bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A15: Distinct gene expression profiles in Lynch syndrome-associated ovarian cancer
Authors: Jönsson Jenny-Maria , Bartuma Katarina , Valentin Mev Dominguez , Harbst Katja , Ketabi Zoreh , Malander Susanne , Jönsson Mats , Carneiro Ana , Måsbäck Anna , Jönsson Göran , Nilbert Mef 
Published: August 2014

Abstract
Background: Ovarian cancers linked to Lynch syndrome represent a rare subset that typically present at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We aimed to identify molecular profiles of Lynch syndrome-associated ovarian cancer for application in refined diagnostics and targeted therapeutics.
Methods: Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation (WG-DASL) was applied to 48 histopathologically matched ovarian cancers, which represented Lynch syndrome-associated tumors and sporadic tumors. The results were validated by application of an external ovarian cancer data set and by immunohistochemistry.
Results: Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, predominantly involved in the mTOR and MAPK/ERK signaling pathways.
Conclusion: The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to different tumorigenic routes and suggest that targets within the mTOR and MAPK/ERK signaling pathways may be relevant to consider for molecular diagnostics and targeted therapeutics.
Citation Format: Jenny-Maria Jönsson, Katarina Bartuma, Mev Dominguez Valentin, Katja Harbst, Zoreh Ketabi, Susanne Malander, Mats Jönsson, Ana Carneiro, Anna Måsbäck, Göran Jönsson, Mef Nilbert. Distinct gene expression profiles in Lynch syndrome-associated ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A15.
Abstract A27: The ovarian tumor tissue analysis (OTTA) consortium
Authors: Ramus Susan J. , Köbel Martin , Sieh Weiva , Anglesio Michael S. , Millstein Joshua , Bowtell David D. , Brenton James D. , Høgdall Estrid , Pharoah Paul DP , Goode Ellen L. , Huntsman David G. 
Published: August 2014

Abstract
Our understanding of ovarian cancer is complicated by disease heterogeneity. There are five major histological types, each with alterations in different pathways and distinct clinical outcomes. Even within these histological types there is clinical and molecular heterogeneity. The Ovarian Tumor Tissue Analysis (OTTA) consortium was established to validate prognostic markers for ovarian cancer in a large population of patients to allow stratification by histological type and molecular subtype. OTTA is currently a collaboration among 38 studies and has tissue microarrays (TMAs) from over 8,000 tumors available for immunohistochemical (IHC) analysis. In addition formalin fixed paraffin embedded (FFPE) tissue on slides or cores are available from the majority of OTTA studies for DNA and RNA analysis. Approximatley 60% of the cases are part of the Ovarian Cancer Association Consortium (OCAC) and have genotype data on over 200,000 single nucleotide polymorphisms and extensive epidemiological data. We recently performed IHC analysis of 12 markers using centralised staining and scoring to reduce heterogeneity and improve power to validate biomarkers. We showed that estrogen receptor and progesterone receptor were prognostic markers for endometrioid and high-grade serous carcinomas by performing the first robust subtype-specific analyses of these biomarkers in nearly 3000 patients. In contrast, FOLR1 expression was not associated with survival in 1507 high-grade serous carcinomas. We have shown that FFPE material from OTTA is suitable for RNA expression analysis on high through-put platforms such as the NanoString GX system. Expression analysis of 50 candidate genes in 244 high grade serous ovarian cancer cases has validated prognostic markers identified by The Cancer Genome Atlas (TCGA) project and investigated a series of novel candidate genes. IHC and RNA expression profiling from formalin fixed paraffin embedded (FFPE) tumor tissue is being used to better subclassify the ovarian tumors for further analysis. We would welcome groups with collections of ovarian tumor samples and corrsponding clinical data to join OTTA and participate in ongoing collaborative projects.
Citation Format: Susan J. Ramus, Martin Köbel, Weiva Sieh, Michael S. Anglesio, Joshua Millstein, David D. Bowtell, James D. Brenton, Estrid Høgdall, Paul DP Pharoah, Ellen L. Goode, David G. Huntsman. The ovarian tumor tissue analysis (OTTA) consortium. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A27.
Abstract A28: Analyses of FOXM1 isoforms in ovarian cancer
Authors: Altadill Tatiana , Rigau Marina , Majem Blanca , Lanau Lucia , Castellví Josep , García Ángel , Pérez-Benavente Assumpció , Sánchez José Luis , Cabrera Silvia , Xercavins Jordi , Campo Josep Maria del , Gil-Moreno Antonio , Llauradó Marta , Reventós Jaume 
Published: August 2014

