bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4692: Local adjuvant treatment of clinical stage I-II melanoma with low dose CpG-B and/or GM-CSF: Long-term follow-up of three randomized controlled phase II trials
Authors: Koster Bas D. , Hout Mari F. van den , Sluijter Berbel J. , Molenkamp Barbara G. , Vuylsteke Ronald J. , Baars Arnold , Leeuwen Paul A. van , Scheper Rik J. , Tol Monique P. van den , Eertwegh Alfons J. van den , Gruijl Tanja D. de 
Published: July 2017

Abstract
Introduction: Currently, there is no widely used adjuvant treatment available to improve survival after surgical excision of localized melanoma. Here, we present the clinical outcome of patients who participated in three randomized phase-II trials and received low-dose local immunotherapy, which was shown to be safe and to boost loco-regional and systemic anti-melanoma T cell immunity.
Patients and Methods: In three single-center, single-blinded, randomized and placebo (saline) controlled phase-II clinical trials, patients with early stage melanoma were treated with 1) Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF), 2) unmethylated CpG type-B oligodeoxynucleotide CpG7909 (CpG-B), and 3) CpG-B, alone or combined with GM-CSF, through 1-4 intradermal injections at the site of the primary melanoma excision scar, within 7 days preceding re-excision and sentinel lymph node (SLN) biopsy. For clinical follow-up analysis, all treated patients were grouped together (treated group n=36) as were the patients who received saline (saline group n=28).
Results: 10-year recurrence-free survival rate in the treated group was 94% (95% CI 78-98) versus 48% (95% CI 21-71) in the saline group (P=0.005), hazard ratio (HR) for recurrence was 0.15 (95% CI 0.06-0.60) for the treated group. This apparent antitumor efficacy was in line with the observation upon pathological examination of less tumor positive SLN in the treated group (P=0.05). The 10-year distant recurrence-free survival rate in treated patients was also higher (94%, 78-98 versus 59%, 28-81, HR 0.22, 0.07-0.93; P=0.04).
Conclusion: Local low-dose immunotherapy in patients with early-stage melanoma may offer durable protection against distant recurrences. These findings warrant further clinical exploration of this local non-toxic immune potentiating regimen.
Citation Format: Bas D. Koster, Mari F. van den Hout, Berbel J. Sluijter, Barbara G. Molenkamp, Ronald J. Vuylsteke, Arnold Baars, Paul A. van Leeuwen, Rik J. Scheper, Monique P. van den Tol, Alfons J. van den Eertwegh, Tanja D. de Gruijl. Local adjuvant treatment of clinical stage I-II melanoma with low dose CpG-B and/or GM-CSF: Long-term follow-up of three randomized controlled phase II trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4692. doi:10.1158/1538-7445.AM2017-4692
Abstract 4700: Poly G oligonucleotide enhances anti-tumor immune response among the patients with primary lung cancer
Authors: Kobayashi Nobuaki , Shibata Yuji , Yamamoto Masaki , Sato Takashi , Shinkai Masaharu , Koizumi Harumi , Takahashi Kenichi , Kudo Makoto , Shirota Hidekazu , Kaneko Takeshi 
Published: July 2017

Abstract
Synthetic oligonucleotides (ODNs) containing specific sequences have an immunomodulatory effect. It is highly expected that such ODNs can be developed into a novel anti-cancer immunotherapy with these effects. Our past data revealed that a novel poly-G ODN has an anti-tumor immune effect in the tumor-bearing murine model. This effect of poly-G ODN was mediated by T cells in a TLR9 independent manner. Poly-G ODN directly induced the phosphorylation of Lck, thereby enhancing the production of IL-2 and T cell proliferation. Meanwhile, our recent data suggested that the immune effect by poly-G ODN against cancer was different in human. We identified poly-G ODN induced T cell proliferation and production of IFN-gamma through the enhancement of monocyte maturation in human mononuclear cells isolated from peripheral blood or malignant pleural effusion of lung cancer patients. Further studies are continued for the establishment of a novel anti-cancer immune therapy with poly-G ODN.
Citation Format: Nobuaki Kobayashi, Yuji Shibata, Masaki Yamamoto, Takashi Sato, Masaharu Shinkai, Harumi Koizumi, Kenichi Takahashi, Makoto Kudo, Hidekazu Shirota, Takeshi Kaneko. Poly G oligonucleotide enhances anti-tumor immune response among the patients with primary lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4700. doi:10.1158/1538-7445.AM2017-4700
Abstract 4724: Combined clinical and biological risk stratification in pediatric hepatoblastoma
Authors: Cairo Stefano , Armengol Carolina , Häberle Beate , Simon-Coma Marina , Guettier Catherine , Leuschner Ivo , Buendia Marie-Annick , Schweinitz Dietrich von , Kappler Roland 
Published: July 2017

