bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4119: Association of plasma hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 with gefitinib resistance in patients with advanced non-small cell lung cancer
Authors: Han Ji-Youn , Kim Jin Young , Lee Soo-Hyun , Lee Geon Kook , Lee Jin Soo 
Published: August 2014

Abstract
Purpose: It has been suggested that hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 are associated with gefitinib resistance in non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic roles of these proteins in NSCLC patients treated with gefitinib.
Methods: Of 106 patients enrolled in the randomized phase II study of gefitinib, 97 had plasma samples available for ELISA testing. Of these samples, seven and eight, respectively, had HGF and IGFBP-3 values that could not be measured. Therefore, the correlations between clinical outcomes and plasma levels of HGF and IGFBP-3 were evaluated in 90 and 89 patients, respectively.
Results: Plasma HGF levels were significantly higher in older patients, male patients, patients with squamous cell carcinoma, current smokers, and patients with EGFR wild-type tumors. Low HGF levels were significantly associated with higher response rate (RR), and longer progression-free survival (PFS) and overall survival (OS) irrespective of EGFR mutation status. In a multivariate analysis, the presence of EGFR mutations (HR, 0.42; 95% CI, 0.24 to 0.73; P=0.002) and low HGF levels (HR, 0.58; 95% CI, 0.35 to 0.95; P=0.031) were independently predictive of longer PFS, and an ECOG PS of 0 (HR, 2.95; 95% CI, 1.57-5.54; P=0.001) and low HGF levels (HR, 0.40; 95% CI, 0.22-0.72; P=0.002) were independently predictive of longer OS. No statistically significant differences were found for IGFBP-3.
Conclusion: High HGF levels are significantly associated with resistance to gefitinib and can be used as a predictive marker for the differential outcome of gefitinib treatment in NSCLC irrespective of EGFR mutation status.
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 4119. doi:10.1158/1538-7445.AM2011-4119
Abstract 4124: Pre-treatment complement system serum protein levels predict pathological response to neoadjuvant chemoradiotherapy for esophageal cancer
Authors: Maher Stephen G. , McDowell Dermot T. , Murphy Sinead A. , Collins Ben C. , Muldoon Cian , Gallagher William M. , Reynolds John V. 
Published: August 2014

Abstract
Introduction: Esophageal cancer has one of the worst prognosis of all cancers, and its incidence is increasing rapidly in the Western world. The standard of care for patients with esophageal cancer involves neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery. Unfortunately, only ∼30% of esophageal cancer patients respond to neo-CRT. The aim of this study was to analyse the serum proteome early into neo-CRT to reveal biomarkers indicative of response to therapy.
Methods: 31 esophageal cancer patients received a standard neo-CRT regimen. Pathological response to therapy was assessed using the Mandard Tumour Regression Grade system. Serum was collected at pre-treatment, 24 h and 48 h timepoints into treatment. Albumin/IgG-depleted serum samples were analyzed using SELDI-TOF-MS. Protein/peptide expression difference mapping was performed and the data applied to the EPO-KB database. Subsequently, high-scoring candidates were assayed by ELISA. A leave-one-out cross validation (LOOCV) predictive algorithm was employed to assess the ability of candidate biomarkers to correctly predict therapeutic outcome.
Results: 16 patients had a poor response to therapy, while 15 had a good response. On CM10 chips, 9 protein peaks were significantly different between the two treatment response groups, some at baseline, others at 24 h and 48 h into neo-CRT. SELDI spectral peaks m/z_8617.685 and m/z_8928.422 were identified as the complement proteins C4a and C3a, respectively, via the EPO-KB. ELISA revealed significantly higher pre-treatment levels of C4a and C3a in serum from poor versus good responders. Subdivision of the response groups by TRG indicated an inverse correlation between levels of C4a and C3a and pathological response to neo-CRT. In a pre-treatment setting, LOOCV analysis revealed that these two serum proteins could predict patient response to neo-CRT with a sensitivity and specificity of 78.6% and 83.3%, respectively.
Conclusion: In a relatively non-invasive approach, this study has identified that pre-treatment levels of serum C4a and C3a are potential pre-treatment biomarkers predicting response to neo-CRT for esophageal cancer. Additional serum proteins are being validated to further improve the sensitivity and specificity of predicting esophageal patient response to treatment.
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 4124. doi:10.1158/1538-7445.AM2011-4124
Abstract 4126: Optimization of clinical sample collection for detection of c-Met phosphorylation
Authors: Nakagawa Takayuki , Kumar Namita , Kuznetsov Galina 
Published: August 2014

