bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C7: Analysis of high-risk prostate cancer markers at RNA and protein level.
Authors: Masarik Michal , Gumulec Jaromir , Hlavna Marian , Sztalmachova Marketa , Cernei Natalia , Babula Petr , Adam Vojtech , Krizkova Sona , Hrabec Roman , Rovny Arne , Kizek Rene 
Published: June 2012

Abstract
Background: In many developed countries, prostate cancer is the second leading cause of cancer-related deaths among men. Current diagnostic possibilities do not differentiate aggressive forms of prostate cancer from latent tumors. Therefore, having reliable and easy-to-detect marker is needed to treat this disease successfully. We determined potential novel tumor markers of high-risk prostate cancer (A) at the cell level, represented by cell lines 22Rv1 and PNT1A and (B) in the serum of 82 histologicaly -verified cases and 51 controls.
Material and Methods: 22Rv1 cell line derived from primary prostate tumor and PNT1A cell line derived from normal prostate epithelium were used in our study. The real time PCR, electrophoretical separation technique, immunochemical detection and novel electrochemical analysis were used in tumor markers determination.
Findings and Interpretation: Cell line 22Rv1 represents Gleason sum 9 primary tumor, compared to widely used cell lines PC-3, LNCaP and PD-145, representing metastasis, therefore, is more related to real tumor tissue. We determined RNA and protein level of genes alpha-methyl acyl-CoA racemase (AMACR), caveolin-1, metalothionein, p53, NF-kB, FOS, JUN, Ki-67, ZIP1 and ZnT-1. At the RNA level in cell lines we found significant (p &lt; 0.01) down-regulation of Cav-1 (50-fold), NF-kB (11-fold) and others and significant (p &lt; 0.01) up-regulation of metalothionein (2.4-fold), AMACR (8.4-fold), Ki-67 (2-fold) and zinc transporters ZnT-1 (25-fold) and ZIP1 (45-fold). Conversely, we observed down-regulation of metallothionein at protein level. In the serum of prostate cancer patients we found no significant differences in AMACR and caveolin-1 level and significantly (p &lt; 0.001) higher metallothionein level suggesting metalothionein as a complementary marker to PSA. We found weak correlation of PSA on caveolin-1 (r = 0.41 at p = 0.002) and, interestingly, significant elevation of caveolin-1 in high-grade tumors (tumor stage 4 (2.3-fold elevation), Gleason sum 9, correlation at r = 0,29 at p = 0,028) suggesting caveolin-1 as potential high-risk prostate cancer marker.
This study provides important new information about selected genes connected with prostate cancer and describes new electrochemical approaches for their determination in lower concentrations.
Financial support from IGA MH of Czech republic no. NS10200–3 is greatly acknowledged.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C7.
Abstract C74: Eradicating cancer stem cells by targeting mTOR pathway with metformin.
Authors: Park Heon Joo , Lee Hyemi , Williams Brent , Song Chang Won 
Published: June 2012

Abstract
Cancer stem cells are resistant to conventional radiotherapy and chemotherapy. It is, therefore, important to eradicate cancer stem cells to achieve complete control of cure of cancer. It has been demonstrated that Akt/mTOR pathway plays a critical role for survival and proliferation of cancer cells, particularly cancer stem cells. We investigated the effect of metformin, ionizing radiation and mild heating alone or combined on mTOR activity and survival of cancer stem cells. Metformin inactivated mTOR via activation of AMPK, thereby preferentially killing stem cells of various cancer cells. For example, the % of cancer stem cells in MCF-7 cells before treatment was about 3.4%, and it decreased to 1.2% after 48 h treatment with 5 mM metformin, as determined with FACS using CD44+/CD24- surface markers. Metformin also selectively killed the stem cells of MIAPaCa-2 pancreatic cancer cells expressing CD44+/CD24+. Mammosphere formation study also demonstrated that metformin is effective to kill cancer stem cells. We observed that irradiation and heating also suppress mTOR activity through activation of AMPK. However, irradiation was ineffective to kill cancer stem cells while heating was effective to kill cancer stem cells. Interestingly, irradiation upregulated Akt activity while mild heating downregulated Akt activity. It appeared that the radiation-induced inhibition of mTOR activity is counterbalance by Akt activation. Treatment of MIAPaCa-2 xenografts with combination of metformin and irradiation was markedly more effective than metformin or irradiation alone. It is concluded that metformin in combination with ionizing radiation and mild hyperthermia are potentially effective to eradicate cancer stem cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C74.
Abstract C75: CYP2S1 and CYP2W1 mediate 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW610, NSC 721648) sensitivity in breast and colorectal cancer cells.
Authors: Leong Chee-Onn , Tan Boon Shing , Tiong Kai Hung , Muruhadas Ashwin , Randhawa Nirmal , Choo Heng Lungh , Stevens Malcolm FG , Bradshaw Tracey D. 
Published: June 2012

