bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5504: Combination of gemcitabine and docetaxel for the treatment of Korean children and adolescents with recurrent or refractory osteosarcoma.
Authors: Lee Jun Ah , Ko Yunmi , Kim Dong Ho , Yoo Ji Young , Park Eun Sil 
Published: August 2014

Abstract
Background: The combination of gemcitabine and docetaxel (GEMDOX) has demonstrated promise in adult sarcomas. Still, its efficacy in children and adolescents with recurrent or refractory osteosarcoma is controversial, due to a relatively small number of cases. We evaluated the efficacy of this combination in Korean pediatric patients with recurrent or refractory osteosarcoma.
Methods: A retrospective case review of 23 patients (15 male, 8 female) with recurrent or refractory osteosarcoma who received gemcitabine (675 – 900 mg/m2 intravenously on days 1 and 8) and docetaxel (100 mg/m2 intravenously on day 8) at the Korea Cancer Center Hospital was undertaken.
Results: The patients (ages 7.8 – 12.4 years) received a total of 78 courses of GEMDOX chemotherapy (median 3 courses; range 1 – 8 courses). For the 23 patients, 13 patients received GEMDOX as adjuvant chemotherapy, and the remaining 10 cases were eligible for response evaluation; there were 3 partial response (PR) and 1 stable disease (SD). The overall objective response was 30% and disease control rate was 40%. Median duration of response was 6.5 months (range, 3 – 13 months). GEMDOX chemotherapy was well tolerated and no treatment related death was observed. The most common toxicity was myelosuppression, however, no infectious complication have occurred.
Conclusion: The poor prognosis of patients with recurrent or refractory osteosarcoma, lack of effective salvage chemotherapy regimen, and case series reporting its activity, including ours, suggest that GEMDOX chemotherapy is beneficial in palliative setting and need to be considered for large scale clinical trials.
Citation Format: Jun Ah Lee, Yunmi Ko, Dong Ho Kim, Ji Young Yoo, Eun Sil Park. Combination of gemcitabine and docetaxel for the treatment of Korean children and adolescents with recurrent or refractory osteosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5504. doi:10.1158/1538-7445.AM2013-5504
Abstract 5510: Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex.
Authors: Li Shaowei , Wang Ji-an , Thangapazham Rajesh L. , Klover Peter , Moss Joel , Darling Thomas N. 
Published: August 2014

Abstract
Pharmacological approaches for treating tumors in patients with tuberous sclerosis complex (TSC) are inadequate. Although mTORC1 inhibitors such as rapamycin represent a major new avenue for treatment, we and others have shown that rapamycin improves but does not eradicate TSC skin tumors. We tested the effects of tranilast, an antiallergic and antifibrotic drug with antiproliferative effects, on fibroblasts grown from angiofibromas, forehead plaques, periungual fibromas, and normal-appearing skin from 5 patients with TSC. Tumor cells showed loss of TSC2 expression and hyperactivation of the mTORC1 signaling pathway. Tranilast (5, 10, 20, 40 μM) inhibited the viability of TSC skin tumor cells from five patients in an MTT assay. These effects on cell viability appeared to be independent of mTORC1 activity, since tranilast did not inhibit phosphorylation of ribosomal protein S6. Four paired samples of RNA from tumor and normal cells, treated with or without tranilast, were studied using gene expression arrays, revealing that tranilast significantly altered the expression of at least 36 genes, of which 12 are involved in transcription. In a xenograft model in which dermal-epidermal constructs comprising normal human keratinocytes with either TSC angiofibroma cells or TSC normal fibroblasts from a TSC patient were grafted to nude mice (6-8 mice per group), tranilast treatment (300 mg/kg/day) reduced the number of skin tumor cells compared to vehicle control group (P&lt; 0.05). Tranilast treatment did not block angiogenesis or lymphangiogenesis in the xenograft model. These results indicate that tranilast has antiproliferative effects independent of mTORC1 and suggest that tranilast may be useful as an adjunctive agent for the treatment of TSC skin tumors.
Citation Format: Shaowei Li, Ji-an Wang, Rajesh L. Thangapazham, Peter Klover, Joel Moss, Thomas N. Darling. Tranilast inhibits growth of skin tumor cells in a xenograft mouse model of tuberous sclerosis complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5510. doi:10.1158/1538-7445.AM2013-5510
Abstract 5516: (R,R’)-4’-methoxy-1-naphthylfenoterol Inhibits GPR55 signaling and the modulation of motility in human cancer cells.
Authors: Paul Rajib K. , Wnorowski Artur , Gonzalez-Mariscal Isabel , Moaddel Ruin , Indig Fred E. , Wainer Irving W. , Bernier Michel 
Published: August 2014