Abstract
The receptor tyrosine kinase c-Met is being investigated as a target for cancer chemotherapy. c-Met and its ligand HGF (hepatocyte growth factor) play important roles in cell growth, survival and migration. Dysregulation of the HGF-c-Met pathway (overexpression, constitutive activation, gene amplification, ligand-dependent activation, mutation or epigenetic mechanisms) can lead to oncogenic changes, and has been described in multiple types of cancer including lung, gastric, and colorectal cancer. For cancer therapies targeting the HGF-c-Met signaling pathway, elevated levels of c-Met expression and increased phosphorylation of c-Met have been explored as both the predictive and PD biomarkers. However, detection of c-Met phosphorylation by IHC in human clinical cancer samples has proven to be extremely challenging.
We have conducted a study aimed at finding a way to detect phosphorylation of c-Met in clinical samples. In the first attempt, we have acquired a set of 30 gastric cancer samples which were fixed in formalin in the presence of phosphatase inhibitors (PhosphoGuardTM fixation kit). While this approach has helped us to improve detection of several other phospho-proteins in tissues, it did not help with the detection of phospho-c-Met. We then hypothesized that this is a very labile phosphorylation which is rapidly lost during the cold ischemia time occurring between the surgical excision of the tissue and its placement in formalin for fixation (which could last 30-60 minutes or longer in the operating room). Studies with xenograft tissues showed that a 15 minute delay in fixation resulted in approximately 50% decrease in c-Met phosphorylation, while a 30 minute delay resulted in almost complete disappearance of phospho-c-Met. We therefore acquired a set of colorectal cancer samples which were placed into formalin within 5 minutes of surgical excision. Using these rapidly fixed samples, we were able to detect strong phosphorylation of c-Met in a small number of samples. The staining pattern for phospho-c-Met correlated with that of phospho-ERK (a downstream signaling molecule in the c-Met pathway) suggesting that the relatively low occurrence of c-Met phosphorylation may reflect the status of activation of this pathway in vivo at a given time point. This work suggests that rapid fixation of human tissues facilitates detection of phospho-c-met and its use as a PD and predictive biomarker in clinical trials.
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 4126. doi:10.1158/1538-7445.AM2011-4126
Abstract 4127: Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with targeted therapies
Authors: Farace Françoise , Cropet Claire , Blanc Ellen , Pérol David , Négrier Sylvie , Escudier Bernard 
Published: August 2014

