bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1828: Omega-3 fatty acids delay the growth of mammary tumors in MMTV-Erbb2 mice
Authors: Wang Jing , Zhang Chunlan , Deng Guorui , Chen Yong , Berquin Isabelle 
Published: June 2012

Abstract
Purpose: Dietary fats have long been suspected of contributing to breast cancer risk, but the effects of various fatty acids are still not clear. We used MMTV-Erbb2 transgenic mice to determine how different fatty acids influence mammary tumor development and what the possible mechanisms are.
Methods and Results: Female MMTV-Erbb2 transgenic mice (FVB-Tg(MMTV-Erbb2)NK1Mul/J, n=13-14 per group) were placed on defined diets with 30% calories from fat, enriched in different types of fatty acids: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), omega-3 polyunsaturated fatty acids (n-3 PUFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) and control diet with a nutritionally balanced mixture of the above fatty acids. The results showed that the incidence of palpable mammary tumors, their multiplicity and average tumor weight were significantly lower in the n-3 PUFA enriched diet group than in other diet groups (p&lt;0.05, ANOVA). Moreover, the tumors from the n-3 PUFA diet group showed decreased cell proliferation and increased apoptosis (as determined by immunohistochemical staining for Ki67 and cleaved caspase3, respectively) compared to other groups. However, there were no significant differences in the number of hyperplasic nodules detected in mammary glands by carmine alum whole mount staining. SFA, MUFA and n-6 PUFA were not statistically different from control.
Conclusions: Our results suggest that n-3 PUFA can inhibit HER-2/neu-induced mammary tumor growth in this mouse model, but that n-3 PUFA has no effect on the very early stage of tumorigenesis. The mechanism of the antitumor effects of n-3 PUFA may be related to inhibition of cell proliferation and promotion of apoptosis.
This project was supported by an Intramural Research Support Grant (Kulynych Fund) entitled: “Pilot study on the effects of different dietary fatty acids on mammary cancer risk”.
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 1828. doi:10.1158/1538-7445.AM2011-1828
Abstract 1837: Clinical diversity and tumor spectrum in Xeroderma Pigmentosum Brazilian patients
Authors: Santiago Karina M. , Maschietto Mariana , Vairo Filippo Pinto , Ashton-Prolla Patricia , Medeiros Paula , Rogatto Silvia Regina , Achatz Maria Isabel Waddington 
Published: June 2012

Abstract
Xeroderma Pigmentosum (XP) is a rare autossomic recessive hereditary disorder in which normal ability to repair DNA damage caused by ultraviolet light (UV) is deficient due to the presence of mutations in nucleotide excision repair pathway genes (XPA, ERCC3, XPC, ERCC2, DDB, ERCC4 and ERCC5) or in POLH gene, responsible for the replication of damaged DNA on the leading strand. These different genetic alteration result in distict phenotypes classifified into eight genetic complementation sub groups, XP-A to XP-G and a variant group XP-V. Clinical characteristics of the syndrome include skin poikiloderma and eye hypersensibility to UV radiation. Carriers have an increased risk of early onset multiple cutaneous, mucocutaneous and ophthalmologic malignancies when compared with normal population. Occasionally neurological impairment is observed in certain variations of the syndrome. Given the paucity of specific literature data about the incidence and clinical profile of the disease in Brazilian population, this study was conducted to describe clinical diversity and tumor spectrum of XP syndrome in Brazilian population. Twenty-nine XP patients from 19 non-related families from Hospital A.C. Camargo (São Paulo, Brazil), Hospital Universitário Alcides Carneiro (Campina Grande, Paraíba) and Hospital de Clínicas de Porto Alegre (Rio Grande do Sul, Brazil). Data collection was performed after genetic counseling and signed informed consent. Clinical characteristics were obtained through medical ascertainment. The median age was 24 (4 to 61 years) in a predominant female population (19/29). Basal cell carcinomas (BCC) were the most frequent neoplasm, present in 86,20% (25/29) of all patients, with the occurrence of up to 60 BCCs in a same patient. Squamous cell carcinomas and melanoma were present in 66,7% and 37,5% respectively. Six patients developed the first malignant tumor before the age of six and four patients developed the first tumor in early adulthood. One male patient developed a diffuse gastric cancer at 50 years old. Visual impairment occurred in 45,83% of the patient. Despite the unknown frequency of affected patients, the Brazilian population of XP cases seems to be underestimated. Genetic counseling is fundamental to provide information to carriers and family members and enable preventive measurements.
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 1837. doi:10.1158/1538-7445.AM2011-1837
Abstract 1841: Dietary morin suppresses colitis-associated colorectal carcinogenesis in rats
Authors: Tanaka Takuji , Yasui Yumiko , Terasaki Masaru , Masuda Sonoko 
Published: June 2012

