tbuckley/cabot-search huggingface dataset:
Abstract 1868: Glycodelin-producing endometrial adenocarcinoma cells are resistant to TGFβ
Authors: Laura Hautala, Hannu Koistinen
Journal: Cancer Research (2016)

Abstract Glycodelin is a secreted glycoprotein belonging to lipocalin protein family. It is expressed mainly in reproductive and glandular tissues. Glycodlin is involved in the regulation of reproductive and immune systems and it drives epithelial differentiation. In endometrium, the expression of glycodelin is abundant in secretory phase of the menstrual cycle, while in proliferative phase it is not expressed. Most studies agree that glycodelin is not expressed in endometrial cancer. To study the effects of glycodelin in endometrial cancer cells, we have made stable glycodelin-producing HEC-1B endometrial adenocarcinoma cells. Previously, we have shown that glycodelin differentiated HEC-1B cells towards less malignant phenotype and the cells formed significantly smaller tumors in preclinical xenograft mice. In addition, glycodelin-producing cells were resistant to phorbol ester-stimulated migration and phenotypic differentiation, which was mediated by repressed activation of PKCδ. Here we studied the effect of TGFβ on glycodelin-induced differentiation of the HEC-1B cells. Glycodelin-producing and control cells were plated on Matrigel and grown with or without TGFβ. The media was changed every second day and the cells were monitored up to one week. For Western blot analysis the cells were grown on Matrigel and TGFβ was added for 0-2h, after which the cells were detached from Matrigel and lysed. TGFβ induced control cells to form net-like structures, similar to those found after phorbol ester exposure. However, the glycodelin-producing cells remained unresponsive. PKCδ siRNA and PKCδ inhibitor Rottlerin inhibited the effects of TGFβ. Western blot analysis showed equal phosphorylation levels of SMAD2 in glycodelin-transfected and control cells. In contrast, PKCδ and ERK1/2 were differently phosphorylated, indicating the involvement of MAPK-pathway in the TGFβ-induced changes of the control cells. Endometrial cancer is the most common cancer of the female reproductive tract in developed countries. However, the molecular mechanisms affecting the pathogenesis of the disease are still poorly understood. It has been suggested that TGFβ is involved in carcinogenesis of endometrial cancer. Therefore, our results showing that glycodelin-producing HEC-1B endometrial adenocarcinoma cells are resistant to the effects of TGFβ, due to the repressed PKCδ phosphorylation, may be important to understand the pathogenic mechanisms of endometrial cancer. Citation Format: Laura Hautala, Hannu Koistinen. Glycodelin-producing endometrial adenocarcinoma cells are resistant to TGFβ. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1868.
P0785 : First real clinical practice data in Spain on sofosbuvir, simeprevir and daclatasvir in post-transplant HCV recurrence: The HepatiC registry experience
Authors: M. Prieto, M. Carlota Londoño, J.M. Pascasio, M. Salcedo, J. Crespo, J.L. Montero, I. Baños, I. Fernández, C. Vinaixa, C. Fernández-Carrillo, J.L. Calleja, X. Forns
Journal: Journal of Hepatology (2015)
Abstract 512: KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer
Authors: Min Kyeong Kim, Yoon Kyong-Ah, Woo Sang Myung, Kim Yun Hee, Park Sang Jae, Kong Sun-Young
Journal: Cancer Research (2016)

