tbuckley/cabot-search huggingface dataset:
Abstract LB-256: Optimal clinical dose-finding strategies: Translational preclinical pharmacokineitcs, pharmacodynamics, and efficacy analysis of HM61713, an orally selective EGFR mutant inhibitor
Authors: Jooyun Byun, Taehun Song, Donghyun Kim, Junhyeng Son, Kwang-Ok Lee, Jaeho Lee, Yong Hoon Kim, Young-Mi Lee, Kwee Hyun Suh
Journal: Cancer Research (2015)

Abstract The first-generation of EGFR1 inhibitors (Gefitinib and Erlotinib) has significant clinical benefits in NSCLC caused by activating mutations, but the efficacy of these agents is often limited due to the emergence of drug resistance conferred by a gatekeeper residue, T790M. HM61713 is a third-generation EGFR tyrosine kinase inhibitor that has been evaluated as a novel therapeutic agent for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. HM61713 is an orally active and a novel EGFR mutant selective inhibitor which is potent on resistance mutation (T790M) without affecting EGFR wild type at efficacious dose level. HM61713 showed an anti-cancer activity in several EGFR mutant lung cancer cell lines including T790M mutation harboring cell line. Integrated pharmacokinetic - pharmacodynamic - xenograft tumor model (PK-PD-XTG) was used to characterize the relationship between HM61713 plasma concentration and tumor growth inhibition (TGI) in H1975 (T790M mutation) xenograft model. Simple one-compartment model applied re-absorption compartment with first-order absorption/elimination was used to describe HM61713 plasma concentration-time profiles. Biophase distribution model with baseline inhibition Emax equation was applied to characterize the PD marker (p-EGFR) and tumor volume shrinkage was explained by michaelis-menten kinetics of p-EGFR. Estimated in vivo IC50 value of p-EGFR inhibition (%) based on plasma free concentration in xenograft mice was 1.14 ng/mL. The human PD marker response curve and the tumor growth inhibition plot were obtained by replacing the mice PK to human PK in our developed model based on the hypothesis thattranslation providesa good relationship of surrogate mice tumor PD to human tumor regression corresponding human PK. According to our simulated curves, we predicted appropriate human active dose from 300 to 800 mg/man and it would be an efficacious dose in patients with NSCLC harboring the EGFR activating and also with T790M resistant mutation. Currently, HM61713 is undergoing in clinical trial phase I/II in NSCLC (ClinicalTrials.gov, NCT01588145). Citation Format: Jooyun Byun, Taehun Song, Donghyun Kim, Junhyeng Son, Kwang-Ok Lee, Jaeho Lee, Yong Hoon Kim, Young-Mi Lee, Kwee Hyun Suh. Optimal clinical dose-finding strategies: Translational preclinical pharmacokineitcs, pharmacodynamics, and efficacy analysis of HM61713, an orally selective EGFR mutant inhibitor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-256. doi:10.1158/1538-7445.AM2015-LB-256
AB1065 Prevalence and Risk Factors of Vertebral Fractures in Women with Rheumatoid Arthritis Using Vertebral Fracture Assessment (VFA)
Authors: M. Djennane, H. Djoudi, S. Salah
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The Rheumatoid Arthritis (RA) is the most frequent inflammatory rheumatism. It affects 0.5 to 1% of the world9s population. The osteoporosis and the vertebral fractures are well known complications of the RA. The vertebral fractures are the most common type of linked to fragility fractures. They cause chronic back pain, loss of size, kyphosis, abdominal pain, handicap and death. <h3>Objectives</h3> Main Objective: To assess the prevalence of vertebral fractures in patients with RA VFA. Secondary Objectives: Identify potential factors vertebral fracture. Assessing the vitamin D status. <h3>Methods</h3> We recruited 154 women with RA; none of whom were taking osteoporosis medications. Patients underwent dual X-ray absorptiometry at the hip and spine and VFA, and completed a questionnaire. The vitamin D level was assessed by measuring the level of the total 250HD. VFA was classified using a combination of Genant semi-quantitative approach and morphometry. <h3>Results</h3> The patients had a mean (S.D) disease duration of (9.1) 6.1 years. Vertebral fractures were detected in 27% (41/154) of the subjects. This group of women showed a lower BMI and a lower BMD in the hip area. They also had a longer disease period and higher corticoid consumption. Stepwise regression analysis showed that the presence of VF was independently associated with a low hip T-score, a low 250HD level, a higher disease activity and to a longer average disease period. <h3>Conclusions</h3> The RA is a risk factor in the development of osteoporosis and vertebral fractures. This risk increases with low weight, the length and severity of the disease. These results may suggest a vertebral fractures prevention program. This program would aim to rapidly treat patients by optimizing the vitamin D status of subjects with RA. <h3>References</h3> El Maghraoui A,Asmaa Rezqi,Aziza mounach,Lahsen Achemlal,Ahmed Bezza and Imad Ghozlani. Prevalence and risk factors of vertebral fractures in women with rheumatoid arthritis using vertebral fracture assessment. Rheumatology 2010;49:1303-1310 <h3>Disclosure of Interest</h3> None declared
Localization of the breast sentinel node after axillary node dissection with diversion of lymphatic drainage to internal mammary lymph nodes and the importance of delayed imaging.
Authors: S M Ansari, S I Heiba, C Mills, H M Abdel-Dayem
Journal: Clinical Nuclear Medicine (2001)

