bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1790: Functional importance of EpCAM for the activity of tumor-initiating cancer cells and their eradication by EpCAM/CD3-bispecific antibody MT110
Authors: Münz Markus , Herrmann Ines , Friedrich Matthias , Murr Alexander , Kufer Peter , Baeuerle Patrick A. , Raum Tobias 
Published: June 2012

Abstract
We have recently shown that tumor-initiating cells (TICs) derived from colorectal cancer tissue express EpCAM and can be eradicated in cell culture experiments as well as established xenograft mouse models by EpCAM/CD3-bispecific BiTE antibody MT110 (Hermann et al., 2010; PLoS ONE, 5: e13474). Here we show that TICs derived from liver and breast cancer tissue grow tumors in SCID mice at cell doses as low as 100 after a latency period of 37-58 days. Like colorectal cancer tissue-derived TICs, they expressed EpCAM and grew colonies in soft agar. In the presence of human T cells, breast and liver cancer-derived TICs could be eradicated by BiTE antibody MT110 as tested in a sensitive soft agar assay.
In order to assess the role of EpCAM expression in colorectal TICs, we used short hairpin RNA molecules for specifically knocking down EpCAM expression. A shRNA molecule binding to the coding, non-translated 3’-UTR of the EpCAM mRNA showed the highest efficacy (ca 10-fold) in suppressing EpCAM expression, as shown at the mRNA level by RT-PCR and at the surface expression level by FACS analysis. Although the EpCAM knockdown was not complete and left ca 10% of the normal EpCAM expression, a strong impact on the phenotype of colorectal TICs was observed. Morphologically, TICs with reduced EpCAM expression adopted in cell culture an epithelial-like phenotype, could no longer efficiently close a scratch in a cell culture experiment, and reduced the expression of epithelial-mesenchymal transition (EMT)-associated proteins such as fibronectin, vimentin and slug. Compared to non-sense control shRNA, colony formation of TICs in soft agar was reduced by &gt;60%. Most importantly, the tumor-initiating potential of TICs appeared to depend on a high level of EpCAM expression. TICs expressing the EpCAM-specific shRNA could no longer form a tumor at a dose of 500 cells after 116 days, whereas the non-sense shRNA-expressing TICs formed during this period a tumor of 0.5 cm3.
Our data suggest that a certain EpCAM expression level is required for maintenance of a stem cell-like phenotype of colorectal TICs. This is consistent with a signal transducing role of EpCAM within a non-canonical wnt pathway (Maetzel et al. 2009; Nature Cell Biol. 11: 162-171), and in the process of EMT of colorectal cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1790. doi:10.1158/1538-7445.AM2011-1790
Abstract 1793: 5-Fluorouracil chemotherapy acts synergistically with adoptive dendritic cell immunotherapy to induce durable anti-tumor responses in vivo
Authors: Williams Patrick , Bouchentouf Manaf , Rafei Moutih , Romieu-Mourez Raphaelle , Yuan Shala , Forner Kathy A. , Birman Elena , Galipeau Jacques 
Published: June 2012