Abstract
(R,R’)-4’-methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR) activation. The synthetic CB1R inverse agonist, AM251, has been shown to block the anti-mitogenic effect of MNF in these cells; however, AM251 is also an agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose upregulation contributes to carcinogenesis. Here, we investigated the role of GPR55 in MNF signaling in human HepG2 and PANC-1 cancer cell lines in culture, with a focus on internalization of the fluorescent ligand Tocrifluor 1117 (T1117), reorganization of actin cytoskeleton, and cell motility as measured by scratch assay. Control experiments indicated that GPR55 knockdown by RNA interference markedly reduced cellular uptake of T1117, a process that was sensitive to MNF inhibition. GPR55 internalization mediated by the atypical cannabinoid O-1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2 and PANC-1 cells with MNF significantly abrogated the induction of ERK phosphorylation in response to AM251, O-1602 and fetal bovine serum, known to contain bioactive lipids. Moreover, MNF exerted a coordinated regulation of AM251 and O-1602 inducible processes, including cell motility. This study shows for the first time that MNF impairs GPR55-mediated signaling and, therefore, may have therapeutic potential for the management of cancer. This work was supported entirely by the Intramural Research Program of the NIA, NIH.
Citation Format: Rajib K. Paul, Artur Wnorowski, Isabel Gonzalez-Mariscal, Ruin Moaddel, Fred E. Indig, Irving W. Wainer, Michel Bernier. (R,R’)-4’-methoxy-1-naphthylfenoterol Inhibits GPR55 signaling and the modulation of motility in human cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5516. doi:10.1158/1538-7445.AM2013-5516
Abstract 5519: In vivo fluorescence lifetime imaging differentiates the bound versus unbound status of a cell surface receptor targeted ligand.
Authors: JeuneSmith Yoli , Cohen Allison S. , Tafreshi Narges K. , Vagner Josef , Gillies Robert , Morse David 
Published: August 2014

Abstract
In vivo fluorescence lifetime imaging allows for the isolation of probe-specific fluorescence lifetime from surrounding tissue auto-fluorescence. Fluorescence lifetime is not affected by agent concentration or depth, or image acquisition parameters. However, fluorescence lifetime can be affected by the in vivo tissue microenvironment, e.g. pH or hypoxia. In this work, fluorescence lifetime is used to characterize the presence and fate of a high-affinity peptidyl delta opioid receptor (δOR) ligand conjugated to the near-infrared fluorescent IRDye800CW (Li-Cor).
HCT116 colorectal cancer cells engineered to over-express the δOR and parental non-expressing HCT116 cells were bilaterally xenografted subcutaneously into the flanks of athymic nude mice. At a series of time-points following tail vein injection of the ligand, in vivo fluorescence images images were acquired using the Optix MX3 scanner (Advanced Research Technologies).
For 24 h, the ligand fluoresence lifetime was significantly different (p&lt;0.05) in the δOR positive tumors relative to the negative tumors. At 48 hours, the fluorescence lifetime in the negative tumor decreased and was no longer different. We hypothesize that the early difference in fluorescence lifetime is attributed to the bound state of the ligand on receptor positive tumors relative to the unbound state in negative tumors. Over time, unbound ligand clears from the negative tumor leaving only a low concentration of ligand retained by non-specific interactions.
In vitro studies demonstrated that the fluoresecence lifetime of this ligand is not altered within the biological pH range. However, the tumor microenvironment is complex and multiple factors may be influencing the observed differences. Future plans include studies of 3D cell cultures using varied microenvironmental conditions and studies on δOR endogenous cell lines.
Citation Format: Yoli JeuneSmith, Allison S. Cohen, Narges K. Tafreshi, Josef Vagner, Robert Gillies, David Morse. In vivo fluorescence lifetime imaging differentiates the bound versus unbound status of a cell surface receptor targeted ligand. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5519. doi:10.1158/1538-7445.AM2013-5519
Abstract 5520: Novel therapy NKP-1339 is active in osteosarcoma.
Authors: Park Amy Y. , Sowers Rebecca , Thein Sajida , Baerga Rebecca , Gorlick Richard 
Published: August 2014

