bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5116: Detection of pancreatic cancer using acidic pH targeted probes detected using multispectral optoacoustic tomography
Authors: Zeiderman Matthew , Khanal Anil , Kimbrough Charles W. , Gomez Jorge , Grizzle William E. , McMasters Kelly M. , McNally Lacey R. 
Published: August 2015

Abstract
Introduction: The use of theranostic nanoparticles for simultaneous tumor imaging and drug delivery is of great research interest. The tumor extracellular environment is significantly more acidic than physiologic pH, often in the range of pH 6.0-6.8. Exploitation the acidic extracellular tumor environment is a promising method of tumor localization with pH sensitive probes and targets. Further, the use of multispectral optoacoustic tomography (MSOT) allows in vivo 3D tumor imaging via gold nanoparticles or near-infrared dyes conjugated to a targeting molecule. Gemzar is used for first-line treatment of pancreatic adenocarcinoma, a malignancy with less than 5% survival at 5 years. We have created chitosan-capped mesoporous silica gold nanorods (C-MS-GNRs) to serve as pH sensitive theranostic nanoparticles for in vivo tumor imaging and targeted drug delivery.
Methods: The chemical nature of all particles were characterized by electron microscopy, UV-Vis, and zeta-potential. Acidic pH specific Gemzar release was measured from C-MS-GNRs by UV-Vis. Cell viability assays on S2VP10 pancreatic adenocarcinoma cells with G-C-MS-GNR and Gemzar alone were performed at pH 6.5 and 7.4. S2VP10 cells were treated in pH 6.5 or 7.4 media with C-MS-GNR loaded with Indocyanin green (ICG) to demonstrate pH-sensitive cell targeting. ICG uptake was read on an Odyssey imaging system.
Results: Particle characterization demonstrated appropriate chemical composition. A drug release assay of G-C-MS-GNR demonstrated 1/10 as much drug release at pH7.4 compared to in pH 6.4 or 6.0 media. Cell viability assays demonstrated enhanced cytotoxicity with Gemzar loaded C-MS-GNR at pH 6.5 and 7.4 compared to Gemzar alone. In vitro treatment of S2VP10 cells with C-MS-ICG in pH 6.5 media demonstrated 8X greater ICG delivery by C-MS-ICG than observed at pH 7.4.
Conclusions: C-MS-GNR provides an efficacious means of targeting the acidic tumor environment for in vivo tumor imaging and drug delivery. C-MS-GNRs may be a suitable vehicle for tumor-targeted, pH-sensitive drug delivery to this currently untreatable tumor.
Citation Format: Matthew Zeiderman, Anil Khanal, Charles W. Kimbrough, Jorge Gomez, William E. Grizzle, Kelly M. McMasters, Lacey R. McNally. Detection of pancreatic cancer using acidic pH targeted probes detected using multispectral optoacoustic tomography. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5116. doi:10.1158/1538-7445.AM2015-5116
Abstract 5117: Fluorescence-guided surgery of liver metastasis in orthotopic nude-mouse models
Authors: Murakami Takashi , Hiroshima Yukihiko , Miwa Shinji , Shuya Yano , Toneri Makoto , Yamamoto Mako , Momiyama Masashi , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Hasegawa Satoshi , Endo Itaru , Hoffman Robert M. 
Published: August 2015

