bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5658: Engineered Salmonella effectively produce and preferentially deliver bacterial cytotoxins to solid tumors
Authors: Jean Adam T. St. , Swofford Charles A. , Brentzel Zachary J. , Forbes Neil S. 
Published: August 2012

Abstract
To effectively treat cancer, therapeutics must specifically target tumor tissue and impart minimal toxicity to healthy tissues. Bacterial toxins, such as Pseudomonas aeruginosa Exotoxin A (PEA) and Staphylococcus aureus Alpha-Hemolysin (SAH), are highly cytotoxic and are promising moieties for cancer treatment. Due to their high toxicity and non-specificity towards all cells types, systemic effects limit their effectiveness as a therapeutic. While efforts have been made to impart cancer-cell specificity to these potent molecules, especially through immunotoxin technology, systemic toxicities still prove to be a challenge. Genetically engineered bacteria, such as Salmonella typhimurium, are known to target cancer by preferential accumulation within tumors and thus can be exploited as tumor-specific drug delivery vectors. By using cellular engineering techniques, the genetic machinery of bacteria can be used to produce exogenous bacterial toxins in situ. In addition to the specificity of bacterial accumulation, inducible promoter systems such as the arabinose-inducible system can be used to minimize systemic toxin levels by controlling the timing of protein expression. By coupling these strategies, we have been able to develop an effective bacterial therapy for targeted tumor treatment. PEA and SAH expressed in Salmonella under the PBAD promoter was secreted into the culture medium following arabinose induction. Monolayer cultures of MCF7 human breast carcinoma cells treated with secreted PEA and SAH for three days were depleted by 82% and 99%, respectively. Mechanism of delivery studies in a murine tumor model showed co-localization of salmonella, toxins and cell death within tumors following arabinose induction, while minimizing the localization of toxins to the healthy organs. Survival studies indicate that bacterial delivery of PEA and SAH can minimize systemic toxicities while decreasing tumor growth and increasing survival. Overall, these data indicate that by using bacteria to produce toxins in situ, we were able to overcome the delivery challenges inherent with non-specific toxin moieties and create a highly efficacious drug delivery system for use in the treatment of solid tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5658. doi:1538-7445.AM2012-5658
Abstract 5661: Pharmaceutically controlled replication of adenoviruses in mesenchymal stem cell-based cell carriers improves oncolytic virotherapy for advanced human renal cell carcinoma
Authors: Hsiao Wan-Chi , Liao Chia-Hui , Sung Shian-Ying , Hsieh Chia-Ling 
Published: August 2012

Abstract
Cell-based carriers were recently exploited as a tumor-targeting tool to improve systemic delivery of oncolytic viruses for cancer therapy. However, the slow clearance of carrier cells from normal organs indicates the need for a controllable system which allows viral delivery only when the carrier cells reach the tumor site. In this communication, we sought to develop a pharmaceutically-inducible cell-based oncolytic adenovirus delivery strategy for effective targeting and treatment of renal cell carcinoma (RCC), which is one of the most malignant tumor types with an unfavorable prognosis. Herein, we demonstrated the intrinsic tumor homing property of human bone marrow-derived mesenchymal stem cells (hMSCs) to specifically localize primary and metastatic RCC tumors after systemic administration in a clinically relevant orthotopic animal model. PDGF-AA secreted from RCC was identified as a chemoattractant responsible for the recruitment of hMSCs. Like endogenous osteocalcin whose barely detectable level of expression was dramatically induced by vitamin D3, the silenced replication of human osteocalcin promoter-directed Ad-hOC-E1 oncolytic adenoviruses loaded in hMSCs was rapidly activated and the released viral progenies sequentially killed co-cultured RCC cells upon vitamin D3 exposure. Moreover, systemic treatment of RCC tumor-bearing mice with Ad-hOC-E1-loaded hMSCs had very limited effect on tumor growth, but when it combined with vitamin D3 treatment induced effective viral delivery to RCC tumors and significant tumor regression. Therapeutic effects of hMSC-based Ad-hOC-E1 delivery were confirmed to be significantly greater than those of injection of carrier-free Ad-hOC-E1. Our results presented the first pre-clinical demonstration of a novel controllable cell-based gene delivery strategy that combines the advantages of tumor tropism and vitamin D3-regulatable human osteocalcin promoter-directed gene expression of hMSCs to improve oncolytic virotherapy for advanced RCC.
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 5661. doi:1538-7445.AM2012-5661
Abstract 5665: Multiplexing markers of response to sorafenib/mapatumumab combination therapy in hepatocellular carcinoma circulating tumor cells
Authors: Dolloff Nathan G. , Zhou Lanlan , Peters Kristi , Navaraj Arunasalam , Allen Joshua , Das Avisnata , Dicker David , El-Deiry Wafik 
Published: August 2012

