tbuckley/cabot-search huggingface dataset:
Does the microenvironment regulate breast tumor progression
Authors: Kornelia Polyak, Min Hu, Jun Yao
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

SY15-03 

Increasing evidence suggests that changes in the cellular microenvironment contribute to tumorigenesis, but the molecular basis of these alterations is not well understood. We have characterized molecular alterations that occur during breast tumor progression using various comprehensive technologies including SAGE (Serial Analysis of Gene Expression) for gene expression profiling, SNP (Single Nucleotide Polymorphism) arrays and array CGH (Comprehensive Genomic Hybridization) for analyzing genetic changes, and MSDK (Methylation Specific Digital Karyotyping) for the characterization of genome-wide DNA methylation profiles. In addition to analyzing the tumor cells themselves we have also investigated all cell types that compose normal breast tissue and in situ and invasive breast carcinomas. Using these approaches we determined that gene expression and epigenetic changes are detected in all cell types during breast tumor progression, while clonally selected genetic alterations are restricted to tumor epithelial cells. By comparing the gene expression and genetic profiles of epithelial cells isolated from normal breast tissue, and in situ and invasive breast carcinomas, we determined that dramatic changes occur in the normal to in situ carcinoma transition, while we were not able to identify distinct in situ and invasive carcinoma molecular signatures. This finding, reconfirmed by several independent studies, suggests that progression from in situ to invasive cancer may be influenced by non-epithelial cells. Correlating with this hypothesis, a significant fraction of abnormally expressed genes encode secreted proteins and receptors implicating a role for abnormal autocrine/paracrine signaling in breast tumorigenesis. To test the hypothesis that cells composing the microenvironment influence breast tumor growth and progression we have used a xenograft model of human DCIS (Ductal Carcinomas In Situ) and primary cultured myoepithelial cells and various fibroblasts. Using this model we determined that fibroblasts promote tumor growth and the in situ to invasive carcinoma transition, while normal myoepithelial cells inhibit tumor growth and progression. We identified several paracrine factors potentially mediating these tumor promoting and suppressive effects of the fibroblasts and myoepithelial cells, respectively. Based on our findings we suggest that interactions among epithelial and stromal cells play a role in tumorigenesis and targeting these interactions may be exploited for cancer therapy and prevention.
Air pollution, outdoor temperatures, and their impact on acute exacerbations of COPD
Authors: Iliya Krachunov, Nikolay Yanev, Nikolay Kyuchukov, Zlatina Ivanova, Petkana Hristova, Plamen Pavlov, Pavlina Glogovska, Tsanya Popova, Yavor Ivanov
Journal: European Respiratory Journal (2014)

Introduction  There is increasing evidence for the deleterious effect of air pollution on respiratory health. Higher levels of PM10 were found to correlate with higher levels of hospitalizations and mortality for respiratory reasons.  Aim  To study the relationships between air pollutants levels, outdoor temperatures and the rate of exacerbations of COPD (AECOPD).  Methods  COPD patients living inPlevenwere prospectively followed for AECPOD for a year. The level of PM10, NO2, SO2 and outdoor temperatures were taken from the regional environmental office. Statgraphics plus v.2.1 was used for statistical analysis.  Results  A total of 304 AECOPD were found. Mean age was 67(SD±10) and 69.9% were men. The mean annual levels of PM10 were 45.48µg/m 3 . There were106 days with mean concentration higher than 50 µg/m 3 . Daily mean concentrations of PM10 were found to correlate with daily mean concentrations of NO2, SO2 and have negative correlation with daily mean temperature. Daily mean temperature correlated with daily mean levels of NO2 and SO2(p 3 (-0.3vs.-0.18).  Conclusions  The levels of PM10 were higher than recommended by the WHO. Lower daily mean temperatures were associated with increased levels of air pollutants. The levels of PM10 correlated with levels of other air pollutants. The daily number of AECOPD correlated with the mean concentration of PM10 in the 6 days preceding the exacerbation.
THE MEDICAL HISTORY: A SUGGESTED TECHNIC FOR INTERNISTS AND GENERAL PRACTITIONERS
Authors: R S LEADINGHAM
Journal: Annals of Internal Medicine (1947)