Abstract
We report here the development of fluorescence-guided surgery of liver metastasis. HT29 human colon cancer cells expressing green fluorescent protein (GFP) were initially injected in the spleen of nude mice. Three weeks later, established liver metastases were then harvested and implanted to the left lobe of the liver in other nude mice in order to make an orthotopic liver metastasis model. Eleven mice with a single liver metastasis were randomized into BLS or FGS groups. Three weeks after the implantation, the left lobe of the liver with a single metastasis was exposed through a median abdominal incision. BLS was performed under white light. FGS was performed using a hand-held portable fluorescence imaging system (Dino-Lite). Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System. Five mice were treated with BLS, six were treated with FGS. Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100. In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100.
Citation Format: Takashi Murakami, Yukihiko Hiroshima, Shinji Miwa, Yano Shuya, Makoto Toneri, Mako Yamamoto, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Satoshi Hasegawa, Itaru Endo, Robert M. Hoffman. Fluorescence-guided surgery of liver metastasis in orthotopic nude-mouse models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5117. doi:10.1158/1538-7445.AM2015-5117
Abstract 5121: Study of a synthetic peptide probe for apoptosis imaging
Authors: Yang Shen , Meng Jie , Liu Huike , Wang Chuan , Yang Yanlian , Guo Hua , Liu Jian , Wang Chen , Xu Haiyan 
Published: August 2015

Abstract
Chemotherapy and radiotherapy can cause a great many apoptosis in the tumor mass. Thus, direct and fast observation for the therapy-induced apoptosis is important and valuable to evaluate the effectiveness of anti-tumor treatments. In this work, a peptide (named as P17) labeling apoptotic cells was designed and chemically synthesized. To validate the labeling function, different tumor cells (Jurkat, THP-1, K562, Hela and MDA-MB-231) were treated with TRAIL (the TNF-related apoptosis-inducing ligand) to induce apoptosis, followed by incubation with FITC-conjugated P17 and then co-stained with annexin v. Flow cytometry results indicate that P17 binding to the cells was markedly increased with apoptosis rates rising. Confocal microscopy observations show that only cells with annexin v staining were labeled by P17, while live cells were not. By pull-down assay and mass spectrometry, P17-binding protein was identified to be heat shock protein 60 (HSP60), a mitochondrial chaperoninm with accumulation in the cytoplasm during apoptosis. And this result is further confirmed by confocal microscopy with anti-hsp60 antibody and a native-gel-based analysis to investigate FITC-P17 binding to HSP60. To evaluate the apoptosis-binding ability of the peptide in vivo, BALB/c mice bearing 4T1 tumor were treated with cyclophosphamide (CTX) to induce apoptosis in the tumor mass, followed by intravenously injection of fluorescent P17 prior to sacrifice. The tumor was removed for ex vivo imaging immediately. It was observed that P17 accumulated in CTX-treated tumors. The tumor tissue was further stained with TUNEL assay, confirming that the fluorescent signal observed was resulted from the labeling of apoptotic cells in tumor, because of the colocalization of P17 and TUNEL. In conclusion, this study demonstrates that P17 is a promising probe for the apoptosis imaging for uses in the evaluation of cancer therapy, drug screening and monitoring the cytotoxicity of therapeutics. (This work is supported by National Key Basic Research Program of China (2011CB933504) and Key project of the Major Research Plan from National Natural Science Foundation of China (91127043).)
Citation Format: Shen Yang, Jie Meng, Huike Liu, Chuan Wang, Yanlian Yang, Hua Guo, Jian Liu, Chen Wang, Haiyan Xu. Study of a synthetic peptide probe for apoptosis imaging. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5121. doi:10.1158/1538-7445.AM2015-5121
Abstract 5126: Establishment of an esophageal small cell carcinoma cell line (TYUC-1)
Authors: Shimada Yutaka , Okumura Tomoyuki , Takei Yoshinori , Watanabe Kazuaki , Hirasawa Akira , Yamane Arito , Nishiyama Masahiko , Nagata Takuya , Tsukada Kazuhiro , Shimizu Kazuharu 
Published: August 2015

