tbuckley/cabot-search huggingface dataset:
A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis
Authors: Kin-Mei Leung, Sarah Batey, Robert Rowlands, Samine J Isaac, Phil Jones, Victoria Drewett, Joana Carvalho, Miguel Gaspar, Sarah Weller, Melanie Medcalf, Mateusz M Wydro, Robert Pegram, Geert C Mudde, Anton Bauer, Kevin Moulder, Max Woisetschläger, Mihriban Tuna, John S Haurum, Haijun Sun
Journal: Molecular Therapy (2015)

FS102 is a HER2-specific Fcab (Fc fragment with antigen binding), which binds HER2 with high affinity and recognizes an epitope that does not overlap with those of trastuzumab or pertuzumab. In tumor cells that express high levels of HER2, FS102 caused profound HER2 internalization and degradation leading to tumor cell apoptosis. The antitumor effect of FS102 in patient-derived xenografts (PDXs) correlated strongly with the HER2 amplification status of the tumors. Superior activity of FS102 over trastuzumab or the combination of trastuzumab and pertuzumab was observed in vitro and in vivo when the gene copy number of HER2 was equal to or exceeded 10 per cell based on quantitative polymerase chain reaction (qPCR). Thus, FS102 induced complete and sustained tumor regression in a significant proportion of HER2-high PDX tumor models. We hypothesize that the unique structure and/or epitope of FS102 enables the Fcab to internalize and degrade cell surface HER2 more efficiently than standard of care antibodies. In turn, increased depletion of HER2 commits the cells to apoptosis as a result of oncogene shock. FS102 has the potential of a biomarker-driven therapeutic that derives superior antitumor effects from a unique mechanism-of-action in tumor cells which are oncogenically addicted to the HER2 pathway due to overexpression.
Abstract P254: Impact of a 12-Weeks Supervised Physical Activity Program After Bariatric Surgery on Cardiorespiratory Capacity; A Randomized Study
Authors: Jany Harvey, Auclair Audrey, Eric Nadreau, Alexandre Sanctuaire, Simon Marceau, Laurent Biertho, Simon Biron, Frederic-Simon Hould, Stefane Lebel, Odette Lescelleur, Paul Poirier
Journal: Circulation (2015)

Bariatric surgery is an effective long-term treatment for the management of severe obesity. Weight loss induced by bariatric surgery is characterized by a greater reduction in the fat mass than the reduction in muscle mass. Severely obese patients have a reduced exercise-capacity reduced and perform external work with higher energy expenditure. There is a lack of data regarding the effect of physical activity on cardiorespiratory capacity after bariatric surgery. The purpose of this study was to measure the impact of bariatric surgery and the impact of a supervised physical activity program, between months 3 to 6 after bariatric surgery, on cardiorespiratory capacity. Patients were randomized either to a supervised physical activity program group (exercise group) or usual care without personalized physical activity follow-up group (control group). Anthropometric measurements, abdominal and mid-thigh computed tomography scans, heart rate variability (HRV) measurement and maximal exercise test were performe...
Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis
Authors: Marcin Majka, Anna Janowska-Wieczorek, Janina Ratajczak, M. Anna Kowalska, Gaston Vilaire, Zhixing K. Pan, Marek Honczarenko, Leah A. Marquez, Mortimer Poncz, Mariusz Z. Ratajczak
Journal: Blood (2000)
638. Therapeutic Antisense-Induced Exon Skipping for Duchenne Muscular Dystrophy
Authors: Annemieke Aartsma-Rus, Anneke A. M. Janson, Wendy E. Kaman, Mattie Bremmer-Bout, Christa L. de Winter, Habte F. Teshale, Gert-Jan B. van Ommen, Johan T. den Dunnen, Judith C. T. van Deutekom
Journal: Molecular Therapy (2004)

