tbuckley/cabot-search huggingface dataset:
Ca-15.3 antigen as predictor of response to EGFR inhibitors in patients with bronchiolo-alveolar carcinoma
Authors: A. Bearz, R. Talamini, E. Vaccher, M. Spina, C. Simonelli, M. Berretta, S. Spazzapan, U. Tirelli
Journal: Journal of Clinical Oncology (2007)

18151 Background: Bronchiolo-alveolar carcinoma (BAC) is a subtype of non-small cell lung cancer (NSCLC). Incidence of pure BAC ranges between 2% and 5% of NSCLC although a BAC histotype may be present in up to 20%. There is no established treatment for BAC, although promising results have been achieved from the use of inhibitors of the Epidermal Growth Factor Receptor (EGFR). It has been demonstrated that there is a very close relationship between responsiveness to EGFR inhibitors Erlotinib and Gefitinib and some factors, including female gender; adenocarcinoma histotype, with BAC features; Asian origin; and never having smoked. No tumor marker has been validated in the diagnosis and follow-up of lung cancer. Ca 15–3 antigen serum levels are reported to be pathologically abnormal in adenocarcinoma of the lung, although it does not seem to be related to the EGFR pathway. We studied this tumor marker in relation with the treatment with EGFR inhibitors in patients affected by BAC. Methods: We collected data from 16 caucasian, female and never smoker pts with BAC. All pts received EGFR inhibitors as first-line therapy. In compliance with the EAP, dosage of Gefitinib and Erlotinib was 250 mg/day and 150 mg/day, respectively. Results: One (6%) pt had a complete response and 6 (38%) showed a partial response to EGFR inhibitors, 1 (6%) pt remained stable for 4 months, while 8 (50%) pts progressed. All 7 pts with normal Ca 15–3 levels before treatment with EGFR inhibitors’ achieved a partial or complete response, but the 8 pts with abnormal Ca 15–3 levels did not (p=0.0001). Among the responders we noticed an increase of Ca 15–3 serum levels at progression. In particular, 5 pts had an increase of Ca 15–3 serum levels up to normal value when their disease progressed; 2 pts have not progressed yet and Ca 15–3 serum levels remain normal. Conclusions: We suggest that Ca 15–3 levels may be a prognostic factor to predict the response to EGFR inhibitors in pts with BAC. We are studying its role in a larger population with BAC and in other NSCLC subtypes as well. No significant financial relationships to disclose.
Abstract 11608: Risk Factors for Atrial Arrhythmia and Thromboembolic Events in D-Transposition of the Great Arteries
Authors: Andrew Foy, Guodong Liu, William R Davidson, Douglas Leslie, Jennifer G Ting
Journal: Circulation (2014)

Introduction: Atrial arrhythmia (AA) is an important problem in patients with adult congenital heart disease (ACHD). Relatively little is known about the prevalence and risk factors for thromboembolic events (TE) in patients with D-TGA and AA and further prospective study on this subpopulation of ACHD patients is difficult. Therefore, we sought to define the prevalence of AA and TE in a large, national sample of patients with D-transposition of the great arteries (D-TGA). Methods: Retrospective analysis of health insurance claims data for a national sample of privately insured patients over the years 2008-2011. Individuals were included in the study cohort if they had a claim submitted for D-TGA at any time over the study period. The primary endpoints were claims submitted for AA, TE, and bleeding events; multivariate logistic regression was performed to identify independent variables associated with AA and TE. Results: 3,414 patients were included in the final cohort, 253 (7.4%) had an AA, 38 (1.1%) had ...
Targeting CXCR4/SDF-1 axis by lipopolymer complexes of siRNA in acute myeloid leukemia
Authors: Breanne Landry, Hilal Gül-Uludağ, Samarwadee Plianwong, Cezary Kucharski, Zoulika Zak, Manoj B. Parmar, Olaf Kutsch, Hongxing Jiang, Joseph Brandwein, Hasan Uludağ
Journal: Journal of Controlled Release (2015)
AKT activation is sufficient for maintenance of Ras-initiated tumour growth in vivo
Authors: Kian-Huat Lim, Christopher M. Counter
Journal: Cancer Research (2005)