Abstract
Introduction & Objectives: Epithelial ovarian cancer (OC) is the most lethal gynaecological malignancy and the fifth leading cause of cancer death in women in the Western world. Forkhead box M1 (FOXM1) transcription factor was already been described to be overexpressed in various malignancies, playing a key role in cell-cycle progression, chromosomal segregation and genomic stability, and oxidative stress. Moreover, it can also promote drug resistance to herceptin, paclitaxel and cisplatin in breast cancer cells. A recent report from our group has shown, for the first time, that FOXM1 is also overexpressed in OC, being associated with tumor grade. This result seem to indicate an interesting role of this molecule in the progression and resistance to therapy in OC. Our aim is to characterize FOXM1 isoforms in OC through the use of human tissue samples.
Material & Methods: Fresh ovarian primary tumors, ascites and peritoneal metastases from patients suffering advanced serous OC were collected from surgery room and processed for microarray analysis to detect FOXM1 expression levels. FOXM1 isoforms were analysed at mRNA expression level by using RTqPCR in a set of new frozen tissue samples.
Results: We found that FOXM1 overexpression is increased in OC peritoneal metastases. Now, we are characterizing the isoforms of FOXM1 in primary, ascites and metastatic tumors. Nevertheless, more samples need to be analysed in order to have conclusive results.
Conclusions: The present study highlights the role of FOXM1 isoforms in OC dissemination and pursues the idea to elucidate the biologic role of FOXM1 in OC tumorigenesis.
Citation Format: Tatiana Altadill, Marina Rigau, Blanca Majem, Lucia Lanau, Josep Castellví, Ángel García, Assumpció Pérez-Benavente, José Luis Sánchez, Silvia Cabrera, Jordi Xercavins, Josep Maria del Campo, Antonio Gil-Moreno, Marta Llauradó, Jaume Reventós. Analyses of FOXM1 isoforms in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A28.
Abstract A41: Harnessing neural stem cell tumor tropism for targeted nanoparticle delivery: Potential for ovarian cancer therapy
Authors: Mooney Rachael , Gilchrist Megan , Weng Yiming , Annala Alexander , Bhojane Sukhada , Garcia Elizabeth , Roma Luella , Schnarr Kenna , Dellinger Thanh , Han Ernest , Karen Aboody S. , Berlin Jacob M. 
Published: August 2014

