bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2771: Development of a non-thermal plasma model for neuroblastoma treatment.
Authors: Srinivasan Priya , Snyder Jason A. , Shashurin Alexey , Keidar Michael , Sandler Anthony D. 
Published: August 2014

Abstract
Neuroblastoma is a common extra-cranial solid tumor in children. There are several clinical categories of this disease, ranging from curable to very poor prognosis in which this cancer is treated with multi-modal therapy. We have tested a novel ablative technology, using non-thermal helium generated plasma jets, as a means to selective targeting of neuroblastoma cells. Plasma consists of partially ionized molecules, free radicals and other species. We have investigated the molecular mechanisms involved in non-thermal plasma mediated tumor cell death, as well as the differences in response between tumor and normal cells. Treatment with non-thermal plasma induced apoptosis in cancer cells, while normal cells appear to be less sensitive to the toxic effects. Levels of reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide are elevated after plasma treatment, suggesting that this may contribute to cell death. Scavengers of ROS were able to abrogate apoptosis in plasma-treated cells. Plasma therapy of tumor cells may be a novel approach to delivery of high levels of ROS, offering the ability to directly target and selectively destroy neoplastic tissue. Methods enhancing the ROS effect and/or technical delivery of the free radicals uniformly to tumor cells within a mass will be needed before this technology could be translated to ablating solid tumors in vivo.
Citation Format: Priya Srinivasan, Jason A. Snyder, Alexey Shashurin, Michael Keidar, Anthony D. Sandler. Development of a non-thermal plasma model for neuroblastoma treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2771. doi:10.1158/1538-7445.AM2013-2771
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2776: Establishment of patient non-small cell lung cancer derived models for test of anticancer drugs.
Authors: Liu Changnian , Sun Connie , Li Wenwei , Zhou Wen , Liu Yong , Zhou Rui , He Fang , Bai Chang 
Published: August 2014

Abstract
BACKGROUND Human tumor xenograft models established by transplantation of human tumor cell lines into immunodifficient mice have been routinely used for preclinical test of anticancer agents. But tumor cell lines have a relatively low transplantability and resulted in a limited number of tumor models available for selection of right models for testing novel agents based on their antitumor mechanism. Recently, we have developed a large number of patient primary non-small cell lung cancer (NSCLC) xenograft models by transplanting patients’ fresh tumor tissues into nude mice, which have been employed for preclinical test of anticancer agents. METHODS The fresh NSCLC tissues were collected from local hospitals. The tumor fragments of 1-2 mm were subcutaneously implanted in the flanks of the nude mice by trocar needle. Sixteen tumor fragments were grafted into four mice from one patient tumor tissue (passage 0). All therapeutic efficacy experiments used female mice bearing passage 5 xenografts. The test drugs included cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, erlotinib, gefitinib, and pemetrexed. RESULTS A total of 213 patient primary NSCLC samples were implanted into nude mice, and 107 primary tumor models have been established with a tumor taking rate of 50% for the first passage. The tumor taking rates were higher (80-100) in the later passages. The therapeutic efficacy of the test drugs in these models is consistent with their clinical findings. The histopathology and gene sequence of the established primary tumor xenografts were analyzed; their architecture, histopathological morphology, and genomic mutation status from five generations of xenografts retained the patients’ original tumor characteristics. CONCLUSIONS The patient primary NSCLC models can be established in a large number for right models selection in preclinical setting, and have been employed for test of standard of care drugs and novel anticancer agents. The primary tumor models retain a similarity in histology and genomic mutation status to their patients’ original tumors. They may predict more relevant clinical response rate and higher correlation with clinical findings than use of traditional xenograft models established from long-term cultured cancer cell lines. Especially, they have advantages for test of target-oriented therapeutics in new drugs discovery and development programs.
Citation Format: Changnian Liu, Connie Sun, Wenwei Li, Wen Zhou, Yong Liu, Rui Zhou, Fang He, Chang Bai. Establishment of patient non-small cell lung cancer derived models for test of anticancer drugs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2776. doi:10.1158/1538-7445.AM2013-2776
Abstract 2781: Champions TumorGraft™ models possess PIK3CA mutations - A great tool to explore the PI3K/AKT pathway.
Authors: Khor Tin Oo , Tiruchinapalli Dhanrajan , Friedman Jay , Anderson Nathan , Sidransky David , Bruckheimer Elizabeth M. 
Published: August 2014

