bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1698: Resveratrol potentiates the cytotoxic profile of docetaxel and doxorubicin via inhibiting the activity and expression of p-glycoprotein molecules
Authors: Al-Abd Ahmed M. , Mahmoud Ali M. , Nofal Salwa M. , El-sherbiny Gamal A. , El-Moselhy Mohammed A. , Ahmed Abdel-Tawab Hekma A. , El-Eraky Wafaa I. , El-Shemy Hany A. 
Published: June 2012

Abstract
P-glycoprotein is membrane protein highly abundant in tumor cells which facilitate the effluxes of several chemotherapeutic agents to the extracellular compartment. Several P-glycoprotein blockers of synthetic origin were suggested as adjuvant therapy for cancer; however, manifested several toxic side effects. Resveratrol was found to block p-glycoprotein with potential use as adjuvant therapy for several p-glycoprotein substrates such as docetaxel and doxorubicin. Herein, we have assessed the interactive characteristics of resveratrol with docetaxel and doxorubicin and further investigated the molecular bases of this interaction in three different solid tumor cell lines (MCF-7, HeLa and HepG2). Resveratrol per se was found to possess anti-cancer properties; however with relatively low potency in all tested cell lines (IC50 ranges from 8.0 to 19.1µg/ml). Doxorubicin and docetaxel showed IC50‘s ranged from 0.28 to 0.42 µg/ml and from 22.3 to 67.1 ng/ml, respectively. Resveratrol combination with doxorubicin and docetaxel significantly increased the potencies of both chemotherapeutic agents showing IC50‘s ranging from 0.07 to 0.2 µg/ml and from 6.2 to 45.7 ng/ml, respectively. The combination index showed synergistic interaction between resveratrol and doxorubicin or docetaxel in MCF-7 cell line, while additive interaction in HeLa and Hep-G2 cell lines. Real time PCR revealed that the expression of BAX and BcL2 were simultaneously elevated due to combination of resveratrol with doxorubicin or docetaxel in all tested cell lines while p-53 showed marginal elevation in MCF-7 and HepG2 cell lines. The p-glycoprotein efflux activity was significantly inhibited with subsequent accumulation of p-glycoprotein substrate within the intracellular compartment of all tested cell lines. Also the expression level of mdr1 gene was down regulated after resveratrol combination with doxorubicin or docetaxel in all tested cell lines. In conclusion, resveratrol potentiates the anti-cancer effects of doxorubicin and docetaxel via increasing their intracellular level due to p-glycoprotein activity inhibition and down regulation of mdr1 gene.
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 1698. doi:10.1158/1538-7445.AM2011-1698
Abstract 17: Bcl-2 is a downstream target of ATF5 that mediates ATF5's pro-survival function in a cell type-dependent manner
Authors: Dluzen Douglus , Li Guangfu , Tacelosky Diana , Moreau Matthew , Liu David X. 
Published: June 2012

Abstract
The activating transcription factor 5 (ATF5) is a member of the ATF/CREB family of basic zipper (bZIP) proteins. Recent reports showed that ATF5 loss-of-function causes apoptotic cell death in glioblastoma and breast cancer cells but not in non-transformed astrocytes and human breast epithelial cells. The mechanism for ATF5's cell type-dependent survival function is unknown. We report here that the anti-apoptotic factor Bcl-2 is a downstream target that mediates ATF5-promoted cancer-cell survival in C6 glioma cells and MCF-7 breast cancer cells. ATF5 binds to an ATF5-specific regulatory element (ARE) that is downstream of and adjacent to the negative regulatory element (NRE) in the Bcl-2 P2 promoter, stimulating Bcl-2 expression. Highlighting the importance of Bcl-2 in ATF5-dependent cancer-cell survival, expression of Bcl-2 blocks death of C6 and MCF-7 cells induced by d/nATF5 and depletion of Bcl-2 impairs ATF5-promoted cell survival. Moreover, we found that Bcl-2 expression is not regulated by ATF5 in non-transformed rat astrocytes, MEFs, and human breast epithelial cells (HBEC), where knock-down of Bcl-2 but not that of ATF5 evokes cell death. These findings identify Bcl-2 as an essential mediator for ATF5's cancer-specific cell survival function in glioblastoma and breast cancer cells and provide direct evidence that the cell type-specific function of ATF5 derives from the differential regulation of downstream targets by ATF5 in different types of 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 17. doi:10.1158/1538-7445.AM2011-17
Abstract 1715: Induction of CYP1B1 expression in non-small cell lung carcinoma cells treated with B(a)P inhibits cisplatin-induced apoptosis
Authors: Park Juwon , Kim Kyungseon , Chae Yang Seok , Ahn Kwang-Sung , Won Nam Hee 
Published: June 2012

