tbuckley/cabot-search huggingface dataset:
Abstract 3403: Telomere shortening in pancreatic cancer is correlated to KRAS mutation
Authors: Yoko Matsuda, Naotaka Izumiyama, Mutsunori Fujiwara, Naoshi Ishikawa, Junko Aida, Kaiyo Takubo, Toshiyuki Ishiwata, Tomio Arai
Journal: Cancer Research (2017)

Abstract Background: Pancreatic cancer is characterized by genomic complexity and chromosomal instability, and atypical mitotic figures are morphological features of this phenotype. Previously we have reported that approximately 30% of total mitosis in pancreatic cancer was atypical including multipolar, lag-type, ring and asymmetrical mitosis, and anaphase bridges, and the number of total mitosis and atypical mitosis in pancreatic cancers was correlated with aggressive phenotype and prognosis (Pancreatology, 2016). In the present study, we clarified the relation between atypical mitotic figures, telomere length, and genetic abnormality in the pancreatic cancer. Methods: We surveyed the mitotic figures of the normal epithelium, pancreatic intraepithelial neoplasias (PanINs), and pancreatic cancers using surgically resected pancreatic cancer specimens (n=40). Telomere length was analyzed using quantitative fluorescent in situ hybridization technique. We also analyzed mutations of Kras codon 12 and 13 by PCR and microsatellite instability by immunohistochemical staining of MLH1, MSH2, MSH6 and PMS2. Results: Pancreatic cancer and duodenal epithelium showed significantly higher mitotic indices as compared with the duct, acinar cells, and PanINs. Normal mitosis was also higher in pancreatic cancers and the duodenal epithelium, while atypical mitosis was significantly elevated only in pancreatic cancers. Number of total mitosis and atypical mitosis were negatively correlated with telomere length, suggesting that telomere shortening plays important roles in cancer proliferation and chromosomal instability. In comparison with normal ducts, telomere length was decreased in PanIN-1, -2 and -3 and cancer. Furthermore, telomere length was gradually shorter among PanIN grades. Most of pancreatic cancers harbored mutations in Kras codon 12, and pancreatic cancer cases with Kras mutation showed shorter telomere length as compared with cases without Kras mutation. All pancreatic cancer cases in the present study were microsatellite stable. Conclusion: Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium plays key roles on carcinogenesis of the pancreas. Citation Format: Yoko Matsuda, Naotaka Izumiyama, Mutsunori Fujiwara, Naoshi Ishikawa, Junko Aida, Kaiyo Takubo, Toshiyuki Ishiwata, Tomio Arai. Telomere shortening in pancreatic cancer is correlated to KRAS mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3403. doi:10.1158/1538-7445.AM2017-3403
Abstract 1410: Proliferation during epithelial-to-mesenchymal transition induces genomic instability
Authors: Valentine Comaills, Lilian Kabeche, Robert Morris, Min Yu, Marissa Wells Madden, Joseph A. LiCausi, Nicola Aceto, Yu Zheng, David T. Miyamoto, Sridhar Ramaswamy, Lee Zou, Daniel A. Haber, Shyamala Maheswaran
Journal: Cancer Research (2017)

Abstract Epithelial to mesenchymal transition (EMT), a morphogenetic process required for proper embryonic development, is adopted by cancer cells during tumor progression. We show that induction of EMT by TGFß or other EMT-inducers such as Snail leads to genomic instability, associated with failed cytokinesis and chromosome missegregation resulting in aneuploidy and polyploidy. These defects are dependent on persistent proliferation of cells undergoing EMT and are absent in normal cells that growth arrest during EMT. While EMT and the associated mitotic abnormalities are reversible upon removal of the EMT-inducer, the resulting chromosomal abnormalities are inherited. TGFß-induced genomic instability is associated with the acquisition of tumorigenic phenotypes and the resulting tumors are enriched for a genomically-altered tumor cell population, which exhibits differential drug sensitivity. In breast and prostate cancer cells circulating in the blood, TGFß and EMT gene signatures are significantly correlated with aneuploid gene