tbuckley/cabot-search huggingface dataset:
Rituximab sensitizes resistant B-NHL cell lines to the proteasome inhibitor NPI-0052-induced apoptosis.
Authors: Eriko Suzuki, Michael Palladino, Benjamin Bonavida
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5429 

We have reported that rituximab treatment of B-NHL cell lines sensitize the drug-resistant cells to drug-induced apoptosis. One of the mechanisms by which rituximab sensitizes the tumor cells to drug-induced apoptosis has been shown to be mediated via inhibition of the NF-κB pathway and downstream the selective inhibition of the anti-apoptotic product BclXL expression. Inhibitors of this pathway mimicked rituximab in sensitizing the cells to drug-induced apoptosis (Jazirehi, et al, 2005, Cancer Research, 65(1):264-76). We hypothesized that proteasome inhibitors that inhibit NF-κB activity and downstream anti-apoptotic gene products may sensitize tumor cells to drug-induced apoptosis. The new proteasome inhibitor NPI-0052 (Nereus Pharmaceuticals), which inhibits NF-κB activity, has been shown to sensitize B-NHL cells to drug (CDDP, adriamycin)-induced apoptosis. NPI-0052 has been shown to directly kill sensitive tumor cells by apoptosis. Also, NPI-0052 induces apoptosis in multiple myeloma cells resistant to conventional and velcade therapies (Chauhan et al., Cancer Cell 2005 In Press). However, with low concentrations of NPI-0052, we were not able to demonstrate significant induction of apoptosis in the Ramos B-NHL cell line. We hypothesized that NPI-0052 may behave like a chemotherapeutic drug and rituximab may therefore sensitize the tumor cells to NPI-0052-induced apoptosis. Ramos cells were treated with rituximab (20ug/ml) (12h to 18h) and the cells were treated with various concentrations of NPI-0052 (1-10nM) for an additional 20h and the cells were examined for apoptosis using the PI method detecting DNA fragmentation by flow cytometry. Rituximab or NPI-0052 treatment alone resulted in no significant induction of apoptosis; however, the combination treatment resulted in significant apoptosis. The synergistic activity was detected with very low concentrations of NPI-0052 >= 1nM. By comparison, several thousand fold higher concentrations of chemotherapeutic drugs (e.g. CDDP, adriamycin) were used for rituximab-mediated chemosensitization of Ramos cells. These results demonstrate that rituximab sensitizes the tumor cells to the proteasome inhibitor NPI-0052-mediated apoptosis. In addition, the findings suggest that rituximab (or chemosensitizing agents) used in combination with NPI-0052 may result in synergistic activity and can reverse drug and/or rituximab resistance of B-NHL. This study was supported in part by a philanthropic contribution from the JCCC/Rosenfield Fund under the direction of David Leveton.
A physical complex between TGM2 and GSTP1 confers cisplatin resistance in glioma cells: Functional mapping of the interaction domain
Authors: James Koh, Jiewu Liu, Francis Ali-Osman
Journal: Cancer Research (2008)

2693   The human glutathione S-transferase P1 (GSTP1) and tissue transglutaminase II (TGM2) proteins are multifunctional regulatory enzymes that can act as potent mediators of drug resistance in human tumors. Previously, we have demonstrated that GSTP1 and TGM2 can form a stable, non-covalent complex in the cytoplasm of actively dividing glioma cells. In the work presented here, we describe the functional characterization of the GSTP1/TGM2 complex. Using a series of deletion mutants, we have mapped the GSTP1 interaction domain of TGM2 to a region between residues 108 and 147 in the N-terminal portion of the protein, a location distinct from the other known functional domains of TGM2. Testing variants of TGM2 that either retain or lack the ability to form a complex with GSTP1, we then compared the capacity of these TGM2 constructs to confer cisplatin resistance in the presence or absence of stably expressed GSTP1 in glioma cells. In the absence of GSTP1, TGM2 expression did not confer cisplatin resistance over background, whereas in the presence of GSTP1, TGM2-expressing cells were approximately 10-fold more resistant to cisplatin than controls. A full length variant of TGM2 that lacked the ability to form a complex with GSTP1 did not confer cisplatin resistance regardless of the presence or absence of GSTP1. These data indicate that in the context of glioma cells, the ability to form a GSTP1/TGM2 complex is essential for TGM2-mediated cisplatin resistance. We then assessed whether depletion of the endogenous GSTP1/TGM2 complex in a cisplatin-resistant glioma cell line could sensitize these cells to the drug. SiRNA-mediated suppression of either GSTP1 or TGM2 alone did not measurably alter cisplatin resistance, but depletion of both proteins resulted in significant sensitization to killing by cisplatin. Collectively, these data demonstrate that the GSTP1/TGM2 complex may play an important role in the drug resistant phenotype displayed by many gliomas. The fact that the complex appears to be required for mediating the drug resistance conferred by TGM2 suggests that interference with the complex may represent a sensitizing strategy for improving the clinical response to chemotherapeutic agents in glioma treatment. Supported by grants RSG MGO-103761 from the American Cancer Society (JK) and RO1 CA112519, RO1 CA 91438, P50 CA108786 (FAO).
Abstract 1734: Focal Atrial Tachycardia Arising From the Non-Coronary Aortic Sinus
Authors: Charalampos Kriatselis, Mattias Roser, Stephan Gotze, Georgios Evangelidis, Martin Hoher, Eckart Fleck
Journal: Circulation (2007)

