bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5398: A primer dose followed by low-bolus dose schedule for safe and efficacious bacterial tumor targeting with S. typhimurium A1-R
Authors: Zhao Ming , Zhang Yong , Liu Fang , Hoffman Robert M. 
Published: June 2012

Abstract
We have previously developed a bacterial cancer therapy strategy by targeting viable tumor tissue with Salmonella typhimurium containing two auxotrophic mutations. These auxotrophs grow in viable as well as necrotic areas of tumors. However, the auxotrophy severely restricts growth of these bacteria in normal tissue, making this a relative safe treatment. The S. typhimurium A1-R mutant, which is auxotrophic for leu-arg, and selected for high antitumor virulence, has been shown to be effective as monotherapy against human prostate, breast, pancreatic, and fibrosarcoma tumors that have been orthotopically implanted in nude mice. In the present study, we developed a strategy to maximize efficacy and minimize toxicity for bacterial tumor treatment. A small dose of S. typhimurium A1-R bacteria was first administered to tumor-bearing animals (the primer dose) as pre-treatment followed by a high dose (106 i.v.) 4 hours later. Compared with very high dose bacteria treatment (5 × 106 per mouse), the primer dose strategy had no observable side effects. The very high dose had toxicity in immunocompetent mice. The primer dose may induce cytokines in the mouse necessary for invasion of the tumor by the bacteria allowing a relatively small subsequent dose to be effective and safe.
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 5398. doi:10.1158/1538-7445.AM2011-5398
Abstract 540: The pro-inflammatory protein S100A9 promotes pancreatic cancer cell growth
Authors: Markowitz Joseph , Mundy Bethany , Jaime-Ramirez Alena C. , Paul Bonnie , Bekaii-Saab Tanios , Carson William E. 
Published: June 2012

Abstract
S100A9 is a pro-inflammatory protein originally found in macrophages which is felt to be important in promoting inflammatory responses and cancer cell growth. The protein is found in cancer cells of gastric, colon, breast cervical and thyroid cancer. Generally, S100A9 is a cytoplasmic, cell surface and secreted protein that promotes cancer cell growth via inflammatory mechanisms and migration of immune cells (e.g. PBMCs) to the cancer microenvironment via non-covalent interactions with glycosaminoglycans on endothelial surfaces. Previously, this protein was reported in the stroma of pancreatic cancers but not in pancreatic cancer cells themselves. This report iilustrates S100A9 up-regulation on the surface of p53 mutant pancreatic cancer cell lines BxPC3 and AsPC1 as determined by immunoblot analysis and flow cytometry. In this study, pentamidine a known inhibitor of S100B, inhibited S100A9 dependent cell growth in BxPC3 cell lines (IC50 = 20.1 +/- 10.3 μM). Pentamidine treated BxPC3 cells (20 μM for 96 hrs) exhibited 30.1% apoptotic cell death as measured by Annexin/PI statining vs less than 3% for control treated cells. Given that S100A9 was found in other cancer models to promote recruitment of pro-infammatory cells (e.g. PBMCs) and subsequent support of cancer cell growth, we studied the effect of pentamidine on PBMC migration. Pentamidine also blocked the migration of PBMC from a metastatic pancreatic cancer patient (67%) to a similar degree as an Anti-s100A9 (68%) Ab or an anti-s100A8/A9 (65%) antibody. S100A8/A9 antibody is known to bind to helix 1 of S100A8 and helix 4 of S100A9, areas of the protein considered important for target interactions. It is likely that pentamidine indiscriminately binds to both the S100A8/A9 heterodimer as well as the homodimer in addition to other S100 proteins. S100A9 levels in BxPC3 cells as detected via Western analysis also increase with 20 μM pentamidine treatment, but not 10 fold as reported in the literature for S100B. As p53 was also shown previously to bind to the S100A9 promoter and S100A9 is not as robustly expressed in mutant p53 cell lines, p53 independent pathways are clearly important for cancer cell survival. This study suggests that S100A9 is up-regulated in pancreatic cancer and that inhibition causes pancreatic cancer cell death.
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 540. doi:10.1158/1538-7445.AM2011-540
Abstract 5400: Antiangiogenic gene therapy with VB111 is active in glioblastoma xenografts
Authors: Brenner Andrew J. , Rogge Jessica , Cohen Yael , Breitbart Eyal , Livnat Bangio 
Published: June 2012

