tbuckley/cabot-search huggingface dataset:
Abstract A4: A novel class of selective ERα degraders acts as full antagonists/ inverse agonists and displays efficacy in pre-clinical models of endocrine-resistant breast cancer and endometrial cancer
Authors: Beatrice Darimont, Ninh Lu, John Sensintaffar, Kyoung-Jin Lee, Anna Aparicio, Joshua Kaufman, Eric Bischoff, Peter Rix, Rich Heyman, Nicholas Smith, Jeffrey Hager, James Joseph, Katherine Grillot, Jing Qian, Shao Gang, Steven Govek, Johnny Nagasawa, Andiliy Lai, Mehmet Kahraman
Journal: Clinical Cancer Research (2012)

Abstract While endocrine therapies are initially effective to treat estrogen receptor (ERα) positive breast cancer tumors, acquired resistance invariably emerges. Although resistant tumors typically display changes in PI3K or other kinase pathways, the majority of these tumors continue to express and depend on ERα for growth and survival. Exploring the hypothesis that endocrine resistance might involve hormone-independent activities of ERα, we have developed two distinct classes of potent, non-steroidal ERα modulators that antagonize hormone-mediated transcriptional activities of ER and lower ERα steady state levels. These compounds showed robust efficacy in pre-clinical models of endocrine-resistant breast cancer, including some with up-regulated PI3K pathways. In contrast to their activity as full antagonists/ inverse agonists in the breast, the two classes of ERα modulators displayed distinct abilities to oppose the activity of estradiol in the uterine endometrium, another well-characterized ERα target tissue. Similar to endocrine-resistant breast cancer, a large percentage of endometrial cancers have altered PI3K pathways and typically respond poorly to endocrine therapy. In mouse xenograft models one of our compounds inhibited the growth of ECC-1 endometrial cancer tumors with substantially higher efficacy than the selective ER modulator arzoxifene, which in a phase II clinical trial exhibited a 30% response rate in patients with recurring ERα-positive endometrial cancers. Hence, beyond their promise as a next generation therapy for the treatment of endocrine resistant ER+ breast cancer, these novel classes of selective estrogen receptor degraders might also open new opportunities for endocrine therapies targeting endometrial cancer.
Nerves at the Ventral Prostatic Capsule Contribute to Erectile Function: Initial Electrophysiological Assessment in Humans
Authors: Yasuhiro Kaiho, Haruo Nakagawa, Hideo Saito, Akihiro Ito, Shigeto Ishidoya, Seiichi Saito, Yoichi Arai
Journal: European Urology (2008)
Abstract C37: Positive involvement of chemokine CXCL14 in osteolytic bone metastasis of lung cancer
Authors: Haruo Iguchi, Soichi Takiguchi
Journal: Cancer Research (2013)

Abstract To investigate the molecular mechanisms for osteolytic bone metastasis, we established a human lung cancer cell line (HARA-B4) with elevated bone metastatic activity. All the experiments employed by HARA-B4 were performed with the parental HARA as a control cell line. Anchorage-independent growth ability was higher in HARA-B4 according to the results by soft agar colony formation assay. Murine macrophage-like and osteoblast-like cell lines (RAW264.7 and MC3T3-E1, respectively) migrated faster toward cultured HARA-B4 in transwell cell migration assay. The spans of bone metastatic emergence and survival were shortened in nude mice inoculated with HARA-B4. CXC chemokine ligand 14 (CXCL14) was overexpressed in HARA-B4 and responsible for the activities described above according to the results performed with the CXCL14 siRNA-treated HARA-B4. Furthermore, in the clinical specimens of the lung cancer-induced bone metastasis, expression of CXCL14 was observed in the infiltrated tumor cells of the bone marrow as well as bone stromal cells in all the specimens examined (n=7). These data indicates the positive involvement of CXCL14 in the bone metastasis from lung cancer. Citation Format: Haruo Iguchi, Soichi Takiguchi. Positive involvement of chemokine CXCL14 in osteolytic bone metastasis of lung cancer. [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 C37.
Endovascular Irradiation From β-Particle–Emitting Gold Stents Results in Increased Neointima Formation in a Porcine Restenosis Model
Authors: Christian Schulz, Christina Niederer, Christian Andres, Robert A. Herrmann, Xilei Lin, Richard Henkelmann, Werner Panzer, Clemens Herrmann, Dieter F. Regulla, Ingo Wolf, Kurt Ulm, Eckhard Alt
Journal: Circulation (2000)

