bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1336: Concurrent Snail expression and Kras mutation promote pancreatic fibrosis
Authors: Shields Mario A. , Khan Mohammad WK , Grippo Paul J. , Munshi Hidayatullah G. 
Published: August 2012

Abstract
One of the hallmarks of pancreatic ductal adenocarcinoma (PDAC), the 4th leading cause of cancer related death in the US, is a pronounced collagen-rich stromal reaction. We recently published that type I collagen induces expression of Snail, a key regulator of epithelial-mesenchymal transition, to promote invasion and scattering of PDAC cells (Shields MA, et al. JBC 2011). To further understand the role of Snail in PDAC progression we generated transgenic mice expressing Snail in the pancreas. While there was robust Snail expression in the mouse pancreas, no phenotypic changes were observed. Since inflammation can promote Snail-mediated invasion and metastasis, we treated the Snail-expressing mice with cerulein to induce chronic pancreatitis. Although there was significant inflammation associated with vacuolization, no difference in the pancreatitis response was observed between control and Snail-expressing mice. Since Kras mutation has been shown to be necessary for tumor development in mouse models of pancreatic cancer, we generated mice expressing both mutant KrasG12D and Snail (Kras+/Snail+). Compared to control mice (Kras+/Snail-), Kras+/Snail+ mice developed significantly more acinar to ductal metaplasia, cystic papillary lesions that were associated with increased fibrosis, increased Smad2 and Stat3 phosphorylation. Experiments are underway characterizing the mechanism by which Snail promotes pancreatic fibrosis in Kras-expressing mice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1336. doi:1538-7445.AM2012-1336
Abstract 1342: Nuclear Apc suppresses colitis-associated tumorigenesis in mice
Authors: Zeineldin Maged , Neufeld Kristi L. 
Published: August 2012

Abstract
Because mutation of tumor suppressor gene APC is the initiating step in most colorectal cancers (CRC), understanding the full spectrum of APC functions will illuminate better diagnostic, preventive and therapeutic strategies for the disease. Although APC shuttles between the cytoplasm and nucleus, testing proposed roles for nuclear APC in the context of a whole organism was only recently made possible using a mouse model compromised for nuclear Apc which we generated by introducing germline mutations that inactivate the Apc nuclear localization signals (ApcmNLS). Our previous analysis of ApcmNLS mice revealed a role for nuclear Apc in regulation of Wnt signal transduction and intestinal cell proliferation as well as in tumor suppression. In humans, chronic colitis significantly increases CRC risk and APC mutations occur late in this cancer progression. In the current study, we show increased expression of inflammatory mediators cyclo-oxygenase-2 (Cox-2) and macrophage-inflammatory-protein-2 (MIP-2) in colon epithelial cells from ApcmNLS/mNLS mice, suggesting a role for nuclear Apc in suppressing colitis-mediated colon cancer. To test this hypothesis, we initiated colon tumors with a single injection of the mutagen, azoxymethane (AOM) and promoted the tumors with repeated oral administration of dextran sodium sulfate (DSS) to induce colonic inflammation. When treated with AOM-DSS, ApcmNLS/mNLS mice developed more colonic tumors than treated wildtype mice. Tumors from treated ApcmNLS/mNLS and wildtype mice had the same spectrum of β-catenin mutations, proliferation rates and histopathological features, consistent with the ApcmNLS allele enhancing colitis-associated tumor initiation rather than progression. ApcmNLS/mNLS mice had increased weight loss and colonic lymphoid follicles implicating nuclear Apc in suppression of AOM-DSS-induced colitis. These findings reveal novel functions for nuclear Apc and also indicate a critical protective role for Apc early in inflammation-induced colon tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1342. doi:1538-7445.AM2012-1342
Abstract 1344: ZAP-70 enhances migration of malignant B lymphocytes toward lymphoid organs in a Burkitt lymphoma xenograft model
Authors: Calpe Eva , Purroy Noelia , Abrisqueta Pau , Carpio Cecilia , Palacio Carles , Gallur Laura , Castellvi Josep , Crespo Marta , Bosch Francesc 
Published: August 2012