Introduction: The majority of focal atrial tachycardias (FAT’s) arise either in the right atrium (preferably crista terminals, coronary sinus ostium) or in the left atrium (pulmonary veins, close t...
The Public's Enthusiasm for Cancer Screening—Reply
Authors: Steven Woloshin, Lisa M. Schwartz, H. Gilbert Welch
Journal: JAMA (2004)

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
Vasopressin in patients with obstructive sleep apnoea syndrome – An interventional, case-control study
Authors: Peter Grendelmeier, Werner Strobel, Thomas Schmid, Kathleen Jahn, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2014)

Background  Hypoxia, sympathetic activation, vascular endothelial dysfunction, metabolic dysregulation, oxidative stress as well as inflammation play a role in the development of cardiovascular disease in OSAS and are related to the release of vasopressin (AVP). We hypothesize that AVP might serve as a potential proxy for prognosis and therapy response in OSAS.   Methods  289 patients with suspicion of OSAS undergoing a diagnostic work-up were included in this prospective, interventional, longitudinal, case-control study. The primary endpoint was the change in AVP levels after 1 month of CPAP treatment. Secondary endpoints included 1) circulating AVP levels before treatment and after 1 and 6 months of treatment respectively; 2) change in circulating AVP levels after 1 night and 6 months of CPAP treatment respectively; 3) assessment of endpoints in subgroups of patients according to OSAS severity.   Results  243 patients with OSAS (age 55.0 ± 13.0 years, 77.8 % male, BMI 31.2 ± 5.6) and 46 controls without OSAS (age 51.2 ± 14.2 years, 50 % male, BMI 30.7 ± 5.8) were analysed. Mean ODI of patients with OSAS was 18 / h ± 15, mean AHI was 17 / h ± 15. 87.9 % of patients with OSAS started cPAP therapy. After 1 month, 85.1 % of patients with OSAS were on cPAP therapy. There was no significant difference in the slope of change of the AVP level between patients and controls and between OSAS patients with or without CPAP therapy. After adjustment for severity of OSAS, comorbidities and duration of CPAP therapy in minutes the differences remained non-statistically significant.   Conclusions  Vasopressin cannot be used as a proxy for prognosis and therapy response in obstructive sleep apnoea syndrome.
Clinical Laboratory Medicine
Authors: Kenneth D. McClatchey
Journal: JAMA (2002)

annum, and three clerks each at $1,800 per annum, and three messengers each at $900 per annum.Section 3.That the director and specialists, it necessary for the proper discharge of their duties, may place themselves in communication with state and municipal and other officials of this and other countries.Section 4. That for the proper equipment of and carrying on the work of said laboratory, the temporary
Abstract 23: Nuclear receptor PPARα activation triggers hepatic cell death in Ikkβ-deficient mice
Authors: Jung-Hwan Kim, Taehyeong Kim, Aijuan Qu, Frank J. Gonzalez
Journal: Cancer Research (2015)

Abstract Peroxisome proliferator-activated receptor α (PPARα) plays a critical role in lipid metabolism, inflammation, carcinogenesis, and cell survival. Recent study showed that PPARα agonist dramatically induced the cell cycle arrest genes, such as p21 and Gadd45b, in the liver of mice. However, the inductions of these genes were not lead to hepatic cell death. Thus, here, we investigated the Ikkb gene whether this can affect the hepatic cell death or survival after induction of p21 and Gadd45b. To exam the function of Ikkb after PPARα activation, the Wild-type (IkkbF/F) and liver-specific Ikkb-null (IkkbF/F-AlbCre) mice were treated with the PPARα agonist Wy-14,643 for two weeks. As results, Hepatic cell death was undergone to apoptosis by increases of cleaved-caspase-3 and cleaved poly (ADP-ribose) polymerase only in the liver of IkkbF/F-AlbCre mice by Wy-14,643 and this was also supported by TUNEL staining. Moreover, Wy-14,643 treatment elevated phosphorylation of c-Jun N-terminal kinase only in the liver of IkkbF/F-AlbCre mice. Liver histology showed notable feature of hepatitis only in the IkkbF/F-AlbCre mice treated with Wy-14,643. And marked increase Tnfa mRNA was followed in Wy-14,643-treated IkkbF/F-AlbCre mice. However, expression of the gene related to lipid metabolism such as Ppara and Acox1 were not significantly changed by Wy-14,163 in both IkkbF/F and IkkbF/F-AlbCre mice. These studies suggest that Ikkb gene may play a critical role in hepatic cell survival against PPARα activation. Citation Format: Jung-Hwan Kim, Taehyeong Kim, Aijuan Qu, Frank J. Gonzalez. Nuclear receptor PPARα activation triggers hepatic cell death in Ikkβ-deficient mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 23. doi:10.1158/1538-7445.AM2015-23
Drug points: Fatal erythroderma associated with pentostatin
Authors: H S Ghura, A J Carmichael, D Bairstow, R Finney
Journal: BMJ (1999)

