bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1568: Plasma-derived circulating microvesicles can both detect and help monitor breast cancer-related pathologies
Authors: Holterman Daniel A. , Duncan Janet E. , Deng Ta , Smith Shannon E. , Spetzler David B. , Kuslich Christine D. 
Published: June 2012

Abstract
Circulating microvesicles (cMV) are membrane-bound structures that play an important role in several biologic processes, including angiogenesis and immune modulation. cMV levels are known to change in response to certain pathologies, and specific subpopulations of cMV can be isolated using antibodies targeted to membrane proteins specific for the secreting cells. We examined whether the levels of specific cMV subpopulations are altered in patients with a disease, specifically breast cancer. In order to characterize individual cancer-associated microvesicles (MVs), advanced breast cancer MVs were compared with normal control MVs. Circulating microvesicles were isolated from breast cancer patients or noncancer control patients, stained with fluorochrome-conjugated antibodies, and analyzed using flow cytometry. Tumor-specific antibodies were paired with process-specific markers, such as DLL4 and VEGFR2 for angiogenic cMV, CTLA4 and FasL for immunosuppressive cMV, and CD80 or CD83 for immunostimulatory cMV, to identify and characterize cMV subpopulations.
Using this approach, distinct and informative cMV subpopulations were identified and quantified between breast cancer patients and healthy controls. For example, immunosuppressive MVs were elevated in the cancer patients compared with noncancer controls (68% vs 44% of CD45+ cMV coexpressed CTLA4). Additionally, angiogenic MVs were elevated in cancer plasma, with 44% coexpressing DLL4 and CD31 compared with 2% of cMV from noncancer controls.
This study suggests that in addition to aiding diagnosis, monitoring specific subpopulations of cMV may offer important information regarding biologic processes perturbed by breast cancer in an individual patient, without the need for an invasive biopsy or a standard pathology evaluation such as immunohistochemistry, and therefore may also aid in prognosis.
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 1568. doi:10.1158/1538-7445.AM2011-1568
Abstract 1586: Oral administration of HIV-protease inhibitors reduces ovarian tumor growth in vivo
Authors: Vandeven Natalie A. , Tan Lijun , Sorenson Dorothy , Liu J. Rebecca 
Published: June 2012

Abstract
INTRODUCTION: Ritonavir boosted lopinavir (LPV/r) is an FDA approved HIV-protease inhibitor combination that is a well tolerated and preferred treatment for HIV patients. Ritonavir is a potent irreversible inhibitor of cytochrome P450 isoform 3A (CYP3A) which can substantially increase bioavailability of lopinavir in vivo. This combination of lopinavir and ritonavir has been shown to increase the efficacy of reducing viral load in AIDS patients. HIV patients taking antiretroviral protease inhibitors such as LPV/r have a lower incidence of HIV associated malignancies such as non-Hodgkin's lymphoma, cervical cancer and Kaposi's sarcoma, leading to the hypothesis that these drugs have antineoplastic activity. Given the need for novel treatment approaches in ovarian cancer, we are investigating the antineoplastic effects of LPV/r, in vivo. METHODS: A xenograph model of ovarian cancer is used to assess the antineoplastic effect of LPV/r in vivo. Oral doses of LPV/r dissolved in corn oil are administered to mice over the course of 2-3 weeks. Tumor area and mouse weight are monitored. After 2-3 weeks tumors are harvested and analyzed. RESULTS: Preliminary results indicate that LPV/r administered orally in combination with a high fat diet inhibits tumor growth in vivo without inducing weight loss. In contrast, the dose of intraperitoneal cisplatin required to attain a similar antineoplastic effect resulted in significant weight loss and morbidity. CONCLUSIONS: Because protease inhibitors can induce both apoptotic and non-apoptotic ovarian cancer cell death in vitro and in vivo, these drugs may circumvent chemoresistance due to alterations in apoptotic response. Our data suggests that LPV/r may also have clinical application in the treatment of ovarian 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 1586. doi:10.1158/1538-7445.AM2011-1586
Abstract 1595: Use of MDV3100 to establish androgen-receptor antagonist resistant LNCaP cells for modelling castrate-resistant progression
Authors: Kuruma Hidetoshi , Matsumoto Hiroaki , Zoubeidi Amina , Thomas Christian , Lamoureux Francois , Gleave Martin 
Published: June 2012

