bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3329: Human prolactin increased chemosensitivity of breast cancer stem cells in MCF-7 and primary breast tumors from HER2/neu transgenic mice
Authors: Lee Eric , Park Jang-pyo , Chen Wen Y. 
Published: February 2011

Abstract
Background. Tumors are organized in a cellular hierarchy, in which cancer stem cells (CSCs) are the only cells that have the ability of self-renewal and differentiation. CSCs generally are in quiescent state and resistant to chemotherapy, which is one of the reasons that using conventional chemotherapeutics often leads to enrichment in CSCs. It is known that adult stem cells (ASCs) and CSCs share many common features. In adult mammary tissue, one of the distinctive features is its ability to go through multiple proliferation and involution cycles during pregnancy, suggesting that ASCs in this organ are readily responsive to female hormone regulations. One such hormone that plays a crucial role in this process is human prolactin (hPRL), which is required for mammary lobuloalveolar formation, terminal differentiation, and for synthesis of milk components. In this study, we hypothesize that simultaneous administration of hPRL with chemotherapeutic agents such as doxorubicin (Dox) will increase the cytotoxic effects of the chemotherapeutic drugs towards CSCs through the induction of CSCs proliferation/differentiation by hPRL.
Methods. MCF-7 human breast cancer cells and primary mouse breast cancer cells isolated from MMTV-neu transgenic mice were used in this study. Tumorsphere formation assay and ALDH activity measured by flow cytometry were used to measure the functional response of the CSCs after co-treatment of hPRL and Dox.
Results. (1) hPRL treatment increased tumorspheres formation in both MCF-7 (1.3-fold ± 0.24, p&lt;0.05) and primary mouse breast cancer cells (2.3-fold ± 0.34, p&lt;0.001). (2) Dox treatment (25ng/ml) increased ALDH+ cell population (7.74-fold ± 0.42, p&lt;0.001), despite the fact that there is no significant change in total tumorspheres number (3) Combination of hPRL and Dox treatment decreased 50% of tumorspheres formation compared that of Dox treatment alone.
Conclusion. Our preliminary results suggest that hPRL is able to improve Dox's efficacy towards CSCs. Further studies are needed to validate the results. This novel therapeutic approach may open doors for designing new strategy for breast cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3329.
Abstract 3336: Upregulated inflammatory cytokines in glioma stem cells: Targets for glioma therapies
Authors: Wang Lei , Real Dalila Del , Seo Gwi-Moon , Pyle Marla , Troyer Dery 
Published: February 2011

Abstract
Gliomas are the most common primary brain tumors in adults. With the highly invasive growth pattern, gliomas often escape current therapeutic modalities including combinations of surgery, radiotherapy and chemotherapy. Recent studies implicate that a minority population of glioma stem cells (GSCs) are responsible for glioma maintenance and recurrence. Interleukin (IL)-1 beta, IL-6 and IL-8 are pleiotropic proinflammatory cytokines and their excessive production in the tumor microenvironment is associated with poor disease outcome in many cancer types, including glioma. These cytokines promote tumor growth via induction of proteins associated with tumor invasion and angiogenesis and anti-apoptosis. We hypothesize that GSCs acquire their chemo-resistance and invasion by excessive cytokine production. To test the hypothesis, we compared the cytokine gene expression of a human GSC-enriched population in serum-free medium (SFM) in the presence of epidermal growth factor and fibroblast growth factor, to that of glioma cells in serum-containing medium (SCM). SFM is the neural stem/progenitor cell (NPC) medium in which NPCs proliferate in neurospheres and this medium also has been used to enrich GSCs. We found that IL-1 beta and IL-6 were upregulated in GSC-enriched population along with increased expression of Nestin, a marker of neural stem cells. More interestingly, Smad interacting protein 1 (SIP1), which is thought to be involved in glioma cell migration and invasion, was also increased in the GSC-enriched population. The paralleled upregulation of IL-1 beta and IL-6 with Nestin and SIP1 in GSC-enriched population suggest that there is a possible correlation between them. The correlation is now under investigation. Since IL-1 beta is elevated in GSC enriched population, we further determined whether IL-1 beta plays a critical role in glioma growth. Glioma cells were co-cultured with mouse NPCs expressing IL-1 receptor antagonist (IL-1ra), which can bind to IL-1 receptors without transmitting activation signals and represents a competitive inhibitor of IL-1. Proliferation of glioma cells, which were modified to express Renilla luciferase, was measured using bioluminescence imaging. Our results showed that proliferation of glioma cells was inhibited in the co-culture with NPCs expressing IL-1ra, but not in the co-culture with NPCs without expression of IL-1ra, compared to glioma cells cultured alone. The results suggest that IL-1 has an important role in glioma cell growth and NPCs engineered to express IL-1ra have therapeutic potential for gliomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3336.
