bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1287: Profile-related evidence to determine individualized cancer therapy (PREDICT): Preliminary results of the Personalized Phase I Clinical Trials program at MD Anderson Cancer Center
Authors: Tsimberidou Apostolia Maria , Hong David S. , Wheler Jennifer J. , Fu Siqing , Piha-Paul Sarina , Naing Aung , Falchook Gerald S. , Luthra Raja , Iskander Nancy G. , Wen Sijin , Kurzrock Razelle 
Published: June 2012

Abstract
Introduction: To assess the outcomes of molecularly targeted therapy, we analyzed the results of mutational analyses in patients seen in our Phase I clinic and assessed patient survival by the number of mutations in patients treated with and without matched targeted therapy. Methods: Mutational analysis was mostly performed in the CLIA-certified pathology laboratory. DNA was extracted from microdissected paraffin-embedded tumor samples. The following genes were analyzed: PIK3CA (exon 9: codons 532-554; exon 20: codons 1011-1062); BRAF (exon 15: codons 595 to 600); KRAS and NRAS (codons 12, 13, 61); EGFR (exons 18 to 21, kinase domain); KIT (exons 9, 11, 13, 17); and RET (exon 10: codons 609, 611, 618, 620; exon 11: codon 634; exon 16: codon 918). The loss of the tumor suppressor nuclear protein (PTEN) was determined by immunohistochemistry. The allocation of patients to clinical trials varied according to protocol availability; eligibility; patient's prior response to therapy, toxicity and preference; and physician's choice. Patients whose tumor had a mutation were preferably treated with a matched targeted agent. Survival was compared between patients treated with and without matched targeted therapy. Results. Of 849 patients who had tissue available, 354 (41.7%) had ≥ 1 mutation (1, n=313; 2, n=38; 3, n=3) (Table 1). The median survival of patients with 0 vs. 1 vs. 2-3 mutations was 9.4 vs. 11.7 vs. 7.3 months, respectively (p =0.02; Table 2). In 278 evaluable patients with 1 mutation, the 2-yr survival rates were 42% and 17% (p = 0.02) for patients treated with and without matched targeted therapy. Conclusion: In patients with 1 mutation, treatment with matched targeted therapy was associated with superior survival compared to treatment without matching. Patients with 1 mutation had longer survival than those with no or &gt;1 mutation, perhaps because most of them were treated with a matched targeted therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1287. doi:10.1158/1538-7445.AM2011-1287
Abstract 1401: SYK promotes tumor progression in ovarian cancer cell lines
Authors: Sultan Aya , Wang Cindy Y. , Duran George E. , Francisco E. Brian , Berek Jonathan S. , Sikic Branimir I. 
Published: June 2012

Abstract
Identification of novel drug targets in ovarian cancers has focused on expression of genes in the tyrosine kinase family. We have previously shown that the spleen tyrosine kinase (SYK) gene was expressed in 73% of 55 ovarian cancer specimens, compared to 26% of 60 breast cancer specimens. Previous studies established the role of SYK in tumor progression. Among its many targets, SYK can bind microtubules and other molecules associated with the cytoskeleton. We found SYK to be expressed in 6 of 10 ovarian carcinoma cell lines. Because of the ability of SYK to bind to microtubules, we studied the relationship of SYK expression to cellular migration. We examined several ovarian cancer cell lines that variably express SYK to elucidate the potential effects of SYK on cell migration. Our results demonstrate that knockdown of SYK expression by siRNA resulted in a decreased capability of cells to migrate using a traditional wound scratch assay. The duration of this effect was dependant upon cell line used suggesting that additional protein targets may be involved in the migratory process. The potential effects of SYK expression on invasion are currently being investigated. We will evaluate potential upstream and downstream targets to elucidate the pathway(s) responsible for SYK effects and compare within the cell lines examined. Understanding the growth signals and proteins potentially responsible for invasion and metastasis in ovarian cancer cell lines and tumor samples may eventually lead to new therapeutic approaches for ovarian cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1401. doi:10.1158/1538-7445.AM2011-1401
Abstract 1416: Development and initial evaluation of the antitumor activity of a functionalized benzophenone thiosemicarbazone inhibitor of cathepsin L
Authors: Trawick Mary Lynn , Pinney Kevin G. , Chaplin David J. , Horsman Michael R. , Chavarria Gustavo E. , Arispe Wara M. , Kishore Kumar G. D. 
Published: June 2012

