tbuckley/cabot-search huggingface dataset:
Abstract 78: IGF-1R inhibition activates p70S6K1 to promote survival via MEK1/2 activation in colon cancer cells
Authors: Qing Wang, Hsin-Sheng Yang
Journal: Cancer Research (2019)

Abstract The insulin-like growth factor 1 receptor (IGF-1R) is a heterotetramer with tyrosine kinase activity, composed of two α subunits containing the ligand-binding site and two β subunits harboring the tyrosine kinase activity. Upon binding with ligands (IGF-1, IGF-2, and insulin), IGF-1R leads to activation of downstream pathways including PI3-K/AKT and Ras/MAPK, two frequently activated pathways for promoting cell survival and proliferation in various cancers including colorectal cancer. Immunohistochemical studies revealed that IGF-1R is over-expressed in colorectal cancer tissues compared to the adjacent normal tissues. Most importantly, a higher expression of IGF-1R is associated with a higher grade and stage in colorectal cancer patients. Since the IGF-1R signaling pathway plays an essential role in development, maintenance, and survival of tumors, many small molecule compounds and antibodies targeting IGF-1R have been developed. Unfortunately, these anti-IGF-1R agents demonstrate very limited efficacy in clinical trials, suggesting the existence of a mechanism to overcome the inhibitory effect of IGF-1R in cancer cells. In this study, we aim to understand the resistance mechanism of IGF-1R inhibition in colon cancer cells. Prolonged treatment of IGF-1R resistant colon cancer cells with IGF-1R inhibitors (OSI-906, BMS-754807, and GSK1838705A) stimulates p70S6K1 activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation is independent of mutation of K-RAS and PIK3CA, frequently occurring in colorectal cancer. Genetic knockdown or pharmacologic inhibition of p70S6K1 efficiently suppresses cell viability in response to IGF-1R inhibition, indicating that p70S6K1 activation contributes to the survival of IGF-1R inhibitor-treated cells. In addition to the increased phosphorylation of p70S6K1, phosphorylation of MEK1/2 is also elevated in colon cancer cells with prolonged inhibition of IGF-1R. Knockdown of MEK1/2 results in reduction of p70S6K1 activation in response to IGF-1R inhibition and subsequently increases apoptosis, suggesting that MEK1/2 is involved in p70S6K1 activation for survival. Furthermore, the combination of BMS754807 and U0126, a MEK1/2 inhibitor, effectively decreases the cell viability and increases apoptosis. Our data suggest that inhibition of MEK1/2 enhances the anti-proliferation effects of IGF-1R inhibitors, pointing out a new direction for overcoming the resistance of IGF-1R inhibition in colorectal cancer. Citation Format: Qing Wang, Hsin-Sheng Yang. IGF-1R inhibition activates p70S6K1 to promote survival via MEK1/2 activation in colon cancer cells [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 78.
Military physicians lend healing hands to Haiti
Authors: A. A. Skolnick
Journal: JAMA (1995)

THE MISSION of US Army medical personnel in Haiti is to protect the health and readiness of United States and other United Nations (UN) armed forces who have occupied this country to restore the democratic government. Although the mandate of the UN mission does not include rehabilitating the country's devastated infrastructure, it has been impossible for US medical operations to ignore the medical needs of Haitians, the likes of which few American physicians have ever seen. In his 1963 novel<i>Cat's Cradle</i>, Kurt Vonnegut describes "scenes of hideous want" on "San Lorenzo," his imaginary depiction of an island very like Haiti. One such scene involved a pile of bodies outside the island's famous charity hospital, "House of Hope and Mercy," which grew so wide and deep that a bulldozer stalled trying to shove them into a mass grave. That was fiction. This is fact: At the University Hospital in Port-au-Prince,
Cardiac Diagnosis—A Physiologic Approach.
Journal: Annals of Internal Medicine (1956)

