bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4792: Prmt6 promotes lung tumor growth via modulation of Ilf2 expression
Authors: Avasarala Sreedevi , Wu Pei-Ying , Scoyk Michelle Van , Baskaran Abinaya , Su Yanlin , David Odile , Winn Robert A. , Bikkavilli Kamesh 
Published: July 2017

Abstract
Lung cancer kills more people in the US than any other malignancy. High mortalities are in part due to the diagnosis at an advanced inoperable stage where the 5-year survival is only 4%. Therefore improving survival will require increased knowledge of genes that drive the complex mechanisms of lung cancer initiation and progression. Emerging data implicate novel roles for protein arginine methylation in lung cancers. In protein arginine methylation, nitrogen/s of arginine can be post-translationally modified via the addition of a methyl group, catalyzed by a class of enzymes, protein arginine methyl transferases (PRMTs). Protein arginine methyl transferase 6 (PRMT6) is a methyl transferase that modifies histone tails, and its expression is upregulated in lung cancers, correlating with a worse overall patient survival. However, the in vivo role of PRMT6 has never been examined. In this study, we show that targeted over-expression of PRMT6 in the mouse lungs (PRMT6 gain-of-function mouse model) results in an increased chemical carcinogen-induced lung tumorigenesis. We also performed proteomics on PRMT6-associated proteins from the mouse lung and identified Interleukin-enhancer binding protein 2 (ILF2) a.k.a. nuclear factor 45 (NF45) as a novel PRMT6 interacting protein. By using a battery of cell-based assays, we show that PRMT6 plays an essential role in the regulation of the pro-proliferative functions of ILF2. Therefore, targeting PRMT6/ILF2 axis might open new possibilities for the therapeutic intervention of lung cancer.
Citation Format: Sreedevi Avasarala, Pei-Ying Wu, Michelle Van Scoyk, Abinaya Baskaran, Yanlin Su, Odile David, Robert A. Winn, Kamesh Bikkavilli. Prmt6 promotes lung tumor growth via modulation of Ilf2 expression [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 4792. doi:10.1158/1538-7445.AM2017-4792
Abstract 4799: Fibroblast growth factor receptor (FGFR) promotes progression of cutaneous squamous cell carcinoma
Authors: Khandelwal Alok R. , Rong Xiaohua , Moore-Medlin Tara , Ma Xiaohua , Warner Amelia , DiGiovanni John , Nathan Cherie-Ann O. 
Published: July 2017

Abstract
Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived invasive and metastatic tumor of the skin. It is the second-most commonly diagnosed form of skin cancer (16%) striking 200,000 Americans annually. Increased understanding of the mechanisms involved in pathogeneses of cSCC could identify means to prevent, inhibit and reverse this process. In our previous studies, inhibition of Fibroblast growth factor receptor (FGFR) significantly decreased Ultraviolet B-induced (UVB) epidermal hyperplasia and hyperproliferation in SKH-1 mice suggesting an important role of FGFR signaling in skin cancer prevention. However, the role of FGFR signaling in the progression of cSCC is not yet elucidated. Analysis of the expression of FGFR2 in cSCC cells and normal epidermal keratinocytes revealed overexpression and increased FGFR2 activity in cSCC cells. Tumor cell-specific overexpression of FGFR2 was detected in human cSCCs and in UVB-induced mouse cSCCs, whereas the expression of FGFR2 was low in premalignant lesions and normal skin. Further, treatment with a selective FGFR inhibitor; AZD4547 significantly decreased proliferation, migration, and invasion of cSCC cells in culture. The decrease in FGFR activation was associated with an inhibition of mTORC1 and mTORC2 signaling markers. Our studies provide mechanistic evidence for the role of FGFR2 in early progression of cSCC and identify FGFR as a putative therapeutic target in the treatment of skin cancer.
Citation Format: Alok R. Khandelwal, Xiaohua Rong, Tara Moore-Medlin, Xiaohua Ma, Amelia Warner, John DiGiovanni, Cherie-Ann O. Nathan. Fibroblast growth factor receptor (FGFR) promotes progression of cutaneous squamous cell carcinoma [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 4799. doi:10.1158/1538-7445.AM2017-4799
Abstract 4801: Collection of lung cancer patient-derived xenograft (PDX) models to evaluate precision therapeutic strategies
Authors: Molina-Pinelo Sonia , Melendez Ricardo , Suarez Rocío , García Laura , Ojeda Laura , Moreno Nicolas , Guijarro María V , Paz-Ares Luis , Ferrer Irene 
Published: July 2017