Abstract
Introduction Advances in chemotherapy and surgery have greatly improved overall survival rates of children with hepatoblastoma (HB). However, prognosis still remains quite poor for HB patients with high risk characteristics such as portal/hepatic venous macrovascular involvement, extrahepatic growth, high extent of the disease, and metastasis, as shown by studies of the International Childhood Liver Tumours Strategy Group (SIOPEL). The aim of our trinational study was to validate recently identified genetic and transcriptional characteristics of HB as prognostic biomarkers to aid development of a new risk stratification system based on clinical and biological factors.
Experimental procedures Tumor tissue of a cohort of 171 hepatoblastoma patients from Germany, France and Spain was analyzed for mutations in CTNNB1, NFE2L2 and TERT (Eichenmüller et al., J Hepatol 2014; 61:1312-1320) by Sanger sequencing and the 16-gene signature (Cairo et al., Cancer Cell 2008; 14:471-84) by real-time PCR. Kaplan-Meier estimates of specific survival time in the various groups were compared using the log-rank Mantel-Cox test.
Results Mutations of CTNNB1, NFE2L2, and TERT were found in 133 (78%), 10 (6%), and 10 (6%) patients, respectively. The adverse C2 subtype of the 16-gene signature was detected in 60 (35%) patients. Kaplan-Meier analyses depicted a significant association of the 16-gene signature (P&lt;0.0001) and NFE2L2 mutations (P&lt;0.0166) with poor outcome. Stratifying the patients of our cohort into a standard and high risk group based on the commonly used clinical SIOPEL criteria (Zsiros et al., J Clin Oncol 2010; 28:2584-2590) also revealed a strong association (P&lt;0.0001) of the high risk group with poor outcome. When added to the SIOPEL risk groups, presence of at least one biomarker could discriminate the SIOPEL high risk patients into an intermediate and a very high risk group (P&lt;0.0001), whereas biomarker positive and negative standard risk patients showed no difference in outcome.
Conclusions We have validated the 16-gene signature and NFE2L2 mutations as highly prognostic biomarkers in HB and propose a new stratification system that is based on the combination of clinical and biological factors, which might facilitate more tailored and risk-adapted therapies and thus better outcome of high risk patients in the future.
Citation Format: Stefano Cairo, Carolina Armengol, Beate Häberle, Marina Simon-Coma, Catherine Guettier, Ivo Leuschner, Marie-Annick Buendia, Dietrich von Schweinitz, Roland Kappler. Combined clinical and biological risk stratification in pediatric hepatoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4724. doi:10.1158/1538-7445.AM2017-4724
Abstract 4741: Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in pediatric osteosarcoma
Authors: Nakka Manjula , Allen-Rhoades Wendy , Li Yiting , Kelly Aaron , Shen Jianhe , Taylor Aaron , Barkauskas Donald A. , Yustein Jason , Andrulis Irene , Wunder Jay , Gorlick Richard , Meltzer Paul , Lau Ching , Man Tsz-Kwong 
Published: July 2017

Abstract
Osteosarcoma is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, osteosarcoma patients who respond poorly towards chemotherapy or develop relapses have a dismal outcome. Identification of biomarkers for active disease may help to monitor tumor burden, detect early relapses, and predict prognosis in these patients, so that they can be treated as early as possible to improve their survival. In this study, we examined if circulating microRNAs (miRNAs) can be used as biomarkers in osteosarcoma patients. We performed genome-wide miRNA profiling on a discovery cohort of OS plasma samples (n=32) collected from the Texas Children’s Hospital. A total of 56 miRNAs were upregulated and 164 miRNAs were downregulated in osteosarcoma samples when compared to normal plasma samples (n=8). miRNA-21, miR-221 and miRNA-106a were selected for further validation based on their known biological importance. We showed that all three circulating miRNAs were expressed significantly higher in OS samples (n=29) than normal samples (n=17) in an independent cohort obtained from the Children’s Oncology Group. Furthermore, we demonstrated that miR-21 was expressed significantly higher in osteosarcoma tumors (n=89) compared with normal bone controls. More importantly, lower expressions of miR-21 and miR-221, but not miR-106a, significantly correlated with a poor outcome. In conclusion, our results indicate that miR-21, miR-221 and miR-106a are elevated in the circulation of osteosarcoma patients, whereas tumor expressions of miR-21 and miR-221 are prognostically significant. Further investigation of the miRNAs may lead to a better prognostic method and potential miRNA therapeutics for osteosarcoma.
Citation Format: Manjula Nakka, Wendy Allen-Rhoades, Yiting Li, Aaron Kelly, Jianhe Shen, Aaron Taylor, Donald A. Barkauskas, Jason Yustein, Irene Andrulis, Jay Wunder, Richard Gorlick, Paul Meltzer, Ching Lau, Tsz-Kwong Man. Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in pediatric osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4741. doi:10.1158/1538-7445.AM2017-4741
Abstract 4755: Calpastatin phosphorylation regulates radiation response in glioblastoma
Authors: Bassett Emily A. , Pearson Mitchell , Palanichamy Kamalakannan , Haque Saikh J. , Chakravarti Arnab 
Published: July 2017

