tbuckley/cabot-search huggingface dataset:
Abstract 5235: Dietary administration of δ- and γ-tocopherol inhibits estrogen-mediated mammary tumorigenesis in ACI rats
Authors: Soumyasri Das Gupta, Joseph Wahler, Min Ji Bak, Mao-Jung Lee, Yong Lin, Weichung Joe Shih, Chung S Yang, Nanjoo Suh
Journal: Cancer Research (2016)

Abstract Tocopherols (T), members of the vitamin E family, occur in four forms designated as α, β, δ and γ. Epidemiological studies suggest that tocopherols could reduce the risk of cancer. α-T is known as the classical vitamin E, being the predominant form of tocopherol found in human blood and tissues. However, clinical studies with α-T to substantiate the role of tocopherols in cancer prevention have provided inconclusive results. Such outcomes indicate that the cancer preventive activity of tocopherols might be attributed to the other forms of tocopherols, but not α-T. γ-T, which is the most abundant tocopherol in vegetable oils, is our major dietary source of tocopherols. Recent studies have demonstrated that δ-T and γ-T have higher anti-cancer activity than α-T in several animal models of cancer. The present study investigated the cancer preventive activity of individual purified forms of tocopherols α-T, δ-T, γ-T as well as a naturally occurring γ-T rich mixture of tocopherols (γ-TmT) in an in vivo model of estrogen receptor (ER)-positive breast cancer, namely estrogen supplemented August-Copenhagen Irish (ACI) rats. ACI rats were subcutaneously implanted with 9 mg of 17β-estradiol (E2) in silastic tubings and administered with diets containing 0.2% α-T, δ-T, γ-T or γ-TmT. Rats were euthanized at 30 weeks of mammary carcinogenesis when the E2 control group exhibited 100% tumor incidence. α-T had no effect on estrogen-induced mammary tumors. However, treatment with 0.2% δ-T, γ-T and γ-TmT reduced the tumor volume by 51% (p&amp;lt;0.05), 60% (p&amp;lt;0.01) and 59% (p&amp;lt;0.01), respectively. Administration of α-T, δ-T and γ-T resulted in a 2.1-, 80- and 62-fold increase of these tocopherols, respectively, in the serum of ACI rats. Supplementation with the individual tocopherols also increased the levels of their respective short chain metabolite, carboxyethyl hydroxychromans (CEHCs) in the serum. Administration of δ-T and γ-T was associated with 185- and 99-fold increase in their CEHC metabolites, respectively. The high serum levels of δ- and γ-CEHC metabolites could contribute to the enhanced chemopreventive activity of δ-T and γ-T. In conclusion, δ-T, γ-T and γ-TmT could be potential natural agents for the prevention of estrogen-induced mammary tumorigenesis. (This work was supported by the NIH grant R01 AT007036 and the New Jersey Commission on Cancer Research Postdoctoral Fellowship to Soumyasri Das Gupta). Citation Format: Soumyasri Das Gupta, Joseph Wahler, Min Ji Bak, Mao-Jung Lee, Yong Lin, Weichung Joe Shih, Chung S Yang, Nanjoo Suh. Dietary administration of δ- and γ-tocopherol inhibits estrogen-mediated mammary tumorigenesis in ACI rats. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5235.
