bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5553: Real-time imaging of αv integrin-GFP expression in osteosarcoma cells trafficking in blood vessels of nude mice
Authors: Tome Yasunori , Sugimoto Naotoshi , Yano Shuya , Momiyama Masashi , Maehara Hiroki , Yamamoto Norio , Tsuchiya Hiroyuki , Tomita Katsuro , Kanaya Fuminori , Bouvet Michael , Hoffman Robert M. 
Published: August 2012

Abstract
We report here real-time imaging of αv integrin-GFP expression during osteosarcoma cell trafficking in blood vessels in nude mice. 143B osteosarcoma cells were transfected with an αv integrin-GFP vector. Confocal microscopy demonstrated that αv integrin immunofluorescent staining colocalized with αv integrin-GFP. Osteosarcoma 143B cells expressing αv integrin-GFP (1×106) were injected in the epigastric cranialis vein. Subsequently, round osteosarcoma cells diffusely expressing αv integrin-GFP were observed in larger veins. In contrast, punctuated αv integrin-GFP was imaged in stretched cells attached to narrow vessel walls. Osteosarcoma cells, arrested in venous valves, were observed to strongly express αv integrin-GFP. αv integrin-GFP allows the imaging of αv integrin expression during cancer cell trafficking and arrest in blood vessels which will enable the further understanding of its role in this process.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5553. doi:1538-7445.AM2012-5553
Abstract 5565: Circulating tumor cells in the peripheral blood and cerebrospinal fluid of patients with central nervous system metastases
Authors: Allen Joshua E. , Patel Akshal S. , Dicker David T. , Sheehan Jonas M. , Glantz Michael J. , El-Deiry Wafik S. 
Published: August 2012

Abstract
The enumeration of circulating tumor cells in peripheral blood is a validated method of monitoring disease status in patients with epithelial malignancies involving the breast, colon, prostate, or lung. As cancer therapies improve and aim to decrease metastatic burden, the central nervous system (CNS) is emerging as an important sanctuary site for metastasis. Current surveillance and clinical markers of metastatic disease progression involving the CNS are lacking adequate sensitivity, reproducibility, and specificity. One of these clinical markers is cerebrospinal fluid (CSF) cytology, which lacks clarity, is insensitive, requires high sample volumes and is subject to interpretation bias by the pathologist. To overcome these limitations, we previously adapted the Cellsearch system (Veridex) to isolate and enumerate tumor cells in the CSF of breast or non-small cell lung cancer patients with CNS metastases. We recently reported that the number of cells in the CSF directly correlated with the subject's clinical condition and Karnofsky performance status (KPS) in metastatic breast cancer. Furthermore, imaging of the neuroaxis in these patients revealed disease presence, however, was not indicative of disease burden. A sharp decline in the number of CSF tumor cells (CSFTCs) was universally noted after the onset and maintenance of such ventricular intrathecal chemotherapy. We have continued to follow these patients and have expanded our patient population to include non-small cell lung cancer. This includes a patient that we have followed from a baseline CSFTC count of &gt;10,000 to zero over the course of intrathecal treatment, which as been accompanied by drastically reduced disease by and complete resolution of clinical symptoms. We have also begun to perform concomitant CTC enumeration from peripheral blood in conjunction with CSFTC analysis. Interestingly, while there appears to be no strong correlation between the two subpopulations, tumor cells seemed to be compartmentalized to either the blood or the CSF. Together, the current data indicates that CSFTCs may serve as viable markers for diagnosis and prognostication in the setting of CNS metastases. This novel method of isolating CSFTCs provides a semi-automated platform that greatly increases sensitivity, accuracy and reliability over the standard CSF cytology. Furthermore, this platform enables studies to elucidate the significance and biology of this unique subpopulation of tumor cells, including its relationship with CTCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5565. doi:1538-7445.AM2012-5565
Abstract 5577: HER2 cytoplasmic staining and penile cancer
Authors: Silva Alice M. , Cunha Isabela W. , Guimarães Gustavo C. , Cubilla Antonio , Lopes Ademar , Soarea Fernando A. 
Published: August 2012

