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  • American Association for Cancer Research (AACR)  (104)
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. SY10-02-SY10-02
    Abstract: Whole-exome sequencing studies have transformed our understanding of recurrent somatic mutations that contribute to cancer pathogenesis; however, these studies limit our ability to identify cancer-associated mutations to those that cause protein-coding changes. To more comprehensively catalogue cancer-associated gene alterations, we have extensively characterized tumor transcriptomes from 1,220 donors with matched whole-genome sequence data to identify recurrent RNA-level aberrations. Specifically, we created a unified RNA-Seq analysis pipeline including sequence alignment and quality control and subsequently identified gene alterations through outlier detection from estimated gene expression levels, alternative splicing, alternative transcription starts, and allele-specific expression and through identified RNA-edited sites and gene fusions. Our data represent an extensive catalog of RNA aberrations for each gene across 27 cancer types. We have also tested for genetic associations with these RNA phenotypes. Using an integrative analysis approach, we have mapped genome-wide cis and trans effects on individual RNA phenotypes, considering both common germline variants as well as somatic SNVs in gene promoters, enhancers, and intronic and other regions. Many of the regulatory associations we identify are not accessible by exome sequencing, underlining the importance of whole-genome sequence data. Utilizing this RNA-centric view, we have identified genes that are recurrently altered, yet have not been previously characterized as cancer genes or identified through DNA-level driver gene analysis. To identify further supporting evidence that these recurrent alterations are potential drivers, we identified genes with mutually exclusive RNA-level alterations. Our findings reveal new insights into selective advantages of somatic changes and molecular mechanisms of cancer. This work is by the Transcriptome Working Group of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium and authors are listed in alphabetical order. Citation Format: Samirkumar Amin, Philip Awadalla, Andrew Biankin, Paul Boutros, Alvis Brazma, Angela Norie Brooks, Claudia Calabrese, David Chang, Aurélien Chateigner, Ken Chen, Zechen Chong, Brian Craft, Chad Creighton, Deniz Demircioğlu, Nuno Fonseca, Milana Frenkel-Morgenstern, Gad Getz, Jonathan Göke, Mary Goldman, Liliana Greger, Syed Haider, Yao He, Katherine Hoadley, Yuan Ji, Andre Kahles, Ekta Khurana, Jan Korbel, Kjong Lehmann, Han Liang, Fenglin Liu, Maximillian Marin, Matthew Meyerson, Akinyemi Ojesina, Francis Ouellette, Chandra Pedamallu, Marc Perry, Gunnar Rätsch, Roland Schwarz, Yuichi Shiraishi, Cameron Soulette, Oliver Stegle, Patrick Tan, Alfonso Valencia, Linda Xiang, Christina Yung, Junjun Zhang, Fan Zhang, Zemin Zhang, Jingchun Zhu. Pan-cancer study of recurrent and heterogeneous RNA aberrations and association with whole-genome variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY10-02. doi:10.1158/1538-7445.AM2017-SY10-02
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 730-730
    Abstract: Background: In the US, liver cancer incidence has been tripled since the 1980s. Beyond alcohol and coffee, the relationship between other dietary factors and liver cancer remains poorly understood. One objective of this study is to comprehensively evaluate the relationship between overall and specific botanical groups of fruit and vegetable intake with liver cancer risk. Although liver disease mortality is the 11th leading cause of death in the US, its relationship with diet remains unclear. We also aimed to evaluate the association between fruit and vegetable intake and liver disease mortality. Methods: The study was conducted in the US NIH-AARP Diet and Health Study with 470,653 participants aged 50-71 years in 1995-1996. Fruits (14 items plus fruit juice) and vegetables (23 items without white potatoes included) were estimated using a validated Food Frequency Questionnaire. Cox proportional hazards regression modeling was used to estimate the multivariable hazard ratios (HR) and 95% confidence intervals (95% CI) for liver cancer incidence and liver disease mortality. We adjusted a priori for potential confounders including age, sex, education, race, alcohol intake, body mass index, smoking, total energy intake, physical activity, diabetes, and aspirin use. Results: During a median follow-up of 15.5 years, 899 incident liver cancers and 934 chronic liver disease deaths occurred. Higher intake of total vegetables was associated with a lower risk of liver cancer (HRQuintile 5 vs Quintile 1=0.66, 95%CI=0.53-0.82, Ptrend & lt;0.01). When further subclassified into botanical groups, the observed inverse association was mainly driven by Cruciferae (broccoli, cauliflower, cabbage, et. al., HRQ5 vs Q1=0.64, 95%CI=0.52-0.79, Ptrend & lt;0.01), Compositae (lettuce, HRQ5 vs Q1=0.67, 95%CI=0.54-0.83, Ptrend & lt;0.01), Leguminosae (dried beans, string beans and peas, HRQ5 vs Q1=0.77, 95%CI=0.62-0.94, Ptrend=0.01), and Umbelliferae (carrots, HRQ5 vs Q1=0.77, 95%CI=0.62-0.95, Ptrend=0.01). Additionally, higher total vegetable intake was associated with a lower risk of liver disease mortality (HRQ5 vs Q1=0.60, 95%CI=0.49-0.74, Ptrend & lt;0.01). Inverse associations were observed for lettuce, cruciferous vegetables, legumes, and carrots and liver disease mortality (all Ptrend & lt;0.01). In contrast, total fruit intake was not associated with liver cancer (HRQ5 vs Q1=0.96, 95%CI=0.77-1.19, Ptrend=0.29) or liver disease mortality (HRQ5 vs Q1=1.07, 95%CI=0.87-1.32, Ptrend=0.71). Conclusions: Based on a large prospective US cohort study, higher intakes of total vegetables, and especially lettuce, cruciferous vegetables, legumes, and carrots, were associated with lower liver cancer incidence and liver disease mortality. Citation Format: Longgang Zhao, Lina Jin, Jessica L. Petrick, Fenglei Wang, Tang Li, Hongmei Zeng, Stephanie A. Smith-Warner, A. Heather Eliassen, Fang Fang Zhang, Peter T. Campbell, Edward Giovannucci, Linda M. Liao, Susan E. Steck, Katherine A. McGlynn, Xuehong Zhang. Fruit and vegetable consumption and risk of liver cancer and liver disease mortality: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 730.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 429-429
    Abstract: KRAS is the predominantly mutated RAS isoform, accounting for 85% of RAS mutations in cancers. KRAS G12C mutation occurs in approximately 14% of lung adenocarcinomas and 3% of colorectal adenocarcinomas. Several drugs have been developed that inhibit the function of KRAS proteins with a “G12C” mutation. The response rate to these drugs in patients with KRAS G12C-mutated NSCLC is approximately 40%. Primary resistance to G12C inhibitors in these patients may be explained in part by a lack of dependency on KRAS signaling. Despite the clinical benefit observed in some patients treated with G12C inhibitors, acquired resistance to single-agent inhibitor therapy eventually develops in most patients. KRAS G12C-mutated NSCLC cell lines treated with G12C- specific inhibitor demonstrated reactivation of the down-stream MAPK pathway as a mechanism of acquired resistance. As a terminal kinase in this pathway, inhibition of ERK1/2 activity could potentially be instrumental in overcoming G12C inhibitor resistance. Moreover, aurora kinase A (AURKA) has been identified as necessary for cancer cell escape from G12C inhibitor-induced quiescence, which may be due to a stabilizing reaction between AURKA, KRAS G12C and the downstream effector CRAF. JSI-1187 is an oral reversible ERK1/2 inhibitor, and VIC-1911 is an oral selective AURKA inhibitor. To evaluate the effects of the concomitant inhibition of JSI-1187 or VIC-1911 with sotorasib, we assessed the response in 4 G12C-mutated cell lines, including two NSCLC and two CRC. Loewe synergy scores calculated showed values between 0.5 to 14.3 in these cell lines, which signified a synergistic effect of JSI-1187 or VIC-1911 combined with sotorasib. JSI-1187 or VIC-1911 combined with sotorasib or adagrasib demonstrated marked enhancement of the antitumor effect compared with single-agent treatment in a H2122 mouse xenograft model. Additionally, the antitumor growth effect of JSI-1187 and sotorasib was significantly better than the combination of the MEK inhibitor, trametinib, and sotorasib. Greater inhibition of tumor growth was also observed for the combination vs. monotherapy in H358 and SW837 CRC- bearing mouse models. Furthermore, KRAS G12C-mutated patient-derived xenografts were used to investigate a synergistic effect. Combined treatment with VIC-1911 and sotorasib demonstrated greater tumor growth inhibition than either monotherapy alone in a NSCLC PDX model. In addition, the combination of JSI-1187 and sotorasib demonstrated a significant increase in tumor growth inhibition in a CRC PDX model. Taken together, our preclinical studies suggest that the combination of an ERK inhibitor, JSI-1187, or an AURKA inhibitor, VIC-1911, may potentially overcome the primary resistance and prevent or delay the acquired resistance to G12C inhibitors. Citation Format: Lei Zhang, Ao Li, Shanzhong Jian, Chengyi Du, Wan Zhu, Yue Tao, Meiwei Wang, Wen Xu, Wenshan Hao, Linda Paradiso, Thomas Myers, Keizo Koya, Jintao Zhang. Efficacy of JSI-1187 or VIC-1911 in combination with KRAS G12C inhibitors for the treatment of KRAS G12C-mutated non-small cell lung cancer and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 429.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 4
