bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4373: Color-coded real-time imaging of the interaction of mesenchymal stem cells and cancer cells
Authors: Ke James , Suetsugu Atsushi , Lee Oscar K. , Hoffman Robert M. 
Published: June 2012

Abstract
Mesenchymal stem cells (MSC) have been reported to promote tumor growth and metastasis. Through paracrine effects, cytokines such as TGFβ or CCL5 produced by MSC play a role in modulating cancer cell behavior. However, the interaction between MSCs and cancer cells is not only via cytokines but involves physical contact as well. In this study, using GFP mesenchymal stem cells and RFP murine mammary cancer cells, the interaction between these cells types was imaged in vivo and vitro. Murine MSCs were isolated from GFP transgenic mice and 4T1 murine mammary cancer cells expressed RFP. Cells were co-cultured in vitro or co-implanted into the mouse mammary fat pad. Cell movement and distribution were recorded with fluorescence video microscopy. 4T1 cells had an epithelial shape and moved toward each other to form clusters when cultured alone. In contrast, 4T1 cells showed a stretched, spindle like morphology when interacting with MSCs. In vivo imaging with the Olympus OV-100 or IV-100, clearly visualized GFP-MSC and RFP-4T1 cells within tumors. When co-injected with MSCs, as few as 5 4T1-RFP cells could form a tumor but could not form tumors at the low cell number without MSCs. The results demonstrate that MSCs have a powerful effect on breast cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4373. doi:10.1158/1538-7445.AM2011-4373
Abstract 4374: Identification and characterization of active components of antrodia camphorata mycelia on targeting cancer initiating cell
Authors: Chang Ching-Wen , Lo Jeng-Fan 
Published: June 2012

Abstract
Background: Cancer initiating cells (CICs) represent a rare subpopulation of cancer cells, which are responsible for tumor growth. Cancer initiating cells such as oral cancer-cancer initiating cells (OC-CICs), are often resistant to either radiotherapy or chemotherapy. Therefore, screening and development for drug candidates that target OC-CICs specifically will benefit for future oral cancer therapy.
Methods: First, we used the in vitro cell-based ALDH activity assay system, which has been demonstrated as a CICs marker, to screen for the active components from purified compounds of Antrodia Camphorata Mycelia extract (ACME), which can target OC-CICs. The growth inhibition and cell differentiation ability of OC-CICs treated with purified compounds from ACME were evaluated. In addition, the self-renewal ability and stemness properties of ACMEs treated OC-CICs were examined. Furthermore, xenotransplantation assay was applied to test the tumorigenicity of OC-CICs treated with isolated ACMEs. Finally, we investigated the molecular mechanisms mediated by ACME treatment on OC-CICs.
Results: Herein, we first found out that an ACME's purified components, CH-190-WS-D, significantly downregulated the ALDH activity of oral cancer cells. Treatment of CH-190-WS-D significantly induced cell death and enhanced the differentiation capability of OC-CICs but not the major population of oral cancer cells. Moreover, we found that treatment of CH-190-WS-D reduced the self-renewal ability and stemness properties of OC-CICs. The in vitro tumorigenic properties, including cell migration and anchorage independent growth of OC-CICs, were lessened by CH-190-WS-D treatment. Furthermore, treatment of CH-190-WS-D suppressed tumor growth of nude mice bearing xenografts. Finally, treatment of CH-190-WS-D results in down-regulation of PI3K/AKT/mTOR molecular mechanisms which play important roles in CICs.
Conclusion: Our studies reveal the ACME's purified components can reduce stemness properties and tumorigenicity of OC-CICs. Eventually, we can discover drug candidates from ACME's purified components for alternative oral cancer therapy.
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 4374. doi:10.1158/1538-7445.AM2011-4374
Abstract 4376: Acquired cancer stem cell like features through Oct4 mediated dedifferentiation
Authors: Kumar Suresh M.K , Liu Shujing , Lu Hezhe , Yang Ruifeng , Pushparajan Anitha , Wei Guo , Xu Xiaowei 
Published: June 2012

