bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5185: Evaluation of biomarker candidate genes for prostate cancer metastasis
Authors: Reyes Niradiz , Bettin Alfonso , Rebollo Juan , Tiwari Raj , Geliebter Jan 
Published: June 2012

Abstract
Prostate cancer is the most frequently diagnosed malignancy in men and although effective treatment is possible for early stage disease, advanced prostate cancer has a very poor prognosis. Thus, identification of biomarkers that can accurately and reliably diagnose prostate cancer in its early stages is urgently needed. MatLyLu and Dunning G are rat prostate cancer cell lines which have different metastatic capabilities. Using microarray analysis we previously identified a set of metastasis-associated genes that are over-expressed in MatLyLu. Genes found to be differentially expressed include several previously associated with the metastatic process, but not previously reported in prostate cancer. We also have found differential expression of genes that code for several proteoglycans involved in epithelial cell-extracellular matrix interaction, cell adhesion molecules, genes related to motility, growth factor receptors, and tumor suppressor genes. We are currently validating the expression of these candidate genes in human prostate cancer cell lines with different metastatic abilities (LNCaP, PC3, PWR-1E) and in clinical samples of prostate cancer at different disease stages using quantitative real time PCR (qRT-PCR) and immunohistochemistry. A better understanding of the molecular events leading to the metastatic prostate cancer phenotype will help to further identify genes or gene-products involved in this process, which may prove useful as biomarkers for diagnosis and/or prognosis of the disease.
Project code: 110745921483. Supported by Colciencias Grant # RC No.462-2008
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 5185. doi:10.1158/1538-7445.AM2011-5185
Abstract 5188: Lrig1, a cell surface negative regulator of ErbB1-4, marks both proliferative and quiescent intestinal stem cells and acts as a tumor suppressor
Authors: Wang Yang , Powell Anne E. , Li Yina , Davenport James R. , Franklin Jeffrey , Haigis Kevin M. , Coffey Robert J. 
Published: June 2012

Abstract
Whether proliferative and quiescent intestinal stem cells coexist in normal and cancerous tissue is controversial. Due to heightened transcript expression in the intestinal epithelial stem cell compartment, detection in quiescent hair follicle stem cells and frequent loss in breast cancer, we hypothesized that Leucine-rich repeats and immunoglobulin-like domain protein 1 (Lrig1) would mark a novel population of intestinal stem cells and may be important for intestinal homeostasis and in cancer. To study this, we generated Lrig1-CreERT2/+; R26R-LacZ mice to study the role of Lrig1. One day after Lrig1-CreERT2/+; R26R-LacZ mice received a single injection of tamoxifen, 1-2 cells were labeled in the progenitor zone. Three months after injection, 10% of colonic crypts were entirely labeled and 8% of crypts contained singly labeled, non-proliferative, Lgr5-negative cells at the crypt-base. In a regenerative response to gut injury, these singly labeled cells proliferated and gave rise to clusters of labeled daughter cells, demonstrating the ability of these quiescent stem cells to become activated. Loss of Lrig1 resulted in heightened expression of ErbB1-3 in the normal intestine, duodenal adenomas and carcinoma, supporting a functional role for Lrig1 in the maintenance of intestinal epithelial homeostasis and its ability to act as a tumor suppressor. In addition, driving stochastic loss of Apc in Lrig1-expressing cells results in multiple, large distal colonic tumors and less frequent, smaller intestinal tumors, which are common features of human familial polyposis. In summary, we show that Lrig1, a cell surface negative regulator of ErbB1-4, marks both proliferative and quiescent intestinal stem cells and acts as a 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 5188. doi:10.1158/1538-7445.AM2011-5188
Abstract 520: Local changes in tissue microenvironment regulate mammary tumor progression
Authors: Krause Silva , Tobin Heather , Brock Amy , Ingber Donald E. 
Published: June 2012