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 24, No. 5 ( 2018-03-01), p. 1073-1081
    Abstract: Purpose: Isocitrate dehydrogenase (IDH) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data. Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming. Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively. Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II–IV glioma using conventional MR imaging using a multi-institutional data set. Clin Cancer Res; 24(5); 1073–81. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2007
    In:  Cancer Research Vol. 67, No. 18 ( 2007-09-15), p. 8580-8587
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 18 ( 2007-09-15), p. 8580-8587
    Abstract: Acid exerts pro-proliferative effects in Barrett's-associated esophageal adenocarcinoma cells. In non-neoplastic Barrett's epithelial (BAR-T) cells, in contrast, we have shown that acid exposure has antiproliferative effects. To explore our hypothesis that the acid-induced, antiproliferative effects are mediated by alterations in the proteins that regulate the G1-S cell cycle checkpoint, we exposed non-neoplastic Barrett's cells to acidic media (pH 4.0) and analyzed G1-S checkpoint proteins' expression, phosphorylation, and activity levels by Western blot. We studied acid effects on growth (by cell counts), proliferation (by flow cytometry and bromodeoxyuridine incorporation), cell viability (by trypan blue staining), and apoptosis (by annexin V staining), and we used caffeine and small interfering RNA to assess the effects of checkpoint kinase 2 (Chk2) inhibition on G1-S progression. Acid exposure significantly decreased cell numbers without affecting cell viability and with only a slight increase in apoptosis. Within 2 h of acid exposure, there was a delay in progression through the G1-S checkpoint that was associated with increased phosphorylation of Chk2, decreased levels of Cdc25A, and decreased activity of cyclin E–cyclin-dependent kinase 2; by 4 h, a continued delay at G1-S was associated with increased expression of p53 and p21. Caffeine and Chk2 siRNA abolished the acid-induced G1-S delay at 2 but not at 4 h. We conclude that acid exposure in non-neoplastic BAR-T cells causes early antiproliferative effects that are mediated by the activation of Chk2. Thus, we have elucidated a mechanism whereby acid can exert disparate effects on proliferation in neoplastic and non-neoplastic BAR-T cells. [Cancer Res 2007;67(18):8580–7]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 6
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 12, No. 11 ( 2019-11-01), p. 809-820
    Abstract: A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-dose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of −4.55 ± 11.52 from baseline 15.44 ± 13.79 ng/mg creatinine for arms combined, P = 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature (P & lt; 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5665-5665
    Abstract: Acute myeloid leukemia (AML) is an aggressive leukemia of myeloid lineage with different subtypes of varying treatments/outcomes and a global annual mortality ~150,000. The first-line treatment of AML is usually induction chemotherapy, followed by further chemo-/radiation therapies or stem cell transplant. Targeted therapy tailored for specific driver mutations could be alternative treatment options, e.g., new inhibitors targeting IDH mutations and FLT3-ITR CSF1R is a receptor tyrosine kinase (RTK) responsible for the growth, survival and polarization of certain myeloid lineages of cells including macrophages. It is also frequently expressed in certain AML patient populations, thus implicated in the pathogenesis, or a new possible drug target of AML. To test this hypothesis, a novel kinase inhibitor, HX301 with strong anti-CSF1R activity (IC50 of ~0.7nM) as well as anti-FLT3 (IC50 of ~7nM), were assessed for anti-AML activity. First, an in vitro proliferation assay was performed using primary macrophages and a panel of AML cell lines, confirming that HX-301 has high potency in primary macrophage culture (IC50 of ~70nM) and also among cultures of a subsets of AML lines (e.g. IC50 & lt; 1µM), such as MV4-11 (medium CSF1R expressing and FLT3-ITD), EOL1, MOL13, etc. Next, HX301 was pharmacologically modeled using four preclinical models to test anti-leukemia activity in vivo, including subcutaneous xenograft of MV4-11 cells (CDX) and systemically engrafted PDX models AM8096 (high CSF1R expression but wild type FLT3), AM7577 (FLT3-ITD but little CSF1R expression) and AM5512 (wild-type FLT3 and little CSF1R expression). Our data demonstrated that HX301 partially inhibited MV4-11 tumor growth as measured by tumor volume, consistent