bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4146: Optical imaging of bladder cancer with cancer-specific molecular contrast agents
Authors: Pan Ying , Liu Jen-Jane , Mach Kathleen E. , Volkmer Jens-Peter , Weissman Irving L. , Liao Joseph C. 
Published: August 2014

Abstract
Introduction and Objectives: Current diagnosis of bladder cancer is by white light cystoscopy, which has suboptimal specificity for differentiating non-papillary cancer from inflammation. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic in vivo imaging of the endoluminal tracts with micron-scale resolution. Real-time analysis of confocal images remains challenging with non-specific contrast agents such as intravesical fluorescein. Tumor imaging specificity may be enhanced by coupling pCLE with fluorescently labeled tumor-specific antibodies or peptides. We report our preliminarily efforts of ex vivo bladder tumor imaging by pCLE using a mouse antibody against a known human tumor-specific surface biomarker and a dodecapeptide that binds human epidermal growth factor receptor (EGFR) as contrast. Studies have shown that both the antibody and peptide bind surface markers abundant in cancer but not present on the superficial layer of normal urothelium.
METHODS: The antibody or peptide was instilled intravesically into a fresh cystectomy specimen (n=4 for antibody; n=1 for peptide). Excess antibody or peptide was drained, and the bladder was opened for pCLE. Imaging was performed of normal-appearing, tumor, and suspicious areas, followed by excision of imaged tissues for histopathology with H&E. Tumor-specific staining of the antibody was further confirmed with anti-mouse IgG.
RESULTS: All bladders had high-grade urothelial carcinoma on pathology. The tumor-specific antibody consistently showed greater fluorescent staining on pCLE in areas of tumor, compared to normal urothelium, in all 4 bladders. A suspicious area was not stained by the antibody and was confirmed to be inflammation by pathology. Immunostaining showed tumor-specific antibody on the most superficial layer of tumor but not on normal urothelium. Similarly, preferential staining of tumor over normal urothelium was also observed when using the EGFR peptide as a contrast agent.
CONCLUSIONS: Both the known tumor-specific antibody and EGFR-specific peptide show specificity for bladder cancer by pCLE ex vivo. Our study shows the feasibility of optical imaging of bladder cancer with pCLE and tumor-specific contrast agents.
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 4146. doi:10.1158/1538-7445.AM2011-4146
Abstract 4152: The detection of circulating tumor cells is a negative prognostic factor in pancreatic cancer
Authors: Srovnal Josef , Benedikova Andrea , Klos Dusan , Lovecek Martin , Havlik Roman , Radova Lenka , Cwiertka Karel , Hajduch Marian 
Published: August 2014

Abstract
Purpose: We tested the hypothesis that the presence of CTC is a negative prognostic factor in patients with pancreatic cancer. Pancreatic cancer is one of the most aggressive malignancies with the poor prognosis. Assessment of the circulating tumor cells (CTC) in patients with this highly malignant disease could prevent burdensome surgery in patients with systemic dissemination.
Patients and methods: This was a prospective study to test for the presence of CTC in systemic blood, portal blood, bone marrow and peritoneal lavage in 90 pancreatic cancer patients at the time of surgery using real-time RT-PCR for carcinoembryonic antigen (CEA), epidermal growth factor receptor 1 (EGFR1) and human telomerase (hTERT). Absolute gene expressions of tested markers were correlated with clinical/pathological characteristics and survival parameters.
Results: Overall, 51 of 90 (56.6%) pancreatic cancer patients died, the overall survival median was 8.8 months. We found a statistically significant association between EGFR and hTERT expression levels in the portal blood and clinical stage. We also showed high expression of EGFR and CEA in the peritoneal lavage of patients with metastatic disease, in contrast to patients without the presence of the metastases.
CTC positive patients measured as hTERT in tumor draining blood and CEA in bone marrow showed significantly poorer overall survival (OS) (p=0.005/ p=0.001). We also found statistically significant shorter OS in patients with EGFR positive peritoneal lavage (p=0.01).
Conclusion: The results of this study demonstrate a high sensitivity and specificity of the real-time RT-PCR method for CTC detection in pancreatic cancer. Detection of CTC seems to be negative prognostic factor for overall survival in pancreatic cancer and can influence the radical surgery decision.
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 4152. doi:10.1158/1538-7445.AM2011-4152
Abstract 4160: Glycoprotein biomarkers for bladder cancer detection identified using LC-MS/MS and label free quantification
Authors: Goodison Steven , Yang Na , Xie Xiaolei , Liu Yashu , Urquidi Virginia , Rosser Charles J. , Lubman David 
Published: August 2014

