bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3075: A novel transcriptional role of spindle assembly checkpoint protein Cdc20 regulating the expression of mitotic ubiquitin carrier protein UbcH10
Authors: Nath Somsubhra , Banerjee Taraswi , Sen Debrup , Das Tania , Roychoudhury Susanta 
Published: June 2012

Abstract
Progression through mitosis requires precisely timed ubiquitin-dependent degradation of specific substrates. UbcH10, an ubiquitin-conjugating enzyme, plays a crucial role with anaphase promoting complex/ cyclosome (APC/C) in progression of and exit from mitotis. Similarly, spindle assembly checkpoint (SAC) protein Cdc20 plays an important role in transition from metaphase to anaphase by activating APC/C. Cdc20 itself gets ubiquitinated by UbcH10 and thus activated to bind with APC/C. Any defect in chromosome alignment activates SAC by blocking Cdc20 and thus anaphase transition is arrested. Earlier our lab reported that Cdc20 overexpression led to defective SAC resulting in aneuploidy. This prompted us to examine the regulation of UbcH10 expression in Cdc20 upregulated condition.
Initially, we observed a correlation in the expression of both Cdc20 and UbcH10 in different primary tumors and cancer cell lines. Next, a dose-dependent increase in endogenous UbcH10 levels was found upon ectopic expression of Cdc20. Alternatively, CDC20 knockdown by siRNA led to downregulation of endogenous UbcH10. Activation of UBCH10 promoter-luciferase activity by Cdc20 indicated the regulation at transcriptional level. ChIP assay showed the presence of Cdc20 on UBCH10 promoter leading to chromatin remodelling by interacting with CBP/p300. APC/C-CBP/p300 complex is reported to be involved in transcription regulation. Here, we established the presence of APC/C on the UBCH10 promoter using ChIP assay. Further from ChIP and Co-IP assay we established that Cdc20 regulates APC/C and CBP/p300 association and thus modulates APC/C-CBP/p300 mediated transcriptional regulation of UBCH10. Also, we found cell cycle specific regulation of expression of UbcH10 by Cdc20. Finally, Cyclin B1 degradation assay showed physiological relevance of Cdc20 mediated UbcH10 regulation on mitotic progression.
In summary, our data showed a novel role of Cdc20 as a transcription regulator and it regulates UbcH10 expression in a cell cycle specific manner. The co-regulated expression of both these proteins maintains proper mitotic progression which otherwise may results in aneuploidy.
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 3075. doi:10.1158/1538-7445.AM2011-3075
Abstract 3087: Regulation of p53 stability and activity by ribosomal protein S27a
Authors: Sun Xiao-Xin , DeVine Tiffany , Dai Mushui 
Published: June 2012

Abstract
Ribosomal proteins (RPs) play a critical role in tightly coordinating p53-dependent cell cycle checkpoint with ribosomal biogenesis. A number of RPs, including L5, L11, L23, L26, and S7, specifically bind to MDM2 and inhibit MDM2-mediated p53 ubiquitination and degradation, leading to p53 activation, in response to nucleolar stress triggered by the perturbation of ribosomal biogenesis. Here, we report S27a, a ribosomal protein from small subunit of ribosome and synthesized as an ubiquitin C-terminal extension protein (CEP80), as a novel MDM2 regulator. S27a interacts with MDM2 at the central acidic domain of MDM2 and suppresses MDM2-mediated p53 ubiquitination, leading to p53 activation and cell cycle arrest. Knockdown of endogenous S27a significantly attenuated p53 activation by treatment with a low dose (5 nM) of actinomycin D (Act D), which specifically inhibits RNA polymerase I activity leading to inhibition of rRNA synthesis and perturbation of ribosomal biogenesis, suggesting that S27a is a non-redundant MDM2 regulator in response to nucleolar stress. Interestingly, we also show that MDM2 ubiquitinates S27a, leading to protesomal degradation of S27a, in response to Act D treatment, suggesting that MDM2, in turn, controls S27a levels in response to nucleolar stress. Taken together, our results reveal that S27a regulates p53 activity in response to nucleolar stress via a novel and dynamic interplay between S27a and MDM2.
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 3087. doi:10.1158/1538-7445.AM2011-3087
Abstract 3121: Study of leukemia inhibitory factor (LIF) system in a murine mammary tumor comprising luminal and myoepithelial cells
Authors: Krasnapolski Martin A. , Quaglino Ana , Kordon Edith , Bal de Kier Joffe Elisa D. 
Published: June 2012

