bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1142: The expression profile of cancer/testis antigens (CTAs) in head and neck cancer
Authors: Karia Bruno Takao R. , Zamuner Fernando Tadeu , Nani Luiz Augusto S. , Rodrigues Dorival M. , Carvalho Andre L. , Vettore Andre Luiz 
Published: August 2012

Abstract
Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most frequent types of cancer. Despite significant improvements in the therapeutic strategies, the overall survival rate in 5 years is around 50%. The development of new therapies and their integration into the current forms of treatment (surgery, radiotherapy and chemotherapy) is of great interest to improve the therapeutic efficacy. Immunotherapy may provide an alternative for current treatment approach, since the natural immune response can be stimulated by active immunotherapeutic interventions which may help in the control of the tumor progression and recurrence. A requirement for the development of immunotherapeutic approaches is the identification of immunogenic gene products expressed predominantly in tumor cells. Cancer/testis antigens (CTAs) fulfill this prerequisite as their expression is restricted to tumors with no expression in normal tissues, except germ line cells. In this study we performed a search on Oncomine, SAGE Anatomic Viewer, CTdatabase and PubMed databases to select among the 153 CTAs genes those that might be expressed in HNSCC. This in silico analysis allowed the selection of 60 CTAs genes to have their expression evaluated in 89 tumors and in 20 normal mucosa by RT-PCR. According this analysis, 13 CTAs were specificaly expressed in HNSCC samples (&gt;25% sensitivity) The expression of CTA1 was significantely associated with perineural invasion (p=0,023) and vascular invasion (p=0,003), whereas the presence of CTA2 or CTA3 was correlated with the presence of tumor cells in the lymph nodes (p=0,023 and p=0,037, repectively). Moreover, the CTA4 expression showed to be associated with capsular rupture (p=0,005). We report here the identification of 13 CTAs frequently expressed in HNSCC and the expression of some of them was significantly associated with poor prognostic factors. These results could be important for the development of immunotherapy strategies for treating HNSCC patients.
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 1142. doi:1538-7445.AM2012-1142
Abstract 1144: Overexpression of Tripartite Motif-containing 24 contributes to human epithelium cell carcinoma and correlates with poor prognosis of patient with local advanced head and neck squamous cell carcinoma
Authors: Lu Yan , Cao Wei , Cui Zhibin , Chen Wantao 
Published: August 2012

Abstract
BACKGROUND: To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC), we performed a genome-wide survey and found that Tripartite motif-containing 24(TRIM24) was a gene that was markedly up-regulated in HNSCC. TRIM24 is a member of transcriptional intermediary factor 1 family, functions as a co-regulator that modulate transcriptional activities of several nuclear receptors, either positively or negatively. Here, we investigated the effects of TRIM24 on proliferation, invasion and apoptotic potential in HNSCC cell lines as well as its clinical significance in HNSCC. METHODS: The expressions of TRIM24 were examined through real-time PCR and western blot in 56 pairs of HNSCC and adjacent normal samples, as well as in 8 HNSCC cell lines and primary normal keratinocytes. Three TRIM24 high-expressed cell line were transfected with TRIM24 siRNA, then the proliferation, invasion and apoptotic potential was assessed by cell-counting kit-8, colony formation, matrigel invasion chambers and flow cytometry. In addition, the clinical implication of TRIM24 was investigated in another independent 91 locally advanced HNSCC by immunohistochemistry. RESULTS: TRIM24 mRNA expression were up-regulated remarkably in HNSCC samples and cell lines through real-time PCR. Correspondingly, elevated TRIM24 translation levels were found in 2 of 3 (67%) HNSCC tissues that were selected randomly from the 56 paired HNSCC tissues and 6 of 8 HNSCC cell lines using Western blot analysis. A significant reduction in cell proliferation and increase in population of apoptotic cells were observed in TRIM24 siRNA transfected cell lines in p53-dependent manner. Moreover, 55%(50/91) of HNSCC samples show high expression of TRIM24 by immunohistochemistry and survival analyses indicated a significant association between TRIM 24 high expression and a reduced overall survival in patients with locally advanced HNSCC (log rank test, P = 0.020). CONCLUSION: Our data indicated that overexpression of TRIM24 may play an important role in HNSCC tumorigenesis and serve as an independent prognostic predictor for patients with locally advanced HNSCC. ACKNOWLEDGMENTS: This study was supported by the National Natural Science Foundation of China (Grant No. 30973343), Projects of the Shanghai Science and Technology Committee (Grant No. 08JC1414400 and 10XD1402500) and the Shanghai Leading Academic Discipline Project (S30206). *Yan Lu and Wei Cao contributed equally to this work.
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 1144. doi:1538-7445.AM2012-1144
Abstract 116: Targeting hypoxia for the identification of novel biomarkers for prostate cancer
Authors: Gomez Christian R. , Munz Jan Marie , Kosari Farhad , Karnes Jeffrey , Cheville John , Ida Cristiane , Sebo Thomas , Vasmatzis George , Vuk-Pavlovic Stanimir 
Published: August 2012

