bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 570: Breast cancer chemopreventive activity of a novel amide derivative of sulindac involves inhibition of PDE5, activation of PKG, and attenuation of Wnt/β-catenin signaling
Authors: Tinsley Heather N. , Gary Bernard D. , Whitt Jason , Zhang Wei , Chen Xi , Keeton Adam B. , Grubbs Clinton J. , Grizzle William E. , Piazza Gary A. 
Published: August 2012

Abstract
The nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX2) inhibitors demonstrate promising chemopreventive activity against a number of cancer types, including breast cancer. Unfortunately, potentially fatal toxicities associated with COX inhibition have precluded the development of these drugs for such indications. However, some studies suggest that their anticancer activity may be due to COX-independent mechanisms, suggesting the ability to target such mechanisms for the development of potentially safer and more effective chemopreventive agents. Here we describe a novel amide derivative of the NSAID sulindac sulfide (SS), termed sulindac sulfide amide (SSA). SSA lacked the ability to inhibit either COX1 or COX2 but demonstrated as much as a twenty-fold increase in potency to inhibit growth and induce apoptosis of breast tumor cells compared to SS. Moreover, SSA was selective for tumor cells, having no measurable effect on apoptosis of nontumorigenic mammary epithelial cells. As we have shown previously with SS, SSA inhibited the cGMP specific phosphodiesterase 5 (PDE5) enzyme. This resulted in accumulation of intracellular cGMP and activation of cGMP-dependent protein kinase (PKG) at concentrations comparable to those that induced breast tumor cell apoptosis. Mirroring the effects on PKG, SSA also resulted in decreased Wnt/β-catenin signaling, including decreased expression of the Tcf/Lef controlled proteins, cyclin D1 and survivin. Furthermore, SSA caused a 50% reduction in the incidence and a 30% reduction in the multiplicity of mammary tumors using the MNU model of mammary carcinogenesis. Interestingly, mammary tumors induced by MNU displayed high levels of PDE5 expression. These findings further demonstrate the COX-independent nature of the anticancer activity of certain NSAIDs, provide additional evidence that PDE5 may serve as an effective target for breast cancer chemoprevention, and reveal the utility of chemically modifying the NSAIDs to remove COX inhibitory activity while enhancing anticancer activity in order to produce safer and more effective chemopreventive agents.
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 570. doi:1538-7445.AM2012-570
Abstract 5705: Orally delivery alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine protect against murine breast cancer
Authors: Liu Ze , Liu Shu , Xiang Rong , Tan Xiaoyue 
Published: August 2012

Abstract
Legumain DNA vaccine has been proven to be a potential treatment approach to protect against breast cancer. However, absence of safe and efficient oral delivery system highly restricts its clinical application. Here, we aim to develop a novel oral delivery system for legumain DNA vaccine with better biocompatibility and efficiency. We constructed alginic acid-coated chitosan NPs (A.C.NPs) and tested its anti-acid characteristics in vitro. DNA agrose electrophoresis data showed that compared to chitosan NPs (C.NPs), A.C.NPs significantly protected DNA from degradation in the condition of pH=1.5. Furthermore, size distribution anlysis showed that when pH&lt;3.0, A.C.NPs aggregated to form the micrometer scale complex and dispersed to nanoparticle sized about 314 nm with the increased pH value. To visualize DNA expression, mice were treated by gavage with the A.C.NPs carrying EGFP expression plasmid. Significant EGFP expression can be detected in the intestinal peryer's patch of mice. Immunoflurescence staining showed that overlapping existed in EGFP and F4/80 (CD11b) positive cells. Full length legumain plasmids were loaded into different delivery systems including chitosan NPs (CL), Salmonella typhi (SL), A.C.NPs (ACL). PBS and A.C.NPs loaded with empty plasmid was also set as control groups (n=5 each group). Oral vaccination was performed in murine orthotropic 4T1 breast cancer model. Animals were scarified when the average tumor size in the PBS group reached 500 mm3. Our data showed that tumor volume was significantly smaller in ACL and SL groups compared to other groups. Further, we isolated splenocytes from mice and co-cultured with 4T1 cells pre-stimulated with hypoxia, which intrigued the translocation of legumain from cytoplasm to membrane. FACS assay showed that active cytotoxic T lymphocytes (CD3+/CD8+/CD25+) in ACL group increased 4.5 folds compared to PBS group and 2.3 folds compared to CL group respectively. Our study suggests that chitosan NPs modified with alginic acid could be a potential safe and efficient tool for oral delivery plasmid DNA. Alginic acid-coated chitosan NPs loaded with legumain DNA vaccine can effectively improve auto-immune response and protect against 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 5705. doi:1538-7445.AM2012-5705
Abstract 5708: Interstitial protein delivery evaluated in multicellular layers model
Authors: Kim Soo-Yeon , Kim Kwang-Suck , Kim Jung Ho , Kim Tae Hyung , Choi Jong Hoon , Lee Kang Choon , Park Ki Dong , Lee Seung-Jin , Na Kun , Kuh Hyo-Jeong 
Published: August 2012

