bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PL04-01: Sipuleucel-T and the active immunotherapy of prostate cancer.
Authors: Urdal David L. 
Published: June 2012

Abstract
Sipuleucel-T is an FDA approved autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. It consists of autologous peripheral blood mononuclear cells, including antigen presenting cells (APCs), which have been activated during a defined culture period with a recombinant human protein, PAP-GM-CSF, consisting of prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-macrophage colony stimulating factor (GM-CSF), an immune cell activator.
The development history will be summarized; the regulatory milestones will be described; and the lessons learned during the development of this novel approach to the treatment of prostate cancer will be discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr PL04-01.
Abstract PL05-03: Molecular basis and novel options for alternative epigenetic treatments against cancer.
Authors: Altucci Lucia 
Published: June 2012

Abstract
Deregulation of the epigenome is recognized as cause of cancer and epigenetic factors are receiving major attention as therapeutic targets; yet the molecular mode of action of existing epidrugs is largely elusive. Investigation of the spectrum of epimutations in cancer has only recently started and Food and Drug Administration-approved epi-drugs are currently limited by a number of factors. Mainly, the lack of knowledge about pathways and targets might have led to unfocused therapeutic applications of epi-drugs. We report here on the decryption of the mechanism of action of a novel epigenetic modifier, that inhibits multiple epi-enzymes. The rationale at the basis of targeting drugs could radically shift with the introduction of molecules interfering simultaneously with multiple targets as this might be more effective than single target agents thus representing a new generation of anti-cancer drugs. In this view, the inhibition of multiple epi-enzymes offers a promising alternative to combo-treatments of cancer using ‘poly-pharmacology’ approaches. Given the ability of cancer to bypass signaling routes via complex networks, the simultaneous modulation of multiple epi-targets promises to open new avenues against cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr PL05-03.
Abstract 1000: Inactivation of notch1 signaling suppresses FGFR1 knockdown-dependent growth inhibition of MDA-MB-231 breast cancer cells
Authors: Evangelou Andreas I. , Andrulis Irene L. 
Published: June 2012

Abstract
Breast cancer is a very heterogeneous disease as an array of expressed genes can be detected in individual tumors with varying phenotypic cellular morphology. However, despite this heterogeneity, two main histological subgroups predominate, basal-like and luminal-like tumors. Ongoing efforts aim to identify and target additional genetic alterations in breast tumors. One of the widely known and clinical distinctive markers between these tumor phenotypes for example is the transmembrane protein E-cadherin. Factors involved in the repression of E-cadherin are also involved in breast cancer progression. We have recently (Bane et al., Breast Cancer Research and Treatment 117:183-191, 2009) identified a set of differentially expressed and potentially additional distinctive markers between basal- and luminal-like breast tumors that have suggested an important role for Notch and FGF signaling in the development and maintenance of these breast cancer phenotypes. Other studies have also demonstrated gene amplifications in Notch and FGF receptors that can predispose in breast cancer pathophysiology. In the present study we have determined that downregulation of FGFR1 in the basal breast cancer cell line MDA-MB-231 decreased cell proliferation and survival. Interestingly, when Notch1 was also concomitantly repressed with siRNA, normal MDA-MB-231 cell proliferation and survival was restored. The current findings suggest and define a novel interplay between FGFR and Notch signaling in breast cancer patients that may be associated with poor prognosis due to ongoing and sustained basal-like phenotype in breast 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 1000. doi:10.1158/1538-7445.AM2011-1000
Abstract 1002: Fatty acid synthase is overexpressed in Middle Eastern epithelial ovarian carcinoma (EOC) and its inhibition potentiates cisplatin-mediated apoptosis in EOC cells
Authors: Bu Rong , Jehan Zeenath , Ahmed Maqbool , Bavi Prashant , Hussain Azhar R. , Olyan Aishah Saad , Dayel Fouad Al , Ghourab Samir , Uddin Shahab , Kuraya Khawla Al 
Published: June 2012

