bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2149: N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 4, a novel tumor suppressor, suppresses tumorigenesis and liver metastasis of colorectal cancer cells in mice
Authors: Jao Tzu-Ming , Tsai Ming-Hong , Tzeng Sheng-Tai , Yang Ya-Chien 
Published: August 2015

Abstract
Colorectal cancer (CRC) is one of the most common causes of cancer deaths in the world, and most of CRC arise sporadically by the emergence of multiple chromosomal aberrations. Allelic losses in the long arm of chromosome 4 are commonly encountered in many human malignancies, but few tumor suppressor genes (TSGs) are identified. By loss of heterozygosity study at chromosome 4 in 114 colorectal carcinomas, we identified N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 4 (NDST4) as a novel TSG that had been published recently. We demonstrated for the first time that the genetic loss of NDST4 was significantly associated with advanced pathological stage and poorer overall survival of patients. Meanwhile, gene expression of NDST4 was obviously decreased in 30 (57.7%) of 52 CRC tumors when compared with their matched normal mucosae. In the present study, tumor suppressor activity of NDST4 was identified by in vitro cell models and mouse xenograft tumor models. Ectopic expression of NDST4 in the human CRC cells induced a significant suppression in cell proliferation, anchorage-independent growth and invasion in vitro. Subcutaneous injection of NDST4-inducible CRC cells in nude mice showed alleviated tumor growth in doxycycline treated mice when compared with doxycycline untreated mice. More importantly, via intrasplenic implantation, re-expression of NDST4 in silenced cells restrained liver metastasis, and also improved survival in nude mice. Taken together, these results indicate that NDST4 is a tumor suppressor gene associated with CRC, and its downregulation might promote tumor progression and distant metastasis. In addition, allelic loss of NDST4 gene could serve as a molecular predictor of metastasis and poor prognosis in patients with CRC.
Citation Format: Tzu-Ming Jao, Ming-Hong Tsai, Sheng-Tai Tzeng, Ya-Chien Yang. N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 4, a novel tumor suppressor, suppresses tumorigenesis and liver metastasis of colorectal cancer cells in mice. [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 2149. doi:10.1158/1538-7445.AM2015-2149
Abstract 2163: Mapping SUMOylation sites of PTEN tumor suppressor
Authors: Wang Yubing , Wong Chiwai , Yan Mingfei , Or Penelope , Chan Andrew M. 
Published: August 2015

Abstract
PTEN tumor suppressor plays crucial function in multiple cellular processes, including proliferation, migration, DNA repair, cell cycle and survival signaling. Its function is tightly controlled by a series of regulatory processes at transcriptional and post-translational levels. Small ubiquitin-related modifier (SUMO) is an essential post-transcriptional modifier which involves in many important biological functions. Previous studies showed that PTEN can be modified by SUMOylation on K254 and K266. SUMOylation on K254 controls the nuclear localization and retention of PTEN and plays essential role in DNA damage repair. On the contrary, SUMOylation on K266 is responsible for its membrane binding, which is required for the down-regulation of PI3K/AKT pathway.
However, most studies mainly focus on SUMO1 modification, function of SUMO2/3 involved PTEN regulation is still unclear. In addition, the dynamic regulation and biological activities of different isoforms of SUMOylated PTEN in different subcellular compartments are not well-defined. Also, how PTEN phosphorylation impacted on PTEN SUMOylated have not been addressed fully.
To address these questions, a series of PTEN SUMOylation defective-mutants targeted to different subcellular compartments were generated. In addition, a panel of phosphorylation sites mutants (T366A, S370A, S380A, T382A, T383A, and S385A) were included. These mutants were cotransfected with His-tagged SUMO1, SUMO2, and SUMO3 in 293T cells. SUMOylated PTEN protein species are affinity absorbed onto nickel columns. The characterization of these mutants will be discussed.
To further delineate the dynamic regulation of SUMOylated PTEN, we are developing a BRET-based live cell imaging system by the ectopic co-expression of a HALO-tagged SUMO and NanoLuc-tagged PTEN expression constructs to monitor the subcellular localization of SUMO-conjugated PTEN in vivo.
This work was supported by Hong Kong Research Grant Council (460713) and Hong Kong PhD Fellowship Scheme (PF-12-13876).
Citation Format: Yubing Wang, Chiwai Wong, Mingfei Yan, Penelope Or, Andrew M. Chan. Mapping SUMOylation sites of PTEN tumor suppressor. [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 2163. doi:10.1158/1538-7445.AM2015-2163
Abstract 218: The new and rapid technique of detecting breast cancer cells using new fluorescent probe ‘gGlu-HMRG’ and its clinical application
Authors: Shinden Yoshiaki , Ueo Hiroki , Tobo Taro , Ganachi Ayako , Komatsu Hisateru , Nambara Sho , Saito Tomoko , Ueda Masami , Hirata Hidenari , Sakimura Shotaro , Takano Yuki , Uchi Ryutaro , Iguchi Tomohiro , Eguchi Hidetoshi , Sugimachi Keishi , Kubota Yoko , Kai Yuichiro , Kijima Yuko , Natsugoe Shoji , Ueo Hiraki , Urano Yasuteru , Mimori Koshi 
Published: August 2015

