tbuckley/cabot-search huggingface dataset:
Topoisomerase II-alpha (Top2A) and chromosome 17 abnormalities in locally advanced soft tissue sarcomas (LASTS)
Authors: R. Ruiz-Soto, N. Auger, P. Terrier, E. Tournay, D. Françoise, S. Bonvalot, C. Le Péchoux, J. Dômont, J. Bénard, A. Le Cesne
Journal: Journal of Clinical Oncology (2008)

10584 Background: High Top2A protein expression seems to be a relevant early predictive marker for good histologic response (GHR) and better PFS in patients (pts) with LASTS treated with doxorubicin-containing induction chemotherapy (CT) (Ruiz-Soto, ASCO 2007). Whether Top2A overexpression is related to TOP2A gene amplification or deletion and/or aneusomy of chromosome 17 (Chr 17) is unknown. Methods: Top2A IHC protein expression and gene Chr 17 anomalies by FISH analysis (TOP2A probe kit, DAKO, Denmark) were performed in paraffin embedded initial biopsies of LASTS pts treated with induction CT. FISH signals from 60 non overlapping intact tumoral nuclei were evaluated and the mean number signal/cell ratio was determined, TOP2A:centromere 17 (Cep 17) and Cep 17:number of cells ratios were calculated. TOP2A was considered amplified when the ratio was >1.85 and deleted when <0.80. Cep 17 levels between 1.5 and 2.25 were considered as disomic, those <1.5 as monosomic and >2.26 as polysomic. Results: Top2A median value was used to separate high and low Top2A expressing tumors. Of the 60 initial samples, 12 were discarded because of bad DNA quality and 25 have been studied so far. No predominant TOP2A amplifications were found, TOP2A was deleted in 2 cases; both were associated to Top2A protein overexpression and harbored Chr 17 anomalies as well. Aneusomy 17 was found in 10 (40%) of LASTS studied, 1 monosomy in a synovial sarcoma and polysomy in 9 cases. The monosomic sarcoma had low Top2A levels; seven polysomic LASTS overexpressed Top2A and 43% of disomic cases had higher levels of Top2A too. There was no significant correlation between Top2A protein expression and TOP2A or Chr 17 copy number anomalies. Seventy percent of aneusomic LASTS achieved GHR against 46% of disomic LASTS (NS). Of note, disomic LASTS have not achieved median PFS and OS versus 41 and 59 months respectively in aneusomic cases (NS). Conclusions: TOP2A gene and aneusomy 17 are not the sole biological events influencing Top2A protein overexpression in LASTS, the search for Top2A mutation and/or TOP2A altered gene regulation may be of relevance. These observations have to be validated in larger prospective studies. No significant financial relationships to disclose.
A phase I study of paclitaxel, carboplatin, and YM155 (survivin suppressor) in subjects with solid tumors.
Authors: R. J. Kelly, A. Rajan, G. Chun, A. Lopez-Chavez, G. Giaccone
Journal: Journal of Clinical Oncology (2011)

3090 Background: To determine the maximum-tolerated dose (MTD) and to assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity of YM155 (Y), a small-molecule selective survivin suppressant, administered in combination with carboplatin (C) and paclitaxel (P). Methods: Patients with advanced malignancies who had received no more than one prior chemotherapy regimen received C (AUC6) and P (200mg/m2) followed by escalating doses of Y administered as a continuous intravenous infusion (CIVI) over 72 hours in 21-day treatment cycles. Results: Twenty two patients (19 lung, 1 adenoid cystic, 1 angiosarcoma, 1 carcinoma of unknown origin) received 98 cycles of Y at six different dose levels from 3.6 to 12mg/m2 with standard doses of C and P. Treatment with Y was well tolerated, grade 3/4 toxicities consisted of grade 3 neutropenia (41%) and thrombocytopenia (14%) and grade 4 neutropenia (41%). Non hematological toxicities consisted of grade 3 hypophosphatemia (18%), hyponatremia (14%), hypokalemia (9%) and grade 4 hyponatremia (9%). Grade 3 amylase and grade 3 pneumonitis during cycle 1 were considered dose limiting at the 12mg/m2 dose. The MTD was determined as 10mg/m2 and the median steady-state concentration, clearance, volume of distribution, and terminal elimination half-life of YM155 were 16.2 ng/mL, 8.6 L/h/m2, 226 L/m2, and 17 hours, respectively. Of 16 evaluable patients, 5 (31%) achieved a partial response and 11 (69%) achieved stable disease. Conclusions: The combination of Y (10mg/m2/d 72 hours CIVI) administered with C and P every 3 weeks exhibited a favorable safety profile. A phase II trial as first line therapy in patients with stage IV non small cell lung cancer is ongoing.
Concordance of 18F-FDG PET Uptake in Tumor and Normal Tissues on PET/MRI and PET/CT
Authors: W Phillip Law, Nicole Maggacis, Susanne J Jeavons, Kenneth A Miles
Journal: Clinical Nuclear Medicine (2016)

