tbuckley/cabot-search huggingface dataset:
Combined Alloreactive CTL Cellular Therapy with Prodrug Activator Gene Therapy in a Model of Breast Cancer Metastatic to the Brain
Authors: Michelle J. Hickey, Colin C. Malone, Kate L. Erickson, Amy Lin, Horacio Soto, Edward T. Ha, Shuichi Kamijima, Akihito Inagaki, Masamichi Takahashi, Yuki Kato, Noriyuki Kasahara, Barbara M. Mueller, Carol A. Kruse
Journal: Clinical Cancer Research (2013)

Individual or combined strategies of cellular therapy with alloreactive CTLs (alloCTL) and gene therapy using retroviral replicating vectors (RRV) encoding a suicide prodrug activating gene were explored for the treatment of breast tumors metastatic to the brain.AlloCTL, sensitized to the HLA of MDA-MB-231 breast cancer cells, were examined in vitro for antitumor functionality toward breast cancer targets. RRV encoding the yeast cytosine deaminase (CD) gene was tested in vivo for virus spread, ability to infect, and kill breast cancer targets when exposed to 5-fluorocytosine (5-FC). Individual and combination treatments were tested in subcutaneous and intracranial xenograft models with 231BR, a brain tropic variant.AlloCTL preparations were cytotoxic, proliferated, and produced IFN-γ when coincubated with target cells displaying relevant HLA. In vivo, intratumorally placed alloCTL trafficked through one established intracranial 231BR focus to another in contralateral brain and induced tumor cell apoptosis. RRV-CD efficiently spread in vivo, infected 231BR and induced their apoptosis upon 5-FC exposure. Subcutaneous tumor volumes were significantly reduced in alloCTL and/or gene therapy-treated groups compared to control groups. Mice with established intracranial 231BR tumors treated with combined alloCTL and RRV-CD had a median survival of 97.5 days compared with single modalities (50-83 days); all experimental treatment groups survived significantly longer than sham-treated groups (median survivals 31.5 or 40 days) and exhibited good safety/toxicity profiles.The results indicate combining cellular and suicide gene therapies is a viable strategy for the treatment of established breast tumors in the brain.
MPs call for review of NHS health checks
Authors: A. O'Dowd
Journal: BMJ (2014)

<h3>Abstract</h3> Pectin methylesterases (PMEs) modify homogalacturonan’s chemistry and thereby play a key role in regulating primary cell wall mechanical properties. How PME activity can fine-tune pectin structure in the growing plant has remained elusive, in part due to the lack of available biochemically-characterized enzymes to empirically test functional properties. Here we report on AtPME2, which we found to be highly expressed during lateral root emergence as well as root and hypocotyl elongation. Production of mature active enzyme in <i>Pichia pastoris</i> allowed its biochemical characterization. We show that AtPME2 can switch from full processivity (at pH 8), creating large blocks of unmethylated galacturonic acid, to low processivity (at pH 5) and relate these observations to the differences in electrostatic potential of the protein. We also produced a generic plant PME antiserum suitable for detecting recombinant and native enzyme independent of species source. In the context of acidified apoplast, we showed using reverse genetics that low-processive demethylesterification by AtPME2 can loosen the cell wall, with consequent increase in cell elongation and etiolated hypocotyl length. Our study brings insights into how the pH-dependent regulation by PME activity could affect pectin structure and associated cell wall mechanical properties in expansion.
The development and first validation of the Manchester Early Morning Symptoms Index (MEMSI) for patients with COPD
Authors: Adam P Garrow, Naimat Khan, Sarah Tyson, Jørgen Vestbo, Dave Singh, Janelle Yorke
Journal: Thorax (2015)