Abstract
There is enormous interest to target cancer stem cells (CSCs) for clinical treatment. CSCs are highly tumorigenic and resistant to chemotherapy. Nevertheless, there is still controversial surrounding CSCs and the origin of CSCs remains elusive. In this study, we showed that expression of Oct4 gene or transmembrane delivery of Oct4 protein promoted dedifferentiation of melanoma cells to CSC-like cells. The dedifferentiated melanoma cells displayed dramatic morphological changes and acquired the ability to form tumor spheroids. They showed markedly increased resistance to chemotherapeutic agents and hypoxic injury. In the subcutaneous xenograft or tail vein injection assays, these cells had significantly increased tumorigenic capacity. The dedifferentiated melanoma cells showed significantly decreased expression of melanocytic markers and acquired many features associated with CSCs such as multipotent differentiation capacity and expression of melanoma CSC markers such as ABCB5 and CD271. Oct4 induced dedifferentiation was associated with endogenous Oct4 promoter activity, expression of Nanog and Klf4, and global gene expression changes that enriched for transcription factors. Furthermore, ShRNA mediated knockdown of Oct4 in dedifferentiated cells led to diminished CSC phenotypes. Oct4 expression was detectable in a subpopulation of tumor cells in clinical melanoma tissues. Our results indicate that CSC phenotype is dynamic and may be acquired through dedifferentiation and Oct4 is a positive regulator of tumor dedifferentiation. These data suggest Oct4 mediated differentiation may play an important role during tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4376. doi:10.1158/1538-7445.AM2011-4376
Abstract 4377: Proper migration of mammalian prostate stem cells to the area of the prostate gland in zebrafish
Authors: Jagadeeswaran Pudur , Radhakrishnan Uvaraj P. , Kim Seongcheol , Rajpurohit Surendra Kumar , Xie Daxing , Hsieh Jer-Tsong 
Published: June 2012

Abstract
Androgen independent prostate cancer contributes to the maximum mortality in prostate cancer patients. One school of thought is that these cancer cells arise in metastatic sites where the cancer cells take on stem cell behavior similar to the stem cell behavior observed in normal prostate gland. Thus, understanding prostate gland stem cells and their migration pattern may provide clues to their biology which may have applications in their migration during metastasis. To understand the migration of mammalian prostate stem cells we used zebrafish as a model. We have previously established zebrafish as a model to study prostate cancer because we found the presence of prostate-like- cells around the zebrafish testes. In this abstract we further characterized location of normal prostate-like cells. We found that they are present in the anterior and posterior aspects of testes. Furthermore, we cloned 2 kb prostate specific antigen promoter into pDsRed 2.1 plasmid and injected this plasmid DNA into single cell-stage zebrafish embryo with I-Sce1 to enhance transgenesis frequency and germline transmission. Larvae injected with PSA promoter-DSRed 2 constructs were screened three days post fertilization (dpf) for the expression of red fluorescence, which was observed in bilaterally arranged spots in gonads. We then used 5 dpf zebrafish larvae and IV-injected cells from four different cell lines expressing either GFP or RFP: two with stem cell phenotype RWPE-1-shDAB2IP (GFP), PZ-HPV7-shDAB2IP (GFP), and two as controls RWPE-1-shCon (GFP) and PC-3 (RFP). After two days, microscopy for green or red fluorescence signal revealed RWPE-1-shDAB2IP and PZ-HPV7-shDAB2IP cells bilaterally migrated to the yolk, i.e. the similar area where PSA promoter expression was found. This specific migration was not observed with RWPE-1-shCon and PC-3 cells lines. These same fluorescence reporter experiments were performed in parallel in 48 hr and 72 hr post fertilization (hpf) dechorinated larvae. We observed similar results in the 72 hpf larvae as were found in 5 dpf larvae but not in the 48 hpf larvae. Taken together, these results suggest that RWPE-1-shDAB2IP and PZ-HPV7-shDAB2IP cells have the homing receptors necessary for migrating to the same area in gonads. Understanding these homing mechanisms may be relevant for controlling the abnormal migration in 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 4377. doi:10.1158/1538-7445.AM2011-4377
Abstract 438: The CFP nude mouse as a host for color-coded imaging of the tumor microenvironment
Authors: Suetsugu Atsushi , Hassanein Mohamed K. , Reynoso Jose , Saji Shigetoyo , Moriwaki Hisataka , Bouvet Michael , Hoffman Robert M. 
Published: June 2012