Recent studies have shown that ionizing radiation reduces neointima formation after balloon angioplasty and stent implantation in experimental models of restenosis and first clinical trials. The objective of this study was to determine the dose distribution of a new beta-particle-emitting radioactive gold stent and to evaluate the dose-dependent vascular response in the coronary overstretch pig model.Sixteen Göttinger minipigs underwent placement of 11 nonradioactive and 36 beta-particle-emitting stents with activity levels of 10.4+/-0.6, 14.9+/-2.4, 22.8+/-1.3, 35.8+/-2. 8, and 55.4+/-5.3 microCi of (198)Au. Three months after implantation, the percent area stenosis, neointimal thickness, neointimal area, and vessel injury were analyzed by quantitative histomorphometry. The lifetime radiation doses at a depth of 1 mm were 3.3+/-0.2, 4.7+/-0.5, 7.2+/-0.4, 11.4+/-0.9, and 17.6+/-1.7 Gy for the different activity groups. No dose-response relationship was observed in the radioactive stents with respect to percent area stenosis (P=0.297), mean neointimal thickness (P=0.82), or mean neointimal area (P=0.65). Significantly lower neointima formation and less luminal narrowing was seen in the control group than in the beta-particle-emitting stents (P<0.001). Multilinear regression analysis revealed that only radioactivity made a significant independent contribution to the degree of percent area stenosis (P<0. 001).Neointima formation in pigs is markedly increased by beta-particle-emitting stents with (198)Au as the radioisotope. This study provides evidence that dosages of 3 to 18 Gy of low-dose-rate beta-particle irradiation via endovascular stents cause pronounced luminal narrowing in the animal model at 3 months.
Prolapse of Ovarian Cyst
Authors: A. W. Stocks
Journal: BMJ (1875)

THE BRITLSH MEDICAL .7RNAL.487 wards during micturition at the umbilicus, welling up into the umbilical cup, filling it, and running over in such quantity that the parents had no reason to entertain any doubt as to the nature of the fluid.The urine was passed with difficulty by the urethra, and fell down from the orifice.No tumour was visible at the umbilicus; the prepuce was
In Vivo Laser Confocal Microscopy Findings of Radial Keratoneuritis in Patients with Early Stage Acanthamoeba Keratitis
Authors: Akira Kobayashi, Hideaki Yokogawa, Natsuko Yamazaki, Yasuhisa Ishibashi, Yosaburo Oikawa, Masaharu Tokoro, Kazuhisa Sugiyama
Journal: Ophthalmology (2013)
Erythrocytapheresis in idiopathic haemochromatosis.
Authors: D Conte, L Brunelli, A Bozzani, L Tidone, M Quatrini, P A Bianchi
Journal: BMJ (1983)

Erythromycin must join the long list of drugs implicated in interstitial nephritis.So far as we know this is the first case of erythromycin induced renal failure proved by renal biopsy.The insidious onset may permit the renal lesion to escape early detection with resultant permanent damage, as in our case.We suggest that renal function should be monitored when erythromycin or other drugs which may induce interstitial nephritis are administered in prolonged or repeated courses.
Potency of Biosynthetic Human Insulin Determined In Vitro
Authors: R D Fussgaenger, H H Ditschuneit, H Martini, H Wiebauer-De Lenardis, H Etzrodt, Ch Thun, H Ditschuneit, E F Pfeiffer, F Enzmann
Journal: Diabetes Care (1981)