Abstract
The limited efficacy of protein drugs is related to their poor distribution in tumor tissue. We examined interstitial delivery of four model proteins of different molecular size and bioaffinity as formulated of non-formulated forms in multicellular layers (MCL) of human cancer cells. Model proteins were tumor necrosis factor-related apoptosis-including ligand (TRAIL), cetuximab, RNase A, and IgG. MCLs were cultured in Transwell inserts, exposed to drugs, then cryo-sectioned for image acquisition using fluorescence microscopy (fluorescent dye-labeled TRAIL, RNase A, IgG) or Immunohistochemistry (cetuximab). TRAIL and cetuximab showed partial penetration into MCLs, whereas RNase A and IgG showed little penetration. At 10-fold higher dose, a significant increase in penetration was observed for IgG only, while cetuximab showed an intense accumulation limited to the front layers. PEGylated TRAIL and a heparin-Pluronic nanogel formulation of RNase A showed significantly improved penetration that was attributed to increased stability and extracellular matrix binding, respectively. IgG penetration was significantly enhanced with PTX pretreatment as a penetration enhancer. MCL culture was successfully used for the evaluation of protein movement in the tumor interstitum. Four proteins showed limited interstitial penetration in MCL cultures. Bioaffinity, rather than molecular size, seems to have a positive effect on tissue penetration, although strong binding affinity may lead to sequestration in the front layers. Nanoformulations, such as PEGylation and heparin-Pluronic (HP) nanogel, or penetration enhancers are potential strategies to increase interstitial delivery of anticancer biologics.
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 5708. doi:1538-7445.AM2012-5708
Abstract 571: Prevention of breast cancer by delaying promotion and progression
Authors: Arumugam Arunkumar , Boopalan Thiyagarajan , Parada Jacqueline , Das Trinath , Suman Suman , Lakshmanaswamy Rajkumar 
Published: August 2012

