bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1736: Skewed usage of TCRVbeta repertoire and predictive role of CD60 and CD49d expression in the survival rate of patients with Sézàry Syndrome
Authors: Scala Enrico , Pomponi Deborah , Narducci Maria Grazia , Lombardo Giuseppe Alfonso , Caprini Elisabetta , Liso Marina , Mari Adriano , Russo Giandomenico 
Published: February 2011

Abstract
Background: Sézary Syndrome (SS) is a rare and aggressive leukemic variant of Cutaneous T-Cell Lymphoma (CTCL) characterised by erythroderma and the presence of a malignant circulating memory CD4+ T cell clone with skin homing characteristics, lack of CD26 and CD49d and over-expression of CD60. The availability of a large panel of monoclonal antibodies to CDR3 Vß epitopes, allows the study of the TCR repertoire by flow cytometry and a more precise identification of the malignant clone phenotypic characteristics.
Objective: The aim of this study was to evaluate both the distribution of TCR-Vß family and CD60/CD49d expression within the clonal T cell population in patients affected by SS.
Methods: We studied, by five-color flow cytometry analysis, TCR-Vß repertoire in 62 patients affected by SS, in 180 patients with MF, 6 cases of B cell Lymphomas (BCL), 19 with chronic Eczema (CE) recruited and followed from 1998 to 2008. A sequential gating strategy was used in order to examine the CD60 and CR49d expression within the neoplastic clonal population identified through the TCR-Vß repertoire analysis.
Results and Conclusion: A skewed usage of only 4 out of 25 TCR-Vß subfamilies was observed in circulating T cell clone in 61.9% of patients affected by SS. TCR-Vß 2 and 5.1 were the most frequently represented (42.8% of TCR-Vß reactive patients), followed by TCR-Vß 12 and 13.1. In 20 cases the TCR-Vß panel was unable to identify the neoplastic clone, recognizing less than 5% of T cells, thus representing an indirect proof for the presence of a clonal population. CD60 was over expressed and CD49d down regulated within clonal T lymphocytes. This phenotype of the dominant T cell clone in the peripheral blood of patients with SS was significantly associated with a lower survival rate (chi-square 5.467, p &lt;0.019).
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1736.
Abstract 1738: Significance of thymidylate synthase expression in prostate cancer
Authors: Mizutani Yoichi , Edagawa Yu , Fujisue Hiroshi , Uchimoto Shinya , Koyama Kohei , Ibuki Naokazu , Inamoto Teruo , Ubai Takanobu , Nomi Hayahito , Azuma Hruhito , Katsuoka Yoji 
Published: February 2011

Abstract
Introduction :
Thymidylate synthase (TS) is an important rate-limiting enzyme in the pathway of de novo DNA synthesis. Several reports demonstrated that TS expression was up-regulated in various cancers. 5-fluorouracil (5-FU) is an anti-cancer agent used clinically against a variety of cancers including prostate cancer. TS is a target enzyme for 5-FU. 5-FU inhibits DNA synthesis by binding TS and folic acid. We then investigated the expression of TS in prostate cancer and investigated its prognostic significance.
Materials and Methods :
Total 100 prostate cancer tissue specimens were obtained from patients who underwent radical prostatectomy for prostate cancer. Fifty-two patients did not received neoadjuvant hormonal therapy, and the rest 48 patients received neoadjuvant hormonal therapy. We examined prostate cancer tissues and normal prostate tissues for TS expression by immunohistochemistry. TS expression was regarded as positive, when more than 25% cells showed positive staining. If less than 25% were positive staining, TS expression was regarded as negative.
Results :
TS in prostate cancer tissues expressed at higher levels in patients without neoadjuvant hormonal therapy, compared with normal prostate tissues. TS expression was positive in approximately 70% prostate cancer tissues. In contrast, TS expression was observed in about 10% normal prostate tissues. The positive rate of TS expression in Stage T3 prostate cancer was higher than that in Stage T2 prostate cancer. In addition, the rate of positive TS expression in Gleason score 7 or greater prostate cancer was higher than that in Gleason score less than 7 prostate cancer. Patients with prostate cancer with negative TS expression without neoadjuvant hormonal therapy had a longer postoperative recurrence-free rate than those with positive expression in the 5 year follow-up. The rate of positive TS expression in prostate cancer tissues was significantly down-regulated in patients who received neoadjuvant hormonal therapy, compared with no neoadjuvant hormonal therapy. Especially, the rate of positive TS expression in stage T2 prostate cancer tissues was decreased by neoadjuvant hormonal therapy.
Conclusions :
The present study has demonstrated for the first time that TS expression may be a prognostic parameter for prostate cancer patients undergoing radical prostatectomy, and that TS may be a molecular therapeutic target for prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1738.
Abstract 1742: Evaluating the prognostic value of EGFR by p16/HPV status in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiation
Authors: Hao Desirée , Lau Harold Y. , Eliasziw Michael , Klimowicz Alexander C. , Suzuki Keiko , Petrillo Stephanie K. , Box Alan , Diaz Roman , Banh Alice , Le Quynh-Thu , Magliocco Anthony M. 
Published: February 2011