Biosynthetic human insulin (BHI) obtained from separately synthesized A- and B-chains by recombinant DNA technology with Escherichia coli fermentation was compared with human and pork insulin of high purity in vitro. Applying four biologic tests (glucose oxidation and glucose incorporation into the lipids by rat epididymal fat pads, inhibition of lipolysis, and ATP depletion of isolated fat cells) and three receptor assays (binding competition with human fat cells, IM-9 lymphocytes, and rat liver cell plasma membranes), we could not discern significant differences of the half-maximum response by these seven methods. The only variance occurred with the ATP-depletion assay. This method disclosed 10% greater maximum reversion of isoproterenol-induced ATP depletion by BHI when compared with pork insulin.
Abstract 15: Targeting cancer stem cells and vasculature by a novel anti-delta-like 4 ligand (DLL4) antibody inhibits triple-negative breast cancer tumor growth and delays tumor recurrence
Authors: Wan-Ching Yen, Marcus Fischer, John Lewicki, Austin Gurney, Timothy Hoey
Journal: Cancer Research (2010)

Abstract Triple negative breast cancer (TNBC, ER−, PR− Her2−) accounts for about 10% of all types of breast cancer and is known to particularly aggressive and refractory to current therapies. Chemotherapeutic agents, such as taxanes, are currently the only treatment option for this type of breast cancer, however, these treatments often result in high rates of local and systemic relapse. It has been suggested that cancer stem cells drive tumor growth and progression and are preferentially resistant to many current therapies. Delta-like 4 ligand (DLL4) is an important component of the Notch signaling pathway which is known to mediate stem cell self-renewal and vascular development. We hypothesized that targeting cancer stem cells and the tumor vasculature by interfering with the DLL4/Notch pathway will improve treatment outcome. We developed anti-DLL4 antibodies that recognize either the human or murine protein and have potent binding and antagonist activities. We used these antibodies to investigate the role of DLL4 in triple negative breast cancer and to probe the mechanism in tumor and stromal cells in xenograft models derived from primary breast tumors. These studies showed that anti-DLL4 was efficacious as a single agent and in combination with paclitaxel (Taxol) against TNBC xenograft tumors. Gene expression analysis showed that anti-DLL4 affected vascular-related genes in the stroma and Notch target genes in the tumor and stroma. Inclusion of anti-DLL4 delayed breast tumor recurrence and decreased the growth rate of recurrent tumors following termination of paclitaxel treatment. Flow cytometric analysis showed that ESA+/CD44+/CD24low expressing breast cancer stem cells, BrCSC, were enriched followed by paclitaxel treatment, whereas the combination of anti-DLL4 and paclitaxel reversed paclitaxel-induced increase in this cell population. Further analysis indicated that blocking DLL4 signaling in tumor cells by anti-human DLL4 delayed tumor recurrence and decreased ESA+/CD44+/CD24low expressing BrCSC fraction and tumorigenic potential, whereas blocking DLL4 in host stroma and endothelial cells by anti-mouse DLL4 interfered with angiogenesis. The combination of both antibodies produced an additive effect. Our findings provide a rationale for targeting cancer stem cells and tumor vasculature through inhibition of the DLL4/Notch signaling for TNBC treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 15.
Transverse Arrest of Head
Authors: B. Williams
Journal: BMJ (1953)

makes them feel like several doubles when on antabuse.It is noticeable, however, that they prefer to omit their anta- buse.The more labile psychoneurotic is often profoundly disturbed by the antabuse-alcohol reaction and avoids alcohol.A small group of patients has emerged, however, who, in spite of recurrent terrifying experiences with the reaction, repeatedly ask to be put back on antabuse.Their assertion that they are now certain that this will stop their drinking appears to be a rationalization, for in a short time they proceed to drink again, even carrying antabuse tablets with them in some cases and swallowing more of them whilst drinking.These patients obviously tend to become rapidly confused, restless, and uncoordinated whilst indulging in this procedure.They also seem to show an increased tendency to self-reproach when sober.Can it be that these patients incorporate antabuse into their drinking pattern not only to achieve more rapid escape from insupportable tension but also to inflict simultaneously the punishment demanded by a harsh super-ego which is, of course, part of that tension ?However this may be, these patients show the surprising tendency to seek antabuse as an adjunct to their drinking, and they thus appear to be unsuitable cases for treatment with the drug.-Iam, etc., Twyford.
48 EARLY VERSUS DELAYED TREATMENT OF ACUTE HEPATITIS C: FINAL RESULTS OF THE RANDOMIZED CONTROLLED GERMAN HEP-NET ACUTE HCV-III STUDY
Authors: K. Deterding, N. Grüner, P. Buggisch, J. Wiegand, P. Galle, U. Spengler, H. Hinrichsen, T. Berg, A. Potthoff, N. Malek, H. Diepolder, S. Feyerabend, M. Cornberg, M.C. Jung, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2012)
US paediatricians withdraw guidance on female genital cutting after criticisms
Authors: Z. Kmietowicz
Journal: BMJ (2010)

The American Academy of Pediatrics has retracted its 2010 policy statement on female genital cutting after criticism and confirmed its opposition to all forms of mutilation, however minor.

