bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1767: Analysis of biomarkers and anthracycline benefit for hormone receptor-negative breast cancer: results from a randomized phase 2 neoadjuvant study (KBOG 1101 Study)
Authors: Ishikawa Takashi , Narui Kazutaka , Oba Mari S. , Yamada Akimitsu , Kida Kumiko , Tanabe Mikiko , Ichikawa Yasushi 
Published: July 2017

Abstract
AIM: We compared 6 cycles of docetaxel and cyclophosphamide (TC6) with 3 cycles of 5-fluorouracil and epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FEC-D) as neoadjuvant chemotherapy for patients with hormone receptor (HR)-negative breast cancer (BC) to identify biomarkers requiring anthracycline treatment.
Methods: In total, 103 patients with operable HR-negative BC were administered TC6 or FEC-D. Triple-negative BC was subdivided by CK5/6 and EGFR into basal- and non-basal BCs. The primary endpoint was pathological complete response (pCR). Secondary endpoints were safety, breast-conserving surgery ratio, disease-free survival, overall survival, and predictive factors (Ki-67, P-53, ALDH1 and TOP2A by IHC and TOP2A by FISH) for each regimen.
Results: Of the 103 patients, 97 completed the study. Overall pCR was higher for patients treated with FEC-D (36%) than for those treated with TC6 (25.5%) (P=0.265). FEC-D was significantly superior to TC6 in basal BC (42.9% vs 13.6%; P=0.033), while no differences in HER2 and non-basal BCs. Aldehyde dehydrogenase 1 (ALDH1) positivity was inversely associated with pCR for both regimens, significantly for FEC-D (FEC-D: p=0.047, TC6: p=0.085). Patients who achieved pCR tended to have longer DFS (P = 0.287) and OS (P = 0.069). Patients with basal and non-basal BC treated with FEC-D had significantly better DFS (P = 0.016) and OS (P = 0.034) than those with TC6.
Conclusion: We found TC6 was less effective than FEC-D for HR-negative BC because it was not sufficient to treat basal-BC. This suggests that DNA damaging agents like anthracyclines are required for treating basal-BC. Additionally, ALDH1 could be a marker for resistance to conventional chemotherapy.
Citation Format: Takashi Ishikawa, Kazutaka Narui, Mari S. Oba, Akimitsu Yamada, Kumiko Kida, Mikiko Tanabe, Yasushi Ichikawa. Analysis of biomarkers and anthracycline benefit for hormone receptor-negative breast cancer: results from a randomized phase 2 neoadjuvant study (KBOG 1101 Study) [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 1767. doi:10.1158/1538-7445.AM2017-1767
Abstract 177: Thymidine quinoxaline conjugates as a novel selective and effective photosensitizer for anticancer photodynamic therapy
Authors: Zhou Qibing , Wang Zhiwei , Yang Rong , Qian Ting , Zhang Dejun 
Published: July 2017

Abstract
Thymidine quinoxaline conjugates are a new class anticancer agent that exhibits selective anticancer activity by targeting the abnormally high level of thymidine kinase of the thymidine salvage pathway in cancer cells. In addition, the conjugated quinoxaline moiety could also act as a photosensitizer to generate reactive oxygen species that would significantly enhance the anticancer activity. Therefore, a variety of structural derivatives were synthesized and investigated for the potential of combined anticancer activity. We found that the thymidine moiety was critical for the accumulation of compounds in cancer cells and thus their activity. On the other hand, the substitutions and additional conjugation of quinoxaline moiety had significant impact on the effectiveness to generate reactive oxygen species for enhanced potency. Among all the compounds studied, dT-QP exhibited a potent activity against liver cancer cells with IC50 at 20 nM under photo-irradiation at 400 nm wavelength for 20 min. This potent activity of dT-QP was 12 times more effective than that of the clinically used photosensitizer protoporphyrin IX (IC50 at 250 nM) under the same condition and 5 times more potent than anticancer drug doxorubicin (IC50 at 100 nM). In addition, thymidine quinoxaline conjugates were found to form aggregates with an average size of 200 nm. Further optimization of the aggregating condition led to a highly stable suspension of 90 nm size nanoparticles containing a tumor-specific peptide that could be used for in vivo study. Therefore, thymidine quinoxaline analogs could be a selective anticancer agent and effective photosensitizer for potential photodynamic therapy.
Citation Format: Qibing Zhou, Zhiwei Wang, Rong Yang, Ting Qian, Dejun Zhang. Thymidine quinoxaline conjugates as a novel selective and effective photosensitizer for anticancer photodynamic therapy [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 177. doi:10.1158/1538-7445.AM2017-177
Abstract 1790: Evaluation of UCK2 protein expression as a potential predictive biomarker of RX-3117
Authors: Lee Young Bok B. , Kim Deog J. , George Christina , Ahn Chang-ho , Frank Julie , Mazhari Reza , Dauffenbach Lisa M. , Olsen Eric P. 
Published: July 2017