Abstract
Tumor-associated hypoxia has been associated with malignant progression, metastasis, resistance to therapy, and poor clinical outcome in prostate cancer (CaP). Prompted by the evidence that hypoxia affects CaP, we studied global gene expression in 100 CaP tissues and 71 samples of adjacent benign tissues. RNA was extracted from cancer cells isolated by laser-capture microdissection (LCM) or without isolation (“bulk tissue”). We found 24 hypoxia-associated genes significantly overexpressed in CaP (p≤0.02), both in bulk tissue and LCM. Among hypoxia-associated genes, the disc large (drosophila) homolog-associated protein 5 (DLG7), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with Gleason score and systemic progression. Since the products of HMMR and CCNB1 have been recently identified as molecular markers of CaP progression, we postulated that DLG7 has prognostic value also. To test this hypothesis we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within five years of surgery) and controls (no progression within seven years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CL, 0.68 to 0.8), independent of the for ERG status. Overall, our data indicate that DLG7, a hypoxia-controlled gene have a prognostic value in high-risk CaP. To better define the value of DLG7 as a molecular predictor of CaP progression, we are currently assessing DLG7 protein levels by immunohistochemistry. Then we will analyze the association of DLG7 levels with clinical parameters. Introduction of oxygen tension as a variable may constitute a tool for the identification of novel biomarkers for CaP. Present address CRG: University of Mississippi Cancer Institute, Jackson, MS, USA. Support: DOD PC094680 (CRG), PCF Creativity Award (CRG), Mayo Clinic Prostate SPORE 5P50CA091956 (SV-P); Mrs. Adelyn L. Luther, Singer Island, Florida and Mayo Clinic Cancer Center (SV-P).
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 116. doi:1538-7445.AM2012-116
Abstract 1177: The mutational status of the p53 tumor suppressor gene is a determinant of GSTP1 expression and mediates GSTP1-dependent drug resistance in human glioblastoma
Authors: Antoun Gamil R. , McLendon R , Friedman H , Friedman A , Bigner D , Ali-Osman F 
Published: August 2012

Abstract
Mutations in the p53 tumor suppressor gene, a transcription factor activated by a variety of cellular stresses, including, those inflicted by anti-cancer agents, is a common genetic abnormality in GBMs. Although, p53 is involved in critical cellular processes, such as, cell cycle arrest, DNA repair and apoptosis, studies of p53 in tumor drug resistance and/or patient response to therapy have yielded mixed results. Thus, in gliomas and other cancers, such as, breast, bladder, and ovarian carcinomas, some studies have associated wild-type p53 with higher tumor drug resistance, while other studies indicate that mutant or functionally inactive p53, rather than wt p53, confers drug resistance. These observations indicate the significant complexity of the role of p53 in tumor response to therapy and suggest that other factors, including, downstream p53 pathways and/or regulation, may be important determinants of the p53 effects on the tumor drug resistance phenotype. We previously reported that the human GSTP1 gene, that encodes a major drug metabolizing protein, cell signaling regulator and a mediator of tumor drug resistance, is transcriptionally activated by p53 via a canonical p53 binding motif located in intron 4 of the GSTP1 gene. Our goal, in this study, is to gain further insight into the relationship between p53-dependent transcriptional control of GSTP1 in GBM and the extent to which it contributes to GSTP1 expression in primary patient tumor and, ultimately, to their response to therapy. For this, we sequenced the p53 gene across exons 2-11 in 42 primary GBM specimens quantified the level of GSTP1 gene expression by RNA-PCR and genotyped the allelic variants in them. The results showed, approx. half of the tumors to harbor wild-type p53. In those with mutant p53, the mutations spanned the entire p53 target region, the majority in the core DNA binding domain with the hot spots in codons 55, 72, 175, 245, 248, and 273. GSTP1 expression was significantly heterogeneous between the tumors, and with a few exceptions, correlated directly with the presence of wild-type p53. In representative tumors, the high GSTP1 gene expression was associated with resistance to cisplatin and temozolomide. These result suggest that, in GBM, transcriptional activation of GSTP1 by wild-type, and some mutant forms of p53, contributes to their resistance to therapy. Supported by NIH grants RO1 CA 153050, RO1CA127872, RO1 CA 112519, P50CA108786 and P30-CA14236.
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 1177. doi:1538-7445.AM2012-1177
Abstract 118: CTCF, a master epigenetic regulator, is a haploinsufficient tumor suppressor gene in multiple cell lineages
Authors: Moore James M. , Moser Russell , Smith Leslie , Gurley Kay , Liggett Denny , Filippova Galina , Kemp Christopher J. 
Published: August 2012

