bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A063: What can we learn from a retrospective evaluation of HER2, P53 and P16INK4A protein expression in rare ovarian tumors?
Authors: Advikolanu-Rao Kavitha M. , Magliocco Anthony M. , Maksymiuk Andrew W. 
Published: March 2024

Abstract
In this retrospective study, we examined the incidence and prevalence of HER2, P53, and P16INK4A protein accumulation patterns in patients diagnosed with rare ovarian cancer. The population-based study included a total of thirteen patients diagnosed at the Saskatoon Cancer Centre during the years 1983-1995. Immunohistochemistry for evaluation of HER2, P53 and P16INK4A protein expression and ploidy status in paraffin-embedded tissue (PET) specimens were correlated with clinicopathologic variables. Immunoexpression studies were with the following rabbit monoclonal antibodies: Erb-B2, 485 and P16INK4A, G175-405, 13251A, except for P53, mouse monoclonal antibody, D07. DNA status was assessed by flow-cytometric analysis. The most prevalent histologic subtype was sex-cord stromal, followed by three germ-cell, while the remaining two tumors were malignant Brenner. The patients’ ages ranged between (15-77 years). The data on stage was unavailable in five patients, two patients had undifferentiated tumor, one had grade 2-3, and data on grade was unavailable in the remaining six cases. Two of the 13 patients died: one patient in stage IV, grade 3, granulosa-theca, P53 immunonegative and near-tetraploid DNA status; the other patient with malignant Brenner histologic subtype, P53 overexpression, and diploid DNA status. Tumor tissues were available in nine of 13 randomly selected patients. Except for one case with P53 overexpression, the remaining 89% tumor specimens had low to zero P53, P16INK4A, and Erb-B2 expression. The nonsignificance of the immunoexpression studies and preclusion from prognostic prediction is likely due to the restricted sample size. Thus, immunoexpression of P53, P16INK4A, and Erb-B2 have not been associated with rare ovarian tumors. Moreover, the observation that malignant Brenner had P53 overexpression and diploid DNA status in one of the patients is a significant finding of this retrospective study. Additionally, these findings argue for routine use of P53 protein expression and ploidy status in the assessment of malignant Brenner tumors. The vast majority of tumors with P53 mutations progress rapidly. Therefore, the subset of patients with malignant Brenner tumors that have P53 protein disruption will likely benefit from therapy using PARP inhibitors. A. Geissel and J. L. Griffin, “Preparation of nuclei for flow cytometry,” in AFIP Advances in Laboratory methods in Histology and Pathology, ed. Mikel UV (Washington DC: American Registry of Pathology, 1944), 111-121.
Citation Format: Kavitha M. Advikolanu-Rao, Anthony M. Magliocco, Andrew W. Maksymiuk. What can we learn from a retrospective evaluation of HER2, P53 and P16INK4A protein expression in rare ovarian tumors? [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A063.
Abstract A112: Mechanisms underlying platinum-induced ovarian cancer stem cell plasticity
Authors: Metcalfe Tara X. , Zhang Shu , Hassel Christiane , O'Hagan Heather M. , Nephew Kenneth P. 
Published: March 2024