Abstract
Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disease characterized by the accumulation and proliferation of mature B-lymphocytes in the blood, bone marrow and secondary lymphoid organs. CLL patients with adverse outcome prognosis can be identified by the presence of a high ZAP-70 expression. ZAP-70, a protein tyrosine kinase that plays a crucial role in cellular activation in T and NK cells, has been related to aggressive features of the CLL cells, such as higher migrative capacity in vitro. In order to analyze the consequences of ZAP-70 ectopic expression in an in vivo model, we stably transfected a Burkitt cell line (Raji) with a vector expressing a ZAP-70-GFP fusion protein. Raji transfectants showed constitutively active ZAP-70 protein. Subsequently, thirty-four 8-week old SCID mice were inoculated intravenously with 5 x106 cells from each cell line (control Raji-GFP, 12 mice; Raji-ZAP-70-GFP, 9 mice). Mice were euthanized when hind legs paralysis, dyspnea, or tumor growth was observed. Organs were obtained to quantify the percentage of GFP-positive cells present in each organ by flow cytometry. Median survival of mice injected with the ZAP-70 cell line did not differ from that observed in the control mice (16 days, p=0.658). Percentage of GFP positive cells was analyzed by flow cytometry in different tissue compartments (Table 1). We observed a significantly higher percentage of infiltrating GFP-positive cells in the bone marrow from mice injected with ZAP-70 expressing cell line (58.8%±6.08 vs 4.2%±1.4, p&lt;0.001), whereas in the rest of organs the infiltration was comparable (Table 1). Raji-ZAP-70-GFP has a differential expression of CCR7 and CD49d among others (Calpe et al, Blood 2011). In conclusion, malignant B-lymphocytes with ectopic expression of activated ZAP-70 protein showed enhanced ability to migrate toward and infiltrate the bone marrow, where soluble factors are produced to mediate homing, survival, and proliferation of tumor cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1344. doi:1538-7445.AM2012-1344
Abstract 1345: The use of optical imaging in a clinically relevant mouse intrafemoral model of leukaemia
Authors: Batey Michael A. , Brown Matthew , Booth Catherine 
Published: August 2012

Abstract
One of the challenges facing preclinical development in non solid tumours, such as leukaemia, is the development and validation of clinically relevant models, both to better understand the biology of disease, and to provide reliable efficacy testing for novel agents. In conventional animal models of leukaemia, cells are implanted using intravenous injection, leading to inconsistent engraftment as cells are not introduced directly to their biological niche. Disease burden is measured using either terminal endpoints, such as hind limb paralysis, or by fluorescence activated cell sorting on bone marrow or peripheral blood samples. Neither of these strategies make it practical to identify animals in the early stages of leukemic disease development, limiting investigators’ ability to examine novel therapies in these models. The use of preclinical imaging strategies, such as in vivo optical imaging, allows disease progression to be followed at orthotopic sites and, in the case of non solid tumours, to monitor systemic disease burden longitudinally in an individual animal over time. Here we describe the use of an intrafemoral (i.f.) transplantation method, in which cells are implanted directly into the biological niche of interest, correlating with the environment in which disease develops in patients. Luciferase-labelled human leukaemia cell lines were injected into the bone marrow cavity of the femur of severely immunocompromised NOG (NOD/Shi-scid/IL-2Rynull) mice via the knee joint. Animals were followed over a period of several weeks from initial transplantation, and disease burden monitored and quantified using bioluminescent detection. This model consistently gives rise to disease disseminating gradually from the site of initial transplantation into systemic leukaemia. The ability to quickly identify engraftment and the predictable development of disease allows for therapeutic intervention at an early stage and extends the window available for therapy. The model provides a clinically relevant environment for the preclinical assessment of novel therapeutics for non solid tumours.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1345. doi:1538-7445.AM2012-1345
Abstract 1347: A human-mouse xenograft model to study the role of TSLP in CRLF2d B-ALL
Authors: Payne Kimberly J. , Su Rui-Jun , Francis Olivia L. , Martinez Shannalee R. , Bennett Terrence , Arogyaswamy Keshav , Morris Christopher L. , Dovat Sinisa 
Published: August 2012