Abstract
Introduction: Glioblastoma is a highly vascular tumor with marked endothelial dependence. While anti-angiogenic therapy has shown transient clinical benefit for the treatment of glioblastoma, persistent vascularization is seen with a normalization of blood vessels within the tumor. VB-111 is a dual-action, anti-angiogenic and vascular disrupting agent for cancer treatment aimed specifically at destroying newly formed and existing tumor blood vessels in a safe and efficient manner. VB-111 consists of a replication incompetent adenovirus together with an endothelial angiogenic-specific promoter and a pro-apoptotic Fas chimera transgene.
Methods: Intracranial xenografts were established in nude rats with a luciferase expressing U87 glioma cell line. Rats were treated intravenously with VB-111 at 1011 viral particles or placebo at 21 days post tumor cell implantation. Tumor growth was followed by in vivo bioluminescent imaging and 7T MRI. Rats were sacrificed when moribund or when marked neurologic deficit was observed. Tumors were evaluated by standard histologic methods for vessel density and necrosis.
Results: Untreated rats bearing U87 tumors showed a median survival of 38 days (95% CI 35.1-40.9 days), while animals treated with VB-111 showed a median survival of 48 days (95% CI 42.1-53.9 days). Log rank analysis of survival distributions between these two groups showed a significant difference (p=0.024) in favor of treatment. Luciferase activity, used as a surrogate for tumor volume, began separating between the two groups in week two post treatment and showed a continued trend for reduced activity in the treatment group thereafter. MRI imaging confirmed decreased tumor size in representative animals from the VB-111 group.
Conclusions: VB-111's Dual action therapy is promising for glioblastoma.
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 5400. doi:10.1158/1538-7445.AM2011-5400
Abstract 5406: Chemosensitization of melanoma by use of the minimalistic nonviral MIDGE expression system for improved TNF-alpha expression in vitro and in vivo
Authors: Walther Wolfgang , Kobelt Dennis , Aumann Jutta , Fichtner Iduna , Schmidt Manuel , Schlag Peter M. 
Published: June 2012

Abstract
Melanomas are often refractory towards chemotherapy. Tumor necrosis factor alpha (TNF-alpha) is known for its strong chemosensitizing potential. However, to exploit this potential, high doses of TNF-alpha are required, which are often associated with severe toxicities limiting the clinical applicability. Alternatively, TNF-alpha can be generated at high level at the tumor site using local application of gene therapy. To achieve this, we employed the nonviral MIDGE vector system for significantly improved TNF-alpha expression. The minimalistic immunologically defined gene expression (MIDGE; Mologen AG, Berlin, Germany) vector system is a linear DNA molecule that is depleted of bacterial backbone, antibiotic resistance sequences and CpG motifs, which significantly reduces its size. In our in vitro experiments using equimolar amounts of luciferase expressing MIDGE vector or plasmid we observed significant up to 13-fold increased MIDGE vector mediated expression in transfected human A375, MeWo and SKMEL-28 melanoma cells. Accordingly the FACScan analysis revealed improved transfection efficiency of MIDGE vectors.
We used the MIDGE vector to efficiently express TNF-alpha in human A375 melanoma cells in vitro. The MIDGE vector generated significantly higher TNF-levels in comparison to plasmid-mediated expression. The in vivo transfer of the TNF-expressing MIDGE vector into A375 melanomas by intratumoral nonviral jet-injection resulted in efficient high level cytokine expression, which was time and vector-dose dependent. Importantly, this high level TNF-expression does not lead to TNF-alpha release into the circulation and does not cause increase in body temperature or losses in body weight. The MIDGE-mediated TNF-alpha expression mediates efficient chemosensitization in the melanoma xenotransplant bearing nude mice by improving the in vivo chemotherapy with vindesine. This is reflected by significant tumor growth inhibition. The study demonstrates the superiority of the MIDGE vector system for nonviral local gene therapy approaches that might be translated into clinical applications.
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 5406. doi:10.1158/1538-7445.AM2011-5406
Abstract 5407: Tumor penetrating microparticles enhance siRNA delivery and expression in pancreatic cancer
Authors: Wang Jie , Lu Ze , Gu Jing , Cui Mingjian , Dorsten Joy , Wientjes M. Guillaume , Au Jessie L-S. 
Published: June 2012

