bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B55: Chemoprevention of obesity- and diabetes-related liver carcinogenesis by branched-chain amino acids and acyclic retinoid
Authors: Shimizu Masahito , Moriwaki Hisataka 
Published: August 2014

Abstract
Obesity and diabetes-related metabolic abnormalities, including insulin resistance, alterations in the IGF/IGF-1R axis, state of chronic inflammation, and induction of oxidative stress increase the risk of hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis, which is frequently associated with obesity and diabetes, can progress to cirrhosis and HCC. On the other hand, these findings indicate that the metabolic disorders caused by obesity and diabetes might be effective targets to prevent HCC development. For instance, branched-chain amino acids (BCAA), which improve protein energy malnutrition in patients with liver cirrhosis, improve insulin resistance and reduce the risk of HCC in obese cirrhotic patients. In an experimental study, BCAA supplementation inhibits the development of liver tumors in obese and diabetic mice by inhibiting the activation of IGF/IGF-1R axis, improving insulin resistance, reducing serum leptin levels, and attenuating hepatic steatosis and fibrosis. BCAA supplementation also inhibits the early phase of obesity-related liver tumorigenesis by attenuating chronic inflammation in both the liver and white adipose tissue. In addition, acyclic retinoid (ACR), which is a promising agent for the chemoprevention of HCC, prevents liver tumorigenesis in obese and diabetic mice by inhibiting the activation of Ras and phosphorylation of ERK and RXRα proteins. ACR administration also inhibits this tumorigenesis via improvement of insulin sensitivity and attenuation of the chronic inflammation induced by excessive fatty deposits. These findings suggest that pharmaceutical and nutraceutical approaches for targeting and restoring metabolic disorders, especially insulin resistance and chronic inflammation, may be an effective strategy for preventing the development of obesity- and diabetes-related HCC. We indicate that BCAA and ACR are considered some of the most promising agents for achieving this purpose.
Citation Format: Masahito Shimizu, Hisataka Moriwaki. Chemoprevention of obesity- and diabetes-related liver carcinogenesis by branched-chain amino acids and acyclic retinoid. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B55.
Abstract B59: Epithelial-mesenchymal interaction in cancer as potential target for anticancer therapy
Authors: Szabo Pavol , Smetana Karel , Dvorankova Barbora , Kodet Ondrej , Strnad Hynek , Kolar Michal 
Published: August 2014

Abstract
Many results demonstrate that cancer cells need for their growth and spread through organism a specific microenvironment'the tumor stroma. Carcinomas represent highly complex tissue composed from cancer cells and stroma including fibroblasts producing extracellular matrix and bioactive substances, inflammatory cells and blood vessels. We focused our research on most abundant cell component of cancer stroma on cancer-associated fibroblasts. We isolated stromal fibroblasts from tumours originated from the squamous epithelium such as basal and squamous cell carcinoma, melanoma and skin metastasis of breast cancer. We expanded them and in vitro evaluated their biological effect on normal keratinocytes and breast cancer keratinocytes (EMG-3). The results were compared with control experiments using normal human dermal fibroblasts, 3T3 mouse fibroblasts, and 3T3 fibroblasts influenced by the fibroblasts prepared from the basal cell carcinoma. Our results demonstrated that expression of luminal marker keratin 8 was influenced only by cancer associated fibroblasts prepared from any tested tumors. In contrast, all tested types of fibroblasts showed a strong stimulatory effect on the expression of basal/myoepithelial marker keratin 14. Since keratin 14 is a marker of basal myoepithelial cells and keratin 8 is a marker of luminal cells, these double-positive cells can be considered for precursor cells with properties close to stem cells. Their presence in clinical samples indeed signals very poor prognosis in cancer-suffering patiens. In conclusion, our data indicate that cancer associated fibroblasts are able to influence the phenotype of a breast cancer cell line and this effect is based on a tumor type-unspecific mechanism.
Citation Format: Pavol Szabo, Karel Smetana, Jr., Barbora Dvorankova, Ondrej Kodet, Hynek Strnad, Michal Kolar. Epithelial-mesenchymal interaction in cancer as potential target for anticancer therapy. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B59.
Abstract C04: HGFL promotes the development and progression mammary tumors and represents an attractive therapeutic target
Authors: Benight Nancy M. , Wagh Purnima , Waltz Susan E. 
Published: August 2014

