bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5538A: Cell size-specific intracellular delivery
Authors: Saung May Tun , Sharei Armon , Adalsteinsson Viktor , Liss Andrew , Cho Nahyun , Kamath Tushar , Ruiz Camilo , Kirkpatrick Jesse , Langer Robert , Love Christopher , Jensen Klavs 
Published: August 2015

Abstract
Among the many methods of intracellular delivery, cell size-selective delivery is particularly applicable to cancer research and therapeutics where tumor cells tend to be larger than blood cells and selective manipulation of a single cell-type while minimally affecting the other cells in a heterogeneous mixture is important. In this study, cell size-selective delivery is achieved using a novel microfluidic device with 75 parallel channels through which cells are pushed under nitrogen pressure. The cells undergo deformation as they transit through the channels, which results in temporary disruption of the cell membrane to facilitate delivery of material into the cytoplasm. For each cell size, there is a specific channel width for which optimal cell viability and fluorophore delivery is achieved, with smaller cells requiring narrower channels. When two cells of different sizes are mixed in solution, the channel width for optimal cell viability and fluorophore delivery for each cell type remains the same, and larger cells can achieve fluorophore delivery at a significantly higher percentage than smaller cells at the former's optimal channel width. One possible application for this technology is tagging circulating tumor cells, and we have been able to selectively deliver fluorophores into tumor cells when spiked into whole human blood with 91% specificity. We were also able to isolate pancreatic tumors cells from a patient's blood sample that matched the genotype of the patient's primary pancreatic tumor. Intracellular delivery of materials has become increasingly important as we delve deeper into understanding cellular processes and developing targeted therapies, and with this device, selective delivery can be achieved in a vector-free environment and without dependence on cell-surface receptors.
Citation Format: May Tun Saung, Armon Sharei, Viktor Adalsteinsson, Andrew Liss, Nahyun Cho, Tushar Kamath, Camilo Ruiz, Jesse Kirkpatrick, Robert Langer, Christopher Love, Klavs Jensen. Cell size-specific intracellular delivery. [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 5538A. doi:10.1158/1538-7445.AM2015-5538A
Abstract 5546: A natural alkaloid, berberine, as a novel transcriptional repressor of RET proto-oncogene in medullary thyroid carcinoma
Authors: Sun Daekyu , Kumarasamy Vishnu 
Published: August 2015

Abstract
The development of several medullary thyroid carcinomas is strongly associated with the gain-of-function mutation of the RET proto-oncogene, which encodes a receptor tyrosine kinase, so that the RET protein has been regarded as a potential therapeutic target for the treatment of progressive and advanced MTC. In our study we have explored a new strategy to repress the transcription of the RET proto-oncogene in MTC using small molecules. Interestingly, we found that a natural product berberine inhibits the RET gene transcription by specifically targeting the promoter region of this gene, thereby reducing the RET protein expression in MTC TT cells. The down-regulation of RET with berberine also results in the suppression of cell proliferation through cell cycle arrest and activation of apoptosis in TT cells. Overall, our results strongly suggest that berberine stabilizes G-quadruplexes formed from the G-rich sequence present on the promoter region of this gene and the stabilization of this structure play a critical role in mediating the repressive effect of berberine on RET transcription.
Citation Format: Daekyu Sun, Vishnu Kumarasamy. A natural alkaloid, berberine, as a novel transcriptional repressor of RET proto-oncogene in medullary thyroid carcinoma. [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 5546. doi:10.1158/1538-7445.AM2015-5546
Abstract 5549: Anti-proliferative effect of Oman's medicinal plants derived active principles on breast cancer cells (MDA MB 231)
Authors: Hakkim Lukmanul 
Published: August 2015

