tbuckley/cabot-search huggingface dataset:
Abstract P6-10-03: The PKC inhibitor PKC412 antagonizes breast cancer cell growth and enhances tamoxifen sensitivity
Authors: J Shou, SA Chew, N Mitsiades, V Kumar, X Fu, G Chamness, K Osborne, R Schiff
Journal: Cancer Research (2012)

Abstract Background: AIB1 (SRC-3, NCoA3), a member of the p160/steroid receptor coactivators family, plays a critical role in cell growth and proliferation. In estrogen receptor-alpha positive (ER+) breast cancer (BC) cells, it coactivates estrogen- and additional transcription factors-dependent gene transcription, reducing the antagonistic activity of tamoxifen and resulting in tamoxifen resistance (TR). We have previously shown that BC patients whose tumors expressed high levels of both AIB1 and HER-2 had worse outcomes with tamoxifen therapy, suggesting that AIB1 may be an important diagnostic and therapeutic target. Our findings that knocking down AIB1 attenuates ER signaling and inhibits breast cancer cell growth further indicate that the manipulation of AIB1 level could be an approach to treating BC and overcoming TR. Recently, it has been shown that protein kinase C (PKC) isoforms phosphorylate AIB1 and prevent its proteasome-mediated degradation. The present study was carried out to test if the multi-targeted kinase and PKC inhibitor PKC412 (midostaurin) is capable of promoting degradation of AIB1, inhibiting BC cell growth, and promoting tamoxifen antagonistic activity. Methods: The ER+ MCF7, T47D, and ZR75-B BC cells and their tamoxifen-resistant derivatives (TR) were used. The Methylene Blue assay was employed to measure cell viability of BC cell lines after treatment with PKC412 or the combination of PKC412 with tamoxifen. To determine the impact of PKC412 on AIB1 and ER proteins and mRNA levels, we used immunoblotting and RT-qPCR, respectively. Results: PKC412 successfully inhibited the growth of MCF7, T47D, and ZR75-B cells, and their tamoxifen-resistant derivatives. Treatment with PKC412 depleted AIB1 protein and reduced the level of ER protein without significant alteration in AIB1 mRNA level. Consequently, ER signaling was disrupted, as reflected by decreased expression of ER target genes such as GREB1. PKC412 also enhanced tamoxifen's antagonistic activity in the parental cell lines and sensitized tamoxifen-resistant MCF7 and ZR75-B cells to tamoxifen. Conclusions: The results of this study suggest that the multi-targeted kinase and PKC inhibitor PKC412 can post-translationally destabilize AIB1 protein and ER, inhibiting BC cell growth and viability. PKC412 enhances tamoxifen's antagonistic activity on BC growth; furthermore, it sensitizes tamoxifen-resistant cells to tamoxifen. Thus, PKC412 is a promising agent to treat BC and, in combination with tamoxifen, to delay or overcome TR. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-10-03.
SECONDARY PAROTITIS DUE TO ORAL STARVATION IN THE MEDICAL TREATMENT OF GASTRIC ULCER
Authors: H. D. Rolleston, M. W. B. Oliver
Journal: BMJ (1909)

After the removal of the sac, gradually thle sinus from the cystic duct contracted and at tlle same time the kinling, or other cause of the occlusion of the common duct, was removed and the bile passed into the intestine and con- tinues to do so, as shown by the colour of the faeces.The age of my patient was less than usually is the case where the gall bladder is much dilated.The rate of dilatation was much greater, as usually the process is a slow one.Twenty-five pints were drawn off within four or five weeks of any swellinag being observed, and not more than seven months after the fal which most probably set up the condition.RXEFERENCE.
Torcetrapib and Atorvastatin — Should Marketing Drive the Research Agenda?
Authors: Jerry Avorn
Journal: New England Journal of Medicine (2005)

