tbuckley/cabot-search huggingface dataset:
Abstract 419: Single cell-driven secreted proteins as a surrogate biomarker for Cetuximab therapy in colorectal cancer
Authors: Ye-Lim Park, Hwang-Phill Kim, Jun Kyu Kang, Yoo Joo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim
Journal: Cancer Research (2019)

Abstract Epidermal growth factor receptor (EGFR) blockade is efficacious in KRAS wild-type of colorectal cancer, but acquired resistance is inevitably generated. Here, we established the 5 acquired resistant single cell models (CR cell lines) to cetuximab and investigated the mechanism of acquired resistance using single cell-based whole-exome sequencing and transcriptional profiling. Of these, 4 cell lines have KRAS Q61L mutation and the other has BRAF V600E mutation. From gene enrichment analysis (GSEA), we found that epithelial to mesenchymal transition (EMT) occurs and CXCL chemokine family, which are known as secreted proteins, are overexpressed in the CR cell lines compared with parental cells. Interestingly, we found that CXCL chemokines were strongly secreted/expressed in KRAS/BRAF mutant cell lines and plasma/serum samples from colorectal cancer patients who acquired KRAS/BRAF mutation during cetuximab therapy. CXCL chemokines are regulated coordinately by Slug and NF-B transcription factors and trans-activate EGFR through CXCR2/MMP1/sHB-EGF axis. This process activates MAPK pathway via autocrine. To overcome the resistance to cetuximab, combination treatment of cetuximab and MEK/BRAF inhibitor had a larger antitumor effect compared to the single agents, decreasing the expression of MAPK pathway and secretion of CXCL chemokines. This finding highlights that CXCL chemokines, as a secreted proteins circulating in the bloodstream, show correlation with KRAS/BRAF mutation and could be clinical biomarkers for predicting resistance to anti-EGFR therapy in CRC. Citation Format: Ye-Lim Park, Hwang-Phill Kim, Jun Kyu Kang, Yoo Joo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim. Single cell-driven secreted proteins as a surrogate biomarker for Cetuximab therapy in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 419.
Terminology-Reply
Authors: Stephan E. Ritzmann
Journal: JAMA (1977)

These comments are, indeed, refreshing, since they are intended to draw attention to the need for improved focusing of certain definitions. Unfortunately, burgeoning subjects of complex areas of medical research, such as HLA and disease associations, are becoming replete with terms that are applied increasingly, but not necessarily, commensurate with the appropriate, strict logic. Critical surveillance and constructive criticism by readers and writers alike perhaps will lead to the necessary adjustments.
The treatment of malignant hypertension and hypertensive emergencies. A statement by the AMA committee on hypertension
Journal: JAMA (1974)

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
ANATOMY AND PHYSIOLOGY.
Journal: JAMA (1885)

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
Kokopelli of Indian Paleology
Authors: Klaus F. Wellmann
Journal: JAMA (1970)

The hot and arid southwestern portion of the United States harbors an imposing array of prehistoric Indian rock paintings and carvings some of which date back thousands of years.<sup>2</sup>The intentional or incidental confrontation with these charming witnesses of bygone cultures evokes one of the most delightful experiences for anyone who travels through this region with a receptive mind. Perhaps the most intriguing of all the petroglyphs and pictographs of the Southwest is a distinguished little anthropomorphic figure known among a small circle of cognoscenti under the euphonious name of "Kokopelli" (a word said to stem from the Zuñi and Hopi dialects<sup>3</sup>; other spellings include Kokopeli, Kokopele, Kokopölö and Kokopeltiyo). Kokopelli (Fig 1 through 5) appears on countless rocks<sup>4-7</sup>(Fig 1 and 3), in rock shelters,<sup>8</sup>ceremonial caves<sup>3</sup>(Fig 4) and kivas, and on the walls of some Pueblo ruins and can be found in
Medicine and War: Recognizing Common Vulnerability of Friend and Foe
Authors: Andrew Skolnick
Journal: JAMA (1991)

THE RELATION between war and medicine is an old one. Hippocrates urged that "he who would become a surgeon should join an army and follow it." While military campaigns have served as schools of medicine for physicians through the ages, medicine in return has done much to restrain war's cruelty and mitigate its ravages. The ethics of the healers, who lent their services to armies, helped to temper the brutality of war. According to E. A. Vastyan (<i>The Encylcopedia of Bioethics</i>. New York, NY: Free Press; 1978:1695-1698), "'When wounded, enemies become brothers,' has been an axiom of the most elementary international law in all epochs. A similar recognition—that all humanity's most basic bond is a bond of common vulnerability—lies at the root of the esteem accorded the physician, the privileges granted him, and the obligations he assumes." Many ancient documents recognize the need for ethical treatment of fallen enemies. For
Let your fingers do walking to get radiologist's report
Authors: B. Merz
Journal: JAMA (1982)

