tbuckley/cabot-search huggingface dataset:
Comparing Psychosocial Profiles and Outcomes between Patients Undergoing Myeloablative and Non-Myeloablative Allogeneic Transplants.
Authors: Linda McLellan, Larry W. Foster, Lisa Rybicki, Jane Dabney, Michele Visnosky, Sungren Sungren, Alison Vellani, Nicole Berry, Kelly Cherni, Laura Bernhard, Jennifer Kosar, Mary Serafin, Karen Sands, Christina Ferraro, Brian J. Bolwell
Journal: Blood (2006)
Dietary iron intake and breast cancer: The Iowa Women’s Heath Study.
Authors: Duk-Hee Lee, Kristin E. Anderson, Lisa J. Harnark, David R. Jacobs
Journal: Cancer Research (2004)

2319  In laboratory and animal studies, excess iron can both induce and promote cancer. Positive associations between high body iron stores or high iron intake and some cancer sites have been also reported in epidemiological studies. Recently, animal studies observed an interaction between estrogen and iron on the development of estrogen-induced cancer, in which high dietary iron intake enhanced the both incidence and severity of estrogen-induced tumor developments. Even though the human body has several defense mechanisms to protect against oxidative damage caused by iron, alcohol has been known to disturb iron homeostasis. Therefore, if iron has any effect on the risk of cancer, it might be stronger among drinkers. This study was performed to examine if 1) there is a relationship between dietary iron intake measured by food-frequency questionnaire and the incidence of breast cancer and 2) the association between dietary iron intake and breast cancer differs depending on level of alcohol consumption. Data collected prospectively as part of the Iowa Women’s Health Study were analyzed to examine these research questions. Among a total analysis cohort of 34,388 postmenopausal women, a total of 2,017 women were diagnosed with breast cancer during 15 years of follow-up. After adjustment for age, parity, age at first birth, age at menarche, family history of breast cancer, history of benign breast disease, body mass index, height, age at menopause, postmenopausal hormone use, intake of alcohol, total energy, animal fat, vegetable fat, beta carotene, vitamin E, and folate, among all subjects, neither dietary non-heme nor dietary heme iron intake at baseline (9% of total dietary iron) were associated with incidence of breast cancer. After stratification by alcohol consumption, both dietary non-heme and heme iron intake was positively associated with risk of breast cancer among drinkers who consumed ≥20g/d (P for interaction
Inhibition of Wnt Signaling By Dimethyl Fumarate Results in in Vitro and in Vivo Clearance of Chronic Lymphocytic Leukemia Cells and Has Additive Activity with Ibrutinib
Authors: Christina C.N. Wu, Fitzgerald Lao, Hongying Li, Laura Rassenti, Thomas J. Kipps, Karen Messer, Dennis A. Carson, Michael Y. Choi
Journal: Blood (2014)
Abstract 4940: Role of Smad3 linker phosphorylation in breast cancer progression
Authors: Fang Liu, Wen Xie, Zhengxue Liu, Tanima Roy, Eunjin Bae, Lalage M. Wakefield, Seong-Jin Kim, Akira Ooshima, Michael Reiss, Isao Matsuura
Journal: Cancer Research (2015)

Abstract Smad3 plays an important role in inhibiting cell proliferation and promoting apoptosis in multiple tissues, including the breast tissue. At late stages, Smad3 promotes breast cancer progression and metastasis. We previously showed that the proline-rich linker region of Smad3 is phosphorylated by several kinases, such as by CDKs and MAP kinases. We have mapped these phosphorylation sites. We show that mutation of the phosphorylation sites in the Smad3 linker region increases the ability of Smad3 to inhibit cell proliferation and promote apoptosis. Interestingly, mutation of the Smad3 linker phosphorylation sites also increases the ability of Smad3 to activate genes that promote metastasis. Accordingly, mutation of the Smad3 linker phosphorylation sites markedly