Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients

Haidn Foster, Keenan J. Piper, Lisa DePledge, Hsin-Fang Li, James Scanlan, Jae-Guen Yoon, Michael Boeckh, and Charles S. Cobbs

Human cytomegalovirus (HCMV) is an oncomodulatory human herpesvirus that has been detected in glioblastoma (GBM) and is associated with worse prognosis in patients with the disease. The effects of HCMV systemic infection on survival in GBM patients, however, are largely unknown. We aimed to determine the association between HCMV serostatus at diagnosis and survival via a retrospective cohort study of glioblastoma patients.

Plasma from 188 glioblastoma patients treated at the Ben and Catherine Ivy Center (Seattle, WA) was tested for HCMV serostatus via enzyme-linked immunosorbent assays of anti-HCMV immunoglobulin (Ig)G. HCMV IgG serostatus was analyzed with respect to each patient’s progression-free and overall survival via log rank and multivariable Cox regression analysis.

Ninety-seven of 188 (52%) patients were anti-HCMV IgG seropositive. Median overall survival (OS) was decreased in the IgG+ cohort (404 days) compared to IgG- patients (530 days; p = 0.0271). Among O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated patients (n = 96), median OS was significantly decreased in IgG+ patients (336 days) compared to IgG- patients (510 days; p = 0.0094). MGMT methylation was associated with improved OS in IgG+ patients vs those who were unmethylated (680 vs 336 days; p = 0.0096), while no such association was observed among IgG- patients.

In this study, HCMV seropositivity was significantly associated with poorer OS in glioblastoma patients. This finding suggests prior infection with HCMV may play an important role in glioblastoma patient outcomes, and anti-HCMV antibodies may therefore prove a valuable prognostic tool in the management of GBM patients.

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Viruses and glioblastoma: Affliction or opportunity?

Haidn Foster and Charles S. Cobbs

Herpesviruses, polyomaviruses, and papillomaviruses have all been detected in glioblastoma cells and/or cell lines. Our group first published evidence of human cytomegalovirus (CMV), a herpesvirus, in glioblastoma specimens from immunocompetent patients in 2002. However, the discovery of CMV and other viruses in glioblastoma has met with controversy following several studies that failed to detect viral particles in GBM. Here we summarize the known relationships between viruses and malignant gliomas, including viral detection in GBM, the oncomodulatory effects of GBM-associated viruses, and the novel ways by which investigators are targeting viruses for the treatment of glioblastoma.

Glioblastoma mimicking viral encephalitis responds to acyclovir: A case series and literature review

Keenan J. Piper, Haidn Foster, Brandon Gabel, Burt Nabors, and Charles S. Cobbs

Viral encephalitis and glioblastoma are both rare conditions with poor prognoses. While the clinical and radiographic presentation of these diseases are often distinctly different, viral encephalitis can sometimes masquerade as glioblastoma. Rarely, glioblastoma can be misdiagnosed as viral encephalitis. In some cases where a high-grade glioma was initially diagnosed as viral encephalitis, antiviral administration has proven effective for relieving early symptoms. We present three cases in which patients presented with symptoms and radiographic findings suggestive of viral encephalitis and experienced dramatic clinical improvement following treatment with acyclovir, only to later be diagnosed with glioblastoma in the region of suspected encephalitis and ultimately succumb to tumor progression.

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Fatal Balamuthia mandrillaris brain infection associated with improper nasal lavage All-Time Top 3k Article, Altmetric

Keenan J. Piper, Haidn Foster, Daniel Susanto, Cynthia L. Maree, Sean D. Thornton, and Charles S. Cobbs

We present a case of a 69-year old female who presented with a chronic nasal skin rash, a new onset focal seizure, and a cerebral ring-enhancing lesion after a year of improper nasal irrigation. Despite aggressive and novel anti-amoebic treatment, she succumbed to a fatal Balamuthia mandrillaris brain infection.

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Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients Best Clinical Research Poster

Haidn Foster, James Scanlan, Keenan J. Piper, Jae-Guen Yoon, and Charles S. Cobbs.

Barriers to healthcare navigation: An inter-organizational analysis of key Cincinnati community stakeholders

Tatiana Capizzano, Haidn Foster, Zachary Higgins, Parker Howard, Melissa Johns, Alyssa Kelder, Max Langer, Mateo Mendoza, John Moon, Mara Nickel, Keith O’Conor, and Alison Perry

Human cytomegalovirus-mediated immunomodulation: Effects on glioblastoma progression

Haidn Foster, Ilya V. Ulasov, and Charles S. Cobbs

The presence of human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM), first established in 2002, has developed into an area of considerable interest and controversy. Numerous studies have found evidence of possible HCMV infection of GBM tumor cells as well as myriad onco- and immunomodulatory properties exhibited by HCMV antigens and transcripts, while recent reports have failed to detect HCMV particles in GBM and question the virus' role in tumor progression. This review highlights the known immunomodulatory properties of HCMV, independent of GBM infection status, that help drive the virus from peripheral blood into the vital tissues and subsequently dampen local immune response, assisting GBM tumors in evading immune surveillance and contributing to the disease's poor prognosis. Emerging antiviral approaches to treating GBM, including antiviral drugs and immunotherapies directed against HCMV, are also examined.

Precision knockdown of EGFR gene expression using radio frequency electromagnetic energy

Ilya V. Ulasov, Haidn Foster, Mike Butters, Jae-Guen Yoon, Tomoko Ozawa, Theodore Nicolaides, Xavier Figueroa, Parvinder Hothi, Michael Prados, John Butters, and Charles S. Cobbs

Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30-70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs. control treated cells. Specificity for EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array. The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures, LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival. The outcomes of this study demonstrate that an RFE signal can induce a specific siRNA-like effect on cells. This technology opens vast possibilities of targeting a broader range of molecules with applications in medicine, agriculture and other areas.

Breaking down barriers: Trilby as an entrance point to genius through the individual and gender transgression

Haidn Foster