tbuckley/cabot-search huggingface dataset:
The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases
Authors: Erik Thunnissen, Alain C. Borczuk, Douglas B. Flieder, Birgit Witte, Mary Beth Beasley, Jin-Haeng Chung, Sanja Dacic, Sylvie Lantuejoul, Prudence A. Russell, Michael den Bakker, Johan Botling, Elisabeth Brambilla, Erienne de Cuba, Kim R. Geisinger, Kenzo Hiroshima, Alberto M. Marchevsky, Yuko Minami, Andre Moreira, Andrew G. Nicholson, Akihiko Yoshida, Ming-Sound Tsao, Arne Warth, Edwina Duhig, Gang Chen, Yoshihiro Matsuno, William D. Travis, Kelly Butnor, Wendy Cooper, Mari Mino-Kenudson, Noriko Motoi, Claudia Poleri, Giuseppe Pelosi, Keith Kerr, Seena C. Aisner, Yuichi Ishikawa, Reinhard H. Buettner, Naoto Keino, Yasushi Yatabe, Masayuki Noguchi
Journal: Journal of Thoracic Oncology (2016)
Abstract 2295: AMP-activated protein kinase (AMPK) signaling in the context of gain-of-function mutant p53 in vivo
Authors: Se-Young Jo, Hye-Min Moon, ChuHee Lee, Se Jin Jang, Young-Ah Suh
Journal: Cancer Research (2015)

Abstract There is growing evidence that tumor cells depend on unique metabolism for their continued growth and survival, and that cancer cells are peculiarly addicted to the rapacious uptake of glucose and glutamine. AMP-activated protein kinase (AMPK) is one of the central regulators of cellular and organismal metabolism in eukaryotes, playing critical roles in regulating cell growth and reprogramming metabolism. Several of the downstream effects of AMPK on metabolic adaptation can be attributed to the AMPK-dependent activation of the p53 tumor suppressor, resulting in its transcriptional activation and initiating a metabolic cell cycle checkpoint. However, in the absence of p53, treatment with the blood glucose-lowering drug metformin delays tumor progression, suggesting that the AMPK-p53 signaling axis responds in diverse manner depending on genetic alteration. Due to the gain-of-function, mutant p53 protein contributes to tumor metastasis and shortening the latency of tumor progression. Thereby activated K-ras/mutant p53 mouse is preferentially used as lung adenocarcinoma preclinical model. Here, we have established mouse tumor cells derived from activated K-ras/mutant p53 mouse to generate syngeneic lung cancer mouse model, allowing in vivo imaging. We asked whether the gain-of-function metastatic phenotype observed in the mouse is responsible for unique metabolic conditions resulting in the formation of lung tumors. We have evaluated tumor metabolic environment of this model and examined AMPK signaling pathways. Citation Format: Se-Young Jo, Hye-Min Moon, ChuHee Lee, Se Jin Jang, Young-Ah Suh. AMP-activated protein kinase (AMPK) signaling in the context of gain-of-function mutant p53 in vivo. [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 2295. doi:10.1158/1538-7445.AM2015-2295
123. Helper-Dependent Ad5/35 Vectors for ZFN Mediated Gene Editing in Hematopoietic Stem Cells
Authors: Kamola Saydaminova, Hongjie Wang, Xun Ye, HongZhuan Chen, Ning Xu, Jin-Soo Kim, Eirini Papapetrou, Michael C. Holmes, Philip D. Gregory, Donna Palmer, Philip Ng, Hans-Peter Kiem, Anja Ehrhardt, Andre Lieber
Journal: Molecular Therapy (2015)

A homozygous [Delta]32 deletion in the CCR5 gene, found in about 1% of Caucasians, confers a natural resistance to HIV-1. In a recent pivotal study it was shown that transplantation of hematopoietic stem/progenitor cells (HSCs) from a donor who was homozygous for CCR5 [Delta]32 in a patient with acute myeloid leukemia and HIV-1 infection resulted in long-term control of HIV. This finding supports the development of gene therapy approaches to eliminate CCR5 in HIV target cells, including approaches based on CCR5-knockout by zinc finger nucleases (ZFNs). Recent trials involved the ex vivo transduction of patient CD4+ T-cells with a CCR5-ZFN expressing adenovirus Ad5/35 vectors. More recent attempts have focused on CCR5 gene knock-out in hematopoietic stem cells (HSCs). Because HSCs are the source for all blood cell lineages, CCR5 knock-out would protect not only CD4 cells but also all remaining lymphoid and myeloid cell types that are potential targets for HIV infection. We generated a helper-dependent, capsid-modified HD-Ad5/35 vector for CCR5-ZFN expression in HSCs from mobilized adult donors. The