Aim The aim of this study was to assess the concordance of PET measurements of 18F-FDG uptake in tumor and normal tissues obtained on Australia’s first clinical PET/MRI scanner in comparison to PET/CT, with comparison against published data. Methods One hundred subjects were prospectively recruited from an unselected, heterogeneous group of cancer patients to undergo 18F-FDG PET/CT and PET/MRI on the same day. SUVs of physiological regions and tumor tissues obtained by PET/MRI and PET/CT were compared and benchmarked against existing published data. Physiological activity was measured in the thoracic aorta and right lobe of the liver. Tumor SUVs were analyzed by cancer type, body region, and a combined group of all lesions. Results There was an excellent correlation between SUV measurements in tumor lesions obtained by PET/MRI and PET/CT, across all body regions and in all tumor types studied. There was a less robust correlation for SUVs measured in areas of physiological activity, but the level of agreement still fell within 2 SDs of mean. Data from this study showed comparable or smaller systemic biases and narrower confidence limits than existing studies in the literature comparing SUVs from PET/MRI and PET/CT. Conclusions 18F-FDG PET/MRI appears promising as an adjunct or alternative to PET/CT for quantitative evaluation in oncology, independent of body region and tumor type, across a wide range of SUVs.
Abstract 3397: ￼A novel clinical tool that provides quantitative and accurate measurement of Met protein
Authors: Fabiola Cecchi, Wei-Li Liao, Sheeno Thyparambil, Marlene Darfler, David Krizman, Todd Hembrough, Jon Burrows, Don Bottaro, Daniel V.T. Catenacci
Journal: Cancer Research (2015)

Abstract BACKGROUND: Overexpression of Met tyrosine kinase receptor is associated with poor prognosis. Overexpression, and particularly MET amplification, are predictive of response to Met-specific therapy in preclinical models. Immunohistochemistry (IHC) of formalin-fixed paraffin-embedded (FFPE) tissues is currently used to select for ‘high Met’ expressing tumors for Met inhibitor trials. IHC suffers from antibody non-specificity, lack of quantitative resolution, and, when quantifying multiple proteins, inefficient use of scarce tissue. METHODS: After describing the development of the Liquid-Tissue-Selected Reaction Monitoring-mass spectrometry (LT-SRM-MS) Met assay, we evaluated the expression level of Met in 130 FFPE gastroesophageal cancer (GEC) tissues. We assessed the correlation of SRM Met expression to IHC and mean MET gene copy number (GCN)/nucleus or MET/CEP7 ratio by fluorescence in situ hybridization (FISH). RESULTS: Proteomic mapping of recombinant Met identified 418TEFTTALQR426 as the optimal SRM peptide. Limits of detection (LOD) and quantitation (LOQ) for this peptide were 150 and 200 amol/μg tumor protein, respectively. The assay demonstrated excellent precision and temporal stability of measurements in serial sections analyzed one year apart. Expression levels of 130 GEC tissues ranged (&amp;lt;150 amol/μg to 4669.5 amol/μg. High correlation was observed between SRM Met expression and both MET GCN and MET/CEP7 ratio as determined by FISH (n = 30; R2 = 0.898). IHC did not correlate well with SRM (n = 44; R2 = 0.537) nor FISH GCN (n = 31; R2 = 0.509). A Met SRM level of &amp;gt;1500 amol/μg was 100% sensitive (95% CI 0.69-1) and 100% specific (95% CI 0.92-1) for MET amplification. CONCLUSIONS: The Met SRM assay measured the absolute Met levels in clinical tissues with high precision. Compared to IHC, SRM provided a quantitative and linear measurement of Met expression, reliably distinguishing between non-amplified and amplified MET tumors. These results demonstrate a novel clinical tool for efficient tumor expression profiling, potentially leading to better informed therapeutic decisions for patients with GEC. Citation Format: Fabiola Cecchi, Wei-Li Liao, Sheeno Thyparambil, Marlene Darfler, David Krizman, Todd Hembrough, Jon Burrows, Don Bottaro, Daniel V.T. Catenacci. ￼A novel clinical tool that provides quantitative and accurate measurement of Met protein. [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 3397. doi:10.1158/1538-7445.AM2015-3397
Influence of Perceived Risk Factors for Bleeding on Venous Thromboembolism Prophylaxis Practices in Acutely Ill Medical Patients: Findings from IMPROVE.
Authors: Manuel Monreal, Rainer B. Zotz, Hervé Decousus, Beng H. Chong, Geno Merli, Ricardo Pavanello, Mario Pini, Alexander G.G. Turpie, Wei Huang, Frederick A. Anderson
Journal: Blood (2005)
Natural History and Potential for Cure of Patients with Chronic Myeloid Leukemia in Chronic Phase Receiving Frontline Therapy with Recombinant Interferon-Alfa: 30-Year Update From M.D. Anderson Cancer Center
Authors: Alfonso Quintás-Cardama, Hagop M. Kantarjian, Susan O'Brien, Elias J. Jabbour, Guillermo Garcia-Manero, Charles Koller, Sherry A. Pierce, Moshe Talpaz, Jorge E. Cortes
Journal: Blood (2012)
Abstract 1890: Dietary intake of 502 polyphenols and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
Authors: Raul Zamora-Ros, Isabelle Romieu, Augustin Scalbert
Journal: Cancer Research (2015)

