bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4145: Characterization of the ODZ receptor family in neuroblastoma
Authors: Andonova Teodora , Kogner Per , Johnsen John Inge , Wickström Malin 
Published: August 2018

Abstract
Neuroblastoma is the most common extracranial solid tumor of childhood, causing 6% of all childhood cancers but 9% of deaths from malignant tumors in children. It is a tumor with highly heterogeneous clinical behavior, believed to originate from undifferentiated neural crest cells that form the sympathetic nervous system. Neuritogenesis is the process during embryonic development when neural crest cells migrate and differentiate into multiple cell types. The Rho/Rac signaling cascade is fundamental for this process. We performed whole genome sequencing of 40 neuroblastoma tumor samples, 32.5% of the samples contained a mutation in a gene associated with Rho/Rac signaling. The most frequently mutated receptor family among the Rho/Rac associated genes was the tenuerins (ODZ1-4). The ODZ genes were mutated in three out of 40 patients, i.e. 7.5%. The ODZ proteins are not fully characterized, however it is known they are highly expressed during the development of the central nervous system and play role in differentiation of the drosophila fly.
Evidence suggests a function for dysregulated expression of the ODZs in human tumors, but investigations of a deeper cellular and molecular understanding in neuroblastoma are missing. The aim of this study is to investigate the ODZ receptors to determine the role and function of these proteins in neuroblastoma tumor development, progression and metastasis. When investigated in publically available and validated neuroblastoma cohorts, low expression levels of ODZ1, ODZ2 and ODZ3 were associated with poor overall survival, while low ODZ4 expression correlated with high overall survival. Our data demonstrated that the ODZ receptors were differently expressed in neuroblastoma cell lines. Preliminary results also showed that siRNA knockdown of ODZ4 in a neuroblastoma cell line led to a 50% decrease in cell viability compared to control, together with morphological changes such as more neurite extensions, suggesting that an inhibition of ODZ4 may result in differentiation. Knockout of the four different ODZ transcripts also showed that the ODZ receptors might have compensatory mechanisms for each other. Our data suggest that activity of the ODZ receptors may be important for neuroblastoma development and that manipulation could offer a possible therapy for neuroblastoma.
Citation Format: Teodora Andonova, Per Kogner, John Inge Johnsen, Malin Wickström. Characterization of the ODZ receptor family in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4145.
Abstract 4148: Role of the photoreceptor gene, CRX (cone-rod homeobox) in pathogenesis of non-WNT, non-SHH medulloblastoma
Authors: Masurkar Shalaka , Moiyadi Aliasagar , Sridhar Epari , Jalali Rakesh , Shirsat Neelam 
Published: August 2018

Abstract
Central nervous system (CNS) tumours are the second most common cancers diagnosed in children after leukemia and continue to be the leading cause of cancer-related mortality in children. Medulloblastoma (MB) is a highly malignant primary brain tumour that occurs in posterior fossa region of the brain. The current standard treatment regimen includes surgical resection, craniospinal irradiation and adjuvant chemotherapy. Although this has resulted in significant increase in survival, approximately one-third of medulloblastoma patients still die because of the disease. Genome-wide gene expression profiling studies have identified four molecularly distinct subgroups of medulloblastoma namely WNT, SHH, Group 3, and Group 4. Among the four subgroups, Group 3 patients exhibit highest incidence of metastasis and worst overall survival rates. Molecular mechanism underlying the pathogenesis of Group 3 medulloblastomas is not understood. Group 3 tumors often express retina photoreceptor-specific genes like CRX (Cone Rod Homeobox) which is a homeodomain transcription factor and it is essential for the normal development and maintenance of cones and rods cells of the retina. We have noted that this expression is also retained by the medulloblastoma cell lines like D425, D283 and D341 which have characteristics of Group 3 tumours. Downregulation of CRX in these cell lines brought about inhibition of cell proliferation and anchorage-independent growth as studied by soft agar colony formation assay. CRX gene, therefore, seems to act as an oncogene similar to OTX2, another homeobox gene overexpressed in medulloblastomas. Transcriptome profiling and CHIP-seq analysis is being carried out to identify genes regulated by CRX transcription factor to delineate the molecular mechanism underlying the oncogenic role of CRX in medulloblastoma pathogenesis.
Citation Format: Shalaka Masurkar, Aliasagar Moiyadi, Epari Sridhar, Rakesh Jalali, Neelam Shirsat. Role of the photoreceptor gene, CRX (cone-rod homeobox) in pathogenesis of non-WNT, non-SHH medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4148.
Abstract 4152: Synergistic gold nanostar-mediated photothermal and immunotherapy for cancer metastasis treatment
Authors: Liu Yang , Maccarini Paolo , Palmer Gregory M. , Inman Brant A. , Vo-Dinh Tuan 
Published: August 2018

