bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3454: Molecular markers for breast carcinogenesis models induced by environmental substances and estrogen
Authors: Calaf Gloria M. , Balajee Adayabalam S. , Roy Debasish 
Published: February 2011

Abstract
Breast cancer is the most common cancer in women throughout the world. Exogenous and endogenous agents such as environmental carcinogens and female hormones seem to be involved in the etiology of breast cancer. It is a multistage process involving a series of genetic alterations, identification of potential genes responsible for breast carcinogenesis is critical for timely diagnosis and prevention of breast cancer. To gain insights into the mechanisms for breast cancer initiation and development processes by exogenous environmental agents, we have developed many experimental breast cancer model systems: In vitro model with the immortalized human breast epithelial cell line, MCF-10F exposed to (I) low doses of high LET (linear energy transfer) alpha particles (150 keV/μm) (Carcinogenesis 21: 769, 2000) and b), (II) organophosphorous pesticides, either with Parathion (P) or Malathion (M) and (III) combination of either P or M in the presence of estrogen (E). Results showed that MCF-10F cells treated either with double dose of 60 cGy alpha particles in the presence of E or pesticides induced malignant transformation of MCF-10F. The malignant transformation was determined by multiple biological assays: increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice, microsatellite instability and loss of heterozygosity in chromosomes 17, 11, 6, 8. Gene expression analysis using cancer pathway specific and affymetrix arrays detected alterations in the expression levels of p53, ErbB2, BRCA1, c-Ha-ras, Rho-A, PTEN, RB, c-Ha-ras, transforming protein Rho-A, F, GDP, TGF alpha, beta receptor, integrin B6, Notch3 and cathepsin. In addition to the in vitro human model, in vivo rat mammary gland model was also generated: (I) control (II) either P or M (III) E and (IV) P or M and E. Animals were treated for 5 days. These combined treatments induced significant progressive morphological and molecular changes. Alterations in the expression levels of RNA and protein were observed for c-fos, c-myc, mutant p53, ErbB2, BRCA1, c-Ha-ras, Rho-A, CYP1A1 gene and protein expression in the rat mammary gland after 240 days of treatment in comparison to control. Such stimulation led to mammary tumor formation. Collectively, our study shows the molecular signature of oncogenic deregulation in breast cancer progression induced by the combination of environmental substances and estrogen. Thus, aberrant expression of multiple genes involved in key signaling pathways renders these models as important tools for monitoring carcinogenic progression and chemo-intervention. Grant FONDECYT # 1080482 (GMC).
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 3454.
Abstract 3464: Epigenetic mechanism is involved in depleted uranium-induced transformation in human lung epithelial cells
Authors: Xie Hong , LaCerte Carolyne , Wise John P. 
Published: February 2011

Abstract
Depleted uranium (DU) is commonly used in military applications and is also used in civilian industry and thus exposure of soldiers and others is frequent and widespread. There is limited research information on the potential health hazards of DU exposure. In our study, we used the human bronchial epithelial cell line (BEP2D) to study the potential carcinogenic effects of DU. DNA strand breaks were observed at 25 ug/cm2 DU treatment. We found that DU induces cell transformation including cell contact inhibition and anchorage independent phenotype. Doses of 0.25, 2.5 and 25 ug/cm2 uranium trioxide induces 23, 24 and 17 growth foci in 30 dishes, respectively. These foci were cloned and were found to exhibit anchorage independent growth and an aneuploid phenotype. We next investigated DU-induced epigenetic modifications. We found that DU decreases trimethylated H3K9 (H3K9me3), along with inhibition of the DNA damage repair protein ATM. Our study demonstrates that DU-induced both genotoxicity and aberrant histone methylation which may contribute to its carcinogenesis. This work was supported by ARO grants # W911NF-04-1-0240 and W911NF-08-0333 (J.P.W.).
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 3464.
Abstract 3465: DNA adducts of tobacco-specific nitrosamines in human pancreatic tissue resulting from pyridylhydroxybutylation and pyridyloxobutylation
Authors: Eggert Heike , Heppel Christopher W. , Peschel Oliver , Kunz Sebastian , Giebe Birkhild , Richter Elmar 
Published: February 2011