Abstract
A standard therapy for breast cancer is the use of receptor tyrosine kinase (RTK) inhibitors. RTKs efficiently target multiple receptors, including the Ron transmembrane receptor, whose activation leads to increased survival, migration, and angiogenesis through signaling pathways such as PI3K/Akt and NF-κB. Ron overexpression is correlated with increased metastasis and poor outcomes in patients. The only ligand for Ron is hepatocyte growth factor-like protein (HGFL), which is an endocrine factor secreted into the circulation from the liver. Published reports demonstrated that ectopic overexpression of HGFL in cancer cells leads to increased metastasis. However, no studies have examined the role of endogenous HGFL in Ron activation during tumor development and metastasis. We sought to test the hypothesis that HGFL is required for Ron receptor activation and mammary tumorigenesis. We utilized mice with mammary-specific Ron overexpression (MMTV-Ron), which develop mammary tumors with 100% incidence. MMTV-Ron mice were crossed to HGFL deficient (HGFL-/-) mice to generate MMTV-Ron X HGFL-/- mice. We compared mammary hyperplasia and tumor latency in MMTV-Ron mice with and without HGFL serially at 2.5, 4, 6, 8 and 10 months. Additional mice were followed to established tumor kinetics and growth and to examine metastatic dissemination. MMTV-Ron X HGFL-/- mice displayed decreased mammary hyperplasia and a significant delay in the time to tumor formation compared to control mice. Kinase assays show that Ron activation is reduced in mice with HGFL loss. Tumor cell proliferation was different between the groups while markers of apoptosis (TUNEL IHC and cleaved caspase 3 expression) were significantly increased in MMTV-Ron X HGFL-/- mice compared to controls. Western blot analysis of tumor lysates showed diminished activation of NF-κB signaling associated with HGFL loss. In conclusion, our data show that HGFL promotes the development of mammary hyperplasia and mammary tumor formation by enhancing tumor cell survival, Ron activation and NF-κB signaling. These data suggest that HGFL represents an excellent target for inhibiting Ron mediated tumor growth in human disease.
Citation Format: Nancy M. Benight, Purnima Wagh, Susan E. Waltz. HGFL promotes the development and progression mammary tumors and represents an attractive therapeutic target. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C04.
Abstract C13: Novel molecular targets for breast cancer stem cells involved in HER-PI3K signaling
Authors: Gotoh Noriko 
Published: August 2014

Abstract
Breast cancer stem cells (BCSCs) are responsible for breast tumorigenesis. To develop more effective cancer therapies, it would be reasonable to target molecules that have a critical role in the maintenance of BCSCs. However, our understanding of the cellular and molecular mechanisms underlying BCSC properties is limited. We have previously shown that heregulin (HRG), a ligand for HER3, induced tumorsphere formation of breast cancer cells through a phosphatidyl inositol 3 (PI3) kinase pathway (Proc. Natl. Acad. Sci., USA, 109, p6584, 2012). To examine dynamic changes in gene expression patterns by stimulation of HER/PI3 kinase signaling, we performed time series microarray analyses under condition of HRG treatment and/or PI3 kinase inhibition by using a specific inhibitor, and obtained a HER/PI3 kinase gene signature that includes 635 genes. We found that the HER/PI3 kinase gene signature is more enriched in high-grade breast tumors than in low-grade tumors and is associated with high-risk patients for relapse. We found that several growth factors, cytokines and cytoplasmic molecules among the molecules in the HER/PI3 kinase gene signature, play important roles for tumorsphere formation derived from the clinical samples form the breast cancer patients. These findings suggest that novel molecular targets for BCSCs can be found in the HER/PI3 kinase signature.
Citation Format: Noriko Gotoh. Novel molecular targets for breast cancer stem cells involved in HER-PI3K signaling. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C13.
Abstract C17: Revealing targetable cancer cell vulnerabilities by in silico pathway profiling
Authors: Joshi Rashika , Komurov Kakajan 
Published: August 2014