2590   While much is understood regarding the molecular events that initiate tumour growth, many of the requirements to maintain this growth remain to be elucidated. One protein often activated in cancer cells that is known to be essential to both the initiation and maintenance stages of tumour progression is the oncogene Ras. Activated Ras binds to and activates a number of downstream proteins or effectors, notably i) Rafs, serine/threonine kinases that trigger the MAP-kinase cascade that is well established to promote cell proliferation, ii) PI3-kinase, a lipid kinase that activates the pro-survival AKT pathway, and iii) RalGEFs, GDP exchange factors for Ral A and B that are critical for the tumourigenic conversion of normal human cells. We now show by activating specific effectors of Ras that oncogenic Ras employs different effectors during the initiation and maintenance steps of tumourigenesis. Specifically, initiation of tumour growth requires all three of these effector pathways whereas when Ras signalling is silenced after tumour initiation, tumour growth continues only if PI3-kinase is still stimulated. This latter effect depended upon activation of the downstream target AKT, as an activated version of AKT or a decrease in the tumour suppressor PTEN, a negative regulator of this pathway5, similarly maintained tumour growth upon the loss of Ras signalling. In fact, just the presence of a malignant cells allowed otherwise non-malignant cells with an activated PI3-kinase pathway to populate tumours to the extent they comprised the majority of the tumour bulk. We therefore conclude that firstly, once tumour growth is initiated, activation of the pro-survival PI3-kinase/AKT pathway is sufficient to maintain this growth, and secondly, pre-malignant cells that activate this pathway can contribute significantly to the neoplastic growth of tumours.
Abstract #5598: Nanoparticle-mediated heating of prostate cancer cells: Does the method of heating matter?
Authors: Robert Ivkov, Mohammed Hedayati, Haoming Zhou, Yonggang Zhang, Theodore DeWeese
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Magnetic nanoparticles have emerged recently as a promising platform for the selective delivery of heat for cancer. When exposed to an alternating magnetic field (AMF), the particles generate heat that depends upon the type of particles, their concentration, and the properties of the AMF. While the dose-dependent effects of heat on cancer cells are generally well documented, little information exists to establish the biologic effects of heat dose and response from nanoparticle-mediated heat delivery, alone or when combined with radiation. Such information is fundamental to the eventual clinical use of this technology. We present results of a comparative study of the heat dose-response of (PC-3) prostate cancer cells to three different forms of heating: 1) Conventional, using water bath exposure for defined time-temperature doses; 2) Particle-mediated \#8220;interstitial\#8221; heating; and, 3) Nanoparticle-mediated intracellular heating. For each, samples were also exposed to 2- or 5-Gy doses of ionizing radiation for varying heat doses. Cell survival was quantified by clonogenic assay. For all nanoparticle-mediated heating, an AMF system was designed and fabricated to produce a field with homogeneous flux density (<+/- 10%) in a volume able to accommodate a variety of cell culture vessels, having variable amplitude between 100 to 500 Oersteds at about 150 kHz. Superparamagnetic iron oxide (SPIO)-dextran particles (100 nm) that were not targeted to the cells generated an \#8220;interstitial\#8221; heat dose by heating the cell media. For intracellular heating, 100 nm citrate-stabilized iron oxide particles were developed. The latter particles were rapidly ingested by the PC-3 cells. In all cases, temperature was monitored at one-second intervals with RF-resistant optical fiber temperature probes. The iron content of the cell cultures, necessary to establish a particle-dependent heat dose, was measured by inductively coupled plasma-mass spectrometry (ICP-MS). Microscopy techniques - electron and light - with appropriate staining were used to confirm the distribution of particles in the cell cultures. The combination of low-dose heating with 5 Gy radiation produced a measurable dose-dependent cytoxicity as the heat dose increased, even for heat doses that were insufficiently cytotoxic alone. On the other hand, the addition of heat to 2 Gy dose had little effect. Differences were observed with nanoparticle-mediated heating when compared with the water bath heating. These results and their implications are discussed.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5598.
Cost comparison of radiation treatment options after lumpectomy for breast cancer: Intraoperative radiotherapy versus alternatives.
Authors: Dennis R. Holmes, Juvairiya Pulicharamveettil, Gary Lee Sutter, Ronald J. Rivera
Journal: Journal of Clinical Oncology (2012)