Abstract
Glioblastoma (GBM) is the most prevalent and aggressive primary malignant brain tumor in adults. Patients diagnosed with GBM have a very poor prognosis and quality of life, with a median survival time of 12-15 months despite receiving the standard of care treatment. GBMs are highly heterogeneous, invasive, and resistant to both chemo- and radio-therapy. The overall goal of this study is to identify novel mechanisms of radioresistance in GBM, so that more effective therapies can be developed in the future. We performed quantitative mass spectrometry-based phosphoproteomic profiling of GBM cell lines before and after radiation treatment, and determined post-radiation fold-changes in phosphorylation for each phosphopeptide. Results show calpastatin as one of the statistically significant differentially regulated phosphopeptides following radiation treatment. Calpastatin is an endogenous inhibitor of calpains, which are calcium-dependent cysteine proteases that control a wide range of cellular processes including cell survival and apoptosis. We hypothesized that phosphorylation inactivates calpastatin resulting in increased calpain activity. Western blot analyses with phospho-specific calpastatin antibodies validated the mass spectrometry results. In order to test the functional significance of phosphorylated calpastatin, we utilized site-directed mutagenesis to generate non-phosphorylatable and phospho-mimetic calpastatin proteins. Western blot analyses of U87 cells stably expressing CAST-S633A or -S633E supported the hypothesis that calpastatin phosphorylation leads to increased calpain activity. In conclusion, we identified increased levels of calpastatin phosphorylation in multiple GBM cell lines following radiation treatment, and shown that this correlates with increased calpain activity. Modulation of calpastatin activity is a potential strategy to increase radiosensitivity of glioblastomas. Targeting calpastatin is advantageous over targeting calpain itself, since many calpain inhibitors exhibit limited selectivity. Results of this study will contribute to our understanding of how GBM tumors become resistant to radiation therapy. Funding: R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).
Citation Format: Emily A. Bassett, Mitchell Pearson, Kamalakannan Palanichamy, Saikh J. Haque, Arnab Chakravarti. Calpastatin phosphorylation regulates radiation response in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4755. doi:10.1158/1538-7445.AM2017-4755
Abstract 4758: Sensitization of nasopharyngeal carcinoma to radiotherapy by targeting GFPT1/TGF-β1 signaling pathways
Authors: Chen Siqi , Gao Wei , Chan Jimmy Yu-Wai , Wong Thian-Sze 
Published: July 2017

