bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3416: IHC assessment of PBRM1 loss in colon and lung carcinomas
Authors: Li Aihua , Gao Yongfu , Zhang Yuekai , Pan Hongyang , Chan Jackie K. , Yang Ximing J. , Chen Taiying 
Published: August 2015

Abstract
PBRM1 (also known as BAF 180) is a chromatin remodeling polybromodomain protein recently identified as the second most frequently mutated gene in renal cell carcinoma (RCC). Loss of PBRM1 protein expression is most frequently observed in clear cell RCC and correlated with tumor progression. Approximately 40-50% of patients with RCC have mutations in PBRM1, and loss of PBRM1 was also reported in 28% of melanocytic neoplasms. However, loss of PBRM1 has not been studied in other tumors using patient tissues. The purpose of this study was to assess the protein expression of PBRM1 in a wide-ranging collection of normal and tumor tissues. Here we report our findings of PBRM1 loss in colon and lung carcinomas using a newly developed rabbit monoclonal antibody (RabMAb), Clone EP342. The antibody was generated by immunization of rabbits with PBRM1 recombinant protein. Sera collected from immunized rabbits were screened by ELISA, WB and IHC. After fusion, antibody from final hybridoma cell line was characterized using ELISA and Western blot (WB). A 180 KDa PBRM1 protein was detected by WB in A431 and MCF7 cell lysates. The antibody was further characterized by extensive IHC testing using formalin-fixed and paraffin-embedded (FFPE) human normal and tumor tissue microarray (TMA). IHC analysis on human tissue microarray (TMA) comprising seventeen types of normal tissues showed that PBRM1 antibody stained positively in the nuclei of all normal cells except cardiac muscle cells. In tumor TMAs comprising of fifteen types of tumors (2-4 cases for each type), negative staining was observed in carcinomas of the lung and colon, as well as clear cell RCC. Further analysis of specific types of tumor TMAs showed that PBRM1 was lost in 5 out of 30 colon carcinomas (17%), 8 out of 35 (14%) lung carcinomas, and 8 out of 1844%) clear cell RCC. In summary, the RabMAb PBRM1 antibody, clone EP342 specifically labels normal cells and most tumor cells. It is a useful tool in identifying cancers with loss of PBRM1 expression on FFPE tissues. The rate of PBRM1 loss in clear cell RCC (44%) detected by this clone is consistent with literature reported. Our study showed that PBRM1 protein was lost in colon and lung carcinomas, but less frequent than that of clear cell RCC. Further studies on colon and lung carcinomas are needed to clarify the role of PBRM1 in tumor progression in these tumors.
Citation Format: Aihua Li, Yongfu Gao, Yuekai Zhang, Hongyang Pan, Jackie K. Chan, Ximing J. Yang, Taiying Chen. IHC assessment of PBRM1 loss in colon and lung carcinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3416. doi:10.1158/1538-7445.AM2015-3416
Abstract 3420: Expression and significance of proliferation markers phosphohistone H3, Ki-67/MIB-1, and survivin in gastrointestinal stromal tumors
Authors: Wang Ming , Grissmann Benedict , Marx Alexander , Weiss Cleo-Aron , Deligianni Maria , Belharazem Djeda , Cao Hui , Hohenberger Peter 
Published: August 2015