Abstract
Cancer has become a severe thread to human health resulting in more than eight million deaths each year. Cancer metastasis is the main mechanism in more than 90 percent of cancer deaths. However, current therapeutic options including chemotherapy and radiation therapy have limited therapeutic effects to treat cancer metastasis. Therefore, there is an urgent need to develop novel methods for cancer treatment. Our group has developed a unique method to synthesize star-shaped gold nanoparticles, gold nanostars (GNS), without using toxic surfactant, which is very suitable for in vivo applications. The synthesized GNS has tip-enhanced plasmonics and tunable strong in the near-infrared “tissue optical window”, enabling it a superior photon-to-heat nanotransducer. The GNS nanoparticles accumulate preferably into tumor with enhanced permeability and retention (EPR) effect after intravenous administration. We have applied GNS for photothermal therapy with 808 nm laser to specifically ablate tumor. Here we report a new cancer treatment method by combing nanophotothermal therapy and anti-PD-L1 immunotherapy. Immunogenic cell death is often insufficient to trigger effective anti-cancer immunity due to the presence of immunosuppressive factors occurring in the tumor microenvironment such as hypoxia, impaired leukocyte trafficking and inhibitory immune checkpoint signaling. The GNS-mediated photothermal ablation can reduce hypoxia and improve leukocyte trafficking to the tumor. In addition, the administration of anti-PD-L1 antibody reverses another critical immunosuppression factor. Experiment results using a mouse bladder cancer model demonstrated that the combined photothermal and immunotherapy have synergistic effect and can not only eradicate primary tumors with laser treatment but also distant metastasis without laser treatment. Furthermore, delayed rechallenge in the cured mice didn't result in new tumor generation, indicating that our combined therapy induced memorized immune response against cancer. The combined GNS-mediated photothermal therapy and anti-PD-L1 immunotherapy has promise to improve therapeutic effect on not only primary tumor but also cancer metastasis.
Citation Format: Yang Liu, Paolo Maccarini, Gregory M. Palmer, Brant A. Inman, Tuan Vo-Dinh. Synergistic gold nanostar-mediated photothermal and immunotherapy for cancer metastasis treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4152.
Abstract 4155: USP11 regulates UV-induced DNA damage repair and cell survival associated with skin cancer
Authors: Shah Palak , Qiang Lei , Yang Seungwon , Soltani Keyoumars , He Yu-Ying 
Published: August 2018