Abstract
A flavonol, morin, found in almonds, mill, fig and other moraceae which are used as dietary agents and also as herbal medicine. Morin acts as a potent antioxidant, xanthine oxidase inhibitor, PKC inhibitor, cell proliferation inhibitor, apoptosis inducer, modulator of LOX and COX activities. Based on our previous studies on chemopreventive ability of morin in tongue and colon carcinogenesis (Carcinogenesis 20: 1477-84, 1999; Int J Cancer 83: 381-6, 1999; Oncol Rep 6:1333-40, 1999), we aimed to determine possible inhibitory potential of this compound in colitis-associated colon carcinogenesis in rats initiated with AOM and promoted by DSS. Male F344 rats initiated with a single s.c. injection of AOM (20 mg/kg bw) were promoted by 1.5% DSS in their drinking water for 7 days. They were then given a basal diet containing 50, 250 and 1000 ppm of morin for 17 weeks. At wk 20, the development of colonic adenocarcinoma was significantly inhibited by feeding with morin at a dose level of 1000 ppm (45% incidence, p=0.0141; and 0.73 +/- 1.01 multiplicity, p&lt;0.05), when compared to the AOM/DSS group (93% incidence and 2.36 +/- 1.95 multiplicity). The incidence and multiplicity of adenocarcinomas in the rats received 50 ppm (60% incidence and 1.20 +/- 1.23 multiplicity) and 250 ppm (64% incidence and 1.09 +/- 1.04 multiplicity) of morin in diet were also smaller than that of the AOM and DSS group, but the differences were insignificant. The treatments inhibited colonic inflammation, and also modulated proliferation, apoptosis, and expression of several pro-inflammatory cytokines, such as NF-kappaB, Stat3, TNF-alpha and IL-1beta in the adenocarcinomas. Feeding with morin lowered tissue polyamine levels of colonic mucosa. Our findings indicate that dietary morin is able to inhibit colitis-related colon carcinogenesis in rats. Also, our model provides knowledge applicable to prevent inflammation-associated colon cancer in humans.
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 1841. doi:10.1158/1538-7445.AM2011-1841
Abstract 2148: Thalidomide and liposomal doxorubicin inhibit differentiation and function of human osteoclasts
Authors: Chen Yu-Jen , Chen Yu-Yawn , Chi Chih-Wen , Liao Hui-Fen 
Published: June 2012

Abstract
Background: Thalidomide inhibits angiogenesis and growth of multiple myeloma. Liposomal doxorubicin is mainly absorbed and degraded by monocyte-macrophage lineage in vivo, implicating a possible targeting effect. Given that osteoclasts (OCs) are derived from precursors of monocyte-macrophage lineage, we hypothesized that thalidomide, liposomal doxorubicin and their combination may affect osteoclastogenesis.
Materials and Methods: We isolated CD14+ monocytes from peripheral blood mononuclear cells of healthy subjects and generated OCs under stimulation with macrophage-colony forming factor and receptor activator of NK-κB ligand. Cell viability, surface CD51/61 expression, and tartrate-resistant acid phosphatase (TRAP) activity were assessed by using MTT, flow cytometry and immunohistochemical staining, respectively. Bone resorption activity of OCs was examined.
Results: The combination of thalidomide (purchased from TTY Biopharm, Taiwan) and liposomal doxorubicin (purchased from TTY Biopharm, Taiwan) profoundly inhibited the amount of harvested viable OCs. The expression of osteoclast-specific surface antigen CD51/61 was markedly inhibited by each drug and their combination. Specifically, the amount of multinucleated TRAP-positive cells characteristics of OCs and bone resorption activity of OCs were suppressed by each drug and, the mostly, their combination.
Conclusion: Thalidomide, liposomal doxorubicin and their combination, beyond currently clinical indications, might be effective regimen to inhibit human osteoclastogenesis.
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 2148. doi:10.1158/1538-7445.AM2011-2148
Abstract 215: Soluble guanylyl cyclase α1 and p53 cytoplasmic sequestration: A novel mechanism for p53 down-regulation in prostate cancer
Authors: Shemshedini Lirim , Gao Shuai 
Published: June 2012

