bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3711: Human colon mucosal crypts in culture: a model to assess colon chemoprevention.
Authors: Dame Michael K. , Jiang Yan , Turgeon Danielle Kim , Appelman Henry , Aslam Muhammad N. , Copley Kelly , Attili Durga , Brenner Dean E. , Varani James 
Published: August 2014

Abstract
Introduction: In order to advance a primary cell culture model of human colonic carcinogenesis we developed methods for the isolation and in vitro maintenance of intact colonic crypts from normal human colon tissue and adenomatous polyps.
Methods: Fresh biopsy samples were transported in culture medium containing 1.5mM Ca2+ and antimicrobials. The mucosa/submucosa was surgically separated from the muscularis propria and incubated in 10mM dithiothreitol followed by 8mM ethylenediaminetetraacetic acid. Crypts were agitated free, washed with slow spins, and immediately embedded in a 3-dimensional environment at a density of 50 crypts/50μl Matrigel. After 3 hours, media was replaced to remove non-viable cellular products. Serum-free medium, containing low Ca2+ (0.15mM), was used to maintain crypt cultures. Cell proliferation and differentiation were assessed with markers Ki67 and E-cadherin by confocal microscopy. The fluorescence signal was quantified for the bottom 1/3 of the crypts (35 cells from base on one crypt edge) using morphometric imaging software. In parallel studies, abnormal crypt-like structures were isolated from adenomatous polyps/adenocarcinoma and maintained in a similar culture system.
Results: At day-1 in culture, Ki67 expression was strong in the proliferating cells at the crypt base, with E-cadherin staining increasing towards the crypt apex. By day-3, E-cadherin expression became much more prominent and Ki67 decreased dramatically. This culture system preserved the in vivo phenotype of the crypts and allowed for the colonic epithelial cells to follow the physiological sequence of progression from proliferation to differentiation. Adenomatous tissue in culture at day-1 showed expression for Ki67 and E-cadherin but lacked spacial organization.
Conclusion: Intact colonic crypts from normal and abnormal human mucosa can be viably maintained in 3-D culture for 72 hours. This primary human in vitro 3-D model may be used to model efficacy of colonic cancer chemopreventives.
Epithelial Cell Proliferation and Differentiation in Cultured Human Crypts (fold changes) Markers Zero-time 24 hours 48 hours 72 hours Ki67 1.00 0.36 0.18 0.00 E-cadherin 1.00 2.00 2.89 3.22
Citation Format: Michael K. Dame, Yan Jiang, Danielle Kim Turgeon, Henry Appelman, Muhammad N. Aslam, Kelly Copley, Durga Attili, Dean E. Brenner, James Varani. Human colon mucosal crypts in culture: a model to assess colon chemoprevention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3711. doi:10.1158/1538-7445.AM2013-3711
Abstract 3713: Chemoprevention of prostate carcinogenesis in TRAMP mice by α-santalol by causing cell cycle arrest and induction of apoptosis.
Authors: Bommareddy Ajay , Eggelston William , Prelewicz Stacy , Antal Andrea , VanWert Adam L. , Patel Hiral , Chinikaylo Aleona , Gutierrez Linda S. , Sreevidya Santha , Dwivedi Chandradhar 
Published: August 2014

