bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3686: Antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast and pancreas cancer cells
Authors: Xiao Yan , Gao Xiugong , Cheung William , Urbas Aaron , Taratula Oleh , Holbrook David , Cavicchi Richard E. , Souchek Joshua J. , Wagner Paul D. , Srivastava Sudhir , Avedisian Thomas , He Huixin , Batra Surinder 
Published: February 2011

Abstract
Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for such applications, i.e., strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and a MUC4 IgG-SWNT complex, and demonstrated in vitro their dual functionality for both detection and selective destruction of breast and pancreas cancer cells.
The two complexes were constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken polyclonal IgY antibody and with anti-MUC4 mouse monoclonal IgG antibody, respectively. Raman signals were recorded on a Raman spectrometer with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 50 W/cm2 for 5 min. Cell viability was examined by calcein AM/ethidium homodimer-1 (EthD-1) staining.
Immunohistochemical studies showed that HER2 IgY-SWNT complex specifically targeted receptor-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells; MUC4 IgG-SWNT complex specifically targeted pancreatic cancer cells but not normal pancreas cells. Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated breast or pancreatic cancer cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast and pancreatic cancer cells without harming receptor-free cells. The death rate after NIR irradiation were 94.1% and 96.6% respectively for complex-treated breast and pancreatic cancer cells, but only 1.3% and 1.8% for the untreated controls of the two cancer cell types, respectively.
These results demonstrated that the antibody-SWNT complexes have the potential to detect cancer cells at the early stages of tumor development. In addition, the complexes are potentially useful for selectively killing cancer cells while sparing healthy ones. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of antibodies can lead to new strategies for cancer detection and therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3686.
Abstract 3694: The mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase as an inhibitory target for cancer therapeutics
Authors: Paschos Athanasios , Laflamme Pierre , Singh Gurmit 
Published: February 2011

Abstract
The hypoxic and glycolytic environment of malignant cells facilitates high levels of reactive oxygen species (ROS) production. Breast, ovarian and prostate cancer etiology is associated with the ROS production, which are thought to play an important role in regulating the cancers cell growth, survival and metastasis. A potent and major cellular, however functional limited characterized source of ROS, is the mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (GPD2). GPD2 is an essential component of the glycerol-3-phosphate shuttle and necessarily expressed in all tissues. In several cancer cell lines, GPD2 is highly expressed and we estimated it accounts for up to 70% of the total ROS production within the prostate cancer cell line PC3. In this study we have utilized this knowledge, to complete a cell-based high throughput-screening (HTS) assay, aimed to identify small molecule inhibitors of the GPD2 dependent ROS formation in PC3 cell lines.
We employed the amplex red hydrogen peroxidase detection assay and adapted it to the HTS format. 133 inhibitory compounds from the Canadian Compound Collection were identified to reduce the ROS production activity within the PC3 cells. In order to validate these hits and to determine their mode of action, we PCR amplified GPD2 form PC3-cell cDNA and purified recombinant human GPD2 from a bacterial overproducing strain to homogeneity by employing Strep-tactin affinity-chromatography. The heterologously expressed enzyme, devoid of its mitochondrial target sequence, displayed glycerol-3-phosphate dependent resazurin, dichlorophenolindophenol, as well as tetrazole/phenazine methosulfate oxidoreductase activity. Follow up enzymatic assays of the primary HTS hits with the artificial electron acceptors identified several GPD2 activity specific inhibitors. Subsequent concentration response studies of the HTS derived inhibitors elucidated their in vitro half maximal inhibitory concentration at the range of 10 μM. In order to map GPD2's ROS production site and determine the inhibitor binding sites within the enzyme, we bioinformatically derived the proteins tertiary structure.
Considering that GPD2 dependent ROS formation may drive the prostate cancer proliferation, we aim by exploiting the results of this work to generate novel lead molecules as promising potential anti-proliferating cancer drug candidates.
(This work was supported by a grant from the Canadian Institutes of Health Research to Gurmit Singh)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3694.
Abstract 3698: Development of a hydrophobic docetaxel prodrug nanoparticle with enhanced plasma circulation lifetime and improved efficacy
Authors: Johnstone Sharon A. , Ansell Steven M. , Harasym Troy O. , Xie Sherwin , Mayer Lawrence D. , Tardi Paul 
Published: February 2011

