bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5622: Effect of novel RhoC inhibitor on breast cancer progression and metastasis in vivo
Authors: Shi Connie R. , Rosenthal Devin T. , Bao Liwei , Pang Judy C. , Wu Zhifen , Allen Steven G. , Merajver Sofia D. 
Published: August 2012

Abstract
Introduction: The oncogene RhoC GTPase is overexpressed in highly aggressive inflammatory breast cancer (IBC) and increases cellular motility and invasiveness in mammary tissue by interacting with downstream effectors to reorganize cytoskeletal elements in the cell. A small molecule inhibitor of RhoC-effector interaction has been identified. This antagonist decreases proliferation and inhibits motility of IBC cells in vitro. Here we evaluate the in vivo effects of the novel RhoC antagonist in a transgenic mouse model of breast cancer. Methods: The PyMT-RhoC transgenic mouse model was used in this study. This double transgenic strain was created by crossing the polyoma middle T antigen (PyMT) breast cancer model to a RhoC-overexpressing strain driven by the mouse mammary tumor virus (MMTV) promoter. The RhoC inhibitor was administered by intraperitoneal injection beginning at 50 days of age. Tumor size was monitored throughout treatment. At the end of the treatment, mammary glands, tumors, and lungs were extracted, fixed, sectioned, and stained with H&E. Results: PyMT-RhoC mice treated with the RhoC inhibitor showed a statistically significant delay in time of onset of the primary tumor and exhibited slower growth of the primary tumor compared to the control group. Western blot showed decreased RhoC protein levels in the treated PyMT-RhoC group relative to control, suggesting that the drug's in vivo activity includes reducing RhoC protein expression. Finally, as determined through H&E staining of lung sections, tumor metastasis to the lungs was decreased in the treated group compared to age-matched controls. Conclusions: We conclude that this novel RhoC antagonist shows promise in vivo as an inhibitor of mammary tumor proliferation and metastasis, and has the potential to be a clinically relevant treatment for inflammatory breast cancer.
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 5622. doi:1538-7445.AM2012-5622
Abstract 5624: HMG box-containing protein 1 (HBP1) participates in the antitumor effect of N-acetylcysteine (NAC) in invasive oral cancer
Authors: Chan Chien-Yi , Lee Ming-Fen , Chou I-Tai , Yee Amy S. , Huang Chun-Yin 
Published: August 2012

Abstract
Aberrant activation of the epidermal growth factor receptor (EGFR) gene is highly associated with poor prognosis and low survival in invasive oral cancer. Resistance to the EGFR-targeting antibodies or kinase inhibitors has been reported. Therefore, it becomes imperative to design alternative and/or additional agents to supplement the existing therapeutic means. N-acetylcysteine (NAC) has been shown to exhibit anti-EGFR function, but the underlying mechanism is not fully clear. Herein, we hypothesized that NAC might inhibit EGFR signaling through the induction of HBP1 in oral cancer. HBP1 is a known transcriptional suppressor of cyclin D1 and p47phox, a regulatory subunit of the NADPH oxidase complex, through which HBP1 regulates cell growth and redox homeostasis. NAC treatment suppressed cell growth, concomitantly with a reduction of the EGFR/Akt/cyclin D1 activation and an increase of HBP1 expression, in EGFR-overexpressing HSC-3 cells. When combined with AG1478, an EGFR inhibitor, NAC synergistically inhibited colony formation of HSC-3 cells, indicating that NAC is an effective anti-EGFR adjuvant. HBP1 disruption activated EGFR signaling as well as increased colony formation, cellular migration, and tumor growth in xenograft mice, and HBP1 knockdown also sensitized HSC-3 cells to AG1478, suggesting that HBP1 is a negative regulator of the EGFR signaling pathway. A significant overlap of the gene expression patterns between an HBP1-knockdown dataset and an existing EGFR signature was also identified. Finally, HBP1 silencing attenuated the anti-EGFR and anti-growth effects of NAC, and HBP1 knockdown also partially abolished NAC-inhibited p47phox expression and EGF-stimulated reactive oxygen species (ROS) generation. Taken together, our data indicate that HBP1 functions as a negative EGFR regulator, and NAC inhibits EGFR signaling presumably through HBP1 induction in invasive oral cancer.
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 5624. doi:1538-7445.AM2012-5624
Abstract 5627: Tumorigenesis and prognostic role of hepatoma-derived growth factor in human gliomas
Authors: Liu Li-Feng , Hsu Shu-Shong , Chen Chih-Hao 
Published: August 2012