187 Background: Increasing constraints on health care resources call for implementation of breast cancer treatment strategies that preserve treatment efficacy while reducing healthcare cost. In this investigation, we model potential cost savings associated with the use of single-fraction intraoperative radiotherapy (IORT) compared to two commonly used alternative radiotherapy approaches. Methods: A database survey was performed of female subjects undergoing breast conserving surgery (BCS) with or without sentinel lymphadenectomy at HealthCare Partners, a major IPA in metropolitan Los Angeles, CA. Subjects were identified by cross-referencing ICD-9 codes (174.0-174.9) for invasive breast cancer, CPT codes for BCS (19120, 19125, or 19301), and CPT codes for sentinel node biopsy without ALND (38500, 38525, or 38740). Calculations were based on the 2011 U.S. Medicare Fee Schedule. Treatment costs and savings were modeled assuming that patients with node-negative disease who underwent BCS were eligible for accelerated partial breast irradiation based on American Society of Breast Surgeons Guidelines (age ≥45, IDCA, DCIS, size ≤3 cm, node and margin negative). Results: A sample of 1,478 women meeting criteria was evaluated to determine the average per-patient cost of breast radiotherapy comparing three modalities: single-fraction IORT ($4,402), 5-day multi-lumen balloon brachytherapy (MLBB) (e.g., MammoSite) ($12,021), and standard 6-week whole breast external beam radiotherapy followed by a tumor bed boost (WBRT) ($8,988). IORT was approximately 49% the cost of standard 6-week WBRT and 37% the cost of MLBB. Conclusions: When eligible breast cancer patients are offered IORT as an alternative to WBRT, the expenditures from this sample may be reduced from $13.3M to $6.5M, a savings of $6.8M. Compared to MLBB, IORT may reduce radiotherapy expenditures from $17.8M to $6.5M, a savings of $11.3M. [Table: see text]
Authors misinterpreted results of study that they cited
Authors: E K Alpar, M King
Journal: BMJ (1996)

Low blood pressure is unlikely to be complication of dementia process EDrrOR,-Zhenchao Guo and colleagues report an association between low blood pressure and different types of dementia, including Alzheimer's disease.' Adults with Down's syndrome have a high prevalence of Alzheimer's disease2; they also have significantly lower diastolic and systolic blood pressures than the general population.3We reviewed data from a five year prospective longi- tudinal study investigating aging in a cohort of adults with Down's syndrome to explore a possible association between low blood pressure and Alzheimer's disease.Measurements of blood pressure and evidence used in making a diagnosis of Alzheimer's disease according to criteria in the International Classification of Diseases (10th revision)4 were available for 80 subjects aged over 45.Twenty one subjects fulfilled the criteria for Alzheimer's disease.The mean age of the group without dementia was 52.6 years and that of the group with dementia was 55.0 years (t=0.32,P=0.75).The mean systolic blood pressure was 109.5 mm Hg and 114.7 mm Hg respectively (t=1.6,P=0.25), and the mean diastolic blood pressure was 76.6 mm Hg and 75.9 mm Hg respectively (t=0.32,P=0.75).Thus there was no significant difference in either blood pressure between the two groups.Incessant hypoperfusion due to persistent low blood pressure in adults with Down's syndrome may predispose to the development of neuropathological changes of Alzheimer's disease.We found no evidence, however, that low blood pressure is a complication of the clinical demen- tia process in people with Down's syndrome.
Transient interaction of activated platelets with endothelial cells induces expression of monocyte-chemoattractant protein-1 via a p38 mitogen-activated protein kinase mediated pathway Implications for atherogenesis
Authors: T Dickfeld
Journal: Cardiovascular Research (2001)

