The immune infiltrate in colorectal cancer has been correlated with outcome, such that individuals with higher infiltrations of T cells have increased survival independent of the disease stage. For patients with lower immune infiltrates, overall survival is limited....
PURPOSE: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.)...
Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural...
An important characteristic of kilovoltage therapy is the narrow penumbra obtainable with a well designed collimator system. A graphical illustration of applicator geometry is used to show that undesirable penumbral broadening and consequent reduction of field...
BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4) blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against...
Although surgery is usually the first-line treatment for nonmelanoma skin cancers, radiotherapy (RT) may be indicated in selected cases. Radiation therapy as primary therapy can result in excellent control rates, cosmetics, and quality of life. Brachytherapy is a...
The hypothalamus is the central regulator of a broad range of homeostatic and instinctive physiological processes, such as the sleep-wake cycle, food intake, and sexually dimorphic behaviors. These behaviors can be modified by various environmental and physiological cues, although the molecular and cellular mechanisms that mediate these effects remain poorly understood. Recently, it has become clear that both the juvenile and adult hypothalamus exhibit ongoing neurogenesis, which serve to modify homeostatic neural circuitry. In this report, we share new findings on the contributions of sex-specific and dietary factors to regulating neurogenesis in the hypothalamic mediobasal hypothalamus, a recently identified neurogenic niche. We report that high fat diet (HFD) selectively activates neurogenesis in the median eminence (ME) of young adult female but not male mice, and that focal irradiation of the ME in HFD-fed mice reduces weight gain in females but not males. These results suggest that some physiological effects of high fat diet are mediated by the stimulation of ME neurogenesis in a sexually dimorphic manner. We discuss these results in the context of recent advances in understanding the cellular and molecular mechanisms that regulate neurogenesis in postnatal and adult hypothalamus.
Daniel A. Lee, Sooyeon Yoo, Thomas Pak, Juan Salvatierra, Esteban Velarde, Susan Aja, and Seth Blackshaw
Download Paper
Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT’s resultant histologic and BBB changes, may aid future brain tumor research.
Baumann BC, Benci JL, Santoiemma PP, Chandrasekaran S, Hollander AB, Kao GD, Dorsey JF.
Download Paper
The technical evolution of radiation therapy for brain cancer has improved both the efficacy of individual radiation treatments and patient safety. The advent of computed tomography (CT)-based planning marked an important initial shift toward target-directed treatment (1). Treatment planning accuracy was further increased by fusing CT planning images with positron emission tomography (PET) and magnetic resonance imaging (MRI) scans (2, 3). Additionally, cone beam CT images acquired before each fraction were added to compensate for any deviations from the simulation CT (4).
Joshua T. Dilworth, Sarah A. Krueger, George D. Wilson, Brian Marples
Download Paper