Abstract
Background: Small cell carcinoma of the esophagus is rare and its prognosis is extremely poor. However, there is currently no in vitro model of this disease.
Methods: After obtaining written informed consent, we obtained a tumor from a 56-year-old female patient with esophageal small cell carcinoma in 2009 and transplanted it into a Severe Combined Immuno Deficiency (SCID) mouse. After successful transplantation, a tumor from the back of this mouse was minced with a sharp scissors without enzymes and was cultured in Ham F12/DMDM supplemented with 5% fetal bovine serum.
Results: Culture cells grew as adherent cells during the initial culture phase and gradually grew as floating aggregated cells. We carefully maintained these floating cells and transferred them without enzymes. These cells could passage to another flask with a split ratio of 1/10. We named these cells “TYUC-1”, and passaged them more than 85 times. The population doubling-time of TYUC-1 was approximately 30 hours. The G-band karyotype confirmed that these cells had a human origin. These cells could be transplanted to SCID mice with the same histological features of primary esophageal small cell carcinoma, and were shown to express TrkA, NGF, NSE, FGFRL1, p53, CD56, ALDH1A1, and CD44, but not CD133. A cDNA array also revealed that 9 genes were overexpressed while the expression of 33 genes was significantly lower than that in 28 esophageal squamous cell carcinoma (ESCC) cell lines. Whole exome sequencing revealed that TYUC-1 had TP53, PIK3CA, KMT2D, CACNA1H, NCOR1 and HRAS mutations. Furthermore, TYUC-1 had mutations in 128 genes, whereas 28 ESCC cell lines had no mutations in these genes.
Conclusions: We newly established TYUC-1 cells that exhibited neuroendocrine characteristics and expressed several stem cell-related molecules. These cells may be useful for understanding the characteristics of esophageal small cell carcinoma.
Citation Format: Yutaka Shimada, Tomoyuki Okumura, Yoshinori Takei, Kazuaki Watanabe, Akira Hirasawa, Arito Yamane, Masahiko Nishiyama, Takuya Nagata, Kazuhiro Tsukada, Kazuharu Shimizu. Establishment of an esophageal small cell carcinoma cell line (TYUC-1). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5126. doi:10.1158/1538-7445.AM2015-5126
Abstract 5137: IQGAP1, an ERK1/2 MAPK scaffold, is an oncogenic target in canine melanoma
Authors: Zehnder Ashley , Lee Becky , Neela Poornima , Khavari Paul 
Published: August 2015

Abstract
BACKGROUND: Human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%). However, human oral melanoma harbors these mutations much less frequently. Similarly, canine oral mucosal melanomas have not been found to have activating Braf or Nras mutations. This makes them an ideal model to study alternative means of ERK1/2 MAPK pathway activation as these tumors are still reliant on MAPK signaling. We have previously studied IQGAP1 as a tumor specific ERK1/2 MAPK scaffold and shown that it is required for cancer progression. METHODS: In this study, we utilized canine oral melanoma cell lines obtained from the University of California-Davis. We examined the expression and localization of IQGAP1, a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human cancer, and validate it as an oncogenic target in the canine melanoma model. Using a CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream pathway activation. Additionally, we assayed proliferation of these cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2.
RESULTS: We observed that canine IQGAP1 is expressed and localizes to a similar extent in human and canine melanoma by qPCR, Western blot and immunofluorescence. Deletion of IQGAP1 from two canine oral melanoma cell lines using CRISPR-Cas9 genome editing reduces MAPK pathway activation, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with the WW blocking peptide in-vitro. We are currently investigating the expression and localization of IQGAP1 in primary canine oral melanoma compared to normal oral mucosa.
CONCLUSION: Building on the above findings to explore alternative MAPK signaling in melanoma using the canine melanoma model may yield novel therapeutic strategies and novel means to target canine and human tumors that are resistant to current Braf and MEK targeted therapies.
Citation Format: Ashley Zehnder, Becky Lee, Poornima Neela, Paul Khavari. IQGAP1, an ERK1/2 MAPK scaffold, is an oncogenic target in canine melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5137. doi:10.1158/1538-7445.AM2015-5137
Abstract 5145: Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes
Authors: Dakic Aleksandra , Divito Kyle , Fang Shuang , Palechor-Ceron Nancy , Simic Vera , Choudhury Sujata , Yu Songtao , Simbulan-Rosenthal Cynthia M. , Rosenthal Dean , Schlegel Richard , Liu Xuefeng 
Published: August 2015

