bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4323: Mitochondrial 22 tRNAs alterations in Iranian breast cancer patients
Authors: Eslamizadeh Sara , Ghaffarpour Massoud , Arabzadeh Mohammad , Houshmand Massoud 
Published: May 2015

Abstract
Introduction: Mitochondrial dysfunction is related to the genesis of many types of cancers, including breast cancer. Mitochondrial tRNA genes perform several functions including processing and translation in which are essential components of mitochondrial protein synthesis. Until now only few somatic mitochondrial tRNA mutations have been reported in cancer cells. The aim of this study was to find out the relationship between mitochondrial DNA mutations and breast cancer.
Patients and Methods: In current this study, 22 mitochondrial tRNAs genes in 30 tumoral tissues and adjacent non-tumoral tissues of patients with breast cancer and 100 blood samples of healthy controls were investigate using PCR-Sequencing methods.
Results and conclusions: From 30 breast cancer cases, twelve genetic variations were found in 22 tRNA MtDNA. Six of twelve (50%) were novel and remaining was polymorphism. Among new variants, which incloding C1631A (tRNA Val), T1633A (tRNA Val), A5565G (tRNA Trp), G5849A (tRNA Tyr) were at hetroplasmic state and remaining which including C12187 (tRNA His) and A15948G (tRNA Thr) were at homoplasmic. Among variants, A12308G, a polymorphic mutation in V-loop (tRNALeu(CUN)), was found in 23% breast tumoral tissues (7 of 30) and 3%in healthy blood controls (3 of 100), indicating a statistically significant association of the A12308G alteration between tumoral tissues and controls(p &lt; 0.05).Our finding indicate that , the A12308G alteration may increase the risk of breast cancer through its impact on the tRNA structure result in mitochondrial dysfunction. Therefore, it may consider as a pathogenic predisposition factor for the breast cancer risk.
Note: This abstract was not presented at the meeting.
Citation Format: Sara Eslamizadeh, Massoud Ghaffarpour, Mohammad Arabzadeh, Massoud Houshmand. Mitochondrial 22 tRNAs alterations in Iranian breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4323. doi:10.1158/1538-7445.AM2014-4323
Abstract 4324: BNip3 connects energy sensing to hepatic lipid metabolism and mitophagy
Authors: Boland Michelle L. , Huang He , Shah Ramilla , Ali Almas , Zhao Yingming , Rhodes Christopher J. , Macleod Kay F. 
Published: May 2015

Abstract
BNip3 is a hypoxia-inducible member of the Bcl-2 family that integrates into the outer mitochondrial membrane as stable homodimers where it acts as a receptor for mitochondrial engulfment through a conserved LC3 interacting region. Hepatic BNip3 levels are constitutively elevated relative to other tissues, and dramatically increase upon nutrient deprivation or glucagon stimulation, suggesting a key role for BNip3 in the fasting response. We have determined that the fasting-induced increase in hepatic BNip3 protein levels is not solely attributable to transcriptional induction and have identified post-translational modification of BNip3 that affects protein stability and function. In a mouse model of BNip3 loss, we observe metabolic defects including increased hepatic lipid synthesis and reduced fatty acid oxidation. Consistent with BNip3's role in mitophagy, defects in liver metabolism were linked to increased mitochondrial mass, but decreased mitochondrial function, including reduced oxygen consumption and loss of mitochondrial membrane potential. Delivery of a mitophagy deficient mutant BNip3 to the BNip3 null liver indicates that defects in lipid metabolism are not simply due to the accumulation of defective mitochondria, but rather BNip3 has another role to regulate lipid metabolism based on nutrient status. Of relevance, BNip3 is epigenetically silenced in the more aggressive and common form of HCC (sub-type A) and thus this work identifies potential mechanisms by which this protein may act as a tumor suppressor.
Citation Format: Michelle L. Boland, He Huang, Ramilla Shah, Almas Ali, Yingming Zhao, Christopher J. Rhodes, Kay F. Macleod. BNip3 connects energy sensing to hepatic lipid metabolism and mitophagy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4324. doi:10.1158/1538-7445.AM2014-4324
Abstract 4332: Diagnostic applications of fatty acid synthase monoclonal antibodies
Authors: Carney Walter P. , Zhang Wendy , Jarosz David , Muraca Patrick , TAM Sunny 
Published: May 2015