Abstract
Background. The androgen receptor (AR) plays a critical role in the development and progression of prostate cancer. Even in castrate resistant prostate cancer (CRPC), the AR is active and drives progression. MDV3100 is a novel AR antagonist with demonstrated anti-tumour activity in preclinical models and patients with CRPC. To define its anti-cancer effects and features of its recurrent/resistant tumour, we assessed dose-dependent activity of MDV3100 in vivo, and set out to establish MDV3100 resistant cell lines and tumors to characterize its resistant phenotype.
Methods. Androgen sensitive human prostate cancer LNCaP cells were inoculated into male athymic nude mice, and when tumour volume reached 150mm3 and serum PSA was 50ng/ml, mice were castrated. When serum PSA levels returned to pre-castrate level, mice were randomly divided into 4 groups of 1, 10 and 50mg/kg of MDV3100 and vehicle treatment groups. Tumour volume and serum PSA were followed weekly. MDV3100 recurrent tumours were harvested and re-cultured in vitro in the presence of MDV3100, or re-implanted into castrated male nude mice treated daily with 10mg/kg of MDV3100. Established cell lines were characterized for response of androgen and MDV3100, and AR and prostate specific antigen (PSA) expressions in vitro.
Results. Serum PSA declined -60.8% at 2 weeks and -88.0% at 5 weeks from baseline in 10 and 50mg/kg of MDV3100, respectively. Vehicle and 1mg/kg of MDV3100 did not decrease serum PSA levels. Time to PSA progression from baseline was 6 and 12 weeks at 10 and 50mg/kg MDV3100, respectively. While high doses (50mg/kg) of MDV3100 resulted in the most anti-tumour effect, there were no complete responses and 90% of tumours eventually recurred within 10 weeks’ of treatment. Fifteen cell-lines derived from 7 animals in the high dose group and 3 cell-lines from the animal allografts have been generated to date. Eleven of 12 cell lines showed resistance against 10uM of MDV3100, as proliferation rates were suppressed by a mean of 19% (range, 64.4-98.9%) compared to 50.7% in parental LNCaP cells. Eleven of 12 lines expressed AR while two were PSA negative.
Conclusions. While dose-dependent anti-tumour effects of MDV3100 was seen in castrate-resistant LNCaP tumors in vivo, all tumor eventually progressed. Generated MDV3100 resistant cell lines and xenografts were characterized as AR(+)/PSA(+), AR(+)/PSA(−), or AR(−)/PSA(−) and may be useful for modelling resistant phenotypes of MDV3100 in patients. Further characterization 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 1595. doi:10.1158/1538-7445.AM2011-1595
Abstract 1596: Human choriocarcinomas: Placental growth factor-dependent preclinical tumor models
Authors: Bagley Rebecca G. , Ren Yi , Kurtzberg Leslie , Weber William , Bangari Dinesh , Teicher Beverly A. 
Published: June 2012