Abstract
BACKGROUND: Although rare in developed regions, penile carcinoma is a serious concern for undeveloped countries such as Brazil, where it can represent up to 10% of all malignancies. HER2 is a well-known growth factor membrane receptor that has its expression level usually associated with aggressive disease. Recently, some studies have shown that soluble fractions of HER2 intracellular domain are found in tumors cytoplasm and they still activate intracellular pathways related to cell proliferation and survival. MATERIAL AND METHODS: Immunohistochemistry against HER2 was carried out in 195 penile carcinoma samples selected from the files of AC Camargo Hospital, Brazil, using the monoclonal CB11 antibody (Novocastra™), which recognizes specifically HER2 intracellular domain. Cases were classified as positive or negative according to membrane and to cytoplasmic staining. All statistical analyses were performed by the SPSS for Windows 18.0, SPSS Inc. Comparison between category variables was performed by the Pearson chi-square test or the Fisher's exact test. Survival rates were calculated using the Kaplan-Meier method and the curves were compared by means of the log-rank test. In all statistical tests, the alpha error was set at 5%. RESULTS: None of the cases showed membrane staining for HER2. However, a clear and strong cytoplasm staining was observed in 28 cases (14,9%), as shown in figure 1. The staining was limited to the tumor cells and does not represent background or artifact. Univariate analyses showed that overexpression is associated with higher histologic grade (p &lt;0,001) and lower overall survival (p=0,007). Multivariate analyses showed that HER2 in the cytoplasm is an independent risk factor for death (RR=2,966; IC 95% [1,6-5,2]; p &lt;0,001). CONCLUSIONS: Corroborating with recent findings that cytoplasmic fragments of HER2 can be active kinases, the present study suggests that the presence of HER2 in tumor cytoplasm is a prognostic marker in penile carcinoma. We have also demonstrated that, although no membrane staining was seen, presence of HER2 in cytoplasm is an independent risk factor for death in this neoplasm.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5577. doi:1538-7445.AM2012-5577
Abstract 5591: A phase I study of bavituximab and sorafenib in patients with advanced hepatocellular carcinoma (HCC)
Authors: Yopp Adam , Arriega Yull , Singal Amit , Mansour John , Balch Glen , Thorpe Phillip 
Published: August 2012

Abstract
Background: HCC is the fastest growing cause of cancer-related deaths in the US, with the majority of patients presenting with advanced stage disease. Despite sorafenib being the only systemic therapy with proven efficacy in advanced HCC, the median survival for these patients is still less than one year. Sorafenib, in pre-clinical HCC models, upregulates phosphatidylserine (PS) exposure on tumor vascular endothelium. The phosphatidylserine (PS)-targeting antibody, bavituximab, given in combination with sorafenib has greater efficacy in pre-clinical HCC models than either therapy alone. Bavituximab acts by directing immune cells to destroy the PS-expressing tumor vasculature, and by reactivating tumor immunity.The aim of our study was to evaluate the maximum tolerated dose (MTD) of bavituximab in combination with 400 mg bid of sorafenib in patients with advanced HCC. Methods: In this single institution, phase I study (NCT01264705), sorafenib-naive adult patients with measurable, advanced HCC, ECOG PS ≤ 2, and Child-Pugh (CP) class A cirrhosis received escalating doses of bavituximab weekly (0.3, 1.0, and 3.0 mg/kg) and sorafenib 400 mg bid for 28 days. Results: Median age of patients was 61(range 43-76) years and seven patients were male. Five patients had CP A5 and 4 patients had CP A6 cirrhosis. The majority of patients had underlying HCV (7/9), one patient had HBV and one patient had NASH. Five patients (4 TACE, 1 resection) received prior treatment. Four patients had metastatic disease at initiation of treatment. No dose limiting toxicities were seen at any dose level. No grade 3/4 treatment-related events in the first 28 days were noted. Common toxicities at all grades were related to sorafenib and included hand-foot syndrome (33% grade I, 22% grade II), fatigue (33% grade I) and anorexia (22% grade I). Conclusions: Bavituximab and sorafenib can be given safely in patients with advanced HCC at 3.0 mg/kg weekly and 400 mg bid, respectively. Hand-foot syndrome, fatigue and anorexia were the most common adverse events and are consistent with known adverse events with sorafenib therapy. These doses are currently being evaluated in an ongoing phase II study in this population.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5591. doi:1538-7445.AM2012-5591
Abstract 5618: Tumor suppressor genes? The status of genes PAX 5&6 in primary and secondary gliomas and glioblastoma multiforme tumors
Authors: Newman Mary B. , Wallace David , Mitchell Brian , Byrne Richard W. 
Published: August 2012

