chen, Suzanne Trudel, Vishal Kukreti, Joseph Mikhael, Mariela Pantoja, Wei Xu, A. Keith Stewart
Journal: Journal of Clinical Oncology (2008)

The combination of oral weekly cyclophosphamide and alternate day prednisone is a convenient regimen for relapsed/refractory multiple myeloma (MM), and we sought to improve its efficacy by adding bortezomib, a proteasome inhibitor with proven antimyeloma activity.We conducted a phase I-II trial evaluating six dose levels to define the maximum tolerated dose (MTD) of this combination in relapsed/refractory MM. An additional 10 patients were evaluated at the highest dose level reached.Thirty-seven patients were treated on this study. The MTD was not defined. Both of the highest dose levels of bortezomib tested (1.3 mg/m(2) on days 1, 4, 8, and 11 and 1.5 mg/m(2) on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m(2) per week and prednisone. At these dose levels, the overall response rate was 95% (complete responses [CR] plus partial response plus minimal response), with CR observed in more than 50% of patients. The weekly bortezomib regimen resulted in fewer instances of grade 3 thrombocytopenia and grade 1 to 2 peripheral neuropathy; the 1-year progression-free and overall survival probabilities with this dose level were 83% (95% CI, 73% to 96%) and 100%, respectively.Weekly bortezomib 1.5 mg/m(2) plus oral cyclophosphamide and prednisone produces an unprecedented response rate and encouraging 1-year survival in relapsed/refractory patients with MM. Further evaluation of this promising regimen is warranted both in relapsed and newly diagnosed disease.
New impact factor number reflects sustained and enhanced growth
Authors: W. K. A. Yung
Journal: Neuro-Oncology (2011)

New impact factor number reflects sustained and enhanced growthNeuro-Oncology is delighted to announce that our 2010 Impact Factor, a metric used to assess journal quality, is 5.483, a substantial increase from the previous year's Impact Factor (4.984).The 2010 number reflects the citation rate for the years 2008 and 2009.Of note, the journal increased its publication frequency from quarterly to bimonthly in 2008, so we are very pleased that our rapid growth was accompanied by sustained quality.Next year's Impact Factor will begin to reflect our increase to a monthly publication schedule in 2010.We are also now ranked 15th of 185 clinical neurology journals (top 8%) and 24th of 184 oncology journals (top 13%); both rankings are higher than last year's rankings (see table ).