bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A6: Cancer-associated fibroblasts (CAF) expressing CD44 high increased the aggressiveness of cancer cells
Authors: Shim Seon-Hui , Hah J. Hun , Sung Myung-Whun 
Published: June 2012

Abstract
Cancer-associated fibroblast (CAF) is considered of one of the most important factors influencing tumor microenvironment. CD44 is known to a marker of head and neck cancer stem cell and is a glycoprotein involved in cell-cell interactions, cell adhesion and migration. Tissues from several head and neck cancer patients were gathered and fibroblasts from tumor tissues and normal tissues away from cancer were isolated. We found CAF overexpressed CD44 when compared to normal part of fibroblast, thus investigated the role of CAF which is overexpressing CD44. Cancer cells which are co-cultured with CAF migrated better than normal fibroblast when wound assay were performed. To test whether this motility of cancer is related to CD44 on CAF, CAF was inhibited by neutralizing antibody of CD44. After treatment with neutralizing antibody, the motility of cancer cells reduced. To confirm that CAF influences tumor cell migration, mixture of CAF and cancer cells were laid on an upper well, then these cells would travel 3D environment which is made by our own idea. Cancer cells which get ability to migrate and can form colonies can survive on the bottom well. When treated neutralizing antibody, cells could neither migrate nor make colonies well than antibody-free mixture. In conclusion, CAF influenced cancer cell migration through the CD44. If CD44 on CAF was blocked, the movement and aggressiveness of cancer cells weakened.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):A6.
Abstract A8: Cdk5 modulates ErbB2/3 phosphorylation and prostate cancer cell growth
Authors: Hsu Fu-Ning , Lin Ho 
Published: June 2012

Abstract
Prostate cancer is an age-related carcinoma and the most commonly diagnosed malignancy in men. We have previously demonstrated a pivotal role for cyclin-dependent kinase (Cdk) 5 activity in modulating the proliferation on thyroid cancer cells. Cdk5 was originally defined as a trophic player in neurons and has been reported to phosphorylate ErbB2/3 and mediate ErbB2/3 activity. ErbB2/3 receptors are mentioned to be important to cancer cell survival. In recent decade, Cdk5 becomes a new target of interests in cancer research. Furthermore, Cdk5 activity is indicated to control cell motility and metastasis of prostate cancer. Initially, our immunohistochemical analysis on prostatic specimen revealed that five out of eight (62.5%) patients expressed relatively higher Cdk5 proteins in clinical tumor tissues than individual normal ones. Next, a Cdk inhibitor roscovitine (Rv, also named Seliciclib or CYC202, a clinical trial drug on non-small cell lung cancer and leukemia) was utilized to inhibit Cdk5 activity in prostate cancer cell line LNCaP. Rv treatment resulted in significant growth inhibition and morphology change of LNCaP cells. The results of in vitro kinase assay also exhibited that the activity of Cdk5 but not Cdk1 was obviously diminished by Rv. Then the association and co-localization between Cdk5 and ErbB2/3 in LNCaP cells were identified and this interaction could be interfered by Rv treatment. In addition, the serine phosphorylation of ErbB2/3 was reduced by inhibition of Cdk5 activity. Moreover, Rv further decreased the phosphorylation of Akt, Erk and STAT3 which were downstream signals of ErbB2/3 in the presence of heregulin (HRG, ligand of ErbB3) treatment. Finally, Rv dramatically blocked the HRG-stimulated growth of LNCaP cells. According to these results, we found that Cdk5 might regulate survival pathways through ErbB2/3 phosphorylation. Therefore, we suggest that Cdk5 may be a potential therapeutic target in prostate or other cancers.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):A8.
Abstract A9: The HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) inhibits vascular endothelial growth factor C-induced lymphangiogenesis
Authors: Cheng Hsuen-Tsen , Hung Wen-Chun 
Published: June 2012

