bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3327: Leptin receptors are expressed in breast cancer stem cells and leptin promotes their self-renewal and survival in mice
Authors: Zheng Qiao , Smith Sarah , Zhu Jinling , Downs-Kelly Erin , Hursting Stephen D , Rich Jeremy N , Berger Nathan A , Reizes Ofer 
Published: June 2012

Abstract
Cancer stem cells (CSCs) are highly important in Breast cancer because they represent a subset of cancer cells that are generally undifferentiated, capable of self-renewal, resistant to therapy, and contribute to post-therapeutic tumor regrowth. CSCs can drive the malignant process and may generate the non-renewing differentiated cancer cells that comprise the bulk of the tumor. Here we show that in the Murine Mammary Tumor Virus (MMTV)-Wnt-1 transgenic mouse, a model of basal-like human breast tumors, leptin promotes tumorigenesis and the survival of breast CSCs. We show that leptin deficiency results in reduced outgrowth and burden of transplanted tumors. Second, leptin deficiency leads to depletion of cancer cells with a stem cell molecular signature. Third, the functional importance of the reduced cells is demonstrated by the fact that tumors from leptin-deficient mice led to reduced tumor outgrowth in vivo. Fourth, breast CSC enriched populations express the full-length leptin receptor. Finally, leptin promotes the viability of CSC enriched populations and increases tumorsphere generation in vitro. These results identify a critical role for leptin stimulation of breast CSCs and provide a strong suggestion that interfering with leptin signaling either via receptor blockade or a downstream pathway may provide therapeutic benefit.
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 3327. doi:10.1158/1538-7445.AM2011-3327
Abstract 3330: MicroRNA100 regulates breast cancer stem cells
Authors: Liu Suling , Bai Shoumin , Ke Jia , Martin-Trvino Rachel , Patel Shivani H. , McDermott Sean , Luther Tahra , Heath Amber , Ibarra Ingrid , Korkaya Hasan , Clouthier Shawn G. , Hannon Gregory , Wicha Max S. 
Published: June 2012

Abstract
There is increasing evidence that many human cancers, including breast cancer, are driven and maintained by a cellular subcomponent that displays stem cell properties. These “cancer stem cells” (CSCs) may also mediate tumor metastasis and contribute to treatment resistance and relapse. Our laboratory has identified cellular markers and developed in vitro and mouse models to isolate and characterize normal and malignant human mammary stem cells. We have previously demonstrated that breast cancer cell lines contain subpopulations with stem cell properties that can be isolated by virtue of their expression of Aldehyde dehydrogenase (ALDH) as assessed by the Aldefluor assay. We demonstrated, among microRNAs differently expressed in Aldefluor-positive and Aldefluor-negative populations of breast cancer cell lines we identified micrRNA100 (mir100). We found that mir100 is significantly increased in Aldefluor-negative compared to Aldefluor-positive populations. Utilizing a tetracycline inducible lentivirus driving mir100 expression, we found that induction of mir100 expression decreased the ALDH-positive population of SUM159 cells in vitro as well as in mouse xenografts where this reduction was associated with decreased tumor growth. Furthermore, induction of mir100 expression immediately upon orthotopic implantation or intracardiac injection completely blocked subsequent tumor growth and metastasis formation. These studies demonstrate that mir100 plays a functional role in the self-renewal and differentiation of breast cancer stem cells. Furthermore, the TET-inducible mir100 system allows for controlled regulation of the cancer stem cell population providing a valuable model to simulate the effects of CSC-directed therapies on breast cancer growth and metastasis.
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 3330. doi:10.1158/1538-7445.AM2011-3330
Abstract 3334: Repression of mammary stem/progenitor cells by p53 is mediated by notch and separable from apoptotic activity
Authors: Tao Luwei , Roberts Amy L. , Dunphy Karen A. , Bigelow Carol , Yan Haoheng , Jerry D. Joseph 
Published: June 2012

Abstract
Breast cancer is the most common tumor among women with inherited mutations in the p53 gene (Li-Fraumeni syndrome). The tumors represent the basal-like subtype which has been suggested to originate from mammary stem/progenitor cells. In mouse mammary epithelium, mammosphere-forming potential was increased with decreased dosage of the gene encoding the p53 tumor suppressor protein (Trp53). Limiting dilution transplantation also showed a 3.3-fold increase in the frequency of long-term regenerative mammary stem cells in Trp53-/- mice. The repression of mammospheres by p53 was apparent despite the absence of apoptotic responses to radiation indicating a dissociation of these two activities of p53. The frequency of long-term label-retaining epithelial cells (LRECs) was decreased in Trp53-/- mammary glands indicating that asymmetric segregation of DNA is diminished and contributes to the expansion of the mammary stem cells. Treatment with an inhibitor of γ-secretase (DAPT) reduced the number of Trp53-/- mammospheres to the level found in Trp53+/+ cells. These results demonstrate that basal levels of p53 restrict mammary stem/progenitor cells through Notch and that the Notch pathway is a therapeutic target to prevent expansion of this vulnerable pool of 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 3334. doi:10.1158/1538-7445.AM2011-3334
Abstract 3337: IL-6 and IL-8 stimulation of breast cancer stem cells contributes to trastuzumab resistance following PTEN deletion
Authors: Hasan Korkaya , Davis April , Kim Gwangil , Quraishi Ahmet A. , Paulson Amanda K. , Chung Susan , D'Angelo Rosemarie C. , Liu Suling , Luther Tahra , Clouthier Shawn G. , Wicha Max S. 
Published: June 2012

