tbuckley/cabot-search huggingface dataset:
Abstract 1855: Structural requirements for the association of the ETS domain transcription factor Elk1 and the androgen receptor in enabling the growth of prostate cancer cells
Authors: Rayna Rosati, Venkatesh Chari, Mugdha Patki, Manohar Ratnam
Journal: Cancer Research (2015)

Abstract The ETS domain transcription factor Elk1 tethers the androgen receptor (AR) to chromatin, enabling sustained activation of a set of genes critical for cell growth in established prostate cancer cell lines. This role of Elk1 is independent of the ability of Elk1 to transiently activate immediate early genes in response to phosphorylation by ERK. We compared the structural requirements for the association of AR and Elk1 with that for activation of Elk1 by phosphorylation using mammalian one- and two-hybrid assays. The critical polypeptide segments were mapped by systematic deletion mutagenesis. The amino-terminal A/B domain of AR, which lacks the ligand-binding domain (LBD), was adequate for association with Elk1 and to activate Elk1-AR target genes in LNCaP prostate cancer cells. The AR A/B domain also supported hormone-independent growth of LNCaP cells reflecting the ability of overexpressed natural splice variants of AR, which also lack LBD, to support prostate tumor growth. The association of AR with Elk1 did not require ERK1/2 or serum response factor (SRF), which are the known binding partners of Elk1. We identified two sites on Elk1 that are critical for its association with the AR A/B domain as well as the whole AR molecule. One of those sites spans amino acid residues 297 to 317, overlapping one of two ERK docking sites. The other site on Elk1 mapped to amino acid residues 387 to 397, adjacent to the downstream ERK docking site. The results suggest that the association of AR with Elk1 in situ is direct rather than through the Elk1 ternary complex and that the association may be disrupted by small molecules to selectively inhibit growth signaling in prostate cancer cells. Citation Format: Rayna Rosati, Venkatesh Chari, Mugdha Patki, Manohar Ratnam. Structural requirements for the association of the ETS domain transcription factor Elk1 and the androgen receptor in enabling the growth of prostate cancer cells. [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 1855. doi:10.1158/1538-7445.AM2015-1855
A Randomized Phase II Study Comparing Imatinib and the Combination of Imatinib and Pegylated Interferon Alpha-2b in Newly Diagnosed Non-High Risk Chronic Myeloid Leukemia (CML) Patients in Complete Hematological Remission After Imatinib Induction Therapy.
Authors: Bengt Simonsson, Tobias Gedde-Dahl, Berit Markevärn, Kari Remes, Jesper Stentoft, Anders Almqvist, Mats Björeman, Max Flogegård, Heikki Hallman, Perttu Koskenvesa, Anders Lindblom, Claes Malm, Satu Mustjoki, Kristina Myhr-Eriksson, Anu Räsänen, Marjatta Sinisalo, Risto Sippola, Anders Själander, Ulla Strömberg, Ole Weiss Bjerrum, Hans Ehrencrona, Franz Gruber, Veli Kairisto, Karin RN Olsson, Arnon Nagler, Johan Lanng Nielsen, Henrik Hjorth-Hansen, Kimmo Porkka
Journal: Blood (2009)
FG-4497, a Pharmacological Stabilizer of HIF-1α Protein, Synergistically Enhances Hematopoietic Stem Cells (HSC) Mobilization in Response to G-CSF and Plerixafor
Authors: Catherine E Forristal, Bianca Nowlan, Valerie Barbier, Ingrid G Winkler, Gail Walkinshaw, Jean-Pierre Levesque
Journal: Blood (2012)
Abstract 4904: Developing a universal target retrieval solution and protocol for RNA <i>in situ</i> hybridization based on RNAscope technology
Authors: Li-chong Wang, Liuliu Pan, Kuang-Jung Chang, Daniel Kim, Xingyong Wu, Hongwei Wang, Casey Kernag, Bingqing Zhang, Mingxiao He, Nan Su, Xiao-Jun Ma, Yuling Luo
Journal: Cancer Research (2015)