In light of the success of the statin drugs, interest in preventive cardiology has shifted to new frontiers of pharmacologic intervention: defining optimal levels of low-density lipoprotein (LDL) cholesterol, inhibiting cholesterol absorption, addressing the inflammatory component of atherosclerosis, and increasing the levels of protective high-density lipoprotein (HDL) cholesterol. This last approach attracted attention last year when it was reported that a new drug, torcetrapib, could substantially increase levels of HDL cholesterol by inhibiting cholesteryl ester transfer protein.1 The drug was heralded as a novel weapon against heart disease that could be an important clinical tool if its effect on lipids . . .
Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation
Authors: S Nikolaus, J Bauditz, P Gionchetti, C Witt, H Lochs, S Schreiber
Journal: Gut (1998)

<i>Background</i>—Concentrations of pro-inflammatory cytokines are increased in the intestinal mucosa of patients with active inflammatory bowel disease (IBD). Polymorphonuclear neutrophil granulocytes (PMN) are the most abundant cell type in intestinal lesions in IBD. Interleukin 10 (IL-10) is an important contra-inflammatory cytokine which induces downregulation of pro-inflammatory cytokines. <i>Aims</i>—To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro-inflammatory cytokines and can be regulated by IL-10. <i>Methods</i>—Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT-PCR) of pro-inflammatory cytokines (IL-1β, TNF-α) and of IL-1 receptor antagonist were assessed in peripheral PMN. <i>Results</i>—PMN from patients with IBD are primed to secrete enhanced amounts of pro-inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL-10 markedly inhibited pro-inflammatory cytokine secretion as well as corresponding mRNA concentrations. <i>Conclusions</i>—PMN are an important source of pro-inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL-10.
The effect of cetirizine on symptoms and wealing in dermographic urticaria
Authors: G. R. SHARPE, S. SHUSTER
Journal: British Journal of Dermatology (1993)

The effect of cetirizine, 10 mg at night, on dermographic urticaria, was studied in 19 patients. The study design was a randomized, double‐blind, crossover comparison with placebo, each treatment being given for 7 days. Patients kept a daily diary of itch and weal severity (100‐mm linear analogue scale), and recorded sleep disturbance. The dermographic weal response was measured objectively with a spring‐loaded stylus, and the weal threshold calculated from the force/response curve. There was a small, insignificant subjective response to placebo, but no objective response. On cetirizine, the subjective assessment of wealing was reduced from 34.3±6.7 (mean ± SEM, 0–100 scale) to 16.8±4.1 (P= 0.02), itch was reduced from 43.2±6.6 to 19.4±4.1 (P=0.001), and nights disturbed from 46.2 to 8.8% (P=0.03). There was a shift to the right in the position of the force/response curve, and the wealing threshold increased from 24.6±3.2 to 54.7±4.4 g/mm2 (P=0.00001), but there was no correlation between change in itch scores and wealing threshold. Cetirizine 10 mg daily is an effective treatment in dermographic urticaria, and its usefulness will depend on the prevalence of unwanted effects.
Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition
Authors: Richard S. Finn
Journal: Liver Cancer (2012)

Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC.
THE ORGANIZED MEDICAL PROFESSION AND SOME OF ITS ENEMIES.
Authors: EDWARD JACKSON
Journal: JAMA (1907)

<h3>THE BASIS OF AN ORGANIZED PROFESSION.</h3> The medical profession becomes organized, medical associations are formed, principally for these two purposes: to increase and diffuse medical knowledge and to elevate and maintain the ethical standards of the profession. Other important purposes may be served by our professional organizations. The guidance of the community in relation to matters of public health and hygiene is often, and properly, matter for consideration in medical societies; and special societies may be formed among the medical profession devoted to such particular purposes, as for the eradication of tuberculosis or trachoma. Again, medical societies sometimes act to protect the interests of the individual members of the profession; as by union for defense against suits for malpractice, or the relief of physicians who have been specially unfortunate, or their families. But this work, too, is taken up after the profession has been organized. Such objects do not primarily
Breaking off the Physician-Patient Relationship: Another Legal Hazard
Authors: William J. Curran
Journal: New England Journal of Medicine (1982)

