Janiel M Cragun

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• Moore, K. N., Chambers, S. K., Hamilton, E. P., Chen, L. M., Oza, A. M., Ghamande, S. A., Konecny, G. E., Plaxe, S. C., Spitz, D. L., Geenen, J. J., Troso-Sandoval, T. A., Cragun, J. M., Rodrigo Imedio, E., Kumar, S., Mugundu, G. M., Lai, Z., Chmielecki, J., Jones, S. F., Spigel, D. R., & Cadoo, K. A. (2022). Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study. Clinical cancer research : an official journal of the American Association for Cancer Research, 28(1), 36-44.
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  This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer.
• Bohnenkamp, S., Cragun, J., Davis, M., Minehart, H., Cottle, S., Moore, C., & McCuen, H. (2018). An Interdisciplinary program to prevent postoperative pneumonia: An Evidenced-Based Project.. MEDSURG Nursing Journal.
• Garcia, A., Frahm, C., Jeter, J. M., Abraham, I., Chambers, S. K., Cragun, J. M., & McBride, A. (2019). Incidence of Hypersensitivity Reactions to Carboplatin or Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer With or Without or Mutations. Journal of the advanced practitioner in oncology, 10(5), 428-439.
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  The association of mutation status with hypersensitivity reactions (HSRs) to carboplatin has gained interest in recent years, particularly in patients with ovarian, fallopian tube, and primary peritoneal cancer. The primary objective of this study is to determine whether the presence of mutations increased the likelihood of HSRs to carboplatin. The incidence of HSRs to paclitaxel and symptom grade based on the Common Terminology Criteria for Adverse Events, version 4.0, were explored as secondary endpoints. A retrospective chart review of patients with ovarian, fallopian tube, or primary peritoneal cancer at the University of Arizona Cancer Center who underwent treatment with carboplatin-containing regimens and received genetic testing was performed. Institutional review board approval was obtained for this study. Fisher's exact test was used to analyze the primary outcome. Out of 167 initial patients, 62 with germline test results constituted the evaluable sample. 15 of 62 (24.2%) -tested patients were treated with carboplatin monotherapy, while 44 of 62 (71.0%) patients were treated with paclitaxel-containing regimens. Hypersensitivity reactions occurred in 4 of 13 (30.8%) -mutated patients and 22 of 49 (44.9%) wild-type patients ( = .5291). Hypersensitivity reactions to paclitaxel occurred in 1 of 13 (7.7%) -mutated patients and 26 of 49 (53.1%) wild-type patients ( = .0039). Overall, there were 11 grade 1 reactions, 14 grade 2 reactions, and 16 grade 3 reactions to carboplatin. All reactions to carboplatin in -mutated patients were grade 1. All paclitaxel reactions manifested as grade 2. The sample size was the main study limitation. The presence of mutations was not statistically significantly associated with a higher incidence of HSRs to carboplatin, but was statistically significant with regards to paclitaxel.
• Barnes, D., Rivera, R., Gibson, S., Craig, C., Cragun, J., Monk, B., & Chase, D. (2018). The utility of patient reported data in a gynecologic oncology clinic. Gynecologic oncology research and practice, 5, 4.
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  Measuring QoL is essential to the field of gynecologic oncology but there seems to be limited standardized data regarding collecting QoL assessments throughout a patient's cancer treatment especially in non-clinical trial patients. The aim of this study is to explore patient characteristics that may be associated with poor quality of life (QoL) in women with gynecologic cancers at two University of Arizona Cancer Center (UACC) sites.
• Garcia, A., Frahm, C., Jeter, J. M., Abraham, I., Chambers, S. K., Cragun, J. M., & McBride, A. (2018). Incidence of Hypersensitivity Reactions to Carboplatin in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer with or without BRCA1 or BRCA2 Mutations. Journal of the American College of Clinical Pharmacy (Manuscript ID 06-18-0076).
• Miller, J. M., Harvey, E. M., Bedrick, S., Mahon, P., Calhoun, E., & Cragun, J. M. (2017). Simple Patient Care Instructions Translate Best: Safety Guidelines for Physician Use of Google Translate. Journal of Clinical Outcomes Management.