Abstract Cell-free DNA (cfDNA) of cancer patients has been known to be a useful marker for minimal residual disease detection and treatment monitoring. However, there are a few studies which showed correlation of cfDNA with pancreatic cancer treatment. Here we investigated applicability of cfDNA as a response and prognosis biomarker through comparing the qualitative and quantitative changes of the KRAS mutant in the patients with pancreatic cancer before and after treatment. Total of 44 pancreatic cancer patients who treated by gemcitabine and cisplatin included in the study. Serum from the blood samples was separated by centrifugation through the method established. cfDNA was extracted through the QIAamp Circulating Nucleic Acid Kit (Qiagen, Germany) from 0.8 ml of serum. Extracted cfDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). QX200 Droplet Digital PCR System (Biorad, USA) was applied to measure frequency of KRAS mutation. We performed digital PCR with KRAS screening multiplex droplet digital PCR kit which covers G12A, G12C, G12D, G12R, G12S, G12V and G13D sites (Biorad, USA). Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA). The positive rate of KRAS mutation was 61% (27/44) and 47% (16/34) in before and after treatment. When we analyzed the treatment response according to the positive presence of KRAS mutation before treatment, 50% and 61% of KRAS mutations were observed in patients who showed either partial response (PR) or stable disease (SD) after chemotherapy, respectively. However, all the 5 patients (100%) with progressive disease (PD) showed KRAS mutation implicating significant correlation (p = 0.046) with treatment response. The fraction change of KRAS mutation was showed decrease in 18 (58.1%) patients and increase in 13 (41.9%) patients comparing before and after treatment status. When we observed the association the fraction change direction (decrease vs. increase) with the survival, there was no significant difference. These results implicate that KRAS mutation in cell-free DNA might be associated with treatment response to gemcitabine/cisplatin chemotherapy. In further studies, we will conduct in prospective study for pancreatic cancer patients. (This study was supported by National cancer center, Korea, Grant no. 1510203-1) Citation Format: Min Kyeong Kim, Yoon Kyong-Ah, Woo Sang Myung, Kim Yun Hee, Park Sang Jae, Kong Sun-Young. KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 512.
Abstract 1158: Differential expression and functional impact of the alternatively spliced transcripts of Extracellular matrix protein 1 in esophageal squamous cell carcinoma
Authors: Valen Zhuoyou YU, Josephine Mun-Yee Ko, Simon Law, Li Dong Wang, Maria Li Lung
Journal: Cancer Research (2016)

Abstract Background: Esophageal squamous cell carcinoma (ESCC) has an especially high incidence in China, with five-year survival rates in Hong Kong being of ∼14%. An oligonucleotide microarray was utilized to identify differentially-expressed genes in ESCC using 31 pairs of matched normal/tumor samples from Hong Kong and Henan, China. Extracellular matrix protein 1 (ECM1) was among the top down-regulated genes, indicating a potential tumor-suppressive role. Public cDNA microarray data also shows significant down-regulation of ECM1 expression in ESCC. Interestingly, this gene has been extensively studied in breast cancer and thyroid cancer for its oncogenic role. There are three alternatively-spliced variants of ECM1. Therefore, this gene was selected for further variant expression and functional analysis in ESCC. Results: RNA sequencing analysis of matched normal/ESCC samples showed that ECM1b (NM_022664) is the dominant expressed variant in esophagus, followed by ECM1a (NM_004425). In tumor samples, the expression of ECM1a is down-regulated and that of ECM1b is down-regulated or lost, as compared to normal counterparts. Expression of ECM1c (NM_001202858) is not detected in either normal or tumor samples. Quantitative PCR using variant-specific primer sets confirms the findings of microarray and RNA sequencing analyses. When re-expressed in ESCC cell lines after lentiviral transduction, ECM1b expression shows a trend of tumor suppression in the orthotopic ESCC mouse tumorigenicity model; ECM1a shows no tumor-suppressive effect in either. ECM1b expression also shows a metastasis inhibitory effect in a tail vein experimental metastasis model. Immunohistochemical staining shows E-cadherin up-regulation in orthotopic tumors re-expressing ECM1b. Conclusions: These results suggest differential roles of variants of ECM1 in ESCC. Unlike the cases in other types of cancer, both expression of ECM1a and ECM1b is down-regulated in ESCC compared to normal esophageal tissues. ECM1b represents the dominantly expressed variants in esophagus epithelium, and its expression is highly reduced in esophageal carcinoma. ECM1b plays a potential suppressive role in tumorigenesis and metastasis. Acknowledgement: We acknowledge the Research Grants Council of Hong Kong Special Administrative Region for funding support (HKU 774413M to M.L.L). Citation Format: Valen Zhuoyou YU, Josephine Mun-Yee Ko, Simon Law, Li Dong Wang, Maria Li Lung. Differential expression and functional impact of the alternatively spliced transcripts of Extracellular matrix protein 1 in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1158.
Chronic myeloid leukemia patients call for quality and consistency when generics are introduced to treat their cancer
Authors: J Geissler, G Sharf, J Cugurovic, R Padua, Š Narbutas, M Remic, V Venkatesh
Journal: Leukemia (2016)

