bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A243: Identification of a target for collismycin A, a cytotoxic microbial product, by proteomic profiling.
Authors: Kawatani Makoto , Inoue Gyo , Muroi Makoto , Futamura Yushi , Aono Harumi , Uramoto Masakazu , Hongo Yayoi , Koshino Hiroyuki , Igarashi Yasuhiro , Takahashi-Ando Naoko , Osada Hiroyuki 
Published: August 2014

Abstract
Background: Collismycin A, a microbial product, has antiproliferative activity against tumor cells, the mechanism of which yet remains unknown. Recently, we reported an indirect drug target identification approach, termed “ChemProteoBase," which is based on specific changes in the intracellular proteome induced by chemical manipulations. Here, we report on the identification of a molecular target for collismycin A by using ChemProteoBase.
Materials and Methods: HeLa cells were treated with collismycin A for 18 h, and the resulting cell lysates were subjected to two-dimensional fluorescence differential gel electrophoresis (2D-DIGE). The gel images were linked to our database containing images that were generated by 134 well-characterized small molecule drugs and probes. The 296 spots that matched on all gel images were quantified, and then hierarchical cluster analysis and similarity ranking analysis were performed.
Results: Collismycin A inhibited cell growth of various human tumor cells with IC50 values ranging from 100 to 400 nM. Flow cytometry and western blot analyses showed that collismycin A arrested cell cycle at G1 phase with the marked decrease of cyclin D1. To predict the mechanism of action of collismycin A, we performed ChemProteoBase profiling. As a result, collismycin A was clustered with Dp44mT, an iron chelator, and Dp44mT was also ranked in the highest position of a similarity ranking among 134 compounds contained in the ChemProteoBase. HR-ESI-MS analysis revealed that collismycin A forms 2 : 1 chelator-iron complex. In addition, the antiproliferative activity of collismycin A was completely abolished by the addition of excessive amounts of Fe(II) or Fe(III) ion but not other metal ions including Cu(II), Zn(II), Mn(II) and Mg(II).
Conclusions: These results strongly suggest that collismycin A acts as an iron chelator, resulting in the inhibition of tumor cell growth. Recent studies have shown that iron contributes to tumor initiation, growth and metastasis, and several iron chelators are under preclinical or early clinical investigation as anticancer therapeutics. Therefore, a new iron chelator, collismycin A, might be useful for the treatment of cancers in which iron has been strongly implicated.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A243.
Citation Format: Makoto Kawatani, Gyo Inoue, Makoto Muroi, Yushi Futamura, Harumi Aono, Masakazu Uramoto, Yayoi Hongo, Hiroyuki Koshino, Yasuhiro Igarashi, Naoko Takahashi-Ando, Hiroyuki Osada. Identification of a target for collismycin A, a cytotoxic microbial product, by proteomic profiling. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A243.
Abstract A25: Using clique relaxations to identify highly connected clusters in molecular networks in cancer.
Authors: Kulemina Lidia V. , Pastukhov Grigory , Veremyev Alexander , Boginski Vladimir L. 
Published: August 2014

Abstract
Graph theory approaches are now increasingly used to navigate through big data from “omics” applications for delineating signature events in cancer subtypes, identification of new molecular targets and assigning significance of specific mutations. While usual suspects such as p53 and Rb are widely known to all researchers, ability to identify additional, highly relevant, potentially targetable genes implicated in cancer remains of great importance.
Identification of cancer signatures and driver mutations turned out to be more challenging/ more complex than we originally thought as frequency of specific mutations can vary significantly leaving some potentially highly relevant (and potentially targetable) events out of the picture. We proposed to identify such targetable genes as parts of large “highly connected” clusters (also known as functional modules) in the corresponding networks. Using our recently developed algorithms, we have been able to exactly identify the largest highly connected cluster in sparse networks with up to several billion nodes.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A25.
Citation Format: Lidia V. Kulemina, Grigory Pastukhov, Alexander Veremyev, Vladimir L. Boginski. Using clique relaxations to identify highly connected clusters in molecular networks in cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A25.
Abstract A29: PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1.
Authors: Ebi Hiromichi , Costa Carlotta , Faber Anthony , Juric Dejan , Della Pelle Patricia , Song Youngchul , Yano Seiji , Mino-Kenudson Mari , Benes Cyril H. , Engelman Jeffrey A. 
Published: August 2014

