tbuckley/cabot-search huggingface dataset:
Ovarian Cancer Incidence Among Asian Migrants to the United States and Their Descendants
Authors: L. J. Herrinton, J. L. Stanford, S. M. Schwartz, N. S. Weiss
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Ovarian Cancer Incidence Among Asian Migrants to the United States and Their Descendants Get access Lisa J. Herrinton, Lisa J. Herrinton Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash., and the Department of Epidemiology, University of WashingtonSeattle, Wash Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet L. Stanford, Janet L. Stanford Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash., and the Department of Epidemiology, University of WashingtonSeattle, Wash Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephen M. Schwartz, Stephen M. Schwartz Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash., and the Department of Epidemiology, University of WashingtonSeattle, Wash Search for other works by this author on: Oxford Academic PubMed Google Scholar Noel S. Weiss Noel S. Weiss * Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash., and the Department of Epidemiology, University of WashingtonSeattle, Wash *Correspondence to present address: Lisa J. Her-rinton, Ph.D., Division of Research, Kaiser Per-manente, 3505 Broadway Ave., Oakland, CA 94611. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 17, 7 September 1994, Pages 1336–1339, https://doi.org/10.1093/jnci/86.17.1336 Published: 07 September 1994 Article history Received: 04 February 1994 Revision received: 20 May 1994 Accepted: 10 June 1994 Published: 07 September 1994
BoCaTFBS: a boosted cascade learner to refine the binding sites suggested by ChIP-chip experiments.
Authors: Lu-yong Wang, Michael Snyder, Mark Gerstein
Journal: Genome biology (2006)

Abstract Comprehensive mapping of transcription factor binding sites is essential in postgenomic biology. For this, we propose a mining approach combining noisy data from ChIP (chromatin immunoprecipitation)-chip experiments with known binding site patterns. Our method (BoCaTFBS) uses boosted cascades of classifiers for optimum efficiency, in which components are alternating decision trees; it exploits interpositional correlations; and it explicitly integrates massive negative information from ChIP-chip experiments. We applied BoCaTFBS within the ENCODE project and showed that it outperforms many traditional binding site identification methods (for instance, profiles).
Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR
Authors: Daphne W Bell, Ira Gore, Ross A Okimoto, Nadia Godin-Heymann, Raffaella Sordella, Roseann Mulloy, Sreenath V Sharma, Brian W Brannigan, Gayatry Mohapatra, Jeff Settleman, Daniel A Haber
Journal: Nature Genetics (2005)
Decreased bioactivity of the guanine nucleotide-binding protein that stimulates adenylate cyclase in hearts from cardiomyopathic Syrian hamsters.
Authors: P D Kessler, A E Cates, C Van Dop, A M Feldman
Journal: Journal of Clinical Investigation (1989)

