tbuckley/cabot-search huggingface dataset:
Risk of Breast Cancer After False-Positive Test Results in Screening Mammography
Authors: M. von Euler-Chelpin, L. M. Risor, B. L. Thorsted, I. Vejborg
Journal: JNCI Journal of the National Cancer Institute (2012)

Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests is unknown.We used data from a long-standing population-based screening mammography program in Copenhagen, Denmark, to determine the long-term risk of breast cancer in women with false-positive tests. The age-adjusted relative risk (RR) of breast cancer for women with a false-positive test compared with women with only negative tests was estimated with Poisson regression, adjusted for age, and stratified by screening round and technology period. All statistical tests were two-sided.A total of 58 003 women, aged 50-69 years, were included in the analysis. Women with negative tests had an absolute cancer rate of 339/100 000 person-years at risk, whereas women with a false-positive test had an absolute rate of 583/100 000 person-years at risk. The adjusted relative risk of breast cancer after a false-positive test was 1.67 (95% confidence interval [CI] 1.45 to 1.88). The relative risk remained statistically significantly increased 6 or more years after the false-positive test, with point estimates varying between 1.58 and 2.30. When stratified by assessment technology phase and using equal follow-up time, the false-positive group from the mid 1990s had a statistically significantly higher risk of breast cancer (RR = 1.65, 95% CI = 1.22 to 2.24) than the group with negative tests, whereas the false-positive group from the early 2000s was not statistically significantly different from the group testing negative.The implementation of new assessment technology coincided with a decrease in the size of excess risk of breast cancer for women with false-positive screening results. However, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening.
Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2
Authors: Michael P. O'Connell, Katie Marchbank, Marie R. Webster, Alexander A. Valiga, Amanpreet Kaur, Adina Vultur, Ling Li, Meenhard Herlyn, Jessie Villanueva, Qin Liu, Xiangfan Yin, Sandy Widura, Janelle Nelson, Nivia Ruiz, Tura C. Camilli, Fred E. Indig, Keith T. Flaherty, Jennifer A. Wargo, Dennie T. Frederick, Zachary A. Cooper, Suresh Nair, Ravi K. Amaravadi, Lynn M. Schuchter, Giorgos C. Karakousis, Wei Xu, Xiaowei Xu, Ashani T. Weeraratna
Journal: Cancer Discovery (2013)

An emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive phenotype to a highly invasive, less proliferative one. This switch may hold significant implications not just for metastasis, but also for therapy resistance. We demonstrate that phenotype switching and subsequent resistance can be guided by changes in expression of receptors involved in the noncanonical Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Furthermore, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. Notably, this receptor switch induces a 10-fold decrease in sensitivity to BRAF inhibitors. In patients with melanoma treated with the BRAF inhibitor vemurafenib, Wnt5A expression correlates with clinical response and therapy resistance. These data highlight the fact that mechanisms that guide metastatic progression may be linked to those that mediate therapy resistance.These data show for the fi rst time that a single signaling pathway, the Wnt signaling pathway, can effectively guide the phenotypic plasticity of tumor cells, when primed to do so by a hypoxic microenvironment. Importantly, this increased Wnt5A signaling can give rise to a subpopulation of highly invasive cells that are intrinsically less sensitive to novel therapies for melanoma, and targeting the Wnt5A/ROR2 axis could improve the efficacy and duration of response for patients with melanoma on vemurafenib.
Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts
Authors: Lydia Usha, Bita Tabesh, Larry E Morrison, Ruta D Rao, Kris Jacobson, April Zhu, Sanjib Basu, John S Coon
Journal: Journal of Hematology & Oncology (2008)