Abstract
α-santalol, a major component of sandalwood oil inhibits growth of cultured prostate cancer cells in vitro by causing apoptosis. The present study was undertaken to determine the in vivo efficacy of α-santalol using TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice as a model. The i.p administration of α-santalol (50 mg/kg) did not cause any side effects or weight loss throughout the study. Administration of α-santalol (50 mg/kg) showed a trend in decrease in average wet weights of urogenital weights compared to control mice (∼34% decrease in α-santalol group compared to control). Furthermore, the dorsolateral sections of prostate from α-santalol-treated mice exhibited decreased cell proliferation in association with induction of apoptosis. Western blotting analysis of prostate tumor samples from α-santalol-treated group revealed an increase in the expression levels of cleaved PARP, phospho p53 (ser 15), cleaved caspase-3, cyclin B, p21 and a modest reduction in antiapoptotic protein Bcl-xL compared to control samples. In agreement with these results, α-santalol treatment resulted in G2/M cell cycle arrest in cultured prostate cancer cells. In conclusion, the present study indicates that α-santalol administration inhibits the development of prostate cancer in TRAMP mice by decreasing cell proliferation, causing cell cycle arrest, and inducing apoptosis. This study was supported by Wilkes University Type I grant, American Association of Colleges of Pharmacy and by Translational Cancer Research Center funded by South Dakota Governor's Office of Economic Development.
Citation Format: Ajay Bommareddy, William Eggelston, Stacy Prelewicz, Andrea Antal, Adam L. VanWert, Hiral Patel, Aleona Chinikaylo, Linda S. Gutierrez, Santha Sreevidya, Chandradhar Dwivedi. Chemoprevention of prostate carcinogenesis in TRAMP mice by α-santalol by causing cell cycle arrest and induction of apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3713. doi:10.1158/1538-7445.AM2013-3713
Abstract 3715: Zoledronic acid inhibits cancer growth and cancer stem cell phenotypes in head and neck squamous cell carcinoma.
Authors: Lee Sung Hee , Kim Reuben , Kang Mo , Park No-Hee , Shin Ki-Hyuk 
Published: August 2014

Abstract
Zoledronic acid (ZA), a third generation of bisphosphonates, is known to have both anti-osteolytic and anti-tumor activities. It exerts anti-osteolytic function by interfering with mevalonate pathway and preventing protein prenylation required for growth and survival in osteoclast cells. Also, similar function has been found to induce cancer apoptosis and inhibit cancer growth in bone-related cancer, but its effect on other cancer types, including head and neck squamous cell carcinoma (HNSCC) is still unclear. In this study, we first monitored the effect of ZA on cancer growth in HNSCC cell lines in vitro. ZA significantly suppressed cancer growth, shown by decreased anchorage independent growth in soft agar assay and diminished cell growth in organotypic raft culture. Because cancer stem cell (CSC; also called tumor-initiating cell) plays a significant role in cancer growth, we further investigated the effect of ZA on CSC in HNSCC. ZA-treated HNSCC cells significantly decreased CSC phenotypes such as sphere forming ability and migratory ability. In SCC4, a tongue squamous cell carcinoma cell line, side population and expression of pluripotency marker genes were significantly decreased by ZA. Also, ZA inhibited the CSC-related Sonic Hedgehog pathway in SCC4 as demonstrated by decreased mRNA expression of transcriptional factor, Gli-1. Taken together, our data suggest that ZA targets CSC and hence inhibits cancer growth in HNSCC.
Citation Format: Sung Hee Lee, Reuben Kim, Mo Kang, No-Hee Park, Ki-Hyuk Shin. Zoledronic acid inhibits cancer growth and cancer stem cell phenotypes in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3715. doi:10.1158/1538-7445.AM2013-3715
Abstract 3718: Taxane-induced hedgehog activation promotes stemness of breast cancer cells.
Authors: Opdenaker Lynn , Sims-Mourtada Jennifer 
Published: August 2014