signatures. Analysis of single circulating tumor cells (CTC) from women with metastatic breast cancer reveals increased in genomic instability in mesenchymal CTCs. Together, these findings identify a novel mechanism whereby tumor microenvironment-derived signals impact heritable genetic changes within cancer cells. Citation Format: Valentine Comaills, Lilian Kabeche, Robert Morris, Min Yu, Marissa Wells Madden, Joseph A. LiCausi, Nicola Aceto, Yu Zheng, David T. Miyamoto, Sridhar Ramaswamy, Lee Zou, Daniel A. Haber, Shyamala Maheswaran. Proliferation during epithelial-to-mesenchymal transition induces genomic instability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1410. doi:10.1158/1538-7445.AM2017-1410
Antibacterial glass-ionomer cement restorative materials: A critical review on the current status of extended release formulations
Authors: Tahereh Mohammadi Hafshejani, Ali Zamanian, Jayarama Reddy Venugopal, Zahra Rezvani, Farshid Sefat, Mohammad Reza Saeb, Henri Vahabi, Payam Zarrintaj, Masoud Mozafari
Journal: Journal of Controlled Release (2017)
Abstract CT141: Longterm survival in glioblastoma patients after tumor treating fields (TTFields) therapy
Authors: Aaron Rulseh, Jan Šroubek, Jan Klener, Josef Vymazal
Journal: Cancer Research (2017)

Abstract Introduction: Glioblastoma multiforme (GBM) is the most common and malignant primary intracranial tumor and traditionally has a median survival of only 10 to 14 months, with only 3 to 5% of patients surviving more than three years. Recurrence (RGBM) is nearly universal, and further decreases the median survival to only 5 to 7 months with optimal therapy. Materials and Methods: Tumor treating fields (TTFields) therapy is a novel treatment technique that has recently shown significant prolonged progression free survival and overall survival innewly diagnosed GBM. This therapy is approved for the treatment of newly diagnosed and recurrent GBM and is based on the principle that low intensity, intermediate frequency alternating electric fields (100 to 300 kHz) have an anti-mitotic effect in specific cell types. The applied fields disrupt the mitotic spindle, microtubule assembly and the segregation of intracellular organelles during cell division, leading to apoptosis or mitotic arrest. Results: Our center was the first in the world to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals (10 GBM and 10 RGBM) in 2004 and 2005, and 4 of the original 20 patients are still alive today (2 GBM, 2 RGBM), in good health and no longer receiving any treatment roughly 12 years after initiating TTField therapy, with no clinical or radiological evidence of recurrence. Two of the 4 surviving patients exhibited radiological signs of tumor growth initially, before the tumor regressed in size after a median of 4 months of continuous treatment. Conclusions: Our results indicate that TTField treatment may be remarkably successful for both newly diagnosed and recurrent GBM patients. Further investigation is needed to identify any unique characteristics of these patients. We recommend that TTField treatment should be applied for a sufficient amount of time, and that initial radiologic progression following treatment initiation should not be considered a reason to discontinue treatment. Citation Format: Aaron Rulseh, Jan Šroubek, Jan Klener, Josef Vymazal. Longterm survival in glioblastoma patients after tumor treating fields (TTFields) therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT141. doi:10.1158/1538-7445.AM2017-CT141
Abstract 4334: Interleukin-6 is a key player in stroma-induced resistance to chemotherapy for gastric carcinomas
Authors: In-Hye Ham, Dakeun Lee, Hyejin Jin, Sang Yong Son, Yong Bae Kim, Sang-Uk Han, Hoon Hur
Journal: Cancer Research (2017)

