bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1256: Humoral autoimmune response to a RNA-binding protein HCC1/CAPER in hepatocellular carcinoma (HCC).
Authors: Dai Liping , Ren Pengfei , Liu Xinxin , Ortega Rosalia , Yao Wu , Wang Kaijuan , Wang Mingan , Tan Eng M. , Zhang Jianying 
Published: August 2014

Abstract
HCC1 was originally cloned as a cell nuclear autoantigen in a patient with liver cirrhosis that progressed to HCC. The full-length sequence of HCC1encodes a protein of 530 amino acids and migrating at 64 kDa in SDS-PAGE. HCC1 has two isoforms of HCC1.4 and HCC1.3. The difference is that HCC1.3 has 6-amino acid deletion located in the RNP-1-like region of the putative third RNP-CS domain. The nucleotides and protein sequences of HCC1 were not found at that time in searching available databases and, therefore, it was considered as a novel gene with unknown function. Several years later, a group showed that HCC1 was a co-activator of activating protein-1 and estrogen receptors and proposed naming it CAPER. Further study by other group has demonstrated that HCC1/CAPER is a novel transcriptional co-activator for v-Rel that strongly suppresses its transforming activity, uncovering a tumor suppressor role for HCC1/CAPER in regulating Rel's oncogenic activity. Our previous studies have demonstrated that autoantibodies against tumor-associated antigens (TAAs) can be regarded as serological biomarkers in cancer immunodiagnosis. Whether autoantibodies to HCC1/CAPER can be also used as one of the markers in HCC remains to be investigated. In the present study, autoantibody responses to HCC1.3 and HCC1.4 were firstly evaluated by ELISA, western blotting and indirect immunofluorescence assay in sera from patients with HCC, liver cirrhosis and chronic hepatitis, as well as from normal human individuals. Immunohistochemistry (IHC) with HCC tissue array slides was also performed to analyze protein expression profiles of HCC1. The prevalence of anti-HCC1.4 antibodies was 13.5% (23/171) in HCC, which was significantly higher than that in normal human sera (1.1%). Whereas the significant difference regarding frequency of anti-HCC1.3 antibodies between HCC patients and normal individuals was not found. The frequency of HCC1 expression in HCC tissues was also significantly higher than that in normal liver tissues (57.5% vs. 0%; P&lt;0.001). The data suggests that anti-HCC1.4 autoantibody may be a potential biomarker for HCC, but not HCC1.3. Further functional study of HCC1 may provide more evidence to address the question why these two isoforms of HCC1 can induce different humoral immune response in HCC patients.
Citation Format: Liping Dai, Pengfei Ren, Xinxin Liu, Rosalia Ortega, Wu Yao, Kaijuan Wang, Mingan Wang, Eng M. Tan, Jianying Zhang. Humoral autoimmune response to a RNA-binding protein HCC1/CAPER in hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1256. doi:10.1158/1538-7445.AM2013-1256
Abstract 1258: The frequency of CD11c+ cells within the gastric cancer tissue is associated with favorable prognosis.
Authors: Jiang Jingting , Wu Changping , Lu Binfeng 
Published: August 2014