Abstract Heat induced target retrieval (HITR) is a widely adopted approach for Immunohistochemistry (IHC) and in situ hybridization (ISH) applications on formalin fixed and paraffin embedded (FFPE) tissues to facilitate target access and increase detection sensitivity. A variety of factors, such as fixative type, fixation time, tissue type, epitope abundance, antibody affinity, and probe length greatly affect the efficiency of HITR. Given such variability, over the decades, multiple HITR buffer formulations and protocols were invented to fit the needs in different experimental scenarios. We have developed a novel HITR solution that allows highly efficient target retrieval for RNA ISH application based on the RNAscope technology. When tested on 15 different tumor types, the new HITR solution resulted in significantly better sensitivity and/or tissue morphology comparing to using traditional HITR buffers, including Citrate, EDTA, and Tris based buffers with various pH. Furthermore, this new HITR solution is highly tolerant to sample variability. When used on multiple human tumor tissue microarrays (TMAs), including breast, colon, lung, and gastric cancers, the new HITR solution improved overall signal-to-noise ratio and reduced core disqualification rate, compared to traditional citrate based HITR buffer for ISH. Moreover, when tested on multiple mouse tissues fixed with different types of fixatives for varying periods of time (6 - 72 hours), a single experimental condition with the new HITR solution showed comparable results in both detection sensitivity and morphological integrity in all the samples. It also allowed detection of a target (Tbp) with extremely low abundance (&amp;lt;5 copies/cell). Given that all the RNAscope probes are synthetic oligonucleotide probes with length shorter than 60 bases, the new HITR solution, in combination with the RNAscope technology, will allow universal detection of any RNA targets with single molecule detection sensitivity in FFPE tissues with minimal requirement for analytical condition optimization. Citation Format: Li-chong Wang, Liuliu Pan, Kuang-Jung Chang, Daniel Kim, Xingyong Wu, Hongwei Wang, Casey Kernag, Bingqing Zhang, Mingxiao He, Nan Su, Xiao-Jun Ma, Yuling Luo. Developing a universal target retrieval solution and protocol for RNA in situ hybridization based on RNAscope technology. [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 4904. doi:10.1158/1538-7445.AM2015-4904
Evaluating a Value-Driven Outcomes Program
Authors: William B. Weeks
Journal: JAMA (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 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
Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525.
Authors: T. S. Armstrong, J. S. Wefel, M. Wang, M. Won, A. Bottomley, T. R. Mendoza, C. Coens, M. Werner-Wasik, D. Brachman, A. K. Choucair, M. R. Gilbert
Journal: Journal of Clinical Oncology (2011)

2016 Background: RTOG 0525, a randomized phase III study compared dose-dense (dd) versus standard dose (sd) temozolomide in patients with newly diagnosed glioblastoma. NCF tests, and Symptom and QOL questionnaires examined the Net Clinical Benefit (NCB) of therapy. The prognostic value of NCB measures for survival outcomes and the differential impact of therapy are reported here. Methods: NCF (Hopkins Verbal Learning Test-Revised, Trail Making Test, Controlled Oral Word Association), and Symptom (M. D. Anderson Symptom Inventory-Brain Tumor Module [MDASI-BT]) and QOL questionnaires (EORTC QLQ-C30/BN20) were completed in a subset of patients at baseline (B) and longitudinally while on study. Univariate (UV) and multivariate (MV) Cox proportional hazard regression modeling determined the prognostic value of a priori selected assessments at baseline (B) and early change from B to cycle 1 (C1Δ) for overall (OS) and progression free survival (PFS). Two-sample proportional test statistic was used to evaluate differences between treatments (dd vs sd) in symptomatic worsening from B to cycle 4 (C4Δ) in patients without progression. Results: Of 182 randomized patients (246 consented) > 85% completed assessment at B. NCF tests and the physical functioning QOL scale were associated with OS and PFS at