Abstract
Cytochrome P450 1B1 (CYP1B1) is a key enzyme involved in metabolizing environment pollutants and whose expression is often significantly increased in human malignancies. In the past years, several studies focused on the possible role of CYP1B1 in tumor progression, invasion and drug resistance. CYP1B1 gene polymorphisms have been associated with the risk of lung and other cancer. However, there is no a evidence that induction of CYP1B1 by B(a)P has relevance to anticancer drug resistance. In this study, we found that CYP1B1 expression was increased by exposure of B(a)P in A549 cells and H1299 cells, respectively. Both A549 cells and H1299 cells prolonged exposed to B(a)P [A549-B(a)P and H1299-B(a)P] were resistant to cisplatin treatments. MTT assay showed that IC50 of A549-B(a)P and H1299-B(a)P was 2.3 folds and 3.2 folds higher than IC50 of parental cells. Results of immuocytostain revealed that induction of CYP1B1 and AhR was detected in A549-B(a)P and H1299-B(a)P. Reduction of CYP1B1 by shRNA of CYP1B1 in A549-B(a)P and H1299-B(a)P became to be sensitized to cisplatin treatments. The similar result was found in A549 cells and H1299 cells transfected with shRNA of AhR. Our data suggested that AhR-mediated CYP1B1 expression affected the response of cisplatin treatments on non-small cell lung cancer cells (NSCLCs). It suggested that, in exposure of B(a)P on lung cancer cells, AhR can modulate CYP 1B1 expression resulting in producing BPDE to form a bulk of DNA adducts. Exposure of B(a)P is committed to controlling proliferative/apoptotic balance, which has obvious and important implications in tumor progression and drug resistance.
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 1715. doi:10.1158/1538-7445.AM2011-1715
Abstract 1794: A novel combination therapeutic approach for targeting murine cancers with IL-13 receptor alpha 2 DNA vaccine and an immunotoxin
Authors: Nakashima Hideyuki , Joshi Bharat H. , Husain Syed R. , Puri Raj K. 
Published: June 2012

Abstract
Iinterleukin-13 receptor α2 (IL-13Rα2), a cancer testis antigen, is frequently over-expressed on human solid tumors and can be effectively targeted by a recombinant fusion immunotoxin composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE). We have previously demonstrated that cDNA vaccine to IL-13Rα2 or IL13-PE alone can cause regression of established murine cancer. Here, we demonstrate that combination therapy with DNA vaccine and IL13-PE can cause a remarkable antitumor effect in advanced tumor metastasis models induced by 4T1 breast carcinoma and MCA304 sarcoma. Murine metastatic tumor models were developed by i.v. injection of either 1×105 4T1 or 1×106 MCA304 cells. Mice with established 4T1 metastasis received twice daily i.p. injections of IL13-PE (50 ug/kg/injection) on five consecutive days beginning day 7 followed by i.m. DNA vaccination (100 μg/day) on day 18, 23, 28 and 33. The combination therapy significantly (p&lt;0.01) prolonged overall survival (56 days) of animals compared to control (32 days), IL-13PE alone (43 days) or DNA vaccine alone (40 days). Similar results were observed in MCA304 sarcoma tumor model. Mice treated with combination therapy showed higher CTL activity and IFN-γ release from splenocytes in vitro compared to the controls in both tumor models. Immunofluorescence analyses exhibited infiltration of CD4+ and CD8+ T cells in lung tissues of immunized mice. The role of CD4+ and CD8+ T cells in tumor immunity was further confirmed by similar treatment of tumor-bearing RAG2 KO mice (deficient in T and B cells), which showed no response to therapy. Interestingly, tumor bearing mice treated with combination therapy recruited much lower number of myeloid-derived suppressor cells (MDSC) in lungs than PBS treated controls. These results indicate that combination therapy with IL13-PE followed by DNA vaccine may be a new therapeutic approach of treating human cancer.
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 1794. doi:10.1158/1538-7445.AM2011-1794
Abstract 18: Deep-sequencing of ovarian cancer stem cells
Authors: Zehir Ahmet , Ertem Server Adil , Moore Malcolm AS 
Published: June 2012