production of these vectors required that ZFN expression in HD-Ad5/35 producer 293-Cre cells was suppressed. To do this, we developed a miRNA-based system for regulation of gene expression based on miRNA expression profiling of 293-Cre and CD34+ cells. We demonstrated that, after in vitro CD34+ cell transduction, the HD-Ad5/35.ZFNmiR vector conferred ccr5 knock-out in primitive HSC (i.e. long-term culture initiating cells and NOD/SCID repopulating cells). Upon transplantation of in vitro transduced CD34+ cells into irradiated NOG mice, the ccr5 gene disruption frequency achieved in engrafted HSCs found in the bone marrow was about 12%. However, we also found in transplantation studies that the HD-Ad5/35.ZFNmiR vector decreased CD34+ engraftment rates 7-10-fold compared to HD-Ad5/35-GFP (control) transduced cells. A possible interpretation of these data is that sustained high-level ZFN expression afforded by the HD-Ad5/35 vector platform might be detrimental to the HSC, particularly if the cells do not actively divide allowing the extended persistence of HD-Ad5/35 vector genome. This deficit has not been observed with previous first generation recombinant adenoviral vector delivery of ZFNs to CD34+ HSCs (Li et al. Mol Ther 2013), thus the source of the engraftment inhibition is unclear. However, we plan to investigate and develop methods for maximal ccr5 knock-out efficiency in HCSs for future HIV challenge experiments.
Final survival analysis of the phase II Study of weekly paclitaxel plus bevacizumab in previously treated non-Sq NSCLC
Authors: Masahiro Kodani, Tadashi Igishi, Hirokazu Touge, Kenichi Takeda, Yasuto Ueda, Haruhiko Makino, Naoki Kinoshita, Hirofumi Nakazaki, Takashi Sumikawa, Eiji Shimizu
Journal: Annals of Oncology (2015)
The prognostic relevance of altered antiglycan antibody profiles in the sera of primary melanoma patients.
Authors: A. Haimovic, M. W. Ma, M. I. Vuskovic, T. Miller, M. DiBenedetto, J. Grossman, R. L. Shapiro, A. C. Pavlick, R. S. Berman, H. I. Pass, M. Huflejt, I. Osman
Journal: Journal of Clinical Oncology (2011)

8562 Background: A blood-based prognostic test to better identify localized melanoma patients at increased risk for recurrence is needed. Modified cell surface glycans have been correlated with tumor progression in solid tumors and anti-glycan antibody (AGA) expression profiles have shown prognostic relevance. AGA expression analysis also offers the advantage of minimally invasive sampling of 15-20ul of sera. Our objective is to compare the AGA profile in recurrent and non-recurrent melanoma patients to create a melanoma AGA recurrence signature. Methods: Stage II melanoma patients enrolled in a prospective database at New York University Medical Center with a minimum of 2.5 years follow-up were studied. Patients who recurred were matched with patients who did not recur for age, gender, primary tumor thickness and ulceration. Patient sera were incubated on Printed Glycan Arrays (PGAs), each imprinted with 289 synthetic glycans found on healthy or cancer cells. Glycan-bound AGA levels were detected with fluorescence and signal intensities were quantified with microarray analysis software. Fluorescence intensities, which are proportional to AGA levels, were used to create each patient’s AGA immunoprofile. Glycans whose corresponding AGA levels had a maximal difference between the two patient groups (recurrence versus no recurrence) were identified by the Wilcoxon-Mann-Whitney test. AGA levels for the most discriminative glycans were used to assign a recurrence risk score for each patient. Results: Sera drawn at initial diagnosis from 59 stage II melanoma patients (28 recurrent, 31 non-recurrent) were examined. 2 of the top 6 glycans (p<0.05) were used to determine the individual risk scores. Based on their risk score and recurrence status, the preliminary sensitivity and specificity were assessed as 71.4% and 77.4% respectively with an overall precision of 74.6%. Conclusions: Our results suggest that the AGA profiles of melanoma patients have prognostic value. Further analyses using a second generation PGA and an expanded sample size with independent validation are needed to define the role of AGAs in improving the risk stratification of melanoma patients at the time of initial diagnosis.
