Lisa M. Rogers

Bio: Lisa M. Rogers is an academic researcher from Vanderbilt University Medical Center. The author has contributed to research in topics: Macrophage & Proinflammatory cytokine. The author has an hindex of 16, co-authored 35 publications receiving 710 citations. Previous affiliations of Lisa M. Rogers include University of Michigan & Vanderbilt University.

Macrophage Extracellular Traps: A Scoping Review.

Abstract: Tissue macrophages are derived from either circulating blood monocytes that originate in the bone marrow, or embryonic precursors that establish residence in tissues and are maintained independent of bone marrow progenitors. Macrophages perform diverse functions including tissue repair, the maintenance of homeostasis, and immune regulation. Recent studies have demonstrated that macrophages produce extracellular traps (ETs). ETs are an immune response by which a cell undergoes “ETosis” to release net-like material, with strands composed of cellular DNA that is studded with histones and cellular proteins. ETs are thought to immobilize and kill microorganisms, but also been implicated in disease pathology including aseptic inflammation and autoimmune disease. We conducted a scoping review to define what is known from the existing literature about the ETs produced by monocytes or macrophages. The results suggest that macrophage ETs (METs) are produced in response to various microorganisms and have similar features to neutrophil ETs (NETs), in that METs are produced by a unique cell death program (METosis), which results in release of fibers composed of DNA and studded with cellular proteins. METs function to immobilize and kill some microorganisms, but may also play a role in disease pathology.

Association of 11C-methionine PET uptake with site of failure after concurrent temozolomide and radiation for primary glioblastoma multiforme.

Abstract: Purpose: To determine whether increased uptake on 11C-methionine-PET (MET-PET) imaging obtained before radiation therapy and temozolomide is associated with the site of subsequent failure in newly diagnosed glioblastoma multiforme (GBM). Methods: Patients with primary GBM were treated on a prospective trial with dose- escalated radiation and concurrent temozolomide. As part of the study, MET-PET was obtained before treatment but was not used for target volume definition. Using automated image registration, we assessed whether the area of increased MET-PET activity (PET gross target volume [GTV]) was fully encompassed within the high-dose region and compared the patterns of failure for those with and without adequate high-dose coverage of the PET-GTV. Results: Twenty-six patients were evaluated with a median follow-up of 15 months. Nineteen of 26 had appreciable (>1 cm{sup 3}) volumes of increased MET-PET activity before treatment. Five of 19 patients had PET-GTV that was not fully encompassed within the high-dose region, and all five patients had noncentral failures. Among the 14 patients with adequately covered PET-GTV, only two had noncentral treatment failures. Three of 14 patients had no evidence of recurrence more than 1 year after radiation therapy. Inadequate PET-GTV coverage was associated with increased risk of noncentral failures. (p

Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study.

Abstract: Purpose: To assess if interval changes in metabolic status in normal cerebral tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift imaging) proton spectroscopy. Materials and Methods: Eleven patients with primary brain tumors undergoing cranial radiation therapy (RT) were included. 2D-CSI MRS was performed before, during, and after the course of RT with the following parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16 16. The metabolic ratios choline/creatine (Cho/Cr), N-acetylaspartate (NAA)/Cr, and NAA/Cho in normal brain tissue were calculated. Results: NAA/Cr and Cho/Cr were significantly decreased at week 3 during RT and at 1 month and 6 months after RT compared to values prior to RT (P 0.01). The NAA/Cr ratio decreased by 0.19 0.05 (mean standard error [SE]) at week 3 of RT, 0.14 0.06 at the last week of RT, 0.14 0.05 at 1 month after RT, and 0.30 0.08 at 6 months after RT compared to the pre-RT value of 1.43 0.04. The Cho/Cr ratio decreased by 0.27 0.05 at week 3 of RT, 0.11 0.05 at the last week of RT, 0.26 0.05 at 1 month after RT and 0.25 0.07 at 6 months after RT from the pre-RT value of 1.29 0.03. Changes in Cho/Cr were correlated with the interaction of the radiation dose and dose-volume at week 3 of RT, during the last week of RT (P 0.005), and at 1 month after RT (P 0.017). Conclusion: The results of this study suggest that MRS can detect early metabolic changes in normal irradiated brain tissue.