Abstract
Introduction: 5-Fluorouracil induces a form of cell death that facilitates the presentation of antigens by dendritic cells and depletes myeloid suppressor cells in vivo. The resulting immune modulation plays a substantial role in prolonging survival of mice with cancer. Our lab has previously demonstrated that a fusion of granulocyte-colony macrophage-stimulating-factor (GM-CSF) and Interleukin (IL) – 21, hereafter GIFT-21, could differentiate monocytes into a novel dendritic cell population (GIFT-21 DC). Characterization of these cells revealed a unique phenotype, with the expression of markers normally associated with both conventional and plasmacytoid dendritic cells. They are effective at cross-presenting antigens and secrete substantial amounts of CCL2, IL-6, TNF-α and IFN-α. When injected into tumor-bearing mice, they migrate to and sample from tumors in vivo, allowing them to educate CD8 T cells to recognize tumor antigens, which then significantly impeded the growth of B16 and D2F2 Neu tumors in mice.
Hypothesis: We propose that 5-Fluorouracil mediated immune modulation can be combined with adoptively transferred autologous GIFT-21 DCs to treat established cancer, and lead to a synergistic anticancer immune response.
Methods and Results: Twelve days following a subcutaneous tumor implantation, mice with established B16 tumors (average volume of 40mm3) were treated daily with 1.5 mg 5-Fluorouracil for 2 days and then injected on the third day with 1.5×106 syngeneic GIFT-21 DCs intraperitoneally. The treatment was repeated one week later. While 5-FU treatment alone or dendritc cell therapy alone had no significant impact on the growth of pre-established melanoma, the combination of 5-Fluorouracil with GIFT-21 DC-based immunotherapy reduced the rate of tumor growth by 75% over 5-FU and 85% over untreated mice, while eventually leading to the regression of the pre-established B16 tumors.
Conclusion: These findings demonstrate how chemotherapy can be combined with immunotherapy to target cancers for which tumors antigens are unknown or ill-defined. While chemotherapy suppresses some elements of the immune system in the short term, we speculate that modulating the endogenous immunological processes secondary to chemotherapy shows promising synergy with adoptive cell therapy and is a promising avenue of future research in cancer immunotherapy.
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 1793. doi:10.1158/1538-7445.AM2011-1793
Abstract 1799: Can trastuzumab enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, Stage II/III or Stage IV gastric cancer
Authors: Oshima Takashi , Kunisaki Chikara , Fujii Shoichi , Yamada Roppei , Rino Yasushi , Masuda Munetaka , Imada Toshio 
Published: June 2012

Abstract
Objectives: Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), in combination with chemotherapy has been reported to significantly prolong survival in patients with HER2-positive, unresectable, advanced gastric cancer. However, the therapeutic usefulness of this regimen for surgically resected gastric cancer remains unclear. Adjuvant chemotherapy with S-1 has been shown to be beneficial in patients with stage II or III gastric cancer. Whether trastuzumab should be given to patients with resected, HER2-positive gastric cancer is a very interesting problem. We therefore examined whether trastuzumab can be expected to enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, stage II/III or IV gastric cancer.
Methods: The study group comprised 183 patients: 116 had stage II or III gastric cancer and received adjuvant chemotherapy with S-1 after surgery from May 2003 through March 2008; the other 67 had stage IV gastric cancer and sequentially received new anticancer agents after surgery from July 1999 through September 2005. HER2 was evaluated by inmmunohistochemistry and FISH according to the protocol of a Study of Trastuzumab in Combination with Chemotherapy Compared with Chemotherapy Alone in Patients with HER2-Positive Advanced Gastric Cancer (ToGA study). Positive expression of HER2 was defined as a score of 3+ on immunohistochemical staining or as a score of 2+ on immunohistochemical staining plus relative HER2 DNA expression of &gt;2.2 on FISH. Cumulative survival rates were compared between HER2-positive patients and HER2-negative patients.
Results: Among patients with stage II or III gastric cancer who received adjuvant chemotherapy with S-1, 20% had HER2-positive tumors; however, cumulative survival rates did not differ significantly between HER2-positive patients and HER2-negative patients. Among patients with stage IV gastric cancer who underwent surgery, 22% had HER2 positive tumors; however, cumulative survival rates did not differ significantly between HER2-positive and HER2-negative patients.
Conclusions: The survival benefit of adding trastuzumab to standard chemotherapy was considered minimal in patients with resected, HER2-positive stage II/III or stage IV 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 1799. doi:10.1158/1538-7445.AM2011-1799
Abstract 180: Suppressor of cytokine signaling 6 (SOCS6) induces apoptosis through promoting mitochondrial fragmentation and Bax activation
Authors: Lin Huan-Yu , Lin Chung-Chih , Lee Hsin-Chen , Wang Fung-Fang , Chen Jeou-Yuan 
Published: June 2012

