bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3754: A prospective imaging biomarker trial for early identification of GBM patients resistant to first line therapy
Authors: Galban Craig J. , Chenevert Thomals L. , Meyer Charles R. , Tsien Christina , Lawrence Theodore S. , Hamstra Daniel A. , Junck Larry , Sundgren Pia C. , Johnson Timothy D. , Rehemtulla Alnawaz , Ross Brian D. 
Published: February 2011

Abstract
We assessed whether quantification of therapeutic-associated tumor cellularity and hemodynamic alterations may help in the early assessment of treatment resistance in patients with high grade glioma. Patients with high grade glioma (n=45) received concurrent chemoradiation. Apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) maps were acquired prior to chemoradiation and at week 3 during treatment on a prospective IRB-approved study. Clinical and conventional MR parameters, including average baseline ADC and rCBV and radiological response, were evaluated as prognostic indicators of one-year survival. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed. Of 45 patients, median survival was found to be 14.9 months with 44% of patients living shorter than one year (median survival of 6.6 months). Baseline ADC was the only single model not found to be predictive of survival at one year, whereas in a multivariate analysis PRMADC+ and PRMrCBV- had a stronger correlation to survival than baseline rCBV. Overall, a composite model of PRMADC+ and PRMrCBV- was found to have the strongest correlation with one-year survival. This study demonstrates the potential of a composite parametric model sensitive to both tumor cellularity and hemodynamic alterations following first line therapy for providing an early assessment of patient resistant to chemoradiation.
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 3754.
Abstract 3759: Discordance of the immunohistochemical expression of phospho-Akt and phosphor-ERK between paired biopsy and hepatectomy specimens of hepatocellular carcinoma
Authors: Shao Yu-Yun , Chen Chi-Long , Huang Chien-Chung , Tu Hui-Ching , Lin Zhong-Zhe , Hsu Chih-Hung , Cheng Ann-Lii 
Published: February 2011

Abstract
Background: Immunohistochemical (IHC) staining using archival tumor tissues is commonly used to study biomarkers of hepatocellular carcinoma (HCC). However, there are no biomarkers proven to be useful for personalized therapy of HCC so far. Since HCC is particularly susceptible to ischemia during and after the operation, the study sought to clarify the consistency of the IHC expression between biopsied and surgically resected HCC tissues.
Methods: HCC patients who had both biopsy and hepatectomy tumor tissues were enrolled. IHC staining was done with rabbit antibodies (Cell Signaling, Beverly, MA, US.) against p-Akt (Ser473) and p-ERK1/2 (Thr202/Tyr204). The staining and its evaluation were performed by a pathologist who was blinded to the identification of the slides. The expression levels of both proteins were graded according to the percentage of positively stained cells in every section, as follows: negative: 0%; 1+: 1-10%; 2+: 10-50%, and 3+: &gt; 50%. Staining results of biopsy and hepatectomy tissues were compared.
Results: Forty-six tissue pairs were enrolled. The results of IHC staining were shown in the table. The expression was significantly decreased in hepatectomy tissues compared to biopsied tissue for both p-Akt and p-ERK (p &lt; 0.001 and p &lt; 0.001, respectively, by paired t test). The correlation of IHC staining results of paired tissues is poor. Spearman correlation coefficients for p-Akt (r = 0.116) and p-ERK (r = 0.112) were low. If using staining results as a continuous variable in analysis, the correlation between paired tissues remained poor, with Pearson correlation coefficients of 0.418 for p-Akt and 0.219 for p-ERK, respectively.
Conclusions: The consistency of p-Akt and p-ERK IHC staining between preoperative biopsy and hepatectomy HCC tissues is poor. This confounding factor should be taken into account in data for biomarkers of HCC. (The study was supported by the grant of NSC 98-3112-B-002-038.)IHC staining results of p-Akt and p-ERKMarkerTissue acquisition01+2+3+p-AktLiver tumor biopsy6.5%6.5%13.0%73.9% Hepatectomy tissue15.2%37.0%32.6%13.0%p-ERKLiver tumor biopsy2.2%10.9%23.9%60.9% Hepatectomy tissue8.7%63.0%17.4%6.5%
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 3759.
Abstract 3765: Prediction of pancreatic cancer growth based on multiple markers
Authors: Aoki-Kinoshita Kiyoko F. , Chen Xi , Ching Wai-Ki , Yokozawa Karin , Shimada Kazuaki , Hiraoka Nobuyoshi , Maeshiro Kensei , Furuta Koh 
Published: February 2011