Abstract
Method
After spraying with gGlu-HMRG reagent to the samples, we took images within 5 minutes and analyzed the fluorescence intensity of them. Comparing the changes of fluorescence intensity and pathological evaluations, we examined how this fluorescent method could reflect the pathological status in resected breast tissues (n = 108 from 36 cases), margins of breast conserving surgery specimens (n = 7 from 5 cases) and axillary lymph nodes (n = 149 from 38 cases).
Result
1. The sensitivity and specificity were 92% and 94% respectively for binary classification (normal / abnormal) of various breast tissues.
2. We could detect all malignant lesions in the surface of surgical margins of breast conserving surgery specimens. Additionally, we could detect large tumor-free lesions as fluorescent negative regions.
3. The sensitivity and specificity were 97% and 79% respectively for diagnosing metastatic and non-metastatic axillary lymph nodes.
Discussion and conclusion
It was well feasible to distinguish breast tumor tissues from normal surrounding tissues by this new method. Since it is simple and non-tissue-destructive, it could be readily adopted in the clinical setting. We anticipate that it will reduce costs and the burden on histopathology services in the intraoperative pathological diagnosis of breast conserving surgery and sentinel lymph node biopsy. This technical innovation enable us to visualize tumor cells in the body intraoperatively and evolve the cancer surgery that needs the complete resection of cancer cells.
*1 Urano, Y. et al. Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe. Sci. Trans. Med. 3, 110ra119 (2011).
Citation Format: Yoshiaki Shinden, Hiroki Ueo, Taro Tobo, Ayako Ganachi, Hisateru Komatsu, Sho Nambara, Tomoko Saito, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Yuki Takano, Ryutaro Uchi, Tomohiro Iguchi, Hidetoshi Eguchi, Keishi Sugimachi, Yoko Kubota, Yuichiro Kai, Yuko Kijima, Shoji Natsugoe, Hiraki Ueo, Yasuteru Urano, Koshi Mimori. The new and rapid technique of detecting breast cancer cells using new fluorescent probe ‘gGlu-HMRG’ and its clinical application. [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 218. doi:10.1158/1538-7445.AM2015-218
Abstract 219: Fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore in combination with neoadjuvant chemotherapy inhibits metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model
Authors: Hiroshima Yukihiko , Maawy Ali , Zhang Yong , Murakami Takashi , Momiyama Masashi , Mori Ryutaro , Matsuyama Ryusei , Katz Matthew H. , Fleming Jason B. , Chishima Takashi , Tanaka Kuniya , ichikawa Yasushi , Endo Itaru , Hoffman Robert M. , Bouvet Michael 
Published: August 2015

Abstract
The efficacy of fluorescence-guided surgery (FGS) in combination with neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model was determined. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS + NAC; FGS only; and FGS + NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS + NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS + NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of FGS in combination with NAC on metastatic recurrence.
Citation Format: Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Takashi Murakami, Masashi Momiyama, Ryutaro Mori, Ryusei Matsuyama, Matthew H. Katz, Jason B. Fleming, Takashi Chishima, Kuniya Tanaka, Yasushi ichikawa, Itaru Endo, Robert M. Hoffman, Michael Bouvet. Fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore in combination with neoadjuvant chemotherapy inhibits metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model. [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 219. doi:10.1158/1538-7445.AM2015-219
Abstract 2206: qPCR array of 84 cell cycle genes in oral squamous cell carcinoma reveals differently expressed genes in larger size tumors in relation to small tumors
Authors: Gomes Carolina C. , Diniz Marina G. , de Souza Fabricio T. , Correia-Silva Jeane F. , Gomez Ricardo S. 
Published: August 2015