Article1 December 1947THE MEDICAL HISTORY: A SUGGESTED TECHNIC FOR INTERNISTS AND GENERAL PRACTITIONERSROY S. LEADINGHAM, M.D., F.A.C.P.ROY S. LEADINGHAM, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-27-6-929 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the light of the experience of those who, like Dunbar,1 believe that many of the errors in medical diagnosis and treatment can be traced to the medical history, a review of the status of the medically acceptable case record should provide material which could be used for determining some of the sources of error and how they might be avoided or minimized.Medical histories have been recorded since the beginning of history itself. Devotees left their stories on the pillars of the temples before Hippocrates braved the dawn of modern medical science, and down the centuries have come the...Bibliography1. DUNBAR F: Psychosomatic diagnosis, 1943, Paul B. Hoeber, Inc., New York. Google Scholar2. GARRISON FH: Introduction to the history of medicine, 1929, W. B. Saunders Co., Philadelphia. Google Scholar3. BARACH JH: An observation chart, New York Med. Jr., 1906, lxxxiv, 339. Google Scholar4. CANNON WB: Bodily changes in pain, hunger, fear and rage, 1929, D. Appleton & Co., New York. CrossrefGoogle Scholar5. COBB S: Technic of interviewing a patient with psychosomatic disorder, Med. Clin. N. Am., 1944, xxviii, 1210-1216. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Atlanta, Georgia*Received for publication June 25, 1946.From the Department of Medicine, Emory University School of Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMedical Interviewing 1 December 1947Volume 27, Issue 6Page: 929-935 ePublished: 1 December 2008 Issue Published: 1 December 1947 PDF downloadLoading ...
The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype
Authors: Sheng Zhou, John D. Schuetz, Kevin D. Bunting, Anne-Marie Colapietro, Janardhan Sampath, John J. Morris, Irina Lagutina, Gerard C. Grosveld, Mitsujiro Osawa, Hiromitsu Nakauchi, Brian P. Sorrentino
Journal: Nature Medicine (2001)
193. Hypoxia-Inducible VEGF Gene Therapy Using the RTP801 Promoter
Authors: Donghoon Choi, Minhyung Lee, David A. Bull, Russel Reiss, Chien-Wen Chang, Lane Christensen, Sung Wan Kim
Journal: Molecular Therapy (2004)

Background; The angiogenic gene therapy using VEGF is a new potential treatment for ischemic disease. Gene expression in ischemic tissue must be locally enhanced and regulated to be safe and effective. Previously, it was reported that the RTP801 promoter was strongly induced under hypoxic conditions. This strong induction of the RTP801 promoter suggests its applicability to the regulation of VEGF gene in the VEGF gene therapy. In this study, we evaluated the role of the RTP801-VEGF plasmid as a therapeutic plasmid in vitro and in vivo study. Method; To identify the cis-regulatory element, the RTP801 promoter was analyzed by various methods. pRTP801-VEGF was constructed by the insertion of the RTP801 promoter upstream of the VEGF cDNA. pEpo-SV-VEGF and pSV-VEGF were used as positive controls and WSLP only injection without plasmid was used as a negative control the in vivo model. In vitro cell transfection study, polyethylenimine (PEI, 25,000 Da) was used as a gene carrier and 293T cells were used. In an in vivo VEGF expression study, we used water-soluble lipopolymer (WSLP) as a gene carrier. The circumflex artery of a New Zealand white rabbit was ligated with a 6-0 Prolene suture and WSLP-plasmid complex (150 ug/750 ul) was injected into the infarcted myocardium using a 30-guage needle. The hearts were harvested 4 days after the injections and homogenized in lysis buffer. The expression level of the VEGF gene was measured by ELISA. Result; In luciferase assay, the region between -495 and -445 was responsible for the hypoxia-induced transcription. In this region, there was a potential Sp1 binding element. The mutation of the Sp1 site reduced the hypoxia-induced transcription of the RTP801 promoter. In addition, co-transfection with antisense Sp1 oligonucleotide decreased the promoter activity. These results suggest that the hypoxia induction of the RTP801 promoter is mediated by Sp1. The pRTP801-VEGF had stronger VEGF expression than pEpo-SV-VEGF, which contained the Epo (erythropoietin) enhancer and the SV 40 promoter system. In addition, the VEGF expression by pRTP801-VEGF was induced under hypoxic condition. In the animal study, the expression level of VEGF by pRTP801-VEGF in the ischemic myocardium was 5.7 times higher than controls (p < 0.001) and 2.5 times higher than the pSV-VEGF (p < 0.01) and 2 times higher than the pEpo-SV-VEGF (p < 0.05). Conclusion; Therefore pRTP801-VEGF will be useful for the VEGF gene therapy for ischemic heart disease with strong induction under hypoxic condition.
Optimal Intervals and Techniques for Screening Sigmoidoscopy—Reply
Authors: Amnon Sonnenberg, David Lieberman
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Donald M. Berwick, MD, MPP
Authors: Donald M Berwick
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fortnightly review: Male pattern androgenetic alopecia
Authors: R. Sinclair
Journal: BMJ (1998)

Androgenetic alopecia is characterised by progressive, patterned hair loss from the scalp. Recently the pathogenesis and genetic basis of the hair loss have been better understood, as has the distress experienced by men who have lost their hair. There have also been breakthroughs in the treatment of androgenetic alopecia.