Abstract
The lymphatic system plays an important role in tissue fluid homeostasis, immune surveillance, and fat absorption and also is involved in various pathological situations. Recent studies showed that lymphangiogenesis is not only important for physiological regulations but also associated with the metastatic spread of cancer. The histone deacetylase (HDAC) inhibitor SAHA has been reported to inhibit tumor cell proliferation, induce apoptosis and reduce angiogenesis in different cancer types. In this study, prox1-overexpressing endothelial cell line EA.hy926-Prox1 with the characteristics of lymphatic endothelial is used to evaluate the anti-lymphangiogenic and anti-cancer activity of SAHA. SAHA at low concentrations inhibits growth of EA.hy926-Prox1 endothelial cells via induction of G2/M arrest. Multiple G2/M cell cycle regulators are changed by SAHA. At high concentrations, SAHA causes significant cell death. SAHA at non-cytotoxic concentrations prevents vascular endothelial growth factor C (VEGF-C)-stimulated sprouting and capillary-like structure of EA.hy926-Prox1 cells. In addition, we find that SAHA treatment can inhibit the expression and secretion of VEGF-C in breast cancer cells. Our results provide evidence that SAHA can inhibit lymphagiogenic through (A) regulating the proliferation, apoptosis, sprouting and tube formation in lypmphatic endothelial cells and (B) reducing the expression and secretion of VEGF-C in cancer cells. Thus, SAHA may function as a therapeutic agent for the treatment or prevention of tumor-induced lymphangiogensis.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):A9.
Abstract B10: Genetic profiling reveals cross-contamination and misidentification of six adenoid cystic carcinoma cell lines
Authors: Phuchareon Janyaporn , Otha Yoshihito , Woo Jonathan M. , Eisele David W. , Tetsu Osamu 
Published: June 2012

Abstract
Cell lines established from human tissues are extensively used to study human diseases and other conditions. Lines derived from malignant neoplasms are particularly useful tools for investigating mechanisms of tumor initiation and development. These cells are often used as preclinical models for the disease, as sources for biomarker or drug target identification, and as vessels to screen for efficacy hits and for early toxicity indicators. Because of the increasing importance of cultured cells in cancer research and other biomedical studies, cross-contamination of cell lines is becoming a more frequently encountered problem. It has been reported that approximately 20% of cell lines are incorrectly designated. Here we report that all six salivary gland adenoid cystic carcinoma (ACC) cell lines had been contaminated with other cells. We performed DNA fingerprint analysis on six ACC cell lines using short tandem repeat (STR) examinations. ACC2, ACC3, and ACCM were determined to be cervical cancer cells (HeLa cells), whereas the ACCS cell line was composed of T24 urinary bladder cancer cells. These observations suggest that future studies using ACC cell lines should include cell line authentication to avoid the use of contaminated or nonhuman cells.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B10.
Abstract B11: An empirical evaluation of array normalization for Agilent microRNA expression arrays
Authors: Qin Li-Xuan , Satagopan Jaya , Singer Samuel 
Published: June 2012

Abstract
Introduction: Array normalization is an essential component of array data preprocessing, which removes array effects resulting from the experimental process. Methods for array normalization have been developed in the context of mRNA expression arrays, such as median normalization and quantile normalization. These methods assume few or symmetric differential expression of markers on the array. These assumptions are likely to be appropriate for mRNA expression arrays that consist of tens of thousands of markers with only a small fraction of these generally associated with the disease under study. In contrast, microRNA expression arrays consist of a few hundred markers and a reasonable fraction of them are anticipated to have disease-relevance; further, the numbers of over- and underexpressed microRNAs are not likely to be the same in studies involving tumors. Consequently, the performance of the existing normalization methods need to be reevaluated when applied to microRNA arrays of tumors.
Methods: In this study, we empirically examined sources of variations in microRNA array data using a set of Agilent microRNA arrays in liposarcoma (n=56) and evaluated methods for normalization using Solexa sequence data on a subset of these tumors (n=29) as the gold standard in the following three aspects: (1) correlation of the target-sequence-specific data on each array; (2) selection of significant microRNAs; (3) estimated direction of change for the significant microRNAs.
Results: We found that there is minimum variation between replicate probes for the same target sequence and moderate variation between multiple target sequences for the same microRNA. There is moderately high correlation between Agilent data and Solexa data on the same tumors, with the Pearson correlation coefficient ranging from 0.517 to 0.794. Quantile normalization has slightly improved the correlation with Solexa data, as well as the detection of differentially expressed microRNAs both in terms of statistical significance and the direction of change.
Conclusions: The number of replicate probes for each target sequence ranges from 4 to 16, which is unnecessarily high and can be reduced. Target sequences for the same microRNA need to be analyzed separately. Quantile normalization improves the accuracy of the analysis. Further investigations with other disease types are needed to validate this finding.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B11.
Abstract B13: OncoPredictor: An integrative genomics platform to systematically predict responsive tumor populations from in vitro drug response data
Authors: Rhodes Daniel R. , Daubresse Gary , Wyngaard Peter , Tomilo Mark , Williams Paul , O'Day Christine , Ovechkina Yulia , Warrior Usha , Sadis Seth 
Published: June 2012