Abstract
Background: Gliomas are the most common brain tumors, and glioblastoma multiforme (GBM) tumors have the poorest prognosis, and due to their molecular heterogeneity, these tumors remain incurable and highly resistant to treatments, in most cases. The PAX (paired box) family of genes is comprised of are nine members that are subdivided based on the products of their protein domain structures. PAX5 and PAX6 are developmental genes that are vital during embryonic stages of development, and their transcription factors have supportive, if not, key functions in tumorigenesis. Interestingly, gene PAX6 has been reported to be over and under expressed in high grade gliomas, GBMs, and glioma cell lines. However, these results could be an effect of upstream or downstream manipulation of other transcription factor(s), the origin of the tissue (PAX6 expression is restricted to the forebrain, optic cup, hindbrain, and spinal cord, lens placode, and nasal epithelium), and the epigenetic regulation of some other gene. In addition, there are no reported mutations in either gene PAX5 or PAX6 in the cells from GBMs. Therefore, confusion exists as to role these genes have in tumorigenesis, and whether either gene has the properties or characteristics of a tumor suppressor gene. Study Objective: The overall study objective was to determine if either PAX5 or PAX6 are tumor suppressor genes, and can be silenced or over-expressed to inhibit the progression of cultured human adult primary glioma tissue samples, by employing small interfering RNA (siRNA) methodology. Methods: Primary cell cultures were incubated in reduced serum conditions for at least 1 month prior to transfections and cells were passed every 7 to 10 days or when flask was 90% confluent. To investigate and measure true inhibition of cell proliferation or progression of the cells, several techniques were used, such as, real-time quantitative reverse transcription PCR, enzyme-linked immunosorbent assays, and immunohistochemistry. Results: The high grade (IV) primary glioma tissue samples and their respective cell cultures showed relatively high expression levels for the gene PAX6 and lower levels of expression for gene PAX5 when compared to GAPDH gene and standard controls. Our initial transfections for knocking down of PAX6 using siRNA (TriFECTA, IDT) showed 90% of control samples were transfected, and our primary cells were knockdown by 82%, 70%, and 65% for each of PAX6 isoforms (N000280.21.1-S, 2-S, and 3-S) respectively. We are currently analyzing the rest of the PAX6 data and all of the PAX5 data.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5618. doi:1538-7445.AM2012-5618
Abstract 5630: Nanotherapeutic silencing of HuR: Targeting a tumor-promoting response in ovarian cancer
Authors: Sawicki Janet A. , Huang Yu-Hung , Yeo Charles J. , Gogoi Radhika P. , Love Kevin , Anderson Daniel G. , Witkiewicz Agnieszka K. , Brody Jonathan R. 
Published: August 2012

Abstract
HuR is a RNA-binding protein that post-transcriptionally regulates genes involved in the normal cellular response to cancer-associated stressors (e.g., DNA damage, nutrient depletion, hypoxia, and therapeutic agents). When triggered by stress, HuR translocates from the nucleus to the cytoplasm where it potently influences translation of key tumor promoting mRNAs by mRNA stabilization and direct facilitation of translation. Previously, it has been shown that HuR expression is a prognostic marker in ovarian cancers. Thus, we tested the effects of manipulating HuR expression levels on ovarian tumor growth characteristics and tested the hypothesis that silencing HuR through delivery of an HuR siRNA would be effective in suppressing the growth of ovarian tumors. Following treatment of A2780 ovarian cancer cells in culture with an adenovirus containing the HuR coding sequence, HuR expression was increased by ∼40% above control cells as determined by qRT-PCR. When these cells were plated in soft agar, the Adeno-HuR-treated cells markedly enhanced anchorage independent growth properties compared to control cells treated with an Adeno-GFP virus. When OvCAR-3 xenografts in nude mice were injected with lipidoid-siHuR formulated nanoparticles (2 injections/wk, 7 mg/kg/injection), HuR expression was reduced by 80% as determined by immunoblot analysis of resected tumors, and tumor growth was suppressed 2.6-fold after 3 weeks compared to control tumors (siLuciferase- and PBS-treated) (p = 0.0004). After 4 weeks of treatment, all control mice were sacrificed due to large tumor size. siHuR-treated mice continued to receive 2 injections/week for an additional 4 weeks during which time tumor size was maintained at 4-5X the baseline size. In our patient cohort, we also detected HuR activation (i.e., cytoplasmic HuR positivity) in twenty-four of thirty-four patients (71%), providing evidence that the majority of patients have activated HuR. Mechanistically, in A2780 ovarian cancer cells, we detected HuR binding to tumor-promoting target mRNAs including dCK, DR5, and HuR itself. These data provide evidence that silencing HuR, even as a monotherapeutic strategy, may be a promising therapeutic approach for the treatment of ovarian cancer. Studies combining HuR inhibition with other chemotherapies (including gemcitabine), and studies exploring targeting strategies, are ongoing. This work was supported by the Marsha Rivkin Center for Ovarian Cancer Research.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5630. doi:1538-7445.AM2012-5630
Abstract 5633: BreastDefend suppresses growth and breast-to-lung cancer metastasis in an orthotopic model of human breast cancer
Authors: Jiang Jiahua , Thyagarajan-Sahu Anita , Loganathan Jagadish , Eliaz Isaac , Terry Colin , Sandusky George , Sliva Daniel 
Published: August 2012

