bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1193: Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma
Authors: Lindsay Holly B. , Kogiso Mari , Qi Lin , Yee Teo Wan , Huang Yulun , Mao Hua , Lin Frank , Baxter Patricia , Su Jack M. , Terashima Keita , Perlaky Laszlo , Lau Ching C. , Parsons Donald W. , Chintagumpala Murali , Li Xiao-Nan 
Published: May 2015

Abstract
Despite comprising up to 10% of pediatric CNS tumors, an animal model of intracranial germinoma has not been previously established. Standard of case for germinoma is radiation therapy, with recent evidence that neo-adjuvant chemotherapy may allow reduction of radiation dose, but concern for neuro-cognitive toxicity remains despite the reduction of radiation. A clinically relevant animal model of germinoma would facilitate investigation and discovery of novel agents which may obviate the need for radiation in the future. To develop xenograft mouse models, we implanted germinoma tumor cells from two children with metastatic disease, one from a surgical specimen of a cervical metastatic tumor and the second from disseminated tumor cells in the CSF, directly into the right cerebral hemispheres of NOD-SCID mice. Both patient tumor samples have undergone whole exome sequencing; one of the two models has a germinoma-associated mutation in c-kit. The tumors have been serially passaged in xenografts for 3-5 times, with each passaged tumor maintaining the ability to generate tumors, suggestive of the persistence of viable tumorigenic/tumor stem cells. Data from additional tumor models established by our lab have confirmed molecular and genetic fidelity between xenograft-initiating human brain tumors and their corresponding murine models. The orthotopic location in the mouse brain of the xenograft model should also reasonably replicate the human germinoma tumor microenvironment. Cultured cells are currently growing from both tumor models in order to establish germinoma cell lines. In summary, our orthotopic xenograft murine models of two metastatic pediatric germinomas are the first to be established for this tumor type. These models will allow much needed pre-clinical drug testing of chemotherapeutics and combination therapies as well as further biologic characterization of pediatric germinomas.
Citation Format: Holly B. Lindsay, Mari Kogiso, Lin Qi, Teo Wan Yee, Yulun Huang, Hua Mao, Frank Lin, Patricia Baxter, Jack M. Su, Keita Terashima, Laszlo Perlaky, Ching C. Lau, Donald W. Parsons, Murali Chintagumpala, Xiao-Nan Li. Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1193. doi:10.1158/1538-7445.AM2014-1193
Abstract 120: Runx3 inhibited epithelial to mesenchymal transition promotes motility and invasiveness of colon cancer cells through reduction of ROS generation
Authors: Kim Bo Ram , Kang Myoung Hee , Kim Jung Lim , Jang Yoo Jin , Lee Sun I. , Kim Jun Suk , Oh Sang Cheul 
Published: May 2015

