Noninvasive Monitoring of Radiation-Induced Salivary Gland Vascular Injury.

Xerostomia is a common side effect of radiation therapy (RT) in patients with head and neck cancer. However, limited information is available on the temporal dynamics of parenchymal and vascular changes in salivary glands following RT. To address this gap in knowledge, we conducted experimental studies in mice employing ultrasound (US) with coregistered photoacoustic imaging (PAI) to noninvasively assess the early and late changes in salivary gland size, structure, vascularity, and oxygenation dynamics following RT. Multiparametric US-PAI of salivary glands was performed in immune-deficient and immune-competent mice before and after RT along with correlative sialometry and ex vivo histologic-immunohistochemical validation. US revealed reduction in gland volume and an early increase in vascular resistance postradiation. This was accompanied by a reduction in glandular oxygen consumption on PAI. Imaging data correlated strongly with salivary secretion and histologic evidence of acinar damage. The magnitude and kinetics of radiation response were impacted by host immune status, with immunodeficient mice showing early and more pronounced vascular injury and DNA damage response compared to immunocompetent animals. Our findings demonstrate the ability of noninvasive US-PAI to monitor dynamic changes in salivary gland hemodynamics following radiation and highlight the impact of the host immune status on salivary gland radiation injury.

Impact of Age on Disease Progression and Microenvironment in Oral Cancer.

Despite the recognized link between aging and cancer, most preclinical studies in experimental tumor models are conducted with 6- to 8-wk-old rodents. The goal of the present study was to examine the impact of age on tumor incidence, growth, and microenvironmental characteristics in mouse models of head and neck squamous cell carcinoma (HNSCC). Experimental studies were conducted with the 4-nitroquinoline-oxide (4NQO) oral carcinogenesis model and orthotopic FaDu HNSCC xenografts, established in young (7 to 12 wk of age) and old (65 to 70 wk of age) female C57BL/6 mice ( n = 44; 4NQO model) and severe combined immunodeficient mice ( n = 13; HNSCC xenografts). Noninvasive whole body magnetic resonance imaging revealed increased subcutaneous and visceral fat in aging animals of both strains. On histologic examination, a higher incidence ( P < 0.001) of severe dysplasia/invasive squamous cell carcinoma was observed in old mice (92%) as compared with young mice (69%). Old C57BL/6 mice exposed to 4NQO exhibited increased incidence of oral and extraoral (peritoneal masses) neoplasms (42%) versus their young counterparts ( P < 0.05). The incidence of extraoral neoplasms was significantly lower (16%) in the younger cohort. Interestingly, no difference in growth rate and oxygen saturation was observed between orthotopic FaDu xenografts established in old and young severe combined immunodeficient mice. Our observations suggest that host age may have an impact on the growth kinetics and progression of HNSCC in the immunocompetent 4NQO model. Further investigation into the impact of aging on tumor response to preventive and therapeutic intervention is warranted.

Nodular pulmonary light chain deposition disease: an entity associated with Sjögren syndrome or marginal zone lymphoma.

BACKGROUND: Light chain deposition disease (LCDD) is usually a systemic disorder characterised by non-amyloid monoclonal immunoglobulin light chain deposition in tissues. Localised nodular pulmonary (NP) LCDD is a rare and poorly characterised entity and, owing to the difficulties in diagnosis, limited data are available. METHODS: We investigated the clinical, radiological and pathological characteristics of a series of six confidently diagnosed cases of NPLCDD. RESULTS: There were three men and three women with ages ranging from 33 to 74 years. In all cases there were single or multiple pulmonary nodules, in one case associated with cysts. Two patients had no previous history of a lymphoproliferative or autoimmune disorder, two had Sjögren syndrome (SS) and two had extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Lung biopsies led to diagnoses of MALT lymphoma in four patients, including both of those with a previous history of lymphoma and one with SS. In five cases the diagnosis was confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and in one by electron microscopy. There was no evidence of systemic LCDD in any of the cases. Five patients had an indolent course in spite of limited therapeutic intervention while, in the patient who died, the cause of death was related to the spread of the lymphoma and was not due to the pulmonary lesions. CONCLUSIONS: NPLCDD is an indolent disease, in most cases associated with MALT lymphoma or autoimmune disease.

Helicobacter pylori decreases gastric mucosal glutathione.

Activation of oxidative stress pathways may contribute to gastric epithelial damage and mutagenesis caused by Helicobacter pylori. We measured the effect of H. pylori on the concentrations of reduced glutathione (GSH), an important endogenous defense against oxidant damage, in gastric epithelial cells in vivo and in vitro. GSH concentrations were significantly lower in gastric biopsies from 19 H. pylori-infected patients than 38 normal controls, and correlated inversely with inflammatory cell numbers. In vitro, H. pylori initially increased GSH levels in AGS cells, but subsequently depleted intracellular GSH stores completely after 24 h. No GSH was detected in H. pylori. Our data suggest that diminished GSH levels with H. pylori colonization of the gastric mucosa may be due to a direct effect of the bacterium as well as through the associated inflammatory response.