Abstract
A major challenge for using siRNA as cancer therapeutics is the delivery to solid tumors, due to their unfavorable physicochemical properties (negative charges, large molecular size, and instability). Our laboratory has developed paclitaxel-loaded tumor-penetrating microparticles (TPM) for intraperitoneal therapy of peritoneal tumors (JPET, 327: 673-682, 2008). Embedded in the design of TPM is the tumor priming technology to promote nanomedicine delivery in solid tumors (JPET, 322:80-88, 2007). The goal of this study was to evaluate whether TPM can improve siRNA delivery and expression for treating solid tumors located in the peritoneal cavity. Nanoparticles containing survivin siRNA (siRNA-NP) were developed. Survivin, a major resistance factor, is selectively expressed in tumors and upregulated by various chemotherapeutic agents. The activity of paclitaxel (agent loaded in TPM) and siRNA was investigated in cultured cells using the clonogenic assay and the survivin level determined using western blotting. In vivo activity was evaluated in peritoneal pancreatic HS766T xenograft tumors; the pharmacodynamic endpoints were reduction of proliferation index (measured by Ki67 labeling), induction of apoptosis (measured by caspase 3 expression), prolongation of survival time, and survivin protein level (measured by immunohistochemical staining and quantitative image analysis using NIH ImageJ). The two negative controls were blank nanoparticles (without siRNA) and non-targeting siRNA. In cultured cells, siRNA-NP produced protein knockdown, decreased cell clonogenicity, and enhanced paclitaxel activity. However, siRNA-NP did not produce protein knockdown or antitumor activity in tumors grown in animals, indicating insufficient delivery in vivo. In contrast, when given in combination with TPM, siRNA-NP produced survivin knockdown and enhanced the antitumor activity of TPM. The results indicate that TPM treatment improves the delivery and transfection of siRNA in intraperitoneal tumors in vivo and suggest potential therapeutic utility of coadministered TPM and siRNA-NP combination. Supported in part by research grants R44CA103133 and R43CA134047 from NCI, DHHS.
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 5407. doi:10.1158/1538-7445.AM2011-5407
Abstract 5425: Potent curcumin analogue FLLL-22, but not natural curcumin, targets the DNA damage pathway for apoptosis in lung and head and neck cancer cells
Authors: Amin A.R.M. Ruhul , Lee Michelle , Rahman Mohammad A. , Fuchs James R. , Chen Zhuo G. , Shin Dong M. 
Published: June 2012

Abstract
Curcumin, 1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadien-3, 5-dione, is the major bioactive compound isolated from the rhizome of Curcuma longa (turmeric). Despite its high margin of safety (no dose-limiting toxicity at doses up to 10 g/day in human) and efficacy against various types of cancers, the potential utility of curcumin as a chemopreventive/chemotherapeutic drug is compromised by its low bioavailability and poor selectivity. To circumvent these problems, more potent and selective curcumin analogues have been introduced. In the current study, we investigated one such synthetic analogue, (1E, 4E)-1, 5-bis (2, 4, 6-trimethoxyphenyl) penta-1, 4-dien-3-one (FLLL-22), against the head and neck cancer cell line Tu212 and lung cancer cell line H460. We conducted an SRB assay to determine IC50 values which showed that FLLL-12 was 24.6-fold and 31.6-fold more potent than natural curcumin against Tu212 and H460 cells, respectively. FLLL-22 also more strongly inhibited colony formation in both cell lines than that of natural curcumin. FLLL-22 at 1 μM was sufficient to completely inhibit colony formation, whereas up to 5 μM of curcumin had only minimal effects on colony formation. FLLL-22 also induced apoptosis more strongly (∼10-fold) than natural curcumin as evidenced by annexin V-PE staining and cleavage of PARP. Interestingly, FLLL-22, but not natural curcumin, activates DNA double strand breaks as evidenced by phosphorylation of H2AX and activation of p53 pathway. Although FLLL-22 strongly phosphorylated H2AX at doses of 3 and 5 μM, no H2AX phosphorylation was observed after curcumin treatment with doses 20 and 30 μM. At these doses, both compounds induced comparable apoptosis. FLLL-22 increased the protein level of p53, its phosphorylation at Ser15 and Ser392, and downstream target p21. A slight increase in p53 expression was observed with 20 μM curcumin, but not with 30 μM. Ablation of p53 by shRNA inhibited FLLL-22-induced p21, suggesting that FLLL-22 activates p53-dependent transcription. We also found that treatment with both FLLL-22 and curcumin inhibited phosphorylation of AKT, S6 and expression of Bcl-2. Taken together, our data strongly suggest that FLLL-22 is a potent curcumin analogue which activates the DNA damage pathway to induce apoptosis and might be a suitable anti-cancer drug for further preclinical and clinical development (supported by U01CA101244, R01CA112643, and P50CA128613 to DMS).
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 5425. doi:10.1158/1538-7445.AM2011-5425
Abstract 5433: Analysis of the short-term and long-term in vitro cytotoxic effects of the anticancer drug Ukrain in breast cancer models
Authors: Bozeman Erica , Mohammadi Hamid , Shashidharamurthy Rangaiah , Daniels Danielle , Selvaraj Periasamy 
Published: June 2012