Abstract
The phosphatidylinositol 3-kinase (PI3K) pathway is genetically activated in excess of 70% of breast cancers, often throughPIK3CA mutation and HER2 amplification. Previous studies with PI3K inhibitors have suggested enhanced sensitivity in this subset of breast cancers, however, the mechanism underlying this sensitivity is mainly unknown. In this study, we investigated the signaling consequences of PI3K inhibition in PIK3CA mutant and HER2 amplified breast cancers, and unexpectedly observed suppression of ERK signaling in these cancers. In contrast to PI3K inhibitors, AKT inhibitors failed to block MEK/ERK signaling and to induce sustained apoptosis, suggesting that a different PI(3,4,5)P3-dependent pathway regulated ERK. We determined that suppression of ERK was due to loss of active Rac1, which led to suppression of PAK/c-RAF/MEK/ERK signaling. Expression of a constitutively active form of Rac1 abrogated the capacity for PI3K inhibitors to inhibit ERK, induce apoptosis, and have anti-tumor activity in vivo. Further studies identified P-Rex1 as the PI(3,4,5)P3-dependent guanine exchange factor for Rac1 responsible for regulation of the Rac1/PAK/c-RAF/MEK/ERK pathway in these breast cancer cells. Furthermore, the expression level of P-Rex1 in these breast cancer cells predicted for capacity for PI3K inhibitors to suppress ERK signaling and correlated with sensitivity to PI3K inhibitors. Thus, PI3K inhibitors have enhanced sensitivity in PIK3CA mutant and HER2 amplified breast cancers where PI3K inhibition downregulates both the AKT and Rac1/ERK pathways. In addition, P-Rex1 may serve as a biomarker to predict response to single-agent PI3K inhibitors within this subset of breast cancers.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A29.
Citation Format: Hiromichi Ebi, Carlotta Costa, Anthony Faber, Dejan Juric, Patricia Della Pelle, Youngchul Song, Seiji Yano, Mari Mino-Kenudson, Cyril H. Benes, Jeffrey A. Engelman. PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A29.
Abstract A32: Novel biomarker algorithm to improve the differential diagnosis of ovarian cancer with in patients with ovarian tumor.
Authors: Lee Shin-Wha , Shin So-Jin , Kyung Min-Sun , Kim Young-Man , Kim Young-Tak 
Published: August 2014

Abstract
Objectives: The objective of this study was to analyze the concentration of serum multivariate markers and find the optimized combination to diagnose ovarian cancer in patients with ovarian tumor.
Methods: We collected serum samples prospectively from patients treated with ovarian tumors. Total 398 samples including malignant and benign ovarian tumor and normal controls, in testing set, were analyzed for their ovarian cancer-related 21 proteins, including CA125, HE4, CA19-9, CA15-3, CEA, Leptin, MIF, OPN, Prolactin, Cyfra21-1, IL-6, IL-8, MIP-1-alpha, Eotaxin, sEGFR, Apo AI, Apo CIII, Prealbumin(TTR), C-reactive protein(CRP), sNCAM, and sVCAM-1 by Luminex methods, which is a multiplexed immunoassay. In validation set, 6 protein markers were analyzed.
Results: More than half of the biomarkers tested were found to differ significantly between benign and malignant cases. Among them, as individual markers, 6 markers including CA-125 and HE4 provided the discrimination between benign and malignant cases. The diverse combination of these 6 biomarkers provided a higher level of discriminatory power than either marker considered alone. We identified that these multimarker panels could discriminate ovarian cancers from benign cases with more than 95% of sensitivity, 95% of negative predictive value and 85% of accuracy in 75% of specificity. These multimarkers showed the improved differentiation diagnosis in early stage cancer and pre-menopausal women comparing to the CA-125 alone.
Conclusions: We describe a blood-based assay using multimarkers that can distinguish women with ovarian cancer from those with benign conditions. Preliminary evaluation of the multimarker panels suggests it has the potential to improve the accuracy to diagnose ovarian cancers. While promising, the performance needs to be assessed in a blinded clinical validation study.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A32.
Citation Format: Shin-Wha Lee, So-Jin Shin, Min-Sun Kyung, Young-Man Kim, Young-Tak Kim. Novel biomarker algorithm to improve the differential diagnosis of ovarian cancer with in patients with ovarian tumor. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A32.
Abstract A36: High T790M detection rate in TKI-naïve NSCLC with EGFR sensitive mutation: Truth or artifact?.
Authors: Ye Xin , Zhu Zhong-zheng , Zhong Lei , Lu Yachao , Sun Yun , Yin Xiaolu , Yang Zhenfan , ZHU Guanshan , Ji Qunsheng 
Published: August 2014