Abstract
Phosphatidylinositol 3-kinase (PI3K) is an important intracellular signal transducer that is involved in many cellular functions such as cell growth, proliferation, and differentiation. PI3K is a heterodimeric molecule composed of a regulatory and a catalytic subunit. PIK3CA, which encodes the p110α catalytic subunit, is often mutated in a range of human cancers, such as colorectal and non-small-cell lung cancers. Increasing our understanding of the biological implications of these mutations and the role of PI3K pathway in cancer proliferation or survival may lead to potential new therapeutic opportunities targeting PI3K signaling.
Champions Oncology focuses on the development of TumorGraft models derived from the direct implantation of patient tumors into immunocompromised mice. Compared to traditional cell line-based xenograft models, the patient derived Champions TumorGraft™ models maintain stable gene-expression patterns and mutational status and correlate to clinical predictability. Through extensively characterization, Champions has identified 19 TumorGraft models with PIK3CA mutations. Out of these 19 models, there are 11 colorectal cancers, 3 non-small cell lung cancers, 3 pancreatic cancers, 1 gastric cancer and 1 melanoma. Genomics analyses using the Ampliseq platform identified the majority of PIK3CA mutations in exon 9 and 20. Mutations in these regions of PIK3CA are known to confer resistance to some anti-cancer agents, such as HER2 antibodies. Additionally, it has been reported that PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. Upon further analysis, we identified the same pattern in Champions TumorGraft models where∼70% (13 out of 19) of the PIK3CA mutant models possess either concurrent RAS or BRAF mutations. Notably, PI3K activates the downstream kinase AKT which ultimately triggers the mTOR pathway. Mutations in cancer often result in constitutive activation of this pathway. Given the role of the PI3K/AKT signaling in cancer and the presence of these specific mutations in the Champions TumorGraft bank, utilization of Champions’ TumorGraft models in oncology drug development allows for greater insight into new therapeutic opportunities targeting the inhibition of PI3K/AKT signaling and offers new promise for patients with these activated pathways.
Citation Format: Tin Oo Khor, Dhanrajan Tiruchinapalli, Jay Friedman, Nathan Anderson, David Sidransky, Elizabeth M. Bruckheimer. Champions TumorGraft™ models possess PIK3CA mutations - A great tool to explore the PI3K/AKT pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2781. doi:10.1158/1538-7445.AM2013-2781
Abstract 2782: Utilization of in vivo human isogenic cancer models in the new era of targeted therapies.
Authors: Sun Yanmei , Zhang Songling , Astley Holly , Foster Rebecca , Schofield Christine , Torrance Chris , Ning Jinying , Chen Taiping , Shi Qian 
Published: August 2014

Abstract
The explosion of knowledge regarding the genetic underpinnings of human cancer heralds a new era of targeted therapy. To date, in vivo cell based screening has proven a useful tool in almost all drug development programs. Cells used in such screens are usually harvested from cancer patients that harbor the specific mutation of interest, but these cells almost invariably contain many other additional mutations making it difficult to ascertain the specific functions of molecules being screened. Thus the lack of true control cells hampers the development of new cancer therapeutics.
Using cell lines generated with Horizon Discovery's proprietary rAAV-based GENESIS™ gene editing platform, we have established a comprehensive range of isogenic cancer models for our in vivo compound screening program to service our clients in academia and industry, with mutations in a wide variety of genes including KRAS, PIK3CA, PTEN, IDH1 and p53. These isogenic tumor models comprise pairs of cell lines which share the same genetic background, differing only by the mutation of interest and therefore allowing definitive studies of specific genetic variances to be performed. The same isogenic pairs of lines can be used for in vitro and in vivo experiments to ensure continuity and relevance of results. We have carried out intensive validation of these models in vivo to ensure the lines generate robust tumor growth in mice and the matched tumors differ only in the genetic composition of target gene.
In a POC study, colon cancer cell lines with the KRAS G13D mutation have been demonstrated to respond to Cetuximab treatment, consistent with recent findings in the clinic. These results challenge the current clinical practice of only using Cetuximab as a therapeutic for KRAS wild type patients, and provide the basis for expanding the usage of the drug to benefit more patients.
In summary, we have established a series of reliable in vivo isogenic models with precise and highly specific genetic modifications as predictors of clinical effect. They will provide a valuable tool in the drug discovery and development arena to drive forward personalized medicine by enabling novel target validation, expansion of the target population for existing therapeutics, and definition of patient responsive genotypes.
Citation Format: Yanmei Sun, Songling Zhang, Holly Astley, Rebecca Foster, Christine Schofield, Chris Torrance, Jinying Ning, Taiping Chen, Qian Shi. Utilization of in vivo human isogenic cancer models in the new era of targeted therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2782. doi:10.1158/1538-7445.AM2013-2782
Abstract 2785: Development program of patient tumor tissue bank to support the drug and target discovery.
Authors: Hillairet de Boisferon Marc , Bichat Francis , Mignard Caroline , Morgand Loïc , Blot Lydia , Venot Corinne , Merino-Trigo Ana , Vrignaud Patricia 
Published: August 2014