Abstract
The discovery of new chemotherapeutic strategies for inhibiting the growth and spread of cancer represents an important goal in the effort to enhance both cancer patient quality of life and survival. Cysteine cathepsins are a family of lysosomal proteases that are often upregulated in a variety of cancers and have been implicated in key processes in cancer progression. Our focus has centered on the development of novel non-peptidic inhibitors of cathepsin L. Small molecule inhibitors of the cysteine protease cathepsin L have the potential to limit degradation of extracellular matrix in the normal tissue surrounding the tumor thus retarding cancer metastasis. It has also been established that cathepsin L is involved in blood vessel development and thus inhibitors have the potential to suppress tumor growth and dissemination through an antiangiogenic effect. We have recently reported the synthesis of a series of functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives several of which are potent inhibitors of cathepsin L with activity in the nM range while exhibiting IC50 values greater than 10 micromolar for cathepsin B. In addition, selected compounds were found to inhibit the migration, and invasion of DU-145 prostate cancer cells through Matrigel. Initial evaluation of the in vivo activity of the lead compound, designated KGP94, has been undertaken in a C3H mammary carcinoma. We have evaluated the effects of five daily doses of 20 mg/kg given to mice with treatment initiated either on the day of tumor inoculation or once the tumors reached 200 mm3 in size. Results to date indicate significant growth retardation is achieved against recently implanted and established tumors. Based on these encouraging results further work with this compound is ongoing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1416. doi:10.1158/1538-7445.AM2011-1416
Abstract 1492: FoxM1 expression and its association with matrix metalloproteinases in diffuse large B-cell lymphoma
Authors: Siraj Abdul K. , Hussain Azhar R. , Ahmed Maqbool , Ahmed Saeeda O. , Bu Rong , Al-Dayel Fouad , Bavi Prashant , Uddin Shahab , Al-Kuraya Khawla S. 
Published: June 2012

Abstract
Forkhead Box M1 (FoxM1) has been shown to play a critical role in pathogenesis of various malignancies however its role in lymphoid malignancies is not fully elucidated. Therefore, in this study, we first investigated the role of FoxM1 in a large series of DLBCL tissues in a tissue micro array (TMA) format by Immunohistochemistry (IHC). We then followed this with in vitro studies on DLBCL cell lines using either pharmacological inhibitors of FoxM1 or siRNA knock down strategy. Using IHC, FoxM1 was detected in 84.6% of DLBCL tumors. FoxM1 expression was found to be significantly associated with early stage (p=0.0149), germinal centre phenotype (p=0.0126) and high proliferative tumor marker Ki67 (p&lt;0.0001). In addition, FoxM1 expression was also significantly associated with expression of SKP2 (p&lt;0.0001) and inversely associated with p27 expression (0.0215). Metalloproteinases, such as MMP-2 and MMP-9 play an important role in invasion and migration of cancer cells were also found to be significantly associated with expression of FoxM1 (p=0.0008 and p=0.0002) respectively. Our in vitro studies showed that treatment of DLBCL cell lines with thiostrepton, a specific inhibitor of FoxM1 inhibited cell proliferation, invasion and migration of DLBCL cells and induced apoptosis in a dose dependent manner. Inhibition of FoxM1 led to down-regulation of MMP-2, MMP-9 and SKP2 expression while the expression of p27 was up-regulated in DLBCL cells. Similar results were obtained using siRNA targeted against FoxM1. Furthermore, treatment of DLBCL cells with thiostrepton caused a dose dependent apoptosis in all DLBCL cell lines used in the study. On dissecting the apoptotic pathway, we found that thiostrepton induced its apoptotic effect via the mitochondrial pathway and activation of caspases. Finally, treatment of DLBCL cells with thiostrepton down-regulated the expression of XIAP, cIAP1 and Survivin. Altogether, these results suggest that FoxM1 signaling contribute in pathogenesis of germinal centre subtype of DLBCL and may serve as useful molecular biomarker and potential therapeutic target.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1492. doi:10.1158/1538-7445.AM2011-1492
Abstract 1561: The white adipose tissue is a rich reservoir of two distinct CD34+ mesenchymal and endothelial progenitor populations with a catalytic role in cancer progression
Authors: Martin-Padura Ines , Mancuso Patrizia , Gregato Giuliana , Marighetti Paola , Calleri Angelica , Corsini Chiara , Lohsiriwat Visnu , Petit Jean-Yves , Bertolini Francesco 
Published: June 2012