inhibits tumorigenicity but promotes metastasis of breast cancer cell lines. Using human breast cancer tissue microarrays, we further show that Smad3 linker phosphorylation is progressively reduced along breast cancer progression. Taken together, our findings strongly suggest that Smad3 linker phosphorylation promotes tumorigenesis but inhibits metastasis. Our findings have important implications for cancer therapy. Citation Format: Fang Liu, Wen Xie, Zhengxue Liu, Tanima Roy, Eunjin Bae, Lalage M. Wakefield, Seong-Jin Kim, Akira Ooshima, Michael Reiss, Isao Matsuura. Role of Smad3 linker phosphorylation in breast cancer 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 4940. doi:10.1158/1538-7445.AM2015-4940
203. Shortened T Cell Culture with IL-7 and IL-15 Provides the Most Potent Chimeric Antigen Receptor (CAR)-Modified T Cells for Adoptive Immunotherapy
Authors: Saba Ghassemi, Felipe Bedoya, Selene Nunez-Cruz, Carl June, Jos Melenhorst, Michael Milone
Journal: Molecular Therapy (2016)

Adoptive T cell immunotherapy involves the isolation, ex vivo expansion and reinfusion of patient T cells. The efficacy of adoptive immunotherapy is dependent on the ability of T cells to engraft, expand and persist upon adoptive transfer. In this therapy, T cells are cultured ex vivo using natural or artificial antigen presenting cells that deliver signal 1 (TCR/CD3) and signal 2 (e.g. CD28 co-stimulation) along with exogenously added cytokines. IL-2 is the most commonly used cytokine for ex vivo T cell culture; however, there is renewed interest in IL-7 and IL-15 due to their ability to enhance the survival and proliferation of stem cell memory (Tscm) and central memory (Tcm) T cells. We show that primary human T cells freshly isolated from peripheral blood are heterogeneous with substantial numbers of Tscm and Tcm cells in addition to effector differentiated T cells. During ex vivo culture, these cells progressively differentiate into a population of T cells with a predominantly CD45RO+, CD27-, CCR7- effector differentiated phenotype. Exogenous IL-7 and IL-15 delay this transition in T cell phenotype and preserve a greater proportion of Tscm and Tcm cells in the final ex vivo culture product. We hypothesize that limited ex vivo culture of T cells in the presence of IL-7 and IL-15 rather than IL-2 will enhance engraftment and persistence of T cells in vivo contributing to enhanced efficacy in adoptive transfer. We show that T cells can be harvested and viably frozen from ex vivo cultures as early as day 3 following activation. Early activated T cells expressing a chimeric antigen receptor targeting CD19 (CART-19) show potent yet specific cytotoxicity and cytokine production in vitro. We investigated the therapeutic potential of cells harvested at day 3 versus later time points using a Nalm-6 leukemic cell xenograft mouse model. We demonstrate that day 3 CART-19 cells show potent anti-leukemic activity compared to day 5 or day 9 cells. Comparing CART19 cells cultured in either IL-2 or IL-7/15, we show that mice treated at a 10-fold lower dose with day 3 cells cultured in IL-7/15 exhibit the greatest anti-leukemic efficacy compared with day 9 cells where the latter fail to control leukemia. In summary, we show that limiting T cell culture ex vivo to the minimum required for lentiviral transduction in the presence of IL-7 and IL-15 provides the most efficacious T cells for adoptive T cell immunotherapy.
Immunoablative Chemotherapy before Reduced-Intensity Allogeneic Stem Cell Transplantation: A Strategy to Provide Disease Control and to Enhance Early Graft-Versus-Lymphoma Effects.
Authors: Robert M. Dean, Daniel H. Fowler, Frances T. Hakim, Jeanne Odom, Kathleen Castro, Tracey Chinn, Wyndham H. Wilson, Ronald E. Gress, Michael R. Bishop
Journal: Blood (2004)
Superiority of Double over Single Autologous Stem Cell Transplantation as First-Line Therapy for Multiple Myeloma.