Abstract Introduction Gastric carcinomas (GCs) are known to progress through the interaction between cancer cells and the tumor stroma. Moreover, recent molecular analysis revealed that the expression of stroma-related genes was significantly associated with poor response to chemotherapy in GCs. However, the specific targets to inhibit the interaction between stroma and cancer cells and to reverse stroma-induced chemoresistance have never been suggested in GCs. Experimental procedures The gene expression in the biopsied GCs tissues from 10 patients, who were treated with preoperative chemotherapy, was analyzed using Nanostring analyzer. We compared the expression pattern of genes involved in the cancer progression panel between chemotherapy response and non-response groups. In addition, we investigated the level of serum interleukin-6 (IL-6) in 39 GCs patients, who underwent curative gastrectomy and postoperative adjuvant chemotherapy. GCs patients were subclassified into recurrence and non-recurrence groups, and the level of IL-6 was compared between two groups. We performed cell proliferation assay, qRT-PCR, ELISA and Western blot to investigate the role of cancer-associated fibroblasts(CAFs)-produced IL-6 on the chemoresistance. Summary of the new data For pretreated biopsied tissues of patients with preoperative chemotherapy, the expression of IL-6 gene in non-response group was significantly higher than response group. In addition, for patients with postoperative adjuvant chemotherapy, the serum level of IL-6 in GCs patients with recurrence was higher than patients without recurrence. Moreover, In vitro studies demonstrate that co-culture with CAFs increased chemoresistance of various GCs cell lines to 5-fluouracil (5-FU) and CAFs-derived IL-6 activated the membrane gp130 and the STAT3 signal pathway in GCs cell lines. When anti-IL-6R monoclonal antibody was added to 5-FU for GCs cell lines in co-culture with CAFs, activation of STAT3 was significantly reduced and apoptosis markers efficiently induced. Conclusion Our study showed that the stroma-induced IL-6 is a key player in the resistance to chemotherapy in GCs. We convinced that the interaction between stroma cells and cancer cells could be inhibited by blockade of IL-6 signal pathway. We suggest the use of IL-6 inhibitor as therapeutic agent to enhance the response to chemotherapy in GCs. Citation Format: In-Hye Ham, Dakeun Lee, Hyejin Jin, Sang Yong Son, Yong Bae Kim, Sang-Uk Han, Hoon Hur. Interleukin-6 is a key player in stroma-induced resistance to chemotherapy for gastric carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4334. doi:10.1158/1538-7445.AM2017-4334
Abstract 3315: Cancer cells upregulate autophagy as a survival mechanism in response to tumor treating fields (TTFields)
Authors: Yaara Porat, Anna Shteingauz, Moshe Giladi, Rosa S. Schneiderman, Tali Voloshin, Mijal Munster, Roni Blat, Eilon D. Kirson, Uri Weinberg, Yoram Palti
Journal: Cancer Research (2017)

Abstract Tumor treating fields (TTFields) are an established anti-neoplastic treatment modality in patients with glioblastoma. TTFields are delivered via noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to the region of the tumor. Previous studies have shown that TTFields treatment lead to increased cellular granularity, which is often associated with autophagy. Autophagy has been shown to regulate cell survival and proliferation under stress conditions and to influence cellular response to cytotoxic drugs. This study evaluated the role of autophagy in cancer cells treated with TTFields. Immunoblot analysis showed significant elevations in levels of lipidated Microtubule Associated Protein Light Chain (LC3-II) in TTFields-treated glioma and lung cancer cells. Increased autophagy following TTFields application in these cell lines was also detected using fluorescence microscopy, where punctate distribution of LC3-II was observed. TEM micrographs demonstrated the presence of autophagy typical, autophagosome-like structures in TTFields-treated U-87 MG cells. Combination of TTFields with autophagy inhibitors, chloroquine and melfoquine, resulted in a significant dose-dependent reduction in cell growth compared with TTFields treatment alone. Inhibition of autophagy with chloroquine triggered apoptosis as indicated by elevated levels of AnnexinV/7AAD double staining. Increased levels of autophagic flux in TTFields-treated cells were not associated with reduced mTOR activity, which was monitored by p70S6K phosphorylation immunoblot analysis. TTFields are known