Abstract
Choriocarcinomas are an aggressive form of cancer that develops in the uterus from tissue that would normally become the placenta. Choriocarcinomas are a trophoblastic gestational disease and the tumors are highly angiogenic. Human placental growth factor (hPlGF) is an angiogenic growth factor that promotes the growth of blood vessels in the placenta. hPlGF levels can be higher under pathological conditions such as cancer. Some human tumor specimens have higher PlGF levels than normal tissue, thus hPlGF is a target for anti-angiogenic therapy. The human choriocarcinoma cell lines BeWo, JAr, and JEG-3 were evaluated as preclinical models of hPlGF overexpression. The levels of hVEGF-A and hPlGF secreted by the choriocarcinomas and 11 human and mouse cancer cell lines in culture were measured by ELISA. The choriocarcinomas secreted higher levels of hPlGF and lower levels of hVEGF-A than 10/11 other cancer cell lines. The hPlGF serum levels in mice bearing subcutaneous choriocarcinoma tumors correlated with tumor volume and reached &gt;2,000 pg/ml. By comparison, no hPlGF was detected in the serum of mice bearing H460 non-small lung carcinoma, HT29 colon carcinoma or MOLM-13 acute myeloid leukemia xenograft tumors. Although choriocarcinoma cells secreted both hPlGF and hVEGF-A in culture, serum levels of hVEGF-A in mice bearing choriocarcinoma xenografts were undetectable or &lt;50 pg/ml at the time points serum was collected indicating that angiogenic factor secretion by the cells in culture was not the same in vivo. JEG-3 tumors grew faster than JAr tumors following the subcutaneous implantantion of 1×106 cells into nude mice. BeWo tumors grew the slowest and had the highest serum PlGF levels. Immunohistochemical methods confirmed expression of hPlGF in the choriocarcinoma xenografts. Studies involving double immunofluorescence on the xenograft tumors are ongoing to investigate endothelial cell and pericyte interactions and stromal involvement in the tumors. sFLT01, a novel fusion protein that neutralizes PlGF and VEGF-A, was added to choriocarcinoma cells in culture and administered to mice bearing choriocarcinoma xenografts in efficacy studies. Exposure of JAr and JEG-3 cells in culture to sFLT01 resulted in a phenotypic change whereby the cells produced less hPlGF and no significant hVEGF-A. In vivo, sFLT01 (25 mg/kg, IP injection, 2x per week) slowed tumor growth in JAr and JEG-3 tumors and increased median survival by 5-30 days compared to vehicle controls. These results indicate that human choriocarcinoma xenograft models are a valuable research tool for evaluating anti-angiogenic agents that target hPlGF.
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 1596. doi:10.1158/1538-7445.AM2011-1596
Abstract 1604: Development of breast cancer patient-derived xenograft models as preclinical tool for drug discovery
Authors: Rymer Isha C. , Wang Jinwei , Zhu Zhou , Schwab Richard , Wallace Anne M. , Blair Sarah L. , Greenberg Norman , Yang Wei J. 
Published: June 2012

Abstract
Based on gene expression profile and hormone receptor status breast cancer is usually classified into the following subtypes, luminal A, luminal B, Her2 overexpressed, basal, normal-like, and the newly identified subtype, claudin-low. For a long time sub-cutaneous and orthotopic xenograft of established human cancer cell lines have served as the primary in vivo models for drug evaluation preclinically, however their prognostic value to clinical trials has not been to our satisfaction. In an effort to overcome the limitations of traditionally used cell line models and to develop preclinical models that better represent the diversity of human breast cancer, we generated a series of human -in-mouse orthotopic xenograft models using primary tumor specimens from patients. These models are characterized in depth, including tumor histology, genomics, gene expression profiles, and chemosensitivities to standard of care compounds. They will serve as great tools to breast cancer research and discovery.
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 1604. doi:10.1158/1538-7445.AM2011-1604
Abstract 162: Profiling of microRNA in oral cancer cells identifying miR-10b functions in oncogenesis and up-regulates in plasma of oral cancer patients
Authors: Lu Ya-Ching , Cheng Ann-Joy 
Published: June 2012

Abstract
Oral cancer is the 6th leading cancer, and is still increasing with years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society. MicorRNAs (miRNAs) are endogenous, non-coding small RNA, which consist of 21-23 nucleotides. They serve widespread functions as regulatory molecules in post-transcriptional gene silencing for the regulation of cellular bio-functions. And the dysregulation of miRNAs has been implicated in malignancy. Agilent system was used to perform miRNA profiling in 6 cancer cell lines and 5 lines of normal keratinocytes for identification of differently expressed miRNAs. There were 23 miRNAs selected as candidates which were shown more than 2-fold change with the FDR&lt;0.1. Among these miRNAs, 19 of them were elevated and 4 were decreased in oral cancer cell lines. miR-10b was validated by qPCR analysis showed significantly up-regulated in cancer cells. Furthermore, the biological function of miR-10b was investigated after alteration of miR-10b expression. Reduction of miR-10b by antisense oligonucleotide further resulted in retard of cell migratory and invasive ability, however, no significant alterations on cell growth or chemo/radio-sensitivity. In analyzing miR-10b expression in 24 normal and 29 plasma samples from oral cancer patients, miR-10b was up-regulated 3.3 fold in the cancer patients (P&lt;0.0001). Taken together, miR-10b plays a role in the carcinogenesis through promoting cancer cell migratory and invasive function, and plasma miR-10b may serve as a biomarker for oral cancer patients.
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 162. doi:10.1158/1538-7445.AM2011-162
Abstract 1622: Inhibition of the acetyltransferase p300 as a novel pro-apoptotic and anti-invasion approach for treatment of prostate cancer
Authors: Santer Frédéric R. , Höschele Philipp P.S. , Oh Su Jung , Erb Holger , Bouchal Jan , Cavarretta Ilaria T. , Meyers David J. , Cole Philip A. , Culig Zoran 
Published: June 2012