The severe Duchenne muscular dystrophy (DMD) is mostly caused by frame disrupting mutations in the dystrophin gene, which result in non-functional dystrophin proteins. Mutations that keep the reading frame intact give rise to internally deleted, semi-functional dystrophins and result in the milder Becker muscular dystrophy (BMD). Antisense oligonucleotides (AONs) have the potential to modulate the pre-mRNA splicing such that a specific exon is skipped. As a result, the reading frame can be restored, which allows the synthesis of a BMD-like dystrophin.
A Textbook of Gynaecological Surgery.
Authors: Comyns Berkeley, Victor Bonney
Journal: JAMA (1921)

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
Identification of the gene causing mucolipidosis type IV
Authors: Ruth Bargal, Nili Avidan, Edna Ben-Asher, Zvia Olender, Marcia Zeigler, Ayala Frumkin, Annick Raas-Rothschild, Gustavo Glusman, Doron Lancet, Gideon Bach
Journal: Nature Genetics (2000)
Anticancer effects of selenium: Linkage from metabolome to signal transduction
Authors: Teresa W. Fan, Marcin Wysoczynski, Mariusz Ratajczak, Shelia Thomas, Donald Miller, Richard M. Higashi, Andrew N. Lane
Journal: Cancer Research (2004)

1380  Selenium (Se) has been shown in clinical trials to be effective in reducing the risk of different cancers including lung cancer. Consequently, the mechanism of this anticancer effect has been under active investigation. Although it is clear that Se induces apoptosis of cancer cells, the regulatory mechanism(s) of this effect is yet to be understood. In addition, different forms of Se appear to have different mechanism(s) of cytotoxicity. To obtain a broad understanding of the toxic effect of Se on lung cancer cells, we employed our metabolomic approach of using NMR and mass spectrometry to define biochemical changes induced by selenite in A549 cells. Figure 1 illustrates the metabolic differences between control and selenite-treated cells, as determined from 1H NMR analysis of crude cell extracts. The accumulation of phosphoryl choline (PC) induced by selenite could be related to an activation of phosphatidylcholine-specific phospholipase C by protein kinase C (PKC). The PC release could also signify increased diacylglycerol production, which in turn modulates PKC activity. Depending on the specific isoforms, activated PKC could inhibit or activate proteins via phosphorylation. The selenite-induced accumulation of metabolites related to the urea cycle ( e.g. Arg, Gln, and ornithine) is consistent with phosphorylation or altered regulation of enzymes such as ornithine decarboxylase and nitric oxide synthase by PKC. Thus, profiling of metabolic changes in response to anticancer agents such as selenite can provide insights into upstream regulatory mechanism(s).
Nonnasal Lymphoma Expressing the Natural Killer Cell Marker CD56: A Clinicopathologic Study of 49 Cases of an Uncommon Aggressive Neoplasm
Authors: John K.C. Chan, V.C. Sin, K.F. Wong, C.S. Ng, William Y.W. Tsang, C.H. Chan, M.M.C. Cheung, W.H. Lau
Journal: Blood (1997)
Challenges to primary care in diagnosing and managing depression in children and young people
Authors: T. Kramer, L. Als, M. E. Garralda
Journal: BMJ (2015)

The National Institute for Health and Care Excellence (NICE) guideline summary recommended that Child and Adolescent Mental Health Services should work with primary healthcare professionals to develop systems for detecting, assessing, supporting, and referring depressed children and young people, with provision for those who are less seriously affected within primary care.1 This recommendation does not take into account the challenges to primary …
Expression of the RET Receptor Tyrosine Kinase and GDNFR-α in Normal and Leukemic Human Hematopoietic Cells and Stromal Cells of the Bone Marrow Microenvironment
Authors: Valter Gattei, Angela Celetti, Aniello Cerrato, Massimo Degan, Angela De Iuliis, Francesca Maria Rossi, Gennaro Chiappetta, Claudia Consales, Salvatore Improta, Vittorina Zagonel, Donatella Aldinucci, Valter Agosti, Massimo Santoro, Giancarlo Vecchio, Antonio Pinto, Michele Grieco
Journal: Blood (1997)
Reducing the price of new hepatitis C drugs in the Tuscany region of Italy
Authors: M. R. Brunetto, A. De Luca, A. Messori, A. L. Zignego
Journal: BMJ (2015)

In most European countries, regulatory agencies are engaged in approving reimbursement schemes for the new interferon-free direct antiviral agents (DAAs) for hepatitis C.1 2 The degree of reimbursement differs across countries and sometimes between regions of the same country.