Abstract
Background: A biomarker allowing to predict the efficacy of targeted therapies would be of great clinical value in patients with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell levels are associated with clinical outcome in mRCC patients undergoing targeted treatments.
Methods: The TORAVA trial was a randomized phase II study aimed to determine the efficacy and safety of temsirolimus and bevacizumab combination (arm A) in comparison to 2 control arms, sunitinib (arm B) or bevacizumab and α-interferon (arm C). Samples were collected at baseline and day 14 for each treatment arm. CEC levels were analysed in 117 patients (pts) using the CellSearch™ (Veridex, Warren, NJ) platform. Bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell levels were measured in 10ml blood samples of 42 pts by four-color flow cytometry after progenitor cell enrichment. Relation between CEC and CD45dimCD34+VEGFR2+ progenitor cell levels and clinico-biological characteristics, response to treatment (determined by RECIST criteria after 2 cycles) and progression free survival (PFS) was examined.
Results: CEC levels were significantly higher in patients without nephrectomy (p&lt;0.001). A trend between the association of high CEC levels and a PS of 2 was observed (p=0.08). CEC and CD45dimCD34+VEGFR2+ progenitor cell levels at both baseline and day 14 were not correlated to response to treatment. No correlation was found between baseline or day 14 CEC values and PFS. However, pre-treatment CD45dimCD34+VEGFR2+ progenitor cell levels were significantly correlated to PFS (p=0.003). Patients with elevated pre-treatment levels of CD45dimCD34+VEGFR2+ progenitor cell had an increased risk of tumor progression.
Conclusion: Our results indicate that pre-treatment CD45dimCD34+VEGFR2+ progenitor cell levels could accurately predict PFS in MRCC patients receiving targeted therapies. The association between CEC and CD45dimCD34+VEGFR2+ progenitor cell levels and overall survival will be presented. These data suggested that measurement of CD45dimCD34+VEGFR2+ progenitor cell levels before targeted therapy in mRCC patients will allow to identify at an early stage patients who will benefit most from treatment.
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 4127. doi:10.1158/1538-7445.AM2011-4127
Abstract 4128: Serum insulin-like growth factor (IGF)-1 levels predict treatment efficacy of anti-angiogenic therapy for patients with advanced hepatocellular carcinoma (HCC)
Authors: Shao Yu-Yun , Hsu Chih-Hung , Huang Chien-Chung , Cheng Ann-Lii 
Published: August 2014

Abstract
Background Patients with liver cirrhosis or HCC were found to have decreased serum IGF-1 levels. Serum IGF-1 levels have been shown to predict the prognosis of patients with various types of cancer. Whether the IGF-1 levels can predict the treatment efficacy of anti-angiogenic therapy for advanced HCC remained unknown.
Methods Advanced HCC patients, enrolled in a phase II study (Hsu et al: J Hepatol 2010) and its extended cohort, were treated with sorafenib plus metronomic oral tegafur/uracil until disease progression. Serum samples were collected before treatment and 4 weeks after the start of treatment. The levels of IGF-1 and IGF-2 were determined by ELISA. The baseline levels and post-treatment changes of these factors were analyzed for their associations with treatment outcomes.
Results Among 68 pts treated with the protocol treatment, 64 were enrolled to this study. Among them, 57 (89%) were male, 49 (72%) were chronically infected with hepatitis B virus, and 40 (63%) had extrahepatic metastasis. All patients had liver reserve graded as Child-Pugh class A. There were 4 partial responder (PR) and 33 patients with stable disease (SD) according to RECIST 1.0. The disease control rate (DCR, defined as PR+SD) was 58%. The median PFS and OS were 3.7 and 7.4 months, respectively. Both IGF-1 and IGF-2 levels significantly decreased after treatment (p &lt; 0.001 and p &lt; 0.001, respectively), but the post-treatment changes were not associated with treatment response or disease control. Patients with higher (≥ median) baseline IGF-1 levels, compared to those with lower levels, had significantly better disease control rates (DCR, 72% vs. 44%, p = 0.023) and longer PFS (median, 5.6 vs. 2.0 months, p = 0.034). OS was also longer in patients with higher baseline IGF-1 levels, but with borderline significance only (median, 8.1 vs. 5.0 months, p = 0.052). In multivariate analysis including all clinicopathologic variables with potential predictive values, high baseline IGF levels remained as an independent predictor for longer PFS (p = 0.008). Baseline IGF-2 levels were not found to be associated with treatment outcomes.
Conclusions High baseline IGF-1 levels can predict better treatment efficacy of anti-angiogenic therapy for patients with advanced HCC. (This study was supported by the grant of NSC 98-3112-B-002-038.)
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 4128. doi:10.1158/1538-7445.AM2011-4128
Abstract 4131: Genetic variant associations with treatment outcome and safety in metastatic colorectal cancer patients treated with sorafenib and bevacizumab (BEV) as salvage therapy
Authors: Lafky Jacqueline M. , Bot Brian M. , Morlan Bruce W. , Grothey Axel 
Published: August 2014