• Cragun, J. M., TenEyk, C., Cui, H., & Chambers, S. K. (2016). The association of miR-let-7i with platinum resistance of a sensitive/resistant ovarian cancer parent/daughter cell line. American Journal of Clinical and Experimental Obstetrics and Gynecology, 4(1), 1-10.
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  Ovarian cancer is the most deadly of the gynecologic malignancies. Most epithelial ovarian cancers respond to initial treatments with platinum agents. However, once the tumor develops platinum resistance, the prognosis for the patient is poor. We investigated the role of microRNA as a potential marker for platinum resistance in a platinum sensitive parent and platinum resistant daughter ovarian cancer cell line (2780S and 2780/CP70). We performed quantitative reverse transcriptase-polymerase chain reaction on 20 microRNA targets in both lines. We identified miR-let-7i and miR-125b as the most differentially over- and under-expressed, respectively, in the resistantline compared to the sensitive line. Down-regulation of miR-let-7i levels in the resistant line suggested improved response to platinum (P
• Cragun, J. M., TenEyk, C., Cui, H., & Chambers, S. K. (2017). The association of miR-let-7i with platinum resistance of a sensitive/resistant ovarian cancer parent/daughter cell line. American Journal of Clinical and Experimental Obstetrics and Gynecology.
• Swisher, E. M., Lin, K. K., Oza, A. M., Scott, C. L., Giordano, H., Sun, J., Konecny, G. E., Coleman, R. L., Tinker, A. V., O'Malley, D. M., Kristeleit, R. S., Ma, L., Bell-McGuinn, K. M., Brenton, J. D., Cragun, J. M., Oaknin, A., Ray-Coquard, I., Harrell, M. I., Mann, E., , Kaufmann, S. H., et al. (2016). Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. The Lancet. Oncology, 18(1), 75-87.
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  Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.
• Coleman, R. L., Swisher, E. M., Oza, A., Scott, C. L., Giordano, H., Lin, K., Konecny, G. E., Tinker, A., O'Malley, D. M., Kristeleit, R. S., Ma, L., Bell-McGuinn, K. M., Brenton, J. D., Cragun, J. M., Oaknin, A., Ray-Coquard, I. L., Kaufmann, S. H., Goble, S., Maloney, L., & McNeish, I. A. (2016). Refinement of prespecified cutoff for genomic loss of heterozygosity (LOH) in ARIEL2 part 1: A phase 2 study of rucaparib in patients (pts) with high grade ovarian carcinoma (HGOC) (abstract). Accepted for presentation at: ASCO Annual Meeting 2016.
• Cragun, J. M. (2016). Feasibility of monitoring response to the PARP inhibitor rucaparib with targeted deep sequencing of circulating tumor DNA (ctDNA) in women with high grade serous carcinoma on the ARIEL2 trial ABSTRACT. 2016 ASCO Annual Meeting.
• Cragun, J. M. (2016). Refinement of prespecified cutoff for genomic loss of heterozygosity (LOH) in ARIEL2 part 1: A phase 2 study of rucaparib in patients (pts) with high grade ovarian carcinoma (HGOC) ABSTRACT. 2016 ASCO Annual Meeting.
• Petkovska, I., Duke, E., Martin, D. R., Irani, Z., Geffre, C. P., Cragun, J. M., Costello, J. R., Arif-Tiwari, H., Czeyda-Pommersheim, F., Udayasankar, U., & Kalb, B. (2016). MRI of ovarian torsion: Correlation of imaging features with the presence of perifollicular hemorrhage and ovarian viability. European journal of radiology, 85(11), 2064-2071.
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  The purpose of our study is to test for: (a) correlation between the presence of a perifollicular T2-hypointense rim on MRI with the presence of perifollicular hemorrhage on histology; and (b) correlation between this finding and diminished ovarian viability after intra-operative detorsion.