Owing to budget constraints, most national approvals for reimbursement have been restricted to patients with more severe disease, according to ethical and clinical considerations.2 3 4 5

In May 2015, the Tuscany region of Italy proposed a regional tendering …
Abstract 4197: Regulators of p21 transcription in melanoma
Authors: Sigurd L. Bøe, Josef Thingnes, Sima Z. Golmakani, Eivind Hovig
Journal: Cancer Research (2014)

Abstract p21(CIP1/WAF1) is a cyclin-dependent kinase inhibitor that directly inhibits the activity of cyclin E/CDK2 and cyclin D/CDK4/6 complexes and thereby functions as a regulator of cell cycle progression. The transcriptional regulation of p21 has been reported to be controlled by a large number of genes. However, the importance of each of these genes upon p21 transcriptional expression in melanoma is not fully explored. Here we have measured p21 mRNA levels in a cell panel consisting of 17 cell melanoma lines with various genetic backgrounds, spanning various stages of the disease. A correlation between p21 expression and p53 status in these cell lines demonstrated low p21 expression in p53 mutant cell lines, such as WM1366, MeWo, SKMEL28, WM45.1, WM983 and WM852 compared to cell lines with wild-type p53. With the use of a number of small molecular inhibitors against the MAPK and cAMP pathways to investigate possible changes in the p21 expression levels, we find that p21 expression levels were more sensitive to regulation by inhibitors in the p53 mutant cell lines compared to cell lines with p53 wild-type. Furthermore, we investigated mRNA expression levels of around 20 genes that previously have been reported to be involved in the regulation of p21 expression, and we find that TBX2 and TBX3 mRNA levels showed the strongest correlation with p21 mRNA levels. Citation Format: Sigurd L. Bøe, Josef Thingnes, Sima Z. Golmakani, Eivind Hovig. Regulators of p21 transcription in melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4197. doi:10.1158/1538-7445.AM2014-4197
Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial
Authors: Kieren A. Marr, Kristy Seidel, Monica A. Slavin, Raleigh A. Bowden, H. Gary Schoch, Mary E. D. Flowers, Lawrence Corey, Michael Boeckh
Journal: Blood (2000)
ATYPICAL FACIAL NEURALGIA IN THE HYPOTHYROID STATE
Authors: FREDERICK B. WATTS, M.D., F.A.C.P.
Journal: Annals of Internal Medicine (1951)

ExcerptA deficiency of the thyroid hormone in the adult may give rise to a syndrome of chronic, recurring pain about the face and neck and recurring headaches, as recently pointed out by Fenichel.1The type and intensity of the pain vary considerably, and may be manifested as a dull aching or throbbing pain in either carotid area, in or about the ear, in the frontal or temporal area, or along the upper or lower jaw or the posterior cervical area. Quite frequently there may be an associated dull pain or sense of constriction over the precordium. The pain may be...
Abstract 773: Restoration of LKB1 defect in EKVX cells leads to resistance to microtubule targeting agents
Authors: Kaisheng Mao, Fakeng Liu, Xiuju Liu, Yulong He, Fadlo Khuri, Adam Marcus, Mingsong Li, Wei Zhou
Journal: Cancer Research (2014)

