tbuckley/cabot-search huggingface dataset:
Abstract 4565:ATMgenotyping modulates the risk of radiation-associated breast cancer among atomic-bomb survivors
Authors: Tomonori Hayashi, Yiqun Hu, Kengo Yoshida, Waka Ohishi, Ayumi Hida, Ikue Hayashi, Seishi Kyoizumi, Yoichiro Kusunoki, Kei Nakachi
Journal: Cancer Research (2015)

Abstract Objective: RERF epidemiological studies among atomic-bomb (A-bomb) survivors have demonstrated significantly-increased incidence of selected cancers with increased radiation dose. It is noteworthy that a great deal of inter-individual variation in susceptibility to radiation-associated cancers could not be explained solely by radiation dose and age at exposure, suggesting the possibility that this variation might be partly ascribed to inter-individual differences in DNA repair capacity. Of 11 known single nucleotide polymorphisms (SNPs) of the DNA repair gene ATM, we selected a particular SNP (rs189037; located in the 5′ untranslated region and therefore thought to be associated with ATM gene expression) and examined the association with radiation-associated breast cancer in the context of an RERF A-bomb survivor cohort study. Materials and Methods: A follow-up survey during 1981-2005 of 2,944 female members of the RERF Immunogenome Study Cohort identified a total of 100 breast cancer cases. ATM genotypes (ATM-G/G, -G/A, and -A/A) were determined by the TaqMan assay method for all cohort members. Relative risks (RRs) of breast cancer were estimated for radiation dose, the ATM genotypes, and the combined categories of dose levels and genotypes. Results and Discussion: Disregarding the genotype effects, RR of breast cancer significantly increased with increased radiation dose (RR = 1.51/Gy, 95% CI: 1.25-1.83). For overall radiation dose levels, A-bomb survivors with ATM-G/G homozygote revealed a significantly-increased RR of breast cancer (RR = 1.85, 95%CI: 1.24-2.75), using as reference the risk of those with ATM-A/A homozygotes combined with ATM-G/A heterozygotes. When radiation dose was categorized into three levels (&amp;lt; 5 mGy referred to as “non-exposed,” 5-530 mGy, and &amp;gt;530 mGy), the survivors with ATM-A/A who were exposed to the highest dose level (&amp;gt;530 mGy) showed the highest risk of breast cancer (RR = 4.76, 95%CI: 2.30-9.88), using as reference the risk of “non-exposed” survivors with ATM-T/T or ATM-A/T. These results suggest the possibility that the ATM genotyping may be involved in individually differing susceptibility to radiation-associated breast cancer. Citation Format: Tomonori Hayashi, Yiqun Hu, Kengo Yoshida, Waka Ohishi, Ayumi Hida, Ikue Hayashi, Seishi Kyoizumi, Yoichiro Kusunoki, Kei Nakachi. ATM genotyping modulates the risk of radiation-associated breast cancer among atomic-bomb survivors. [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 4565. doi:10.1158/1538-7445.AM2015-4565
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Patients Aged 65 Years or Older with AML and MDS.
Authors: Marcos de Lima, Munir Shahjahan, Jorge Alamo, Patricia Williams, Brigitte von Wolff, Daniel Couriel, Issa Khouri, Gabriela Rondon, Brandy Wheeler, Elihu Estey, Naoto Ueno, Partow Kebriaei, Richard Champlin, Sergio Giralt
Journal: Blood (2004)
656. Small Molecule Induced Robust Erythroid Differentiation of Cord Blood CD34+ Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands
Authors: Eyayu K. Belay, David W. Emery, Beverly Torok-Storb
Journal: Molecular Therapy (2015)

Erythropoiesis take place in a specialized microenvironment called the erythroblastic island (EI) in the bone marrow. EIs are the functional unit of erythropoiesis with a central "nursing" macrophage surrounded by developing erythroblasts. The presence of EIs in in vitro erythroid differentiation of hematopoietic stem cells has not been explored. Recently, we reported the presence and expansion of macrophages along with the robust erythroid differentiation of Cell Growth Switch engineered cord blood (CB) CD34+ cells in response to a small drug molecule. Here, we further characterize the physical, cellular and molecular interaction between the macrophages and erythroid cells in culture. Scanning electron microscopy of in situ fixed cells revealed a patterned direct association of erythroblasts with the pseudopodia of a central macrophage [See Figure 1]. This interaction was further confirmed by gene expression studies which detected erythroblast macrophage protein (EMP), vascular cell adhesion molecule 1 (VCAM1) and Ephrin type-B receptor 4 (EphB4), all of which are known to be involved in macrophage-erythroblast interactions. In addition, both macrophages and erythroid cells express Ferroportine indicative of iron channeling between the two cells. Phenotypically, the macrophages were CD206+, CD14+, CD11C+, CD169-, CD115- and CD106-. Proteomics analysis of the culture supernatant showed the secretion of EI associated factors: MCP1 (7454 pg/ml), VEGF (760 pg/ml), GMCSF (66 pg/ml), HGF (65 pg/ml), IL-6 (46 pg/ml), MCSF (28 pg/ml) and RANTEs (23 pg/ml), while the control basal medium has no detectable level of these factors. Overall, the in vitro macrophage-erythroid association mimics the bone marrow EI micro environment and supports the robust erythroid commitment of CB CD34+ cells in response to a small drug molecule, without the addition of exogenous cytokines. Further studies are required to determine the extent to which the robust erythropoiesis that takes place in the cell growth switch cultures triggers the commitment of CB CD34+ cells into macrophages.