false fabrication, oi tnat tallacy called by Whitehead "the fallacy of misplaced concreteness."Another fallacy is in- volved, "the belief that it is not too difficult to know the truth."Another precept which has always guided the best physi- cians, "So far as possible do no harm.""You can do harm by the process that is quaintly called telling the truth.You can do harm by lying.""The doctor is never privileged to lie to the patient, but he is privileged to tell the patient part of the truth."Even though this series of essays and opinions does not give a final answer to the question, it does give much help in telling how much or how little of the truth should be told.The most valuable parts of the book are those written by nurses, religious leaders and psychiatrists.They seem to point the way toward a more cooperative effort on the part of all concerned.
Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).
Authors: Edward Samuel James, Xiaopan Yao, Xiangyu Cong, Stacey Stein, Kristin Kaley, Carol Hahn, Charles Cha, Ronald R Salem, Howard S. Hochster, Jill Lacy
Journal: Journal of Clinical Oncology (2014)

256 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, we are conducting a prospective phase II open label study to evaluate the efficacy &amp; tolerability of mFOLFIRINOX in pts with advanced pancreatic cancer (PC). Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX with 25% dose reductions of irinotecan &amp; bolus 5-FU given every two wks until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. FDG-PET scans were obtained at baseline &amp; after 2 cycles. CAT scans were obtained after every 4 cycles. Toxicities &amp; response rate (RR) were compared to historical data reported by Conroy. Results: 53 pts with ECOG PS ≤1 have been enrolled to date between 11/11 and 08/13, Pt characteristics: LAPC 22; MPC 31; median age 62 yrs (range 46-86); male 30. Median # of cycles was 8 (range 1-21). Grade 3/4 toxicities were: anemia, febrile neutropenia (FN) &amp; peripheral sensory neuropathy (PSN) – 3.8% each; ALT increased &amp; thromboembolism – 5.7% each; diarrhea 7.5%; fatigue 11.3%; neutropenia 17%; thrombopenia 11.3% &amp; vomiting 1.9%. Anemia ( p&lt; 0.04), FN (p&lt;0.04), PSN (p&lt;0.04) and vomiting (p&lt;0.02) were significantly decreased compared to historical data (Conroy). Response by RECIST (CR+PR) in 26 evaluable pts with MPC was 29% (0 CR, 9 PR, 14 SD, 3 PD) &amp; similar to historical data (31.6%; p 0.85). 6/13 evaluable pts with LAPC underwent resection (46%).13/36 pts evaluable for PET response had a &gt;50% decrease in SUV(max)(36%). Evaluation for OS &amp; PFS is ongoing. Conclusions: Findings from our interim analysis suggests that mFOLFIRINOX, given along with prophylactic pegfilgrastim is associated with a similar RR and improved tolerability compared to full dose FOLFIRINOX in advanced PC. In pts with LAPC, neoadjuvant FOLFIRINOX appears to have substantial activity with 46% of evaluable pts undergoing resection. Accrual will continue to reach a goal of 70 pts. Clinical trial information: NCT01523457.
Abstract 3535: Identification of multiple hepatocellular carcinoma using genomic approach
Authors: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Tadatoshi Takayama, Hiroyuki Aburatani
Journal: Cancer Research (2019)

