bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4820: Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women.
Authors: Nimptsch Katharina , Zhang Xuehong , Giovannucci Edward , Cassidy Aedin , O'Reilly Éilis J. , Pischon Tobias , Rimm Eric B. , Lin Jennifer , Willett Walter C. , Fuchs Charles S. , Wu Kana 
Published: August 2014

Abstract
Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a recent randomized controlled trial, the Polyp Prevention Trial, a higher intake of one sub-class, flavonols, was significantly associated with a 76% reduced risk of recurrent advanced adenoma. Cohort studies that have examined the association between flavonoid intake and risk of colorectal cancer (CRC) have yielded inconsistent results, but most previous studies only evaluated habitual intake of a limited number of subclasses and there is growing evidence for differential effects depending on subtle difference in structure between the sub-classes
Objective: To examine whether higher habitual dietary intake of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones and polymers) are associated with lower risk of CRC.
Methods: Using data from validated food frequency questionnaires administered every four years and an updated USDA flavonoid food composition database flavonoid intakes were calculated for 73,666 participants from the Nurses’ Health Study I, and for 32,059 participants from the Health Professionals Follow-up Study.
Results: During 16 years of follow-up, 1,405 colorectal cancer cases (652 in men, 753 in women) were identified. Intakes of total flavonoids and subclasses were not associated with risk of CRC (hazard ratios (95% confidence interval) multivariable adjusted for age, smoking before age 30, family history of colorectal cancer, history of endoscopy, aspirin use, body mass index, physical activity, postmenopausal hormone use in women, alcohol consumption, intake of total energy, calcium and vitamin D; highest vs. lowest quintile: total flavonoids, men: 0.97 (0.75-1.26), women: 1.00 (0.80-1.26); flavonols, men: 0.98 (0.76-1.26), women: 1.21 (0.96-1.52); flavones, men: 0.86 (0.67-1.11), women: 0.90 (0.72-1.13); flavanones, men: 0.98 (0.75-1.28), women: 1.00 (0.80-1.26); flavan-3-ols, men: 1.00 (0.78-1.29), women: 0.96 (0.76-1.21); anthocyanins, men: 0.89 (0.69-1.15), women: 1.25 (0.98-1.60); polymers, men: 0.92 (0.71-1.18), women: 0.88 (0.69-1.11)).
Conclusion: Our findings do not provide support for the hypothesis that a higher intake of flavonoids or any specific sub-class decrease risk of CRC.
Citation Format: Katharina Nimptsch, Xuehong Zhang, Edward Giovannucci, Aedin Cassidy, Éilis J. O'Reilly, Tobias Pischon, Eric B. Rimm, Jennifer Lin, Walter C. Willett, Charles S. Fuchs, Kana Wu. Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4820. doi:10.1158/1538-7445.AM2013-4820
Abstract 4866: CLEFMA induces apoptosis and downregulates inflammatory markers in lung cancer model.
Authors: Yadav Vivek R. , Sahoo Kaustuv , Awasthi Vibhudutta 
Published: August 2014

Abstract
Background: Inflammation is a precursor for many cancers. NF-kB plays an important role in inflammation, is associated with cancerous growth and has been identified as a potential target for development of anticancer therapies. Lung cancer is a classic example of inflammation-induced carcinogenesis where it prevents apoptosis and stimulates production of pro-inflammatory cytokines. CLEFMA or 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] is a new molecule that potently inhibits proliferation of various cancer cells without affecting normal cells. In this study, we evaluated the antiproliferative activity of CLEFMA in a mouse xenograft model of human lung cancer.
Methods: Cell viability was determined in human lung cancer cells H441 and A549 after treatment with CLEFMA. Immunobloting studies were performed in cell lysates and tissue homogenates for anti-apoptotic and pro-apoptotic markers. These were further confirmed by immunohistochemical studies. The ability of CLEFMA in reducing the metabolic turnover in tumor tissue was examined by positron emission tomography using F-18-FDG as a biomarker of glucose metabolism.
Results: We found that CLEFMA-induced suppression of lung adenocarcinoma H441 and A549 cell proliferation was associated with cleavage of caspases 3/9 and PARP, suggesting apoptotic cell death. In vivo, CLEFMA demonstrated a dose-dependent suppression of tumor growth associated with reduction of tumor proliferation marker Ki-67. Non-invasive PET imaging with F-18-flurodeoxyglucose also showed abrogation of glucose uptake in tumor tissue. In the tumor tissue homogenates, we found inhibition of anti-apoptotic markers cIAP1, Bcl-XL, BCL2 and survivin, and upregulation of pro-apoptotic BID cleavage, BAX and PARP. Further, CLEFMA inhibited NF-kB at mRNA level and reduced phospho-p65 translocation into the nucleus. It also reduced the expression of COX-2 in tumor tissue, and significantly reduced serum pro-inflammatory cytokines TNF-α and IL-6.
Conclusions: The findings suggest that CLEFMA inhibits growth of lung cancer xenografts by activating caspase-dependent apoptotic pathway, and the tumor suppression is associated with anti-inflammatory and anti-metastatic effects, perhaps mediated by NF-kB.
Citation Format: Vivek R. Yadav, Kaustuv Sahoo, Vibhudutta Awasthi. CLEFMA induces apoptosis and downregulates inflammatory markers in lung cancer model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4866. doi:10.1158/1538-7445.AM2013-4866
Abstract 4869: β-caryophyllene inhibits solid tumor growth and metastasis of B16F10 melanoma cells in C57BL/6 mice fed on a high-fat diet.
Authors: Jung Jae In , Kim Eun Ji , Jung Yoo Jin , Chun Hyang Sook , Park Jung Han Yoon 
Published: August 2014