Amplification of the ERBB2 (Her-2/neu) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for topoisomerase II alpha (TOP2A), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy.Archival tissue samples from 63 breast cancer patients with ERBB2 amplification, stages 0-IV, were previously analyzed with FISH probes for genes located near ERBB2. In the present study, the clinical outcome data were determined for all patients presenting at stages I-III for whom adequate clinical follow up was available.Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted TOP2A had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. TOP2A deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between TOP2A deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06).TOP2A deletion is associated with poor prognosis in ERBB2-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.
Comment on Sarkar et al. Exenatide Treatment for 6 Months Improves Insulin Sensitivity in Adults With Type 1 Diabetes. Diabetes Care 2014;37:666–670
Authors: Ajay Chaudhuri, Nitesh Kuhadiya, Husam Ghanim, Paresh Dandona
Journal: Diabetes Care (2014)

We read with interest the article by Sarkar et al. (1) that reported that when exenatide in high doses is administered to patients with type 1 diabetes it has an insulin-sensitizing action. In spite of this effect, there was no improvement in HbA1c levels; however, there was a reduction in insulin dose. As the aim of the study was to investigate the effect of exenatide on insulin sensitivity and the baseline HbA1c in this group of patients was 7%, it is possible that the investigators were cautious in preventing …
Therapeutic Nanoparticles for Drug Delivery in Cancer
Authors: Kwangjae Cho, Xu Wang, Shuming Nie, Zhuo (Georgia) Chen, Dong M. Shin
Journal: Clinical Cancer Research (2008)

Abstract Cancer nanotherapeutics are rapidly progressing and are being implemented to solve several limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. To improve the biodistribution of cancer drugs, nanoparticles have been designed for optimal size and surface characteristics to increase their circulation time in the bloodstream. They are also able to carry their loaded active drugs to cancer cells by selectively using the unique pathophysiology of tumors, such as their enhanced permeability and retention effect and the tumor microenvironment. In addition to this passive targeting mechanism, active targeting strategies using ligands or antibodies directed against selected tumor targets amplify the specificity of these therapeutic nanoparticles. Drug resistance, another obstacle that impedes the efficacy of both molecularly targeted and conventional chemotherapeutic agents, might also be overcome, or at least reduced, using nanoparticles. Nanoparticles have the ability to accumulate in cells without being recognized by P-glycoprotein, one of the main mediators of multidrug resistance, resulting in the increased intracellular concentration of drugs. Multifunctional and multiplex nanoparticles are now being actively investigated and are on the horizon as the next generation of nanoparticles, facilitating personalized and tailored cancer treatment.
Overall Survival and Development of Stage IV Chronic Kidney Disease in Patients Undergoing Partial and Radical Nephrectomy for Benign Renal Tumors
Authors: Dharam Kaushik, Simon P. Kim, M. Adam Childs, Christine M. Lohse, Brian A. Costello, John C. Cheville, Stephen A. Boorjian, Bradley C. Leibovich, R. Houston Thompson
Journal: European Urology (2012)
Effects of a web based decision aid on parental attitudes to MMR vaccination: a before and after study
Authors: Cate Wallace, Julie Leask, Lyndal J Trevena
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine whether an evidence based decision aid on the measles, mumps, and rubella (MMR) vaccine changed parents9 attitudes towards vaccination. <b>Design</b> Before and after study. <b>Setting</b> Website promoted through search engines and online parenting and health websites. <b>Participants</b> 158 people completing online questions out of 1277 who accessed the website. <b>Intervention</b> Evidence based decision aid with text and graphical representation of the possible outcomes of measles, mumps, and rubella diseases compared with MMR vaccination. <b>Main outcome measures</b> Attitudes towards MMR vaccination. <b>Results</b> Significantly more participants indicated they were “leaning towards” vaccination after using the decision aid (39% before <i>v</i> 55% after, P &lt; 0.001). Compared with those who were undecided or “leaning away from” vaccination after using the decision aid, participants “leaning towards” it were more likely to strongly value its potential to protect their children from the serious side effects of disease (98% <i>v</i> 84%) and other children who could not be vaccinated for medical reasons (68% <i>v</i> 25%). Participants with an unfavourable attitude to vaccination were more likely to be very concerned about the rare side effects of vaccination (78% <i>v</i> 57%), have residual concerns about autism and bowel disease (78% <i>v</i> 27%), and anticipate guilt should their child have an adverse reaction (77% <i>v</i> 50%). Those with a positive attitude to vaccination after using the decision aid were also more likely to feel well informed (83% <i>v</i> 48%). <b>Conclusions</b> A web based decision aid significantly improved parental attitudes to MMR vaccination. Residual concerns about autism and bowel disease and the rare chance of serious complications remained as attitudinal barriers to some parents.
Atrial enlargement as a consequence of atrial fibrillation. A prospective echocardiographic study.
Authors: A J Sanfilippo, V M Abascal, M Sheehan, L B Oertel, P Harrigan, R A Hughes, A E Weyman
Journal: Circulation (1990)