Abstract
The presence of LIF, a cytokine that activates JAK/STAT and ERK pathways, its receptor (LIFRb) and the constitutive activation of Stat3 (a molecule downstream LIFRb) have been described in tumors, primary cultures and several cancer-derived cell lines, suggesting a role for this pathway in tumor progression. Also, Stat3 activation was widely related to an immunosuppressive phenotype in many tumor models.
From the murine mammary adenocarcinoma M38 comprising luminal (LEP) and myoepithelial (MEP) cells (both transformed) we derived LM38-LP (LEP & MEP), LM38-HP (epithelioid) and LM38-D2 (MEP) cell lines. While the mixed cell line presents a malignant behavior, the last two show a lower growth rate and metastatic potential than the parental tumor. Previously we demonstrated that this lower malignancy is partially caused by their inability to suppress the host's immune system, underscoring the importance of cellular interactions in complex tumor behaviors.
Our purpose was to evaluate LIF and LIFRb mRNA expression levels and to study LIF effects on Stat3 and ERK activation, as well as on the proliferation and clonogenic capacity in the LM38 family of cell lines.
Using RT-PCR we could see that LM38-LP cell line expresses high LIF and LIFRb mRNA levels, LM38-HP expresses LIF mRNA but not it receptor's mRNA and LM38-D2 has low levels of both molecules. By Western blot we studied LIF (80 ng/ml) effect over Stat3 and ERK activation. While in LM38-LP and LM38-D2 cells Stat3 and ERK phosphorylation was rapidly induced at 5 min, in LM38-HP cells, that don't express LIFRb, no response was detected. Then, we evaluated the effect of a prolonged 48 h treatment with LIF (1, 5, 20 and 80 ng/ml) on cell viability using MTS assay. While LIF slightly reduced cell viability (20%) in LM38-LP and LM38-D2 cell lines, LM38-HP cells were not affected. Finally, since LIF is also involved in stem cell maintenance, the effect of LIF in a low density/clonogenic setting was evaluated. While in LM38-LP and LM38-D2 cell lines LIF significatively (p&lt;0.05) increased the number of colonies, LM38-HP cells were unaffected.
We can conclude that LIF could be involved in LEP-MEP interaction and although it induced a subtle viability reduction, LIF could be nevertheless promoting tumor progression by increasing the number of clonogenic cells. In addition, LIF-induced Stat3 activation could be the responsible of the immunosuppresive characteristics of the mix tumor cell line, a proposal that deserves future studies.
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 3121. doi:10.1158/1538-7445.AM2011-3121
Abstract 3123: Differential effects of polyoma virus middle tumor antigen mutants upon gap junctional, intercellular communication
Authors: Greer Samantha N. , Geletu Mulu , Raptis Leda H. 
Published: June 2012