Abstract Introduction. Epidemiological evidence on the association between polyphenol intake and colorectal cancer (CRC) risk is still inconsistent. Case-control studies suggest inverse associations, but these were not confirmed in cohort studies so far. Moreover, to date, only some polyphenol classes (flavonoids and lignans) have been studied. We aimed to explore the association between polyphenol intake and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Design. The study included 477,386 subjects (29.8% men) aged 35-70 years from 10 European countries. Both lifestyle and dietary questionnaires were collected at enrollment. Dietary polyphenol intakes were estimated using dietary questionnaires and the Phenol-Explorer database, including data on 502 individual polyphenols in 452 plant-based foods. Retention factors for processed and cooked food from the Phenol-Explorer database were also applied. Results. After a mean follow-up of 11 years, 4,701 validated incident CRC cases (2,979 colon cancer and 1,722 rectal cancer) were identified and included in the analysis. A wide range of total polyphenol intake and a South-to-North geographical gradient (ranging from 584mg/d in Greek women to 1,786mg/d and Danish men) were observed. Phenolic acids (52.6%) were the main contributors to total polyphenol intake, followed by flavonoids (42.4%), alkylphenols (2.7%), tyrosols (1.0%), lignans, stilbenes and other minor polyphenols (&amp;lt;0.3%). Coffee, tea and fruits were the most important food sources of total polyphenols. Cox proportional hazards model will be used to calculate hazard ratios and 95% confidence intervals of CRC for categories of dietary polyphenols intake (total and by classes and subclasses). All analyses will be done separately for CRC and by anatomical subsite: colon, proximal and distal colon, and rectum. Several risk factors known or suspected to influence CRC risk will be considered as potential confounders. Conclusions. This will be the first study evaluating the association between all polyphenol classes and CRC risk. EPIC is a convenient study to assess these relationships due to the large number of CRC cases, its longitudinal study design, and the high variability in the polyphenol intake amongst the participants across Europe. Citation Format: Raul Zamora-Ros, Isabelle Romieu, Augustin Scalbert, EPIC Study group. Dietary intake of 502 polyphenols and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. [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 1890. doi:10.1158/1538-7445.AM2015-1890
Predictive value of contrast enhancement on computed tomography for the responses to oxaliplatin-based chemotherapy with bevacizumab for hepatic metastases from colorectal cancer.
Authors: G. Osawa, K. Yoshimatsu, H. Yokomizo, T. Otani, A. Matsumoto, M. Nakayama, Y. Yano, K. Ogawa
Journal: Journal of Clinical Oncology (2011)