Authors: Michele Cavo, Claudia Cellini, Elena Zamagni, Patrizia Tosi, Delia Cangini, Paola Tacchetti, Antonio De Vivo, Giulia Perrone, Roberto Massimo Lemoli, Sante Tura, Michele Baccarani
Journal: Blood (2004)
Abstract 4249: High-Frequency of TMPRSS2-ERG fusion gene identifies a non-random androgen-driven event of chromosomal instability in BRCA mutated prostate cancer
Authors: Elena Castro, Floortje Van de Poll, Elena Piñeiro, Paz Nombela, Elizabeth Bancroft, Koveela Govindasami, Michelle Guy, G Kovacs, Steve Ellis, Antonis Antoniu, Douglas Easton, Zsofia Kote-Jarai, Fatima Al-Sharour, David Olmos, Rosalind Eeles
Journal: Cancer Research (2015)

Abstract INTRODUCTION: Germline BRCA mutations are an independent prognostic factor for PrCa prognosis and treatment outcomes. BRCA tumours are associated with chromosomal instability due to underlying DNA repair deficiency; however, recurrent patterns of genomic aberrations in this context have not been explored. METHODS: We collected PrCa formalin-fixed paraffin-embedded samples from diagnostic biopsies and/or prostatectomies from 5 BRCA1 and 24 BRCA2 germline mutation carriers, which were matched with at least 1 sporadic PrCa (ie PrCa with no germline mutation) by stage and treatment. All samples were reviewed by an expert pathologist, and the tumour relevant areas were selected for further analyses. Recurrent chromosomal abnormalities in PrCa were also analyzed using previously described fluorescence in situ hybridization (FISH) “break-apart” and/or “fusion” assays, including a novel FISH “combined break-fusion” assay for TMPRSS2-ERG designed with probes flanking 3´and 5´of ERG and 5´of TMPRSS2. Genomic abnormalities were confirmed by a second method (qPCR or IHC) whenever possible. RESULTS: No differences in Gleason score between mutation carriers and non-carriers were seen (p = 0.134). Neuroendocrine phenotype was not identified in any sample. The “break-apart” assay identified interstitial deletion of genomic sequences between TMPRSS2 and ERG in all BRCA mutated tumours in at least one focus (100%), compared with 45% of non-carriers (P&amp;lt;0.001). The novel “break-fusion” assay allowed us to identify TMPRSS2 as the fusion partner in all cases, excluding other potential partners previously described. ETV1 rearrangements were identified in 3.5% of carriers and in 4% of non-carriers (P = 0.662). CONCLUSIONS: The presence of TMPRRSS2-ERG fusion gene in all BRCA mutated tumours in our series identifies a non-random androgen-driven event on the background of high chromosomal instability. Our findings suggests that BRCA mutated PrCa is androgen-dependent which may have important implications for the management of these patients. Citation Format: Elena Castro, Floortje Van de Poll, Elena Piñeiro, Paz Nombela, Elizabeth Bancroft, Koveela Govindasami, Michelle Guy, G Kovacs, Steve Ellis, Antonis Antoniu, Douglas Easton, Zsofia Kote-Jarai, Fatima Al-Sharour, David Olmos, Rosalind Eeles. High-Frequency of TMPRSS2-ERG fusion gene identifies a non-random androgen-driven event of chromosomal instability in BRCA mutated prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4249. doi:10.1158/1538-7445.AM2015-4249
Abstract 4825: Association between genetic profiles and histological classifications of 18 Japanese pseudomyxoma peritonei
Authors: Rei Noguchi, Hideaki Yano, Yoshimasa Gohda, Ryuichiro Suda, Toru Igari, Yasunori Ohta, Naohide Yamashita, Kiyoshi Yamaguchi, Yumi Terakado, Tsuneo Ikenoue, Yoichi Furukawa
Journal: Cancer Research (2015)

Abstract Pseudomyxoma peritonei (PMP) is a rare disease occurring in 1-2 / 1000,000 and shows a distinct clinical feature caused by cancerous cells that produce mucin or gelatinous fluid in the abdominal cavity. Tumor cells are the most frequently originated from appendiceal mucinous cancer, and less frequently from mucinous tumors of the ovary. PMP is histologically classified into two types; disseminated peritoneal adenomucinosis (DPAM) showing milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) exhibiting more aggressive phenotype. Several molecular studies have shown frequent mutations in the KRAS and GNAS genes. However molecular profiles associated with different histological and/or clinical characteristics