Abstract
A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived circulating endothelial progenitors (CEPs). However, in preclinical and clinical studies the quantitative role of marrow-derived CEPs in cancer vascularization was found to be extremely variable. We have found that the human and murine white adipose tissue (WAT) is a very rich reservoir (containing a mean of 320 times more CD45-CD34+ progenitors/mL than the marrow) of two distinct CD45-CD34+ perivascular cell populations with mesenchymal and endothelial differentiation potential. When compared to marrow-derived CD34+ cells in gene expression array studies, purified WAT-CD34+ cells expressed similar levels of stemness-related genes such as Nanog, Sox2, Lin28 and others, and significantly increased levels of angiogenesis-related genes such as CD144, VEGFR2, ALK1 and others. In vitro the two WAT-CD34+ human populations generated fibroblasts, mature mesenchymal cells and mature endothelial cells and endothelial tubes. In aging mice, the number of WATCD34+ cells significantly declined in some WAT compartments but not in the mammary fat pad. When compared to marrow-derived progenitor cells, WAT-CD34+ cells expressed significantly increased (8 fold) levels of FAP-alpha, a crucial suppressor of anti-tumor immunity (Kraman et al, Science 2010). The co-injection of human WATCD34+ cells from lipofilling procedures significantly increased tumor growth and metastases in orthotopic models of human breast cancer in NSG mice, where human WATCD34+ cells contributed to tumor stroma and vascularization. A novel brain/adipocyte-BDNF/leptin axis has been recently proposed to play a potentially relevant role in cancer progression (Cao et al, Cell 2010). WATCD34+ progenitors express high levels of the receptors involved in this axis and our studies suggest a catalytic role in cancer progression and metastases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1561. doi:10.1158/1538-7445.AM2011-1561
Abstract 160: Altered levels of circulating microRNAs in the plasma of non-small cell lung cancer patients: Potential as biomarker
Authors: Qian Xuemin , Fujioka Naomi , Kratzke Robert , Xu Wayne W. , Melkamu Tamene , Kassie Fekadu 
Published: June 2012

