bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4636: AMF-1c-120: an antibody specific for misfolded prion protein expressed on ovarian cancer cells.
Authors: Uger Marni D. , Chai Viengthong , Ciolfi Veronica , Chen Hui , Plawinski Ewa , Mutukura Tapfuma , Sage Andrew , Demers Ryan , Lau Leo , Lee Pierre , Liu Xiuwen , Guan Jun , Wang Yuzhuo , Guest William C. , Plotkin Steven S. , Cashman Neil R. 
Published: August 2014

Abstract
We tested the hypothesis that cancer cells might display misfolded protein molecules at the cell surface, due to oxidative covalent modifications, defective glycosylation, and/or other factors relevant to cancer. We developed a computational algorithm to predict regions of proteins which were most likely to undergo loss of structure and resemble free unstructured peptides against which antibodies could be generated and screened. Antibodies directed against these misfolding-prone regions, termed disease-specific epitopes (DSEs), are therefore expected to recognize cancer cells while sparing natively folded proteins on healthy cells. We have applied this strategy to develop an antibody that is specific for ovarian cancer cells, which does not bind to normal ovarian epithelium. Using the ProMIS™ computational algorithm to predict unstable regions in proteins, three DSEs in the prion protein (PrP) were identified. Ultra-high sensitivity antibodies are required for binding to isolated misfolded protein molecules at the cell surface, and thus rabbits were immunized with peptides corresponding to the PrP DSE sequences and rabbit monoclonal anti-peptide antibodies were generated. One antibody, AMF-1c-120, has sub-nanomolar binding affinity for denatured PrP, but does not bind to native PrP. AMF-1c-120 binds to four ovarian tumor cell lines and one ovarian tumor implanted and propagated in mice, but does not bind to normal ovarian epithelial cells. Proteinase K sensitivity of the AMF-1c-120 epitope is consistent with partial denaturation of PrP at the cell surface of ovarian cancer cell lines. Preclinical efficacy studies are in progress to investigate the anti-tumor effects of AMF-1c-120.
Citation Format: Marni D. Uger, Viengthong Chai, Veronica Ciolfi, Hui Chen, Ewa Plawinski, Tapfuma Mutukura, Andrew Sage, Ryan Demers, Leo Lau, Pierre Lee, Xiuwen Liu, Jun Guan, Yuzhuo Wang, William C. Guest, Steven S. Plotkin, Neil R. Cashman. AMF-1c-120: an antibody specific for misfolded prion protein expressed on ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4636. doi:10.1158/1538-7445.AM2013-4636
Abstract 464: Tumor derived vacuolar ATPase subunit promotes M2 type polarization of macrophages.
Authors: Katara Gajendra K. , Jaiswal Mukesh K. , Gilmam-Sacks Alice , Beaman Kenneth D. 
Published: August 2014

Abstract
Tumors and tumor associated macrophages (TAMs) express a unique surface vacuolar ATPase (V-ATPase) on the plasma membrane. In tumor cells, a 20 kd peptide is cleaved from a2 isoform of V-ATPase and is referred to as a2NTD; it is associated with in vitro induction of pro-tumorigenic properties in monocytes and IL-β secretion. In this study, we evaluated the immuno-modulatory properties of a2NTD in inducing murine peritoneal macrophage polarization and activation of inflammasome components both ex vivo and in vivo. Peritoneal macrophages from BALB/c mice were stimulated with recombinant a2NTD and the mRNA and protein expression of M1 (CD11c, TNF-α), M2 (Mannose receptor-1, Arginase-1, IL-10) markers, IL-1β and NLRP3 (inflammasome marker) were analyzed using quantitative real time PCR and flow cytometry. Further, mice were injected with a2NTD i.p. and peritoneal cells were analyzed for M1/M2 specific markers. The results of both in vivo and ex vivo analysis showed an elevated population of M2 subtype in a2NTD-treated mice compared to control (P&lt;0.05). a2NTD upregulated the expression of IL-1β and NLRP3 in macrophages. These data demonstrated that a2NTD modulates macrophage polarization towards the M2 subtype functionally similar to tumor associated macrophages (TAMs). Since, tumor progression requires sterile inflammation and maturation of resident macrophages into TAMs; our data provide evidence that the surface expression of V-ATPase in tumor cells has a role in inducing the unique inflammatory environment of tumors by modulating macrophage phenotype and inducing IL-1β production through the action of a2NTD. The study also provides indication for the involvement of a2NTD in NLRP3 mediated inflammasome activation.
Citation Format: Gajendra K. Katara, Mukesh K. Jaiswal, Alice Gilmam-Sacks, Kenneth D. Beaman. Tumor derived vacuolar ATPase subunit promotes M2 type polarization of macrophages. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 464. doi:10.1158/1538-7445.AM2013-464
Abstract 4657: MET amplification as a potential therapeutic target in gastric cancer.
Authors: Kawakami Hisato , Okamoto Isamu , Arao Tokuzo , Okamoto Wataru , Matsumoto Kazuko , Taniguchi Hirokazu , Kuwata Kiyoko , Yamaguchi Haruka , Nishio Kazuto , Nakagawa Kazuhiko , Yamada Yasuhide 
Published: August 2014