Imatinib is a tyrosine kinase inhibitor (TKI) used in the treatment of multiple cancers, most notably chronic myeloid leukemia (CML).A patent application for imatinib was filed in Switzerland in 1992, as well as in the EU, the USA and for other countries in 1993.Companies began selling generic formulations of imatinib in India in the early 2000s, surrounded by controversial patent disputes. 16][7][8] Physicians and patient organizations have been increasingly confronted with the issue of generics and copies of patented drugs in the treatment of CML.This has raised concerns about the outcomes when patients are switched between different products for non-medical reasons. 2 At the same time, significantly lower prices of generics and copies of patented drugs have allowed more patients to afford treatment, and healthcare cost savings have been realized. 6,9The CML Advocates Network, a patient-run network of CML patient organizations from more than 70 countries, undertook a survey to investigate some of the concerns that patients experience when an alternative, less expensive formulation of the originator TKI is prescribed for management of their cancer.During 2013, the CML Advocates Network designed a questionnaire (see supplementary material) to survey 80 patient advocacy organizations of the worldwide CML Advocates Network as well as a physicians registered at the International CML Foundation.Questions included the availability of different TKI products, availability of certificates of quality to the public, bioequivalence and/or effectiveness of these products, duration of availability, as well as observations of unusual side effects or efficacy compared with the experience of the established original/ patent-protected TKIs.There were 86 responses from 55 countries.On the basis of the data received from the 2013 survey, representatives of CML patient organizations from 58 countries met in 2014 for their annual global advocacy meeting in Belgrade, Serbia.Joint recommendations for the optimal use of TKI generic formulations in the management of CML were discussed and agreed.According to the results of the 2013 survey, imatinib was available in 55 countries, nilotinib in 44, dasatinib in 30, bosutinib in 6 and ponatinib in 4. Generic formulations or copies of imatinib had become available in 15 countries (Bosnia-Herzegovina, China, Colombia, Costa Rica, Egypt, Guatemala, Hong Kong, India, Lebanon, Lithuania, Nepal, Nigeria, Russia, Serbia and Uruguay) and similarly for dasatinib in three countries (Costa Rica, Guatemala and India).At the annual CML global advocacy meeting in Belgrade during 2014, representatives of the 58-country patient organizations present determined that generic formulations or copies of imatinib and dasatinib had become available in 32 countries: Argentina,
Abstract 1674: Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein
Authors: Chunli Wei, Jingliang Cheng, Hanchun Chen, Dianzheng Zhang, Junjiang Fu
Journal: Cancer Research (2016)