Abstract
Gap junctions are channels that connect the cytoplasm of adjacent cells. Gap junctional, intercellular communication (GJIC) is blocked in cells transformed by oncogenes such as the middle Tumor antigen of polyoma virus (mT), an oncoprotein which associates with and is tyrosine-phosphorylated by cSrc family members. Specific phosphotyrosines provide docking sites for the phosphotyrosine binding domain of Shc (mT-tyr250) and the SH2 domain of the phosphatidylinositol 3-kinase (mT-tyr315), resulting in the activation of their downstream signaling cascades, Ras/Raf/Erk and PI-3 kinase/Akt, respectively.
To examine the effect of these mT-initiated pathways upon gap junctional communication and neoplasia, GJIC was assessed in mT-mutant-expressing, rat liver epithelial T51B cells which normally have extensive GJIC, using a novel technique of in situ electroporation we developed. The results show that although low levels of wt-mT are sufficient to interrupt gap junctional communication, GJIC suppression still requires an intact tyr250 site, that is activation of the Ras pathway. In sharp contrast, activation of the PI-3 kinase pathway is not required for GJIC suppression. It is remarkable that T51B cells expressing a mutant deficient in binding of Shc, hence activation of the Ras pathway, are still morphologically transformed and do grow into tumors in syngeneic rats, albeit with an altered morphology. These results indicate that GJIC suppression requires Ras/Erk but not PI-3 kinase/Akt signalling, and is independent of neoplastic conversion in rat liver epithelial cells.
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 3123. doi:10.1158/1538-7445.AM2011-3123
Abstract 3161: Increased expression of MUC1 and claudin-10 is associated with poor prognosis of patients with gastric cancer
Authors: Park Keon Uk , Kim Jin Young , Do Young Rok , Song Hong Suk , Hwang Ilseon , Ha Eunyoung , Ryoo Hun Mo , Min Young Joo 
Published: June 2012

Abstract
Background: Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. Several studies have shown the aberrant expression profile of mucins in gastric cancer. Claudins are the proteins that participate in the formation of tight junctions. Tight junction proteins are believed to be involved in the regulation of proliferation, differentiation, and other cellular functions. Expression of claudin family in gastric cancers has been studied by many laboratories, but the results are conflicting. Therefore, we investigated the potential of MUC and claudin family to be used as a prognostic marker in gastric cancer.
Methods: One-hundred eighty gastric adenocarcinoma patients who underwent surgical resection and had not received any pre- or -post surgery therapy, were selected for this study. Among the 180 gastric cancer samples tested here, 63 (34%) were early gastric cancer, and 117 (66%) were advanced. We made tissue microarrays with paraffin-embeded formalin fixed blocks of gastric cancer and these microarrays were evaluated for phenotypic expression of MUC1, MUC4, Claudin 1, 3, 4, 5, 7 and 10 using anti-human rabbit or mouse polyclonal antibody. The expression levels were correlated with key clinicopathologic features and patient outcomes.
Results: There was no significant difference of MUC and claudin expression between early and advanced gastric cancer. Gastric cancer patients with increased MUC1 expression were significantly associated with shorter overall survival as compared to those with low expression of MUC1 (log rank, p=0.039). MUC4 expression were significantly associated with decreased overall survival only in N0 patients (log rank, p=0.046). Increased expression of Claudin-10 was significantly associated with shorter disease free survival (log rank, p=0.038). Claudin 1,3,4,5 and 7 expression was not associated with significant difference of overall survival or disease free survival.Conclusion: Our present findings show that the increased expression of MUC1 and claudin-10 is a prognostic indicator of poor survival of patients with early and advanced gastric 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 3161. doi:10.1158/1538-7445.AM2011-3161
Abstract 3184: Diagnostic value of Annexin A1 as a marker for myoepithelial cells in normal breast glands but is lost in malignant breast glands
Authors: Elshimali Yahya I. , Wu Yanyuan , Chen Daniel , Vadgama Jaydutt V. 
Published: June 2012

