tbuckley/cabot-search huggingface dataset:
Abstract C13: The role of cancer heterogeneity in metastasis
Authors: Yoojin Shin, Hyo Eun Jeong, Sewoon Han, Jihee Won, Seok Chung
Journal: Cancer Research (2013)

Abstract Breast cancer doesn't contain only one colony of tumor cells. It appears to have heterogeneous cell composition of characteristically different subtypes with distinct molecular and gene expression signatures. Due to the tumor heterogeneity, which determines the risk of metastatic progression and drug resistance, it is difficult to predict progression patterns of cancer and provide the most suitable treatment to patients. Most research has focused on molecular definition and genetic association for the cancer heterogeneity studies. However, lack of in vitro models to precisely mimic the heterogeneous conditions of tumors has made it difficult to understand the role of heterogeneity in metastasis, especially invasion. So, to precisely regulate heterogeneous microenvironment of tumors and evaluate the role of the heterogeneity on invasion &amp; metastasis, we developed a microfluidic in vitro assay incorporating 3D ECM scaffolds that emulate in vivo tumor microenvironment in 3D. We cultured highly invasive breast cancer cell, MDA-MB-231, and non-invasive breast cancer cell, MCF-7, together in a mixed population and let the cells interact with other cells and ECMs. As a result, we found that heterogeneity in cancer cell population promotes metastatic potential. Highly invasive breast cancer cells, MDA-MB-231, made microtracks in ECM and leaded collective migration of non-invasive breast cancer cells, MCF-7, into the microtracks. When MCF-7 were cultured alone, MCF-7 cells didn't invade into ECM. It has been widely announced that only stromal cells such as fibroblast remodel ECM and enhance the invasion potential of cancer cells. However, from the result of our experiment, cancer cells that have different characteristics in single tumor can promote the metastatic potential, result from that ECM remodeling (generating microtracks) by highly invasive cancer cells. It was precisely investigated by IF, rt-PCR and TEM analysis in microfluidic environments. Understanding about not only genetic and molecular definition of cancer heterogeneity, but also the role of heterogeneous cancer cell population in metastatic dissemination, could help new drugs and therapeutic strategies development. Citation Format: Yoojin Shin, Hyo Eun Jeong, Sewoon Han, Jihee Won, Seok Chung. The role of cancer heterogeneity in metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C13.
The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects
Authors: F Khan
Journal: Cardiovascular Research (2003)

Objective: Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years. Methods: In a double-blind, randomised, placebo controlled study, 173 healthy volunteers took one of six oil supplements for 8 months. Supplements were placebo, oleic acid rich sunflower oil, evening primrose oil, soya bean oil, tuna fish oil, and tuna/evening primrose oil mix. Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside, respectively. Results: Acetylcholine, but not sodium nitroprusside responses were significantly improved after tuna oil supplementation ( P =0.02). Additionally, there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation. No significant changes in vascular response were seen after supplementation with any of the other oils. Conclusions: Fish oil supplementation has a beneficial effect on endothelial function, even in normal healthy subjects. Modification of the diet by an increase of 6% in eicosapentaenoic acid and 27% in docosahexaenoic acid (equivalent to eating oily fish 2–3 times/week) might have significant beneficial effects on cardiovascular function and health.
Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas
Authors: Howard A. Fine, Patrick Y. Wen, Elizabeth A. Maher, Elene Viscosi, Tracy Batchelor, Nehal Lakhani, William D. Figg, Benjamin W. Purow, Craig B. Borkowf
Journal: Journal of Clinical Oncology (2003)

The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas.Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated.A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls.This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.
GE-40 * COMPARATIVE GENOMIC ANALYSES IDENTIFIES NON-SILENT MUTATIONS PRESENT IN BOTH MURINE AND HUMAN MEDULLOBLASTOMA
Authors: L. Wei, B. L. Murphy, M. Parker, G. Wu, J. Easton, M. F. Roussel, J. Zhang
Journal: Neuro-Oncology (2014)