to exert anti-mitotic effects by disrupting highly dipolar structures that play critical roles in mitosis. Our results demonstrate that TTFields additionally induce cellular autophagy by an mTOR-independent mechanism. TTFields- treated cell lines appear to utilize autophagy as a survival mechanism. Thus, inhibition of autophagy sensitizes tumor cells to TTFields treatment, resulting in elevated apoptotic cell death. Future studies are warranted to examine the extent to which TTFields-elicited autophagy may affect treatment outcomes and to investigate the therapeutic implications of combining TTFields with autophagy inhibitors in vivo. Citation Format: Yaara Porat, Anna Shteingauz, Moshe Giladi, Rosa S. Schneiderman, Tali Voloshin, Mijal Munster, Roni Blat, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Cancer cells upregulate autophagy as a survival mechanism in response to tumor treating fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3315. doi:10.1158/1538-7445.AM2017-3315
Abstract 5718: Outcome prediction in colorectal cancer using digitized tumor samples and machine learning
Authors: Dmitrii Bychkov, Riku Turkki, Caj Haglund, Nina Linder, Johan Lundin
Journal: Cancer Research (2017)

Abstract Additional prognostic stratification of colorectal cancer patients is needed to improve management of patients. Visual microscopic assessment of tumor samples remains the standard method for disease subtyping. However, visual analysis of samples is subjective and weakly reproducible due to inter- and intra-observer variations. Recent progress within machine learning, especially its novel branch called deep learning, enables accurate evaluation of complex patterns observed in microscopic tissue images. Here, we combined deep learning techniques to evaluate a set of digitized formalin fixed paraffin embedded hematoxylin-eosin stained tumor tissue microarray (TMA) samples from 420 randomly selected patients with colorectal cancer. For each patient a set of clinicopathological characteristics including histological grade, Dukes stage and age at diagnosis are available as well as outcome data. Using convolutional neural networks and Long Short-Term Memory networks we validated the predictive power of the colorectal TMAs with regards to patient outcome. Univariate Cox proportional hazard regression analysis demonstrated that the prognostic accuracy of the deep learning algorithm on TMAs (hazard ratio 2.3; CI 95% 1.79-3.03) outperforms visual histological grading performed by a certified pathologist on a whole slide level (hazard ratio 1.65; CI 95% 1.30-2.15). In multivariate Cox proportional hazard regression, the deep learning based model was a prognostic factor, independent of histological grade, Dukes stage and age at diagnosis (Wald p-value &amp;lt; 0.001). Thus, we demonstrate that novel deep learning models can serve as digital prognostic biomarkers in colorectal cancer. Citation Format: Dmitrii Bychkov, Riku Turkki, Caj Haglund, Nina Linder, Johan Lundin. Outcome prediction in colorectal cancer using digitized tumor samples and machine learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5718. doi:10.1158/1538-7445.AM2017-5718
Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients
Authors: John R. Teerlink, Min Qian, Natalie A. Bello, Ronald S. Freudenberger, Bruce Levin, Marco R. Di Tullio, Susan Graham, Douglas L. Mann, Ralph L. Sacco, J.P. Mohr, Gregory Y.H. Lip, Arthur J. Labovitz, Seitetz C. Lee, Piotr Ponikowski, Dirk J. Lok, Stefan D. Anker, John L.P. Thompson, Shunichi Homma
Journal: JACC Heart Failure (2017)
Abstract 4003: Acral lentiginous melanoma and infiltrating lymphocytes in a Latin American population
Authors: Carlos Castaneda, Carlos Torres-Cabala, Sandro Casavilca, Miluska Castillo, Valeria Villegas, Joselyn Sanchez, Claudio Flores, Henry Gomez, Tatiana Vidaurre
Journal: Cancer Research (2017)