Abstract
We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of invasive human breast cancer cells MDA-MB-231 in vitro. In the present study we have evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. An oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastrical gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver spleen, kidney, lung and heart tissues in mice. Moreover, BD significantly decreased the change in tumor volume over time when compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67 % (control) to 20% (BD) (p&lt;0.05) and number of metastasis from 2.8 [0.0, 48.0] in the control group to 0.0 [0.0, 14.2] in the BD treatment group (p&lt;0.05). Finally, anti-metastatic activity of BD in vivo was further confirmed by the down-regulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5633. doi:1538-7445.AM2012-5633
Abstract 5636: Preclinical data of a microRNA-based therapy for hepatocellular carcinoma
Authors: Bader Andreas G. , Daige Christopher L. , Kelnar Kevin , Priddy Leslie , Dysart Sarah , Wiggins Jason , Zhao Jane , Leatherbury Neil , Omotola Michael , Stoudemire Jay , Lammers Paul , Brown David 
Published: August 2012

Abstract
MicroRNA (miRNA) mimics have emerged as a novel class of therapeutics with promising anti-oncogenic activity. These mimics are modeled after naturally occurring tumor suppressor miRNAs that are ubiquitously expressed in normal cells but frequently show a loss-of-function in human malignancies. The premise for the strong inhibitory activity is based on the observation these endogenous miRNAs control multiple oncogenic pathways commonly deregulated in cancer. Therefore, “miRNA replacement therapy” acts in accordance with our current understanding of cancer as a pathway disease that can only be successfully treated when intervening with multiple cancer pathways. We have identified a series of key tumor suppressor miRNAs, including miR-34, and validated the therapeutic potential in cultured cancer cells and mouse models of cancer. The translation of this potential into future medicines, however, was hampered by the lack of a robust clinically relevant delivery system. To facilitate a rapid route to the clinic, we have screened a panel of external delivery systems that are in pre-clinical development or have already reached the clinic featuring another oligonucleotide. Here, we present the pharmacologic and pharmacodynamic parameters of miRNA mimics complexed in ionizable NOV340 liposomes (SMARTICLEs, Marina Biotech, Bothell, WA) in an orthotopic tumor model of hepatocellular carcinoma. Treatment of mice carrying existing tumors mimics led to significant tumor regression, prolonged survival and lacked notable drug-related side effects. Some of the mice appeared to be tumor-free. The data demonstrate the therapeutic utility of the NOV340/miRNA formulation and support the initiation of IND-enabling studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5636. doi:1538-7445.AM2012-5636
Abstract 5638: New synthetic analogs of migrastatin as potent cell migration inhibitors to block overall metastasis in lung cancer and colorectal carcinoma
Authors: Lecomte Nicolas 
Published: August 2012

Abstract
Tumour metastasis is the leading cause of death within cancer patients. Therefore the development of new small molecules targeting this process is crucial in the therapeutic arsenal. Migrastatin is a biologically active natural product isolated from Streptomyces that shows a high potency inhibition of tumor cell migration. Upon completing the first total synthesis of migrastatin, sets of structurally simplified synthetic analogs were developed. In the light of extensive in vitro screening leading to informative structureαactivity relationship, a new generation of analogs was launched which demonstrated higher levels of in vitro inhibitory activity, stability and synthetic accessibility. We investigated two promising ether-derivative analogs, the migrastatin core ether (ME) and the carboxymethyl-ME (CME). Both compounds exhibited high efficacy in blocking tumor cell migration in vitro with IC50 values in the micromolar range, more than two orders of magnitude less than the LD50 values. In the light of these results, in vivo efficacy of these compounds in inhibiting tumor metastasis was assessed in human tumor xenograft models established in NOD/SCID IL2R gamma null (NSG) mice. First in a human Small-Cell Lung Cancer (SCLC) primary xenograft model, developed by subcutaneous injection of tumor cells, ME and CME compounds were found to be highly potent in inhibiting overall metastasis even at the lowest dosage used (degree of inhibition: 96% and 99%, for ME and CME at 10mg/kg or 12mg/kg respectively). Next, in a human Colorectal Carcinoma (CRC) xenograft model, developed by intrasplenic injection of tumor cells, ME at the highest dosage (100mg/kg) was found to significantly reduce the metastatic spread to the liver, the lungs and the GI tract (degree of inhibition: 97%, 84% and 95% respectively). CME and ME selectively inhibited tumor cell migration in vitro and in vivo but neither compound inhibited tumor proliferation at the primary site of tumor injection or at the metastatic site if tumor metastases occurred prior inhibition by drug treatment. All together these very encouraging findings suggest that these analogs have promise as potent anti-metastatic agents in epithelial tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5638. doi:1538-7445.AM2012-5638