Abstract
Breast cancer (BC) is leading cause of death among females in United States and it is one of the emerging threats in Oman. Heavy doses of current clinical drugs are too toxic to patient and often failed to abort the recurrence after therapy. Despite huge number of reports on development of breast cancer chemotherapeutic drugs, median survival of BC patients not improved due to extreme ongoing and post treatment toxicity. Searching of drugs which can kill BC cells in a low dose by sparing normal cells is life time goal of many cancer researchers. Keeping the above fact in mind, we searched for potential natural products from Oman's medicinal plants which can kill BC cells potentially. We tested different doses (25, 50, 75 and 100 μg/ml) of sixty crude extracts and seventeen pure compounds obtained from Omani medicinal plants along with different dilutions (1:1000, 1:1500 and 1:2000 - prepared in medium) of Omani frankincense derived heavy oil for their ability to induce the cell death in MDA MB 231 cells with normal skin fibroblast as control. Doxorubicin used as positive drug control. After 24 hrs cells were checked for cell viability by MTT assay.
We set the criteria to select the potent anti-cancer active principle out of tested extracts and compounds that it should induce more than 50% cell death in ≤ 50 μg/ml drug concentration. As per this end point, fifteen extracts induced cell death in the range of 60%-90% and five pure compounds killed MDA MB 231 cells in the range of 75%-90%. Noticeably heavy oils can induce 90% cell death in very low dose (1:2000 dil.) of treatment by sparing normal skin fibroblast. Although it is primitive data, but this forms rationale for us to test this oil and other compounds and extracts in in vivo BC xenograft model and subsequently on BC heterogeneity, recurrence and metastasis.
Citation Format: Lukmanul Hakkim. Anti-proliferative effect of Oman's medicinal plants derived active principles on breast cancer cells (MDA MB 231). [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 5549. doi:10.1158/1538-7445.AM2015-5549
Abstract 5558: Growth inhibitory effect of perganum, sage, and olive leaves plant extracts on breast and lung cancer cell lines
Authors: Gibbs Carla , Almusallam Ola , Malone Trent E. , Myles Elbert L. 
Published: August 2015

Abstract
There are many different types of cancer, and generally each is defined by the type of cell that is affected. Cancer occurs in cells by which mutant genes are responsible for cell growth. This may result in metastasis which may affect one or more parts of the body. The current student attempts to address cancer treatment from Natural product sources. Sage leaves (Salvia officanlis), Perganum leaves (harmala), and Olive leaves (Olea europaea) were used in this study to determine their effects on two cancer cell lines, A549 and MCF-7. Our findings revealed that Salvia officanlis, Perganum harmala, and Olea europaea have significant effect on both cell lines (MCF-7 Brest cancer cell line and A549 lung cancer cell line). Salvia officanlis leaf extracts had a greater effect on MCF-7 and A549 than Perganum harmala and Olea europaea. Salvia Officanlis demonstrated a significantly decreased the growth rate and cell survival of both cancer cell lines at all concentrations. In future studies, Salvia officanlis, Perganum harmala, and Olea europaea act with MCF-7 Brest cancer cell line and A549 lung cancer cell line to inhibit their growth
Citation Format: Carla Gibbs, Ola Almusallam, Trent E. Malone, Elbert L. Myles. Growth inhibitory effect of perganum, sage, and olive leaves plant extracts on breast and lung cancer cell lines. [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 5558. doi:10.1158/1538-7445.AM2015-5558
Abstract 5560: Quercetin overcomes chemotherapy resistance in triple negative breast cancer
Authors: Srinivasan Asha , Thangavel Chellappagounder , Liu Yi , Shoyele Sunday , Den Robert B. , Selvakumar Ponniah , Lakshmikuttyamma Ashakumary 
Published: August 2015