Abstract
UV radiation is a major risk factor for skin cancer, the most common cancer in the United States. UV exposure leads to DNA damage by formation of dimers between adjacent pyrimidine bases. The nucleotide excision repair (NER) process is responsible for removal of UV-induced DNA damage. When the damage is left unrepaired due to inefficient NER in disorders like xeroderma pigmentosum, it leads to skin tumorigenesis. Although the main players of the NER pathway have been characterized, the molecular regulation of the pathway is less understood. Understanding the regulation, particularly post-translational regulation, of the NER pathway has the potential to yield modulators of NER efficiency to prevent skin cancer. We found that chronic UV irradiation led to down-regulation of ubiquitin specific peptidase 11 (USP11) in mouse skin tissue. We also found that USP11 is decreased in skin tumors in mice and humans. Moreover, high-throughput proteomics analysis had predicted that USP11 may interact with NER factor XPC. Hence, we undertook this study to determine the role of USP11 in NER and cellular response to UV. We found that USP11 promoted the NER pathway by regulating XPC activity. USP11 promoted XPC deubiquitination and retention at the DNA damage sites. We also found that USP11 interaction with ubiquitinated XPC was enhanced post-UV irradiation, and that USP11 was recruited to the chromatin post-UV damage. Further, squamous cell carcinoma cells showed reduced survival with inhibition of USP11 after UV exposure. Our findings indicate that USP11 plays an important role in maintaining NER capacity, and suggest that USP11 acts as a tumor suppressor via its role in DNA repair.
Citation Format: Palak Shah, Lei Qiang, Seungwon Yang, Keyoumars Soltani, Yu-Ying He. USP11 regulates UV-induced DNA damage repair and cell survival associated with skin cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4155.
Abstract 4156: Inhibition of NF-kB improves sensitivity to radiation and EGFR inhibitor and decreases radiation-induced lung toxicity in lung cancer
Authors: Wang Wei , Wang Rong , Peng Shunli , Li Qi , Zhang Xiaojuan , Ma Yueyun 
Published: August 2018

Abstract
Combination with EGFR-TKIs and radiation seems to be a good strategy against lung cancer, since radiation could enhance EGFR expression. However, the results of clinical trials were controversial. MET activation was involved in resistance to both radiation and EGFR inhibitor, while NF-kB was reported to closely relate to HGF/MET signaling axis. Furthermore, NF-κB has been proved to play a role in bleomycin-induced pulmonary fibrosis, which could be ameliorated by IKKB inhibitor (IMD-0354). Therefore, we evaluated the influence of NF-kB/MET inhibition to the sensitivity of radiation and EGFR-TKIs in lung cancer cells in vitro and in vivo. we also examined the role of NF-κB in radiation-induced lung toxicity. Our data showed that radiation enhanced activation and expression of MET and EGFR, whereas only activation of MET could be reversed by IMD-0354 and p65 depletion, suggesting that radiation-induced MET activation was mediated by NF-kB signaling. Furthermore, NF-kB inhibition increased radiation-induced DNA damage and apoptosis in lung cancer cells. On the other hand, radiation decreased sensitivity to EGFR inhibitor in EGFR mutant lung cancer cells, while inhibition of NF-kB or MET overcame the resistance. Importantly, IMD-0354 increased sensitivity to radiation, EGFR-TKIs, or their combination in mouse xenograft tumors by arresting cell proliferation and inducing cell apoptosis. Interestingly, IMD-0354 significantly reduced the lung toxicity in a mouse model of radiation-induced pneumonia and lung fibrosis. Our preclinical findings indicated that inhibition of NF-kB/MET could improve sensitivity to radiation and EGFR inhibitor and decrease radiation-induced lung toxicity in lung cancer.
Citation Format: Wei Wang, Rong Wang, Shunli Peng, Qi Li, Xiaojuan Zhang, Yueyun Ma. Inhibition of NF-kB improves sensitivity to radiation and EGFR inhibitor and decreases radiation-induced lung toxicity in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4156.
Abstract 416: Impact of virus integration into the genomes of hepatocellular carcinoma patients with prior hepatitis B virus infection
Authors: Midorikawa Yutaka , Tatsuno Kenji , Yamamoto Shogo , Nagae Genta , Koike Kazuhiko , Moriyama Mitsuhiko , Takayama Tadatoshi , Moriya Kyoji , Aburatani Hiroyuki 
Published: August 2018