Abstract
Background: A novel, orally bioavailable nucleoside analogue, RX-3117, is a prodrug activated intracellularly by Uridine Cytidine Kinase 2 (UCK2) that is thought to be expressed predominantly in tumor tissue. RX-3117 is currently being evaluated in a Phase Ib/IIa multi-center, open-label clinical study in patients with advanced pancreatic and bladder cancer. In this study, we aimed to determine the relation between UCK2 tissue protein expression and the efficacy of RX-3117 in mice xenograft models and also UCK2 protein expression in a panel of human cancer tissues relative to normal tissue.
Methods: The UCK2 protein expression in tumor tissues was analyzed by immunoblotting using clone 22-1 rabbit monoclonal antibody. The validated procedure for the immunohistochemistry (IHC) of UCK2 with clone 22-1 was performed in a panel of human formalin-fixed paraffin-embedded (FFPE) cancer and normal tissues.
Results: The immunoblotting protein level of UCK2 normalized to β-actin and corresponding tumor growth inhibition (oral RX-3117 dose of 500mg/kg, TIWK) were 57 and 67% in MiaPaCa2, 30 and -5% in BxPC3, 199 and 92% in Colo-205, 21 and 90% in Caki-1, 2 and 39% in A549, and 146 and 79% in H460, respectively. This data indicates an anti-tumor efficacy trend in a UCK2-dependent manner. The IHC of UCK2 showed that positive staining of UCK2 in cancer tissues was observed in 20/20 bladder cancer tissues (100% frequency), 19/20 CRC tissues (95% frequency), 18/20 NSCLC tissues (90% frequency), and 19/20 pancreatic cancer tissues (95% frequency). Average H-Scores of UCK2 in cancer tissues vs. normal tissues were 104 vs. 9 in lung, 97 vs. 20 in bladder, 67 vs. 41 in pancreas and 39 vs. 21 in colon, respectively.
Conclusions: The current data showed a correlation trend between UCK2 protein expression level and degree of antitumor activity of RX-3117 in xenograft models. It also supports a higher UCK2 protein expression level in human cancer tissues compared to their normal tissues. This suggests that RX-3117 activity may be specific to tumor tissue, and quantification of UCK2 expression in human cancer tissues may be useful as a predictive biomarker to select patients for their sensitivity to RX-3117 in future clinical studies.
Citation Format: Young Bok B. Lee, Deog J. Kim, Christina George, Chang-ho Ahn, Julie Frank, Reza Mazhari, Lisa M. Dauffenbach, Eric P. Olsen. Evaluation of UCK2 protein expression as a potential predictive biomarker of RX-3117 [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 1790. doi:10.1158/1538-7445.AM2017-1790
Abstract 1800: Noninvasive approach to assess metastatic lesion of advanced colorectal cancer by denoised deep target sequencing
Authors: Kang Jun-Kyu , Kim Hwang-Phill , Cheon Seul-Ki , Park Ye-Lim , Lim Yoojoo , Han Sae-Won , Kim Tae-You 
Published: July 2017