Mouse models of human cancers are now widely used in cancer biology and therapeutics. However, these models have, more recently, been scrutinized regarding the degree with which they faithfully recapitulate their human counterparts. To determine whether mouse and human tumors are driven by similar genetic alterations we chose medulloblastoma, the most common malignant pediatric brain tumor, and performed whole-exome sequencing on 12 animals representing models of three distinct medulloblastoma subgroups: WNT, SHH and G3 (C-MYC). Without sequencing data from matching normal tissue, we developed a robust germline-filtering pipeline that removes known single nucleotide polymorphisms (SNPs) in commonly used mouse strains. We rigorously compared putative mutation calls to raw control mouse binary alignment map (BAM) files to filter out remaining polymorphisms. Sequencing tumor and non-tumor DNA from ancestral mouse strains validated the presence of a mutation with somatic success rates of 61% and 14% for high quality and low quality calls, respectively. Using this approach, we identified 75 somatic mutations (73 single nucleotide variation [SNVs] and 2 small insertions & deletions [INDELS]), including 40 with predicted amino acid changes. Of these 40 mouse MB amino-acid change mutations, the human ortholog of eight genes also harbored amino acid change mutations. Lrfn2, Smyd1 and Wdr11 were mutated in a mouse G3 medulloblastoma and tested in vivo using intracranial allografts. Each gene was overexpressed in mouse G3 tumor spheres by lentiviral gene transfer followed by cell sorting and intracranial stereotactic implants. Wdr11 significantly repressed tumor progression, and increased the survival of tumor-bearing mice by ten and eleven days compared to tumor cells uninfected or infected with empty vector. Our pipeline successfully filtered out most germ-line SNPs even without matching normal tissue data, and identified Wdr11 as a novel target in medulloblastoma.
A tale of two families
Authors: C. R Paterson
Journal: BMJ (2008)

Since about the age of 12 years I have been a self appointed family archivist. I really wanted to know how everyone I met fitted into the scheme of things. In the early 1960s I was taken by an elderly cousin of my father to an old churchyard near Closeburn in Dumfriesshire. She showed me the monument for the family of her grandmother’s half-brother, a miller, William Rogerson. Born in 1817, he and his wife had eight children between 1843 and 1861. All were interred with him.

William himself died aged 43; according to the certifying …
Better commissioning is needed to deal with combined effects of physical and mental illnesses
Authors: M. Limb
Journal: BMJ (2011)

Making mental health services more efficient will improve the care of people with long term conditions and save the NHS money, a conference has heard.

Hugh Griffiths, the acting national clinical director for mental health, said that better commissioning was “absolutely crucial” and that more integration of services would help to support people with combined physical and mental healthcare needs.

At the conference on improving mental healthcare of people with long term conditions, run by the healthcare think tank the King’s Fund in London on 22 September, experts explored …
Pulmonary Edema and Salicylate Intoxication
Authors: Gary Hrnicek
Journal: JAMA (1974)

A patient experienced pulmonary edema associated with salicylate intoxication. As proved by dynamic vascular measurements, the pulmonary edema was of noncardiac origin. Recovery followed therapy with diuretics and positive end-expiratory pressure (PEEP). The etiology of this form of pulmonary edema is unknown, but it is a potentially fatal complication of salicylate intoxication. (<i>JAMA</i>230:866-867, 1974)
Consensus report of the 2nd International Conference on Double Balloon Endoscopy
Authors: J. Pohl, J. Blancas, D. Cave, K. Choi, M. Delvaux, C. Ell, G. Gay, M. Jacobs, N. Marcon, T. Matsui, A. May, C. Mulder, M. Pennazio, E. Perez-Cuadrado, K. Sugano, P. Vilmann, H. Yamamoto, T. Yano, J. Zhong
Journal: Endoscopy (2008)

