bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A49: Investigating the expression of inhibitory surface molecules in ovarian cancer tumor-infiltrating lymphocytes.
Authors: Chacon Jessica , Yamamoto Tori , Garrabrant Thomas , Kari Gabor , Best Andrew , Ye Qunrui , Powell Daniel 
Published: May 2016

Abstract
Ovarian cancer causes more deaths than any other cancer of the female reproductive system. However, novel therapies, including immunotherapy are now being utilized to treat this cancer. In addition, efforts have been made to identify and evaluate the subsets of cells within the tumor environment that correspond with patient overall survival. Although the presence of intraepithelial CD3+ T cells and CD8+ T cells have been correlated with patient survival and CD137, a co-stimulatory molecule, has been identified as a biomarker for tumor-reactive cells, studies have not thoroughly investigated the phenotype of the T cells, specifically the CD4+, CD8+, and CD137+ subsets. In our study, we used a multi-parameter flow cytometry to measure inhibitory molecules, Th1 cytokines, and the effector phenotype in the T-cell subsets. We observed that the CD4+ and CD8+ T cells found within the tumor environment express inhibitory receptors, very limited Th1 cytokine producing cells and a decreased expression of Granzyme B within the CD8+ subset. The CD137+ population also expressed inhibitory molecules, but was still able to exhibit an effector phenotype and comprise Th1 cytokine producing cells. In conclusion, using multi-parameter flow cytometry enabled us to investigate the expression of inhibitory molecules on the CD4+, CD8+, and CD137+ subsets and measure their effector phenotype. We found that the T cells express many inhibitory receptors and this may hinder their ability to become optimal effector cells that maintain tumor control. However, future studies utilizing antibodies that block these inhibitory receptors may increase the T cells' ability to exhibit an increased effector phenotype and contain more Th1 cytokine producing cells.
Citation Format: Jessica Chacon, Tori Yamamoto, Thomas Garrabrant, Gabor Kari, Andrew Best, Qunrui Ye, Daniel Powell, Jr. Investigating the expression of inhibitory surface molecules in ovarian cancer tumor-infiltrating lymphocytes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A49.
Abstract A53: Combining oncolytic virotherapy with immunotherapy for ovarian cancer treatment.
Authors: McGray AJ Robert , Eppolito Cheryl , Stephenson Kyle , Pol Jonathan , Lichty Brian , Odunsi Kunle 
Published: May 2016

Abstract
While spectacular responses have been observed in some patients following cancer immunotherapy, the majority of responses are short-lived with ultimate tumor relapse. Therefore, it is crucial to identify strategies that will effectively synergize with immunotherapies to improve clinical outcome. Oncolytic viruses (OV) are replication-competent viruses that can infect and kill tumor cells, while also acting as potent immune adjuvants. Additionally, as OV can be engineered to express tumor antigens, we are investigating the use of OV as vaccine vectors with the capacity to enhance immune responses to defined tumor antigen targets. Based on these unique attributes of OV, we hypothesized that OV could be effectively combined with multiple immunotherapeutic strategies currently in clinical testing as a means of enhancing anti-tumor immunity and improving tumor growth control/treatment outcome. Targeting a model tumor antigen in a pre-clinical ovarian cancer model, we observed that delivery of oncolytic Maraba virus (MRB) following vaccination enhanced tumor-specific CD8+ T cell expansion and trafficking to the tumor microenvironment, reduced intratumoral Tregs and MDSC frequencies, and resulted in improved survival compared to vaccination alone. Additionally, when MRB was combined with adoptive T cell transfer (ACT) of tumor-specific CD8+ T cells, this combination resulted in improved persistence of the transferred T cells and enhanced tumor control compared to treatment with MRB or ACT alone. Lastly, a dramatic improvement in treatment efficacy was observed when MRB was combined with checkpoint blockade (anti-PD-L1) compared to either monotherapy. These data suggest that OV can effectively synergize with multiple cancer immunotherapies currently being explored. Our current studies are focused on combining OV with either vaccines or ACT strategies that target clinically relevant ovarian cancer antigens (WT1, Sp17, and NY-ESO-1) using syngeneic and humanized mouse models. Additionally, we are exploring the transcriptional profile of tumors treated with immunotherapy + OV to identify gene signatures that correlate with improved therapeutic efficacy.
Citation Format: AJ Robert McGray, Cheryl Eppolito, Kyle Stephenson, Jonathan Pol, Brian Lichty, Kunle Odunsi. Combining oncolytic virotherapy with immunotherapy for ovarian cancer treatment. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A53.
Abstract A72: Dissecting the role of NF-kappaB signaling in ovarian cancer tumor-initiating cells.
Authors: House Carrie D. , Annunziata Christina M. 
Published: May 2016