Abstract
Background: Translational cancer research needs appropriated preclinical models to discover predictive biomarkers and evaluate precision therapeutic strategies. Conventional available preclinical models have proven not been optimal to this end, since cell lines based xenografts do not reconstitute the complexity of human cancer and carry acquired mutations not found in the original tumor. For these reasons our aim was generate and completely characterize a collection of non-small cell lung cancer (NSCLC) PDX models useful for translational lung cancer research.
Materials and methods: Resected primary tumors from NSCLC patients were subcutaneous xenografted in athymic nude mice and expanded in successive groups of mice to get a perpetual live bank of each tumor. Every tumor, which successfully grew in mice, was analyzed by histologic and molecular techniques (NGS gene panel, exome and RNA Seq). Furthermore, a bank of frozen pieces of tumor was expanded and stored in order to generate later cohorts of tumor-bearing mice suitable for preclinical drug evaluation.
Results: Our collection consists on 42 PDX models (26 SCC, 12ADC, 3LCC). We have characterized all of them histologically and molecularly with a 22 genes NGS panel. Furthermore, we have analyzed the exome and transcriptome of 33 models (20 SCC, 10 ADC and 3 LCC). All PDX models mostly retain the principal histologic and molecular characteristics of their donors and recapitulate the heterogeneity of human lung tumors. In our PDX collection we have sufficiently represented all the NSCLC histology and the most relevant molecular alterations in lung cancer in order to perform precision medicine evaluation studies.
Conclusions: We have generated a collection of 42 PDX models of NSCLC characterized at the histological, genomic and transcriptomic level, which represents the most frequent histological and molecular subtypes of this type of lung cancer. This collection will be really useful to integrate drug screening with biomarker discovery and to evaluate precision therapeutic strategies. Our future aim will be to use this collection for biomarkers identification and preclinical evaluation of new therapeutic strategies targeted to bad prognostic lung tumors with suboptimal therapeutic approaches.
Citation Format: Sonia Molina-Pinelo, Ricardo Melendez, Rocío Suarez, Laura García, Laura Ojeda, Nicolas Moreno, María V Guijarro, Luis Paz-Ares, Irene Ferrer. Collection of lung cancer patient-derived xenograft (PDX) models to evaluate precision therapeutic strategies [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 4801. doi:10.1158/1538-7445.AM2017-4801
Abstract 4806: Strategies to overcome the heterogeneity of tumor cells in breast cancer therapy
Authors: Calaf Gloria M. , Gallardo Marcela , Roy Debasish , Ponce-Cusi Richard 
Published: July 2017