Abstract
Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of fatty acids has been shown to be deregulated in several cancers including epithelial ovarian carcinoma (EOC). In this study, we investigated the function of Fatty acid Synthase (FASN) signaling pathway in a large series of middle eastern EOC patient samples, using a panel of cell lines, and nude mouse model. Using immunohistochemistry, we detected FASN in 75.5 %(114/151) tumor samples. Overexpression of FASN was significantly associated with tumor proliferative marker Ki-67 (p=0.0009), activated AKT (p=0.0117) and XIAP(p=0.0046). Treatment of EOC cell lines with C75 a selective inhibitor of FASN causes inhibition of EOC cell proliferation via induction of apoptosis. Inhibition of FASN by C75 led apoptosis via involving mitochondrial pathway, activation of caspases and downregulation of XIAP, and survivin. FASN inhibition causes down regulation of activated AKT. In addition, inhibition by FASN siRNA causes downregulation of FASN and activation of caspases suggesting the role of FASN in C75 mediated apoptosis. Furthermore, treatment of EOC cells with subtoxic doses C75 augmented the effect of cisplatin mediated inhibition of cell proliferation and induction of apoptosis. Finally, treatment of EOC cell line xenografts with combination of C75 and cisplatin resulted in growth inhibition of tumors in nude mice through downregulation of FASN and activation of caspases Altogether, our results suggest that overexpression of FASN in Middle eastern EOC suggests that FASN may be a potential therapeutic target in a subset of EOC, alone or in combination with other conventional chemotherapeutic agents.
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 1002. doi:10.1158/1538-7445.AM2011-1002
Abstract 101: Claudin-4 overexpression is associated with epigenetic derepression in gastric carcinoma
Authors: Kwon Mi Jeong , Kim Seok-Hyung , Jeong Hae Min , Kim Sung-Su , Lee Jae Eun , Gye Myung Chan , Koh Sang Seok , Park Cheol Keun , Shin Young Kee 
Published: June 2012

Abstract
The tight junction protein claudin-4 is aberrantly up-regulated in gastric cancer, but its clinical significance and the molecular mechanism underlying claudin-4 overexpression in gastric cancer remain unclear. Here, we investigated its roles and epigenetic mechanism regulating CLDN4 expression in gastric cancer. We show that increased membranous expression of claudin-4 in gastric carcinoma is associated with better patient prognosis, whereas cytoplasmic claudin-4 expression didn't show a significant association with prognosis. Consistent with the correlation of increased membranous claudin-4 with favorable clinicopathological factors, claudin-4 overexpression inhibited the migration and invasion of gastric cancer cells; in contrast, it didn't affect cell growth. Claudin-4 expression also increased the barrier function of tight junctions. Claudin-4 up-regulation was strongly correlated with DNA hypomethylation in both gastric tissues and gastric cancer cells. Moreover, loss of repressive histone methylations and gain of active histone modifications were associated with CLDN4 overexpression in gastric cancer cells. Interestingly, CLDN4 repression could be markedly derepressed by combined treatments that simultaneously target both histone modifications and DNA demethylation in CLDN4-hypermethylated cells, whereas concomitant changes in histone methylations and acetylations are required for CLDN4 induction in CLDN4-repressed cells with low DNA methylation. Taken together, this study reveals that membranous claudin-4 expression is associated with gastric cancer progression as well as it is an independent positive prognosis marker in gastric carcinoma. Furthermore, our findings suggest that epigenetic derepression may be a possible mechanism underlying CLDN4 overexpression in gastric cancer and that claudin-4 may have potential as a promising target for the treatment of gastric 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 101. doi:10.1158/1538-7445.AM2011-101
Abstract 102: Hypermethylation of Keap1 promoter and expression of the downstream genes in human colorectal cancer cell lines
Authors: Hanada Naoyuki , Takahata Takenori , Itoh Jugoh , Saijo Yasuo 
Published: June 2012