e14105 Background: The addition of bevacizumab (Bev) to chemotherapy is associated with improved survival by anti-angiogenic mechanism in colorectal cancer (CRC). Therefore, the antitumor effect of Bev may correlate with the degree of the contrast-enhancement (CE) of targets reflecting tumor microvessels on the computed tomography (CT). The purpose of this study was to determine whether responses to chemotherapy with bevacizumab correlated with the degree of CE of hepatic metastatic lesions of colorectal cancer (CRC). Methods: Thirty one patients with hepatic metastases from CRC who underwent at least three course of mFOLFOX6 or XELOX therapy as the first-line chemotherapy between September 2006 and April 2010 were analyzed retrospectively. The patients were divided into two groups with or without Bev (17 in the Bev group and 14 in the non-Bev group). CT scans were performed during the late arterial phase following intravenous injection with a nonionic contrast medium at a dose of 600 mgI/kg, using a multi detector CT. Using an imaging control system, the diameter and mean CT values of metastatic lesions before chemotherapy were determined in each patient. The degree of CE was evaluated by the ratio of the CT value of hepatic metastases in the late arterial phase by in the noncontrast phase (i.e., CE ratio), whereby the patients were divided into the high or low CE group by the median CE ratio. Results: There was significant correlation between the CE ratio and the tumor shrinkage rate in the Bev group (R2 =0.3817, p=0.0082), whereas no such relationship was noted in the non-Bev group. In the high CE group (n=16), the tumor shrinkage rate increased to 35.9% in the Bev group from 8.6% in the non-Bev group (p=0.0716). In the low CE group, however, no significant difference was noted. Conclusions: The present study demonstrated the correlation between the CE ration and the tumor shrinkage in patients treated with Bev. The results suggest that the CE ratio on CT scanning in hepatic metastatic lesion can be a predictive value for the response to chemotherapy with Bev, although generalization of the CE ratio and the prospective study should be need.
Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site
Authors: Carlos R. Zárate-Bladés, Reiko Horai, Mary J. Mattapallil, Nadim J. Ajami, Matthew Wong, Joseph F. Petrosino, Kikuji Itoh, Chi-Chao Chan, Rachel R. Caspi
Journal: Gut Microbes (2017)

Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology. It is unknown where and how autoreactive T cells become primed to trigger disease in the eye, which is an immune privileged site. We recently reported data supporting the notion that retina-specific T cells receive a signal in the gut from commensal microbiota-derived cross-reactive antigen(s) and trigger autoimmune uveitis in the R161H mouse model. Here we discuss our published findings, as well as our recent attempts to identify the responsible microbe(s) by using different antibiotic treatments, 16S rDNA sequencing and homology searches for candidate antigenic mimic(s) of the retinal antigen.
First Achievements of MPN&amp;MPNr-EuroNet (COST Action BM0902), a New European Network Dedicated to the Diagnosis of Myeloproliferative Neoplasms and Hereditary Erythrocytosis and Thrombocytosis
Authors: Sylvie Hermouet, Eric Lippert, Niels Pallisgaard, Jiri Schwarz, Mary Frances McMullin, Lars Palmqvist, Heike L Pahl, Beatriz Bellosillo Paricio, Celeste Bento, Serge Carillo, Stephane Giraudier, Francois Girodon, Melanie Percy, Lukas Plank, Susanne Schnittger, Radek C. Skoda, Alessandro M. Vannucchi
Journal: Blood (2011)
The Women, Infants, and Children Food Package and 100% Fruit Juice
Authors: Ronald E. Kleinman, Theresa Nicklas
Journal: JAMA Pediatrics (2016)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Abstract 1909: Effect of Coronary Artery Calcium Score on Complete Coronary Tree Visualization by 64-Slice Computed Tomographic Coronary Angiography
Authors: Victor Cheng, Hooman Madyoon, Ashkan L Naraghi, Shervin Eshaghian, Norman E Lepor
Journal: Circulation (2006)