Abstract
The cell-free DNA (cfDNA) represents a minimally invasive and alternative source of tumor DNA for molecular profiling. Despite next-generation sequencing (NGS) technique is qualified for genotyping cancer using cfDNA as a noninvasive method, it has caused problems as sequencing error and reproducibility. cfDNA in plasma and gDNA of Peripheral Blood Mononuclear Cells (PBMC) were isolated from each 54 advanced colorectal cancer patients. 39 available tumor tissues were isolated from same patients. Deep target-sequencing was performed with paired-end library enriched exons of 10 genes which are recurrently mutated in colorectal cancer. To reduce sequencing error, we devised ‘Denoising’ and calculated concordance of somatic variants between cfDNA and tumor tissue sequencing data. In addition, correlation of concordance data was analyzed with the clinical information. As a result, we selectively could detect clinically important somatic alteration among low/high variant allele frequency (0.31%~79.42%). For somatic alteration of 10 genes, sensitivity, specificity and accuracy were increased from 84.5%, 74.6% and 76.9% to 87.6%, 92.0% and 91.1% respectively after ‘Denoising’. On the other hand, patients with high cfDNA concentration(&gt;50ng/ml) had higher somatic mutant fragments and larger metastatic lesion in liver than patients who have low cfDNA concentration. Our study showed that denoised deep target-sequencing is a suitable method for cfDNA genotyping and provides insights into strategies for monitoring metastatic lesion of advanced colorectal cancer.
Citation Format: Jun-Kyu Kang, Hwang-Phill Kim, Seul-Ki Cheon, Ye-Lim Park, Yoojoo Lim, Sae-Won Han, Tae-You Kim. Noninvasive approach to assess metastatic lesion of advanced colorectal cancer by denoised deep target sequencing [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 1800. doi:10.1158/1538-7445.AM2017-1800
Abstract 1824: Endothelial mTORC2 deficiency inhibits tumor angiogenesis, tumor progression and metastasis in non-small cell lung cancer (NSCLC)
Authors: Wang Shan 
Published: July 2017

Abstract
Vascular endothelial cells (ECs) are specialized components of the tumor microenvironment that orchestrates tumor growth and invasion. They form tumor-associated blood vessels (angiogenic) that supply nutrients and oxygen, remove waste products, and also provide an entry site for tumorigenic cells to spread to secondary sites in various organs. One of the major signaling events in tumor vessels is PI3K/PDK-AKT-mTOR activation. mTOR is a serine/threonine kinase that functions in two distinct complexes, mTORC1 and mTORC2,which regulate a diverse array of cellular processes including cell growth, survival and metabolism. Although mTORC1, and to lesser extent, mTORC2, has been broadly studied in cancers and diseases, little is known regarding the relative contributions of mTORC1 versus mTORC2 in tumor endothelium. Using mouse model of endothelium-specific Rictor (a mTORC2 specific cofactor) gene targeting, we discovered that endothelial Rictor deletion decreased tumor neovascularization, suppressed tumor growth, and prevented metastasis in vivo. Direct co-culture of endothelial cells and NSCLC tumor cells in vitro showed that knockdown of endothelial Rictor inhibited tumor cell proliferation while Raptor (a mTORC1 specific cofactor) depletion had a modest effect. However, loss of endothelial Rictor or Raptor both markedly decreased tumor cell extravasation in response to endothelial cells, and also inhibited tumor spheroid formation in a direct co-culture system. Furthermore, a screen of phospho-kinase arrays revealed that Raptor or Rictor depletion in endothelial cells decreased various phosphor-RTKs in tumor cells that were co-cultured with ECs, including members of the Eph receptor family, Insulin receptor family and FGF receptor family. Additionally, endothelial Rictor knockdown suppressed phosphorylation levels of nerve growth factor receptors TrkB and TrkC in tumor cells. Collectively, these data suggest that endothelial mTORC1 and mTORC2 play critical roles in regulating tumor progression through distinct signaling pathways.
Note: This abstract was not presented at the meeting.
Citation Format: Shan Wang. Endothelial mTORC2 deficiency inhibits tumor angiogenesis, tumor progression and metastasis in non-small cell lung cancer (NSCLC) [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 1824. doi:10.1158/1538-7445.AM2017-1824
Abstract 1827: Using Drosophila to study the role of metabolic enzyme mutations in glioblastoma and leukemia
Authors: Fabiano Julia , Chiaramida Gabriela , Magner Mira , O'Connor Meghan , Stallone Joseph , DiDuca Nicholas , Neville Kathryn , Tartarini Richard , Tipping Marla 
Published: July 2017