Abstract
Background: Overexpression of the epidermal growth factor receptor (EGFR) has been correlated with a worse prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN), however the prognostic value of EGFR has not been fully evaluated in the context of human papillomavirus (HPV) status. Methods: Records from 91 consecutive SCCHN patients treated with concurrent chemoradiation at the Tom Baker Cancer Centre between August 2000 and March 2005 were reviewed. Triplicate 0.6 mm cores from available pre-treatment formalin-fixed paraffin-embedded (FFPE) biopsies were assembled into a tissue microarray. Immunofluorescence combined with automated quantitative analysis (AQUA™) was used to evaluate EGFR and p16 protein expression. Phosphorylated EGFR (pEGFR) was assessed by proximity ligation assay. HPV infection status was determined by colorimetric in-situ hybridization using the INFORM HPV Family 16 Probe (CISH). PCR was used to detect HPV DNA. EGFR and pEGFR were correlated with clinical outcomes according to p16-status and HPV-status. Results: FFPE biopsies were available from 49 patients (54%). Patient characteristics were as follows: mean age 55 years, 82% male, 49% oropharyngeal primaries. The complete response rate was 88%. With a median follow-up of 42 months (range 3 to 60), the 5 year overall survival (OS) was 54%. EGFR and pEGFR protein expression were classified as high in 14 (29%) and 13 (27%) tumours respectively. 27 tumours were p16 positive; 30 were HPV positive by either PCR or CISH. p16 was strongly correlated with HPV status (Spearman r=0.80). In univariate analyses, tumours with high EGFR, low p16, and HPV negative were associated with significant 3-, 7-, and 5-fold increases, respectively, in locoregional recurrence, recurrence at any site, disease-specific mortality and worse OS. pEGFR did not predict outcome. Neither EGFR nor pEGFR predicted response. After adjusting for age, smoking status, T- and N-stage, p16, and HPV there was no relationship between EGFR and outcome. p16 and EGFR were inversely related (Spearman r=-0.3). Conclusions: In our small cohort of patients, EGFR did not have prognostic value after correction for p16 / HPV status.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1742.
Abstract 1749: The downregulated expression of adiponectin receptors (AdipoR1, R2) in human colorectal cancer
Authors: Hiyoshi Masaya , Kitayama Joji , Tsuno Nelson H. , Sunami Eiji , Kawai Kazusige , Otani Kensuke , Nishikawa Takeshi , Shuno Yasutaka , Yasuda Koji , Hongo Kumiko , Kikkawa Yoshiko , Sasaki Kazuhito , Kaneko Manabu , Takahashi Koki , Nagawa Hirokazu 
Published: February 2011