Abstract
Breast carcinogenesis is a multistage process that involves mutations and alterations attributed to exposure to exogenous environmental substances and endogenous agents as female hormones. To overcome the heterogeneity of tumor cells in breast cancer therapy several strategies must be considered from the bench to clinical settings. It is proposed four strategies: Analysis to determine 1) Apoptosis, 2) Epithelial-mesenchymal transition (EMT), 3) CD44/CD24 gene and protein expression in cells derived from mammospheres and 4) MicroRNAs as miR34a and others by the effects of chemotherapeutic drugs (as pamidronate (Pam), 5-Fluorouracil (5-FU) and antioxidants as Curcumin (Cur) (diferuloylmethane) derived from Curcuma longa. Pam, a bisphosphonate is used in the treatment of breast cancer. 5-FU is a chemotherapeutic agent for the treatment of a variety of solid cancers that arrest cell cycle and induce apoptosis in cancer cells. We evaluated genes and proteins targeted by these drugs and antioxidants in a triple positive cell line, as MCF7 and a negative, MDA-MB-231 for hormonal receptors, respectively and in an in vitro breast cancer model induced by radiation and estrogen that was developed with a normal immortalized breast epithelial cell line, MCF-10F exposed to low doses of high LET (linear energy transfer) alpha particles (150 keV/μm) of radiation, and cultured in presence of 17β-estradiol. We used: i) MCF-10F, ii) Alpha3, a malignant non-tumorigenic, iii) Alpha5, a tumorigenic one and iv) Tumor2 cell line derived from Alpha5 injected into the nude mice. Previous results showed increased cell proliferation, anchorage independency, invasive capabilities and tumor formation in nude mice, microsatellite instability and loss of heterozygosity in chromosomes 6, 8, 11 and 17 and mutations of c-Ha-ras and Rho-A in Alpha5 and Tumor2 compared to the control MCF-10F and their counterparts. Pam, 5-FU and Cur inhibited migration and invasion in both cell lines, and also decreased c-Ha-ras, Rho-A, p53, and Cav-1 gene expression by RT-qPCR. These compounds also induced 1) apoptotic effect on Bcl-xL and Bax gene and protein expression and by flow cytometry; 2) changes in EMT markers such as Snail, Slug, Axl, 3) CD44/CD24 alterations and 4) target MicroRNAs as miR34a on different process. It can be concluded that strategies to overcome the heterogeneity of tumor cells can be used to interfere with genes involved in critical steps in breast carcinogenesis. Grant: Tarapacá University, Arica, Chile (GMC).
Short tittle: Strategies in breast cancer therapy
Citation Format: Gloria M. Calaf, Marcela Gallardo, Debasish Roy, Richard Ponce-Cusi. Strategies to overcome the heterogeneity of tumor cells in breast cancer 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 4806. doi:10.1158/1538-7445.AM2017-4806
Abstract 4820: Developing a xenograft human tumor model in immunocompetent mice
Authors: Basel Matthew T. , Narayanan Sanjeev , Ganta Chanran , Shrestha Tej B. , Pyle Marla , Bossmann Stefan H. , Troyer Deryl L. 
Published: July 2017

Abstract
Animal models are essential to preclinical cancer research and are used clinically to determine optimal treatment regimens, but current xenograft models are limited in their utility, especially due to the lack of a competent immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and, after birth, mice were challenged again with A375 cells to determine their ability to develop tumors. Intravenous injections of A375 cells after tolerization resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR. The development of lung neoplasms was dependent on fetal tolerization; non-tolerized mice did not develop tumors after injection. Interestingly, subcutaneous injected cells did not form tumors, but this was shown to be due to an innate, non-adaptive immune response and did not create lasting rejection of tumor cells. This procedure was repeated with several different tumor lines to show the universal nature of the method: BxPC3 (human pancreatic cancer), M21 (human melanoma), HeLa (human cervical cancer), and MDA231 (human breast carcinoma).
Citation Format: Matthew T. Basel, Sanjeev Narayanan, Chanran Ganta, Tej B. Shrestha, Marla Pyle, Stefan H. Bossmann, Deryl L. Troyer. Developing a xenograft human tumor model in immunocompetent mice [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 4820. doi:10.1158/1538-7445.AM2017-4820
Abstract 4833: Perfusion-based bioreactor culture of primary cancer tissue maintains tumor microenvironment complexity and allow in-vitro testing of immune blockade therapy
Authors: Muraro Manuele Giuseppe , Muenst Simone , Manfredonia Celeste , Mele Valentina , Daester Silvio , Tzankov Alexandar , Terracciano Luigi , Weber Walter , Spagnoli Giulio C. , Iezzi Giandomenica , Martin Ivan , Soysal Savas D. 
Published: July 2017