The transition of some terminal hairs into vellus hairs is a universal physiological secondary sexual characteristic.1 Androgenetic alopecia becomes a medical problem only when the hair loss is subjectively seen as excessive, premature, and distressing.

The prerequisites for premature androgenetic alopecia are a genetic predisposition and sufficient circulating androgens.2 Eunuchs do not go bald.3 Every white man possesses the autosomal inherited predisposition,4 and 96% lose hair to some degree,5 but because of the variabity of gene expression far fewer have appreciable premature hair loss.

#### Summary points

This article is based largely on my experience in the management of hair loss. Original articles and expert reviews from major journals cited in Medline between 1966 and 1997 have been supplemented by information and articles cited in recently published textbooks. The following keywords were used for the Medline search: androgenetic alopecia, androgenic alopecia, common baldness and balding, premature baldness and balding, hereditary balding and baldness, male pattern and female pattern alopecia, …
Abstract 13221: Family Caregivers’ Perceptions of Illness Severity in Heart Failure Patients with Limited Life Expectancy
Authors: Lisa Kitko, Judith Hupcey, Maureen Palese
Journal: Circulation (2014)

Introduction: End-of-life (EOL) services, such as hospice and palliative care are often lacking even for the sickest heart failure (HF) patients. Use of these services have been hampered by the lack of availability, lack of referrals due to the unpredictable course in HF, and refusal of services by patients and caregivers due to a lack of understanding of the terminality of HF. The purpose of this study was to determine whether caregivers of HF patients with a predicted survival of less than 2 years, understood disease terminality prior to and after the patient’s death. Methods: As part of a longitudinal study of 100 patient-caregiver dyads, caregivers were interviewed monthly until the patient’s death and then twice post-death. Caregiver interviews immediately preceding and post-patient death were analyzed to determine caregivers’ perceptions of the terminality of heart failure. Results: There were 49 caregivers of patients who died. Patients died an average of 8 months after study enrollment. Most caregivers did not understand the severity of the patient’s disease and 51% (25/49) viewed the death as unexpected. When caregivers retrospectively reflected on the patient’s illness trajectory, they recounted downward trends in patient’s health, but were not aware of the terminality of the patient until after death occurred. Those few caregivers who perceived the illness severity prior to death came to this realization late in the disease trajectory. At the point of recognition, advanced treatments were limited or withdrawn and the short-term use of EOL services such as palliative care or hospice was instituted. Conclusions: The lack of perceived illness severity/terminality has profound implications for patients, caregivers, and healthcare providers. Patients and caregivers who do not understand the seriousness of the illness are less likely to accept EOL services, if offered. Clinicians need to understand the HF EOL trajectory and that EOL discussions and advance care planning help patients and caregivers make informed choices and receive quality care at EOL. We also need to educate all healthcare providers about having these discussions, so palliative care becomes a philosophy of care not merely a referral service immediately preceding death.
Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders
Authors: JD Rosenblatt, JV Giorgi, DW Golde, JB Ezra, A Wu, CD Winberg, J Glaspy, W Wachsman, IS Chen
Journal: Blood (1988)
Waiting Room, Mt Sinai Hospital
Authors: Kristin Camitta Zimet
Journal: JAMA (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
In brief
Authors: C Marwick
Journal: BMJ (2001)

The healthcare system in the United States rewards inefficiency, is slanted towards care for acute rather than chronic conditions, and fails to take full advantage of electronic technology. The result is that it consistently fails to provide safe, high quality medical care. It is disjointed and inefficient and urgently needs reorganisation and reform. These were the conclusions of a new report from the US Institute of Medicine, National Academy of Sciences.

The current healthcare system cannot do the job. Building on or modifying it will not work, said the institute's committee on quality of health care in its latest report, published last week.

The committee was formed in 1998 and was charged with drawing up a strategy that would lead to substantial improvement in the quality of health care over the next 10 years. The report presents general principles rather than a detailed blueprint for the building of a new system of …
The targeted cytotoxic prodrug, AQ4N, has significant activity in the breast adenocarcinoma model MDA-MB-231.
Authors: Susan E. Alters, Alvin Wong, Alshad S. Lalani, W. D. Henner
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5545 