Abstract
In the clinical laboratory, large amounts of laboratory data are accumulated, which may provide clues to aid in the prediction of various disease states. However, most work has focused on finding a single marker for diagnosis, which oftentimes perform poorly. The reason for this is that combinations of multiple markers are what need to be used for prediction, complicating matters. In the bioinformatics field, support vector machines (SVMs) for classification and feature extraction have gained much popularity due to their ability to handle multi-dimensional data and to pinpoint (combinations of) specific features that are key to the classification problem at hand. Using our preoperative clinical laboratory data based on 254 surgically operated and histologically confirmed pancreatic cancer patients, we attempted to classify the extent of cancer growth by (1) first finding the most pertinent markers, or features, for classification, (2) training the SVM classifier using the selected features, and (3) using the discrimination scores returned by the SVM to draw a line between the classes such that predictions can be made directly from the clinical laboratory data. We tested various classifications, such as between poorly- and well-differentiation of cancer growth, and as a result of (1), we found that previously suspected markers always ranked highly: CA19-9, elastase I, amylase, and fibrinogen. After performing step 2, we were able to establish an equation for each classification using the corresponding features such that new clinical laboratory data can be automatically classified as belonging to one of the trained classes. Thus, by specifying the values of CA19-9, elastase I and amylase for a new patient, for example, if the result of the equation is &gt; 0, we may predict well differentiated cancer whereas a value of &lt; 0 indicates poorly differentiated cancer. Using these equations, we could accurately classify our current data at a rate of almost 90% accuracy. Previous work have shown that SVMs are useful in prediction, but this is the first work that presents a mathematical model that can directly utilize clinical laboratory data for diagnosis, indicating its strong potential as an indicator for cancer growth prediction based on multiple markers.
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 3765.
Abstract 3767: Detection biomarkers for squamous cell bladder carcinoma in a global setting
Authors: Al-Delaimy Wael , Shokeir Ahmed 
Published: February 2011

Abstract
Bladder cancer is the fifth common malignancy in the US, and internationally it is the second most common cause of mortality from genitourinary malignancies after prostate cancer. Current clinical practice and recommendations do not include early screening for prevention. The use of cystoscopy cannot become a routine screening method of early detection due to limitations, including cost, while cytology is specific but not sensitive. Biomarkers that screen for bladder cancer before it becomes invasive are an alternative viable solution if validated and made cost-effective. Studies have mostly looked at translational cell bladder cancer and not squamous cell bladder cancer that is much more common in many parts of Africa, including Egypt and related to Schistomiasis parasitic infection. The aim in this study was to validate the use of three FDA approved biomarkers of early detection of translational baldder cancer on squamous bladder cancer in Egypt. The NMP22, Telomerase, and CD44 test kits were used for urine sample from 60 squamous bladder cancer patients and 60 non-cancer population controls. The cases and the controls were recruited from the Urology and Nephrology Center at Mansora University in Mansora, Egypt. Patients were diagnosed by cytoscopy and cytology. There was a significant difference in mean NMP22, CD44 and Telomerase levels among cases compared to controls. However, when adjusting for age and sex, only NMP22 and Telomerase remained significant. There was no significant difference among bladder cancer patients for presence or absence of a mass or schistomiases infection. CD44 and NMP22 mean levels were higher among patients if they were with stages 3 or 4 of bladder cancer compared to stages 1or 2 but this did not reach statistical significance. NMP22 and Telomerase biomarkers had better specificity and sensitivity than CD44 in predicting bladder cancer as shown by the Receiver Operating Characteristics (ROC) curves. In Conclusion, these biomarkers are satisfactory for detection of squamous cell bladder cancer, especially NMP22 and telomerase, and can become routinely used in the clinical setting in developing countries with high percentage of squamous cell bladder cancer. The next phase of biomarker validation for these assays among high-risk populations is warranted.
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 3767.
Abstract 377: Inhibition of c-Met and VEGFR by XL184 reduces tumor invasiveness and metastasis and prolongs survival of RIP-Tag2 transgenic mice
Authors: Sennino Barbara , Naylor Ryan M. , Tabruyn Sebastien P. , You Weon-Kyoo , Aftab Dana T. , McDonald Donald M. 
Published: February 2011