Abstract
Hepatocellular carcinoma (HCC) accounts for approximately 600,000 deaths per year worldwide. Effective therapeutic strategies for advanced stage patients are lacking, and the median survival rate for patients who are not eligible for surgical resection is a mere 6 months. Circulating tumor cells (CTCs) are detectable in the peripheral blood of cancer patients, are accessible through a minimally invasive procedure, and may provide a source of tumor tissue for analyzing molecular markers of therapeutic response that may help guide treatment protocols. To demonstrate this potential, we developed a system for imaging and quantifying multiplexed molecular markers of response to sorafenib/mapatumumab combination therapy in an HCC CTC model. The sorafenib/mapatumumab combination regimen is currently in phase 2 clinical trials for the treatment of HCC, and molecular markers that mediate the synergistic anti-tumor activity of this combination have been identified. These markers include phospho-p42/44 MAPK (p-ERK), Mcl-1, c-IAP2, and apoptotic markers such as cleaved caspase-3. We developed a technical approach using MultiSpectral Imaging (MSI) to quantitatively measure multiplexed fluorescent signals from primary antibodies specific to phospho-ERK, Mcl-1, c-IAP-2, and cleaved caspase-3 that had been conjugated to quantum dots (Qdots) with distinct fluorescence emission spectra. We first confirmed the ability to modulate marker expression and uncouple multiplexed Qdot signals by MSI in cultured HCC cells that had been treated with sorafenib or sorafenib/mapatumumab combinations. We then applied this detection system to HCC cells that were spiked into human blood and recovered using FDA-approved CTC isolation technology (CellSearch CTC Test by Veridex). Our data demonstrate the potential for studying molecular markers of therapeutic response in CTCs. Information gained from this technology may be used to guide therapeutic decisions or serve as pharmacokinetic/pharmacodynamic endpoints in experimental clinical protocols.
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 5665. doi:1538-7445.AM2012-5665
Abstract 5673: Mechanisms responsible for the antitumor effect of metronomic chemotherapy with cyclophosphamide (Cy) and doxorubicin (Dox) in murine tumor models of mammary adenocarcinoma
Authors: Mainetti Leandro E. , Rozados Viviana R. , Rico María J. , Roggero Eduardo , Scharovsky O. Graciela 
Published: August 2012