In the past 6 years new techniques have expanded the endoscopic evaluation of the small bowel up to total enteroscopy. In 2001, video capsule endoscopy (VCE) was approved by the FDA for the evaluation of small-bowel diseases. VCE can provide an endoscopic view of most of the small intestinal mucosa, but the diagnosis depends on the analysis of recorded images, and neither biopsy nor endoscopic treatment can be performed. The latter has become possible with double balloon endoscopy (DBE), which was first described by Yamamoto and colleagues in 2001 [1] and enables complete enteroscopy to be carried out. Additional applications of potential clinical use include difficult colonoscopies and access to the pancreatic and biliary tract in patients with altered postoperative anatomy. Within a short time period several feasibility studies, including data on diagnostic and therapeutic yield of DBE, have been published. Here we report the consensus on the current status of DBE that was developed during the 2nd International Conference on DBE in Berlin, 14 - 15 June 2007, which was sponsored by Fujinon. The paper does not fulfill the formal criteria for a consensus, but may be regarded as a guide to the clinical application of DBE techniques based on published evidence, as well as on the personal opinions and experiences of the participants. Moreover, it also shows that many clinically relevant questions need to be addressed by further studies. The new development of single balloon enteroscopy has not been included in the conference, as only preliminary data existed in abstract form (DDW 2007), reporting about feasibility and comparative data between both techniques are missing.
PATHOLOGICAL CONDITIONS FOLLOWING PIERCING OF THE LOBULES OF THE EAR.Read in the Section on Otology, Pan-American Medical Congress, Washington, Sept. 6, 1893.
Authors: MAX THORNER
Journal: JAMA (1894)

The custom of piercing the lobules of the ear dates from the remotest historical antiquity, being first mentioned in the Book of Genesis. It was practiced by the people of the Orient and by those of the West, and was transmitted from the races of classic antiquity, through the Middle Ages, down to our present times. Ear-rings were held among certain nations in high repute as talismans or amulets. They were, and I believe are still, superstitiously valued as remedies for eye affections. But their principal use was at all times, and certainly is now, that of ornaments, to be worn generally by women. And thus it happens that mothers, who would otherwise protect their little ones from every harm and pain, will not shrink from subjecting them to an unnecessary, inexcusable, and painful procedure, only to adorn them with the coveted jewel. This explains why such a barbaric custom
Walking in the Peachtree Road Race
Authors: Joseph E. Hardison
Journal: JAMA (1982)

I had to do something about my midlife crisis! I was finally convinced that nothing functioned better with age. I had to see what there was left. Many of my friends entered the midlife crisis on the jog. They seemed to be outrunning their crises. I envied them, their faces contorted and drenched with sweat, as they stood gasping and grasping their knees to keep from pitching headlong to the pavement. There was nothing left to do, but try it! I bought running shoes with lightning bolts on the sides, shorts, and a brightly colored undershirt. I began slowly and built up. It was no problem getting my heart rate to 170 or 180 beats per minute. In fact, it would climb to 200 with the slightest exertion. Finally, I was running 2 miles every other day. I thought it was normal for my knees and ankles to swell and
Antibiotics and Gram-Negative Bacteremia-Reply
Authors: Joseph T. Curti
Journal: JAMA (1975)

<h3>In Reply.—</h3> I welcome the thoughtful comments of Dr McGowan on the data that I presented in the March 31 communication (231:1361,1975) and would like to elaborate further on some of these points. Dr McGowan implies that the emergence of the Gram-negative organisms<i>Klebsiella, Enterobacter</i>, and<i>Serratia</i>as causative agents in bacteremia since the 1930s is the result of the introduction and use of penicillin and the broad-spectrum antibiotics. This is true only in the sense that these antibiotics have been successful in treating the Gram-positive infections that previously were the sources of bacteremia and in keeping alive people who, when older, become more susceptible to Gram-negative bacteremia.<sup>1</sup>Other factors operative in the hospital, such as more debilitated patients, imperfect sterile technique, wider use of immunosuppressant agents, and greater use of respiratory, vascular, and urinary instrumentation are unquestionably contributing substantially to the increased incidence of Gram-negative bacteremia.<sup>2-4</sup>Some
It's always worth trying
Authors: F. Kelly
Journal: BMJ (2003)

As an anaesthetic registrar, I was always advised to pass all the necessary exams before having any children, and very sensible advice it sounded too. So imagine my dilemma when I found myself pregnant with a due date bang in between the final written and viva exams for my FRCA.