Abstract
Recurrence of breast cancer after chemotherapy is thought to arise from resistant breast cancer stem cells which are eventually able to repopulate the tumor. The hedgehog (HH) signaling pathway has been shown to regulate the proliferation and survival of breast cancer stem cells, and has been shown to promote resistance to chemotherapy through the activation of multi-drug resistance and prosurvival pathways. Here we report that exposure of heterogenous breast cancer cell lines (T47D and SKBr3) to low doses (1-10nM) of docetaxel resulted in activation of HH signaling. Increased levels of sonic HH were detected in supernatants of breast cancer cells at 6- hours post-treatment. This release was accompanied by increased expression and nuclear translocation of Gli-1, peaking at 24 hours after exposure. Additionally, increased expression of the PTCH receptor was observed by western blotting in these cells 24 hours after treatment, indicating activation of a Gli-1 induced negative feeback loop. Increased mammosphere formation was observed in cells after preincubation with low dose docetaxel. Secondary sphere forming efficiency (SFE) was also increased in pretreated cells. The increase in SFE was similar to that of cell lines cultured in the presence of recombinant SHH. Additionally, the increase in SFE observed after docetaxel treatment could be blocked by the addition of sublethal doses of the hedgehog inhibitor cyclopamine. These results suggest that hedgehog pathway activation induced by docetaxel treatment could result in increased stemness of breast cancer cell lines. We propose that chemotherapy may activate stem cell signaling pathways, resulting in expansion of cancer stem cells and increased drug resistance.
Citation Format: Lynn Opdenaker, Jennifer Sims-Mourtada. Taxane-induced hedgehog activation promotes stemness of breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3718. doi:10.1158/1538-7445.AM2013-3718
Abstract 372: Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling.
Authors: Chen Hong , Satish Pasula , Cai Xiaofeng , Dong Yunzhou , Chang Baojun 
Published: August 2014

Abstract
To examine the angiogenic role of endothelial epsins, a family of ubiquitin binding endocytic clathrin adaptors, we generated mice with constitutive or inducible deletion of epsins 1 and 2 in vascular endothelium. These mice exhibited no abnormal phenotypes under normal conditions, suggesting that lack of endothelial epsins 1 and 2 does not affect normal blood vessels. However, adult mice lacking endothelial epsins 1 and 2 exhibited highly disorganized tumor vasculature, significantly increased vascular permeability, and markedly retarded tumor growth. Mechanistically, we show that VEGF promotes binding of epsin to ubiquitinated VEGF receptor 2 (VEGFR2). Loss of epsins 1 and 2 specifically impairs endocytosis and degradation of VEGFR2 which results in excessive VEGF signaling that compromises tumor vascular function by exacerbating non-productive leaky angiogenesis. This suggests that tumor vasculature requires a balance in VEGF signaling to provide sufficient productive angiogenesis for tumor development, and that endothelial epsins 1 and 2 negatively regulate the output of VEGF signaling. Thus, promoting excessive VEGF signaling within tumors via a block of epsin 1 and 2 function, may represent a strategy to prevent normal angiogenesis in cancer patients who are resistant to anti-VEGF therapies.
Citation Format: Hong Chen, Pasula Satish, Xiaofeng Cai, Yunzhou Dong, Baojun Chang. Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 372. doi:10.1158/1538-7445.AM2013-372
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3720: Rad51 is involved in PARP inhibitor resistance in triple-negative breast cancer stem cells (TNBCSCs).
Authors: Liu Yajing , Martin Rachel , Bai Shoumin , Wicha Max , Liu Suling 
Published: August 2014