Abstract
Mitochondria are highly motile organelles that constantly undergo fission and fusion. Impairment of mitochondrial dynamics is associated with mitochondrial dysfunction and frequently linked to the pathogenesis of neurodegenerative diseases and cancer. We have previously shown that loss-of-function of suppressor of cytokine signaling 6 (SOCS6) is a frequent event in human gastric cancer. In this study, we recapitulated the event of loss of SOCS6 in cancer-derived cell lines where endogenous SOCS6 was expressed, and we showed that elimination of SOCS6 expression delays UV-induced apoptosis process. By contrast, overexpression of SOCS6 in cancer cell lines that express endogenous SOCS6 at minimal levels promotes apoptosis. SOCS6 induces intrinsic apoptotic process and facilitates cytochrome c release by enhancing Bax conformational change, mitochondrial targeting and oligomerization. We further demonstrated that SOCS6 is a novel mitochondrial protein that regulates mitochondrial dynamics. By confocal microscopy, we showed that ectopically expressed SOCS6 is predominantly localized in mitochondria, and the carboxyl-terminal SOCS box is important for its mitochondrial localization. Localization of SOCS6 in mitochondria is accompanied with concomitant mitochondrial fragmentation, both of which can be reversed by coexpression of mitochondrial fusion proteins (Mfn1 and Mfn2) or a dominant-negative form of Drp1. Ectopic expression of SOCS6 severely impairs the dynamics and function of mitochondria. Taken together, our data suggest that SOCS6 is a novel mitochondrial protein that induces intrinsic apoptosis pathway through perturbing mitochondrial dynamics and facilitating Bax activation.
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 180. doi:10.1158/1538-7445.AM2011-180
Abstract 1805: Integration of 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) in combinational immunotherapy targeting tumor antigen EphA2
Authors: Rao Aparna , Kawabe Mayumi , Storkus Walter J. 
Published: June 2012

Abstract
Introduction: EphA2 and HSP90 play important roles in tumor growth, survival and metastasis. An effective therapeutic approach would promote decreased expression of EphA2 on tumor cells, while increasing presentation of EphA2-derived peptides on tumor MHC class I complexes, thereby enhancing the recognition of tumors by anti-EphA2 CD8+ T effector cells. Aim: We are assessing the safety and effectiveness of the HSP90 inhibitor 17-DMAG in enhancing anti-tumor immunotherapy with EphA2-specific T cells in murine tumor models. Methods: We tested the effect of 17-DMAG on tumor cell expression of EphA2 and the MHC I antigen-processing machinery in vitro. Efficacy of 17-DMAG in an MCA205 sarcoma model was also evaluated in vivo. Results: 17-DMAG facilitated a dose-dependent reduction in EphA2 expression, but had no adverse effects on the antigen-processing machinery of the tumors. Similar effects were seen in an MCA205 sarcoma model in vivo, where reduction in EphA2 levels in tumors corresponded with increased recognition by EphA2-specific CD8+ T cells in vitro. 17-DMAG treatment also facilitated increased infiltration of CD4 and CD8 T cells in the tumor, compared to untreated cohorts. Conclusion: 17-DMAG treatment promotes immunologically-preferred alterations tumor cells in vitro as well as In vivo. Our preliminary in vivo studies suggest that decreased EphA2 levels in tumors is accompanied by increased presentation of EphA2 peptides in tumor MHC class I complexes. Further in vivo studies are warranted to assess the net anti-tumor impact of combinational immunotherapies integrating 17-DMAG.
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 1805. doi:10.1158/1538-7445.AM2011-1805
Abstract 183: Loss of Bad phosphorylation and Mcl-1 expression is necessary for rapid apoptosisinduced by combination of TGFα-PE and ZSTK474 in prostate cancer cells
Authors: Baiz Daniele , Yancey Dana , Choi Young A. , Baurin Vitaliy , Karpova Yelena , Hassan Sazzad , Debinski Waldemar , Kulik George 
Published: June 2012

