bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 598: Utilization of Meditope Biosciences SnAP technology to enhance antibody internalization
Authors: Dumitru Calin D. , Gardiner Elisabeth , Williams John , Zer Cindy 
Published: July 2016

Abstract
Therapeutic antibodies can bind to cell-surface receptors, prompting receptor internalization and effectively blocking further stimulation by the cognate receptor ligands. Receptor internalization is also exploited by antibody-drug conjugates (ADC) to promote effective delivery of cytotoxic payload to the inside of the cell. Meditope Biosciences has developed a way to use its SnAP (Site-specfi novel Antibody Platform) technology to promote enhanced internalization of antibody receptor complexes. The Meditope's SnAP technology functionally enables antibodies to bind to specific peptides, termed “meditopes’, and this property can be used to directly facilitate receptor crosslinking when meditope enabled antibodies are bound to cell surface receptors. Here we show that the affinity of the meditope enabled antibodies (trastuzumab anti-HER2 and gemtuzumab anti-CD33) for cell surface receptors results in the formation of an antibody receptor complex that can be detected by native gel electrophoresis and gel filtration. Binding of the meditope peptide to the enabled antibody does not interfere with normal antigen-antibody interaction and the formation of the peptide bound antibody:receptor complexes results in accelerated internalization of the complex, as shown by decreased surface fluorescence of Alexa 488-labeled SnAP peptides as well as by increased pHrodo-Red increased fluorescence of internalized antibodies when they reach the endosomal compartment. Finally, as a result this increased internalization, the downregulation of specific antibody mediated signaling events are much more effectively downregulated in the presence of the meditope peptide complex as compared to the antibody alone.
Citation Format: Calin D. Dumitru, Elisabeth Gardiner, John Williams, Cindy Zer. Utilization of Meditope Biosciences SnAP technology to enhance antibody internalization. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 598.
Abstract 60: PTEN expression, cholesterol metabolism, and lethal prostate cancer
Authors: Stopsack Konrad H. , Gerke Travis A. , Mucci Lorelei A. , Rider Jennifer R. 
Published: July 2016

Abstract
BACKGROUND: We previously showed that mRNA expression of squalene monooxygenase (SQLE), part of the cholesterol synthesis pathway, is associated with lethal prostate cancer. In-vitro studies suggest that loss of PTEN expression and resulting PI3K pathway activation drive cholesterol ester accumulation in aggressive prostate cancers through sterol regulatory element-binding protein (SREBP) and acyl coenzyme A-cholesterol acyltransferase (ACAT1) activity. In two prospective cohorts, we studied whether lower PTEN expression is associated with cholesterol metabolism and how this relates to lethal prostate cancer.
METHODS: We analyzed men with prostate cancer from the prospective prostatectomy Health Professionals Follow-up Study and Physicians’ Health Study. 105 men had lethal cancer and 284 men non-lethal disease without metastases at 8 years of follow-up. Whole-transcriptome mRNA expression profiling data was available from diagnostic prostate tumor specimens. Linear regression models were used to assess continuous and categorical associations, and Pearson correlation coefficients were calculated. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of lethal prostate cancer.
RESULTS: Both lower PTEN and higher SQLE expression were associated with higher Gleason grade (p trend &lt; 0.001 each). Correlations of PTEN with SREBF1 (r = -0.08, p = 0.1), SREBF2 (r = -0.09, p = 0.07), and ACAT1 (r = 0.04, p = 0.4) were weak. SREBF2 was correlated with SQLE (r = 0.33, p &lt; 0.001) but not with ACAT1 (r = -0.01, p = 0.8). Low PTEN was associated with lethal cancer (OR, 1.50 per 1 standard deviation [SD] decrease; 95% CI, 1.20 to 1.87; p = 0.001). High SQLE was associated with lethal cancer (OR 2.13 per 1 SD increase, 95% CI, 1.63 to 2.79; p &lt; 0.001). SREBF1, SREBF2, and ACAT1 were not associated with lethal cancer (all p &gt; 0.05). Adjusting for PTEN mildly attenuated the association of SQLE with lethal cancer (OR, 2.07; 95% CI, 1.57 to 2.73), as did additional adjustment for age, Gleason grade, and stage (SQLE: OR, 1.75; 95% CI, 1.29 to 2.40). In the lowest quartile of PTEN expression, SQLE was less strongly associated with lethal cancer (OR 1.74; 95% CI, 1.20 to 2.52) compared to the upper three quartiles (OR 2.47; 95% CI, 1.69 to 3.60; p interaction = 0.2).
CONCLUSION: Low PTEN mRNA expression and high SQLE are features of aggressive prostate cancers. However, at the time of prostatectomy, SREBF1/2 expression and resulting ACAT1 expression do not appear to be major characteristics of prostate cancers with lethal outcomes.
Citation Format: Konrad H. Stopsack, Travis A. Gerke, Lorelei A. Mucci, Jennifer R. Rider. PTEN expression, cholesterol metabolism, and lethal prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 60.
Abstract 624: Humanized mouse models for evaluation of cancer therapies
Authors: Duchamp Olivier , Bichat Francis , Mignard Caroline , Ghiringhelli François , Mirjolet Jean-François ,   IMODI Consortium
Published: July 2016