Abstract
Breast cancer is one of the most prominent cancers in women with approximately 40,000 women dying each year of the disease in the United States alone. Although cancer has a strong genetic basis, the tissue microenvironment also plays a significant role in tumor formation and progression. To explore this process in greater detail, we analyzed tissue structure, cellular biochemistry and gene expression change during tumor progression in a previously developed FVB C3(1)-SV40Tag transgenic mouse model in which the females spontaneously develop mammary tumors that undergo changes in cell tissue morphology that closely mimic those observed during human breast cancer progression. Histological characterization of breast tissues isolated from 8, 12, 16 and 20 week old female mice confirmed that this model is extremely robust with normal glandular morphology being observed at 8 weeks, ductal carcinoma in situ (DCIS) morphology appearing at 12 weeks and 16 weeks and large tumors with metastatic lesions by 20 weeks of age. More careful analysis revealed that tumor formation did not scale directly with expression of SV40 large T antigen that is the drive gene in this transgenic model, and instead appeared to be more closely related to variations in the tissue microenvironment. This was supported by the observation that the number of myoepithelial cells and expression levels of known breast cancer differentiation markers, including estrogen and progesterone receptors, varied among ducts within tissues at each time point even though the majority of epithelial cells in these ducts expressed T antigen. Gene microarray analysis of mammary tissues from these time points revealed consistent changes in genome-wide expression profiles, and several interesting candidates are currently being analyzed regarding their potential involvement in early microenvironmental changes that might drive the tumor progression. In summary, our preliminary results showed that despite expression of constitutively active large T antigen in the breast epithelial cells of these transgenic mice, we observe heterogeneous tumor formation within mammary tissues. These local variations in tumor progression may be related to regional changes in stromal and extracellular matrix components that are currently being analyzed by immunohistochemical analysis. Our long-term goal is to leverage the information we uncover through this effort to design differentiation therapies that suppress tumor cell growth, induce differentiation and hence, reverse breast cancer progression.
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 520. doi:10.1158/1538-7445.AM2011-520
Abstract 5200: Effect of cancer-associated fibroblast on the progression of gastric cancer stem cells
Authors: Hasegawa Tsuyoshi , Yashiro Masakazu , Matsuoka Junko , Kashiwagi Shinichiro , Fuyuhiro Yuhiko , Sakurai Katsunobu , Sakurai Katsunobu , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Yamada Nobuya , Yamada Nobuya , Maeda Kiyoshi , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: June 2012

Abstract
Introduction: Cancer stem cells (CSCs) are thought to possess the ability to initiate tumor growth and sustain self-renewal, which explains the tumorigenicity and the maintenance of bulk. There is an increasing evidence of the importance of the host microenvironment in conditioning the CSCs status, such as the stemness and the tumor initiation. Recently, cancer-associated fibroblasts in the cancer microenvironment have been suggested to be associated with the tumor progression. Then, the aim of this study is to clarify the relation between CSCs and cancer-associated fibroblasts.
Material and Methods: A gastric cancer cell line, OCUM-12, and cancer-associated gastric fibroblasts, CaF-37, were used. Side population (SP) cells, known as CSCs rich population, were isolated from OCUM-12 cells by flowcytometry using Hoechst 33342, and were named as OCUM-12/SP. OCUM-12/SP cells or OCUM-12 cells were cultured with or without CaF-37 fibroblasts. The percentage of SP cells was evaluated by flowcytometry, and the growth of cancer cells was examined by cell number count. In vivo tumorigenicity of OCUM-12/SP cells was evaluated by subcutaneous inoculation in the presence or absence of CaF-37 fibroblasts.
Results: The percentage of SP fraction of OCUM-12/SP cells was increased in the presence of CaF-37 fibroblasts. In contrast, CaF-37 fibroblasts significantly decreased the proliferation of OCUM-12/SP cells, while that of OCUM-12 cells was significantly increased by CaF-37 cells. The inoculation of 3×105, 1×105, and 3×104 OCUM-12/SP cells with 1×106 CaF-37 fibroblasts resulted in tumor formation in 5 (100%) of 5 mice, 4 (80%) of mice, 5 (100%) of 5 mice, respectively. However, the inoculation of 3×105, 1×105, and 3×104 OCUM-12/SP cells alone results in poor tumor formation at 3 (60%) of 5 mice, 0 (0%) of 5 mice, and 0 (0%) of 5 mice, respectively.Conclusion: Cancer-associated fibroblast might sustain the CSCs phenotype of stemness, and might increase the tumor initiation.
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 5200. doi:10.1158/1538-7445.AM2011-5200
Abstract 5203: Schlafen-3 decreases cancer stem cell marker expression and autocrine/ juxtacrine signaling in FOLFOX-resistant colon cancer cells
Authors: Oh Phil-Sun , Patel Vaishali B. , Sanders Matthew A. , Kanwar Shailender S. , Yu Yingjie , Nautiyal Jyoti , Patel Bhaumik B. , Majumdar Adhip P. N. 
Published: June 2012