Abstract
We previously observed that chronic consumption of a high-fat diet (HFD) increased the melanoma progression and lymph node metastasis in C57BL/6N mice injected with B16F10 melanoma cells. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils especially clove and oregano oils. In the present study, we examined whether BCP inhibits HFD-induced melanoma growth and metastasis in the B16F10 allograft model. Four-week old, male C57BL/6 mice were fed on a HFD (60 kcal% fat) or control diet (CD, 10 kcal% fat) with or without BCP (0.15, 0.3% in diet) for a period of 21 weeks. Following 16 weeks of either CD or HFD in the absence or presence of BCP, B16F10 melanoma cells were subcutaneously injected into mice and all mice were continuously fed identical diets. Three weeks post-injection, tumors were resected and mice were sacrificed three weeks post-resection. The body weights and the growth of solid tumors were markedly increased in the HFD group as compared to the CD group, and these increases were suppressed by BCP treatment. The expression of proteins related to cell proliferation (Ki67, CDK4, cyclin A, and cyclin D1), angiogenesis (VEGF-A, VEGFR-2, and CD31) and lymphangiogenesis (VEGF-C, VEGF-D, VEGFR-3, and LYVE-1) was markedly increased in tumor tissues of the HFD group as compared to the CD group, and these increases were blocked by BCP treatment. HFD feeding increased the infiltration of CD45+ leukocytes and F4/80+ macrophages into tumor tissues. The administration of BCP significantly suppressed HFD-induced the infiltration of the immune cells into tumor tissues. HFD feeding reduced TUNEL-positive apoptotic cells in the tumor tissues, which was prevented by BCP treatment. Two weeks after tumor resection, the mice evidenced lung and lymph node metastasis. Lung and lymph node metastasis were increased in the mice fed on HFD, and these increases were markedly suppressed by BCP treatment. The present results demonstrate that BCP suppressed HFD-stimulated melanoma progression and metastasis, which may have been mediated via the suppression of cell cycle progression, angiogenesis and lymph angiogenesis, and induction of apoptosis in tumor tissues. These results suggest that BCP has potential as an anti-cancer agent for the prevention of obesity-stimulated melanoma progression.
Citation Format: Jae In Jung, Eun Ji Kim, Yoo Jin Jung, Hyang Sook Chun, Jung Han Yoon Park. β-caryophyllene inhibits solid tumor growth and metastasis of B16F10 melanoma cells in C57BL/6 mice fed on a high-fat diet. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4869. doi:10.1158/1538-7445.AM2013-4869
Abstract 4882: Differential BMP4 and GREM1 protein expression in uterine leiomyosarcoma and leiomyoma.
Authors: Garcia Natalia , Souza Faila Catarina , Cunha Isabela Werneck , Soares Fernando Augusto , Maciel Gustavo Arantes Rosa , Baracat Edmund Chada , Carvalho Katia Candido 
Published: August 2014

