tbuckley/cabot-search huggingface dataset:
Abstract P5-04-05: E-Cadherin is Required for In Vivo Growth of Inflammatory Breast Cancer: Importance of Mesenchymal-Epithelial Transition (MET) and Role of HIF1α
Authors: K Chu, KM Boley, M Cristofanilli, FM Robertson
Journal: Cancer Research (2012)

Abstract Background: Inflammatory breast cancer (IBC) is the most aggressive and deadly form of breast cancer and is phenotypically distinct from other forms of locally advanced breast cancer. The 5-year survival for IBC patients (40%) has not improved even with the implementation of multi-disciplinary care and targeted therapies (e.g. anti-HER2 or anti-estrogen therapies). Lymph node involvement is common at first diagnosis and the accelerated metastasis program that characterizes IBC account for a disproportionate number of the 40,000 women who will die from breast cancer. The most common molecular marker for IBC is the cell adhesion surface glycoprotein, E-Cadherin. Classically, E-Cadherin is thought to be a tumor suppressor and its loss is associated with the epithelial-mesenchymal transition (EMT) and acquisition of an invasive phenotype. The importance of EMT in metastasis is well accepted in numerous tumor models although the presence of EMT in patient samples is rarely demonstrated. Given the propensity of IBC to metastasize, one would expect a strong EMT signature in IBC cell lines, however the persistent robust expression of E-Cadherin in IBC patient tumors and in IBC cell lines, with a lack of expression of ZEB1, a transcriptional repressor of E-cadherin and diminished expression of genes within the transforming growth factor beta signaling pathway, suggests otherwise. Methods: To further define the role of E-Cadherin in IBC, we used the SUM149 IBC cell line to manipulate E-Cadherin via shRNA knockdown and by overexpression of ZEB1 a known transcriptional repressor of E-cadherin. Results: While the lack of E-Cadherin or ZEB1 overexpression in SUM149 cells led to an EMT phenotype in vitro, E-Cadherin was required for in vivo growth of SUM149 tumor cells. Gene profiling identified novel E-Cadherin signaling pathways including an hypoxia gene signature through HIF1a as well as cytokine responsive pathways. The requirement of HIF-1a for in vivo growth of SUM149 cells was confirmed by shRNA knockdown of HIF-1a. Conclusions: The absolute requirement for E-Cadherin and maintenance of the mesenchymal-epithelial transition in IBC tumor growth is demonstrated. Furthermore, a novel functional link between E-Cadherin and HIF-1a and in their critical role in survival of IBC tumors is identified for the first time and warrants further investigation. Supported in part by The Susan G Komen Organization Promise Grant KG081287 (FMR and MC) Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-05.
Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice
Authors: T CSONT, E BERECZKI, P BENCSIK, G FODOR, A GORBE, A ZVARA, C CSONKA, L PUSKAS, M SANTHA, P FERDINANDY
Journal: Cardiovascular Research (2007)

We have previously shown that cholesterol diet-induced hyperlipidemia (marked hypertriglyceridemia and moderate hypercholesterolemia) increases cardiac formation of peroxynitrite and results in a moderate cardiac dysfunction in rats. Here our aim was to further clarify the mechanism of hyperlipidemia-induced nitrosative stress in a transgenic mouse model and to test if high cholesterol or high triglyceride is responsible for the hyperlipidemia-induced cardiac dysfunction.To determine the effect of cholesterol-enriched diet on cardiac performance and oxidative/nitrosative stress, wildtype and human apoB100 transgenic mice were fed a 2% cholesterol-enriched or a normal diet for 18 weeks. Serum cholesterol and LDL-cholesterol levels were significantly elevated only in the cholesterol-fed apoB100 transgenic mice, while serum triglycerides were increased in the transgenic mice fed a normal diet. Cholesterol-enriched diet significantly increased cardiac superoxide generation and NADPH oxidase expression and activity in apoB100 mice but not in wildtypes. Cardiac NO content and NO synthase activity did not change in either group. As assessed in isolated working hearts, aortic flow was significantly decreased only in apoB100 transgenic mice fed a cholesterol-enriched diet. The peroxynitrite decomposition catalyst FeTPPS attenuated the decrease in aortic flow in cholesterol-fed apoB100 mice. Immunohistochemistry showed elevated nitrotyrosine in the hearts of apoB100 mice fed the cholesterol-enriched diet.We conclude that hypercholesterolemia but not hypertriglyceridemia leads to increased formation of superoxide and peroxynitrite, and thereby results in cardiac dysfunction in hearts of human apoB100 transgenic mice.
A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial
Authors: M. Klintman, F. Nilsson, P.-O. Bendahl, M. Fernö, G. Liljegren, S. Emdin, P. Malmström
Journal: Annals of Oncology (2013)

