bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1392: Differential effects of Cancer Stem Cells (CSCs) and non-CSCs-targeted therapies on lung primary tumors and metastasis
Authors: Larzabal Leyre 
Published: August 2012

Abstract
Cancer stem cells (CSCs) are thought to be responsible for tumor initiation and recurrence after chemotherapy. Targeting CSCs and non-CSCs with specific compounds may be an effective approach to reduce lung cancer growth and metastasis. Salinomycin was recently identified as a selective inhibitor of CSCs. The aim of this study was to investigate the effect of salinomycin with or without combination with paclitaxel in the Lewis lung carcinoma (LLC) metastatic model. Salinomycin reduced the proportion of ALDH+ CSCs in LLC cells, whereas paclitaxel increased such population. The same effect was observed for the human H460, H1299 and H272 lung cancer cell lines. Salinomycin reduced the tumorsphere formation capacity of LLC by more than 7-fold, but paclitaxel showed no effect. For in vivo experiments, LLC cells were injected subcutaneously and, after surgical removal of the primary tumors, animals were checked for lung metastasis. Paclitaxel reduced primary tumor volume but increased the number of metastatic nodules (p&lt;0.05), whereas salinomycin had no effect on primary tumors but reduced metastasis (p&lt;0.05). Combination of both drugs did not improve the effect of single therapies. mRNA levels of ALDH, CXCR4 and SDF-1 were higher in metastatic lesions than in primary tumors, and were significantly elevated in both locations by paclitaxel treatment. On the contrary, such levels were reduced (or in some cases did not change) when mice were administered with salinomycin. The number of F4/80+ (macrophages) was also decreased upon administration of paclitaxel or salinomycin in both primary tumors and metastasis. The number of mast cells was only reduced in primary and metastatic lesions of paclitaxel-treated mice. These results show that salinomycin targets ALDH+ lung CSCs, which has important therapeutic effects in vivo by reducing metastatic lesions. On the contrary, paclitaxel (although reducing primary tumor growth) promotes the selection of ALDH+ cells that likely modify the lung microenvironment to foster metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1392. doi:1538-7445.AM2012-1392
Abstract 1393: Chitinase-3-like-1 protein overexpression in lung epithelial cells enhances breast cancer metastasis to the lung
Authors: Libreros Stephania , Garcia-Areas Ramon , Onwuha-Ekpete Lilllian , Iragavarapu-Charyulu Vijaya 
Published: August 2012

Abstract
Breast cancer is the most common cancer in women in the US. Metastasis is responsible for a majority of these deaths in spite of significant improvements in diagnosis and treatments. Recently it was reported that under conditions of asthma, metastasis to the lung is increased. Patients with pulmonary inflammatory illnesses demonstrate higher levels of chitinase-3-like-1 protein (CHI3L1) in their lungs and in circulation. We have shown that there are elevated levels of CHI3L1 in circulation with increased tumor growth, higher levels of metastasis to the lung with shorter survival rates in mice with asthma. However, the direct role of CHI3L1 in promoting metastasis is not clearly delineated. It is also unknown if exposure to high levels of CHI3L1 previous to tumorigenesis directly predisposes to accelerated metastasis. We hypothesize that CHI3L1-induced pulmonary inflammation generates the proper environment for recruiting circulating breast cancer cells, thus increasing the rate of metastasis to the lung. To determine if inflammation associated with CHI3L1 in the lung alters the pulmonary environment to attract circulating breast tumor cells and accelerate metastatic growth, pulmonary inflammation is induced by either ragweed allergen sensitization or by locally expressing CHI3L1 in the lung using AAV-CC10-CHI3L1 vector. The role of CHI3L1 in pulmonary metastasis is delineated in CHI3L1 over-expressing lung epithelia by assessing the effects on the host immune system and the downstream effects. The studies proposed here will provide a greater understanding of the role of CHI3L1 in enhancing metastasis and the tissue-specific molecular signals that act to exacerbate metastasis under conditions of chronic inflammation
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1393. doi:1538-7445.AM2012-1393
Abstract 1400: Mouse models for detection of circulating tumor cells from breast cancer
Authors: Navaraj Arunasalam , Dicker David T. , El-Deiry Wafik S. 
Published: August 2012

