bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5563: The anti-cancer and anti-hyperlipidemia effects of triterpenoids from Gynostemma pentaphyllum in the Apcmin/+ mouse model
Authors: Tai William Chi-Shing , Wong Wing Yan , Wang Yu , Hsiao Wen-Luan Wendy 
Published: February 2011

Abstract
Apcmin/+ mice, a commonly used mouse model for colorectal cancer, manifest both high number of intestinal polyps and hyperlipidemia, which make the min/+ mouse an ideal animal model for drug intervention studies for both hyperlipidemia and colorectal cancer Triterpenoids, produced in many plants, are widely used in Asian medicine. Gynostemma pentaphyllum (Gp), also called jiaogulan, is a rich source of dammarane-type triterpenoids and is used as a traditional Chinese herbal medicine for the treatment of various diseases including cancer and hyperlipidemia. However, the proven efficacy and the underlying mechanism have not been investigated systematically. Using the Apcmin/+ mouse as the animal model, treatment with Gp total triterpenoids (GpMix) markedly reduce the numbers and sizes of polyps. In conjunction with 5-fluorouracil (5-FU), the size and numbers of polyps of the treated animals were further reduced. Besides the anti-cancer effect of GpMix, we have also shown that the GpMix can effectively suppress the plasma triglycerides and cholesterol levels in Apcmin/+ mice. To delineate the precise mechanisms of the anti-cancer and anti-hyperlipidemia effects of GpMix, we performed molecular and proteomic analysis of the plasma obtained from animals treated with and without GpMix.
Results showed that lipoprotein lipase, PPARα and adiponectin are upregulated and HMG-CoA reductase is down-regulated upon GpMix treatment. Plasma protein profiling revealed that several downregulated proteins are directly related to cancer, inflammatory, cell proliferation, including serum amyloid A1 and A2, serum amyloid P-component, major urinary proteins, glutathione peroxidase 3, complement C3 and serotransferrin. In the same treated animals, four lipogenesis proteins including apolipoprotein A-I, apolipoprotein A-II, apolipoprotein A-IV, and apolipoprotein C-III by which the activity of lipoprotein lipase is tightly regulated are downregulated. These protein profiling data, together with the adipocyte-specific signaling data shown above provide solid evidence of the anti-cancer and anti-hyperlipidemia effects of GpMix. [This study was financially supported by Research Grants Council of Hong Kong under HKBU2/07C and FRG/07-08/II-50 and FRG/08-09/II-61 Grants to WLWH.]
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 5563.
Abstract 5565: Quantitative proteomics identifies phosphorylation targets, modulators and pathway signatures of oncogenic RAS-mediated MAPK signaling in lung adenocarcinoma
Authors: Sudhir Putty-Reddy , Hsu Chia-Lang , Wang Yi-Ting , Sung Ting-Yi , Hsu Wen-Lian , Chen Yu-Ju , Yang Ueng-Cheng , Chen Jeou-Yuan 
Published: February 2011

Abstract
Functional phosphoproteomics is applied to gain the molecular insights into oncogenic RAS-mediated signaling pathway in lung adenocarcinoma. By means of immobilized metal affinity chromatography, mass spectrometry and a robust label-free quantitative system, we compared the phosphorylation profiles of five cell lines including immortalized normal human bronchial epithelial cells (HBECs) (wt KRAS), 3KTR (KRASG12V-transfected HBECs), A549 (KRASG12D), H322 (amplified KRAS), and H1299 (NRASQ61K). This resulted in the quantification of 1508 phosphorylation events and detection of regulated events across the cell lines. NetworKIN analysis of 2-fold regulated events (n=77) induced by oncogenic RAS in HBECs revealed 20 novel site-specific phosphorylation targets of MAP kinases. By browsing through STRING database, we identified 44 known substrates of MAP kinases in the interactome of phosphoproteins in this study. Further analysis of the site-specific upstream kinases of regulated phosphorylation events revealed the significant increase in basal kinases such as PAK, AKT/PKB and PKA in H1299 (large cell carcinoma) relative to A549 and H322 (adenocarcinoma). This increase in basal kinases may in-turn modulate the output of RAS-mediated MAPK signaling in large cell carcinoma cells (H1299). Supporting these results, majority of the regulated phosphorylation events (n=77) including MAPK, identified in HBECs expressing oncogenic RAS, were also differentially regulated in A549 and H322 but not in H1299. Further, inferring pathway signatures by integrating expression data of phosphorylation profiles to pathway interaction database, revealed the activation of MAPK signaling in 3KTR, A549 and H322 but not in H1299, whereas the activation of AKT and inactivation of mTOR signaling in H1299. Taken together, we demonstrate the phosphorylation targets, molecular regulation, and pathway activity signatures of onogenic RAS-mediated MAPK signaling in lung adenocarcinoma. Furthermore, the method introduced here to infer the pathway signatures is adaptable for future studies.
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 5565.
Abstract 5570: An affinity lectin chromatography approach to characterize N-linked glycoproteome in metastatic osteosarcoma
Authors: Flores Ricardo J. , Li Yiting , Lau Serrine S. , Leung Eastwood , Lau Ching C. , Man Tsz-Kwong 
Published: February 2011