Abstract
It has been elucidated that hepatitis B virus (HBV) DNA is frequently integrated to some cancer related genes such as TERT or KMT2B in patients with chronic HBV infection. On the other hand, it has not yet become clear of the integration of HBV to the genome of patients with prior infection with HBV. To identify the integration sites of HBV, we performed next generation of target capture technology for hepatocellular carcinoma samples obtained from 73 HBc antibody positive patients but negative for HBs antigen nor hepatitis C antibody (HCV) (Group 1; prior infection), 78 HBs antigen positive patients (Group 2; positive control), and 33 patients without any antigens nor antibodies for HBV (Group 3; negative control). Among these patients, overall HBV integration in Group 2 (54 patients, 69.2%) was significantly frequent compared with that in Group 1 (12, 16.4%) (P &lt; 0.001), and was not detected in any patients of Group 3. On the other hand, HBV integration occurred in the known driver genes; TERT in seven (9.5%) and 12 (15.3%) patients (P = 0.332), MLL4 in two (3.5%) and four (5.1%) patients (P = 682), and CCNE1 in 0 and one (1.2%) patient (P = 1.000) in Group 1 and 2, respectively. Notably, integration of any driver genes was not observed in 56 patients with prior infection with HBV who were positive for HCV infection.Taken together, despite the disappearance of HBV, the frequency of driver events by HBV integration in patients with prior HBV infection is similar to those with chronic HBV infection, and patients with prior HBV infection are still at the risk of hepatocellular carcinoma.
Citation Format: Yutaka Midorikawa, Kenji Tatsuno, Shogo Yamamoto, Genta Nagae, Kazuhiko Koike, Mitsuhiko Moriyama, Tadatoshi Takayama, Kyoji Moriya, Hiroyuki Aburatani. Impact of virus integration into the genomes of hepatocellular carcinoma patients with prior hepatitis B virus infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 416.
Abstract 4163: Space radiation-induced persistent DNA damage and alterations in cytoskeletal remodeling pathways affect intestinal epithelial cell migration in mice
Authors: Kumar Santosh , Suman Shubhankar , Fornace Albert , Datta Kamal 
Published: August 2018

Abstract
Lombardi Comprehensive Cancer Center, and Department of Biochemistry and Molecular & Cellular Biology Georgetown University, Washington, DC 20057, USA.
Heavy ion space radiation is considered as a risk factor of gastrointestinal (GI) cancer and perturbed intestinal epithelial cell (IEC) migration has been implicated in GI carcinogenesis. The purpose of the current study was to assess rate of IEC migration as well as dissect key IEC migration signaling events after exposure to heavy ion 56Fe irradiation and compare the results to sham- and γ-irradiation. Male C57BL/6J mice were exposed to 0.5 Gy of either γ or 56Fe radiation and control mice were sham irradiated. IEC migration distance was measured 7 and 60 d after exposure using BrdU pulse labeling. We also analyzed cell polarity, microtubule dynamics, and adhesion dynamics using immunoblots and immunofluorescence. Measure of IEC migration rate showed a greater decrease after 56Fe relative to γ radiation at both the time points. At the molecular level, compared to sham and γ radiation, 56Fe radiation exhibited significantly greater impairment of cell adhesion dynamics evidenced by altered integrins and Rock1 as well as cytoskeletal dynamics evidenced by altered MLCK expression. Similarly, perturbed cell polarity, tight junction, and microtubule dynamics was revealed by the deregulation of Par3, Claudin1, Scribble, Occludin, ZO-1, phospho-Tau and MAP1B. Also, the Wnt/β-catenin and EphB/EphrinB pathways critical for IEC migration consistently showed greater deregulation at both the time points tested after 56Fe radiation relative to γ -rays. Taken together, our molecular findings correlate with the BrdU pulse labeling data, and demonstrate greater effects of heavy ion 56Fe on IEC migration relative to γ -rays. In summary, our results have demonstrated for the first time that radiation can disrupt cell migration dynamics through alteration of signaling molecules involved in crucial cellular processes and these results have implications for heavy ion space radiation-induced gastrointestinal homeostatic deregulation and carcinogenesis.
Citation Format: Santosh Kumar, Shubhankar Suman, Albert Fornace, Kamal Datta. Space radiation-induced persistent DNA damage and alterations in cytoskeletal remodeling pathways affect intestinal epithelial cell migration in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4163.
Abstract 4164: Fasting protects mice from lethal radiation by promoting small intestinal stem cell survival
Authors: Bonilla Marimar de la Cruz , Stemler Kristina M. , Fujimoto Tara N. , Jeter-Jones Sabrina , Molkentine Jessica M. , Torres Gabriela M. Asencio , Taniguchi Cullen M. , Piwnica-Worms Helen 
Published: August 2018