Activated platelets induce alterations of chemotactic and adhesive properties of endothelial cells, a critical initial step in atherogenesis. We investigated the effect of transient interaction of activated platelets with cultured human umbilical vein endothelial cells (HUVECs) on secretion of monocyte chemoattractant protein-1 (MCP-1), a key molecule in monocyte chemotaxis and transmigration.Transient interaction of alpha-thrombin-activated platelets with endothelial cells for 10-120 min substantially induced endothelial secretion of MCP-1, monocyte chemotaxis and adhesion to HUVECs. Platelet-induced secretion of MCP-1 and monocyte-endothelium adhesion was reduced by the MAP kinase p38-specific inhibitor SB203580, but not by other kinase inhibitors including PD98059, wortmannin, or rapamycin. In addition, activated platelets induced transcription of a luciferase reporter construct containing a MCP-1 promotor, an effect that could be inhibited by SB203580. Overexpression of dominant-negative mutants of MAP kinase p38, CSBP2-(D168A) and CSBP2-(T180E,Y182E) reduced platelet-induced expression of MCP-1.Activation of the p38 MAP kinase and consecutive endothelial secretion of MCP-1 induced through transient interaction of activated platelets might play an important role in atherogenesis.
Low-dimensional versus high-dimensional chaos in brain function – is it an and/or issue?
Authors: Márk Molnár
Journal: Behavioral and Brain Sciences (2001)

We discuss whether low-dimensional chaos and even nonlinear processes can be traced in the electrical activity of the brain. Experimental data show that the dimensional complexity of the EEG decreases during event-related potentials associated with cognitive effort. This probably represents increased nonlinear cooperation between different neural systems during sensory information processing.
Cerebral Cysticercosis
Authors: E. R. Bickerstaff
Journal: BMJ (1955)

Of the children who were vomiting food more than once daily 57.7% stopped vomiting within a few days after the treatment, and in another 20% vomiting was relieved.Decompression treatment is usually unsuccessful at a stage of the disease earlier than two and a half weeks and is harmful to the acutely ill case with pyrexia, cyanosis, or appreciable atelectasis.The results reported are based on careful selection of cases and combined assessment by parents and doctors.An adequate controlled experiment has not yetbeen done but should be attempted when opportunity offers.The mechanism of the action of decompression in whooping-cough has not been elucidated.Further trials should preferably include biochemical studies.I thank my colleague Dr. L. J. M. Laurent for his valuable co- operation throughout, for reporting on a visit to Dr. Richou and others in Paris in 1948, for his part in the conduct of the
Abstract CS1-1: Clinical implications of contralateral prohylactic mastectomy
Authors: Ismail Jatoi
Journal: Cancer Research (2015)

Abstract Contralateral prophylactic mastectomy (CPM) refers to the removal of the opposite uninvolved breast in women with unilateral breast cancer, and rates are increasing worldwide. Several factors may explain this trend. Greater use of genetic testing in women with unilateral breast cancer may result in the identification of women at increased risk for contralateral breast cancer, and prompt CPM. However, most women who undergo CPM appear to be at low to moderate risk for developing contralateral breast cancer, so the wider use of genetic testing can only partly account for the trend towards greater utilization of CPM. Wider use of pre-operative breast MRI, although not shown to be beneficial, has also been associated with increased use of CPM. Moreover, some women with unilateral breast cancer may overestimate their risk of contralateral breast cancer, experience considerable anxiety over this issue, and request CPM. In this regard, it is somewhat ironic that CPM rates are increasing during a period when contralateral breast cancer rates are decreasing due to better adjuvant systemic therapies. Finally, several observational studies have demonstrated associations between CPM and reductions in breast cancer-specific and all-cause mortality, and these reports may influence treatment decisions. Yet, the results of such observational studies may reflect the selection of a healthier cohort of women for CPM (selection bias). Thus, there is no clinical justification for the wider use of CPM in the management of patients with unilateral breast cancer, and a better understanding of factors contributing to this trend is necessary. Citation Format: Ismail Jatoi. Clinical implications of contralateral prohylactic mastectomy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr CS1-1.
Exemestane Is Superior to Megestrol Acetate After Tamoxifen Failure in Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Randomized Double-Blind Trial
Authors: Manfred Kaufmann, Emilio Bajetta, Luc Yves Dirix, Luis Enrique Fein, Stephen E. Jones, Nicoletta Zilembo, Jean-Louis Dugardyn, Cristina Nasurdi, Robert G. Mennel, Jozica Cervek, Camilla Fowst, Anna Polli, Enrico di Salle, Alexei Arkhipov, Gabriella Piscitelli, Langdon L. Miller, Giorgio Massimini
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This phase III, double-blind, randomized, multicenter study evaluated the efficacy, pharmacodynamics, and safety of the oral aromatase inactivator exemestane (EXE) versus megestrol acetate (MA) in postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen. PATIENTS AND METHODS: A total of 769 patients were randomized to EXE 25 mg/d (n = 366) or MA (n = 403) 40 mg four times daily. Tumor response, duration of tumor control, tumor-related signs and symptoms (TRSS), quality of life (QOL), survival, and tolerability were evaluated. RESULTS: Overall objective response (OR) rates were higher in patients treated with EXE than in those treated with MA (15.0% v 12.4%); a similar trend was noted in patients with visceral metastases (13.5% v 10.5%). Median survival time was significantly longer with EXE (median not reached) than with MA (123.4 weeks; P = .039), as were the median duration of overall success (OR or stable disease ≥ 24 weeks; 60.1 v 49.1 weeks; P = .025), time to tumor progression (20.3 v 16.6 weeks; P = .037), and time to treatment failure (16.3 v 15.7 weeks; P = .042). Compared with MA, there were similar or greater improvements in pain, TRSS, and QOL with EXE. Both drugs were well tolerated. Grade 3 or 4 weight changes were more common with MA (17.1% v 7.6%; P = .001). CONCLUSION: EXE prolongs survival time, time to tumor progression, and time to treatment failure compared with MA and offers a well-tolerated treatment option for postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen.
Mitogenomic Meta-Analysis Identifies Two Phases of Migration in the History of Eastern Eurasian Sheep
Authors: Feng-Hua Lv, Wei-Feng Peng, Ji Yang, Yong-Xin Zhao, Wen-Rong Li, Ming-Jun Liu, Yue-Hui Ma, Qian-Jun Zhao, Guang-Li Yang, Feng Wang, Jin-Quan Li, Yong-Gang Liu, Zhi-Qiang Shen, Sheng-Guo Zhao, EEr Hehua, Neena A. Gorkhali, S. M. Farhad Vahidi, Muhammad Muladno, Arifa N. Naqvi, Jonna Tabell, Terhi Iso-Touru, Michael W. Bruford, Juha Kantanen, Jian-Lin Han, Meng-Hua Li
Journal: Molecular Biology and Evolution (2015)