Abstract
We have developed a color-coded model to study the tumor microenvironment using cancer cells expressing RFP or GFP implanted in nude mice expressing cyan fluorescent protein (CFP). When RFP or GFP HCT-116 were injected subcutaneously in CFP expressing nude mice, CFP expressing cancer-associated fibroblasts migrated to the tumor site. CFP-expressing tumor blood vessels were observed in the tumor. Other CFP host stromal cells were observed throughout the tumor mass. When RFP HCT-116 cells were transplanted in the spleen of CFP nude mice, they formed tumors in the liver. When RFP HCT-116 cancer cells were transplanted in the tail vein of CFP nude mice and they formed tumors in the lung. CFP-expressing host cells were observed in these tumors. When the RFP mouse mammary cancer cell line (RFP MMT) was injected subcutaneously in the CFP nude mouse, numerous CFP-expressing fibroblasts and CFP-expressing blood vessels was observed in the resulting tumor. A large inflammatory population of different CFP-expressing white blood cells surrounded the necrotic area of the tumor suggesting a relationship of these cells to tumor necrosis. GFP and RFP HCT-116 cancer cells were co-injected subcutaneously in CFP-nude mice and tumor growth was followed for 21 days. This three-color model enabled visualization of the tumor mass and its neovasculature in addition to a detailed visualization of other host reactions. GFP HCT-116 cancer cells were initially injected subcutaneously in RFP-nude mice and tumors formed within 14 days. At this point, the tumor mass which consisted of GFP cancer cells and RFP stroma derived from the RFP nude mouse, was harvested and transplanted to a CFP-nude mouse. CFP host cells invaded the growing transplanted tumor containing dual-color cancer cells and RFP stroma. Thus the CFP-nude mouse adds another color to the pallet to study the human tumor microenvironment allowing 4 types of cells to be simultaneously imaged in tumors.
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 438. doi:10.1158/1538-7445.AM2011-438
Abstract 4388: LipoplatinTM: A less neurotoxic formulation of Cisplatin
Authors: Canta Annalisa , Chiorazzi Alessia , Carozzi Valentina A. , Oggioni Norberto , Sala Barbara , Zucchetti Massimo , Cavaletti Guido A. 
Published: June 2012

Abstract
Purpose: Cisplatin is one of the most effective cytotoxic agent in the treatment of solid malignancies, but its use is limited by several side effects. Among them, peripheral neurotoxicity can be dose-limiting. A liposomal formulation of cisplatin, LipoplatinTM, was developed to reduce the systemic toxicity of cisplatin but preventing its efficacy. Aim of this study was to test in an animal model through a multimodal approach if chronic treatment with two different schedules of LipoplatinTM selected in the range of its anticancer effective dose is less neurotoxic than cisplatin administrations.
Methods: Female Wistar rats were treated intraperitoneally with cisplatin at the dose of 4mg/kg or with LipoplatinTM 12 and 24mg/kg once weekly for 4 times. General toxicity was assessed by daily observation, body weight change, hematological and blood chemistry analysis and histopathology of liver and kidney. The onset of the peripheral neurotoxicity was assessed using tail nerve conduction velocity (NCV), morphological and morphometrical analysis of dorsal root ganglia (DRG) and by morphological analysis of sciatic nerve.
Results: Cisplatin induced a statistically significant reduction in body weight, the development of renal failure and the impairment in NCV with pathological alterations in the DRG and sciatic nerve. By contrast no significant weight gain reduction was observed in animals treated with both doses of LipoplatinTM. Moreover the lowest dose induced a less severe damage to the peripheral nervous system with a moderate decrease of NCV and mild pathological alterations of DRG and sciatic nerve.
Conclusions: The results suggest that LipoplatinTM 12mg/kg is less neurotoxic than cisplatin 4mg/kg, thus opening the possibility to use this new formulation in future studies where its anticancer activity and the peripheral neurotoxicity will be assessed in parallel.
This study was supported by “Fondazione Banca del Monte di Lombardia”
Regulon supported this study exclusively by providing LipoplatinTM
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 4388. doi:10.1158/1538-7445.AM2011-4388
Abstract 4396: Evaluation of gene expression and transcriptional activation in patients treated with vorinostat
Authors: Kolesar Jill M. , Lau Elim , Seo Songwon , Eickhoff Jens , Kim KyungMan , Traynor Anne , Bailey Howard , Wilding George , Schelman William 
Published: June 2012

