tbuckley/cabot-search huggingface dataset:
Abstract 3270: Combination strategy to circumvent the acquired resistance to VEGF receptor tyrosine kinase inhibitor in M24met melanoma in mice
Authors: Lianglin Zhang, Maruja E. Lira, Keith A. Ching, Enhong Chen, Tina Lu, James G. Christensen, Dana D. Hu-Lowe
Journal: Cancer Research (2011)

Abstract Anti-angiogenic therapy targeting the tumor vasculature has demonstrated clinical benefits in certain types of tumors. However, many patients develop resistance and eventually progress on anti-angiogenic therapy. The mechanism of resistance is largely unknown and warrants extensively investigation. We developed a human xenograft tumor model (M24met/R) in mice that has acquired resistance to VEGF receptor tyrosine kinase inhibitors (VEGFR TKI), by chronically treating the parental M24met tumors (M24met/P) with PF-0337210 (20-40 mg/kg, QD, PO) and serially passaging resistant tumor fragments in nude mice. M24met/R tumors were also resistant to axitinib, a selective VEGFR TKI in late stage clinical development. Immunohistochemical (IHC) staining revealed higher degree of hypoxia and lower microvessel density in M24met/R tumors compared to parental tumors. Compared with those in M24met/P, vessels in M24met/R tumors appeared to be larger in diameter and more mature as shown by high incidence of co-localization between endothelial cells and perivascular cells (CD31+Desmin+). Microarray analysis of tumor lysates (human UA133 2.0, mouse 430 2.0 chip) revealed distinct gene expression profiles between M24met/R tumors and size-matched M24met/P tumors. Of note, several angiogenesis-related genes, including human VEGF, bFGF, integrin α5β1, IL-8, PDGF,CSF and murine VEGF, integrin α5β1, ALK1 (activin receptor-like kinase 1), IL-8, c-Met, IL-6 were up-regulated in M24met/R tumors, whereas murine VEGFR1 and 2, PROX1, PDGFR and endogenous angiogenic inhibitor TSP-1 were down-regulated in the resistant tumors. The above observations were verified with ELISA and/or IHC. Next, targeted combination approaches were applied in an attempt to circumvent M24met/R resistance to axitinib. Concurrent administration of axitinib plus either anti-IL-8 monoclonal antibody (mAb), c-Met inhibitor, anti-integrin α5 mAb or anti-ALK1 mAb significantly improved anti-tumor efficacy compared to single agents alone. IHC analyses showed that combinatorial therapy of anti-ALK1 plus axitinib reduced the amount of CD31+Desmin+ vessels compared to axitinib alone, suggesting that targeting ALK1 destroyed VEGFR TKI-resistant vessels. Together, our results suggested that multiple alternative angiogenic factors contributed to the acquired resistance of M24met/R melanoma to VEGFR TKI. Combination treatment using inhibitor of IL-8, c-Met, integrin α5β1 or ALK1 with VEGFR TKI may represent a new strategy to mitigate resistance to VEGFR TKI in the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3270. doi:10.1158/1538-7445.AM2011-3270
Reversal of dyskinesis by increased end diastolic segment length in ischaemic-reperfused myocardium
Authors: J VINTEN-JOHANSEN, P. J CARROLL, W. E JOHNSTON, W. C LITTLE, V. CHIANTELLA, J S. JULIAN, A R. CORDELL
Journal: Cardiovascular Research (1989)