A 59 year old woman presented with weight loss and hepatosplenomegaly Her medical history was unremarkable with no history of skin disease She was not taking drugs systemically and gave no history of allergy Full blood count showed a haemoglobin concentration of 142 g/l, a white cell count of 164×109/1 and a platelet count of 105×109/l. The results of cell marker and morphological studies confirmed the diagnosis to be T cell chronic prolymphocytic leukaemia. Her renal function was normal.

She was treated with chlorambucil 10 mg/day. However, despite treatment for 12 weeks, her white cell count rose to 324×109/1 and …
The Great Doctors: A Biographical History of Medicine
Authors: Henry Ernest Sigerist
Journal: JAMA (1934)

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
832. Radioscintigraphy of sec-R Directed CFTR Gene Transfer in CF Mice Following Intranasal Administration
Authors: Assem G. Ziady, Gregory Wojtkicwicz, Pamela B. Davis, Zhenghong Lee
Journal: Molecular Therapy (2004)

Previously, we have shown that compacted DNA targeted to the serpin enzyme complex receptor (sec-R) can deliver amounts of a human CFTR vector sufficient for partial correction of the chloride transport defect and NOS-2 downregulation in the CF knock out mouse nose. To examine the distribution of these compacted DNA particles in vivo following administration, we used radioscintigraphy imaging. We modified our DNA compacting agent (a polymer of poly-L-lysine, chemically conjugated to the C105Y sec-R targeting ligand) with radiolabeled I-125. Prior to dosing, 12 S489X/FABP-hCFTR were imaged by X-ray for proper anatomical alignment with radiograph images. Following complex formulation, 9 mice were dosed intranasally (IN) with 25 μg of sec-R targeted radiolabeled hCFTR DNA (specific activity 50 μCi each), while 3 control mice received administration of free I-125 (specific activity 50 μCi each). We used a small animal gamma scanner produced at Thomas Jefferson National Lab to analyze radio images at 2, 4, 24, and 48 hrs following nasal administration of the dose. At each time 3 animals were sacrificed, frozen and stored for subsequent sectioning. For each mouse, I-125 scintigraphic images, x-ray images, and autoradiographs were aligned and analyzed. Targeted delivery resulted in higher total retained activity than the carrier control at the assayed time points. Both test and control groups begin to exhibit thyroid uptake by 2 hrs. By 2 hrs, scintigraphic and autoradiographic data indicated high activities in the nasal and lower airways in animals that received the targeted complexes compared to controls. The highest observed activity was in thyroid, liver and bladder. Autoradiographic images correlated well with their corresponding in vivo scintigraphic images. For mice that received targeted complexes, strong signals were measured in both abdominal (stomach and liver) and bladder regions indicating possible ingestion during or aspiration following administration, as well as secretion into the bladder. This rapid clearance by 2 hrs was observed for all mice. Regional analysis showed significantly (p < 0.05) higher activities for the targeted delivery in nose, lung and liver compared with controls, 2 and 4 hrs post administration. By 24 hrs, activities in the upper airways (nasal region) and lungs were back to the background level, while activity in the thyroid remained significant at 24 and 48 hrs. The data indicate a rapid clearance of sec-R targeted compacted DNA (by 2 hrs), followed by the appearance of at least the labeled component of the complex (the ligand) in the thyroid and bladder by 4 hrs. Intranasal administration may also result in aspiration or ingestion of the targeted complexes. Alternatively, these complexes or their components may have access to and enter the circulation and accumulate in the liver.
Abstract #LB-281: MicroPET/CT Evaluation of 64Cu Labeled Bevacizumab as A New Tumor Early Detection Probe for PET Imaging In Breast Cancer Orthotopic and Bone Metastasis Model, Compared With 18FDG
Authors: Ting-Tung Chang, Zheng Wang, Long Wang, William Phillips, LuZhe Sun, Beth Goins
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Purpose: To develop and demonstrate the feasibility of a new positron emission tomography (PET) imaging probe targeting vascular endothelial growth factor (VEGF) with higher tumor specificity and decreased background compared with fluorine-18 fluorodeoxyglucose (18FDG) for local and metastatic tumor detection in breast cancer orthotopic and bone metastasis model. Method and Materials: Bevacizumab is a FDA approved monoclonal antibody (mAb) targeting VEGF, the most dominant pro-angiogenesis factor. Bevacizumab was conjugated to a macrocyclic ligand (DOTA) and labeled with a positron emitter, 64Cu. MicroPET/CT imaging was conducted in mouse orthotopic and bone metastasis model by implanting GFP expressing MDA-MB-231 breast cancer cell line (n = 5 for each model). 64Cu-bevacizumab was administered intravenously into each mouse at a dose of 200µCi/40µg mAb. Mice were imaged with microPET/CT scanner at 1h, 4h, 24h and 44h post-injection (p.i.). For comparison with 64Cu-bevacizumab imaging, 18FDG was injected one day before the administration of 64Cu-bevacizumab in the same mouse, and the images were acquired at 1h post-injection. Optical imaging was conducted to verify the tumor location and compare with the PET localization. Biodistribution studies were performed at 44h p.i. Results: With 64Cu-bevacizumab PET imaging, tumors were successfully detected with clear contour and contrast at corresponding sites determined by optical imaging in orthotopic model. Biodistribution results confirmed high accumulation of 64Cu-DOTA-bevacizumab in tumors. In the metastatic model, 64Cu-bevacizumab not only successfully detected the bone metastasis at joints, scapula, and jaw, but also detected the brain metastasis. Tumor findings were confirmed by optical and CT imaging. 18FDG imaging had decreased tumor contrast and failed in detecting the majority of the tumors, especially the metastatic tumors. On 64Cu-bevacizumab images, conventional non-tumor related sites of high 18FDG uptake such as brain, muscle, kidneys and bladder did not appear and there was much less activity in the heart. Conclusion: Results in these mouse breast cancer model studies suggest that 64Cu-DOTA-bevacizumab can be used as a tumor detection agent for local and metastatic breast cancer with good sensitivity, improved tumor-tissue contrast and lower non-tumor tissue related background activity compared to 18FDG imaging.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-281.
Transcatheter Aortic Valve Replacement for Severe Symptomatic Aortic Stenosis Using a Repositionable Valve System
Authors: Ian T. Meredith AM, Darren L. Walters, Nicolas Dumonteil, Stephen G. Worthley, Didier Tchétché, Ganesh Manoharan, Daniel J. Blackman, Gilles Rioufol, David Hildick-Smith, Robert J. Whitbourn, Thierry Lefèvre, Rüdiger Lange, Ralf Müller, Simon Redwood, Dominic J. Allocco, Keith D. Dawkins
Journal: Journal of the American College of Cardiology (2014)
Earthquakes and Takotsubo Cardiomyopathy
Authors: Tomaso Gnecchi-Ruscone
Journal: JAMA (2005)