Abstract
Background: Nasopharyngeal carcinoma (NPC) is a unique cancer with high susceptibility to radiation and mainstay treatment is radiotherapy. Effectiveness of NPC treatment is therefore dependent on the sensitivity of cancer cells to ionizing radiation treatment. Further, development of radio-resistant phenotype is a risk factor for distant metastasis and disease recurrence. Therefore, enhancing the degree of radiation sensitivity could improve prognosis and reduce the toxicity of radiotherapy with the use of lower radiation dose. Transforming growth factor β1(TGF-β1) expression is responsive to radiation treatment and the increase is important in the post-irradiation DNA repair. Tumor with low TGF-β1 level is more responsive to radiation treatment. Therefore, inhibiting TGF-β1 production can enhance the radiation damage to cancer cell DNA and also intensify the sensitivity of cancer cells to radiation. Our preliminary results indicate that TGF-β1 production in NPC is mediated by hexosamine pathway. Of which, GFPT1 (glucosamine-fructose-6-phosphate aminotransferase) is the rate-limiting enzyme.
Purpose of the study: To enhance radiation sensitivity by targeting GFPT1/ TGF-β1 cascade in NPC.
Experimental procedures: Radiation protective effects of TGF-β1 was examined by colony formation assay and Danio rerio (zebrafish) embryonic system. Production of TGF-β1 by activated hexosamine pathway in NPC was revealed by glucose and glucosamine treatment. Effects of GFPT1 silencing on radiosensitization are revealed by GFPT1 siRNA treatment followed by colony formation assay and gamma-H2AX formation assays.
Results: Pretreatment of HONE1 cells with recombinant TGF-β1 protein enhanced the clonogenic ability of irradiated cells. TGF-β1 significantly increased the survival of zebrafish embryos after irradiation. Glucose and glucosamine treatment increased the expression of TGF-β1 protein in HONE1 cells. Silence of GFPT1 reduced TGF-β1 mRNA and protein expression in HONE1 cells. Silencing GFPT1 reduced the clonogenic capacity of head and neck cancer cells after radiotherapy and enhanced the degree of radiation-induced DNA double-strand breaks.
Conclusions: Targeting GFPT1 enhances head and neck cancer cell sensitivity to radiation. GFPT1 inhibition can enhance the radiation sensitivity of head and neck cancer cells by inhibiting the expression of TGF-β1.
Citation Format: Siqi Chen, Wei Gao, Jimmy Yu-Wai Chan, Thian-Sze Wong. Sensitization of nasopharyngeal carcinoma to radiotherapy by targeting GFPT1/TGF-β1 signaling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4758. doi:10.1158/1538-7445.AM2017-4758
Abstract 4767: Identifying CDCA7 as a novel regulator of tumor-initiating cells in triple-negative breast cancer
Authors: Lin Chang-Ching , Lo Miao-Chia , Moody Rebecca , Stevers Nicholas , Tinsley Samantha , Wicha Max , Sun Duxin 
Published: July 2017

Abstract
Tumor-initiating cells (TICs) are a small fraction of cancer cells that stands at the apex of the tumor hierarchy. Given their tumor-initiating ability and resistance to conventional chemotherapies, TICs are considered potential therapeutic targets for preventing the relapse and metastasis of malignancies. Our group has identified a novel gene, Cell division cycle associated 7 (CDCA7), as an important regulator of TICs in triple-negative breast cancer (TNBC). CDCA7 is a target gene of MYC and NOTCH. Ectopic expression of CDCA7 has been demonstrated to induce neoplastic transformation in vitro and tumorigenesis in vivo. Despite its potential tumor-initiating ability, CDCA7 has not yet been well-studied in breast cancer. We found that CDCA7 was highly expressed in TNBC compared to other subtypes of breast cancer according to the RNA-sequencing data from The Cancer Genome Atlas. Furthermore, our Kaplan-Meier analysis of multiple datasets demonstrated that higher expression of CDCA7 was associated with poor prognosis in breast cancer. When we knocked down CDCA7 by siRNA in TNBC cell lines including SUM149, HCC1937, MDA-MB-231, and MDA-MB-436, CD44+/CD24- stem-like cell population and primary and secondary mammosphere formation were significantly decreased. In addition to suppressing the stem-like properties, knockdown of CDCA7 also inhibited the invasion and migration of breast cancer cells. These phenotypes indicated the inhibition of epithelial-to-mesenchymal transition (EMT), which was in accordance with the up-regulation of E-Cadherin and down-regulation of Vimentin after CDCA7 knockdown in TNBC cell lines. In conclusion, our results have demonstrated that CDCA7 is an important regulator of TICs in TNBC. Loss-of-function of CDCA7 leads to the inhibition of EMT and stemness in TNBC cells.
Citation Format: Chang-Ching Lin, Miao-Chia Lo, Rebecca Moody, Nicholas Stevers, Samantha Tinsley, Max Wicha, Duxin Sun. Identifying CDCA7 as a novel regulator of tumor-initiating cells in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4767. doi:10.1158/1538-7445.AM2017-4767
Abstract 4777: Cancer stemness and resistance: Napabucasin (BBI-608) sensitizes stemness-high cancer cells to Paclitaxel by inhibiting the STAT3-MUC1 pathway
Authors: Rogoff Harry A. , Li Juying , Li Chiang 
Published: July 2017