Abstract
B-cell precursor ALL where genetic defects lead to overexpression of CRLF2 (CRLF2d B-ALL) are high-risk with poor prognosis. CRLFd B-ALL occurs 5 times more frequently among children of Hispanic/Latino ethnicity and is a major contributor to the health disparity in survival of Hispanic children with ALL. CRLF2, together with the IL-7Rα, forms a receptor complex that is activated by the cytokine, TSLP. The JAK-STAT5 pathway is phosphorylated downstream of receptor activation. The activating JAK mutations found in some CRLF2 B-ALL have led to speculation that TSLP stimulation is not a factor in CRLF B-ALL. In preliminary studies to address this question we evaluated the effect of TSLP on two CRLF2d B-ALL cell lines with JAK defects and which have been reported to exhibit constitutive JAK-STAT5 activation. Our data show that TSLP increases STAT5 phosphorylation in both of these cell lines and in primary B-ALL cells that overexpress CRLF2. Our next step was to evaluate the role of TSLP-CRLF2 interaction in vivo in the human-mouse xenograft model. However, mouse TSLP is different from most other cytokines produced in the xenograft in that it is species-specific and does not activate the human TSLP receptor complex that contains CRLF2. Thus, traditional xenograft models do not provide the TSLP-CRLF2 interactions that we believe to be a major factor in CRLF2 B-ALL. To overcome this obstacle we have engineered immune deficient NOD/SCID IL-2Rγ null (NSG) mice to express human TSLP (hTSLP+ mice) as well as control mice that lack the TSLP cytokine (hTSLP- mice). ELISA assays show plasma hTSLP levels in the hTSLP+ mice that approximate the normal range in human plasma. We have used this hTSLP+/− system to expand a sample of primary pre-B ALL cells from a patient that includes clones of CRLF2-HI and CRLF2- B-ALL cells. Preliminary data indicate that the pre-B ALL cells expanded in hTSLP+ mice show higher expression levels of the TSLPR components (CRLF2 and IL-7Rα) than cells expanded in the hTSLP- mice. This data provide evidence that the TSLP produced in this model is active and that it impacts primary pre-B ALL cells. The hTSLP+ mice that we produce will allow for the first time the study of normal and malignant B lymphopoiesis in a model that provides the complex bone marrow architecture of the xenograft while providing the full range of cytokines that are known to act on early B lineage cells (IL-7, FL and TSLP). This model will be particularly important for identifying therapies that can effectively target CRLF2-d B-ALL and reduce cancer health disparities in Hispanic childhood B-ALL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1347. doi:1538-7445.AM2012-1347
Abstract 1349: Xenograft models of human acute myeloid leukemia (AML) with biomarker strategies are valuable in development of new drugs targeting AML
Authors: Zhang Lan , Chen Taiping , Shi Qian , Zhang Juan 
Published: August 2012