Abstract
Aim: CD11c is a marker for dendritic cells which help initiating adaptive antitumor immunity. The study was designed to investigate correlation between the frequency of CD11c+ cells in the gastric cancer tissue and the clinical and pathological parameters of gastric cancer patients.
Methods: CD11c expression in gastric cancer tissues was examined by immunohistochemistry. Surface CD11c expression on the leukocytes within cancer tissues was examined by flow cytometry.
Results: The number of CD11c+ cells was higher in gastric cancer tissues than that in gastritis or gastric polyps tissues. The number of CD11c+ cells in tumor specimens from the early-stage gastric cancer was significantly higher than that in specimens from the late-stage gastric cancer (t=2.77,P=0.0064). Flow cytometry found that CD11c surface expression was stronger in specimens from the early stages than those from the late stages of gastric cancer. The Univariate analysis revealed that the frequency of intratumoral CD11c+ cells showed association with gender and tumor location, and was reversely correlated with tumor size, depth of infiltration, nodal metastasis, tumor histological grade and cancer stages. The median survival time (MST) for the subgroups of patients with stronger and weaker CD11c expression were 67.0 months (95%CI, 39.0-112.0 months) and 29.0 months (95%CI, 21.0-39.0 months), respectively. And MSTs were significantly different between the CD11c higher and lower subgroups (χ2=11.6425,P=0.0006). Among patients who suffered from late-stage diseases, those with higher numbers of intratumoral CD11c cells had a significantly lower risk of death than those with lower numbers of CD11c cells (χ2=8.549,P=0.0035), and the lowered risk of death was statistically significant after adjusting gender, age, tumor size and infiltrating depth (RR=0.52,95%CI=0.29-0.94).
Conclusions: The number of CD11c+ cells within gastric cancer tissue is a favorable prognostic marker for gastric cancer. Our study suggests gradual elimination of dendritic cells is characteristic of gastric cancer progression.
Citation Format: Jingting Jiang, Changping Wu, Binfeng Lu. The frequency of CD11c+ cells within the gastric cancer tissue is associated with favorable prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1258. doi:10.1158/1538-7445.AM2013-1258
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1286: FANCA binds to nucleic acids and stimulates endonuclease activity of FEN1.
Authors: Qian Liangyue , Yuan Fenghua , Rodriguez-Tello Paola , Zhao Xinliang , Song Limin , D'Urso Gennaro , Jain Chaitanya , Zhang Yanbin 
Published: August 2014

Abstract
Fanconi anemia is a rare autosomal recessive or X-linked genetic disease characterized by progressive bone marrow failure, various developmental anomalies, and cancer predisposition. Fanconi anemia complementation group A (FANCA) gene is one of the 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Except for its constituent role in the ubiquitin ligase of the Fanconi anemia core complex, no other biochemical activity has been identified thus far.
Using purified protein, we observed that human FANCA has intrinsic affinity to nucleic acids. FANCA binds to both single-stranded and double-stranded DNA; however, its affinity to single-stranded DNA is dramatically higher. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. A patient-derived FANCA truncation mutant, Q772X, has diminished affinity to both DNA and RNA. On the contrary, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acids binding activity (RNA&gt;ssDNA&gt;dsDNA), indicating that the nucleic acids binding domain of FANCA is primarily located at its C-terminus. Using DNA and RNA ladders, we determined that the minimum numbers of nucleotides required for FANCA recognition are ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5’ flap or tail on DNA facilitates its interaction with FANCA. In addition, we observed that FANCA greatly stimulates the endonuclease activity of flap endonuclease 1 (FEN1), which processes 5’ flap structures.
Our study reported that purified human FANCA binds to nucleic acids with strong preference for single-stranded forms. Our finding suggests that FANCA FANCA may participate in maintenance of replication forks by regulating removal of Okazaki fragment during maturation of lagging strand replication.
Citation Format: Liangyue Qian, Fenghua Yuan, Paola Rodriguez-Tello, Xinliang Zhao, Limin Song, Gennaro D'Urso, Chaitanya Jain, Yanbin Zhang. FANCA binds to nucleic acids and stimulates endonuclease activity of FEN1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1286. doi:10.1158/1538-7445.AM2013-1286
Abstract 1287: Epigenetic deregulation of breast cancer is associated with DNA Repair Capacity.
Authors: Matta Jaime , Hadar Tal , Morales Luisa , Ostrow Kim , Sidransky David , Guerrero-Preston Rafael E. 
Published: August 2014