Abstract
The aim of the study is to investigate if larger oral squamous cell carcinoma (OSCC) tumors show a different transcriptional signature of cell cycle genes in relation to small OSCC tumor samples. To address this issue, 17 fresh OSCC tumor samples were included in the study, including T1(n = 5),T2 (n = 9),T3 (n = 2) and T4 (n = 1) samples. All tumors were either from the tongue or from the floor of the mouth and only two patients were non-smokers. Two samples were from female patients, while the other 15 were from men. Samples were categorized according to clinical tumor size in tumors ≤ 2cm (T1 n = 5) or tumors &gt; 2cm (T2, T3 and T4, n = 12). The median age of both groups was similar (57 and 62, respectively). The group of tumors ≤ 2cm was considered the reference group in the qRT-PCR results interpretation, while the larger tumors were considered the test group. The RNA was extracted and the cDNA was synthesized. A commercially available 84 cell cycle genes PCR array kit was used (PAHS-020, Cell Cycle PCR Array - Human, Qiagen). The results were analyzed according to the formula 2^-deltaCT and differential expressions were considered statistically significant when p&lt;0.05. The target genes expressions were normalized to two housekeeping endogenous genes B2M and HPRT1, considering both, the geometric and arithmetic CT means (that differed less than 1 CT between the reference and test groups). The following genes were downregulated in the test group (larger tumors) compared to the reference group (smaller tumors), showing a minimum fold change of 4: ANAPC4, E2F4, CUL1, PCNA, KNTC1, RPL13A, KPNA2, NBN, CCNG2 and SUMO1. These results need to be further confirmed in a larger cohort of samples. In conclusion, these findings suggest that the transcriptional activity of specific cell cycle genes changes according to the size of the OSCC tumor, which probably reflects tumor molecular evolution.Supported by: FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais), CNPq (National Council for Scientific and Technological Development) and CAPES (Coordination for Improvement of Higher Education Personnel), Brazil
Note: This abstract was not presented at the meeting.
Citation Format: Carolina C. Gomes, Marina G. Diniz, Fabricio T. de Souza, Jeane F. Correia-Silva, Ricardo S. Gomez. qPCR array of 84 cell cycle genes in oral squamous cell carcinoma reveals differently expressed genes in larger size tumors in relation to small tumors. [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 2206. doi:10.1158/1538-7445.AM2015-2206
Abstract 2215: Transcriptional co-regulation of Nox4 by p53 and SMAD3
Authors: Boudreau Howard E. , Park Jonathan J. , Leto Thomas L. 
Published: August 2015

Abstract
Recent studies suggest p53 plays an important role in TGF-beta-mediated cell signaling and migration. Previously, we showed that wild-type (WT) and mutant forms of p53 differentially regulate reactive oxygen species (ROS) generation by NADPH oxidase-4 (Nox4). We found that WT-p53 is a potent suppressor of TGF-beta-induced Nox4, ROS production, and cell migration, whereas tumor-associated mutant p53 proteins enhanced Nox4 mRNA and protein expression and cell migration by both TGF-beta-dependent and independent mechanisms (Boudreau et al. Br J Cancer. 2014 May 13;110(10):2569-82). In this study, we examined the basis of human Nox4 promoter regulation by p53 and SMAD3. By constructing a deletion series of Nox4 promoter-reporter constructs, we discovered two regions (-4.76kb to -3.9kb and -1.8kb to - 0.2kb) upstream of the transcription start site that induce promoter activity upon activation of the TGF-beta/SMAD3 pathway. Interestingly, TGF-beta/SMAD3-mediated Nox4 promoter activity was abolished by heterologous expression of p53-WT in p53-null cell lines Hep3B (hepatocytes) and H1299 (lung epithelial). This activity was repressed by wild-type p53 in a dose-dependent manner. In contrast, expression of common tumor-associated mutant-p53 proteins (R175H, R248H, R249Q, R273H) did not repress but enhanced Nox4 promoter activity. We observed this enhancement of Nox4 promoter activity by mutant p53 (R273H) in H1299 cells expressing T204D, a constitutively active TGF-beta receptor. When individual p53 response elements were mutated, however, both untreated and R273H-expressing cells showed 50% reduction in promoter activity. These results indicate that the Nox4 promoter region between -3.97kb and -4.76kb, containing candidate p53 response elements, plays a role in modulating Nox4 expression. Preliminary chromatin immunoprecipitation results suggest that endogenous mutant p53 R249S in PLC/PRF/5 hepatoma cells complexes with the Nox4 promoter region between -3.97kb and -4.76kb. Furthermore, constructs lacking this region show significantly reduced Nox4 promoter activity in response to TGF-beta. Our results provide a basis for Nox4 co-regulation by SMAD3 and mutant p53 that may be involved in tumor progression and metastasis.
Citation Format: Howard E. Boudreau, Jonathan J. Park, Thomas L. Leto. Transcriptional co-regulation of Nox4 by p53 and SMAD3. [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 2215. doi:10.1158/1538-7445.AM2015-2215
Abstract 2223: C-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy
Authors: Ng Kai Yu , Chai Stella , Tong Man , Guan Xin-Yuan , Cheng Alfred S. , Ma Stephanie 
Published: August 2015