Abstract
[Background] Adiponectin is 30 kDa adipocytokine hormone secreted by the adipose tissues, which mediates antineoplastic as well as anti-angiogenic effects after binding to its receptors, Adipo-R1 and Adipo-R2, which has been reported to be expressed in colorectal cancer tissue and cell lines. Recent studies have shown decreased levels of adiponectin in sera of patients with various types of cancer, including colorectal. And a recent study demonstrated that adiponectin expression is significantly associated with high histological grade tumors and low microvessel density count in colorectal cancer, suggestive of an anti-angiogenic role for adiponectin in colorectal cancer. However, presently, the expression and function of adiponectin receptors in tumor tissue have not been well characterized. Thus, in the present study, we aimed to study the expression of adiponectin receptors in colorectal cancer tissues, and investigate on their clinicopathological implications.
[Methods] Surgically resected specimens from 48 patients with colorectal cancer, receiving surgical operation in our surgical department in the period between November 2008 and July 2009, were analyzed. The study was approved by the Human Ethics Committee of the University of Tokyo. The messages and protein expressions of AdipoR1 and AdipoR2 were evaluated by real-time RT-PCR and immunohistochemistry, respectively, in cancer tissues and the matched normal counterparts.
[Results] The mean age of the patients was 66.79±11.85 years. The levels of expression of both AdipoR1/AdipoR2, normalized with the internal control (beta-actin), were significantly lower in cancer specimens compared with normal mucosa (0.966±0.392, vs1.366±0.408, p&lt;0.001 and 0.918±0.309, vs1.596±0.459, p&lt;0.001, respectively for AdipoR1 and Adipo R2). The mRNA levels of AdipoR1 and AdipoR2 showed a tendency of decrease in tumors with nodal metastases and the difference was significant with AdipoR2 (p&lt;0.05). Immunohistochemistry with polyclonal Abs showed a consistent reduction in protein expression of both receptors in cancer tissues in comparison with the normal counterparts.
[Conclusion] Both receptors were downregulated in colorectal cancer, as confirmed by the mRNA and the protein expressions, and AdipoR2 seemed to be associated with nodal metastases. This downregulation seems to be associated with poorer prognosis of colorectal cancer, and may be an escape mechanism of cancer cells from the suppressive effects of adiponectin.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1749.
Abstract 1755: Utility of anti-p53 antibody in blood as a predictive marker for the detection of early recurrence in postoperative patients with esophageal carcinoma
Authors: Hagiwara Nobutoshi , Takahashi Ken , Uchida Eiji , Makino Hiroshi , Nomura Tsutomu , Okawa Keiichi , Akagi Ichiro , Fujita Itsuro , Fujita Itsuro , Sakurazawa Nobuyuki , Onodara Hiroyuki , Yamashita Naoyuki , Miyashita Masao 
Published: February 2011

Abstract
Background: Circulating anti-p53 antibody(p53-Ab) in blood can be detected in various cancers. Serum p53-Ab has been applied as a tumor marker in detecting esophageal squamous cell carcinoma (ESCC). However, little is known about prognostic value for postoperative patients with ESCC. We evaluate the significance of preoperative serum p53-Ab as a potential marker of early recurrence after curative resection for ESCC.
Methods: Anti-p53 antibodies in serum was measured with Enzyme-linked immunosorvent assay (ELISA) to analyze serum p53-Ab before treatment in 44 patients with ESCC. Squamous cell carcinoma antigen(SCC-Ag) and Carcinoembryonic antigen (CEA) as popular tumor markers for ESCC were measured simultaneously by immunoradiometric assay to compare with the p53-Ab results. Clinicopathological characteristics were also examined. Kaplan-Meier survival analyses were used to analyze the association with prognosis.
Results: The recurrence-free rate was significantly higher in patients negative for p53-Ab in serum than those strongly positive for p53-Ab (p=0.0002). The patients positive for p53-Ab in serum were more likely to have early recurrence after curative resection than patients negative for p53-Ab (p=0.05). On the other hand there were no significant correlations between CEA, SCC-Ag positivity and early recurrence. Conclusions: This study suggests that p53-Ab in serum is a promising tumor marker to predict a risk of early recurrence after curative surgical resection for ESCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1755.
Abstract 176: The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands
Authors: Takeshima Hideyuki , Yamashita Satoshi , Shimazu Taichi , Niwa Tohru , Ushijima Toshikazu 
Published: February 2011