Abstract
Intraperitoneal as compared to intravenous administration of chemotherapy has shown improved survival rates for stage III ovarian cancer. While this demonstrates that concentrating chemotherapy at the tumors has therapeutic benefit, intraperitoneal therapy was also accompanied by significantly increased toxic side effects. There is thus an urgent need for a targeted delivery system that could localize therapy at the tumors and decrease the side-effects. Here we show that stem cell/nanoparticle hybrids may be used for such targeted therapy. In pre-clinical brain and other invasive and metastatic tumor models, neural stem cells have been shown to overcome a variety of biological barriers and migrate selectively to invasive tumor foci, even penetrating hypoxic tumor regions. Here we present data confirming that neural stem cells also migrate selectively to ovarian cancer. Moreover, the neural stem cells can engineered to transport to the tumors nanoparticles that either contain chemotherapy drugs or can be induced to heat. The combination of neural stem cells and nanoparticles that can either be used for thermal ablation or slowly release chemotherapy drugs offers the potential to realize a modular and general drug targeting system for the treatment of stage III ovarian cancer.
Citation Format: Rachael Mooney, Megan Gilchrist, Yiming Weng, Alexander Annala, Sukhada Bhojane, Elizabeth Garcia, Luella Roma, Kenna Schnarr, Thanh Dellinger, Ernest Han, Aboody S. Karen, Jacob M. Berlin. Harnessing neural stem cell tumor tropism for targeted nanoparticle delivery: Potential for ovarian cancer therapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A41.
Abstract A47: The LKB1-AMPK pathway mediates the metabolic stress response of dormant ovarian cancer spheroids
Authors: Peart Teresa , Fazio Elena , Ramos-Valdes Yudith , Bertrand Monique , McGee Jacob , Prefontaine Michel , Sugimoto Akira , DiMattia Gabriel E. , Shepherd Trevor G. 
Published: August 2014

Abstract
Metastatic epithelial ovarian cancer (EOC) cells can form multicellular spheroids while in suspension and disperse throughout the peritoneum via ascites to seed secondary lesions. We hypothesize that EOC spheroids are key mediators of metastasis, which use specific signaling pathways to alter cell metabolism for increased survival. Our lab discovered that AKT signaling is reduced during spheroid formation leading to cellular quiescence and autophagy. Given the induction of quiescence and autophagy in EOC spheroids, we are studying the 5′-AMP-activated protein kinase (AMPK) pathway as a master controller of the metabolic stress response and dormant phenotype of EOC spheroids. We demonstrate AMPK activity and its upstream kinase LKB1 are increased in quiescent EOC spheroids compared with proliferating adherent EOC cells. We also show elevated AMPK activity in spheroids isolated directly from patient ascites. Targeted knockdown of STK11, encoding LKB1, reduces cell viability in ovarian cancer cell line spheroids; PRKAA1 (AMPKα1) knockdown has little to no effect on EOC cell or spheroid viability. Combination of STK11 knockdown with carboplatin treatment leads to a synergistic enhancement in EOC spheroid cell death. In contrast, AICAR treatment of proliferating adherent ovarian cancer cell lines and primary EOC cells induces AMPK activity and causes either cytostasis or cell death. In addition, AICAR treatment of spheroids during reattachment decreases the dispersion capacity of migrating EOC cells. These results offer a glimpse of the potential important contributions of LKB1-AMPK pathway in stress signaling related to EOC cell survival during metastasis. In addition, downstream effectors of upregulated LKB1-AMPK signalling may provide additional mechanisms by which EOC evades chemotherapy. It is foreseeable that these findings will allow us to identify new therapeutic targets within this pathway critical to EOC progression for ultimate translation to the clinic.
Citation Format: Teresa Peart, Elena Fazio, Yudith Ramos-Valdes, Monique Bertrand, Jacob McGee, Michel Prefontaine, Akira Sugimoto, Gabriel E. DiMattia, Trevor G. Shepherd. The LKB1-AMPK pathway mediates the metabolic stress response of dormant ovarian cancer spheroids. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A47.
Abstract A67: Obesity promotes growth of ovarian cancer through adipose stem cells
Authors: Zhang Yan , Solley Travis , Nowicka Aleksandra , Klopp Ann 
Published: August 2014