Abstract
Most women diagnosed with late-stage high grade serous ovarian cancer (HGSOC) develop recurrent, platinum-resistant tumors. Ovarian cancer stem cells (OCSCs) are hypothesized to contribute to the emergence of these resistant tumors. CSCs have been postulated to reside in a plastic state, which can allow for the conversion of non-CSC to CSC. This process of dedifferentiation continues during tumor development and chemotherapeutic agents like platinum can exaggerate CSC plasticity. We have previously demonstrated that acute platinum treatment enriched for OCSCs. However, whether platinum transforms non-OCSCs into OCSCs to contribute to this subpopulation of cells remains unclear, and the underlying mechanism remains incompletely understood. To examine OCSC plasticity, aldehyde dehydrogenase (ALDH; functional marker) and fluorescence activated cell sorting were used to isolate OCSCs (ALDH+) and non-OCSCs (ALDH-) from HGSOC cell lines, OVCAR5 and OVCAR3. To determine the stability of the non-OCSC phenotype, ALDH- cells were cultured for 3 and 5 days and ALDH activity was measured using flow cytometry. At both timepoints examined, ALDH- cells remained ALDH-, with approximately less than 1% being ALDH+ (p&lt;0.05). To determine if platinum can induce conversion of non-OCSC to OCSC, ALDH- cells were treated with cisplatin (12µM or 15 µM for 16h), and the percent of ALDH+ cells was measured using flow cytometry. Treatment of ALDH- cells with cisplatin resulted in conversion of approximately 4% and 10% of ALDH- cells into ALDH+ cells (p&lt;0.05) in OVCAR5 and OVCAR3 cells, respectively. Furthermore, both cell lines displayed increased expression (p&lt;0.05) of stemness genes BMI1, NANOG, OCT4, and SOX2 and spheroid formation was observed in converted OCSCs compared to parental ALDH+ and whole cell populations treated with cisplatin, suggesting that platinum induced the observed differences in the stemness phenotype. With the goal of targeting key genes and pathways to inhibit platinum-induced OCSC conversion, RNA-sequencing was performed using converted OCSCs. Activated pathways in converted OCSCs were identified, including protein kinase signaling, inhibition of matrix metalloproteases, SPINK1 pathway, and VDR/RXR activation. We are further investigating if these pathways contribute to the mechanism involved in OCSC plasticity and whether targeting these pathways can reduce the OCSC population, which is critical to blocking the persistence of OCSCs and ultimately reduce mortality in patients.
Citation Format: Tara X. Metcalfe, Shu Zhang, Christiane Hassel, Heather M. O'Hagan, Kenneth P. Nephew. Mechanisms underlying platinum-induced ovarian cancer stem cell plasticity [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A112.
Abstract B024: Maintenance therapy inhibition of ptk2 yields decreased disease in preclinical HRP/HRD models of recurrent HGSOC
Authors: Hill Breana , Bondre Ioana , Soylu H Meryem , Antoine Juliette , Chen Xiao Lei , Tahon Elise , Zhang Yichi , Olajill Marjaana , Kinkel Sarah , Cock Terrie-Anne , Binder Pratibha , Burns Chris , Schlaepfer David , McHale Michael McHale T. , Stupack Dwayne G 
Published: March 2024

Abstract
High grade serous ovarian cancer remains the most lethal of the gynecologic malignancies, in part, because of the high incidence of recalcitrant and rapidly recurring disease. Disease recurrence is now better controlled due to maintenance therapy with PARP inhibitors, particularly in homologous repair deficient tumors. Efficacy in homologous repair proficient tumors represents an unmet need. We previously demonstrated that inhibitors of protein tyrosine kinase 2 (ptk2), a gene that is frequently gained in HGSOC, compromises the expression of tumor repair genes, decreases stemness, and limits immune evasion. The low toxicity of ptk2 inhibitors appears to be well suited for a maintenance role. Here, we tested the effect of six weeks of ptk2 inhibitor maintenance treatment, post-chemotherapy, in two preclinical models. In a homologous repair proficient model (KMF), and in a PARP inhibitor-resistant model (HGS2), ptk2 inhibitor treatment yielded lower tumor burden, fewer solid tumors, and decreased bloody ascites accumulation relative to treatment with Niraparib. The low toxicity and overall efficacy provide strong support for future clinical trials with ptk2 inhibitors in the maintenance role, for patients with HGSOC.
Citation Format: Breana Hill, Ioana Bondre, H Meryem Soylu, Juliette Antoine, Xiao Lei Chen, Elise Tahon, Yichi Zhang, Marjaana Olajill, Sarah Kinkel, Terrie-Anne Cock, Pratibha Binder, Chris Burns, David Schlaepfer, Michael McHale T. McHale, Dwayne G Stupack. Maintenance therapy inhibition of ptk2 yields decreased disease in preclinical HRP/HRD models of recurrent HGSOC [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B024.
Abstract B048: Evaluating the impact of pulmonary diseases on the use of microRNAs as biomarkers for early detection of ovarian cancer
Authors: Moore Monica , Wollborn Laura , Mishra Sudhanshu , Webber James , Elias Kevin M. 
Published: March 2024

