bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4352: Using human neural stem cells to model pediatric high grade gliomas: The role of p53, c-myc, and EGFRvIII in neoplastic transformation
Authors: Raabe Eric H. , Maciaczyk Jarek , Kahlert Ulf , Nikkhah Guido , Eberhart Charles 
Published: February 2011

Abstract
Brain tumors are a heterogeneous group of cancers that can arise at multiple locations in the central nervous system. Some brain tumors are restricted to specific anatomical sites, such as medulloblastoma, which is found only in the cerebellum. In the context of this heterogeneity, there are common molecular pathways which are altered across different types of brain tumors. Some of these molecular lesions include inactivation of tumor suppressors such as p53, overexpression of pro-proliferative factors such as c-myc, and alteration of cytokine pathways involving PDGF and EGF. We have isolated neural stem and progenitor cells from multiple sites in the developing human brain, including spinal cord, brain stem, cerebellum, thalamus, and cerebral cortex. These cells can be grown as neurospheres in long term culture, and can differentiate into neurons, astrocytes and oligodendrocytes. To test the hypothesis that these human neurosphere cells can give rise to brain tumors, we infected them with lentivirus encoding hTERT as well as dominant-negative p53, c-myc, and EGFRvIII. The resultant clones derived from cortex, brain stem and spinal cord grow at an increased rate compared to control GFP-infected cells. Interestingly, thalamus-derived cells in the initial analysis do not proliferate rapidly in response to dominant negative p53 and c-myc overexpression, highlighting the potential differences in neural stem and progenitor cell response to oncogenic stimuli. Dominant negative p53 and c-myc overexpressing cells maintain an ability to differentiate in vitro, similar to that observed in human glioblastoma neurosphere lines. Experiments to test the in vitro clonogenic potential and in vivo engraftment of control and infected cells are pending. Our studies suggest that, in contrast to some previous reports, human neural precursor cells can be transformed. They also form the basis for future experiments aimed at creating genetically and pathologically relevant models for pediatric brain tumors.
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 4352.
Abstract 4353: Identification of proteins regulated by mTOR in brain tumors of patients with tuberous sclerosis complex
Authors: Tyburczy Magdalena E. , Kotulska Katarzyna , Pokarowski Piotr , Mieczkowski Jakub , Grajkowska Wieslawa , Jozwiak Sergiusz , Kaminska Bozena 
Published: February 2011

Abstract
Tuberous sclerosis complex (TSC) is characterized by the formation of benign tumors in many organs (mainly brain, heart, kidneys, skin or lungs) and is often associated with epilepsy, mental retardation and autism. Brain lesions include subependymal giant cell astrocytomas (SEGAs), low-grade tumors of a mixed glioneuronal lineage, which are the major cause of morbidity in children and young adults with TSC. The disease is caused by mutations in tumor suppressor genes: TSC1 (Hamartin) or TSC2 (Tuberin) leading to enhancement of mammalian Target Of Rapamycin (mTOR) kinase activity, deregulation of cell growth and tumorigenesis. Signaling via mTOR participates in complex genomic responses but its effectors in the brain are largely unknown. Therefore, we performed first genome-wide expression profiling on SEGAs using Affymetrix Human Genome arrays. We identified differentially expressed specific genes involved in tumorigenesis (up-regulated) and the nervous system development (down-regulated) in SEGAs and SEGA-derived cell cultures when compared to the normal brain or cultured human astrocytes. Out of genes differentially expressed in TSC, 11 were validated by real time PCR on independent tumor samples and 3 SEGA-derived cultures. Immunohistochemistry on paraffin-embedded sections confirmed up-regulated levels of several identified proteins in SEGAs. ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4 and NPTX1 were shown to be mTOR effector genes in SEGA, as their expression was modulated by an mTOR inhibitor - rapamycin in SEGA-derived cell cultures. We are currently investigating the role of ANXA1, GPNMB and S100A11 in regulation of cell viability, migration, adhesion, size and shape of cultured SEGA cells using RNA interference. Furthermore, we observed that combined pharmacological inhibition of mTOR and extracellular signal regulated kinase (ERK) signaling pathways in SEGA cells affected their viability (MTT metabolism test), proliferation (BrdU assay), migration (scratch assay), morphology and size (volume, area and height measured with confocal microscopy). For the first time, we identified genes related to the occurrence of SEGA and regulated by mTOR, and showed an effective modulation of SEGA growth by inhibition of both mTOR and ERK signaling pathways, which could represent a novel therapeutic approach. The study was supported by Ministry of Science and Higher Education grant N N301 263536.
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 4353.
Abstract 4367: Cigarette smoke condensate-induced oxidative DNA damage and its removal in cervical cancer cell lines
Authors: Moktar Afsoon , Vadhanam Manicka V. , Singh Rajesh , Gairola C. Gary , Lillard James W. , Gupta Ramesh C. 
Published: February 2011