Abstract 3933: The landscape and clonal architecture in lower grade glioma
Authors: Hiromichi Suzuki, Kosuke Aoki, Kenichi Chiba, Yusuke Sato, Yusuke Shiozawa, Yuichi Shiraishi, Atsushi Niida, Teppei Shimamura, Masashi Sanada, Satoru Miyano, Toshihiko Wakabayashi, Atsushi Natsume, Seishi Ogawa
Journal: Cancer Research (2015)

Abstract Lower grade gliomas (LGGs, WHO grade II/III gliomas) account for approximately one third of all gliomas. Although LGGs are typically slowly progressive, their clinical course is invariably indolent and most patients ultimately succumb to death. In contrast to glioblastoma (GBM), our knowledge about the genetic lesions and clonal evolution in LGG is still incomplete. So, to obtain a complete registry of gene mutations involved in LGG pathogenesis and their role in clonal evolution, we performed whole exome sequencing (WES) and/or targeted sequencing of 335 LGG cases. Clonal evolution in LGG was investigated using paired primary/relapsed tumor specimens from 10 cases as well as multiple tumor specimens (median 5) from 4 cases. Massive parallel sequencing revealed LGGs were clearly grouped into three subgroups with or without IDH1/2 mutation and 1p19q loss of heterozygous (LOH). Type I tumor with IDH1/2 mutation and 1p19q LOH had a most favorable survival and harbored mutations in TERT promoter, CIC, FUBP1 and NOTCH1. Type II tumor with IDH1/2 mutant/1p19q intact subtype represented TP53 bialleleic inactivation and/or ATRX mutations. Type III tumor with IDH1/2 intact showed GBM like mutation profile and poor prognosis. Large scale samples allowed to obviously detect strong positive/negative correlations with each other driver genes. Extensive analysis of variant allele frequencies among co-existing mutations revealed temporal orders of gene mutations in each subtypes. Multi regional/time-points sampling analysis suppoted mutational order and revealed regional and special heterogeneity with tumor evolution in LGGs. LGG contiguously developed and generated heterogeneity through acquiring new mutations in a complex but ordered fashion. In conclusion, our findings delineated the landscape of gene mutations in LGG. LGG had mutually exclusive mutational patterns with hierarchical order in discrete subtypes. IDH1/2 and TERT promoter mutations and 1p19q LOH were thought to exist in the major clone and important role in tumor initiation. In contrast, common occurrence of parallel mutations found in TP53, ATRX, CIC, FUBP1 and NOTCH1 genes indicated central roles of these mutations in LGG development. Citation Format: Hiromichi Suzuki, Kosuke Aoki, Kenichi Chiba, Yusuke Sato, Yusuke Shiozawa, Yuichi Shiraishi, Atsushi Niida, Teppei Shimamura, Masashi Sanada, Satoru Miyano, Toshihiko Wakabayashi, Atsushi Natsume, Seishi Ogawa. The landscape and clonal architecture in lower grade glioma. [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 3933. doi:10.1158/1538-7445.AM2015-3933
Effect of G-CSF and Intramyocardial Injection of Bone Marrow Cells on Cardiac Function in Mouse Model of Myocardial Infarction: A Word for Neo-Vasculogenesis.