ANSARI, SELIM M. M.D.,*†; HEIBA, SHERIF I. M.D.,†; MILLS, CHRISTOPHER M.D.‡; ABDEL-DAYEM, HUSSEIN M. M.D.† Author Information
PTU-253 The development of a bsg/acpgbi minimum dataset proforma for the multidisciplinary assessment and management of large nonpedunculated colorectal polyps
Authors: A Chattree, J Barbour, S Dolwani, MD Rutter
Journal: Gut (2015)

<h3>Introduction</h3> The lack of a structured framework for the assessment and management of large non-pedunculated colorectal polyps (LNPCPs) appears to have resulted in a wide variation in decision making with regards to endoscopic and surgical management and suboptimal outcomes.<sup>1</sup>Multidisciplinary team discussion has been advocated to better coordinate management. The development of an evidence based and expert approved minimum dataset proforma may complement this process and encourage optimal management resulting in improved outcomes. <h3>Method</h3> Following an extensive literature review, various patient and polyp parameters relevant to LNPCP assessment and management were selected. A 14 person BSG/ACPGBI approved multidisciplinary panel participated in Delphi consensus methodology to vote anonymously on the proposed parameters with ≥80% agreement required for consensus to be achieved. The draft proforma was then assessed on a sample of 20 LNPCP cases, resulting in modification after a further voting round. <h3>Results</h3> The final proforma comprised of 17 parameters encompassing all patient and lesion factors considered essential to the decision making process in LNPCP management. Patient parameters included patient symptoms, treatment preferences and comorbidity. Lesion parameters included morphology and surface characteristics (e.g. Paris classifications and Pit pattern) and the specification of any lesion features associated with increased complexity such an increased risk of malignancy, unsuccessful endoscopic resection or adverse endoscopic events.<sup>2</sup>Parameters regarding relevant histology and radiology results and guidance on obtaining adequate lesion imaging were also agreed. <h3>Conclusion</h3> The development and validation of a BSG/ACPGBI minimum dataset proforma allows for structured and comprehensive multidisciplinary discussion in LNPCP management, ensuring that all important factors are discussed and resulting in more coordinated and robust decision-making. This proforma can be used to structure discussions during a multidisciplinary team meeting and all related discussions such as referral to the tertiary setting, in addition to being used as a checklist for comprehensive lesion assessment. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Lee TJ, Rees CJ, Nickerson C, <i>et al</i>. Management of large sessile or flat colonic polyps in the English bowel cancer screening programme. Br J Surg. 2013;100:1633–9 Moss A, Bourke MJ, Williams SJ, <i>et al</i>. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 2011;140:1909–18
Drosophila glucose dehydrogenase and yeast alcohol oxidase are homologous and share N-terminal homology with other flavoenzymes.
Authors: D R Cavener, P A Krasney
Journal: Molecular Biology and Evolution (1991)