To test the hypothesis that atrial enlargement can develop as a consequence of atrial fibrillation, left and right atrial dimensions were measured echocardiographically at two different time points in patients with atrial fibrillation. Patients were selected who initially had normal atrial sizes and who had no evidence of significant structural or functional cardiac abnormalities other than atrial fibrillation either by history or two-dimensional and Doppler echocardiography. Fifteen patients were studied (12 men and three women; mean age, 67.3 years). Average time between studies was 20.6 months. Three orthogonal left atrial dimensions and two right atrial dimensions were measured, and all were found to increase significantly between studies. Also, highly significant increases in calculated left atrial volume (from 45.2 to 64.1 cm3, p less than 0.001) and right atrial volume (from 49.2 to 66.2 cm3, p less than 0.001) were observed. The relative extents of left and right atrial volume increase did not differ, and left ventricular size did not change significantly between studies. These results indicate that atrial enlargement can occur as a consequence of atrial fibrillation. The maintenance of sinus rhythm, therefore, may prevent atrial enlargement and its adverse clinical effects.
Mast Cell Tryptase Deficiency Attenuates Mouse Abdominal Aortic Aneurysm Formation
Authors: Jie Zhang, Jiusong Sun, Jes S. Lindholt, Galina K. Sukhova, Mark Sinnamon, Richard L. Stevens, Roberto Adachi, Peter Libby, Robert W. Thompson, Guo-Ping Shi
Journal: Circulation Research (2011)

Mast cells (MCs) contribute to the formation of abdominal aortic aneurysms (AAAs) by producing biologically active mediators. Tryptase is the most abundant MC granule protein and participates in MC activation, protease maturation, leukocyte recruitment, and angiogenesis-all processes critical to AAA pathogenesis.To test the hypothesis that tryptase participates directly in AAA formation.Immunohistochemistry demonstrated enhanced tryptase staining in media and adventitia of human and mouse AAA lesions. Serum tryptase levels correlated significantly with the annual expansion rate of AAA before (r = 0.30, P = 0.003) and after (r = 0.29, P = 0.005) adjustment for common AAA risk factors in a patient follow-up study, and associated with risks for later surgical repair or overall mortality before (P = 0.009, P = 0.065) and after (P = 0.004, P = 0.001) the adjustment. Using MC protease-6-deficient mice (Mcpt6(-/-)) and aortic elastase perfusion-induced experimental AAAs, we proved a direct role of this tryptase in AAA pathogenesis. Whereas all wild-type (WT) mice developed AAA at 14 or 56 days postperfusion, Mcpt6(-/-) mice were fully protected. AAA lesions from Mcpt6(-/-) mice had fewer inflammatory and apoptotic cells, and lower chemokine levels, than did those from WT mice. MC from WT mice restored reduced AAA lesions and lesion inflammatory cell content in MC-deficient Kit(W-sh/W-sh) mice, but those prepared from Mcpt6(-/-) mice did not. Mechanistic studies demonstrated that tryptase deficiency affected endothelial cell (EC) chemokine and cytokine expression, monocyte transmigration, smooth-muscle cell apoptosis, and MC and AAA lesion cysteinyl cathepsin expression and activities.This study establishes the direct participation of MC tryptase in the pathogenesis of experimental AAAs, and suggests that levels of this protease can serve as a novel biomarker for abdominal aortic expansion.
Yersinia and chronic glomerulopathy in the savannah region of Nigeria.
Authors: C Awunor-Renner, R V Lawande
Journal: BMJ (1982)