Abstract
Amphiphilic block co-polymers can form highly stable micellar-nanoparticles which can be used to trap hydrophobic chemotherapeutic agents. While block co-polymer formulations effectively retain drugs in vitro, nanoparticles frequently display burst release of trapped agents upon injection into animals. As a result, nanoparticles often show only limited improvements in drug circulation lifetime and likely provide little improvement in drug delivery to the tumor site. To address this issue, we previously generated hydrophobic prodrugs of paclitaxel to enhance retention within the nanoparticle and observed a correlation between drug circulation lifetime and the hydrophobicity of the anchor. When these formulations were evaluated for anti-tumor efficacy, the longest circulating paclitaxel prodrugs were the most efficacious. We have now extended our assessment to hydrophobic docetaxel prodrug formulations and have related plasma circulation characteristics of the docetaxel prodrug nanoparticles to suppression of tumor growth in mice bearing HT-29 human colorectal tumor xenographs. Docetaxel-docosanyl diglycolate (procet 7), and docetaxel-cholesteryl diglycolate (procet 8) were formulated in PS-PEG nanoparticles at a drug:polymer weight ratio of1:2 and injected i.v. into mice. The plasma half-life of the docetaxel prodrug was enhanced relative to the corresponding paclitaxel prodrug and significantly greater than docetaxel formulated in polysorbate 80. When dosed at their respective maximum tolerated dose (MTD), docetaxel, procet 7 and procet 8 nanoparticles resulted in a tumor growth delay (TGD) of 66%, 213% and 241% respectively. In addition docetaxel prodrugs administered at equimolar doses to docetaxel displayed greater antitumor activity than the free drug (77% and 105% TGD for procet 7 and procet 8 nanoparticles respectively). We attribute the increased potency of docetaxel prodrugs over paclitaxel prodrugs to the extended plasma circulation lifetimes of the former. These results confirm that hydrophobic docetaxel prodrugs can be formulated into block co-polymer nanoparticles to achieve prolonged circulation kinetics which result in enhanced therapeutic activity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3698.
Abstract 3701: A targeted delivery system for anticancer drugs based on functionalized carbon nanotubes
Authors: Heister Elena , Neves Vera , Silva Ravi P. , McFadden Johnjoe , Coley Helen M. 
Published: February 2011

Abstract
Carbon nanotubes have emerged as a promising nanomaterial for the development of customizable drug delivery system due to their ability to penetrate cell membranes and to attach high loads of drugs and targeting agents on their surface. In the field of oncology, this promotes the development of therapies with improved effectivity and fewer side effects by assisting the targeting of therapeutic agents to the desired site of action. Our work focuses on the targeted delivery of the anthracycline and anthracenedione anticancer drugs doxorubicin and mitoxantrone to human colon cancer cells (WiDr) by means of a carbon nanotube-based drug delivery system. The drugs are attached to the nanotube surface in a non-covalent manner, resulting in a weight ratio (drug: CNTs) of 4:1 owing to the high surface area of CNTs. As drug binding is higher at physiological pH than at a slightly acidic pH, this method allows for the release of the drug from the nanotubes in such environments, for example late endosomes and lysosomes. In a previous study, we have shown that doxorubicin-loaded carbon nanotubes are are taken up by WiDr colon cancer cells and release their drug payload upon cellular internalization, which then translocates to the nucleus [1]. Current work is focusing on the targeting aspect: to increase the specificity of our system, we further attach a monoclonal antibody to the nanotube carrier that recognizes/binds to carcinoembryonic antigen (CEA), a target structure overexpressed by WiDr colon cancer cells. In vitro cytotoxicity studies show that the targeted drug-CNT complexes indeed have a greater therapeutic effect on WiDr cells than on MCF7 breast cancer cells, which do not express CEA. Future work will include in vivo studies on mice bearing tumor xenographs to evaluate the feasibility and behavior of our system in a setting of clinical relevance.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3701.
Abstract 3708: Carbon nanotubes: Feasibility as nano-bio agents to target cancer
Authors: Neves Vera , Heister Elena , McFadden Johnjoe , Silva Ravi P. , Coley Helen M. 
Published: February 2011

Abstract
The targeting of genes in cancer cells to stop tumour growth and kill the cancer cells has emerged as a promising approach for cancer therapy. The key challenges for the application of this kind of approach are largely dependent on the development of suitable delivery systems. None of the current transfection methods are ideal, mainly because they often provoke immune responses. Recently, carbon nanotubes (CNTs) have been shown to transverse cellular membranes and shuttle biological molecules, including DNA, siRNA, and proteins into cancer cells. The main advantages of carbon nanotubes compared with other delivery agents are their biocompatibility and the large surface area.
To consider carbon nanotubes as nano-bio agents for gene therapy it is important first, understand how they behave at a cellular level. In our lab, we have carried out studies to determine the fate and trafficking of carbon nanotubes in cancer cells. Evidence of carbon nanotube uptake and release has been shown with no significant changes in cell components, such as DNA/RNA, proteins and lipids. Moreover, no significant stress was induced when cells were exposed to carbon nanotubes. Intracellular localisation and trafficking of carbon nanotubes was carried out by antibody staining of specific compartments within the cell and reveal that an endocytic pathway is involved on the internalisation of carbon nanotubes.
Finally, our work is currently focusing on the development of an in vitro model to examine the feasibility of using functionalized, CNTs as a means of delivering gene therapy using siRNA. We will then use this as a basis for further in vivo work using human tumour xenograft models with characterised genotypes (e.g. mutated p53 etc) to validate this approach.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3708.
Abstract 3709: Synthesis of chlorin-based fatty acid conjugate as photosensitizer for photodynamic therapy
Authors: Gantumur Battogtokh , Kim Sook Hee , Bae Sumi , Bae Su Jin , Kang Uk , Shick Ahn Woong 
Published: February 2011