Human Intestinal Lamina Propria CD1c + Dendritic Cells Display an Activated Phenotype at Steady State and Produce IL-23 in Response to TLR7/8 Stimulation

Abstract: Intestinal dendritic cells (DCs) play key roles in mediating tolerance to commensal flora and inflammatory responses against mucosal pathogens. The mechanisms by which intestinal "conditioning" influences human DC responses to microbial stimuli remain poorly understood. Infections with viruses, such as HIV-1, that target mucosal tissue result in intestinal epithelial barrier breakdown and increased translocation of commensal bacteria into the lamina propria (LP). It is unclear whether innate LP DC responses to concurrent viral and bacterial stimuli influence mucosal HIV-1 pathogenesis. In this study, direct ex vivo phenotype and in vitro constitutive cytokine production of CD1c+ DCs in human intestinal LP were compared with those in peripheral blood (PB). To evaluate innate responses to viral and bacterial stimuli, intracellular cytokine production by LP and PB DCs following stimulation with ligands for TLRs 2, 4, 5, and 7/8 was evaluated. At steady state, LP CD1c+ DCs expressed higher levels of activation markers (CD40, CD83, CD86, HLA-DR, and CCR7) than did PB CD1c+ DCs, and higher frequencies of LP CD1c+ DCs constitutively produced IL-6 and -10 and TNF-alpha. LP DCs had blunted cytokine responses to TLR4 ligand and TLR5 ligand stimulation relative to PB DCs, yet similarly produced IL-10 in response to TLR2 ligand. Only synthetic TLR7/8 ligand, a mimic of viral ssRNA, induced IL-23 production by LP CD1c+ DCs, and this proinflammatory cytokine response was synergistically enhanced following combined TLR7/8 and TLR4 stimulation. These findings highlight a potential mechanism by which viruses like HIV-1 may subvert homeostatic mechanisms and induce inflammation in the intestinal mucosa.

Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes.

Abstract: Puerperal sepsis is a leading cause of maternal mortality worldwide. Streptococcus pyogenes [group A Streptococcus ; (GAS)] is a major etiologic agent of severe postpartum sepsis, yet little is known regarding the pathogenesis of these infections. Tissue macrophages provide innate defense against GAS, and their actions are highly regulated. The intracellular second messenger cAMP can negatively regulate macrophage actions against GAS. Because leukotriene (LT) B 4 has been shown to suppress intracellular cAMP in macrophages, we hypothesized that it could enhance innate defenses against GAS. We assessed the capacity of LTB 4 to modulate antistreptococcal actions of human macrophages, including placental and decidual macrophages and used a novel intrauterine infection model of GAS in mice lacking the 5-lipoxygenase enzyme to determine the role of endogenous LTs in host defense against this pathogen. Animals lacking 5-lipoxygenase were significantly more vulnerable to intrauterine GAS infection than were wild-type mice and showed enhanced dissemination of bacteria out of the uterus and a more robust inflammatory response than did wild-type mice. In addition, LTB 4 reduced intracellular cAMP levels via the BLT1 receptor and was a potent stimulant of macrophage phagocytosis and NADPH oxidase–dependent intracellular killing of GAS. Importantly, interference was observed between the macrophage immunomodulatory actions of LTB 4 and the cAMP-inducing lipid PGE 2 , suggesting that interplay between pro- and anti-inflammatory compounds may be important in vivo. This work underscores the potential for pharmacological targeting of lipid mediator signaling cascades in the treatment of invasive GAS infections.

Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas.

Abstract: This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose ((18)F-FDG) and amino acid tracers ((11)C-MET, (18)F-FET, and (18)F-FDOPA). An increasing number of studies have been published on PET imaging in the setting of diagnosis, biopsy, and resection as well radiotherapy planning, treatment monitoring, and response assessment. Recommendations are based on evidence generated from studies which validated PET findings by histology or clinical course. This guideline emphasizes the clinical value of PET imaging with superiority of amino acid PET over glucose PET and provides a framework for the use of PET to assist in the management of patients with gliomas.

Radiation-induced brain injury: A review

Abstract: Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their integration at clinically relevant doses and schedules. Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.