Abstract
Breast cancer is the most frequent malignancy among women, causing at least 373,000 deaths per year worldwide, and in United States alone an estimated 208,000 women were diagnosed with breast cancer in 2010. Recent studies indicate that breast cancer is initiated by breast cancer stem cells (BCSCs) that express CD44+/high CD24-/low surface markers. Mammospheres are non-adherent spherical cell clusters grown in selective culture conditions. Our experimental results using mammosphere cultures of different breast cancer cells such as MDA-MB-231 show drastic enrichment of breast cancer stem-like cells with the phenotype of CD44+/high CD24-/low by flow cytometry analysis. We have implanted mammosphere-derived cells into mammary fat pads of nude mice and sampled blood from such tumor-bearing animals to look for the presence of unique breast cancer cells with metastatic potential {circulating tumor cells (CTCs)}, by scoring for Epcam+/cytokeratin+/CD45- tumor cells using the FDA-approved Veridex CellSearch Sysytem. As these metastatic breast cancer cells stably express ZS-Green protein, isolated ZS-Green positive CTCs are being further subjected to breast cancer-specific multiplexed molecular marker analysis. When a mouse with the metastatic breast cancer cell line - 4T1, stained with the CellVue dye is implanted in mammary fat pads, high levels of metastasis are detected with the CellVue marker in different internal organs such as the lungs, liver, heart and lymph nodes. Fluorescence microscopy analysis of blood withdrawn from animals bearing orthotopic 4T1 breast xenograft tumors, could detect ZS-Green positive mouse breast cancer CTCs. These mouse animal models bearing xenograft tumors are facilitating our understanding of CTC detection as well as analysis methods and also in understanding of human breast cancer metastasis. Open questions we are addressing include heterogeneity of CTCs, relationships in stem cell markers and prognostic markers when CTCs are compared with the primary tumors, relationships between tumor burden and tumor aggressiveness with CTC numbers in this mouse model. In addition the model provides an opportunity for testing candidate therapeutic agents and drug combinations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1400. doi:1538-7445.AM2012-1400
Abstract 1407: Sonic hedgehog signaling and Androgens are linked in tumor-stromal interaction through Epithelial-Mesenchymal transition (EMT) in prostate cancer progression
Authors: Shigemura Katsumi , Meligy Fatma , Behnsawy Hosny , Yamamichi Fukashi , Haung Wen-Chin , Li Xiangyan , Chung Leland , Yamanaka Kunito , Hanioka Keisuke , Yamashita Masuo , Shirakawa Toshiro , Tanaka Kazushi , Arakawa Soichi , Fujisawa Masato 
Published: August 2012

Abstract
Backgrounds: Sonic hedgehog (Shh) signaling is known to relate to cancer progression but the detail about how to correlate and link with another signaling is debating. The purpose of this study is to investigate the link between Shh signaling, androgens and epithelial-mesenchymal transition (EMT) in prostate tumor-stroma interaction during prostate cancer (PCa) progression. Materials and Methods: We investigated cell proliferation in LNCaP PCa cells, Normal Prostate Fibroblasts (NPF), and Cancer-associated Prostate Fibroblasts (CPF) in the presence of representative androgen, dihydrotestosterone (DHT) and/or Shh signaling inhibitor, cyclopamine (Cyc). With these stimulators or inhibitors, real time RT-PCR was performed to investigate downstream transcriptional factors of Shh signaling, Gli-1, EMT markers (E-cadherin, N-cadherin, and Vimentin), and Osteonectin (ON), a possible Shh target gene shown in our previous work. Expression levels of AR, Gli-1, Ki-67, Shh, and ON in specimens from PCa patients were measured by immunohistochemical (IHC) staining and correlated with clinical data. Results: While significant cell proliferation was induced by DHT in LNCaP, NPF, and CPF, Cyc inhibited these enhanced growths. CPF tended to react to DHT more but less to Cyc than LNCaP or NPF. RT-PCR results showed Shh induced EMT and DHT induced the expression of Gli-1, ON and EMT, and those inductions were blocked by Cyc. IHC staining showed that Stromal ON (ONstr) had significant correlation with serum PSA (p=0.031), high Gleason Scores had significant correlation with Ki-67, and PSA recurrence was related significantly to Gli-1 expression and lower expression of ONstr, suggesting PCa recurrence had a significant correlation with Shh-Gli-1 signaling. Conclusions: Shh signaling is involved in tumor-stromal interaction through a link with Androgens and EMT, and thus plays a pivotal role in PCa progression. Cyclopamine may therefore be a possible therapeutic agent for blocking PCa progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1407. doi:1538-7445.AM2012-1407
Abstract 1413: Rapamycin inhibits lymph node metastasis in an orthotopic model of head and neck squamous cell carcinoma: A possible role for a suppression of VEGFR-3 expression
Authors: Ekshyyan Oleksandr , Moore-Medlin Tara N. , Raley Matthew C. , Sonavane Kunal , Brodt Michael A. , Rong Xiaohua , Abreo Fleurette , Alexander Jonathan S. , Nathan Cherie-Ann O. 
Published: August 2012