Abstract
Introduction 226,870 women are estimated to be diagnosed with breast cancer in 2012. Search for accurate methods for screening, diagnosis and treatment follow up, that will be minimally invasive are ongoing.
Hypermethylation of gene promoters occurs frequently in the pathogenesis of breast cancer, and causes silencing of tumor suppressor genes. Hypermethylation of Mal, Kif1a and OGDHL in breast cancer cell lines and tissue samples was previously reported.
Aberrant DNA repair capacity (DRC) has been studied and shown to elevate the risk for breast cancer.
However, information on the association between the epigenetic promoter hypermethylation and DRC is lacking in the literature.
Objective The aim of this study is to assess the association between breast cancer and promoter hypermethylation of Mal, Kif1a and OGDHL in serum of breast cancer patients and controls in association with the DRC.
Methods 240 serum samples from breast cancer patients and controls from Puerto Rico were collected. DNA was extracted and methylation levels were measured after bisulfite treatment, by QMSP. DRC was assessed by host reactivation assay of blood samples. The overall risk for breast cancer was calculated and adjusted for patient characteristics including DRC.
Results Methylation of at least one of the genes was found in 49% of breast cancer samples compared to 20% of controls. ROC curves for individual genes showed values of 0.64 for MAL, 0.51 for Kif1a and 0.53 for OGDHL. In the linear regression unadjusted analysis, mean methylation levels (what are the values?) of the three genes and odds ratio (OR) were higher in breast cancer cases compared to controls, with Kif1a and OGDHL values being statistically significant. These values became non significant after adjusting for DRC. Hypermethylation of Kif1a, but not MAL or OGDHL was found to be significantly associated with DRC.
Conclusion Correlation between promoter hypermethylation of the genes Mal, Kif1a and OGDHL and breast cancer was non significant when adjusted for DRC.
A significant association between hypermethylation of Kif1a and DRC was shown.
The association between promoter hypermethylation and DRC needs to be further studied.
Citation Format: Jaime Matta, Tal Hadar, Luisa Morales, Kim Ostrow, David Sidransky, Rafael E. Guerrero-Preston. Epigenetic deregulation of breast cancer is associated with DNA Repair Capacity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1287. doi:10.1158/1538-7445.AM2013-1287
Abstract 1290: Investigations to evaluate the role of Twist1 during tumor promotion and epithelial carcinogenesis.
Authors: Srivastava Jaya , Macias Everardo , Rao Dharanija , Kiguchi Kaoru , DiGiovanni John 
Published: August 2014

Abstract
Recent studies have identified the involvement of receptor tyrosine kinases (RTKs) and their downstream signaling pathways, including MAPK, PI3K/Akt/mTOR, and Stat3, as key regulatory factors of epidermal proliferative capacity during skin carcinogenesis. Through development and study of transgenic mice with overexpression of a constitutively active form of Stat3 (Stat3C) in the basal cell layer, previous studies in the laboratory discovered that constitutive Stat3 activation accelerates tumor progression in the two-stage skin carcinogenesis model, which utilizes the tumor initiator 7,12-dimethylbenz[α]anthracene (DMBA) and tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Twist1, a well-known inducer of EMT, has been shown to be regulated by Stat3 in a number of systems. Western blot analysis of epidermal protein lysates from Stat3C transgenic mice indicated a two-fold induction of Twist1 expression as compared to wild type mice. In addition, immunofluorescence staining analysis of tumors from wild type mice [papillomas and squamous cell carcinomas (SCCs)] and Stat3C mice (SCCs) showed nuclear co-localization of Twist1 and Stat3. In the present study, we investigated the activation and subsequent downstream signaling of Twist1 during TPA-induced epidermal hyperproliferation. Western blot analysis of epidermal lysates from mice treated topically with multiple applications of TPA showed an initial decrease (4-6 h) followed by a subsequent rebound of Twist1 protein at 18 hours post TPA treatment. This initial decrease and then rebound coincided with that of the cell cycle regulatory proteins cyclin D1, cyclin E1, E2F-1, and c-myc. Interestingly, basal levels of Twist1 were reduced in epidermis specific Stat3 deficient mice. Furthermore, Stat3 deficient mice treated with TPA failed to show a rebound in expression of Twist1 in the epidermis. Immunofluorescence experiments of TPA treated epidermis revealed that nuclear localization of Twist1 was restricted to the proliferative compartment. Collectively, these results, combined with other data to be presented, suggest that Stat3 regulates basal levels of Twist1. This protein is localized in the nucleus of cells found primarily in the proliferative compartment of hyperplastic epidermis and skin tumors. The current results further suggest that Twist1 may play a role in cell cycle progression in keratinocytes during tumor promotion. Research supported by CA76520.
Citation Format: Jaya Srivastava, Everardo Macias, Dharanija Rao, Kaoru Kiguchi, John DiGiovanni. Investigations to evaluate the role of Twist1 during tumor promotion and epithelial carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1290. doi:10.1158/1538-7445.AM2013-1290
Abstract 1296: Involvement of RSK2 in human skin cancer.
Authors: Lee Cheol-Jung , Lee Hye Suk , Lee Ji-Young , Cho Yong Yeon 
Published: August 2014