Abstract
Ovarian cancer is the most lethal gynecological malignancy in the United States with high morbidity and mortality due to recurrence and chemoresistance. Our data suggest tumor-initiating cells (TICs) play an important role in disease biology. We previously showed that a subset of ovarian cancer cells depends on NF-kappaB signaling, and that expression of NF-kappaB proteins is associated with poor survival. To investigate this pathway in TICs, we designed a novel method to enrich for TICs from cell lines and patient samples by culturing non-adherent, floating cells in stem cell conditions. Preliminary data show these cells have higher stem cell marker expression, are chemoresistant, and are more tumorigenic in nude mice compared to their adherent counterparts. Given that NF-kappaB expression correlates with a poor outcome in ovarian cancer, and NF-kappaB activity supports drug resistance and tumorigenicity, we hypothesize that NF-kappaB supports a TIC program responsible for ovarian cancer relapse. Preliminary data show TIC-enriched culture conditions increased NF-kappaB expression and activity in TICs and stimulation of NF-kappaB signaling enhanced chemoresistance and stem cell marker expression. Current studies focus on dissecting the role of individual NF-kappaB proteins in TICs using inducible shRNAs to measure changes in spheroid formation, chemoresistance, tumorigenesis, and disease relapse following chemotherapy in a xenograft model. Future studies will measure system level changes induced by these shRNAs, and identify a gene signature specific to NF-kappaB in ovarian TICs. Clarifying the nuances of NF-kappaB signaling in TICs will increase our understanding of ovarian cancer recurrence and may lead to improved therapeutic strategies.
Citation Format: Carrie D. House, Christina M. Annunziata. Dissecting the role of NF-kappaB signaling in ovarian cancer tumor-initiating cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A72.
Abstract A77: Validation of the EORTC QLQ-OV28 instrument for the assessment of quality of life in women with ovarian carcinoma in Mexico.
Authors: Gallardo-Rincon Dolores , Munoz-Montano Wendy , Leon David Cantu de , Coronel-Martinez Jaime , Morales Flavia , Onate-Ocana. Luis F. 
Published: May 2016

Abstract
Objective: Health-related quality of life (HRQL) is an important outcome measurement in Oncology. Our aim was to validate the Mexican-Spanish version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-OV28 questionnaire to assess HRQL in patients with Ovarian cancer (OC).
Patients and Methods: The QLQ-C30 and QLQ-OV28 instruments were applied to Mexican patients with OC at a cancer referral centre. Reliability and validity tests were performed, and test-retest analysis was carried out in a subgroup of patients.
Results: Two hundred fifty-two women were included in this cohort. Questionnaire compliance rates were high and the instrument was well accepted; internal consistency tests demonstrated good convergent and divergent validity. Cronbach's α; coefficients of 8 of 9 multi-item scales of the QLQ-C30 and of 6 of 8 scales of the QLQ-OV28 instruments were &gt;0.7 (range, 0.22 to 0.89). Scales of the QLQ-C30 and QLQ-OV28 instruments distinguished among clinically distinct groups of patients; some were highly sensitive to change over time after the use of induction chemotherapy, and some were associated to overall survival.
Conclusion: The Mexican-Spanish version of the QLQ-OV28 questionnaire is reliable and valid for the assessment of HRQL in patients with OC and can be broadly used in clinical trials.
Citation Format: Dolores Gallardo-Rincon, Wendy Munoz-Montano, David Cantu de Leon, Jaime Coronel-Martinez, Flavia Morales, Luis F. Onate-Ocana. Validation of the EORTC QLQ-OV28 instrument for the assessment of quality of life in women with ovarian carcinoma in Mexico. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A77.
Abstract B02: Oxidized hemoglobin promotes survival of ROS-stressed and DNA damaged fallopian tube epithelial cells with p53 loss, resulting in a copy number variation phenotype of HGSC.
Authors: Huang Hsuan-Shun , Hsu Che-Fang , Chu Tang-Yuan 
Published: May 2016