We investigated regulation of cardiac adenylate cyclase in 29-d-old BIO 14.6 Syrian hamsters, which inherit cardiomyopathy as an autosomal recessive trait. Pharmacologic stimulation of adenylate cyclase in cardiac membranes with isoproterenol, fluoride ion, guanine nucleotide, forskolin, and manganous ion indicated that there was defective coupling of the guanine nucleotide-binding protein that stimulates adenylate cyclase (Gs) to adenylate cyclase. Cyc complementation assays revealed congruent to 50% less Gs activity in cardiac and skeletal muscle from cardiomyopathic hamsters. Despite this decrease in functional Gs, there were no changes in immunologic levels of the alpha-subunit of Gs (alpha Gs) or in levels of mRNA encoding alpha Gs. The defect in Gs bioactivity was limited to cardiac and skeletal muscle, occurred only in animals homozygous for the dystrophic trait, and was demonstrable before any cardiac abnormalities were evident on light microscopy. By contrast, cardiac levels of beta-adrenergic receptors were not different in cardiac membranes from BIO 14.6 hamsters. We conclude that a functional defect in alpha Gs may contribute to a contractile abnormalities in the cardiomyopathic BIO 14.6 hamster. However, the etiology of the alpha Gs defect remains obscure.
Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer
Authors: Yasmine Nadler, Robert L. Camp, Candice Schwartz, David L. Rimm, Harriet M. Kluger, Yuval Kluger
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The cell cycle mediators Aurora A and B are targets of drugs currently in clinical development. As with other targeted therapies in breast cancer, response to therapy might be associated with target expression in tumors. We therefore assessed expression of Aurora A and B in breast tumors and studied associations with clinical/pathologic variables. Experimental Design: Tissue microarrays containing primary specimens from 638 patients with 15-year follow-up were employed to assess expression of Aurora A and B using our automated quantitative analysis method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot and measured Aurora A and B expression within the mask using Cy5-conjugated antibodies. Results: Aurora A and B expression was variable in primary breast tumors. High Aurora A expression was strongly associated with decreased survival (P = 0.0005). On multivariable analysis, it remained an independent prognostic marker. High Aurora A expression was associated with high nuclear grade and high HER-2/neu and progesterone receptor expression. Aurora B expression was not associated with survival. Conclusions: Aurora A expression defines a population of patients with decreased survival, whereas Aurora B expression does not, suggesting that Aurora A might be the preferred drug target in breast cancer. Aurora A expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted treatment. Prospective studies are needed to confirm the prognostic role of Aurora A as well as the predictive role of Aurora A expression in patients treated with Aurora A inhibitors.
Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26+ cancer stem cells in colorectal carcinoma
Authors: Ariel KM Chow, Nathan SM Cheng, Colin SC Lam, Lui Ng, Sunny KM Wong, Timothy MH Wan, Johnny HW Man, Alvin HK Cheung, Thomas CC Yau, Jensen TC Poon, Wai-Lun Law, Roberta WC Pang
Journal: Molecular Cancer (2015)

In colorectal carcinoma (CRC), activation of the Raf/MEK/ERK signaling pathway is commonly observed. In addition, the commonly used 5FU-based chemotherapy in patients with metastatic CRC was found to enrich a subpopulation of CD26+ cancer stem cells (CSCs). As activation of the Raf/MEK/ERK signaling pathway was also found in the CD26+ CSCs and therefore, we hypothesized that an ATP-competitive pan-Raf inhibitor, Raf265, is effective in eliminating the cancer cells and the CD26+ CSCs in CRC patients. HT29 and HCT116 cells were treated with various concentrations of Raf265 to study the anti-proliferative and apoptotic effects of Raf265. Anti-tumor effect was also demonstrated using a xenograft model. Cells were also treated with Raf265 in combination with 5FU to demonstrate the anti-migratory and invasive effects by targeting on the CD26+ CSCs and the anti-metastatic effect of the combined treatment was shown in an orthotopic CRC model. Raf265 was found to be highly effective in inhibiting cell proliferation and tumor growth through the inhibition of the RAF/MEK/ERK signaling pathway. In addition, anti-migratory and invasive effect was found with Raf265 treatment in combination with 5FU by targeting on the CD26+ cells. Finally, the anti-tumor and anti-metastatic effect of Raf265 in combination with 5FU was also demonstrated. This preclinical study demonstrates the anti-tumor and anti-metastatic activity of Raf265 in CRC, providing the basis for exploiting its potential use and combination therapy with 5FU in the clinical treatment of CRC.
Climbing RAS, the Everest of Oncogenes
Authors: Mariangela Russo, Federica Di Nicolantonio, Alberto Bardelli
Journal: Cancer Discovery (2014)

Abstract Summary: Mutations that activate the small GTP-binding protein KRAS are the most common oncogenic event in human tumors. Thirty years after its discovery, mutant KRAS has yet to be therapeutically conquered. Cancer Discov; 4(1); 19–21. ©2014 AACR. See related article by Faber et al., p. 42
An alternative way for epithelial-to-mesenchymal transition in colorectal cancer via EIF5A2?: Figure 1
Authors: Frank T Kolligs
Journal: Gut (2011)