Abstract
A full term pregnancy early in life reduces the risk of breast cancer in women. A similar phenomenon is also observed in rats and mice. Short-term treatment with pregnancy levels of estradiol is also highly effective in preventing mammary carcinogenesis. In the current study our objective was to determine whether short-term treatment with pregnancy levels of estradiol conferred protection against mammary carcinogenesis by blocking initiation or promotion. Rats were injected with N-methyl-N-nitrosourea at 7 weeks of age and treated with 20 µg, 100 µg, 200 µg or 30 mg of estradiol in silastic capsules for 3-weeks. The experiments were terminated 9 months post carcinogen treatment. Mammary gland wholemounts were prepared at termination and examined for the presence of latent microscopic mammary cancers. Short-term treatment with pregnancy levels of estradiol drastically reduced the incidence of overt mammary cancers. 100 µg, 200 µg and 30 mg doses of estradiol resulted in levels of estradiol equivalent to pregnancy level and were effective in preventing overt mammary cancer incidence compared to control or 20 µg estradiol treatment which did not result in pregnancy levels of estradiol in the circulation. Although a significant reduction of overt cancers was observed in the pregnancy levels of estradiol treated groups, there was no difference in the incidence of microscopic mammary cancers between the estradiol treated and the controls. Proliferation of microscopic mammary cancers was examined using immunohistochemistry for cyclin D1 expression. Proliferation in the microscopic mammary cancers of the protected groups was significantly lower (∼ 2-3 fold) than the microscopic mammary cancers in the unprotected groups. These findings clearly demonstrate that short-term treatment with pregnancy levels of estradiol confers protection against mammary cancer development by blocking promotion and progression of carcinogen initiated cells.
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 571. doi:1538-7445.AM2012-571
Abstract 5734: Role of the inflammasome complex in Cr(VI)-induced lung injury and inflammation
Authors: Hopkins Lauren , Forbes Thomas , Schneider Brent , Constant Stephanie L. , Leitenberg David , Schwartz Arnold M. , Patierno Steven R. , Ceryak Susan 
Published: August 2012

Abstract
Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, leading to fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. While considerable information exists regarding Cr(VI) genotoxicity in cell culture, the mechanisms by which Cr(VI) causes lung injury and carcinogenesis in vivo are still unknown. We postulate that early inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis. We have previously established that intranasal (IN) particulate Cr(VI) administration in Balb/c mice induced a pronounced innate inflammatory response in the lung. Our present aim was to directly test the contribution of inflammasome-mediated inflammatory processes to chromate-mediated lung cancer development. We used WT and inflammasome-deficient (ASC knockout) BALB/c mice for weekly IN delivery of either saline or 10 ug particulate basic zinc chromate, which is an intermediately water soluble chromate typically encountered in mining/chromate production facilities and which is also present as an environmental atmospheric contaminant in urban areas surrounding ferrochrome production facilities. After 9 weeks, immune cells, cytokines, MMPs and pathologic features of lung injury and inflammation were measured in airway lavage fluid and lung tissue. Inflammasome-deficient mice exhibited a markedly reduced number of airway leukocytes in response to Cr(VI) challenge when compared to their WT counterparts, which was particularly evident for macrophages. Moreover, the Cr-induced increase in airway levels of IL6 (8-fold), CXCL/KC (3-fold), as well as pro-MMP9 (100-fold) was significantly attenuated in the inflammasome-deficient mice. In contrast, histological examination of lung tissue in animals challenged with chromate revealed a similar increase in peribronchiolar inflammation in both WT and ASC-/- mice, suggesting that Cr-induced lung inflammation may involve ASC-dependent and independent mechanisms, and that tissue infiltration may be less impacted by ASC-dependent mechanisms. In conclusion, particulate chromate is a potent inducer of inflammatory responses in the lung, mediated in part through the inflammasome complex. We postulate that these early inflammatory processes may contribute to the etiology of Cr(VI) carcinogenesis. The findings may also be relevant to other lung particulates that induce injury and cancer. Supported by NIH grants CA107972 and ES017334 to SC and ES017307 to SRP.
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 5734. doi:1538-7445.AM2012-5734
Abstract 5747: Elucidating the mechanisms by which Snail transcription factor promotes resistance to chemotherapy in breast carcinomas
Authors: Smith Bethany N. , Nagappan Peri , Chetram Mahandranauth , Taliaferro-Smith Latonia , Saintil Tamar , Yates Clayton , Hinton Cimona , Odero-Marah Valerie 
Published: August 2012