Abstract
Aberrant DNA methylation of promoter CpG islands (CGIs) is deeply involved in cancers and other disorders. Contrary to our initial expectations, aberrant methylation is now recognized to possess several unique characteristics different from mutations [Ushijima and Asada, Cancer Sci, 2010]. One of the remarkable differences is target gene specificity. Specific cancers have aberrant methylation of specific genes, and specific inducers of methylation, such as Helicobacter pylori infection, induce methylation of specific genes [Nakajima et al, Int J Cancer, 2009]. As the mechanism of target gene specificity (namely, instructive mechanism), low transcription levels and trimethylation of histone H3 lysine27 (H3K27me3) in precursor cells are known to promote methylation induction. However, factors that protect genes from aberrant methylation are unknown.
To identify protective factors, we first isolated 5,510 and 521 genes resistant and susceptible, respectively, to aberrant methylation induction by methylated DNA immunoprecipitation (MeDIP)-on-chip analysis of nucleosome-free regions of promoter CGIs in normal prostatic epithelial cells and four prostate cancer cell lines. Then, by gene expression analysis, the susceptible genes were shown to have low transcription levels in normal prostatic epithelial cells. Finally, by ChIP-on-chip analysis in normal prostatic epithelial cells, we revealed that, even among the genes with low transcription, genes with high active histone modifications and binding of RNA polymerase II (Pol II) had marked resistance to aberrant methylation induction, and confirmed that genes with high H3K27me3 had marked susceptibility to aberrant methylation induction. On the other hand, another repressive histone modification, trimethylation of histone H3 lysine9 (H3K9me3), was not associated with resistance or susceptibility. By multivariate analysis, Pol II binding showed stronger influence on the resistance than active histone modifications, and H3K27me3 showed independent influence on the susceptibility. The same was true in normal mammary epithelial cells for 5,430 and 733 genes resistant and susceptible, respectively, to aberrant methylation in breast cancers [Takeshima et al, Genome Res, 2009].
These results indicated that the presence of Pol II, active or stalled, protects promoter CGIs from aberrant DNA methylation, independently of transcription levels.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 176.
Abstract 1762: Clinical relevance of plasma IL-6 and IL-6 levels in chronic lymphocytic leukemia (CLL)
Authors: Johnston James B. , Yoon Ju-Yoon , Lakhi Sunjay , Kuschak Brenda , Hewitt Donna , Gibson Spencer B. 
Published: February 2011

Abstract
It has been suggested that cytokines play an important role in the survival and proliferation of chronic lymphocytic leukemia (CLL) cells and these growth factors may be derived from a variety of cell types, including CLL cells. The plasma levels of the inflammatory cytokines, IL-6 and IL-8, vary in CLL and increased levels have been associated with a poor prognosis. This phenomenon has been related to the inhibition of apoptosis of CLL cells by the cytokines. In the present study, plasma IL-6 levels were measured by an ELISA assay in 193 CLL patients (107 males, 86 females; ages, 37-92 yr (median, 67.6 yr)) and the plasma IL-8 levels in 66 patients (31 males, 35 females; ages, 37-92 yr (median, 69 yr)). Samples were obtained from patients followed in the CLL Clinic at CancerCare Manitoba. Among the patients, plasma IL-6 levels ranged from &lt; 0.01 to 1058 pg/mL, with a median value of 5.23 pg/mL. The median plasma IL-6 level in 37 age- and sex-matched controls was significantly lower at 0.83 pg/mL (range, 0.06-8.11 pg/mL)). Plasma IL-8 levels in the patients ranged from &lt;0.01 to 1058 pg/mL, with a median value of 5.23 pg/mL. There were 22 normal age- and sex-matched controls for IL-8 levels, and the median IL-8 level here was 3.86 pg/mL (range, 1.42-11.60 pg/mL). A significant correlation was observed between plasma levels of IL-6 and IL-8 (Spearman r = 0.4810, p-value &lt;0.0001), and the levels of both cytokines correlated positively with age and β2-microglobulin. There was also a trend between cytokine levels and RAI stage. There was no correlation between cytokine levels and CD38, IgVH mutation status or the Zap-70 level. For patients aged ≥65 yrs, approximately 22% had increased levels of plasma IL-6 (&gt;3 pg/mL, 8% in normals) and 25% had increased IL-8 (&gt;10 pg/mL, 8% in normals). Plasma from CLL patients with high IL-6 levels was able to induce IL-6 expression in CLL cells whereas plasma from CLL patients with low IL-6 levels failed to induce IL-6 expression in CLL cells. This indicates that factor(s) within the microenvironment are contributing to increased IL-6 levels in CLL.
We have previously shown that the relative survival decreases in CLL after age 65 yrs. The present study suggests that this may be related to a potentiation in the age-related increase in IL-6/IL-8 that is observed in the normal population. Whether the increase in mortality in elderly CLL patients is related to frailty/cardiovascular disease or to CLL progression is being investigated.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1762.
Abstract 1763: Quantitative gamma-H2AX immunoassay for pharmacodynamic monitoring anticancer cytotoxic agents
Authors: Zhang Yiping , Parchment Ralph , Tomaszewski Joseph , Doroshow James , Ji Jay 
Published: February 2011