Abstract Multiple hepatocellular carcinoma (HCC) is categorized into two types; multicentric hepatocarcinogenesis (MC) and intrahepatic metastasis (IM). Although clinical discrimination of the types of multiple HCC has been proposed, it is quite difficult to determine it correctly even after histological diagnosis. In order to diagnose multiple HCC as MC or IM, we compared pairs of multiple HCC samples from 60 patients with multiple HCC and 2 patients with pairs of primary HCC and extrahepatic metastasis such as adrenal grand and lung metastasis with regard to molecular aberrations. Exome or capture sequences showed that more than 70% of somatic mutations were common in the pairs of IM, which were consistent with the result of a pair of primary HCC and extrahepatic metastasis, while no common somatic mutations was detected in genomic MC pairs. Notably, more than 60% of patients who were clinically diagnosed metachronous MC were genetically IM due to the concordance of mutation and shows significantly frequent tumor thrombus, suggesting that genomic IM pairs developed from the common ancestor. Epigenetically, methylation profiles were similar in a pair of IM, while those of MC were different each other. Consequently the accuracy of clinical diagnosis of multiple HCC was only 53.3%. In addition, cell-free DNA was analyzed using exome sequence in five patients with recurrent HCC, and found that somatic mutations of cell free DNA were similar to the primary HCC only in genomic IM but not in genomic MC cases. Intriguingly, overall survivals of patients with clinical IM was significantly shorter than those with clinical MC, while overall survivals of patients with genomic IM and genomic MC were almost similar. Taken together, comparison of mutations in a pair of HCCs makes it possible to classify multiple HCC into MC and IM, which is difficult to be correctly determined in clinical practice. In addition our data showed that it is not clinically important to determine the types of multiple HCC. Furthermore liquid biopsy for mutation analysis is available to make treatment plans for multiple HCC patients. Citation Format: Yutaka Midorikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Tadatoshi Takayama, Hiroyuki Aburatani. Identification of multiple hepatocellular carcinoma using genomic approach [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 3535.
Accelerated oral cholecystography using ipodate supplementation
Authors: T. Klepetar
Journal: JAMA (1970)

We advocate the use of ipodate (Oragrafin) calcium in routine oral cholecystography. If the gallbladder fails to be visualized adequately following administration of 3 gm of iopanoic acid (Telepaque), ipodate should be administered without delay and the study repeated in five hours. This method of supplemental ipodate resulted in same-day diagnostic concentration of contrast material in 30 (41%) patients. Persistent nonvisualization following ipodate supplementation is probably equivalent to non-visualization after a two-day iopanoic acid study.
Ophthalmology's new tools may have profound impact on refractive surgery
Authors: T. F. Kirn
Journal: JAMA (1987)

A NEW SURGICAL PROCEDURE, a growth factor, and a new laser could be a boon to ophthalmology, if their research promise holds out. Many ophthalmologists are optimistic. They hope that adding these tools to their physician's bag will improve the ophthalmic surgeon's ability to change the shape of the cornea and reduce or eliminate refractive errors. Most say that, although all three are still in the highly experimental stage, they are excited by the potential. And, they say, they think if any (or all) of the three live up to that avowed potential, it could dramatically improve refractive corneal surgery, a field that George O. Waring III, MD, chief of refractive surgery at Emory University School of Medicine, Atlanta, and director of the Prospective Evaluation of Radial Keratotomy (PERK) study, describes as "constantly in a state of flux, that is, change and development." Perhaps the most exciting and the most
Lessons from the Enemy. How Germany Cares for Her War Disabled.
Journal: JAMA (1918)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
New inactivated polio vaccine expected soon
Authors: C. Marwick
Journal: JAMA (1990)

A NEW (to the United States at any rate) inactivated poliomyelitis vaccine is likely to become available before the end of the year. If the new inactivated vaccine is licensed, it will become the primary agent for use in those patients in whom live-virus oral polio vaccine is contraindicated or who prefer to be immunized with the inactivated vaccine, replacing the currently licensed, enhanced inactivated polio vaccine made by Connaught Laboratories Inc, Swiftwater, Pa. The two vaccines are similar in safety, immunogenicity, and efficacy. Their great advantage is that there is no incidence of vaccine-associated paralysis as occurs in rare instances with the oral live-virus vaccine. <h3>Cultivated on Different Cells</h3> Indeed, the only real difference between the two vaccines is the cells on which the vaccine virus is cultivated. The currently licensed product is grown on human diploid cells; the new agent is grown on VERO cells, a monkey kidney
RESUSCITATION FROM CARBON MONOXIDE POISONING
Journal: JAMA (1926)

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
Gastrointestinal Endocrinology
Authors: Z. Myron Falchuk
Journal: JAMA (1987)