The practice of medicine in the United States is still a matter of free determination. There are no compulsory duties on the part of physicians — or of patients, for that matter. One of the unclear aspects of this freedom, however, is the proper method of breaking off an existing professional relationship with a patient. As it is usually stated, the attending doctor should continue to treat a patient under care for a particular disease or condition until the patient no longer needs care or dismisses the doctor. Termination of a continuing relationship is clearly allowed, but the physician must . . .
Biopsy of Colonic Polyps
Authors: Robert G. Norfleet
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 August 1988Biopsy of Colonic PolypsRobert G. Norfleet, MD, Michael E. Ryan, MDRobert G. Norfleet, MDSearch for more papers by this author, Michael E. Ryan, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-3-251 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Wrenn has challenged (1) the recommendation of the Health and Public Policy Committee of the American College of Physicians that persons learning fiberoptic sigmoidoscopy should be trained to do forceps biopsy (2). He argues that patients with polyps should be referred for colonoscopy and polypectomy without biopsy because biopsy may not show malignant foci or adenomatous changes and because synchronous lesions may lurk more proximally in the colon.We wish to call attention to new data that were not available to Dr. Wrenn when his letter was written. We have found that 97% of polyps larger...References1. Wrenn K. Flexible sigmoidoscopy for screening [Letter]. Ann Intern Med. 1988;108:494. LinkGoogle Scholar2. . Clinical competence in the use of flexible sigmoidoscopy for screening purposes. Ann Intern Med. 1987;107:589-91. LinkGoogle Scholar3. NorfleetRyanWyman RMJ. Adenomatous and hyperplastic polyps cannot be reliably distinguished by their appearance through the fiberoptic sigmoidoscope. Dig Dis Sci. 1988;[In press]. CrossrefMedlineGoogle Scholar4. MutoBussyMorson THB. The evolution of cancer of the colon and rectum. Cancer. 1975;36:2251-70. CrossrefMedlineGoogle Scholar5. RyanNorfleetKirchner MRJ. The significance of diminutive colonic polyps found at flexible sigmoidoscopy. Gastrointest Endosc. 1988;[In press]. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Marshfield Medical Center Marshfield, WI 54449 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDiminutive colonic polypsHyperplastic Colon Polyps—Are They Markers?Jerome D. Waye, MD 1 August 1988Volume 109, Issue 3Page: 251-252KeywordsBiopsyColonColonoscopyLesionsPolypectomiesPrevention, policy, and public healthPublic policy Issue Published: 1 August 1988 PDF DownloadLoading ...
THE EVIL OF EPONYMS.CHAIRMAN'S ADDRESS BEFORE THE SECTION ON LARYNGOLOGY AND OTOLOGY, AT THE FIFTY-FOURTH ANNUAL SESSION OF THE AMERICAN MEDICAL ASSOCIATION AT NEW ORLEANS, MAY 5-8, 1903.
Authors: GEORGE L. RICHARDS
Journal: JAMA (1903)

As Chairman of the Section on Laryngology and Otology of the American Medical Association, I bid you, the members of this Section, a most cordial welcome to the Fifty-fourth Session of this Association and to the Fifteenth Session of this Section. The secretary, Dr. Barnhill, and myself have labored for some months in the preparation of the annual feast, and I am sure that the menu which we have now ready for you will be in no way inferior to the banquets which we are accustomed to enjoy. For many years the papers which have been read before this Section of the American Medical Association have not been surpassed by the papers presented in the meetings of any of the special societies in the United States; while this Section has the great advantage that it has no red tape attached to it, but is open to every earnest worker
Prof. Weismann's Theories.
Authors: James L. Taylor
Journal: JAMA (1893)