Journal Article Reversal of dyskinesis by increased end diastolic segment length in ischaemic-reperfused myocardium Get access J VINTEN-JOHANSEN, J VINTEN-JOHANSEN **From the Cardiovascular Research Laboratories, Department of Cardiothoracic Sergery, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA†From the Cardiovascular Research Laboratories, Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA‡From the Cardiovascular Research Laboratories, Department of Physiology, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Address for correspondence and reprints: J Vinten-Johansen, PhD, Section on Cardiothoracic Surgery, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem, NC 27103, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar PAUL J CARROLL, PAUL J CARROLL §From the Department of Anesthesia, Tulane University, New Orleans, Louisiana, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar WILLIAM E JOHNSTON, WILLIAM E JOHNSTON †From the Cardiovascular Research Laboratories, Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar WILLIAM C LITTLE, WILLIAM C LITTLE ¶From the Cardiovascular Research Laboratories, Department of Medicine (Section on Cardiology), Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar VIRGINIA CHIANTELLA, VIRGINIA CHIANTELLA ‖From the Cardiovascular Research Laboratories, Department of Surgery, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar J STEVE JULIAN, J STEVE JULIAN ‖From the Cardiovascular Research Laboratories, Department of Surgery, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar A ROBERT CORDELL A ROBERT CORDELL **From the Cardiovascular Research Laboratories, Department of Cardiothoracic Sergery, Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 9, September 1989, Pages 810–820, https://doi.org/10.1093/cvr/23.9.810 Published: 01 September 1989 Article history Accepted: 05 April 1989 Published: 01 September 1989
Prophylaxis in haemophilus meningitis.
Authors: H P Lambert
Journal: BMJ (1984)

members admit the lack of short simple training courses around the country for citizens who want to acquire these skills.The first aid organisations appear still to be undecided about the merits of short, single session training in cardiopulmonary resuscitation as opposed to longer, fuller training in first aid.An initiative needs to be taken by a body that can stamp its authority on details of the techniques, train the trainers, and coordinate publicity with the help of journalists on newspapers, radio, and television.
High Risk of Malignant Melanoma in Melanoma-Prone Families with Dysplastic Nevi
Authors: MARK H. GREENE
Journal: Annals of Internal Medicine (1985)

The risk of hereditary cutaneous malignant melanoma was evaluated in 401 members of 14 families with an autosomal dominant form of melanoma. We documented 127 primary melanomas in 69 family members, including 39 new melanomas diagnosed in 22 study participants from the time of first examination through a maximum of 8 years of follow-up. The 39 newly diagnosed melanomas occurred only in family members with dysplastic nevi, a known precursor of familial melanoma. Of 77 patients with dysplastic nevus syndrome without prior melanomas, 4 developed their first melanoma during prospective follow-up, as compared with 0.03 cases expected. The prospective age-adjusted incidence for melanoma was 14.3/1000 patients with dysplastic nevus per year, with a cumulative melanoma risk (±SE) of 7.2% (±3.6) at 8 years. The actuarial probability of melanoma developing in family members with dysplastic nevi was 56.0% (±10.1) from age 20 to age 59. This study confirms that dysplastic nevi are clinical markers of high risk for, and precursors of, hereditary melanoma.
Surgery and Supervoltage Therapy in Treatment of Carcinoma of Lung
Authors: William L. Caldwell
Journal: JAMA (1962)

To the Editor:—  The convictions of David P. Boyd, M.D., et al. in their abstract of the article ( JAMA  179 :253 [Jan. 27] 1962), Surgery and Supervoltage Therapy in the Treatment of Carcinoma of the Lung, are of keen interest to me. On the basis of their material, how can they honestly state (as so many others have in the past) that: When surgery can be applied, it is the best treatment currently available for bronchogenic carcinoma? This is stated in a different, but no less subtle, way in the opening sentence: Our experience shows that of 628 patients with carcinoma of the lung, only 340 or 54% were submitted to operation and thereby given a chance for cure.  It is from such parenthetical remarks that medical maxims are born. Obviously, selection has always been in favor of surgery. In this series the 152 patients ( with only 2 exceptions ) treated
Use of Ether at Battle of Wilderness.
Authors: Jacob L. Williams
Journal: JAMA (1904)