The Bristol anaesthetic community was evenly split as to what I should do. One camp told me that I was mad even to consider taking the exams, while the other told me just to give it a go. I'm not sure what made me do it, but I decided to hope for the best and sit the exams.

I have to say it was much harder than I anticipated. Pregnancy to …
CARE OF THE NEWBORN PREMATURE INFANT
Authors: ALLAN C. BARNES
Journal: JAMA (1942)

As a result of a better understanding of the physiology of the premature infant, neonatal deaths due to prematurity have declined steadily in the past few years. The present survey reports the survival rate of premature infants in the obstetric service of the University of Michigan Hospital during the past ten years. Throughout this period the equipment which has been available for care of these infants is equipment which can be obtained by any hospital regardless of size or location. While a special nursing unit is planned for the near future, premature babies have in the past been cared for in the regular maternity nurseries. This report, accordingly, presents a program of care for the newborn premature infant applicable to any neonatal nursery. The progress which has been made in the care of these infants during the past decade has been sufficient to warrant subdivision into two five year periods,
Endoscopic removal of an ingested toothbrush
Authors: C. Gomes
Journal: Endoscopy (2013)

A 17-year-old female student reported that a piece of meat she had swallowed after chewing had become impacted in the region of the hypopharynx. After unsuccessfully attempting to remove the piece of meat with her fingers, she tried to dislodge it using an adult toothbrush, which measured about 18 cm. However, both the piece of meat and the toothbrush slipped down her esophagus. The patient reported mild nausea and chest pain of short duration. Thoracic and abdominal X-rays demonstrated bristles in parallel rows in the stomach ([Fig. 1]). About 10 hours later, the patient had an endoscopy under intravenous sedation with midazolam (5 mg) and fentanyl citrate (78.5 μg). It showed a toothbrush head with bristles in the gastric body, with the rest of the toothbrush impacted in the pylorus ([Fig. 2]). An attempt was made to remove the toothbrush first with a foreign body forceps. The brush was dislodged from the pylorus, which facilitated its removal with a polypectomy snare without injury to the stomach or esophagus. The fingers had to be used to remove the toothbrush from the pharynx.
Effects of Endothelin-1 and Endothelin-A Receptor Antagonist on Recovery After Hypothermic Cardioplegic Ischemia in Neonatal Lamb Hearts
Authors: Takeshi Hiramatsu, Joseph Forbess, Takuya Miura, Stephen J. Roth, Mark A. Cioffi MAT, John E. Mayer
Journal: Circulation (1995)

Background Prior studies suggest an important role for coronary endothelium in ischemia/reperfusion (I/R) injury. Decreased endothelial release of the vasodilator nitric oxide occurs after I/R, but the role of the endothelium-derived vasoconstrictor endothelin-1 (ET-1) in I/R is unknown. Methods and Results We measured plasma ET-1 concentrations by radioimmunoassay in isolated blood-perfused neonatal lamb hearts before and after 2 hours of 10°C cardioplegic ischemia and examined the effects of ET-1 and the endothelin-A (ET-A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts. ET-1 levels in coronary sinus blood before ischemia and at 0 and 30 minutes of reperfusion in 8 control hearts were constant (2.2±1.2 fmol/L, 2.2±1.3 fmol/L, and 2.5±1.0 fmol/L, respectively). In group 2 (n=6), 10 μmol/L of BE-18257B was given just before reperfusion. In group 3 (n=8), 10 pmol/L ET-1 was given just before the start of reperfusion. At 30 minutes of reperfusion, the ET-A antagonist hearts had significantly greater recovery of LV systolic (positive dP/dt and dP/dt at V10) and diastolic function (negative dP/dt), coronary blood flow (CBF), and MV̇ o 2 compared with controls ( P &lt;.05). The ET-1 hearts showed significantly reduced recovery of LV systolic (positive maximum and volume-normalized dP/dt) and diastolic (negative maximum dP/dt) function, CBF, and myocardial oxygen consumption compared with controls ( P &lt;.05). Conclusions These results, combined with prior studies, suggest that I/R causes reduced production of endogenous vasodilators (eg, nitric oxide), leaving unopposed the vasoconstriction that is caused by the continued presence of ET-1. This imbalance may contribute to I/R injury. ET-A receptor antagonists may be useful therapeutic agents in reducing the injury that results from I/R.
COINCIDENT DIPHTHERIA AND VINCENT'S ANGINA
Authors: F. W. Sears
Journal: JAMA (1927)