Abstract
Recent studies strongly implicated breast cancer stem cells (CSC) in therapeutic resistance and recurrence. Despite the benefits of HER2 targeted therapeutics including trastuzumab for the treatment of HER2 amplified breast cancer, one third of tumors do not respond and resistance develops in patient with chronic exposure. Although the mechanisms mediating HER2 resistance have not been completely elucidated, there is evidence that PTEN deletion plays a role. We have previously demonstrated that HER2 regulates the breast cancer stem cell population through regulation of Akt signaling resulting in Wnt activation. In order to investigate the mechanisms of trastuzumab resistance, we overexpressed HER2 and/or knocked down PTEN in luminal MCF7 and basal SUM159 breast cancer cells. In addition, we knocked down PTEN in two HER2 amplified breast cancer cell lines BT474 and SKBR3. In each case, PTEN knock down increased the CSC population as determined by the Aldefluor assay as well as markedly increasing the production of the cytokines IL-6 and IL-8. Cytokine production was partially mediated through Akt activation of NF-κB. Short term trastuzumab treatment decreased the CSC population in HER2 amplified breast cancer cell lines, an effect that was completely abrogated by PTEN knockdown. Long term trastuzumab treatment of HER2 amplified and PTEN deleted cell lines generated resistant populations that secreted significantly elevated levels of IL-6 and IL-8. In vivo, intrinsically or experimentally amplified HER2 cells with PTEN knockdown were highly tumorigenic and produced metastasis in multiple organs. We previously demonstrated that the Akt inhibitor perifosine is able to reduce CSCs in PTEN-deleted tumors. In order to examine the role of IL-6 and IL-8 in mediating trastuzumab resistance, we treated mice bearing HER2 overexpressing PTEN deleted xenografts with perifosine alone or in combination with an anti-IL-6 receptor and/or anti-IL-8 antibodies. Tumor growth was substantially suppressed by the addition of IL-6 and IL-8 targeting antibodies. These studies suggest that resistance to trastuzumab in PTEN deleted cells may be partially mediated by the activation of cytokine loops involving IL-6 and IL-8. The use of agents which block these cytokine loops may provide a novel approach to overcome trastuzumab resistance.
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 3337. doi:10.1158/1538-7445.AM2011-3337
Abstract 334: Evaluation of ProEx C (MCM2 and TOP2A), p16 and Ki-67 as biomarkers for cervical carcinoma
Authors: Wang Hong-Wei , Terinate Paul , Gao Youfang , Wei May , Poongothai A.R. , Kalra Krishan L. 
Published: June 2012

Abstract
Background: Cervical cancer is the second most common cancer among women worldwide. Many studies have confirmed a strong correlation between p16 overexpression and high-grade premalignant or malignant lesions of the cervix. A newer biomarker ProEx C has been implicated as a useful indicator for cervical cancer. However, data on comparison between these biomarkers in cervical cancer remain limited. In this study, we investigated the expression of ProExC, p16 and Ki-67 in cervical carcinoma and ovarian tumors as comparison.
Objective: To determine the value of ProEx C combined with p16 and Ki-67 in detection of cervical carcinoma.
Methods: Total of 28 cases of cervical carcinoma biopsies were included in this study, among these one was adenocarcinoma and 27 cases were squamous cell carcinoma type. Ovary tissue microarray (TMA) samples (BioGenex TS-4212) were used for comparison. ProEx C antibody cocktail was prepared from rabbit monoclonal antibodies against minichromosome maintenance protein 2 (MCM2, clone ID: EPR4120) and Topoisomerase II alpha (TOP2A, clone ID: EP1102Y). All tissue samples were examined for expression of p16 and Ki67. Co-localization of ProEx C/p16 and ProEx C/Ki-67 was determined by simultaneous double stain method. Fully automated Xmatrx® system was used for the IHC staining.
Results: Overexpression of ProEx C was found in all 28 cases of cervical carcinoma tissues. All the cancer cells and some other proliferative cell types showed nucleus staining pattern. Upregulated expression of p16 was observed in all 28 cases, with both nucleus and cytoplasmic staining. The p16 staining was limited within those cancer cells. Simultaneous double stain for ProEx C/p16 demonstrated that over 90% of cancer cells co-expressing these two biomarkers. Although Ki-67 staining was also observed in all the cases, a variable portion (less than 50%) of cancer cells was Ki-67 positive. ProEx C/Ki-67 double positive cells were ranging from 20% to 40% of total ProEx C positive cells. Of the 41 ovary tissues from TMA, 35 were ovarian tumor samples and ProEx C positive, 17/35 was p16 positive (48.6%).
Conclusions: 1) ProEx C is a sensitive proliferation biomarker for diagnosis of cancer, which is more sensitive in determining proliferation status than that of Ki-67. 2) p16 is a more specific biomarker for cervical carcinoma than that for ovarian cancer. 3) Combination of ProEx C and p16 may increase the sensitivity and specificity in cervical cancer detection.
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 334. doi:10.1158/1538-7445.AM2011-334
Abstract 3341: TGFβ/ TNFα-mediated epithelial-mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype
Authors: Asiedu Michael K. , Ingle James N. , Behrens Marshall D. , Radisky Derek C. , Knutson Keith L. 
Published: June 2012