Abstract
Metronomic chemotherapy (MCT) refers to the chronic, equally spaced, delivery of low doses of different chemotherapeutic drugs, without extended interruptions. We have already demonstrated that the administration, as an intervention strategy, of metronomic CY + DOX in M-406 and M-234p mammary adenocarcinomas-bearing mice inhibited tumor growth, increasing the survival rate. Our present aim was to study the mechanism/s by which that therapeutic effect was achieved. CBi and Balb/c inbred mice were s.c. challenged on day 0 with M-406 and M-234p mammary tumors, respectively, and treated from day 9 (M-406) and 10 (M-234p) on with: I) no further treatment (controls); II) CY in the drinking water (20mg/kg body weight/day); III) Dox (0.5 mg/kg i.p.), three times/week; IV) Treated as II + III. Blood samples were taken on days 0 and 20 (M-406) or 30 (M-324p) to evaluate VEGF and IL-10 serum levels determined by ELISA. Tumors were excised on days 25 and 31 for M-406 and M-234p, respectively, fixed and paraffin embedded for detection of Ki67 molecule by immunohistochemistry and apoptosis by the TUNEL technique. In the M-234p model the VEGF serum concentration of control animals (group I) was, on day 31, significantly higher than that measured on day 0 (p&lt;0,005), while on day 31, groups II, III y IV showed lower values than group I (p&lt;0.005) in the same day, and similar than those on day 0. The IL-10 serum levels in group IV were significantly higher than those found in group I and III. The apoptosis level in tumor cells in group IV was significantly higher when compared to control group (p&lt;0.05). Also, the staining for the proliferation marker Ki67 showed values significantly lower in the tumors of animals treated with CY + DOX than those in group I. A similar behavior was seen in the M-406 tumor model. In conclusion, opposing to the expected results, the animals with the better therapeutic outcome showed the highest IL-10 concentration, a result that could indicate a possible immunostimulatory effect of this cytokine; the antitumor effect of MCT with CY plus DOX in mammary tumor models would be achieved, at least in part, by the inhibition of both tumor angiogenesis and proliferation in addition to the stimulation of tumor cells 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 5673. doi:1538-7445.AM2012-5673
Abstract LB-237: In vitro and in vivo characterization of CPI-267203, a potent Inhibitor of bromodomain-containing proteins
Authors: Normant Emmanuel , Cummings Richard , Bellon Steven , Bailey Christopher , Albrecht Brian , Hewitt Michael , Pardo Eneida , Campbell Robert , Jayaram Hari , Poy Florence , Sandy Peter , Gangurde Pranoti 
Published: August 2012

Abstract
The transcription factor c-Myc regulates diverse biological processes including growth, proliferation, differentiation, quiescence, and senescence or apoptosis. c-Myc proto-oncogene overexpression has been implicated in the genesis of many human malignancies. Identification of compounds that selectively and potently inhibit the expression of c-Myc hence could be beneficial for the treatment of these diseases. We and others have recently shown that inhibiting the binding of bromodomain-containing proteins such as Brd4 to their acetylated histone substrates leads to the specific suppression of c-Myc transcription. We report here the characterization of CPI-267203, a potent, selective and competitive inhibitor of BET domain proteins (Brd4 IC50 = 26 nM and CBP IC50 = 6.0 uM). In vitro, this molecule inhibits IL-6 production (EC50 = 11 nM) induced by lipopolysaccharide (LPS) in acute monocytic leukemia cells (THP1) and c-Myc mRNA production (EC50 = 27 nM) in Burkitt lymphoma cells (Raji). c-Myc mRNA and protein levels decline as early as 4hrs after treatment with CPI-267203, leading to cell cycle arrest and apoptosis. In vivo, CPI-267203 has 84% oral bioavailability and a plasma half-life of 1.9 h. In a xenograft model of human acute myelogenous leukemia (MV4:11), CPI-267203 inhibits the production of c-Myc mRNA and protein, inhibits tumor growth, and triggers tumor apoptosis. Reduction of c-Myc protein levels can also be detected in the normal skin of treated animals, suggesting that the level of c-Myc in the skin might be a useful surrogate pharmacodynamic marker to aid clinical trials.
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 LB-237. doi:1538-7445.AM2012-LB-237
Abstract LB-43: Community health advisors: a model in community outreach and health education
Authors: Kyles Brenda M. 
Published: August 2012

Abstract
The Shelby County Health Department's goal is to become the healthiest and safest community in Tennessee. Our mission is to promote, protect and improve the health and environment of all Shelby County residents. We place emphasis on the following programs: environmental health, epidemiology, health education, maternal and child health, immunizations, STD, HIV and AIDs, breast and cervical cancer screening and treatment and Tuberculosis management. We are committed to closing the gaps in health status and access to care among our community's diverse populations and reducing the occurrence of preventable disease and premature death among all Shelby County residents.
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 LB-43. doi:1538-7445.AM2012-LB-43
Abstract LB-440: Low density array profiling of head and neck squamous cell carcinoma utilizing a 25-gene signature can reliably identify hypoxic tumors
Authors: Williamson Amanda , Betts Guy NJ , Patiar Shalini , Valentine Helen R. , Irlam Joely J. , Ramachandran Anassuya , Merve Ashirwad , Homer Jarrod J. , Moller-Levet Carla , Buffa Franscesca M. , Hall Gillian , Miller Crispin J. , Harris Adrian L. , West Catharine ML 
Published: August 2012