Abstract
Osteosarcoma (OS) is the most common bone cancer in children and adolescents. Approximately 20% of OS patients have clinically detectable metastasis at the time of diagnosis, which is the most consistent indicator of poor outcome. Therefore, an easy-to-use and sensitive method is urgently needed to detect and monitor metastatic patients in order to offer an intensified or personalized therapy. By analyzing glycoproteins in OS cells, we may identify biomarkers that would help detect early metastasis and shed light on how this cancer develops. Thus, we used a tumor-targeted glycoproteomic approach in order to identify metastasis-associated glycoproteins in OS cells, and test if these can be used as blood biomarkers to indicate metastasis or spread of disease at diagnosis. In this pilot study, we have analyzed a previously established human OS metastatic cell line (LM7). We captured a specific subset of N-linked glycoproteins from LM7 cells by Wheat Germ Agglutinin (WGA) affinity chromatography. Subsequently, we identified the captured glycoproteins by a multidimensional protein identification technology (MudPIT). In addition, two samples with or without PNGase treatment were tested to estimate the impact of protein glycosylation on the MS/MS analysis. A total of 121 and 368 unique peptides were identified in the non-treated and PNGase treated samples, respectively. All of the proteins identified with two or more distinct peptides were predicted to have potential N-linked glycosylation sites, and 57% of these were found to have one or more typical Asn-X-Ser/Thr N-glycosylation sites. Many of the identified glycoproteins are known to be involved in tumorigenesis. To this end, we have optimized the affinity lectin chromatography and mass spectrometry to capture and identify N-linked glycoproteins in metastatic osteosarcoma cells. Differentially expressed glycoproteins in metastatic OS will be further identified by comparing LM7 with a non-metastatic control. The candidate biomarkers will be validated in the plasma and tumor samples collected from OS patients.
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 5570.
Abstract 5571: Identification of autoantibody biomarkers in metastatic osteosarcoma using a high-density protein microarray approach
Authors: Li Yiting , Yu Alexander , Okcu Fatih , Hicks John , Chintagumpala Murali , Lau Ching C. , Man Tsz-Kwong 
Published: February 2011

Abstract
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. A leading cause of death in OS is the development of metastasis. Therefore, it is important to detect metastatic patients as early as possible, so these patients can be stratified and treated while the disease is still in its early stages and potentially curable. Autoantibodies represent a promising class of plasma proteins that can be used for the early detection of cancer. These immunoglobulins can recognize aberrant proteins in the tumor cell during the development of metastasis. We have used a new high-density protein microarray platform, ProtoArray Human Protein Array (HPA), to identify significant autoantibody biomarkers that are associated with metastatic OS at the time of diagnosis. ProtoArray HPA consists of over 8,000 purified human proteins from different functional classes. Plasma samples from metastatic and localized OS patients, and children with non-cancerous diseases were analyzed by the microarrays. The results showed that the amounts of 136 distinct autoantibodies were significantly different between the plasma samples of metastatic and localized OS cases (p &lt; 0.01). Among these autoantibodies, 66 were higher while 70 were lower in metastatic patients. Two of these autoantibodies, which target CTTN and PFKFB1, were selected for further investigation. We found that the phosphorylated form (p85) of the CTTN protein in two metastatic OS cell lines was expressed higher relative to the non-metastatic parental cells. This result is consistent with the previous finding that increased phosphorylation of CTTN is important for the metastatic phenotype of cancer cells. The PFKFB1 autoantibody in the localized patients was higher than the metastatic patients; however, both groups of OS patients had a higher PFKFB1 level relative to the control group. When compared to normal osteoblasts, Western blotting showed that PFKFB1 protein was overexpressed in seven of the eight OS cell lines. PFKFB1 is involved in the Warburg effect, which is important to the energy metabolism of cancer cells. Our results suggest that the high-density protein microarray approach is useful for identifying metastasis-associated autoantibodies in cancer patients. Further validation and investigation of the candidate autoantibody biomarkers may lead to discovery of novel biomarkers and unravel the underlying mechanism in metastatic OS.
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 5571.
Abstract 5574: Altered glycerophospholipid metabolism in non-small cell lung carcinoma
Authors: Hoang Chuong D. , Wu Manhong , Xu Yue , Merrit Robert , Whyte Richard , Shrager Joseph , Peltz Gary 
Published: February 2011