Abstract
Purpose: Excess visceral adiposity increases the risk of ovarian cancer. Intraperitoneal spread to omental adipose is a frequent event and a major cause of morbidity and mortality in women with ovarian cancer. We have recently described a population of tumor tropic adipose stem cells from omental adipose. We hypothesized that visceral obesity alters the visceral adipose population to enhance the initiation and progression of ovarian cancer.
Results: Intraperitoneally injected ID8 ovarian cancer cells grew significantly faster in mice with diet-induced obesity (p&lt;0.05). To determine if the tumor promoting effects of obesity was due to ASC, ASC were isolated from omental (O-ASC) and subcutaneous adipose (SC-ASC) of mice with and without diet induced obesity. Both O-ASC and SC-ASC from Lean/obese mice expressed same mesenchymal cell surface markers. 106 mouse ovarian cancer cells ID8 were co-injected with equal number of different ASC isolates. ASC from all sources increased the cancer cell proliferation in vitro and increased ovarian cancer cell ID8 survival under the treatment of chemo drug Taxol at different concentrations. There were no significant differences in ASC isolates in migration towards tumor-conditioned media. Tumor growth was accelerated by ASCs, but O-ASC and SC-ASC derived from obese mice more potently promoted tumor progression and produced more ascites.
Conclusions: Obesity promotes ovarian tumor progression and this effect is mediated at least in part by adipose stem cells. We propose that obese derived ASCs, especially O-ASC express specific factors that enhance tumor progression, promoting survival and proliferation of tumor cells.
Citation Format: Yan Zhang, Travis Solley, Aleksandra Nowicka, Ann Klopp. Obesity promotes growth of ovarian cancer through adipose stem cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A67.
Abstract B28: The stress phenotype makes ovarian cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase
Authors: Olivero Martina , Dettori Daniela , Arena Sabrina , Zecchin Davide , Lantelme Erica , Renzo Maria Flavia Di 
Published: August 2014

Abstract
CDT2/L2DTL/RAMP is one of the substrate receptors that binds the CRL4 ubiquitin ligase and confers it specificity for a number of substrates, such as CDT1, p21 and CHK1. Previously, we reported that in ovarian cancer cell lines increased susceptibility to cisplatin is associated to the down-regulation of the CDT2 gene. Here we show that CDT2 depletion was alone able to induce the apoptotic death not only in ovarian cancer cell lines but also in 10/10 other human cancer cell lines from different tissues, irrespective of p53, ATM and ATR status and CDT2 expression level. Conversely, CDT2 depletion did not affect non-transformed human cells, such as immortalized kidney, lung and breast cell lines, and primary cultures of endothelial cells and osteoblasts. After CDT2 suppression, all cancer cells underwent rereplication associated to the inability to destroy CDT1 and to cell death. The ectopic over-expression of an activated oncogene, such as the mutation-activated RAS or the amplified MET in non-transformed immortalized breast cell lines and primary human osteoblasts, respectively, made cells transformed in vitro, tumorigenic in vivo, and susceptible to CDT2 loss. Conversely, the knock-down of the tumor suppressor genes PTEN or RB1 did not transform immortalized breast cells and did not sensitize them to CDT2 loss. These data show that transformation makes cells “addicted” to CDT2. The widespread effect of CDT2 depletion in different cancer cells suggests that CDT2 is not in a synthetic lethal interaction to another specific gene or pathway but becomes dominant in these cells because of their stress phenotype, due to DNA damage, replication and mitotic stress.
Citation Format: Martina Olivero, Daniela Dettori, Sabrina Arena, Davide Zecchin, Erica Lantelme, Maria Flavia Di Renzo. The stress phenotype makes ovarian cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B28.
Abstract B41: Proteomic characterization of carboplatin resistance in ovarian cancer cells
Authors: Wrzeszczynski Kazimierz O. , Fan Gaofeng , Fu Cexiong , Pappin Darryl J. , Lucito Robert , Tonks Nicholas K. 
Published: August 2014