Abstract
Recent studies have shown that inhibition of VEGF signaling can promote tumor invasiveness and metastasis in some preclinical models. The mechanism underlying the increased aggressiveness is not fully understood but activation of the hepatocyte growth factor/c-Met pathway may be a factor. We addressed this mechanism by determining whether inhibition of VEGFR and c-Met together can reduce tumor growth and invasiveness and improve host survival. Our approach was to compare the effects of a tyrosine kinase inhibitor, XL184 (BMS-907351), which blocks VEGFR and c-Met, with the effects of an antibody that selectively blocks mouse VEGF. After treatment of pancreatic islet cell tumors in 14-week-old RIP-Tag2 mice withanti-mouse VEGF antibody for 3 weeks, the tumors were smaller (tumor area 4.3 ± 0.8 mm2 in antibody group versus 17.3 ± 6.5 mm2 in vehicle group, P &lt; 0.05) but had greater expression of c-Met. Tumors treated with anti-VEGF antibody also had more irregular borders, indicative of invasion of the surrounding acinar pancreas (invasion index 18.9 versus 12.7 in vehicle group, P &lt; 0.05), and more abundant liver metastases (metastases 2.73 ± 1.83 /mm2 versus 0.45 ± 0.12 /mm2 in vehicle group, P &lt; 0.05). By comparison, mice treated with XL184 not only had smaller tumors (tumor area 0.7 ± 0.1 mm2, P &lt; 0.05) than in the other groups but also had less invasive tumors (invasion index 4.5, P &lt; 0.05), and lacked liver metastases. All mice treated with XL184 from 14 weeks of age survived until 20 weeks (n = 6), but none treated with vehicle (n = 14) or anti-VEGF antibody (n = 8) reached that end point. These results show that selective inactivation of VEGF reduces tumor growth but leads to greater invasiveness and metastasis in the RIP-Tag2 model. However, inhibition of VEGFR and c-Met by XL184 not only slows tumor growth but also decreases tumor invasiveness and liver metastasis and prolongs host survival.
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 377.
Abstract 3783: RRIG1 suppress growth and invasion of prostate cancer cell lines through inactivation of Src and RhoA
Authors: Hoque Ashraful , Chen Hongli , Guan Baoxiang , Xu Xiao-chun 
Published: February 2011

Abstract
In our previous studies, we have demonstrated that expression of retinoid receptor-induced gene 1 (RRIG1) was significantly reduced in different human cancers and that restoration of RRIG1 expression suppressed tumor cell growth in vitro and in vivo. In prostate cancer, we have showed that PC3 cells do not express RRIG1 but 22RV1 express high levels of RRIG1 mRNA. In this study, we first analyzed RRIG1 expression in prostate cancer tissue specimens and then transfected RRIG1 cDNA into PC3 cells and RRIG1 antisense cDNA into 22RV1 cells to restore or knockdown RRIG1 expression in these cells, respectively. We found that expression of RRIG1 protein was significantly downregulated in prostate cancer tissues compared to the normal tissues. Moreover, stably RRIG1-transfected prostate cancer cells grew much slower than that of the controls, whereas the antisense RRIG1-transfected 22RV1 cells grew faster than that of the controls. After that, we assessed the ability of migration and invasion of these stable cells using Boyden chamber assay and found that RRIG1 transfection reduced tumor cell migration and invasion in PC3 cells compared to the control transfections. In contrast, the antisense RRIG1 transfection promoted the tumor cell migration and invasion in 22RV1 cells. Molecularly, we found that RRIG1 was binding to Src protein and suppressed Src phosphorylation as well as RhoA activation. Consequently, RRIG1 reduced expression of phosphorylated Erk1/2 and AKT as well as expression of c-Jun, COX-2, and cyclinD1. The results from the current study demonstrated a tumor-suppressive effect of RRIG1 in prostate cancer, suggesting that RRIG1 gene may play a role in suppressing prostate tumorigenesis and progression.
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 3783.
Abstract 3797: Luteolin induces cytotoxicity in lung cancer cells depending on superoxide-mediated MKP-1 degradation and JNK activation
Authors: Bai Lang , Xu Shanling , Wang Xia , Ju Wei , Chen Wenjie , Lin Yong 
Published: February 2011

Abstract
Epidemiological studies have suggested luteolin (3′,4′,5,7-tetrahydroxyflavone) as a potential cancer preventive agent. Recently we found that luteolin selectively kills lung cancer but not immortalized human normal bronchial epithelial cells (HBECs). To elucidate the mechanism of luteolin's cancer cell killing activity, we investigated the cytotoxic cellular signaling pathway in lung cancer cells. The results show that luteolin potently induced both apoptosis and necrosis, which was associated with mitochondrion-dependent superoxide accumulation in lung cancer cells. The c-Jun N-terminal kinase (JNK) was substantially activated in luteolin treated cancer cells and luteolin-induced cytotoxicity was effectively blocked when JNK was inhibited. The reactive oxygen species scavengers BHA and NAC, which effectively block luteolin-induced superoxide accumulation, potently suppressed luteolin-induced JNK activation and cytotoxicity, suggesting that luteolin's lung cancer cell killing requires superoxide-mediated JNK activation. Furthermore, JNK activation was tightly associated with a superoxide-dependent rapid reduction of the JNK inactivating phosphatase MKP-1, which was mainly due to destabilizing MKP-1 protein. These results suggest that inhibiting MKP-1 is the main mechanism for luteolin-induced JNK activation. Thus, luteolin activates a novel cytotoxic pathway consisting of superoxide, MKP-1 and JNK in lung cancer cells. Interestingly, luteolin failed in inducing MKP-1 degradation and JNK activation and cell death in the HBECs, although superoxide induction by luteolin was comparable to that in lung cancer cells. Therefore, luteolin-induced cellular signaling in normal and lung cancer cells diverges at JNK activation. Taken together, our results suggest that activation of the speroxide/MKP1/JNK pathway underlies the main mechanism of luteolin's selective ctyotoxicity in lung cancer cells and manipulation of this pathway could be a useful approach for applying luteolin for lung cancer prevention and therapy.
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 3797.
Abstract 3803: 3,3-Diindolylmethane enhances Taxotere-induced apoptosis in breast cancer cells through FoXM1 downregulation
Authors: Rahman KM , Ahmad Aamir , Ali Shadan , Wang Zhiwei , Sethi Seema , Sakr Wael 
Published: February 2011