Abstract
Advanced androgen-independent prostate cancer is notoriously resistant to conventional systemic therapies, and at the moment there is no effective protocol for hormone-refractory advanced prostate cancer affected patients.
One of possible mechanisms of such resistance is activation of the anti-apoptotic signaling PI3K/Akt pathway that is constitutively active in the 60% of advanced prostate cancers. However, multiple inhibitors of PI3K are just well studied and some have just gone on to clinical trials, but unfortunately they showed limited efficacy against prostate cancer alone.
Our recent experiments has shown remarkable synergy in inducing rapid and massive apoptosis when PI3K inhibitor ZSTK474 is used in combination with Pseudomonas aeruginosa exotoxin A fragment fused with Transforming Growth Factor Alpha (TGFα-PE38).
Time lapse video microscopy of prostate cancer C4-2 cell line has shown the substantial cell death within 4-6 hours with combined administration, compared to limited cell death in single agents-treated cells.
Analysis of PARP and cleaved-caspase 3 fragment by Western blotting confirmed that cell death occurs via apoptosis. Quantitation of caspase 3 and 7 activity with luminescent AFC-DEVD substrate confirmed synergy in apoptosis activation by combination of TGFα-PE38 and ZSTK474, while single agents even in higher concentration did not induce substantial apoptosis within 6 hours time period.
Analysis of the mechanisms underlying this synergy has shown that PI3K inhibitor ZSTK474 triggers Bad dephosphorylation, while TGFα-PE38 reduces expression levels of Mcl-1. A slight increase of Bim protein was detected and related with ZSTK474 administration. No major variations were detected in the expression levels of pro- and anti-apoptotic proteins Bax, Bcl-2 and Bcl-XL.
To address the role of Bad phosphorylation and Mcl-1 expression in apoptosis induction by PI3K inhibitor ZSTK474 and TGFα-PE38, we examined apoptosis in C4-2 cells that express phosphorylation-deficient mutant Bad (BAD2SA). Results indicated that the expression of BAD2SA sensitized C4-2 cells to apoptosis induced by TGFα-PE38. Experiments that address the role of Mcl-1 loss in apoptosis induced by TGFα-PE38 are ongoing.
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 183. doi:10.1158/1538-7445.AM2011-183
Abstract 1831: Using narrative to transform cancer communication: Impact of a cervical cancer storyline on primetime television
Authors: Murphy Sheila T. , de Castro Buffington Sandra , Hether Heather , Baezconde-Garbanati Lourdes A. 
Published: June 2012

Abstract
Epidemiological evidence reveals that Hispanic women lag behind all other ethnic groups in their rate of cervical cancer screening (National Health Interview Survey, 2006). Can stories succeed where more traditional cancer campaigns have faltered? Funding by the National Cancer Institute enabled researchers at Hollywood, Health & Society, the Annenberg School for Communication and Journalism, and the Institute for Prevention Research at the University of Southern California to encourage writers of primetime programming to include accurate information regarding cervical cancer.
Purpose of study: This study examined whether a popular Spanish language telenovela could impact Hispanic viewers’ knowledge, attitudes and behavior with respect to cervical cancer screening.
Experimental procedures: This was assessed by a quantitative survey of viewers before and after the fictional character of Dora in a Telemundo telenovela, El Clon, had an abnormal pap test.
Results: Statistical comparisons between the pretest and posttest surveys revealed that after seeing cervical cancer storyline viewers were 6 times more likely to know that a pap test detects cervical cancer; 4 times more likely to know that pap tests are available for free or at low cost; 80 percent more likely to know pap women should have a pap test at least every 2 years; and 80 percent more likely to intend to have pap in next 2 years. This shift was strongest among viewers who identified with Dora and reported being absorbed or “transported” while viewing.
Conclusions: A cervical cancer storyline on a popular telenovela was significantly associated with greater level of knowledge and intention to have pap test in the next 2 years. Implications of these results and the use of entertainment education in cancer communication more generally will be discussed.
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 1831. doi:10.1158/1538-7445.AM2011-1831
Abstract 1843: An unintended consequence of Nrf2-directed cytoprotection against a major human bladder carcinogen and a counteracting solution
Authors: Ding Yi , Paonessa Joseph D. , Randall Kristen L. , Argoti Dayana , Munday Rex , Vouros Paul , Zhang Yuesheng 
Published: June 2012