Boston, April 23, 1904.  To the Editor:  —I am sorry to see in The Journal of this date a magazine written article, mainly for the purpose of repeating the old falsity that W. T. G. Morton discovered and introduced ether anesthesia, when he himself at first acknowledged that Dr. C. T. Jackson gave him the prescription with directions, later given to Massachusetts General Hospital and by it given to the world.
Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation
Authors: Miguel-Angel Perales, Jenna D. Goldberg, Jianda Yuan, Guenther Koehne, Lauren Lechner, Esperanza B. Papadopoulos, James W. Young, Ann A. Jakubowski, Bushra Zaidi, Humilidad Gallardo, Cailian Liu, Teresa Rasalan, Jedd D. Wolchok, Therese Croughs, Michel Morre, Sean M. Devlin, Marcel R. M. van den Brink
Journal: Blood (2012)
Radiation After Lumpectomy Can Be Omitted for Certain Women With Breast Cancer
Authors: Mike Mitka
Journal: JAMA (2010)

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
Association between coronary heart disease and the C3F-gene in essential hypertension.
Authors: B O Kristensen, G B Petersen
Journal: Circulation (1978)

The occurrence of the C3F allele was investigated in the following three groups: 69 consecutive referred patients with untreated essential hypertension, including borderline hypertension; 70 patients with established and treated essential hypertension, already attending the same outpatient clinic, and 62 age- and sex-matched normotensive healthy subjects without clinical signs of atherosclerosis or familial predisposition to hypertension. In the three groups the C3F allele was found in 38.2%, 29% and 20%, respectively. Among the treated hypertensive patients with C3F gene, 40% had coronary heart disease (CHD) compared to 6.1% among the C3F negative (P less than 0.005), and the relative risk of CHD among the treated hypertensive patients with this allele was found to be 10.2 (P less than 0.002). The C3F gene was present in 72.7% of the treated patients with CHD. In the untreated patients the occurrence of CHD was low, and no differences between C3F positive and negative patients could be demonstrated. No association of the C3F allele with familial predisposition to hypertension was found. This study provides further evidence of a positive association of the C3F allele with atherosclerosis, and it is concluded that this allele in a hypertensive patient might accelerate the atherosclerotic process, with subsequent premature development of vascular complications.
Multidisciplinary Approach to the Geriatric Oncology Patient
Authors: Catherine Terret, Gilbert B. Zulian, Arash Naiem, Gilles Albrand
Journal: Journal of Clinical Oncology (2007)

Given the dramatic demographic shift observed in developed countries, the medical community, especially oncologists, geriatricians, and primary care providers, are confronted with the expanding challenge of the management of elderly people with cancer. Ageing is associated with the accumulation of multiple and various medical and social problems. With a prevalence comparable to that of other chronic conditions in this age group, such as diabetes or dementia, cancer holds a prominent place among diseases of the elderly. The care of elderly cancer patients is fundamentally interdisciplinary. Communication and collaboration between geriatricians/primary care providers and oncologists represent key features of effective care in geriatric oncology. The combination of the disease-oriented approach of oncologists and the patient-oriented approach of geriatricians is the most powerful way to better serve this specific population. The medical approach of elderly cancer patients should ideally be under the lead of geriatricians or primary care providers sensitive to geriatric issues. Oncologists should manage the biologic consequences of the interplay between cancer and ageing. Close collaboration between clinicians will help promote active dedicated clinical research and the development of guidelines on the management of elderly people with cancer.
Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice
Authors: Ilka Mathar, Rudi Vennekens, Marcel Meissner, Frieder Kees, Gerry Van der Mieren, Juan E. Camacho Londoño, Sebastian Uhl, Thomas Voets, Björn Hummel, An van den Bergh, Paul Herijgers, Bernd Nilius, Veit Flockerzi, Frank Schweda, Marc Freichel
Journal: Journal of Clinical Investigation (2010)