Abstract
Background: Efforts are ongoing to develop new biomarkers to diagnose ovarian cancer at earlier, more curable stages. microRNAs (miRNAs) have emerged as a promising new class of circulating biomarkers for ovarian cancer diagnosis and prognosis. As other biomarkers, such as CA-125, are non-specifically elevated in pulmonary diseases, evaluating how miRNA expression is affected by various lung conditions will inform the interpretation of miRNAs as a potential clinical test. Asthma and bronchitis are of particular interest because miRNA expression in the lung is markedly affected by environmental respiratory irritants such as cigarette smoke and air pollution. Moreover, as the burden of asthma and bronchitis in the United States falls disproportionately on minority communities, so a test confounded by asthma might be less generalizable to a diverse patient population. Methods: Serum samples from 1,614 women enrolled in the Mass General Brigham Biobank were analyzed for miRNAs using a focused panel of 179 miRNA Fireplex® probes optimized for serum profiling. In addition to the miRNA data, electronic health records were reviewed to pair the biomarker data with demographics such as age, race, ethnicity, zip code, reproductive health histories, and comorbidities, including pulmonary diseases like asthma/bronchitis. miRNAs associated with pulmonary diseases were identified by univariate analysis, adjusting for multiple comparisons using Bonferroni correction. Results: The analysis compared the circulating miRNA profiles of 446 asthma/bronchitis subjects vs. 1168 non-asthma/non-bronchitis subjects. Among the miRNAs examined, there was only one miRNA, miR-133a-3p, that showed a significant difference between the two groups. We further focused on 8 specific miRNAs that have been proposed as diagnostic biomarkers for ovarian cancer and found no significant difference in expression between asthma/bronchitis subjects vs. non-asthma/non-bronchitis subjects.Conclusion: Asthma and bronchitis do not significantly confound measurements of miRNAs that are potential biomarkers for ovarian cancer. This further supports miRNAs as biomarkers for early detection of ovarian cancer and suggests that miRNAs are likely to generalize well if deployed as part of a screening test among the general population.
Citation Format: Monica Moore, Laura Wollborn, Sudhanshu Mishra, James Webber, Kevin M. Elias. Evaluating the impact of pulmonary diseases on the use of microRNAs as biomarkers for early detection of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B048.
Abstract IA003: Advancing novel therapeutics through reverse translation
Authors: Adams Sarah F. 
Published: March 2024

Abstract
Background: The established paradigm for cancer drug development was designed to advance cytotoxic agents targeting tumor cells. An increased appreciation of the role of the tumor microenvironment in treatment efficacy and disease outcomes has identified tumor-extrinsic therapeutic targets. The different mechanisms of action employed by anti-angiogenic drugs or immunotherapeutics highlight the need for updated study endpoints to identify the maximally effective dose for clinical applications. These advances, and the translation of novel therapeutics, can be accelerated through reverse translation, a term used to describe research using patient samples to inform mechanistic studies – going from bedside-to-bench. Objective: To present an example of reverse translation in the development of an immune therapy combination for ovarian cancer. Preclinical studies demonstrated therapeutic synergy of CTLA4 immune checkpoint blockade and poly(ADP ribose) polymerase (PARP) inhibition in high grade serous ovarian cancer models. These results were translated to two clinical trials for the treatment of recurrent ovarian cancer. Tumor samples from study subjects have been collected to support ongoing mechanistic investigations and exploratory biomarker studies. Both targeted and unbiased approaches identified candidate biomarkers of response to treatment for further development. Ongoing mechanistic studies are examining the significance of top prognostic markers. Conclusions: Strategies are needed to support the integration of translational studies with clinical research to inform next generation trials and to optimize clinical applications of novel therapeutics.
Citation Format: Sarah F. Adams. Advancing novel therapeutics through reverse translation [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr IA003.
Abstract PR-011: Role of cancer associated fibroblasts in ovarian cancer relapse
Authors: Fang Yiming , Ghosh Argha , Wang Ji , Dasari Subramanyam , Zamarin Dimitriy , Mitra Anirban Kumar 
Published: March 2024