Abstract
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Mitotic index (MI) is an essential risk factor for predicting recurrence of GIST. However, the inter-observer disagreement and the selection bias of the area for counting limit the reliability and reproducibility of risk-stratification based on traditional MI counting method. Phosphohistone H3 (PHH3), a novel mitosis-specific antibody, has been proven as a promising marker for facilitating MFs identification in several types of tumors. The purpose of present study is to explore the feasibility and reliability of PHH3-based mitosis counting methods in GISTs and to study the correlation between PHH3 and other two proliferation markers Ki67/MIB-1 and survivin.
Methods: 83 GIST formalin-fixed paraffin-embedded (FFPE) specimens were enrolled in this study. The mitotic count was assessed either on hematoxylin and eosin sections (H&E) or on PHH3 immuno-stained sections. The proliferation activity of tumors was also evaluated by immuno-staining of Ki67/MIB-1 and survivin. The interrelationship between these indices was analyzed statistically with Spearman rank coeffcients. Continuous variables not following the normal distribution were compared using Mann-Whitney U test between two groups or using Kruskal-Wallis H test among more than two groups. SPSS statistical software program, version 20.0 was used and all results were considered significant if p&lt;0.05.
Results: PHH3-based mitosis counting showed better inter-rate reliability (ICC 0.909 vs 0.821, p&lt; 0.03) and stronger correlation with risk grade and clinical outcome than H&E-based mitoses counting. Both the labeling indices (LI) of Ki67/MIB-1 and survivin (r = 0.737, p&lt;0.0001) were strongly correlated to risk grade, clinical outcome, and PHH3-based mitoses count, which was also validated by immunofluorescence and immunocytochemical staining (r = 0.644, p&lt;0.002).
Conclusion: PHH3 could significantly facilitate determining the mitotic rate in GIST evaluation with superior inter-rate reliability. PHH3, Ki67/MIB-1, and survivin are co-expressed in GIST and their expressions are strongly correlated. Combined use of these markers is a promising technique for evaluating the prognosis of GIST and tailoring the treatment.
Citation Format: Ming Wang, Benedict Grissmann, Alexander Marx, Cleo-Aron Weiss, Maria Deligianni, Djeda Belharazem, Hui Cao, Peter Hohenberger. Expression and significance of proliferation markers phosphohistone H3, Ki-67/MIB-1, and survivin in gastrointestinal stromal tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3420. doi:10.1158/1538-7445.AM2015-3420
Abstract 3432: Dietary modifications of rectal cancer survivors to improve bowel function symptoms
Authors: Krouse Robert S. , Wendel Christopher S. , Demark-Wahnefried Wendy , Bulkley Joanna E. , McMullen Carmit K. , Grant Marcia , Hornbrook Mark C. , Altschuler Andrea , Sun Virginia , Herrinton Lisa J. 
Published: August 2015

Abstract
Purpose: Rectal cancer (RC) survivors with and without permanent ostomy have similar bowel function challenges, and seek improvement of symptoms through dietary modifications. Identifying patient-reported dietary modifications among survivors with different surgical reconstructions can guide postoperative supportive care and improve health-related quality of life (HRQOL).
Methods: We mailed a survey to long-term (≥5 years post-diagnosis) RC survivors enrolled in Kaiser Permanente (Northern California and Northwest). It included a question eliciting foods that were helpful with bowel function and the bowel symptoms that were impacted. Food types were recoded into broader categories based on food families developed around nutrition and common usage patterns and frequencies of food types and symptoms addressed were compared by sex and surgery type (ostomy vs. anastomosis).
Results: Of the 577 RC survivors who responded to the survey, 201 (35%) responded to the question related to foods that helped bowel function. Food groups that most commonly were used were fruits other than prunes (16.3%) and vegetables (15.5%). Water was often used (9.2%). The only specific food that was commonly used was prunes (7.6%). Most foods cited were credited with helping prevent the constellation of symptoms and signs of constipation or bloating, followed by predictability. A few foods (e.g., bananas, bread, rice) were more likely to help with diarrhea. Helpful foods addressing constipation/bloating were more likely cited by women than men (55% vs. 44%, p = .007). Vegetables were more likely cited by anastomosis than ostomy subjects (18% vs. 11%, p = .03).
Conclusions: Multiple dietary alterations are attempted by RC survivors. It appears very individualized, although multiple strategies can be suggested to improve bowel function. Through this exploratory analysis, strategies can be developed and tested for RC survivors.
Citation Format: Robert S. Krouse, Christopher S. Wendel, Wendy Demark-Wahnefried, Joanna E. Bulkley, Carmit K. McMullen, Marcia Grant, Mark C. Hornbrook, Andrea Altschuler, Virginia Sun, Lisa J. Herrinton. Dietary modifications of rectal cancer survivors to improve bowel function symptoms. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3432. doi:10.1158/1538-7445.AM2015-3432
Abstract 3469: Measuring antitumor effect of c-Myc-Max heterodimerization inhibitor 100258-F4 on ovarian cancer cells using cellometer image cytometry
Authors: Chan Leo Li-Ying , Wang Jiandong , Ma Xiaoli , Song Fang , Zhang Weiyuan , Jones Hannah M. , Bae-Jump Victoria L. , Zhou Chunxiao 
Published: August 2015