The presence of similar nucleotide cofactor-binding domains in otherwise unrelated enzymes has been rationalized on the basis of the exon-shuffling model of protein evolution (Gilbert 1978). In the common case of enzymes which share a similar nucleotide-binding domain but exhibit different specificities for primary substrates, the degree of sequence similarity is restricted to small regions specifically demonstrated to bind to the nucleotide cofactor. This pattern of restricted similarity suggests that dissimilar regions arose from nonhomologous exons. We show herein that the sequence similarity of two unrelated flavoenzymes, Drosophila glucose dehydrogenase ( GLD ) and yeast alcohol/methanol oxidase ( AOX / MOX ) are unexpectedly similar throughout their primary sequence. In addition these enzymes share considerable similarity both with other unrelated flavoenzymes and with the ras protein for a small amino-terminal region encoding their nucleotide-binding sites. The genes encoding GLD (E.C. 1.1.99.10) and AOX/MOX (E.C. 1.1.3.13) recently have been isolated from fruit flies (Cavener et al. 1986~; Krasney et al. 1990) and yeast (Ledeboer et al. 1985; Koutz et al. 1989), respectively. The biochemical properties of Drosophila GLD are very similar to those of Aspergillus oryzue GLD, which catalyzes the oxidation of D-glucose to D-glucono-l Cavener et al. 1986b). AOX/MOX is associated with the ability of four yeast genera to utilize methanol as the sole carbon source (Lee and Komagata 1980). It catalyzes the oxidation/reduction of methanol and oxygen to formaldehyde and hydrogen peroxide, respectively. Thus, GLD and AOX/MOX exhibit remarkably different biochemical and functional properties. A search of both the National Biomedical Research foundation (NBRF) protein data base and the GenBank nucleic acid data base unexpectedly revealed a significant degree of similarity between D. melanogaster GLD and Hansenula polymorpha (yeast) MOX and Pichia pastoris (yeast) AOX 1. The statistical significance was evaluated by comparing the similarity of the primary amino acid sequence of GLD with 200 randomized sequences of AOXl and MOX by using the RDF2 program of W. Pearson (University of Virginia). The randomized sequences were of the same length and amino acid composition as AOXI and MOX. The optimized alignment scores for the comparison of AOX 1 with GLD and for the comparison of MOX with GLD were greater than 30 SD above the mean of the randomized scores and are more than threefold higher than those of the highest random sequence. Percentage similarities
Characterization by Certain Drugs of Four Morphologically Indistinguishable Cell Lines
Authors: Henry C. Orr, Morris Belkin
Journal: JNCI Journal of the National Cancer Institute (1960)

During investigations of cellular damage induced by various chemical agents, characteristic responses to certain of these were elicited in cell strains HeLa, D164, D189, and D227. The last three arose as a transformation of normal fibroblasts from infant's foreskin and are now morphologically indistinguishable. When hydrocortisone or Suramin sodium (naphuride sodium) was added to cultures of each cell line, these lines could be distinguished from each other by their differential responses as follows: Strain D227, after exposure for 1 to 2 days to 1 mg. per ml. Suramin sodium, showed fragmentation and beading of the cell membrane, cytoplasmic granularity, loss of spindle cells, and disruption of the typical reticulum-like pattern of early growth. The other three cell lines, when similarly exposed to Suramin at the same concentration, showed no response to this drug. Strain D189 exhibited marked cytoplasmic vacuolization after exposure to 0.01 mg. per ml. hydrocortisone for 3 days. Strain D164 exhibited moderate cytoplasmic vacuolization after exposure to a tenfold dose of hydrocortisone (0.1 mg. per ml.) for 10 days or more. Strain HeLa exhibited cell enlargement and nuclear aberration when similarly exposed to the same dose of hydrocortisone for 10 days. The typical responses of these morphologically identical cell lines demonstrate their pharmacologic distinctions. They also indicate the freedom from contamination of the D lines, among themselves and by strain HeLa.
Personality disorder in the families of depressed, schizophrenic, and never-ill probands
Authors: W H Coryell, M Zimmerman
Journal: American Journal of Psychiatry (1989)

In a blind family study of 176 probands with nonpsychotic major depression, psychotic major depression, schizophrenia, or no history of DSM-III disorders, only the relatives of depressed probands with mood-incongruent psychotic features had a risk for personality disorders higher than that for the relatives of never-ill probands. The authors did not find a high rate of borderline personality in relatives of depressed probands or of schizotypal personality disorder in relatives of probands with schizophrenia or any psychosis. However, depressed probands with normal dexamethasone test results had a significantly higher familial loading for the DSM-III cluster of histrionic, antisocial, borderline, and narcissistic personality disorders.
Endogenous opioid activity and beta-endorphin immunoreactivity in CSF of psychiatric patients and normal volunteers
Authors: D Naber, D Pickar, R M Post, D P Van Kammen, R N Waters, J C Ballenger, F K Goodwin, W E Bunney
Journal: American Journal of Psychiatry (1981)