Abstract
Hepatoma derived growth factor (HDGF) is a neurotrophic factor found in mouse spinal cord and hippocampal neurons. In various malignant tumors, the role of HDGF in tumor progression and its use as a diagnostic biomarker or therapeutic target have been extensively explored. However, the prognostic function and mitogenic role of HDGF in gliomagenesis is yet to be verified. In this study, we found a significant incidence of HDGF prevalence between the different pathological types and stages of glioma in 105 patients. We also found a prognostic significance in 41 glioblastoma multiforme (GBM) patients with the prevalence of nucleus HDGF predicts the short survival of GBM after surgery. To delineate the mitogenic role of HDGF in gliomagenesis, an adenoviral-expressed HDGF small interfering RNA (Ad-HDGF siRNA) was used to knock down the expression of nucleus HDGF. After knocking down the nuclear HDGF expression in human GBM cells, cell growth and cell invasion and induction on apoptosis by caspase-3 activation were significantly inhibited. We concluded that HDGF is a mitogenic growth factor in the progression of glioma and it can be a useful prognostic marker for GBM and therapeutic target for clinical management of glioma in the future.
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 5627. doi:1538-7445.AM2012-5627
Abstract 5629: Arginine depravation therapy with arginine deiminase and autophagy inhibition is a novel therapeutic approach for the treatment of metastatic sarcomas that lack argininosuccinate synthetase expression
Authors: Weich Dean , Li Shunqiang , Kitchens Tom , Tanas Munir R. , Boone Philip , Chen David Y. , Adkins Douglas R. , Bomalski John , Rubin Brian P. , Van Tine Brian A. 
Published: August 2012

Abstract
While sarcomas are a rare group of tumors, the poor response to current clinical regimens represents an important unmet need in oncology. A better therapeutic understanding of the biology and metabolism of sarcoma growth is necessary to develop novel therapies to treat patients with this group of tumors. Argininosuccinate synthase 1 (ASS1) is the rate-limiting enzyme in the conversion of citrulline to arginine. When ASS1 is not expressed arginine becomes an essential amino acid to a cancer cell that must be delivered from the diet. Immunohistochemical analysis of 701 patient specimens representing 45 subtypes of sarcoma demonstrates that ASS1 is not expressed in over 85% of sarcomas (619 of 701 patient samples). This suggests that sarcomas may be sensitive to the arginine deprivation therapy using pegylated arginine deiminase (ADI-PEG20). Treatment of a panel of leiomyosarcoma, osteosarcoma, alveolar soft part sarcoma, malignant peripheral nerve sheath tumor and Ewing's sarcoma cell lines with ADI-PEG20 resulted in cell cycle arrest but not apoptosis when ASS1 expression was low, whereas the ASS1 high osteosarcoma cell line MG63 continued to divide. Response in sarcoma cell lines is dependent on ASS1 expression, as bone sarcomas, soft tissue sarcomas, complex cytogenetic sarcomas and translocation dependent sarcomas all demonstrate cell cycle inhibition upon treatment with ADI-PEG20. The IC50 for treated cell lines treated with ADI-PEG20 ranged from 0.02-0.1ug/mL in ASS1 low sensitive cell lines. Treatment of sarcomas that lack ASS1 with ADI-PEG20 induces autophagy. Depletion of arginine by ADI-PEG20 in ASS1 negative sarcomas when combined with chloroquine, an inhibitor of autophagy, induces cell death as measured by Annexin V. Xenograft of the ASS1 low expressing osteosarcoma cell line MNNG into nude mice followed by treatment with ADI-PEG20 demonstrated a significantly slower tumor growth rate as compared to PBS treated controls. Experiments are now ongoing in mice using the combination of chloroquine and ADI-PEG20. Successful control of tumor burden by using arginine deprivation therapy and autophagy inhibition in our preclinical studies will help to justify and orient future clinical trials for this innovative treatment for patients with sarcoma that lack ASS1 expression.
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 5629. doi:1538-7445.AM2012-5629
Abstract 564: Bim-independent apoptosis by benzyl isothiocyanate in human breast cancer cells is mediated by PUMA
Authors: Antony Marie Lue , Kim Su-Hyeong , Singh Shivendra V. 
Published: August 2012