Abstract
PURPOSE: Cancers of the urinary bladder are the fifth most commonly diagnosed malignancy in the US. Early clinical diagnosis of bladder cancer remains a major challenge and the development of noninvasive methods for detection and surveillance is desirable for both patients and health care providers.
METHODS: In order to identify urinary proteins with potential clinical utility we enriched and profiled the glycoprotein component of urine samples using a dual-lectin affinity chromatography and LC-MS/MS platform.
RESULTS: From a primary sample set obtained from 56 cancer patients and 47 healthy individuals, a total of 265 distinct glycoproteins were identified with high confidence, and changes in glycoprotein abundance between groups were quantified by a label-free spectral counting method. Validation of candidate biomarker disease association was performed on second set of 70 independent samples using an antibody-lectin sandwich microarray and ELISA. Increased levels of urinary alpha-1-antitrypsin (A1AT) glycoprotein were identified and confirmed as being indicative of the presence of bladder cancer (p value &lt; 0.0001).
CONCLUSION: The described strategy can be used to discover biomarkers for disease status in other body fluids. Application of the strategy in this study has provided novel candidate biomarkers for the non-invasive molecular detection of bladder cancer.
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 4160. doi:10.1158/1538-7445.AM2011-4160
Abstract 4168: PI3K/AKT pathway alterations in paired primary and recurrent endometrial carcinoma
Authors: Wethington Stephanie L. , Garg Karuna , Olvera Narciso , Dao Fanny , Bogomolniy Faina , Soslow Robert A. , Levine Douglas A. 
Published: August 2014

Abstract
Objectives: The PI3K/AKT pathway is frequently deregulated in endometrial cancer due to somatic mutations and other molecular mechanisms. New drugs directed toward these pathways are currently in clinical trials. Many patients have available primary tumor specimens for correlative studies or enrollment eligibility. It is unknown if the same genomic alterations found in primary disease are also present in recurrent specimens. We hypothesize the genomic landscapes of primary and recurrent endometrial cancers are similar.
Methods: We identified 18 patients with available paired primary and recurrent endometrial cancer specimens. Histologic diagnoses were confirmed and categorized based on current FIGO criteria. DNA was extracted from microdissected FFPE tissue sections. Mass spectrometry mutation detection was used to assess 40 hot spot mutations in AKT1, KRAS, NRAS, and PIK3CA. Sanger sequencing was used to identify mutations in PTEN. PTEN IHC was performed using validated antibodies.
Results: Specimens included 9 cases with endometrioid histology, 8 with serous histology and 1 with mixed serous-endometrioid histology. Five patients had specimens from 2 separate recurrences. Of the 18 primary tumors, 4 (22%) had PIK3CA mutations, 5 (28%) had PTEN mutations, and 1 (5.5%) had a KRAS mutation. One PIK3CA and two PTEN mutations were each present in a primary tumor but not identified in the paired recurrent specimen. One NRAS mutation was identified in a secondary recurrent specimen but not found in either the paired primary or initial recurrent specimen. One AKT1 mutation was identified in both an initial and secondary recurrent specimen but not found in the corresponding primary specimen. PTEN immunostaining was absent in 9 (50%) primary specimens and in one of these cases PTEN staining found to be present in the recurrence.
Conclusions: As clinical trials increasingly incorporate molecularly targeted agents, mutational and other genomic profiling of tumors will be helpful to identify patients most likely to benefit from these drugs. These data suggest that most recurrent endometrial carcinomas harbor similar genomic alterations in the PI3K/AKT pathway as their primary counterparts. Further studies will be required to expand upon these preliminary findings and determine if repeat biopsy of recurrent disease in clinical trial participants is necessary.
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 4168. doi:10.1158/1538-7445.AM2011-4168
Abstract LB-187: Identification of CIT-0665, a novel inhibitor of LSD1
Authors: Stephens Bret J. , Warner Steven L. , Vankayalapati Hari , Bearss David J. , Sharma Sunil 
Published: August 2014

Abstract
Lysine-specific demethylase 1 (LSD1/AOF2/KDM1A) is a flavin-dependent histone demethylase that catalyzes the posttranslational oxidative demethylation of mono- and dimethylated lysines on histones. Methylation of lysine residues on histones can signal transcriptional activation or repression depending on the specific residue involved. H3K4me2 is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by LSD1 is thought to prevent expression of tumor suppressor genes important in human cancer. In contrast, methylation of H3K9 is a repressive mark and LSD1 activity has been shown to upregulate tumor promoting pathways. Thus, LSD1 is emerging as an important target for the development of specific inhibitors as a new class of antitumor drugs. Currently, only a few existing compounds, such as monoamine oxidase inhibitors, have been shown to act as inhibitors of LSD1. More potent and specific inhibitors of LSD1 are needed to advance LSD1 biology and test for potential efficacy in tumor models. We utilized the 3-D crystal structure of LSD1 to computationally dock more than 10 million virtual compounds into the active site of the protein. From the docking experiments, we physically screened 52 compounds in an LSD1 biochemical assay (resorufin-based assay measuring the amount of hydrogen peroxide generated by LSD1). The compound CIT-0665 was identified as a potent inhibitor of LSD1 enzymatic activity, with an IC50 of 290nM. Additionally, cell lines treated with CIT-0665 show increased levels of H3K4 methylation. A large panel of cancer cell lines was also tested for sensitivity to CIT-0665, using a cell viability assay. We are currently engaged in determining possible mechanisms of sensitivity from the cell line panel and making analogs of CIT-0665 with improved drug-like qualities. In conclusion, CIT-0665 is a novel LSD-1 inhibitor with activity in biochemical and cell-based assays.
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 LB-187. doi:10.1158/1538-7445.AM2011-LB-187
Abstract LB-188: Chk1 suppresses bypass of mitosis and tetraploidization in p53-deficient cells
Authors: Wilsker Deborah F. , Chung Jon H. , Bunz Fred 
Published: August 2014

