tbuckley/cabot-search huggingface dataset:
Abrogation of the requirement for feeder cell interaction and T cell receptor stimulation of lymphocytes infected with retroviral vectors.
Authors: C Laker, G Gräning, A Kelso, C Stocking, W Ostertag
Journal: The Journal of Experimental Medicine (1990)

Infection of sensitive adult mice with myeloproliferative sarcoma virus (MPSV) results in a myeloproliferative syndrome. Two components of the viral genome are required to induce this unique pathology: the mos oncogene and sequences within the U3 region of the long terminal repeat (LTR). In studies designed to identify the target cell of MPSV and thus better understand the mechanism by which a myeloproliferative syndrome is induced, we have infected a series of T cell lines with MPSV-based vectors. The results presented here show that infection with neoR MPSV abrogates the requirement for an antigen-specific or feeder cell-dependent stimulation, without altering the requirement for interleukin 2. Significantly, this response is not dependent on the mos oncogene, but requires sequences within the U3 region of the MPSV LTR. No alteration in the constitutive or induced levels of lymphokines released by these cells was observed. These results suggest a model in which T cells acquire a proliferative advantage by uncoupling the proliferative response from the lymphokine synthesis that is induced by activation of the T cell receptor. These cells are thus poised for antigen stimulation and secretion of cytokines that stimulate myelopoiesis.
Efficacy of MRI and Mammography for Breast-Cancer Screening in Women with a Familial or Genetic Predisposition
Authors: Mieke Kriege, Cecile T.M. Brekelmans, Carla Boetes, Peter E. Besnard, Harmine M. Zonderland, Inge Marie Obdeijn, Radu A. Manoliu, Theo Kok, Hans Peterse, Madeleine M.A. Tilanus-Linthorst, Sara H. Muller, Sybren Meijer, Jan C. Oosterwijk, Louk V.A.M. Beex, Rob A.E.M. Tollenaar, Harry J. de Koning, Emiel J.T. Rutgers, Jan G.M. Klijn
Journal: New England Journal of Medicine (2004)

The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women.Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups.We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups.MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer.
Retrospective survival of COPD patients according to disease stage and pulmonary rehabilitation program
Authors: Audhild Hjalmarsen, Tormod Brenn, Marijke Jongsma Risberg, Kathrine Meisler Antonsen, Elisabeth Kristiansen Benum
Journal: European Respiratory Journal (2012)

The aim of this study was to examine the retrospective survival of patients with chronic obstructive pulmonary disease (COPD) according to type of pulmonary rehabilitation (PR) program and Global Initiative for Obstructive Lung Disease (GOLD) stage.  Retrospectively, 193 patients (m / f 92 / 101, mean age 69.2 ± 8.6 SD) receiving PR were studied with lifetable analyses. FEV 1  % pred. was significantly different in the in-patient (n = 72), out-patient (n = 72), and maintenance group (n = 49) [mean 54.5 ± 21.8 SD, 52.2 ± 17.7, and 42.9 ± 15.0, respectively (p  1  and the use of long-term oxygen therapy (LTOT) (p  10 in stage 1 (n = 18) and 2 (n = 74). The impact of the evaluated variables on survival in the GOLD stages was significant for age, LTOT and stage 3 (p   In conclusion, patients with GOLD stage 4 lived significantly longer than stage 3. Older age, decreased pulmonary function and LTOT predicted poorer survival in all PR groups. In addition to older age and LTOT, stage 3 predicted significantly poorer survival.
The rate of NSAID-induced endoscopic ulcers increases linearly but not exponentially with age: a pooled analysis of 12 randomised trials
Authors: M. Boers, M. J D Tangelder, H. van Ingen, J. G Fort, J. L Goldstein
Journal: Annals of the Rheumatic Diseases (2006)

The risk of major ulcer complications on treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is known to increase exponentially with age. However, in a pooled analysis of 12 trial arms, the incidence of endoscopic ulcers on treatment with NSAID was found to increase with age in a roughly linear fashion. Thus, it is concluded that increasing age is associated with both more frequent and more serious NSAID gastropathy.
Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration
Authors: Jeffrey S. Dome, Norbert Graf, James I. Geller, Conrad V. Fernandez, Elizabeth A. Mullen, Filippo Spreafico, Marry Van den Heuvel-Eibrink, Kathy Pritchard-Jones
Journal: Journal of Clinical Oncology (2015)

Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level.
Brief Report: A Novel Application of Buccal Micronucleus Cytome Assay in Systemic Lupus Erythematosus: A Case–Control Study
Authors: Ziad S. Al‐Rawi, Faiq I. Gorial, Rana Fawzi Tawfiq, Ahmed Khaled Mohammed, Ahmed S. Al‐Naaimi, Mohammed A. Al'aadhmi, Ali A. Hayyawi
Journal: Arthritis & Rheumatology (2014)