Abstract
Triple negative breast cancer (TNBC) is one of the most aggressive breast cancers and is characterized by poor prognosis and high possibilities of tumor relapse. TNBC lacks specific receptors that are targets for breast cancer treatment options. Plant flavonoids have been identified to inhibit tumor growth and metastasis in various cancers. Our study revealed that quercetin, one of the major flavonoids present in fruits, vegetables, green tea, and red wine inhibit TNBC migration and invasion. Our data indicate that quercetin is able to induce the expression of E-cadherin and also down regulate vimentin levels in TNBC cells. Further the cellular localization of β-catenin is also altered by quercetin treatment. Also, studies identified that quercetin is capable of inhibiting the chemotherapy induced TGF-β signaling in TNBC cells, and that it would decrease the development of chemotherapy resistance in TNBC. Quercetin inhibits the TGF-β induced phosphorylation status of smad-2 in drug resistant cells. Further, quercetin is able to inhibit the enhanced migration and mammosphere formation of chemoresistant TNBC cells. Taken together, our findings revealed that quercetin is a promising natural product that increases the anti-cancer effect of chemotherapy drug in TNBC. Future studies in TNBC animal models are needed to confirm the therapeutic efficacy of quercetin in TNBC.
Citation Format: Asha Srinivasan, Chellappagounder Thangavel, Yi Liu, Sunday Shoyele, Robert B. Den, Ponniah Selvakumar, Ashakumary Lakshmikuttyamma. Quercetin overcomes chemotherapy resistance in triple negative breast 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 5560. doi:10.1158/1538-7445.AM2015-5560
Abstract 5563: Tripterygium induces apoptosis in NSCLC via mitochondria dysfunction
Authors: Fan Xing-Xing , Li Na , Wu Jin-Lin , Zhou Yan-Ling , Liu Liang , He Jian-Xing , Leung Elaine L. 
Published: August 2015

Abstract
Lung cancer remains the leading cause of cancer deaths globally. Patients with non-small cell lung cancer (NSCLC) account for 80% of all lung cancer cases. Active mutation of EGFR was identified as one of the key anti-cancer target for NSCLC patients. Recently, tyrosine kinase inhibitor, like gefitinib which can specifically inhibit the activation of EGFR, emerges as a new potential anticancer drug. However, drug resistance remains an unsolved problem. Most of patient acquired resistance to this inhibitor within 12 months. Therefore, it is necessary and urgent to discover more effective potential agents as candidate drugs for treating gefitinib resistant NSCLC. Tripterygium, a triterpene extracted from the Chinese herb “Thunder of God Vine”, has been shown to have multiple bioactivities. Its anti-cancer effect has been proved in many kinds of cancers. However, the effect of Tripterygium on gefitinib-resistant NSCLC cells is still unknown. In this study, we examined the potency of Tripterygium in induction of apoptosis in a gefitinib-resistant NSCLC cell line and explored its underlying anti-cancer mechanism. Our results demonstrated that Tripterygium induced its apoptotic effect on NSCLC cells in a dose- and time-dependent manner. Moreover, the function of mitochondria was disrupted by the treatment of Tripterygium. The mitochondria membrane potential was gradually loss, and the ratio of Bax/Bcl-2 which is the indicator of mitochondria membrane integrity, was significantly up-regulated after the treatment of Tripterygium. Although the caspases were activated, the treatment of pan-caspase inhibitor could only partially inhibit the level of apoptosis. Moreover, the level of Hsp90 client proteins, EGFR and its downstream target AKT, were measured. Interestingly, both of them were remarkably decreased after Tripterygium treatment. Taken together, our data suggest that Tripterygium, which may be developed as a promising agent for gefitinib-resistant NSCLC patient, induced apoptosis through mitochondria dysfunction and EGFR degradation in gefitinib-resistant NSCLC cells.
Citation Format: Xing-Xing Fan, Na Li, Jin-Lin Wu, Yan-Ling Zhou, Liang Liu, Jian-Xing He, Elaine L. Leung. Tripterygium induces apoptosis in NSCLC via mitochondria dysfunction. [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 5563. doi:10.1158/1538-7445.AM2015-5563
Abstract 5587: Personalized risk prediction tool for esophageal adenocarcinoma in Caucasian population
Authors: Pu Xia , Ajani Jaffer A. , Gu Jian , Gu Xiangjun , Ye Yuanqing , Wu Xifeng 
Published: August 2015