Abstract
The development of molecular markers for lung cancer could offset the deficiencies of currently available early detection and staging approaches. To this end, blood markers are particularly attractive since samples are obtained in a minimally invasive way at any stage of lung carcinogenesis. In this study we compared the levels of 10 microRNAs (miR-21, miR-31, miR-155, miR-147, miR-218, miR-377, miR-551b*, miR-569, miR-1283, and miR-1468) in the blood plasma of 27 non-small-cell lung cancer (NSCLC) patients and 38 healthy controls, using quantitative reverse transcription- polymerase chain reaction (qRT-PCR), to determine if these miRNAs might have a diagnostic value for NSCLC. The results of the area under the receiver operating characteristic curve (ROC), which measures the ability of the test to correctly classify those with and without the disease, were 0.98, 1.00, 0.8, and 0.98 for miR-21, miR-155, miR-377 and miR-1468, respectively, indicating that plasma levels of miR-21, miR-155, miR-377 and miR-1468 are powerful discriminators between patients and controls. At the optimum cutoff point for the cycle threshold (CT) value of the four miRNAs, the sensitivities of miR-21, miR-155, miR-377 and miR-1468 were 92.5%, 100%, 84%, and 100%, respectively; the corresponding values for the test specificity were 100%, 100%, 88%, and 100%, respectively. These results indicate the great potential of miR-21, miR-155, miR-377 and miR-1468 as diagnostic markers for NSCLC but need to be proved in prospective studies with larger samples.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 160. doi:10.1158/1538-7445.AM2011-160
Abstract 1624: SIRT1 overexpression in pancreatic adenocarcinomas correlates with shortened patient survival and small molecule inhibition as well as target knockdown of SIRT1 induces growth arrest and apoptosis in pancreatic cancer cells
Authors: Stenzinger Albrecht , Göppert Benjamin , Kamphues Carsten , Sinn Bruno , Bahra Markus , Neuhaus Peter , Weichert Wilko 
Published: June 2012

Abstract
Aims: Several lines of evidence indicate that the nuclear enzyme SIRT1 belonging to the class III histone deacetylases is implicated in the initiation and progression of various malignancies. SIRT1 exerts its function by regulating deacetylation of histone and non-histone substrates leading to transcriptional repression of tumor suppressor genes. Recently, SIRT1 gained attraction as druggable target. Since chemotherapeutic treatment options are still very limited in pancreatic cancer we aimed at investigating the potential of SIRT1 in this regard by evaluating the effects of SIRT1 inhibition in vitro and SIRT1 expression in vivo.
Methods: Employing immunohistochemistry SIRT1 expression was analyzed in a large cohort of pancreatic ductal adenocarcinomas and subsequently correlated with clinicopathological data and patient survival. Furthermore, we investigated the impact of SIRT1-specific small molecule inhibition and target knock down as well as combinatorial regimens including conventional chemotherapy and small molecule inhibitors directed against the EGFR in pancreatic cancer cell culture models. Using the xCELLigence system, cellular events were measured quantitatively in real time and corroborated by secondary conventional readouts including FACS analysis.
Results: We found nuclear SIRT1 expression in 36 (27.9%) of 129 pancreatic carcinomas. SIRT1 expression was significantly higher in poorly differentiated carcinomas (p=0.002). SIRT1 expression was positively correlated with the expression of conventional HDACs suggesting a shared regulation. Strong SIRT1 expression was a significant predictor of poor survival both in univariate (p=0.002) and multivariate (HR 1.65, p=0.045) analysis under inclusion of WHO stage and grade.
Small molecule inhibition and target knockdown of SIRT1 lead to a rapid growth arrest and influenced cell viability. This effect was even more pronounced in combinatorial regimens with Gefitinib, but not in combination with Gemcitabine.
Conclusions: SIRT1 is shown to be an independent prognostic biomarker for pancreatic adenocarcinomas. Moreover our data suggest that SIRT1 plays an important functional role in pancreatic cancer cell growth, which can be levered out by combinatory small molecule inhibition.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1624. doi:10.1158/1538-7445.AM2011-1624
Abstract 1626: Polyribosome-associated proteins targeted by HDACi promote the selective degradation of oncogenic transcripts
Authors: Scott Gary K. , Gabriel Bianca , Held Jason , Lee Elbert , Benz Christopher C. 
Published: June 2012