<h3>Abstract</h3> <h3>Background</h3> At present, evidence is inconclusive regarding what factors influence vaccine intent, and whether there are widespread disparities across populations and time. The current study provides new insights regarding vaccine intent and potential differences across 23 countries and over time. <h3>Methods</h3> Our data come from a unique longitudinal survey that contains responses from Facebook users (N=1,425,172) from the 23 countries from four continents collected in 18 waves from July 2020 through March 2021. <h3>Results</h3> We find that vaccine intent varies significantly across countries and over time. Across countries, there are notable disparities in intent to vaccinate. Regarding time, intent has recently reached an all-time high. Our data demonstrates that intent to vaccinate has increased as countries have deployed vaccines on larger scales with undecidedness declining. However, there are some countries where vaccine intent is stagnant and in one country – Egypt – where it seems to have declined. <h3>Interpretations</h3> Large numbers of citizens across the world are willing to get vaccinated. In the vast majority of countries in our sample, these were high enough to reach more conservative levels of herd immunity<sup>1</sup> if combined with numbers of persons already infected. As such, the main barrier to vaccination is not vaccine hesitancy, but the shortage of vaccines. This sends a clear message to politicians who need to work on a quick and fair distribution of vaccine; and to scientists who need to focus their attention on understanding remaining pockets of vaccine skepticism or undecidedness and on factors that explain actual vaccine behavior, rather than intent.
Considerations in the Management of Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitor Therapy
Authors: Hagop Kantarjian, Jorge Cortes
Journal: Journal of Clinical Oncology (2011)

The phenomenal success of therapy with tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome (Ph) –positive chronic myeloid leukemia (CML) has drastically changed the prognosis of this disease. With imatinib mesylate, the estimated 7- to 10-year survival is 80% to 85%, 90% to 93% if only CML-related deaths are considered.1–5 Nilotinib and dasatinib are more potent second generation TKIs with activity in CML after imatinib failure.6–8 In randomized trials of first-line CML therapy, nilotinib and dasatinib, compared with imatinib, demonstrated significantly higher rates of complete cytogenetic response (CCyR) and of major molecular response (MMR) at 12 to 18 months, reductions in the incidence of transformation to accelerated and blastic phases, and, on average, better tolerance.9,10 Both nilotinib (300-mg twice daily) and dasatinib (100-mg once daily) were recently approved for first-line CML therapy. In the accompanying article, Hehlmann et al11 report the results of first-line CML therapy with standard dose imatinib with or without interferon alfa, and with high-dose imatinib. They analyze the incidence of MMR as the study primary end point.11 This emphasis on MMR as a primary end point in CML therapy, and the availability of three TKIs for CML therapy, raise important questions related to the management of chronic phase CML in our daily practice. What are the important early end points of therapy with TKI in CML that predict long-term prognosis (eg, achievement of CCyR, MMR)? How should we monitor response to therapy (cytogenetic, fluorescent in situ hybridization [FISH], molecular studies, mutational analysis)? What are the long-term end points relevant to therapeutic decisions (survival, progression-free survival [PFS], event-free survival [EFS])? Imatinib will become available in generic formulations in the next few years, at a significantly lower cost than second generation TKIs. Oncologists are then faced with important therapeutic questions. Would it be better to use the less expensive TKI, imatinib, as first-line CML therapy and reserve the second generation TKIs for imatinib failure, or should second generation TKIs be used as first-line therapy? What is a clinically relevant definition of poor response to imatinib? If imatinib is selected for first-line therapy, is it better to change to second generation TKIs at the time of suboptimal response to imatinib, or at the time of cytogenetic or hematologic relapse? These questions raise several important issues related to how best to integrate the new generation of TKIs into the management of patients with CML.
Bortezomib (Velcade) Induces p27Kip1 Expression through S-Phase Kinase Protein 2 Degradation in Colorectal Cancer
Authors: Shahab Uddin, Maqbool Ahmed, Prashant Bavi, Raafat El-Sayed, Nasser Al-Sanea, Alaa AbdulJabbar, Luai H. Ashari, Samar Alhomoud, Fouad Al-Dayel, Azhar R. Hussain, Khawla S. Al-Kuraya
Journal: Cancer Research (2008)