Abstract
T790M in epidermal growth factor receptor (EGFR) accounts for about 50% of the acquired resistance to EGFR tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC) carrying sensitive EGFR mutations. Earlier studies suggested that T790M mutation was also detected in about 2% of TKI-naive NSCLCs. Recently, three groups reported that, by using highly sensitive assays, T790M mutation was detected in about 40% of TKI-naive NSCLC with sensitive EGFR mutations. When we carefully studied these reports, we realized that all of those data were generated from formalin-fixed paraffin embedded (FFPE) tumor tissue samples, which raised a concern that the high mutation positivity could be consequence of formalin fixation. To address this, we assessed the T790M mutation in 36 pairs of frozen and FFPE tumor tissues of TKI-naïve NSCLC with sensitive EGFR mutations using an enzyme-based mutant-enriched PCR assay (ME-PCR) with 0.1% sensitivity. In addition, frozen and FFPE adjacent normal tissues from the same patients were also assessed for a further comparison. While 41.7% (15/36) T790M positive rate was detected in the tumor FFPE samples which was consistent with previous reports, only 1 of the 36 (2.8%) frozen counterparts was T790M positive. As suspected, 48.5% (16/33) of T790M mutation rate was also identified in FFPE adjacent normal tissues but none of the 35 frozen adjacent normal tissues was T790M positive. Our results indicate that the high T790M positivity detected in TKI-naïve NSCLC using some highly sensitive methods may in some cases be FFPE-derived artifacts.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A36.
Citation Format: Xin Ye, Zhong-zheng Zhu, Lei Zhong, Yachao Lu, Yun Sun, Xiaolu Yin, Zhenfan Yang, Guanshan ZHU, Qunsheng Ji. High T790M detection rate in TKI-naïve NSCLC with EGFR sensitive mutation: Truth or artifact?. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A36.
Abstract A41: Pre-clinical investigation of predictive biomarkers for drug candidates using a molecularly profiled large cancer cell line panel.
Authors: Aida Satoshi , Mizuno Hideaki , Sakamoto Hiroshi , Nakanishi Yoshito , Mutoh Hironori , Cai James , Burtscher Helmut , Aoki Masahiro , Aoki Yuko , Ishii Nobuya 
Published: August 2014