• Piskorz, A., Lin, K., Morris, J. A., Mann, E., Oza, A., Coleman, R. L., O'Malley, D. M., Friedlander, M., Cragun, J. M., Ma, L., Giordano, H., Raponi, M., McNeish, I. A., Swisher, E. M., & Brenton, J. D. (2016). Feasibility of monitoring response to the PARP inhibitor rucaparib with targeted deep sequencing of circulating tumor DNA (ctDNA) in women with high-grade serous carcinoma on the ARIEL2 trial (abstract). Accepted for presentation at: ASCO Annual Meeting 2016.
• Wang, X., Li, L., Cragun, J. M., Chambers, S. K., Hatch, K. D., & Zheng, W. (2016). Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 26(5), 918-23.
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  The aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC).
• Cragun, J. M. (2015). Association of Microscopic Findings of OVarian High-Grade Serous Carcinoma (HGSC) and Status of BRCA Mutation ABSTRACT. US and Canadian Academy of Pathology.
• Ferguson, D. C., Ferguson, D. C., Han, L. M., Han, L. M., Wang, Y., Wang, Y., Cragun, J. M., Cragun, J. M., Hatch, K. D., Hatch, K. D., Chambers, S. K., Chambers, S. K., Zheng, W., Zheng, W., Ferguson, D. C., Han, L. M., Wang, Y., Cragun, J. M., Hatch, K. D., , Chambers, S. K., et al. (2015). The role of the fallopian tube in ovarian serous carcinogenesis; biologic mechanisms and clinical impacts. American Journal of Clinical and Experimental Obstetrics and Gynecology, 2(1), 1-13.
• Ferguson, D. C., Han, L. M., Wang, Y., Cragun, J. M., Hatch, K. D., Chambers, S. K., & Zheng, W. (2015). The role of the fallopian tube in ovarian serous carcinogenesis: biologic mechanisms and clinical impacts. American Journal of Clinical and Experimenta Obstetrics and Gynecology, 2(1), 1-13.
• MacKerricher, W., Zheng, W., Wang, Y., Chambers, S. K., Klein, R. R., Hatch, K. D., Cragun, J. M., Cragun, J. M., Hatch, K. D., Klein, R. R., Wang, Y., Chambers, S. K., Zheng, W., & MacKerricher, W. (2015). Association of microscopic findings of ovarian high-grade serous carcinoma (HGSC) and status of BRCA mutation (abstract). Accepted for Presentation at: US and Canadian Academy of Pathology.
• Jia, L., Yuan, Z., Wang, Y., Cragun, J. M., Kong, B., & Zheng, W. (2014). Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 28(1), 118-27.
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  Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (
• Yuan, Z., Wang, L., Wang, Y., Zhang, T., Li, L., Cragun, J. M., Chambers, S. K., Kong, B., & Zheng, W. (2014). Tubal origin of ovarian endometriosis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 27(8), 1154-62.
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  Endometriosis is a puzzling and debilitating disease that affects millions of women around the world. Ovary is the most common organ site involved by endometriosis. Despite various hypotheses about its cell of origin, uncertainty remains. On the basis of our clinicopathologic observations, we hypothesize that fallopian tube may contribute the histogenesis of ovarian endometriosis. To examine if the hypothesis, tubal origin of ovarian endometriosis, has scientific supporting evidence, we identified a set of novel genes, which are either highly expressed in the normal fallopian tube or in the endometrium through a gene differential array study. Among many differentially expressed genes, FMO3 and DMBT1 were selected as the initial biomarkers to test the hypothesis. These biomarkers were then validated in ovarian sections with foci of endometriosis by comparing their expression levels in the fallopian tube and the endometrium within the same patients with real-time PCR, western blot and immunohistochemistry analysis. FMO3 was highly expressed in the tubal epithelia while low in the paired endometrium. In contrast, DMBT1 was high in the endometrium but low in the fallopian tube. In 32 ovarian endometriosis cases analyzed by real-time PCR, 18 (56%) showed a high level of FMO3 and a low level of DMBT1 expression. However, 14 (44%) endometriosis cases showed a reversed expression pattern with these two markers. Results were similarly seen in the methods of western blot and immunohistochemistry. The findings suggest that approximately 60% of the ovarian endometriosis we studied may be derived from the fallopian tube, whereas about 40% of the cases may be of endometrial origin. The fallopian tube epithelia may represent one of the tissue sources contributing to ovarian endometriosis. Such novel findings, which require confirmation, may have a significant clinical impact in searching for alternative ways of prevention and treatment of endometriosis.