Abstract 2333: Possible prediction of tumor specific checkpoint inhibitor response based on TCGA somatic mutation load
Authors: Leandro Machado Colli, Mitchell J. Machiela, Timothy Myers, Lea Jessop, Kai Yu, Stephen J. Chanock
Journal: Cancer Research (2016)

Abstract Immune checkpoint inhibitor therapy has been shown to be effective in a subset of patients with melanoma, non-small cell lung cancer (NSCLC) and kidney cancer. Recent studies have suggested that the number of non-synonymous mutations (NsM) can be used to select melanoma and NSCLC patients most likely to benefit from immune checkpoint inhibitor treatment. It is hypothesized that NsMs generate novel epitopes and gene products which can be detected by the immune system. The aim of this study is to apply prior information on NsM count and immune checkpoint inhibitor treatment to a range of tumor subtypes in the TCGA database to evaluate the proportion cases that could be possible responders. In our analysis of published studies of melanoma and NSCLC, the receiver operator characteristic (ROC) curve suggests a cutoff of 192 NsM would have a maximum combination of sensitivity (74%) and specificity (59.3%) for potential clinical benefit for patients. We conducted an analysis of 7,757 samples from 26 different TCGA tumor types and observed that approximately 16.2% of TCGA samples harbor more than 192 NsM, and thus could be in the category associated with a higher likelihood of response to immune checkpoint inhibitors. Based on NsM count, bladder, colon, gastric, and endometrial cancers each contained more than 30% of tumors with a high NsM and thus, could be possible candidates for checkpoint immune therapy. Although our model estimates clinical response to immune checkpoint treatment from NsM count is preliminary and needs future validation, information on NsM count can be useful for selecting tumor types most likely to benefit in clinical trials of immune checkpoint inhibitor treatment. Citation Format: Leandro Machado Colli, Mitchell J. Machiela, Timothy Myers, Lea Jessop, Kai Yu, Stephen J. Chanock. Possible prediction of tumor specific checkpoint inhibitor response based on TCGA somatic mutation load. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2333.
Reply to L.E. Daly et al
Authors: Susanne Blauwhoff-Buskermolen, Marian A.E. de van der Schueren, Jacqueline A.E. Langius, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2016)

We thank Daly et al 1 for providing valuable comments regarding our recent paper on the prognostic role of muscle loss during anticancer treatment in patients with metastatic colorectal cancer. 2We have found that muscle mass decreased significantly during chemotherapy and a decrease in muscle mass was independently associated with poor survival in patients with metastatic colorectal cancer.Daly et al 1 correctly note that we observed no associations between a low skeletal muscle index at baseline and reduced survival, in contrast to some but not all previous studies.In our article, we provide some explanations for this discrepancy, for example, the heterogeneity regarding treatment regimens and follow-up time. 2 Daly et al add a possible explanation as there may be a possible difference in body composition reference values between a North American (Canadian) and European population.Daly et al suggest that extrapolating cutoff points from a Canadian population to a cohort of Dutch patients may have been a suboptimal approach to identify the true prevalence of low SMI and the relationship between low SMI and survival within this cohort.We acknowledge the importance of differences in body composition between countries.For example, the Dutch population, on average, is taller and the prevalence of overweight and obesity is lower compared with the Canadian population. 3,4Although a large percentage of the Canadian population consists of (European) immigrants, 5 we agree that it would be better to compare our study data with normative values derived from a European, or even a Dutch, population.Although we did find a new publication with cutoff values for an Asian population, 6 normative data for a European population are not available yet.There are several options to consider to overcome the question of ethnic variation in body composition in the near future.Data on body composition measured with computed tomography scans from recent European studies 7-10 could be pooled to build a database with reference values for the European population.Another approach is to derive normative values from a healthy population, which is what our group is working on at the moment.It would then be interesting to repeat the statistical analyses of our study and to investigate whether our population truly displayed a low skeletal muscle index compared with European reference values.Only then we will be able to understand why skeletal muscle index was not associated with survival in our cohort and whether this may have been caused by choosing the wrong reference group.In the meantime, while we await reference values for different countries and/or ethnic groups, we recommend that future studies on body composition display patient characteristics with regard to ethnicity, especially when cutoff values or reference values are being used.This does not apply to Europe alone, but also to other regions across the world.
BRAF, PIK3CA, and PTEN status and benefit from cetuximab (CET) in the treatment of advanced colorectal cancer (CRC): Results from NCIC CTG/AGITG CO.17.