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the US. Surgical resection is the only potentially curative treatment; however, only 15%-20% of patients present with tumors that can be resected. There is no consensus regarding standard of care in unresectable cases, however many academic centers use stereotactic body radiotherapy (SBRT) to give tumor-directed radiotherapy (RT). Unfortunately, even this conformal technique can still cause severe gastrointestinal (GI) toxic effects caused by the proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic effects of radiation may enable dose escalation that could achieve more effective local control of disease. We and others have previously shown that a prolonged fast of 24 hours protects mice from lethal doses of etoposide. In this study, we extend and build on our previous finding to demonstrate that a similar 24 hour fast also protects from lethal doses of total abdominal radiation. Histologic analyses, using the Withers-Elkind microcolony assay, show that fasting protected small intestinal (SI) stem cells from radiation damage and promoted early regeneration. To show a proof-of-principle for the use of this radioporotective maneuver in cancer therapy, we developed an orthotopic model of pancreatic cancer using KPC tumor cells syngeneic to C57BL/6. Here, we show that fasting-mediated intestinal protection enabled dose escalated SBRT for treatment of these orthotopic tumors. RT with fasting radioprotection delayed tumor growth and improved survival compared to controls. Given this robust phenotype, we developed a 3D culture ex vivo assay using intestinal stem cell enriched epithelial spheroid cultures. We modified these intestinal spheroids with a bioluminescent reporter and used these cells to develop a modified clonogenic assay for 3D culture that can be used to identify novel radioprotectors, such as a fasting mimetic. Taken together, these results suggest that fasting protects small intestinal stem cells sufficiently to allow animals to receive potentially curative doses of abdominal radiation that would other wise be lethal. Future work will aim to identifying the mechanism by which fasting confers intestinal protection and drug candidates that can be used to mimic this fasting-mediated protection.
Citation Format: Marimar de la Cruz Bonilla, Kristina M. Stemler, Tara N. Fujimoto, Sabrina Jeter-Jones, Jessica M. Molkentine, Gabriela M. Asencio Torres, Cullen M. Taniguchi, Helen Piwnica-Worms. Fasting protects mice from lethal radiation by promoting small intestinal stem cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4164.
Abstract 4167: MUC3A promotes lung cancer progress via activating NFκB pathway and attenuates radiosensitivity
Authors: Sun Yingming , You Chengcheng , Ma Shijing , Luo Yuan , Gong Yan , Xiao Yu , Zhang Junhong , Xie Conghua 
Published: August 2018

Abstract
MUC3A is highly expressed in 40% of lung adenocarcinoma, but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 patients' tumor samples from Chinese National Human Genetic Resources Sharing Service Platform indicated that highly expression of MUC3A was associated with poor prognosis, advanced staging and low differentiation. IP-MS and co-IP results revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. MUC3A knockdown significantly suppressed cell proliferation and induced G1 arrest via down-regulating cell cycle checkpoints such as CDK2/4/6 and Cyclin D1. MUC3A deficiency increased γ-H2AX phosphorylation and increased radiation-induced DNA double strain breaks. MUC3A knockdown inhibited the BRCA-1/RAD51 pathway and nuclear translocation of P53 and XCRR6, suggesting that MUC3A promote DNA damage repair and attenuate radiation sensitivity. Moreover, MUC3A deficiency induced autophagy in lung cancer cells and increased the protein levels of LC3 II and Beclin-1. MUC3A knockdown significantly suppressed tumor growth in H1975 xenograft model and had a synergistic effect with radiation. Less nuclear translocation of RELA and P53 was also observed in tumor tissue in vivo. Our studies indicated that MUC3A was a potential oncogene and its highly expression was associated with unfavorable clinical outcomes in patients with lung adenocarcinoma, who should be more frequently follow-up, and might benefit less from radiotherapy.
Citation Format: Yingming Sun, Chengcheng You, Shijing Ma, Yuan Luo, Yan Gong, Yu Xiao, Junhong Zhang, Conghua Xie. MUC3A promotes lung cancer progress via activating NFκB pathway and attenuates radiosensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4167.