Abstract
Ovarian cancer remains to be one of the most fatal cancer types in women due to a lack of proper identification of therapies that will completely eradicate tumor cells in patients. Cancer stem cell (CSC) hypothesis states that there is a sub-population of cells in tumors that can self-renew and give rise to a differentiated tumor tissue. CSCs are also postulated to be resistant to conventional therapies, which might explain the recurrent nature of some of the cancer types. We have recently identified a novel cellular structure consisting of a chain of 4-72 cells with a pericellular glycocalyx, free-floating in the ascites of NOD/SCIDIL2Rγ-/- mice with intraperitoneal human serous ovarian adenocarcinoma (OvCa) xenografts. We have termed these “catenae” (Latin for “chains”). While the catena has the features of conventional CSCs, such as self-renewal, resistance to chemotherapy and ability to generate tumors in mice with as few as one cell; it also presents with unusual phenotypes. To elucidate the molecular mechanisms responsible for these phenotypes, as well as to get a transcriptional snapshot of pure CSCs; we performed SOLID deep-sequencing of catena on both whole cell RNA sample and polysomal RNA sample. We obtained 80millions and 60millions reads respectively. By comparing whole RNA sample to polysomal RNA sample, we have identified transcripts that are abundant in numbers but are not translated preferentially. We also identified alternative splicing events that might lead to the CSC phenotypes that catena have. Using public databases, we compared our data to differentiated cell states and generated comparative GO analysis of catena deep-sequencing data. The power of deep sequencing methodology will allow a deeper understanding of how CSCs might operate and will enable us to generate new therapies for eradicating CSCs.
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 18. doi:10.1158/1538-7445.AM2011-18
Abstract 1809: Stimulation of antibody dependent cell-mediated cytotoxicity by interleukin-15 is equivalent to interleukin-2
Authors: McDowell Kimberly A. , Hank Jacquelyn A. , Sondel Paul M. 
Published: June 2012

