bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5006: Interleukin-1 receptor type II regulates matrix metalloproteinases expression and plays oncogenic roles in HaCaT cells
Authors: Lee Hui-Ju , Mar Ai-Chung , Lee Te-Chang 
Published: June 2012

Abstract
Interleukin-1 receptor type II (IL1R2) is an IL-1 decoy receptor, which plays a role to inhibit exogenous IL-1 signaling. Intriguingly, IL1R2 also performs as a pro- inflammatory factor via activation of intracellular IL-1α signaling in a variety of cells. In our previous study, we reported that long term arsenic exposure resulted in increased IL1R2 expression which led to increased motility of human urothelial cells. In the present study, we similarly found that the expression of IL1R2 was increased in long-term arsenic exposed HaCaT cells (A1, A2) and the tumorigenic derivative, T4R2 cells. Since matrix metalloproteinases (MMPs) are frequently increased in a variety of malignant tissues including skin cancer, we also revealed that a positive association of IL1R2 and MMP1 and MMP7 at either mRNA or protein levels, which were analyzed by quantitative real time RT-PCR and western blotting, respectively. To reveal the involvement of IL1R2 in up-regulation of MMPs, we adopted shRNA technique to silence the expression of IL1R2 in T4R2 cells. Our results demonstrated that MMP1 and MMP7 were suppressed in IL1R2 silencing T4R2 cells. Meanwhile, we found the enhanced expression of MMP1 and MMP7 in HaCaT cells with ectopically expressed IL1R2. Furthermore, we confirmed our previous finding showing that IL1R2 overexpression was accompanied with increased expression of precursor form of IL-1α protein (preIL-1α). Immunofluorescence staining showed the colocalization of IL1R2 and preIL-1α in the nucleus. In a xenograft mouse model, we found that HaCaT cells with ectopical expression of IL1R2 formed tumor in nude mice whereas IL1R2 silencing in T4R2 cells suppressed the tumorigenicity. Taken together, these results implicate that IL1R2 plays an oncogenic role in human keratinocyte transformation by upregulation of MMPs expression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5006. doi:10.1158/1538-7445.AM2011-5006
Abstract 5009: The expression pattern of claudin-1, claudin-3, claudin-4, claudin-5 and claudin-7 in penile squamous cell carcinoma
Authors: Bulgarelli Adriana , Lourenço Silvia V. , Coutinho-Camillo Cláudia M. , Buim Marcilei EC , Begnami Maria Dirlei F.S. , Soares Fernando A. , Vassallo José 
Published: June 2012

Abstract
Claudins are a family of proteins that are structural and functional components of tight junctions and have crucial roles in the maintenance of cellular arrangement, adhesion and paracellular transport. Recent studies have shown that changes and/or loss of claudin expression plays an important role in tumorigenesis and tumor progression, and altered expression of claudins has been reported in various human carcinomas. Penile squamous cell carcinoma (SCC) is a major health problem in Brazil, corresponding to 2,1% of all brazilian men tumors and 5-year survival rate drops dramatically in patients with lymph node metastasis. Purpose: The aim of this study was to investigate claudins expression profile in penile SCC. Method: We analyzed expressions of claudin-1, -3, -4, -5 and -7 in 14 cases of penile SCC by relative gene expression method using real time PCR. Results: The expression of claudin-1, -4 and -5 was downregulated 15.9-, 6.9- and 9.1-fold, respectively, in 72% of penile SCC cases in comparison to normal penile squamous cells (p=0.0052 for both claudin-1 and -4 and p=0.0002 for claudin-5). Claudin-3 expression was variable, with 7 of the 14 cases (50%) showing low expression of claudin-3. Claudin-7 was upregulated 101.4-fold in 10 of 14 cases analyzed (p=0.067). Conclusion: Our data suggests that loss of claudin-1,-4 and -5 expression and gain of claudin-7 expression might be associated with the tumorigenic process in penile SCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5009. doi:10.1158/1538-7445.AM2011-5009
Abstract 501: Characterization of lung cancer stem/initiating cells from non-small-cell lung cancer patients
Authors: Chen Wan-Jiun , Chen Huei-Wen , Ho Chao-Chi , Chen Hsuan-Yu , Yang Pan-Chyr 
Published: June 2012