Authors: Larissa Verda, Kehuan Luo, Xiaoqiang Han, Andrew Wasserstrom, Jon Lomasney, Barbara Kowalska, Richard K. Burt
Journal: Blood (2004)
Continued Transmission of Parvovirus B19 in Plasma-Derived Factor Concentrates After the Implementation of B19 Nucleic Acid Plasma Minipool Screening,
Authors: J. Michael Soucie, Christine De Staercke, Meera B. Chitlur, Ralph A. Gruppo, W Craig Hooper, Craig M. Kessler, Roshni Kulkarni, Marilyn J. Manco-Johnson, Paul E. Monahan, Meredith Oakley, Jerry Powell, Meredith Pyle, Michael Recht, Brenda Riske, Hernan Sabio, Sean Trimble
Journal: Blood (2011)
Unrelated Cord Blood Transplantation for Children with Juvenile Myelomonocytic Leukemia.
Authors: Franco Locatelli, Adrienne B.M. Madureira, Vanderson Rocha, Pierre Teira, Martin Champagne, Tracey A. O’Brien, Ajay Vora, Jerry Stein, Teresa Olive, Carmem S. Bonfim, Jan Stary, Yves Bertrand, Federico Garnier, Irina Ionescu, Charlotte Niemeyer, Eliane Gluckman
Journal: Blood (2007)
Abstract 4561: Cancer preventive effect of antioxidants for spontaneous liver cancer in XPA(-/-) mice
Authors: Ying Fu, Shana Silverstein, Marcin Dyba, Heidi Coia, Elizabeth Sinclair, Jishen Pan, Bhaskar Kallakury, Michael D. Johnson, Fung-Lung Chung
Journal: Cancer Research (2015)

Abstract γ-Hydroxy-1, N2-propanodeoxyguanosine (γ-OHPdG), a widely studied acrolein-derived cyclic adduct arisen from oxidized ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), is a mutagenic lesion that is repaired by nucleotide excision repair (NER) pathway. C3H/HeN xeroderma pigmentosum group A (XPA) knockout mice which are deficient on NER pathway showed a significant elevation in liver tumors. We hypothesized that accumulation of γ-OHPdG is playing a role in liver tumorigenesis of XPA(-/-) mice; suppressing the formation of γ-OHPdG by dietary antioxidants should result in the prevention of liver cancer in this model. In this work, we investigated the chemoprotective efficacy of three antioxidants: α-lipoic acid, polyphenon E and vitamin E against liver tumorigenesis in XPA(-/-) mice. Autopsy at 19 months of age revealed that all the antioxidants exhibited significant inhibition effects on the development of liver tumors. Polyphenon E showed the most potent effects with 80% of the mice showing complete protection. The formation γ-OHPdG was measured in the livers of XPA(-/-) mice. An age-dependent increase of γ-OHPdG was found in the liver DNA of XPA(-/-) mice, but not in lungs (a non-target tissue). All the antioxidants decreased the formation of γ-OHPdG. Immunohistochemistry (IHC) for Ki-67 (proliferation index marker) was performed on all the liver samples, and the results showed that dietary antioxidants significantly decrease the proliferation in the liver tumors. α-Lipoic acid and vitamin E showed significant inhibitory effect, although to a lesser extent than Polyphenon E, against the spontaneous liver carcinogenesis in XPA gene-deficient mice model. A correlation between the cancer preventive efficacy and suppression of γ-OHPdG adduct level is observed, indicating a possible role of γ-OHPdG in the liver cancer development in this model. We also explored the feasibility of next-generation sequencing (NGS) to validate the mutation frequency changes as a result of feeding the antioxidant diets. This work was supported by the NCI grant: RO1-CA-134892. Y.F. thanks the Prevent Cancer Foundation for his fellowship (Marcia and Frank Carlucci Charitable Foundation Award in Cancer Prevention and Early Detection) Note: This abstract was not presented at the meeting. Citation Format: Ying Fu, Shana Silverstein, Marcin Dyba, Heidi Coia, Elizabeth Sinclair, Jishen Pan, Bhaskar Kallakury, Michael D. Johnson, Fung-Lung Chung. Cancer preventive effect of antioxidants for spontaneous liver cancer in XPA(-/-) mice. [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 4561. doi:10.1158/1538-7445.AM2015-4561
517. Anti-Tumor Immunity Is Elicited by a Conditionally Replicative Adenovirus in Canine Osteosarcoma