Abstract
Successful targeted therapy of cancers relies on comprehensive understanding of vulnerabilities of the tumorigenic platform. Recent cancer genomics efforts have provided with an unprecedented opportunity to gain an unbiased insight into the functional make-up of human cancers. We have devised a computational strategy to leverage cancer genomic datasets to identify candidate pathway vulnerabilities in cancers. The core of our approach is in the delineation of molecular pathways that are activated in tumor cells as a result of secondary selection events during tumor evolution. These secondary pathways are likely to be required for tumorigenesis in the given tumor context. We applied this strategy on HER2+ breast cancers using breast cancer genomic data in the TCGA, the recently published METABRIC and the Cancer Cell Line Encyclopedia (CCLE) datasets. Although HER2+ breast cancers are treated with HER2-targeting agents in the clinic, the response is usually short-lived due to de novo and acquired resistance. We have found that HER2+ breast cancers are characterized by extensive and robust secondary upregulation of the endoplasmic reticulum (ER) quality control (ERQC) pathways, including the ER-associated degradation (ERAD) and PERK/eIF2 pathways. Our follow-up combined in silico and in vitro analyses on a panel of HER2+ and HER2- breast cancer cell lines revealed a model of HER2-driven tumorigenesis where yin-yang interplay between hyperactive HER2/mTOR signaling and the ERQC machinery regulate the ER protein homeostasis to control survival of HER2+ cells. Furthermore, we report that this delicate regulatory architecture can be exploited for therapeutic purposes, such that, combinatorial targeting of ERQC pathways to disturb the proteostatic balance synergized in selectively inducing proteotoxic cell death in therapy-refractory HER2+ cells. This study presents a computational method for identification of cancer pathway vulnerabilities, and suggests that exploiting proteotoxic ER stress may be an effective therapeutic strategy in therapy-refractory HER2+ breast cancers.
Note: This abstract was not presented at the conference.
Citation Format: Rashika Joshi, Kakajan Komurov. Revealing targetable cancer cell vulnerabilities by in silico pathway profiling. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C17.
Abstract C24: High systemic cholesterol increases blood vessel endothelial permeability and favors metastasis: Are these events related?
Authors: Magalhaes Ana , Santos Catarina R. , Domingues Germana , Carvalho Tãnia , Dias Sergio 
Published: August 2014

Abstract
Here we hypothesize that systemic cholesterol favors metastasis by increasing blood vessel endothelial permeability. The majority of metastatic dissemination occurs through the hematogenous route and factors that alter blood vessel properties can affect the entry of cancer cells in circulation. It is generally accepted that high levels of systemic cholesterol, in particular low density lipoprotein (LDL), have a negative impact in endothelial function. This has been demonstrated mainly in large arteries but less is known about how LDL affects the microvasculature of different organs. High cholesterol has also been associated with poor prognosis in several cancers. In our lab, using orthotopic mouse models of breast cancer, we were able to show that mice in which increased LDL in circulation is induced by a high cholesterol diet, have more metastasis. Here we also show in an “in vitro” system, that LDL increases endothelial permeability and that this can be reverted by blocking the interaction of LDL with the LDL-receptor. Additionally we observe that this higher endothelial permeability is due to cholesterol enrichment of endothelial cells, as nystatin, a cholesterol sequestering agent is also able to revert the phenotype. Back to “in vivo”, using the same orthotopic breast cancer model, we are able to show that high systemic cholesterol increases the number of circulating cancer cells in the blood. We are now testing the hypothesis of whether this is due to increased permeability of tumor blood vessels or of the vessels surrounding the tumor.
Citation Format: Ana Magalhaes, Catarina R. Santos, Germana Domingues, Tãnia Carvalho, Sergio Dias. High systemic cholesterol increases blood vessel endothelial permeability and favors metastasis: Are these events related? [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C24.
Abstract C35: Neural stem cells transduced with adenovirus Interferon-beta prolonged lives of MDA 231 lung tumor bearing SCID mice
Authors: Rachakatla Raja S. , Reuter Ashley , Hassan Sherif S. 
Published: August 2014