Abstract
Purpose: Polymorphisms in genes involved in the angiogenesis pathway have been investigated as predictive markers for efficacy and tolerability to anti-angiogenesis treatment, such as BEV. This study examines single nucleotide polymorphisms (SNPs) in VEGF, VEGFR2, and HIF-1α for their potential association with outcome and safety in metastatic colorectal cancer (mCRC) patients treated with the combined vertical blockade of VEGF signaling (i.e., sorafenib and BEV) as salvage therapy.
Experimental procedures: Genomic DNA was extracted from peripheral blood for 78/79 evaluable patients in the North Central Cancer Treatment Group (NCCTG) Phase II study, N054C (Grothey, et al., ASCO 2010). TaqMan or direct sequencing was used for genotyping VEGF (rs25648, rs3025039, rs2010963, rs1005230, rs833061, rs699947, rs1570360), VEGFR2 (rs2305948, rs2219471, rs2071559, rs1870377), and HIF-1α (rs11549465, rs11549467) SNPs. Chi-square or Fisher's exact test was used to determine genotype associations with the study's primary endpoint, progression-free rate at 3 months of follow-up, as well as genotype associations with the most common grade 3+ adverse events at least possibly related (AE rels) to treatment (i.e., fatigue, hypertension, skin reaction).
Results summary: The presence of a mutant T allele in the 5’ UTR of VEGF (rs25648; C534T) was associated with fewer successes in progression-free rate at 3 month follow-up (Fisher's exact test, p=0.0187). In addition, the presence of a C allele in the promoter region of VEGFR2 (rs2071559, T-604C) was associated with fewer grade 3+ hypertension AE rels (Fisher's exact test, p=0.0101). However, after correcting for multiple comparisons using the method of Benjamini & Hochberg none of the p-values were significant at a 0.05 level. At the same time, no differences were observed between the genotype subgroups and either progression-free rate at 3 months or the most common grade 3+ AE rels for the remaining SNPs that were analyzed, before or after correction.
Conclusions: This study provides preliminary evidence that mCRC patients with the VEGF C534T (rs25648) variant may not benefit from combined treatment of sorafenib and BEV, whereas patients with the VEGFR2 T-604C (rs2071559) polymorphism may experience fewer grade 3+ AE rels. Further prospective validation of these SNPs and their association with this treatment combination in mCRC is warranted.
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 4131. doi:10.1158/1538-7445.AM2011-4131
Abstract 4138: Five prognostic subgroups differ in expression of Akt pathway genes: Biomarkers for therapy selection
Authors: Joy Anna M. , Smirnov Ivan , Ramesh Archana , Kim Seungchan , Bachoo Robert , Sarkaria Jann , Ram Prahlad , Shapiro William , Mills Gordon , Feuerstein Burt 
Published: August 2014

Abstract
Biomarkers that select patients for therapeutics would benefit clinical trial design and patient care. The Akt pathway is a therapeutic target in Glioblastoma Multiforme (GBM) and an important determinant of patient outcome. However, it is not known whether activity of this pathway varies among GBM tumors. To investigate we used Akt pathway genes from published GBM expression datasets. We detected 5 patterns of Akt pathway gene expression and these Akt subgroups correlated with prognosis. We analyzed networks within subgroups using both gene set enrichment analysis and a novel method that scores relevance based on both expression and local network connectivity (Komurov et al., PLoS Comput Biol. 2010 6:8, 1-10). The results suggest therapeutic targets within the individual subgroups. Furthermore, preliminary analysis indicates that human GBM xenograft models and primary human GBM manifest similar Akt subgroups. We are investigating rodent xenograft models of Akt subgroups to evaluate subgroup-specific drug sensitivity, and will present a method and examples of analysis integrating gene expression data from human GBM xenografts and primary human GBM. We hypothesize that Akt subgroups will help personalize treatment for GBM therapeutics. Supported by Barrow Neurological Foundation, Halle Family Foundation, and NIH 1 K01 NS064952-01A1 (AMJ).
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 4138. doi:10.1158/1538-7445.AM2011-4138
Abstract 4143: Photodynamic detection using 5-aminolevulinic acid (ALA) of prostate cancer cells in the urine obtained following prostate massage
Authors: Anai Satoshi , Nakai Yasushi , Miyake Makito , Kuwada Masaomi , Chihara Yoshitomo , Tanaka Nobumichi , Fujimoto Kiyohide , Hirao Yoshihiko 
Published: August 2014