Abstract
Breast cancer recurrence is believed to be caused by a potently tumorigenic sub-population of cancer cells possessing stem cell attributes of resistance to chemotherapy, radiation and other forms of treatment. Recently, we and others have reported the generation of breast cancer stem cell (BCSC) characteristics by inducers of epithelial to mesenchymal transition (EMT). Both EMT and acquisition of BCSC properties are therefore important steps in cancer progression, although the physiological process by which BCSCs arise in vivo remains unclear. We show here that exposure to TGFβ and TNFα induces a stable BCSC phenotype, characterized by self-renewal, greatly increased tumorigenicity, and increased resistance to oxaliplatin, etoposide and paclitaxel. We further found that the TGFβ/TNFα-derived cells showed downregulated expression of Claudins 3, 4 and 7 and the luminal marker KRT18, demonstrating a shift to the claudin low molecular subtype, a recently identified breast cancer subtype characterized by the expression of mesenchymal and stem cell-associated markers and correlation with poor prognosis. Furthermore, pathway analyses of the generated BCSCs showed deregulation of a number of breast cancer-associated genes and pathways including inflammatory cytokine and receptors, chemokines, homeobox, hedgehog, notch and metastases genes. These results confirm the role of EMT and BCSCs in resistance of breast cancer to conventional chemotherapy and identify novel target genes and pathways for validation as potential therapeutic targets. Our demonstration that stable BCSCs can be produced by specific microenvironmental signals also provides a valuable tool for studying cancer stem cells, as well as a means for screening potential cancer drugs for efficacy of targeting cancer stem cells to prevent recurrence.
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 3341. doi:10.1158/1538-7445.AM2011-3341
Abstract 3347: Characterization of an epithelial micro-pattern within ducts and lobules of the human breast: The topography of estrogen receptor expression
Authors: Villadsen Rene , Fridriksdottir Agla , Kim Jiyoung , Ronnov-Jessen Lone , Petersen Ole W. 
Published: June 2012

Abstract
The human breast is a unique organ in that it undergoes most of its development after birth under the control of systemic hormones. The adult human breast undergoes cycles of cell proliferation and apoptosis not only during pregnancy but also within the menstrual cycle throughout the reproductive life of women. These highly dynamic changes are thought to rely on the presence of a mammary stem cell population. Recently, we have succeeded in defining a stem cell hierarcy as well as a stem cell zone located to ducts in the normal human mammary gland.
In the present study we have utilized multiparameter cell sortings to isolate two types of progenitors present in the luminal compartment of the mammary gland. One population defines a lineage-restricted progenitor with the capacity of expressing endocrine receptors. The other compartment is enriched for cells with stem cell activity, including the ability to form TDLU-like structures in Matrigel. Further characterization of these populations include testing of expression markers for stem cell activity, lineage-differentiation, anti-apoptotic pathways, as well as finding optimal culture conditions for propagating the cells in vitro.
This may lead to identification of those long-term breast resident(s) that accumulate enough genetic hits for clonal expansion and tumor development, i.e. the cellular origin(s) of breast cancer.
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 3347. doi:10.1158/1538-7445.AM2011-3347
Abstract 335: Mutation analysis of KRAS and BRAF genes in sebaceous lesions and keratoacanthomas sporadic or related to hereditary syndrome
Authors: Meireles Sibele I. , Stamboni Merin B. , Crespo Rodrigo , Gomes Marina , Landman Gilles , Coudry Renata A. 
Published: June 2012