Authors: Derek J. Jonker, Christos Stelios Karapetis, Christopher J. O'Callaghan, Celia Marginean, John Raymond Zalcberg, John Simes, Malcolm J. Moore, Niall Christopher Tebbutt, Timothy Jay Price, Manijeh Daneshmand, Jennifer Hanson, Jeremy David Shapiro, Nick Pavlakis, Peter Gibbs, Guy A. Van Hazel, Ursula Joan Yu Min Lee, Rashida Haq, Shakeel Virk, Dongsheng Tu, Ian Lorimer
Journal: Journal of Clinical Oncology (2012)

3515 Background: CET, a monoclonal antibody targeting the epidermal growth factor receptor, improves overall survival (OS) and progression free survival (PFS) in patients (pts) with KRAS wild-type (WT) chemotherapy refractory CRC. BRAF and PIK3CA mutation status, and PTEN expression levels may further predict benefit from CET therapy. Methods: Available colorectal tumour samples were analyzed from a phase III trial of CET plus best supportive care (BSC) vs BSC alone (NEJM 2007; 357(20)). BRAF and PIK3CA mutations (MUT) identified in tumour-derived DNA using a high resolution melting analysis to identify amplicons with mutations were confirmed by sequencing. PTEN expression by immunohistochemistry (IHC) was performed on tissue microarrays constructed from available tumour blocks. For each biomarker, prognostic (treatment independent) effects were assessed in patients on the BSC alone arm. Predictive effects (benefit from CET) on OS and PFS among all patients and those in the KRAS wild-type subset were examined using a Cox model with tests for treatment-biomarker interaction, adjusting for covariates. Results: Of 401 pts assessed for BRAF status (70% of CO17 population), 13(3%) had mutations. Of 407 pts assessed for PIK3CA status (71% of CO17 population), 61(15%) had mutations. Of 205 pts assessed for PTEN (36% of CO17 population), 148(72%) were negative for IHC expression. No biomarker was prognostic for OS or PFS, and none were predictive of benefit from CET, either in the whole study population or the KRAS WT subset. Conclusions: In chemotherapy-refractory CRC, neither PIK3CA mutation status nor PTEN expression were predictive of benefit from CET therapy. BRAF mutations are uncommon in this setting. Larger sample sizes would be required to determine if BRAF status is predictive for CET benefit. [Table: see text]
Abstract 1502: Three intrinsic subtypes of prostate cancer with distinct pathway activation profiles differ in prognosis and treatment response
Authors: Sungyong You, Beatrice Knudsen, Nicholas Erho, Mohammed Alshalalfa, Mandeep Takhar, Hussam Al-deen Ashab, Elai Davicioni, Robert Jeffrey Karnes, Eric A. Klein, Robert B. Den, Ashley E. Ross, Edward M. Schaeffer, Isla P. Garraway, Jayoung Kim, Michael R. Freeman
Journal: Cancer Research (2016)

Abstract In the era of precision medicine, genomic classifications of prostate cancer (PC) have not broadly impacted patient care. Here we present an integrative transcriptome analysis of 14 disease-related pathways in over 4,600 clinical specimens and 25 PC preclinical models. This approach provides a novel classification scheme, inclusive of 3 PC subtypes (PCS1-3), which predict disease progression and drug resistance. The PCS1 and PCS2 categories possess characteristics of luminal cells, while PCS3 exhibits basal features. Castration-resistant and metastatic cancers are over-represented in PCS1 and PCS3 tumors. All 3 subtypes are represented in commonly used PC cell lines; however, none of the mouse models we analyzed resembles PCS3. PCS classification using RNA expression data appears to be stable across primary and metastatic human tumors, cell lines, xenografts and mouse models. This new subtyping method provides novel opportunities for patient stratification that reflect specific features of tumor biology and may influence therapeutic decisions. Citation Format: Sungyong You, Beatrice Knudsen, Nicholas Erho, Mohammed Alshalalfa, Mandeep Takhar, Hussam Al-deen Ashab, Elai Davicioni, Robert Jeffrey Karnes, Eric A. Klein, Robert B. Den, Ashley E. Ross, Edward M. Schaeffer, Isla P. Garraway, Jayoung Kim, Michael R. Freeman. Three intrinsic subtypes of prostate cancer with distinct pathway activation profiles differ in prognosis and treatment response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1502.