Abstract
The high-risk HPV E6 and E7 genes are sufficient to immortalize human foreskin keratinocytes (HFKs) through activation of telomerase and inactivation of the RB/p16 pathway, respectively. Our previous work has shown that Myc (via induction of hTERT) may substitute for E6 and immortalize HFKs when combined with HPV E7. When expressed alone, however, Myc induced p53 expression and apoptosis. In the current study we found that Myc, in combination with the ROCK inhibitor (Y-27632), led immortalization of human foreskin keratinocytes. Our data confirmed that Myc induced apoptosis and blebbing of human keratinocytes when cultured in serum free synthetic medium (KGM) and that Y-27632 rapidly inhibits this process. Thus, our data demonstrate that Myc is capable of independently immortalizing HFKs when apoptosis pathways are blocked.
Citation Format: Aleksandra Dakic, Kyle Divito, Shuang Fang, Nancy Palechor-Ceron, Vera Simic, Sujata Choudhury, Songtao Yu, Cynthia M. Simbulan-Rosenthal, Dean Rosenthal, Richard Schlegel, Xuefeng Liu. Y-27632 inhibits Myc-induced apoptosis and cooperates with Myc to immortalize human keratinocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5145. doi:10.1158/1538-7445.AM2015-5145
Abstract 5150: Drosophila models of Ret fusions in papillary thyroid carcinoma
Authors: Levinson Sarah , Cagan Ross 
Published: August 2015

Abstract
Ret fusion proteins, including PTC1 (CCDC6-RET) and PTC3 (NcoA4-RET), drive a subset of Papillary Thyroid Carcinomas (PTC). There is currently no treatment for refractory, metastatic PTC, which results in 1500 deaths in the US each year. A challenge in identifying targeted therapies for Ret fusion driven cancers has been the lack of predictive models. We created transgenic, over-expression Drosophila models of PTC1 and PTC3, and found that they cause cancer phenotypes such as delamination, cell migration, and EMT. We conducted a genetic screen of the Drosophila kinome (252 alleles) and a drug screen of FDA approved cancer therapeutics (62 compounds) against flies expressing either PTC1 or PTC3. We found that PTC1 and PTC3, despite containing identical Ret kinase domains, have a different signaling output and are sensitive to different kinase inhibitors. Of the 19 kinases that were identified as hits from the PTC3 kinome screen, only 5 overlap with PTC1 hits. PTC3 is most sensitive to Ponatinib, where as PTC1 is most sensitive to Cabozantinib. These findings suggest that patients may greatly benefit from targeted treatment directed against the specific Ret fusion that they harbor.
Citation Format: Sarah Levinson, Ross Cagan. Drosophila models of Ret fusions in papillary thyroid carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5150. doi:10.1158/1538-7445.AM2015-5150
Abstract 5166: THE WNT SIGNALING PATHWAY IN THE OVARIAN CARCINOMA
Authors: chehover michal , Tropé Claes , Reich Reuven , Davidson Ben 
Published: August 2015