Fatigue, Quality of Life and Related Symptoms: Patient Reported Outcomes in Myelodysplastic Syndrome, Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria
Authors: Carmelita P. Escalante, Stephanie Chisolm, Juhee Song, Marsha Richardson, Salkeld Ellen, Tony Lam, Etsuko Aoki, Guillermo Garcia-Manero
Journal: Blood (2015)
Separation of breast cancer from normal tissues using GC-MS-based metabolite profiling.
Authors: J. Budczies, C. Denkert, B. Mueller, S. F. Brockmoeller, M. Dietel, C. Radke, S. Loibl, G. Von Minckwitz, J. L. Griffin, M. Oresic, G. Wohlgemut, O. Fiehn
Journal: Journal of Clinical Oncology (2011)

10514 Background: Methods of analytical chemistry allow a global view on metabolic changes occurring during the malignant transformation. Methods: Metabolite profiling of 369 fresh-frozen breast tissues by gas chromatography mass spectrometry (GC-MS) was executed by the METAcancer consortium. 271 samples contained cancer tissue and had tumor area ≥40% (T), out of the remaining cancer-free tissues, 27 had ≥40% normal breast tissue (N) and 71 were adipose-rich (A). The samples were divided in a training set (TS, 2/3 of the samples) and a validation set (VS, 1/3 of the samples) with comparable clinicopathological features. Results: GC-MS analysis was done at the Fiehn lab and led to detection of 468 metabolites, 162 had known chemical structures. Metabolite-by-metabolite analysis of the TS led to identified of 427 significantly (p<0.05, Welch’s t-test) changed metabolites between cancer and non-cancer tissues. Out of these changes, 368 (86%) could be validated by analysis of the VS. Using PROFILE clustering, a method developed before, the metabolic changes were analysed in context of the underlying reaction network. In cancer tissues, we found up-regulation of the most amino acids and nucleotides, changes in TCA cycle and choline metabolism, down-regulation of benzoic acids, sugars and free fatty acids. To develop a test for cancer detection, we identified 20 metabolites that separate T from N and T from A with sensitivity and specificity >80%. Out of these, 13 were tumor markers (up-regulated in T) and 7 normal tissue markers (up-regulated in N and A). We built ratios by dividing the tumor markers by the normal tissues markers leading to 13×7=91 predictors. A voting scheme was used to predict the malignancy of tissues from the metabolite profiles. The metabolite classification reproduced the histopathological classification with sensitivity of 97.0% and specificity of 93.9%. Conclusions: As a proof of principle of the GC-MS approach, we showed that cancer can be separated from non-cancer tissues at high sensitivity and specificity. These results together with recent progress in the miniaturization of GC- and LC-MS devices are promising with regard to applications of metabolomics in biomarker research.
Rapid T Cell Recovery and Possible Auto-GVHD Following Adoptive Transfer of Ex-Vivo Costimulated Autologous T Cells at Day +2 Post-Transplant.
Authors: Aaron P. Rapoport, Stephan A. Grupp, Edward A. Stadtmauer, Robert H. Vonderheide, Bruce L. Levine, Hongbin Fang, Kelly Yager, Anne Chew, Elizabeth Veloso, Carl H. June
Journal: Blood (2007)
Abstract 4579: The role of carnosol in reducing skin cancer development and progression
Authors: Lingying Tong, Shiyong Wu
Journal: Cancer Research (2015)

Abstract Carnosol is a natural compound extracted from rosemary and sage, which are commonly used in traditional Mediterranean cuisine. Among all the compounds extracted from Mediterranean herbs, carnosol, first isolated from sage in 1941, has been demonstrated to be beneficial to health for its anti-inflammation, anti-oxidation and anti-cancer properties. Because of its structure similarity to sex hormones, research has been done on the effect of carnosol mainly on breast and prostate cancers. However, very little is known on the effect of carnosol on UV-induced skin cancer. In this report, we studied the effect of carnosol on UV-induced skin cancer formation and progression. Our data showed that carnosol could partially reduce UVB-induced reactive oxygen species (ROS) elevation and thus protect UV-induced DNA damage in normal skin cells. We also showed that carnosol could inhibit the UVB-induced NF-κB activation. As a result, the normal cell apoptosis induced by UV radiation was partially protected. Moreover, it could also prohibit skin cancer cell progression with or without UV radiation. Therefore, we propose that carnosol could be a potential therapeutic for chemoprevention and treatment of UVB-induced skin cancers. Citation Format: Lingying Tong, Shiyong Wu. The role of carnosol in reducing skin cancer development and progression. [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 4579. doi:10.1158/1538-7445.AM2015-4579
63. Rapid and Sensitive Detection of Circulating Tumor Cells with Nuclease-Activated Oligonucleotide Probes
Authors: David D. Dickey, William H. Thiel, Karen C. Clard, Elliot Burghardt, Justin P. Dassie, James O. McNamara II, Paloma H. Giangrande
Journal: Molecular Therapy (2015)