Abstract
Frequent relapse and development of chemoresistance leads to poor prognosis in ovarian cancer (OC). Cancer stem cells (CSCs) consist of a small subpopulation in the tumor that are typically resistant to cytotoxic chemotherapy and are a potential cause of relapse and chemoresistance. Using patient specimens as well as in vitro models, we determined that CSCs are enriched in a niche adjacent to cancer associated fibroblasts (CAFs) after chemotherapy. Cancer associated fibroblasts (CAFs) are a major constituent of the ovarian cancer tumor microenvironment and are highly enriched in the residual tumors following chemotherapy. Therefore, we studied the role of CAFs in promoting ovarian cancer chemoresistance and disease relapse by providing an optimal microenvironment for CSCs. CAFs isolated from ovarian cancer patient tumors were used in heterotypic 2D or 3D coculture systems with high-grade serous ovarian cancer cell lines or with patient-derived ovarian cancer cells to study their effect on CSCs and chemoresistance. Matched pre-and post-chemotherapy patient tumors were used to confirm our findings. CAFs significantly increased resistance to carboplatin and enriched CSCs by increasing their symmetric division as well as dedifferentiation of bulk ovarian cancer cells. Pre-coculture with CAFs increased in vivo tumor initiation capacity of the ovarian cancer cells by 10-fold. The CSC-CAF crosstalk responsible for CSC induction was found to be mediated by Wnt5a signaling. CRISPR knockdown of Wnt5a in CAFs or treatment with a specific Wnt5a inhibitor abrogated the induction of CSCs by CAFs. Only cancer cells with ROR2 Wnt coreceptor respond to Wnt5a signaling triggered by CAFs and developed into CSCs. Responders were found to signal through a non-canonical Wnt pathway involving the coreceptor ROR2, protein kinase C (PKC), and CAMP Responsive Element Binding Protein 1 (CREB1). Inhibition of each of them prevented CSC induction and functional rescue experiments confirmed the sequence of the Wnt5a-ROR2-PKC-CREB1 axis. Treatment of mouse xenografts was established by co-injection of CAFs and ovarian cancer cells, with the Wnt5a inhibitor sensitized them to carboplatin, and eliminated the CSCs in the residual tumors. Our results indicate that CAF-derived Wnt5a is instrumental in ovarian cancer CSC growth and maintenance. In the long term, our studies will broaden the understanding of the mechanism of CSC maintenance by the tumor microenvironment and contribute towards the development of novel therapeutic approaches to prevent ovarian cancer chemoresistance and relapse.
Citation Format: Yiming Fang, Argha Ghosh, Ji Wang, Subramanyam Dasari, Dimitriy Zamarin, Anirban Kumar Mitra. Role of cancer associated fibroblasts in ovarian cancer relapse [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr PR-011.
Effects of silver nanowires and their surface modification on electromagnetic interference, transport and mechanical properties of an aerospace grade epoxy
Authors: Özkutlu Demirel Merve , Öztürkmen Mahide B , Savaş Müzeyyen , Mutlugün Evren , Erdem Talha , Öz Yahya 
Published: March 2024