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Whereas cigarette smoking is a well established important risk factor for pancreatic cancer, the contribution of smokeless tobacco consumption is still a matter of debate. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the only known compound present in tobacco and tobacco smoke which induces pancreatic tumors in animal models. In rats, the major NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), proved to be an even more potent pancreatic carcinogen. NNK and NNAL have been detected in pancreatic juice. However, activation of NNK and NNAL leading to pyridyloxobutyl (POB) and pyridylhydroxybutyl (PHB) DNA adducts, respectively, has not been proven in human pancreas. Determination of POB DNA adducts was achieved by acid hydrolysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) from DNA after addition of [3,3,4,4-D4]-HPB as internal standard, derivatization with pentafluorobenzoyl chloride (PFBC) and quantification by gas chromatography/high resolution mass spectrometry with negative chemical ionization according to Heppel et al. (Anal Bioanal Chem 393:1525-30, 2009). POB DNA adducts could be easily detected in 8 of 11 pancreatic samples of sudden death victims from Germany at 2.95±1.08 fmol/µg DNA (mean±standard error; values below detection limit set at zero). Using [3,3,4,4-D4]-diol as internal standard, this analytical method also revealed the presence of PHB adducts in pancreatic DNA releasing 4-hydroxy-1-(3-pyridyl)-1-butanol (diol). However, because of massive peak broadening the PFBC ester of diol could not be quantified reliably. To improve the chromatographic resolution, the PFBC ester of diol was further derivatized according to Kao and Giese (Chem Res Toxicol 18:70-5, 2005) with pivalic anhydride to cap the secondary hydroxy group. The resulting tert-butyl esters of the PFBC esters of diol and [3,3,4,4-D4]-diol show excellent performance in capillary gas chromatography and allow quantification by single ion monitoring at the molecular masses of m/z 445.13 and m/z 449.16, respectively. In summary, the presence of POB and PHB DNA adducts in human pancreatic tissue has been clearly demonstrated for the first time. Further studies will show the specificity of these pancreatic DNA adducts for smoking and smokeless tobacco consumption and the correlation with other tobacco-specific biomarkers. Supported by a grant of the Institute for Science and Health, St. Louis, MO.
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 3465.
Abstract 3470: Effects of combined phytochemicals on skin tumorgenesis in SENCAR mice
Authors: Kowalczyk Magdalena C. , Junco Jacob , Kowalczyk Piotr , Tolstykh Olga , Hanausek Margaret , Slaga Thomas J. , Walaszek Zbigniew 
Published: February 2011

Abstract
The purpose of our study was to determine the effect of combined action of phytochemicals on early stages of skin tumorgenesis, i.e., initiation and promotion. We tested calcium D-glucarate (CG) given in the diet, while resveratrol (RES) and ursolic acid (URA) were applied topically. The 7,12-dimethylbenz[a]anthracene (DMBA)-initiated, 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted multistage skin carcinogenesis model in SENCAR mice was used. Mice (6-7 weeks old) with shaved backs received one topical dose of DMBA (20 nmol), then after one month, two weekly doses (2 µg each) of TPA (tumor promoter) for 14 weeks until sacrifice. The phytochemicals RES (2.5 μmol) or URA (1 μmol) were applied topically 20 min prior to DMBA or TPA treatment and 2% dietary CG was given in the AIN-93G diet from 2 weeks prior to 2 weeks after the DMBA dose or continually beginning 2 weeks prior to the first dose of TPA. We determined the tumor incidence (% of mice with tumors) and tumor multiplicity (number of tumors per mouse) and using RT-PCR and immunochistochemical analyses, we checked the expression of some cell proliferation and inflammation related genes. URA applied alone and in combination with CG during the promotion stage was a strong inhibitor of tumor multiplicity and tumor incidence. Combinations of URA with dietary CG appeared to show some synergistic effects. All compounds and their combinations reduced epidermal proliferation, but only URA and a combination CG/URA applied during promotion significantly reduced hyperplasia, as determined by epidermal thickness measurements taken at 14 weeks of TPA treatment. DMBA/TPA treatments resulted in epidermal hyperplasia, characterized by significant increase in transcription factor AP-1 components and nuclear factor kappa B (NFkB) expression levels with a simultaneously increased expression of the inflammation markers COX-2 and IL-6, compared to untreated controls. All anti-promotion treatments (either single compounds or their combinations) caused a marked decrease of inflammation related genes levels compared to the DMBA/TPA control. On the other hand, only URA and URA with dietary CG diminished the induced expression of proto-oncogenes c-jun and c-fos (components of AP-1) and the expression of NFkB protein p50. These results show that URA is a potent inhibitor of skin tumor promotion and it may be useful in the prevention of skin cancer and other epithelial cancers in humans. Supported by NIH grants CA 102747 and P30 CA 54174-16S1.
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 3470.
Abstract 348: Prognostic value of mTOR activation and therapeutic effects of everolimus in esophageal squamous cell carcinoma
Authors: Hirashima Kotaro , Baba Yoshifumi , Saito Seiya , Kinoshita Kouichi , Satou Nobutaka , Kurashige Junji , Karashima Ryu-ichi , Imamura Yu , Ikeda Osamu , Hayashi Naoko , Watanabe Masayuki , Iyama Ken-ichi , Baba Hideo 
Published: February 2011