Yersinia and chronic glomerulopathy in the savannah region of Nigeria Glomerular disease secondary to Yersinia enterocolitica infection is well recognised in some parts of the world.1 2 It has been suggested3 that the glomerulopathy from this infection might progress to chronic glomerulopathy.In this study, which formed part of an investigation into the pattern of glomerular disease in the savannah belt in Nigeria, we investigated the association between Y enterocolitica and chronic glomerular disease.
Impaired Cognitive Function and Hippocampal Neurogenesis following Cancer Chemotherapy
Authors: Lori-Ann Christie, Munjal M. Acharya, Vipan K. Parihar, Anna Nguyen, Vahan Martirosian, Charles L. Limoli
Journal: Clinical Cancer Research (2012)

A substantial proportion of breast cancer survivors report significant, long-lasting impairments in cognitive function, often referred to as "chemobrain." Advances in detection and treatment mean that many more patients are surviving long-term following diagnosis of invasive breast cancer. Thus, it is important to define the types, extent, and persistence of cognitive impairments following treatment with cytotoxic cancer drugs.We examined the effects of chronic treatment with two agents commonly used in patients with breast cancer, cyclophosphamide and doxorubicin (Adriamycin). Athymic nude rats were given 50 mg/kg cyclophosphamide, 2 mg/kg doxorubicin, or saline injections once per week for 4 weeks. A novel place recognition task and contextual and cued fear conditioning were used to characterize learning and memory ability. Immunofluorescence staining for immature and mature neurons and activated microglia was used to assess changes in neurogenesis and neuroinflammation.Cyclophosphamide- and doxorubicin-treated rats showed significantly impaired performance on the novel place recognition task and the contextual fear conditioning task compared with untreated controls, suggesting disrupted hippocampal-based memory function. Chemotherapy-treated animals showed a significant decline in neurogenesis [80%-90% drop in bromodeoxyuridine (BrdUrd)-labeled cells expressing NeuN]. Activated microglia (ED1-positive) were found after cyclophosphamide but not doxorubicin treatment.Our results show that chronic treatment with either of two commonly used chemotherapeutic agents impairs cognitive ability and suggest that strategies to prevent or repair disrupted hippocampal neurogenesis may be effective in ameliorating this serious side effect in cancer survivors.
TREATMENT OF SOLAR KERATOSES WITH TOPICALLY-APPLIED CYTOSTATIC AGENTS
Authors: JAMES MARSHALL
Journal: British Journal of Dermatology (1968)

Journal Article TREATMENT OF SOLAR KERATOSES WITH TOPICALLY‐APPLIED CYTOSTATIC AGENTS Get access JAMES MARSHALL JAMES MARSHALL Department of Dermatology, Stellenbosch University, South Africa Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 8, 1 August 1968, Pages 540–542, https://doi.org/10.1111/j.1365-2133.1968.tb12345.x Published: 01 August 1968 Article history Accepted: 22 April 1968 Published: 01 August 1968
Donor smoking reduces recipient survival after lung transplant
Authors: Robert Derrick
Journal: Thorax (2012)