The aerospace industry has progressively grown its use of composites. Electrically conductive nanocomposites are among important modern materials for this sector. We report on a bulk composite containing silver nanowires (AgNW) and an aerospace grade epoxy for use in carbon fiber reinforced polymers (CFRPs). AgNWs’ surfaces were also modified to enhance their ability to be dispersed in epoxy. Composites were obtained by use of three-roll milling which is of major interest for industrial applications, especially for the aerospace sector, since the process is scalable and works for aerospace grade resins with high curing temperatures. Our main objective is to improve the electromagnetic interference (EMI) shielding performance of CFRPs via improving the properties of the resin material. The addition of AgNWs did not considerably alter the flexural strength of the epoxy, however the composite with surface-modified AgNWs has a 46 % higher flexural strength. Adding AgNWs over a low threshold concentration of 0.05 wt% significantly enhanced the electrical conductivity. Conductivities above the percolation threshold lie around 102 S/m. At a concentration of 5 wt% AgNW, the EMI shielding efficiency (SE) of epoxy increased from 3.49 to 12.31 dB. Moreover, the thermal stability of the epoxy was unaffected by AgNWs. As a result, it was discovered that (surface modified) AgNWs improved the (multifunctional) capabilities of the aerospace grade epoxy resin which might be used in CFRPs to further enhance properties of composites parts, demonstrating suitability of AgNWs’ as a reinforcement material in aerospace applications.
Safety and efficacy of the yellow sub-threshold micropulse laser for uveitic macular edema: A pilot study
Authors: Bellucci Carlo , Bruni Francesco , Radice Lorenzo Marco , Tedesco Salvatore Antonio , Rossi Maurizio , Gandolfi Stefano , Mora Paolo 
Published: March 2024

Purpose To assess the safety and efficacy of the yellow sub-threshold micropulse laser (YSML) in eyes with uveitic macula edema (UME). Methods A prospective interventional study. Eyes with non-infectious UME and an unsatisfactory response to prior conventional treatments underwent navigated YSML (NAVILAS®). The treatment was planned on an imported macular OCT scan. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were recorded immediately before the treatment (baseline) and again after 1 and 3 months. The end of the follow up (FU) was the last available evaluation in the case of no UME recurrence; or when the CMT increase required rescue therapy. Results Eight eyes of as many patients were included. The mean duration of the FU was 252 days (range: 170–398 days). No adverse events were observed. In the whole cohort the mean values improvement over time was significant for both CMT ( p = 0.011) and BCVA ( p < 0.001). The indication for a new treatment was stated in 4 eyes (50%) after a mean FU of 277 ± 43 days. This time was statistically comparable with the mean FU of eyes without UME recurrence. At the baseline the non-UME recurrence eyes had a significantly lower mean CMT (326 ± 80 vs 485 ± 112 μm, p = 0.03). Conclusions The application of YSLM for UME has not previously been mentioned in literature. Our results were promising in terms of both safety and efficacy. This would authorize further studies on the procedure, also as a first line treatment in naif UME cases.
Systemic immune-inflammation index as a novel hematological marker for predicting the recurrence of deep venous thrombosis
Authors: Donmez Ibrahim , Muduroglu Ayhan 
Published: March 2024

Objective To determine whether there was a possible predictive relationship between systemic immune-inflammation index (SII) and recurrence of deep venous thrombosis (DVT). Methods A total of 231 patients with DVT who met the study criteria and whose data could be accessed were enrolled to this retrospective single-centered cross-sectional study. Of them 26 patients with DVT recurrence consisted of the study group (Group 1) while remaining 205 cases without recurrence were considered as the control population (Group 2). The patients’ basic clinical features and laboratory results from the complete blood count (CBC) test were recorded and compared between groups. Following univariate analyses, a multivariate logistic regression analysis was performed to identify the independent predictors of the recurrence of DVT. Additionally, a receiver-operating characteristic (ROC) curve analysis was performed to detect the cut-off values of the predictors with sensitivity and specificity rates. Results There were no significant differences between the groups for basic clinical features, except for diabetes mellitus, pulmonary embolism, and atrial fibrillation. Although the univariate analysis revealed that the median values of NLR, PLR, and SII were significantly higher in the DVT recurrence group, only SII was determined to be a significant and independent predictor of DVT recurrence in the multivariate logistic regression analysis. According to ROC curve analysis, SII of 1685 × 103/mm3 constituted the cut-off value for predicting DVT recurrence with 61.5% sensitivity and 76.6% specificity (AUC = 0.686, p = .001). Conclusion The present study demonstrated for the first time in the literature that SII significantly predicted the recurrence of DVT.