Abstract
Purpose
Our aim was to investigate both the prevalence of MET amplification in gastric cancer as well as the potential of this genetic alteration to serve as a therapeutic target in gastric cancer.
Experimental Design
MET amplification was assessed by initial screening with a PCR-based copy number assay followed by confirmatory FISH analysis in formalin-fixed, paraffin-embedded specimens of gastric cancer obtained at surgery. The effects of MET tyrosine kinase inhibitors (MET-TKIs) in gastric cancer cells with or without MET amplification were also examined.
Results
The median MET copy number in 266 cases of gastric cancer was 1.7, with a range of 0.41 to 21.3. We performed FISH analysis for the 15 cases with the highest MET copy numbers. MET amplification was confirmed in the four assessable cases with a MET copy number of at least 4, whereas MET amplification was not detected in those with a gene copy number of &lt;4. The prevalence of MET amplification was thus 1.5% (4 out of 266 cases). Inhibition of MET by MET-TKIs resulted in the induction of apoptosis accompanied by attenuation of downstream MET signaling in gastric cancer cell lines with MET amplification but not in those without this genetic change.
Conclusion
MET amplification identifies a small but clinically important subgroup of gastric cancer patients who are likely to respond to MET-TKIs. Furthermore, screening with a PCR-based copy number assay is an efficient way to reduce the number of patients requiring confirmation of MET amplification by FISH analysis.
Citation Format: Hisato Kawakami, Isamu Okamoto, Tokuzo Arao, Wataru Okamoto, Kazuko Matsumoto, Hirokazu Taniguchi, Kiyoko Kuwata, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa, Yasuhide Yamada. MET amplification as a potential therapeutic target in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4657. doi:10.1158/1538-7445.AM2013-4657
Abstract 4695: Predictive role of FDG PET-CT in monitoring locally advanced rectal cancer (LARC) during preoperative radiochemotherapy with an experimental bevacizumab schedule.
Authors: Avallone Antonio , Delrio Paolo , Pecori Biagio , Tatangelo Fabiana , Di Gennaro Elena , Petrillo Antonella , Iaffaioli Vincenzo Rosario , Leone Alessandra , caracò Corradina , Budillon Alfredo , Lastoria Secondo , Aloj Luigi 
Published: August 2014