Abstract
Purpose: Administering hypoxia modifying therapy to patients with head and neck squamous cell carcinoma (HNSCC) improves outcomes in those with identified hypoxic tumors. As no method for measuring tumor hypoxia has demonstrated clinical utility, this study aimed to validate use of a gene expression signature with a TaqMan Low Density Array (TLDA) platform. Experimental design: Tumor samples (n=201) from 80 HNSCC patients were collected prospectively from two centers. Fifty-three patients received pimonidazole prior to surgery. Hypoxia scores (TLDA HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customized TLDA cards. Assay performance was assessed as coefficient of variation (CoV). Relationships with outcome were determined by log-rank analysis. Results: The assay was sensitive with linear reaction efficiencies across a 4log10 range of inputted cDNA (0.001-10 ng/µl). Intra- (CoV=0.5%) and inter- (CoV=0.1%) assay reproducibility were excellent. Intra-tumor heterogeneity was lower for TLDA HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA HS in HNSCC cell lines increased with decreasing pO2 and was reduced but not completely abrogated in HIF1A silenced cells. TLDA HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p&lt;0.01) and pimonidazole scores (p=0.021). High TLDA HS was associated with worse overall (p=0.037) and recurrence free (p=0.036) survival. Conclusions: Gene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumor heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for application in clinical trials.
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 LB-440. doi:1538-7445.AM2012-LB-440
Abstract LB-442: The nuclear matrix anchor domain of the DNA replication factor Ciz1 is commonly disrupted in tumours and is a circulating biomarker for lung cancer
Authors: Higgins Gillian , Cook Heather , Roper Katherine , Munckley Jennifer , Watson Irene , Blackhall Fiona , Rom William , Pass Harvey , Ainscough Justin , Coverley Dawn A. 
Published: August 2012

Abstract
The DNA replication protein Ciz1 promotes initiation of mammalian DNA replication in cooperation with cyclin A-dependent kinase, most likely by delivering cyclin A to sites where cyclin E-dependent pre-replication complex assembly has taken place. Normally, Ciz1 is anchored within nuclear matrix-associated foci that co-localize with sites of DNA replication, but in the absence of anchor domain Ciz1 retains the ability to promote initiation of DNA replication in isolated nuclei so attachment to the nuclear matrix is not essential for function. Expression of DNA replication and nuclear matrix anchor domains of Ciz1 are uncoupled and uneven at the transcript level in a wide range of common solid tumours, including breast and lung. In cell-based assays, recombinant anchor domain protein interferes with attachment of endogenous Ciz1 to the nuclear matrix, revealing a dominant negative effect that also impacts on nuclear matrix-recruitment of key components of the pre-replication complex. This suggests that Ciz1 normally plays a role in localizing initiation of DNA replication to the nuclear matrix. These findings implicate spatially unconstrained DNA replication as a source of nuclear disorder in cancer cells. We identified a variant Ciz1 isoform with alterations in the nuclear matrix attachment domain and tumour-restricted expression. RNAi-mediated selective inhibition of variant Ciz1 expression is sufficient to restrain the growth of tumour cells that express it, identifying variant Ciz1 as a functionally relevant driver of cell proliferation. We also present evidence that this form of Ciz1 is expressed in 34/35 lung tumours but not adjacent tissue, giving rise to stable protein quantifiable in less than a microlitre of patient plasma by western blot. Using two independent sets, with 170 and 160 samples, variant Ciz1 correctly identified stage 1 lung cancer patients with clinically useful accuracy. For set 1, mean variant Ciz1 level (+SD) in individuals without diagnosed tumours established a threshold that correctly classified 94% of small cell lung cancers (SCLC) and non-SCLC patients. Within set 2, comparison of stage 1 non-SCLC with asymptomatic age-matched smokers correctly classified 85% of patients, while comparison with individuals with benign lung nodules correctly classified 83% of patients. The data show that this cancer-specific, single marker is capable of indentifying early stage lung cancer within at-risk groups, without resort to invasive procedures.
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 LB-442. doi:1538-7445.AM2012-LB-442
Abstract LB-45: Real people- real stories: survivors teaching students
Authors: Fornia Judith L. 
Published: August 2012