Abstract
Cancer stem cells (CSCs) have been proposed to be responsible for chemoresistant, tumor recurrent, and metastasis. To culture and characterize the CSCs become urgent and may be helpful to develop novel diagnostic and therapeutic strategies. Accumulated evidences indicated the importance of CSCs in tumor formation and successfully isolated the CSCs from patients or cell lines with different cancer types; however, this has not been well explored in lung cancer. Not alike previous isolation through specific markers and quiescent condition, we cultured the lung cancer stem/initiating cells from patient with lung adenocarcinoma and the CSCs formed tumor sphere as fed by the surrounding stroma cells. These lung cancer stem/initiating cells were characterized with highly expressed levels of the stemness makers, nanog, oct4, sox2, and klf4 (53.3-, 37.7-, 13.0, and 4.4-folds changes) as comparing to the feeder cells, also, showed relative higher percentages of side population (27.4%), ALDH activity (14%), higher tumorigenesity compared to other lung cancer cell lines including adenocarcinoma (A549, H522, H23, Hop62, and EKVX), large cell carcinoma (Hop92), squamous cell carcinoma (H226), and bronchi alveolar carcinoma (H322M). These lung CSCs also showed higher drug resistance capacity represented by IC50 to chemotherapy drugs including docetaxel, cisplatin, vinorelbine distrate, and etoposide (13.0-, 1.55, 27.2- and 103.3-folds increased). Furthermore, we found that as less as 100 cells could generate adenocarcinoma formation both in orthotropic or subcutaneous models in severe combined immunodeficient (NOD/SCID) mice. Interestingly, the lung CSCs could spontaneous differentiate into epithelial types of cancer cells as removing the feeder cells in vitro or different phenotypes of adenocarcinoma cells in vivo. Transcriptomic analysis indicated that the Wnt, Notch, TGF-β and HGF signaling pathways are highly expressed in the lung CSCs and quickly down-regulated as removing the feeder cells. The gene expression profiles also provide the novel markers for selection CSCs from lung cancer cell lines and lung cancer patients. To sum up, we have cultured the cancer stem/initiating cells from lung cancer patient with the feeder cells, which providing the tumor microenvironment to maintain the stemness of the cancer stem cells. This model should be helpful not only for isolating and cultured the lung CSCs from patients, but also in developing the anti-cancer strategy targeting on lung CSCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 501. doi:10.1158/1538-7445.AM2011-501
Abstract 5011: Difference in expression of STAT3 and STAT5b in Swedish and Egyptian patients with activated b-cell subtype of diffuse large b-cell lymphoma
Authors: Jacobson Therese , Bahnassy Abeer A. , Lundahl Joachim , Tamm Katja Prokovskaja , Porwit Anna , Zekri Abdel-Rahman N. , Khaled Hussein M. , Mellstedt Håkan , Moshfegh Ali 
Published: June 2012