Abstract
Objective: It is hypothesized that accumulation of specific metabolites precedes morphologic changes in human lung tumors during malignant transformation, and that this may be exploited to develop a lung cancer biomarker.
Methods: We performed metabolomic profiling on 24 fresh-frozen specimens from patients with biopsy proven lung adenocarcinoma. The following tissues from each of the patients were analyzed: tumor, adjacent-to-tumor tissues, and normal lung. The metabolites were extracted by a methanol chloroform technique and separated by high resolution liquid chromatography. They were analyzed using the 6520 hybrid quadrupole time-of-flight mass spectrometer (Agilent). Mass Profiler Professional software (Agilent) was used for statistical analysis and metabolite profiling. To identify a metabolite of interest, the retention time and elemental composition data were searched against databases: METLIN Personal Metabolite (Agilent). After multiple data filtering steps we derived a non-small cell lung carcinoma-specific metabolomic fingerprint. We performed metabolic network analysis to assess which gene(s) may be associated with the metabolomic biosignatures.
Results: We detected an average of 2232 unique metabolites in the tumor specimens, 1795 in the adjacent-to-tumor specimens, and 1613 in the normal lung. When tumor and normal lung samples were compared, 201 metabolites were significantly over-expressed and 105 were under-expressed in the tumor tissue. The metabolic biosignature for the tumor group was highly distinct from the other lung regions (several fold change). The metabolites within the tumor-specific signature included the following families: lactate, amino acids, phospholipids, eicosanoids, and glycine derivatives. In particular, multiple phosphatidylethanolamines showed dramatic differential expression in tumor tissues compared to normal lung. Metabolic network analysis suggests that the altered metabolite levels could affect critical cellular functions, including: cell signaling, growth and invasiveness.
Conclusion: Metabolomic analysis has identified metabolites that were uniquely found in human lung adenocarcinomas. The specific metabolic biosignature of lung adenocarcinoma could suggest novel biomarkers that could be used for diagnosis, as well as suggest altered molecular pathways contributing to the pathogenesis of lung cancer.
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 5574.
Abstract 5577: Global analysis of protein kinase activity during hematopoietic differentiation
Authors: Nomanbhoy Tyzoon K. , Ng Dana M. , Patricelli Matthew P. 
Published: February 2011

Abstract
Cell proliferation and differentiation are highly regulated processes, and the deregulation of these processes can lead to a number of diseases including cancer. Protein kinases are key regulators of cell proliferation and differentiation, and consequently, potential targets for a number of oncology indications. A detailed understanding of the changes in kinase activity/expression during cell proliferation and differentiation may be one of the keys to the identification of novel biomarkers and targets for the diagnosis and treatment of these diseases. The HL-60 cell line is promyeloblastic, and protocols for the differentiation of these cells into either macrophages by 12-O-tetradecanoylphorbol-13-acetate (PMA), or granulocytes by retinoic acid (RA) are well-established. Importantly, HL-60 cell differentiation is a model system for the treatment of myelocytic leukemia, and identifying the mechanisms that induce terminal differentiation of these cells may reveal effective targets for treatment of this disease. With this in mind, we evaluated the kinase activity and expression profiles of HL-60 cells throughout the differentiation process using desthiobiotin acyl phosphate ATP and ADP probes and liquid chromatography-mass spectrometry. Greater than 150 protein kinases in resting, RA, and PMA HL-60 cells were analyzed. Significant changes in activity/expression were seen for a number of protein kinases in both differentiation pathways. These changes in kinase activity were generally consistent with changes in protein expression levels, as determined by Western blot. In both RA and PMA-induced HL60 differentiation, the kinetics for the changes in activity of the kinases was determined, and the results suggest that there is a well-defined sequence during which these changes occur. In summary, using activity based protein profiling, we identified a subset of kinases whose activity changed significantly during RA and PMA-induced HL-60 differentiation. Importantly, this methodology is widely applicable to other cellular systems and disease models, and has applications in the identification of biomarkers and targets for the management of these diseases.
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 5577.
Abstract 5579: Novel proteins highly expressed in tumor identified by a high throughput immunoproteomic approach
Authors: Grifantini Renata Maria , Pileri Piero , Pierleoni Andrea , Campagnoli Susanna , Grandi Alberto , Nogarotto Renzo , Parri Matteo , Canidio Elena , Cattaneo Davide , Pagani Massimiliano , Camilli Elisa De , Abrignani Sergio , Grandi Guido , Viale Giuseppe , Sarmientos Paolo 
Published: February 2011