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
Modernising the NHS: Patient care (empowerment): the view from a national society
Authors: M. Baker
Journal: BMJ (2000)

These two papers form the sixth article in a series of seven 

This week our series on modernising the NHS (in which we are responding to the prime minister's desire to create a national plan for the NHS) covers patient care (empowerment). We asked two people to respond—from different perspectives. In this article Mary Baker writes from her position as chief executive of a prominent national organisation representing people with a specific chronic disease. In the accompanying article on p 1663 Marie Taylor writes as a patient advocate running a local advocacy service .

These are challenging times. People are living longer, and with old age comes frailty and more long term illnesses. At the same time there is a decrease in the availability of informal carers because of the falling birth rate, changes in family structure, and changes in the role of women in society, with more now taking part in higher education and following a career. An urgent need therefore exists to focus more sharply on families affected by chronic disorders so that their needs can be met appropriately. People want to participate in the management of their illness, and we can no longer afford to waste time, scarce resources, and finance. The challenge is to harness the knowledge of patients—and their desire to manage their own condition—to ensure that resources are used wisely and services provided appropriately.

#### Summary points

The NHS needs to work closely with organisations that represent patients and draw on their knowledge and experience

Information technologies can help marshall information for patients—and for healthcare professionals

Commissioning guidance for specific conditions, drawn up with input from patients as well as professionals, can help ensure appropriate services

Patient groups need to support research of all types, from clinical trials to quality of life surveys

Firstly, we must turn …
The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein
Authors: Carsten M. Pusch, Christina Zeitz, Oliver Brandau, Katrin Pesch, Helene Achatz, Silke Feil, Curt Scharfe, Johannes Maurer, Felix K. Jacobi, Alfred Pinckers, Sten Andreasson, Alison Hardcastle, Bernd Wissinger, Wolfgang Berger, Alfons Meindl
Journal: Nature Genetics (2000)