Biology subjects

McCutcheon, I. E.

Publications and source records attributed to McCutcheon, I. E..

3 recordsLinked to original sources

bioRxiv2026

Cross-species Study of Canine and Human Peripheral Nerve Sheath Tumors: Clinical and Molecular Perspectives

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas. An obstacle to treating MPNSTs is a lack of effective systemic therapies. Although over 70% of human MPNSTs have lost or inactivated the epigenome regulator polycomb repressive complex 2 (PRC2), its activity and contribution to canine PNST progression remain unclear. This study compared canine peripheral nerve sheath tumors (PNSTs) and human MPNSTs across biological and clinical features, including PRC2 activity. Immunohistochemical analysis was performed for a human tissue microarray of 54 neurofibromas and 139 MPNSTs, and 63 canine PNSTs for H3K27me3, a repressive histone mark deposited by intact PRC2, and H3K27ac, which increases globally upon H3K27me3 loss. To understand the genomic alterations present in canine PNSTs, we analyzed tumor mutation burden, copy number alteration, and transcriptomes of eight canine PNST/normal pairs. The results suggested that H3K27me3 loss and associated gain of H3K27ac epigenetically drive human and canine tumors. These findings warrant further studies to evaluate whether these epigenetic deregulations alter similar gene signatures across species.

cancer biology↗

bioRxiv2021

New cellular models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models led us to generate additional cell lines to study these rare cancers further. Patient-derived tumors were used to establish 5 new UPS models, including one radiation-associated UPS--UPS060.1, UPS271.1, UPS511, UPS0103, and RIS620--and 3 new models of MPNST--MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of each cell line was determined by either subcutaneous injection of cells or implantation of tumor tissue into immunocompromised mice. UPS060.1, UPS271.1, and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Mutation analysis of a panel of genes frequently mutated in sarcomas showed that two of the three MPNST cell lines had NF1 mutations. Two of the three MPNST cell lines had mutations in polycomb repressive complex 2 members. These new cellular models provide the scientific community with powerful tools for detailed studies of sarcomagenesis and investigate novel therapies for UPS and MPNST.

cancer biology↗

bioRxiv2018

Pituitary Carcinoma: The University of Texas MD Anderson Cancer Center Experience.

Background: Pituitary carcinoma (PC) is an aggressive neuroendocrine tumor diagnosed when a pituitary adenoma (PA) becomes metastatic. PCs are typically resistant to therapy and frequently recur. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits accurate assessment. Methods: We describe a single-center experience in managing PC over a 22-year period and review previously published PC series. Results: 17 patients were identified. Median age at PC diagnosis was 44 years (range 16-82), and the median PA-to-PC conversion time was 5 years (range 1-29). Median follow-up was 28 months (range 8-158) with 7 deaths. Most PC were hormone-positive based on immunohistochemistry (n=12): ACTH (n=5), PRL (n=4), LH/FSH (n=2), GH (n=1). All patients underwent at least one resection and one course of radiation after PC diagnosis. Immunohistochemistry showed high Ki-67 labeling index (>3%) in 10/15 cases. Eight patients (47%) had metastases only to the CNS, and 6 (35%) had combined CNS and systemic metastases. The most commonly used chemotherapy was TMZ, and TMZ-based therapy was associated with the longest period of disease control in 12 (71%) cases, as well as the longest period from PC diagnosis to first progression in 8 (47%) cases. The 2, 3 and 5-year survival rate of the entire cohort was 71%, 59% and 35%, respectively. All patients surviving >5 years were treated with TMZ-based therapy. Conclusions: PC treatment requires a multidisciplinary approach and multimodality therapy including surgery, radiation and chemotherapy. TMZ-based therapy was associated with higher survival rates and longer disease control.\n\nPrecisWe describe 17 PC patients who were diagnosed and treated at MDACC over a 22-year period. We have found that TMZ-based therapy correlated with longer disease control and higher survival rate.

cancer biology↗