Abstract
Phortress, the lysylamide prodrug of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F203, NSC 703786) is under clinical evaluation. CYP1A1-catalyzed bioactivation of 5F203 is crucial for antitumor activity. 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW610, NSC 721648) is a structurally related experimental antitumor agent. In order to understand the mechanism of action of GW610, we investigated roles of cytochrome P450 enzymes CYP2S1 and CYP2W1 in mediating benzothiazoles activity. Stable isogenic breast (MCF-7, MDA-MB-468) and colorectal (HCC2998, KM12) cancer cell lines depleted for CYP1A1, CYP2S1 or CYP2W1 were generated. The sensitivity of these cells to 5F203 and GW610 was compared with vector control cells.
5F203 exhibited potent activity against breast cancer cells, whereas GW610 was effective against both breast and colorectal carcinoma cells.
CYP1A1 was induced in breast and colon cancer cells, whereas induction of CYP2S1 and CYP2W1 was observed in breast cancer cells only following treatment with 5F203 or GW610. Depletion of CYP1A1 abrogated 5F203 and GW610 activity; in contrast, CYP2S1 depletion enhanced sensitivity of breast and colon cancer cells to 5F203 and GW610. Intriguingly, CYP2W1 knockdown caused marked resistance to GW610 in HCC2998 (&gt;7-fold) and KM12 (&gt;90-fold) colorectal cancer cells only.

The results indicate that CYP2S1 is involved in deactivation of benzothiazoles, but CYP2W1, expressed in colorectal tumors and a putative therapeutic target, is important for bioactivation of GW610 in colorectal carcinoma cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C75.
Abstract C77: Sangivamycin-like molecule 6 (SLM6) exhibits potent and selective anti-multiple myeloma activity through inhibition of P-TEFb.
Authors: Dolloff Nathan G. , Talamo Giampaolo , Dicker David T. , El-Deiry Wafik S. 
Published: June 2012

Abstract
We previously reported the anti-tumor and anti-angiogenic activity of a new class of sangivamycin-like molecules (SLMs). In this study we aimed to further the preclinical development of these compounds by identifying tumor types with the highest sensitivity to their cytotoxic effects. Of 35 tumor cell lines from 8 different tissues of origin that we screened, we found that multiple myeloma (MM) cells were approximately 3–10 times more sensitive to SLMs than other tumor types. SLM3 as well as SLM5, SLM6, and SLM7 reduced viability and induced apoptosis of MM cells at sub-micromolar concentrations in vitro. By contrast, SLMs induced negligible amounts of apoptosis in other tumor and normal cell lines. SLM6 exhibited the most potent activity in vivo where it significantly inhibited the growth of xenografted MM tumors. We found that SLM6 inhibited cyclin dependent kinase 9 (CDK9) resulting in hypophosphorylation of RNA polymerase II (Ser2) and transcriptional repression of oncogenes that are known to drive MM progression and resistance to therapy (c-Maf, cyclin D1, c-Myc, L-Myc, and Mcl-1). Furthermore, we found that SLM6 increased the cytotoxic activity of therapies that are currently approved for MM treatment (bortezomib, lenalidomide, dexamethasone, and doxorubicin). These findings suggest that CDK9 inhibition is a particularly effective targeted strategy for MM, and SLM6 is a promising CDK9-targeted agent, both as a single agent and in combination with currently approved therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C77.
Abstract C85: ck2 inhibitors in luminal and basal-like breast cancer cells.
Authors: Patton Michelyn C. , Williams Christopher 
Published: June 2012

Abstract
Protein kinase casein kinase II (CK2) is a heterotetrameric serine/threonine kinase involved in proliferation, apoptosis and embryonic development. It is expressed at elevated levels in proliferating tissue, human cancer cell lines and virtually all forms of solid cancers. Recently it has been shown that CK2 inhibition induces apoptosis in cell models of acquired anti-estrogen resistance. These findings suggest that there may be tumor phenotype specific effects of CK2 in breast cancer and consequently phenotype specific sensitivity to CK2 inhibition. As such we sought to determine if luminal and basal cell types display differential sensitivity to selective CK2 inhibitors. Utilizing crystal violet and alamar blue assays, it was found that CK2 inhibition decreased viability of both luminal and basal breast cancer cell lines, with basal-like ER(−) MDA MB 231 cells showing notable sensitivity. Hypertrophic morphologic changes consistent with cellular senescence were noted upon inhibition of CK2. Additionally, flow cytometric analysis revealed an increase in mean vimentin expression in basal but not luminal breast cancer cells following CK2 inhibition. These studies suggest that CK2 utilizes multiple molecular mechanisms to promote tumorigenesis, and that CK2 inhibition may disrupt cell-type specific signaling pathways to induce breast cancer cell death.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C85.
Abstract C91: Systematically analyzing molecular mechanism of growth inhibition induced by liver × receptor agonists in HT-29 human colon cancer cells using high-throughput micro-Western array and microarray.
Authors: Lin Ching-Yu , Huo Chiech , Lin Hui-Ping , Jiang Shih Sheng , Chiang Chi-Yi , Chuu Chih-Pin 
Published: June 2012