Abstract
Metabolic reprogramming is a common hallmark shared by nearly all proliferating cancer cells, and thus has emerged as an exciting new direction in cancer research. Many signaling pathways have been implicated in mechanisms leading to the shift of metabolic programs in tumors, but more recently a small number of metabolic enzymes have also been identified in this process. Genes encoding the metabolic enzymes Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) were found to be mutated in up to 70% of low-grade and medium grade gliomas, and in 15-20% of adult acute leukemia samples. These findings were the first to link the IDH gene to tumorigenesis. IDH1 and IDH2 function to irreversibly catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). We are studying how mutations in IDH affect the metabolism and cellular processes of the cell. To this end, we have expressed IDH-R132H in Drosophila glial cells and hemoctyes to learn more about the impact of neomorphic activity of IDH in gliobastoma and chronic myeloid leukemia. We have verified that these cells now produce 2-HG, as is known in human tumors harboring IDH mutations. We have observed different cellular responses to IDH mutations in glia versus hemoctyes and have begun to investigate why this may be. Ultimately, the goal of our research is to elucidate the mechanism(s) that cause IDH to contribute to oncogenic activity in specific tissues, and use this knowledge to design tailored therapeutics.
Citation Format: Julia Fabiano, Gabriela Chiaramida, Mira Magner, Meghan O'Connor, Joseph Stallone, Nicholas DiDuca, Kathryn Neville, Richard Tartarini, Marla Tipping. Using Drosophila to study the role of metabolic enzyme mutations in glioblastoma and leukemia [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 1827. doi:10.1158/1538-7445.AM2017-1827
Abstract 1830: Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant lung cancer
Authors: Momcilovic Milica , Bailey Sean T. , Lee Jason T. , Braas Daniel , Graeber Thomas G. , Works Melissa , Parlati Francesco , Demo Susan , Walser Tonya C. , Dubinett Steven M. , Sadeghi Saman , Christofk Heather , Shackelford David B. 
Published: July 2017

Abstract
Cancer cells exhibit increased use of nutrients including glucose and glutamine to support the bioenergetic and biosynthetic demands of proliferation. We tested CB-839, a small molecule inhibitor of glutaminase that impairs glutamine utilization, in combination with erlotinib on EGFR mutant non- small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here we show that CB-839 synergizes with erlotinib to drive energetic stress and activate the AMPK pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F- fluoro-2-deoxyglucose (18F-FDG) and 11C-Glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following CB-839 + erlotinib treatment. Therefore, PET imaging with 18F-FDG and 11C-Gln can be used to non-invasively monitor tumor metabolic and therapeutic response to CB-839 and erlotinib combination therapy.
Note: This abstract was not presented at the meeting.
Citation Format: Milica Momcilovic, Sean T. Bailey, Jason T. Lee, Daniel Braas, Thomas G. Graeber, Melissa Works, Francesco Parlati, Susan Demo, Tonya C. Walser, Steven M. Dubinett, Saman Sadeghi, Heather Christofk, David B. Shackelford. Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant 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 1830. doi:10.1158/1538-7445.AM2017-1830
Abstract 1841: Characterization of neuronal alterations in a new mouse model of low grade glioma
Authors: Torres Daniela , Mela Angeliki , Sharma Sohani Das , Hornstein Nicholas , Sims Peter , Canoll Peter 
Published: July 2017