Abstract
Inhibitors of histone deacetylases have been approved for clinical application in cancer treatment. On the other hand, histone acetyltransferase inhibitors have not been investigated for their potential use in cancer therapy. In prostate cancer the histone acetyltransferases and coactivators p300 and CBP are upregulated and induce transcription of androgen-receptor responsive genes, even in the absence or in the presence of low levels of androgen receptor. To discover a potential anti-cancer effect of p300/CBP inhibition we used two different approaches: i) downregulation of p300 and CBP by specific siRNA and ii) chemical inhibition of the acetyltransferase activity by a newly developed small molecule. Knockdown of p300 by specific siRNA, but surprisingly not of CBP led to an increase of caspase-dependent apoptosis involving both extrinsic and intrinsic cell death pathways in androgen-dependent and castration-resistant prostate cancer cells. Induction of apoptosis was mediated by several pathways including inhibition of androgen-receptor responsive genes and decrease of expression levels of the NF-κB subunit p65 due to a higher turnover of the protein. Furthermore, cell invasion was decreased upon p300, but not CBP depletion and was accompanied by a lower MMP-9 transcription. Thus, p300 and CBP have differential roles in the processes of survival and invasion of prostate cancer cells. Induction of apoptosis in prostate cancer cells was confirmed by the use of the cell permeable small molecule inhibitor of p300/CBP′s acetyltransferase domain. Taken together, those results suggest that p300 inhibition is a promising approach for the development of new anti-cancer therapies.
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 1622. doi:10.1158/1538-7445.AM2011-1622
Abstract 1630: The PKC inhibitor Sotrastaurin selectively inhibits the growth of CD79 mutant diffuse-large B-cell lymphoma
Authors: Naylor Tara , Enns Andreas , Warmuth Markus , Lenz Georg , Stegmeier Frank P. 
Published: June 2012

Abstract
The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by constitutive activation of the oncogenic NF-κB pathway and is associated with poor prognosis. Recent studies demonstrated dependence on NF-κB pathway activation and identified genetic lesions in NF-κB pathway regulators, including CARD11/CARMA1, A20/TNFAIP3, and CD79A/B. In this study, we evaluated the therapeutic potential of the selective PKC inhibitor sotrastaurin (STN) in preclinical models of DLBCL. We found that a significant fraction of ABC DLBCL cell lines exhibited strong sensitivity to sotrastaurin and detected that responsiveness can be predicted based on the molecular nature of NF-κB pathway lesions. While mutations in CD79A/B correlate with sensitivity to PKC inhibitors, mutations in CARD11 render ABC DLBCL cell lines insensitive to PKC inhibitors. The growth inhibitory effect of PKC inhibitors correlates with NF-κB pathway inhibition and is mediated by the induction of a G1 cell cycle arrest and/or apoptosis. Collectively, our study provides a strong rationale for the clinical evaluation of sotrastaurin in ABC DLBCL patients that harbor CD79 mutations, and furthermore illustrates the necessity to stratify DLBCL patients according to their genetic abnormalities.
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 1630. doi:10.1158/1538-7445.AM2011-1630
Abstract 1632: Anti-β1 integrin antibody inhibits osteosarcoma lung seeding and metastasis
Authors: Kimura Hiroaki , Tome Yasunori , Grzesiak John , Momiyama Masashi , Hayashi Katsuhiro , Bouvet Michael , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: June 2012