Abstract
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults. Despite significant advancements in the diagnosis and treatment of OS, overall survival trends have remained stagnant with conventional chemotherapy. New chemotherapeutic agents and combination regimens are being studied to target pathways that are believed to be active in OS. NKP-1339 is a novel small molecule anti-cancer compound that targets the GRP78 pathway. A NKP-1339 single agents Phase I has been completed [1]. GRP78 is a master regulator of endoplasmic reticulum stress. High GRP78 levels are found in a wide variety of cancer types and have been correlated with tumor proliferation, metastasis, angiogenesis and tumor cell survival. Treatment with anti-cancer agents, both cytotoxic and targeted agents, has been shown to give rise to further induction of GRP78, and such elevation been correlated to resistance. NKP-1339 down-regulates GRP78 levels selectively in tumor cells leading to tumor cell death. In this study, we explore NKP-1339 activity against OS cell lines. In vitro cytotoxicity assays were performed with NKP-1339, as a single agent, on both standard and patient derived OS cell lines. Three out of four standard cell lines (75%) and two out of four patient derived cell lines (50%) showed IC50 of 80-100 uM. These results, in terms of uM range and activity against tumor lines that are resistant to other agents, are consistent with previous in vitro studies of NKP-1339 with other tumor types. The IC50 uM levels of NKP-1339 are achievable in patient plasma. In vitro combination studies are underway to determine the synergistic anti-tumor effects of NKP-1339 with standard chemotherapeutic agents used in OS. Future studies will include treatment of OS xenograft models with NKP-1339 as a single agent and in combination, and if promising, an OS clinical trial will be initiated.
[1] Thompson et al. ASCO 2012 abstract #3033
Citation Format: Amy Y. Park, Rebecca Sowers, Sajida Thein, Rebecca Baerga, Richard Gorlick. Novel therapy NKP-1339 is active in osteosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5520. doi:10.1158/1538-7445.AM2013-5520
Abstract 5531: A bioluminescent cell viability assay optimized for 3D microtissues.
Authors: Valley Michael P. , Zimprich Chad , Cali James J. , Lazar Dan F. 
Published: August 2014

Abstract
It has been well demonstrated that the morphology, gene expression, and overall biological response of cells assessed in 3-dimensional (3D) culture models are frequently more physiologically relevant than that of cells studied in standard 2D culture formats. In spite of rapidly growing interest, one hindrance to the use of 3D models for drug discovery and other research efforts is the lack of convenient and effective assays explicitly validated for application to 3D microtissues. Here we report on a bioluminescent ATP-detection assay comprised of both an improved formulation and an optimized protocol specifically designed to measure the viability of cells grown in 3D culture. The ability of the 3D-optimized reagent to effectively lyse cells from throughout the full thickness of 3D microtissues, including cancer cell spheroids, was clearly demonstrated by use of confocal laser fluorescent microscopy in conjunction with a fluorogenic, membrane-impermeant DNA-binding dye. Importantly, the assay's ability to accurately report the ATP content, and therefore viability, of various 3D microtissues (including a range of cancer cell line spheroids) was demonstrated by comparison to a trichloroacetic acid ATP extraction method. In scaffold-free as well as scaffold-dependent 3D models, recovery and detection of greater than 80% of ATP present was routinely observed. In contrast, another frequently used ATP-detection assay was found to have greatly reduced lytic and ATP detection properties (&lt;50% recovery). This new, homogeneous 3D-assay format requires minimal sample manipulation, a brief incubation period (generally less than 30 min), and exhibits excellent sensitivity. It should be amenable to both low- and high-throughput applications and accurately report drug sensitivities of cells assayed in both 2D and 3D culture models.
Citation Format: Michael P. Valley, Chad Zimprich, James J. Cali, Dan F. Lazar. A bioluminescent cell viability assay optimized for 3D microtissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5531. doi:10.1158/1538-7445.AM2013-5531
Abstract 5536: NAD+ Kinase inhibition synergizes with ROS-inducing chemotherapies.
Authors: Tedeschi Philip M. , Kerrigan John , Banerjee Debabrata , Bertino Joseph R. , Abali Emine E. 
Published: August 2014