with the in vitro observation, possibly due to the inhibition of CSF1R or FLT3-ITD, or both. On the other hand, HX301 completely suppressed leukemogenesis of AM8096, likely due to the inhibition of CSF1R. This observation suggested that CSF1R is likely the driving mechanism for the leukemogenesis of this model; or in another word, for being a PDX, CSF1R likely drives pathogenesis in the original patient. HX301 also suppressed AM7577 growth, likely due to the suppression of FLT3-ITD activity since we previously reported FLT3-ITD being the driver mutation in this model which responded to AC220, a FLT3 TKi. Lastly, HX301 has little activity against AM5512. All the data suggests that HX301 can potentially be explored for the treatment of AML, at least a subset of the patients with CSF1R and FLT3-ITD as leukemogenic drivers. Further preclinical/translational studies are being conducted in order to reveal predictive biomarkers, in addition to FLT3 mutation and CSF1R expression/mutations. We believe that HX301 could be a potential candidate for treating subset of AML, warranting further clinical investigation. Citation Format: Xiaoyu An, Henry Li, Linda Xue, Jinping Liu, Lingxin Xiong, Hang Ke, Cen Chen, Bing Gao, Jia Zheng, Zhengzheng Bao, Sheng Guo, Lei Zhang, Faming Zhang. HX301 (ON1232580) a novel kinase inhibitor with potent activity against CSF1R and FLT3, shows strong anti-AML activity in defined preclinical models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5665.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 8
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2842-2842
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2842-2842
    Abstract: Macrophages are abundant in the tumor microenvironment and enhance malignancy through their promotion of angiogenesis and invasion at the primary tumor site as well as extravasation, target organ seeding and persistent growth at distant metastatic sites. To determine the origin and recruitment of tumor associated macrophages, different populations of monocytes were FACS sorted and adoptively transferred into mice bearing MMTV-PyMT induced mouse mammary tumors with or without spontaneous pulmonary metastases. Ly6C+ inflammatory monocytes were preferentially recruited to pulmonary metastases but not primary tumors in a CCL2 (also known as MCP1) dependent manner. Human inflammatory monocytes were also preferentially recruited to pulmonary metastases of human breast cancer cells in immuno-compromised mice in a CCL2 dependent manner. These inflammatory monocytes promote tumor cell trans-endothelial migration in vitro, a process that is abrogated by an anti-CCL2 neutralizing antibody. Neutralizing CCL2 in vivo blocks the recruitment of metastasis associated macrophages and their direct interaction with metastasizing tumor cells, leading to inhibition of tumor cell extravasation and metastatic seeding. Inhibition of tumor cell-derived CCL2 inhibits their metastatic seeding. Secretory factors from inflammatory monocytes were identified to mediate their metastasis-promoting function in vitro and in vivo. Both CCL2 expression and macrophage infiltration are correlated with poor prognosis in human breast cancer. Our data strongly suggest that recruitment of Ly6C+ inflammatory monocytes is the mechanistic link between these two clinical associations and suggests new therapeutic targets for treating metastatic breast disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2842. doi:10.1158/1538-7445.AM2011-2842
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 9
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 9, No. 12 ( 2019-12-01), p. 1673-1685
    Abstract: A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy. Significance: This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy. This article is highlighted in the In This Issue feature, p. 1631
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 10
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 12 ( 2021-12-01), p. 2217-2226
    Abstract: Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary Nϵ-carboxymethyl-lysine (CML)–AGE intake and mortality among women diagnosed with breast cancer. Methods: Postmenopausal women aged 50 to 79 years were enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease. Results: After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer–related, and 129 were cardiovascular disease–related). Postdiagnosis CML-AGE intake was associated with all-cause (HRT3vsT1, 1.37; 95% CI, 1.09–1.74), breast cancer (HRT3vsT1, 1.49; 95% CI, 0.98–2.24), and cardiovascular disease (HRT3vsT1, 1.91; 95% CI, 1.09–3.32) mortality. Conclusions: Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer. Impact: Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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