Abstract
Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. In this work, we aimed to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian cancer cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using Cellometer image cytometry for cell cycle and Annexin V apoptosis assays, flow cytometry, MTT assay, and colony formation, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. These novel findings suggest that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Leo Li-Ying Chan, Jiandong Wang, Xiaoli Ma, Fang Song, Weiyuan Zhang, Hannah M. Jones, Victoria L. Bae-Jump, Chunxiao Zhou. Measuring antitumor effect of c-Myc-Max heterodimerization inhibitor 100258-F4 on ovarian cancer cells using cellometer image cytometry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3469. doi:10.1158/1538-7445.AM2015-3469
Abstract 347: Mechanism of c-Met TKI resistance and role of epithelial mesenchymal transition in melanoma
Authors: Rajanna Supriya , Rastogi Ichwaku , Palani Sunil , Puri Neelu 
Published: August 2015

Abstract
Various tyrosine kinase inhibitors (TKI’s) are approved for the treatment of melanoma, but their efficacies are limited due to development of drug resistance. To analyze the resistance to c-Met inhibitors we used two melanoma cell lines: MU which has mutated BRAF (V600E +ve) and RU which has wild type BRAF. These cell lines were also made resistant to c-Met inhibitor, SU11274 by growing them in progressively increasing concentrations of drug.
In earlier studies we observed activation of Wnt pathway in both of the aforementioned cell lines indicating the role of active β-Catenin in transcription and hence cell proliferation. β-Catenin levels when localized and accumulated in the nucleus binds to TCF/LEF and activates transcription. The level of β-Catenin in the cytosol is regulated by the adherens junction proteins (E-Cadherin) along with the Wnt pathway. Increased levels of β-Catenin might be a possible result of loss of E-Cadherin which is related to epithelial mesenchymal transition. During epithelial mesenchymal transition (EMT) cells transition from epithelial (attached, non-migratory) to mesenchymal (unattached and migratory) cells which promotes metastasis.
We examined the role of EMT in the development of resistance in the c-Met TKI resistant melanoma cell lines. We quantified the β-Catenin activity using luciferase assay and observed a 5 fold upregulation in the SU11274 resistant MU cells when compared to MU parental cells in the presence of HGF. Additionally, we performed immunoblotting, where we observed modulation in EMT related proteins in MU and RU parental and resistant cells. E-Cadherin, ZO-1, Claudin-1 and Slug were found to be downregulated 1.5 - 2.7 fold, 1.5 - 2.0 fold, 2 - 9 fold and 1.5 - 2 fold respectively and N-Cadherin and β-Catenin were found to be upregulated 1.8 - 5.3 and 2.4 - 3.7 fold respectively in the SU11274 resistant MU cells in the presence and absence of HGF and SU11274 treatments. Similarily we observed upregulation of β-Catenin by 1.7 fold and downregulation of E-Cadherin and ZO-1 by 2 - 3.5 fold and 6 - 9 fold respectively in SU11274 resistant RU cells when compared to RU parental cells in the presence and absence of HGF and SU11274 treatments. Further studies are being carried to understand the role of EMT in the development of this acquired resistance.
These results may help in development of novel therapies for melanoma patients or may help in increasing the efficacy and beneficence from the currently available therapeutics.
Citation Format: Supriya Rajanna, Ichwaku Rastogi, Sunil Palani, Neelu Puri. Mechanism of c-Met TKI resistance and role of epithelial mesenchymal transition in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 347. doi:10.1158/1538-7445.AM2015-347
Abstract 3470: Atypical protein kinase C inhibition in prostate cancer cells: A study of ICA-1 and ACPD
Authors: Apostolatos Andre H. , Apostolatos Christopher , Acevedo-Duncan Mildred 
Published: August 2015

