tbuckley/cabot-search huggingface dataset:
A novel role of DNA fragmentation factor as a tumor suppressor through maintaining genomic stability
Authors: B. Yan, H. Wang, J. S. Bedford, M. W. Dewhirst, C. Li
Journal: Journal of Clinical Oncology (2006)

10023 Background: DNA fragmentation is a hallmark of apoptosis. However, the biological function of apoptotic DNA fragmentation remains unclear. Genes encoding the nuclease responsible for DNA fragmentation, DFF40/CAD and DFF45/ICAD, are deleted, mutated, or aberrantly expressed in many human tumor types. Abnormalities in this gene are associated with aggressive tumors and poor prognosis in cancer patients. Tumor-specific DFF45 gene mutations were identified in human tumors, indicating the involvement of this gene in tumor development. Methods: We studied genetic instability, cellular transformation and tumorigenesis in cells and mice deficient in DNA fragmentation. We applied two methods to inhibit DNA fragmentation, overexpressing a modified ICAD which inhibits DNA fragmentation during apoptosis in stable cell lines and disrupting cad gene in transgenic mice. Genetic instability was studied by gene amplification assay, mutation assay and cytogenetic analysis including chromosomal aberrations and translocations. Cellular transformation was studied by soft agar assay using CAD-/- MEF cells. Tumorigenesis in DFF/CAD-knockout mice was studied by radiation carcinogenesis and two-stage skin chemical carcinogenesis. Results: (1) Human and mouse cancer cell lines with their CAD activity inhibited exhibited significantly more genetic instability under spontaneous or mutagen (ionizing radiation) induced conditions. These are reflected as elevated frequencies of chromosomal aberrations, gene amplifications, and gene mutations; (2) Mouse cells with targeted disruption of the cad gene exhibit a similar, increased level of genetic instability when the host animal is irradiated; (3) Mechanistically, CAD maintains genetic instability through the removal of cells with DNA damage, a role that is similar to genomic “gatekeepers” like p53; (4) CAD-null mouse embryo fibroblasts exhibited enhanced cellular transformation; (5) Significantly enhanced susceptibility to chemical and radiation-induced tumor development was observed in mice with targeted disruption of the CAD gene, indicating that it plays a role in suppressing tumor development. Conclusions: CAD plays an important role in maitaining genetic stability and suppressing tumor development. No significant financial relationships to disclose.
Clinical impact of epidermal growth factor receptor (EGFR) coexpression in early breast cancer with human epidermal growth factor receptor 2 (HER2) overexpression.
Authors: S. Park, E. Cho, Y. Shin, S. Hong, M. Lee, Y. Park, S. Nam, J. Yang, Y. Choi
Journal: Journal of Clinical Oncology (2010)

e21081 Background: Activation of the EGFR signaling can lead to the activation of MAPK, PI3K/AKT, the STAT pathway resulting in tumor growth, inhibition of apoptosis, cell migration and invasion. Tumor cells that over-express both EGFR and HER2, exhibit aggressive tumor cell growth, owing to the increased potential for EGFR/HER2 heterodimerization and signaling. HER2 overexpression has been found to correlate with a worse prognosis in breast cancer. However, the clinical significance of EGFR status in the HER2 positive early breast cancer remains to be evaluated. Methods: This study aims to evaluate EGFR status and its clinical impact in HER2 positive in early breast cancer. To address this issue, biomarker evaluation was performed using immunohistochemistry to semiquantitate estrogen (ER), progesterone (PR), HER2, and EGFR expression in the large cohort of cases with early breast cancers. Amplification of HER2 was confirmed by fluorescent in situ hybridization. Results: HER2 overexpression was found in 24.8% of early breast cancers with available tissue specimens from the primary tumor (236 of 952 cases) EGFR coexpression was identified in 10.6% of HER2 overexpressing early breast cancers. (25 of 236 patients) EGFR expression was significantly associated with age greater than 50 years (p = 0.032), absence of ER (p < 0.001) and PR (p = 0.028). The EGFR coexpression in patients with HER2 amplified early breast cancers demonstrated trends toward poorer overall survival (EGFR positive vs. EGFR negative, 86.1 months [95% confidence interval {CI}, 69.7-102.4 months] vs. 122.3 [C.I. 115.5-129.0], p = 0.109). Conclusions: EGFR co-expression was found in 10.6% of early breast cancer with HER2 overexpression. Our data demonstrated that simultaneous EGFR and HER2 expression is negatively correlate with hormone receptor expression in early breast cancer. The molecular significance of EGFR and HER2 co-expression in early breast cancer needs to be further investigated. No significant financial relationships to disclose.
Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia
Authors: Sarah K. Tasian, David T. Teachey, Yong Li, Feng Shen, Richard C. Harvey, I-Ming Chen, Theresa Ryan, Tiffaney L. Vincent, Cheryl L. Willman, Alexander E. Perl, Stephen P. Hunger, Mignon L. Loh, Martin Carroll, Stephan A. Grupp
Journal: Blood (2016)
Constitutive Cyclin A1 Expression Impairs Retinoic Acid-Induced Growth Arrest and Differentiation of Myeloid Leukemia Cells
Authors: Tsuyoshi Nakamaki, Kunihiko Fukuchi, Takashi Maeda, Norimichi Hattori, Hirotsugu Ariizumi, Bungo Saito, Takaji Yanagisawa, Isao Matsuda, Shigeru Tomoyasu
Journal: Blood (2010)
The tumor metabolic marker Tumor M2-PK in stool: A new biomarker for colorectal cancer
Authors: H. U. Kloer, P. D. Hardt, P. Schlierbach, M. Toepler
Journal: Journal of Clinical Oncology (2005)

3598 Background: Proliferating cells, especially tumor cells, express a special isoenzyme of pyruvate kinase, termed M2-PK which can occur in a tetrameric form with a high affinity to its substrate phosphoenolpyruvate (PEP) and in a dimeric form with a low PEP affinity. In tumor cells the dimeric form is usually predominant and is therefore termed Tumor M2-PK. The dimerisation of M2-PK takes place through direct binding of oncoproteins and leads to decreased enzyme activity as well as the channeling of glucose for the synthesis of nucleic acids, phospholipids and amino-acids. Methods: The present study includes 303 patients that underwent complete colonoscopy after the determination of Tumor M2-PK in a single spot stool sample. Stool samples of patients with colorectal cancer (CRC) and patients without pathological findings were tested. Histology was obtained from the routine biopsies and/or from surgery. Tumor M2-PK in stool extracts was determined immunologically with a quantitative ELISA,which is based on two monoclonal antibodies. Results: Data from 173 controls and 130 patients with CRC have been evaluated. There is a highly significant difference (p < 0.001; Kruskal-Wallis ANOVA test) between tumor patients and controls. At a cut off point of 4 U/ml, the sensitivity was calculated to be 83% for colon cancer and 73% for rectal cancer and the specificity as 82%. Fecal Tumor M2-PK levels of 76 patients with CRC are correlated with tumor staging according to Dukes and TNM classification. Conclusions: The present study shows that the determination of Tumor M2-PK in a single spot stool sample is a valuable tool for the early detection of CRC. No significant financial relationships to disclose.