Abstract
In vitro culture of primary cancer tissue is still very limited and the generation of patient derived xenograft determine the loss of human-cancer associated stroma. In this context, the use of 3D in vitro systems based on human tissue may be an innovative system to be exploited for keeping the tumor microenvironment (TME) complexity of the tissue in vitro.
Freshly excised colorectal (CRC) and breast cancer (BrCa) specimens were fragmented and cultured in 3D “sandwich-like format” between porous collagen scaffolds under perfusion flow (U-CUP, Cellec Biotek AG). The maintenance of tumor and immune-infiltrating cells, survival and phenotypic characterization were histologically assessed. In a second step cancer treatment were tested.
U-CUP culture allowed the preservation, viability and expansion of tumor tissue with concomitant stromal and immune cells. Expanding cancer cells were viable after 10 and 21 days (CRC and BrCa, respectively). Administration of anti-ER treatment to Lumina A ER+ BrCa was associated with decreased expansion of cancer tissue into the scaffold after 21 days. The maintenance of immune-infiltrating cells allowed testing of immune blockade therapy. Administration of anti-PDL1 antibody, alone or in combination with anti-CTLA4, to the culture medium was associated with increased expression of markers of immune-activation (i.e. IFNγ) and decreased expression of immunosuppressive cytokine IL10.
Preserving malignant, interstitial and immunocompetent cells comprised in surgically excised tumor specimens might allow a direct evaluation of the effects of various treatments on the complex TME. This engineered in vitro model could allow animal-free testing and it could be extended as a platform allowing the testing of innovative approaches for the treatment of human malignancies. Our findings shed the light on a promising system for selecting personalized treatment based on a patient’s tumor specific microenvironment.
Note: This abstract was not presented at the meeting.
Citation Format: Manuele Giuseppe Muraro, Simone Muenst, Celeste Manfredonia, Valentina Mele, Silvio Daester, Alexandar Tzankov, Luigi Terracciano, Walter Weber, Giulio C. Spagnoli, Giandomenica Iezzi, Ivan Martin, Savas D. Soysal. Perfusion-based bioreactor culture of primary cancer tissue maintains tumor microenvironment complexity and allow in-vitro testing of immune blockade 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 4833. doi:10.1158/1538-7445.AM2017-4833
Abstract 4838: Optimization of prostate cancer organoid culture methods to grow PDX and human biopsy tissue
Authors: Beshiri Mike L. , Tran Crystal , Sowalsky Adam G. , Nguyen Holly M. , Agarwal Supreet , Tice Caitlin M. , Corey Eva , Kelly Kathy 
Published: July 2017

Abstract
A major obstacle in the field of prostate cancer research is the limited capacity to culture prostate cancer-derived cells in vitro. There are relatively few established prostate cancer cell lines in use today. Those that are available are amenable to in vitro drug assays and mechanistic studies, but do not well-represent the genetic diversity of the disease, nor do they accurately predict in vivo response. Recently, organoid culture techniques have been developed for prostate cancer by the laboratories of Hans Clevers and Charles Sawyers that have increased our ability to grow metastatic tumor-derived prostate cancer cells in vitro. This represents a great step forward, but we are still restricted by the limited availability of biopsy tissue and the relatively low success rate (~20%) in establishing new organoid lines. The LuCaP series of patient-derived xenografts (PDXs) represents a well-characterized set of prostate cancer specimens that is genetically diverse, reflective of a range of treatment histories, and available to the research community. We have modified the organoid culture technique based upon systematic comparisons and analysis for organoid growth of the LuCaP PDXs. Our modified conditions represent an improvement upon the original growth conditions. We have successfully cultured 21 out of 24 LuCaPs attempted, for at least one generation, and 16 out of 24 are able to grow long-term over several generations. This includes 3 of the newest LuCaPs (167, 170.2, and 189.3) that we have genomically characterized. Comparison of the PDX and various organoid generations showed significant conservation of genomic changes ranging from 75-90% for nonsynonymous point mutations. The modified organoid culture method immediately and significantly increases the number of prostate cancer lines that are available by making the LuCaP PDXs accessible to in vitro culture. In addition to the PDXs, our method has improved the success for culturing metastatic samples grown from biopsies. We show here that 2 out of 3 patient-derived organoid lines that we have established, grow well in the modified conditions but poorly in the original culture conditions, the third grows equally well in both conditions.
Citation Format: Mike L. Beshiri, Crystal Tran, Adam G. Sowalsky, Holly M. Nguyen, Supreet Agarwal, Caitlin M. Tice, Eva Corey, Kathy Kelly. Optimization of prostate cancer organoid culture methods to grow PDX and human biopsy tissue [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 4838. doi:10.1158/1538-7445.AM2017-4838
Abstract 4839: Ephrin-A ligands regulate cutaneous tumor etiology and metastasis through cell autonomous and non-autonomous mechanisms
Authors: Zheng Ji , White Bethany Perez , Kaplan Nihal , Zhao Zhe , Blumenberg Miroslav , Getsios Spiro , Wang Bingcheng 
Published: July 2017