Abstract 3342: Specific inhibition of IKKβ induces caspase-independent cell death in the ovarian cancer stem cells
Authors: Alvero Ayesha B. , Montagna Michele K. , Holmberg Jennie , Mor Gil 
Published: February 2011

Abstract
Introduction: Current studies show that the cancer stem cells represent the chemo-resistant phenotype and therefore may survive chemotherapy to eventually rebuild the tumor. Our group previously identified and characterized the ovarian cancer stem cells using CD44 and MyD88 as a marker and showed that these cells have a constitutively active IKKβ/NFκB axis. We hypothesize that specific targeting of this pathway may affect survival of the ovarian cancer stem cells.
Methods: A panel of CD44+/MyD88+ ovarian cancer stem cells were treated with increasing concentrations of the specific IKKβ inhibitor, BAY 11-7082 (0.1, 0.5 1, 5, and 10 μg/ml). Effect on cell growth was monitored using the Incucyte real time imaging system and cell viability was determined using the Celltiter 96 assay. Specific inhibition of IKKβ was determined by: (a) the effect on the mTOR pathway by analyzing levels of phospho-S6 kinase and (b) by determining the effect on TNFα-induced NFκB activity by measuring levels of IκB. Activity of caspases- 3/7, −8, and −9 was measured using Caspase-Glo assay and levels of XIAP monitored using western blot analysis. Effect on mitochondrial membrane potential was measured using flow cytometry after staining with JC1 dye. In vivo activity was monitored using a s.c. ovarian cancer xenograft model in nude mice. The effect of BAY 11-7082 (10 mg/kg every other day given i.p.) was compared to carboplatin (40mg/kg q7d given i.p.) and paclitaxel (10mg/kg q3d given i.p.).
Results: Treatment with BAY 11-7082 inhibited cell growth and decreased cell viability in all ovarian cancer stem cell cultures tested in a dose and time dependent manner with GI50 at ∼ 5μg/ml. Specific inhibition of IKKβ was observed at this dose by a decrease in phospho-p70S6 kinase and inhibition of TNFα-induced IκB degradation. Cell death was caspase-independent with no significant increase in caspases 3/7, 8, nor 9 and no effect on the levels of XIAP. Cell death was associated with loss of mitochondrial membrane potential with more than 90% of cells showing a shift in JC1 fluorescence from red to green in 4h. In vivo studies showed that BAY 11-7082 is able to inhibit tumor growth with T/C of 64%, significantly better than carboplatin and paclitaxel (T/C 87% and 74%, p=0.009 and 0.0025, respectively).
Conclusion: The capacity of the cancer stem cells to survive chemotherapy and rebuild the tumor represent a major target to inhibit recurrence in ovarian cancer patients. The demonstration that specific targeting of IKKβ can induce cell death in the ovarian cancer stem cells opens new therapeutic options for ovarian cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3342.
Abstract 3347: Enrichment of a CD44+/CD24- putative cancer stem cell population drives tumor progression and growth factor independence in a mouse model of postmenopausal breast cancer
Authors: Smith Sarah M. , Chiao Lucia J. , Salcido Crystal D. , Varticovski Lyuba , Hursting Stephen D. 