Metastatic breast cancer is the second leading cause of female cancer deaths in the United States. Despite substantial progress in its treatment, metastatic breast cancer remains incurable. Early identification of breast cancer patients at greatest risk of developing metastatic disease is thus an important goal that would enable oncologists to aggressively treat these patients while the cancer is still vulnerable. In addition, this would spare patients who do not need or would not benefit from further treatments from having to endure the harmful side-effects of chemotherapeutic drug regimens. Circulating tumor cells (CTCs) are rare cancer cells found in the blood circulation of cancer patients that provide a non-invasively accessible cancer cell specimen (liquid biopsy) from patients. The number of circulating tumor cells (CTCs) in cancer patients has recently been shown to be a valuable diagnostic indicator of the state of metastatic breast cancer. In particular, patients with few or no CTCs were found to have a better overall prognosis compared to patients with high numbers of CTCs. Despite the implications of CTCs as diagnostics for advanced breast cancer treatment, a critical challenge for adopting CTC-based diagnostic tests has been the development of methods with sufficient sensitivity to reliably detect the small number of CTCs that are present in the circulation. Furthermore, current tests for CTC detection are expensive, have high false positives and negatives, have high background noise, are time consuming and require a significant level of expertise to conduct. To overcome the limitations of current CTC detection assays and develop more sensitive, rapid and cost effective CTC detection methods, we explored the potential of detecting CTCs by measuring their nuclease activity with nuclease-activated probes (1). We present data towards the development of a rapid and highly-sensitive CTC detection assay based on nuclease-activated oligonucleotide probes that are selectively digested (activated) by target nucleases expressed in breast cancer cells. We confirm that these probes are not activated by serum nucleases or nucleases from a lymphoblastic cell line (e.g. K-562). Furthermore, we present extensive data towards the optimization of activity and sensitivity of these probes in cell lysates from various breast cancer cell lines and in blood from breast cancer patients. Future studies will focus on developing similar probes for the detection of CTCs in patients with pancreatic and ovarian cancer where early detection would greatly improve survival outcomes. In conclusion, this work describes a robust assay for detection of breast cancer CTCs that will be straightforward to implement in most clinical diagnostic labs.
High Risk AML Outpatient Management: A Retrospective Analysis of Bacteremia Incidence Following Chemotherapy.
Authors: Timotheus Y. Halim, Julye C. Lavoie, Michael J. Barnett, Stephen H. Nantel, Thomas J. Nevill, John D. Shepherd, Heather J. Sutherland, Donna E. Hogge, Kevin W. Song, Donna L. Forrest, Cynthia L. Toze, Clay A. Smith
Journal: Blood (2004)
Abstract 1220: MDM2 promotes p53-independent breast cancer metastatic phenotypes
Authors: Chong Gao, Nandini Kundu, Jill Bargonetti
Journal: Cancer Research (2015)

Abstract Many human cancers overexpress the E3 ubiquitin ligase MDM2. The cancer genome atlas (TCGA) found that increased MDM2 expression is one of four gene pathways that correlate with all breast cancer subtypes. An increasing body of literature strongly suggests that overexpression of MDM2 can drive breast oncogenesis in the presence of mutant p53 (mtp53), as well as through molecular pathways that do not require wild-type p53 degradation. Therefore, the canonical wild-type p53 degradation pathway by MDM2 is clearly not the only important pathway. MDM2 expression has been shown to influence breast cancer cell invasion and metastasis. One potential mechanism for this is through the activation of SLUG (a transcription repressor of E-Cadherin) and the process of E-cadherin degradation. To investigate the p53-independent influence of MDM2 we engineered human breast cancer clones with inducible shRNA to knockdown MDM2 in MDA-MB-231 (mtp53 R280K), T47D (mtp53 L194F) and MCF-7 (wild-type p53) cells. Wound healing assays showed that MDM2 knockdown in all three cell lines reduced cell migratory capacity without altering p53 protein levels. In T47D.shmdm2 cells, a decrease in SLUG expression was observed with MDM2 knockdown indicating SLUG is a p53-independent target of MDM2. The knockdown of MDM2 also decreased slug and mmp9 mRNA detected by quantitative RT-PCR. To determine the biological significance of MDM2 in a system to recapitulate breast cancer architecture we examined T47D.shmdm2 cells in a 3-dimensional (3D) cell culture model. Importantly, the depletion of MDM2 in T47D.shmdm2 cells grown in 3D culture promoted luminal clearance. Our findings suggest that MDM2 can influence SLUG and MMP9 levels associated with breast cancer metastasis through a mechanism that does not require degradation of wild-type p53. Moreover our work suggests that MDM2 may promote changes to breast cancer architecture that drive metastasis. Acknowledgements. This work was supported by a grant to JB from the Breast Cancer Research Foundation. Citation Format: Chong Gao, Nandini Kundu, Jill Bargonetti. MDM2 promotes p53-independent breast cancer metastatic phenotypes. [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 1220. doi:10.1158/1538-7445.AM2015-1220
A Severe Case of Delayed Haemolytic Transfusion Reaction in a Sickle Cell Disease Patient: Immuno-Haematological Study, Cytokine Transcripts and Lymphocyte Subsets Analysis.