Abstract
Snail (Snail1) is a zinc finger transcription factor that can induce EMT and is expressed at high levels in tumors. Maspin is a potential tumor suppressor, whose expression is lost as breast and prostate tumors progress during EMT. Maspin can be transcriptionally repressed by androgen receptor (AR) in prostate cancer cells. We hypothesized that overexpression of Snail will inhibit maspin expression and confer resistance to chemotherapy. Initially, we examined the expression of Snail and maspin in a panel of breast epithelial and breast cancer cells by RT-PCR and Western blot analysis. Preliminary results suggest that breast cancer cells express variable levels of Snail that is higher in breast cancer cells than in the normal MCF10A cells. We then utilized MCF-7 cells transfected stably with an empty Neo vector (MCF-7 Neo) or constitutively active Snail cDNA (MCF-7 Snail) that have been shown previously to represent an EMT model, and examined maspin, estrogen receptor alpha (ER-α) and AR levels by western blot analysis. MCF-7 Snail cells had upregulated levels of Snail and lower levels of maspin, ER-α and AR, as compared to MCF-7 Neo. MCF-7 Neo and MCF-7 Snail cells were also xenografted into nude mice and tissue sections stained immunohistochemically for Snail, maspin, and ER-α. Tumor volumes of MCF-7 Snail tumor xenografts were significantly larger than the MCF-7 Neo xenografts. MCF-7 Snail tissue sections expressed higher levels of Snail and lower levels of maspin and ER-α as compared to MCF-7 Neo sections. MCF-7 Neo and MCF-7 Snail cells were also treated with estradiol (E2, 0.01uM), tamoxifen (TAM, 10uM), and docetaxel (DOX, 1uM) individually; and in combination with E2 plus TAM and TAM plus DOX for periods of 24h and 72h to analyze changes in cell morphology and EMT marker expression. No effect on cell morphology or cell death was observed in MCF-7 Snail cells after TAM treatments, whereas TAM induced cell death in MCF-7 Neo. Expression of Snail was increased with E2 treatments and decreased with TAM, DOX, and combination treatments in MCF-7 Neo and MCF-7 Snail. AR expression decreased further in MCF-7 Snail cells and MCF-7 Neo following treatments with TAM and DOX. Overall, the Snail overexpression appears to promote resistance to TAM and DOX chemotherapeutic agents. The mechanism of Snail-regulated EMT needs to be investigated further to determine changes in breast cancer progression.
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 5747. doi:1538-7445.AM2012-5747
Abstract 578: Apigenin blocks medroxyprogesterone acetate-dependent progression of BT-474 human breast tumor xenografts by inducing apoptosis
Authors: Mafuvadze Benford , Liang Yayun , Besch-Williford Cynthia L. , Hyder Salman M. 
Published: August 2012

Abstract
Recent clinical and epidemiological evidence suggests that hormone replacement therapy (HRT) containing both estrogen and progestin increases the risk of metastatic breast cancer in post-menopausal women compared with estrogen monotherapy or placebo treated women. The biological mechanisms behind this phenomenon remain obscure. We showed that medroxyprogesterone acetate (MPA), a commonly used progestin in HRT, increases the production of the potent angiogenic growth factor VEGF in breast cancer cells. The anti-progestin RU-486 blocks this effect, suggesting the involvement of progesterone receptors in the process (Int J Cancer, 2001, 92:469). This led to our hypothesis that progestins increase the angiogenic potential of latent tumorigenic cells in the breast, leading to development of palpable tumors. Using a xenograft model that was developed in our laboratory (Cancer Res., 2007, 67:9929), we previously showed that progestins promote the growth and development of BT-474 human xenograft tumors, as well as increasing BT-474 cell metastasis. In this study, we sought to determine whether apigenin, a low molecular weight flavonoid with known anti-carcinogenic properties, inhibits MPA-induced growth of BT-474 xenografts in nude mice. BT-474 human breast cancer cells were inoculated in immune-deficient mice that had been pre-inoculated with estradiol pellets. As was previously reported with this model, estradiol supported a short burst of tumor cell growth, which was followed by tumor regression. Implantation of MPA pellets rescued and stimulated further tumor growth. Administration of apigenin (50 mg/kg i.p.) inhibited the MPA-induced progression and development of BT-474 xenograft tumors. Immunohistochemical analysis revealed that the anti-tumor effects of apigenin occur through induction of tumor cell apoptosis, as measured using TUNEL assay, and also in part by suppression of cell proliferation (Ki67). Apigenin therefore appears to have therapeutic potential against progestin-dependent breast cancer and might be considered as a neutraceutical for treating progestin-dependent tumors in women already exposed to progestins. This study was supported by a COR award from the College of Vet Medicine, and research funds from RADIL, University of Missouri.
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 578. doi:1538-7445.AM2012-578
Abstract 589: Benzyl isothiocyanate effectively inhibits solid tumor growth and lung metastasis of 4T1 mammary carcinoma cells in BALB/c mice fed on a high-fat diet
Authors: Kim Minhee , Park Jung Han Yoon 
Published: August 2012