Systemic lupus erythematous (SLE) is a systemic autoimmune disease, and both genetic and environmental factors are implicated in its pathogenesis. The aim of this study was to assess cellular and nuclear morphology of SLE using a buccal micronucleus cytome assay.This study included 58 SLE patients and 58 healthy age- and sex-matched controls. Patients' baseline characteristics were recorded, and a buccal micronucleus cytome assay was used to measure cellular and nuclear abnormalities in both groups.Significantly higher frequencies of micronuclei, nuclear buds, binucleated cells, basal cells, condensed chromatin cells, karyorrhectic cells, pyknotic cells, and karyolytic cells were seen in SLE patients as compared to controls. A buccal micronucleus cytome assay score of ≥4 had the highest accuracy (93.1%), almost perfect positive predictive value (98.1% at 50% pretest probability and 99.8% at 90% pretest probability), 87.9% sensitivity, and 98.3% specificity for the diagnosis of SLE.Biomarkers of DNA damage, proliferative potential, and cell death were significantly increased in SLE patients. The buccal micronucleus cytome assay was a valid and easy way for clinicians to assess individuals at high risk of developing SLE.
“Re-educating” tumor-associated macrophages by targeting NF-κB
Authors: Thorsten Hagemann, Toby Lawrence, Iain McNeish, Kellie A. Charles, Hagen Kulbe, Richard G. Thompson, Stephen C. Robinson, Frances R. Balkwill
Journal: The Journal of Experimental Medicine (2008)

The nuclear factor κB (NF-κB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-κB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive “alternative” phenotype that requires IκB kinase β–mediated NF-κB activation. When NF-κB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a “classically” activated phenotype; IL-12high, major histocompatibility complex IIhigh, but IL-10low and arginase-1low. Targeting NF-κB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12–dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to “re-educate” the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies.
Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes
Authors: Philip R. Schauer, Sangeeta R. Kashyap, Kathy Wolski, Stacy A. Brethauer, John P. Kirwan, Claire E. Pothier, Susan Thomas, Beth Abood, Steven E. Nissen, Deepak L. Bhatt
Journal: New England Journal of Medicine (2012)

Observational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.In this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49±8 years, and 66% were women. The average glycated hemoglobin level was 9.2±1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment.Of the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P=0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P=0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5±1.8% in the medical-therapy group, 6.4±0.9% in the gastric-bypass group (P<0.001), and 6.6±1.0% in the sleeve-gastrectomy group (P=0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (-29.4±9.0 kg and -25.1±8.5 kg, respectively) than in the medical-therapy group (-5.4±8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications.In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.).
Is the lack of physical activity strategy for children complicit mass child neglect?
Authors: Richard Weiler, Sam Allardyce, Gregory P Whyte, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2013)

A rapidly burgeoning evidence base demonstrates a link between academic performance and physical fitness (closely linked to physical activity) for children of all ages and socioeconomic groups.1–3 There is also an inverse association between physical fitness and reported violent and antisocial incidents in school.2 Physical education, games and sport for children have a demonstrable positive impact on physical health, and affective, social and cognitive function.4 Furthermore, physical activity habits in childhood seem to determine, in part, adult physical activity behaviour,5 ,6 which is a key determinant of adult health.7

A recent BMJ editorial8 suggested that child health in the UK lags behind most European counterparts,9 and that despite numerous initiatives since 1999, only children from wealthier and more advantaged families seem to have benefited.10 A recent British Medical Association (BMA) report called for the need for a total prevention approach for children, but the leadership and strategy for such urgent and challenging public health measures are totally absent.11 The apparent importance and pervasiveness of physical inactivity among school children has led to a recent Lancet call for physical activity to be ‘a priority for all schools’ that requires ‘whole school’ strategies and government support12 and the Welsh government has committed ‘to make physical literacy as important a development skill as reading and writing’, yet has failed to deliver this pragmatic strategy.13 The English Secretary of State for Education recently announced a set of reforms to school curriculums for 2014, but showed no commitment to revolutionising physical activity and physical education for children. These physical activity-lacking reforms were announced with a great fanfare to the media and praised by the Prime Minister as providing the ‘very best education for their future and for our country’s future’.