A Novel Regimen of Unmanipulated HLA-Haploidentical Transplantation Using a Small Dose of Anti-T-Lymphocyte Globulin for Patients in High Tumor Burden
Authors: Shinichi Ishii, Kazuhiro Ikegame, Katsuji Kaida, Satoshi Yoshihara, Masaya Okada, Ruri Kato, Takayuki Inoue, Hiroya Tamaki, Yoshihiro Fujimori, Toshihiro Soma, Hiroyasu Ogawa
Journal: Blood (2012)
GW26-e2452 A Study in Construction of Short Hairpin Small Interfering RNA Expression Vector Target Lectin Like Oxidized Low Density Lipoprotein Receptor-1 Gene and Its Effect on foam cells
Authors: Huiyu Yang, Yunfei Bian, Bin Liang, Rui Bai, Zhiming Yang
Journal: Journal of the American College of Cardiology (2015)
Abstract B17: Disrupting tumor growth through targeting TEM8
Authors: Anette M. Høye, Sofie Tolstrup, Thomas R. Cox, Jeremy P. Mauldin, Arthur E. Frankel, Janine T. Erler
Journal: Cancer Research (2016)

Abstract Tumor Endothelial Marker 8 (TEM8) is an integrin-like cell-surface receptor originally identified being specific to tumor endothelial cells in colorectal cancer (CRC) blood vessels. Further investigation showed upregulated TEM8 expression in tumor vessels of various tumor types, as well as in certain tumor cells. We observe an increase in TEM8 expression in metastatic cancer cell lines compared to their non-metastatic counterpart in both colon and breast cancer cell lines. In order to investigate whether TEM8 is required for tumor growth and metastasis we have developed a humanized anti-TEM8-toxin-conjugated antibody. The antibody shows preclinical effectiveness in a CRC model in vivo. We have also utilized the CRISPR-Cas9 technology to create TEM8 knockout cell lines, which show impaired proliferation and invasion in vitro and reduced tumor growth in vivo compared to control cell lines. Intriguingly, microarray analysis showed a significant increase in TEM8 mRNA levels in breast cancer cells seeded on collagen modified by the crosslinking enzyme lysyl oxidase (LOX). We have previously shown that LOX plays a role in tumor progression, metastasis, and pre-metastatic niche formation through its ability to modulate matrix stiffness. Importantly, both high TEM8 and LOX expression is correlated with decreased survival in ER- breast cancer patients. Collagen VI, a TEM8 ligand, and their interaction have been implicated in being important for migration and for stimulating Wnt-signaling in breast cancer stem cells. Using global quantitative mass spectrometry we observe an increase in collagen VI in the extracellular matrix of CRC tumors overexpressing catalytically active, but not catalytically inactive, LOX compared to low-LOX expressing tumors. Furthermore, using publicly available databases TEM8 and collagen VI are found to be co-expressed in CRC patient datasets. Thus, we speculate that another possible mechanism of LOX mediated tumor and metastasis progression is through TEM8. Further, that combined targeting of TEM8 and LOX may inhibit primary and metastatic tumor growth. Citation Format: Anette M. Høye, Sofie Tolstrup, Thomas R. Cox, Jeremy P. Mauldin, Arthur E. Frankel, Janine T. Erler. Disrupting tumor growth through targeting TEM8. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B17.
The Pan-Bcl-2 Inhibitor GX15-O70 Induces Apoptosis in Human Myeloma Cells by Noxa Induction and Strongly Enhances Melphalan, Bortezomib or TRAIL-R1 Antibody Apoptotic Effect.
Authors: Patricia Gomez-Bougie, Sophie Maïga, Catherine Pellat-Deceunynck, Sandrine Jouan, Regis Bataille, Martine Amiot
Journal: Blood (2006)
Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality
Authors: Dong Hoon Lee
Journal: Annals of Internal Medicine (2016)

Letters18 October 2016Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause MortalityDong Hoon Lee, MDDong Hoon Lee, MDFrom Kaiser Permanente, Redwood City, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0335 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Padwal and colleagues' analysis of body fat percentage, body mass index (BMI), and all-cause mortality (1) was interesting in terms of addressing the uncertainty surrounding traditionally used anthropometric measurements represented by BMI. Their study must be robust given its large population and long duration; furthermore, although it was done retrospectively, there could be no better design to examine the question being evaluated. However, I question the interpretation and expression of this study's results.The authors state that mortality increased as BMI decreased and body fat percentage increased, showing figures for hazard ratios for death according to the ...Reference1. Padwal R, Leslie WD, Lix LM, Majumdar SR. Relationship among body fat percentage, body mass index, and all-cause mortality. A cohort study. Ann Intern Med. 2016;164:532-41. [PMID: 26954388] doi:10.7326/M15-1181 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Kaiser Permanente, Redwood City, California.