remain largely unknown. To elucidate molecular mechanisms underlying PMP, we analyzed 18 Japanese PMP tumors comprising of 10 DPAMs and 8 PMCAs. DNA was extracted from tumor tissues and their matched normal samples, and was subjected to amplicon sequencing using Ion AmpliSeq Cancer Panel v2 (Life Technologies) containing 49 cancer-related genes. In the 18 tumors, we identified a total of 42 somatic mutations (34 missense, 1 deletion, 1 insertion, 2 intron, 1 splice site mutations, and 3 synonymous mutations) in 13 genes. Of the 42 mutations, 35 were judged as pathogenic, and the remaining seven as non-pathogenic by the search of public databases and reports, or by in silico analysis. KRAS and GNAS mutations were found in 14 (77.8%) and 8 (44.4%) tumors, respectively. Interestingly, no mutations were detected in APC or CTNNB1. Notably, TP53 mutation was found in 3 of the 8 PMCAs, but not in the 10 DPAMs. Two of the 8 PMCAs carried mutation in either PIK3CA or AKT1. These data suggest that KRAS and/or GNAS mutations play a vital role in the development of both types of PMP, and that inactivation of Wnt signaling pathway may not be involved in the tumorigenesis. Furthermore, mutations in TP53 and/or genes related to PIK3CA-AKT pathway may be associated with malignant properties of PMCA. Further studies will facilitate the elucidation of molecular mechanism underlying PMP, and contribute to the development of effective therapeutic and preventive strategies to this disease. Citation Format: Rei Noguchi, Hideaki Yano, Yoshimasa Gohda, Ryuichiro Suda, Toru Igari, Yasunori Ohta, Naohide Yamashita, Kiyoshi Yamaguchi, Yumi Terakado, Tsuneo Ikenoue, Yoichi Furukawa. Association between genetic profiles and histological classifications of 18 Japanese pseudomyxoma peritonei. [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 4825. doi:10.1158/1538-7445.AM2015-4825
Abstract 3358: SOCS3 deficiency in myeloid cells promotes tumor development: Involvement of STAT3 activation and myeloid-derived suppressor cells
Authors: Hao Yu, Hongwei Qin, Etty (Tika) Benveniste
Journal: Cancer Research (2015)

Abstract Suppressor Of Cytokine Signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway, and generally function as tumor suppressors. The absence of SOCS3 in particular leads to heightened activation of the STAT3 transcription factor, which has a striking ability to promote tumor survival while suppressing anti-tumor immunity. We report for the first time that genetic deletion of SOCS3 specifically in myeloid cells significantly enhances tumor growth, which correlates with elevated levels of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment, and diminished CD8+ T-cell infiltration in tumors. Furthermore, SOCS3-deficient bone-marrow-derived cells exhibit heightened STAT3 activation and preferentially differentiate into the Gr-1+CD11b+Ly6G+ MDSC phenotype. Importantly, we identify granulocyte-colony stimulating factor (G-CSF) as a critical factor secreted by the tumor microenvironment that promotes development of MDSC via a STAT3-dependent pathway. Abrogation of tumor-derived G-CSF reduces the proliferation and accumulation of Gr-1+CD11b+ MDSC and inhibits tumor growth. These findings highlight the critical function of SOCS3 as a negative regulator of MDSC development and function, via inhibition of STAT3 activation. Note: This abstract was not presented at the meeting. Citation Format: Hao Yu, Hongwei Qin, Etty (Tika) Benveniste. SOCS3 deficiency in myeloid cells promotes tumor development: Involvement of STAT3 activation and myeloid-derived suppressor 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 3358. doi:10.1158/1538-7445.AM2015-3358
Malignant Astrocytic Tumor Progression Potentiated by JAK-mediated Recruitment of Myeloid Cells
Authors: Prajwal Rajappa, William S. Cobb, Emma Vartanian, Yujie Huang, Laura Daly, Caitlin Hoffman, Jane Zhang, Beiyi Shen, Rachel Yanowitch, Kunal Garg, Babacar Cisse, Sara Haddock, Jason Huse, David J. Pisapia, Timothy A. Chan, David C. Lyden, Jacqueline F. Bromberg, Jeffrey P. Greenfield
Journal: Clinical Cancer Research (2016)