CLUB Donor smoking reduces recipient survival after lung transplantThis study investigated whether lung transplantation from donors with a positive smoking history was associated with increased morbidity and mortality in recipients.Data were analysed from 2181 lung transplant waiting-list patients in whom 1295 lung transplants from brain-dead donors were carried out in the UK between 1999 and 2010.Sequential stratification was used to assess survival from waiting list registration in those receiving lung transplants from donors with positive smoking histories as compared with matched controls on the waiting list not receiving such transplants.Primary outcome was survival post transplant at 3 years and secondary outcomes included recipients' cause of death, post-transplant hospital and intensive therapy unit (ITU) length of stay and FEV 1 at 2 years in those receiving bilateral transplants.Recipients of lungs transplanted from donors with a positive smoking history had lower survival (median 4.9 years vs 6.5 years), longer hospital/ITU stays and a 10% reduced FEV 1 at 2 years compared with those receiving lungs from non-smokers.All cause survival was inferior at 30 days and rates of death due to graft failure were increased after 90 days in patients receiving lungs from donors with a positive smoking history.Lungs from donors with predicted cigarette consumption >20/day were associated with the worst recipient outcomes.Thirty-nine per cent of transplants were from donors with a positive smoking history.Although transplantation of such lungs is associated with increased morbidity and mortality compared with those from non-smokers, overall waiting list mortality is reduced by their acceptance (adjusted HR for death at 3 years 1.36).Recipients with the greatest benefit were those with septic and fibrotic lung diseases.Whether a pack-year threshold above which lungs from donors who smoke should be rejected is yet to be established but caution is advised in those with greater than 20 pack years.
Cardiac-Specific Deletion of <i>Mkk4</i> Reveals Its Role in Pathological Hypertrophic Remodeling but Not in Physiological Cardiac Growth
Authors: Wei Liu, Min Zi, Jiawei Jin, Sukhpal Prehar, Delvac Oceandy, Tomomi E. Kimura, Ming Lei, Ludwig Neyses, Arthur H. Weston, Elizabeth J. Cartwright, Xin Wang
Journal: Circulation Research (2009)

Mitogen-activated protein kinase kinase (MKK)4 is a critical member of the mitogen-activated protein kinase family. It is able to activate the c-Jun NH(2)-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase in response to environmental stresses. JNK and p38 are strongly implicated in pathological cardiac hypertrophy and heart failure; however, the regulatory mechanism whereby the upstream kinase MKK4 activates these signaling cascades in the heart is unknown. To elucidate the biological function of MKK4, we generated mice with a cardiac myocyte-specific deletion of mkk4 (MKK4(cko) mice). In response to pressure overload or chronic beta-adrenergic stimulation, upregulated NFAT (nuclear factor of activated T-cell) transcriptional activity associated with exacerbated cardiac hypertrophy and the appearance of apoptotic cardiomyocytes were observed in MKK4(cko) mice. However, when subjected to swimming exercise, MKK4(cko) mice displayed a similar level of physiological cardiac hypertrophy compared to controls (MKK4(f/f)). In addition, we also discovered that MKK4 expression was significantly reduced in heart failure patients. In conclusion, this study demonstrates for the first time that MKK4 is a key mediator which prevents the transition from an adaptive response to maladaptive cardiac hypertrophy likely involving the regulation of the NFAT signaling pathway.
Hippocampal Volume and First Major Depressive Episode After Cancer Diagnosis in Breast Cancer Survivors
Authors: Masatoshi Inagaki, Yutaka Matsuoka, Yuriko Sugahara, Tomohito Nakano, Tatsuo Akechi, Maiko Fujimori, Shigeru Imoto, Koji Murakami, Yosuke Uchitomi
Journal: American Journal of Psychiatry (2004)

Patients experiencing their first major depressive episode after receiving a diagnosis of cancer are frequently seen in clinical oncology settings; however, little is known about the neurobiological basis of the first episode. In previous studies, a smaller hippocampus than in healthy comparison subjects has been observed in patients with a history of recurrent and prolonged major depressive episodes. The purpose of the present study was to investigate whether there is an association between hippocampal volume and a first major depressive episode after cancer diagnosis in cancer survivors.The subjects were 68 female cancer survivors who had undergone breast cancer surgery 3 or more years earlier (mean interval=4.3 years, SD=0.9). The hippocampal volume and delayed recall function of the 17 cancer survivors who had their first major depressive episode after receiving their cancer diagnosis and the 51 with no history of major depressive episode at any time during their lives were measured by magnetic resonance imaging and the Wechsler Memory Scale-Revised, respectively.The mean duration of the major depressive episode after cancer diagnosis was 11.9 weeks (SD=14.2). There were no significant differences in left or right hippocampal volume or in delayed recall function between the cancer survivors with and without a major depressive episode after cancer diagnosis.First major depressive episodes after cancer diagnosis in female cancer survivors do not appear to be associated with hippocampal volume. However, a longitudinal study with healthy comparison subjects is needed to draw a definite conclusion.