• Cragun, J. M., Baggs, J. H., Rollins, C., & Chambers, S. K. (2013). Hypersensitivity reaction to parenteral nutrition after severe hypersensitivity reaction to paclitaxel: a case report. American Journal of Clinical and Experimental Obstetrics and Gynecology.
• Li, J., Ning, Y., Abushahin, N., Yuan, Z., Wang, Y., Wang, Y., Yuan, B., Cragun, J. M., Chambers, S. K., Hatch, K., Kong, B., & Zheng, W. (2013). Secretory cell expansion with aging: risk for pelvic serous carcinogenesis. Gynecologic oncology, 131(3), 555-60.
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  Recent advances suggest that precancerous lesions of pelvic serous carcinoma (PSC) originate from tubal secretory cells. The purpose of our study was to determine if increased number of secretory cells shows difference in age and location and to examine their association with serous neoplasia.
• Ning, Y., Kong, F., Cragun, J. M., & Zheng, W. (2013). Struma ovarii simulating ovarian sertoli cell tumor: a case report with literature review. International journal of clinical and experimental pathology, 6(3), 516-20.
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  Struma ovarii, as a monodermal variant of ovarian teratoma, constitutes about less than 3% of ovarian teratomas. It is difficult to be macroscopically recognized. Multiple appearances under microscope serve as another reason to mislead the accurate pathologic evaluation. Here, we report an unusual case of struma ovarii occurred in a 77 years old woman, which is currently known as the oldest age for this disease. The frozen section morphologically showed sex cord like elements and was suspicious for a sex-cord stromal tumor, probably a Sertoli cell tumor. Final pathological diagnosis was confirmed as struma ovarii based on the typical morphologic thyroid follicles and immunohistochemical staining results.
• Wang, Y., Wang, Y., Li, J., Cragun, J., Hatch, K., Chambers, S. K., & Zheng, W. (2013). Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium. Journal of hematology & oncology, 6, 22.
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  Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. LS is the most common presentation of hereditary colorectal cancer (CRC), accounting for about 2-5% of all CRC cases. More recently, it is found that a similar number of endometrial cancers is also due to one of the MMR gene mutations. There has been significant progress in LS-related CRC in terms of molecular pathogenesis, risks, genetic basis, and cancer prevention. In contrast, the advance about LS-related endometrial cancer (EC) is very much limited. In this commentary, we summarize the main clinicopathologic features of LS-related EC and propose universal screening for LS in individuals with endometrial cancer.
• Wang, Y., Wang, Y., Li, J., Yuan, Z., Yuan, B., Zhang, T., Cragun, J. M., Kong, B., & Zheng, W. (2013). PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy. Journal of hematology & oncology, 6, 60.
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  Neoadjuvant chemotherapy followed by cytoreduction surgery has been used where an accurate cytologic or pathologic diagnosis is usually required before the initiation of neoadjuvant chemotherapy. However, it is difficult to make definitive diagnosis of presence of cancer cells, particularly gynecologic versus non-gynecologic origin, from those ascites specimens due to the absence of specific biomarkers of gynecologic cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy.
• Chambers, S. K., Chow, H. S., Janicek, M. F., Cragun, J. M., Hatch, K. D., Cui, H., Laughren, C., Clouser, M. C., Cohen, J. L., Wright, H. M., Abu Shahin, N., & Alberts, D. S. (2012). Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 18(9), 2668-78.
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  This phase I trial evaluated intraperitoneal (i.p.) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.
• Cragun, J. M. (2011). Screening for ovarian cancer. Cancer control : journal of the Moffitt Cancer Center, 18(1), 16-21.