Authors: Bruce F. Smith, Payal Agarwal, Elizabeth Gammon, David T. Curiel, Igor Dmitriev, Elena Kashentseva
Journal: Molecular Therapy (2016)

Conditionally replicative viruses have been proposed as a potential therapy for a wide variety of tumors. Initially, these viruses were thought to exert their anti-tumor properties through the lysis of infected tumor cells. However, there is the potential that oncolytic viruses may also elicit anti-tumor immune responses in both the context of viral antigens and potentially tumor antigens. Canine osteosarcoma is an excellent intermediate animal model in which the ability of a conditionally replicative adenovirus (CRAd) to induce anti-tumor immunization can be uniquely ascertained. This tumor exhibits many of the same characteristics of the human disease, including metastasis to the lungs. A CRAd based on canine adenovirus type 2 with the E1 gene driven by the osteocalcin promoter was administered to canine patients with confirmed osteosarcoma of the appendicular skeleton. Cellular and humoral immune responses, as well as cytokine profiles and regulatory T-cells were assessed before and after treatment. The number of dogs surviving past one year was approximately 20%. No changes were identified in levels of cytotoxic T-cells after therapy, when using autologous tumor cells as targets. Likewise, no significant changes in a panel of cytokines were observed. However, evaluation of humoral immune responses by western blot and flow cytometry, using autologous tumor, indicated that all dogs in the study had pre-existing antibodies to their own tumors and that these antibodies increased post treatment. This increase consisted of both an increase in the amount of antibody present and the recognition of new antigenic determinants. Serum from treated dogs also cross-reacted with tumor cells from unrelated dogs as well as a canine melanoma cell line. These results indicate that treatment with a CRAd does result in active immunization against the tumor, however it is unclear if the observed immune responses play any role in patient outcomes. Based upon these findings, we can now hypothesize that manipulation of these immune responses by including immune modulating genetic constructs in the CRAd may serve to alter the type and efficacy of the patient's immune response and enhance survival.
The Reciprocal t(9;22) p96ABL/BCR fusion Protein Eenhances the Transformation Potential of BCR/ABL and Increases Therapy Resistance in Models of Ph+ Acute Lymphatic Leukemia
Authors: Anahita Rafiei, Afsar Mian, Anna Metodieva, Claudia Oancea, Hubert Serve, Heike Pfeifer, Oliver G. Ottmann, Martin Ruthardt
Journal: Blood (2012)
718. Cell Therapy Commercialization: An Assessment of Translational Barriers
Authors: David Pettitt, Georg Hollander, David Brindley
Journal: Molecular Therapy (2016)

Cellular based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics - offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular based therapeutics from "bench to bedside" remains challenging, and the number of industry products available for widespread clinical use remains comparatively low. This systematic review identifies unique intrinsic and extrinsic barriers in the cell based therapy domain. Key electronic databases were searched and manuscripts subjected to pre-defined inclusion and exclusion criteria. Two independent reviewers examined the retrieved publications, and performed data extraction. 3374 unique publications were identified. 138 of these qualified for full assessment and subsequent data extraction. A number of key themes were identified, enabling examination of current challenges and opportunities facing cell therapy development, including manufacturing, regulatory, reimbursement, ethical and clinical adoption issues. In addition to an up-to-date analysis of the current landscape, we discuss a number of pragmatic solutions to facilitate future development and translation.