Abstract
Benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables, is a promising agent for chemoprevention of breast cancer as evidenced by efficacy against xenografted breast cancer cells (e.g., MDA-MB-231 cells) and in a transgenic mouse model (MMTV-neu). We have shown previously that mammary cancer chemoprevention with dietary BITC administration in the MMTV-neu mice is associated with apoptosis induction. In cellular models of human breast cancer (MCF-7 and MDA-MB-231 cells), the BITC-induced apoptosis is initiated by reactive oxygen species (ROS) resulting from inhibition of complex III of the mitochondrial respiratory chain. The present study builds upon these observations to provide insights into the molecular circuitry of BITC-induced apoptosis downstream of ROS production. Because BITC-induced apoptosis in different cell types is associated with activation of c-Jun N-terminal kinase (JNK), we initially focused on Bim as this protein is a downstream mediator of JNK-regulated apoptosis. Bim protein expression (extra-long form) was increased by about 2-3-fold upon 24-hour treatment of MDA-MB-231 cells with pharmacologically relevant concentrations of BITC (2.5 and 5 μM BITC). However, RNA interference of Bim had no effect on BITC-induced apoptosis as judged by analysis of cytoplasmic histone-associated DNA fragment release into the cytosol. Moreover, the BITC-treated MCF-7 cells exhibited a marked decrease in Bim (extra-long form) protein level. BITC treatment resulted in induction of PUMA in both MCF-7 and MDA-MB-231 cells, but as expected, this response was more pronounced in the MCF-7 cells which express wild-type p53. The BITC-induced apoptosis was partially but statistically significantly attenuated by RNA interference of PUMA in MCF-7 cells. Consistent with these observations, genetic depletion of PUMA in HCT-116 cells conferred partial but significant protection against BITC-induced apoptosis. Attenuation of BITC-induced apoptosis in PUMA knockout cells was accompanied by enhanced G2/M phase cell cycle arrest compared with isogenic wild-type HCT-116 cells. The BITC-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with PUMA induction in the tumor as evidenced by immunohistochemistry and western blotting. In conclusion, these results indicate that Bim-independent apoptosis by BITC is partly mediated by PUMA. This investigation was supported by the US PHS grant CA129347 awarded by the National Cancer Institute.
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 564. doi:1538-7445.AM2012-564
Abstract 5640: Preclinical of assessment of oxidative stress and apoptotic mechanisms of garlic extract in the prevention of acute promyelocytic leukemia
Authors: Yedjou Clement G. , Tchounwou Paul T. 
Published: August 2012

Abstract
INTRODUCTION: Garlic supplementation in diet has been shown to benefit patients with cancer. Recently, the pharmacological role of garlic in the prevention and treatment of cancer has received increasing attention. However, the mechanisms by which garlic extract (GE)-induced cytotoxicity, oxidative stress, and apoptosis in cancer cell remain largely unknown. OBJECTIVE: The present study was designed to use HL-60 cells as test model to evaluate whether or not GE-induced cytotoxicty and apoptosis in human leukemia (HL-60) cells is mediated through oxidative stress. METHODS: Human leukemia (HL-60) cells were treated with increasing concentrations of GE for 12 h. Cell survival was determined by MTT assay. The extent of oxidative cell/tissue damage was determined by measuring lipid peroxidation (malondialdehyde) concentrations by spectrophotometry. Cell apoptosis was measured by flow cytometry assessment (Annexin-V and caspase-3 assays) and DNA laddering analysis, respectively. RESULTS: Data obtained from the MTT assay indicated that GE significantly (p &lt; 0.05) reduced the viability of HL-60 cells in a dose-dependent manner. We detected a significant (p &lt; 0.05) increase in malondialdehyde (MDA) concentrations in GE-treated HL-60 cells compared to the control. Flow cytometry data showed a strong concentration-response relationship between GE exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and dose-dependent increase (p &lt;0.05) was recorded with regard to caspase-3 activity in HL-60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in GE-treated cells. CONCLUSION: Our finding indicates that GE-induced cytotoxicity and apoptosis in HL-60 cells are executed by cell death, phosphatidylserine externalization, activation of caspase-3, and nucleosomal DNA fragmentation under the overproduction of MDA, a by-product of lipid peroxidation and biomarker of oxidative stress. We conclude that GE at therapeutic concentrations induces cytotoxic effect and apoptosis in human leukemia (HL-60) cells through oxidative stress.
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 5640. doi:1538-7445.AM2012-5640
Abstract 5643: CRLX301, a novel tumor-targeted taxane nanopharmaceutical
Authors: Lazarus Douglas , Kabir Sujan , Eliasof Scott 
Published: August 2012