Abstract
Emerging evidence suggests that the transcription factor Forkhead Box M1 (FoxM1) is associated with the aggressive human carcinomas, including breast cancer. Since elevated expression of FoxM1 is observed in human breast cancers, FoxM1 has attracted growing attention as a potential target for the prevention or therapeutic intervention in breast cancer. However, no information is currently available regarding how down-regulation of FoxM1 could be achieved by any agents without toxicity, and whether this down-regulation could result in any benefit for patients diagnosed with breast cancer. 3,3′-diindolylmethane is a chemopreventive agent that has shown anti-tumor effects in various tumors. Currently there are no reports documenting the role of DIM in the inhibition of FoXM1, which will sensitize breast cancer cells to conventional therapeutic agents. Using a variety of breast cancer cells, we investigated the effect of DIM alone and in combination with Taxotere. Using multiple approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, gene transfection, flow cytometry, real-time reverse transcription-PCR, Western blotting, migration, invasion, and angiogenesis assays, we found that DIM enhanced Taxotere-induced apoptotic cell death in breast cancer cells. These enhancing effect were related to the down-regulation of FoxM1, as well as the inhibition of cell growth, decrease in cell migration, and invasion of breast cancer cells. We also found that knockdown of FoXM1 expression by small interfering RNA transfection increased DIM-induced cell growth inhibition and apoptosis, whereas overexpression of FoxM1 by cDNA transfection minimized DIM-induced cell growth inhibition and apoptosis in breast cancer cells. Furthermore, combination treatment significantly inhibited tumor growth, and the results were correlated with the down-regulation of FoXM1. From these results, we conclude that inactivation of FoxM1 and its target genes by DIM enhanced the therapeutic efficacy of Taxotere in breast cancer, which could be useful for the treatment and/or prevention of aggressive breast cancer.
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 3803.
Abstract 3804: Transcriptional repression of androgen receptor in human prostate cancer cells by plant flavone apigenin
Authors: Shukla Sanjeev , Gupta Sanjay 
Published: February 2011

Abstract
Accumulating evidence suggest that androgen receptor (AR)-mediated signaling plays an important role in the development and progression of prostate cancer. Although Prostate Cancer Prevention Trial (PCPT) showed controversial results however manipulation of AR signaling pathway reduced the incidence of prostate cancer. Safer agents are needed that can modulate AR signaling pathways with effective suppression of prostate cancer. Plant flavonoids have been shown to possess weak oestrogenic and anti-androgen activity. Apigenin, a naturally occurring plant flavone, has shown promising anticancer activity by modulating several signaling pathways that have relevance to prostate cancer. However, the effect of apigenin on AR signaling has not been fully investigated. Using androgen-responsive human prostate cancer LNCaP and 22Rv1cells, we determine the effect of apigenin on androgen receptor signaling. Exposure of these cells with 5-40μM apigenin suppressed cell proliferation and arrested cells in sub G0-G1 phase of the cell cycle after 5nM dihydrotestosterone (DHT) stimulation. Apigenin inhibited endogenous prostate-specific antigen (PSA) transcription and reduced intracellular and secreted PSA protein levels induced by DHT in these cells. In LNCaP cells apigenin inhibited AR expression in a concentration-dependent manner by restricting its translocation into the nucleus. Co-transfection of PC-3 cells with wild-type AR-GFP-tag plasmid demonstrated that apigenin has ability to inhibit DHT-induced AR translocation into the nucleus. Additionally, receptor binding assays indicated that apigenin is a strong competitive inhibitor of DHT binding to the AR. These observations matched with the results of structural modeling studies exhibiting that apigenin is remarkably similar in conformational geometry and surface charge distribution to synthetic AR antagonist, flutamide, although the atomic compositions of the two substances were quite different. Taken together, our results indicate that apigenin exhibits potent anti-proliferative and anti-androgenic properties and may be developed as useful and safer agent for prevention/therapy of 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 3804.