Abstract
Purpose: Ovulation is a strong risk factor for high grade serous carcinoma (HGSC) of ovary known to largely originate from the fallopian tube fimbriae. Previously, we have showed ROS in the mature follicular fluid (FF) is mutagenic and cytotoxic to fimbria epithelial cells, and induces DNA double strand breaks (DSB) in the context of p53 loss. We hypothesized that hemoglobin (Hb) in FF accumulated in cul-de-sac (CDS) after ovulatory bleeding may protect the bathed fimbria from cell death and enhance cancer initiation.
Results: Peritoneal fluids collected from the CDS after ovulation contained high level of oxidized Hb and ROS, so did ovarian FFs retrieved from IVF patients. When treating E6/E7-immortalized fimbria secretory cells (FE25) with FFs with various ROS levels ranging from 100-1200 μM of H2O2 equivalence, a positive correlation of Hb levels (ranging from 100-1100 μg/ml) in FF and cell viability was observed. This was further confirmed in treating FE25 cells with H2O2 where Hb dose-dependently rescued cell death. As a consequence, FE25 cells treated with either Hb-high FF or with H2O2 plus Hb accumulated high level of DSB and showed an extensive DNA copy number variation compatible with the copy number variation (CNV) phenotype of HGSC. The resulted DNA aneuploidy rates were 50±5% and 65±7% in FE25 treated with 500 μM H2O2 supplemented with 100 μg/ml Hb or 3% Hb-hgih FF, respectively; as compared to 15±2% at baseline and 31±8% with H2O2 only. In the case of primary fimbria epithelial cells the figures were 2±0.3% and 1.3±0.2%, respectively. Finally, the p53 deficiency dependent rescuing effect of Hb on ROS-stressed tubal epithelial cells, and the consequent CNV phenotype were confirmed ex vivo with oviducts of wild type and Trp53-null mice.
Conclusion: While ROS in FF induces DNA damage and cytotoxicity of p53-deficient fimbria epithelial cells, oxidized Hb in peritoneal fluid rescues cells from death and results in a CNV phenotype, a major characteristic of HGSC.
Citation Format: Hsuan-Shun Huang, Che-Fang Hsu, Tang-Yuan Chu. Oxidized hemoglobin promotes survival of ROS-stressed and DNA damaged fallopian tube epithelial cells with p53 loss, resulting in a copy number variation phenotype of HGSC. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B02.
Abstract B08: Genomics analyses of less common epithelial ovarian cancer subtypes.
Authors: Gorringe Kylie L. , Wakefield Matthew , Hunter Sally M. , Ryland Georgina L. , Cheasley Dane , Anglesio Michael S. , Christie Michael , Sharma Raghwa , Yoland Antill , Rowley Simone M. , Li Jason , Gilks Blake , Allan Prue E. , Stephens Andrew N. , Ananda Sumi , Pyman Jan , Koebel Martin , McAlpine Jessica , Gourley Charlie , Huntsman David G. , deFazio Anna , Bowtell David DL , Campbell Ian G. , Scott Clare 
Published: May 2016