<h3>To the Editor:</h3> —InThe Journal, April 16, page 1234, Dr. R. S. Spray refers to a case in which he thinks both Vincent's angina and diphtheria were present. While this may be true, I think that the majority of the cases in which are found both the laboratory evidence of Vincent's angina and diphtheria are cases of Vincent's angina in patients who are diphtheria carriers. This has quite frequently happened under my observation. There is no reason why a carrier of a virulent diphtheria germ may not have Vincent's angina and yet be immune to diphtheria. The methods of detecting this condition are the Schick test, which in such a case should prove negative for diphtheria, and the fact that large doses of antitoxin have little effect on the course of the disease, but the disease will promptly respond to proper treatment for Vincent's angina.
Gender and risk of autoimmune diseases: possible role of estrogenic compounds.
Authors: S A Ahmed, B D Hissong, D Verthelyi, K Donner, K Becker, E Karpuzoglu-Sahin
Journal: Environmental Health Perspectives (1999)

A striking common feature of many autoimmune diseases in humans and experimental animals, despite differences in pathology, is that females are highly susceptible to autoimmune conditions compared to males. In several animal models, estrogens promote, whereas androgens abrogate, B-cell-mediated autoimmune diseases. To understand mechanisms by which estrogens regulate autoimmunity, it is first necessary to decipher estrogen effects on the normal immune system. Estrogen treatment of nonautoimmune mice diminished lymphocyte numbers in both developmental and mature lymphoid organs. Estrogen dysregulated T- and B-cell balance by inducing selective T-cell hypoactivity and B-cell hyperactivity. Even though estrogen did not alter the relative percentages of splenic T-cell subsets, splenic lymphocytes had a reduced proliferative response to T-cell stimulants and were refractory to rescue from activation-induced apoptosis compared to cells from placebo-treated mice. In contrast, estrogen induced B-cell hyperactivity (promoted autoantibodies to double-stranded DNA and phospholipids, increased numbers of plasma cells, and increased autoantibody yield per B cell). Note that treatment of normal mice with estrogen can alter T- and B-cell regulation and overcome B-cell tolerance to result in autoimmunity in normal individuals. Could environmental estrogens promote some human autoimmune disorders? Is there a link between environmental estrogens and autoimmune disorders, especially since these disorders are reported possibly more frequently? These provocative questions warrant investigation. Our findings on immunomodulatory effects may serve as a benchmark to examine whether endocrine-disrupting chemicals will have similar immunologic effects.
GYNECOMASTIA ASSOCIATED WITH LUNG CANCER
Authors: James D. Hardy
Journal: JAMA (1960)

Gynecomastia occurring in three men aged 44, 51, and 60 years was found to be associated with bronchogenic carcinoma. In the first patient the primary complaint was painful swelling of the knees, and the gynecomastia was noted two years later when the patient was hospitalized. In the second patient the gynecomastia was the initial symptom. It developed in the third patient weeks after thoracotomy at which an unresectable carcinoma of the lung had been found. Assessment of the patients' endocrine status, including determinations of 24-hour excretion of estrogens and of 1 7-ketosteroids, failed to identify any one endocrine factor that would explain the gynecomastia in all patients.