Abstract
Tumor relapse after chemotherapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. Chronic infection with hepatitis B virus (HBV) has long been linked to the development of HCC. Upon chronic infection, random HBV genome integration can lead to truncation of hepatitis B virus X (HBx) protein at the C-terminus. The resulting C-terminal-truncated HBx (HBx-ΔC) was previously shown to confer enhanced invasiveness and diminished apoptotic response in HCC cells. In this study, we found HBx-ΔC to be more frequently detected in HCC clinical samples than their matched non-tumor counterparts. In addition, we also identified a strong positive correlation between HBx-ΔC and the liver cancer stem cell marker CD133, in a panel of liver cell line tested. Subsequently, we delineated the role of a naturally occurring HBx-ΔC (HBx-Δ14) in promoting stemness and aggressive behaviors in HCC cells. The stable overexpression of HBx-Δ14 in HCC cell line (Huh7) and immortalized normal liver cell line (MIHA) promoted expression of stemness markers, EpCAM and SOX2. In vitro functional studies with HBx-Δ14 stably overexpressed in Huh7 demonstrated an increased ability to self-renew, resist chemotherapy (5-fluorouracil) and targeted therapy (sorafenib), migrate and induce capillary tube formation in endothelial cells. Similar functional results were also obtained when HBx-Δ14 was stably overexpressed in MIHA cells. Taken together, in addition to its role in enhancing HCC metastasis, we find HBx-Δ14 to confer cancer and stem cell-like features in HCC, and to play an important role in driving tumor relapse in this deadly disease.
Citation Format: Kai Yu Ng, Stella Chai, Man Tong, Xin-Yuan Guan, Alfred S. Cheng, Stephanie Ma. C-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy. [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 2223. doi:10.1158/1538-7445.AM2015-2223
Abstract 2228: Requirement of JNK signaling for self-renewal and tumor-initiating capacity of ovarian cancer stem cells
Authors: Seino Manabu , Okada Masashi , Shibuya Keita , Seino Shizuka , Suzuki Shuhei , Takeda Hiroyuki , Ohta Tsuyoshi , Kurachi Hirohisa , Ito Kiyoshi , Nagase Satoru , Kitanaka Chifumi 
Published: August 2015

Abstract
Background/Aim: Activation of the c-JUN N-terminal kinase (JNK) signaling pathway has been associated with poor survival of patients with ovarian cancer, but the role(s) and significance of JNK signaling in ovarian cancer cells remain poorly understood. Here in this study, we aimed to investigate the role of JNK specifically in ovarian cancer stem cells (CSCs).
Materials and Methods: The effect of JNK inhibition on the self-renewal (CSC marker expression, sphere-forming ability) and tumor-initiating capacity was examined in CSCs derived from A2780 human ovarian cancer cell line. JNK inhibition was achieved either pharmacologically or genetically by use of RNA interference.
Results: Both pharmacological and genetic targeting of JNK resulted in loss of self-renewal and tumor-initiating capacity of A2780 CSCs.
Conclusion: Our findings demonstrate, to our knowledge for the first time, that JNK has a pivotal role in the maintenance of ovarian CSCs.
Citation Format: Manabu Seino, Masashi Okada, Keita Shibuya, Shizuka Seino, Shuhei Suzuki, Hiroyuki Takeda, Tsuyoshi Ohta, Hirohisa Kurachi, Kiyoshi Ito, Satoru Nagase, Chifumi Kitanaka. Requirement of JNK signaling for self-renewal and tumor-initiating capacity of ovarian cancer stem cells. [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 2228. doi:10.1158/1538-7445.AM2015-2228
Abstract 2229: CD117 expression and activation in prostate cancer progression
Authors: Kerr Bethany 
Published: August 2015

Abstract
We have demonstrated that CD117/c-kit expression on circulating tumor cells and in primary tumors correlates with advanced disease in prostate cancer patients. In addition, the ligand for CD117, stem cell factor (SCF) is increased in high-grade prostate cancer patients. To examine the effects of CD117 activation and expression on prostate cancer progression, we sorted CD117 positive and negative RM1 murine prostate cancer cells and LNCaP-C4-2 human prostate cancer cells. Sorted cells were then examined for tumorigenicity, proliferation, cell signaling, cell migration, angiogenesis and epithelial-mesenchymal transition. A xenograft model demonstrated that CD117 positive LNCaP-C4-2 tumors generate larger tumors characterized by increased vascularization and proliferation. In vitro, SCF induced CD117 activation results in altered cell signaling, migration and epithelial-to-mesenchymal transition. In addition, in vivo imaging of tumor growth demonstrated changes in tumor cell organization between CD117 positive and negative cell populations. In summary, CD117 expression and activation enhances prostate cancer progression.
Citation Format: Bethany Kerr. CD117 expression and activation in prostate cancer progression. [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 2229. doi:10.1158/1538-7445.AM2015-2229