Person:
Elias, Kevin

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Elias

First Name

Kevin

Name

Elias, Kevin
Author's Publications: search.filters.isAuthorOfPublication.2743ecec-f6eb-4881-9b29-09904da92cb2

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Publication
    RNA‐Peptide nanoplexes drug DNA damage pathways in high‐grade serous ovarian tumors
    (John Wiley and Sons Inc., 2018) Dreaden, Erik C.; Kong, Yi Wen; Quadir, Mohiuddin A.; Correa, Santiago; Suárez‐López, Lucia; Barberio, Antonio E.; Hwang, Mun Kyung; Shi, Aria C.; Oberlton, Benjamin; Gallagher, Paige N.; Shopsowitz, Kevin E.; Elias, Kevin; Yaffe, Michael; Hammond, Paula T.
    Abstract DNA damaging chemotherapy is a cornerstone of current front‐line treatments for advanced ovarian cancer (OC). Despite the fact that a majority of these patients initially respond to therapy, most will relapse with chemo‐resistant disease; therefore, adjuvant treatments that synergize with DNA‐damaging chemotherapy could improve treatment outcomes and survival in patients with this deadly disease. Here, we report the development of a nanoscale peptide‐nucleic acid complex that facilitates tumor‐specific RNA interference therapy to chemosensitize advanced ovarian tumors to frontline platinum/taxane therapy. We found that the nanoplex‐mediated silencing of the protein kinase, MK2, profoundly sensitized mouse models of high‐grade serous OC to cytotoxic chemotherapy by blocking p38/MK2‐dependent cell cycle checkpoint maintenance. Combined RNAi therapy improved overall survival by 37% compared with platinum/taxane chemotherapy alone and decreased metastatic spread to the lungs without observable toxic side effects. These findings suggest (a) that peptide nanoplexes can serve as safe and effective delivery vectors for siRNA and (b) that combined inhibition of MK2 could improve treatment outcomes in patients currently receiving frontline chemotherapy for advanced OC.
  • Thumbnail Image
    Publication
    Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer
    (eLife Sciences Publications, Ltd, 2017) Elias, Kevin; Fendler, Wojciech; Stawiski, Konrad; Fiascone, Stephen; Vitonis, Allison F; Berkowitz, Ross; Frendl, Gyorgy; Konstantinopoulos, Panagiotis; Crum, Christopher; Kedzierska, Magdalena; Cramer, Daniel; Chowdhury, Dipanjan
    Recent studies posit a role for non-coding RNAs in epithelial ovarian cancer (EOC). Combining small RNA sequencing from 179 human serum samples with a neural network analysis produced a miRNA algorithm for diagnosis of EOC (AUC 0.90; 95% CI: 0.81–0.99). The model significantly outperformed CA125 and functioned well regardless of patient age, histology, or stage. Among 454 patients with various diagnoses, the miRNA neural network had 100% specificity for ovarian cancer. After using 325 samples to adapt the neural network to qPCR measurements, the model was validated using 51 independent clinical samples, with a positive predictive value of 91.3% (95% CI: 73.3–97.6%) and negative predictive value of 78.6% (95% CI: 64.2–88.2%). Finally, biologic relevance was tested using in situ hybridization on 30 pre-metastatic lesions, showing intratumoral concentration of relevant miRNAs. These data suggest circulating miRNAs have potential to develop a non-invasive diagnostic test for ovarian cancer.
  • Thumbnail Image
    Publication
    Prior appendectomy does not protect against subsequent development of malignant or borderline mucinous ovarian neoplasms
    (Elsevier BV, 2014) Elias, Kevin; Labidi-Galy, S. Intidhar; Vitonis, Allison F.; Hornick, Jason; Doyle, Leona; Hirsch, Michelle; Cramer, Daniel; Drapkin, Ronny
    Background Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. Methods The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. Results From the New England Case-Control study, 287 cases of MON were compared against 2,339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83–1.92, p=0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48–2.80, p<0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. Conclusion Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases.
  • Thumbnail Image
    Publication
    Elafin drives poor outcome in high grade serous ovarian cancers and basal-like breast tumors
    (2014) Labidi-Galy, S. Intidhar; Clauss, Adam; Ng, Vivian; Duraisamy, Sekhar; Elias, Kevin; Piao, Hui-Ying; Bilal, Erhan; Davidowitz, Rachel A.; Lu, Yiling; Badalian-Very, Gayane; Györffy, Balázs; Kang, Un-Beom; Ficarro, Scott; Ganesan, Shridar; Mills, Gordon B.; Marto, Jarrod; Drapkin, Ronny
    High grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirmed that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies, and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.