Abstract
Conventional cancer therapies are not selective and leave patients of metastatic breast cancer with poor prognosis and serious adverse effects. It has been shown that neural stem cells (NSCs) migrate specifically to cancer affected tissues and can be engineered to carry anti-cancer drugs; Therefore, NSCs may be used as drug delivery vehicles to specifically target cancer cells. Our goal was to determine if NSCs transduced with adenovirus expressing IFN-beta (NSC-IFN-beta) would target and kill MDA 231 human breast cancer in vitro and in vivo. In vitro: transwells were used to determine if NSCs and NSC-IFN-beta migrate towards and kill MDA 231 cells in vitro. NSCs and NSC-IFN-beta migrate towards MDA 231 cells (P &lt; 0.05) and conditioned MDA 231 media (P &lt; 0.05). However, only NSC-IFN-beta kill MDA 231 cells in vitro (P &lt; 0.05). In vivo: A survival study was performed to test the efficacy of NSC-IFN-beta on MDA 231 lung tumor bearing SCID mice. Tumor bearing mice had greater lung weights (P &lt; 0.05). Tumor bearing mice treated with NSC-IFN-beta lived longer than untreated mice (PBS) (median survival: 45 days versus 37 days, difference = 8 days, P = &lt;0.05 and tumor bearing mice treated with NSCs (median survival: 45 days versus 31 days, difference = 14 days, P &lt; 0.05). Conclusion: These results suggest that NSCs with IFN-beta may be able to target and reduce human breast cancer in a metastatic SCID mice tumor model.
Citation Format: Raja S. Rachakatla, Ashley Reuter, Sherif S. Hassan. Neural stem cells transduced with adenovirus Interferon-beta prolonged lives of MDA 231 lung tumor bearing SCID mice. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C35.
Abstract C37: Reduced annexin A6 expression enhances EGFR degradation and sensitizes invasive breast cancer cells to EGFR-targeted tyrosine kinase inhibitors
Authors: Koumangoye Rainelli B. , Ochieng Josiah , Sakwe Amos M. 
Published: August 2014

Abstract
The role of annexin A6 (AnxA6), a calcium-dependent phospholipid binding protein, in breast carcinogenesis remains poorly understood. Some reports suggest that AnxA6 inhibits the activation and down-stream signaling of epidermal growth factor receptor (EGFR). On the contrary, other studies have shown that AnxA6 not only stabilizes activated receptors on the cell surface but also promotes the expression of differentiation markers in chondrocytes. Together with our recent study showing that AnxA6 expression is reduced in breast cancer, we investigated whether AnxA6 expression status influences breast cancer outcome in patients and whether this may be attributed to its modulation of EGFR expression. We show that low AnxA6 expression correlates with reduced distant metastasis-free and overall survival, but is associated with a higher probability for recurrence-free survivalof patients with basal-like breast cancer. To determine whether these effects are mediated via EGFR, a predictive marker of basal-like breast cancer, we examined the effects of altered expression of AnxA6 in AnxA6-high invasive triple negative breast cancer cells. Interestingly, depletion of AnxA6 in invasive BT-549 cells was accompanied by decreased expression of EGFR protein and mRNA. We also show that in invasive breast cancer cells, AnxA6 expression is required for sustained membrane localization of activated EGFR and persistent downstream signaling. Consequently, AnxA6-depleted cells exhibited decreased cell motility, and increased sensitivity to the tyrosine kinase inhibitors (TKIs), lapatinib and PD153035. On the contrary, over-expression of AnxA6 in AnxA6-low HCC1806 cells did not affect their motility but as expected, inhibited their growth in 3D matrigel cultures. These data suggest that AnxA6-modulation of EGFR expression and activity underlies at least in part, the changes in proliferation, metastatic potentials and sensitivity to EGFR-targeted TKIs of invasive breast cancer cells. Our data also suggest that AnxA6 expression status may predict the survival and likelihood to respond to EGFR-targeted therapies of patients with basal-like breast cancer.
Citation Format: Rainelli B. Koumangoye, Josiah Ochieng, Amos M. Sakwe. Reduced annexin A6 expression enhances EGFR degradation and sensitizes invasive breast cancer cells to EGFR-targeted tyrosine kinase inhibitors. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C37.
Abstract C41: Chc1L is a tumor suppressor involved in development of histiocyte-rich neoplasms
Authors: Spillane David , Wang Ding Yan , Shi Changxin , Wang Youdong , Gramolini Anthony , Stewart Keith , Newbigging Susan , Liu Mingyao , Wen Xiao-Yan 
Published: August 2014