Abstract
Background: NAD+ kinase (NADK) is at present the only known enzyme that converts NAD+ to NADP+, which is subsequently reduced to NADPH. The demand for NADPH in cancer cells is elevated as reducing equivalents are required for the high levels of nucleotide, protein and fatty acid synthesis found in proliferating cells, as well as for neutralizing high levels of reactive oxygen species (ROS) present in these cells. The aim of this study was to determine whether inhibitors of NADK synergize with chemotherapeutic drugs known to induce ROS.
Methods: Using a NADK inhibitor our group previously identified, thionicotinamide adenine dinucleotide phosphate (NADPS), (Mol Pharmacol., in press), we explored combinations of NADPS with various classes of drugs known to induce ROS: tubulin inhibitors (docetaxel, paclitaxel, vinblastine), a nucleoside analog (gemcitabine), topoisomerase I and II inhibitors (irinotecan and doxorubicin, respectively), and a DNA crosslinking agent (cisplatin). Fixed ratios of NADPS and the combination drug based on their EC50 values were tested in a colon cancer cell line (C85) using a MTS assay. The combination index (CI) was determined by the Chou-Talalay method for drug combination based on the median effect analysis.
Results: All drugs were found to synergize with NADPS. Knockdown of NADK with siRNA or inhibition of NADK by NADPS in combination with MTX revealed equivalent efficacy. Quantification of intracellular NADPH and ROS levels are currently underway.
Conclusions: NADK inhibitors along with drugs that increase ROS- mediated stress may represent an efficacious antitumor combination and should be explored further against in vivo tumor models.
Citation Format: Philip M. Tedeschi, John Kerrigan, Debabrata Banerjee, Joseph R. Bertino, Emine E. Abali. NAD+ Kinase inhibition synergizes with ROS-inducing chemotherapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5536. doi:10.1158/1538-7445.AM2013-5536
Abstract 5553: Development of novel selenium-NSAIDs as potential cancer therapeutics.
Authors: Plano Daniel , Karelia Deepkamal , Pandey Manoj , Amin Shantu , Sharma Arun K. 
Published: August 2014

