ColoPrint significantly improves the prognostic accuracy of pathologic factors and MSI in patients with stage II and III CRC and facilitates the identification of patients with stage II disease who may be safely managed without chemotherapy.
Tumor-associated macrophages (TAMs) and microglia (MG) are potent regulators of glioma development and progression. However, the dynamic alterations of distinct TAM populations during the course of therapeutic intervention, response, and recurrence have not yet been fully explored. Here, we investigated how radiotherapy changes the relative abundance and phenotypes of brain-resident MG and peripherally recruited monocyte-derived macrophages (MDMs) in glioblastoma. We identified radiation-specific, stage-dependent MG and MDM gene expression signatures in murine gliomas and confirmed altered expression of several genes and proteins in recurrent human glioblastoma. We found that targeting these TAM populations using a colony-stimulating factor–1 receptor (CSF-1R) inhibitor combined with radiotherapy substantially enhanced survival in preclinical models. Our findings reveal the dynamics and plasticity of distinct macrophage populations in the irradiated tumor microenvironment, which has translational relevance for enhancing the efficacy of standard-of-care treatment in gliomas.
Gastric carcinogenesis is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. We analysed the patterns of chromosomal instability in 35 gastric carcinomas and their clinical correlations. With microarray competitive genomic hybridization, genomewide chromosomal copy number changes can be studied with high resolution and sensitivity. A genomewide scanning array with 2275 BAC and P1 clones spotted in triplicate was used. This array provided an average resolution of 1.4 Mb across the genome. Patterns of chromosomal aberrations were analysed by hierarchical cluster analysis of the normalized log 2 tumour to normal fluorescence ratios of all clones, and cluster membership was correlated to clinicopathological data including survival. Hierarchical cluster analysis revealed three groups with different genomic profiles that correlated significantly with lymph node status (P ¼ 0.02). Moreover, gastric cancer cases from cluster 3 showed a significantly better prognosis than those from clusters 1 and 2 (P ¼ 0.02). Genomic profiling of gastric adenocarcinomas based on microarray analysis of chromosomal copy number changes predicted lymph node status and survival. The possibility to discriminate between patients with a high risk of lymph node metastasis could clinically be helpful for selecting patients for extended lymph node resection.
Pathohistological hepatic abnormalities are common in non-thiopurine using IBD patients. The association between thiopurine use, NRH and sinusoidal dilatation may be weaker than as reported in recent literature, as there is relatively high background prevalence in selected series.
The morphological development of motoneuron pools of two hindlimb muscles of the rat, soleus (SOL) and tibialis anterior (TA), was studied in rats ranging in age between 8 and 30 postnatal days (P8-P30). Motoneurons were retrogradely labelled by injecting a cholera toxin B subunit solution directly into the muscles. This resulted in extensive labelling of motoneurons as well as their dendritic trees. The distribution of cross sectional areas of neuronal somata was determined for both muscles at various ages. Somal size increased considerably between P8 and P12, whereas growth was moderate between P12 and P20. The size distribution of SOL motoneurons was bimodal from P20, whereas the size distribution of TA motoneurons remained largely unimodal. The morphological development of the dendritic tree was studied qualitatively. The development of dendritic arborization within the SOL and the TA motoneuron pool showed major differences. The arborization pattern of dendrites of TA motoneurons was basically multipolar at all ages. In contrast, dendrites of SOL neurons tended to line up with the rostro-caudal axis and became organized in longitudinal bundles from P16 onwards. The relatively late appearance of dendrite bundles in the soleus motoneuron pool suggests that they might be related to the fine-tuning of neuronal activity rather than patterning of motor activity. The occurrence of dendrite bundles in SOL and not in TA motoneuron pools suggests that they may be related to the different afferent organization of this postural muscle or to its tonic activation pattern.
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