Abstract
Background: Vorinostat is a histone deacetylase (HDAC) inhibitor that is approved for treatment of cutaneous T-cell lymphoma and is being investigated in a number of solid tumors. Inhibition of HDAC by vorinostat leads to an accumulation of acetylated histones which induces apoptosis though a mechanism that is not completely characterized. This study was performed to assess the potential mechanisms responsible for induction of apoptosis following treatment with vorinostat. Methods: Sixty subjects with advanced malignancies received vorinostat orally days 1-14 combined with bortezomib IV on days 2, 4, 8, and 11 of a 21-day cycle. Peripheral blood mononuclear cells (PBMCs) were collected before and 2hr and 6hr after dosing on Days (D) 1 and 9. Paired tumor biopsies were obtained in ten patients on D0 and D9. Gene expression of downstream targets was evaluated by semi-quantitative RT-PCR in PBMCs, and the interaction between candidates genes and acetylated histone H3 were evaluated in biopsies by the chromatin precipitation assay. A nonparametric Wilcoxon signed rank test was used to examine changes from the pre-treatment value of 1 on D1 based on complete case analysis without multiplicity adjustment. Results: p21, Nur77 and HSP70 gene expression in PBMCs were all significantly induced two hours after vorinostat administration compared to baseline (Table 1). AKT, ERB1 and ERB2 expression were not statistically significantly altered in PBMCs. The expression of all targets increased in tumor biopsies by Day 9, with p21 2.37, Nur77, 1.33 and HSP70 2.35 times baseline expression levels. The chromatin precipitation assay demonstrated that Nur77, HSP70 and p21 interacted with acetylated histone H3, after nine days of treatment with vorinostat, in tissue biopsies. Conclusion: This data suggests that acetylated histones interact transcriptionally with p21, Nur77 and HSP77 to induce gene expression and are a potential mechanism by which vorinostat induces apoptosis.

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 4396. doi:10.1158/1538-7445.AM2011-4396
Abstract 4398: MEK inhibitors prevent rebound reactivation of ERK signaling by the RAF inhibitor PLX4032 and enhance its antitumor activity
Authors: Pratilas Christine A. , Joseph Eric W. , Tadi Madhavi , Gabay Maytal , Wong Wai , De Stanchina Elisa , Bollag Gideon , Rosen Neal 
Published: June 2012

Abstract
Activation of ERK signaling occurs in the majority of melanomas and tumors with BRAF mutation are especially sensitive to its inhibition with MEK or RAF inhibitors. The latter inhibit ERK signaling only in tumors with V600E mutant BRAF and activate the pathway in cells with WT BRAF. These data implied that RAF inhibitors would have a wider therapeutic index than MEK inhibitors with a greater therapeutic effect, but could also cause toxicity by activating the ERK pathway in normal tissue. These predictions were born out in clinical trials, in which the RAF inhibitor PLX4032 caused tumor regression in most patients with metastatic melanoma with mutant BRAF, but also caused squamous cell carcinoma of the skin in one third of patients. Unfortunately, these responses are rarely complete and the median time to relapse is approximately nine months.
We now find that prolonged treatment of BRAF mutant cells with PLX4032 is associated with a rebound of ERK phosphorylation from its nadir that is associated with an increase in the transcriptional output of the pathway and could therefore limit the therapeutic effects of the drug. In this new steady state, ERK phosphorylation and output are sensitive to MEK inhibitors but not readdition of RAF inhibitors. The rebound of ERK signaling is associated with upstream activation in the RAS pathway. We therefore determined the effects of combined RAF and MEK kinase inhibition in a panel of melanoma cells with mutant BRAF. Combined inhibition delayed pathway rebound and resulted in more prolonged suppression of ERK output, enhanced cell death, and tumor growth inhibition compared to treatment with the RAF inhibitor alone. These results suggest that combined RAF and MEK kinase inhibition may be a useful strategy to improve the extent and duration of responses to RAF inhibitors and minimize toxicity caused by ERK activation in normal tissue.
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 4398. doi:10.1158/1538-7445.AM2011-4398
Abstract 4399: In vitro and in vivo evaluations of correlation between the activation status of signaling pathways and the efficacy of anticancer compounds in a panel of JFCR39 human cancer cell lines
Authors: Dan Shingo , Okamura Mutsumi , Seki Mariko , Yamazaki Kanami , Mukai Yumiko , Yamori Takao 
Published: June 2012