Abstract
To deliver investigational drugs to appropriate patients from the early clinical development stage, it would be ideal to identify biomarker candidates at the preclinical stage. To investigate prediction biomarkers in preclinical models, a large cell panel consisting of over 500 cell lines from various tumor types was molecularly profiled. To find their gene expression profiles, gene copy number variations, single nucleotide variations and gene fusions, we conducted a comprehensive analysis with GeneChip, CGH array, exon sequencing and RNA sequencing by collaborative efforts between Chugai Pharmaceutical and F. Hoffmann-La Roche in the CELLO/CACTEL program (CELl Line profiling in Oncology/Chugai ACcumulative Tumor EncycLopedia). We further integrated the multidimensional profiling data of in-house cell lines together with those of tumor tissues in the public domain into our CELLO/CACTEL database by vocabulary controlling among databases. Using 300 cell lines in a molecularly profiled cell panel, we investigated the drug sensitivity profiles of representative investigational drug candidates, and identified potentially novel predictive features for sensitivity to these drugs. In summary, the CELLO/CACTEL database provides an effective platform for exploring biomarkers at the preclinical stage.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A41.
Citation Format: Satoshi Aida, Hideaki Mizuno, Hiroshi Sakamoto, Yoshito Nakanishi, Hironori Mutoh, James Cai, Helmut Burtscher, Masahiro Aoki, Yuko Aoki, Nobuya Ishii. Pre-clinical investigation of predictive biomarkers for drug candidates using a molecularly profiled large cancer cell line panel. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A41.
Abstract A43: Investigation of dipeptidyl peptidase IV/CD26 role in cervical cancer cell lines.
Authors: Buffon Andréia , Beckenkamp Aline , Santana Danielle Bertodo , Nascimento Jéssica , Paccez Juliano , Zerbini Luiz Fernando , Wink Márcia Rosangela , Bruno Alessandra Nejar 
Published: August 2014

Abstract
Cervical cancer is a common type of cancer in women and an important public health problem, mainly in developing countries. The glycoprotein DPPIV/CD26 is expressed at the membrane of many cells. It is able to inactivate some bioactive peptides and chemokines, thereby regulating cell proliferation and survival, being involved in processes related to cancer. This enzyme is also present in a soluble form (DPPIV/sCD26), in biological fluids. In this study, we evaluated, the expression and enzymatic properties of the DPPIV/CD26 and its relation with tumoral mechanisms in cervical cancer cell lines. The cervical cancer cells exhibit DPPIV/CD26 enzymatic activity in both membrane bound and, its soluble form, which was confirmed by the inhibition of the enzymatic DPPIV/CD26 activity for sitagliptin phosphate. The CD26 mRNA expression was observed in the SiHa and C33A cells, while the HeLa cells showed no transcripts. The DPPIV/CD26 expression was correlated with the enzymatic activity in these cell lines. We also observed a higher migratory capacity of HeLa (cervical cancer cell line that less express CD26) compared to SiHa (cervical cancer cell line that more express CD26), moreover in the presence of the specific inhibitor we observed that SiHa cell line shows an increase in migration, thus confirming a relationship of this enzyme with the migratory ability. Our results show, that cervical cancer cells present DPPIV/CD26 enzymatic activity in both membrane bound form, as in its soluble form, revealing a differential expression as well as its relationship to cell migration and adhesion. Considering that DPPIV/CD26 plays an important role in tumor biology, this protein may become an important therapeutic target although additional work is required to elucidate the molecular mechanisms associated with DPPIV/CD26 in cervical cancer.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A43.
Citation Format: Andréia Buffon, Aline Beckenkamp, Danielle Bertodo Santana, Jéssica Nascimento, Juliano Paccez, Luiz Fernando Zerbini, Márcia Rosangela Wink, Alessandra Nejar Bruno. Investigation of dipeptidyl peptidase IV/CD26 role in cervical cancer cell lines. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A43.
Abstract A63: NVP-BEZ235, a dual PI3K/mTOR inhibitor, elicits an alternate route for induction of cell death in PTEN null prostate cancer cells.
Authors: Kim Jeong Eun , Hong Seoung-Woo , Shin Jae-Sik , Moon Jai-Hee , Kim Ye-Seul , Kim Kyu-pyo , Hong Yong Sang , Lee Jae-Lyun , Jin Dong-Hoon , Kim Tae Won 
Published: August 2014