Abstract
Increased oxidative stress is implicated in the etiology of cancer. Exposure to cigarette smoke is well documented to increase oxidative stress in smoker tissues and probably plays a role in the incidence of cervical cancer. The cervical pre-cancerous lesions, initiated by HPV infection, generally regress in the absence of the known risk factors such as smoking. The oxidation of deoxyguanosine results in a highly mutagenic and extensively studied oxidative DNA lesion, 8-oxodeoxyguanosine (8-oxodG). The present study was performed to determine i) the effect of cigarette smoke condensate (CSC) on 8-oxodG formation in HPV-transfected cervical cell lines (ECT1/E6 E7); ii) the removal of the oxidative damage from HPV-positive (CaSki), HPV-negative (C33A) and ECT1/E6 E7 cells; and iii) the cell-cycle progression and apoptosis in the CSC-treated ECT1/E6 E7. We found that CSC induced 8-oxodG lesion in a dose- and time-dependent manner in the transfected cervical cell line. A 2.4-fold higher damage was observed in the HPV-positive tumor cell line compared to the HPV-negative cell line. Flow-cytometric and ImageStream (Amnis) analysis indicated that CaSki cells most efficiently removed the oxidative lesion in 48 h (93%). On the contrary, C33A cells did not reveal any significant removal of 8-oxodG up to 48 h. This difference could be explained by the presence of residual p53 activity in CaSki cells while the p53 is mutated in the C33A cell line. ECT1/E6 E7 cell line showed only a modest (22%) removal after 48 h. Interestingly, 8-oxodG was almost completely removed 72 h post-exposure in all the cervical cell lines. Furthermore, a dose-dependent increase in apoptosis was observed in ECT1/E6 E7 cells with an arrest at G0/G1 phase of cell cycle. We conclude that cigarette smoke induces oxidative stress with higher burden in HPV-positive cells; however, HPV exposure may not play a role in the kinetics of 8-oxodG removal (Supported from Agnes Brown Duggan Endowment and, in part, USPHS grant ES-011564).
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 4367.
Abstract 4368: Vitamin E and the green tea active agent EGCG suppress radiation-induced carcinogenesis by different molecular mechanisms
Authors: Mendonca Marc S. , Borgman Anthony , Chin-Sinex Helen , Dhaemers Ryan 
Published: February 2011

Abstract
Treatment induced secondary malignancies after successful radiation and/or chemotherapy cure of primary tumors is a growing area of concern. The identification of chemopreventive compounds that reduce radiation-induced secondary malignancy but are both nontoxic and tolerated with long-term use is a critical need. We investigated the chemopreventive potential and mechanism of action of Vitamin E and EGCG (the active agent in green tea) with the human CGL1 radiation neoplastic transformation assay. The molecularly characterized CGL1 assay allows both alterations of the quantitative neoplastic transformation as well the potential underlying molecular processes of the chemoprevention to be determined. We found long-term treatment with 15 microM EGCG or 50 microM Vitamin E beginning 72 hours after 7 Gy irradiation, significantly reduce radiation-induced neoplastic transformation frequency by a factor of 2.3. We determined that Vit E suppressed radiation-induced carcinogenesis by the induction of a p53 and pro-apoptotic Bax dependent apoptosis in the progeny of the irradiated cells. In addition, we demonstrated that EGCG does not reduce radiation-induced carcinogenesis by increased apoptosis, but rather by the onset of p16 dependent senescence in the irradiated CGL1 progeny. Vit E and EGCG are excellent candidate nontoxic chemopreventive agents for radiation-induced carcinogenesis that work by two distinct molecular mechanisms. We propose that this information should also aid in the development of next generation chemopreventive compounds. These studies were supported by a grant from the DOD awarded to MSM.
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 4368.
Abstract 4371: PI3K/Akt/JNK/c-Jun signaling pathway is a mediator for arsenite-induced cyclin D1 expression and cell growth in human bronchial epithelial cells
Authors: Cai Tongjian , Zuo Zhenghong , Ding Jin , Zhang Dongyun , Li Jingxia , Huang Chuanshu 
Published: February 2011