Abstract
Docetaxel is one of the most commonly prescribed anticancer agents. While efficacious, the therapeutic benefits of docetaxel are often compromised by immunosuppression and neurotoxicity, incurring a discontinuation rate of over 25%. Cerulean has developed a novel class of tumor-targeted nanopharmaceuticals designed to enhance both efficacy and tolerability. CRLX301, a self-assembling docetaxel nanopharmaceutical, possesses significantly enhanced efficacy and improved pharmacokinetics compared to the parent drug. IND-enabling toxicity studies for CRLX301 are currently underway. Compared to docetaxel, CRLX301 showed a superior PK profile, with a significantly longer half-life and a &gt;20-fold higher drug concentration in tumor tissue 7 days after a single administration. The improved PK and biodistribution of CRLX301 docetaxel translated into superior antitumor activity in murine syngeneic and human xenograft models. In the murine B16.F10 tumor model, median survival at the MTD exceeded 100 days for CRLX301 compared to 38 days for the parent drug docetaxel. CRLX301 also demonstrated superior efficacy over docetaxel in tumor models representative of other cancer types as well, including cure rates between 50 and 83% in xenograft models representing triple-negative breast and squamous non-small cell lung cancer tumors, compared to no cures for docetaxel. Further, in the human prostate xenograft tumor model DU-145, CRLX 301 achieved a 100% cure rate compared to a relatively poor cure rate of 25% with docetaxel, 146 days after three weekly doses at the MTD. In summary, CRLX301 represents a new and potent anticancer therapeutic that has the potential to be a best-in-class taxane.
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 5643. doi:1538-7445.AM2012-5643
Abstract 5645: Lentiviral-mediated cell-specific RNA interference in regulatory T cells
Authors: Byrne William L. , Forde Patrick , O'Sullivan Gerald 
Published: August 2012

Abstract
Regulatory T cells (TRegs) constrain anti-tumour immunity and remain the most significant obstacle to successful immunotherapy of cancer. The immunosuppressive influence of these cells can be abrogated by depletion strategies, modulation of T cell plasticity and inhibition of function or migration. A novel and attractive strategy for inhibiting TReg function is RNA interference directed against their crucial transcription factor, FOXP3. RNA interference (RNAi) is still in its infancy as a therapeutic modality but holds great promise in terms of specificity and potency. Foremost within the TReg microRNA signature is micro-RNA 31 (miR-31) which specifically silences FOXP3, abolishing the suppressor capability of these cells. Translation of this promising therapeutic into the clinic hinges on surmounting an obstacle common to all gene therapy strategies - delivery. Cognisant of the dangers of off-target effects, our aim was to mediate cell-specific delivery of RNA interference. This would greatly enhance the clinical utility of this treatment modality. To achieve this objective we used a lentiviral vector, pseudotyped with mutated measles virus glycoproteins bearing an antibody single chain fragment variable. This strategy circumvents the native tropism of the measles virus potentially allowing for cell-specific RNA interference.
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 5645. doi:1538-7445.AM2012-5645
Abstract 5654: Novel tissue-targeted virogeneimaging system for squamous cell carcinoma therapy expressing cell cycle regulator cdk2ap1
Authors: Zolochevska Olga , Figueiredo Marxa L. 
Published: August 2012

Abstract
Oral squamous cell carcinoma (OSCC) affects about 30,000 Americans each year, and although the overall prognosis has improved in recent years for localized carcinomas, metastases can decrease survival rates by half. For tongue and palate lesions, surgery is usually the initial treatment, but metastases aggressively develop at sites where conventional therapies are ineffective. Therefore, our goal has been to develop more effective therapeutic modalities for the disease utilizing expression of cell cycle arrest and apoptosis-modulating genes. Our efforts have focused on gaining understanding of the biology and therapeutic potential of p12cdk2ap1 (p12), an S-phase growth suppressor and proapoptotic gene commonly downregulated in OSCC. In vivo, we have showed that expressing p12 using a nonviral vector can result in effective reduction in tumor size and a dramatically altered tumor phenotype. Moreover, we have showed that p12 can have cell growth inhibitory effects in a cell-autonomous as well as non-cell autonomous manner, rendering expression of this cell cycle regulator a very promising new gene therapy strategy. Therefore, we hypothesized that this growth regulator molecule will comprise a highly efficient antiumor gene therapy for OSCC. We have developed a novel viral delivery vector system with high activity and high specificity expression in oral tumor cells. This Adenovirus (Ad) utilizes a two-step transcriptional amplification system driven by the SCCA2 promoter and a bidirectional target cassette containing the sequences for the p12 and ether firefly luciferase (Luc) or thymidine kinase (TK) imaging genes. We constructed and are characterizing novel configurations of these dE1dE3 Ad-SCCA2-p12/Luc or p12/TK bidirectional vectors for gene therapy and virogeneimaging (VGI) applications. We are currently testing the specificity of these vectors and their effectiveness in tumor growth inhibition at either floor of mouth, orthotopic, or distant sites following intratumoral or systemic administration. We propose VGI can be adapted to a nonviral system as well and may hold promise not only as a novel SCC-specific gene therapy but perhaps as a molecular imaging detection agent for tumor cells that have metastasized to distant and thus difficult to treat sites.
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 5654. doi:1538-7445.AM2012-5654