Abstract
Mice with a humanized immune system, so called “humanized” mouse models, have been established to study the complex interaction of the human immune system during human disorders. In case of cancer research, the in vivo model ideally should recapitulate the biological characteristics of the human tumor and of the related tumor microenvironment in patient such as immune system.
Human immune system is reconstituted in immunodeficient mice using either human PBMCs or hematopoietic stem cells (HSCs). Humanized mice bearing human target tumor cells constitute relevant models for evaluation of cancer therapeutics such as bispecific antibodies, immune cell targeting antibodies.
In vivo proof of concept studies were performed with humanized mice xenografted with either human disseminated lymphoma or with human solid tumors (tumor cell line and Patient Derived Xenograft model, Her2 positive breast, colon, ovarian and lung cancers) and treated with therapeutic antibodies.
Biomarkers of response to immune cell targeting therapies were evaluated by flow cytometry as well as immunohistochemistry analyses. In case of disseminated B-cell lymphoma grafted into mice reconstituted with human PBMC, efficacy of antibody was evidenced by an increased survival and a high decrease of human B cells in mouse bone marrow. Lung and ovarian PDX developed in HSC reconstituted BRGS mice induced an increase in Tregs and a change in T/B ratio in blood and spleen samples. Furthermore, we evidenced the presence of Tregs within human PDX tumor by immunohistochemistry.
Citation Format: Olivier Duchamp, Francis Bichat, Caroline Mignard, François Ghiringhelli, Jean-François Mirjolet, IMODI Consortium. Humanized mouse models for evaluation of cancer therapies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 624.
Abstract 632: Establishment and characterization of xenografts and cell lines trom nasopharyngeal carcinoma
Authors: Lin WT , Xia L , Wen Dan Dan , Tsang CM , Lo KW , Lung ML , Tsao George Sai-Wah 
Published: July 2016

Abstract
Nasopharyngeal carcinoma (NPC) is a common cancer among ethnic Cantonese living in Hong Kong and southern China. It is closely associated with Epstein-Barr virus (EBV) infection. Unfortunately, there are very few representative xenografts and cell lines established from NPC available for investigation. Most of the NPC xenografts established have been passaged in immune deficient animals for over 20 years and may not be representative of the original NPC in patients. For in vitro NPC cell lines, there is only one cell line which retains the EBV genomes. Other NPC cell lines have all lost their EBV episomes. Furthermore, many of these NPC cell lines are found to be contaminated with genetic components from HeLa cells (HPV16 genome) which raised issues on their origins and limited their uses as NPC cells. There is great urgency in establishment new NPC cell lines both in vivo and in vitro for various research investigations and for the study of pathogenic role of EBV infection in NPC. We have carried out continuous efforts since 2010 to attempt establishment of new NPC xenografts and cell lines from surgical and biopsies NPC tissues. NPC tissues from resected recurrent NPC and biopsies from primary NPC were explanted to subrenal capsular sites and maintained for four months to one year to observe for growth of new NPC xenografts. Attempts to establish new NPC celles were also carried out. At present, we have successfully established 3 NPC xenografts (Xeno 23, Xeno 32, Xeno 47) which could be passages at subcutaneously sites and one in vitro NPC cells (NPC43) which harbors EBV genomes. The growth properties and genetic alterations of these newly established NPC cell lines have been characterized. Novel genetic alterations and growth signaling pathways were observed in these newly established NPC cell lines and may represent driver mutations and signaling pathways essential for progression of NPC. Profiling of EBV gene expression of these newly established NPC cell lines revealed predominant latent EBV infection and expression of EBV-encoded mRNA from the BART transcripts which are characteristic of EBV infection in NPC. The establishment of new NPC cells will contribute to investigate the pathogenesis of NPC and its intimate relationship with EBV infection.
Funding acknowledgement: University Grant Council (HK) grants (AoE NPC (AoE/M-06/08); TBRS (T12-401/13R); GRF); University of Hong Kong (CRCG and SRT cancer)
Citation Format: WT Lin, L Xia, Dan Dan Wen, CM Tsang, KW Lo, ML Lung, George Sai-Wah Tsao. Establishment and characterization of xenografts and cell lines trom nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 632.
Abstract 637: Establishment of a realistic patient-derived xenograft (PDX) model for prostate cancer bone metastasis
Authors: Konkol Yvonne , Valta Maija , Bernoulli Jenni , Taimen Pekka , Boström Peter , Härkönen Pirkko , Halleen Jussi , Tuomela Johanna M. 
Published: July 2016