Abstract
Our lab has identified soluble guanylyl cyclase α1 (sGCα1) as a novel androgen- regulated gene involved in prostate cancer cell proliferation. A well-known biological function of sGCα1 is to heterodimerize with sGCβ1 forming the enzyme sGC, which mediates nitric oxide(NO) signaling. Our published data demonstrated that the sGCα1 effect on prostate cancer cell growth is independent of the classical mediators of NO signaling, suggesting that sGCα1 acts via a novel signaling pathway. Furthermore, sGCα1 expression is highly elevated in prostate tumors and this expression is directly correlated to the progression stage of prostate cancer. Interestingly, we have recently discovered that sGCα1 can inhibit the transcriptional activity of p53 via a mechanism that does not depend on classical mediators of NO signaling.
Immunoprecipitation and immunocytochemistry assays have shown an association between sGCα1 and p53 and these data suggest that sGCa1 inhibits p53 by mediating the cytoplasmic sequestration of this tumor suppressor protein, which would represent a previously unknown mechanism for p53 regulation. sGCa1 can also regulate in a gene-specific manner p53-regulated gene expression, targeting genes involved in apoptosis. In addition, sGCa1 makes prostate cancer cells resistant to the chemotherapeutic and apoptosis-inducing drug Etoposide. Finally, analysis of prostate tumors has shown a direct correlation in expression between sGCα1 and p53. Collectively, these data suggest that sGCa1 regulation of p53 activity is important in prostate cancer biology and may represent an import mechanism of p53 down-regulation in those prostate cancers that express significant levels of p53.
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 215. doi:10.1158/1538-7445.AM2011-215
Abstract 2181: Tumor suppressor role of Notch3 in medullary thyroid carcinoma
Authors: Jaskula-Sztul Renata , Eide Jacob , Kunnimalaiyaan Muthusamy , Chen Herbert 
Published: June 2012