Abstract 4510: KIT melanomas are developmentally racially biased
Authors: Margaret I. Sanchez, James M. Grichnik
Journal: Cancer Research (2016)

Abstract KIT is a critical pathway for melanocytic homeostasis and it is often down-regulated in cutaneous melanoma. However, KIT activation plays a critical role in a subpopulation of melanomas especially those in acral locations and melanomas on chronically sun damaged skin. We analyzed exome and RNAseq data from The Cancer Genome Atlas (TCGA) Network (321 cutaneous melanomas in the data set) to identify patterns unique to KIT activation. The melanomas were divided based on known mutually exclusive mutations (BRAF, NRAS and KIT) vs those without (WT). We compared RNA data between each group. KIT group had significantly higher expression of KIT than BRAF, NRAS and WT (p&amp;lt;0.01, FDR&amp;lt;0.01) and isoform 2 expression was higher than 1. KIT melanomas were found to overexpress Wnt pathway, pigmentation and genes involved epithelial-mesenchymal transition. From the exome data, germline SNPs with incidence in ethnic groups (Caucasian, Asian and African) and more likely to be present in a specific melanoma groups were selected. Comparing the 3 ethnicity groups across the 4 tumor groups Asian SNPs were significantly enhanced in KIT tumors, African in WT and Caucasian in BRAF and NRAS melanomas. We evaluated the tumors for the primary type of genetic damage. The three signatures that appeared most divergent were CC&amp;gt;TT for UV, (G/A)C(G)&amp;gt;(G/A)T(G) for deamination, and G&amp;gt;T for oxidative damage. UV and deamination appeared inversely proportional, while oxidative damage appeared to be independent of those other two features. KIT and WT had a greater% of non UV high deamination tumoral environments. A fraction of these tumors also had very high oxidative signatures. We then compared 2 KIT subgroups UV vs non UV (absence of CC&amp;gt;TT mutations) for germline ethnicity differences. Asian SNPs were highly increased in non UV subgroup whereas Caucasian SNPs were in UV subgroup. Further, we divided KIT non UV subgroup into deamination and oxidative damage subgroups and compared ethnicity differences. Deamination was significantly higher in Asians whereas oxidative damage was higher in Caucasians. A similar analysis was done to the WT group, where African SNPs were significantly increased in the non UV subgroup and were primarily associated with oxidative damage. This data implies that KIT mutant melanomas develop in a unique genetic and mutational environments and makes this an ideal system to in which study racial disparities at the molecular level. Citation Format: Margaret I. Sanchez, James M. Grichnik. KIT melanomas are developmentally racially biased. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4510.
Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils
Authors: Yanfang Liu, Yan Gu, Yanmei Han, Qian Zhang, Zhengping Jiang, Xiang Zhang, Bo Huang, Xiaoqing Xu, Jianming Zheng, Xuetao Cao
Journal: Cancer Cell (2016)
Pulmonary Hypertension in Sickle Cell Disease: Correlation With Echocardiographic Assessment and Serum Brain Natriuretic Peptide Concentration
Authors: Salam Alkindi, Zeba Jabeen, Anil Pathare, Mohammed Al-Huneini, Murtadha Al Khabori, Khalil Al-Farsi, Adil Al Riyami, Majdah Al-Raesi, David Dennison
Journal: Blood (2013)
Abstract 1101: The role of miR-601 in prostate cancer progression
Authors: Jessica L. Fleming, Erica Hlavin Bell, Kathryn Andrews, Arnab Chakravarti
Journal: Cancer Research (2016)

Abstract Prostate cancer (PCa) is the second most common cancer among men worldwide. In order to advance treatment options for these men, it is crucial to understand the molecular underpinning behind this cancer. Previously, our group identified miR-601 as a predictive biomarker in PCa. Few studies to date have functionally validated molecular biomarkers and currently nothing is known about the function of miR-601 in PCa. Based on our previous publication, we hypothesized that miR-601 is playing a role in PCa progression. In order to assess this, in vitro experiments were conducted in three PCa cell lines, DU-145, PC-3, and LNCaP. miR-601 was over-expressed and knocked down in each cell line and assays were performed evaluating cell proliferation, colony formation, and apoptosis. Additionally, to provide more information regarding miR-601-associated pathways, we identified putative gene targets of miR-601 using in silico prediction programs, microrna.org and TargetScan.org and evaluated top gene targets in vitro. The results of our experiments indicate that miR-601 is playing a role of a tumor suppressor. Over-expression of miR-601 in cell lines resulted in a significant reduction in cell viability. This was confirmed both by MTS as well as colony formation assays. We looked into the mechanism behind the reduction in cell viability and found that cells over-expressing miR-601 had reduced levels of full-length caspase-3, signifying that these cells are undergoing apoptosis. Two putative gene targets of miR-601 were identified and investigated in vitro, SIRT1, a histone deacetylase known to be both an oncogene and tumor suppressor, and BCL2L2, an anti-apoptotic gene known to be an oncogene. SIRT1 and BCL2L2 had strong scores on both online prediction programs as likely targets of miR-601. Our in vitro results confirmed this. We saw reduced mRNA and protein expression of these targets in cells over-expressing miR-601. Our data thus far suggest that miR-601 is acting as a tumor suppressor in PCa. Targeted therapies for miR-601 and/or its targets may be promising in the treatment of PCa, however additional work is needed to warrant this. This work was supported by R01CA108633 (To AC), 1RC2CA148190 (To AC) U10CA180850-01 (To AC), 1R01CA169368 (To AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (To AC), Ohio State University Comprehensive Cancer Center Award (To AC). Citation Format: Jessica L. Fleming, Erica Hlavin Bell, Kathryn Andrews, Arnab Chakravarti. The role of miR-601 in prostate cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1101.