A late thoughtful editorial inThe Journalon "Studies of Heredity," commenting on Dr. Weismann's published essays on this subject, seems to endorse the German professor's doctrines as the latest accepted conclusions of science. No mention is made of the widespread criticisms which Weismann's theories have called forth, the most notable of which perhaps are from the pen of Herbert Spencer in the<i>Contemporary Review</i>. After expressing surprise at the wide acceptance of Prof. Weismann's theories by the biological world, Mr. Spencer proceeds to show that the most fundamental proposition in his "Essays"—that on which the whole superstructure of his biological arguments rest—is untenable. Prof. Weismann's primary contention is that animal organisms consist essentially of two kinds of ultimate cells —the somatic or nutritive cells and the reproductive germ cells; that the former are perishable but that the latter are immortal; that is, that in the propagation of the species
Kidney trafficking is "big business," says Council of Europe
Authors: C. Kovac
Journal: BMJ (2003)

The Council of Europe's parliamentary assembly has issued a report saying that, because of a rapidly increasing demand for kidney transplants, trafficking in kidneys has become a hugely profitable business for international organised crime—and for the doctors who perform the procedures.

Between 15% and 30% of European patients die while waiting for a kidney transplantation, owing to a chronic shortage of organs, the report says, noting that the average wait for a legal transplant is now three years and is expected to increase to 10 years by 2010. …
Gallium Imaging of Esophageal Carcinoma
Authors: SAMUEL SOSTRE, IRAIDA ROMERO, JULIO V. RIVERA, LUIS BAEZ, ELSIE CINTRON
Journal: Clinical Nuclear Medicine (1990)

Ga-67 imaging has not been very successful in the detection of espphageal carcinoma. In most reports, sensitivity for the primary tumor ranged from 25–61%, but imaging had been done only in anterior and posterior (A-P) projections. We performed gallium scans in 30 patients with esophageal carcinoma, adding lateral views to the routine A-P projections, to study the effect of lateral views on tumor detection. The A-P views detected only 57% of the tumors while the right lateral visualized 89%, and the left lateral detected 100%. Some lesions may be hidden by the sternum and the spine in the routine A-P views. Previous disappointments with Ga-67 imaging of esophageal carcinoma were probably due to this technical factor. Being gallium-avid, esophageal tumors deserve further studies with this agent to determine the role of Ga-67 imaging in this condition. These studies should be performed with multiple views of the thorax or, better yet, with SPECT imaging of the chest, to circumvent the problem of sternum and spine interference.
TERT Promoter Eyed With Suspicion and Hope
Authors: Cathryn Delude
Journal: JNCI Journal of the National Cancer Institute (2014)

Cancer researchers yearning for a robust universal biomarker of malignancy and tumor grade have long found telomerase a tempting candidate. This enzyme maintains the telomeres at the tips of chromosomes in early development and stem cells but is then usually inactivated, allowing telomeres to erode and limiting cell division. Most cancer cells, however, reactivate telomerase in their quest to become immortal.

Current methods to measure telomerase levels for clinical diagnosis and prognosis through DNA, RNA, or protein analysis have technical difficulties, including lack of reliable antibodies and inability to use in paraffin-embedded tissues, said Uri Tabori, M.D., from the Hospital for Sick Children in Toronto, Canada. In the past year, he and others took a different approach, looking at the promoter for the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT) instead of directly at the gene.
Exaggerated Earlobe Ptosis Due to Habitual Ear Pulling
Authors: Ross J. Brothers, Marla N. Jahnke, Steven Daveluy
Journal: JAMA Dermatology (2014)

A certain degree of earlobe drooping, known as earlobe ptosis, occurs with normal aging of the skin. We report the case of a woman with exaggerated earlobe ptosis due to habitually pulling the earlobes.
Review of publication bias in studies on publication bias: Meta-research on publication bias does not help transfer research results to patient care
Authors: Peter Kranke
Journal: BMJ (2005)