Abstract
Acute myeloid leukemia (AML) is a malignant disease caused by disorder of progenitor cells in myeloid hematopoiesis. The rapid progress and high fatality make it difficult to cure the patients suffering from AML. Choice of treatment is limited, consisting primarily of chemotherapy and hematopoietic stem cell transplantation. Pharmaceutical companies are focused on designing new drugs that may be efficacious in treating the disease and prolong the survival of the patients. However, the lack of AML model and specific biomarkers hinder the progress of research on this cancer type. Here we successfully validated subcutaneous and systemic models derived from a number of AML cell lines, such as MV4-11, HL-60, Molm-16, and ML-2, in NOD/SCID mice to evaluate the antitumor activities of new compounds. Biomarkers, such as CD45, CD38 and CD15 in PBMC, spleen and bone marrow from the systemic models, are used in detecting and monitoring the disease progress. These biomarkers correlated with tumor take rate, disease progression and response to standard of care treatments. In conclusion, AML xenograft models with biomarker strategies provide valuable platforms for the development of new compounds targeting this deadly disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1349. doi:1538-7445.AM2012-1349
Abstract 135: Integrated analysis of cell signaling pathway-associated miRNAs using protein expression array data in NCI-60 cells
Authors: Kim Sang-Bae , Park Yun-Yong , Sohn Bo-Hwa , Jeong Woojin , Lee Sung Sook , Kim Ji Hoon , Davies Micheal A. , Mills Gordon B. 
Published: August 2012

Abstract
MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules and on average only 22 nucleotides long that regulate gene expression at the post-transcriptional level. The current approaches with miRNA-mRNA association were not enough to verify real functional targets at protein level, which could affect on biological signaling pathway. In this study, we developed a correlation based approach (sequence-independence) to predict potential miRNA targets with genomic and proteomic data including the expression of phosphorylated proteins in NCI-60 cells. To do this we calculated the number of correlated probe-pairs between miRNA(439)-mRNA(22k) and protein(222)-mRNA probe pairs. Then, two significant output pair sets were combined by mRNA probes and then counted the number of common probes. With these count numbers, finally we generated Association score matrix between miRNA and protein probes. Using those score matrix, we evaluated the highly associated miRNAs with 36 biological pathways, which play critical roles in cell cycle, proliferation and metastasis. Among these associations, we found that miR-500 cluster is highly associated with ERK/MAPK signaling pathway through activating MEK1/2 phosphorylation in Melanoma and breast cancer cells. In conclusion, we developed a novel expression profile based approach to systematically predict potential miRNA functional targets which play critical roles in cell signaling pathways from the NCI-60 genomic and proteomic data at whole genomic scale.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 135. doi:1538-7445.AM2012-135
Abstract 1353: Inactivation of ribosomal protein L22 promotes transformation by induction of Lin28B
Authors: Rao Shuyun , Lee Sangyun , Guitierrez Alejandro , Perrigoue Jacqueline Jacqueline , Thapa Roshan , Tu Zhigang , Jeffers John , Rhodes Michele , Hunger Stephen , Downing James , Zhang Rugang , Balachandran Siddharth , Zambetti Gerard , Testa Joseph , Look A. Thomas , Wiest David 
Published: August 2012

Abstract
The molecular basis by which mutations in some ribosomal proteins (RP) predispose to development of hematologic malignancies remains unclear. We show here that germline inactivation of the ribosomal protein L22 (Rpl22), which selectively blocks T cell development, also predisposes T lineage progenitors to transformation. Indeed, RPL22 was found to be inactivated in ∼9% of human T-acute lymphoblastic leukemias (T-ALL). Moreover, mono-allelic loss of Rpl22 accelerates development of thymic lymphoma in a mouse model of T cell malignancy and in acute transformation assays in vitro. Furthermore, we show that Rpl22 inactivation enhances transformation potential through induction of Lin28B. These findings represent the first mechanistic insight into how an RP mutation promotes transformation.Our finding that Rpl22 inactivation promotes transformation by inducing expression of Lin28B provides insight into the mechanistic basis by which mutations in Rpl22, and perhaps other RP genes, increase cancer risk. In addition, because we have determined that Lin28B induction is dependent upon NF-kB activity, our findings may provide new opportunities for therapeutic intervention both in aggressive forms of T-ALL, where we have found Rpl22 to be inactivated, and perhaps in other diseases caused by mutations in RP genes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1353. doi:1538-7445.AM2012-1353
Abstract 1356: Vascular endothelial growth inhibitor - potential role in targeted therapy in kidney neoplasma via angiogenic inhibition
Authors: Cai Jie , Zhang Ning , Zhao Xueqing , Su Dan , Song Xiaoming , Wu Liyang , Wang Wei , Sun Yanmei , Shi Qian , Chen Taiping , Yang Yong 
Published: August 2012