Abstract
Diffusely infiltrating gliomas are the most common type of primary brain tumor seen in adults. Patients with low grade glioma (LGG) can survive for many years, but often suffer from seizures and cognitive impairment, and these symptoms are associated with an unfavorable prognosis. Glioma cells diffusely infiltrate cortical tissue, where tumor cells aggregate around neuronal cell bodies, a growth pattern referred to as perineuronal satellitosis, however the effects of tumor cells on neurons has not been well defined. To address this important issue we generated a mouse model that recapitulates the genetic and histological features of diffusely infiltrating LGG. In our model tumor growth is driven by PDGFA overexpression and p53 deletion in a RiboTag-Camk2a-Cre transgenic mouse. The RiboTag system allows for the isolation and sequencing of ribosome-bound transcripts from Camk2a neurons to obtain a measure of transcription and translation. Our analysis in non-tumor bearing brains identified neuron-specific genes that are highly regulated at the level of translation. mTOR signaling regulates cell growth, proliferation, and translation in response to diverse stimuli. To characterize mTOR signaling in our model we used immunohistochemical staining of pS6 as a marker of mTOR activity and found that neurons within the glioma infiltrated cortex have lower levels of pS6 staining compared to neurons in the surrounding cortex. To further assess these results we are using the RiboTag system to identify alterations in neuronal transcription and translation that occur in our model during glioma formation and in response to mTOR targeted treatments. These studies will provide new insights into the neuronal alterations contributing to seizures and cognitive impairment in glioma and enable the identification of potential molecular targets for novel therapies to treat the devastating consequences of cortical dysfunctions associated with glioma.
Citation Format: Daniela Torres, Angeliki Mela, Sohani Das Sharma, Nicholas Hornstein, Peter Sims, Peter Canoll. Characterization of neuronal alterations in a new mouse model of low grade glioma [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 1841. doi:10.1158/1538-7445.AM2017-1841
Abstract 1867: Near infrared fluorescent imaging of brain tumor with IR780 dye incorporated phospholipid nanoparticles
Authors: Li Shihong , Johnson Jennifer , Peck Anderson , Xie Qian 
Published: July 2017

Abstract
Background: Near-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic properties limit its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor.
Methods: Self-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized. The intracellular accumulation of IR780-nanoparticles in glioma cells were determined using confocal microscopy. The in vivo brain tumor targeting and NIRF imaging capacity of IR780-nanoparticles were evaluated using U87MG glioma ectopic and orthotopic xenograft models and a spontaneous glioma mouse model driven by RAS/RTK activation.
Results: The loading of IR780 into liposomes or phospholipid micelles was efficient. The particle diameter of IR780-liposomes and IR780-phospholipid micelles were 95 nm and 26 nm, respectively. While stock solutions of each preparation were maintained at ready-to-use condition, the IR780-phospholipid micelles were more stable. In tissue culture cells, IR780-nanoparticles prepared by either method accumulated in mitochondria, however, in animals the IR780-phospholipid micelles showed enhanced intra-tumoral accumulation in U87MG ectopic tumors. Moreover, IR780-phospholipid micelles also showed preferred intracranial tumor accumulation and potent NIRF signal intensity in glioma orthotopic models at a real-time, non-invasive manner.
Conclusion: The IR780-phospholipid micelles demonstrated tumor-specific NIRF imaging capacity in glioma preclinical mouse models, providing great potential for clinical imaging and image-guided surgery of brain tumors.
Citation Format: Shihong Li, Jennifer Johnson, Anderson Peck, Qian Xie. Near infrared fluorescent imaging of brain tumor with IR780 dye incorporated phospholipid nanoparticles [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 1867. doi:10.1158/1538-7445.AM2017-1867
Abstract 1868: Molecular imaging of human esophageal cancer for early detection
Authors: Ma Xibo , Meng Hui , Tian Jie 
Published: July 2017

Abstract
Esophageal cancer was the sixth common cancer for incidence and ranks fourth for death rate in China, and squamous cell carcinoma is the main histological type. It is usually in an advanced stage at the time of diagnosis, resulting in an overall 5-year survival rate of &lt;15%. Early detection can lead to an improvement in patient outcomes but is limited by nonspecific contrast mechanisms. As all we know, antibody and peptides establish a biological basis for image contrast, which could achieve sufficient target-to-background ratio for in vivo detection. In this paper, an EGFR antibody (Cetuximab) conjugated with an NIR dye (NIRDye800) was used for early detection of esophageal cancer. We demonstrated our technology could identify esophageal cancer in small size (&lt;1 mm) and high-grade dysplasia from low-grade dysplasia. And 4.2-fold greater fluorescence intensity for esophageal cancer compared with surrounding normal esophageal tissues. No toxicity was observed in our experiments. The result indicated that this targeted, antibody-based imaging agents have great potential in early detection of esophageal cancer and other epidermal cancer.
Citation Format: Xibo Ma, Hui Meng, Jie Tian. Molecular imaging of human esophageal cancer for early detection [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 1868. doi:10.1158/1538-7445.AM2017-1868