Abstract
Colon cancer is the third leading cause of cancer-related death in the world. Previously, we and other groups reported that agonists for liver × receptors (LXRs) suppressed the proliferation of several human cancer cell lines. LXR and LXR are nuclear receptors and are important regulators of cholesterol, fatty acid, and glucose homeostasis. We recently developed a high-throughput proteomics technology named Micro-western arrays (Ciaccio et al., Nature Methods, 2010), which is an array-based Western blotting assay enable quantitative, sensitive and high-throughput assessment of protein abundance and modifications after electrophoretic separation of micro-arrayed cell lysates. This method allowed us to measure 96 to 384 different phosphosites on multiple proteins of a set of 6 to 15 different samples at the same time at. In order to study the molecular mechanism lying underneath the anticancer activity of LXR agonists (22(R)-hydroxycholesterol, T0901317, and GW3965) on colon cancer cells, we use 96-well proliferation assay, colony formation assay, flow cytometry analysis, invasion/migration assay, gene overexpression and shRNA/siRNA knockdown, qRT-PCR, gene microarray, and Micro-Western Array to systematically investigate the suppressive effect of LXR agonists on HT-29 human colon adenocarcinoma cells. LXR agonists suppress proliferation of HT-29 cells dose-dependently at the range from 100 nM to 10 μM. LXR agonists treatment cause G1 cell cycle arrest and affect several cell cycle regulating proteins. Micro-Western Array and microarray reveals that several signaling pathways regulating survival, stress, proliferation, and cell cycle of cells are being affect by LXR agonists. Our observation suggests that LXR agonist treatment may serve as a potential adjuvant therapy for human colon cancer.
This work was supported by CS-100-PP-12 (National Health Research Institutes, NHRI) and NSC 99–2320-B-400–015-MY3 (National Science Council, NSC) in Taiwan for CPC, as well as DOH100-TD-C-111–014 (Department of Health) for SSJ and CPC. We thank support from Protein Chemistry Core Facility of Core Instrument Center in NHRI and Taiwan Bioinformatics Institute Core Facility of the National Core Facility Program for Biotechnology by NSC (NSC100–2319-B-400–001).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C91.
Abstract PL04-03: Engineering improved cancer vaccines.
Authors: Dranoff Glenn 
Published: June 2012

Abstract
Efficacious cancer immunotherapies will likely require combinations of strategies that enhance tumor antigen presentation and antagonize negative immune regulatory circuits. We demonstrated that vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF followed by antibody blockade of CTLA-4 accomplishes clinically significant tumor destruction with minimal toxicity in some advanced cancer patients. The detailed analysis of patients achieving sustained clinical benefits from these therapies illustrated the importance of a coordinated cellular and humoral anti-tumor immune response. Indeed, the extent of tumor necrosis in post-treatment biopsies was linearly related to the natural logarithm of the ratio of infiltrating CD8+ effector T cells to FoxP3+ Tregs. Moreover, therapy induced a potent antibody response to several key tumor cell surface and secreted proteins; these antibodies manifest functional activity in vitro, antagonizing tumor cell survival, invasive potential, and angiogenesis.
Through an analysis of cytokine deficient mice, we delineated a critical role for GM-CSF in Treg homeostasis. GM-CSF is required for the expression of the phosphatidylserine binding protein MFG-E8 in antigen presenting cells, whereas the uptake of apoptotic cells by phagocyte-derived MFG-E8 maintains peripheral Treg activity. While blockade of MFG-E8 can enhance therapeutic immunity in the context of cancer vaccines, loss of Treg homeostasis with MFG-E8 deficiency can lead to chronic inflammation. Mice deficient in GM-CSF and IFN-develop at high frequency germinal center derived lymphomas and nonsmall cell lung carcinomas. The pathogenesis of these tumors reflects a combination of tumor-promoting inflammation and a loss of protective tumor immunity. Taken together, these findings highlight dual roles for immunity in cancer pathogenesis and therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr PL04-03.
Abstract 1176: The expression of RN7SK paralogs in tumors of renal cell carcinoma is associated with patient survival
Authors: Zhang Xiaofan , Hildebrandt Michelle A. , Horikawa Yohei , Pu Xia , Wood Christopher G. , Gu Jian 
Published: June 2012