Abstract
Cancer biomarker discovery is an extremely active research track in both academia and pharma industries. Several high throughput technologies were applied through the years to identify proteins specifically related to cancerous phenotype. However, most putative biomarkers identified from conventional proteomic/transcriptomic strategies still need to be clinically validated. Here we present a cancer biomarker discovery approach based on the use of a large library of antibodies raised against recombinant human proteins to detect tumor-associated proteins by immune-histochemistry analysis of clinical tumor tissues. Starting from the whole human genome, genes encoding proteins predicted as membrane- or secreted were selected and high through-put cloned and expressed. Recombinant proteins were used to build a polyclonal antibody library (YOMICS®) currently comprising more than 1700 murine immune sera. The ability of sera to recognize specific targets predominantly present in tumors was assessed by Tissue MicroArray (TMA, a miniaturized immunohistochemistry analysis) of tumor tissue samples and healthy controls from pedigreed patients affected by the most common human tumor types, including colon, ovary, breast, lung, ovary and prostate cancers.
While the screening is still in progress, six antibodies were identified showing high reactivity on a high percentage (ranging from 40 to 95%) of tumor tissues on one or more cancer type, with negative staining on normal tissues. The corresponding protein targets, being novel tumor-associated proteins, were validated and characterized at cellular and molecular level by analyzing their expression, cellular localization and biological role in a panel of tumor cell lines. Interestingly, two of the six proteins are localized at the plasma membrane, while the other proteins are intracellular. Data so far available indicate that one of the six proteins confers an invasive phenotype to tumor cell lines. The newly identified proteins are promising candidates as new biomarkers and could be exploited to develop target-specific drug therapies.
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 5579.
Abstract 5584: DNA vaccine encoding prostatic acid phosphatase (PAP) elicits long-term T-cell responses in patients with recurrent prostate cancer
Authors: Becker Jordan T. , Johnson Laura E. , McNeel Douglas G. 
Published: February 2011

Abstract
Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer, and several clinical trials have used this as a tissue-specific target for anti-tumor vaccines. Ultimately the goal of anti-tumor vaccines is to elicit a sustainable immune response able to eradicate a tumor or at least restrain its growth. We have investigated plasmid DNA vaccines encoding PAP and have previously reported the results of a phase I trial in which 22 patients with biochemically recurrent prostate cancer (clinical stage D0) were immunized six times at biweekly intervals using a DNA vaccine encoding PAP (pTVG-HP). In previous reports we identified that PAP-specific T-cells were elicited, including PAP-specific cytolytic T cells, two weeks following the six immunizations. In the current study we investigated the immunological efficacy of subsequent booster immunizations in two individuals, and conducted more detailed immunological analysis by IFNγ ELISPOT and T cell proliferation, with cells obtained prior to immunization, after every two immunizations, and quarterly for one year following immunization. These studies were conducted to determine when immune responses were elicited, and whether these responses were durable over time, to guide the schedule of vaccine administration to be used in future clinical trials with this particular DNA vaccine. We found that the majority of immune responses elicited with vaccination were only detectable after four to six immunizations. In addition, PAP-specific T-cell responses did persist in several individuals for many months, or were detectable only after several months. Finally, we identified that immune responses previously elicited could be further amplified by subsequent booster immunizations months later. These results suggest that future trials using this DNA vaccine, and potentially other anti-tumor DNA vaccines, should investigate ongoing, rather than limited, schedules of administration with periodic booster immunizations. Moreover, these results suggest that DNA vaccines targeting PAP could potentially be combined with other vaccine strategies targeting this particular antigen to augment PAP-specific T-cell immunity. A pilot trial to evaluate different schedules of DNA vaccine administration for the establishment of persistent PAP-specific memory T cells is currently underway.
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 5584.
Abstract 559: Human ovarian cancer mesenchymal stem cells demonstrate abnormal BMP signaling and promote tumorigenesis
Authors: Buckanovich Ronald J. , McLean Karen , Silva Ines , Gong Yusong , Pennington Kathryn 
Published: February 2011

Abstract
Numerous recent reports indicate a critical role for MSC in solid tumor growth. Unfortunately, very little is known about human solid tumor associated MSC. We analyzed over 15 samples of primary ovarian tumors for the presence MSC. MSC were isolated from over 90% of these samples. These cells had the morphologic appearance of CFU-F (colony forming unit-fibroblastic), a normal karyotype, and were non-tumorigenic. Phenotypic characterization of these cells indicates they express the surface markers normally associated with MSC; they express traditional MSC markers including SH2, SH3, and CD90, and do not express hematopoietic markers such CD34, CD14, or CD4. Functional characterization demonstrates that these cells are multipotent, capable of differentiating into adipose, cartilage, and bone. However, ovarian cancer-derived MSC appear to be somewhat less efficient at differentiation than the healthy donor control MSC. When combined with tumor cells in immune deficient mice, the promotion of tumor growth by ovarian cancer associated MSC was significantly greater than that seen with healthy donor control MSC. Gene expression analysis demonstrated that cancer associated MSC have significantly altered BMP family member expression. These studies suggest that cancer associated MSC are unique from their healthy tissue associated counterparts and play a critical role in cancer cell growth.
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 559.