Abstract
Aggressive and metastatic prostate cancers are highly lethal tumors and are one of the leading causes of death among men. Certain prostate cancers are highly lethal tumors due to the emergence of therapy-resistant cancer cells. There is a gap in knowledge relating to which intracellular chemicals confer the emergence of therapy-resistant prostate cancer cells, which intracellular chemicals are responsible for prostate cancer survival and which chemicals regulate intracellular signaling pathways in prostate cancer. To address this critical problem, we investigated two drugs that act as inhibitors of atypical protein kinase C. The objective of this study was to test the effectiveness of ACPD [Diabetes. 63:2690-2701 (2014)] as an atypical PKC inhibitor and ICA-1 as an inhibitor of PKC-iota [The Inter. J. Biochem. & Cell Biol. 43:784-794(2011)]. DU-145 prostate carcinoma cells and non-malignant prostate RWPE-1 cells were each cultivated in separate flasks. They were treated with drugs of interest for three consecutive days. The cells were counted before and after the treatments and a statistical analysis was performed. The cells were lysed and levels of PKC-iota and PKC-zeta were measured by Western blotting and immunoprecipitation. Our preliminary results demonstrated that treatment of DU-145 showed a statistically significant decrease in cells that was proportional to the concentration in both drugs. Treatment of the RWPE-1 cells showed no statistically significant change in population. Western blotting showed that both drugs decreased PKC-iota. In conclusion ACPD is an effective inhibitor of PKC-iota and PKC-zeta and consequently significantly reduced the neogenesis of the prostate DU-145 carcinoma cells while having negligible effect on the non-malignant prostate RWPE-1 cells.
Citation Format: Andre H. Apostolatos, Christopher Apostolatos, Mildred Acevedo-Duncan. Atypical protein kinase C inhibition in prostate cancer cells: A study of ICA-1 and ACPD. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3470. doi:10.1158/1538-7445.AM2015-3470
Abstract 3480: Combinatorial apoptotic activity of capsaicin and camptothecin in human small cell lung cancer
Authors: Perry Haley E. , Brown Kathleen C. , Stevenson Cathryn D. , Rollyson William D. , Stover Cody A. , Dasgupta Piyali 
Published: August 2015

Abstract
Small cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases and is the most aggressive form of lung cancer. Cisplatin and cisplatin-based combination therapies are the cornerstone of SCLC treatment. Platinum refractoriness is defined as disease which has persisted or progressed (grown) while receiving cisplatin chemotherapy. Patients with platinum resistant or refractory disease have very limited options, as the only standard chemotherapy with an FDA-approved drug, topotecan, has an objective response rate of approximately 3% and little or no survival benefit. Topotecan is a derivative of camptothecin. The objective of our study was to examine whether capsaicin could sensitize human SCLC cells to the apoptotic effects of camptothecin. We observed that the combination of capsaicin and camptothecin displays significantly higher apoptotic activity in human SCLC cell lines as compared to either agent alone. Chou-Talalay analysis showed that the interactions between capsaicin and camptothecin were synergistic. We also measured the effect of capsaicin-camptothecin combination on several Bcl-2 family proteins, namely Bcl-2, Bax, Bak, Bcl-XL, Mcl-1, etc. The results of our studies may be of importance in therapy of platinum-refractory SCLCs.
Citation Format: Haley E. Perry, Kathleen C. Brown, Cathryn D. Stevenson, William D. Rollyson, Cody A. Stover, Piyali Dasgupta. Combinatorial apoptotic activity of capsaicin and camptothecin in human small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3480. doi:10.1158/1538-7445.AM2015-3480
Abstract 3481: Sigma-2 ligands sensitize triple negative breast cancer cells to PARP inhibitor treatment
Authors: Zeng Chenbo , Mankoff Julia , Mach Robert H. 
Published: August 2015