Abstract
Approximately 90% of all cancer deaths arise from the metastatic spread of primary tumours. Most colon cancer metastasis occurs. Runx3(runt-related transcription factor3) is known as tumor suppressor gene in gastrointestinal epithelium. Recent reports have been shown that loss of Runx3 induce proliferative effect in gastric cancer cells. However, their roles and underlying mechanism in colon cancer cell lines are not yet known. In this study, we investigated the function of Runx3 in human colon cancer cells. The proliferation, migration, and invasion of colon cancer cells in response to using the Runx3 expression vector for various times were investigated using MTT, wound healing, and Matrigel invasion assay, respectively. The morphologic changes of colon cancer cells through the EMT process were monitored by immunofluorescence staining and Western blot assay for EMT markers Twist and Vimentin. We found that Runx3 overexpressing cell inhibited cell motility and invasiveness in colon cancer, and this process was enhanced by Runx3 siRNA. We observed that the mRNA expressions of Runx3 was enhanced by Runx3 overexpressing cell, whereas no increase of these factors was observed when the Runx3 siRNA was transfection. Overexpression of Runx3 decreases protein expression of EMT (Epithelial-Mesenchymal transition) markers. In addition, Runx3 knockdown upregulates MMP2 activity. The ROS production was decreased in Runx3-overexpressing cells. These results indicate that Runx3 signaling pathway can contribute to ROS generation enhancing the metastatic potential of tumor cells. Our findings suggest that Runx3 signaling processes through ROS and MMP2 the inhibition of these pathway blocked the metastatic potential of colon cancer cell lines.
Citation Format: Bo Ram Kim, Myoung Hee Kang, Jung Lim Kim, Yoo Jin Jang, Sun Il Lee, Jun Suk Kim, Sang Cheul Oh. Runx3 inhibited epithelial to mesenchymal transition promotes motility and invasiveness of colon cancer cells through reduction of ROS generation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 120. doi:10.1158/1538-7445.AM2014-120
Abstract 1200: Characterization of a novel radiation-induced sarcoma cell line
Authors: Lang Julie E. , Nokes Brandon , Sheth Grishma , Novak Petr , Fuchs Laura , Watts George S. , Futscher Bernard W. , Mineyev Neal , Zhu Weizhu , LeBeau Lauren , Nagle Ray , Cranmer Lee 
Published: May 2015

Abstract
Background: Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models currently exist to facilitate studies of RIS. Methods: We derived a primary human cell line, UACC-SARC1, from a RIS. Short tandem repeat (STR) genotyping was used to confirm that this cell line was propagated from the tumor. Further characterization of this cell line involved comparing 24 markers using immunocytochemistry (ICC) to immunohistochemistry (IHC) of the tumor, a Matrigel invasion assay, karyotyping of the cell line, comparative genomic hybridization (CGH), DNA sequencing using the Ion AmpliSeq Cancer panel and in vivo mouse xenografts after subcutaneous injection of UACC-SARC1 in immunodeficient mice. Results: STR profiling of UACC-SARC1 was virtually identical to its parental tumor. IHC analysis of the tumor and ICC analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. CGH provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. SCID mice xenografts exhibited tumor formation but resulting tumors failed to metastasize. Further xenografts with NOD SCID gamma (NSG) mice are planned. The doubling time of UACC-SARC1 was 28.3 hours. Conclusion: Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease.
Citation Format: Julie E. Lang, Brandon Nokes, Grishma Sheth, Petr Novak, Laura Fuchs, George S. Watts, Bernard W. Futscher, Neal Mineyev, Weizhu Zhu, Lauren LeBeau, Ray Nagle, Lee Cranmer. Characterization of a novel radiation-induced sarcoma cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1200. doi:10.1158/1538-7445.AM2014-1200
Abstract 1201: Establishment and characterization of cell lines derived from a murine model of PTEN-deficient prostate cancer
Authors: Yoshikawa Kazuhiro , Velasco Marco A. De , Kura Yurie , Ando Naomi , Fukushima Emiko , Hatanaka Yuji , Yamamoto Yutaka , Shimizu Nobutaka , Yoshimura Kazuhiro , Nozawa Masahiro , Nishio Kazuto , Uemura Hirotsugu 
Published: May 2015