Abstract
Introduction: NOTCH3 is a transmembrane receptor that appears to be absent in the neuroendocrine (NE) tumors. We have previously demonstrated that transient expression of the active portion of NOTCH3 (NICD3) alters the NE phenotype and inhibits the proliferation of carcinoid tumor cells in vitro. However, the long term effect of activation this pathway is not clearly understood in Medullary Thyroid Carcinoma (MTC). To elucidate the role of Notch3 in NE, we established a doxycycline inducible NOTCH3 intracellular domain in MTC TT cells. The aim of this study was to assess the long term effect of NOTCH3 and determine the mechanism of inhibition of TT cells growth.
Methods: Doxycycline inducible TT-NOTCH3 cells were created by stable transfection of Tet-On vector followed by transfection of pRevTRE-NOTCH3 plasmid. Functional analysis of NICD3 was done by measuring the degree of luciferase activity by CBF binding assay. Quantification of HES and HEY gene expression (Notch signaling mediators) was done by real time RT-PCR. Effect of Notch3 on NE markers -chromogranin A (CgA) and achaete-scute complex-like1 (ASCL1) – was assessed by Western blot analysis. The influence of NOTCH3 overexpression on TT-NOTCH cell proliferation was measured by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) rapid colorimetric assay. The mechanism of growth inhibition was determined for apoptosis markers by Western blot and flow cytometry analyses.
Results: Treatment of TT-NOTCH3 cells with doxycycline led to an induction of NOTCH3 protein in a dose-dependent manner. Increase in the CBF1 binding activity showed that the NOTCH3 protein is functional and this is associated with changes in transcriptional level of HES and HEY families. More importantly, NOTCH3 activation led to a dose dependant reduction of NE markers ASCL1 and CgA. In addition, NOTCH3 activity is required to suppress MTC cell proliferation and the level of growth regression depends on the amount of NOTCH3 protein expressed. Finally, Western blot analysis and flow cytometry experiments indicated that the growth inhibition is due to apoptosis.
Conclusions: We demonstrate, for the first time, that overexpression of NOTCH3 in MTC cells suppresses tumor cells growth by promoting apoptosis. Moreover, Notch3 pathway is functional as active NOTCH3 triggers the CBF-dependent transcriptional network. Finally, the activation of Notch3 in the in vitro model resulted in down-regulation of NE markers indicated that this pathway is conserved in MTC. Therefore, activation of Notch3 could be a therapeutic strategy to treat patients with MTC.
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 2181. doi:10.1158/1538-7445.AM2011-2181
Abstract 2190: ADAMTS8 at 11q25 is a tumor suppressor antagonizing Ras-signaling and methylated in multiple carcinomas
Authors: Choi Gigi C. , Wang Yajun , Li Jisheng , Li Lili , Ying Jianming , Ma Brigette B. , Tao Qian , Chan Anthony T. 
Published: June 2012

Abstract
As opposed to most matrix metalloproteinases which facilitate tumor progression, a growing list of ADAMTS secreted protease members was reported to display tumor suppressive properties with their expressions frequently altered in diverse types of tumors. Here, ADAMTS8 was shown to be located at an LOH locus at 11q25 by array CGH. We further showed that ADAMTS8 was frequently downregulated or silenced in multiple cancer cell lines while broadly expressed in normal tissues. Analysis on the methylation status of the ADAMTS8 promoter CpG island showed that methylation was cancer-specific and ADAMTS8 methylation was correlated with the silencing of ADAMTS8. In addition, expression of ADAMTS8 could be restored with pharmacological or genetic demethylation and hence indicating that CpG methylation directly contributes to the downregulation of ADAMTS8. Aberrant methylation was also frequently detected in primary NPC, gastric and colorectal tumors, but seldom in normal tissues. Ectopic expression of ADAMTS8 led to marked inhibition of cell growth in colony formation assays and cell migration in wound healing assay along with the reduction of phosphorylated ERK protein. The inhibitory effect on tumor cell growth and Ras-ERK pathway by ADAMTS8 indicates its role as a functional tumor suppressor.
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 2190. doi:10.1158/1538-7445.AM2011-2190
Abstract 2191: The Wnt/DVL signaling antagonist DACT2 is a pro-apoptotic tumor suppressor epigenetically silenced in multiple tumors and inhibits tumor cell proliferation and migration
Authors: Fan Yichao , Ying Ying , Li Lili , Chan Anthony TC , Tao Qian 
Published: June 2012