Abstract
Photodynamic therapy (PDT) is promising an approach to cancer treatment that requires the combination of photosensitizer (PS), tissue oxygen, and light. Many PSs have been developed for the PDT; however, very few have made in clinical trials because improved drugs that are more selective and that can be used conveniently and without sustained skin photosensitivity are needed. Tumor targeting drug delivery is another attractive strategy in cancer treatment.
In this study, our purpose is to improve their selectivity on tumor cell as conjugating of chlorin-based PSs with unsaturated fatty acids (UFAs) that are taken up rapidly by tumors from the arterial blood, presumably for use as biochemical precursors and energy sources.
We have selected methyl pyropheophorbide-d-OH (MPPd) and pyropheophorbide-a-173-N-hexanol (PPa-N-He) that possess reactive hydroxyl groups for the molecule as developing photosensitizers, which were conjugated with docosahaxaenoic acid (DHA) and oleic acid (OA) by esterification reaction DCC-mediated, respectively, and gave in enough yield. Our selected PSs were obtained according to Tamiaki et al.1 and Smith et al.2 reported. Novel MPPd-DHA, MPPd-OA, PPa-N-He-DHA, and PPa-N-He-OA were prepared and structure of them was confirmed by spectroscopy's methods (1D and 2D NMR, UV-vis, and MS). The spectrum data of the compounds was clear and easy to characterize.
Our synthesized chlorin-based fatty acid conjugates that could be present a synergistic effect for PDT through a more accumulation of the conjugates on tumor cells due to both of those produce a reactive oxygen substrate (ROS). The conjugates have a high lipophilicity because the UFAs were linked to the PSs and the lipophilicity of PS has proven to be an important factor because it influences the biodistribution and clearance and thus the bioactivity of drugs.
References
1. Tamiaki, H.; Miyata, S.; Kureishi, Y.; Tanikaga, R. Tetraheddron. 1996, 52, 12421-12432.
2. Smith, K. M.; Goff, D. A.; Simpson, D. J. J. Am. Chem. Soc. 1985, 107, 4946-4954.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3709.
Abstract 3712: 2-Methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and aggressive phenotypes through differential regulation of β-catenin-E-cadherin-axis
Authors: Kambhampati Suman , Banerjee Snigdha , Dhar Kakali , Mehta Smita , Haque Inamul , Dhar Gopal , Majumder Monami , Ray Gibanananda , Vanveldhuizen Peter J. , Banerjee Sushanta K. 
Published: February 2011

Abstract
The purpose of this study was to evaluate whether 2-methoxyestradiol (2-ME2), a promising anticancer agent, modulates Barrett's esophageal adenocarcinoma (BEAC) cell growth and behavior through cellular pathway involving beta-catenin in partnership with E-cadherin, which appears to play a critical role in the induction of antitumor responses in cancer cells. We found that 2-ME2 markedly reduced the BEAC cell proliferation via regulating apoptotic machinery such as Bcl-2 and Bax. It may nullify the aggressive behavior of the cells by reducing the migratory behavior. Expressions of beta-catenin and E-cadherin and binding of these two proteins is activated in a 2-ME2-dependent fashion in Bic-1 cells. Moreover, over expressions of these two proteins may be due to the stabilization of these proteins by 2-ME2. We found that 2-ME2-induced anti-migratory effects are mediated through the beta-catenin -E-cadherin signaling pathways. In view of these results, we determined whether 2-ME2 reduces BEAC tumor growth. Administration of 2-ME2 significantly decreased the growth of BEAC cells xenografted on the flank of nude mice. The evidence presented points out that the impact of 2-ME2 on beta-catenin-orchestrated signal transduction plausibly plays a multi-faceted functional role to inhibit the proliferation and cell migration of 2-ME2 treated malignant cells and it could be a potential candidate in novel treatment strategies for Barrett's esophageal adenocarcinoma
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3712.
Abstract 3727: Phase 0 trials, obligation to research and ethical implications of health-care reform
Authors: Camporesi Silvia , Mameli Matteo 
Published: February 2011