Abstract
Although the mortality rate in breast cancer (BC) has been reduced by the advancing technology, the outcome of patients with “triple-negative” (TN) BC (accounts for 10-17% of invasive BC) has achieved little progression. Recently, inhibitors of poly (adenosine-disposphate-ribose) polymerase (PARP) have been developed to target cells with defective DNA repair molecules such as BRCA1-deficient cells. Despite the tumor regression induced by these agents in a subset of BCs, their ability to effect patient outcome remains inconclusive. According to the CSC hypothesis, a hierarchical tumor organization exists whereby dysregulated self-renewing CSCs drive tumorigenesis. Our preliminary results showed that PARP inhibitor significantly decreased cell number in BRCA1-deficient SUM149 cells in a dose-dependent manner, whereas BRCA1 wild type SUM159 cells were relatively resistant. However, there was little change in absolute CSC number in SUM149 cells after PARP inhibitor treatment, suggesting PARP inhibitor only targets the non-CSC population in SUM149 cells. More interestingly, the resistant population expressed higher active Rad51 as measured for Rad51 foci formation. Our pervious study also showed that Rad51 mRNA level was significantly higher in ALDH+ cells of some breast cancer cell lines. Therefore, in this study, we established an inducible knock-down system using lentivirus and found that knocking down Rad51 sensitizes SUM159 (both CSC and non-CSC) as well as ALDH+ SUM149 cells to PARP inhibitor, suggesting the expression of Rad51 is associated with PARP inhibitor resistant population. This system was also tested in mouse model where cells carrying Rad51 shRNA were injected into the mammary fat pads of female NOD/SCID mice. Knock-down of Rad51 alone and combination treatment with PARP inhibitor dramatically inhibited tumor growth in the xenografts of both SUM149 and SUM159 cells, whereas, tumor grew back after Rad51 expression was restored. However the inhibitory effect remained in the combined treatment group after the treatment was terminated. Furthermore, the combination treatment decreased ALDH+ cells by IHC staining. It also showed a significant decrease in tumor-initiating cells in the combined treatment group by limiting dilution transplantation. Our results suggest that Rad51 plays an important role in resistance to PARP inhibitor in TNBCSCs thus Rad51 inhibitor may be a novel therapeutic approach in addition to PARP inhibition for treating TNBC patients.
Citation Format: Yajing Liu, Rachel Martin, Shoumin Bai, Max Wicha, Suling Liu. Rad51 is involved in PARP inhibitor resistance in triple-negative breast cancer stem cells (TNBCSCs). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3720. doi:10.1158/1538-7445.AM2013-3720
Abstract 3724: Salinomycin reduced breast cancer stem cell properties by reducing SOX2 and OCT4.
Authors: An Hyun Sook , Kang Han Na , Kang Myoung Hee , Kim Jung Lim , Kim Jun Suk , Seo Jae Hong 
Published: August 2014

Abstract
Salinomycin isolated from Streptomyces albus and a potassium ionophore. It has been used to eliminate bacteria, fungi and parasites. Also, Cancer stem cells (CSCs) are a subpopulation of cells within the tumor that has ability to self-renew and undergo differentiation to phenotypically diverse cell populations. So, CSCs are involved in metastasis, chemoresistance and even cancer relapse. Recently, there are many evidences to CSCs subpopulations enhance capability of DNA repair and reduce the apoptosis. Furthermore, salinomycin has been reported to act as selective breast cancer stem cell inhibitor based on its property of reducing the cancer stem cell and to induce the apoptosis in cancer cell. Therefore, we investigated the effect of salinomycin on breast cancer stem cells.
First, Mammosphere formation assay was performed to observe stem cell-like property after salinomycin treat in anchorage-independent state. We confirmed salinomycin reduces number and size of mammosphere at 3, 6, 9 day. Also, we compared mRNA expressing level of stem cell marker such as SOX2 and OCT4 by RT-PCR. Consequently, salinomycin was the down-regulated stem cell marker mRNA level as well as protein level.
To confirm the reduction of the side population level, we performed FACS analysis using CD44+ and CD24- markers. Results by FACS analysis revealed that salinomycin treated with breast cancer stem cell reduced stemness by downregulating CD44+/CD24- population. Consistently, when mammosphere implanted into the mammary fat pads of BALB/c female nude mice cleared of endogenous epithelium, the tumor size was decreased. In conclusion, we concluded that effect of salinomycin to reduce stemness is mediated by downregulation of SOX2 and OCT4 in human breast cancer cell.
Citation Format: Hyun Sook An, Han Na Kang, Myoung Hee Kang, Jung Lim Kim, Jun Suk Kim, Jae Hong Seo. Salinomycin reduced breast cancer stem cell properties by reducing SOX2 and OCT4. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3724. doi:10.1158/1538-7445.AM2013-3724
Abstract 3729: Targeting breast cancer stem cells via oxidative stress with inhibitors of hydroperoxide metabolism and decyl-triphenylphosphonium.
Authors: Conley Sarah J. , Baker Trenton , Theisen Rebecca , Gheordunescu Elizabeth , Zhu Yueming , Aykin-Burns Nukhet , Fath Melissa , Spitz Douglas , Wicha Max 
Published: August 2014