Abstract
We have previously demonstrated that expression of the novel gene schlafen (Slfn)-3 correlates with intestinal epithelial cell differentiation. The current investigation was undertaken to examine whether Slfn-3 plays a role in regulating differentiation of FOLFOX-resistant (5-Fluorouracil + oxaliplatin) colon cancer cells that are highly enriched in cancer stem cells (CSCs). Transfection of Slfn-3 in FOLFOX-resistant colon cancer HCT-116 and HT-29 cells resulted in reduction of mRNA and protein levels of the CSC markers CD44, CD133, CD166, and aldehyde dehydrogenase 1 (ALDH1). This was accompanied by decreased formation of tumorosphere/colonosphere (an in vitro model of tumor growth) in stem cell medium and inhibition of expression of the chemotherapeutic drug transporter protein ABCG2. Additionally, Slfn-3 transfection of FOLFOX-resistant HCT-116 and HT-29 cells reduced Hoechst 33342 dye exclusion. Finally, Slfn-3 transfection inhibited the expression of transforming growth factor-α (TGF-α) in both FOLFOX-resistant cell lines but stimulated apoptosis. In summary, our data demonstrate that Slfn-3 expression inhibits multiple characteristics of CSCs enriched FOLFOX-resistant colon cancer cells including reduction in tumorosphere/colonosphere formation, drug transporter activity and autocrine stimulation of proliferation. Thus, Slfn-3 expression may render colon CSCs more susceptible to cancer chemotherapeutics.
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 5203. doi:10.1158/1538-7445.AM2011-5203
Abstract 5206: Nanog family members are essential for spherogenicity and metastasis in colorectal carcinoma
Authors: Zhang Jingyu , Thorgeirsson Snorri S. , Jessup J. Milburn 
Published: June 2012