Abstract
Wnt/DVL/β-catenin signaling pathway is aberrantly activated in a wide range of human cancers which frequently involves the disruption of its negative regulators, hence we would like to identify tumor suppressor as the antagonist to this signaling pathway. We identified a DACT (Dpr/Frodo) family member DACT2 as a downregulated gene in human tumors. Further epigenetic study revealed that, in contrast to its broad expression in normal tissues and cell lines, DACT2 is silenced or downregulated in multiple tumor cell lines including nasopharyngeal (NPC), esophageal (ESCC), gastric, colorectal (CRC), breast, lung, renal (RCC), hepatocellular (HCC), prostate and cervix carcinomas, due to its promoter methylation which could be reversed by pharmacological demethylation. DACT2 promoter methylation was also frequently detected in multiple primary tumors, suggesting that DACT2 is a potential tumor marker. DACT2 encodes a cytoplasm protein localized in endosome. Ectopic expression of DACT2 dramatically inhibited tumor cell colony formation in silenced tumor cell lines, mainly through inducing apoptosis. DACT2 interacts and downregulates Dishevelled (DVL) protein, thus protecting glycogen synthase kinase 3β (GSK-3β) from inactivation by WNT/DVL and allowing GSK-3β to form a complex with Axin and APC to promote the phosphorylation and proteasomal degradation of β-catenin. Overexpression of DACT2 disrupted β-catenin activation and accumulation in nucleus, thus preventing its binding to transcription factors of the Lef/Tcf family. This caused the downregulation of target oncogenes such as c-Myc, CCND1 and fibronectin and the inhibition of tumor cell proliferation and migration. We also observed that DACT2 could upregulate epithelial cell marker E-cadherin, and modulate Akt/GSK-3β/β-catenin signaling pathway, another pathway involved in tumor cell epithelial mesenchymal transition. Our data demonstrate that DACT2 is a functional tumor suppressor epigenetically silenced in multiple tumors which acts as a negative regulator of the Wnt/DVL/β-Catenin pathway, and could be a promising biomarker for human tumors.
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 2191. doi:10.1158/1538-7445.AM2011-2191
Abstract 2206: SOCS1 and SOCS3 attenuate Lck-mediated cellular transformation through distinct mechanisms
Authors: Venkitachalam Srividya , Chueh Fu-Yu , Yu Chao-Lan 
Published: June 2012

Abstract
The suppressor of cytokine signaling (SOCS) proteins are negative feedback inhibitors of Janus kinase (JAK) – signal transducer and activator of transcription (STAT) signaling in response to cytokine stimulation. Among eight SOCS family members, SOCS1, SOCS2, SOCS3 and CIS (cytokine-inducible SH2-containing protein) are best characterized both structurally and functionally. We showed previously that CIS, SOCS1 and SOCS3 were not expressed in Lck-transformed cells (Cell Signal 18:851; Int J Oncol 36:1201). It suggests that defective negative feedback control may contribute to constitutive JAK-STAT5 activation in Lck-mediated oncogenesis (J Immunol 159:5206; Mol Cancer Res 4:39). These findings also raise the possibility that SOCS proteins may function as tumor suppressors. Indeed, by enforced SOCS1 and SOCS3 expression, we were able to reduce Lck-induced cellular transformation (Int J Oncol 36:1201). In this report, we further examine the molecular mechanisms underlying SOCS tumor-suppressing activity. Through comparative studies of SOCS1, SOCS2, SOCS3 and CIS, we demonstrate here two distinct properties of SOCS1 and SOCS3 toward oncogenic Lck kinase. First, SOCS1 has the highest affinity in binding to oncogenic Lck kinase. We identified the positive regulatory phospho-tyrosine 394 residue (Y394) in the kinase domain as the key interacting determinant in Lck. Additionally, the Lck kinase domain alone is sufficient to bind SOCS1. While the SH2 domain in SOCS1 is important in its association with the oncogenic Lck kinase, other functional domains may also contribute to overall binding affinity. These data suggest that SOCS1 may inhibit Lck kinase activity in a manner similar to JAK kinases. Second, only SOCS3 becomes phosphorylated in the presence of oncogenic Lck kinase. We identified the phosphorylation sites as Y204 and Y221 located in the C-terminal SOCS box of SOCS3. We further analyzed the contribution of SOCS3 tyrosine phosphorylation on its tumor suppressor activity. Preliminary studies suggested that SOCS3 phosphorylation on Y204 and Y221 might play an important role in blocking cell proliferation and cell cycle progression of Lck-transformed cells. SOCS3 tyrosine phosphorylation can lead to altered protein stability and crosstalk with other signal transduction pathways, such as MAPK signaling. Experiments are in progress to further define the molecular details of SOCS3 phosphorylation involved in tumor suppression. All together, these results provide important mechanistic insights into the distinct roles of SOCS proteins as tumor suppressors in cells transformed by oncogenic protein tyrosine kinases. This work is supported in part by NIH grant CA107210.
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 2206. doi:10.1158/1538-7445.AM2011-2206