The phrase "Physician phone RTAS" may one day be as familiar to hospital personnel as "ET phone home" has recently become to moviegoers. RTAS is the acronym for Rapid Telephone Access System, a computerized information system that has markedly reduced the time lag between the radiologists' assessments of patient roentgenograms and attending physicians' receipt of that information. The system promises to increase efficiency in other medical departments as well. Manufactured by Sudbury Systems, Inc, Sudbury, Mass, the system is simple in design, consisting of a computer terminal with CRT (cathode ray tube) screen and a touchtone telephone equipped with four additional buttons on the receiver. It is also easy to use. Patients' assigned codes are entered when they are x-rayed. The radiologist reads the films, accesses the system via the receiver buttons, punches the identifying code on the touch-tone buttons, and dictates the report. The report becomes immediately available to
Expressions of p53 and PCNA do not correlate with the international index or early response to chemotherapy in non‐Hodgkin's Lymphoma
Authors: Akira Sakai, Kenji Oda, Hideki Asaoku, Sadanori Shintaku, Shuji Hoshino, Hajime Okita, Akiro Kimura
Journal: American Journal of Hematology (1998)

The expression of p53 and PCNA on deparaffinized sections of tumor was assessed in relation to the International Index and response to chemotherapy. Thirty-five non-Hodgkin's lymphoma (NHL) patients were divided into three groups: aggressive NHL, mantle cell lymphoma (MCL), and low-grade NHL. None of the expressions correlated with the International Index or early response to chemotherapy in any group. In low-grade NHL, none of the patients expressed p53. Only one of three patients with overexpression of p53 showed conformational change and alteration of sequence in exon 7 by PCR-SSCP and DNA sequencing. The results showed that p53 and PCNA staining were not useful for predicting early response to chemotherapy, and that their expressions had no correlation with the International Index. Am. J. Hematol. 58:42–48, 1998. © 1998 Wiley-Liss, Inc.
Abstract 4137: Circulating TGFâ and TNFá in metastatic breast cancer patients treated with eribulin. The TRANSERI project
Authors: Ornella Garrone, Cristiana Lo Nigro, Andrea Michelotti, Fillippo Montemurro, Anna Maria Vandone, Andrea Abbona, Matteo Paccagnella, Antonella Falletta, Elena Genua, Claudia De Angelis, Federica Tonissi, Paola Vanella
Journal: Cancer Research (2019)

Abstract Background: Eribulin (E) is approved for the treatment of metastatic breast cancer (mBC) patients (pts) after failure of antracyclines and taxanes. E interferes with microtubule leading to apoptosis and G2/M cell cycle arrest. In human cancer cell lines and in mice, it reverses epithelial mesenchimal transition (EMT) and reduces metastases in mice. TGFβ, an immunosuppressive cytokine, acts as growth factor for cancer-associated fibroblasts (CAFs) and promotes EMT. TNFα synergizes with TGFβ to promote EMT. The TRANSERI study investigates the modifications of TGFβ and TNFα levels in 40 mBC pts treated with E. Methods: Plasma levels of TGFβ and TNFα were determined by ELISA assay at baseline, before cycle (C) 3, 5 and at disease progression in mBC pts treated with E at 1.23 mg/m2, d 1-8 every 21 d. Statistical analysis of the changes in the longitudinal samples was performed by GraphPad 5. Clinical outcome was monitored according to standard internal follow up procedure. Results: We report analyses in pts who completed 5 C or progressed before C 5. So far, we have evaluated TGFβ level in 34 pts and TNFα in 26 pts. The median (M) basal TGFβ value was higher in pts than in 9 healthy volunteers (201.9 pg/ml vs 115.1 respectively). At C 5, 14 pts had a decrease in TGFβ with a M value approaching the one of healthy controls (161.9 pg/ml vs 115.1 pg/ml respectively). 19 pts progressed before C 5. Overall 26/33 pts experienced progression. The M value of TGFβ in pts at progression was 293.4 pg/ml. A significant difference of TGFβ was observed between non progressed vs progressed pts (p=0.021). The M TNFα value at baseline was higher in pts than in healthy volunteers, even if in both groups it was close to the lower sensitivity cut-off of the assay. Altogether 20/26 pts experienced progression, that occurred before C 5 in 14 out of them.Intriguingly, at C 5, the TNFα / TGFβ ratio was significantly lower in pts who did not progressed compared to the value at progression (p=0.048). Conclusions: TGFβ levels changed during treatment with E and correlate with outcome. We are evaluating the role of tumor burden in modulating the TNFα / TGFβ ratio. Definitive data will be presented. Citation Format: Ornella Garrone, Cristiana Lo Nigro, Andrea Michelotti, Fillippo Montemurro, Anna Maria Vandone, Andrea Abbona, Matteo Paccagnella, Antonella Falletta, Elena Genua, Claudia De Angelis, Federica Tonissi, Paola Vanella. Circulating TGFâ and TNFá in metastatic breast cancer patients treated with eribulin. The TRANSERI project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4137.
Transcriptional regulation of FGF-2 gene expression in cardiac myocytes
Authors: S JIMENEZ
Journal: Cardiovascular Research (2004)

