Odontoid metastasis: a potential lethal complication

Nearly one third of cervical spine metastasis has a primary breast malignancy. Patients with cervical metastasis have higher mortality due to advanced stage of the malignancy. Treatment is palliative to relieve pain, prevent pathological fracture, improve mobility and function, and prolong survival. We describe a 40-year-old woman with a history of breast cancer who presented with neck and shoulder pain of 1 week duration with no neurological deficit. Following clinical examination, radiographs taken of the cervical spine was normal. Radiographs repeated 3 weeks later revealed a large lytic lesion of the odontoid occupying 70–80% of the peg. Further investigation including magnetic resonance imaging and bone scan showed no further spinal lesions. She underwent cyclical radiotherapy with complete resolution of the odontoid peg lesion and clinically was asymptomatic at 2 years. Metastatic lesions of the odontoid are atypical, and this case reinforces the necessity of early detection to evade disastrous consequences

Targeting Signal Transduction Pathways in Metastatic Breast Cancer: A Comprehensive Review

This review summarizes some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for the treatment of metastatic breast cancer patients

Long-Term Impact of Radiation on the Stem Cell and Oligodendrocyte Precursors in the Brain

Background. The cellular basis of long term radiation damage in the brain is not fully understood. Methods and Findings. We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries. Conclusions. This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursor

Evaluation of Poly-Mechanistic Antiangiogenic Combinations to Enhance Cytotoxic Therapy Response in Pancreatic Cancer

Gemcitabine (Gem) has limited clinical benefits in pancreatic ductal adenocarcinoma (PDAC). The present study investigated combinations of gemcitabine with antiangiogenic agents of various mechanisms for PDAC, including bevacizumab (Bev), sunitinib (Su) and EMAP II. Cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. In vivo experiments were performed via murine xenografts. Inhibition of in vitro proliferation of AsPC-1 PDAC cells by gemcitabine (10 µM), bevacizumab (1 mg/ml), sunitinib (10 µM) and EMAP (10 µM) was 35, 22, 81 and 6 percent; combination of gemcitabine with bevacizumab, sunitinib or EMAP had no additive effects. In endothelial HUVECs, gemcitabine, bevacizumab, sunitinib and EMAP caused 70, 41, 86 and 67 percent inhibition, while combination of gemcitabine with bevacizumab, sunitinib or EMAP had additive effects. In WI-38 fibroblasts, gemcitabine, bevacizumab, sunitinib and EMAP caused 79, 58, 80 and 29 percent inhibition, with additive effects in combination as well. Net in vivo tumor growth inhibition in gemcitabine, bevacizumab, sunitinib and EMAP monotherapy was 43, 38, 94 and 46 percent; dual combinations of Gem+Bev, Gem+Su and Gem+EMAP led to 69, 99 and 64 percent inhibition. Combinations of more than one antiangiogenic agent with gemcitabine were generally more effective but not superior to Gem+Su. Intratumoral proliferation, apoptosis and microvessel density findings correlated with tumor growth inhibition data. Median animal survival was increased by gemcitabine (26 days) but not by bevacizumab, sunitinib or EMAP monotherapy compared to controls (19 days). Gemcitabine combinations with bevacizumab, sunitinib or EMAP improved survival to similar extent (36 or 37 days). Combinations of gemcitabine with Bev+EMAP (43 days) or with Bev+Su+EMAP (46 days) led to the maximum survival benefit observed. Combination of antiangiogenic agents improves gemcitabine response, with sunitinib inducing the strongest effect. These findings demonstrate advantages of combining multi-targeting agents with standard gemcitabine therapy for PDAC

A strong conditional mutualism limits and enhances seed dispersal and germination of a tropical palm

Seed predation and seed dispersal can have strong effects on early life history stages of plants. These processes have often been studied as individual effects, but the degree to which their relative importance co-varies with seed predator abundance and how this influences seed germination rates is poorly understood. Therefore, we used a combination of observations and field experiments to determine the degree to which germination rates of the palm Astrocaryum mexicanum varied with abundance of a small mammal seed predator/disperser, Heteromysdesmarestianus, in a lowland tropical forest. Patterns of abundance of the two species were strongly related; density of H. desmarestianus was low in sites with low density of A. mexicanum and vice versa. Rates of predation and dispersal of A. mexicanum seeds depended on abundance of H. desmarestianus; sites with high densities of H. desmarestianus had the highest rates of seed predation and lowest rates of seed germination, but a greater total number of seeds were dispersed and there was greater density of seedlings, saplings, and adults of A. mexicanum in these sites. When abundance of H. desmarestianus was experimentally reduced, rates of seed predation decreased, but so did dispersal of A. mexicanum seeds. Critically, rates of germination of dispersed seeds were 5 times greater than undispersed seeds. The results suggest that the relationship between A. mexicanum and H. desmarestianus is a conditional mutualism that results in a strong local effect on the abundance of each species. However, the magnitude and direction of these effects are determined by the relative strength of opposing, but related, mechanisms. A. mexicanum nuts provide H. desmarestianus with a critical food resource, and while seed predation on A. mexicanum nuts by H. desmarestianus is very intense, A. mexicanum ultimately benefits because of the relatively high germination rates of its seeds that are dispersed by H. desmarestianus

Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer

Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity. The analysis of neutrophils from cancer patients showed a higher proportion of neutrophils positive for intracellular H3Cit compared to severely ill patients. Moreover, the presence of plasma H3Cit in cancer patients strongly correlated with neutrophil activation markers neutrophil elastase (NE) and myeloperoxidase (MPO), and the inflammatory cytokines interleukin-6 and -8, known to induce NETosis. In addition, we show that high levels of circulating H3Cit strongly predicted poor clinical outcome in our cohort of cancer patients with a 2-fold increased risk for short-term mortality. Our results also corroborate the association of NE, interleukin-6 and -8 with poor clinical outcome. Taken together, our results are the first to unveil H3Cit as a potential diagnostic and prognostic blood marker associated with an exacerbated inflammatory response in patients with advanced cancer

Moose and snowshoe hare competition and a mechanistic explanation from foraging theory

Moose ( Alces alces ) and snowshoe hare ( Lepus americanus ) appear to compete with each other. This was determined using the “natural experiments” of populations found in sympatry and allopatry on islands at Isle Royale National Park, Michigan, and manipulated exclosures. The population densities from these areas are fit to a series of competition models based upon different competitive mechanisms (Schoener 1974a), using non-linear regression techniques. A model of competition for food where the food can be separated into exclusively used and shared categories is found to predict observed densities of moose and hare best. Finally, the competition model's parameters (fraction of food shared and competition coefficients) are shown to agree with values predicted independently from a foraging model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47750/1/442_2004_Article_BF00396753.pd

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function