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0335. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRelationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality Raj Padwal , William D. Leslie , Lisa M. Lix , and Sumit R. Majumdar Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality Raj Padwal , Sumit R. Majumdar , and William D. Leslie Metrics 18 October 2016Volume 165, Issue 8Page: 603-604KeywordsAdipose tissueBody mass indexConflicts of interestDisclosureGlobal healthHazard ratioMortalityObesityRetrospective studies ePublished: 18 October 2016 Issue Published: 18 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Vorinostat (suberoylanilide hydroxamic acid, SAHA) is clinically active in advanced cutaneous T-cell lymphoma (CTCL): Results of a phase IIb trial
Authors: E. Olsen, Y. H. Kim, T. Kuzel, T. R. Pacheco, F. Foss, S. Parker, J. G. Wang, S. R. Frankel, J. Lis, M. Duvic
Journal: Journal of Clinical Oncology (2006)

7500 Background: Vorinostat is a histone deacetylase inhibitor that has demonstrated clinical activity at tolerable dose levels in patients (pts) with advanced CTCL in phase I and IIa trials. Methods: Open-label, single-arm, nonrandomized phase IIb trial of oral vorinostat 400 mg daily until disease progression or intolerable toxicity. Eligibility: advanced CTCL; ≥ 2 prior systemic therapies which must have included bexarotene unless unable to tolerate; adequate hematologic, hepatic and renal function. Planned sample size: ≥ 50 evaluable pts with clinical stage ≥ IIB. Primary endpoint: objective response rate (OR = CR + PR) as measured by a modified skin severity weighted assessment tool. The study would be positive if OR in ≥ stage IIB pts was ≥ 20%. Secondary endpoints: assessment of response duration (DOR), time to progression (TTP), time to response (TTR), pruritus relief and safety. Results: Seventy-four pts (median age, 60 y [range, 39–83]; median 3 prior systemic therapies) were enrolled (61 pts ≥ stage IIB) from 9/04 to 5/05 at 18 centers. Data cut-off was 11/05 with a median follow-up of 4 months. Efficacy data are shown in Table 1 . The OR was 29.5% (18 PR including 1 with later CR) in ≥ stage IIB pts. Median TTP was 148 d for all pts and 203.5+ d for responders. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%) and anorexia (26%), and were mostly ≤ Grade 2. Drug-related ECG changes were Grade 1 in 5 pts (7%) and Grade 2 in 1 pt (1%), but not associated with cardiac symptoms. Seven pts discontinued and 10 had dose modification due to drug-related AE. Drug-related AE ≥ Grade 3 included fatigue (5%), pulmonary embolism (5%), nausea (4%) and thrombocytopenia (4%). Twenty-five pts discontinued due to progressive disease. Causes of the 3 deaths on study were: unknown (d 2), ischemic stroke (d 227) and disease progression (d 52). Conclusion: Oral vorinostat is effective in the treatment of advanced CTCL with an acceptable safety profile. [Table: see text] [Table: see text]
Prospective Multicenter Trial Comparing Repeated Immunosuppressive Therapy (IST) with Stem Cell Transplantation (SCT) from an Alternative Donor as a Second-Line Treatment for Children with Acquired Aplastic Anemia (AA).
Authors: Yoshiyuki Kosaka, Ryoji Kobayashi, Hiroshi Ayukawa, Koji Kato, Takashi Kaneko, Hisato Kigasawa, Hiromasa Yabe, Masahiro Tsuchida, Hideo Mugishima, Akira Ohara, Akira Morimoto, Masuji Yamamoto, Shouichi Ohga, Fumio Bessho, Tatsutoshi Nakahata, Ichiro Tsukimoto, Seiji Kojima
Journal: Blood (2004)
Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps
Authors: Juwon Park, Robert W. Wysocki, Zohreh Amoozgar, Laura Maiorino, Miriam R. Fein, Julie Jorns, Anne F. Schott, Yumi Kinugasa-Katayama, Youngseok Lee, Nam Hee Won, Elizabeth S. Nakasone, Stephen A. Hearn, Victoria Küttner, Jing Qiu, Ana S. Almeida, Naiara Perurena, Kai Kessenbrock, Michael S. Goldberg, Mikala Egeblad
Journal: Science Translational Medicine (2016)

Treatment with DNase I–coated nanoparticles prevents metastasis by targeting neutrophil extracellular traps induced by cancer cells in a mouse model.