Abstract
Purpose: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and also the most lethal type of genitourinary cancer. RN7SK RNA, a highly expressed non-coding RNA, was originally found to negatively regulate the transcription elongation factor P-TEFb, which can activate RNA polymerase II and pre-mRNA processing. Previous studies have shown the important role of this machinery in growth control and tumorigenesis. In human genome, eleven homologous non-coding RN7SK RNAs (http://www.noncode.org) have been speculated to possess similar function, but no experimental data have been reported. In this study, we determined the function of these RN7SK paralogs and evaluated their association with RCC development and prognosis.
Experimental Design: Co-immunoprecipitation (Co-IP) was performed to determine the involvement of these RN7SK paralogs in the transcription elongation using antibody of LARP7, a RN7SK specific binding protein. Then, 114 paired tumor tissues and corresponding adjacent normal tissues from histologically confirmed RCC patients were used to measure the expression level of these predicted RN7SK RNAs by real-time PCR. Associations with overall survival, recurrence, and stage were analyzed with adjustment for age, gender, race, smoking status, family hypertension, and family history of cancer.
Results: Co-IP results showed that eight of the eleven RN7SK paralogs were present in RN7SK ribonucleoprotein complex. Each detectable RN7SK RNA showed high expression level in both normal and tumor tissue, with significantly higher expression in tumor than in normal tissue except for n6233. High expression of n283 and n6233 was significantly associated with increased risk of death in RCC patients with hazard rations (HRs) of 3.23 (95% confidence interval [CI], 1.33-7.82; p=0.009) and 2.23 (95% CI; 1.03-4.79; p=0.041), respectively. Four other RN7SK paralogs were also significantly associated with survival, including n206 (p=0.022), n274 (p=0.037), n283 (p=0.007), and n6233 (p=0.014). No significant associations were identified for recurrence risk for any of the eight RN7SKRNAs. N133 (p=0.0005) and n139 (p=0.02) showed significantly different expression level between early (stage I&II) and late stage (stage III&IV) tumors.
CONCLUSIONS: Our results suggest that RN7SK paralogs may be involved in RCC tumorigenesis and the expression of select RN7SK may be valuable biomarkers of RCC prognosis.
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 1176. doi:10.1158/1538-7445.AM2011-1176
Abstract 1348: The discovery of novel inhibitors that downregulate human thymidylate synthase
Authors: Repalli Jayanthi , Chapman James , McInnes Campbell , Berger Sondra H. 
Published: June 2012

Abstract
Inhibitors of the enzyme thymidylate synthase (TS) are typically used as anti-cancer drugs to limit the growth of cancer cells. These inhibitors deplete TTP which is essential for DNA replication and repair. The enzyme in humans is postulated to undergo conformational switching between active and inactive forms. We are testing the hypothesis that stabilization of the inactive conformation will lead to increased turnover of hTS. Stabilization of hTS to degradation is observed after exposure to TS inhibitors in clinical use, which are active site-targeted. X-ray crystallographic studies of 1,3-propanediphosphonic acid (PDPA) bound to hTS led to the prediction that PDPA stabilizes the inactive conformation. Furthermore, PDPA exhibited competitive-noncompetitive behavior in TS catalytic reactions, consistent with allosteric inhibition. A cell-permeable isostere of PDPA inhibited hTS in catalytic assays, inhibited cell proliferation in a thymidine-dependent manner, and induced down regulation of hTS in cultivated cells. This is the first TS inhibitor to decrease the stability of hTS to degradation. To identify lead compounds that bind to the inactive conformation, molecular docking and structure-based virtual screening techniques were applied. Putative interaction sites were obtained from crystal structures of liganded hTS (with PDPA) and docked with 10,000 compounds using Ligand Fit (Drug Discovery Studio). Lead molecules with highest binding scores were selected and their efficacy analyzed in in vitro catalytic assays with hTS. Several compounds showed 30% – 50% inhibition of TS activity at 10 μM concentration. These derivatives were more potent than PDPA and inhibited the growth of cells expressing hTS, with IC50s of 100 µM – 200 µM. Data derived from computational and in vitro experiments are being employed in iterative cycles in the design of more potent, allosteric TS inhibitors.
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 1348. doi:10.1158/1538-7445.AM2011-1348