Hypertension is an underlying risk factor for cardiovascular disease. Despite this, its pathogenesis remains unknown in most cases. Recently, the transient receptor potential (TRP) channel family was associated with the development of several cardiovascular diseases linked to hypertension. The melastatin TRP channels TRPM4 and TRPM5 have distinct properties within the TRP channel family: they form nonselective cation channels activated by intracellular calcium ions. Here we report the identification of TRPM4 proteins in endothelial cells, heart, kidney, and chromaffin cells from the adrenal gland, suggesting that they have a role in the cardiovascular system. Consistent with this hypothesis, Trpm4 gene deletion in mice altered long-term regulation of blood pressure toward hypertensive levels. No changes in locomotor activity, renin-angiotensin system function, electrolyte and fluid balance, vascular contractility, and cardiac contractility under basal conditions were observed. By contrast, inhibition of ganglionic transmission with either hexamethonium or prazosin abolished the difference in blood pressure between Trpm4-/- and wild-type mice. Strikingly, plasma epinephrine concentration as well as urinary excretion of catecholamine metabolites were substantially elevated in Trpm4-/- mice. In freshly isolated chromaffin cells, lack of TRPM4 was shown to cause markedly more acetylcholine-induced exocytotic release events, while neither cytosolic calcium concentration, size, nor density of vesicles were different. We therefore conclude that TRPM4 proteins limit catecholamine release from chromaffin cells and that this contributes to increased sympathetic tone and hypertension.
Regulation of Collagen Production by the β-Adrenergic System
Authors: Richard A. Berg, Joel Moss, Bruce J. Baum, Ronald G. Crystal
Journal: Journal of Clinical Investigation (1981)

The suppression of collagen production by increasing the cyclic (c) AMP content of cultured cells was examined vis-à-vis the beta-adrenergic system. Cultured human fetal lung fibroblasts incubated for 6 h with the beta-agonists isoproterenol or epinephrine produced approximately 30% less collagen per cell than in the absence of the hormones. To demonstrate that the beta-agonists were operating by their interaction with the beta-receptor to stimulate adenylate cyclase to increase the intracellular content of cAMP, d- and l-isoproterenol were incubated separately with the cultured cells. Only l-isoproterenol increased intracellular cAMP and decreased collagen production. While 20 nM l-isoproterenol was effective, the d-isomer was ineffective even at 2muM. An increase in cAMP from 40 to 73 pmol/mg protein was effective in suppressing collagen production; increasing the cAMP content to much higher levels had little additional effect on collagen production. 3-Isobutyl-1-methylxanthine, an analog of theophylline that inhibits phosphodiesterase, potentiated the effect of isoproterenol in suppressing collagen production. Further support for the concept that isoproterenol suppressed collagen production by acting through the beta-receptor was provided by the finding that only the l-isomer of propranolol, a beta-blocker, was effective in blocking both the increase in intracellular cAMP and the suppression of collagen production caused by isoproterenol. These results demonstrate that collagen production in human fibroblasts can be regulated by the beta-adrenergic system and indicate that when the cAMP content is increased beyond a threshold value, collagen production is suppressed. Since collagen production is sensitive to the small changes of cAMP content of cells brought about by beta-stimulation in cultured cells, the results point to a possibly important mechanism for the regulation of collagen production in the body.
AN INDIVIDUAL DRINKING CUP.
Authors: D. LICHTY
Journal: JAMA (1898)

Since the universally acknowledged advantages of the solitary or individual drinking cup are so readily recognized the adoption of a cup whose introduction into common and general use would not impose a burden or hardship on the user is an object much to be desired and if obtained to be promptly commended. It is to be admitted that the agitation on hygienic lines has been most successfully conducted through the medium of the church communion cup, and that the success attending its introduction at this most sacred function has quite generally been satisfactory to those participating and most able to judge. That an innovation of this kind has many difficulties to encounter and overcome is to be expected, as it invades the precincts of the holiest of ecclesiastic ordinances, besides it introduces a new element of expense that the feebler village and rural congregations are illy able to bear. The
Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis
Authors: Andreas Geier, Christoph G. Dietrich, Sebastian Voigt, Suk-Kyum Kim, Thomas Gerloff, Gerd A. Kullak-Ublick, Johann Lorenzen, Siegfried Matern, Carsten Gartung
Journal: Hepatology (2003)