Purpose: While the tumor microenvironment has been known to play an integral role in tumor progression, the function of nonresident bone marrow-derived cells (BMDC) remains to be determined in neurologic tumors. Here we identified the contribution of BMDC recruitment in mediating malignant transformation from low- to high-grade gliomas.Experimental Design: We analyzed human blood and tumor samples from patients with low- and high-grade gliomas. A spontaneous platelet-derived growth factor (PDGF) murine glioma model (RCAS) was utilized to recapitulate human disease progression. Levels of CD11b+/GR1+ BMDCs were analyzed at discrete stages of tumor progression. Using bone marrow transplantation, we determined the unique influence of BMDCs in the transition from low- to high-grade glioma. The functional role of these BMDCs was then examined using a JAK 1/2 inhibitor (AZD1480).Results: CD11b+ myeloid cells were significantly increased during tumor progression in peripheral blood and tumors of glioma patients. Increases in CD11b+/GR1+ cells were observed in murine peripheral blood, bone marrow, and tumors during low-grade to high-grade transformation. Transient blockade of CD11b+ cell expansion using a JAK 1/2 Inhibitor (AZD1480) impaired mobilization of these cells and was associated with a reduction in tumor volume, maintenance of a low-grade tumor phenotype, and prolongation in survival.Conclusions: We demonstrate that impaired recruitment of CD11b+ myeloid cells with a JAK1/2 inhibitor inhibits glioma progression in vivo and prolongs survival in a murine glioma model. Clin Cancer Res; 23(12); 3109-19. ©2016 AACR.
Abstract 3697: Development of a focused non-hydrolyzable phosphopeptide library based on a high affinity SHP2 substrate
Authors: Harshani R. Lawrence, Yunting Luo, Steven Gunawan, Andreas Becker, Yuan Ren, Ernst Schonbrunn, Jie Wu, Nicholas J. Lawrence
Journal: Cancer Research (2015)

Abstract The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2), a widely expressed cytoplasmic tyrosine phosphatase with two src-homology 2 (SH2) domains, has received much attention in the signal transduction field. SHP2 is a transducer of growth factor, cytokine, integrin, and hormone signaling pathways that regulate processes such as cell proliferation, differentiation, adhesion, migration, and apoptosis and plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with several types of leukemias, and solid tumors; this makes SHP2 is an attractive target for cancer therapy Several small molecules have been developed for inhibition of this important phosphatase, which serve as chemical tools to probe the role of SHP2 in disease and lead compounds for optimization. Nevertheless it is challenging to improve these lead compounds with better potency, selectivity and cell permeability. To gain structural insights for development of potent and selective SHP2 inhibitors, we synthesized a non-hydrolyzable phosphotyrosine peptide mimetic based on reported SHP2 substrate peptide sequence (10-mer). The non-hydrolyzable phosphopeptide, containing the phosphotyrosyl surrogate difluoromethylphosphonate, was synthesized using solid phase peptide synthesis methods from the known building block N-FMOCF2Pmp and we improved the coupling reaction conditions to generate a peptide library of difluoromethylphosphonate to understand the SHP2 affinity. We will present the synthesis of the peptide library, analysis of SHP2 phosphatase inhibition, and the binding mode (X-ray crystal structure) of the phosphopeptide mimic to SHP2. Citation Format: Harshani R. Lawrence, Yunting Luo, Steven Gunawan, Andreas Becker, Yuan Ren, Ernst Schonbrunn, Jie Wu, Nicholas J. Lawrence. Development of a focused non-hydrolyzable phosphopeptide library based on a high affinity SHP2 substrate. [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 3697. doi:10.1158/1538-7445.AM2015-3697
MDM2 Promoter SNP309 Is Associated with An Increased Susceptibility to Chronic Lymphocytic Leukemia and Correlates with MDM2 mRNA Expression In Chinese Population
Authors: Hua-Jie Dong, Cheng Fang, Lei Fan, Dan-Xia Zhu, Dong-Mei Wang, Hua-Yuan Zhu, Yun Zhuang, Kou-Rong Miao, Peng Liu, Wei Xu, Jianyong Li
Journal: Blood (2010)
The REVLIRIT CLL5 AGMT Study - a Phase I/II Trial Combining Fludarabine/Rituximab with Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL): Results of a Planned Interim Analysis.