Abstract
Arsenite exposure is associated with an increased risk of lung cancers. Although efforts have been made, the precise mechanisms of the arsenite-induced lung carcinogenesis remain enigmatic. Aberrant cyclin D1 expression is an early event in carcinogenesis often accompanies human malignancies in the lung. Our previous study has shown that arsenite was able to induce cyclin D1 expression in human keratinocyte HaCat and mouse epidermal Cl41 cells to promote cell cycle transition, cell proliferation and transformation, which accounts for its ability to induce skin carcinogenesis. However, the role of Cyclin D1 underlying the arsenite-induced human lung carcinogenesis remain elusive. In the present study, arsenite exposure induced the cell cycle transition, resulting in growth promotion of human bronchial epithelial cells. The promoter activity and the expression of cyclin D1 were augmented in response to arsenite treatment. To further evaluate the effect of cyclin D1 in arsenite-induced cell proliferation, a cyclin D1 siRNA construct was stably introduced into Beas-2B cells. The siRNA blocked the induction/expression of cyclin D1. It has been reported that JNKs mediate the cyclin D1 expression in hematopoietic cells. Therefore, we investigated the potential contribution of JNKs to cyclin D1 expression induced by arsenite. Our results strongly suggest that JNK1 is a major kinase responsible for maintaining the basal level of C-Jun phosphorylation, and both JNK1 and JNK2 are critical for arsenite-induced C-Jun phosphorylation. Moreover, using a loss of function mutant Dp85 or DN-Akt, we demonstrated that the PI-3K/Akt pathway was involved in arsenite-induced upregulation of cyclin D1 and cell proliferation. The introduction of Dp85 or DN-Akt into the cells also inhibited JNKs activation as well as c-Jun phosphorylation, while the growth promotion induced by arsenite was significantly inhibited by the PI3K inhibitor Ly294002 and JNK inhibitor, or by over expression of DN-Akt. Overall, our data suggest a signaling pathway of PI-3K/Akt/JNK/c-Jun/cylin D1 signaling in response to arsenite in human bronchial epithelial cells, which leading to the growth promotion.
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 4371.
Abstract 4376: Biological, biochemical, and molecular targets for dietary catechin-induced suppression of breast cell chronic carcinogenesis
Authors: Rathore Kusum , Song Xiaoyu , Siriwardhana Nalin , Wang Hwa-Chain R. 
Published: February 2011