Abstract
We previously demonstrated that histone deacetylase inhibitors (HDACi), including several HDAC6-selective inhibitors, rapidly induce the accelerated decay of ERBB2 mRNA as well as ∼ 300 other oncogenic transcripts possessing U-rich sequences in their 3’UTR. While the mechanism underlying this oncogene transcript decay switch remains unknown, more recent evidence indicates that HDACi induced ERBB2 mRNA decay occurs on actively translating polyribosomes; and current studies are attempting to define the polyribosome proteins mediating this switch as they might represent novel therapeutic target candidates. A screen for proteins rapidly modified, recruited to, or released from polyribosomes following HDACi exposure (trichostatin-A, TSA) was undertaken in the ERBB2-positive human breast cancer cell line, SKBR3. Monosome and polyribosome enriched cytosols from control or TSA treated cells were either sucrose gradient fractionated for Northern and Western blot analysis of fractions, or the proteins were resolved by 2-dimensional (2-D) gel electrophoresis using three different isoelectric focusing gradients (ranging from pH 12 to pH 4). Western blots confirmed that monosome and polyribosome fractions contained the 40S ribosome scaffold protein, RACK1. Northern blots confirmed that HDACi (TSA × 6h) induced decay of ERBB2 mRNA, which could be completely prevented by co-treatment with the translational inhibitor cycloheximide, was confined to the polyribosome fractions. Comparison of the protein stained 2-D gels from control and treated samples indicated that 2-4 h of TSA exposure changes the isoelectric migration of &gt;80 proteins, suggesting that HDACi induces post-translational modifications (PTMs) in various polyribosome proteins. Altered 2-D protein spots were excised, trypsin digested, and identified by nano-liquid chromatography (LC)-tandem mass spectrometry (MS/MS) using a 4000 QTRAP (Applied Biosystems, with Mascot v. 2.2 search database); in addition to RACK1, other TSA modified proteins include YB-1 (Y-box binding protein), DBPA (DNA-binding protein A), PRKRA (interferon-inducible double stranded RNA-dependent protein kinase activator A), NPM (nucleophosmin), and HNRPC (heterogeneous nuclear ribonucleoproteins C1/C2). Western blots looking for differential lysine acetylation (Ac-K) revealed that TSA induces Ac-K protein isoforms in the sucrose gradient polyribosome fractions containing decaying ERBB2 mRNA; induced Ac-K isoforms were also observed on the 2-D gels. MS/MS analysis of these TSA induced Ac-K isoforms is expected to reveal novel polyribosome HDAC substrates and candidate effectors of oncogene transcript decay.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1626. doi:10.1158/1538-7445.AM2011-1626
Abstract 1653: Vasodilator-stimulated phosphoprotein ser157 and ser239 are antimetastatic targets in colon cancer
Authors: Ali Mehboob , Pitari Giavanni Mario 
Published: June 2012

Abstract
Colorectal cancer is the third deadly cancer worldwide. Patient mortality is largely the result of metastatic disease progression, in which tumor cells undergo dramatic morphological changes characterized by the formation of membrane protrusive structures mediating invasion (lamellipodia, filopodia, invadopodia). These events are driven by the activity of actin-regulatory proteins, including the vasodilator-stimulated phosphoprotein (VASP), which reorganize the actin cytoskeleton to promote cell migration and invasion. In colon cancer, cAMP- and cGMP-dependent VASP phosphorylation at Ser157 (pVASP-Ser157) and Ser239 (pVASP-Ser239) represent opposing molecular switches, which regulate the invasive cell shape. Here, pVASP-Ser157 and pVASP-Ser239 differentially affected the metastatic potential of colon cancer cells, including tumor proliferation, colony formation, migration, adhesion and metastasis in vivo. Investigations employed intestinal cancer cells, human tumor cells expressing serine phosphoresistant VASP mutants, cGMP or cAMP analogs, agonists selectively elevating intracellular cGMP or cAMP levels, and orthotopic mouse models of colorectal cancer. Collectively, results demonstrated pVASP-Ser239 suppresses, while pVASP-Ser157 promoted, the metastatic phenotype of colon cancer cells. Thus, differential VASP serine phosphorylation is a novel targeted strategy to prevent colon cancer metastasis. Clinical translation of these findings may provide original therapeutic interventions to reduce mortality in patients with colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1653. doi:10.1158/1538-7445.AM2011-1653