Abstract
Objectives : We have shown that pathological regression of LARC and relapse free survival can be predicted by early changes in FDG uptake during preoperative radiochemotherapy. We have attempted to improve efficacy of our neo-adjuvant treatment by adding an experimental bevacizumab (BEV) schedule. FDG PETCT was utilized to monitor response and correlate with pathological outcome.
Methods : Forty six patients with poor prognosis LARC received 3 biweekly courses of oxaliplatin/ raltitrexed (day 1) and FU/ folinic acid (day 2) during pelvic RT (45 Gy). BEV (5 mg/kg) was administered on day -4 for the first 2 courses. PET-CT was performed at baseline, on day 12 and prior to surgery and lesion TLG (mean SUV x volume) values determined. Pathologic response was defined using a modified Mandard tumor regression grade (TRG) scale. Responders were defined as TRG1-2, non-responders as TRG3-4.
Results : Thirty-seven patients (80%) showed pathologic response (65% with previous scheme). Eight patients (17%, previously 35%) were non-responders. Responders showed significantly higher TLG reduction on day 12 PET-CT (median -72% range -90%+31%) compared to non-responders (TRG3-4, median -38%, range -45% +25%, p &lt; 0.05), confirming previous findings. Preoperative PET-CT studies, on the other hand, were not predictive of pathologic response (responders TLG change median -92%, range -100% +4%, non-responders median 86%, range -94%-76%, p = ns). Ongoing studies to define a correlation between FDG uptake and biomarkers of angiogenesis such as Circulating endothelial cells (CEC) will be presented.
Conclusions : Our findings indicate that the current scheme significantly increases pathologic response. PET-CT confirms to be a powerful early surrogate marker of treatment efficacy. PET-CT may be used to tailor more aggressive treatment for non-responsive patient
Citation Format: Antonio Avallone, Paolo Delrio, Biagio Pecori, Fabiana Tatangelo, Elena Di Gennaro, Antonella Petrillo, Vincenzo Rosario Iaffaioli, Alessandra Leone, Corradina caracò, Alfredo Budillon, Secondo Lastoria, Luigi Aloj. Predictive role of FDG PET-CT in monitoring locally advanced rectal cancer (LARC) during preoperative radiochemotherapy with an experimental bevacizumab schedule. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4695. doi:10.1158/1538-7445.AM2013-4695
Abstract 4709: EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells in vitro.
Authors: Kumai Takumi , Harabuchi Yasuaki , Kobayashi Hiroya 
Published: August 2014

Abstract
Despite immunotherapy is a promising approach for cancer treatment, there are many obstacles remain to be overcome. The characteristics of tumor evasion of immune surveillance are produced by decreased expression of immune molecules and secretion of immunoregulatory cytokines. To break these tumor microenvironment which act as suppressor of antitumor immunology, we evaluated the value of EGFR inhibitors as immune-modulators. Following two days EGFR tyrosine kinase inhibitor treatment, expression of HLA-DR molecule of head and neck squamous cancer (HNSCC) cell lines were increased, meanwhile EGFR blocking antibody treatment augmented HLA-DR expression. Furthermore, EGFR inhibitors decreased spontaneous secretion of IL-8 and TGF-β from HNSCC cell lines. To confirm the immune supporting activity of EGFR inhibitors, tumor antigen specific CD4 helper T lymphocyte (HTL) responses to EGFR-expressing tumor were investigated. We identified novel EGFR HTL epitope using MHC class II binding algorithms. The candidate EGFR peptide elicited HTL responses against EGFR-expressing HNSCC in vitro. The EGFR peptide shares high homology to HER2, HER-3 and c-Met, so that these were able to stimulate EGFR peptide reactive HTLs responses in a HLA-DR restricted manner indicating that the EGFR peptide serves a universal tumor-associated peptide in HER family and c-Met. Finally, we evaluated EGFR reactive HTL responses against HNSCC cell lines treated with EGFR inhibitors. As a result, EGFR inhibitors drastically increased HTL IFN-γ production and cytotoxic response. Since HER family and c-MET have been considered as targets of alternative pathway of EGFR inhibition, therapeutic strategy combining EGFR inhibitors with novel HTL epitope identified in this study might be attractive option for antitumor immunotherapy.
Citation Format: Takumi Kumai, Yasuaki Harabuchi, Hiroya Kobayashi. EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4709. doi:10.1158/1538-7445.AM2013-4709
Abstract 4712: Chemotherapy-enhanced NFkB pathway activation in gynecological cancers increases the differentiation of monocytes to M2 macrophages instead of dendritic cells.
Authors: Van Der Burg Sjoerd H. , Dijkgraaf Eveline M. , Welters Marij J.P. , Kroep Judith R. 
Published: August 2014