Abstract
Introduction: Annexin AI belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins. Annexin I has been of interest for use as a potential target for anticancer drugs. Upon induction by modified NSAIDS and other potent anti-inflammatory drugs, annexin I inhibits the NF-κB signal transduction pathway, which is exploited by cancerous cells to proliferate and avoid apoptosis. ANXA1 inhibits the activation of NF-κB by binding to the p65 subunit.
Methods: We used immunohistochemistry stain of Annexin A1 monoclonal antibody to study its expression in 100 cases of breast tissue, 50 cases of normal tissue vs. 50 cases of malignant tissue, using tissue micro array (TMA).
Results: Our analysis show a decreased expression of Annexin A1 in malignant tissues compared to non-malignant tissues. Annexin A1 stains myoepithelial cells in 95 % of normal glands, but it is absent in 90 % of the periphery malignant glands. This is most likely due to the absence of the myoepithelial cells.
Conclusion: We conclude that Annexin A1 has diagnostic value in breast pathology by staining myoepithelial cells of normal gland in addition to its characteristic in staining of normal ductal cells at different intensity. Annexin A1 could be used as a biomarker for myoepithelial cells in surgical pathology practice.
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 3184. doi:10.1158/1538-7445.AM2011-3184
Abstract 3188: Discovery and validation of non-invasive biomarkers for benign prostate hyperplasia and prostate cancer
Authors: Curatolo Adam S. , Roy Roopali , Jedinak Andrej , Loughlin Kevin , Meyers Michael , Libermann Towia A. , Dillon Simon , Bhasin Manoj , Moses Marsha A. 
Published: June 2012

Abstract
Although the PSA test is successfully used to determine how well a prostate cancer patient is responding to therapy, it cannot reliably distinguish between the presence of prostate cancer and benign prostate diseases such as benign prostatic hyperplasia (BPH) or prostatitis. These conditions and early prostate cancer can all result in low to moderate levels of PSA in the blood. The absence of sensitive and specific biomarkers that can distinguish between benign conditions and prostate cancer often leaves patients and their doctors with little recourse than to utilize invasive approaches to diagnose prostate cancer that can result in harmful and undesirable side effects. With the goal of identifying and validating non-invasive biomarkers that can distinguish between neoplastic and non-neoplastic disease of the prostate, we have utilized iTRAQ (isobaric tag for relative and absolute quantitation) as our technique of choice to sensitively and accurately identify and quantify proteins that are differentially present in the urine of men with BPH and prostate cancer. This approach resulted in the identification of 26 proteins that were differentially expressed at a significant level, with high confidence, in urines obtained from men from each of the two groups of interest. These proteins represent a number of functional categories including cell assembly and organization, cell signaling, cell morphology, carbohydrate metabolism, cellular growth and proliferation, lipid metabolism, androgen and estrogen metabolism and DNA replication, recombination and repair, among others. Validation of ten proteins with the greatest differential expression between the two groups has been completed. Immunoblot analyses have confirmed the significant differential presence of these proteins in a larger number of patient samples analyzed thus far. Large scale validation studies are ongoing. These data suggest that the ability to non-invasively monitor the levels of these proteins in the urine of patients with uninformative PSA levels has the potential to provide clinically relevant information for reliable diagnosis of BPH and prostate cancer. These proteins may also serve as potential therapeutic targets for the treatment of men with BPH and prostate cancer. (Supported by The Ellison Foundation)
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 3188. doi:10.1158/1538-7445.AM2011-3188
Abstract 3202: Decreased Dkk3 protein expression is associated with a poor prognosis of cervical cancer
Authors: Lee Eun-Ju , Kim Mi Kyung , Park Hyung Moo , Lee Sang-Hoon , Kim Dong-Ho , Lee Moo-Yul , Myung Soon-Chul , Kim Won Yong 
Published: June 2012