Abstract
Several non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents in both pre-clinical and clinical studies on various cancer types. Here in, we developed several selenium (Se)-NSAID hybrid molecules and evaluated their efficacy as cancer therapeutics. The rationale for introducing Se into the NSAIDs is that this redox-active trace element is an essential micronutrient and a normal component of diets with chemopreventive and anticancer properties. Our recent studies have also shown that appropriately designed organoselenium compounds exhibited promising anti-tumor properties in various preclinical cancer models. We hypothesized that the rational incorporation of Se into NSAIDs should enhance their anti-cancer properties and therefore, we synthesized 16 novel Se-NSAID hybrid agents designed by incorporating Se moieties into the structures of aspirin, ibuprofen, and naproxen. In the first phase, a selenocyanate moiety was incorporated to these NSAIDs and screened for their cytotoxicity in various cancer cell lines. The cell viability results at 24 and 48 h showed that the introduction of this Se functionality on aspirin scaffold achieved a dramatic increase in the activity as compared to aspirin, as well as other NSAIDs or their Se hybrids. Thus, we continued optimization of aspirin with a variety of Se moieties, such as selenides and selenomethyl functionalities. Most of these compounds reduced cell viability in a dose dependent manner, while aspirin had no significant effect. Based on these studies we identified two Se-aspirin hybrid compounds; ASD-43, having a selenide functionality and ASD-49, with a selenocyanate functionality, as the most potent compounds for further development. The IC50 values after 48 h treatment in HCT116 cells were 2.5μM and 1.0 μM and in MiaPaCa-2 cells were 5.0 μM and 2.5 μM for ASD-43 and ASD-49, respectively. To further establish the cytotoxic potential of these compounds, an esterase staining (live and dead) assay was performed in colon (HCT116) and pancreatic (MiaPaCa-2) cancer cells. Treatment of ASD-43 and ASD-49 reduced cell viabilities dose dependently in both HCT116 and MiaPaCa-2 cells, while aspirin had no significant effects. In addition, both these compounds induced caspase-mediated PARP cleavage as early as 24 h in HCT116 cells. In conclusion, new Se-NSAID hybrid agents have been developed which showed a solid potential to be effective cancer therapeutics in our initial studies. Detailed results of these investigations will be presented.
Citation Format: Daniel Plano, Deepkamal Karelia, Manoj Pandey, Shantu Amin, Arun K. Sharma. Development of novel selenium-NSAIDs as potential cancer therapeutics. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5553. doi:10.1158/1538-7445.AM2013-5553
Abstract 5557: BoxA and ethyl pyruvate offer novel therapeutic approaches for human malignant mesothelioma.
Authors: Jube Sandro L. , Rivera Zeyana , Casalgrandi Maura , Bianchi Marco , Pass Harvey I. , Gaudino Giovanni , Carbone Michele , Yang Haining 
Published: August 2014

Abstract
Human malignant mesothelioma (MM) is an aggressive and highly lethal cancer that has been linked to asbestos and erionite exposure. MM causes about 3,000 deaths per year in the US and more than 100,000 deaths per year worldwide. We previously found that the damage-associated molecular pattern (DAMP) high-mobility group box-1 protein (HMGB1) plays a critical role in the early carcinogenic events in MM development by inducing tumor necrosis factor-alpha (TNF-α) secretion, potentiating survival of fiber-exposed primary human mesothelial cells (HM) and enabling HM malignant transformation. We recently showed that HMGB1 is upregulated in MM tumor tissues and cell lines and its levels to be significantly higher in the blood of MM patients compared to healthy individuals. Moreover, MM cells are “addicted” to HMGB1 and HMGB1 promotes proliferation, viability, motility and invasiveness of MM cells. Here we show that the use of the HMGB1 antagonists BoxA or ethyl pyruvate (EP) inhibit the motility, survival and progression of MM cells in vitro and reduce the growth of MM xenografts in SCID mice. BoxA is a fragment of HMGB1 protein that corresponds to the one of the two highly conserved DNA binding domains, and behaves as a competitive inhibitor. EP is the ethyl ester of pyruvic acid, is known to suppress oxygen radical formation, and suppresses HMGB1 secretion. Both BoxA and EP have been shown to down-regulate the activation of the proinflammatory transcription factor, NF-κB, as well as the expression of several proinflammatory proteins, such as TNF-α, IL-6, and HMGB1 itself. Taken together, our results provide a preclinical proof-of-principle that inhibition of HMGB1 activity using either BoxA or EP is sufficient to elicit therapeutic activity, offering novel therapeutic approaches for MM treatment.
Citation Format: Sandro L. Jube, Zeyana Rivera, Maura Casalgrandi, Marco Bianchi, Harvey I. Pass, Giovanni Gaudino, Michele Carbone, Haining Yang. BoxA and ethyl pyruvate offer novel therapeutic approaches for human malignant mesothelioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5557. doi:10.1158/1538-7445.AM2013-5557