Abstract
Nrf2-Keap1 system is a master regulator of phase 2 detoxifying and antioxidant genes including NAD(P)H-quinon oxidoreductase 1[NQO-1] and aldo-keto reductase C1 (AKRC1). Somatic mutation of Keap1 gene and aberrant hypermethylation of Keap1 gene promoter region was found in human lung cancer. Loss of keap1 function activates Nrf2 activity and enhanced the lung cancer cell growth in vitro and in vivo. However, there has not been studied Keap1 gene status in colorectal cancer. In this study, we investigated status of keap1 gene in 10 human colorectal cancer cell lines. No somatic mutation of keap1 gene was found in all 10 cell lines. Hypermethylation of Keap1 promoter region was found in 8 cell lines. Keap1 mRNA and protein expression tended to be lower in these hypermethylated cell lines. The keap1 mRNA in a methylated cell line (HT29) was re-expressed by treatment with the DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-azadC) and Trichostatin A (TSA). mRNA of the downstream genes, such as NQO-1 and AKRC1, were over expressed in the methylated cell line (HT29) compared to a nonmethylated cell line (Colo320DM) in Real time PCR analysis. In addition, we examined the methylation status of keap1 promoter region in primary tumors of 30 patients with colorectal cancer using methylation-specific PCR. An aberrant methylation in keap1 promoter was detected in 16 of 30 (53%). These findings suggest that hypermethylation of Keap1 promoter region in human colorectal cancer upregulates the expression of the downstream genes of keap1/nrf2 system which can be associated with the advantage for cancer progression and resistance to the anticancer agents.
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 102. doi:10.1158/1538-7445.AM2011-102
Abstract 1022: TNFα-induced apoptosis is reduced, but inflammation is increased by combined exposure with common food additive carrageenan
Authors: Bhattacharyya Sumit , Dudeja Pradeep K. , Tobacman Joanne Kramer 
Published: June 2012

Abstract
Tumor necrosis factor (TNF)-α, a homotrimeric, pleiotropic cytokine, mediates both apoptosis and inflammation. Following exposure to TNF-α, activation of caspases leads to apoptotic cell death and stimulation of an inflammatory cascade through the non-canonical pathway of NF-κB activation leads to increased nuclear RelB and p52. In contrast, the common food additive carrageenan (CGN), which contains sulfated galactose residues, stimulates inflammation through both the canonical and non-canonical pathways of NF-κB activation. CGN-induced inflammation utilizes B-cell leukemia/lymphoma (BCL)-10 to activate a pathway of innate immunity that is initiated by interaction with toll-like receptor (TLR)-4. CGN also stimulates inflammation through a reactive oxygen species-mediated pathway. In a series of cell-based experiments, colonic epithelial cells and mouse embryonic fibroblasts were treated with TNF-α and CGN, in order to simulate the possible effects of exposure to dietary CGN in the setting of TNF-α-mediated effects. Marked increase in secretion of Interleukin (IL)-8 occurred, attributable to synergistic effects on phospho-NIK in the non-canonical pathway. TNF-α induced the ubiquitination of TNF receptor-associated factor (TRAF)-2 which interacts with NFκB-inducing kinase (NIK), and CGN induced phosphorylation of BCL10, which is required for NIK-phosphorylation. These results suggest that TNF-α and CGN in combination act to increase NIK phosphorylation, thereby increasing activation of the non-canonical pathway of NF-κB activation. In contrast, the apoptotic effects of TNF-α, including activation of caspase-8 and poly [ADP-ribose] polymerase (PARP)-1 fragmentation, were markedly reduced in the presence of CGN. CGN exposure caused reduction in Fas by cDNA microarray and by ELISA. The study results demonstrate that exposure to CGN drives TNF-α stimulated cells toward inflammation, rather than toward apoptotic cell death. The findings suggest that CGN exposure may compromise the effectiveness of anti-TNF-α therapy. Average consumption of CGN in the typical Western diet is reported to be 250 mg/day, in contrast to therapeutic glycosides, such as digoxin that are prescribed in doses of ∼0.1 mg/day. Ingestion of CGN-containing foods has the potential to both inhibit the pro-apoptotic effect and to increase the pro-inflammatory effect of TNF-α and may contribute to malignant transformation.
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 1022. doi:10.1158/1538-7445.AM2011-1022
Abstract 1036: ProNGF/p75NTR signaling promotes survival of merlin-deficient vestibular schwannoma cells by activating NF-kB
Authors: Yue WeiYing , Ahmad Iram , Clark James Jason , Tryggvason Geir , Woodson Erika A. , Hansen Marlan R. 
Published: June 2012