BackgroundIn a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status (PR), and tumour size identified one-third of patients as high risk, with a sixfold increased risk of breast cancer death. This prospective multicenter cohort study was set up to validate the index.Patients and methodsIn 576 T1-2N0 patients <60 years, prospective analyses of PR and SPF were carried out. High risk was defined as ≥2 of the following: size >20 mm, PR-negativity, and high SPF (in the absence of SPF, Bloom–Richardson grade 3). Median follow-up was 17.8 years.ResultsThirty-one percent were high risk. In univariate analysis, the index was prognostic for breast cancer-specific survival after 5 years [hazard ratio (HR) = 4.7, 95% confidence interval (95% CI) 2.5–8.9], 10 years (HR = 2.2, 95% CI 1.5–3.3), and 15 years (HR = 1.7, 95% CI 1.2–2.5), and remained significant after adjustment for adjuvant medical treatment and age. In the 37% of patients with no risk factors, only one patient died of breast cancer the first 5 years.ConclusionsThis prospective study validates a prognostic index consisting of a proliferation factor, PR-status, and tumour size. The index may be helpful for prognostic considerations and for selection of patients in need of adjuvant therapy.
Target-specific nanoparticles containing a broad band emissive NIR dye for the sensitive detection and characterization of tumor development
Authors: Thomas Behnke, Julia E. Mathejczyk, Robert Brehm, Christian Würth, Fernanda Ramos Gomes, Christian Dullin, Joanna Napp, Frauke Alves, Ute Resch-Genger
Journal: Biomaterials (2012)
The Acquired Immunodeficiency Syndrome
Authors: Michael Mills, Constance B. Wofsy, John Mills
Journal: New England Journal of Medicine (1986)

Because they can be transmitted to others, infectious diseases of all kinds have for many years been the subject of statutes, regulations, and court decisions imposing special constraints on both the patient's freedom and the physician's practice. The acquired immunodeficiency syndrome (AIDS) is now known to be an infectious disease. Three laboratories have recovered from patients with AIDS unique T-lymphocyte–associated retroviruses (the so-called AIDS retroviruses) that are almost certainly the etiologic agent.1 2 3 Serologic studies have confirmed the relation between AIDS retrovirus infection, AIDS, and the AIDS-related complex.2 , 3 The legality of measures to control the spread of infectious diseases is determined . . .
Ceramide Promotes Apoptosis in Lung Cancer-Derived A549 Cells by a Mechanism Involving c-Jun NH2-Terminal Kinase
Authors: Svitlana M. Kurinna, Chun Chui Tsao, Alina Felicia Nica, Tilahun Jiffar, Peter P. Ruvolo
Journal: Cancer Research (2004)

Abstract Ceramide regulates diverse signaling pathways involving cell senescence, the cell cycle, and apoptosis. Ceramide is known to potently activate a number of stress-regulated enzymes, including the c-Jun NH2-terminal kinase (JNK). Although ceramide promotes apoptosis in human lung cancer-derived A549 cells, a role for JNK in this process is unknown. Here, we report that ceramide promotes apoptosis in A549 cells by a mechanism involving JNK. The JNK inhibitor SP600125 proved effective at protecting cells from the lethal effects of ceramide. To understand which JNK-mediated pathway may be involved, a number of JNK target proteins were examined, including the transcription factor, c-Jun, and the apoptotic regulatory proteins Bcl-XL and Bim. A549 cells exhibited basal levels of phosphorylated c-Jun in nuclear fractions, revealing that active c-Jun is present in these cells. Ceramide was found to inhibit c-Jun phosphorylation, suggesting that JNK-mediated phosphorylation of c-Jun is not likely involved in ceramide-induced apoptosis. Ceramide did not promote Bcl-XL phosphorylation. On the other hand, ceramide promoted phosphorylation of Bim and induced translocation of active JNK from the nucleus to the cytoplasm and mitochondrial fraction. Ceramide-mediated changes in localization of JNK were consistent with the observed changes in phosphorylation status of c-Jun and Bim. Furthermore, ceramide promoted Bim translocation to the mitochondria. Mitochondrial localization of Bim has been shown recently to promote apoptosis. These results suggest that JNK may participate in ceramide-induced apoptosis in A549 cells by a mechanism involving Bim.
Effects of regular walking on cardiovascular risk factors and body composition in normoglycemic women and women with type 2 diabetes.
Authors: K Z Walker, L S Piers, R S Putt, J A Jones, K O'Dea
Journal: Diabetes Care (1999)