Abstract
While changes in the epigenetic landscape are ubiquitous in cancer, the origin and causal effects of most of these changes on neoplastic progression are largely unknown. The DNA binding protein Ctcf, regulates a diverse array of epigenetic processes, including DNA methylation spreading, but is role in cancer is unclear. Here we show that Ctcf heterozygous knockout mice are remarkably susceptible to spontaneous, ionizing radiation, and chemically-induced neoplasia in a broad range of tissues. Analysis of lung tumors from Ctcf+/− mice establishes Ctcf as a haploinsufficient tumor suppressor gene whose loss cooperates with mutant Kras to accelerate tumor growth and malignant progression. Increased DNA methylation at Ctcf binding sites in normal tissues from Ctcf+/− mice indicates that reduction of Ctcf leads to epigenetic deregulation and this occurs prior to overt neoplastic transformation. This indicates epigenetic instability can predispose a broad range of tissues to neoplastic transformation. A mouse model of Ctcf regulated epigenetic stability provides a useful setting to dissect the mechanistic link between environmental exposure, and risk of cancer or other diseases with an epigenetic component.
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 118. doi:1538-7445.AM2012-118
Abstract 1306: p63 functions as an essential oncogene in squamous cell carcinoma in vivo and is required for tumor maintenance
Authors: Ramsey Matthew R. , Wilson Catherine , Ory Benjamin , Rothenberg S. Michael , Faquin William , Mills Alea A. , Ellisen Leif W. 
Published: August 2012

Abstract
Transcription factors mediate diverse functions in normal development and tumorigenesis. The p53-related transcription factor p63 (TP63) plays an essential role in development of stratified epithelial tissues, as germline loss of p63 leads to abnormal proliferation and differentiation of ectoderm-derived precursors. The role of p63 in human cancer, however, is controversial. Loss of p63 is associated with neoplastic progression in some animal models and in a subset of human tumors. Nevertheless, p63 is rarely targeted for somatic mutational inactivation and is indeed overexpressed in squamous cell carcinomas (SCCs), where is has been postulated to function either as a key tumor maintenance factor or as a lineage marker not essential to the malignant process. Here, we show that SCCs are profoundly dependent on p63 expression in vivo, and we identify a key, therapeutically relevant pathway through which p63 mediates tumor maintenance. Conditional genetic ablation of p63 in an endogenous SCC model induces rapid and dramatic tumor regression owing to apoptosis of p63-expressing cells. We identify the FGFR2 oncogene as a direct transcriptional target of p63 that signals through AKT to mediate survival of SCC cells. Finally, we employ the clinical FGFR2 inhibitor AZD4547 to demonstrate the potential therapeutic effect of extinguishing FGFR2 signaling in p63-expressing SCCs. These results define p63 as a key tumor maintenance factor through regulation of FGFR2 signaling in SCC. More broadly, this demonstrates the potential for targeting oncogenic transcription factor pathways in tumors such as SCC that rarely exhibit somatic oncogene-activating mutations.
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 1306. doi:1538-7445.AM2012-1306
Abstract 1311: Expression and activity of nuclear factor TOX3 in breast cancer
Authors: Seksenyan Akop , Kadavallore Asha , de la Torre Brian , Aliahmad Parinaz , Asirvatham Ananthi , Walts Ann E. , Bose Shikha , Berel Dror , Strom Samuel , Funari Vincent , Audeh William , Kaye Jonathan 
Published: August 2012

Abstract
Our laboratory has shown that thymocyte selection-associated HMG-box protein (TOX) is a member of a small subfamily of DNA binding factors, and a key regulator of multiple aspects of immune system development. Recently, genome wide association studies have mapped a breast cancer susceptibility locus to the gene encoding the TOX-family member TOX3. However, little is known concerning the pattern of expression or biological functions of TOX3 in breast cancer and normal mammary epithelial cells. We find that TOX3 is specifically expressed in estrogen receptor (ER+) mammary luminal epithelial cells. Interestingly, using a TOX3 monoclonal antibody developed by our laboratory, we identify a subset of breast tumors that highly express TOX3. Moreover, using the MCF-7 breast cancer cell line, we find that TOX3 regulates a subset of ER target genes in an estrogen independent but ER dependent manner, potentially revealing a novel mechanism of ER target gene activation. In addition, TOX3 enhances cell migration. Together, these studies lend support to the idea of altered TOX3 expression influencing breast cancer development and/or progression.
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 1311. doi:1538-7445.AM2012-1311
Abstract 1316: N-acetyl-L-cysteine sensitizes pancreatic cancer therapy by targeting NFκB pathway: Translation into animal model
Authors: Qanungo Suparna , de Klerk Uys Joachim , Distler Anne , Mieyal John J. , Lemasters John J. , Townsend Danyelle M. , Nieminen Anna-Liisa 
Published: August 2012