Abstract
This study is to identify biological, biochemical, and molecular targets for dietary catechins in early prevention of breast cell carcinogenesis induced chronically by environmental carcinogens. Breast cell carcinogenesis is a multiyear, multistep, and multipath disease process and is the most common type of cancer among women in northern America and northern Europe. Epidemiologic and experimental evidence suggests that dietary constituents in fruits and vegetables prevent human cancers; dietary prevention is a cost-efficient strategy to reduce the risk of this disease. However, the mechanisms for dietary prevention of cellular carcinogenesis induced by chronic exposure to environmental carcinogens remain to be elucidated. To identify dietary components for prevention of chronic human breast cell carcinogenesis, we studied biological, biochemical, and molecular target endpoints that were induced by low doses of carcinogens and suppressed by dietary catechins. Immortalized, non-cancerous human breast epithelial MCF10A cells were repeatedly exposed to carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or benzo[α]pyrene (B[α]P), each at picomolar concentrations, to induce cancer-associated biological, biochemical, and molecular properties in cells. We then used these changes as target endpoints to reveal the activity of various dietary catechins in suppression of NNK- and B[α]P-induced cellular carcinogenesis. We identified that cells acquiring the biological properties of reduced dependence on growth factors, anchorage-independent growth, and acinar-conformational disruption were reduced by treatment with dietary catechins. We identified that hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) played a novel role in NNK- and B[α]P-induced cellular carcinogenesis, and its expression acted as a molecular target endpoint in catechin-induced suppression of cellular carcinogenesis. The ability of catechins to reduce gene expression of cytochrome P450 enzymes CYP1A1 and CYP1B1, which can bioactivate NNK and B[α]P, may be involved in the preventive mechanism for catechins in suppression of cellular carcinogenesis. Our model system with biological, biochemical, and molecular target endpoints verified the value of dietary catechins for prevention of human breast cell carcinogenesis induced by repeated exposures to low doses of multiple environmental carcinogens.
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 4376.
Abstract 438: Hif-2α expression and radioresistance of cervical cancer
Authors: Kim Min Kyu , Kim Tae Joong , Choi Chel Hun , Lee Jeong Won , Lee Je Ho , Bae Duk Soo , Kim Byoung Gie 
Published: February 2011

Abstract
ABSTRACT
Objective: Hypoxia is now established as a key factor influencing the pathophysiology of malignant growth. Hypoxia-induced changes in gene expression are coordinated mainly by the hypoxia-inducible factor-1(HIF-1α) and HIF-2α. The aim of this study was to determine whether HIF-2α expression is associated with survival and response to radiation in cervical cancer.
Methods: After reviewing the medical records of 119 patients treated in our institution by primary radiotherapy for stage IIB-IVA cervical cancer, we performed a case-control study. Cases (n = 12) were selected from patients with local recurrence or radiation failure after primary radiation therapy with or without concurrent chemoradiation. For each case, we selected two controls from patients who showed no local recurrence. Using pretreatment paraffin-embedded tissues, we evaluated expression of HIF-2α by immunohistochemistry. Staining was scored based on intensity (Intensity Score (IS) 0- 3) and proportion (Proportion Score (PS) 0-100). Results were analyzed by Student t-test, Mann-Whitney U test, Fisher's exact test, and Cox proportional hazards regression model.
Results: HIF-2α expression representing degree of hypoxia has a relationship with poor response to radiotherapy.
Conclusion: HIF-2α expression may have an important role in radioresistance in locally advanced cervical cancer.
Key Words: Cervical neoplasm, Radiation, HIF-2α, Survival, Hypoxia
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 438.
Abstract 4380: Cadmium-induced toxicity in human liver carcinoma (HepG2) cells: Involvement of oxidative stress, phosphatidylserine externalization, and nucleosomal DNA fragmentation
Authors: Skipper Anthony C. , Yedjou Clement , Ndebele Kenneth , Tchounwou Paul B. 
Published: February 2011

Abstract
Human liver carcinoma (HepG2) cells were used as a test model to evaluate the in vitro cytotoxicity of cadmium and to determine whether oxidative stress plays a key role in cadmium induced apoptosis. To achieve this goal, we performed the MTT assay to measure cell viability and lipid peroxidation to determine the level of oxidative cell/tissue damage. The annexin V assay and DNA fragmentation analysis were performed for early and late apoptosis, respectively. The results of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a dose-dependent manner, showing a 24 h-LD50 of 3.6 µg/mL. We detected a significant increase in lipid peroxidation (malondialdehyde) concentrations in cadmium chloride-treated HepG2 cells compared to the control. Similarly, a strong dose-response relationship (p &lt; 0.05) was obtained in connection with cadmium chloride-induced apoptosis. Cadmium chloride-induced apoptosis was characterized by a significant increase in the percentage of annexin-V positive cells (apoptotic cells), as well by the occurrence of nucleosomal DNA fragmentation. In summary, this study indicated cadmium chloride is highly cytotoxic to HepG2 cells. This cytotoxic effect may be mediated at least in part through oxidative cell/tissue damage, phosphatidylserine externalization and occurrence of nucleosomal DNA fragmentation.
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 4380.
Abstract 4384: Differential expression and function of peroxiredoxin genes in normal vs. cancerous breast epithelial cell lines
Authors: Gongalves Kevin , Sullivan Katie , Phelan Shelley A. 
Published: February 2011