Aim Early morning symptoms (EMS) in people with COPD are associated with poor health, impaired activities and increased exacerbation risk. We describe the development and preliminary validation of the Manchester Early Morning Symptom Index (MEMSI) to quantify EMS in COPD. Methods Focus groups and cognitive debriefing with patients with COPD were used to develop the potential item list, followed by a cross-sectional study to finalise the items for inclusion. In addition to test-retest reliability, comparisons with the St George's Respiratory Questionnaire-C (SGRQ-C), modified Medical Research Council Dyspnoea Scale, Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Hospital Anxiety and Depression Scale (HADS) evaluated construct validity. Hierarchical methods informed item deletion and Rasch analysis was applied to assess scale unidimensionality. Results 23 items were identified from the focus groups and debriefings. The cross-sectional study involved 203 patients with COPD (mean age 64.7 SD 7.5 years, male 63%, Global Initiative for Chronic Obstructive Lung Disease (GOLD): 1:14% 2:41% 3:25% 4: 7%). 13 items were removed during item reduction. MEMSI contains 10 items, demonstrates good overall fit to the Rasch model (χ 2 p=0.26) and item score distribution; excellent reliability (Person Separation Index: 0.91) and good test-retest repeatability (r=0.82). It correlates with the SGRQ-C (r=0.73), FACIT-F (r=−0.65) and HADS (r=0.53–0.54) indicating good construct validity. Conclusions MEMSI is a reliable and valid unidimensional measure of EMS for patients with COPD. It is simple to use and score supporting its suitability for research and clinical use. Work is underway to determine the minimal clinical important difference and cross-cultural validity.
Epidemiology of obstructive sleep apnoea syndrome in Chinese children: a two-phase community study
Authors: A. M. Li, H. K. So, C. T. Au, C. Ho, J. Lau, S. K. Ng, V. J. Abdullah, T. F. Fok, Y. K. Wing
Journal: Thorax (2010)

<h3>Objective</h3> To determine the prevalence and risk factors of obstructive sleep apnoea syndrome (OSAS) in Chinese children using a two-phase community-based study design. <h3>Methods</h3> Children from 13 primary schools were randomly recruited. A validated OSAS screening questionnaire was completed by their parents. Children at high risk of OSAS and a randomly chosen low-risk group were invited to undergo overnight polysomnographic study and clinical examination. The the sex-specific prevalence rate was measured using different cutoffs (obstructive apnoea hypopnoea index ≥1, ≥1.5, ≥3 and ≥5 and obstructive apnoea index ≥5) and risk factors associated with OSAS were evaluated with logistic regression. <h3>Results</h3> 6447 completed questionnaires were returned (out of 9172 questionnaires; 70.3%). 586 children (9.1%; 405 boys and 181 girls) children belonged to the high-risk group. A total of 619 (410 and 209 from the high and low-risk group, respectively) subjects underwent overnight polysomnagraphy. Depending on the cutoffs, the prevalence rate of childhood OSAS varied from 4.8% to 40.3%. Using the International Criteria of Sleep Disorders version II, the OSAS prevalence for boys and girls was 5.8% and 3.8%, respectively. Male gender, body mass index z-score and increased adenoid and tonsil size were independently associated with OSAS. <h3>Conclusions</h3> The prevalence rate of OSAS in children was contingent on the cutoff used. The inclusion of symptoms as a part of the diagnostic criteria greatly reduced the prevalence. A further prospective and outcome study is needed to define a clinically significant diagnostic cutoff for childhood OSAS.
Serum Bilirubins in Hepatobiliary Disease: Comparison With Other Liver Function Tests and Changes in the Postobstructive Period
Authors: Philippe Van Hootegem, Johan Fevery, Norbert Blanckaert
Journal: Hepatology (1985)