Abstract
An important strategy for the treatment of cancer involves administration of tumor-specific antibodies that target tumor cells for destruction by the individual's leukocytes via antibody dependent cell-mediated cytotoxicity (ADCC). However, ADCC is frequently depressed in individuals with cancer. Interleukin-2 (IL-2), a pro-inflammatory cytokine, enhances ADCC and is used clinically for this purpose. Interleukin-15 (IL-15) is a cytokine that shares many functions with IL-2, including stimulation of ADCC and proliferation and activation of natural killer cells. In contrast to IL-2, IL-15 supports the survival of CD8+ memory T cells, does not produce T cell activation-induced cell death and has no marked effects on Treg cells. Since these different functions may prove beneficial when using a cytokine to stimulate ADCC in vivo in cancer immunotherapy, we compared the in vitro effect of IL-15 (generously provided by Dr. Stephen Creekmore, NCI-Frederick) versus IL-2 to enhance ADCC. Using a standard 51Cr release assay, M21 human melanoma cells were loaded with 51Cr and incubated for four hours at 37° with human peripheral blood mononuclear cells (PBMC), hu14.18K322A, (generously provided by Dr. Fariba Navid of St. Jude Children's Research Hospital) a monoclonal antibody specific for GD2 (disialoganglioside) that is overexpressed on M21 cells (5 ng/ml), and either media, IL-2 (10 ng/ml) or IL-15 (10 ng/ml). The ratio of effectors (PBMCs) to targets (M21) was 10:1 or 30:1 and % cytotoxicity was determined from which lytic units were calculated. Incubation with IL-2 augmented ADCC from 163±39 to 230±40 lytic units (n=6, mean±SEM) while incubation with IL-15 enhanced ADCC from 148±27 to 229±36 lytic units (n=6). ADCC response was comparable for IL-2 and IL-15 (p=0.4857) and similar results were obtained using higher and lower concentrations of hu14.18K322A (0.1 – 100 ng/ml) and IL-2 and IL-15 (5 – 25 ng/ml), and after pre-incubation of PBMCs with IL-2 or IL-15 (4 – 44 hours). These experiments indicate that IL-2 and IL-15 demonstrate comparable stimulation of ADCC in vitro. If IL-15 produces equivalent enhancement of ADCC compared to IL-2 in vivo, it may be a potential immunotherapeutic for cancer.
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 1809. doi:10.1158/1538-7445.AM2011-1809
Abstract 1810: The effects of adoptive T cell transfer on the population of regulatory T cells in the mouse colorectal cancer transplant model
Authors: Okajima Manabu , Kokura Satoshi , Matsumoto Tsuguhiro , Ishikawa Takeshi , Matsuyama Ryuichi , Funaki Jun , Adachi Satoko , Matsuura Yuko , Sakamoto Naoyuki , Naito Yuji , Yosikawa Toshikazu 
Published: June 2012

Abstract
Background and Aim: Recent evidence has demonstrated that regulatory T cells (Tregs) mediated immunosuppression is one of the most crutial tumor immune-evasion mechanisms. We clinically demonstrated that the number of peripheral Tregs in the patients with variety of cancer which received ACT, which is non-specific CD3-LAK significantly decreased and that the clinical outcome of the patients of which peripheral Tregs decreased was better. ACT, which contains even only the non-specific lymphocytes might have the potential to not only directly kill malignant cells but also manipulate the population of Tregs in tumor bearing hosts in strong immunosuppressive states. The aim of this study is to investigate the effect of ACT which is composed of non-specific T lymphocytes on the population of Tregs in local tumor, draining lymph nodes and spleen in the mice colorectal cancer transplant model. We have also investigated the effect of activated T cells on the induction of Tregs from CD4+ T cells by IL-2 and TGF-β.
Materials and Methods: In vivo study: Male Balb/c mice were injected s.c. with colon26. The population of Treg in the tumor, the lymph node, and the spleen was analyzed after ACT(non-specific CD3-LAK) administration via a tail vein. In vitro study: The inducible system of Tregs was established. CD4+cells sorted from murine splenocytes were expanded for 72 hours in culture media containing IL-2 and TGFβ. LAK cells were co-cultured non-contactly with CD4+cells. Then we investigated the changes in the system after the co-culture. We also measured the concentration of IFN-γ in the culture solution to reveal the mechanism.
Results: The accumulation of Tregs in the draining LNs and tumor was significantly suppressed by ACT. The induction of Tregs in vitro was inhibited by co-culture with LAK cells. The concentration of IFN-γ in the culture solution increased in LAK+ group.Conclusions: We have demonstrated that ACT has the potential to reduce the number of Tregs in tumor and draining lymph nodes in the mouse colorectal cancer transplant model. As one of the mechanisms of this phenomenon, IFN-γ secreted from LAK cells might blockade the conversion of CD4+ cells into Tregs. These findings suggest a novel therapeutic position of ACT in variety of cancer immunotherapies.
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 1810. doi:10.1158/1538-7445.AM2011-1810
Abstract 1818: Identification of men with a genetic predisposition to prostate cancer: Targeted screening of BRCA1/2 mutation carriers and controls; The IMPACT study
Authors: Bancroft Elizabeth K. , Castro Elena , Dalby Elizabeth C. ,   The IMPACT Study Steering Committee & Collaborators, Eeles Rosalind A. 
Published: June 2012

