bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B15: Unveiling the mechanism of ovarian cancer dissemination through a comparative study among primary tumors, ascites and metastases
Authors: Lanau Lucia , Rigau Marina , Majem Blanca , Altadill Tatiana , Castellví Josep , Sánchez-Iglesias José-Luis , Pérez-Benavente Assumpció , Cabrera Silvia , García Angel , Xercavins Jordi , Campo Josep-Maria Del , Gil-Moreno Antonio , Ruiz Anna , Reventós Jaume , Llauradó Marta 
Published: August 2014

Abstract
Introduction & Objectives: Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy and the fifth cause of cancer deaths in women in the western world. Largely asymptomatic, OC is frequently detected at late stage (75-80%). Five-year survival rate for women with advanced stage disease is less than 20%, while the cure rate is almost 90% when are diagnosed at early stages. Epithelial OC metastasizes by direct extension from the ovary seeding the cells into the peritoneal wall and to neighbouring organs. Our aim is to study the OC dissemination comparing human paired ovarian primary tumors, ascites and metastases.
Material & Methods: Fresh ovarian primary tumor, ascites and peritoneal metastases from patients suffering advanced serous OC were collected at the surgery room and processed for further analysis. Formalin-fixed paraffin-embedded (FFPE) tissues were collected from the Pathology Department for further immunohistochemical analysis. Discovery phase: We determined the global gene expression profile of 5 fresh-paired samples (primary tumor, ascites and metastases) by microarray analysis. Validation phase: We analysed mRNA and protein levels from 10 unpaired fresh samples by RTqPCR and Western-blot, respectively. We further evaluated protein expression by immunohistochemistry from 10-paired tumor and metastasis FFPE-samples.
Results: GREM1 was shown to be upregulated in metastases versus ascites and in metastases versus primary tumors. FABP4 and INHBA were significantly overexpressed in metastases when compared to primary tumors. INHBA and FABP4 were validated at RNA and protein level, whereas GREM1 only at RNA level.
Conclusions: The present study highlights the role of previously unknown candidates in OC dissemination that might be used as tumor biomarkers, to clinically monitor the progression of the disease, or as target therapies, to block the OC dissemination.
Citation Format: Lucia Lanau, Marina Rigau, Blanca Majem, Tatiana Altadill, Josep Castellví, José-Luis Sánchez-Iglesias, Assumpció Pérez-Benavente, Silvia Cabrera, Angel García, Jordi Xercavins, Josep-Maria Del Campo, Antonio Gil-Moreno, Anna Ruiz, Jaume Reventós, Marta Llauradó. Unveiling the mechanism of ovarian cancer dissemination through a comparative study among primary tumors, ascites and metastases. [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 B15.
Abstract B16: Resources for research: Identification and validation of ovarian cancer cases from the Synthetic Derivative
Authors: Beeghly-Fadiel Alicia , Lovett Whitney , Delahanty Ryan J. , Khabele Dineo , Zhang Wei 
Published: August 2014