Abstract
Current therapy of gynecological malignancies consists of platinum-containing chemotherapy. Resistance to therapy is associated with increased levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2), two inflammatory mediators known to skew differentiation of monocytes to tumor-promoting M2 macrophages. We investigated the impact of cisplatin and carboplatin on 10 different cervical and ovarian cancer cell lines as well as on the differentiation and function of monocytes cultured in the presence of these tumor cells in vitro. Treatment with cisplatin or carboplatin increased the potency of tumor cell lines to induce IL10-producing M2 macrophages which displayed increased levels of activated signal transducer and activator of transcription-3 (STAT3) due to tumor-produced IL-6 as well as decreased levels of activated STAT1 and STAT6 related to the PGE2-production of tumor cells. Blockade of canonical NFκB signaling showed that the effect of chemotherapy depended on the enhanced activation of the NFκB pathway and subsequent increased production of PGE2 and IL-6 by tumor cell lines originally producing these factors. Treatment with cyclooxygenase (COX)-inhibitor indomethacin and/or the clinical monoclonal antibody against IL-6 receptor (IL-6R), tocilizumab, prevented M2-differentiation. Importantly, no correlation existed between the production of PGE2 or IL-6 by cancer cells and their resistance to chemotherapy induced death, indicating that other mechanisms underlie the reported chemoresistance of tumors producing these factors. Our data suggests that a chemotherapy-mediated increase in tumor-promoting M2 macrophages may form an indirect mechanism for chemoresistance. Hence, concomitant therapy with COX-inhibitors and/or IL-6R antibodies might increase the clinical effect of platinum-based chemotherapy in otherwise resistant tumors.
Citation Format: Sjoerd H. Van Der Burg, Eveline M. Dijkgraaf, Marij J.P. Welters, Judith R. Kroep. Chemotherapy-enhanced NFkB pathway activation in gynecological cancers increases the differentiation of monocytes to M2 macrophages instead of dendritic cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4712. doi:10.1158/1538-7445.AM2013-4712
Abstract 4726: Phagocytic regulation through exogenous caffeine exposure in whole-blood macrophages.
Authors: Steck Ryan , Gustafsson Marcus , Liu PingGuo , Elnaggar Atif , Robison Richard A. , O'Neill Kim L. 
Published: August 2014

Abstract
Caffeine is the most widely used neurostimulant in the world, and it has been shown that 79% of the United States population drinks coffee at least occasionally. Previous research has suggested that caffeine may be involved in the regulation of phagocytosis in immune cells through anti-inflammatory and pro-inflammatory signals. To investigate this effect, we used a macrophage engulfment assay, which was optimized in our lab to measure phagocytosis after exogenous caffeine exposure. Human leukocytes were isolated and incubated to allow for monocyte differentiation. After being allowed to differentiate for 1hr, 24hrs, 3-days, or 7-days, macrophages were incubated with varying concentrations of caffeine (35 μM-20 mM) for 1-24 hours. Cells were treated with lipopolysaccharide, and then incubated for 2 hours with fluorescently-labeled microspheres conditioned by incubation with fetal bovine serum. Engulfment was measured using flow cytometry, indicating the phagocytosis of microspheres in integral ratios. It was observed that engulfment was dependent on cell differentiation time, as well as caffeine concentration and exposure time. After &lt;12 hour differentiation, cells exposed to caffeine showed a concentration-dependent reduction in engulfment when compared to those that were not treated. During incubation for 12 - 72 hours, however, results showed a 20% down-regulation of engulfment at &lt;5 mM caffeine, whereas those cells exposed to 5-10 mM caffeine exhibited a 20% higher-engulfing phenotype, compared to the controls. At caffeine concentrations above 10 mM cell viability and engulfment was decreased up to 50%. It was concluded that the effect of caffeine on macrophages is dependent on incubation time and concentration, as well as the state of macrophage differentiation. Because of the implications of macrophage phenotype in many diseases involving inflammation, including cancer, these findings suggest further research should be continued to explore the therapeutic potential of caffeine and/or its analogs.
Citation Format: Ryan Steck, Marcus Gustafsson, PingGuo Liu, Atif Elnaggar, Richard A. Robison, Kim L. O'Neill. Phagocytic regulation through exogenous caffeine exposure in whole-blood macrophages. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4726. doi:10.1158/1538-7445.AM2013-4726
Abstract 4777: Cytomegalovirus infection leads to pleomorphic rhabdomyosarcomas in Trp53 +/- mice.
Authors: Price Richard L. , Bingmer Katherine , Harkins Lualhati , Iwenofu Hans , Kwon Chang-Hyuk , Cook Charles , Pelloski Christopher , Chiocca E Antonio 
Published: August 2014