Abstract
Background: The mammalian target of rapamycin (mTOR) plays central roles in cell growth and homeostasis. Aberrant activation of mTOR in relation to clinical outcome has been reported in several types of cancers. mTOR inhibitor, particularly everolimus (RAD001), has been attracting attentions as a promising anticancer drug. Nonetheless, no study has shown the prognostic value of mTOR activation in oesophageal squamous cell carcinoma (ESCC) and the therapeutic effect of everolimus on human ESCC cell lines. The aims of this study are [1] to evaluate phosphorylated-mTOR (i.e., mTOR activation) expression in ESCC and to clarify its clinical, pathologic, and prognostic features and [2] to examine the therapeutic effect of everolimus on ESCC cell lines.
Methods: We examined p-mTOR expression (i.e., mTOR activation) by immunohistochemistry using 143 ESCC specimens. The present study involved 143 consecutive patients with ESCC who underwent the curative surgical resection at Kumamoto University Hospital from January 1996 to December 2006. We determined its clinical, pathologic, and prognostic features. Prognostic significance of p-mTOR expression was examined by Cox regression and Kaplan-Meier analysis. Subsequently. the effects of everolimus on ESCC cell lines were evaluated by in vitro assays (proliferation, cell cycle, apoptosis, invasion).
Results: p-mTOR expression was detected in 71 (49.7 %) tumors and was independently associated with higher overall mortality. Compared to p-mTOR negative patients, p-mTOR positive patients experienced high overall mortality [HR 2.44; 95% confidence interval (CI), 1.24-4.83, P = 0.01], which persisted in multivariate analysis (adjusted HR 2.92; 95% CI, 1.48-5.78, P = 0.002). p-mTOR expression was not related with clinical or pathologic variables including age at diagnosis, sex, tumor location, histological grading, T classification (tumor invasion) or N classification (lymph-node metastasis). In vitro, in both TE4 (p-mTOR expression-high in vitro) and TE11 (p-mTOR expression-low in vitro) squamous cell carcinoma cell lines, everolimus suppressed the phosphorylation of downstream p70S6 kinase and 4E-BP1in a dose-dependent manner. Everolimus significantly inhibited cancer cells proliferation and invasion, and induced cells apoptosis in vitro. Conclusion: p-mTOR expression in ESCC was independently associated with poor prognosis, supporting the potential for mTOR as a therapeutic target for ESCC. Everolimus may be useful as an anticancer drug for ESCC.
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 348.
Abstract 3495: Targeting gliomas with a dual kinase inhibitor and stem-cell delivered TRAIL
Authors: Bagci-Onder Tugba , Wakimoto Hiroaki , Anderegg Maarten , Shah Khalid 
Published: February 2011