Published: February 2011

Abstract
MMTV-Wnt-1 transgenic mice develop heterogeneous mammary tumors that accurately recapitulate human basal-like breast cancer. Additionally, targeted alterations in the Wnt signaling pathway in mammary epithelial cells preferentially induce mammary cancers from progenitor cells. Therefore, we hypothesized that MMTV-Wnt-1 mammary tumors harbor cells with cancer stem cell characteristics. To test this hypothesis, we characterized (in vitro and in vivo) two newly generated, clonal mammary epithelial cell lines (WA4 and WG4) from MMTV-Wnt-1 transgenic mouse tumors. The cell lines were analyzed using flow cytometry for CD44 and CD24 cell surface markers (a CD44+/CD24- profile is indicative of putative human and murine mammary cancer stem cells), mammosphere formation (low density seeding on non-adherent plates in stem-cell media), in vitro scratch assay (to measure wound healing), and by an in vitro Matrigel invasion chamber assay (to quantitate cell invasion). Finally, unsorted WA4 and WG4 cell lines were transplanted into syngeneic mammary fat pads of female ovariectomized (to model the postmenopausal state) C57BL/6 mice (1×10^7 cells/mouse; n=5/cell line), and tumor burden was assessed after 3 weeks. Tumors were analyzed by qRT-PCR and immunohistochemistry (IHC) for pathological and genetic markers of progression. Flow cytometric analysis demonstrated that the percentage of CD44+/CD24- cells was 62.2% in the WA4 line and 2.4% in the WG4 line. Serum starvation enriched the WA4 line for CD44+/CD24- cells (from 62.2% to 82.0%), without altering the composition of the WG4 line. Approximately 30% of unsorted WA4 cells, but &lt;1% of unsorted WG4 cells, formed mammospheres. Additionally, the WA4 line showed increases in wound healing by scratch assay and significant increases in invasion (226-fold increase versus WG4 cells after 30 hours). In vivo, the WA4 cell line was associated with larger, more aggressive tumors on average (+/− SD) than the WG4 line (2.09 +/− 0.68 g and 0.03 +/− 0.02 g, respectively, p&lt;0.0001). WA4 tumors were characterized by increased cellular proliferation, microvascular proliferation, and a basal appearance lacking ductal structures. WA4 tumors also demonstrated a loss of ERα/β expression (qRT-PCR), lacked IGF1-R activation (by IHC), and showed an increase in Wnt-1 progenitor signaling (qRT-PCR). In conclusion, MMTV-Wnt-1 transgenic mouse mammary tumors harbor a CD44+/CD24- putative cancer stem cell population, and an enrichment of this population corresponds with a more aggressive tumor phenotype in a mouse model of postmenopausal breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3347.
Abstract 3353: The CD44 hi cell population from malignant pleural effusion derived lung tumors displays increased tumorigenic potential
Authors: Basak Saroj , Veena Mysore , Oh Scott , Srivatsan Eri , Batra Raj K. 