Abstract
Background:
Uterine leiomyosarcoma (ULMS) and leiomyoma (ULM) are smooth muscle tumors with distinct clinical behavior. Little is known about the factors that influence these tumors biology. Differential diagnosis among low grade ULMS and the several clinical forms of ULM is a challenge both in laboratory and pathological routine. Thus, the identification of new molecular markers can help in the differential diagnosis between ULM from ULMS and clinical management. Our aim was to evaluate expression of bone morphogenetic protein - 4 (BMP-4) and Gremlin-1 (GREM1) in uterine leiomyosarcoma and leiomyoma (including leiomyoma with atypia) using immunohistochemistry. Method: 57 patients with ULMS and 30 with ULM, among them
10 ULM with atypia (ULMA) were select. The tissues were used in tissue microarray construction. Immunohistochemistry reaction was performed with monoclonal antibody against BMP-4 and GREM-1 and evaluated using semi-quantitative method.
Results: BMP-4 was positive in 43% of the ULMS, 5% ULM and 80% ULMA, respectively. GREM-1 was positive in 67% of the ULMS, 20% ULM and 10% ULMA. BMP-4 is a potent growth factor that is involved in many important biological processes. Gremlin-1 can specifically bind to BMP-4 precursor protein inside cells, which prevents the production and secretion of mature BMP-4. This regulation determines BMP-4 biological effects on cells in the local microenvironment.
However, the molecular mechanism of GREM-1/BMP-4 interaction remains unexplored.
Conclusion: Ours preliminary results showed that expression of BMP-4 and GREM-1 play an important role in uterine smooth tumors, in while atypical leiomyomas presented higher levels of BMP-4 protein expression and lower levels of GREM-1. However, the role of these proteins interactions must be clarified.
Citation Format: Natalia Garcia, Faila Catarina Souza, Isabela Werneck Cunha, Fernando Augusto Soares, Gustavo Arantes Rosa Maciel, Edmund Chada Baracat, Katia Candido Carvalho. Differential BMP4 and GREM1 protein expression in uterine leiomyosarcoma and leiomyoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4882. doi:10.1158/1538-7445.AM2013-4882
Abstract 4886: Caffeine normalizes breast stromal fibroblasts and suppresses their pro-carcinogenic effects.
Authors: Al Ansari Mysoon M. , Aboussekhra Abdelilah 
Published: August 2014

Abstract
Breast cancer is the leading cause of morbidity and second-leading cause of death in women worldwide. Breast stromal fibroblasts, the most abundant and the most reactive cells of the tumor stroma, actively promote tumor growth, invasion, migration, angiogenesis and metastasis through elevated secretion of several factors including SDF1, MMP-2 and vascular endothelial growth factor A (VEGF-A). These secretions are under the control of several tumor suppressor genes such as p16, p53 and CAV-1, which were fond to be down-regulated in most active fibroblasts. Therefore, our major aim in this study was to study the potential use of caffeine to up-regulate these tumor suppressor genes and hence reduces the secretion of these cancer-promoting factors. We have shown that low doses of caffeine up-regulate the tumor suppressor proteins p16, p21, p53 and CAV-1 in breast stromal fibroblasts. Consequently, the expression and secretion of MMP-2 and VEGF-A was reduced following caffeine treatment. Moreover, caffeine reduced the expression of SDF-1, TGF-β and α-SMA, three important markers of active fibroblast, suggesting that caffeine has the ability of “normalizing” stromal fibroblasts. To further confirm this, we have shown that caffeine suppresses stromal fibroblast-related enhancement of invasion/migration of breast cancer cells. Importantly, this effect was mediated through caffeine-dependent inactivation of the two major invasion/migration protein kinases Akt and Erk, through up-regulating PTEN in breast stromal fibroblasts. Furthermore, caffeine suppressed the expression/secretion of VEGF-A in breast stromal fibroblasts and their paracrine enhancement of angiogenesis in vitro. This effect was mediated through inhibition of the VEGF-A activator HIF-1α. Therefore, we have clearly shown here that caffeine, a natural and pharmacologically safe product, has the potential to normalize breast stromal fibroblasts and consequently suppresses their paracrine procarcinogenic effects.
Citation Format: Mysoon M. Al Ansari, Abdelilah Aboussekhra. Caffeine normalizes breast stromal fibroblasts and suppresses their pro-carcinogenic effects. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4886. doi:10.1158/1538-7445.AM2013-4886
Abstract 4889: Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck.
Authors: Sakakura Koichi , Murata Takaaki , Chikamatsu Kazuaki 
Published: August 2014

Abstract
Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells (CSCs) from various tumors. In squamous cell carcinoma of the head and neck (SCCHN), various cell surface markers, including CD44, CD133 and ALDH1, have been identified as the potential markers to isolate CSCs. Evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs.
Histone deacetylase inhibitors (HDACi) have multiple biologic effects consequent to alteration in patterns of acetylation of histones and are promising new group of anticancer agents. In this study, we investigate the effects of two HDACi, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) on two CD44+ cancer stem-like cell lines from SCCHN cultured in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. SAHA and TSA inhibited the growth of SCCHN cell lines in a dose dependent manner as measured by MTS assays. Moreover, SAHA and TSA induced G2/M cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD44 and ABCG2 on SCCHN cell lines were decreased by SAHA or TSA treatment. HDACi also decreased the mRNA expression levels of stemness-related genes (Notch and Nanog) and TGF-β. As expected, HDACi markedly increased the expression of E-cadherin. In addition, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel had a synergistic effect on SCCHN cell lines.
Taken together, our data indicate that HDACi not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter stem-like properties of the SCCHN cells, raising the possibility that HDACi may have therapeutic potentials for cancer stem cells of SCCHN.
Citation Format: Koichi Sakakura, Takaaki Murata, Kazuaki Chikamatsu. Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4889. doi:10.1158/1538-7445.AM2013-4889
Abstract 4892: Hypoxia enhances tumor vascularization by endothelial differentiation of endometrial cancer stem cells.
Authors: Nakamura Mitsuhiro , Zhang Xiuzhi , Takakura Masahiro , Maida Yoshiko , Mizumoto Yasunari , Bono Yukiko , Sasagawa Toshiyuki , Kyo Satoru 
Published: August 2014