Abstract
Bone metastases are frequent and fatal outcome of advanced prostate cancer. Many of the currently used preclinical models lack typical characteristics of the heterogenic human disease. We improved existing methodology by using fresh patient-derived material in a xenograft model of bone metastasis.
Clinical prostate tumor specimens were collected from robotic-assisted laparoscopic radical prostatectomy operations in Turku University Hospital (Turku, Finland). Patient-derived tumor tissue of Gleason grade 8-10 tumors (n = 5) were cut into small pieces, digested overnight, and then cell suspension was intratibially inoculated into the bone marrow cavity of nude mice (n = 8-10/patient). X-ray pictures were taken and blood samples were collected once a month. Mice were sacrificed 6 months after tumor cell inoculation, and hind limbs and lungs were collected for histological and immunohistochemical analysis. PSA was measured from serum using commercial kit.
X-rays demonstrated osteosclerotic bone lesions. Immunohistochemical analysis showed that 80% of tumors in bone expressed similar characteristics compared with original tumor (androgen receptor AR, prostate specific antigen PSA, proliferation marker Ki67). However, no changes were seen in serum PSA. Lung metastases were detected in 50% of tumor-bearing mice. Interestingly, the most of lung metastases were negative for AR and PSA, which indicates that the cell population that forms metastases may be undifferentiated clone of heterogenic tumor and therefore the most aggressive.
Our platform provides new tools for prostate cancer research.
Citation Format: Yvonne Konkol, Maija Valta, Jenni Bernoulli, Pekka Taimen, Peter Boström, Pirkko Härkönen, Jussi Halleen, Johanna M. Tuomela. Establishment of a realistic patient-derived xenograft (PDX) model for prostate cancer bone metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 637.
Abstract 645: The effect of rhBMP-2 on in vitro osteosarcoma tumorigenesis and on pulmonary growth and development
Authors: Geller David S. , Chung So Hak , Zhang Wendong , Piperdi Sajida , Freeman Carrie , Hoang Bang , Yang Rui , Roth Michael , Gill Jonathan , Gorlick Richard 
Published: July 2016

Abstract
Introduction: Complete surgical resection is a critical component of care for patients with osteosarcoma (OS). Limb-salvage surgery is performed in over 90% of cases. Non-union is a well-recognized complication of allograft reconstructions, frequently performed following tumor extirpation. Bone Morphogenetic Protein-2 (BMP-2) has been shown to be osteoinductive and could theoretically improve allograft-host bone union. The purpose of this investigation is to evaluate the effect of exogenous recombinant human BMP-2 (rhBMP-2) on osteosarcoma.
Methods: Functional assays were performed using five standard osteosarcoma cell lines and three patient derived xenograft cell lines. Random migration motility was measured via wound healing scratch assay. Migration (haptotaxis) was quantitatively measured using Boyden Chamber assay. Invasion was assessed using the Biocoat Matrigel Invasion Kit. Cell proliferation rate was measured by using MTT reagent. Metastatic disease was assessed using a xenograft murine model.
Results: Findings suggest that exogenous rhBMP-2 does not meaningfully affect osteosarcoma migration, invasion or proliferation across all tested lines. Average corrected lung weight in the single-dose rhBMP-2 experiment was 1.56 g in the experimental group versus 1.67 g in the control group (p = 0.69). Average corrected lung weight in the triple-dose rhBMP-2 experiment was 1.23 g in the experimental group versus 1.06 g in the control group (p = 0.07).
Conclusions and Future Directions: Results support the contention that exposure of osteosarcoma to exogenous rhBMP-2 does not increase either in vitro tumorigenesis or pulmonary disease growth and development within this experimental model. While results are compelling, additional characterization and confirmation of these findings are necessary safety prerequisites prior to proposing clinical application.
Citation Format: David S. Geller, So Hak Chung, Wendong Zhang, Sajida Piperdi, Carrie Freeman, Bang Hoang, Rui Yang, Michael Roth, Jonathan Gill, Richard Gorlick. The effect of rhBMP-2 on in vitro osteosarcoma tumorigenesis and on pulmonary growth and development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 645.
Abstract 649: Biobank collaboration enables cancer modeling with high quality biospecimens and data
Authors: Shopland Lindsay S. , Emery Ivette , Hoffert Todd , Aalberg Rise , Helbig Petra , LaPierre Susan E. , Sanders Vicky , Mills Kevin D. , Hill Tara , Sheikh Aysha , Jones Michael , Breggia Anne , Rueter Jens 
Published: July 2016