Published: February 2011

Abstract
We have developed a new model system (http://dx.plos.org/10.1371/journal.pone.0005884) to test whether we can isolate candidate Cancer Stem Cell (CSC) populations from clinical specimens and validate that they possess increased tumorigenic and/or metastogenic potential. The model utilizes primary tumor cell populations derived from human malignant pleural effusions (MPE), which are cultured in an autologous tumor microenvironment (TME). This model system maintains intratumoral heterogeneity, and contains molecular signatures, surface phenotypes, and metabolic biomarkers that are associated with candidate CSC. The current study compares isogenic primary tumor subpopulations, separated on the basis of a surface biomarker expression, in terms of differences in molecular marker expression, and bioassays that measure clonogenic efficiency and tumorigenic potential. CD44, a surface CSC-biomarker, is expressed on most of the primary tumor cells (75-95%) derived from MPE. The CD44 expressing tumor cells can be divided into two groups (CD44hi) and (CD44lo) on the basis of CD44 surface labeling intensity. The CD44hi and CD44lo tumor cells were sorted (10% of each) from total tumor cell populations by FACS and evaluated for their clonogenicity on plastic (colony forming efficiency) and for colony forming units in soft agar (anchorage independent growth). Studies show that the CD44hi tumor cells are 40-60% more efficient in forming colonies, and give rise to larger colonies than CD44lo tumor cells. Expression of other candidate CSC biomarkers was also compared in the two cell subsets to determine the molecular correlates of CD44hi versus CD44lo cells. CD44hi cells coexpress higher levels of BMI-1, hTERT, EZH2, and OCT-4 by RT-PCR than CD44lo tumor cells, but there is no apparent difference in the expression of SUZ12 between these two populations. CD44hi cells also have increased ALDH expression based on the Aldefluor assay. To determine whether these subpopulations differed in terms of tumorigenic potential, limiting dilutions of cells were heterotopically (subcutaneous flank region) injected in NOD/SCID (IL-2gRnull) mice in comparison to CD44lo tumor cells. Low numbers of CD44hi cells (down to 300 cells) efficiently formed tumors, whereas isogenic CD44lo tumor cells failed to form tumors at the same cell doses. Thus, CD44hi cells have higher tumorigenic potential than CD44lo cells, and these studies suggest that these primary tumor populations are preferentially enriched for the candidate CSC phenotype.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3353.
Abstract 3356: A controversial study on well reported liver cancer stem cell marker
Authors: Ko Ching-Huai , Tseng Hsiang-Wen , Chen Ting-Shou , Wang Wei-Hsin , Lin Mai-Wei , Lai Chin-Pen , Wang Chun-Chung , Sun Chung-Yuan , Tseng Shih-Heng , Li Jen-Ming , Chou Ting-Yu , Wang Ling-Mei 
Published: February 2011

Abstract
Recent studies suggest that the presence of cancer stem cells (CSC) could be linked with patients’ survival. The ability of cancers to grow indefinitely has fueled the idea that cancer and stem cells may have common underlying mechanisms. It has been suggested that tumors are initiated from cancer stem cells (CSCs) with proliferation potential drives the growth of cancer. CSCs are resistant to chemotherapy and radiation. However, the suggested cancer stem cell markers in human hepatocellular carcinoma cells are variable and confused. In this study, we profiled some of the most reported CSC markers, including CD133, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase (ALDH), CD90, CD24, c-kit, global-H and stemness genes in eight human hepatocellular carcinoma cell lines. Through specific marker expressed cell sorting by FACs aria or magnetic beads, the CSC associated drug resistance and tumorigenicity were further evaluated. However, there is no obvious difference among parental group, marker-positive group and marker-negative group in these CSC characteristics evaluated. It seems no good correlation between reported markers in liver cancer stem cells. Therefore, presence of markers alone should be taken with caution as single prognostic parameters. Through harsh culture condition, spheroid cell grew and had been isolated, which perform CSC-like properties. Moreover, forced activation of an ESC-like gene expression program can reprogram HCC cells into CSC-like cells and achieve pathologic self-renewal. The ability to create induced cancer stem cells (iCSC) may provide opportunities to better define the biology of cancer stem cells in order to trace or eliminate them in human patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3356.
Abstract 3358: Immunohistochemical features of stem cell transcription factors on colorectal carcinoma and adenoma in familial adenomatous polyposis
Authors: Tanaka Koji , Morimoto Yuhki , Toiyama Yuji , Yasuda Hiromi , Saigusa Susumu , Yokoe Takeshi , Araki Toshimitsu , Inoue Yasuhiro , Miki Chikao , Kusunoki Masato 
Published: February 2011

Abstract
Background: The pathogenesis of colorectal cancer in familial adenomatous polyposis (FAP) has been studied genetically. Recently, intestinal stem cell (ISC) or cancer stem cell (CSC) is being focused on colorectal carcinogenesis. The aim of this study is to investigate the immunohistochemical features of stem cell transcription factors on colorectal adenocarcinomas, adenomataous polyps, and normal crypts in patients with FAP.