Abstract
A key challenge in drug development is identifying clinically relevant genomic biomarkers from preclinical data. Here, we developed OncoPredictor, a cellular screening and bioinformatics platform to (1) evaluate multiple types of genomic biomarkers for association with in vitro drug response and (2) analyze identified biomarkers in clinical tumor populations, thereby suggesting potential drug development strategies. We examined data for 18 targeted, anticancer agents tested across more than 200 cancer cell lines for which detailed genomic data were collected. To support association analysis of drug response and genomic biomarkers, a cell line biomarker catalog was constructed including gene and pathway mutations, copy number aberrations and gene expression changes, in addition to tumor-derived gene expression molecular subtypes. Similarly, to support the rapid translation of in vitro biomarkers to clinical tumor populations, a tumor biomarker catalog was developed, characterizing the frequency of biomarkers across the Oncomine database, which includes more than 40,000 genomic profiles from tumor specimens. Notably, our analysis uncovered several known and novel drug- biomarker-tumor population associations providing a series of cancer treatment hypotheses. For example, within Ras/Raf mutant cell lines, overexpression of a novel biomarker associated with sensitivity to CI-1040, a MEK inhibitor, and identified a sub-population of Ras/Raf mutant colorectal cancer and melanoma that may be more likely to benefit from MEK inhibitors. Similarly, we showed that a growth factor activation network associated with a dramatic response to sunitinib and identified a fraction of glioblastoma and particular types of sarcoma with activation, suggesting that these indications may benefit from a tumor intrinsic response to sunitinib. Finally, for everolimus, an mTOR inhibitor, we found that a gene expression-based molecular subtype of breast cancer were particularly sensitive and demonstrated that the while subtype-positive breast cancers have a good prognosis, 10% of breast cancers that metastasize are subtype-positive, suggesting a defined clinical population that could benefit from mTOR inhibitors. In summary, our platform provides a comprehensive and clinically relevant framework to discover and apply genomic biomarkers of drug response.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B13.
Abstract B15: Genetic variation in DNA repair pathway genes and melanoma risk
Authors: Zhang Mingfeng , Qureshi Abrar , Guo Qun , Han Jiali 
Published: June 2012