Abstract
Background: The humanization of mice with various tissues named Chi-mice® aimed to reproduce the human situation to be more predictive than conventional models. Despite significant progress in identifying malignancy of cancer cells, a more detailed understanding of tumor generation is needed. Xenograft of tumor cells into immunodeficient rodents has constituted the major preclinical screen for the development of new drugs. These models have identified efficacious agents, but their chemosensitivity, genetic drift and clonal selection induced by cell culture have been part of the high attrition rate observed in the clinical development. Patient-derived tumor xenograft (PDX) obtained in xenografting fresh patient tumor samples in mice are reported as being more predictive to the clinical situation in maintaining the histopathology and molecular diversity of the patient tumors.
Methods: The PDXs collection has been set up under ethical agreement with informed consent of patients. The patients have been screened for absence of HIV, HBV and HCV. The anonymized patient's clinical history and tissue banking (including normal tissue when available) are centralized in our internal biological resource center. Tumor samples were freshly implanted in nude or SCID mice.
Results:
PDX Passage 0 Passage 1 Take rate (%) Breast 152 10 6 Lung 18 7 39 Bladder 31 11 35 Liver 31 4 13 Stomach 17 7 41 Kidney 28 8 29 Pancreas 21 4 19 Prostate 57 5 9 Total 355 56 Xenograft Passage 0 Lymphoma Established model SCID mice 85 16 (19%) 19 (22%) Nude mice 270 0 (0%) 37 (14%)
Cryopreservation of the PDX is performed at early passages allowing using these PDX only at low passage. The histopathology, EGFR, PSA, AR, HER, ER and PR statute for lung, prostate and breast carcinoma and tumor growth characteristics of these PDX are being performed. Lymphoma characterization was performed using immunohistochemistry (hCD20, m/hKi67). Lymphoma detection, probably related to EBV infection, leads to switch to nude mice for xenografting.Conclusion: To create a highly diversified panel of PDX, we organized a global process from multiple centers. These PDX are currently being used in preclinical development of new therapies and clinical positioning including biomarkers identification.
Citation Format: Marc Hillairet de Boisferon, Francis Bichat, Caroline Mignard, Loïc Morgand, Lydia Blot, Corinne Venot, Ana Merino-Trigo, Patricia Vrignaud. Development program of patient tumor tissue bank to support the drug and target discovery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2785. doi:10.1158/1538-7445.AM2013-2785
Abstract 2787: PrimePanel provides a high throughput in vitro drug screening platform that intimately links to in vivo pharmacological analysis in PDX models.
Authors: Zhang Yanxia , Ge Yuqiang , Liu Yanan , Zhao Jing , Li Lanhua , Qiao Meng , Ning Jinying , Zha Jiping , Liu Guizhong 
Published: August 2014

Abstract
Patient derived xenografts (PDX) are in vivo animal tumor models established directly from patient tumor samples without any in vitro manipulation. It has been shown that these tumor xenografts maintain essential histopathological features and genetic profiles of the original tumors, and thus are the most clinically relevant animal models for cancer drug discovery. Comparing to the traditional cell line derived xenograft (CDX) tumor models, however, one challenge encountered by the PDX in vivo studies is the lack of corresponding in vitro cell culture system for cost-effective and high throughput drug screening and model selection. Here we set out to establish such an in vitro platform, so-called PrimePanelTM, by deriving homogeneous primary cancer cell cultures from the PDX tumors in several major tumor types. These cells are early passage cultures (usually p&lt;10), which maintain similar cellular characteristics as the corresponding tumor xenografts, including the genomic mutational status, biochemical signaling, and responses to tumor cell autonomously targeted therapeutics. Thus, PrimePanelTM offers a higher throughput, faster turnaround, more versatile and lower cost platform to assess drug efficacy prior to in vivo study, which could fulfill a critical need in early stage drug discovery.
Citation Format: Yanxia Zhang, Yuqiang Ge, Yanan Liu, Jing Zhao, Lanhua Li, Meng Qiao, Jinying Ning, Jiping Zha, Guizhong Liu. PrimePanel provides a high throughput in vitro drug screening platform that intimately links to in vivo pharmacological analysis in PDX models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2787. doi:10.1158/1538-7445.AM2013-2787
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2788: Characterization of an in vivo generated subpopulation of human LnCaP prostate cancer cells as an improved testosterone-dependent in vivo mouse xenograft model for compound testing.
Authors: Lingnau Andreas , Hoffmann Steffen , Schaefer-Obodozie Cynthia , Leisegang Ulrike , Klotzbuecher Andreas , Schaechtele Christoph 
Published: August 2014