Abstract
Glycophosphatidylinositol-anchored ephrin-A ligands target EphA receptor tyrosine kinases (RTKs) to promote keratinocyte differentiation. Accordingly, genetic ablation of the major epidermal EphA subtype, EphA2, increases susceptibility to DMBA/TPA-induced cutaneous chemical carcinogenesis. Defining the corresponding role of ligands for EphA2 in skin cancer has been more cumbersome as the three ephrin-A genes (Efna1, Efna3, Efna4) are all prominently expressed in skin. We met this challenge by utilizing a triple Efna1/3/4 knockout (TKO) mice that reflects the pattern of reduced Efna gene expression found in mouse and human cutaneous SCCs. Skin tumors developed earlier and grew faster in mice lacking EphA2 or these three ephrin-A ligands. Interestingly TKO mice displayed accelerated malignant progression toward invasive SCC that metastasized to the lymph nodes and lungs by 25 weeks following DMBA-TPA treatment. Using keratinocyte culture models, we found that ephrin-A ligands act within the epidermis to limit keratinocyte migration in a manner that depends on their targeting of EphA2. We also illustrated a key role for ephrin-A ligands in the surrounding tumor microenvironment by re-introducing isogenic SCC cell lines into the skin of wild-type or TKO mice on congenic FVB background; tumor growth and metastasis was facilitated in mice lacking ephrin-A ligands. Importantly, the invasive phenotype of TKO mouse tumor cell lines was normalized by genetic reintroduction of either Efna1 or Efna3. Integrating our findings from human tumors, mouse models, primary cell cultures, and allograft models provides strong support for the notion that ephrins operate within tumor cells and also in the microenvironment to suppress skin tumor initiation and metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Ji Zheng, Bethany Perez White, Nihal Kaplan, Zhe Zhao, Miroslav Blumenberg, Spiro Getsios, Bingcheng Wang. Ephrin-A ligands regulate cutaneous tumor etiology and metastasis through cell autonomous and non-autonomous mechanisms [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 4839. doi:10.1158/1538-7445.AM2017-4839
Abstract 4843: ANKRD52 inhibited tumor metastasis through dephosphorylation of PAK1 in lung adenocarcinoma
Authors: Lin Yen-Fan , Liu Ying-Pu , Lee Ting-Fang , Wu Cheng-Wen 
Published: July 2017

Abstract
As a leading cause of cancer-related deaths, metastasis is the ultimate challenge in our effort to fight cancer as a life-threatening disease. A member of ankyrin repeat proteins, ankyrin repeat domain 52 (ANKRD52), is studied here to be involved in the regulation of lung adenocarcinoma metastasis. Ankyrin repeat proteins are known to function as a platform for protein-protein interactions, and ANKRD52 was shown to interact with protein phosphatase 6 (PP6). This study aimed to investigate the anti-metastatic roles of ANKRD52 in lung adenocarcinoma. Immunohistochemistry staining in lung cancer tissue revealed prolonged disease-free survival in high ANKRD52 expressing cases. Using lung cancer cell lines, ANKRD52 knockdowns showed significantly increased cell mobility while forced expressed ANKRD52 decreased cell mobility. Using mass spectrometry analysis, p21-activated kinases (PAK1) was identified to interact with ANKRD52. Upregulated PAK1 phosphorylation was detected in ANKRD52 or PP6 knockdowns. Our model demonstrated a novel anti-metastatic protein, ANKRD52, that regulates cell mobility through interactions with PP6 and dephosphorylation of PAK1.
Citation Format: Yen-Fan Lin, Ying-Pu Liu, Ting-Fang Lee, Cheng-Wen Wu. ANKRD52 inhibited tumor metastasis through dephosphorylation of PAK1 in lung adenocarcinoma [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 4843. doi:10.1158/1538-7445.AM2017-4843