Abstract
Liver is the most common site for colorectal cancer (CRC) distant metastasis and hepatic metastasis is one of the main causes of death in CRC patients. Inhibition of liver metastases in patients with CRC may increase the survival of patients. Our postulate is that genes involved in early embryogenesis, Nanog, Oct4 and SOX2, may be reactivated and control the malignant properties of metastasis and resistance to chemo- and radiotherapy. Nanog is a family of 11 pseudogenes with the original parent gene on chromosome 12. In order to identify which gene product is expressed in human CRC, we developed a novel endonuclease restriction enzyme assay, which was used in six human CRC cell lines. Monolayer cultures of CRC cells express Nanog, NanogP8, and NanogP7 but spheroids cultured in serum-free medium only express NanogP8 which was confirmed by direct sequencing. In addition, two potential DNA methylation regions are detected in the promoters of Nanog and NanogP8 by sodium bisulfite sequencing of genomic DNA in hES and CRC CloneA cells. In hES cells, the methylation status of Nanog and NanogP8 was about 30% and 60%, respectively. In contrast, in CloneA cells, it was 65% for Nanog and about 40% for NanogP8 and lower for CX-1 CRC cells. These results suggest that NanogP8 is re-activated in CRC through promoter demethylation in CRC spheroids that are enriched for putative stem cells. Overexpression of NanogP8 in CloneA and CX-1 significantly increased the spherogenicity of single CRC cells. In addition, lentiviral shRNA to Nanog inhibited spherogenicity in vitro and tumorigenicity in vivo whereas shRNA to OCT4 and SOX2 actually increased spherogenicity and tumorigenicity. Lentiviral shRNA inhibition of Nanog prevented liver colonies after intrasplenic injection of CX-1 cells whereas 45% of NOD/SCID mice developed experimental metastases after injection of the untreated CX-1 cells or CX-1 cells treated with negative control shRNA. As a result, targeting Nanog and its family members expressed in CRC may block the progression of CRC.
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 5206. doi:10.1158/1538-7445.AM2011-5206
Abstract 5207: FGFR inhibitor regulates CD133 expression in FGFR2-amplified gastric cancer cells
Authors: Matsumoto Kazuko , Arao Tokuzo , Furuta Kazuyuki , Nagai Tomoyuki , Kudo Kanae , Kaneda Hiroyasu , Tamura Daisuke , Aomatsu Keiichi , Sakai Kazuko , Fujita Yoshihiko , Kimura Hideharu , Yamada Yasuhide , Nishio Kazuto 
Published: June 2012

Abstract
The underlying mechanism regulating the expression of the cancer stem cell / tumor-initiating cell marker CD133/prominin-1 in cancer cells remains largely unclear, although knowledge of this mechanism would likely provide important biological information regarding cancer stem cells. We recently have reported that the expression of CD133 in cancer cells could be regulated though the inhibition of signal transduction by molecular-targeted drugs (Matsumoto K. et al. Cancer Res. 2009).
Here, we screened the expression changes of CD133 using wide variety of molecular-targeted drugs in FGFR2-amplified and CD133-overexpressing gastric cancer cell lines. CD133 expression was remarkably upregulated by FGFR inhibitor PD173074 exposure in these cells. Further analysis revealed that PD173074 upregulated the CD133 expression both mRNA and protein levels in dose- and time-dependent manners. In addition, the expression change was correlated with the mRNA expression levels of stem cell factors including OCT3/4, SOX2 and NANOG. As expected, PD173074 exhibited a potent growth inhibitory effect on FGFR2-amplified gastric cancer cells in vitro. These results suggest that the mechanism regulating the expression of CD133 is involved in FGFR2 signaling and also in addicted signaling pathway for cancer cells in FGFR2-amplified gastric cancer cells.
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 5207. doi:10.1158/1538-7445.AM2011-5207
Abstract 5210: Over-expression of cancer stem cell markers predicted poor prognosis in colorectal cancer
Authors: Ozawa Mayumi , Ichikawa Yasushi , Oshima Takashi , Kondo Akihisa , Nakazawa Kenichi , Miyata Hidetoshi , Zheng Yunwen , Shimozawa Manabu , Akaike Makoto , Suwa Hirokazu , Tatsumi Kenji , Watanabe Kazuteru , Ota Mitsuyoshi , Fujii Shoichi , Endo Itaru , Taniguchi Hideki 
Published: June 2012