Abstract
BACKGROUND: Sebaceous lesions comprises: hyperplasias, adenomas, sebaceomas and carcinomas, which can be sporadic or related to hereditary syndrome. Keratoacanthomas, as sebaceous lesions, can be associated with hereditary cancer, known as Muir-Torre syndrome (MTS), accepted as the presence of those lesions with visceral malignancies, mainly colorectal cancer (CRC). Besides, a subset of MTS shares clinical, pathological and molecular characteristics with hereditary nonpolyposis colorectal cancer (HNPCC). BRAF mutation has already been described in sebaceous hyperplasia but not in CRC in an onset of HNPCC. BRAF oncogene is part of the MAPKinase pathway, as KRAS gene, and both have an important role in cellular proliferation, differentiation and apoptosis. OBJECTIVE: The aim of this study was to evaluate the role of KRAS and BRAF genes in sebaceous lesions and keratoacanthomas in a sporadic setting or related with hereditary syndrome. METHODS: KRAS (codons 12 and 13) and BRAF (V600E) mutations of 52 sebaceous lesions and 42 keratoacanthomas samples was evaluated using Sanger sequencing. 24 (46%) patients had at least one internal malignancy and thus were diagnosed as having MTS. 7 (14%) patients presented clinical or molecular diagnosis of HNPCC. RESULTS: Mutations in KRAS was identified in 7 of 52 cases (14%) of sebaceous lesions and 10 of 42 cases (24%) of keratoacanthomas. BRAF mutation was observed in 2 of 52 cases (4%) of sebaceous lesions and 2 of 42 cases (5%) of Keratoacanthomas. Mutation in both genes occurred in just one sample. There was no statistical significance observed with clinical variables. BRAF mutation was not observed in patients with diagnosis of MTS or HNPCC. CONCLUSION: The results indicate that KRAS and BRAF mutations play a distinct role in carcinogenesis of sebaceous lesions and KRAS a more important event in keratoacanthomas. KRAS mutation was observed in sporadic lesions and also related to hereditary syndrome. However, BRAF mutation was not observed in patients with HNPCC, concordant with observed in CRC with the same origin.
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 335. doi:10.1158/1538-7445.AM2011-335
Abstract 3355: Identification of unique tumoricidal genes in rat umbilical cord matrix stem cells
Authors: Uppalapati Lakshmi D. , Ohta Naomi , Zhang Yongqing , Pyle Marla , Becker Kevin G. , Troyer Deryl L. , Tamura Masaaki 
Published: June 2012

Abstract
Umbilical cord matrix stem cells (UCMSC) represent a promising source of therapeutics for various diseases including cancer. We have shown that naïve rat UCMSC significantly attenuate Fisher 344 rat-derived mammary adenocarcinoma (Mat B III) cell proliferation both in vivo and in vitro. To study the underlying mechanisms and genes involved in the Mat B III growth attenuation, we investigated gene expression profiles of naive rat UCMSC alone co-cultured with Mat BIII cells by cDNA microarray analysis. Total RNA was extracted from the naïve rat UCMSC alone and those co-cultured with Mat B III in transwell culture dishes. The comparison of gene expression profiles between untreated and co-cultured rat UCMSC identified five up-regulated (Follistatin (FST), Sulfatase1 (SULF-1), Glucose phosphate isomerase (GPI), HtrA serine peptidase (HTRA1), and Adipocyte differentiation-related protein (ADRP)) and two down-regulated (Transforming growth factor, beta-induced (TGFBI), Podoplanin (PDPN)) candidate genes based upon the following screening criteria: 1) candidate gene expression should show at least a 1.5 fold change in rat UCMSC co-cultured with Mat B III cells; 2) candidate genes encode secretory proteins; and 3) candidate genes encode cell growth-related proteins. Following confirmation of gene expression by real time-PCR, ADRP, SULF-1 and GPI were selected for further analysis. Addition of specific neutralizing antibodies against these three gene products individually or all together in the co-culture of Mat B III cells and 1/20 cell number of rat UCMSC significantly increased [3H] thymidine uptake in the Mat B III cells implying that these gene products are functionally produced under the co-cultured condition and attenuate cell growth. Immunoprecipitation followed by Western Blot analysis demonstrated that these proteins are indeed secreted into the culture medium. We are investigating the siRNA-dependent down regulation of these genes in rat UCMSC to confirm their tumor suppressor function. These results suggest that ADRP, SULF-1 and GPI act as tumor suppressor genes and these genes might be involved in rat UCMSC-dependent growth attenuation of rat mammary tumor. This work was supported by the Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU College of Veterinary Medicine Dean's Fund, NIH P20 RR017686, p20RR1556, R21CA135599, Kansas Bioscience Authority research fund and by the Intramural Research Program of the NIH, National Institute on Aging.
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 3355. doi:10.1158/1538-7445.AM2011-3355