Abstract
Diffuse Large B-cell lymphoma (DLBCL), the most common type of lymphoma in adults, accounts for approximately 30 to 40% of newly diagnosed lymphomas. Using gene expression profiling, DLBCL can be divided into three immunologically indistinguishable subtypes: the germinal center B-cell like (GBC), the activated B-cell like (ABC) and the primary mediastinal B-cell lymphoma (PMBL) subtype. The aim of the study was to compare gene expression profiles of Swedish and Egyptian ABC DLBCL patients.
Formalin fixed and paraffin embedded material of 67 Egyptian and 15 Swedish ABC DLBCL patients were used in the study. Affymetrix gene expression platform was used for profiling and the analysis was carried out using GeneSpring GX software. Quantitative PCR (qPCR) and confocal microscopy was used to verify the findings.
The GeneSpring GX analysis showed that 3247 genes were at least 2 fold up- or downregulated comparing the two patient groups. Among these were 1827 genes upregulated and 1420 genes downregulated. Gene expression analysis was verified using qPCR showing that STAT3 was upregulated with a fold change of 3.1 in the Swedish patients and that STAT5b was upregulated with a fold change of 1.3 in the Egyptian patients. Confocal microscopy showed protein activity of STAT3 and 5b in the nucleus of Swedish and Egyptian patients respectively using monoclonal antibodies.
This is the first study that reveals diversity in expression of STATs in different populations of ABC DLBCL patients. STAT3 and 5b are known to have different pathways of activation and targeted disruption has shown their functional differences. Using gene expression profiling, we revealed different expression levels of STAT3 and STAT5b in Swedish and Egyptian ABC DLBCL patients. Since the populations of Sweden and Egypt are exposed to different infectious agents, the results of the present study further raise the question concerning viral etiology in ABC-DLBCL possibly due to repeated infections and chronic inflammation. In general, these findings give additional evidence to the importance of signaling pathways involving STATs in ABC DLBCL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5011. doi:10.1158/1538-7445.AM2011-5011
Abstract 5018: Adherence to free breast cancer screening among uninsured black and Hispanic women
Authors: Okoronkwo Nneoma O. , Onojobi Gladys , Burnside Clinton , Williams Carla , McDonald-Pinkett Shelly , Frederick Wayne A.I. , Laiyemo Adeyinka O. 
Published: June 2012

Abstract
Background: Studies have shown that blacks have a higher mortality rate from breast cancer. However, it is unclear if this can be mainly attributed to their different biological susceptibilities or lower health care access or lack of adherence to scheduled procedures such as screenings and treatments or a combination of everything.
Aim: We sought to examine the extent to which uninsured black and Hispanic women adhere to free breast cancer screening appointments.
Methods: This study included a cohort of 410 participants from a monthly program in Howard University Cancer Center that offers free breast cancer screening (clinical breast examination and mammogram) for uninsured women who are aged 40 and older in the Washington DC area. These participants were referred from community health organizations in Maryland, District of Columbia and Maryland. Data was extracted from July 2009 to June 2010. The participants were categorized as non-adherent (no shows) if they did not cancel their appointments and did not show up for the breast cancer screening. We used Poisson regression models to evaluate the association of race with adherence to the scheduled breast cancer screening and adjusted for potential confounders. We calculated Relative Risks (RR) for no shows and 95% Confidence Intervals (CI).
Results: There were 195 (47.6%) Hispanic and 215 (52.4%) black women. A total of 314 (76.6%) women showed up for screening but 96 (23.4%) were non-adherent. When compared with Hispanic women, black women were older (mean age = 50.7 years vs 48.4 years; P = 0.0005), and more likely to be born in the United States (29% vs 2%; P &lt; 0.0001) but were less likely to be married (31% vs 49%; P &lt; 0.0001). A total of 42 (21.6%) Hispanic and 54 (25.1%) black women did not show up for the breast cancer screening, adjusted RR = 1.06: 95% CI: 0.71 – 1.57; P = 0.788.
Conclusions: There is a high rate of non-adherence to scheduled free breast cancer screening among underserved black and Hispanic women. Increased outreach effort and community education about this potentially preventable cancer is needed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5018. doi:10.1158/1538-7445.AM2011-5018
Abstract 5023: Pretreatment blame, physical symptoms, and distress in patients undergoing radiotherapy for head and neck cancer
Authors: Ojo Bukola , Badr Hoda , Milbury Kathrin , Genden Eric M. 
Published: June 2012