Abstract
Objectives: We evaluated the feasibility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (ALA) for detecting of prostate cancer (PCa) cells in the urine obtained following prostate massage.
Material and methods: Urine samples were collected from 97 men who had prostate massage (attentive digital rectal examination) before prostate needle biopsy. Urine sediments were exposed to 5-ALA (1mM) for 2 hours and cytospun onto glass slides. Protoporphyrin IX (PPIX), which is the metabolite of 5-ALA in the heme biosynthetic pathway, was observed using the fluorescent microscope (excitation filter 380-420 nm, emission filter 590 nm) as a positive signal of cancer cell. Any fluorescent signal in the samples was evaluated as positive. After histological diagnosis, the result of 5-ALA detection was compared with the histological diagnosis.
Results: Prostate cancer cells were successfully visualized by the PPIX. Of the 65 cases with biopsy-proven prostate cancer, 45 were evaluated as positive by 5-ALA exposure (sensitivity: 75 %). Although 32 cases were diagnosed as no cancer with biopsy, 10 5-ALA positive cases were detected (specificity: 68 %). The positive predictive value of 5-ALA cancer detection was 83 %.
Conclusions: We have successfully demonstrated that PPIX in urine sediments treated with 5-ALA could be detected in the PCa patients. Furthermore, the false positive patients could be diagnosed as PCa in the future re-biopsy. So this cancer detecting system appears to have the useful clinical application.
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 4143. doi:10.1158/1538-7445.AM2011-4143
Abstract 4145: “Real-time” monitoring of oncolytic viral delivery to solid tumors using contrast-enhanced computed tomography
Authors: Penheiter Alan R. , Dingli David , Russell Stephen J. , Bender Claire E. , Carlson Stephanie K. 
Published: August 2014

Abstract
RATIONALE: The inability to deliver viruses homogeneously throughout solid tumors is a universal obstacle encountered in oncolytic virotherapy. The initial intratumoral viral dispersion volume is a critical determinant of virotherapy efficacy, and depends not only on the number of infected cells, but also on the spatial distribution of the infected cells. In this study, we determined the feasibility and usefulness of monitoring the initial intratumoral delivery of oncolytic viruses to solid tumors using contrast-enhanced computed tomography (CT).
EXPERIMENTAL PROCEDURES: Human BxPC-3 pancreatic tumor xenografts were established in nude mice. An engineered oncolytic measles virus expressing the sodium iodide symporter reporter (MV-NIS) was mixed with a 1:10 dilution of Omnipaque-300 contrast material and injected directly into mouse tumors. Mice were imaged with micro-CT immediately pre and post-injection of the virus + Omnipaque solution and on day 3 post-injection with 99mTcO4 micro-SPECT/CT. Tumors were harvested immediately after micro-SPECT/CT imaging for autoradiography and immunistochemistry analysis of radioactivity uptake and viral infection. Linear regression and Spearman correlation analyses were performed to determine the relationship between intratumoral contrast enhancement and subsequent intratumoral viral infection.
RESULTS: This dilution of Omnipaque was found to have no effect on viral infectivity or cell viability in vitro, yet was more than adequate for CT imaging of the virus + Omnipaque injectate distribution following intratumoral injection. Ex vivo autoradiography and immunohistochemistry confirmed a strong correlation between intratumoral CT contrast enhancement, SPECT activity, viral infection, and sodium iodide symporter activity.
CONCLUSIONS: This injection method is translatable to the clinic and should allow optimization of intratumoral injection in humans.
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 4145. doi:10.1158/1538-7445.AM2011-4145