Objective: Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium.One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix.Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection.Methods and results: To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with f 1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, À1058FGF -2p.luc and À110FGF -2p.luc, and treated with or without FGF-2.FGF-2 promoter activity was significantly increased f 2.5-fold with both genes.The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors.Overexpression of Egr-1 and Sp1 increased À1058FGF -2p.luc expression by 4.4-and 8.7-fold, respectively.Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of À110FGF -2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity.Transgenic mice expressing À1058FGF -2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release.FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected.In contrast, no effect of IsP was seen on À1058FGF -2p.luc or À110FGF -2p.luc in transfected NRCMs.Conclusions: FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level.The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region.This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.
THE SUBOXIDATION SYNDROME IN CHILDHOOD
Journal: JAMA (1920)

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
Population-based medicine merges clinical care, epidemiologic techniques
Authors: R. Voelker
Journal: JAMA (1994)

IN A BURGEONING era of accountability through outcomes, the provision of preventive and primary care services is taking on an epidemiologic twist. Rather than focusing only on individual patients' ills, experts are urging physicians to consider<i>the population</i>as their patient and begin documenting its incidence and prevalence of disease. Without such a shift, specialists in preventive medicine and public health say clinicians won't be able to provide the most effective care. And in the equally burgeoning era of managed care and capitation, the shift toward population-based medicine can spell financial success. "It doesn't do any good if your only [health status] measure is that all the kids are immunized, but you haven't reduced infectious diseases in your community," says Jonathan Weisbuch, MD, MPH, medical director of the Los Angeles County (Calif) Department of Health Services. "This is not part of the black bag of medicine," Weisbuch told participants at
Contents
Authors: Martin Mainster, Patricia Turner, Jose Artigas, Adelina Felipe, Amparo Navea, Cristina Artigas, Maria Garcı ´a-Domene, Emilio Perea-Milla, Silvia Vidal, Eduardo Briones, Urko Aguirre, Marisa Bare, Nerea Ferna ´ndez De Larrea, Jose ´marı ´a Beguiristain, Jose ´marı ´a Quintana, Caiyun You, Xiaoming Wu, Yingying Zhang, Yunhai Dai, Yusen Huang, Lixin Xie, Andre ´s, J Ferreri, Silvia Govi, Annalisa Colucci, Roberto Crocchiolo, Giulio Modorati, Pravin Vaddavalli, Prashant Garg, Savitri Sharma, Virender Sangwan, Gullapalli Rao, Ravi Thomas, Mark Terry, Neda Shamie, Michael Straiko, Daniel Friend, David Davis-Boozer, Yifei Huang, Jifeng Yu, Li Liu, Gaiping Du
Journal: Ophthalmology (2011)
Marginal zone lymphoma
Authors: Eva Kimby
Journal: HemaSphere (2018)

Karolinska Institute, Stockholm, Sweden This is an open access Abstract Book distributed under the Attribution-NonCommercial-NoDerivs (CCBY-NC-ND), which allows third parties to download the abstracts and share them with others as long as they credit the author and the abstract book, but they cannot change the content in any way or use them commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
LONG-TERM PROGNOSTIC SIGNIFICANCE OF ADMISSION TRICUSPID REGURGITANT PRESSURE GRADIENT IN HOSPITALIZED HEART FAILURE PATIENTS WITH PRESERVED EJECTION FRACTION: A REPORT FROM JAPANESE REAL-WORLD MULTICENTER REGISTRY
Authors: Kazunori Omote, Toshiyuki Nagai, Kiwamu Kamiya, Tadao Aikawa, Yoshiya Kato, Hirokazu Komoriyama, Hiroyuki Iwano, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
Journal: Journal of the American College of Cardiology (2019)
Environmental Occurrence, Abundance, and Potential Toxicity of Polychlorinated Biphenyl Congeners: Considerations for a Congener-Specific Analysis
Authors: Victor A. McFarland, Joan U. Clarke
Journal: Environmental Health Perspectives (1989)