Despite much attention, history of sheep (Ovis aries) evolution, including its dating, demographic trajectory and geographic spread, remains controversial. To address these questions, we generated 45 complete and 875 partial mitogenomic sequences, and performed a meta-analysis of these and published ovine mitochondrial DNA sequences (n = 3,229) across Eurasia. We inferred that O. orientalis and O. musimon share the most recent female ancestor with O. aries at approximately 0.790 Ma (95% CI: 0.637–0.934 Ma) during the Middle Pleistocene, substantially predating the domestication event (∼8–11 ka). By reconstructing historical variations in effective population size, we found evidence of a rapid population increase approximately 20–60 ka, immediately before the Last Glacial Maximum. Analyses of lineage expansions showed two sheep migratory waves at approximately 4.5–6.8 ka (lineages A and B: ∼6.4–6.8 ka; C: ∼4.5 ka) across eastern Eurasia, which could have been influenced by prehistoric West–East commercial trade and deliberate mating of domestic and wild sheep, respectively. A continent-scale examination of lineage diversity and approximate Bayesian computation analyses indicated that the Mongolian Plateau region was a secondary center of dispersal, acting as a “transportation hub” in eastern Eurasia: Sheep from the Middle Eastern domestication center were inferred to have migrated through the Caucasus and Central Asia, and arrived in North and Southwest China (lineages A, B, and C) and the Indian subcontinent (lineages B and C) through this region. Our results provide new insights into sheep domestication, particularly with respect to origins and migrations to and from eastern Eurasia.
Azithromycin for episodes with asthma-like symptoms in young children aged 1–3 years: a randomised, double-blind, placebo-controlled trial
Authors: Jakob Stokholm, Bo L Chawes, Nadja H Vissing, Elín Bjarnadóttir, Tine M Pedersen, Rebecca K Vinding, Ann-Marie M Schoos, Helene M Wolsk, Sunna Thorsteinsdóttir, Henrik W Hallas, Lambang Arianto, Susanne Schjørring, Karen A Krogfelt, Thea K Fischer, Christian B Pipper, Klaus Bønnelykke, Hans Bisgaard
Journal: The Lancet Respiratory Medicine (2015)