Abstract
Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables. We previously observed that chronic consumption of a high-fat diet increased the breast cancer progression and lung metastasis in the 4T1 orthotopic BALB/c mouse model. In the present study, we determined whether BITC inhibits high-fat diet-induced acceleration of breast cancer growth and metastasis in the 4T1 model. 4-week old, female BALB/c mice were fed on a high-fat diet (HFD, 60 kcal% fat) or control diet (CD, 10 kcal% fat) and BITC was administered daily with oral gavage (0, 5, or 10 mg/kg body weight/day). After 16 weeks, 4T1 cells (5 × 104 cells) were injected into the mammary fat pads of syngeneic, female, BALB/c mice and the mice were continuously fed on the same diets and BITC. 26 day after the cancer cell injection, animals were killed. The weights of tumors and lungs were significantly increased in the HFD group as compared to the CD group, and the increases were suppressed by BITC treatment. Additionally, chronic consumption of the HFD markedly increased the number and volume of tumor nodules in the lung; the increases were markedly suppressed by BITC treatment. Immunohistochemical staining of tumor tissues revealed that the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31, an angiogenesis marker), vascular endothelial growth factor (VEGF)-A, LYVE-1 (lymphatic vessel endothelial receptor-1), VEGF-D, Ki67, cyclin-dependent kinase 2, cyclin A, cyclin D1, and hypoxia-inducible factor 1α (HIF-1α) was markedly increased in the HFD group as compared to the CD group; the increases were blocked by BITC treatment. Chronic consumption of the HFD reduced TUNEL-positive apoptotic cells, which was prevented by BITC treatment. The present results demonstrate that BITC suppressed HFD-stimulated breast cancer progression, which may have been mediated via the suppression of cell cycle progression, tumor angiogenesis and lymph angiogenesis, and induction of apoptosis.
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 589. doi:1538-7445.AM2012-589
Abstract 595: Non-motorized voluntary running does not affect experimental and spontaneous metastasis in mice
Authors: Yan Lin , DeMars Lana C. 
Published: August 2012

Abstract
The present study investigated the effects of non-motorized voluntary running on experimental metastasis of B16BL/6 melanoma and spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice. After 9 weeks of running, mice (n = 30 per group) received an intravenous injection of B16BL/6 cells or a subcutaneous injection of LLC cells, and then they continued with their running activities. Experiments were terminated 2 weeks after the intravenous injection of B16BL/6 cells or 2 weeks after surgical removal of the primary tumor from mice subcutaneously injected with LLC cells. Mice in the running group ran an average of 4-6 km/day for the duration of the experiment. Voluntary running reduced body weight compared with sedentary controls, but there were no differences in the number and size of lung metastases between groups with either model. Voluntary running significantly reduced plasma insulin and leptin levels and increased adiponectin level in mice with and without LLC compared with their respective sedentary controls. Having LLC significantly increased plasma concentrations of vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), PDGF-AB and monocyte chemotactic protein-1 (MCP-1) in mice. Voluntary running significantly increased plasma PDGF-BB and PDGF-AB, but not VEGF and MCP-1, in mice with LLC compared with their sedentary counterparts. In summary, non-motorized voluntary running was favorable to body weight and the expression of related adipokines, but at 4-6 km/day it did not affect either experimental or spontaneous metastasis in mice.
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 595. doi:1538-7445.AM2012-595