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  Ovarian cancer remains the most deadly of the gynecologic cancers. It is difficult to diagnose until in advanced stages. An effective screening test may help to decrease mortality from ovarian cancer. Due to the low incidence of ovarian cancer in the general population, a good screening test must have high sensitivity and specificity to allow accurate detection without excessive false-positive results. Thus, effective screening for ovarian cancer has remained elusive.
• Klein, R. L., Brown, A. R., Gomez-Castro, C. M., Chambers, S. K., Cragun, J. M., Grasso-Lebeau, L., & Lang, J. E. (2010). Ovarian cancer metastatic to the breast presenting as inflammatory breast cancer: a case report and literature review. Journal of Cancer, 1, 27-31.
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  Background. Primary ovarian carcinoma with metastasis to the breast is rare, with only 39 cases reported in the current literature. Ovarian metastasis to the breast presenting as inflammatory breast carcinoma is even more infrequent, with only 6 cases reported.Case. We present a patient who developed metastatic inflammatory cancer of the breast from a stage IIIC papillary serous ovarian adenocarcinoma approximately 1 year after the original diagnosis. Pathologic analysis confirmed the origin of the tumor: a high-grade adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. In addition, the tumor was strongly positive on immunohistochemistry for CA-125, identical to the ovarian primary. The patient died of diffuse metastasis 5 months after the breast tumor was noted.Conclusion. Although ovarian metastasis to the breast presenting as inflammatory breast cancer is rare, it should be included in the differential diagnosis for any patient with a personal history of ovarian cancer. Accurate differentiation is necessary because treatment differs significantly for patients with ovarian metastasis to the breast, as compared with patients with primary inflammatory breast cancer. Ovarian metastasis to the breast confers a poor prognosis: patient survival ranged from 3 to 18 months, with a median survival of 6 months after the diagnosis of the breast metastasis.
• Kamath, S. G., Chen, N., Xiong, Y., Wenham, R., Apte, S., Humphrey, M., Cragun, J., & Lancaster, J. M. (2009). Gedunin, a novel natural substance, inhibits ovarian cancer cell proliferation. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 19(9), 1564-9.
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  The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways.
• Cragun, J. M., Ellestad, S. C., & Panni, M. K. (2008). Amniotic fluid embolism presenting after uterine manipulation under general anesthesia: a case with a positive outcome. Resuscitation, 77(1), 145-6.
• Dressman, H. K., Berchuck, A., Chan, G., Zhai, J., Bild, A., Sayer, R., Cragun, J., Clarke, J., Whitaker, R. S., Li, L., Gray, J., Marks, J., Ginsburg, G. S., Potti, A., West, M., Nevins, J. R., & Lancaster, J. M. (2007). An integrated genomic-based approach to individualized treatment of patients with advanced-stage ovarian cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 25(5), 517-25.
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  The purpose of this study was to develop an integrated genomic-based approach to personalized treatment of patients with advanced-stage ovarian cancer. We have used gene expression profiles to identify patients likely to be resistant to primary platinum-based chemotherapy and also to identify alternate targeted therapeutic options for patients with de novo platinum-resistant disease.
• Havrilesky, L. J., Cragun, J. M., Calingaert, B., Alvarez Secord, A., Valea, F. A., Clarke-Pearson, D. L., Berchuck, A., & Soper, J. T. (2007). The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer. Gynecologic oncology, 104(2), 401-5.
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  The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment.
• Strosberg, J., Nasir, A., Cragun, J., Gardner, N., & Kvols, L. (2007). Metastatic carcinoid tumor to the ovary: a clinicopathologic analysis of seventeen cases. Gynecologic oncology, 106(1), 65-8.
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  To evaluate the clinical behavior and histologic characteristics of metastatic carcinoid tumors to the ovary.