Abstract
NF-E2 related factor 2 (Nrf2) plays a pivotal role in cytoprotection against carcinogens and oxidants. Activating Nrf2 has been widely suggested as a key chemopreventive strategy against cancer and other diseases. Here, we show that Nrf2 faces a serious dilemma in dealing with 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other sources. ABP is metabolized/activated primarily in the liver. While Nrf2 significantly protected mouse liver against ABP in vivo, bladder DNA damage was approximately 2.6 fold higher in Nrf2+/+ mice than in Nrf2-/- mice after ABP exposure, as measured by dG-C8-ABP, the predominant ABP-DNA adduct formed in bladder cells and tissues. Interestingly, Nrf2 significantly protected bladder cells against ABP in vitro. Subsequent experiments revealed that UDP-glucuronosyltransferase (UGT) might be the principal, if not the only mediator of the dichotomous effects of Nrf2. Nrf2 upregulated UGT, promoted glucuronide conjugation of ABP in the liver, and increased urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is generally a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine and deliver the parent compounds to bladder. Hence, higher liver UGT activity may protect liver against ABP but increases bladder exposure to ABP. We further show that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT), a promising cancer chemopreventive dithiolethione, was able to significantly activate Nrf2 cytoprotective signaling and to inhibit dG-C8-ABP formation in the bladder in vivo, but did not modulate liver UGT expression. Thus, CPDT exemplifies a counteracting solution to the dilemma faced by Nrf2 with regard to ABP. In conclusion, our study shows that Nrf2 increases ABP genotoxicity in the bladder in vivo and that UGT may be the key mediator. Using CPDT, we also demonstrate how the adverse effect of Nrf2 may be mitigated.
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 1843. doi:10.1158/1538-7445.AM2011-1843
Abstract 2146: Role of apoptosis-inducing factor in the death of MDA-MB-231 breast carcinoma cells after DNA damage
Authors: Feng Xiaoxing , Zhou Yiran , Koh David W. 
Published: June 2012

Abstract
Apoptosis-inducing factor (AIF) is a flavoprotein that plays a cytoprotective role within mitochondria and induces cell death when it translocates to the nucleus in response to apoptotic signals. The objective of this study was to pursue the relevance of AIF in cancer. We showed that AIF translocated to the nucleus and mediated caspase-independent cell death in MDA-MB-231 breast cancer cells following treatment with the DNA alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). We utilized small interfering RNA (siRNA) to down-regulate AIF expression in various human cancer cell lines and mouse trophoblast stem (TS) cells. AIF levels were reduced approximately 90% compared to untransfected cells. Analysis of AIF levels after subcellular fractionations demonstrated that nuclear translocation was compromised in these AIF knockdown cells. FACS analysis showed that AIF knockdown protected MDA-MB-231 against apoptosis induced by the chemotherapeutic agent cyclophosphamide. Furthermore, siRNA knockdown of AIF increased MDA-MB-231 cell survival following UV radiation. Taken together, the results demonstrate a role for AIF in cancer cell death following radio- or chemotherapeutic treatments. Thus, the activation of AIF mediated cell death is a promising method to improve the treatment of breast cancer patients.
This research was supported by funding from the American Cancer Society and the Pharmaceutical Research Manufacturers of America.
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 2146. doi:10.1158/1538-7445.AM2011-2146