Unconjugated bilirubin and its mono- and diester conjugates were measured by alkaline methanolysis and normal-phase high-performance liquid chromatography (AMHPLC) in 195 serum specimens obtained from 63 patients with various hepatobiliary disorders and from 47 healthy adult controls. With this assay, esterified bilirubins were undetectable in the controls, and detection of esterified pigment in a sample was interpreted as an abnormal result. Using this criterion, the AMHPLC result in the clinical anicteric patients (n = 39) was more frequently abnormal (87%) than the corresponding value of fasting serum bile acids (48%), SGPT (52%), total bilirubins (55%), alkaline phosphatase (71%) or gamma-glutamyl transpeptidase (71%). The cumulative frequency of abnormality of these tests was comparable to that of an abnormal AMHPLC result alone. All icteric patients had detectable esterified bilirubins as well as an increased alkaline phosphatase level, while a normal result was found for serum bile acids in 34%, for SGPT in 29% and for gamma-glutamyl transpeptidase in 11%, respectively. In most hyperbilirubinemic patients, total serum bilirubin levels, as determined by a conventional diazo method, exceeded the value obtained by AMHPLC. This discrepancy, which appears to reflect the presence of bilirubin covalently bound to serum protein, was particularly pronounced following desobstructive intervention in patients with obstructive jaundice, in whom the decline of serum bilirubins showed a fast and a slow disappearance component. The latter portion seemed to correspond with slow plasma clearance of bilirubin covalently linked to serum albumin, disappearing at a rate comparable to that of the albumin moiety.
Diabetic Nephropathy
Authors: Katalin Susztak, Erwin P. Böttinger
Journal: Journal of the American Society of Nephrology (2006)

Diabetic nephropathy (DNP) develops after latency periods that may vary by several years in approximately one third of patients with diabetes. This diabetic complication is a complex disorder whereby various genetic and environmental factors determine susceptibility and progression to ESRD. Despite rapid research progress, robust predictors to assess prospectively with high precision the risk for DNP in individuals with diabetes are still lacking. Thus, currently available therapies are usually initiated at more advanced stages of DNP characterized by clinically overt manifestations, including increased urinary albumin excretion and decreased glomerular filtration. In addition, although these interventions have proven efficacy in slowing the progression of DNP, they typically cannot prevent ESRD. New insights into the molecular mechanisms that underlie the origin and progression of DNP are emerging rapidly from advanced large-scale genetic and molecular studies in experimental models and humans. Thus, genetic loci that confer risk for albuminuria and/or progression of kidney disease associated with diabetes are being refined to identify the relevant genetic variants in specific genes. Molecular mRNA profiles that are obtained through microarray screens are being validated to elucidate further their potential as molecular markers and to identify new targets for novel preventive or therapeutic approaches aiming at curing DNP. The challenge before the field is to translate the large amount of new genetic and molecular data to empower clinicians and investigators with reliable predictors of DNP for improved design of preventive clinical trials and for individualized clinical management for millions of individuals affected by diabetes worldwide.
Pretreatment Health Behaviors Predict Survival Among Patients With Head and Neck Squamous Cell Carcinoma
Authors: Sonia A. Duffy, David L. Ronis, Scott McLean, Karen E. Fowler, Stephen B. Gruber, Gregory T. Wolf, Jeffrey E. Terrell
Journal: Journal of Clinical Oncology (2009)