Abstract Background: Acral lentiginous melanoma (ALM) is unusual in Caucasian but is the most common subtype in Hispanic populations, and has been associated to poor prognosis. Herein we compare clinicopathological features associated to ALM in a Latin-American population and prospectively evaluate its association with tumor infiltrating lymphocytes (TIL). Patients and Methods: All patients with melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, were retrospectively identified. Analysis of association between clinicopathological features and ALM was performed. Survival analysis compared the outcome of ALM to whole group and extremity NALM. We performed prospective evaluation of TIL following Azimi et al recently presented classification. Results: A total of 537 ALM and 287 NALM cases were identified. Older age (p= 0.02), thicker Breslow (p= 0.008), positive lymph node (p= 0.051) and ulceration (p&amp;lt;0.001) were found to be more frequent in ALM. Acral had worse OS compared with both whole group (p= 0.04) and extremity NALM (p &amp;lt;0.001). Stage I-II patients had a median OS of 5.3 (95%CI: 4.3-6.2) for ALM and 9.2 (95% CI: 5.0 - 7.0) for extremity NALM (p=0.016). TIL was prospectively evaluated in 490 cases, and Grade 0-1, II and III of TIL represented 44.7%, 33.6% and 27.1%, respectively. Higher TIL grade was associated to less Breslow thickness (p= 0.021), less mitosis index and NAM. Higher TIL grade was also associated to better OS (p&amp;lt; 0.001) Conclusion: ALM is highly prevalent in Latin-America and carry poor outcome. Lower TIL levels was associated to poor outcome and ALM. Citation Format: Carlos Castaneda, Carlos Torres-Cabala, Sandro Casavilca, Miluska Castillo, Valeria Villegas, Joselyn Sanchez, Claudio Flores, Henry Gomez, Tatiana Vidaurre. Acral lentiginous melanoma and infiltrating lymphocytes in a Latin American population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4003. doi:10.1158/1538-7445.AM2017-4003
Abstract 5810: microRNAs targeting EMT transcription factors may be associated to lymph node metastasis in breast cancer tumors
Authors: Elisa Pérez-Moreno, Gabriela Valarezo, Valentina Zavala, Wanda Fernández, Pilar Carvallo
Journal: Cancer Research (2017)

Abstract Breast cancer is the leading cause of cancer-associated deaths in women. Lymph node near to the primary breast tumor have a high chance of developing a secondary tumor, representing one of the first signs of metastasis in breast cancer. Metastasis is promoted by epithelial-mesenchymal transition (EMT), process leaded by the transcription factors SNAIL, SLUG, ZEB and TWIST. MicroRNAs are small non-coding RNAs, whose expression has been demonstrated to be altered in different cancer types. Because of their ability to regulate large sets of genes involved in cancer growth and metastasis, microRNAs have emerged as candidate molecular biomarkers and novel therapeutic targets. The aim of this study is to identify microRNAs differentially expressed in breast tumors in relation to EMT-transcription factor expression and lymph node metastasis, and that are involved in epithelial-mesenchymal transition. For this purpose, we used microRNA microarray data from 50 fresh frozen breast tumors with different tumor grades (1 to 3), 28 from patients with lymph node metastasis. Microarray data analysis using RankProd (R package) revealed approximately 40 microRNAS down-regulated in breast tumors with expression of EMT-transcription factors (p&amp;lt;0.05). Several of the identified microRNAs have been previously described to regulate early steps of metastasis in different cancer types, like members of the miR-200 family (miR-200c and miR-141), miR-205 and miR-30a. In addition we found other microRNAs not previously associated to metastasis. Our results suggest that down regulation of specific microRNAs, and up regulation of their targets, may induce a metastatic behavior of tumor cells of the primary breast tumors, promoting invasion and colonization of the lymph nodes. In this sense, the changes in the expression of microRNAs may serve as biomarkers of breast cancer prognosis in patients. Citation Format: Elisa Pérez-Moreno, Gabriela Valarezo, Valentina Zavala, Wanda Fernández, Pilar Carvallo. microRNAs targeting EMT transcription factors may be associated to lymph node metastasis in breast cancer tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5810. doi:10.1158/1538-7445.AM2017-5810