Abstract
Backgrounds: Esophageal adenocarcinoma (EAC) is a deadly disease with the greatest increasing incidence rate among all cancers in the past few decades in the U.S. We aimed to develop a powerful risk prediction tool for EAC to assist in the prevention and early detection of this disease. Methods: A large case control study consisting of 924 EAC patients with 925 frequency-matched healthy controls was used to identify potential risk factors for EAC by univariate logistic regression. Stepwise logistic regression was used to select significant predictors in the final multivariate model. Discriminatory accuracy was measured by generating the receiver operator curve (ROC) and calculating the area under the curve (AUC). We also calculated the 5-year and 10-year absolute risk of developing EAC for hypothetical individuals with varying risk factor combinations. A simplified risk score (RS) was developed for easier risk communications and disseminations. Results: BMI, physical activity, smoking, family history, dietary intake, exposure to exhaust, Barrett's esophagus, hernia, esophageal ulcer, and GERD were included in the final model. The discriminative ability is excellent AUC of 0.884. Individuals with the highest RS have a 99% chance to be EAC cases compared to 1.4% for those with the lowest RS. Conclusions: We developed a comprehensive risk prediction model for EAC with excellent model performance. This model has the potential to be utilized in the clinic and public health settings to provide evidence-based risk mitigation strategy and identify high-risk population for targeted screening or prevention trials and for early detection of EAC.
Note: This abstract was not presented at the meeting.
Citation Format: Xia Pu, Jaffer A. Ajani, Jian Gu, Xiangjun Gu, Yuanqing Ye, Xifeng Wu. Personalized risk prediction tool for esophageal adenocarcinoma in Caucasian population. [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 5587. doi:10.1158/1538-7445.AM2015-5587
Abstract 591: Prognostic implications of PI3K mutation and amplification in curatively resected liposarcoma
Authors: Kim Joo Hoon , Kim Hyo Song , Lee Jae Seok , Kim Ki Hyang , Cho Yong Jin , Park Kyu Hyun , Kim Soo Hee , Ahn Joong Bae , Yang Woo Ik , Lee Young Han , Suh Jin-Suck , Shin Kyoo-Ho , Rha Sun Young 
Published: August 2015

Abstract
Background: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutation/amplification in curative resected liposarcoma. Methods: A total of 125 liposarcoma tissue samples were collected over a 12-year period (2000-2012). PIK3CA mutation and amplification of gene copy number were analyzed by pyrosequencing method and fluorescence in situ hybridization (FISH).
Results: Nine of the 105 liposarcoma patients (8.6%) showed activating PIK3CA mutation.PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic type vs well differentiated/dedifferentiated type (11.1% vs 88.9%, P = 0.044). In FISH analysis of PIK3CA, amplification of PIK3CA was detected in 31 of the 102 patients (30.4%) and histologic differences was not statistically significant in patients with PIK3CA amplification (48.4% vs 51.6%, p = 0.328). In survival analysis, PIK3CA amplified patients showed worse prognosis compared with PIK3CA-non amplified patients (median disease free survival (DFS) 119.2 vs 38.3 months p = 0.01). In multivariate analysis, positive PI3KCA amplification was an independent worse prognostic factor for DFS (p = 0.04; HR, 2.6; 95% CI 1.36 to 5.1). PIK3CA mutation was not associated with significant difference for DFS (p = 0.739)
Conclusion: We demonstrated that histologic differences according to PIK3CA mutation or amplification status. PIK3CA amplification was an independent worse prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutation and amplification in liposarcoma.
Citation Format: Joo Hoon Kim, Hyo Song Kim, Jae Seok Lee, Ki Hyang Kim, Yong Jin Cho, Kyu Hyun Park, Soo Hee Kim, Joong Bae Ahn, Woo Ik Yang, Young Han Lee, Jin-Suck Suh, Kyoo-Ho Shin, Sun Young Rha. Prognostic implications of PI3K mutation and amplification in curatively resected liposarcoma. [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 591. doi:10.1158/1538-7445.AM2015-591
Abstract 596: Differential cellular localization of Ephrin receptor tyrosine kinase B4 (EphB4) in melanoma progression
Authors: Chakravarti Nitin , Curry Jonathan L. , Bassett Roland L. , Prieto Victor G. 
Published: August 2015