B. C1Δ in all NCB components were associated with OS and PFS. The MDASI-BT and global QOL detected symptomatic differences between arms (dd > sd) at C4Δ. Conclusions: Longitudinal collection of NCB measures is feasible and complementary (Table) in cooperative group studies providing an added dimension to standard outcome measures. NCF and QOL at baseline were prognostic for OS and PFS and may impact stratification; NCB early changes were associated with OS and PFS and may help to assess response or progression; and MDASI-BT and QOL changes demonstrated sensitivity to adverse treatment effects (dd>sd) arm and may help in risk/benefit analyses. Support: NCI U10CA 21661, U10CA37422, ABC2, and Merck Pharmaceuticals. P<0.05 OS PFS Toxicity dd vs sd + = 1, ++ > 1 module UV MV UV MV B NCF ++ ++ ++ + MDASI QOL + + + + B→C1Δ NCF ++ ++ ++ + MDASI ++ + + + QOL + + B→C4Δ NCF MDASI ++ QOL +
Minimal Residual Disease Detection By Multiparametric Flow Cytometry in Newly Diagnosed Multiple Myeloma Patients: A Preliminary Analysis of the EMN02/HO95 MM Study
Authors: Stefania Oliva, Manuela Gambella, Milena Gilestro, Francesca Gay, Alessandra Larocca, Anna Marina Liberati, Francesca Bonello, Giulia Benevolo, Giovannino Ciccone, Tommaso Caravita, Vittorio Emanuele Muccio, Simona Caltagirone, Stefano Spada, Barbara Gamberi, Simone Ferrero, Marina Ruggeri, Giuseppe Rossi, Elona Saraci, Massimo Offidani, Maria Teresa Petrucci, Mario Boccadoro, Pieter Sonneveld, Antonio Palumbo, Paola Omedè
Journal: Blood (2015)
D-dimer test and multidetector-row CT as the diagnostic test in suspected venous thromboembolism in colorectal cancer patients with pharmacokinetic modulating chemotherapy (PMC)
Authors: R. Yoshikawa, H. Yanagi, M. Noda, M. Gega, M. Tanooka, T. Nasada, S. Higasa, T. Hashimoto-Tamaoki, T. Yamamura
Journal: Journal of Clinical Oncology (2004)

8118 Background: Colorectal cancer patients with central venous catheter using PMC have a substantial risk of venous thromboembolism (VTE), although we have had clinical success with PMC, whose regimen was designed as a hybrid of lower metronomic (UFT, Taiho Pharmaceutical Co., Tokyo, Japan) and higher shorter plasma 5-FU concentration (cumulative 5-year survival rate of Dukes' C; 95% in PMC versus 67% in non-PMC group, Proc Am Soc Clin Oncol 22: 1175, 2003). To determine the effectiveness and safety of using D-dimer test and multidetector-row CT (MDCT) as the diagnostic test in cancer patients with suspected VTE, a clinical outcome study was performed in PMC patients through outpatient clinic. Methods: Patients asymptomatically underwent D-dimer test before and after the commencement of PMC regimen. MDCT was additionally performed after showing positive D-dimer. When CT results were positive for VTE, anticoagulation was started. Quality inspection for used catheters (6Fr. Anthrone P-U catheter and Cell site port, Toray Medical Co., Tokyo, Japan) of these patients with VTE through measurement of macro property, toluidineblue dyeing test, and scanning electron microscope were carried out. Results: The overall prevalence of VET in PMC patients have been 2.0% (7 of 350 patients) so far. In this study, 55 patients were enrolled who underwent a curative operation for Dukes' B or C colorectal cancer after December 2002, performed PMC as an adjuvant chemotherapy, and followed over 6 months. 17 out of 55 patients showed positive D-dimer test (30.9%). CT identified venous thrombi in 2 patients (3.7%) and mural thrombosis on catheterized veins in 6 patients (10.9%). The catheters of these patients per se didn't show any significant abnormalities. Patients with negative D-dimer test showed no signs and symptoms of VET. No patients died of fatal VET. Conclusions: In colorectal cancer patients who underwent PMC via central venous catheter, D-dimer test can be used safely as the primary screening test to rule out VET. MDCT can be informative in diagnosis for such patients. No significant financial relationships to disclose.