Purpose Our prior work has shown that the health behaviors of head and neck cancer patients are interrelated and are associated with quality of life; however, other than smoking, the relationship between health behaviors and survival is unclear. Patients and Methods A prospective cohort study was conducted to determine the relationship between five pretreatment health behaviors (smoking, alcohol, diet, physical activity, and sleep) and all-cause survival among 504 head and neck cancer patients. Results Smoking status was the strongest predictor of survival, with both current smokers (hazard ratio [HR] = 2.4; 95% CI, 1.3 to 4.4) and former smokers (HR = 2.0; 95% CI, 1.2 to 3.5) showing significant associations with poor survival. Problem drinking was associated with survival in the univariate analysis (HR = 1.4; 95% CI, 1.0 to 2.0) but lost significance when controlling for other factors. Low fruit intake was negatively associated with survival in the univariate analysis only (HR = 1.6; 95% CI, 1.1 to 2.1), whereas vegetable intake was not significant in either univariate or multivariate analyses. Although physical activity was associated with survival in the univariate analysis (HR = 0.95; 95% CI, 0.93 to 0.97), it was not significant in the multivariate model. Sleep was not significantly associated with survival in either univariate or multivariate analysis. Control variables that were also independently associated with survival in the multivariate analysis were age, education, tumor site, cancer stage, and surgical treatment. Conclusion Variation in selected pretreatment health behaviors (eg, smoking, fruit intake, and physical activity) in this population is associated with variation in survival.
Effects of Reproductive and Demographic Changes on Breast Cancer Incidence in China: A Modeling Analysis
Authors: E. Linos, D. Spanos, B. A. Rosner, K. Linos, T. Hesketh, J. D. Qu, Y.-T. Gao, W. Zheng, G. A. Colditz
Journal: JNCI Journal of the National Cancer Institute (2008)

Breast cancer incidence is currently low in China. However, the distribution of reproductive and lifestyle risk factors for breast cancer among Chinese women is changing rapidly. We quantified the expected effect of changes in breast cancer risk factors on future rates of breast cancer in China. We first validated and calibrated the Rosner–Colditz log-incidence breast cancer model in Chinese women who participated in the Shanghai Women's Health Study cohort (N = 74 942). We then applied the calibrated model to a representative sample of Chinese women who were aged 35–49 years in 2001 using data from the Chinese National Family Planning and Reproductive Health Survey (NFPRHS, N = 17 078) to predict the age-specific and cumulative breast cancer incidence among all Chinese women of this age group. We evaluated the relative impact of changes in modifiable risk factors, including alcohol intake, parity, postmenopausal hormone use, and adult weight gain, on cumulative incidence of breast cancer. Breast cancer incidence in China is expected to increase substantially from current rates, estimated at 10–60 cases per 100 000 women, to more than 100 new cases per 100 000 women aged 55–69 years by 2021. We predicted 2.5 million cases of breast cancer by 2021 among Chinese women who were 35–49 years old in 2001. Modest reductions in hormone and alcohol use, and weight maintenance could prevent 270 000 of these cases. China is on the cusp of a breast cancer epidemic. Although some risk factors associated with economic development are largely unavoidable, the substantial predicted increase in new cases of breast cancer calls for urgent incorporation of this disease in future health care infrastructure planning.
Sphingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis
Authors: Heiko Sic, Helene Kraus, Josef Madl, Karl-Andreas Flittner, Audrey Lilly von Münchow, Kathrin Pieper, Marta Rizzi, Anne-Kathrin Kienzler, Korcan Ayata, Sebastian Rauer, Burkhard Kleuser, Ulrich Salzer, Meike Burger, Katja Zirlik, Vassilios Lougaris, Alessandro Plebani, Winfried Römer, Christoph Loeffler, Samantha Scaramuzza, Anna Villa, Emiko Noguchi, Bodo Grimbacher, Hermann Eibel
Journal: Journal of Allergy and Clinical Immunology (2014)
Neoadjuvant Chemotherapy Without Routine Use of Radiation Therapy for Patients With Locally Advanced Rectal Cancer: A Pilot Trial
Authors: Deborah Schrag, Martin R. Weiser, Karyn A. Goodman, Mithat Gon̈en, Ellen Hollywood, Andrea Cercek, Diane L. Reidy-Lagunes, Marc J. Gollub, Jinru Shia, Jose G. Guillem, Larissa K.F. Temple, Philip B. Paty, Leonard B. Saltz
Journal: Journal of Clinical Oncology (2014)

Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.
Epidermal Growth Factor Receptor–Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer
Authors: Zhiwei Wang, Radha Sengupta, Sanjeev Banerjee, Yiwei Li, Yuxiang Zhang, K.M. Wahidur Rahman, Amro Aboukameel, Ramzi Mohammad, Adhip P.N. Majumdar, James L. Abbruzzese, Fazlul H. Sarkar
Journal: Cancer Research (2006)