Abstract
Dkk3 has tumor suppressor properties in various cancers. Recently, we reported that the mRNA level of Dkk3 gene was down-regulated by epigenetic alteration in cervical cancer and that forced expression of Dkk3 resulted in the growth inhibition of cervical cancer cells. The aim of this study was to assess the expression of Dkk3 protein in cervical cancer tissue and determine potential clinical correlations. Immunohistochemical analysis was performed on 94 cervical cancer tissues. Clinical and pathological parameters were obtained from medical record. Survival data were estimated using Kaplan-Meier estimates and compared with log-rank test where indicated. Out of 94 tissue samples, negative, weak, moderate and high expression of Dkk3 were observed in 29 (30.9%), 31 (33.0%), 18 (19.1%) and 16 (17.0%) tissue samples. Dkk3 expression was negatively correlated with FIGO clinical stage (p&lt;0.03, Mann-Whitney test). The 5-year disease free survival of patients with a negative or weak expression was significantly lower than that of those with moderate or high expression (70.6% versus 86.3%, respectively, p=0.04, log-rank test). The result of this study showed that down-regulation of Dkk3 is associated with advanced FIGO clinical stage and poor survival outcome of cervical 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 3202. doi:10.1158/1538-7445.AM2011-3202
Abstract 3225: Influence of localized vibration loading on bone targeting of bisphosphonate
Authors: Papineni Rao V. , Pan Jingyi , Geldhof Benjamin 
Published: June 2012

Abstract
Targeting of bisphosphanate analog to specific skeletal sites is investigated by using localized vibration loading. Breast, lung, and prostate cancer cells metastasize frequently at bone resulting in debilitating pain, which is one of the major complications in majority of patients. The palliative bone pain management includes the bisphosphanate therapy. Bisphosphonates apart from being a potent inhibitor of bone resorption, also provides pain relief and improves bone health. However these medications result in complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Our continued efforts in investigating site-selective skeletal targeting of bisphosphonates are primarily to establish modes to overcome such drug-related side-effects. Non-invasive near-infrared (NIR) fluorescence imaging was used to monitor binding of NIR dye conjugated bisphosphonate (osteosense) to specific skeletal sites in response to localized vibration loading. Vibration loading, was performed on multiple sets of mice- subjecting them to vibration frequency of 70 Hz for five min (5 times/week) duration at the right thigh region. Osteosense and was injected intravenously after 21-day exercise regime. Both noninvasive and ex vivo imaging show significantly increased NIR signals at the right surface of the lumbar vertebrae. The unequivocal outcome in both the cohort studies, following the localized vibration loading confirms the role of direct high-frequency vibration stimulation in bisphosphonate targeting. Histochemical analysis of the bone and the muscle describe the mechanistic role in the targeted binding of the bisphosphonate.
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 3225. doi:10.1158/1538-7445.AM2011-3225
Abstract 3281: Functional characterization of a fusion angioinhibitor molecule “Combostatin”
Authors: Boosani Chandra Shekhar , Gunda Venugopal , Laknaur Archana , Akulapalli Sudhakar 
Published: June 2012

Abstract
Angiogenesis, a process of new blood vessel formation is observed during pathological and physiological conditions, can be controlled by circulating endogenous angioinhibitory molecules derived from non-collagenous domains of type IV and type XVIII collagen. In the present study we developed a fusion protein (Combostatin) from functional domains of three known endogenous angioinhibitors [α1(IV)NC1 (arresten), α3(IV)NC1 (tumstatin) and type XVIII collagen (endostatin)] using recombinant DNA technology and expressed using Baculovirus expression system. We then tested the angioinhibitory functions of Combostatin in-vitro using cellular proliferation, invasion, migration and tube formation assays. Combostatin was found to inhibit endothelial cell proliferation and invasion in a dose dependent manner, similar to its parent molecules. Interestingly, inhibition of endothelial migration and tube formation by Combostatin was significantly higher compared to its parent molecules. In addition Combostatin binds to different cell surface integrins and inhibits multiple signaling pathways. Taken together, our studies identify that Combostatin is a more potent angioinhibitor molecule compared to its parent molecules. Our results support earlier studies that showed multiple angioinhibitors which are promising candidates with clinical importance compared to single inhibitor molecules. Further pre-clinical validation of Combostatin is essential to characterize its use in the treatment of vascular diseases including cancer, diabetic retinopathy etc.
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 3281. doi:10.1158/1538-7445.AM2011-3281