Abstract
Prostate cancer is one of the most frequently diagnosed cancer entities in men. It can be estimated that in 80% of all men reaching the age of 80 years prostate tumors are present. Since a depletion of testosterone in prostate cancer therapies is often performed, androgen-dependent and -independent prostate carcinoma cell lines have been widely used to establish mouse in vivo xenograft models in order to identify novel drugs helping to eliminate prostate tumors.
A commercially available LnCaP cell line was shown to be androgen-dependent since addition of synthetic androgens to androgen-free culture medium was able to restore proper cell proliferation in cell culture. However, when implanted in SCID mice in order to establish a xenograft model, the take rate turned out to be very low and tumor growth was highly heterogeneously. Therefore, we resected and recultivated one of the few well-growing tumors and reimplanted the arising subpopulation subcutaneously in mice. After performing two rounds of this “subpopulationing” procedure we could generate a new cell line, LnCaP-Z2, which was able to form tumors in mice with a take rate of nearly 100%, but still shows heterogenous tumor growth similar to other subcutaneously implanted prostate cancer cells (e.g. PC-3).
In order to demonstrate an androgen dependency of our new LnCaP subpopulation model in vivo we used castrated mice and implanted them subcutaneously with two different prostate cancer cell lines in the absence or presence of also subcutaneously inoculated testosterone pellets. Whereas no influence of testosterone was detectable on the growth behavior of subcutaneous PC-3 xenograft tumors, the development of the LnCaP-Z2 xenografts was strictly dependent on testosterone release.
Finally, treatment of Bicalutamide, a typical member of the class of anti-androgens, which is frequently used in the treatment of prostate cancer, led to significant inhibition of tumor growth using our improved subpopulation LnCaP-Z2 in vivo model. Thus, we could demonstrate the model's potency as a testosterone-dependent in vivo tool suitable for screening and development of novel anti-prostate cancer drugs.
Citation Format: Andreas Lingnau, Steffen Hoffmann, Cynthia Schaefer-Obodozie, Ulrike Leisegang, Andreas Klotzbuecher, Christoph Schaechtele. Characterization of an in vivo generated subpopulation of human LnCaP prostate cancer cells as an improved testosterone-dependent in vivo mouse xenograft model for compound testing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2788. doi:10.1158/1538-7445.AM2013-2788
Abstract 279: A small molecular miR-21 inhibitor inhibits glioma cell invasion and mesenchymal transition via upregulation of VHL expression.
Authors: Shi Zhendong , Zhang Junxia , Han Lei , Zhang Kailiang , Chen Luyue , Qian Xiaomin , Pu Peiyu , Kang Chunsheng 
Published: August 2014

Abstract
Glioblastomas (GBMs) are the most common malignant brain tumors which characterized by rapid and invasive growth. Accumulating evidence points to a critical role of EMT like events during glioma progression and malignant transformation. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. In this study, we identified a small molecular miR-21 inhibitor through a high-throught screening approach and found it significantly repressed the U87 and LN229 glioma cell migration and invasion. Meanwhile, VHL, a direct target of miR-21, was increased expression in mRNA and protein level after this miR-21 inhibitor treatment, but the β-catenin expression was reduced. Silencing of VHL using small interefering RNA (siRNA) also reduced β-catenin expression. Furthermore, suppression of β-catenin transactivation by miR-21 inhibitor, through upregulation of VHL expression, increased E-cadherin expression and partially reversed the epithelial-mesenchymal transition (EMT). On the other hand, confocal microscopy and Western blot assay presented that N-cadherin, ZEB1, ZEB2 and MMP9 expression were reduced. Additionally, in a U87 intracranial glioma xenograft nude mice model, we found a less invading tumor edge of miR-21 inhibitor treated group in comparison with DMSO group. Moreover, there was an increased expression of E-cadherin and reduced expression of β-catenin, N-cadherin, ZEB1, ZEB2 and MMP9 in tumor samples after the inhibitor treatment. Together, these results provided insight into the specific treatment efficacy of this small molecular inhibitor in EMT and tumor metastasis, which achieved via up-regulation of VHL expression. Therefore, it might be a novel and potentially antimetastatic agent for therapeutic intervention in glioblastomas in future.
Citation Format: Zhendong Shi, Junxia Zhang, Lei Han, Kailiang Zhang, Luyue Chen, Xiaomin Qian, Peiyu Pu, Chunsheng Kang. A small molecular miR-21 inhibitor inhibits glioma cell invasion and mesenchymal transition via upregulation of VHL expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 279. doi:10.1158/1538-7445.AM2013-279