Abstract
Despite not being considered oncogenic, cytomegalovirus (CMV) has been detected in an increasing number of malignancies. However, recent studies have suggested mechanisms through which CMV may modulate the tumor environment, encouraging its study as a positive modifier of tumorigenesis. In this study, we investigated the effects of CMV infection in Trp53 heterozygous mice. Animals were infected with murine CMV (MCMV) after birth at 2 days (P2) or 4 weeks of age via intraperitoneal injection and then monitored for tumor formation. Additional control cohorts were mock-infected (saline vehicle) or infected with HSV-1, a similar herpes virus. Following MCMV infection, widespread systemic infection ensued followed by immune clearance of the virus resulting in seroconversion. Mice infected at P2 developed tumors at a high frequency (43%) by 9 months of age. In contrast, only 3% of mock-infected or mice infected at 4 weeks developed tumors. The majority of tumors from P2 MCMV-infected mice were pleomorphic rhabdomyosarcomas (RMS) as evidenced by MyoD1, Desmin, and Myogenin staining. Importantly, MCMV-infected tumors contained MCMV DNA, RNA, and protein. An examination of clinical cases revealed that human RMS (embryonal, alveolar, and pleomorphic) harbored human CMV IE1 and pp65 protein as well as viral RNA. All of the cases (n=18) tested positive for CMV genetic material. CMV protein was found throughout the tumor including pleomorphic cells. Additionally, perivascular areas demonstrated intense staining consistent with other reports of linking CMV with angiogenesis. To confirm the selective presence of HCMV DNA in human RMS, quantitative PCR analysis showed that tumors expressed an average of 81.1 copies/ng of HCMV-UL83 and of 22.2 copies/ng of HCMV-UL146 compared to 0 and 0.49 copies/ng in normal muscle, respectively. The amplified products’ nucleotide sequence was greater than 95% identical to that of a clinical strain Taken together, our findings offer support for the hypothesis that CMV contributes to the development of pleomorphic RMS in the context of Trp53 mutation, a situation which occurs with high frequency in human RMS.
Citation Format: Richard L. Price, Katherine Bingmer, Lualhati Harkins, Hans Iwenofu, Chang-Hyuk Kwon, Charles Cook, Christopher Pelloski, E Antonio Chiocca. Cytomegalovirus infection leads to pleomorphic rhabdomyosarcomas in Trp53 +/- mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4777. doi:10.1158/1538-7445.AM2013-4777
Abstract 4779: HERV-K env plays important roles in cell proliferation, migration and tumor progression in melanoma.
Authors: Li Ming , Johanning Gary L. , Wang-Johanning Feng 
Published: August 2014

Abstract
Human endogenous retroviruses (HERVs) are remnants from ancient retroviral infections, and most of them are inactive in normal tissues. However, one family of HERV, HERV-K, is reportedly active in several cancers, including melanoma. Increased expression of HERV-K in melanoma cells correlates with malignant transformation, while a serological response to HERV-K in melanoma patients correlates with survival probability. The mechanism behind these observations remains obscure. Our group reported that anti-HEEV-K envelope (env) protein antibodies shows antitumor potential in targeting breast tumors, indicating that HERV-K env may play an important role in tumorigenesis. In this study, we produced a cell line derived from melanoma cell line A375, in which the expression of HERV-K env was stably knocked down by a lentivector based shRNA. Compared to the control cells, these cells exhibit lower proliferation/migration/invasion rates and lower tumorigenicity in vitro. In vivo, their tumorigenic potential was found to be reduced after inoculation into NOD/SCID gamma mice. Moreover, results of antibody array, RNAseq and Western blotting indicate that altered HERV-K env expression led to changes in expression of several proteins important in oncogenesis and metastasis. These results suggest that HERV-K env plays specific and important roles in melanoma carcinogenesis.
Citation Format: Ming Li, Gary L. Johanning, Feng Wang-Johanning. HERV-K env plays important roles in cell proliferation, migration and tumor progression in melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4779. doi:10.1158/1538-7445.AM2013-4779