Childhood cancer and power linesWhat do the data mean?Editor-Draper et al used distance of mother's home from high voltage overhead transmission lines (predominantly 275 kV and 400 kV) at the time of her child's birth as a proxy for her child's subsequent exposure to power-frequency magnetic fields (reviewed by Ahlbom et al). 1 2 As they acknowledge, this is a crude estimate since, in contrast to other reports, 2 no household measurements were taken, no data on more prevalent low voltage distribution sources were collected, no information from other time points in the child's life was obtained, variations during the 33 years period studied were not considered, and no validatory home visits were carried out.A recent report into residential exposures to magnetic fields in the United Kingdom estimated that proximity to high voltage lines, 275 kV and above, explained only 9% of those with measurements ≥ 0.2 microtesla ( T). 3 National data on the distribution of houses in relation to high voltage lines in the UK were provided (J Swanson, National Grid Transco, personal communication, 2000) to the UK Childhood Cancer Study (UKCCS) Group for its study of power lines and childhood cancer, to assess the representativeness of study subjects. 4 An equivalent comparison using National Grid data spanning the far longer period investigated in the paper by Draper et al was not undertaken.The assessments of distance to power lines in the UKCCS were made for all registered controls, who have been shown to represent the general population. 5plot of the distributions of the leukaemia and non-leukaemia cases and controls in the study by Draper et al, national populations, and UKCCS populations by distance from high voltage lines (figure) seems to show that the leukaemia controls used in the analysis presented by Draper et al are systematically different.Their positive result over 100 m may therefore be explained not by an excess of cases but by a deficit of controls in the early years of the study.
A major founder Y–chromosome haplotype in Amerindians
Authors: Sérgio D.J. Pena, Fabrício R. Santos, Néstor O. Bianchi, Claudio M. Bravi, Francisco R. Carnese, Francisco Rothhammer, Tudevdagva Gerelsaikhan, Bjamba Munkhtuja, Tsendsuren Oyunsuren
Journal: Nature Genetics (1995)
Granulocyte Alkaline Phosphatase. STUDIES OF PURIFIED ENZYMES FROM NORMAL SUBJECTS AND PATIENTS WITH POLYCYTHEMIA VERA
Authors: Daniel Rosenblum, Shirley J. Petzold
Journal: Journal of Clinical Investigation (1973)

To characterize the biological changes which result in increased granulocyte alkaline p-nitrophenyl phosphatase activity in patients with polycythemia vera, the enzyme was purified from granule fractions of sucrose homogenates made from dextran-sedimented leukocytes of normal subjects and patients with polycythemia vera. Polycythemic blood yielded 3-10 times as much granulocyte alkaline phosphatase per 10(9) leukocytes as did normal blood. Sodium dodecyl sulfate extracts of granules were purified by DEAE-cellulose chromatography and sucrose gradient centrifugation to apparent homogeneity as judged by polycarylamide disk gel electrophoresis. Granulocyte alkaline phosphatase from normal subjects was purified 6910-fold with a 60% yield and a specific activity of 47 U/mg. Granulocyte alkaline phosphatase from polycythemic patients was purified 1.166-fold with a 50% yield and a specific activity of 70 U/mg. The two enzymes did not differ in molecular weight; both appeared to be about 160,000 daltons by sucrose gradient centrifugation. Both appeared to be zinc metalloenzymes, in that they were specifically inhibited by o-phenanthroline. Their elution requirements when adsorbed to DEAE-cellulose suggested they were lipoproteins although the content of phosphorus was below the threshold of detection. The identity of the two enzymes was suggested by immunological studies in which antibody prepared against purified polycythemia vera enzyme gave a precipitation reaction of identity with another polycythemia vera enzyme and two pools of normal enzyme. It is possible to account for the difference in alkaline phosphatase activity between the granulocytes of patients with polycythemia vera and normal subjects by differences in the quantity of enzyme synthesized.
US heart association endorses active video games
Authors: J. Lenzer
Journal: BMJ (2010)

The American Heart Association announced that it has entered into a “strategic relationship” with Nintendo of America to endorse the company’s active video games, known as Wii. 

The videos include titles such as Wii Tennis and Battalion Wars 2. Players gesture with hand-held devices that interact with the videos to simulate action, such as playing a sport or killing an opponent with a nunchuk.

The association endorsed the video games as part of its campaign against obesity, saying that 70% of US citizens don’t get adequate exercise. The association’s logo will be stamped on all Wii game packaging, indicating that it is a “healthy …