Abstract
As a rare and highly lethal cancer, research on ovarian cancer is prone to sample size limitations. To build a research resource, we set out to identify women with ovarian cancer from a large database of de-identified electronic medical records (EMR) of subjects who received medical care from the Vanderbilt University Medical Center. Known as the Synthetic Derivative (SD), this database was initiated in 2006, and now includes more than 20 years of EMR for approximately 1.7 million subjects. We developed a computational algorithm to identify subjects whose EMR included a minimum of three occurrences of an International Classification of Disease (ICD) code of 183 (Malignant neoplasm of ovary and other uterine adnexa) or with local Tumor Registry data that included a primary cancer site of ovary (C569) or fallopian tube (C570). A total of 1,755 women were identified; review of EMR and data abstraction is currently underway. Automated data downloads were conducted for Tumor Registry data, demographics and vital status, CA125 levels and dates, and surgical types and dates. Of the 1,755 women, the majority were Caucasian (83.7%) and deceased (61.7%). Tumor Registry data was available for 1,500 women; epithelial ovarian or fallopian tube cancers were confirmed for 1,141 women. In agreement with national numbers, the 5 year survival rate of these women was only 42.7%. Stored DNA is currently available for 424 women; genotyping data from a variety of platforms is available for 132 women. After additional EMR review and data abstraction, we anticipate being able to verify approximately 1,415 cases of epithelial ovarian cancer. This approach can be utilized at other institutions in the Electronic Medical Records and Genomics (eMERGE) Network; our goal is to build a large resource of validated ovarian cancer cases to support both etiologic and prognostic investigations of this insidious disease.
Citation Format: Alicia Beeghly-Fadiel, Whitney Lovett, Ryan J. Delahanty, Dineo Khabele, Wei Zhang. Resources for research: Identification and validation of ovarian cancer cases from the Synthetic Derivative. [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 B16.
Abstract B24: Using a unique genetically modified ovarian cancer cell line model to identify the targets for siRNA directed therapies
Authors: Tonin Patricia N. , Greenwood Celia MT , Provencher Diane MT , Mes-Masson Anne-Marie 
Published: August 2014

Abstract
We reported that though &gt;90% of high-grade serous ovarian carcinomas (HGSC) harbor somatic TP53 mutations, cases with missense mutations have significantly longer progression free and overall survival than cases with “null” mutations, and that HGSCs defined by TP53 mutation type exhibit unique differences in their genomic landscapes. Large-scale molecular genetic analyses by The Cancer Atlas Group (TCGA) have identified numerous genes/molecular pathways that could be targeted for therapy in HGSC. A large number of candidates were reported, whereby the results were affected by heterogeneity of samples. We have analyzed the transcriptomes from a unique HGSC cell line model with altered in vivo tumorigenic and in vitro growth characteristics to understand the biology of HGSC as we have shown in previous analyses that the pathways affected intersected those found altered in tumors. We posit that investigating phenotypically defined cancer cell line models could facilitate the identification of targets for siRNA-based therapeutics (as an example). Towards this goal, we have characterized the transcriptomes (n~700 RNAs) derived from our parental HGSC cell line model and derived genetically modified cell lines. The cell line was derived from long term passage of ovarian ascites, harbors a somatic missense TP53 mutation and exhibits suppression of tumorigenicity in murine models. The genetically modified derivative cell lines have lost tumorigenic potential and exhibit altered growth characteristics. We compared their transcriptomes, derived a list a genes correlated with these alterations and then compared them to transcriptomes from public data sets: ovarian surface epithelial cells (n=10) and HGSC (n=56); and (2) TCGA samples (n~300). A defined list of known and new genes was identified by these comparative analyses pointing to targets that could be used to affect tumorigenic potential. The genetically modified model provides a new avenue of research that has the potential to elucidate pathways important in HGSC, especially those involved in tumorigenicity, as well as define targets for the development of RNA-based targeted therapeutics.
Citation Format: Patricia N. Tonin, Celia MT Greenwood, Diane MT Provencher, Anne-Marie Mes-Masson. Using a unique genetically modified ovarian cancer cell line model to identify the targets for siRNA directed therapies. [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 B24.
Abstract B61: Proteomic profiling of ovarian cancer and mesothelial cells reveals novel mediators implicated in the metastatic progression of ovarian cancer to the peritoneum
Authors: Musrap Natasha , Karagiannis George S. , Diamandis Eleftherios P. 
Published: August 2014