To examine the impact of a 12-week walking program on body composition and risk factors for cardiovascular disease in women with type 2 diabetes and in normoglycemic women with first-degree diabetic relatives.There were 11 postmenopausal women with type 2 diabetes and 20 normoglycemic women of similar age and BMI who were asked to walk 1 h per day on 5 days each week for 12 weeks. Fitness (estimated VO2max) was assessed with a 1.6-km walking test; body composition was measured by dual-energy X-ray absorptiometry; and sex hormone, metabolic, and lipid concentrations were measured in serum.After 12 weeks, estimated VO2max improved in both groups (P < 0.005). In the diabetic women, BMI and fat content of the upper body and android waist region decreased (P < 0.05). Concentrations of fasting blood glucose (P < 0.05) HbAlc (P < 0.05), total cholesterol (P < 0.005), and LDL cholesterol (P < 0.05) decreased, while HDL cholesterol and sex hormones were unchanged. In contrast, normoglycemic women failed to lose body fat after 12 weeks of exercise in a walking program. However, their HbAlc, total cholesterol, LDL cholesterol, sex hormone-binding globulin, and total testosterone concentrations decreased (P < 0.05). On pooling the data and including diabetes as a categorical grouping variable, stepwise multiple regression analysis indicated that the change in centralized body fat, but not the change in VO2max, was related to change in fasting blood glucose.Twelve weeks of walking increased the fitness of diabetic and normoglycemic women. Improvement of fasting blood glucose was related to the loss of centralized body fat rather than to improved fitness.
Protection against Western diet-induced obesity and hepatic steatosis in liver fatty acid-binding protein knockout mice
Authors: Elizabeth P. Newberry, Yan Xie, Susan M. Kennedy, Jianyang Luo, Nicholas O. Davidson
Journal: Hepatology (2006)

Liver fatty acid-binding protein (L-Fabp) regulates murine hepatic fatty acid trafficking in response to fasting. In this study, we show that L-Fabp(-/-) mice fed a high-fat Western diet for up to 18 weeks are less obese and accumulate less hepatic triglyceride than C57BL/6J controls. Paradoxically, both control and L-Fabp(-/-) mice manifested comparable glucose intolerance and insulin resistance when fed a Western diet. Protection against obesity in Western diet-fed L-Fabp(-/-) mice was not due to discernable changes in food intake, fat malabsorption, or heat production, although intestinal lipid secretion kinetics were significantly slower in both chow-fed and Western diet-fed L-Fabp(-/-) mice. By contrast, there was a significant increase in the respiratory exchange ratio in L-Fabp(-/-) mice, suggesting a shift in energy substrate use from fat to carbohydrate, findings supported by an approximately threefold increase in serum lactate. Microarray analysis revealed increased expression of genes involved in lipid synthesis (fatty acid synthase, squalene epoxidase, hydroxy-methylglutaryl coenzyme A reductase), while genes involved in glycolysis (glucokinase and glycerol kinase) were decreased in L-Fabp(-/-) mice. Fatty acid synthase expression was also increased in the skeletal muscle of L-Fabp(-/-) mice. In conclusion, L-Fabp may function as a metabolic sensor in regulating lipid homeostasis. We suggest that L-Fabp(-/-) mice are protected against Western diet-induced obesity and hepatic steatosis through a series of adaptations in both hepatic and extrahepatic energy substrate use. (HEPATOLOGY 2006;44:1191-1205.).
Identification of the C5a des Arg cochemotaxin. Homology with vitamin D-binding protein (group-specific component globulin).
Authors: H D Perez, E Kelly, D Chenoweth, F Elfman
Journal: Journal of Clinical Investigation (1988)