Abstract
Fatty acid synthase (FASN), is an enzyme capable of de novo fatty acid synthesis and highly expressed and activated in most human carcinomas. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis and is not a single enzyme but a whole enzymatic system composed of two identical 272 KDa multifunctional polypeptides. Fatty-acid synthesis is now associated with clinically aggressive tumor behavior, tumor-cell growth and is associated with poor prognosis in prostate and breast cancer. Its inhibition is selectively cytotoxic to human cancer cells. Thus, FASN and fatty acid metabolism have become an important focus for the diagnostic and treatment of cancer. We have developed a panel of anti-human FASN Mab for application to several diagnostic platforms. Recombinant full length intact FASN protein (rFASN) was used to immunized C57BL/6 mice, sera were collected from pre- and post-immunized mice and tested by ELISA and Western blot on rFASN protein or rFASN immobilized on Western blot. Spleens from mice with the highest anti-FASN antibody titer was fused with a mouse myeloma cell line Sp2/0-Ag14 for hybridoma production. Among the panel of positive anti-FASN clones selected, two clones with isotype of IgG1kappa have shown strong reactivity to the rFASN and native FASN protein on Western analysis. Upon further Western analyses with cell lysates, we have demonstrated specific detection of FASN protein in human embryonic kidney cells (HEK), HEK cells overexpressing the rFASN protein, HOP-62 cells which express low levels of FASN and MALME cells, which express high levels of FASN. Additional biochemical characterization of these antibodies is ongoing, and includes epitope mapping and reactivity to various FASN protein fragments. These anti-FASN antibodies will be tested by IHC, ELISA to compare tissues expression levels of FAS by IHC or circulating levels of the FASN in both normal and cancer patients. With the increasing development of FAS inhibitors these antibodies will be tested as Companion Diagnostics and tested to see if the rise and fall of the FASN circulating levels correspond with cancer progression or therapy response.
Citation Format: Walter P. Carney, Wendy Zhang, David Jarosz, Patrick Muraca, Sunny TAM. Diagnostic applications of fatty acid synthase monoclonal antibodies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4332. doi:10.1158/1538-7445.AM2014-4332
Abstract 4335: A p53/HIF-1alpha-mediated metabolic response to stress
Authors: Ganapathy Suthakar , Yuan Zhi-Min 
Published: May 2015

Abstract
p53 is a key player in the cellular stress response. Apart from its canonical role in cell checkpoint functions, p53 also regulates cellular metabolism by blocking glycolysis and promoting oxidative phosphorylation. The hypoxia-inducible factor 1(HIF-1), on the other hand, is a master transcription factor promoting glycolysis. We describe a previously unrecognized metabolic response to low levels of stress, including low doses of ionizing radiation or arsenic. By using an integrated approach, we demonstrate that low-level stress induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis leading to increased stress tolerance in both cell and animal models. Low-level stress-induced metabolic changes are mediated by a functional cooperation between p53 and HIF-1α. Our work provides a novel metabolic mechanism of the stress response.
Citation Format: Suthakar Ganapathy, Zhi-Min Yuan. A p53/HIF-1alpha-mediated metabolic response to stress. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4335. doi:10.1158/1538-7445.AM2014-4335
Abstract 4336: Design of a chamber for studying glucose metabolism by anoxic cancer cells
Authors: Lankelma Jan , Ahmed Mohamed , Nadal Adrià López , Dorsman Josephine C. , Joenje Hans , Westerhoff Hans V. 
Published: May 2015