Abstract
Over the past decade, numerous studies have highlighted the impact of the cancer microenvironment on tumor progression. It is now well understood that tumor cell behaviour is largely influenced by various stromal cell types and extracellular matrix components within their surrounding environments. A key hallmark of epithelial ovarian cancer (EOC) progression is the attachment of cancerous cells to the mesothelium and the formation of invasive peritoneal implants. Given that metastatic dissemination to the peritoneum is associated with poor prognosis, delineating the factors involved in cancer-peritoneal cell interaction, and the mechanisms they employ, is vital to improving patient survival as it may lead to the discovery of novel therapeutic targets. As such, we aimed to elucidate proteins that participate in this interaction by comparing the secreted proteome (referred to as the secretome) of an in vitro co-culture model containing ovarian cancer (OVCAR-5) and mesothelial cells (LP-9) to that of their monoculture secretomes. Using two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we identified 1584 proteins that were secreted by co-cultures, and 1644 and 1420 proteins by OVCAR-5 and LP-9 cells, respectively. After comparative analysis and application of our filtering criteria, we identified 53 proteins that were differentially secreted during cancer and mesothelial interaction, and of these, mucin 5AC (MUC5AC) displayed significantly elevated secretion in the co-culture secretomes. Relative mRNA expression of candidates was assessed using quantitative PCR, which also revealed an increase in MUC5AC gene expression in three different co-culture models (OVCAR-5 and LP-9; BG-1 and LP-9; OV-90 and LP-9) (p&lt;0.05). Immunocytochemistry analysis also revealed increased expression of MUC5AC in ovarian cancer and peritoneal co-cultures. Taken together, these findings reveal novel proteins that may potentially regulate the progression of ovarian cancer to the peritoneum, particularly MUC5AC, and elucidation of its role in EOC warrants further investigation.
Citation Format: Natasha Musrap, George S. Karagiannis, Eleftherios P. Diamandis. Proteomic profiling of ovarian cancer and mesothelial cells reveals novel mediators implicated in the metastatic progression of ovarian cancer to the peritoneum. [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 B61.
Abstract B73: Human omental-derived adipose stem cells: Modulator of ovarian cancer proliferation, migration and chemoresistance
Authors: Nowicka Aleksandra , Solley Travis , Marini Frank C. , Sharp Hadley J. , Broaddus Russell R. , Mikhail Kolonin G. , Mok Samuel C. , Woodward Wendy A. , Lu Karen H. , Klopp Ann H. 
Published: August 2014

Abstract
Objectives: Adipose tissue contains a population of multipotent mesenchymal stromal cells (ASC) which exhibit tumor tropism, similar to bone marrow derived mesenchymal stem cells (MSC). Excess visceral adipose tissue increases the risk of ovarian cancer. The omentum is a prominent site for ovarian cancer metastasis. We hypothesize that the omentum serves as a source of ASC which promote ovarian cancer progression.
Materials and Methods: ASC were isolated from the omentum (O-ASCs) of three patients with ovarian cancer. O-ASC1 was isolated from a patient with synchronous adenocarcinoma of endometrial and ovarian cancer without peritoneal metastasis; and O-ASC4 and O-ASC5 were isolated from patients with peritoneally disseminated serous ovarian cancer. Gene expression array profiling was performed with using Nimblegen arrays (Roche NimbleGen, Inc., Madison, WI). The impact of stromal cells on proliferation and chemoresistane and radio-protection of ovarian cancer cells was tested with co-culture assays using luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASC and control cell lines. To evaluate of O-ASCs tumor tropism in-vivo experiment was performed.
Results: Human O-ASCs were detected engrafted within the stroma of human ovarian cancer xengrafts. O-ASC significantly promoted in-vitro proliferation and migration of ovarian cancer cell lines OVCA 429, OVCA 433, A2780. Co-culture of ovarian cancer cells with O-ASCs increased resistance to chemotherapeutic drugs and radiation. Gene expression array analysis revealed significant differences in expression profiles for group of 415 genes in sub-populations of O-ASCs.
Conclusions: Adipose stem cells derived from human omentum promoted the proliferation, migration, chemoresistance and radioresistance of ovarian cancers. Clinical isolates demonstrate heterogenous effects in- vitro. Future studies will determine if tumor promoting effects of O-ASC can be predicted on the basis of clinical or disease related characteristics.
Citation Format: Aleksandra Nowicka, Travis Solley, Frank C. Marini, Hadley J. Sharp, Russell R. Broaddus, Kolonin G. Mikhail, Samuel C. Mok, Wendy A. Woodward, Karen H. Lu, Ann H. Klopp. Human omental-derived adipose stem cells: Modulator of ovarian cancer proliferation, migration and chemoresistance. [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 B73.
Abstract IA13: The Fanconi anemia-BRCA pathway and chemosensitivity of cancer cells
Authors: Taniguchi Toshiyasu 
Published: August 2014