Abstract
Gliomas are difficult to eradicate due to several factors: a) the lack of efficient delivery of anti-tumor agents to the tumors without affecting the normal brain tissue; b) the inherent or acquired resistance of tumor cells to anti-tumor agents; and c) the highly invasive nature of tumor cells that escape the primary tumor mass and subsequently cause recurrence. We previously established that a secreted form of tumor necrosis factor-related apoptosis inducing ligand (S-TRAIL) specifically eradicates glioma cells when delivered by various stem cell types in culture and in orthotopic glioma models. However, recent evidence has shown that a number of established and primary glioma lines have varying degrees of resistance to TRAIL, due to the heterogeneity of genetic alterations and possibly due to the over-activation of phosphatidylinositol 3 kinase (PI3K) pathway. In this study, we report the effect of a novel PI3K inhibitor, PI-103, alone or in combination with neural stem cell (NSC)-delivered S-TRAIL in mouse models of malignant and invasive gliomas. Using established and primary CD133+ glioma initiating cells engineered to express fluorescent and bioluminescent markers, we show that PI-103 alone inhibits proliferation and invasion, and causes G0-G1 arrest in cell cycle of most of the glioma cells tested. Furthermore, PI-103 augments the response of glioma cells to stem cell delivered S-TRAIL in co-cultures of NSCs and glioma cells suggesting that it can synergize with S-TRAIL-induced apoptosis. Using orthotopic malignant glioma models and bioluminescence imaging, PI-103 treatment in combination with NSC-derived S-TRAIL was shown to result in significant reduction in tumor volumes compared to either treatment alone in vivo. Our results reveal that combination of the novel PI3K inhibitor, PI-103, and stem cell delivered TRAIL might represent a novel therapy for malignant gliomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3495.
Abstract 3516: Targeting cancer by cisplatin-containing nanovectors
Authors: Sengupta Poulomi , Soni Shivani , Basu Sudipta , Sengupta Shiladitya 
Published: February 2011

Abstract
Cisplatin [cis-dichlorodiammineplatinum(II)] is a first-line chemotherapeutic agent, and is widely used for the treatment of many malignancies including testicular, ovarian, cervical, head and neck, and non-small cell lung cancer. Its use is dose-limited mainly because of nephrotoxicity. To address this limitation, we have engineered novel nanovector to deliver the drug directly to the tumor site with reduced toxicity.
In this study, we have functionalized cholesterol with succinic acid and ethyelene diammine to complex platinum through a monocarboxylato and a coordinate bond. The Chol-Pt complex was mixed with phosphatidylcholine and DSPE-PEG at 5:10:1 weight ratio and cisplatin containing nanoparticles were synthesized through evaporation-hydration-extrusion technique. The nanoparticles were found to be in the size range of 100-150 nm and spherical in morphology (characterized by DLS and TEM respectively). The physicochemical release kinetics of cisplatin from the nanoparticles in different hypoxic cell lysates showed a sustained release of the drug.
Our in vitro studies of the cisplatin liposomes indicate that cisplatin liposomes are highly effective in 4T1 breast cancer and LLC (Lewis Lung Carcinoma) cell lines in 48 hours, as compared with free cisplatin. Most interestingly, our cisplatin containing liposomes demonstrated efficacy in cisplatin resistant CP20 (liver adenocarcinoma) cell line at 10 μM concentration. Hence, our study showed that our novel cisplatin nanovector delivery device could potentially be harnessed for lung, breast and cisplatin resistant cancer chemotherapy with increased therapeutic index compared to cisplatin.
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 3516.
Abstract 3517: Complete remission of xenograft tumor in nude mice induced by N-mustard-quinoline conjugates bearing hydrazinecarboxamide linker
Authors: Su Tsann-Long , Kakadiya Rajesh , Dong Huajin , Kumar Amit , Lee Te-Chang , Tsai Tung-Hu , Chou Ting-Chao 
Published: February 2011