Abstract
Our previous study demonstrated that the total p90 ribosomal S6 kinase 2 (RSK2) protein level was significantly higher in human skin cancer tissues and cancer cells compared with normal skin tissues and premalignant cell lines. However, the role of RSK2 activation and signaling in human skin cancer has not yet been fully elucidated. In this study, we provided evidences that RSK2 plays a key role in human skin cancer. We examined the effect of knocking down RSK2 expression on EGF-induced anchorage-independent transformation in the premalignant HaCaT human skin keratinocyte cell line and on soft agar colony growth of SK-MEL-28 malignant melanoma (MM) cells. We found that UVB stimulation induced increased in not only the total and phosphorylated protein levels of ERKs and RSK2, but also the nuclear localization and gene expression of RSK2. Moreover, RSK2−/− mouse embryonic fibroblasts (MEFs) showed enhanced sub-G1 accumulation induced by UVB stimulation compared with RSK2+/+ MEFs, indicating that RSK2 might play an important role in tolerance against stress associated with UV. RSK2 knockdown inhibited proliferation and anchorage-independent transformation of HaCaT cells and soft agar colony growth of MM cells. We found that the phosphorylated protein levels of RSK2 were enhanced in cancer tissues compared with normal tissues in a human skin cancer tissue array. Importantly, activated RSK2 protein levels were highly abundant in human skin cancer tissues compared with matched skin normal tissues. Taken together, our results demonstrated that RSK2 plays a key role in neoplastic transformation of human skin cells and in skin cancer growth.
Citation Format: Cheol-Jung Lee, Hye Suk Lee, Ji-Young Lee, Yong Yeon Cho. Involvement of RSK2 in human skin cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1296. doi:10.1158/1538-7445.AM2013-1296
Abstract 1306: SR48692 inhibits EGF receptor transactivation and proliferation of lung cancer cells.
Authors: Moody Terry W. , Jensen Robert T. 
Published: August 2014

Abstract
Neurotensin (NTS) is an autocrine growth factor for some lung cancer cells (Moody et al., 1985;Life Sci 36:1727). NTS binds with high affinity to the GPCR NTSR1 causing phosphatidyl inositol turnover and proliferation of lung cancer cells; SR48692 is a NTSR1 antagonist (Moody et al., 2001; Peptides 22:109). NTSR1 expression is associated with poor survival of non-small cell lung cancer (NSCLC) patients (Alfano et al., 2010; Clin Cancer Res 16:4401). NSCLC cells express the epidermal growth factor receptor (EGFR) whose tyrosine kinase activity is inhibited by gefitinib. Here the abillity of SR48692 to block EGFR transactivation caused by NTS was investigated. NTS and NTS8-13 but not NTS1-8 addition to NSCLC cell lines NCI-H1299 or A549 cells increased phosphorylation of Tyr1068 of the EGFR after 2 min which was blocked by 10 uM SR48692 or 10 ug/ml gefitinib. The ability of NTS to regulate EGF receptor transactivation was blocked by GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), N-acetylcysteine (anti-oxidant) and transforming growth factor TGF) α antibody. By ELISA, NTS significantly increased secretion of TGFα from lung cancer cells. NTS but not levocabastine (NTSR2 agonist) increased cytosolic Ca2+ within seconds after addition to NCI-H1299 cells which was antagonized by SR48692. NTS addition to NCI-H1299 cells increased tyrosine phosphorylation of beta-catenin, ERK, FAK, PYK-2 and Src which was antagonized by SR48692. SR48692 inhibited the proliferation of NCI-H1299 and A549 cells which have wild type EGFR. Also, SR48692 potentiated the ability of gefitinib to inhibit growth of NCI-H1299 and A549 cells. These results indicate that SR48692 is a NTSR1 antagonist which increases the potency of gefitinib in lung cancer cells.
Citation Format: Terry W. Moody, Robert T. Jensen. SR48692 inhibits EGF receptor transactivation and proliferation of lung cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1306. doi:10.1158/1538-7445.AM2013-1306
Abstract 136: Statins and breast cancer mortality.
Authors: Murtola Teemu J. , Visvanathan Kala , Artama Miia , Vainio Harri , Pukkala Eero 
Published: August 2014