Abstract
Inactivation of the tumor suppressor PTEN is a common event in human prostate cancer that leads to increased activation of the PI3K pathway. Crosstalk between the PI3K signaling cascade and other cancer regulatory pathways contributes to the growth and survival of cancer cells. To better understand the mechanisms involved in the transformation process and to establish an in vivo screening system for novel treatment strategies, we previously developed a genetically engineered mouse model of prostate cancer that is based on the conditional inactivation of PTEN. In this model, inactivation of PTEN results in the stage-specific development of prostate cancer that recapitulates most features of the human disease including the development of castration-resistant prostate cancer (CRPC). The purpose of our study was to establish and characterize a panel of cell lines derived from this model in order to study the disease mechanisms at the cellular level and to establish a cell-based assay system to complement our in vivo program for pre-clinical screening of novel anticancer drugs. A panel of 7 cell lines derived from castration-naïve prostate tumors and 6 cell lines derived from CRPC were established. Cells lines were characterized for morphological, growth, differentiation, and molecular profiles in vitro as well as for their tumorigenic potential in vivo. The cell lines were also tested against a panel of cytotoxic and molecular targeting drugs and compared to the sensitivity of human prostate cell lines. Overall, our comprehensive analysis summarizes the functionality and potential application as cell-based system for developing treatment strategies against prostate cancer.
Citation Format: Kazuhiro Yoshikawa, Marco A. De Velasco, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuto Nishio, Hirotsugu Uemura. Establishment and characterization of cell lines derived from a murine model of PTEN-deficient prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1201. doi:10.1158/1538-7445.AM2014-1201
Abstract 1204: Establishment of a patient-derived orthotopic xenograft (PDOX) model of patient cervical cancer
Authors: Hiroshima Yukihiko , Zhang Yong , Maawy Ali , Sato Sho , Murakami Takashi , Yamamoto Mako , Uehara Fuminari , Miwa Shinji , Yano Shuya , Momiyama Masashi , Chishima Takashi , Tanaka Kuniya , Maawy Ali , Endo Itaru , Hoffman Robert M. 
Published: May 2015

Abstract
We implanted a tumor resected from a patient with metastatic HER-2-positive cervical cancer from 8 NOD/SCID mice (F1; NOD/SCID-sc) and 10 nude mice (F1; Nude-sc) subcutaneously, and 8 nude mice (F1; Nude-soi) orthotopically. Five out of 8 NOD/SCID mice died within 7 days after implantation. Infections around the surgical wound, loss of weight and of lethargy were observed in post-operatively in other mice. We examined the tumor-take rate of each model 8 weeks after implantation. Tumors grew in 3 out of 3 mice in F1; NOD/SCID-sc (100 %); 7 out of 10 mice in F1; nude-sc (70 %) and 6 out of 8 mice in F1; nude-soi group (75 %), respectively. The metastatic tumors (peritoneal dissemination, liver metastasis, lung metastasis or lymph node metastasis) were detected in 4 mice in F1; nude-soi mice (50 %). We found all xenografts including the metastatic tumors had histological structures similar to the original tumor and were stained by anti-human HER-2 antibody. Next, we implanted the small fragments of subcutaneous tumors from F1; Nude-sc mice (F2; sc-sc) or the primary tumors of F1; nude-soi mice (F2; soi-sc) to another set of nude mice (20 mice each) subcutaneously, and examined the tumor-take rate of each group 4 weeks and 8 weeks after implantation. Eight mice in the F2; sc-sc group (40 %) and 16 mice in the F2; soi-sc group (80 %) had tumors at week 4, and 15 mice in the F2; sc-sc group (75 %) and 19 mice in the F2; soi-sc group (95 %) had tumors at week 8. These results suggest that PDOX in nude mouse model recapitulates the biological behaviors of the original tumor and has the sufficient tumor-take rate.
Citation Format: Yukihiko Hiroshima, Yong Zhang, Ali Maawy, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Ali Maawy, Itaru Endo, Robert M. Hoffman. Establishment of a patient-derived orthotopic xenograft (PDOX) model of patient cervical cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1204. doi:10.1158/1538-7445.AM2014-1204
Abstract 1207: Pharmacodynamic evaluation of ADCC mediated effects in humanized IL2 or IL15 NOG mice models
Authors: Mignard Caroline , Mirjolet Jean-Francois , Duchamp Olivier , Ohnishi Yasuyuki , Katano Ikumi , Ito Mamoru 
Published: May 2015