Abstract
Reduced DNA repair capacity has been proposed as a predisposing factor for melanoma. We comprehensively evaluated 1465 genetic variants across 60 DNA repair-related pathway genes in relation to melanoma risk in a nested case-control study of 218 melanoma cases and 218 matched controls within the Nurses’ Health Study (NHS). We then genotyped the two variants with the smallest P value in two replication sets: 184 melanoma cases and 184 matched controls in the Health Professionals Follow-Up Study (HPFS); and 183 melanoma cases and 183 matched controls in the NHS. The SNP rs3219125 in the PARP1 gene was significantly associated with melanoma risk in the discovery set (odds ratio (OR) 3.14; 95% confidence interval (CI) 1.70-5.80) and in the HPFS replication set (OR, 1.92; 95%CI, 1.05-3.54), but not in the NHS replication set (OR, 1.07; 95%CI, 0.58-1.97), while in the joint analysis, the OR was 1.89 (95%CI, 1.34-2.68) for this polymorphism. Given that DNA repair protects against UV-induced melanoma, the sun-exposed body sites are more prone to insufficiency in DNA repair capacity. Thus, we further conducted subgroup analysis of this SNP by body sites and found that the increased risk of this variation was more pronounced among patients with lesions in head/neck (OR, 3.19; 95% CI, 1.77-5.73 for head/neck, and OR, 1.54; 95% CI, 1.03-2.30 for other sites, P value for heterogeneity test = 0.036), which further suggested the involvement of this locus in the etiology of melanoma via its influence on DNA repair capacity. In addition, there were significantly fewer head/neck melanoma cases in the NHS replication set (20.4% in the discovery set, 28.1 % in the HPFS replication set, and 9.5% in the NHS replication set, P &lt; 0.001), which may explain the failure of the replication in the NHS replication set. In conclusion, our findings implicate the PARP1 variant in the etiology of melanoma cancer, especially for sites with high sun exposure. Further work is needed to replicate these results and clarify the mechanism by functional studies.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B15.
Abstract B16: Indigeneously synthesized inorganic coordination complex act as apoptotic agent in cancerous cells
Authors: Banerjee Payel , Majumder Paramita , Mazumder Santasree 
Published: June 2012

Abstract
Objective: Metal complexes play an important role in chemotherapy. Arguably the most prominent metal complex in medicine is the anticancer agent cisplatin (cis-diamineplatinum (II) dichloride). Cisplatin and other chemotherapeutic metal complexes also have certain reported side effects and their cost is very high for a country like India. In the present study we aim to evaluate the effect of novel inorganic coordination complexes in comparison to cisplatin in the treatment of cancer of different origin such as lung, cervix, and ovary.
Method: The decrease in cell viability was determined by MTT assay followed by wound healing and DNA hypoploidy assay Apoptosis has been studied by Annexin V-FITC/PI dual staining flow cytometric assay. Following this: (1) chromosomal condensation by DAPI staining, (2) determination of ROS generation by DCFDA staining, and (3) measurement of altered mitochondrial membrane potential with JC1 dyes was performed. Changes in Bcl 2/Bax ratio and release of Cytochrome-C protein by Western blot technique confirm apoptosis.
Results: Our results establish that both cisplatin and the novel inorganic complex can inhibit the proliferation of A549, Hela, and PA 1 cells. The novel inorganic coordination complex in the study shows the IC 50 at 75 µM,150 µM, and 250 µM in Hela, A 549 and PA 1 respectively with respect to cisplatin which shows the IC 50 at 50 µM, 100 µM and 300 µM in Hela, PA 1, and A 549 respectively. After treatment with cisplatin and inorganic cooedination complex, Bax/Bcl-2 ratio was strongly up regulated in Hela cells and moderately elevated in A 549 and PA 1 cells. We demonstrate that a combination of anti proliferative measures such as delay in cell cycle progression, induction of apoptosis and generation of ROS act together to mediate the effects of cisplatin and the novel inorganic complex on cancer cells.
Conclusion: The present study showed that Hela is more sensitive than A 549 and PA1 to cisplatin and the novel inorganic complex. Although the novel inorganic complex is found to be more effective anticancer agent than cisplatin in case of A 549 when compared with the other two cell lines, Hela and PA1. These results have pointed out that cisplatin and the novel inorganic complex might exert chemopreventive effect through ROS generation and induction of apoptogenic signals via mitochondrial death cascade in human lung, cervical and ovarian carcinoma cells. The novel inorganic coordination complex is more effective anticancer agent in lung carcinoma cells when compared to cervical and ovarian cancer cells.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B16.
Abstract B17: PDL192, a humanized antibody to TweakR exhibits potent antitumor activity in pancreatic cancer models
Authors: Hylander Bonnie L. , Choi Donghee , Sho Mien , Chao Debra T. , Starling Gary C. , Culp Patricia A. , Repasky Elizabeth A. 
Published: June 2012