S-phase kinase protein 2 (SKP2), an F-box protein, targets cell cycle regulators including cycle-dependent kinase inhibitor p27Kip1 via ubiquitin-mediated degradation. SKP2 is frequently overexpressed in a variety of cancers. We investigated the role of SKP2 and its ubiquitin-proteasome pathway in colorectal carcinoma using a panel of cell lines, clinical samples, and the NUDE mouse model. Using immunohistochemical analysis on a large tissue microarray of 448 samples, an inverse association of SKP2 expression with p27Kip1 protein levels was seen. A colorectal cancer (CRC) subset with high level of SKP2 and low level of p27Kip1 showed a decreased overall survival (P = 0.0057). Treatment of CRC cell lines with bortezomib or expression of small interfering RNA of SKP2 causes down-regulation of SKP2 and accumulation of p27Kip1. Furthermore, treatment of CRC cells with bortezomib causes apoptosis by involving the mitochondrial pathway and activation of caspases. In addition, treatment of CRC cells with bortezomib down-regulated the expression of XIAP, cIAP1, and survivin. Finally, treatment of CRC cell line xenografts with bortezomib resulted in growth inhibition of tumors in NUDE mice via down-regulation of SKP2 and accumulation of p27Kip1. Altogether, our results suggest that SKP2 and the ubiquitin-proteasome pathway may be potential targets for therapeutic intervention for treatment of CRC.
A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up
Authors: N. Krawtchenko, J. Roewert-Huber, M. Ulrich, I. Mann, W. Sterry, E. Stockfleth
Journal: British Journal of Dermatology (2007)

Journal Article A randomised study of topical 5% imiquimod vs. topical 5‐fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1‐year follow‐up Get access N. Krawtchenko, N. Krawtchenko Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar J. Roewert‐Huber, J. Roewert‐Huber Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Ulrich, M. Ulrich Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar I. Mann, I. Mann Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar W. Sterry, W. Sterry Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar E. Stockfleth E. Stockfleth Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital, Berlin, Germany Correspondence: Eggert Stockfleth. E‐mail: eggert.stockfleth@charite.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue s2, 1 December 2007, Pages 34–40, https://doi.org/10.1111/j.1365-2133.2007.08271.x Published: 01 December 2007
Subtle variations in Pten dose determine cancer susceptibility
Authors: Andrea Alimonti, Arkaitz Carracedo, John G Clohessy, Lloyd C Trotman, Caterina Nardella, Ainara Egia, Leonardo Salmena, Katia Sampieri, William J Haveman, Edi Brogi, Andrea L Richardson, Jiangwen Zhang, Pier Paolo Pandolfi
Journal: Nature Genetics (2010)
Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis
Authors: Y. Chen
Journal: Journal of Clinical Investigation (2006)

IL-23 is a member of the IL-12 cytokine family that drives a highly pathogenic T cell population involved in the initiation of autoimmune diseases. We have shown that IL-23-dependent, pathogenic T cells produced IL-17 A, IL-17 F, IL-6, and TNF but not IFN-gamma or IL-4. We now show that T-bet and STAT1 transcription factors are not required for the initial production of IL-17. However, optimal IL-17 production in response to IL-23 stimulation appears to require the presence of T-bet. To explore the clinical efficacy of targeting the IL-23 immune pathway, we generated anti-IL-23p19-specific antibodies and tested to determine whether blocking IL-23 function can inhibit EAE, a preclinical animal model of human multiple sclerosis. Anti-IL-23p19 treatment reduced the serum level of IL-17 as well as CNS expression of IFN-gamma, IP-10, IL-17, IL-6, and TNF mRNA. In addition, therapeutic treatment with anti-IL-23p19 during active disease inhibited proteolipid protein (PLP) epitope spreading and prevented subsequent disease relapse. Thus, therapeutic targeting of IL-23 effectively inhibited multiple inflammatory pathways that are critical for driving CNS autoimmune inflammation.
Cardiovascular Mortality in Chronic Kidney Disease Patients Undergoing Percutaneous Coronary Intervention Is Mainly Related to Impaired P2Y12 Inhibition by Clopidogrel
Authors: Olivier Morel, Soraya El Ghannudi, Laurence Jesel, Bogdan Radulescu, Nicolas Meyer, Marie-Louise Wiesel, Sophie Caillard, Umberto Campia, Bruno Moulin, Christian Gachet, Patrick Ohlmann
Journal: Journal of the American College of Cardiology (2011)
The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell.
Authors: D Billadeau, G Ahmann, P Greipp, B Van Ness
Journal: The Journal of Experimental Medicine (1993)