Abstract
Background: Tumor cell dissemination to cervical lymph nodes via the lymphatic system represents the first step in the metastasis of head and neck squamous cell carcinoma (HNSCC) and is the most significant prognostic factor for tumor recurrence decreasing survival by 50%. The anti-lymphangiogenic properties of mTOR inhibitors are not yet well understood nor have the effects of rapalogues’ on tumor-associated lymphangiogenesis been investigated in HNSCC. Methods: The lymphatic suppressing effects of rapamycin were evaluated in vitro using lymphatic endothelial cell lines (SV-LEC; HMEC-1a). An orthotopic model of HNSCC was used to evaluate anti-lymphangiogenic effects of rapamycin in vivo. OSC-19 cells were injected into the basolateral tongue of SCID mice. After 5 days mice were given daily IP injections of vehicle (control group) or rapamycin at 5 mg/kg. On day 21 after OSC-19 administration mice were sacrificed and tongues, cervical lymph nodes and serum collected. The incidence of cervical lymph node metastasis, the number of tumor-free and tumor-associated lymphatic vessels in mouse lingual tissue, and expression of pro-lymphangiogenic markers were assessed. Results: We found that LEC proliferation was significantly reduced by rapamycin. LEC growth inhibition by rapamycin was linked with decreased expression of VEGFR-3 in both LECs, and in some HNSCC cell lines. Rapamycin significantly lowered the fraction of tumor-associated lymphatic vessels in mouse tongues (p=0.0167) and decreased the number of metastasis-positive lymph nodes (p=0.04). Rapamycin also significantly attenuated the extent of metastatic tumor cell spread within the lymph nodes (p&lt;0.0001). Conclusion: The results of this study demonstrate anti-lymphangiogenic properties of mTOR inhibitors in HNSCC. These findings provide preclinical data showing that rapalogues exert anti-lymphatic effects in head and neck cancer via suppressing ofVEGFR-3 expression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1413. doi:1538-7445.AM2012-1413
Abstract 1418: Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through down-regulation of NF-kappa-B activity
Authors: takuya kuramoto 
Published: August 2012