Abstract
INTRODUCTION: Head and Neck Cancer (HNC) patients report higher rates of psychiatric morbidity than other cancer patients, suggesting that psychological adjustment is an important component of their quality of life. One factor contributing to patients’ distress is the degree to which they experience physical symptom morbidity. Given that HNC is often attributed to unhealthy lifestyle factors (i.e., tobacco, alcohol, and risky sexual behaviors resulting in HPV), another possible contributor, that has not been studied, is patients’ attributions of self-blame regarding their disease cause. The objective of this study was to explore the associations between lifestyle factors, symptoms, self-blame, and distress in this population. Understanding these potential interactions may provide targets for future psychosocial interventions.
METHODS: Data for this exploratory study was collected from a cross-sectional survey of 70 HNC patients (87 % male; 63% oropharyngeal) prior to the initiation of radiotherapy.
RESULTS: In terms of lifestyle factors, 70% of patients had a tobacco history and 7% had screening scores indicative of alcohol dependence as measured by the AUDIT; 61 % of the oropharyngeal patients were HPV positive. Behavioral self-blame was significantly greater among patients with a history of tobacco use (t(66) = 2.52, p = 0.01) and characterological self-blame was highest among patients with HPV positive tumors (t(66) = 2.28, p = 0.03). Although patient distress (BSI-18) was significantly associated with higher levels of cancer symptom severity (p = 0.0001) and interference (p = 0.0001), as measured by the MDASI-HN, the association of distress with blame also approached significance (p &lt; 0.10).
CONCLUSION: Results suggest that blame is prevalent in head and neck cancer patients and is related to lifestyle factors that may have caused the disease. The finding that patient distress was associated with both symptom severity and self-blame is interesting and suggests that psychosocial interventions should not only address patients’ current level of symptoms but also their attributions of blame regarding the cause of their disease. Our future work will prospectively examine whether changes in symptoms and blame affect the course of distress in this vulnerable population.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5023. doi:10.1158/1538-7445.AM2011-5023
Abstract 5032: Targeting Src in mucinous ovarian carcinoma
Authors: Matsuo Koji , Nishimura Masato , Stone Rebbeca L. , Komurov Kakajan , Shahzad Mian MK , Bottsford-Miller Justin N. , Enomoto Takayuki , Kimura Tadashi , Ram Prahlad T. , Schmeler Kathleen M. , Frumovitz Michael , Gallick Gary G. , Wong Kwong K. , Sood Anil K. 
Published: June 2012

Abstract
BACKGROUND: Mucinous ovarian carcinomas have a distinct clinical pattern compared to other subtypes of ovarian carcinomas. We evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of src kinase in pre-clinical models of mucinous ovarian carcinoma.
METHODS: 1302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinomas were evaluated for survival analyses. Gene microarrays with src specific functional analysis were performed to identify biomarkers for 2 mucinous ovarian cancer cell lines compared with 5 serous ovarian cancer cell lines. Biological effects of src kinase inhibition were tested in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2) using dasatinib-based therapy, an oral src kinase inhibitor.
RESULTS: Patients with advanced-stage (stage III/IV) mucinous ovarian cancer had significantly worse survival compared to those with serous histology: median overall survival, 1.67 versus 3.41 years, p=0.002; and median survival time after recurrence, 0.53 versus 1.66 years, p&lt;0.0001. Gene expressions of mucinous ovarian cancer cell lines were distinct from serous ovarian cancer cell lines. Pathway analyses showed that src kinase might be a key factor in regulating a number of signaling pathways. Among 10 ovarian cancer cell lines, the RMUG-S-ip2 mucinous ovarian cancer cells showed the highest src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of src kinase and Akt. These induced activities were inhibited with concurrent administration of dasatinib. Combination therapy of oxaliplatin with dasatinib further demonstrated significant synergistic effects on reducing cell viability (interaction index &lt;1), increasing apoptosis (mean percentage of total apoptotic cells in RUMG-S-ip2, untreated vs dasatinib alone vs oxaliplatin alone vs oxaliplatin and dasatinib, 4.1% vs 8.5% vs 9.5% vs 26.8%, p&lt;0.01), and in vivo anti-tumor effects in the RMUG-S-ip2 model (tumor reduction rate in combination therapy: versus oxaliplatin monotherapy 79.1%, and versus dasatinib monotherapy 74.7%, both p&lt;0.01).
CONCLUSION: Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting src kinase with combination of dasatinib and oxaliplatin may be an attractive approach for further clinical development in mucinous ovarian carcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5032. doi:10.1158/1538-7445.AM2011-5032
Abstract 5033: Stromal-derived conditioned media activates STAT3 via JAK2 and TYK2 and results in de novo resistance to Nilotinib
Authors: Nair Rajesh R. , Tolentino Joel H. , Argilagos Raul F. , Zhang Ling , Pinilla-Ibarz Javier , Hazlehurst Lori A. 
Published: June 2012

