Browsing by Author "Savage, Jesse J."

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Cyclooxygenase-2 Expression in Hamster and Human Pancreatic Neoplasia
    (Elsevier, 2006-06) Crowell, Pamela L.; Schmidt, C. Max; Yip-Schneider, Michele T.; Savage, Jesse J.; Hertzler II, Dean A.; Cummings, William O.; Biochemistry and Molecular Biology, School of Medicine
    Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation.
  • Thumbnail Image
    Item
    Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial
    (Biomed Central, 2018-12-20) Huff, Wei X.; Agrawal, Namita; Shapiro, Scott; Miller, James; Kulwin, Charles; Shah, Mitesh; Savage, Jesse J.; Payner, Troy; Vortmeyer, Alexander; Watson, Gordon; Dey, Mahua; Neurological Surgery, School of Medicine
    BACKGROUND: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases. METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival.
  • Thumbnail Image
    Item
    Endoscopic transpterygoid approach for resection of trigeminal neurotropic melanoma: Case report and technical note
    (Elsevier, 2019-08-21) Kovanda, Timothy J.; Rabbani, Cyrus; Ting, Jonathan Y.; Bonnin, Jose M.; Williams, Brian J.; Savage, Jesse J.; Neurological Surgery, School of Medicine
    Background The endoscopic transpterygoid approach to Meckel's cave is an established technique for resection of trigeminal schwannomas. Modern endoscopes provide excellent intraoperative visualization of anatomic structures and relevant pathology while the minimally-invasive nature of the procedure allows for rapid postoperative recovery. Neurotropic melanoma is a rare clinical entity that often involves the head and neck and can lead to cranial neuropathies when nerve invasion occurs. Pathological diagnosis of this lesion can be challenging due to its rarity and lack of classic melanoma markers such as Melan-A and HMB-45. Case description In this article, the authors describe the endoscopic transpterygoid approach to a neurotropic melanoma involving the maxillary and infraorbital nerves. To our knowledge, this is the first use of this surgical approach for resection of neurotropic melanoma. Conclusions Endoscopic approaches to the trigeminal nerve allow for safe and effective resection of these lesions. However, a strong understanding of the microsurgical anatomy is necessary prior to such an undertaking.
  • Thumbnail Image
    Item
    Geniculate neuralgia successfully treated with microvascular decompression
    (Elsevier, 2020-03) Pecoraro, Nathan C.; Zaazoue, Mohamed A.; Koivuniemi, Andrew S.; Savage, Jesse J.; Neurological Surgery, School of Medicine
    Background First described by John Nottingham in 1857, geniculate neuralgia remains a rare condition associated with vascular compression of the nervus intermedius by the anterior inferior cerebellar artery (AICA), which results in paroxysmal unilateral periauricular pain. Furthermore, limited and controversial treatment options for symptom relief exist given the rarity of the condition and limited cases reported in the literature. Case description This is a case of a 37-year-old one-pack-per-day smoker with diabetes mellitus who presented to our clinic for evaluation of episodic lancinating pain localizing to the right periauricular region. The patients symptoms were attempted to be managed medically, however, remained refractory to medical management for a period greater than one year. The patient’s exam demonstrated a trigger point slightly anterior and inferior to the right tragus, and the pain was reproducible when touched or tapped. The patient was otherwise neurologically intact. Magnetic resonance imaging (MRI) was performed and demonstrated a loop of the AICA in contact with the root entry zone of the facial nerve. This patient was offered an elective microvascular decompression (MVD) for treatment of geniculate neuralgia. Conclusions Surgical microvascular decompression is a safe and effective treatment option for patients suffering from neuralgia refractory to medical therapy. Furthermore, our case report demonstrates that MVD is an effective treatment option for patients suffering from geniculate neuralgia with imaging evidence of AICA compression of the nervus intermedius that is refractory to medical management.
  • Thumbnail Image
    Item
    Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure
    (Elsevier, 2024-03-27) Shireman, Jack M.; White, Quinn; Ni, Zijian; Mohanty, Chitrasen; Cai, Yujia; Zhao, Lei; Agrawal, Namita; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of Medicine
    Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.
  • Thumbnail Image
    Item
    Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge
    (medRxiv, 2023-04-24) Shireman, Jack M.; White, Quinn; Agrawal, Namita; Ni, Zijian; Chen, Grace; Zhao, Lei; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of Medicine
    Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.