• Lancaster, J. M., Dressman, H. K., Clarke, J. P., Sayer, R. A., Martino, M. A., Cragun, J. M., Henriott, A. H., Gray, J., Sutphen, R., Elahi, A., Whitaker, R. S., West, M., Marks, J. R., Nevins, J. R., & Berchuck, A. (2006). Identification of genes associated with ovarian cancer metastasis using microarray expression analysis. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 16(5), 1733-45.
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  Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.
• Lutman, C. V., Havrilesky, L. J., Cragun, J. M., Secord, A. A., Calingaert, B., Berchuck, A., Clarke-Pearson, D. L., & Soper, J. T. (2006). Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology. Gynecologic oncology, 102(1), 92-7.
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  To determine whether pelvic lymph node count is associated with patterns of recurrence or survival in patients with FIGO stage I and II endometrial cancer.
• Potti, A., Dressman, H. K., Bild, A., Riedel, R. F., Chan, G., Sayer, R., Cragun, J., Cottrill, H., Kelley, M. J., Petersen, R., Harpole, D., Marks, J., Berchuck, A., Ginsburg, G. S., Febbo, P., Lancaster, J., & Nevins, J. R. (2006). Genomic signatures to guide the use of chemotherapeutics. Nature medicine, 12(11), 1294-300.
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  Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signatures can accurately predict clinical response in individuals treated with these drugs. Notably, signatures developed to predict response to individual agents, when combined, could also predict response to multidrug regimens. Finally, we integrated the chemotherapy response signatures with signatures of oncogenic pathway deregulation to identify new therapeutic strategies that make use of all available drugs. The development of gene expression profiles that can predict response to commonly used cytotoxic agents provides opportunities to better use these drugs, including using them in combination with existing targeted therapies.
• Chen, L., Li, L., Goldgof, D., George, F., Chen, Z., Rao, A., Cragun, J., Sutphen, R., & Lancaster, J. (2005). Improving Reliability of Response Prediction to Platinum-Based Therapy by AdaBoost and Multiple Classifiers. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 5, 4822-5.
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  It is a challenge to construct a reliable classifier based on microarray gene expression data for prediction of chemotherapy response, because usually only a small number of samples are available and each sample has thousands of gene expressions. This paper uses boosting and bootstrap approaches to improve the reliability of prediction. Specifically, AdaBoost and multiple classifiers based methods are used, in which support vector machines (SVMs) are utilized as the classifiers due to their good generalization ability. We compare the performance of proposed methods with a single SVM classifier system using MAS gene expression dataset in prediction of the response to platinum-based therapy for advanced-stage ovarian cancers. Statistical tests show both of the proposed methods achieve better prediction performance and have good reliability in terms of mean and standard deviation of the prediction performance for different number of selected features.
• Cragun, J. M., Havrilesky, L. J., Calingaert, B., Synan, I., Secord, A. A., Soper, J. T., Clarke-Pearson, D. L., & Berchuck, A. (2005). Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 23(16), 3668-75.
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  Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy.
• Havrilesky, L. J., Cragun, J. M., Calingaert, B., Synan, I., Secord, A. A., Soper, J. T., Clarke-Pearson, D. L., & Berchuck, A. (2005). Resection of lymph node metastases influences survival in stage IIIC endometrial cancer. Gynecologic oncology, 99(3), 689-95.
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  Surgical staging of endometrial cancer identifies those patients with microscopic metastatic disease most likely to benefit from adjuvant therapy and may also confer therapeutic benefit. Our objective was to compare survival of patients who underwent resection of grossly positive lymph nodes (LN) to those with microscopically positive LN.
• Li, L., Chen, L., Goldgof, D., George, F., Chen, Z., Rao, A., Cragun, J., Sutphen, R., & Lancaster, J. (2005). Integration of clinical information and gene expression profiles for prediction of chemo-response for ovarian cancer. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 5, 4818-21.
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  Ovarian cancer is the fifth leading cause of cancer death among women in the United States and western Europe. Platinum drugs are the most active agents in epithelial ovarian cancer therapy. In order to improve the prediction of response to platinum-based chemotherapy for advanced-stage ovarian cancers, we describe an integrated model which combines clinical information tumor and treatment information, with gene expression profile. This integrated modeling framework is based on the support vector machine classifier that evaluates the contributions of both clinical and gene expression data. The results show that the integrated model combining clinical information and gene expression profiles improve the prediction accuracy compared to those made by using gene expression predictor alone.