Last month the UK Royal College of Obstetricians and Gynaecologists and the Royal College of Paediatrics and Child Health voiced concerns about the guidance, which suggested that doctors …
"FRIENDS OF MEDICAL PROGRESS"
Authors: Charles A. Gordon
Journal: JAMA (1924)

To the Editor:  —At a recent meeting of the Medical Society of the County of Kings, Mr. Ernest Harold Baynes of the Friends of Medical Progress told us of the aims of that organization and showed us how it proposes to combat the vicious attacks on scientific medicine that are constantly going on everywhere in this country.  In the legislatures of almost all the states, there is an annual onslaught on medicine. In many states quackery is recognized and pseudoscience is given an opportunity to grow at the expense of the public health. The proponents of chiropractic are busy introducing a standardized bill in the legislature of every state in the Union. Year after year, the same organized effort is made to break down the bulwarks of quarantine, vaccination and scientific investigation.  A few weeks ago, at a legislative hearing in the assembly chamber of the state of New York,
Role of the Teaching Hospital in the Goal of the Community
Authors: Morton C. Creditor
Journal: JAMA (1964)

THE SOLE JUSTIFICATION for the existence of the hospital in the community is to provide an idealized medical care facility for members of that community, while the only justification for the existence of a graduate  program in a hospital is to provide an educational experience for the students enrolled in the program. While many would protest that the co-existence of these premises is incompatible with the objective of each, it is not only possible to reconcile these goals with each other, but to indicate that the ultimate fulfillment of one is dependent upon the existence of the other, giving significance to the term teaching hospital. In fact, what is it we aim to teach if not idealized medical care?  A definition of good or idealized patient care is required, but attempts at definition are frequently hampered by provincial, prejudicial, and limited connotation. Furthermore, definition is difficult since we have
Commercial Hair Analysis: Science or Scam?
Authors: Robert S. Waters
Journal: JAMA (1986)

<h3>To the Editor.—</h3> I am very surprised to have seen the publication of such an unscientific and opinionated article as Stephen Barrett's<sup>1</sup>appear in<i>JAMA</i>. For a scientist to publish only "high," "normal," and "low" values for the results of the measurement of hair minerals, when he, in fact, could have published the actual raw data in numerical form so a legitimate statistical analysis could have been performed is outrageous and borders on dishonesty. I would very much like to receive the numbers he has and subject them to a multivariate analysis to see where the variation really lies. As a physician who routinely uses hair mineral analysis as a screening tool for evaluation of toxic and essential mineral status, I am very aware that many laboratories measuring hair elements are giving spurious results and also that not all the elements are readily measurable, let alone useful, in health
Viral-Mediated Gene Transfer to Mouse Primary Neural Progenitor Cells
Authors: Stephanie M. Hughes, Farid Moussavi-Harami, Sybille L. Sauter, Beverly L. Davidson
Journal: Molecular Therapy (2002)