Authors: Alexander Egle, Michael Steurer, Thomas Melchardt, Marion Stoll, Richard Greil
Journal: Blood (2009)
Pediatric Hodgkin Lymphoma Patients Treated with ABVD Chemotherapy with or without Low-Dose Radiation Therapy.
Authors: Amani Al-Kofide, Asim F. Belgaumi, Yasser Khafaga, Nicey Joseph, Rubina J. Malik, Waleed Mourad, Gamal-Eldin H. Mohamed, Rajeh S. Sabbah
Journal: Blood (2006)
Abstract 1223: LIF is a novel negative regulator of p53 in colorectal cancers
Authors: Wenwei Hu, Haiyang Yu, Xuetian Yue, Yuhan Zhao, Cen Zhang, Ken Young, Juan Liu, Zhaohui Feng
Journal: Cancer Research (2015)

Abstract Leukemia inhibitory factor (LIF), a cytokine of the interleukin 6 superfamily,is involved in multiple biological functions. Recently, we identified that LIF is a p53 target gene which mediates the role of p53 in maternal implantation under normal physiological conditions in both mice and humans. However, to date, the role of LIF in tumorigenesis, especially colorectal cancers, is poorly understood. Here, we report that LIF is a negative regulator of p53; LIF downregulates p53 protein levels and function in transcriptional activity, apoptosis and senescence in human colorectal cancer cells. The downregulation of p53 by LIF is mediated by the activation of Stat3; blocking the Stat3 pathway largely abolishes the inhibitory effect of LIF on p53. We further identified that Stat3 transcriptionally induces ID1, the helix-loop-helix (HLH) protein inhibitor of differentiation and DNA binding to mediate its role in the negative regulation of p53. ID1 upregulates MDM2, a key negative regulator of p53, and promotes MDM2-mediated p53 protein degradation. We found that LIF is overexpressed in a large percentage of colorectal cancers. In turn, LIF overexpression promotes cellular resistance towards chemotherapeutic agents in cultured colorectal cancer cells and colorectal xenograft tumors in a largely p53-dependent manner. Furthermore, we found that overexpression of LIF is associated with a poor prognosis in colorectal patients. Taken together, LIF is a novel negative regulator of p53, overexpression of LIF is an important mechanism for the attenuation of p53, which promotes chemoresistance in colorectal cancers. Targeting LIF, Stat3 as well as ID1 to reactivate p53 is a potential therapeutic strategy to enhance chemosensitivity in colorectal cancer, especially in tumors with LIF overexpression. Citation Format: Wenwei Hu, Haiyang Yu, Xuetian Yue, Yuhan Zhao, Cen Zhang, Ken Young, Juan Liu, Zhaohui Feng. LIF is a novel negative regulator of p53 in colorectal cancers. [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 1223. doi:10.1158/1538-7445.AM2015-1223