Abstract
Pancreatic cancer has the worst prognosis of all major cancers with 97% treatment failure. First-line systemic therapy for pancreatic cancer is the antimetabolite gemcitabine. Although, tumors may initially respond to the gemcitabine treatment, soon tumor resistance and excessive toxicity develops leading to treatment failure. Efforts to optimize and improve the efficacy of gemcitabine therapy through combination with other agents have little success. Previously, we demonstrated that N-acetyl-L-cysteine (NAC), a glutathione (GSH) precursor prevents NFκB activation and promotes pancreatic cancer cell death. The mechanism of inactivation of NFκB by NAC supplementation is a post-translational sulfhydryl modification called S-glutathionylation on p65-NFκB that inhibits its DNA-binding capacity and thus prevents activation of the survival genes. Mass spectrometric analysis indicated that four of the 9 cysteines of p65 are potentially S-glutathionylated. Our hypothesis is that chemoresistance against gemcitabine arises from a combination of hypoxia- and gemcitabine-induced NFκB activation. The objective of this study is to test the hypothesis and investigate if thiol donors like NAC can suppress NFκB signaling and augment a therapeutic response to gemcitabine in vivo. Here we determined the anti-tumor effect of gemcitabine and NAC on pancreatic tumors in mice. MIA PaCa-2 pancreatic cancer cells were injected into nude mice to grow subcutaneous tumors. Treatment groups were untreated, NAC, gemcitabine and gemcitabine+NAC. Results indicated that neither gemcitabine nor NAC by itself was effective in decreasing tumor growth. However, NAC and gemcitabine in combination inhibited tumor growth by 33%. Gemcitabine activates NFκB, although the mechanism for this phenomenon is unclear. NFκB activity was indeed increased in gemcitabine-treated tumors (3-fold) and combination with NAC treatment blunted this effect (p&lt;0.005). The results confirm gemcitabine-induced NFκB activation and NAC bioavailability in tumors. To assess whether combined treatment of gemcitabine and NAC induces apoptosis, we performed TUNEL staining in tissues. Gemcitabine plus NAC increased apoptosis by 35-fold compared to gemcitabine alone. Taken together, our data suggest that NAC first inhibits NFκB activation arising from hypoxic regions of tumors and secondarily block gemcitabine-activated NFκB in hypoxic and normoxic regions of tumors, and therefore sensitizes cells to gemcitabine-induced killing. This could be used as an effective adjunct to gemcitabine chemotherapy of pancreatic cancer.
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 1316. doi:1538-7445.AM2012-1316
Abstract 1319: Establishment and characterization of fresh primary human colorectal tumor implants
Authors: Miagkov Alexei , Uzgare Rajneesh , Zhong Shaobin , Leary Lisa , Ondrus Janine , Hundley Thomas , Sathyamoorthy Malathi , Tiruchinapalli Dhanrajan , Todaro Nicole , Griffin Christina , Mulpuri Rao , Hostin Damon , Otto Jeffery , Chen Hao 
Published: August 2012

Abstract
A personalized approach towards the therapy of colorectal carcinoma is critical for a successful outcome. In recent years, direct transfer xenograft models (or the “tumor graft”) have proven to be highly predictive and are being adapted in clinical practice. However, direct drug evaluation in tumor graft models for each individual patient is not feasible due to time and cost constraints. Predictive biomarker discovery is an extremely promising application of the tumor graft model, since the discovered biomarker signatures will direct therapy choice in a much broader patient population. In collaboration with the Catholic Health Initiatives Center for Translational Research we at Caliper Life Sciences have established a collection of tumor graft samples of primary human colorectal carcinomas. All samples were collected fresh from consenting patients following an IRB-approved protocol and implanted in vivo on the day of surgical tumor resection. Tumors were grafted either orthotopically or subcutaneously in female NIH-III mice. We present here the results of a comparative study of gene and protein expression profiles for the primary tumor (clinical samples) and the direct transfer xenografts. These data will be correlated with drug sensitivity profiles generated by using the same samples. The resulting data sets will be used to characterize predictive biomarker signatures that will be a valuable tool for selection of the most effective therapy tailored to the individual patient.
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 1319. doi:1538-7445.AM2012-1319