<h2>Abstract</h2> Neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. The expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. To address this issue, we cultured cells from embryonic day 16–18 mouse brain in serum-free medium containing epidermal growth factor or basic fibroblast growth factor, and investigated how transduction with recombinant viral vectors affected maintenance and differentiation properties of progenitor cells. Neurosphere cultures were incubated with feline immunodeficiency virus (FIV), adeno-associated virus (AAV) or ade-noviral (Ad) constructs expressing either β-galactosidase or enhanced green fluorescent protein at low multiplicity of infection. Nestin-positive neurospheres were regenerated after incubation of single progenitor cells with FIV, indicating that FIV-mediated gene transfer did not inhibit progenitor cell self-renewal. In contrast, adenovirus induced differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes. The AAV serotypes tested did not effectively transduce progenitor cells. FIV-transduced progenitors retained the potential for differentiation into neurons and glia <i>in vitro</i>, and when transplanted into the striatum of normal adult C57BL/6 mice differentiated into glia, or remained undifferentiated. In the presence of tumor cells, FIV-transduced progenitors migrated significantly from the injection site. Our results suggest that FIV-based vectors can transduce progenitor cell populations <i>in vitro</i>, with maintenance of their ability to differentiate into multiple cell types or to respond to injury within the central nervous system. These results hold promise for the use of genetically manipulated stem cells for CNS therapies.
PWE-004 Extracolonic Findings On Ct Colonography
Authors: A Ashcroft, S Jawad, P Mahendran, R Greenhalgh, A Poullis
Journal: Gut (2014)

<h3>Introduction</h3> Colonoscopy is often the first line investigation for detection of lesions within the large bowel and remains the gold standard in investigating for suspected colon cancer. However if endoscopy is either incomplete, determined too hazardous or declined computed tomographic colongraphy is the next investigation of choice.<sup>1</sup> One of the additional and potentially beneficial features of CT is in the detection of extracolonic lesions, with studies suggesting approximately 40% of scans reveal one or more extracolonic abnormality including 14% detecting ‘significant findings’ requiring further investigation.<sup>2</sup> <h3>Methods</h3> We performed a retrospective analysis of all patients undergoing CT imaging of the large bowel, both CT colonography or plain abdominal CT (if CT colonography was not possible) at one south London hospital in a 13 month period between 2012–2013. Any extracolonic findings were determined either significant, where requiring further investigation or treatment, or insignificant by the reviewer. Any subsequent outcome of the significant findings was also sought. <h3>Results</h3> A total of 257 scans were reviewed comprising of 250 (97%) CT colonography and 7 (3%) plain abdominal CTs in 104 (40%) male and 153 (60%) female patients. The average age was 68 years (range 39–91). A total of 163 (63%) of scans detected at least one extracolonic finding, with 55 (21%) of these significant. Sites included 13 liver, 7 lung, 6 pancreatic, 5 renal and 5 adrenal. Further investigation based on these findings revealed 5 (1.9%) malignancies. One patient was found to have a renal cell carcinoma and went on to have curative surgery. One patient was diagnosed with pancreatic cancer and one with hepatocellular carcinoma, both of which were managed palliatively, and one patient was found to have peritoneal recurrence of a previously treated colonic adenocarcinoma. One scan discovered lung and liver metastases along with the causative colonic primary. Other notable findings included a 5.3cm AAA and a pulmonary embolus seen in a segmental lower lobe pulmonary artery. There were a 209 insignificant findings in 139 (54%) of the CTs, with a maximum of 5 in a single scan. <h3>Conclusion</h3> This study helps to highlight the potential additional benefit of CT colonography over endoscopic visualisation of the large bowel. The prevelance of extracolonic findings in this cohort was high, in keeping with previous studies, with CT colonography having value is its detection of extracolonic malignancies, staging and other serious conditions. However there was also a substantial rate of additional investigation for subsequently benign findings. <h3>References</h3> Taylor SA <i>et al</i>. Guidelines for the use of imaging in the NHS Bowel Cancer Screening Programme: Second Edition. 2012 Xiong T <i>et al</i>. <i>Br J Radiol</i> 2005 Jan;78(925):22–9 <h3>Disclosure of Interest</h3> None Declared.
Surcharge for Paper Version of the <i>JRSM</i>
Authors: John Zorab, H M C Corfield
Journal: Journal of the Royal Society of Medicine (2005)

For those who can seldom use the handsome metropolitan facilities of the RSM and have no need for its IT facilities a particular benefit of membership is the JRSM, with its excellent and wide-ranging review of the medical scene. To impose a surcharge on Fellows who prefer (and possibly need) the convenience of the printed page, rather than the online version, is not just damaging to the Society's known reputation for inclusivity but also a disrecommendation to further recruitment. Council should reconsider this misguided attempt to appease the auditors.