Abstract
Vascular endothelial growth inhibitor (VEGI, also known as TNFSF15) is an anti-angiogenic cytokine found to be associated with tumour-related vasculature in certain maligancies. Three isoforms, VEGI 251, VEGI192, and VEGI174, have been identified, all sharing a common extracellular domain of 151 C-terminal amino acid sequence critical for biological activity of all three isoforms. Previous studies showed tumor inhibitory effect of truncated recombinant VEGI proteins in breast and colorectal cancer xenograft models, however, the antitumor activity of the full length VEGI molecules have not been well characterized in other malignancies, including kidney neoplasm. The objective of the present study was set to evaluate biological impact of forced expression of full length VEGI-174 in a renal cell carcinoma (RCC) cell line, 786-O, and in 786-O derived xenograft models. We found that Increased VEGI-174 expression in 786-O cells did not affect cell growth and apoptosis in vitro, but did reduce cell adhesion and the ability of endothelial cells to form capillary-like structures in co-culture. Subcutaneous xenograft models were successfully established using the 786-O RCC cells with or without forced expression of VEGI-174. Significantly reduced tumor volume, accompanied by reduced tumor microvessel density and decreased Ki67 and VEGFR2 expression, was observed in animals injected with VEGI-174 transfected 786-O cells compared to those in the control groups. Our results demonstrated that increased expression of full length VEGI-174 in RCC 786-O cells resulted in significant reduction in tumor volume most likely via angiogenic inhibition rather than on tumor growth per se. Despite the lack of antitumor effect of full length VEGI174 in some xenograft tumor models in other studies, our results suggest that antitumor effect of the full length VEGI-174 may be cancer type specific, and VEGI-174 may still be a valuable candidate toward angiogenesis based cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1356. doi:1538-7445.AM2012-1356
Abstract 1357: Creation and establishment of xenograft model for uterine leiomyoma in immunodeficient mice
Authors: Cho Chi-Heum , Shin So-Jin , Kwon Sang-Hoon , Cha Soon-Do 
Published: August 2012

Abstract
Objective: Uterine leiomyomas are the most prevalent benign tumors in women of reproductive age and the leading indication for hysterectomy in premenopausal women. The underlying causes of uterine leiomyomas are poorly understood, as a result, in part, of the absence of a good model system with which to study these tumors. To overcome this problem, this study was undertaken to develop a murine model for human leiomyoma. Study design: Human leiomyoma tissues were cut into small pieces and some of those were cultured. Tissue pieces and cultured cells were inserted subcutaneously in the flank of each severe immunodeficiency (NOD/SCID gamma, NSG) mice (n=6). Estrogen supplement was needed to maintain serum estrogen level 3 days before the tissue or cultured cells transplantation. Xenograft tissues or cells were harvested after 6wks and analyzed. Results: Six uterine leiomyoma xenografts were successfully established with the tumor tissue derived from six patients. The xenografted human uterine leiomyoma tissues retained their gross appearance with small vessels around the implant tissues and did not change in size up to 6wks after implantation. H&E staining showed that xenografts retained major histologic features of the original leiomyoma. The immunohistochemical staining of SMA(smooth muscle actin) revealed strong cytoplasmic and membranous positivity of spindle tumor cells of xenografts.Conclusions: In summary, transplantation of surgical specimens from uterine leiomyoma patients into NSG mice results in an attractive model for the study of the uterine leiomyoma and may also be useful for analysis or new experimental therapeutic approaches for the treatment of this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1357. doi:1538-7445.AM2012-1357