The authors measured total opioid activity by radioreceptor assay in the CSF of 41 normal subjects and 89 unmedicated psychiatric patients, including schizophrenic, schizoaffective, depressed, and manic diagnostic groups. Schizophrenic men had significantly lower levels of opioid activity than the normal men, although these levels did not significantly differ from levels of other male patients. The authors observed higher opioid activity during mania than during depression in paired samples for 4 manic-depressive patients. beta-Endorphin immunoreactivity in a subsample of the same subjects was no different in the patient group than in the normal group, suggesting that the differences in CSF opioid activity between schizophrenic men and normal patients may be related to opioids other than beta-endorphin.
DEVELOPMENT OF AORTIC INSUFFICIENCY AFTER HEART MATE II LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION IN 71 PATIENTS
Authors: Ashim Aggarwal, Rashmi Raghuvir, Gregory Macaluso, Rojina pant, Colleen Gallagher, Antone Tatooles, Patroklos Pappas, Geetha Bhat
Journal: Journal of the American College of Cardiology (2012)
ADMINISTRATIVE NOTES
Authors: WERNER TUTEUR
Journal: American Journal of Psychiatry (1957)

Chlorpromazine and reserpine, as a result of their tranquilizing action have a considerable effect on the budget of mental institutions. Repair work, performed by highly paid union labor, decreases considerably. While savings in skilled labor can be demonstrated, this becomes more difficult when clinical improvement, rehabilitation and happiness of human beings is under consideration, the last likewise applying to families and friends. The evaluations tabulated must not, however, be compared with a profit and loss statement. Clinical improvement of any illness is well worth the effort in human and personal investment, and certainly the money involved. It appears that the cost of maintenance of special chlorpromazine-reserpine clinics to prevent once-disturbed patients from relapsing and returning will be low in the long run.
&lt;emph type="ital"&gt;The Gardener&lt;/emph&gt;
Authors: Thomas B. Cole
Journal: JAMA (2011)

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
Dicer-regulated micro RNAs 222 and 339 promote immune-escape of cancer cells through downregulation of ICAM-1
Authors: Ryo Ueda, Gary Kohanbash, Kotaro Sasaki, Mitsugu Fujita, Xinmei Zhu, Michael Lotze, Robert Sobol, Hideho Okada
Journal: Cancer Research (2008)