Polychlorinated biphenyls (PCBs) as environmental contaminants often cannot be adequately described by reference to Aroclors or to total PCBs. Although there are 209 possible PCB configurations (congeners), perhaps half that number account for nearly all of the environmental contamination attributable to PCBs. Still fewer congeners are both prevalent and either demonstrably or potentially toxic. If potential toxicity, environmental prevalence, and relative abundance in animal tissues are used as criteria, the number of environmentally threatening PCB congeners reduces to about thirty-six. Twenty-five of these account for 50 to 75% of total PCBs in tissue samples of fish, invertebrates, birds, and mammals. A few PCB congeners that are sterically similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) are directly toxic. Other PCB congeners, as well as those that are directly toxic, may also be involved in toxicity indirectly by stimulating the production of (inducing) bioactivating enzyme systems. The most consequential of these have the ability to induce aryl hydrocarbon metabolizing mixed-function oxidases (MFOs). A result can be an increased capacity for bioactivation of otherwise nontoxic foreign compounds such as certain polynuclear aromatic hydrocarbons (PAH) to cytotoxic or genotoxic metabolites. The effectiveness of specific PCB congeners as inducers of different types of cytochrome P-450-dependent MFO systems is determined by their stereochemistry. Although MFO induction is not a proximate cause, it is a strong correlate of certain kinds of toxicities. Structural patterns can thus be used to discriminate among PCB congeners on the basis of toxic potential, if not entirely on toxicity per se. Congeners that demonstrate 3-methylcholanthrene-type (3-MC-type) and mixed-type MFO induction have the greatest toxic potential. These congeners most closely resemble 2,3,7,8-TCDD in their structures and in their toxic effects. The larger group of phenobarbital-type (PB-type) inducers have considerably less potential for contributing to toxic effects. Weak inducers and noninducing congeners have the least potential for toxicity. Using the rationale described in this paper, we assigned the most evironmentally threatening PCB congeners to four groups. Congeners assigned to Group 1 are considered most likely to contribute to adverse biological effects attributable to PCBs in an environmental sample. Group 1A contains the three most potent (pure 3-MC-type inducer) congeners, IUPAC numbers 77, 126, and 169. Six congeners, numbers 105, 118, 128, 138, 156, and 170, are assigned to Group 1B. These congeners are mixed-type inducers that have been reported frequently in environmental samples.(ABSTRACT TRUNCATED AT 400 WORDS)
Portacaval anastomosis induces region-selective alterations of the endogenous opioid system in the rat brain
Authors: J DEWAELE, R AUDET, D LEONG, R BUTTERWORTH
Journal: Hepatology (1996)

Portacaval anastomosis (PCA) in the rat results in a broad spectrum of neurological and neurobehavioral changes, including alterations of circadian rhythms, impaired locomotor activity, and reflexes, as well as decreased threshold to noxious stimuli. In addition, following portacaval shunting, rats drink significantly more ethanol in a free- choice drinking paradigm. Available evidence suggests that many of these behavioral changes may be modulated by the endogenous opioid system of the brain. To evaluate this possibility, the effects of PCA on circulating beta-endorphin (beta-EP), as well as beta-EP content in the pituitary and specific brain nuclei, was evaluated using a sensitive radioimmunoassay. Furthermore, the characteristics and regional densities of mu and delta opioid receptors in the brains of PCA and sham-operated control rats were studied using an in vitro technique, as well as quantitative receptor autoradiography and the specific ligands 125I [D-Ala2, MePhe4, Met(o)ol5]enkephalin (FK 33-824) and 125I [2-D-penicillamine, 5-D-penicillamine]-enkephalin (DPDPE) for micro and delta sites, respectively. PCA resulted in region-selective modifications of beta-EP in brain, but not in pituitary or blood. Autoradiographic studies revealed a generalized decrease in mu binding sites (up to 70% decreases compared with sham-operated controls) and region-selective alterations of delta receptor densities following PCA. Portacaval-shunted rats drank significantly more ethanol in a free- choice drinking paradigm, an effect that was significantly attenuated by the administration of the opiate antagonist naloxone. Increased ethanol preference thus appeared to result from modifications of the endogenous opioid system in nucleus accumbens of rats following PCA. (Hepatology 1996 Oct;24(4):895-901)