Abstract
Complete eradication of CML has not been possible in patients because of the presence of minimal residual disease (MRD) in sanctuary sites like the bone marrow (BM). One of the reasons for MRD is the milieu of cytokines and growth factors present in the BM microenvironment, that contribute to BCR-ABL independent drug resistance in CML. For example, in the present study, we demonstrate the importance of STAT3-mediated drug resistance in the BM microenvironment by showing that conditioned media (CM) derived from both normal and patient-derived mesenchymal stem cells and osteoblasts leads to STAT3 phosphorylation (pSTAT3-Y705) and concomitant drug resistance to Nilotinib in CML cells. Inhibiting the activity or reducing the expression of JAK2 and TYK2 was necessary for sensitizing cells to Nilotinib in CM. Moreover, increased pSTAT3-Y705 levels were associated with increased STAT3 transcriptional activity and up-regulation of Mcl-1 and cyclin D1. Our study indicates that there is an inherent redundancy in CM-mediated STAT3 activation pathway because concomitant neutralization of two potent activators of STAT3, IL-6 and G-CSF, does not reverse CM-mediated protection against Nilotinib. Furthermore, utilizing a SCID-hu bone implant in vivo model, we show that K562 cells with reduced STAT3 showed significantly lower tumor burden, which could be attributed to not only the slower proliferation rate, but also to the observation that these cells underwent cell death in BM stromal derived CM. Finally, CD34+ cells from CML patients when exposed to CM showed an increase in STAT3 phosphorylation which correlated with the development of de novo resistance to Nilotinib-mediated cell death. Taken together our data indicate that STAT3 is an important target in CML and its direct inhibition, along with BCR-ABL inhibitors, will likely be the most effective therapeutic strategy for reversing resistance within the BM microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5033. doi:10.1158/1538-7445.AM2011-5033
Abstract 5043: Norcantharidin induces melanoma cell apoptosis through TR3 pathway
Authors: Liu Shujing , Yu Hong , Kumar Suresh , Martin James , Xu Xiaowei 
Published: June 2012

Abstract
Norcantharidin (NCTD) is the demethylated analog of cantharidin, a naturally occurring toxin isolated from Mylabris. NCTD has been used to treat hepatocellular carcinoma with clinical efficacy and limited side effects. However, the underlying mechanism of its antitumor effects remains elusive. We have previously shown that TR3 expression is significantly decreased in metastatic melanomas and it is implicated in regulation of melanoma cell apoptosis. In this study, we showed that NCTD inhibited melanoma cell viability and induced apoptosis in vitro. NCTD induced translocation of TR3 from nucleus to mitochondria where it colocalized with Bcl-2 in melanoma cells. NCTD also increased Cytochome c release from mitochondria to the cytoplasm. There was also increased expression of Bax and cleaved caspase-3, accompanied with decreased expression of Bcl2 and Nf-kB2. The effects of NCTD were inhibited by knockdown TR3 expression in melanoma cells. To study its function in vivo, we treated Tyr::cre;BRAFCa/+;Ptenlox/lox mice with NCTD. Temozolomide and PBS were used as controls, and ten mice were used in each group. Temozolomide modestly increased mice survival, whereas NCTD significantly improved the survival of treated mice. Our data indicates that NCTD inhibits melanoma growth by inducing cell apoptosis via activation of a TR3 dependent pathway. These results suggest that NCTD is a potential therapeutic agent for melanoma.
Financial support was provided by CA-093372, CA-116103 to XX.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5043. doi:10.1158/1538-7445.AM2011-5043