The chemotactic activity of human C5a des Arg is enhanced significantly by an anionic polypeptide (cochemotaxin) in normal human serum and plasma. The cochemotaxin attaches to sialic acid residues within the oligosaccharide chain of native C5a des Arg to form a complex with potent chemotactic activity for human PMN. We investigated the nature of the cochemotaxin and found that vitamin D-binding protein is the putative cochemotaxin. Vitamin D-binding protein enhanced the chemotactic activity of native C5a des Arg, but had no effect on the chemotactic activity of either native C5a or FMLP. Sialic acid prevented both enhancement by vitamin D-binding protein of the chemotactic activity of native C5a des Arg and formation of C5a des Arg-vitamin D-binding protein complexes, detected by molecular sieve chromatography. Furthermore, vitamin D-binding protein and cochemotaxin exhibited identical molecular weights, isoelectric points, antigenic reactivity, and amino acid composition.
Neoplasia after ureterosigmoidostomy.
Authors: A. R. Brown
Journal: BMJ (1968)

massage failed to produce a palpable femoral pulse, and we assumed that the reason for this was that the grossly over-distended lungs cushioned the pressure applied to the anterior chest wall, and prevented it from being trans- mitted to the heart.In the next two cases external cardiac massage was similarly in- effective, but open massage immediately pro- duced a palpable femoral pulse and was rapidly followed by a restoration of spon- taneous cardiac pulsation in sinus rhythm.Unfortunately, in one case open cardiac massage was not started in time to prevent irreparable cerebral damage.Open cardiac massage may seem a formid- able undertaking, particularly to a physician, but it is in fact a simple procedure, and in almost every hospital the services of a sur- geon can readily be obtained to close the wound.In the light of our recent experience, which is happily not extensive, we now take the view that when a patient with status asthmaticus develops cardiac arrest in hos- pital and this is shown to be due to ventricular asystole the proper course is to under- take open cardiac massage without delay.-Weare, etc., I.
Media's treatment of Roy Meadow was “unfair,” says High Court judge
Authors: Clare Dyer
Journal: BMJ (2006)

<h3>Objective</h3> To evaluate lacrimal sac (LS) pump failure in patients with lower motor neuron facial nerve palsy (FNP) using ultrasound biomicroscopy (UBM). <h3>Methods</h3> This was a prospective observational case series. Patients with unilateral lower motor neuron FNP of different aetiologies, age groups and gender were enrolled in this study. Anatomical patency was confirmed through irrigation of the lacrimal drainage system. The degree of lagophthalmos and House–Brackmann grade (HBG) were evaluated, and the dye disappearance test performed. UBM evaluation of the LS during opening and closure of the eyelids was performed for both sides; the control side and the side with assumed lacrimal pump failure (attributed to FNP). Any changes in the orbicularis oculi muscle and fluid turbulence within the sac were reported. <h3>Results</h3> A total of 17 patients with unilateral lower motor neuron FNP were evaluated. The average age (±SD) was 33.2±20.1 years. UBM evaluation of control side LS showed obvious fluid turbulence of different patterns within the sac during opening and closure of the eyelids. Fluid turbulence was absent in the LS with HBG V and VI FNP and reduced in the LS with HBG III and IV FNP. <h3>Conclusions</h3> UBM can be used as a safe, non-invasive and office-based tool to evaluate the LS pump.
Lichen simplex: morphodynamic correlates*
Authors: R. MARKS, G.C. WELLS
Journal: British Journal of Dermatology (1973)

The rate of epidermal cell proliferation has been examined by autoradiographic methods in lichen simplex chronicus in sixteen patients. The corrected labelling index was found to be 25.9% in eleven biopsies removed 50 min to I h after intracutaneous injection of tritiated thymidine (i.e. similar to that in psoriasis). Twelve biopsies were removed 1–8 days subsequent to injection with tritiated thymidine, and in the autoradiographs that resulted it was found that the rate of travel of labelled cells was not fast as in psoriasis. The possible explanations for the finding of a labeling index similar to that of psoriasis but a slower transit time include; the presence of a greater epidermal volume in lichen simplex; the inclusion of'high level labelled cells'in the labelling index; and epidermal damage from the trauma of scratching resulting in intra‐epidermal cell death of labelled cells.
Parenteral B12 in Acute Leukaemia
Authors: R. D. Barnard
Journal: BMJ (1953)