Abstract The epidermal growth factor receptor (EGFR) signaling network plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting EGFR would be extremely valuable for pancreatic cancer therapy. EGFR-related protein (ERRP), a recently identified pan-erbB inhibitor, has been shown to inhibit growth and induce apoptosis of pancreatic cancer cells in vitro and tumor growth in a xenograft model. However, the precise molecular mechanism(s) by which ERRP exerts its antitumor activity remains unclear. The current investigation was undertaken to delineate the tumor growth inhibitory mechanism(s) of ERRP in pancreatic cancer cells. Using multiple molecular assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis, gene transfection, real-time reverse transcription-PCR, Western blotting, invasion, and electrophoretic mobility shift assay for measuring DNA-binding activity of nuclear factor-κB (NF-κB), we found that ERRP caused marked inhibition of pancreatic cancer cell growth. This was accompanied by increased apoptosis and concomitant attenuation of Notch-1 and NF-κB and down-regulation of NF-κB downstream genes, such as matrix metalloproteinase-9 and vascular endothelial growth factor, resulting in the inhibition of pancreatic cancer cell invasion through the Matrigel. We also found that down-regulation of Notch-1 by small interfering RNA before ERRP treatment resulted in enhanced cell growth inhibition and apoptosis. Our data suggest that the ERRP-mediated inactivation of EGFR, Notch-1, NF-κB, and its downstream target genes contributed to the inhibition of cell growth and invasion. We conclude that ERRP could be an effective agent for inhibiting tumor growth and invasion for the treatment of pancreatic cancer. (Cancer Res 2006; 66(15): 7653-60)
Lifecourse Childhood Adiposity Trajectories Associated With Adolescent Insulin Resistance
Authors: Rae-Chi Huang, Nicholas H. de Klerk, Anne Smith, Garth E. Kendall, Louis I. Landau, Trevor A. Mori, John P. Newnham, Fiona J. Stanley, Wendy H. Oddy, Beth Hands, Lawrence J. Beilin
Journal: Diabetes Care (2011)

In light of the obesity epidemic, we aimed to characterize novel childhood adiposity trajectories from birth to age 14 years and to determine their relation to adolescent insulin resistance.A total of 1,197 Australian children with cardiovascular/metabolic profiling at age 14 years were studied serially from birth to age 14 years. Semiparametric mixture modeling was applied to anthropometric data over eight time points to generate adiposity trajectories of z scores (weight-for-height and BMI). Fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were compared at age 14 years between adiposity trajectories.Seven adiposity trajectories were identified. Three (two rising and one chronic high adiposity) trajectories comprised 32% of the population and were associated with significantly higher fasting insulin and HOMA-IR compared with a reference trajectory group (with longitudinal adiposity z scores of approximately zero). There was a significant sex by trajectory group interaction (P < 0.001). Girls within a rising trajectory from low to moderate adiposity did not show increased insulin resistance. Maternal obesity, excessive weight gain during pregnancy, and gestational diabetes were more prevalent in the chronic high adiposity trajectory.A range of childhood adiposity trajectories exist. The greatest insulin resistance at age 14 years is seen in those with increasing trajectories regardless of birth weight and in high birth weight infants whose adiposity remains high. Public health professionals should urgently target both excessive weight gain in early childhood across all birth weights and maternal obesity and excessive weight gain during pregnancy.
Letter to the editor: Diagnosis of a single imported dengue case who had travelled to Japan – how serious is it for travellers?
Authors: R Ueno, H Nishiura
Journal: Eurosurveillance (2014)

Preview this article: Letter to the editor: Diagnosis of a single imported dengue case who had travelled to Japan – how serious is it for travellers?, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/19/8/art20715-en-1.gif