Abstract LKB1 is frequently inactivated in non-small cell lung cancers, probably because of its role in suppressing tumor metastasis. Here, we identified a novel LKB1 mutation in the EKVX lung adenocarcinoma cell line, where serine216 in the kinase domain was mutated to phenylalanine. Genomic sequencing revealed this change to be homozygous, suggesting that the other allele was probably eliminated through a loss of heterozygosity mechanism. We also demonstrated that EKVX cells are defective in energetic stress-induced AMPK phosphorylation, which can be restored by the re-establishment of wild-type but not mutant LKB1 expression. This is consistent with the role of LKB1 as an upstream kinase for AMPK in energetic stress conditions. Interestingly, expression of wild-type LKB1 in EKVX cells was found to be resistant to microtubule targeting agents, such as paclitaxel or vinblastine by SRB analysis. Cell cycle analysis indicated that while the parental or LKB1-mutant expressing cells enter mitotic arrest after 25nM paclitaxel treatment, EKVX-LKB1 cells failed to enter G2/M arrest. Immunofluorescence analysis also revealed a decrease in microtubule bundling after 50nM paclitaxel treatment in EKVX cells with wild-type LKB1 expression. This phenomenon, however, was not observed in other natural LKB1-null A549 or H460 cells. Therefore, our data suggest that the re-establishment of LKB1 expression might lead to resistance to microtubule targeting agents in a subset of non-small cell lung cancer cells with LKB1 mutation. Citation Format: Kaisheng Mao, Fakeng Liu, Xiuju Liu, Yulong He, Fadlo Khuri, Adam Marcus, Mingsong Li, Wei Zhou. Restoration of LKB1 defect in EKVX cells leads to resistance to microtubule targeting agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 773. doi:10.1158/1538-7445.AM2014-773
748. Generation of Novel Double-Stranded AAV Vectors with an Expanded Packaging Capacity Using Linearized 1-AAV ITR DNA Molecules
Authors: Ognjen Petras, Timothy J. Davern, Ryan McTaggart
Journal: Molecular Therapy (2004)

Introduction: The double-stranded AAV (dsAAV) vector is a new entity in the field of AAV based technologies. DsAAVs bypass a key requirement of AAV mediated transduction-conversion of the single stranded AAV genome into a double-stranded DNA template capable of RNA transcription. Currently, the only reported method for efficient and practical synthesis of double-stranded AAV's involves a standard AAV plasmid that has had one of its two AAV-inverted terminal repeat sequences mutated. Here we report a novel and practical method to synthesize double-stranded AAV vectors with a slightly increased packaging capacity as compared to the recently published technique.
Paroxysmal Supraventricular Tachycardia Induction in Patients with Wolff-Parkinson-White Syndrome
Authors: PABLO DENES
Journal: Annals of Internal Medicine (1979)

In 54 patients with pre-excitation, 30 (56%) had inducible A-V re-entrant paroxysmal tachycardia. Of these 30, 20 had spontaneous paroxysmal tachycardia (four also had atrial fibrillation), four had spontaneous paroxysmal atrial fibrillation, five had a history of palpitation without arrhythmia, and one was asymptomatic. In 24 patients (44%), paroxysmal tachycardia was not inducible. Of these 24, none had documented paroxysmal tachycardia, four had atrial fibrillation, nine had palpitation without arrhythmia, and 11 were asymptomatic. The incidence of documented paroxysmal tachycardia was higher in the patients with inducible tachycardia (P < 0.001). Tachycardia induction was noted in 20 of 20 patients with spontaneous paroxysmal tachycardia, eight of 12 patients with paroxysmal atrial fibrillation, five of 14 patients with palpitation and no arrhythmia, and one of 12 asymptomatic patients. The frequency of ability to induce paroxysmal tachycardia was significantly higher in both the patients with documented spontaneous paroxysmal tachycardia and the patients with paroxysmal atrial fibrillation than in the asymptomatic group (P < 0.01).
Primary cutaneous large B-cell lymphoma of the legs and malignant melanoma: coincidence or association?
Authors: None Koeppel, None Grego, None Andrac, None Berbis
Journal: British Journal of Dermatology (1998)