Abstract
Triple-negative breast cancer (TNBC) accounts for 15-25% of breast cancer cases. Effective targeted treatment for TNBC is lacking. Poly (ADP-ribose) polymerase (PARP) is a key enzyme involved in single-strand DNA break repair. PARP inhibitors have been used in combination with various chemotherapeutic agents in TNBC with limited success. The sigma-2 receptor is associated with cellular proliferation and quiescence and has been used as the target for imaging solid tumors by positron emission tomography. The sigma-2 receptor has been identified as progesterone receptor membrane component 1 (PGRMC1) protein complex. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target. In this study we looked for potential synergy between PARP inhibitors and sigma-2 ligands using a triple negative breast cancer cell line, MDA-MB231.
We showed that the sigma-2 ligand, SW43, and a PGRMC1 ligand, AG205, induced cell toxicity and caspase 3 activation in a dose-dependent manner. The combination of SW43 and PARP inhibitor, Olaparib, resulted in additive cytotoxicity by cell viability assay and colony forming assay. Olaparib inhibited PARP activity in MDA-MB231 cell line, suggesting that the single-strand DNA break repair may be inhibited. SW43 and AG205 treatment decreased PGRMC1 and EGFR protein levels, suggesting that sigma-2/PGRMC1 ligands reduce growth factor signaling. In conclusion, SW43 and Olaparib induce cell death by separate signaling pathways. Sigma-2 ligands may selectively sensitize tumors to PARP inhibitor treatment in triple negative breast cancer patients.
Citation Format: Chenbo Zeng, Julia Mankoff, Robert H. Mach. Sigma-2 ligands sensitize triple negative breast cancer cells to PARP inhibitor treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3481. doi:10.1158/1538-7445.AM2015-3481
Abstract 3484: Synergism from combination of targeted therapy with tumor active phytochemicals in ovarian tumor models and changes in protein expression
Authors: Huq Fazlul 
Published: August 2015

Abstract
Introduction
Ovarian cancer is most lethal cause of gynecological types of cancer mainly because of acquired drug resistance and poor diagnosisis. In majority of cases it is detected at an advanced stage when it is likely to have spread beyond ovaries. Combination of platinum drugs with paclitaxel is the current mode of treatment. Although cancer cells respond well to the drug combination, relapse often occurs for which drugs fail to function. We have designed a number of novel platinums aimed to overcome platinum resistance in ovarian cancer. We also applied combinations of platinums and tumor active phytochemicals such as curcumin, EGCG, thymoquinone, resveratrol, ursolic acid and genistein to overcom drug resistance. This presentation will provide a brief overview of novel platinums designed in our lab with special emphasis on recent studies on combinations of platinum with phytochemicals and protein expression.
Methods
Activity of the compounds alone and in sequenced combination in ovarian cancer cell lines including A2780, A2780cisR and A2780ZD0473R were determined using MTT reduction assay. Drug uptake and drug-DNA binding were determined using developed protocols. Proteomic studies involving 2D gel electrophoresis and mass spectrometry were carried out to characterize key proteins associated with platinum resistance.
Results
Generally but not always sequenced combinations with 2 to 4 h time gap were found to be synergistic. The variation in combined drug action with the change in sequence of administration clearly indicates that the action of one drug has modulated that of the other. Proteomic studies have identified over thirty proteins believed to be associated with platinum resistance in ovarian cancer. They belong to six major groups including cytoskeletal proteins, molecular chaperone and stress related proteins, proteins involved in detoxification and drug resistance, proteins involved in metabolic processes and mRNA processing proteins. The proteins are restored to normalcy due to treatment with synergistic combinations.
Conclusion
If confirmed in vivo, the results of the study indicate that appropriate combinations of targeted therapy and tumor active phytochemicals may providing an effective and affordable means of overcoming drug resistance in ovarian cancer.
Citation Format: Fazlul Huq. Synergism from combination of targeted therapy with tumor active phytochemicals in ovarian tumor models and changes in protein expression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3484. doi:10.1158/1538-7445.AM2015-3484