Abstract 3307: Chemopotentiation by low dose fractionated radiation therapy in colon cancer cells
Authors: Teresa Smith, Palak R. Parekh, Elizabeth T. Chang, Michael Chuong, France Carrier
Journal: Cancer Research (2015)

Abstract Response rates for patients with primary and metastatic colorectal cancer treated with modern chemotherapy regimens such as 5-FU, leucovorin, oxaliplatin (FOLFOX) have routinely exceeded 50% and are frequently as high as 60-70%. However, as in most chemotherapy regimens, toxicity to normal cells is often a significant limitation. Tumors of the gastrointestinal (GI) track are also sensitive to radiation but the inability to combine radiation therapy (RT) with full-dose chemotherapy can be detrimental to patients, particularly those that may have disseminated micrometastatic disease. Therefore, new treatment strategies that incorporate chemotherapy that could increase tumor response without increasing toxicity are highly desirable. Laboratory and clinical data suggest that using low-dose fractionated radiation therapy (LDFRT) as a chemopotentiator may allow for full-dose chemotherapy with improved efficacy without adding to the toxicity of the systemic treatment. Here we show that twice daily radiation doses as low as 0.15 Gy for three consecutive days can significantly increase FOLFOX killing efficiency in human colon cancer RKO cells. In addition, our data indicate that the chemopotentiation by LDFRT may be mediated by the stress inducible hnRNP A18 protein. Down regulation of hnRNP A18 sensitizes RKO cells to LDFRT and FOLFOX independently and increases further the chemopotentiation by LDFRT. Moreover, overexpression of hnRNP A18 increases radio-resistance and chemo-resistance to FOLFOX. hnRNP A18 is a new regulator of protein translation in cancer cells that specifically targets transcripts devoted to confer growth advantages. This data suggest that hnRNP A18 could be targeted to increase further the systemic effect of chemopotentation by LDFRT. The identification of hnNRP A18 as a new cellular pathway responsive to low dose radiation and its contribution to chemopotentiation provide a novel opportunity for better measurement of the therapeutic response and could contribute to the rationale designs of new mechanism based clinical trials. Citation Format: Teresa Smith, Palak R. Parekh, Elizabeth T. Chang, Michael Chuong, France Carrier. Chemopotentiation by low dose fractionated radiation therapy in colon 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 3307. doi:10.1158/1538-7445.AM2015-3307
Prevalence and Prognostic Impact of CEBPA mutations in Children with AML Treated with the AIEOP-LAM 2002/01 Protocol.
Authors: Giovanni Cazzaniga, Riccardo Masetti, Giulia Ferrari, Tiziana Coliva, Carmelo Rizzari, Roberto Rondelli, Fiorina Casale, Franca Fagioli, Luca Lo Nigro, Matteo Luciani, Concetta Micalizzi, Giuseppe Menna, Maria Caterina Putti, Nicola Santoro, Giuseppe Basso, Franco Locatelli, Andrea Biondi, Andrea Pession
Journal: Blood (2009)
Abstract 4868: CODEX: a normalization and copy number variation detection method for whole-exome sequencing
Authors: Yuchao Jiang, Derek A. Oldridge, Sharon J. Diskin, Nancy R. Zhang
Journal: Cancer Research (2015)

Abstract Background: High throughput sequencing of DNA coding regions has become a common way of assaying genomic variation in the study of cancer. Copy number aberration (CNA) is an important type of genomic change, but detecting and characterizing CNA from whole-exome sequencing (WES) is challenging due to the high level of biases and artifacts. Methods: We propose CODEX, a normalization and CNA calling procedure for WES data. The Poisson latent factor model in CODEX includes terms that specifically remove biases due to GC content, exon capture and amplification efficiency, and latent systemic artifacts. CODEX also includes a Poisson likelihood-based recursive segmentation procedure that explicitly models the count-based WES data. CODEX can be used to detect both germline and somatic CNAs in cancer samples with or without matched normal. Results: Compared to existing approaches, CODEX is shown to be more effective in removing the biases in WES, and attains better sensitivity and specificity in detecting copy number aberrations by in silico spike-in studies. We further evaluate performance on 222 neuroblastoma samples with matched normal from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Project. We carry out systematic genome-wide analysis and detailed characterization of both germline and somatic copy number events. With a focus on a well-studied rare somatic CNV within the ATRX gene, we show that the cross-sample normalization procedure of CODEX is more effective in removing noise than the standard pipeline of normalizing the tumor against the matched normal, and that the segmentation procedure performs well in detecting CNVs with recurrent complex nested structures. For detecting germline mutations, CODEX is compared to existing methods on a population analysis of HapMap samples from the 1000 Genomes Project, and shown to be perform well on three microarray-based validation data sets. Conclusions: The cross-sample normalization procedure of CODEX, when applied to the matrix of tumor and normal samples, is more effective in reducing noise than normalizing each tumor to its matched normal. The somatic deletions in the ATRX region have a nested structure, which CODEX was able to recover. Through multiple types of validation, CODEX is shown to be applicable to a wide range of study designs for copy number estimation using WES data. Citation Format: Yuchao Jiang, Derek A. Oldridge, Sharon J. Diskin, Nancy R. Zhang. CODEX: a normalization and copy number variation detection method for whole-exome sequencing. [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 4868. doi:10.1158/1538-7445.AM2015-4868