Abstract
Peroxiredoxins are thiol-specific antioxidants that reduce a wide variety of cellular peroxides and protect cells from oxidative stress-induced damage and death. These proteins have been implicated in numerous disease processes associated with increased oxidative stress, including cancer. We sought to compare peroxiredoxin expression between the normal MCF10A and cancerous MCF7 breast epithelial cell lines and examine the effect of Prdx1 and Prdx6 suppression in each line. Prdx1 and Prdx6 suppression was achieved through transient transfection of siRNA, and the relative expression of all six mammalian peroxiredoxin genes was determined by real time PCR and western blotting. We also examined the effect on peroxide-induced reactive oxygen species (ROS) accumulation and cytotoxicity. We demonstrated that MCF7 cells express significantly higher levels of Prdxs 1-5, while Prdx6 levels are comparable in the two lines. We achieved approximately 90% mRNA suppression of Prdx1 and Prdx6 in both lines using siRNA. Interestingly, Prdx1 suppression in both lines led to a marked reduction in Prdx2 expression and significant induction of Prdx4 expression. In addition, several Prdx genes were upregulated in MCF10 cells when either Prdx1 or Prdx6 were suppressed. We further demonstrated that Prdx1 and Prdx6 suppression caused a differential increase in peroxide-induced ROS levels and cytotoxicity in the two lines, and that simultaneous knock-down of both genes in MCF10 cells leads to a much more pronounced effect than in MCF7 cells. Together, these data suggest coordinated and complex regulatory interactions between the peroxiredoxin genes, and implicate a potentially different function for these proteins in transformed vs. untransformed cells. The elevated expression of peroxiredoxins in MCF7 cells may also represent a cellular adaptation to the cancerous state.
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 4384.
Abstract 4386: Androgen Receptor Requires JunD as a Co-activator to Switch on an Oxidative Stress Generation Pathway in Prostate Cancer Cells
Authors: Mehraein-Ghomi Farideh , Basu Hirak S. , Church Dawn R. , Wilding George 
Published: February 2011

Abstract
The relatively high oxidative stress in the prostate is postulated to be one of the major factors for prostate carcinogenesis and prostate cancer (CaP) progression. We focused on elucidating metabolic pathways of oxidative stress generation in CaP cells. Previously, we have shown that the transcription factor JunD is essential for the androgen-induced reactive oxygen species (ROS) production in androgen-dependent LNCaP human prostate cancer cells. We have also recently demonstrated that androgen induces the first and the regulatory enzyme spermidine/spermine N1-acetyl transferase (SSAT) in a polyamine catabolic pathway that produces copious amounts of metabolic ROS. Here, we present co-immunoprecipitation and Gaussia luciferase reconstitution assay data that show that JunD forms a complex with activated AR in situ. Our chromatin immnoprecipitation (ChIP) assay data demonstrate that JunD binds directly with a specific SSAT promoter sequence only in androgen-treated LNCaP cells. Using a vector containing a luciferase reporter gene connected to the SSAT promoter and a JunD silenced LNCaP cell line, we show that JunD is an essential co-activator of androgen-induction of SSAT gene expression. As there is no Androgen Response Element (ARE) in the SSAT promoter, we hypothesize that JunD mediates binding of androgen-activated AR to the SSAT promoter for the induction of SSAT that leads to polyamine oxidation and ROS production in prostate cells. Elucidation of this pathway may help the design of inhibitors of oxidative stress generation specifically in prostate cells to prevent prostate cancer occurrence and progression.
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 4386.