Abstract
Introduction: Previous reports have demonstrated that CD133+CD44+ cells might be putative colorectal cancer stem cells (CSCs). Intestinal stem cell marker is already identified as LGR5 in mice, and it is also reportedly in human. However the correlation of CSCs and normal stem cell are unclear. The stem-cell-specific loss of APC (adenomatous polyposis coli) results in progressively growing neoplasia. Therefore, LGR5 may play a crucial role in the carcinogenesis and tumorigenesis. In this study, we investigated the possibility of LGR5 as shared common markers by CSCs and normal stem cells, furthermore to address the correlation among LGR5, CD44 and CD133.
Material and Methods: We used surgical specimens of cancer tissue to digest it into single cell suspension. The cells were immuno-stained for flow cytometory, the antigenic profiles of CD133 and CD44 were analyzed. Furthermore, the fractionated cells were sorted and transplanted into NOD/SCID mice. The xenograft tumors were analyzed by flow cytometory again or quantitative real-time PCR (qRT-PCR). And more, total RNA isolated from colorectal cancer and adjacent normal mucosa in 202 patients with untreated colorectal cancer was prepared and complementary DNA (cDNA) was synthesized from total RNA. qRT-PCR was performed to observe the expressions of LGR5, CD44 and CD133. Results: In vivo subcutaneous transplantation showed that as few as 100 CD133+CD44+ cells from primary tumor tissue had tumorigenicity in NOD/SCID mice, where in this cell fraction LGR5 was higher positive compared with other fractions. In xenograft, proportion of LGR5, CD133 and CD44 were expanded as compared with primary cancer and adjacent normal mucosa. In 202 clinical specimens, LGR5, CD44 or CD133 was expressed strongly compared with normal mucosa (p&lt;0.0001). However, with any single marker was not enough to predict the prognosis. Instead, combined with CD44 or CD133, the group of LGR5 over-expression showed significantly low survival rate (p&lt;0.022).
Conclusion: LGR5+, CD133+ or CD44+ cells expressed the characters of cancer stem cells in xenograft tumors as well as in primary colorectal cancers. Importantly, LGR5 is a potentially critical factor determining prognosis in clinics.
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 5210. doi:10.1158/1538-7445.AM2011-5210
Abstract 5222: Metabolomic patterns of tumors and metastases of human colon cancer xenografts
Authors: Stein Ulrike S. , Grötzinger Carsten , Detjen Katharina , Eckardt Änne , Lisec Jan , Willmitzer Lothar 
Published: June 2012

Abstract
Prognostic assessment of colon cancer metastasis and intervention in metastatic disease represent critical clinical challenges. Metabolomic platforms now offer the potential for a systematic survey of the metabolic profile of tumor tissues, which may allow to link key metabolites to distinct aspects of tumor biology such as metastatic capacity. Here we addressed these issues by testing the hypothesis that metastatic disease is characterized by distinct metabolites. In preparation for subsequent analyses of human tumor samples from existing tissue collections, here we employed human colon cancer lines harboring metastatic capacities to induce cancer xenografts in mice. In a first set of experiments using human colon xenografts, and applying GC-MS based metabolomics technology, we characterized the metabolite patterns of the primary tumors and of liver metastases, as well as of the mouse spleens (organ of transplantation) and the mouse livers (main target organ of distant metastasis). Subjecting the metabolite data to a Principal Component Analysis resulted in the separation of the samples into four clusters discriminating on the one hand mouse from human tumor xenograft tissues. Furthermore, mouse spleen was easily separated from mouse liver. More importantly, we identified clearly distinct metabolomic clusters comprising the primary tumor samples vs. the liver metastasis although originating from the same human colon cancer cell line. These different metabolic profiles of primary tumors and metastases were highly reproducible between independent experiments and were conserved in primary tumors or metastases of different size, suggesting they offer a representation of distinct biological features, rather than reflect tumor cell mass or common features of the tumor cell microenvironment. In addition, defined metabolites were identified that are characteristic for particular mouse organs (spleen vs. liver), and for discrimination of mouse tissues vs. human xenograft tumors. Moreover, metabolites were identified that allow discrimination of the primary tumor vs. its corresponding liver metastasis, although both tissues originate from the same human colon cancer cells. We also addressed methodological topics, such as the influence of time until sample cryo-asservation, time of storage, size and amount of the tissue samples, and reproducibility in independent in vivo experiments, on the metabolomic patterns and specific metabolites. In summary, we identified metabolomic patterns as well as defined metabolites that allow discrimination of the primary tumor vs. its corresponding liver metastasis of colon cancer xenografts in mice.
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 5222. doi:10.1158/1538-7445.AM2011-5222