Abstract
Ovarian carcinoma is the most lethal gynecological cancer and currently ranks as the fifth in causing cancer-related deaths among women. This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure.
Three WNT signaling pathways have been characterized: the canonical WNT pathway, the non-canonical planar cell polarity pathway, and the non-canonical WNT/calcium pathway. All three WNT signaling pathways are activated by the binding of a WNT-protein ligand to a Frizzled family receptor, which passes the biological signal inside the cell. Several lines of research indicate on the involvement of these pathways also in ovarian carcinomas. However, the specific pathway or their regulation in the process of tumor progression in this disease has not been elucidated, so far.
The aim of the current study is to identify the acting components of these pathways during tumor progression namely, which receptors and which ligands are activated at the different stages of ovarian carcinoma. We have analyzed the expression 7 frizzle genes (fzd1, 2, 4, 5, 6, 7, 8, 10), 4 WNT genes (wnt 2,3,4,5a,7) and 2 co-receptors LRP (5,6) on 222 samples (143 effusions, 44 primary, and 35 metastatic lesions) using real-time PCR. All the tested genes were found to be expressed at all sites. FRZ5 (p = 0.002), FRZ6 (p&lt;0.001), Wnt2 (p = 0.029), Wnt3 (p = 0.034) and Wnt6 (p = 0.022) were lower in effusion-derived cells compared to solids lesions. Further, Wnt2 expression was higher in pre-chemo (p = 0.037) samples compared to post-chemo ones. FRZ6 expression was higher in FIGO stage IV compared to stage III of the disease (p = 0.041), and FRZ4 expression was higher in cases with lower residual disease volume (p = 0.002). Wnt5a was higher in patients with better (complete) response (p = 0.019). FRZ6 expression was associated with poor overall survival (p = 0.045) and progression-free survival (p = 0.009). FRZ10 expression was associated with better overall survival (p = 0.005) and progression-free survival (p = 0.005).
Citation Format: michal chehover, Claes Tropé, Reuven Reich, Ben Davidson. THE WNT SIGNALING PATHWAY IN THE OVARIAN CARCINOMA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5166. doi:10.1158/1538-7445.AM2015-5166
Abstract 5172: Developing a lung metastasis gene signature using a lung tropism model in melanoma
Authors: Wen Yu , Shan Maung Naing Lin , Li Jiadong , Goydos James 
Published: August 2015

Abstract
A patient with metastatic melanoma has a 5-year survival rate of only 15%. As with most cancers, approximately 90% of fatalities are caused by metastatic spread of tumor cells to vital organs like the liver, lung, brain, bone, etc. Lung is one of the leading metastatic sites of melanoma at initial presentation, yet the mechanisms that lead to melanoma lung metastases are not well understood. For our study we have developed an in vivo ‘spontaneous lung-metastasis model’ using two human melanoma cell lines, UACC903 and C8161, with different genetic backgrounds. Parental melanoma cells were injected subcutaneously into nude mice. After the tumors reached the maximum allowable size of 1.5 cm, survival surgery was performed to remove the subcutaneous tumors and the animals were observed for an additional 4 weeks or until the animals appeared ill. The animals were sacrificed and lung metastases were surgically removed and re-cultured. The two new cell lines were designated as UACC903-LM and C8161-LM. This process was repeated using these new cell lines to obtain a second round of lung metastasizing lines we designated as UACC903-LMM and C8161-LMM. Using the parental and metastasizing cell lines we have been able to identify a lung metastasis gene signature using PCR array analysis, validated by PCR and Western Blot. This lung metastasis gene signature was further supported by the identification of increased expression of the same set of genes in lung metastasis as compared to primary tumors from patients with melanoma. We have also observed increased migration in metastasizing cell lines as compared to the parental lines using a trans-well migration assay with fetal bovine serum as chemo-attractant. CXCR-4 was one of gene products up-regulated in the metastasizing cell lines and the FDA-approved CXCR-4 antagonist, AMD-3100, inhibited trans-well migration of the metastasizing cell lines far more than parental cell lines. Our ongoing studies are examining the potential of inhibiting CXCR-4, and other gene products from our metastasis gene signature, as a therapeutic option in patients with advanced melanoma.
Funding: NIH RO1-563057
Note: This abstract was not presented at the meeting.
Citation Format: Yu Wen, Maung Naing Lin Shan, Jiadong Li, James Goydos. Developing a lung metastasis gene signature using a lung tropism model in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5172. doi:10.1158/1538-7445.AM2015-5172