Abstract
Stemness-high cancer cells, or cancer stem cells (CSC) represent a subpopulation of cancer cells with enhanced tumorigenic capacity, metastasis-forming potential, and resistance to conventional chemotherapy and radiation. One such key CSC pathway is regulated by STAT3, a transcription factor that is downstream of several cytokines and growth factor receptors which controls the expression of a broad range of target genes and plays essential roles in CSC biology in many tumor types. Cancer stemness inhibitor Napabucasin (BBI-608), a small molecule that inhibits gene transcription driven by STAT3, can inhibit stemness gene expression, block spherogenesis, and kill CSCs. In vivo, BBI-608 effectively blocks cancer relapse and metastasis in xenograft models while sparing normal hematopoietic stem cells, suggesting that targeting stemness-high cancer cells is a feasible approach for developing next-generation cancer therapeutics to combat cancer recurrence.
SOX2 (sex-determining region Y-box protein 2), a transcription factor that is essential for self-renewal and pluripotency, is amplified in various cancer types and has been shown to be required for CSC self-renewal and maintenance. Mucin 1 (MUC1), a glycoprotein normally expressed at the apical surface of epithelial cells, is overexpressed in most human epithelial cancers. MUC1 has been implicated in regulating tumor proliferation, metabolism, invasion, angiogenesis, chemoresistance, and inflammation.
Here, we generated a stemness-high culture system based on the reporter activity of a SOX2-regulatory region construct in MKN28 gastric cancer cells (MKN28 SOX2-reporter GFP+ cells). BBI-608 treatment inhibited the STAT3-MUC1 pathway in stemness-high cells. High MUC1 status in stemness-high cells was associated with Paclitaxel resistance. Down-regulation of MUC1 sensitized stemness-high cells to Paclitaxel. Moreover, BBI-608 synergized with Paclitaxel in inhibiting spherogenesis of stemness-high cells. This study provides a new mechanism for the association of cancer stemness with drug resistance. Our findings support this combination therapy, which pairs a conventional chemotherapy (Paclitaxel) with a cancer stemness inhibitor (BBI-608), as a promising strategy to combat cancer.
Citation Format: Harry A. Rogoff, Juying Li, Chiang Li. Cancer stemness and resistance: Napabucasin (BBI-608) sensitizes stemness-high cancer cells to Paclitaxel by inhibiting the STAT3-MUC1 pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4777. doi:10.1158/1538-7445.AM2017-4777
Abstract 4788: Abraxane eliminates cancer stem cells in triple-negative breast cancers
Authors: Yuan Hebao , Guo Hongwei , Li Feng , Burnett Joseph , He Miao , Truchan Nathan , Myers Ila , Sun Duxin 
Published: July 2017

Abstract
Triple-negative breast cancer (TNBC) represents about 20 percent of all breast cancers, with a poorer survival rate and being associated with high-grade tumors and the least favorable prognosis. Due to the absence of hormone receptors and Her2 receptor, no targeted therapy is available and chemotherapy is the standard treatment for TNBC patient. Paclitaxel is a widely used chemotherapy drug for various cancers with severe side effects due to its solvent. Abraxane is an albumin-bound nanoparticle of paclitaxel with less severe side effects.
Here we investigated whether cancer stem cells (CSCs) in TNBC response differentially to abraxane and paclitaxel both in cell culture and xenograft mouse models.
Using a series of human TNBC cell lines, we showed that there is no difference between solvent-based paclitaxel and abraxane in vitro in term of efficacy and eliminating cancer stem cells using MTS assay, mammosphere formation assay, and flow analysis of cancer stem cells. Interestingly, we demonstrated that abraxane shows superior efficacy than solvent-based paclitaxel in human SUM149 xenograft NOD SCID mouse model in adjuvant treatment. More important, we demonstrated that abraxane eliminates cancer stem cells in xenograft NOD SCID mouse model in advanced treatment, while solvent-based paclitaxel increases cancer stem cells. Cell uptake assay indicated that TNBC cells take more abraxane than solvent-based paclitaxel, which partially attributes to its superior efficacy in xenograft mouse models. Taken together, our data confirmed that abraxane is superior to solvent-based paclitaxel and may be a better option for TNBC patients in adjuvant or metastatic treatment.
Citation Format: Hebao Yuan, Hongwei Guo, Feng Li, Joseph Burnett, Miao He, Nathan Truchan, Ila Myers, Duxin Sun. Abraxane eliminates cancer stem cells in triple-negative breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4788. doi:10.1158/1538-7445.AM2017-4788