Methods: Lgr5 as an ISC marker, CD133 and CD44 as CSC markers, and NANOG, OCT4, and SOX2 as embryonic stem cell transcription factors were evaluated immunohistochemically. Matched specimens of colorectal adenocarcinoma, adenomatous polyps, and adjacent normal crypts were obtained from individual FAP patients (n=4), to clarify the association between stepwise progression from normal crypt to adenomatous polyp to adenocarcinoma and expression of stem cell transcription factors.
Results: Lgr5, NANOG, OCT4, and SOX2 were mainly located in cytoplasm of cancerous and adenomatous cells. CD133 showed cytoplasmic or intraluminal membranous staining in cancerous and adenomatous cells. Immunoreactive CD44 protein was present in cell membrane or cytoplasm of cancerous and adenomatous cells. Immunoreactive positivity and intensity was greater in colorectal adenocarcinomas than in adenomatous polyps, except for NANOG. Adjacent normal crypts showed negative or weak staining of all markers. CD133, CD44, Lgr5, OCT4, and SOX2 were strongly expressed on cancerous cells at the advancing front of colorectal adenocarcinoma.
Conclusions: ISC or CSC may be associated with colorectal carcinogenesis of FAP. Stem cell transcription factors may be involved in tumor invasion of colorectal adenocarcinoma in FAP patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3358.
Abstract 3364: Evaluation of CD133/CD44 expression level in resected gastric cancer tissues after neoadjuvant chemotherapy
Authors: Yoshida Hiroshi , Nakajima Takako Eguchi , Taniguchi Hirokazu , Horita Yousuke , Masutomi Kenkichi , Shimoda Tadakazu , Yamada Yasuhide 
Published: February 2011

Abstract
BACKGROUND: Increasing evidence suggests that there is a small subset of cells, called cancer stem cells (CSC), that are responsible for cancer initiation, development, metastasis and treatment resistance. Although CD133 and CD44 are thought to be the putative markers to characterize CSC of various solid tumors such as brain cancer, colorectal cancer, breast cancer and prostate cancer, the link between expression status of CD133/44 and the clnical future of resected gastric cancer tissues after neo-adjuvant chemotherapy has not yet studied. We evaluated CD133/44 expression status in resected gastric cancer issue after neoadjuvant chemotherapy.
PATIENTS AND METHODS: 32 cases were selected from advanced gastric cancer specimens of patients who underwent neo-adjuvant chemotherapy (S-1 and cisplatin or irinotecan and cisplatin or S-1 monotherapy) and surgical resection between 2001 and 2007 at the National Cancer Center Hospital. Immunohistochemical staining with anti-CD133 and anti-CD44 antibody were performed with these specimens. Immunopositive cells were counted from 10 fields in the representative section and expressed as a percentage. The specimen with necrosis or disappearance of the tumor cells in more than 1/3 of the whole lesion was defined as positive histological response specimen. Correlation of immunoreactivity with clinicopathological variables was evaluated and survival curves were compared between CD133/CD44 positive and negative cases.
RESULTS: Patient characteristics: median age 57 years (range 31-74); male/female 22/10; histological type diffuse-type/intestinal-type 25/7. CD133 and CD44 expression (positive cells: 0% &lt;) were detected in 24 specimens (75%), and 29 specimens (91%), respectively. There was no significant difference of histological response rate between the CD133 positive and negative group (17% vs 50%, P=0.152). Median survival times were 30.4months in CD133+ group and 27.7months in CD133- group (P=0.65). Median relapse free survivals were 22.1months in CD133+ group and 17.6months in CD133- group (P=0.33). Histological type of gastric cancer (intestinal type vs diffuse type) was not correlated with CD133/CD44 expression.
CONCLUSION: CD133 and CD44 were frequently expressed in gastric cancer tissues after neoadjuvant chemotherapy. This study had limited numbers of patient sample and we were unable to study the CD133/44 status before treatment. Further study to identify the usefulness of CD133 and CD44 to predict the prognosis in gastric cancer patients is warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3364.