Abstract
According to the National Cancer Institute, the lack of standardized, high-quality biospecimens is one of the most significant roadblocks to progress in cancer research. This shortage especially affects the generation of murine xenograft models of human cancers. Maine, with the third largest age-adjusted cancer incidence rate in the nation, has abundant cancer specimens potentially available for research. To meet the need for quality biospecimens, the biobanks at Eastern Maine Medical Center and Maine Medical Center have established a collaboration to jointly procure cancer specimens from Maine patients. Through this collaboration, the cooperating biobanks provide researchers with tissue, blood, bone marrow and other body fluid specimens from a broad spectrum of solid and hematologic cancers. The specimens from hematologic cancer patients have &gt; 90% viability and demonstrate anticipated biomarker composition by flow cytometry. The comparatively high frequency of engraftment of solid tumors in immunodeficient mice is also indicative of the quality of the samples procured by both repositories. Currently, the biobanks are providing fresh ovarian tumors to develop new xenograft models for poorly engrafting tumors in collaboration with the Jackson Laboratory's Patient Derived Xenograft Program. Both biobanks are integrated with clinical and pathology practices and, therefore, the specimens are annotated with in-depth, de-identified patient datasets. With support from the Maine Cancer Foundation, the biobanks have created the Maine Cancer Biospecimen Portal (MBCP), a website that provides one-stop access to annotated cancer biospecimens and to consultation services for translational research study design. The collaboration of the EMMC and MMC biobanks provides a resource of high quality biospecimens for advancement of both in vivo and in vitro translational research such as mouse models of human cancers.
Citation Format: Lindsay S. Shopland, Ivette Emery, Todd Hoffert, Rise Aalberg, Petra Helbig, Susan E. LaPierre, Vicky Sanders, Kevin D. Mills, Tara Hill, Aysha Sheikh, Michael Jones, Anne Breggia, Jens Rueter. Biobank collaboration enables cancer modeling with high quality biospecimens and data. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 649.
Abstract 65: In vivo pooled shRNA library screens identify cancer genes driving epithelial ovarian cancer
Authors: Kodama Michiko , Kodama Takahiro , Newberg Justin , Copeland Neal G. , Jenkins Nancy A. 
Published: July 2016

Abstract
Background & Aims: Epithelial ovarian cancer (EOC) is the 5th leading cause of cancer-related deaths in the USA. Most cases of EOC are diagnosed at an advanced stage with peritoneal carcinomatosis (PC), which seriously affects mortality. To identify therapeutic targets for EOC, we performed in vivo loss of function screens using pooled shRNA libraries. Methods: To discover tumor suppressor genes (TSGs) involved in PC formation, the human EOC cell line, SKOV3, was transduced with a pooled shRNA library containing 42,450 shRNAs targeting 7490 druggable genes. Transduced cells that were highly evasive as measured in Boyden chamber assays were then injected intraperitonealy into female nude mice. Eighteen PC tumors that developed were then sequenced and enriched shRNAs identified. SKOV3 cells transduced with the druggable shRNA library were also injected into nude mice without further in vitro manipulation and 12 PC tumors sequenced in order to identify potential oncogenes as measured by shRNA depletion. Results: Enrichment screening of invasive cells identified 34 potential TSGs targeted by two or more shRNAs. Knockdown of the two most highly ranked genes, RAD51C and TXN, by individual shRNAs, was subsequently shown to accelerate PC formation following intraperitoneal injection of transduced SKOV3 cells. Individual knockdown of these two genes was subsequently shown to increase cell invasion in Boyden chamber assays and adhesion to the extracellular matrix in vitro. These results suggest that RAD51C and TXN are suppressors of human EOC metastasis through their negative regulation of cell adhesion and cell invasion. Finally, shRNA depletion screening identified 17 potential oncogenes. These genes included three known oncogenes, ERBB2, RAF1 and FOS, in addition to eight genes that showed a significant positive correlation between their mRNA levels and poor patient survival in human EOCs. Knockdown of the second ranked oncogene, KPNB1, significantly decreased in vitro cell proliferation in multiple human EOC cell lines, suggesting that KPNB1 may be a new potential therapeutic target of human EOC. KPNB1 knockdown in SKOV3 cells downregulated AURKA, MYBL2, CCNE1 and CDK2 mRNA levels, suggesting that KPNB1 may function by positively regulating the cell cycle. Conclusion: In vivo pooled shRNA library screens are a powerful tool for identifying novel cancer genes and new potential drug targets in human epithelial ovarian cancer.
Citation Format: Michiko Kodama, Takahiro Kodama, Justin Newberg, Neal G. Copeland, Nancy A. Jenkins. In vivo pooled shRNA library screens identify cancer genes driving epithelial ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 65.