School age boys …
Monitoring the Response of Orthotopic Bladder Tumors to Granulocyte Macrophage Colony-Stimulating Factor Therapy Using the <b> <i>Prostate-Specific Antigen</i> </b> Gene as a Reporter
Authors: Qinghui Wu, Kesavan Esuvaranathan, Ratha Mahendran
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Although orthotopic animal models of cancer best reflect the disease in humans, a major drawback of these models is the inability to monitor tumor growth accurately. Our aims were to produce a bladder tumor cell line (MB49) that secreted human prostate-specific antigen (PSA), analyze the feasibility and accuracy of PSA as a biomarker for monitoring orthotopic bladder tumor growth, and evaluate the effectiveness of granulocyte macrophage colony-stimulating factor (GM-CSF) gene therapy using this model. Experimental Design: PSA secretion was assessed after both s.c. and orthotopic implantation of MB49-PSA cells in C57BL/6 mice. PSA levels in mouse serum and urine samples were monitored at 2- to 3-day intervals by ELISA. Using the orthotopic model, mice with confirmed tumors were given liposome-mediated GM-CSF gene therapy twice a week for 3 weeks intravesically and PSA levels monitored. Results: The MB49-PSA cells behaved similarly as the parental cell line and produced high levels of PSA both in vitro and in vivo. In the s.c. model, the level of PSA produced correlated with tumor volume (r = 0.96). In the orthotopic model, PSA could be detected in serum and urine on the fourth day after implantation. PSA levels over the treatment period indicated that tumor growth was inhibited by GM-CSF gene therapy. Up to 50% of the treated mice were cured. Cytokine array analysis revealed that GM-CSF gene therapy induced the production of other cytokines and chemokines. Conclusions: MB49 cells modified to secrete PSA are a reliable method to evaluate therapeutic modalities for bladder cancer.
A prospective randomised study of "covered" versus "uncovered" diamond stents for the management of distal malignant biliary obstruction
Authors: H Isayama
Journal: Gut (2004)

<b>Background and aim:</b> Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking. <b>Patients and methods:</b> We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55). <b>Results:</b> Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group. <b>Conclusions:</b> Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.
Parents’ Preferences for Enhanced Access in the Pediatric Medical Home
Authors: Joseph S. Zickafoose, Lisa R. DeCamp, Lisa A. Prosser
Journal: JAMA Pediatrics (2015)

Efforts to transform primary care through the medical home model may have limited effectiveness if they do not incorporate families' preferences for different primary care services.To assess parents' relative preferences for different categories of enhanced access services in primary care.Internet-based survey that took place with a national online panel from December 8, 2011, to December 22, 2011. Participants included 820 parents of children aged 0 to 17 years. Hispanic and black non-Hispanic parents were each oversampled to 20% of the sample. The survey included a discrete choice experiment with questions that asked parents to choose between hypothetical primary care practices with different levels of enhanced access and other primary care services.We estimated parents' relative preferences for different enhanced access services using travel time to the practice as a trade-off and parents' marginal willingness to travel in minutes for practices with different levels of services.The response rate of parents who participated in the study was 41.2%. Parents were most likely to choose primary care offices that guaranteed same-day sick visits (coefficient, 0.57 [SE, 0.05]; P < .001) followed by those with higher professional continuity (coefficient, 0.36 [SE, 0.03]; P < .001). Parents were also significantly more likely to choose practices with 24-hour telephone advice plus nonurgent email advice (0.08 [0.04]; P < .05), evening hours 4 or more times a week (0.14 [0.04]; P < .001), and at least some hours on weekends. Parents were significantly less likely to choose practices that were closed during some weekday daytime hours or had wait times longer than 4 weeks for preventive care visits. There was very little variation in preferences among parents with different sociodemographic characteristics. Parents' marginal willingness to travel was 14 minutes (95% CI, 11-16 minutes) for guaranteed same-day sick visits and 44 minutes (95% CI, 37-51 minutes) for an office with idealized levels of all services.As primary care practices for children implement aspects of the medical home model, those that emphasize same-day sick care and professional continuity are more likely to meet parents' preferences for enhanced access. Practices should seek to engage families in prioritizing changes in practice services as part of medical home implementation.
SPINK1 Protein Expression and Prostate Cancer Progression
Authors: Richard Flavin, Andreas Pettersson, Whitney K. Hendrickson, Michelangelo Fiorentino, Stephen Finn, Lauren Kunz, Gregory L. Judson, Rosina Lis, Dyane Bailey, Christopher Fiore, Elizabeth Nuttall, Neil E. Martin, Edward Stack, Kathryn L. Penney, Jennifer R. Rider, Jennifer Sinnott, Christopher Sweeney, Howard D. Sesso, Katja Fall, Edward Giovannucci, Philip Kantoff, Meir Stampfer, Massimo Loda, Lorelei A. Mucci
Journal: Clinical Cancer Research (2014)

Abstract Purpose: SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer–specific survival. Experimental Design: The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983–2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays. Results: Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P &amp;lt; 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29–1.76). Conclusions: Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested. Clin Cancer Res; 20(18); 4904–11. ©2014 AACR.