Recommendations for Premature Ovarian Insufficiency Surveillance for Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Report From the International Late Effects of Childhood Cancer Guideline Harmonization Group in Collaboration With the PanCareSurFup Consortium
Authors: Wendy van Dorp, Renée L. Mulder, Leontien C.M. Kremer, Melissa M. Hudson, Marry M. van den Heuvel-Eibrink, Marleen H. van den Berg, Jennifer M. Levine, Eline van Dulmen-den Broeder, Natascia di Iorgi, Assunta Albanese, Saro H. Armenian, Smita Bhatia, Louis S. Constine, Andreas Corrias, Rebecca Deans, Uta Dirksen, Clarisa R. Gracia, Lars Hjorth, Leah Kroon, Cornelis B. Lambalk, Wendy Landier, Gill Levitt, Alison Leiper, Lillian Meacham, Alesandro Mussa, Sebastian J. Neggers, Kevin C. Oeffinger, Alberto Revelli, Hanneke M. van Santen, Roderick Skinner, Andrew Toogood, William H. Wallace, Riccardo Haupt
Journal: Journal of Clinical Oncology (2016)

Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were treated with alkylating agents and/or radiation, with potential exposure of the ovaries, have an increased risk of premature ovarian insufficiency (POI). Clinical practice guidelines can facilitate these survivors' access to optimal treatment of late effects that may improve health and quality of survival; however, surveillance recommendations vary among the existing long-term follow-up guidelines, which impedes the implementation of screening.The present guideline was developed by using an evidence-based approach and summarizes harmonized POI surveillance recommendations for female survivors of CAYA cancer who were diagnosed at age < 25 years. The recommendations were formulated by an international multidisciplinary panel and graded according to the strength of the evidence and the potential benefit gained from early detection and intervention. The harmonized POI surveillance recommendations were developed by using a transparent process and are intended to facilitate care for survivors of CAYA cancer.The harmonized set of POI surveillance recommendations is intended to be scientifically rigorous, to positively influence health outcomes, and to facilitate the care for female survivors of CAYA cancer.
Gene Expression Distinguishes Burkitt Lymphoma from Other Aggressive Lymphomas and Identifies Patients Who Are Highly Curable with Intensive Chemotherapeutic Regimens.
Authors: Sandeep S. Dave, K. Fu, G. Wright, Lloyd Lam, T. C. Greiner, Dennis D. Weisenberger, P. M. Kluin, E. Boerma, A. Rosenwald, G. Ott, H. K. Muller-Hermelink, R. D. Gascoyne, J. Delabie, L. M. Rimsza, R. M. Braziel, T. M. Grogan, E. Campo, E. S. Jaffe, J. Vose, J. O. Armitage, J. M. Connors, E. B. Smeland, S. Kvaloy, H. Holte, T. P. Miller, R. I. Fisher, E. Montserrat, W. H. Wilson, M. Bahl, H. Zhao, L. Yang, J. Powell, R. Simon, W. C. Chan, L. M. Staudt
Journal: Blood (2005)