Abstract
Many checkpoint-deficient cancer cells are unable to maintain a numerically stable chromosome complement. The Chk1 kinase has a well-established role in the DNA damage checkpoint responses and is also essential for viability; however little is known about its role throughout the unperturbed cell cycle. Here, we rigorously examine the role of Chk1 in the maintenance of cell ploidy and mitotic progression. Using recombinant adeno-associated virus-based gene targeting techniques, we disrupted one allele of CHK1 in human cancer cell lines that are proficient or deficient for the tumor suppressor p53. We assessed ploidy by fluorescence in situ hybridization and metaphase chromosome analysis, and examined cell cycle progression by live cell time-lapse fluorescent microscopy, DNA labeling, flow cytometry and biochemical analysis. Loss of one CHK1 allele caused an elevated frequency of mitotic bypass in p53-deficient cells. CHK1-haploinsufficient, p53-deficient cells frequently underwent sequential rounds of DNA synthesis without an intervening mitosis, which caused whole genome endoreduplication and tetraploidization. CHK1 haploinsufficient cells exhibited reduced Cdk1 activity, which has been shown to lead to the bypass of mitosis. This mitotic bypass phenotype could be suppressed by targeted reversion of a p53 mutation or by exogenous Cdk1 expression. Interestingly, the rate of mitotic bypass was independent of upstream signaling by ATR to Chk1 and was not associated with DNA damage. These findings demonstrate a previously unrecognized role for Chk1 in promoting the initiation of mitosis during the cancer cell cycle and thereby maintaining ploidy.
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 LB-188. doi:10.1158/1538-7445.AM2011-LB-188
Abstract LB-19: The Smac mimetic LBW242 induces apoptosis in melanoma in a TLR-3-dependent and TNFR-independent manner
Authors: McHenry Kevin T. , Jacobson Elena , Donovan Jerry , Levine Kymberly , Zhang Jingxin , Fisher David E. , Zawel Leigh , Porter Dale 
Published: August 2014

Abstract
Toll-like Receptor-3 (TLR-3), a pattern recognition receptor family member, has been shown to activate immune system pathways; however, it has also been shown to induce apoptosis in certain cancer cells. Combination of the synthetic TLR-3 ligand, poly I:C, with the Smac mimetic LBW242, an inhibitor of apoptosis protein (IAP) antagonist, has been shown to potently induce apoptosis in melanoma cells which are insensitive to either single agent. To better elucidate the mechanism responsible for this combination induced cell death, we performed a pooled shRNA screen. We identified receptor interacting protein kinase-1 (RIPK1) and as an important component of this process. Constitutive knockdown of RIPK1 prevents the LBW242 and poly I:C combination induced apoptosis. The IAP proteins cIAP1 and cIAP2 have been shown previously to regulate Caspase-8 activation downstream of Tumor Necrosis Factor Receptor-1 (TNFR1). Interestingly, we found that the combination induced apoptosis was independent of TNF signaling. Utilizing both gain of function and loss of function studies, we found that expression of TLR-3 is necessary for the combination induced apoptosis in melanoma cells. Taken together, our data indicate that the combination of the Smac mimetic LBW242 and TLR-3 agonist poly I:C induces a novel type of TLR-3 dependent apoptosis in melanoma cells that is independent of TNFR1.
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 LB-19. doi:10.1158/1538-7445.AM2011-LB-19
Abstract LB-199: SN38-dextran prodrug synthesis and cell delivery in a murine metastatic pancreatic cancer model
Authors: Shrestha Tej B. , Basel Matthew T. , Balivada Sivasai , Seo Gwi Moon , Pyle Marla , Bossmann Stefan H. , Troyer Deryl L. 
Published: August 2014