Abstract
Dysregulation of the PI3K-AKT & mTOR pathway by (mutation and/or) deletion of tumor suppressor gene PTEN frequently occurs in human prostate cancer and is therefore considered to be attractive molecule as therapeutic targets. Here, we investigated the antitumor effect of NVP-BEZ235 in human prostate cancer cells dependent on PTEN genotype. In this setting, NVP-BEZ235 induced cell death in the PTEN-independent manner. However, NVP-BEZ235 selectively induced apoptotic cell death in prostate cancer cells presenting wild-type PTEN, DU145, but not in cells with deletion of PTEN, PC3. Treatment with NVP-BEZ235 resulted in autophagic cell death in PC3 cells with PTEN loss of function. Consistently, NVP-BEZ235 treatment did not result in the cleavage of caspase-3 and was link to active LC3-I/II as an indicator of autophagic cell death process, suggesting an alternate route for induction of cell death after exposure to NVP-BEZ235 in PTEN-null prostate cancer cells. These results suggest that PTEN/PI3K/Akt pathways are critical for prostate cancer survival and targeting PI3K signaling by NVP-BEZ235 may be beneficial in prostate cancer independent on PTEN genotype.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A63.
Citation Format: Jeong Eun Kim, Seoung-Woo Hong, Jae-Sik Shin, Jai-Hee Moon, Ye-Seul Kim, Kyu-pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Dong-Hoon Jin, Tae Won Kim. NVP-BEZ235, a dual PI3K/mTOR inhibitor, elicits an alternate route for induction of cell death in PTEN null prostate cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A63.
Abstract A76: Enhancement of cetuximab-induced antibody-dependent cellular cytotoxicity with lenalidomide in advanced solid tumors: A Phase I trial.
Authors: Bertino Erin M. , Rose Jeffrey S. , Wu Christina , Bekaii-Saab Tanios , Savvides Panayiotis S. , Goldberg Richard M. , Villalona Miguel , Lozanski Gerard , Carson William , Grever Michael , Otterson Gregory 
Published: August 2014

Abstract
Introduction: Antibody-dependent cellular cytotoxicity (ADCC) is one mechanism of action of monoclonal antibody (mAb) therapy. ADCC occurs via the innate immune system's ability to recognize mAb coated cancer cells and activate effector cells. Lenalidomide is an immunomodulatory agent with capacity to stimulate T cell proliferation, activate natural killer cells, and effect immune cytokines including IL-2, IL-12, and interferon gamma. Both preclinical and clinical data demonstrate the ability of lenalidomide to increase ADCC activity of mAb therapy. This Phase I CTEP sponsored trial aims to evaluate the combination of cetuximab with lenalidomide to enhance ADCC activity in advanced colorectal (CRC) and head and neck squamous cell cancers (HNSCC).
Patients/Methods: This Phase I dose escalation trial included patients with locally advanced or metastatic CRC (KRAS wild type) or HNSCC. Treatment consisted of cetuximab 500 mg/m2 IV every 2 weeks with lenalidomide orally days 1-21 every 28 days. Cetuximab dose was the same in all cohorts although dose reductions were permitted for toxicity. Three dose levels of lenalidomide were evaluated (15 mg, 20 mg, and 25 mg). Prior treatment with cetuximab, panitumumab, or other EGFR directed therapy was allowed. Planned correlative studies include measurement of ADCC using an in vitro chromium release assay, serum interferon gamma and NK cytokine profiles, and Fc gamma receptor polymorphisms.
Results: A total of 22 patients have been treated (19 CRC, 3 HNSCC). Grade 3 fatigue has been the only observed dose-limiting toxicity. One partial response was observed and 7 patients had stable disease as best response. Two patients remain on treatment. The recommended Phase II dose is cetuximab 500 mg/m2 with lenalidomide 25 mg daily days 1-21.
Conclusions: Cetuximab and lenalidomide was well-tolerated with minimal activity. Although response was not a primary endpoint, there is evidence of anti-tumor activity and clinical efficacy.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A76.
Citation Format: Erin M. Bertino, Jeffrey S. Rose, Christina Wu, Tanios Bekaii-Saab, Panayiotis S. Savvides, Richard M. Goldberg, Miguel Villalona, Gerard Lozanski, William Carson, Michael Grever, Gregory Otterson. Enhancement of cetuximab-induced antibody-dependent cellular cytotoxicity with lenalidomide in advanced solid tumors: A Phase I trial. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A76.