Abstract
Approximately 42,000 new cases of pancreatic cancer were diagnosed in the United States in 2009, and the 5-year survival rate for this disease is exceedingly low (approximately 5%). Given the lack of therapeutic success with current standards of care, new therapies are clearly needed to treat this disease. We have generated PDL192, a humanized IgG1 antibody to TweakR (Fn14, TNFRSF12A, CD266), a cell surface protein and member of the TNF receptor superfamily. PDL192 has been shown to exhibit antitumor activity in xenograft models on a range of solid tumor types via both direct tumor cell growth inhibition and by antibody-dependent cellular cytotoxicity. In this study, we explored the activity of PDL192 in pancreatic cancer models. Approximately 60% of primary pancreatic cancers express TweakR protein at high levels, as determined by immunohistochemistry. PDL192 exhibited potent anti-tumor activity in two cell line xenograft models, Panc1 and MiaPaCa2. PDL192 also exhibited significant anti-tumor activity against 3 of 6 primary tumor xenograft models derived from pancreatic patients. PDL192 was also tested in combination with gemcitabine, the most common treatment for pancreatic cancer patients. In the Panc1 and MiaPaCa2 xenograft models, the combination of PDL192 and gemcitabine exhibited more potent activity than either agent alone. In three of five primary tumor xenograft models tested, combining PDL192 and gemcitabine also resulted in greater anti-tumor activity than either agent alone. In one of the primary tumor models, where neither PDL192 nor gemcitabine alone exhibited significant anti-tumor activity, the combination completely inhibited tumor growth. The activity of PDL192 in multiple pancreatic xenograft models using both cell lines and primary tumors is supportive of the use of PDL192 for the treatment of pancreatic cancer. PDL192 is currently being evaluated in a phase1 safety study in patients with solid tumors.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B17.
Abstract B2: Alterations of p53, PTEN, and EGFR genes in glioblastoma multiforme
Authors: Bankovic Jasna , Milinkovic Vedrana , Rakic Miodrag , Jokovic Milos , Andjelkovic Tijana , Podolski-Renic Ana , Tanic Nikola , Ruzdijic Sabera 
Published: June 2012

Abstract
Glioblastomas are the most frequent and the most aggressive human brain tumors. Glioblastoma multiforme is one of the most intensively investigated human malignancy but the molecular mechanisms associated with the evolution of this type of tumor are still poorly understood. The aim of this study was to investigate alterations in EGFR oncogene and PTEN and p53 tumor supressor genes in 35 glioma specimen and to evaluate their role in glioma pathogenesis. DNA from tumor and blood of 35 patients with glioma was isolated and used to perform analysis of p53 mutational status using single-strand conformational polymorphism analysis (PCR- SSCP) and sequencing, evaluate loss of heterozigosity (LOH) in p53 and PTEN by fragment analysis, and to asseess EGFR gene amplification by differential PCR. Obtained results were further correlated with clinicopathological parameters. Loss of heterozygosity of PTEN was the most frequent alteration present in 62.86% of samples, followed by EGFR amplification detected in 40% of cases, while p53 gene was mutated in 28.57% of cases and inactivated by LOH in 20% of cases. All three genes were altered in 11.43% of samples, while 45.71 % of samples had only one of these three genes aberrant. We also identified 5 novel mutations in p53 that were not associated with brain tumors before. Correlation analysis indicated that p53 alterations were significantly associated with younger age (&lt;50) and lower tumor grade in contrast to PTEN and EGFR. Concomitant PTEN inactivation and EGFR amplification appeared significantly more frequent in higher grade tumors. This suggests that p53 alteration could be an early event in tumor development, while PTEN inactivation and EGFR amplification may lead to tumor progression and therefore indicate a subgroup of patients with more aggressive disease. Further investigations, that are underway, including analysis of other genes involved in glioma pathogenesis, will enable us to gain more detailed insight into the glioma pathogenesis.
Citation Information: Clin Cancer Res 2010;16(14 Suppl):B2.