Abstract
Many tumors contain anoxic areas. In vitro studies of anoxia can easily be hampered by contamination with traces of oxygen. In order to find out how temporal depletion of extracellular glucose effects anoxic cell death in vitro we have developed a chamber in which 50 000-500 000 cells can be exposed to approximately 30 μl of medium, resulting in rapid depletion of oxygen and nutrients. Before the experiments, cancer cells were seeded on a glass plate, which was the lower glass plate after clamping with an upper plate that contained an 80-100 μm thick silicone spacer. The medium of the cavity between the two flat glass plates could be flushed through an inlet and outlet hole in the upper plate, located in the corners of the cavity. Samples were collected from the outlet hole for analysis.
Most cancer cell lines use both anaerobic and aerobic metabolism to generate ATP, resulting in a more rapid depletion of oxygen than of glucose. We found that after 3 hours the glucose was completely consumed by the MCF-7 human breast cancer cells and that overnight exposure resulted in cell death, except in the immediate proximity of the holes, where oxygen could diffuse into the medium. An interesting observation was that the lactate produced was more than double the glucose used from the medium, suggesting that also intracellular glycogen stores had been consumed by the cancer cells.
We are especially interested in using this system to simulate the effect of dietary restriction on individual dormant breast tumors that have not (yet) started angiogenesis. These are hypothesized to contain an outer ring of anoxic cells, that depend on and rapidly consume the lowest concentrations of glucose “at the end of the glucose gradient” from the nearest capillary blood vessel. A temporary decrease of blood glucose may kill these anoxic cells and perhaps affect non-Warburg cells less. The time dependence of cell killing on this decrease will be investigated using this system.
Citation Format: Jan Lankelma, Mohamed Ahmed, Adrià López Nadal, Josephine C. Dorsman, Hans Joenje, Hans V. Westerhoff. Design of a chamber for studying glucose metabolism by anoxic cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4336. doi:10.1158/1538-7445.AM2014-4336
Abstract 4341: Metabolomic analysis of HER2-positive breast cancer cells
Authors: Sahni Malika K. , Ravindran Resmi K. , Khan Imran H. , Bush Jason A. , Krishnan V. V. 
Published: May 2015

Abstract
Purpose: HER2-positive breast cancer accounts for more than 20% of the diagnosed cases and is characterized by aggressive growth, increased disease recurrence, and poor prognosis. While much of the signaling mechanism(s) have been elucidated, the impact of HER2 positivity on cellular metabolism is not well understood. We examined (1) gene expression profiles of mammalian breast cancer cell lines with increasing HER2 expression levels (MCF10A, MDA-MB-468, MDA-MB-453, HCC1954, HCC2218) and correlated changes to metabolic expression profiles and (2) the effect of serum starvation and pervanadate treatment on the metabolic profiles of these HER2-expressing cell lines.
Methods: Our study used a combination of 1H-NMR and 2D-NMR (TOCSY), bioinformatics analyses, and protein expression validation in human breast cancer cell lines (untreated, serum-starved, serum-starved with pervanadate treatment).
Results: We found that both gene and metabolic expression profiles of HER2-positive cell lines correlated with leucine and isoleucine biosynthesis (p-value &lt; 0.05). Comparative analyses of profiles from untreated, serum-starved, and serum-starved with pervanadate-treated cell samples revealed that lactate concentration (p-value &lt;0.05) dropped significantly with serum starvation and pervanadate treatment consistent with reduced glycolytic metabolism and potentially mediated through suppression of tyrosine phosphatase activity.
Conclusion: This study highlights important new metabolites that are potential biomarkers of HER2-positive breast cancer and suggests alternate/novel pathways to consider for future understanding and treatment.
Citation Format: Malika K. Sahni, Resmi K. Ravindran, Imran H. Khan, Jason A. Bush, V. V. Krishnan. Metabolomic analysis of HER2-positive breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4341. doi:10.1158/1538-7445.AM2014-4341
Abstract 4344: Tumor suppressive miR-137 targets Aurora-A and leads to apoptosis in colorectal cancer cells
Authors: Huang Yu-Chuan , Hung Liang-Yi 
Published: May 2015

Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and the third leading cause of death in the world. Early diagnosis, early therapy, finding of new biomarkers and specific therapeutic targets are urgent necessities for CRC patients. Previous reports indicated that loss of miR-137 expression, which is a potential tumor suppressor microRNA and always loses its expression in cancer cells, may contribute to the progression of CRC. However, the detailed underlying mechanism is still unclear. Here, we demonstrated that Aurora-A, a centrosomal serine/threonine kinase that plays essential roles in regulating various important events during cell cycle progression, is one of the targets of miR-137. By luciferase reporter assay, Q-PCR, and Western blot analysis, we demonstrated that miR-137 can target Aurora-A and inhibit its expression. Overexpression of miR-137 results in cell apoptosis in colorectal cancer cells. Expression of miR-137 and Aurora-A in colorectal cancer tissues and colon polyps, the pre-lesion colon tissue, is negative correlated. In addition, the down-regulated miR-137 expression in colon polyps is positive correlated with its size. The treatment of cells with methyltransferase inhibitor 5-Azacytidine induces the expression of miR-137. Our results suggest that losses of miR-137 expression may contribute to the early stage neoplasia in CRC progression. The investigation of the regulatory mechanism of miR-137 mediated Aurora-A inhibition may provide a novel therapeutic strategy for CRC.
Citation Format: Yu-Chuan Huang, Liang-Yi Hung. Tumor suppressive miR-137 targets Aurora-A and leads to apoptosis in colorectal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4344. doi:10.1158/1538-7445.AM2014-4344
Abstract 4347: Interphase reduction in ZEB1 and tubulin isotypes in breast cancer cells associated with antimitotic drug treatment
Authors: Lobert Sharon , Graichen Mary E. 
Published: May 2015

Abstract
We recently demonstrated that paclitaxel treatment (10X IC50) reduces mRNA for the epithelial to mesenchymal protein ZEB1 and β-tubulin isotype classes I, III and IVB in MDA-MB-231 breast cancer cells, commonly used as a model for triple-negative breast cancers [Lobert et al., Biochemistry Aug 13;52(32):5482-9]. This work showed that miR-200c, which regulates ZEB1, contributes to the changes in β-tubulin isotype mRNA. The current question is whether these parallel changes in ZEB1 and β-tubulin isotype mRNA were unique to antimitotic drug treatment. We treated MDA-MB-231 cells with equipotent (3X IC50) concentrations of paclitaxel, vincristine, eribulin or doxorubicin for 24 hours. Flow cytometry demonstrated that 27-30% of cells were in G2/M (paclitaxel, vincristine and eribulin) compared to 25% of control cells. Thus the cells had similar cell cycle profiles and were not blocked in mitosis. At 24 hours, there were no measurable changes in total tubulin protein by Western blotting. As shown previously, paclitaxel treatment significantly reduced ZEB1 and β-tubulin isotype classes I, III and IVB mRNA. Eribulin treatment significantly reduced ZEB1 and β-tubulin isotype classes I and IVB mRNA, but not β-tubulin class III. Vincristine treatment only reduced β-tubulin class I mRNA. These data together indicate that although antimitotic drugs all target tubulin, they alter signaling pathways that do not overlap. Doxorubicin did not reduce ZEB1 or β-tubulin isotypes; nor did it increase levels of miR-200c, suggesting that these changes may require tubulin or microtubules as a mediator of the effects. These data show that signaling during interphase is altered by antimitotic drug treatment, leading to changes in β-tubulin isotype mRNA levels. A reduction in β-tubulin isotype class III mRNA in interphase cells is associated specifically with paclitaxel treatment. Next generation sequencing for micro-RNAs comparing control cells to those treated with paclitaxel under the conditions described above suggests that nineteen micro-RNAs are either up or downregulated, indicating that the efficacy of paclitaxel may in part be due to micro-RNA regulation of mRNA. (supported by funding from UMMC School of Nursing)
Note: This abstract was not presented at the meeting.
Citation Format: Sharon Lobert, Mary E. Graichen. Interphase reduction in ZEB1 and tubulin isotypes in breast cancer cells associated with antimitotic drug treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4347. doi:10.1158/1538-7445.AM2014-4347
Abstract 4357: Long noncoding RNA HOTAIR is targeted and regulated by microRNA-141 in renal carcinoma cells
Authors: Chiyomaru Takeshi , Fukuhara1 Shinichiro , Saini Sharanjot , Majid Shahana , Deng Guoren , Shahryary Varahram , Chang Inik , Tanaka Yuichiro , Enokida Hideki , Nakagawa Masayuki , Dahiya Rajvir , Yamamura Soichiro 
Published: May 2015