Abstract
While the genomics of high-grade serous carcinoma are well-studied in large international consortia, the less common subtypes have been neglected. We have sought to rectify this gap by analyzing international collections of low-grade serous and mucinous ovarian carcinomas and their putative benign and borderline precursors.
Exome sequencing and copy number analysis of low-grade serous carcinomas (n=9) and serous borderline tumours (n=13) and targeted sequencing and copy number analysis in additional carcinomas (n=10) and borderline tumours (n=44) identified recurrent mutations in novel drivers such as EIF1AX and USP9X, as well as the known drivers KRAS, BRAF and NRAS. Copy number changes including 9p and 1p losses were significantly associated with progression from borderline to carcinoma. Exome and targeted sequencing analysis of mucinous carcinomas (GAMuT study) found a surprisingly high proportion (~50%) with TP53 mutations, and mutations in new drivers like RNF43 and ELF3. Despite similarities in early RAS/RAF pathway oncogenic drivers and CDKN2A disruption, the genetics of these two subtypes are otherwise distinct, suggesting differing etiologies and selective pressures.
We also present here the first whole-genome sequencing analysis of a high-grade mucinous ovarian carcinoma collected from multiple sites at autopsy (CASCADE study). The patient, aged just 41 when diagnosed with Stage I mucinous ovarian carcinoma, had a 26-month progression-free interval, including normal CA125 and CA19-9 measurements at 21 months. The primary tumor was mostly borderline in appearance, with only a small focus of carcinoma. At autopsy, the carcinoma was widespread in the body, and whole-genome sequencing data was obtained from deposits in the omentum, iliac lymph node, para-aortic lymph node and upper diaphragm. These data were compared to the primary ovarian tumor and nine other sites sampled at autopsy.
Citation Format: Kylie L. Gorringe, Matthew Wakefield, Sally M. Hunter, Georgina L. Ryland, Dane Cheasley, Michael S. Anglesio, Michael Christie, Raghwa Sharma, Antill Yoland, Simone M. Rowley, Jason Li, Blake Gilks, Prue E. Allan, Andrew N. Stephens, Sumi Ananda, Jan Pyman, Martin Koebel, Jessica McAlpine, Charlie Gourley, David G. Huntsman, Anna deFazio, David DL Bowtell, Ian G. Campbell, Clare Scott. Genomics analyses of less common epithelial ovarian cancer subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B08.
Abstract B16: Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated ovarian cancers.
Authors: Bitler Benjamin , Shih Ie-Ming , Zhang Rugang 
Published: May 2016

Abstract
ARID1A, a chromatin remodeler, shows one of the highest mutation rates across many cancer types. Notably, ARID1A is mutated in ~50% of ovarian clear cell carcinomas and ~30% of ovarian endometrioid carcinomas. To date, clinically applicable targeted cancer therapy based on ARID1A mutational status has not been described. Here we show that inhibition of the EZH2 methyltransferase acts in a synthetic lethal manner in ARID1A mutated ovarian cancer cells. ARID1A mutational status correlates with response to the EZH2 inhibitor. We identified PIK3IP1 as a direct ARID1A/EZH2 target, which is upregulated by EZH2 inhibition and contributes to the observed synthetic lethality by inhibiting PI3K/AKT signaling. Significantly, EZH2 inhibition causes regression of ARID1A mutated, but not wild-type, ovarian tumors in vivo. Together, these data demonstrate for the first time a synthetic lethality between ARID1A mutation and EZH2 inhibition. They indicate that pharmacological inhibition of EZH2 represents an urgently needed, novel treatment strategy for ARID1A mutated ovarian cancers.
Citation Format: Benjamin Bitler, Ie-Ming Shih, Rugang Zhang. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated ovarian cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B16.
Abstract B31: Circulating periostin as a potential biomarker to predict platinum-resistant epithelial ovarian cancer.
Authors: Ryner Lisa , Noyes Amy , Nazzal Denise , Vu Paul , Guan Yinghui , Lu Shan , Morimoto Alyssa , Brignoli Sue , Wang Yulei 
Published: May 2016