Abstract
The phosphoinositide 3-kinase (PI3K) pathway and the Ras/mitogen-activated protein kinase (MAPK) pathway are frequently activated in cancer. Activation of these pathways contribute to cell survival, cell cycle progression and cell growth in the tumor, and are expected to influence the efficacy of antitumor compounds including conventional antitumor drugs, PI3K pathway inhibitors and Ras/MAPK pathway inhibitors. However, it is not well understood whether the efficacies of anticancer compounds can be predicted based on these aberrations and on the activation status of signaling pathway members. To clarify this issue, we first examined the mutation, expression and phosphorylation status of PI3K and Ras/MAPK pathway members in a panel of 39 pharmacologically well-characterized human cancer cell lines (JFCR39). Second, we evaluated the in vitro efficacy of various anticancer compounds including PI3K and Ras/MAPK pathway inhibitors and conventional anticancer drugs, combining these data to construct an integrated database of pathway activation status and drug efficacies (JFCR39-DB). In silico analysis of JFCR39-DB enabled us to evaluate correlations between the status of pathway members and the drug efficacies in vitro. For example, KRAS/BRAF mutation prominently correlated with the efficacy of a MEK inhibitor and the inefficacy of PI3K inhibitors, respectively, while phosphorylation levels of Akt correlated with the efficacy of PI3K inhibitors. Some of these correlations were confirmed in human tumor xenografts in vivo, consistent with their ability to serve as predictive biomarkers. Our findings show that JFCR39-DB is a useful tool to identify predictive biomarkers and to study molecular pharmacology of the PI3K and Ras/MAPK pathways in cancer therapy.
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 4399. doi:10.1158/1538-7445.AM2011-4399
Abstract 4400: Blockade of Her2 binding to Hsp90 by emodin azide methyl anthraquinone derivative induces proteasomal degradation of Her2
Authors: Fu Liwu , Zheng Lisheng , Yan Yan-yan 
Published: June 2012

Abstract
Overexpression of HER2/neu, a transmembrane tyrosine kinase acting as a coreceptor for other EGFR family members, is well known to be associated with a poor prognosis in cancer. In the present study, we observed that emodin AMAD, a novel emodin azide methyl anthraquinone derivative, extracted from the nature giant knotweed rhizome of traditional Chinese herbs, potently decreased Her2/neu protein in dose- and time-dependent manners and also inhibited the downstream MAPK and PI3K-Akt signaling pathway. Intriguingly, reserve transcription-PCR and protein turn-over assay revealed that the decrease of Her2/neu was independent of mRNA level but primarily owing to its protein stability. Meanwhile, proteasome inhibitor MG132 but not lysosome inhibitor chloroquine could restore Her2/neu and polyubiquitination of Her2/neu was augmented during emodin AMAD treatment. Furthermore, immunofluorescence study with anti-Her2/neu antibody showed that emodin AMAD disturbed the subcellular distribution of Her2/neu, with decreased location in the plasma membrane. Importantly, coimmunoprecipitation with anti-Hsp90 antibody revealed that emodin AMAD markedly impaired the binding between Hsp90 and Her2/neu. In addition, combination of emodin AMAD treatment and SiRNA against Her2 synergistically inhibited proliferation and induced apoptosis. Taken together, these data suggest that blockade of Her2/neu binding to Hsp90 and following proteasomal degradation of Her2/neu was involved in emodin AMAD-induced apoptosis in Her2/neu-overexpressing cancer cells. Our results provide suggestions that emodin AMAD could be promising as a new targeting therapeutic strategy in the treatment of Her2/neu-overexpressing cancers.
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 4400. doi:10.1158/1538-7445.AM2011-4400