Abstract
Vestibular schwannomas (VSs) represent benign Schwann cell (SC) neoplasms arising from the eighth cranial nerve and result from loss of function of the tumor suppressor gene, merlin. The mechanisms by which loss of merlin function promotes tumorigenesis in SCs is not well-defined. Denervation by axotomy leads to increased merlin inactivation by phosphorylation, increased p75NTR expression, JNK activation, and eventual death of normal SCs. In contrast to SCs, VS cells survive in the absence of axons. We found that p75NTR expression is elevated in sciatic nerves of mice harboring a SC specific dominant negative merlin mutation (P0SchΔ36-121) compared to nerves from wild-type mice suggesting that merlin status regulates p75NTR expression. Consistent with this we also find that p75NTR is over-expressed in primary human VS tissue compared with normal nerves. Treatment of normal rat SCs with proNGF, a high affinity p75NTR ligand, induces apoptosis by activating JNK. Primary cultured human VS cells, by contrast, display persistent JNK activity which promotes cell survival. Treatment of human primary VS cultures with the JNK inhibitors (I-JIP and SP600125) or JNK siRNA knock down results in decreased proliferation and increased apoptosis; treatment with proNGF protects cells from apoptosis due to JNK inhibition suggesting a p75NTR-mediated pro-survival signal in primary cultured VS cells. We explored the possibility that the pro-survival effect of p75NTR signaling results from activation of NF-κB. Indeed, proNGF treatment activated NF-κB in primary cultured VS cells while inhibition of JNK with SP600125 or siRNA-mediated JNK1/2 knockdown reduced NF-κB activity. Significantly, proNGF also activated NF-κB in primary cultured VS cells treated with JNK inhibitors. Thus, persistent JNK activity appears to be required for basal levels of NF-κB activity, but not for proNGF-induced NF-κB activity. To confirm that the increase in NF-κB activity by proNGF contributes to the prosurvival effect, we infected primary human VS cultures with Ad.IκB-SermutS32/36A virus which inhibits NF-κB activation. Compared to control virus, Ad.IκB-SermutS32/36A significantly increased VS cell apoptosis in VS cultures including those treated with proNGF. These results suggest that, in contrast to normal SCs which undergo apoptosis in response to p75NTR and JNK signaling, proNGF/p75NTR signaling provides a prosurvival response by activating NF-κB independent of JNK in merlin deficient VS cells. Such differences may account for the ability of human VS cells to proliferate and survive in the absence of axons.
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 1036. doi:10.1158/1538-7445.AM2011-1036
Abstract 1040: Downregulation of PI3K/Akt signaling is related to DHA-induced cytotoxicity in A549 human lung cancer cells
Authors: Kim Nayeong , Song Kyoung-Sub , Jing Kaipeng , Jeong Soyeon , Shin Soyeon , Oh Hyerim , Heo Jun-Young , Park Ji-Hoon , Seo Kang-Sik , Kwon Hyun-Joo , Park Jong-Il , Park Seung-Kiel , Kweon Gi-Ryang , Yoon Wan-Hee , Hwang Byung-Doo , Lim Kyu 
Published: June 2012