Hepatobiliary transporters are down–regulated in toxic and cholestatic liver injury. Cytokines such as tumor necrosis factor α (TNF–α) and interleukin 1β (IL–1β) are attributed to mediate this regulation, but their particular contribution in vivo is still unknown. Thus, we studied the molecular mechanisms by which Ntcp, Oatp1, Oatp2, and Mrp2 are regulated by proinflammatory cytokines during liver injury. Rats were injected intraperitoneally with either carbon tetrachloride or endotoxin. Inactivation of TNF–α and IL–1β was achieved by repetitive intraperitoneal injection of etanercept and anakinra, respectively. Messenger RNA (mRNA) levels of transporters and binding activities as well as nuclear protein levels of Ntcp , Oatp2 , and Mrp2 transactivators were determined 20 to 24 hours later. In contrast to IL–1β, TNF–α inactivation alone fully prevented down–regulation of Ntcp, Oatp1, and Oatp2 mRNA as well as reduced binding activity of hepatocyte nuclear factor 1 (HNF–1) in CCl 4 –induced toxic injury. In endotoxemia, down–regulation of Mrp2, and partially in case of Ntcp, could be prevented by IL–1β but not TNF–α blockade. However, inactivation of either cytokine led to preservation of HNF1 and partially of retinoid X receptor/retinoic acid receptor (RXR/RAR) binding activity. No effect of anticytokines was seen on pregnane X receptor (PXR) and constitutive androstane receptor (CAR) binding activity as well as nuclear protein mass. In conclusion, TNF–α represents the master cytokine responsible for HNF1–dependent down–regulation of Ntcp , Oatp1 , and Oatp2 in CCl 4 –induced toxic liver injury. IL–1β predominates in a complex signaling network of Ntcp and Mrp2 regulation in cholestatic liver injury. In contrast to in vitro studies, HNF1 and RXR/RAR–independent mechanisms appear to be more important in regulation of Mrp2 and Ntcp gene expression in endotoxemia.
MMP-2, MMP-9 and their inhibitors TIMP-2 and TIMP-1 production by human monocytes in vitro in the presence of different forms of hydroxyapatite particles
Authors: Patrice Laquerriere, Alexia Grandjean-Laquerriere, Salima Addadi-Rebbah, Edouard Jallot, Dominique Laurent-Maquin, Patrick Frayssinet, Moncef Guenounou
Journal: Biomaterials (2003)
The American College of Physicians Honorary Fellowship Lecture: Rigidity and Mobility in Spinal Disease.
Authors: E. G. L. Bywaters
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973The American College of Physicians Honorary Fellowship Lecture: Rigidity and Mobility in Spinal Disease.E. G. L. Bywaters, M.B., F.R.C.P.E. G. L. Bywaters, M.B., F.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-813_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe biology of connective tissue has advanced much with the definition of molecular structures such as that of collagen and the proteoglycans, but there is still more to learn in this field than in most others. Least is known about the spine. Recent studies of its diseases have shown how its peculiar blend of rigidity and mobility is compromised by various processes, ranging from metabolic derangements (neoplastic, hereditary, or acquired) through degenerative processes to inflammatory diseases of largely unknown origin. Such syndromes as relapsing polychondritis and ankylosing spondylitis have widespread systemic manifestations, but the major problems seem to involve the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Taplow, Maidenhead, Berks England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 813-813KeywordsAnkylosing spondylitisConnective tissueFellowshipsGenetic diseasesMetabolic disordersMetabolic processesSpine Issue Published: 1 May 1973 PDF downloadLoading ...