Abstract
Roughly a third of ovarian cancer patients are intrinsically resistant to platinum-based treatment. However, predictive and therapeutic strategies are lacking to treat these patients due to a poor understanding of the underlying molecular mechanisms. We previously identified and validated a “reactive stroma” gene signature that is associated with primary chemoresistance in epithelial ovarian cancers (EOCs). In addition this signature was further validated in an independent dataset and high expression level of the signature genes predicts shorter progression free survival following front line chemotherapy. One of the key components of this gene signature is periostin (POSTN), an extracellular matrix protein known for its role in a variety of tissue remodeling conditions as well as overexpression in many types of cancers. Interestingly, POSTN is also involved in aspects of allergic inflammation and is used as a circulating biomarker for TH2-driven asthma. To investigate whether circulating POSTN could be used to predict chemoresistance in EOC, we developed an ELISA assay for detecting circulating POSTN in serum and plasma. Serum POSTN levels were measured in panels of serum samples from 143 EOC patients, 102 normal healthy subjects (NHS) and from 126 patients with other cancers. The serum POSTN ELISA was sensitive down to 1.88ng/mL and POSTN was detected in the serum of all patients and NHS. Although the range of POSTN expression in the EOC patients was highly overlapping with that of normal healthy subjects, a positive correlation was observed with the stage of disease. Retrospective and prospective studies are underway to determine whether baseline serum-POSTN levels can predict chemoresistance in EOC patients. Our study may lead to the development of a novel diagnostic strategy for predicting response to chemotherapy in ovarian cancer.
Citation Format: Lisa Ryner, Amy Noyes, Denise Nazzal, Paul Vu, Yinghui Guan, Shan Lu, Alyssa Morimoto, Sue Brignoli, Yulei Wang. Circulating periostin as a potential biomarker to predict platinum-resistant epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B31.
Abstract B67: The impact of parity on the metastatic success of ovarian cancer.
Authors: Loughran Elizabeth A. , Phan Ryan , Leonard Annemarie K. , Tarwater Laura , Asem Marwa , Klymenko Yuliya , Liu Yueying , Yang Jing , Johnson Jeff , Ravosa Matthew , Stack. M. Sharon 
Published: May 2016

Abstract
Ovarian cancer is the most fatal gynecological cancer. Epithelial ovarian cancer (OvCa), the most common subtype, usually goes undetected until metastatic and often fatal stages of the disease. OvCa follows a unique form of metastasis, spreading through the peritoneal cavity and forming metastatic sites on the peritoneum. Epidemiologic data suggest that child-bearing, or parity, reduces a woman's risk of developing ovarian cancer, with more births providing greater protection. Despite the association of parity with a decreased incidence of ovarian cancer, very few studies have explored the relationship between parity and metastatic success. A recent study compared metastatic success to the omentum in 12-month-old C57Bl/6 retired breeders and 5-month-old virgin mice, reporting that parous mice are less susceptible to metastasis due to the parity-associated differences in the immune compositional profile in the omental fat band (Cohen et al. 2013). This tumor study compared mice of different ages and did not report specific numbers of pregnancies. To further investigate the role of parity number in OvCa metastasis, we designed a study that controls for age and compares mice with specific parity number. Three age-matched C57Bl/6 groups were evaluated: nulliparous (V), parous 1 (P1), and parous 3 (P3) mice. We tested the effect of parity on metastatic success in vivo with an allograft study using the C57Bl/6 syngeneic ID8 mouse ovarian surface epithelial cell line. ID8 ovarian cancer cells (106) were injected into the peritoneal cavity of V, P1 and P3 mice. In contrast to the results of Cohen at al. that utilized a different syngeneic ovarian cancer cell line, we found no significant difference in metastasis to the omentum in the parous animals, but significantly reduced metastasis to the fat-enveloped ovaries and visceral fat pads in the P3 mice. This suggests that the visceral fat adjacent to the uterus and ovaries in multi-parous animals is a unique environment, resilient to metastasis. Factors in fat tissue responsible for this phenomenon are being investigated.
Citation Format: Elizabeth A. Loughran, Ryan Phan, Annemarie K. Leonard, Laura Tarwater, Marwa Asem, Yuliya Klymenko, Yueying Liu, Jing Yang, Jeff Johnson, Matthew Ravosa, M. Sharon Stack. The impact of parity on the metastatic success of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B67.