Abstract
Biomedical knowledge is a public good; and people have a right to it. These two widely accepted assumptions are also at the core of the US Health Care reform. On the one hand, a public good needs the community's contribution in order to exist. On the other hand, people have also duties concerning public goods. Indeed, current patients rest on the shoulders of previous patients who contributed to the advancement of biomedical knowledge. Therefore, it can be argued that participation to research should be considered a “moral duty,” based on the arguments of free riding, reciprocity and fairness; and that default option should be to “opt in” to clinical trials.
While the debate revolving around a “obligation to research” dates back at least to the 1980s, it recently cropped up again, thanks to bioethicists John Harris and Ezekiel Emanuel (the latter, currently Special Advisor for Health Policy at the White House).
The 2006 FDA guidelines concerning first-in human clinical studies, also known as Phase 0 trials, are relevant to this discussion. Phase 0 studies aim to reduce the gap of translational research, and at speeding up the drug rate of approval. They are not suitable for all drug candidates, but only for those agents for which the molecular target and mechanism of effect are known. As they offer no therapeutic benefits to the participants, it has been argued that they pose an ethical dilemma. But a broader outlook on the ethical aspects needs to be taken here. Indeed, the existence of a scientific rationale for the design of study is a necessary, even if not sufficient, condition for its ethical justification; and it can be argued that the current framework of Phase 1 studies is not suitable for molecularly targeted agents, for which the maximum tolerate toxicity does not correlate with maximum efficacy.
Furthermore, if future trials will confirm the results of the first ABT-888 Phase 0 trial completed at NCI-NIH, and demonstrate that the risks of toxicity are negligible, it could be argued that Phase 0 trials represent the turning point for the envisaged cultural shift towards participation to research, as only in this context patients are offered the unique opportunity to contribute in a purely altruistic manner to the public good of biomedical knowledge. As a visiting PhD student at NCI-NIH sponsored by an UICC-ICRETT fellowship, I am currently developing a questionnaire to assess the comprehension of patients to Phase 0 clinical trials and their broader attitude towards participation to research. I will present my work in progress.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3727.
Abstract 3743: 18F-Fluorothymidine (18F-FLT) as tumor response predictor for anti-epidermal growth factor receptor antibody in human lung cancer xenograft
Authors: Takeuchi Satoshi , Zhao Songji , Kuge Yuji , Zhao Yan , Nishijima Ken-ichi , Hatano Toshiyuki , Shimizu Yasushi , Kinoshita Ichiro , Tamaki Nagara , Dosaka-Akita Hirotoshi 
Published: February 2011

Abstract
Background: Specific inhibition of epidermal growth factor receptor (EGFR) is one of the most promising treatment in the clinical setting. Cetuximab, a chimeric monoclonal antibody that binds to the extracellular domain of EGFR, has activity in colorectal cancer, non-small cell lung cancer, and so on. Because cetuximab is very expensive and has unique side effects, the development of appropriate evaluation for the therapeutic effects is necessary to use this drug effectively. Measurement of tumor proliferative activity by PET using 18F-Fluorothymidine (18F-FLT) may serve to assess early therapeutic effect. The purpose of this study is to determine whether 18F-FLT is useful to evaluate response to cetuximab treatment at a very early time-point in human lung cancer cell line xenograft.
Methods: Human tumor xenograft model was established in male BALB/c athymic mice by human lung cancer cell line NCI-H1975. These mice were assigned to two groups (n=5, each group): control and cetuximab-treated groups. Cetuximab was intra-peritoneally given 1.0 mg/body on the first day. 3H-FLT was given intravenously on day 3 and radioactivity in the tumor and other tissue samples (%Injected Dose/g/kg) was measured using liquid scintillation one hour later. Immunohistochemical labeling index (LI, %positive cells) staining of nuclear antigen Ki-67 was also studied in tumor tissues as a tumor cell proliferation marker.
Results: 3H-FLT uptake was higher in tumors compared with any other organs. The mean value of 3H-FLT uptake in tumor was significantly decreased to 55% of control value (0.38 ± 0.03 %ID/g/kg in control group vs. 0.21 ± 0.07 %ID/g/kg in cetuximab-treated group; p &lt; 0.05). As compared with control, Ki-67 LI was significantly decreased in cetuximab-treated group (21.8 ± 6.7 %positive cells in control group vs. 2.2 ± 1.2 %positive cells in cetuximab-treated group; p &lt; 0.001), while there was no significant changes in tumor volume and body weight between two groups.
Conclusions: In this animal model, 3H-FLT uptake and Ki-67 expression were decreased in cetuximab-treated group just two days after the treatment start. These results indicate 18F-FLT-PET can be a useful predictor to evaluate response to molecular targeted medicine such as cetuximab at a very early time-point of treatment before significant change of tumor size.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3743.