Abstract
Background: Melanoma is an aggressive cancer with high metastatic potential, and is the most lethal skin malignancies. Ephrin receptor tyrosine kinase B4 (EphB4) modulates diverse physiologic and developmental processes, and may play an important role in melanoma tumorigenesis. In addition, Mertens-Walker et al., reported nuclear translocalization of EphB4 and hypothesized that it may directly regulate gene expression contributing to more aggressive biologic behavior in prostate cancer (Cancer Res 2011; 71 (8 Suppl): Abstract nr 1085). It is unknown whether differential cellular expression of EphB4 contributes to the pathogenesis of melanoma.
Methods: To explore the role of EphB4 in melanomagenesis, we have performed semiquantitative immunohistochemical analysis of EphB4 expression as measured by percentage and intensity of cells immunoreactive with anti-EphB4 in melanocytic nevi (n = 59), primary melanomas without metastasis during follow-up (n = 22), primary melanomas with metastasis (n = 17), and metastatic melanoma (n = 32).
Results: Melanocytic nevi had significantly higher nuclear EphB4 expression (p = 0.007) and lower cytoplasmic EphB4 expression (p = 0.002) when compared to all categories of melanoma. In fact we observed a dramatic decrease in nuclear EphB4 expression in metastatic melanoma compared to melanocytic nevi (p = 0.0009). In contrast, compared to melanocytic nevi, cytoplasmic expression for EphB4 were higher in primary melanoma (p = 0.005) as well as in melanoma metastases (p = 0.03). Although there was no significant difference in nuclear or cytoplasmic EphB4 expression between primary melanomas with or without metastasis, primary melanomas without metastasis showed significantly higher number of tumor cells having intense nuclear immunoreactivity for EphB4 protein than did metastatic melanomas (p = 0.006).
Conclusion: In conclusion, our data indicated that there is a gradual loss of nuclear EphB4 protein as well as increase in the levels of cytoplasmic expression of EphB4 protein associated with melanomagenesis. In addition, our results suggest a potential role for EphB4 as a therapeutic target in melanoma.
Citation Format: Nitin Chakravarti, Jonathan L. Curry, Roland L. Bassett, Victor G. Prieto. Differential cellular localization of Ephrin receptor tyrosine kinase B4 (EphB4) in melanoma progression. [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 596. doi:10.1158/1538-7445.AM2015-596
Abstract 601: Glycodelin expression in lung cancer and melanoma
Authors: Hautala Laura , Koistinen Hannu 
Published: August 2015

Abstract
Glycodelin (PAEP) is a lipocalin protein mainly expressed in well-differentiated epithelial cells in reproductive tissues. Previously, glycodelin has been shown to induce cell differentiation in endometrial and breast cancer cells. In breast cancer this was associated with reduced xenograft tumor growth. In ovarian and breast cancers glycodelin expression has been found to associate with a favorable prognosis as compared to glycodelin non-expressing tumors. Some preliminary studies suggest that glycodelin expression is increased also in lung cancer and melanoma. We studied the expression of glycodelin in these cancers using immunohistochemical staining of tissue arrays. Furthermore, the levels of mRNA were addressed utilizing in silico transcriptomics database (IST Online).
Glycodelin transcripts were more abundant in lung adenocarcinoma and melanoma as compared to non-malignant lung or squamous cell carcinoma of the lung and skin tissues, respectively. While immunohistochemical staining also showed increased staining of glycodelin in lung adenocarcinoma as compared to squamous cell carcinoma of the lung, there was no clear difference in staining as compared to normal lung tissue. Weak staining of glycodelin was observed both in normal skin and melanoma tissues. However, some melanoma cases showed very strong staining.
In conclusion, our data show that glycodelin is expressed both in melanoma and lung adenocarcinoma, and in some cases the expression is increased. However, the clinical relevance of these findings remains to be established.
Citation Format: Laura Hautala, Hannu Koistinen. Glycodelin expression in lung cancer and 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 601. doi:10.1158/1538-7445.AM2015-601