Abstract
Human chromosome 13q14 is one of the hotspots of chromosomal deletion in prostate cancer, multiple myeloma, and chronic lymphocytic leukemia. Chromosome Condensation 1-like (CHC1L) is an uncharacterized gene in this region. CHC1L is found within the smallest common region of loss of heterozygosity in prostate cancer, and its decreased expression is linked to pathogenesis and progression of both prostate cancer and multiple myeloma. In the present study, we describe the generation and characterization of Chc1L gene knockout mice. Knockout mice develop normally and display an exaggerated proliferative response to LPS stimulation of cultured bone marrow and spleen cells at ten weeks of age. At approximately two years of age, both homozygous and heterozygous mice have markedly increased incidence of tumorigenesis, 80% and 56% respectively, compared to wild-type mice, 26%. The tumors are distributed most commonly to the spleen, mesenteric lymph nodes, liver and small intestine. The morphologic and immunophenotypic features of the tumor cells are consistent with those of tissue histiocytes, and most Chc1L knockout and heterozygote mice succumb to either Histiocytic Sarcoma or Histiocyte-Associated Lymphoma. These data provide the first direct evidence that Chc1L is a tumor suppressor gene involved in suppression of histiocyte-rich neoplasms.
Citation Format: David Spillane, Ding Yan Wang, Changxin Shi, Youdong Wang, Anthony Gramolini, Keith Stewart, Susan Newbigging, Mingyao Liu, Xiao-Yan Wen. Chc1L is a tumor suppressor involved in development of histiocyte-rich neoplasms. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C41.
Abstract C57: Observation of experimental and clinic curative effect on Z-C medicine treating malignancy
Authors: Xu Ze , Xu Jie , Zhu Shiping , Qio Shaoming , Wu Bin 
Published: August 2014

Abstract
• Objectives: To find traditional Chinese medicines of treating carcinoma which are good for curative effect and have no side effect.
• Methods We use liver cancer H2,2 to inoculate 260 Kun Ming little white mice which are divided into group Z-C1 and group Z-C4, group of chemical treatment (CTX) and group of contrapose.
• Results: We observe that the repression rate of mice H22 in liver cancer to of group Z-C1 for 2, 4, 6 weeks is 40%, 45% and 58%, and repression rate of mice H22 in liver cancer to of group Z-C4 for 2, 4, 6 weeks is 55%,68% and 70%, while repression rate of group CTX for 2, 4 and 6 weeks is 45%, 45% and 49%. For ten years' clinic abservation of 4277 middle and later period cancer patients, we find that Z-C medicine has good effect to prolong survival and has no side response for long time taking patients.
• Conclusions: Through experimental research and clinic validation, it is proved that Z-C1, Z-C4 medicine can improve the survival quality and immunity of middle and later period patients, and control the increase of carcinoma cells to get a further curative effect
Citation Format: Ze Xu, Jie Xu, Shiping Zhu, Shaoming Qio, Bin Wu. Observation of experimental and clinic curative effect on Z-C medicine treating malignancy. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C57.