Abstract
Humanized mice (i.e. immunodeficient NOG mice engrafted with human hematopoietic stem cells (HSC)) have demonstrated their usefulness for studying the human immune system. These models should help recapitulating some pathology such as viral infection and then are suitable system to evaluate new human specific therapies. Nevertheless, one issue of these models is the incomplete maturation of natural killer (NK) cell subpopulation.
This lake of NK cell functionality was solved by the Central Institute for Experimental Animals (CIEA) with the second generation of transgenic NOG mice expressing human IL2 or IL15 (NK-NOG). The serum levels of hIL-2 and hIL-15 in mice were 1-2 and 0.1-0.2 ng/mL, respectively. In these mice, human NK cells differentiated from HSC are well distributed in the mouse body (peripheral blood, bone marrow, spleen…). They expressed various NK receptors such as NKp30, NKp44, NKp46, etc., granzyme A and perforin, indicating their maturity in the mice. They are also fully functional as evidenced using an ex vivo 51Cr release assay demonstrating lysis properties of human NK cells from collected spleen of HSC-humanized mice.In vivo proof of concept studies were successfully performed with humanized NK-NOG mice xenografted with either human Burkitt's disseminated lymphoma cells or with human solid tumors treated with humanized therapeutic antibodies. Prediction of ADCC-mediated antitumor activity of humanized antibodies is now routinely feasible for preclinical evaluation using these new in vivo NK-NOG models.
Citation Format: Caroline Mignard, Jean-Francois Mirjolet, Olivier Duchamp, Yasuyuki Ohnishi, Ikumi Katano, Mamoru Ito. Pharmacodynamic evaluation of ADCC mediated effects in humanized IL2 or IL15 NOG mice models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1207. doi:10.1158/1538-7445.AM2014-1207
Abstract 1209: Comparison of lung adenocarcinoma development in genetically engineered mouse and in humans - similarities and differences
Authors: Popper Helmut H. , Grabner Beatrice , Casanova Emilio , Eferl Robert , Shuan Rao , Penninger Josef 
Published: May 2015

Abstract
Lung adenocarcinoma (AC) induced by carcinogen inhalation never came close to the human counterpart. This has changed with the creation of genetically engineered models.
Different types of mouse AC were studied, some of them with a KRAS codon12 mutation background, others with HRAS mutants inserted; in most additional hits were introduced (ATG5, PTEN, PI3K, p53). Development of AC was followed for 28 weeks. Human lung AC subtypes and precursor lesions served for comparison.
AC in mice starts with papillary growth at the bronchoalveolar junction (baJ). Tumor spreads into the alveolar periphery. Due to different cell to alveolar size alveoli are filled almost completely, simulating solid growth. At a certain size hypoxic necrosis is seen in centers, followed by neoangiogenesis and desmoplastic stroma formation. Finally invasion of tumor cells into stroma occur. Metastasis is rare, due to high tumor load, causing early death. Vascular invasion is seen, if second carcinogenic hits are applied.
Dissimilarities with human precursor and AC types are: AC in mice are all non-mucinous, they are predominant papillary or solid, often with a high degree of signet ring cell formation; in addition there seems to be a requirement of large tumor size before invasion and metastasis occur. To understand AC development knowledge of the anatomy and histology of mouse and human lung is necessary, but these models open a new way of investigating lung AC.
Citation Format: Helmut H. Popper, Beatrice Grabner, Emilio Casanova, Robert Eferl, Rao Shuan, Josef Penninger. Comparison of lung adenocarcinoma development in genetically engineered mouse and in humans - similarities and differences. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1209. doi:10.1158/1538-7445.AM2014-1209
Abstract 121: Sulforaphene inhibited migration through down-regulating the Hedgehog signaling in SUM159 human breast cancer cells
Authors: Bao Cheng , Lee Jaehoo , Ko Jiwon , Park Hyun-Chang , Lee Hong jin 
Published: May 2015