Abstract
Cancer stem cells (CSCs) exhibit lower intracellular reactive oxygen species (ROS) levels than non-CSCs, which may be due to the increased expression of free radical scavenging systems. Exogenous agents may be useful to increase ROS and selectively kill CSCs by oxidative stress. Here we tested a combination approach to increase ROS as an effective strategy to eradicate breast CSCs and metastases. Buthionine sulfoximine (BSO) and auranofin (AU) were used to deplete glutathione (GSH) and inhibit thioredoxin reductase (TR), respectively, while mitochondrial-targeted decyltriphenylphosphonium (dTPP) was used to elevate ROS levels. In vitro clonogenicity assays using SUM159 cells showed that treatment with dTPP alone resulted in &lt;30% survival, while AU+BSO, BSO+dTPP and AU+BSO+dTPP all resulted in &lt;1% survival. These effects were reversible with N-acetylcysteine pre-treatment. The Aldefluor+ (CSC) population was also measured following drug treatment in vitro. dTPP or AU treatment alone resulted in &lt;50% of CSCs remaining, while BSO+AU or BSO+dTPP resulted in &lt;25% of CSCs remaining, and treatment with all three compounds resulted in &lt;1% of CSCs remaining. In a preclinical model of breast cancer metastasis, long-term adjuvant treatment with each individual compound significantly reduced the amount of metastases and increased survival, with dTPP treatment alone resulting in 100% survival rate. Interestingly, the combination of all three compounds resulted in increased metastases compared to the single agents. This may potentially be a stress-induced effect resulting from drug toxicity. In conclusion, the approach of increasing ROS in breast cancer cells may be an effective way to target CSCs and useful for adjuvant therapy to reduce metastases in patients.
Citation Format: Sarah J. Conley, Trenton Baker, Rebecca Theisen, Elizabeth Gheordunescu, Yueming Zhu, Nukhet Aykin-Burns, Melissa Fath, Douglas Spitz, Max Wicha. Targeting breast cancer stem cells via oxidative stress with inhibitors of hydroperoxide metabolism and decyl-triphenylphosphonium. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3729. doi:10.1158/1538-7445.AM2013-3729
Abstract 3733: Defining and targeting a Glioblastoma cancer stem cell population with EGF Receptor Variant III.
Authors: Emlet David R. , Vecchio Catherine Del , Gupta Puja , Mitra Siddhartha , Han Shuang-Yin , Holgado-Madruga Marina , Li Gordon , Jensen Kristen , Vogel Hannes , Skirboll Stephen , Wong Albert J. 
Published: August 2014

Abstract
The relationship between mutated proteins and the relatively rare cancer stem cell population is unclear since driver mutations are present throughout a tumor. Glioblastoma (GBM) tumors frequently express EGFRvIII, an EGFR variant that arises via gene rearrangement and amplification. The expression of EGFRvIII is restricted despite the prevalence of the alteration. Here we show that EGFRvIII is expressed in a population of human GBM cancer stem cells. EGFRvIII positive cancer stem cells demonstrate greater self-renewal and tumor initiation than the more abundant EGFRvIII negative cells. EGFRvIII positive cells are associated with stem/progenitor markers while markers of differentiation are found in EGFRvIII negative cells. EGFRvIII is highly co-expressed with CD133, and the EGFRvIII positive/CD133 positive sub-population defines the highest self-renewal and tumor initiating population. Surprisingly, wildtype EGFR was infrequently co-expressed with EGFRvIII but present in the majority of cells, both in primary GBM and cultured GBM neurospheres. Elimination of the EGFRvIII positive or the EGFRvIII/CD133 dual positive population with an engineered anti-EGFRvIII/CD133 bi-specific antibody reduced tumorigenicity of implanted tumor cells. This work demonstrates that a mutated oncogene can have CSC specific expression and be used to specifically target this population.
Citation Format: David R. Emlet, Catherine Del Vecchio, Puja Gupta, Siddhartha Mitra, Shuang-Yin Han, Marina Holgado-Madruga, Gordon Li, Kristen Jensen, Hannes Vogel, Stephen Skirboll, Albert J. Wong. Defining and targeting a Glioblastoma cancer stem cell population with EGF Receptor Variant III. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3733. doi:10.1158/1538-7445.AM2013-3733