Abstract
Enzyme activated prodrugs have been investigated and sought after as highly-specific, low side effect treatments, especially for cancer therapy. We synthesized an SN38-dextran prodrug and utilized it in a cell delivery system that can carry both the prodrug and an activating enzyme to the cancer site. For delivery of our prodrug, we engineered Raw264.7 cells (mouse monocyte/macrophage like cells, Mo/Ma) to express intracellular rabbit carboxylesterase (InCE), which cleaves the prodrug to activate SN38. InCE expression was regulated by the TetOn® system, which silences the gene unless a tetracycline, such as doxycycline is present. To test the system, a murine pancreatic cancer model was generated by intraperitoneal (i.p.) injection of Pan02 cells. Engineered Mo/Ma cells were loaded with the SN38-dextran prodrug and were injected i.p. into the mice. Two days following injection, doxycycline was given i.p. to activate the InCE, which in turn activates the prodrug into active SN38. A survival study demonstrated that this system significantly increased survival in a murine pancreatic cancer model, with an average post-diagnosis life expectancy increase of 20%. Thus, for the first time, a prodrug/activating enzyme system self-contained within tumor-homing cells has been demonstrated that can significantly prolong the life of i.p. pancreatic tumor bearing mice.
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 LB-199. doi:10.1158/1538-7445.AM2011-LB-199
Abstract LB-202: Therapeutic efficacy of coencapsulated cisplatin and arsenic trioxide nanobins in murine models of breast cancer
Authors: Ahn Richard W. , Swindell Elden P. , Doan Ninh B. , Ugolkov Andrey , Malin Dmitry , Raja Meera R. , Mazar Andrew P. , Cryns Vincent L. , O'Halloran Thomas V. 
Published: August 2014

Abstract
We have developed a novel strategy to encapsulate a combination of cisplatin and arsenic trioxide as a precipitate inside 100 nm liposomal nanobins, NB(Pt, As). Cisplatin is a widely used chemotherapeutic but has significant dose-limiting toxicity. Arsenic trioxide (ATO) is a potent FDA-approved therapy for acute promyelocytic leukemia; however, ATO has not been effective in clinical trials of solid tumors. Encapsulation in nanoliposomes can improve the anti-cancer efficacy of chemotherapeutic agents by extending serum half-life, increasing tumor drug delivery and attenuating toxicity. We have tested the therapeutic efficacy of NB(Pt, As) in orthotopic xenograft models of triple negative breast cancer using MDA-MB-231 and MDA-MB-435/LvBr1 cancer cell lines. Treatment with either NB(Pt, As) or cisplatin for three weeks inhibited growth of MDA-MB-231 mammary tumors in vivo. However, the NB(Pt, As) did not cause weight loss in treated animals and did not result in abnormal serum chemistries.
NB(Pt, As) was also evaluated for its ability to inhibit lung metastases. Mice inoculated intraductally with highly metastatic MDA-MB-435/LvBr1 cancer cells develop mammary tumors that metastasize and form macroscopic lesions in the lung. Treatment with NB(Pt, As) was initiated when primary tumors reached∼250 mm3. Both NB(Pt, As) and cisplatin inhibited primary tumor growth in this model, whereas only NB(Pt, As) treatment significantly reduced lung metastatic burden.
Our results suggest that nanobin encapsulated cisplatin and ATO is a promising nanoscale therapeutic agent for metastatic breast cancer.
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 LB-202. doi:10.1158/1538-7445.AM2011-LB-202
Abstract LB-206: A novel scaffold that targets the IKK complex
Authors: Bryant Vashti C. , Radhakrishnan Prakash , Hollingsworth Michael A. , Natarajan Amar 
Published: August 2014

Abstract
The IκB kinase (IKK) complex is a central component of the NF-κB pathway. The expression of a number of gene products are controlled and regulated by NF-κB. Dysregulation of the NF-κB pathway proteins has been implicated in a number of cancers including pancreatic cancer. A cell-based luciferase reporter assay was used to screen in house chemical libraries and identify NF-κB inhibitors. This led to the identification of quinoxaline urea (QU) analog as a validated hit. We found that QU inhibits the nuclear translocation of p65 in response to TNF-α stimulation. Our studies also indicate that QU inhibits a constitutively active form of the IKK complex. QU induced growth inhibition and apoptosis in a panel of pancreatic cancer cell lines with low-μM potency. NF-κB is an important player in the invasion and metastases of pancreatic cancer. The in vitro migration and matrigel invasion assay results with QU shows that it inhibits the migratory and invasive ability of pancreatic cancer cell lines. QU has comparable activities in all our assays to known NF-κB inhibitors, parthenolide and curcumin, that are in clinical trials for pancreatic cancer therapy. In summary, we present a novel scaffold that targets the constitutively active IKK complex with the potential to be developed as pancreatic cancer therapeutic.
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 LB-206. doi:10.1158/1538-7445.AM2011-LB-206