• Martino, M. A., Balar, A., Cragun, J. M., & Hoffman, M. S. (2005). Delay in treatment of invasive cervical cancer due to intimate partner violence. Gynecologic oncology, 99(2), 507-9.
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  Intimate partner violence (IPV) is underreported and creates a complex psychosocial medium that adversely affects the health of its victims. We present the first case report in the literature, though likely not the first time, in which a patient delayed her cancer treatment due to domestic abuse and her disease progressed.

Presentations

• Irani, Z., Petkovska, I., Kalb, B. T., Geffre, C., Cragun, J. M., Arif Tiwari, H., Czeyda-Pommersheim, F., & Martin, D. R. (2015, MARCH). MRI’s tale of Ovary Twist.. RSNA.
• Petkovska, I., Irina, Z., Kalb, B. T., Geffre, C., Cragun, J. M., Arif Tiwari, H., Czeyda-Pommersheim, F., & Martin, D. R. (2015, MARCH). The “Onyx Rim” sign in pelvic MRI: Perifollicular Hemorrhage as a Potential Predictor of viability in the setting of ovarian torsion.. RSNA2015.

Poster Presentations

• Jeter, J. M., Abraham, I., Chambers, S. K., Cragun, J. M., & McBride, A. (2018, Spring). Incidence of Hypersensitivity Reactions to Carboplatin in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer with or without BRCA1 or BRCA2 Mutations (ABSTRACT). ASCO.
• Jeter, J. M., Abraham, I., Chambers, S. K., Cragun, J. M., & McBride, A. (2017, March). CT10 Comparison of Hypersensitivity Reaction Incidence to Carboplatin in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients with or without the BRCA1 or BRCA2 Mutations. Hematology Oncology Pharmacy Association Conference. Anaheim, CA: Hematology Oncology Pharmacy Association.
• Eldersveld, J. M., Chen, H., Klein, R. R., Chambers, S. K., Cragun, J. M., & Zheng, W. (2016, Fall). Mismatch Repair Protein Loss of Expression in Endometrial Hyperplasia (poster). Poster Presentation at College of American Pathologist (CAP) Conference 2016. Las Vegas, NV: College of American Pathologists.
• Cragun, J. M., Elahi, A., Boulware, D., Beam, C., Sayer, R., Maxwell, G. L., Sutphen, R., Berchuck, A., & Lancaster, J. M. (2005, Summer). Characterization of the insulin-like growth factor pathway in endometrial cancers. ASCO Annual Meeting Proceedings.

Others

• Irani, Z., Martin, D. R., Petkovska, I., Czeyda-Pommersheim, F., Kalb, B. T., Arif Tiwari, H., Geffre, C., Cragun, J. M., Geffre, C., Cragun, J. M., Arif Tiwari, H., Kalb, B. T., Czeyda-Pommersheim, F., Petkovska, I., Irani, Z., & Martin, D. R. (2015, MARCH). MRI’s tale of Ovary Twist.. Abstract; RSNA.
• Martin, D. R., Czeyda-Pommersheim, F., Arif Tiwari, H., Cragun, J. M., Geffre, C., Kalb, B. T., Irina, Z., & Petkovska, I. (2015, MARCH). The “Onyx Rim” sign in pelvic MRI: Perifollicular Hemorrhage as a Potential Predictor of viability in the setting of ovarian torsion.. Abstract; RSNA2015.
• Petkovska, I., Irina, Z., Kalb, B. T., Geffre, C., Cragun, J. M., Arif Tiwari, H., Czeyda-Pommersheim, F., & Martin, D. R. (2015, MARCH). The “Onyx Rim” sign in pelvic MRI: Perifollicular Hemorrhage as a Potential Predictor of viability in the setting of ovarian torsion.. Abstract; RSNA2015.