Abstract
Lung cancer is leading cause of all cancer deaths. Although omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been reported to inhibit cell growth in several cancers, the anti-cancer mechanism of ω3-PUFAs on lung cancer is still unclear. In this study, we have investigated the mechanism of anti-cancer action of DHA, one of ω3-PUFAs, in A549 human non-small cell lung cancer (NSCLC) cell line. Following treatment of DHA, the viability of A549 cells was decreased in a dose-dependent manner. DHA induced apoptotic cell death as revealed by increased cleaved PARP, TUNEL positive cells and subG1 population. The amounts of PI3K and phospho-Akt proteins were decreased after DHA treatment dose-dependent manner. In addition, DHA decreased the level of phospho-phosphatase and tensin homolog deleted on chromosome ten (p-PTEN) protein, which is an inactive form of PTEN. Moreover, transient transfection of constitutive active Akt cDNA and full length of Akt cDNA into A549 cells partially restored DHA-dependent inhibition of cell growth compared with the cells transfected with kinase dead form of Akt. Taken together, these data suggest that inhibition of PI3K/Akt signaling pathway may be related to anti-cancer action of DHA in A549 human NSCLC cells. Therefore, utilization of DHA may represent a potential effective therapy for the chemoprevention and treatment of human non-small cell lung cancer. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (R13-2007-020-01000-0)]
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 1040. doi:10.1158/1538-7445.AM2011-1040
Abstract 1043: Role of protein kinase Cι in alveolar rhabdomyosarcoma
Authors: Kikuchi Ken , Soundararajan Anuradha , Zarzabal Lee Ann , Weems Capella R. , Nelson Laura D. , Hampton Sheila T. , Michalek Joel A. , Rubin Brian P. , Fields Alan P. , Keller Charles 
Published: June 2012

Abstract
Background: Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer showing skeletal muscle differentiation. New therapeutic targets are required to improve the dismal cure rates for patients with metastatic ARMS. Protein Kinase C iota (PRKCI) has been shown to play an important role in many cancers but little to date is known of this kinase's role in rhabdomyosarcoma.
Materials and Methods: Human samples were obtained from the Pediatric Cooperative Human Tissue Network (Columbus, OH). Mouse samples were obtained from a Myf6Cre, Pax3: Fkhr, p53 conditional mouse model of ARMS and a Pax7CreER, Ptch1, p53 conditional model of embryonal rhabdomyosarcoma (ERMS). Expression of PKCι in tumors was evaluated by quantitative RT-PCR, western blotting and immunohistochemistry. To elucidate the functional role of PKCι in ARMS, we performed invasion assays, anchorage-independent colony formation assays and in vitro growth inhibition assays using primary cell lines obtained from mouse ARMS tumors, treating either with the PKCι specific inhibitor Aurothiomalate (ATM) or by PKCι RNA interference.
Results: Over-expression of PKCι at the mRNA and protein level was confirmed in human and mouse ARMS and ERMS. Immunoblotting confirmed that PKCι and its downstream targets, mitogen-activated protein kinase and nuclear factor-kappa B were expressed and highly activated in primary cell cultures. Inhibition of PKCι by RNA interference resulted in a dramatic decrease in cell viability and colony formation. Treatment of primary cell culture using ATM resulted in decreased cell viability (IC50: 54.3 – 256.9 uM) and colony formation, and increased G2/M blockade. Co-treatment with ATM and vincristine, a microtubule inhibitor currently used in rhabdomyosarcoma treatment regimens, resulted in a Combination Index of 0.572 – 1.017, suggesting cooperativity between these agents.
Conclusion: These results suggest that PKCι has an important function in proliferation of ARMS and that the PKCι specific inhibitor ATM shows activity in ARMS at clinically-feasible drug concentrations. Furthermore, these results suggest that combination therapy with vincristine and ATM should be investigated further in ARMS.
Ken Kikuchi and Anuradha Soundararajan contributed this presentation equally.
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 1043. doi:10.1158/1538-7445.AM2011-1043