The Ancient Remedies of Alopecia
Authors: Valencia Long
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Readmission Rates After Passage of the Hospital Readmissions Reduction Program
Authors: Jason H. Wasfy, Corwin Matthew Zigler, Christine Choirat, Yun Wang, Francesca Dominici, Robert W. Yeh
Journal: Annals of Internal Medicine (2016)

Whether hospitals with the highest risk-standardized readmission rates (RSRRs) subsequently experienced the greatest improvement after passage of the Medicare Hospital Readmissions Reduction Program (HRRP) is unknown.To evaluate whether passage of the HRRP was followed by acceleration in improvement in 30-day RSRRs after hospitalizations for acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia and whether the lowest-performing hospitals had faster acceleration in improvement after passage of the law than hospitals that were already performing well.Pre-post analysis stratified by hospital performance groups.U.S. acute care hospitals.15 170 008 Medicare patients discharged alive from 2000 to 2013.Passage of the HRRP.30-day readmission rates after hospitalization for AMI, CHF, or pneumonia for hospitals in the highest-performance (0% penalty), average-performance (>0% and <0.50% penalty), low-performance (≥0.50% and <0.99% penalty), and lowest-performance (≥0.99% penalty) groups.Of 2868 hospitals serving 1 109 530 Medicare discharges annually, 30.1% were highest performers, 44.0% were average performers, 16.8% were low performers, and 9.0% were lowest performers. After controlling for prelaw trends, an additional 67.6 (95% CI, 66.6 to 68.4), 74.8 (CI, 74.0 to 75.4), 85.4 (CI, 84.0 to 86.8), and 95.1 (CI, 92.6 to 97.5) readmissions per 10 000 discharges were found to have been averted per year in the highest-, average-, low-, and lowest-performance groups, respectively, after passage of the law.Inability to distinguish between improvement caused by the magnitude of the penalty or by different levels of health improvement in different patient populations.After passage of the HRRP, 30-day RSRRs for myocardial infarction, heart failure, and pneumonia decreased more rapidly than before the law's passage. Improvement was most marked for hospitals with the lowest prelaw performance.National Institutes of Health.
Abstract 2957: Investigating methyl-CpG DNA recognition in cancer
Authors: Tommy W. Terooatea, Megan J. Wallace, Marta W. Szulik, Alan C. Chugg, Sven Miller, Bethany A. Buck-Koehntop
Journal: Cancer Research (2015)

Abstract DNA methylation is an essential epigenetic modification in eukaryotes required for genomic stability, control of gene expression and regulation of chromatin structure. Consequently, abhorrent alterations in methyl-CpG modifications across the genome, leading to inappropriate transcription, are associated with many diseases including cancer. Thus, an interest in discerning the regulatory mechanisms linking DNA methylation with gene expression in the disease state has emerged. The ZBTB methyl-CpG binding proteins (MBPs) are specialized transcription factors that mediate transcription by specifically targeting both methylated and sequence-specific DNA sites through a conserved set of Cys2His2 zinc fingers. While ZBTB MBP expression has become increasingly associated with higher grade tumors, we have only begun to understand the underlying complexities by which this family mediates gene expression. Here we combine interdisciplinary in cell genomic with in vitro biophysical approaches to begin to delineate the mechanisms by which this family of MBPs recognize DNA and regulate transcription in cancer. Specifically, for the founding member of this MBP family we utilized multiple genome-wide methodologies to identify its genomic targets, the methylation status at these sites and the transcriptional effect of this protein in cancer cell lines. We observed that protein expression levels, gene occupations and transcriptional responses were variable between cancer phenotypes. Additionally, ZBTB depletion results in variable phenotypic alterations between cell types indicating that protein presence may provide a means for defining these pathological states. Further, we have designed multiple protein constructs around the zinc finger domains of the ZBTB MBPs. Biophysical characterization of the binding interactions of these protein regions with various epigenetically modified DNAs has provided preliminary understanding for the differential mode of DNA recognition exhibited by the ZBTB MBP family members. Together, these findings provide initial insights into the molecular basis by which these proteins preferentially recognize, interpret and translate epigenetic signals into transcriptional responses in cancer cells. Citation Format: Tommy W. Terooatea, Megan J. Wallace, Marta W. Szulik, Alan C. Chugg, Sven Miller, Bethany A. Buck-Koehntop. Investigating methyl-CpG DNA recognition in cancer. [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 2957. doi:10.1158/1538-7445.AM2015-2957