Abstract
Accumulating evidences have demonstrated the antineoplastic properties of sulforaphane, a major isothiocyanates present in cruciferous vegetables. However, the natural analogue of sulforaphane, sulforaphene, rich in radish, has yet not been extensively studied for its potential in preventing cancer. In this study, sulforaphene exerted inhibiting effect on migration of SUM159 human breast cancer cells, the migrated cells were reduced from 72.3% in control group to 17.5% in sulforaphene(10uM) treated group. The Hedgehog signaling, known to be involved in cancer invasiveness, was found to be regulated by sulforaphene. The mRNA and protein expression of Gli1 and Smoothened(Smo) which were Hedgehog signaling activating mediators were significantly suppressed by sulforaphene, but the expression of Patched1(Ptch1) an inhibiting mediator, was induced. In addition, the Hedgehog signaling inhibitors, cyclopamine and vismodegib, strongly inhibited the migration of SUM159 breast cancer cells, suggesting the association of Hedgehog signaling with the migration of breast cancer cells. Taken together, sulforaphene significantly inhibited the migration via down-regulating the Hedgehog signaling pathway and suggest that sulforaphene may be considered as a potent phytochemical in suppressing the mammary carcinogenesis.
Citation Format: Cheng Bao, Jaehoo Lee, Jiwon Ko, Hyun-Chang Park, Hong jin Lee. Sulforaphene inhibited migration through down-regulating the Hedgehog signaling in SUM159 human breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 121. doi:10.1158/1538-7445.AM2014-121
Abstract 1210: A patient derived xenograft tumor model platform for “mouse trials”
Authors: Yan Ying , Yu Tengfei , Du Wei , Tong Guosheng , Yang Yuefei , Tan Tingting , Yang Xuqin , Liu Zhenhua , Gu Jiali , Hua Liang , Zhang Wei , Ye Xin K. , Gu Zhenyu 
Published: May 2015

Abstract
From Chinese cancer patients, close to 600 patient derived xenograft (PDX) tumor models have been established (&gt; P3, three passages in mice) at GenenDesign through serial passages in the immune-compromised nude mice. The major collection of GenenDesign PDX tumor model platform represents cancer types that are prevalent in Asian patients, including gastric cancer (&gt; 200 models), esophageal cancer (&gt;100 models), liver cancer (∼50 models), pancreatic cancer (&gt;60 models) and lung cancer (&gt; 80 models). Establishment of variant PDX models from the same patient tumor is on-going to support translational studies of tumor heterogeneity.
Initial characterization indicates that the mouse PDX models have captured the major histopathological characteristics of the original human tumors. Reproducible growth curves for PDX models (&gt;P3) support their usage in efficacy analysis of anti-cancer therapeutic agents. Response curves to SoC (standard of care) chemotherapies such as Paclitaxel for lung cancer, FOLFOX for gastric cancer and Sorafenib for liver cancer have been established in the PDX tumor models, providing a baseline for further investigation of novel therapies in a combination setting.
On-going molecular characterization including oncogene mutational analysis and target specific IHC and FISH analysis has identified panels of PDX tumor models with aberrations in key oncogenic signaling pathways, including lung panels with EGFR overexpression or KRAS mutations, gastric panels with FGFR2 amplification or being HER2 positive, lung and gastric panels with cMET overexpression. Testing of Herceptin in the gastric HER2 positive tumor panel resulted in observations similar to that from the ToGA trial. At the same time, Herceptin resistant PDX tumor variants (de novo or acquired) were identified or established. The PDX tumor model panels facilitate translational studies in a “mouse trial” format in a setting similar to clinical trials to test patient stratification strategies and drug response predictive biomarkers for emerging therapeutic modalities.
Citation Format: Ying Yan, Tengfei Yu, Wei Du, Guosheng Tong, Yuefei Yang, Tingting Tan, Xuqin Yang, Zhenhua Liu, Jiali Gu, Liang Hua, Wei Zhang, Xin K. Ye, Zhenyu Gu. A patient derived xenograft tumor model platform for “mouse trials”. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1210. doi:10.1158/1538-7445.AM2014-1210