Abstract
The efficacy of anti β1 integrin monoclonal antibody (clone AIIB2) to inhibit lung seeding and colony formation of human osteosarcoma cells was imaged in real time. To visualize cancer cell seeding and metastasis in the lung, human osteosarcoma cells were used in which green fluorescent protein (GFP) is expressed in the nucleus and RFP is expressed in the cytoplasm. 143B cells were preincubated with AIIB2 or control antibody, and then injected into the nude mice via tail vein. Twenty four hours later, the lungs were fluorescently-imaged in live mice with the lung exposed. 143B cells which arrested in the lung were counted. Two weeks after the first observation, the animals were sacrificed and the lungs were resected and fluorescently imaged to quantitate resulting lung metastatic colonies. AIIB2 significantly inhibited osteosarcoma cells seeding and colony formation in the lung. This result indicates that β1 integrin plays an important role for osteosarcoma cell adhesion to lung. To evaluate efficacy of the AIIB2 antibody on primary tumor growth and spontaneous metastases, 143B osteosarcoma cells were orthotopically transplanted in the tibia. Two weeks later, mice were treated with either 40 µg or 200 µg AIIB2, or control antibody biweekly. After three weeks treatment, primary tumors and lung metastases were evaluated. Neither 40 µg nor 200 µg of AIIB2 significantly inhibited primary tumor growth. In contrast, both doses of AIIB2 significantly inhibited spontaneous lung metastasis. AIIB2 appears to be a specific anti-metastatic agent since it inhibited lung metastasis while not inhibiting primary tumor growth. This is consistent with AIIB2 inhibition of adhesion of 143B cells to the lung. These results suggest that anti-β1 integrin antibody treatment has clinical potential as an anti-metastatic agent.
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 1632. doi:10.1158/1538-7445.AM2011-1632
Abstract 1633: C-terminal binding proteins are novel drug targets
Authors: Straza Michael W. , Kovi Ramesh C. , Paliwal Seema , Rajeshkumar Barur , Hilbert Brendan , Doughty Tyler , Parker Daniel , Royer William , Whalen Giles F. , Lyle Stephen , Schiffer Celia A. , Grossman Steven R. 
Published: June 2012

Abstract
The CtBP transcriptional corepressors have been identified as proto-oncogenes. CtBP represses pro-apoptotic genes and promotes cancer cell migration and invasion in a redox sensitive manner through a regulatory dehydrogenase domain. The CtBP dehydrogenase substrate 4-methylthio-2-oxobutyric acid (MTOB) can act as a CtBP inhibitor at high concentrations, and induces apoptosis in the human colorectal cancer cell line HCT116. MTOB induced apoptosis is dependent upon expression of the BH3 only protein BIK, a previously established CtBP target. Treatment of both native and transformed Mouse Embryonic Fibroblasts revealed a wide therapeutic index for CtBP inhibition. In human colon cancer cell peritoneal xenografts, MTOB treatment reduced tumor growth and induced apoptosis in vivo without notable toxicity. To verify the potential utility of CtBP as a therapeutic target in human cancer, the expression of CtBP and its negative regulator ARF was studied in a series of resected human colon adenocarcinomas. CtBP and ARF levels were inversely-correlated, with elevated CtBP levels (compared with adjacent normal tissue) observed in greater than 60% of specimens, with ARF absent in nearly all specimens exhibiting elevated CtBP levels. Thus, CtBP is a viable therapeutic target in human cancer. In order to identify novel CtBP inhibitors, a simple dehydrogenase assay was developed that utilizes the spectrophotometric measurement of enzymatic conversion of NADH to NAD+ by the CtBP dehydrogenase activity. This assay successfully detects MTOB substrate and inhibitor activity, as well as inhibition of CtBP activity by the related compound 4-methylthio-2-hydroxybutyric acid (MTHB). This assay will be adapted for high throughput screening of small molecule libraries for novel CtBP inhibitors that can be further characterized in pre-clinical models.
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 1633. doi:10.1158/1538-7445.AM2011-1633