Abstract
The Fanconi anemia-BRCA pathway has emerged as an important pathway in cancer biology. Fanconi anemia (FA) is a rare genetic disease characterized by chromosomal instability, cancer-susceptibility and cellular sensitivity to interstrand DNA crosslink (ICL)-inducing agents. Sixteen FA genes have been identified (FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, FANCO/RAD51, FANCP/SLX4 and FANCQ/XPF). The FA proteins and breast/ovarian cancer susceptibility proteins, BRCA1 and BRCA2, cooperate in a common pathway required for cellular resistance to ICL-inducing agents. This pathway is called the FA-BRCA pathway or FA pathway. The main function of the pathway is to coordinate multiple DNA repair mechanisms (including homologous recombination) during ICL repair.
Inactivation of this pathway in cancer cells can lead to sensitivity to anti-cancer ICL-inducing agents, such as cisplatin, while reactivation of this pathway is implicated in acquired resistance to ICL-inducing agents. Since a part of the FA-BRCA pathway regulates homologous recombination, integrity of the pathway is also important for cellular resistance to PARP inhibitor. Therefore, inhibition of the FA-BRCA pathway is an attractive therapeutic strategy to overcome drug resistance of tumor cells.
In this talk, I will introduce what the FA-BRCA pathway is and how this pathway is inactivated in human cancer. I will also mention our finding that secondary BRCA1/2 mutations, which restore normal function of BRCA1/2 proteins, are involved in acquired drug resistance of BRCA1/2-mutated cancer.
Citation Format: Toshiyasu Taniguchi. The Fanconi anemia-BRCA pathway and chemosensitivity of 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 IA13.
Abstract IA15: Targeting acquired platinum resistance in ovarian cancer
Authors: Gabra Hani 
Published: August 2014

Abstract
Platinum is an important cornerstone of chemotherapy for ovarian cancer. Platinum resistance is a multifactorial process, and may be intrinsic to the presenting tumor (refractory disease) or more commonly acquired after initial platinum sensitivity (acquired resistant disease). Although induction of acquired platinum resistance through adaptation of the primary tumor is thought to be one expression of these multifactorial mechanisms, there is evidence that selection of pre-existing resistance generated through clonal heterogeneity prior to clinical presentation may be a significant process that results in selection of acquired platinum resistant clinical relapse. This hypothesis has led to the identification by expression microarray difference analysis of upregulated targets which through targeting may reverse acquired platinum resistance. These targets include HDAC4, STAT1, FOLR2, and PI3K components, particularly AKT. In acquired platinum resistance, but not platinum sensitive ovarian cancer, there is nuclear relocalization of AKT with DNA damage mediated nuclear phosphorylation-activation of AKT resulting in survival signaling. Functional validation of these targets in-vitro and preclinically in-vivo has led to development of a translational proof of concept platform in the clinic with sequential biopsy within trials to test the hypothesis of targeting acquired resistance derived through clonal diversity at the outset of disease. Through this science, subsequent clinical trials of AKT inhibitors in platinum resistant ovarian cancer have demonstrated activity, underscoring the validity of this approach. The clinical development of such targeting of acquired resistance through international consortia within the EUTROC group will be discussed. It is hoped that this approach will improve the prognosis of ovarian cancer by early intervention to delete resistant disease before it becomes a clinical problem.
Citation Format: Hani Gabra. Targeting acquired platinum resistance 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 IA15.
Abstract IA8: Discovering drivers in rare ovarian cancer subtypes
Authors: Huntsman David G. 
Published: August 2014