Abstract
Introduction: Men with a mutation in either the BRCA1 or BRCA2 gene have an increased risk of prostate cancer, estimated as 3-5% for BRCA1 and up to 20% for BRCA2 by age 70. It has been demonstrated that men with BRCA2 develop aggressive disease but the real incidence and prevalence of cancer in mutation carriers remains unknown. IMPACT is a multi-national targeted prostate cancer screening study of men with a known germline mutation which is thought to predispose to the disease. The study is recruiting male BRCA1/2 mutation carriers and a control group who have tested negative for a mutation present in their family from 37 centres in 14 countries.
The aims of the study are to establish an international targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers; to determine the sensitivity and specificity of PSA screening for prostate cancer in this group; to determine the incidence of abnormal biopsy as a result of PSA screening in this group and to determine whether the pathology of tumours is different from screen-detected disease in controls.
Method: Eligible men aged 40-69 years are offered annual serum PSA testing for five years. The PSA threshold used to determine prostate biopsy is &gt;3ng/ml. All men are offered a biopsy irrespective of PSA level after 5 years of screening. Men are also invited to take part in a Quality of Life sub-study.
Results: To date 1000/1700 men have been recruited, 77 have undergone biopsy and 30 men have been diagnosed with prostate cancer (18 BRCA2 carriers, 7 BRCA1 carriers and 5 controls). 80% of cases diagnosed in BRCA1/2 carriers were Gleason score ≥7 and T2 or higher (in the intermediate/high risk group for immediate radical treatment and not active surveillance, according to NICE guidelines) while in the general population (ERSPC study), 72% had a Gleason ≤6 and 61% were T1 (low risk group, suitable for active surveillance). The estimated positive predictive value for PSA screening in BRCA carriers is 44% vs 24% in the general population (ERSPC study).
Conclusions: Our preliminary results show that annual PSA screening using a cut-off of 3.0ng/ml detects aggressive prostate cancer in BRCA1/2 carriers. The higher risk of PrCa observed in BRCA1 and BRCA2 carriers will need to be confirmed with further data. Early data indicate that a larger proportion of gene carriers have developed clinically significant prostate cancers (those that would need radical treatment on UK treatment guidelines) compared with the control group.
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 1818. doi:10.1158/1538-7445.AM2011-1818
Abstract 182: Novel hydroxamic acid-derivative, MHY218, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells
Authors: Kim Dong Hwan , Kang Yong Jung , Kim Min Young , Hossain Mohammad Akbar , Jang Jung Yoon , Mon Hyung Ryong , Chung Hae Young , Choi Yung H. , Kim Nam Deuk 
Published: June 2012

Abstract
In this study, we investigated the anti-proliferative and pro-apoptotic properties of novel hydroxamic acid-derivative, MHY218, in HCT116 human colon cancer cells. We found that treatment of cells with MHY218 resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner. The induction of apoptosis was showed by decreased viability, cleavage of poly(ADP-ribose) polymerase (PARP), alteration in the ratio of Bax/Bcl-2 protein expression, and activation of caspase-8 and -9 together with caspase-3. In addition, MHY218 induced G2/M phase cell cycle arrest which was related to a decrease in the protein expression of cyclin B1 and its activating partners Cdc25c and Cdc2. MHY218 also caused an increase in the expression levels of p21WAF1/CIP1 in a p53-independent pathway. Nuclear transcription factor-kappa B (NF-κB) has been reported to be an implicated factor in apoptotic cell death of various cancer cells. Therefore, we found the effect of MHY218 on NF-κB signaling pathway. Treatment of cells with MHY218 resulted in inhibition of the expression levels of NF-κB and IκBα in a dose-dependent manner. These results suggest that MHY218 may have potential as a chemotherapeutic agent for prevention against colon cancer.
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 182. doi:10.1158/1538-7445.AM2011-182