Preoperative sodium concentration as a possible predictor of survival in patients with renal cell carcinoma
Authors: N. S. Vasudev, J. E. Brown, S. R. Brown, K. Cocks, D. O'Donnell, P. M. Patel, P. Harnden, R. E. Banks, P. J. Selby
Journal: Journal of Clinical Oncology (2007)

10601 Background: Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. In this cross-sectional study of RCC, a large number of parameters including hematological and biochemical as well as traditional tumor-related factors have been assessed for their prognostic significance. Methods: Consecutive, unselected patients undergoing nephrectomy for newly diagnosed RCC were invited to participate. Primary end-points were overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). A subset analysis of patients presenting with localized N0 disease was planned. Univariate and multivariate Cox's proportional hazards models were used. Results: 212 patients with RCC formed the study population. Tumor-related factors including grade, stage, presence of necrosis and vascular invasion were prognostic for survival on multivariate testing, in agreement with previous reports. In multivariate analyses pre-operative serum sodium (sNa) was found to be independently and significantly associated with OS and DFS when considered as a continuous variable (see table ). In a further exploratory analysis for all patients when sNa was dichotomized into above/below the median value (139 mmol/l; normal range: 135–145 mmol/l), 3-year OS estimates above and below the median were 74%, 95% CI [64%, 85%] and 54%, 95% CI [44%, 64%]; corresponding figures for 5 years were 68%, 95% CI [54%, 81%] and 44%, 95% CI [33%, 56%]. Conclusions: We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to demonstrate that pre-operative sodium concentration may be an important factor associated with survival in patients with RCC. This result suggests that sNa should be considered with established prognostic parameters in modeling survival in RCC. [Table: see text] No significant financial relationships to disclose.
Detection of Novel Mutations In MDS/AML by Whole Genome Sequencing
Authors: Matthew J. Walter, Dong Shen, Li Ding, Jin Shao, Sarah Witowski, Ken Chen, Daniel C. Koboldt, David J. Dooling, Rachel Maupin, Robert S. Fulton, Heather Schmidt, Michelle O'Laughlin, Michael D. McLellan, John Frater, Peter Westervelt, John F DiPersio, Elaine R Mardis, Richard Wilson, Timothy J Ley, Timothy Graubert
Journal: Blood (2010)
Parametric Response Mapping as an Imaging Biomarker in Lung Transplant Recipients
Authors: Elizabeth A. Belloli, Irina Degtiar, Xin Wang, Gregory A. Yanik, Linda J. Stuckey, Stijn E. Verleden, Ella A. Kazerooni, Brian D. Ross, Susan Murray, Craig J. Galbán, Vibha N. Lama
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The predominant cause of chronic lung allograft failure is small airway obstruction arising from bronchiolitis obliterans. However, clinical methodologies for evaluating presence and degree of small airway disease are lacking.To determine if parametric response mapping (PRM), a novel computed tomography voxel-wise methodology, can offer insight into chronic allograft failure phenotypes and provide prognostic information following spirometric decline.PRM-based computed tomography metrics quantifying functional small airways disease (PRMfSAD) and parenchymal disease (PRMPD) were compared between bilateral lung transplant recipients with irreversible spirometric decline and control subjects matched by time post-transplant (n = 22). PRMfSAD at spirometric decline was evaluated as a prognostic marker for mortality in a cohort study via multivariable restricted mean models (n = 52).Patients presenting with an isolated decline in FEV1 (FEV1 First) had significantly higher PRMfSAD than control subjects (28% vs. 15%; P = 0.005), whereas patients with concurrent decline in FEV1 and FVC had significantly higher PRMPD than control subjects (39% vs. 20%; P = 0.02). Over 8.3 years of follow-up, FEV1 First patients with PRMfSAD greater than or equal to 30% at spirometric decline lived on average 2.6 years less than those with PRMfSAD less than 30% (P = 0.004). In this group, PRMfSAD greater than or equal to 30% was the strongest predictor of survival in a multivariable model including bronchiolitis obliterans syndrome grade and baseline FEV1% predicted (P = 0.04).PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRMfSAD helps further stratify the risk of death in patients with diverse spirometric decline patterns.
A Phase 2 Study of Bortezomib Plus High-Dose Melphalan (Mel/Vel) Conditioning for Autologous Hematopoietic Cell Transplantation In Multiple Myeloma,
Authors: Taiga Nishihori, Leonel Ochoa, Joseph Pidala, Kenneth H. Shain, Rachid Baz, Christine Simonelli, Dan Sullivan, Claudio Anasetti, Melissa Alsina
Journal: Blood (2011)