Journal Article Primary cutaneous large B‐cell lymphoma of the legs and malignant melanoma: coincidence or association? Get access M-C. Koeppel, M-C. Koeppel Department of Dermatology, Hôpital Nord, 23 Chemin des Bourrelly, 13,915 Marseille Cédex 20, France, Search for other works by this author on: Oxford Academic Google Scholar F. Grego, F. Grego Department of Dermatology, Hôpital Nord, 23 Chemin des Bourrelly, 13,915 Marseille Cédex 20, France, Search for other works by this author on: Oxford Academic Google Scholar L. Andrac, L. Andrac Department of Pathology, Faculté Nord, 51 Boulevard Pierre Dramard, 13,015 Marseille, France Search for other works by this author on: Oxford Academic Google Scholar P. Berbis P. Berbis Department of Dermatology, Hôpital Nord, 23 Chemin des Bourrelly, 13,915 Marseille Cédex 20, France, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 4, 1 October 1998, Pages 751–752, https://doi.org/10.1046/j.1365-2133.1998.02488.x Published: 01 October 1998
Enhanced response of radiation via the adenovirus-mediated transfer of antisense MMP-9 in a breast cancer tumor model
Authors: Sateesh S. Kunigal, Sajani Lakka, Pushpa Joseph, Norman Estes, Jasti S. Rao
Journal: Cancer Research (2006)

4400   The high mortality rates of several cancers are due to resistance to radiation therapy. Novel strategies are needed to prevent treatment-related morbidity in patients with tumors. Once the deleterious effects of radiation begin, attempts to reverse or limit the damage generally fail, leading to severe tumor metastasis. Matrix metalloproteinases (MMPs) and plasminogen activators comprise two categories of extracellular matrix-degrading proteolytic enzymes, which are induced by radiation. Considerable evidence suggest that these enzymes, particularly MMP-9, play a role in the growth of primary and secondary tumors including angiogenesis. On the other hand, hypoxia is also a common feature of tumors, and HIF1α is upregulated in more than 60% of tumors due to intratumoral hypoxia, or even constitutively, as a result of cellular transformation. Clinical studies have confirmed that the upregulation of the HIF pathway in tumors is linked to tumor resistance to radiotherapy. Angiogenesis, erythropoiesis, glycolysis, and other pathways are directly regulated by HIF. As these studies draw a potential link between MMP-9 upregulation and radiotherapy, we sought to determine the combined effect of radiation and anti-MMP-9 therapy using adenoviral-mediated transfer of the antisense MMP-9 gene (Ad-MMP-9). Intratumoral injection of Ad-MMP-9 into breast tumors in TRAMP mice resulted in delayed tumor growth, a 50% reduction in tumor size, and a nearly 70% reduction in tumor size after irradiation with one dose of 10 gy. A further decrease in tumor size was observed in the tumors treated with Ad-MMP-9 and radiation as compared to tumors only treated with radiation. Western blot analysis revealed downregulation of HIF1α in the Ad-MMP-9-treated tumors when compared to the controls. Conversely, the HIF1α levels were higher in the irradiated tumors than the levels present in the control tumors. VEGF, VEGF R2 and MMP-9 levels were decreased in the Ad-MMP-9-treated tumors while the levels in irradiated and control tumors were comparable. As determined by gelatin zymography, MMP-9 activity also decreased in the Ad-MMP-9-treated tumors. All of the above-mentioned results were confirmed using immunohistochemistry and RT-PCR analysis. Furthermore, we investigated the possible role of TIMP-1 in the induction of apoptosis in Ad-MMP-9 treated tumors. The results from western blot and immunohistochemical analyses demonstrate increased levels of TIMP-1 in Ad-MMP-9-treated tumors, as well as irradiated tumors. As determined by TUNEL assay and caspase-3 levels, the number of apoptotic cells was also increased in Ad-MMP-9-treated tumors as compared to irradiated and control tumors. In summary, this study suggests a synergistic effect from integrating gene therapy (adenovirus-mediated inhibition of MMP-9) with radiotherapy, which may improve the survival rate of patients by inhibiting tumor growth.
The Warburg Effect Revisited—Lesson from the Sertoli Cell
Authors: Pedro F. Oliveira, Ana D. Martins, Ana C. Moreira, C. Yan Cheng, Marco G. Alves
Journal: Medicinal Research Reviews (2014)

Abstract Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism. The Warburg effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a “Warburg‐like” metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear “Warburg‐like” metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg effect and cell proliferation.