Abstract
Over the past several years it has become accepted that subtypes of ovarian carcinomas (high grade serous, endometriod, clear cell, low grade serous and mucinous carcinoma) are discrete diseases. Therefore, if we are to improve ovarian cancer morbidity and mortality, cancer prevention, early detection and/or screening strategies must be developed to deal with the challenges posed by each of these diseases. Whereas high grade serous carcinoma is relatively common, the other ovarian carcinoma subtypes represent 30% of cases in total and therefore are all rare. Rare cancers are usually marked by a combination of an unusual cells of origin and unusual mutations or other genomics drivers. We have undertaken a series of genomics studies to identify key drivers in rarer ovarian cancers. Some cancers such as granulosa cell tumors of the ovary and sertoli cell mutations have been found which are either pathognomonic or highly specific for that cancer type. Those mutations have great promise as diagnostics. Since the target cancers are rare such work is not possible without broad ranging international collaborations. For more common entities such as clear cell carcinoma concentrations of mutations can be found such as mutations in ARID1a. As such mutations are nonspecific they are less likely to be used diagnostically however this increases their potential therapeutic value. However, it is likely that the mutations or mutated genes have a specific role in the cell of origin of the cancers involved and therefore cell context specific cell lines of model systems will be required for functional validation.
Although rare cancers are by definition unusual and therefore represent smaller medical problems they are of course highly significant to the patients involved and provide a model through which the stratification of management for common cancers can be undertaken.
Citation Format: David G. Huntsman. Discovering drivers in rare ovarian cancer subtypes. [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 IA8.
Abstract A07: Targeting SETD2 knockout cells: A synthetic lethal approach to treating ccRCC
Authors: Fahey Catherine C. , Hacker Kathryn E. , Jin Jian , Davis Ian J. , Rathmell W. Kimryn 
Published: August 2014

Abstract
Background: Kidney cancer is estimated to affect 65,150 newly diagnosed individuals in 2013. Approximately 70% of these diagnoses will be clear cell renal cell carcinoma (ccRCC). Many targeted therapies for ccRCC are currently being pursued, as ccRCC is resistant to radiation and often does not respond to chemotherapy. The most commonly mutated tumor suppressor gene in ccRCC is VHL, located on chromosome 3. The loss of chromosome 3p is a high frequency event in ccRCC, which often also encompasses the genes PBRM1, BAP1, and SETD2. Mutations in one or more of these genes represent the next most common common genetic alterations in ccRCC. In our preliminary data, we have observed that mutations in SETD2, in particular, area associated with global deficits in chromatin packaging and organization.
Methods: We are pursuing the opportunity to exploit SETD2 loss as a source of cellular fragility by performing a small molecule screen on SETD2 wild type and SETD2 knockout cell lines. We will use a screening set of epigenetically targeted compounds to perform a high throughput screen with cell viability as the endpoint, as well as use a selected few compounds to compare effect on wild type and knockout cells in a more in depth manner.
Results: Preliminarily, we have tested SETD2 knock-down lines to confirm that we can effectively preform all aspects of this screen, and we have observed that one compound may specifically target SETD2 knock-down lines for reduced viability. In our current studies, we are repeating testing with the selected few compounds and beginning the high throughput screen with a SETD2 knockout cell line.
Conclusion: Mutations in chromatin modifying genes in ccRCC present an opportunity for synthetic therapeutic approaches to induce reduced cell viability, as well as to identify unique meaningful interactions between chromatin modifier genes.
Citation Format: Catherine C. Fahey, Kathryn E. Hacker, Jian Jin, Ian J. Davis, W. Kimryn Rathmell. Targeting SETD2 knockout cells: A synthetic lethal approach to treating ccRCC. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Synthetic Lethal Approaches to Cancer Vulnerabilities; May 17-20, 2013; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(5 Suppl):Abstract nr A07.