Abstract
Purpose: The Notch signaling regulates cell-fate decisions during development and postnatal life. Recent studies have demonstrated that the signaling through Notch and its ligand Dll4 in tumor endothelial cells plays an important role in cancer angiogenesis. Little is known, however, about the role of Dll4-Notch signaling between cancer cells, and how it affects on cancer metastasis. We therefore assessed the importance of cancer cell Dll4-Notch signaling in cancer metastasis produced by human small lung cancer cells. Experimental Design: On the basis of previous studies, we generated retroviral vectors encoding a soluble dimerized form of Dll4 fused to the human IgG1 Fc constant region (Dll4-Fc) that acts as a blocker of Dll4-Notch interactions. Dll4-Fc was introduced into human small cell lung cancer cell lines that express high level of Dll4 and Notch (SBC-3 and H1048 cells), and low level of Dll4 (SBC-5 cells). The cells were intravenously inoculated to natural killer cell-depleted SCID mice, and the multiple-organ metastases were evaluated. Result: The number of liver metastasis in the mice inoculated with SBC-3 and H1048 cells expressing Dll4-Fc were significantly lower than that of liver metastasis formed by control transfectant cells. However, the number of liver metastasis formed by SBC-5 cells was not significantly different between Dll4-Fc expressing and control cells, suggesting that Dll4-Notch signaling in cancer cells plays important role in liver metastasis of small cell lung cancer. Metastatic colonies in other organ such as lung, kidney and bone were not affected by Dll4-Fc overexpression in each cell lines. In order to study the molecular mechanism of the effect of Dll4-Fc on liver metastasis, genes associated with metastasis were screened by PCR array system. Seven genes (MMP7, IL1B, MMP1, S100A4, MMP10, CXCR4, SERPINE1) were down-regulated in Dll4-Fc-overexpressing SBC-3 and H1048, but not SBC-5 cells, compared with control transfectant cells. Since most of the selected genes were NF-kappa-B target genes, we explored whether NF-kappa-B is involved in cancer cell Dll4-Notch signaling. By using luciferase assay, we observed that NF-kappa-B activity was down-regulated in Dll4-Fc-overexpressing SBC-3 and H1048 cells, but not SBC-5 cells, compared with control transfectant cells, indicating that Dll4-Fc inhibits NF-kappa-B activity in small cell lung cancer cells by suppressing Dll4-Notch signaling. Conclusion: These results suggest that Dll4-Notch signaling in cancer cells plays a critical role in liver metastasis of small cell lung cancer, by regulating the NF-kappa-B signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1418. doi:1538-7445.AM2012-1418
Abstract 157: Optimizing the flow cytometric analysis of cell signaling in heterogeneous samples
Authors: Gao Guojian , Coveney Christopher , Wang Xiao , Wu Xiaowei , Wei Ai-Li , Ji Xiang-dong , Anderson Lori , Kotecha Nikesh , Rohrer Jurg , O'Donnell Erika 
Published: August 2012

Abstract
Unlike conventional biochemical methods for cell signaling analysis, analyzing protein levels by flow cytometry allows measurements to be made at the single-cell level. Multiparameter flow cytometry provides a powerful tool for the analysis of protein expression and phosphorylation status within complex populations, such as those found in lymphoid tissues or blood. However, different intracellular and cell surface proteins often require different conditions for optimal detection, creating challenges for analyzing multiple protein types in a single sample. To facilitate the design of multiparameter staining panels for analysis of intracellular and cell surface proteins, we tested over 250 fluorescently conjugated antibodies in cells fixed and permeabilized under various conditions. Multiple fluorescent conjugates of each antibody were tested in human PBMCs, human whole blood, mouse spleen, and/or mouse bone marrow following fixation with BD Phosflow™ Lyse/Fix or BD Cytofix™ Fixation Buffer and permeabilization with one of the four BD Phosflow™ Perm buffers. These studies demonstrated that certain intracellular epitopes required harsh permeabilization conditions for optimal detection, whereas others were detectable under milder conditions. Surface marker stains often required optimization, particularly under harsh permeabilization conditions. Factors such as antibody clone, fluorophore, and concentration had a considerable impact on staining resolution, and alternative staining protocols were required for optimal staining of some surface markers. To facilitate the optimization of fixation, permeabilization, and staining conditions for multiparameter flow cytometry, experimental data and protocols from this study are available through an interactive database freely accessible at www.cytobank.org/facselect.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 157. doi:1538-7445.AM2012-157
Abstract 1570: Frameshift peptides as prophylactic cancer vaccines antigens
Authors: Luhui Shen , Sykes Kathryn , Johnston Stephen Albert 
Published: August 2012