Abstract
Designing DNA-directed alkylating agents is a promising strategy to overcome the drawbacks of alkylating agents by enhancing DNA specific cross-linking and reducing the chemical reactivity of N-mustard. These compounds are generally synthesized by linking the alkylating warhead (such as alkyl or phenyl N-mustard pharmacophore) to the DNA-affinic carrier (such as DNA intercalating or groove binding agents). Recently, we reported that N-mustard-9-anilinoacridine conjugates via a urea, carbamate, or carbonate linker exhibited potent cytotoxicity and therapeutic efficacy against various human tumor xenografts indicating that these linkers are able to stabilize the reactive alkylating war head. Thus, these derivatives have a long half-life in plasma. Some of these conjugates are able to induce complete tumor remission (CR) in inhibiting human tumor xenograft model with low toxicity. To continue our research in finding potent DNA-directed alkylating agents, we have recently synthesized a series of N-mustard-quinoline conjugates bearing a hydrazinecarboxamide linker. These conjugates were prepared in good yield by the condensation of appropriate 4-hydrazinoquinolines with 4-bis(2-chloroethyl)- aminophenyl isocynate. The results showed that these conjugates possessed significant cytotoxicity against human lymphoblastic leukemia (CCRF-CEM) and various solid tumor xenografts (such as MX-1, HCT-116, H1299, CL 1-0, CL 1-5, PC3 and MCF-7) cell growth in vitro. Among these agents, BO-1392 and BO-1393 were able to induce CR against human breast carcinoma MX-1 xenograft and significantly suppress against human ovarian SK-OV3 xenograft in animal model with relative low toxicity. Interestingly, we found that BO-1393 (iv. injection) can significantly prolong the life span of nude mice bearing human glioma SK-NA-S xenograft (orthotropic implanted in brain). The experiment was compared with Temozolomide (oral administration). The modified comet assay and alkaline agarose gel shift assay showed that these conjugates are capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells. In conclusion, the present studies demonstrated that the newly synthesized N-mustard-quinoline conjugates having a hydrazinecarboxamide linker exhibited a broad spectrum of antitumor activity and are chemically stable. The remarkable therapeutic efficacy of BO-1393 demonstrated that this agent has high potential for clinical development.
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 3517.
Abstract 3539: Overexpression of the ATP Binding Cassette Gene ABCA1 determines resistance to curcumin in M14 melanoma cells
Authors: Kronski Emanuel , Iancu Cristina M. , Killian Peter , Mirisola Valentina , Jochum Marianne , Nerlich Andreas , Pfeffer Ulrich , Bachmeier Beatrice 
Published: February 2011

Abstract
Background: Curcumin induces apoptosis in many cancer cells and it reduces xenograft growth and the formation of lung metastases in nude mice. Moreover, the plant derived polyphenol has been reported to be able to overcome drug resistance to classical chemotherapy. These features render the drug a promising candidate for tumor therapy especially for cancers known for their high rates concerning therapy resistance like melanoma.
Results: We show here that the melanoma cell line M14 is resistant to Curcumin induced apoptosis, which correlates with the absence of any effect on NFkappaB signaling. We show that CXCL1 a chemokine that is down regulated in breast cancer cells by Curcumin in an NFkappaB dependant manner is expressed at variable levels in human melanomas. Yet in M14 cells, CXCL1 expression did not change upon Curcumin treatment. Following the hypothesis that Curcumin is rapidly removed from the resistant cells, we analyzed expression of known multi drug resistance genes and cellular transporters in M14 melanoma cells and in the Curcumin sensitive breast cancer cell line MDA-MB-231. ATP-binding cassette transporter ABCA1, a gene involved in the cellular lipid removal pathway is over-expressed in resistant M14 melanoma as compared to the sensitive MDA-MB-231 breast cancer cells. Gene silencing of ABCA1 by siRNA sensitizes M14 cells to the apoptotic effect of Curcumin most likely as a result of reduced basal levels of active NFkappaB. Moreover, ABCA1 silencing alone also induces apoptosis and reduces p65 expression. Conclusion: Resistance to Curcumin thus follows classical pathways and ABCA1 expression should be considered as response marker.
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 3539.