Introduction: An ideal anti-tumor treatment is the use of highly selective compounds to eliminate neoplastic cells while having minimal systemic toxicity to normal tissues. AQ4N (banoxantrone; 1,4 bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione bis N-oxide) is designed to have little or no toxicity until selectively activated by bioreduction to AQ4, a highly potent DNA topoisomerase II inhibitor. In vitro , AQ4 has potent cytotoxicity on a panel of solid tumor lines and treatment with AQ4N has been shown to have significant anti-tumor activity in xenograft models of colon and pancreatic carcinoma. Here we investigate the anti-tumor potential of AQ4N in a breast adenocarcinoma tumor model, MDA-MB-231. Experimental Methods: The cytotoxic activity of AQ4 and AQ4N was determined by MTT assay following a 24 hour incubation with drug in vitro . To investigate the anti-tumor effects of AQ4N in vivo , human MDA-MB-231 breast carcinoma cells were subcutaneously implanted into nude mice (10 mice per group). Mice were randomized and treatment initiated when tumors reached 80-120mm3; the endpoint of the study was defined as tumors of 1500mm3. AQ4N was dosed intravenously and two treatment groups included 75 mg/kg every other day (qod) × 6 and 90mg/kg every three days (q3d) × 6. Paclitaxel, a highly effective anti-neoplastic agent in this model, was used as a positive control. Treatment outcome was determined from tumor growth delay, defined as the increase in median time to endpoint (TTE) in the treatment group as compared to untreated mice; statistical significance was determined by log-rank test. Results: AQ4N and AQ4 were screened against the human breast cell line, MDA-MB-231 in vitro . Whereas the parent AQ4N molecule was shown to be inactive, the bioreduced AQ4 metabolite demonstrated potent cytotoxic activity with an IC50 of 2.71μM. In vivo , both AQ4N dose groups demonstrated significant tumor growth delay compared to the no treatment control (TTE = 26.4 days for untreated) in the MDA-MB-231 tumor model. AQ4N dosed at 90mg/kg q3d × 6 yielded a median TTE of 36.7 days corresponding to a 10.3 day (39%) tumor growth delay (P=0.005). In addition, AQ4N dosed at 75mg/kg qod x6 resulted in a median TTE of 34.1 days corresponding to a 7.7 day (29%) tumor growth delay (P=0.02). As expected, paclitaxel dosed at 30mg/kg qod × 5 had 100% day 60 survival (P<0.0001). Conclusions: The cytotoxic prodrug AQ4N demonstrates significant anti-tumor activity in the MDA-MB-231 breast adenocarcinoma tumor model, at doses below the MTD. This extends our observations showing significant anti-tumor effects in pancreatic and colon carcinoma xenograft models and indicates that AQ4N may have potential as single agent therapy in multiple solid tumor malignancies. AQ4N is currently being investigated in human clinical studies.
Abstract 15852: PKR-Like Endoplasmic Reticulum Kinase (PERK) and Glycogen Synthase Kinase (GSK)-3α/β Signaling Regulate Atherosclerosis Development
Authors: Cameron McAlpine, Geoff Werstuck
Journal: Circulation (2014)

Background:  Recently, a role for endoplasmic reticulum (ER) stress signaling through glycogen synthase kinase (GSK)-3α/β has been proposed in atherogenesis; this study sought to delineate the underlying molecular mechanisms.   Methods and Results:  Cultured THP1-derived macrophages were treated with the ER stress-inducing agents, glucosamine, thapsigargin or palmitate in the presence or absence of inhibitors of the unfolded protein response (UPR) pathways (PERK, IRE, ATF6) or GSK3α/β (CT99021). ER stress enhanced GSK3α/β activity while inhibition of the PERK pathway, but not the IRE or ATF6 pathways, attenuated GSK3α/β activity. GSK3α/β inhibition did not affect adaptive components of the UPR but did repress the expression of factors downstream of PERK (ATF4 and CHOP). ER stress enhanced the mRNA expression of genes controlling lipid biosynthesis and uptake; while GSK3α/β inhibition attenuated this effect. GSK3α/β inhibition blocked ER stress-induced cholesterol accumulation in macrophages. To investigate the roles of macrophage GSK3α and GSK3β in a mouse model of atherosclerosis, LDLR-/- myeloid cell GSK3α knockout (LDLR-/-GSK3αflox/floxLyzMCre+/-) and GSK3β knockout (LDLR-/-GSK3βflox/floxLyzMCre+/-) mice were placed on a high fat diet. Myeloid cell GSK3α deficiency, but not GSK3β deficiency, attenuated atherogenesis.   Conclusions:  Our findings support a role for macrophage PERK - GSK3α signaling in atherosclerosis development.
Executing Timothy McVeigh
Authors: George Dunea
Journal: BMJ (2001)

Even many of the most vociferous opponents of capital punishment were subdued in their protests when Timothy McVeigh, the Oklahoma bomber, was put to death in the early hours of 11 June in Terre Haute, Indiana. The execution, which was the first federal application of the death penalty in the United States for 38 years, was carried out painlessly and aseptically with an injection of sodium thiopental, pancuronium, and potassium …