The editors of this book intended to write summaries of the major issues with regard to current knowledge in gastrointestinal endocrinology and to integrate this material into a proposal for a program project to be funded by the National Institutes of Health. The course of this work produced such extensive material that the leaders of the research effort, most of whom are in the Department of Surgery at the Galveston Branch of the University of Texas, decided to formulate a book, the results of which are the present effort. In fact, what we have is a compendium of much of the research efforts to have come from the surgical laboratories of the authors. In this regard, many of the chapters have authoritative detail. Others, such as the chapters in the "Methods" section, are essentially manuals regarding procedures carried out in the laboratories of these investigators. Most of the chapters are
A new antidepressant: desipramine hydrochloride (Norpramin, Pertofrane)
Journal: JAMA (1965)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
An evaluation of iridology
Authors: A. Simon
Journal: JAMA (1979)

Iridology is an analysis of health based on examination of the iris of the eye. One hundred forty-three patients had photographs taken of both eyes. Ninety-five patients were free of kidney disease, defined as a creatinine level of less than 1.2 mg/dL (mean, 0.8 mg/dL), and 48 had kidney disease severe enough to raise the plasma creatinine level to 1.5 mg/dL or greater (mean, 6.5 mg/dL). Three ophthalmologists and three iridologists viewed the slides in a randomized sequence without knowledge of the number of patients in the two categories or any information about patient history. Iridology had no clinical or statistically significant ability to detect the presence of kidney disease. Iridology was neither selective nor specific, and the likelihood of correct detection was statistically no better than chance. (<i>JAMA</i>242:1385-1389, 1979)
Acquired immunodeficiency syndrome and the nervous system
Journal: JAMA (1990)

<h3>To the Editor.—</h3> As reported by Dalakas and colleagues,<sup>1</sup>human immunodeficiency virus (HIV) is not only lymphotropic but also neurotropic and can invade the central and peripheral nervous systems early, resulting in a latent or overt infection. The neurotropism of HIV should not be entirely surprising if this retrovirus is to be considered a human representative of the lentivirus subfamily. The primary neuropathy, which seems to be a direct result of HIV infection of the central nervous system (CNS), has important pathological and clinical implications. In adults, neurological symptoms may sometimes be the sole manifestations of acquired immunodeficiency syndrome.<sup>2</sup>In pediatric patients, the CNS is often the primary site of HIV infection rather than the immune system, and the neuropathy may progress even with minimal immunologic abnormalities,<sup>3</sup>indicating that neural tissue is a principal target of the retrovirus. In infants and children we have observed intellectual
Medical ethics
Authors: R. M. Veatch
Journal: JAMA (1978)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Association of Carcinoma Yield with Early Papilloma Development in SENCAR Mice
Authors: Richard J. Bull, Merrel Robinson, R. Dana Laurie
Journal: Environmental Health Perspectives (1986)

The responsiveness of SENCAR mouse skin to 20 different chemicals with known carcinogenic properties was assessed in initiation/promotion experiments. The purpose of these experiments was to evaluate the extent of false negative responses in mouse skin initiation/promotion protocols and to determine the extent to which early papilloma development can be used to predict the eventual development of malignant tumors. The chemicals were administered as initiators by four different routes: oral, intraperitoneal, subcutaneous, and topical. Following the initiating dose of carcinogen, the animals were subjected to topical applications of 1 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) 3 times per week for a period of 20 weeks. The yield of papillomas at 24 weeks was selected as a potential predictor of carcinoma yields at 52 weeks following the start of the promotion schedule. Positive responses were observed with only eight of the compounds tested. Where positive results were observed, there was some evidence that the response could depend both qualitatively and quantitatively on the route of administration. However, no route was clearly superior, i.e., different chemicals gave greater responses by different routes. Papilloma yield at 24 weeks following the start of the promotion schedule was clearly related to the development of carcinomas at 52 weeks. No simple linear relationship existed between papilloma yield and carcinoma development, since the number of malignant tumors per papilloma decreased with increasing papilloma yields. The relationship between papilloma and carcinoma yields appeared to be independent of the carcinogen used. These data indicate that there are some limitations in using mouse skin initiation/promotion experiments as the sole basis for identifying substances with carcinogenic activity.(ABSTRACT TRUNCATED AT 250 WORDS)