Abstract
Background: The goal of the project is to develop a universal, prophylactic cancer vaccine. We are integrating bioinformatics, genetics, proteomics and immunological methods to identify tumor DNA-encoded components for the development of an effective vaccine. In a previous study, we used bioinformatic and genetics analyses to identify a list of abberant transcripts associated with tumor cells that encode frameshift-derived (FS) neo-peptides. These FS peptides are a result of various gene mutations and abnormal splicings in tumor cells that would cause expression of gene sequences in alternate reading frames. The transcript encoding one of these vaccine component candidates, SMC1A (Structural Maintenance of Chromosomes 1A) FS was detected in numerous mouse and human tumor cell lines and primary human breast and pancreatic tumors. One dose genetic immunization with a plasmid expressing SMC1A FS significantly delayed tumor growth in C57BL/6 mice transplanted with the B16F10 melanoma cell line. To exam protection of SMC1A FS in a more realistic prophylactic model, we investigated the protection of SMC1A FS in two mouse spontaneous breast tumor models. Results: We similarly detected the transcript corresponding to the SMC1A FS peptide in tumors from spontaneous mouse breast tumor models: FVB/N-NeuT and BALB-NeuT. The SMC1A FS expression increases with the expression of Rat Her-2 in mouse mammary gland. Wild type and mutated Rat Her 2 are the oncogenes that induce spontaneously breast tumor development in FVB/N-NeuT and BALB-NeuT respectively. Both anti-SMC1A FS IgG and SMC1A FS peptide induced IFN-γ released splenocytes were detected in non-treated tumor bearing FVB/N-NeuT mice. One dose genetic immunization of mice with an SMC1A FS expression plasmid significantly reduced spontaneous breast tumor development in FVB/N-NeuT mouse as compared to that in non-treated mice. Genetic immunization followed by a protein boost (prime/boost regimen) in BALB-NeuT mice also significantly reduced tumor development and the reduction is associated with antibody reactivity to SMC1A FS. Discussion: The protection of SMC1A FS prophylactic immunization in spontaneous mouse tumor models indicates SMC1A S can be a potential prophylactic cancer vaccine candidate to prevent a variety of tumors types. We are applying the same basic approach to accumulate sufficient antigens to constitute a broadly protective, prophylactic cancer vaccine. (This research is supported by an Innovation Award from the DoD and The Keck Foundation to SAJ.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1570. doi:1538-7445.AM2012-1570
Abstract 1571: Developing antigen-specific Th1 epitope based vaccines by excluding immunosuppressive peptide sequences
Authors: Cecil Denise L. , Holt Gregory E. , Herendeen Dan , Gad Ekram , Rastetter Lauren , Park Kyong Hwa , Disis Mary L. 
Published: August 2012

Abstract
We have determined that IGFBP-2 is immunogenic in ovarian cancer. Our aim is to develop a multi-epitope vaccine that will elicit Th1 immunity to IGFBP-2. Antigen specific Th1 can modulate the tumor microenvironment to enhance cross priming, supporting the proliferation of cytotoxic T cells which are capable of eradicating ovarian cancer cells. Although some clinical benefit has been demonstrated with this strategy, recent ex vivo analyses of human PBMC have described the presence of antigen-specific CD4+ T regulatory cell (Tregs) in cancer patients that were not detected in healthy individuals. Thus, we questioned if we could optimize our vaccine to include only Th1-stimulating epitopes. Using a combined scoring system from five algorithms for predicting class II binding to determine Th epitopes, we identified 14 IGFBP-2 peptides. Th1 immunogenicity (IFN-gamma) and potential immunosuppression (IL-10) was evaluated by ELISPOT for 40 different donors. Twenty-two percent of the donors only responded with IL-10 secretion to any peptide, 22% only responded with IFN-gamma and 53% of the patients had a mixed IFN-gamma and IL-10 response. To determine which peptides would induce a predominantly Th1 response in the greatest number of people, we used a ratio of IFN-gamma to IL-10 and analyzed both the magnitude and frequency of ELISPOT responses for each of peptides using the following algorithm: (corrected mean SPW) x (percent of responding donors). The peptides were then ranked from highest IL-10 response to highest IFN-gamma response. Interestingly, 6 of the 14 peptides demonstrated a preference to secrete IFN-gamma over IL-10 and are only located in the N-terminus (amino acids 1-163) of IGFBP-2; the remaining potentially immunosuppressive peptides are located in the C-terminus (amino acids 164-328). Vaccination with p1-163 in MMTV-neu mice demonstrated a robust Th1 response (p=0.03) and concomitant inhibition of tumor growth by 70% compared to adjuvant only control animals, p164-328-vaccinated or full length protein-vaccinated mice (p&lt;0.001 for all). Vaccination with p164-328 or full length protein did not inhibit tumor growth. These data suggest that more effective vaccines can be designed when both Th1 epitopes and immunosuppressive epitopes are screened simultaneously and epitopes that are most likely to induce robust Th1 responses in the majority of individuals can be identified and included as vaccine components.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1571. doi:1538-7445.AM2012-1571