2468   The RNase III endonuclease Dicer plays a key role in generation of mature, approximately 22-nucleotide-long micro RNAs (miRNAs) in cells. Recent studies suggest that Dicer is required for Type-2 T-cell response, which counteracts anti-tumor immunity. Furthermore, Dicer expression is associated with malignant phenotype of prostate cancers through regulation of miRNAs. These observations led us to hypothesize that expression of Dicer in cancer cells might regulate their susceptibility against immune-surveillance through processing of miRNAs.  Among three human colorectal cancer cell lines (HCT116, DLD-1 and RKO) in which exon 5 of the human  Dicer  gene is disrupted (ex5-/-) (Cummins, J.M et al. 2006), HCT116 (ex5-/-) cells expressed human leukocyte antigen (HLA)-A2 as well as tumor antigens interleukin-13 receptor alpha2 (IL-13Rα2) and EphA2. Compared to wild-type HCT116 cells, HCT116 (ex5-/-) cells were found to be remarkably more susceptible to antigen-specific lysis by cytotoxic T lymphocytes (CTLs) raised against IL-13Rα2 or EphA2. To identify causative molecules that promoted the susceptibility of HCT116 (ex5-/-) cells, we examined expression of a panel of proteins that are known to mediate CTL-tumor cell interactions, including HLA class I, intercellular cell adhesion molecule (ICAM)-1, Fas, CD40, death receptor (DR)5 as well as tumor antigens IL-13Rα2 and EphA2 in the three ex5-/- cell lines and corresponding wild-type cells. Among these, ICAM-1 was up-regulated in all ex5-/- cell lines, while none of the other molecules evaluated were differentially expressed in ex5-/- vs. wild-type cells. Antibody-mediated blockade of the ICAM-1-LFA-1 interaction inhibited the specific lysis of the CTLs against HCT116 (ex5-/-) cells, indicating a pivotal role of this interaction. We next sought to identify specific miRNAs that can modulate ICAM-1 expression. Based on the miRBase algorithm (http://microrna.sanger.ac.uk), miRNAs 222 and 339 were predicted to bind to ICAM-1. Indeed, quantitative RT-PCR analysis showed the decrease of miRNAs 222 and 339 in all three ex5-/- cell lines compared to wild-type lines. Moreover, inhibition of these miRNAs in the parental cells by transfection with anti-miRNA 222 and 339 RNA-based inhibitor constructs up-regulated ICAM-1 expression and susceptibility of these cells against CTLs. Taken together, our results suggest that Dicer is responsible for the generation of miR-222 and miR-339, which suppress ICAM-1 expression on cancer cells, thereby down-regulating the susceptibility of cancer cells to CTL-mediated lysis.
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Authors: Sarah B Goldberg, Scott N Gettinger, Amit Mahajan, Anne C Chiang, Roy S Herbst, Mario Sznol, Apostolos John Tsiouris, Justine Cohen, Alexander Vortmeyer, Lucia Jilaveanu, James Yu, Upendra Hegde, Stephanie Speaker, Matthew Madura, Amanda Ralabate, Angel Rivera, Elin Rowen, Heather Gerrish, Xiaopan Yao, Veronica Chiang, Harriet M Kluger
Journal: The Lancet Oncology (2016)
Endoscopic Ultrasound for the Staging of Non-Small-Cell Lung Cancer
Authors: M B Wallace, A Fritscher-Ravens, T J Savides
Journal: Endoscopy (2003)

The purposes of cancer staging are to determine the optimal therapy and prognosis of a disease, and to allow uniformity in conducting clinical trials for different stages of disease. In the case of non-small-cell lung cancer (NSCLC), the most important determinants of optimal treatment and prognosis are the presence of cancer spread to the lymph nodes within the mediastinum, and to distant organs. Endoscopic ultrasound (EUS) has become a valuable tool for detection of mediastinal lymph nodes, and in some cases, distant organ metastases, because of its ready access to these sites through a transesophageal or transgastric approach. The ability to perform EUS-guided fine-needle aspiration (FNA) has greatly improved the accuracy and acceptance of EUS for lung cancer staging.
The time course of information-processing deficits in schizophrenia
Authors: D L Braff, D P Saccuzzo
Journal: American Journal of Psychiatry (1985)

A visual backward masking task was used to specify the time course of the information-processing dysfunction in 19 schizophrenic patients and 15 matched control patients using novel interstimulus intervals. The authors found that the information-processing deficit in schizophrenic subjects occurred at interstimulus intervals of greater than 60 msec and less than 500 msec. These data are compared with the results of evoked-potential and other psychophysiological studies. The visual-processing impairment is specific and time-linked rather than a reflection of the effects of gross psychopathology or medication in schizophrenic individuals.
Attitudes of psychiatric residents toward payment of psychotherapy fees
Authors: B S Meyers
Journal: American Journal of Psychiatry (1976)

A preliminary exploration of psychiatric residents' thinking on the subject of psychotherapy fees revealed a pattern of inconsistencies in attitudes and a divergence between attitudes and practice. The author discusses these findings in the light of theoretical considerations and the effect of such attitudes on clinic administration and patient treatment. He emphasizes education about and discussion of fees as important aspects of residency training.
Breast cancer associated with palmar fasciitis and arthritis.
Authors: S B Saxman, D Seitz
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.12.3515 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9396405 Breast cancer associated with palmar fasciitis and arthritis. S B SaxmanxS B SaxmanSearch for articles by this author , D SeitzxD SeitzSearch for articles by this author Show More Indiana University School of Medicine, Indianapolis, USA. https://doi.org/10.1200/JCO.1997.15.12.3515 PDF "Breast cancer associated with palmar fasciitis and arthritis.." Journal of Clinical Oncology, 15(12), pp. 3515–3516© 1997 by American Society of Clinical Oncology