Background: Coronary artery calcium (CAC) is known to significantly limit visualization of the coronary arterial tree by 4- and 16-slice computed tomographic coronary angiography (CTCA). We aimed t...
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia
Authors: Esther Meyer, Keren J Carss, Julia Rankin, John M E Nichols, Detelina Grozeva, Agnel P Joseph, Niccolo E Mencacci, Apostolos Papandreou, Joanne Ng, Serena Barral, Adeline Ngoh, Hilla Ben-Pazi, Michel A Willemsen, David Arkadir, Angela Barnicoat, Hagai Bergman, Sanjay Bhate, Amber Boys, Niklas Darin, Nicola Foulds, Nicholas Gutowski, Alison Hills, Henry Houlden, Jane A Hurst, Zvi Israel, Margaret Kaminska, Patricia Limousin, Daniel Lumsden, Shane McKee, Shibalik Misra, Shekeeb S Mohammed, Vasiliki Nakou, Joost Nicolai, Magnus Nilsson, Hardev Pall, Kathryn J Peall, Gregory B Peters, Prab Prabhakar, Miriam S Reuter, Patrick Rump, Reeval Segel, Margje Sinnema, Martin Smith, Peter Turnpenny, Susan M White, Dagmar Wieczorek, Sarah Wiethoff, Brian T Wilson, Gidon Winter, Christopher Wragg, Simon Pope, Simon J H Heales, Deborah Morrogh, Alan Pittman, Lucinda J Carr, Belen Perez-Dueñas, Jean-Pierre Lin, Andre Reis, William A Gahl, Camilo Toro, Kailash P Bhatia, Nicholas W Wood, Erik-Jan Kamsteeg, Wui K Chong, Paul Gissen, Maya Topf, Russell C Dale, Jonathan R Chubb, F Lucy Raymond, Manju A Kurian
Journal: Nature Genetics (2016)
194. Lymphatic Transport Mediates Systemic Leakage of Peripherally Administered AAV9 Vectors
Authors: Ruth M. Castellanos Rivera, Lavanya Rao, Giridhar Murlidharan, Travis Corriher, Aravind Asokan
Journal: Molecular Therapy (2015)

Adeno-associated viruses (AAV) have emerged as promising vector candidates for gene therapy of central nervous system (CNS) disorders. Preclinical studies in rodents as well as large animal models such as cats and non-human primates have shown that AAV9 mediates robust and widespread gene expression in the brain and spinal cord. In particular, after intracranial or intrathecal administration, leakage into the systemic circulation and accumulation of vector genomes in off-target organs such as the liver or spleen presents a potential safety concern. Here, we demonstrate that intrathecal administration of AAV9 transduces not only systemic and peripheral tissues, but also the peripheral lymph nodes. Significantly higher vector genome copy numbers were recovered from both systemic and lymphoid organs. Furthermore, AAV9 vectors are found specifically in the draining popliteal lymph nodes following hind footpad injection, an established model for studying lymphatic transport. Vector genomes from the blood circulation were recovered as early as 1 hour postadministration through intrathecal or footpad routes suggesting rapid transport. Similar observations were made in case of AAV8 vectors. In contrast, AAV2 vectors injected through either route were only recovered at the site of injection. Mutation of heparin binding residues on the AAV2 capsid mediated robust spread of vectors through the lymphatic drainage and systemic leakage. Together, these observations suggest that lymphatic vessels and lymph nodes are likely conduits for the systemic spread of AAV9 vectors following intrathecal administration. Further investigation is required to study the mechanisms that determine lymphatic transport of AAV9 vectors. These findings are important towards establishing the safety of gene therapy-based approaches to treat neurological diseases.
Phlebotomy vs. Myelosuppressive Medications in Controlling Erythrocytosis in Polycythemia Vera (PV) Patients: Impact upon Fatigue in a Survey of 405 PV Patients.
Authors: Ruben A. Mesa, Joyce Niblack, Angelina D. Tan, Pamela J. Atherton, Jeff A. Sloan, Ayalew Tefferi
Journal: Blood (2006)
Pregnancy Outcome Following Haematopoietic Stem Cell Transplantation.
Authors: Samar Kulkarni, Mark Ethell, Jennifer Treleaven, Radovan Saso, Joy Brennan, Pawel Kaczmarek, Caroline Alvares, Clive Horton, Frank Saran, Pamala Kanagasabapathy, Prashant Hiwarkar, Stella Appiah-Cubi, Moez Dungarwala, Raymond Powles, Gareth Morgan, Michael Potter
Journal: Blood (2006)
Influence of Gender and Coagulation Factors on Efficacy and Safety of Rivaroxaban in Adolescents &amp; Young Adults with Venous Thromboembolism
Authors: Manuela Krause, Verena Limperger, Anna Henningsen, Hartmut Clausnizer, Gili Kenet, Dorothee Kowalski, Ulrike Nowak-Gottl
Journal: Blood (2015)