Abstract 2926: DR5-targeting sensitizes Lgr5+ stem cells to p53 and Chk2-dependent chemotherapy-induced cell death and produces dose-limiting gastrointestinal toxicity (GIT)
Authors: Niklas K. Finnberg, Prashanth Gokare, Arunasalam Navaraj, Krystle A. Lang Kuhs, George Cerniglia, Hideo Yagita, Kazuyoshi Takeda, Noboru Motoyama, Wafik S. El-Deiry
Journal: Cancer Research (2015)

Abstract Current ongoing clinical trials are exploring combined targeting of the TRAIL-death receptor DR5 with radiochemotherapy. It is not clear mechanistically why targeting of the DR5 increasingly sensitizes cancer cells to cell death without affecting cells in normal tissues. Preclinical data suggests that integration of DR5 agonist antibodies into chemotherapy protocols has the promise to significantly improve cancer specific responses without negatively impacting dose-limiting toxicities. Here we show that targeting of DR5 in mice with the mouse-specific mAb MD5-1 in combination with chemotherapy triggers synergistic gastrointestinal toxicities (GIT) that is associated with the death of Lgr5+ crypt basal columnar (CBC) cells. This type of GIT is mediated by p53 and in the case of irinotecan, the cell cycle checkpoint kinase 2 (Chk2). Pharmacologic targeting of Chk2 sensitized syngeneic mouse colorectal cancer tumors lacking P53 to the irinotecan/MD5-1 combination while at the same time protecting the gastrointestinal tract from injury. Our data indicates that blockade of cell cycle checkpoint kinases can help prevent GIT triggered by a combination of DNA damaging chemotherapy and DR5 agonists. Pharmacologic targeting of Chk2 can improve the anti-tumor response of such drug combinations and subsequently provides a rationale on how to improve therapeutic indices of DR5-targeting in the context of chemotherapy usage. Citation Format: Niklas K. Finnberg, Prashanth Gokare, Arunasalam Navaraj, Krystle A. Lang Kuhs, George Cerniglia, Hideo Yagita, Kazuyoshi Takeda, Noboru Motoyama, Wafik S. El-Deiry. DR5-targeting sensitizes Lgr5+ stem cells to p53 and Chk2-dependent chemotherapy-induced cell death and produces dose-limiting gastrointestinal toxicity (GIT). [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 2926. doi:10.1158/1538-7445.AM2015-2926
631. Novel Polymer-Coated Stealth Oncolytic Measles Virus Overcame Immune Suppression and Induced Stronger Antitumor Activity
Authors: Kaname Nosaki, Katsuyuki Hamada, Yuto Takishima, Miyako Sagara, Yumiko Matsumura, Shohei Miyamoto, Michiyo Okada, Yasuki Hijikata, Toshihiko Okazaki, Kazunari Yamada, Hiroyuki Inoue, Yoichi Nakanishi, Kenzaburo Tani
Journal: Molecular Therapy (2015)

Background: Although there have recently been much progress in cancer treatment including surgery, chemotherapy and radiotherapy, cancers have long been the leading cause of death in Japan in the last 30 years and the development of new therapeutic modalities is imminently required. As a new modality, there has recently been great interest in oncolytic virotherapy. Particularly, measles virus is one of the candidate viruses expected for strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the immune response of the host in previous clinical trials. Methods: To enhance and prolong the antitumor activity of the virotherapy in vivo, we combined newly developed tools of the genetically engineered measles virus (MV-NPL) and multilayer virus coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with naked MV-NPL in vitro and in vivo. Results: In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than naked MV-NPL in vitro. We also examined the antitumor immunity in virus treated mice. Complement-dependent cytotoxicity activities in mice treated with polymer-coated MV-NPL were higher than those with naked virus and stronger antitumor activity was observed in these mice. Conclusion: This novel polymer-coated MV-NPL may be promising for future clinical cancer therapy.