Abstract
Emerging evidence has shown that a small subpopulation of cancer cells plays critical roles in tumorigenesis, establishing the cancer stem cells (CSCs) theory. CSCs have properties of tumorigenesis, self-renewal and multilineage differentiation. Previous our study demonstrated that CD133+ enodometrial cancer cells showed tumorigenic and self-renewal ability, suggesting that CD133 was a potential CSC marker in endometrial cancer. In this study, we focused on multilineage differentiation and investigated an ability of endothelial differentiation in endometrial CSCs. Immunohistochemistry of subcutaneous xenografts showed that human endometrial tumors contained human vessels labeled by human-specific anti-CD31 and vWF antibodies. Endothelial tube formation assay (in vitro angiogenesis) revealed that isolated CD133+ endometrial cancer cells could show tube formation while CD133- cells could not. CD133+ cells expressed CD31 and VEGFR-1 higher than CD133- cells. In some cell types of endometrial cancer cells, flow cytometric analysis showed expression of CD31 was high ratio under hypoxia compared to normoxia. Furthermore, in vitro angiogenesis assay demonstrated hypoxic condition could promote and keep tube formation in CD133+ cells, but not CD133- cells. These results suggest that CSCs have potential of endothelial differentiation and hypoxia enhances endothelial differentiation of CSCs. These findings shed light on the establishment of new target therapy for endometrial cancer.
Citation Format: Mitsuhiro Nakamura, Xiuzhi Zhang, Masahiro Takakura, Yoshiko Maida, Yasunari Mizumoto, Yukiko Bono, Toshiyuki Sasagawa, Satoru Kyo. Hypoxia enhances tumor vascularization by endothelial differentiation of endometrial cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4892. doi:10.1158/1538-7445.AM2013-4892
Abstract 4895: A cancer stem cell instigator pathway revealed by transcriptomics, stem cell mutagenesis, and in-vivo tumor initiation.
Authors: Krtolica Ana , Glanville Jacob , Giritharan Gnanaratnam , Caceres Eduardo , Canino Erica , Kim Kyung-Ah 
Published: August 2014

Abstract
We have developed a multi-stage Cancer Stem Cell (CSC) model that recapitulates the natural process of carcinogenesis. Isogenic human embryonic stem cells (ESCs) exposed to non-biased mutagens were found to undergo rare spontaneous CSC transformation. Progenitor induced CSC (iCSC) clones exhibited classical CSC/SC marker expression, tumorsphere formation, resistance to common chemotherapeutic agents, and a capacity to form serially transplantable tumors in immunocompromised animals. A subset of progenitor clones formed tumors that took on a glioma-like morphology and produced more highly drug resistant mature CSCs that exhibited phenotypic characteristics of the primary patient glioma CSCs. Computational comparison to expression profiles of 313 human tumor lines confirmed that the mature CSCs had adopted a glioma-like expression profile.
An integrated molecular model of the instigator pathway was assessed by comprehensive RNASeq transcriptomics, tandem MS proteomics, microRNA profiling, and mutagen-induced molecular polymorphisms. Progenitor iCSCs were found to have an ESC expression phenotype, significantly differing in the expression of only 32 genes, with some bearing direct evidence of mutagenesis in the expressed transcript. The instigator genes formed a proto-oncology seed pathway that was expanded by progressive expression changes to a more classical oncology profile in the glioma-like tumors and mature iCSCs derived in vivo from the progenitor iCSC. Classical oncology targets evident in the late-stage tumor model were absent in the progenitor iCSCs. However, computational repositioning analysis identified a limited set of existing molecules that could act directly to mitigate the progenitor pathway in the iCSCs.
Citation Format: Ana Krtolica, Jacob Glanville, Gnanaratnam Giritharan, Eduardo Caceres, Erica Canino, Kyung-Ah Kim. A cancer stem cell instigator pathway revealed by transcriptomics, stem cell mutagenesis, and in-vivo tumor initiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4895. doi:10.1158/1538-7445.AM2013-4895