Abstract Regulation of gene expression by TRIM28 is not only by transcriptional repression but also by post-translational regulation. Here we report that TRIM28 promotes breast cancer cell metastasis through TRIM28-TWIST1-EMT pathway. We find that TRIM28 is highly expressed in metastatic cancer cell lines and advanced breast cancer tissues. The expression of TRIM28 and TWIST1 is positively correlated with most of the invasive breast carcinomas. Notably, we find that overexpression of TRIM28 upregulates TWIST1 protein, whereas TRIM28 depletion downregulates TWIST1 protein, indicating that TWIST1 upregulation likely occurs at post-transcriptional level, not at transcriptional level. Overexpression of TRIM28 in BT549 breast cancer cell line promotes cell migration and invasion functionally; conversely, knockdown of TRIM28 reduces TWIST1 protein level, up-regulates E-cadherin and down-regulates N-cadherin, and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull down reveal that TRIM28 interacts with TWIST1 directly, thereby preventing from proteasomal degradation. Moreover, TWIST1 degradation rate is reduced after cycloheximide blocking protein synthesis through the depletion of TRIM28 in BT549 cells. Taken together, our findings suggest that TRIM28 functionally stabilizes TWIST1 protein, reveals a novel mechanism, and provides an effective therapeutic strategy to target TRIM28 in breast cancer treatments. Citation Format: Chunli Wei, Jingliang Cheng, Hanchun Chen, Dianzheng Zhang, Junjiang Fu. Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1674.
Mid-Treatment Plasma Levels of Thymus Activated and Regulated Chemokine (TARC) Predict Treatment Outcome In Classical Hodgkin Lymphoma Patients
Authors: Wouter Plattel, Anke Van Den Berg, Anne Marijn Van der Graaf, Hans Vos, Lydia Visser, Arjan Diepstra, Gustaaf van Imhoff
Journal: Blood (2010)
Abstract 2894: Impact of honokiol on sialylation in breast cancer cells
Authors: Padmamalini Thulasiraman, Galen Garriga
Journal: Cancer Research (2016)

Abstract Metastasis is a process in which malignant cells spread form the tumor of origin and colonize at distant organs. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1). High levels of MUC1 have been found in tumor tissues, including breast cancer, and have been implicated in reduced survival rate. After translation of the protein, carbohydrate groups are attached to MUC1, a process called glycosylation. The resulting glycocalyx, which serves as a protective layer on epithelial surfaces, is involved in cell-cell interactions, signaling and metastasis. Glycosylation patterns differ on MUC1 in normal breast tissue in comparison with MUC1 in breast tumors. Not only do breast tumors have simpler and fewer carbohydrate chains than MUC1 from normal breast epithelial tissue, they also have increased levels of the carbohydrate derivative, sialic acid. Altered addition of sialic acid (sialylation) has been associated with cancer transformation and metastatic progression of the disease. The enzyme, α-2,3 sialyltransferase (ST3Gal I) which adds the α-2,3-linked sialic acids to MUC1 is increased in breast tumors and has been correlated with poor prognosis. Shortening of the carbohydrates units on MUC1 in breast tumors unmasks peptides that would otherwise be covered by the carbohydrates in normal MUC1, and current studies seek to identify antibodies that would directly target MUC1 on the cancer cells and in turn prevent cancer metastasis. Plant derived natural product honokiol is being studied for its anti-tumor activities. To assess the effect of honokiol on ST3Gal I, we treated breast cancer cell lines, MDA-MB-231 and MCF-7 cells with honokiol and analyzed its effect on ST3Gal I mRNA and protein expression using RT-PCR and Western Blotting, respectively. Honokiol suppressed ST3Gal I at the mRNA and protein level in both cancer cell lines. To investigate specifically whether honokiol reduces free sialic acid, we treated mammary carcinoma cells with honokiol and using the Sialic Acid Kit, we observed reduction in sialic acid in honokiol-treated mammary carcinoma cells. Future immunoprecipitation studies are underway to investigate specifically whether honokiol suppresses sialylation of MUC1. We propose that these studies will lead to the understanding on how sialylation of MUC1 alters the cellular signaling processes involved in the transformation of breast cancer and eventually to the spread of the disease. Citation Format: Padmamalini Thulasiraman, Galen Garriga. Impact of honokiol on sialylation in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2894.
Abstract 4744: Targeting nitric oxide signaling with nNOS inhibitors as a novel strategy for the therapy and prevention of human melanoma
Authors: SUN YANG, Zhen Yang, Richard B. Silverman, Thomas Poulos, Frank L. Meyskens
Journal: Cancer Research (2016)