Abstract
The analysis of quantitative protein expression is necessary for the determination of actual biochemical protein concentrations that can lead to a more accurate description of cellular function. A knowledgebase of cancer function founded on cellular protein levels can more directly implicate potential gene candidates for the detection and treatment of disease. Therefore, we analyzed iTRAQ (Isobaric tag for relative and absolute quantification) data from 11 serous ovarian cancer cell lines and 2 normal ovarian surface epithelial cell lines. We profiled cellular protein abundance in over 2600 proteins with 746 proteins common to all 13 cell lines. Of the 746, 52 proteins exhibited elevated expression and 46 proteins had diminished expression in the cancerous cells when compared to the two normal cell lines. We identified the 300 most variable iTRAQ expressed proteins based on median absolute deviation within 8 carboplatin sensitive and resistant cell lines. Using iTRAQ protein expression profiles from these 300 we successfully segregated the cell lines based on carboplatin sensitivity and resistance measurements. Next, we further examined correlations among iTRAQ protein expression, individual gene RNA expression and DNA methylation data. There was no substantial correlation between protein abundance and RNA expression or epigenetic data. Furthermore RNA expression and DNA methylation data alone did not show any significant discrimination for chemosensitivity or resistance. Our clustering proteomics-based profile used to identify chemotherapy response contained proteins involved in homologous recombination and repair, specifically RPA, MCM2/MCM5 and PALB2. We therefore present the potential of proteomics based discovery for carboplatin response in ovarian cancer and also identify putative gene candidates that may be functionally responsible for chemotherapy response which otherwise would not have been predicted by other singular whole genome data sources.
Citation Format: Kazimierz O. Wrzeszczynski, Gaofeng Fan, Cexiong Fu, Darryl J. Pappin, Robert Lucito, Nicholas K. Tonks. Proteomic characterization of carboplatin resistance in ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B41.
Abstract B67: IG-001: A non-biologic nanoparticle paclitaxel for the treatment of ovarian cancer
Authors: Hwang Larn , Cheng Catherine , Trieu Vuong 
Published: August 2014

Abstract
Introduction: IG-001(Genexol-PM), like nab-paclitaxel, is a polymer bound nanoparticle paclitaxel. IG-001 utilizes biodegradable di-block copolymer composed of methoxy poly (ethylene glycol)-poly (lactide) to form nanoparticles with Paclitaxel containing hydrophobic core and a hydrophilic shell. IG-001 is being developed for difficult to perfuse hypoxic tumors such as pancreatic cancer and ovarian cancer. Methods: Clinical efficacy was evaluated across multiple cancer indications including metastatic breast cancer (MBC), non small cell lung cancer (NSCLC), pancreatic cancer and ovarian cancer. Phase I ovarian trial design: six patients/dose level were treated with IG-001 at 220, 260, and 300 mg/m2. Phase II ovarian trial design: randomized, two-arm trial, primary advanced epithelial ovarian cancer consisting of 100 pts (50/each arm). Control Arm: Solvent based paclitaxel 175mg/m2 IV + Carboplatin 5 AUC IV, 3 weeks, 6 cycles and Experimental Arm: IG-001 260mg/m2 IV + Carboplatin 5 AUC IV 3 weeks, 6 cycles. Phase III ovarian trial design- planning phase to consist of therapeutic drug monitoring and biomarker testing. Results: Clinical trials conducted with IG-001 demonstrated significant antitumor activities comparable to historical data for Abraxane. Across three cancer indications (MBC, NSCLC, and Pancreatic Cancer), IG-001 was more active than historical Taxol. Since Pancreatic Cancer is known to be poorly-perfused, IG-001 activity in this indication is consistent with it being able to penetrate poorly-perfused tumors. Conclusions: IG-001 is effective across multiple cancer indications. Clinical development of IG-001 in ovarian cancer is ongoing. Phase I data was encouraging and phase II data forthcoming. IG-001 could be considered to be superior to Cremophore based paclitaxel because of the possibilities of delivering higher paclitaxel dose without additional toxicities. Phase III trial design incorporating therapeutic drug monitoring and biomarker testing should further improve on IG-001 clinical activities.
Citation Format: Larn Hwang, Catherine Cheng, Vuong Trieu. IG-001: A non-biologic nanoparticle paclitaxel for the treatment of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B67.