Authors: France Noizat-Pirenne, Helene Ansart-Pirenne, Anne Plonquet, Philippe Chadebech, Anoosha Habibi, Dora Bachir, Frederic Galacteros, Philippe Bierling
Journal: Blood (2005)
In Newborn Mice, Tpo Signaling Is Required for Normal Megakaryocyte Proliferation, Maturation, Platelet Formation, and Platelet Survival
Authors: Haley Ramsey, Francesca Ferrer-Marin, Renata Grozovsky, Hoffmeister Karin, Joseph E. Italiano, Zhongbo Hu, William B. Slayton, Martha Sola-Visner
Journal: Blood (2014)
Abstract LB-082: FLJ25439, a novel cytokinesis-associated protein, induces tetraploidization and maintains chromosomal stability via enhancing expression of endoplasmic reticulum stress chaperones
Authors: Pin Ouyang
Journal: Cancer Research (2015)

Abstract Purpose of the study: Identify and characterize a novel D box-containing protein, FLJ25439 for tetraploid induction and maintenance of genomic stability. Pertinent experimental procedures: Immunofluorescent microscopy and flow cytometry for cell cycle determination. Proteomics and bioinformatics approaches for protein category profiling. Summary of the data: Investigation of the mechanisms leading to aneuploidy and polyploidy is critical to cancer research. Previous studies have provided strong evidence of the importance of tetraploidization as an early step in tumorigenesis. In cancer cells, tetraploid cells may contribute to abnormal mitotic progression, which may be associated with cytokinesis failure. Tetraploidy leads to genomic instability due to centrosome and chromosome over-replication. Until now, the mechanism by which cells maintain tetraploid status has been unknown. Here, we identified a novel D box-containing protein, FLJ25439, which displays a dynamic expression profile during mitosis/cytokinesis with the midbody as the most prominent associated structure. To understand the function of FLJ25439, we established stable cell lines overexpressing FLJ25439. FLJ25439-overexpression cells grew slower and displayed a tetraploid DNA content in comparison with diploid parental cells. They also showed aberrant mitosis and dysregulated expression of p53, pRb and p21, suggesting a defect in cell cycle progression. To explore the molecular mechanisms responsible for FLJ25439-induced tetraploidization, we conducted a comparative analysis of the global protein expression patterns of wild type and overexpressors using proteomics and bioinformatics approaches. Protein category profiling indicated that FLJ25439 is involved in pathways related to anti-apoptosis, protein folding, the cell cycle, and cytoskeleton regulation. Specifically, genotoxic-stress- and ER stress-related chaperone proteins greatly contributed to the FLJ25439 overexpression phenotypes. Conclusion: The results of this study pave the way to our further understanding of the role of FLJ25439, a novel cytokinesis-related protein in protecting cells from environmental stress and tetraploid formation. Note: This abstract was not presented at the meeting. Citation Format: Pin Ouyang. FLJ25439, a novel cytokinesis-associated protein, induces tetraploidization and maintains chromosomal stability via enhancing expression of endoplasmic reticulum stress chaperones. [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 LB-082. doi:10.1158/1538-7445.AM2015-LB-082