Abstract
The Ovarian Cancer Alliance of Oregon and SW Washington is a proud partner member of the Ovarian Cancer National Alliance (OCNA). We actively bring the OCNA's program Survivors Teaching Students: Saving Women's Lives to the local level. Since 2002, the Ovarian Cancer National Alliance has been working to save the lives of women by helping healthcare practitioners learn to diagnose ovarian cancer earlier. Through OCNA's innovative educational program future healthcare professionals-physicians, nurse practitioners, nurses and physician assistants increase their understanding of ovarian cancer symptoms and risk factors so that they will be able to diagnose the disease when it is in its earlier, most treatable stages. Survivors Teaching Students brings ovarian cancer survivors into health professionals’ classrooms to share their stories and key information about the disease. At the local level, we also speak to pharmacy and naturopath students. Based on students’ evaluations we are accomplishing our goal of increasing awareness of this deadly cancer. Our local organization's mission is to promote awareness of ovarian cancer and to provide education to women and the health care community; to offer support to all ovarian cancer survivors by providing opportunities for networking, education and community outreach; and to advocate for public policy and funding for ovarian cancer research. In addition to the Survivors Teaching Students program, we are active in community health fairs/events, and have a presence in local Gynecological Cancer Support Groups.
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 LB-45. doi:1538-7445.AM2012-LB-45
Abstract LB-451: Treatment with hormonal blockade in estrogen receptor-positive tumors and correlation with molecular markers: a phase I pilot study of anastrozole in combination with everolimus, bevacizumab, sorafenib or erlotinib
Authors: Wheler Jennifer J. , Moulder Stacy , Falchook Gerald , Janku Filip , Naing Aung , Fu Siqing , Piha-Paul Sarina , Tsimberidou Apostolia Maria , Kurzrock Razelle 
Published: August 2012

Abstract
Background: Estrogen receptors are expressed across a variety of solid tumor types and may predict response to hormonal therapy. Objectives: Objectives were to evaluate safety, response signals and correlation with molecular aberrations. Methods: Beginning December 7, 2010 patients with estrogen receptor positive (ER+), advanced cancers were treated with anastrozole combinations. Toxicities were monitored and imaging evaluations were performed every 3 cycles (1 cycle = 4 weeks). Results: Patients were treated with anastrozole (1 mg) alone or in combination with everolimus (5 or 10 mg PO daily) (N = 18), bevacizumab (10mg/kg or 15 mg/kg IV q21d) (N = 5), sorafenib (200 mg PO BID or 400 mg qam/200 mg qhs) (N = 23), or erlotinib (75 mg PO daily) (N = 3). No dose-limiting toxicities or serious toxicities (≥ grade 3) were observed. On anastrozole/everolimus, 6/18 patients (33%) had either stable disease (SD) ≥ 6 months or partial response (PR) (breast cancer, 4; ovarian cancer, 2). 3 of 4 patients with SD ≥ 6 months or PR and available molecular results showed either PTEN loss or PIK3CA mutation or both. On anastrazole/bevacizumab, 1/5 patients (20%) had SD (11 months+; ovarian cancer). On anastrozole/sorafenib, 23/23 patients had progression of disease (PD). On anastrozole/erlotinib, 3/3 patients had PD. Conclusions: Treatment with anastrozole in combination with everolimus, bevacizumab, sorafenib or erlotinib is feasible and anastrozole/everolimus has demonstrated response signals in ER+ tumors (breast and ovarian), particularly in patients with PTEN loss or PIK3CA mutations. Study expansion and molecular profiling are ongoing.
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 LB-451. doi:1538-7445.AM2012-LB-451