Abstract
Background: Breast cancer is a common malignancy and cause of cancer death. Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could have beneficial effects against recurrence and progression of breast cancer. We evaluated breast cancer-specific and overall mortality among statin users in a cohort of breast cancer patients.
Methods: Our study cohort included all newly diagnosed breast cancer patients in Finland during 1995-2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use during these years was obtained from a national prescription database. We used Cox proportional hazards regression method to estimate mortality among statin users separately for pre- and post-diagnostic usage.
Results: A total of 4,169 participants had ever-used statins. During the median follow-up of 3.25 years (range 0.08-9.0 years), a total of 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. Post-diagnostic statin use was inversely associated with breast cancer mortality (participants with localized tumors: HR 0.33, 95% CI 0.24-0.42; metastatic tumors: HR 0.52, 95% CI 0.31-0.86) and also overall mortality. The association between statin use and mortality was dose-dependent. In stratified analyses, the reduction did not significantly vary by lipophilicity of statins. Additionally, long-term pre-diagnostic statin use was also associated with lower breast cancer mortality.
Conclusion: Lower breast cancer mortality observed for both pre-diagnostic and post-diagnostic statin use suggests that statins could lower risk of death in breast cancer patients. A clinical trial testing statins’ effect on survival in breast cancer patients is feasible.
Citation Format: Teemu J. Murtola, Kala Visvanathan, Miia Artama, Harri Vainio, Eero Pukkala. Statins and breast cancer mortality. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 136. doi:10.1158/1538-7445.AM2013-136
Abstract 1365: Sun protection practices among melanoma survivors.
Authors: Puthumana Jeremy , Ferrucci Leah , Mayne Susan , Lannin Donald , Chagpar Anees 
Published: August 2014

Abstract
Purpose: Unprotected sun exposure is a key risk factor for melanoma and further exposure to ultraviolet radiation after a melanoma diagnosis may increase the risk of a subsequent melanoma. We sought to determine whether melanoma survivors observed sun protection practices more vigilantly than the rest of the population.
Methods: The National Health Interview Survey (NHIS) is an annual, cross-sectional survey of the civilian, non-institutionalized population of the United States on a wide range of health topics. We used the 2010 NHIS data on self-reported history of melanoma, sun protection practices, and indoor tanning to determine if individuals with a previous history of melanoma adhered more to sun protection practices than the general population.
Results: In 2010, the NHIS surveyed 27,120 adults, of whom 171 (0.74%) had a prior history of melanoma. 54.8% of melanoma survivors were men, and 10.2% were under the age of 40. More melanoma survivors reported they always stay in the shade than the general population (15.6% vs. 10.5%, p&lt;0.001); however, 15.4% of melanoma survivors still reported rarely or never staying in the shade. Melanoma survivors were more likely (than their general population counterparts) to always wear a baseball cap/visor (31.3% vs. 18.4%, p=0.028), a wide-brimmed hat (20.5% vs. 6.1%, p&lt;0.001), and a long-sleeved shirt (12.0% vs. 5.2%, p=0.003) when going outside on a warm, sunny day for more than one hour. They were also more likely to report always using sunscreen (32.0% vs. 17.2%, p=0.005); however, 27.3% of melanoma survivors reported never wearing sunscreen when going outside on a warm sunny day for more than one hour. No significant relationship was found between melanoma survivors and the general population in wearing long pants/skirts on a sunny day (22.2% of melanoma survivors always wear such clothing versus 17.7% of the general population, p=0.404). In addition, melanoma survivors were less likely to have used indoor tanning devices in the past 12 months than the general public (2.1% vs. 5.5%, p=0.009).
Conclusion: Melanoma survivors, in general, engage in more sun protection practices than the general population. However, the fact that many do not seek shade and never use sunscreen, and some reported tanning bed use, remains a concern for their skin cancer risk.
Citation Format: Jeremy Puthumana, Leah Ferrucci, Susan Mayne, Donald Lannin, Anees Chagpar. Sun protection practices among melanoma survivors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1365. doi:10.1158/1538-7445.AM2013-1365