Abstract The incidence of cutaneous melanoma (CM) has increased markedly over the past four decades although there have been some dramatic advances recently in the treatment of advanced melanoma. The development of novel therapeutic interventions blocking melanoma progression would be of high impact. Recently, our group has identified that neuronal NO synthase (nNOS) activated by UV radiation and growth factor plays an important role in melanoma progression, in parallel with generating constitutive NO stress. Knockdown of nNOS significantly reduced tumor growth and lung metastasis in vivo. The newly developed nNOS inhibitors HHs (HH044 and HH045) exhibited potent anti-melanoma activity both in vitro and in vivo. The IC50s of HH compounds in human melanoma cells are less than 10 μM, which are comparable or even better than that of chemotherapeutic drug cisplatin (4.2μM and 14.3μM in A375 and Sk-Mel28 cells, respectively). Notably, the inhibition by HHs is more predominant in metastatic melanoma A375 cells compared to primary early stage Wm3211 cells, which supports our hypothesis that nNOS/NO signaling is more critical to melanoma progression than in the initiation phase. In a melanoma xenograft tumor model, we further determined the effects of HH044 and HH045 in tumor growth in vivo. Treatments with HH044 and HH045 (50mg/kg i.p for 21 days) significantly reduced the tumor size to 12% and 19% of control respectively with no apparent systematic toxicities observed. The body weight in treated mice was even moderately higher than the control’s. Taken together, these results are consistent with our hypothesis that targeting nNOS is an efficient and practicable approach for human melanoma therapy. Citation Format: SUN YANG, Zhen Yang, Richard B. Silverman, Thomas Poulos, Frank L. Meyskens. Targeting nitric oxide signaling with nNOS inhibitors as a novel strategy for the therapy and prevention of human melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4744.
PD-L1 expression in mononuclear cells and not in tumor cells, correlated with prognosis in metastatic urothelial carcinoma.
Authors: Stephanie A. Mullane, Lillian Werner, Marcella Callea, Andre Poisl Fay, Jeffrey J. Leow, Toni K. Choueiri, Gordon James Freeman, Sabina Signoretti, F. Stephen Hodi, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2014)

4552 Background: Programmed death-1 (PD-1) receptor negatively regulates T cell-mediated responses.PD-1 ligand (PD-L1) is expressed in several malignancies and is associated with higher grade, 9p24 loss and worse clinical outcome. Its role as potential predictive biomarker for immunotherapy is of clinical relevance. The prognostic impact of PD-L1 expression in tumor cells versus its expression in mononuclear (MNC) infiltrates in urothelial carcinoma (UC) is unknown. Methods: Formalin-fixed paraffin embedded (FFPE) tumor samples from 160 clinically annotated UC patients were retrieved. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). The assay was validated using FFPE cell line controls known to be positive or negative for PD-L1 expression by flow cytometry. PD-L1 tumor positivity (PD-L1+) was defined as ≥5% tumor cell membrane staining. For PD-L1 expression in MNC, a score based on the extent of infiltrate and percentage of positive cells was used. Fisher’s exact test was used to assess the associations with clinical variables (smoking history, prior BCG treatment and stage at diagnosis) and 9p24 copy number variation (CNV). Log rank test was used to assess the association of PD-L1 expression with overall survival (OS). Results: Among 160 UC patients, PD-L1+ expression was seen in 32 (20%) of tumors cell membrane and in 58 (37%) of MNC. Smoking history did not correlate with expression of PD-L1 in tumor cells or in MNC. PD-L1+ in MNC was non significantly higher in stage III/IV versus stage I/II tumors at diagnosis (41.8% versus 30%; p=0.56). In the subgroup of patients that developed metastatic disease (89 patients), MNC PD-L1+ was significantly associated with a longer OS (p=0.04). In patients that developed metastatic disease, PD-L1+ was seen in 14% of tumor cells and did not correlate with OS (p=0.45). Correlation with prior BCG exposure and CNV of 9p24 will be presented. Conclusions: PD-L1 is widely expressed in tumor cell membrane and MNC in UC. PD-L1+ in MNC is significantly associated with survival in those patients that subsequently develop metastatic disease.
Dissecting the Core Fear in Anorexia Nervosa
Authors: Stuart B. Murray, Katharine L. Loeb, Daniel Le Grange
Journal: JAMA Psychiatry (2016)

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