Abstract
HOTAIR is a long non-coding RNA (lncRNA) which interacts with the Polycomb Repressive Complex and suppresses its target genes. HOTAIR has also been demonstrated to promote malignancy. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. We found that HOTAIR expression is inversely correlated to miR-141 expression in renal carcinoma cells. HOTAIR promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in renal carcinoma cells. miR-141 binds to HOTAIR in a sequence specific manner, and suppresses HOTAIR expression and functions including proliferation and invasion. Both HOTAIR and miR-141 were associated with the immunoprecipitated Argaunaute2 (Ago2) complex and the Ago2 complex cleaved HOTAIR in the presence of miR-141. These results demonstrate that HOTAIR is suppressed by miR-141 in an Ago2 dependent manner.
Citation Format: Takeshi Chiyomaru, Shinichiro Fukuhara1, Sharanjot Saini, Shahana Majid, Guoren Deng, Varahram Shahryary, Inik Chang, Yuichiro Tanaka, Hideki Enokida, Masayuki Nakagawa, Rajvir Dahiya, Soichiro Yamamura. Long noncoding RNA HOTAIR is targeted and regulated by microRNA-141 in renal carcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4357. doi:10.1158/1538-7445.AM2014-4357
Abstract 4362: miR-211 is contributive to the progression of oral carcinoma through targeting transcription factor 12 (Tcf12)
Authors: Chen Yi-Fen , Chang Kuo-Wei K. , Lin Shu-Chun 
Published: May 2015

Abstract
Oral squamous cell carcinoma (OSCC) is one of the prevalent malignancies worldwide. MicroRNAs are short RNA molecules that regulate pathogenesis, including OSCC carcinogenesis, by post-transcriptional down-regulation of target genes. Our previous study has identified a relationship between high miR-211 expression and the invasion of OSCC. This study further dissects the molecular mechanisms underlying the progression of OSCC as affected by miR-211. Tcf12 is a helix-loop-helix transcription factor with unclear implications in oral malignancies. MiR-211 was predicted to target the 3′UTR of transcription factor 12 (Tcf12). Reporter assays confirmed the direct targeting of miR-211 on Tcf12. MiR-211 expression decreased both endogenous and exogenous Tcf12 expression. Exogenous Tcf12 expression suppressed proliferation, migration and anchorage-independent colony formation of OECM-1 OSCC cells. On the contrary, knockdown of endogenous Tcf12 expression enhanced these oncogenic phenotypes. Furthermore, in tumor cells with miR-211 overexpression, Tcf12 can reduce its oncogenic potential; whereas miR-211 can also rescue the suppression of Tcf12 to tumor cells. Down-regulation of Tcf12 was identified in 75% (27/36) human OSCC samples. To elucidate the in vivo oncogenic roles of miR-211 in OSCC carcinogenesis, K14 promoter driven murine miR-211 transgenic mouse lines (K14-GFP- miR-211) were established. The Tcf12 expression in squamous epithelium was down-regulated in transgenic mice relative to wild type mice. After tumor induction by 4-nitroquinoline 1-oxide treatment, the transgenic mice exhibited more advanced tongue and esophageal tumorigenesis comparing to wild type mice. In summary, this study reveals that Tcf12 is suppressive to OSCC. MiR-211 regulates OSCC progression by targeting Tcf12. The K14-GFP-miR-211 transgenic mice will help future investigation of the pathogenic mechanisms underlying OSCC progression and the development of therapeutic strategy.
Citation Format: Yi-Fen Chen, Kuo-Wei K. Chang, Shu-Chun Lin. miR-211 is contributive to the progression of oral carcinoma through targeting transcription factor 12 (Tcf12). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4362. doi:10.1158/1538-7445.AM2014-4362