One of the distinguishing features of multiple myeloma (MM) is the proliferation of a clonal plasma cell population in the bone marrow (BM). It is of particular interest that the tumor plasma cells appear to be restricted to the microenvironment of the BM and are rarely detected in the peripheral system, yet the disease is found widely disseminated throughout the axial skeleton. Furthermore, isolation of MM tumor cell lines has proven to be quite problematic due to their slow growth rate. These observations have instigated the search for earlier cells in the B cell lineage that are clonally related to the plasma cell tumor and that may represent the growth fraction of the tumor. We used allele-specific oligonucleotides (ASO) derived from the third complementarity determining region of the rearranged tumor immunoglobulin heavy chain gene to detect isotypes clonally related to the plasma cell tumor. By reverse transcribing RNA from the BM with a panel of CH primers (mu, delta, alpha, and gamma), followed by ASO-polymerase chain reaction amplification, we demonstrate the existence of preswitch isotype species that are clonally related to the myeloma tumor. Furthermore, we show that separation of the BM cells into CD45+ and CD38+ cell populations results in a lineage-specific expression of the clonally related RNA molecules, with the C mu and C delta in the CD45+, and C gamma in the CD38+ population. Interestingly, clonally related C alpha transcripts are also derived from the CD45+ fraction. These results confirm the presence of B cell populations clonally related to the plasma cell tumor and are consistent with models that propose the existence of myeloma precursors.
Self-management approaches for osteoarthritis in the hand: a 2×2 factorial randomised trial
Authors: Krysia Dziedzic, Elaine Nicholls, Susan Hill, Alison Hammond, June Handy, Elaine Thomas, Elaine Hay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis is the leading cause of disability in older adults. Evidence of effectiveness for self-management of hand osteoarthritis is lacking. <h3>Methods</h3> In this randomised, factorial trial, we evaluated the effectiveness of joint protection versus no joint protection, and hand exercise versus no hand exercise in adults, 50 years of age or older, with hand osteoarthritis. Following a population survey (n=12 297), eligible individuals were randomly assigned (1:1:1:1) to: leaflet and advice; joint protection; hand exercise; joint protection plus hand exercise. Joint protection and hand exercises were delivered by nine occupational therapists, over four group sessions. The primary outcome was the OARSI/OMERACT responder criteria at 6 months. Outcomes were collected blind to allocation (3, 6, 12 m). Analysis was by intention to treat. <h3>Results</h3> Of 257 participants randomised (65:62:65:65) (mean age (SD) 66 years (9.1); female 66%) follow-up was 85% at 6 m (n=212). Baseline characteristics and loss to follow-up were similar between groups. There were no reported treatment side effects. At 6 m 33% assigned joint protection were responders compared with 21% with no joint protection (p=0.03). Of those assigned hand exercises, 28% were responders compared with 25% with no exercises (n.s.). Differences in secondary outcomes were not statistically significant, except for improvement in pain self-efficacy with joint protection (3 m p=0.002; 6 m p=0.001; 12 m p=0.03). <h3>Conclusions</h3> These findings show that occupational therapists can support self-management in older adults with hand osteoarthritis, and that joint protection provides an effective intervention for medium term outcome. (Funded by the Arthritis Research UK ISRCTN 33870549).