We previously showed that within primary tumors there exist subpopulations of cells expressing stem cell markers. Using immunofluorescence and western blotting, we examined the expression of stem cell markers tumor-rejection antigen 1-60 (TRA1-60) and octamer-binding transcription factor 3/ 4 (OCT3/4) to determine their relationship with cell invasiveness. Six human oral cancer cell lines were examined and a direct correlation was found between expression of these stem cell markers and invasion. Poor expression of E-cadherin and increased expression of N-cadherin was also found in TRA1-60- and OCT3/4- expressing cells. Phosphorylation of the major signaling molecule mitogen activated protein kinase (MAPK) was greatest in the TRA1-60- and OCT3/4- expressing cells. These results suggest that expression of specific stem cell markers in tumors may help guide a clinician9s choice of treatment.
Prevention of Deep Vein Thrombosis by Intermittent Pneumatic Compression of Calf
Authors: N. H. Hills, J. J. Pflug, K. Jeyasingh, L. Boardman, J. S. Calnan
Journal: BMJ (1972)

A consecutive, randomly allocated, controlled clinical trial of the prophylactic effect of intermittent pneumatic compression of the calf on the incidence of postoperative deep vein thrombosis showed that in patients without malignant disease there was a highly significant reduction in the incidence of thrombosis. In patients with malignant disease the incidence of thrombosis was higher than in those without, and there was no reduction in incidence by the application of intermittent compression. In the absence of malignant disease, severity of operation and the age of the patient were the most significant aetiological factors. We found no relation between the incidence of deep venous thrombosis and obesity, length of preoperative stay, location of hospital, or duration of anaesthesia. We suggest that intermittent pneumatic compression as used in this trial is a safe, effective, and extremely practical method of preventing postoperative deep vein thrombosis in patients not suffering from malignant disease.
Inhalation exposure of animals.
Authors: R F Phalen
Journal: Environmental Health Perspectives (1976)

Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed.
FDA: Flush Certain Unused Medications
Authors: Mike Mitka
Journal: JAMA (2009)

military-specific curricula such as trauma training and cold-weather medicine, which would be open to all medical students at that university,” said Harrison. Such exposure could be particularly important in this country. “In the turbulence of Afghanistan, any physician might find themselves called to heal the victims of war,” said CDR Kenneth Lankin, MC, USN, who is former liaison to the Afghan Ministry of Public Health. “The medical school will provide a long-term source of highly trained medical officers to care for the Afghan National Security Forces and their families.” “Students want to be involved in providing care and security to people in such a war-torn society,” said LCDR Sunny Ramchandani, MC, USN, who helped establish the medical school’s curriculum. Students were chosen from all provinces of Afghanistan, and some will be sent to the Afghan National Army Regional Hospitals in their home provinces for much of their clinical training after completing their coursework. “On graduation, every effort will be made to assign the doctors to duty stations close to their home provinces,” said retired COL Gary Davis, MC, USA, who has been contracted by the US military and is the students’ medical mentor. “This will ensure that even the remote regions will have well-trained physicians to provide state-of-the-art medical care for the soldiers and their dependants.”
The Physician as a Patient.
Authors: J. F. Jenkins
Journal: JAMA (1896)

Tecumseh, Mich., Nov. 18, 1896. <h3>To the Editor:</h3> —Why is it, that an error in diagnosis is so frequently made when the patient is a physician? Within the past thirty years, a number of cases have come under the writer's observation, where an error in diagnosis has been made, and where the patient has been a member of the medical guild; it therefore has occurred to the writer, that if the patient had not been a member of the medical profession the mistaken diagnosis would not so frequently have been made. Recently a case illustrating the above statement was reported to the writer, as follows: A physician, age about 53 years, had been complaining for a few days with a feeling of general malaise, some fever which increased from day to day, until the patient was taken to bed. A neighboring physician was called to attend him, who diagnosed the
Double-blind Cross-over Trial of Flurbiprofen and Phenylbutazone in Ankylosing Spondylitis
Authors: A. Calin, R. Grahame
Journal: BMJ (1974)

A double-blind cross-over study in 35 patients with ankylosing spondylitis was carried out comparing flurbiprofen (150 mg daily)-a new non-steroidal anti-inflammatory agent-with phenylbutazone (300 mg daily) over a four-week period. Flurbiprofen was well tolerated and shown to have therapeutic efficacy approaching that of phenylbutazone. The results suggest that flurbiprofen may prove a valuable alternative in the treatment of ankylosing spondylitis, and longterm efficacy and tolerance studies are clearly indicated.