Abstract
Ukrain is a semisynthetic compound derived from the extract of the plant Chelidonium majus L. Studies indicate that this anticancer drug exhibits cytostatic and cytolytic activity against several human cancer cell lines including colon, brain, ovarian, melanoma and lymphoma without adverse harmful side effects on healthy human cells. However, such activity has not been thoroughly investigated in a breast cancer model. In order to assess the in vitro cytotoxicity of Ukrain, we used mouse (4T07 and TUBO) and human (SKBR-3) breast cancer cell lines. 4T07 and TUBO are highly tumorigenic, nonmetastic tumor cell lines derived from spontaneous carcinomas in BALB/cfC3H and BALB-neuT mice, respectively. The TUBO and SKBR-3 cell lines constitutively express the HER-2/neu oncogene, which is overexpressed in 30% of human breast cancer patients. Tumor cells were trypsinized after reaching 90-95% confluency and plated with varying concentrations of Ukrain. Following 24, 48 and 72 hour treatment with Ukrain, cell number and viability was determined using the trypan blue exclusion method. To assess whether the tumor cells retained the capacity for unlimited proliferation, a clonogenic assay was conducted. Cells were seeded out in appropriate dilutions to form colonies within 2-3 weeks. Colonies were fixed and stained with crystal violet (0.5% w/v) and counted by microscopy. Lastly, to determine whether the cytotoxic effects of Ukrain are due to the induction of apoptosis, we carried out intracellular staining for active caspase-3. We observed a dose-dependent and time-dependent inhibition of tumor cell growth. As low as 50 υg/mL of Ukrain led to a significant decrease in tumor cell viability when compared to untreated cells. The clonogenic assay showed the inability of treated tumor cells to form colonies and regain their proliferative capacity whereas the untreated cells formed multiple colonies. We observed a several fold increase in caspase 3 activation of Ukrain treated cells compared to untreated cells confirming apoptosis as the cytotoxic mechanism of action. In conclusion, our data suggest that Ukrain could be effective as an anticancer drug for breast cancer due to its short-term and long-term inhibitory effects on tumor cell viability and proliferation.
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 5433. doi:10.1158/1538-7445.AM2011-5433
Abstract 5434: Functional screening for impact on cancer hallmarks migration, transformation and angiogenesis identifies potential new drug leads isolated from marine organisms
Authors: Ehlert Jan E. , Weber Holger , Mueller Melanie , Siedentopf Oliver , Lin Wenhan , Proksch Peter , Kubbutat Michael HG 
Published: June 2012

Abstract
Marine organisms represent a potential new source for lead compounds applicable for cancer therapy. Traditionally, natural sources have been in the focus of drug discovery and have so far yielded an impressive number of drugs that are indispensable in modern therapy. About two thirds of all anti-cancer drugs approved today are in fact either natural products or have been developed on the basis of knowledge gained from natural products. This is especially pronounced in the field of cancer chemotherapy. Of special interest to us were compounds from so far under-explored and under-exploited marine organisms from China and Vietnam. In this study compounds from such organisms have been isolated and analysed in phenotypic cellular assays for their inhibitory impact on critical hallmarks of cancer. For that purpose, we have developed medium throughput phenotypic assays to look at transformation, angiogenesis and migration, indicated by soft agar growth, endothelial sprouting and wound healing, respectively. We report on a phenotypic screen of 160 compounds derived from marine organisms, which lead to the identification of several differentially inhibitory substances which are subsequently analysed in detail.
This project was funded by the German ministry of Science and Education; Grant No 0315322.
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 5434. doi:10.1158/1538-7445.AM2011-5434
Abstract 5437: Novel drug sensitivity test using three-dimensional primary lung cancer cell culture on microfabricated surface
Authors: Shimomura Manami , Sakamoto Ruriko , Yoshida Kaori , Ueda Ikuyo , Yonemura Masahito , Shimada Yoshihisa , Nakatsura Tetsuya 
Published: June 2012

Abstract
Purpose: The behavior of cells cultured within three-dimensional structures more closely reflects their in vivo responses than onto two-dimensional culture. We established novel 3D primary cell culture on microfabricated surface and studied whether it was useful for drug sensitivity test in lung cancer. Experimental design: The cancerous portions of the lung cancer specimens were disrupted into single cell suspension and the 5 × 104 cells per well were seeded on novel nanotechnology-based 3D culture plate (Nanoculture plate®: NCP, SCIVAX Corp.), which has approximately 2-3μm diameter of micro fabrications on the culture surface. When the cancer cells formed the multicellular spheroids, anticancer drugs (GEM and Gefitinib; each concentration was 1uM and 10uM) were added and measured ATP quantity of living cells after 72 h. Fluorescence immunostaining of cytokeratin-18, the marker of lung epithelial cells, and α-SMA, the marker of fibroblast, were performed to examine the constituent cells. Results: Lung cancer cells rapidly formed multicellular spheroids on the NCP. It was revealed that these multicellular spheroids consisted of cancer cells and fibroblasts by staining α-SMA and cytokeratin-18. In one case showed sensitivity against Gefitinib but not against GEM, there was exon 19 deletion of EGFR in the cancer specimen. Discussion and Conclusion: This culture system could be useful for further evaluation such as individual chemotherapy sensitivity assays and for finding novel molecular targets for cancer drug.
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 5437. doi:10.1158/1538-7445.AM2011-5437