Abstract
Phosphorylated H2AX (gamma-H2AX) has been reported as a biomarker for DNA double-strand breaks and programmed cell death. We have developed a 96-well plate based ELISA test for quantifying gamma-H2AX with the lowest limit quantiation at 16 pg/mL. The gamma-H2AX immunoassay is a cell- free assay with chemiluminescence readout using one unique pair of anti- gamma-H2AX antibodies as a sandwich bracketing the gamma-H2AX antigen from cell lysis extracts. The high affinity antibodies used in the assay provide high sensitivity and specificity allowing simple cell lysis procedures for antigen capture from crude extracts. The gamma-H2AX quantitation is normalized based on either cell numbers or total protein through BCA assay. We have performed gamma-H2AX quantitation in selected NCI60 cell lines from nine groups of human cancers. The gamma-H2AX levels among the NCI60 cell lines ranged from undetectable (&lt; 16 pg/ml) to 6325 pg/10 million cells with an average of 711 pg. The gamma-H2AX quantitation results from ionic radiation and topotecan treated cell lines, topotecan treated human PBMC and selected patient specimens will be reported. The applications of the assay include target discovery and drug screening with selected human cancer cell lines, preclinical development and pharmacodynamic evaluation with xenograft tumors and animal models under treatment of investigational drugs, as well as clinic testing for patient enrollment, regiment selection and therapy monitoring of anti-cancer agents involving in DNA replication, repair, cell cycle and apoptosis.
Funded by NCI Contract No. HHSN261200800001E
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1763.
Abstract 1777: The skin cancer chemotherapeutic agent PEP005 is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature
Authors: Li Luowei , Shukla Suneet , Lee Andrew , Ambudkar Suresh , Yuspa Stuart H. 
Published: February 2011

Abstract
Ingenol-3-angelate (PEP005), extracted from Euphorbia peplus, is currently in clinical trials for eradicating basal cell carcinoma (BCC), actinic keratosis and squamous cell carcinoma (SCC) in situ by topical application. Although structurally related to phorbol esters and a PKC activator, topical PEP005, but not phorbol 12-myristate 13-acetate (PMA), inhibited the growth of subcutaneous tumors derived from PAM212 (mouse SCC) and B16 (mouse melanoma). PEP005 and PMA both induced acute neutrophilic inflammation on mouse skin, but only PEP005 caused subcutaneous hemorrhage and vascular damage. Both PEP005 and PMA activated Erk1/2 in epidermis, but PEP005 also activated Erk1/2 in skin dermal fibroblasts and endothelial cells. Pretreatment with topical cyclosporin A (CsA), verapamil or XR9576, modulators of P-glycoprotein (P-gp), prevented PEP005-induced hemorrhage but not neutrophil infiltration. CsA also impaired Ing3A's anti-cancer activity while the anti-inflammatory dexamethasone did not. PEP005, but not PMA, blocked photoaffinity labeling of human P-gp with [125I]-Iodoaryazidoprazosin and inhibited P-gp mediated drug resistance to HCT-15 cells. The intracellular levels of PEP005 were significantly lower in P-gp expressing cells and treatment with XR9576 increased the levels to those of cells that do not express P-gp, demonstrating that PEP005 binds to and is transported by P-gp. Taken together, our results suggest that P-gp mediated absorptive transport, dermal penetration and vascular damage contribute to the anti-cancer activity of PEP005 in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1777.