Identification of prognostic biomarkers for breast cancer brain metastases based on the bioinformatics analysis

PurposeThe prognosis of breast cancer (BC) patients who develop into brain metastases (BMs) is very poor. Thus, it is of great significance to explore the etiology of BMs in BC and identify the key genes involved in this process to improve the survival of BC patients with BMs.Patients and methodsThe gene expression data and the clinical information of BC patients were downloaded from TCGA and GEO database. Differentially expressed genes (DEGs) in TCGA-BRCA and GSE12276 were overlapped to find differentially expressed metastatic genes (DEMGs). The protein-protein interaction (PPI) network of DEMGs was constructed via STRING database. ClusterProfiler R package was applied to perform the gene ontology (GO) enrichment analysis of DEMGs. The univariate Cox regression analysis and the Kaplan-Meier (K-M) curves were plotted to screen DEMGs associated with the overall survival and the metastatic recurrence survival, which were identified as the key genes associated with the BMs in BC. The immune infiltration and the expressions of immune checkpoints for BC patients with brain relapses and BC patients with other relapses were analyzed respectively. The correlations among the expressions of key genes and the differently infiltrated immune cells or the differentially expressed immune checkpoints were calculated. The gene set enrichment analysis (GSEA) of each key gene was conducted to investigate the potential mechanisms of key genes involved in BC patients with BMs. Moreover, CTD database was used to predict the drug-gene interaction network of key genes.ResultsA total of 154 DEGs were identified in BC patients at M0 and M1 in TCGA database. A total of 667 DEGs were identified in BC patients with brain relapses and with other relapses. By overlapping these DEGs, 17 DEMGs were identified, which were enriched in the cell proliferation related biological processes and the immune related molecular functions. The univariate Cox regression analysis and the Kaplan-Meier curves revealed that CXCL9 and GPR171 were closely associated with the overall survival and the metastatic recurrence survival and were identified as key genes associated with BMs in BC. The analyses of immune infiltration and immune checkpoint expressions showed that there was a significant difference of the immune microenvironment between brain relapses and other relapses in BC. GSEA indicated that CXCL9 and GPR171 may regulate BMs in BC via the immune-related pathways.ConclusionOur study identified the key genes associated with BMs in BC patients and explore the underlying mechanisms involved in the etiology of BMs in BC. These findings may provide a promising approach for the treatments of BC patients with BMs.     

Histological changes in spleen and lymph nodes of mice administered cyclophosphamide and levan

Summary Morphological changes in spleen and lymph nodes of C57B1 mice induced by the cytotoxic agent cyclophosphamide and the polysaccharide levan, separately and in combination were studied. In the spleen, an early decrease (phase 1) and a late increase (phase 2) in weight were found to result from all drug administrations. The hypocellularity of phase 1 was due to a depletion in the white pulp affecting mainly the B-region. Splenic weight decrease was parallel to B-cell depletion and most marked in animals exposed to cyclophosphamide with levan. The splenomegaly observed during phase 2 with all treatments was due to extramedullary hematopoiesis in the red pulp. In the lymph nodes, administration of cyclophosphamide and levan produced opposite effects on the B-cell region: cyclophosphamide eliminated the germinal centers for 8 days, but levan seemed to enhance B-cell activity. In animals given both cyclophosphamide and levan, inhibition of B-cell activity began earlier than with cyclophosphamide alone. Levan does not antagonize the suppressive effect of cyclophosphamide on the B-cell component at the early phase when the drugs are given together.     

Micropropagation of <Emphasis Type="Italic">Pongamia pinnata</Emphasis> through enhanced axillary branching

A complete protocol is presented for the first time for the micropropagation of Pongamia pinnata, a biofuel tree, using cotyledonary nodes derived from axenic seedlings. Multiple shoots were induced in vitro from nodal segments through forced axillary branching. Murashige and Skoog (MS) medium supplemented with 7.5 μM benzylaminopurine (BAP) induced up to 6.8 shoots per node with an average shoot length of 0.67 cm in 12 d. Incorporation of 2.5 μM gibberellic acid (GA₃) in the medium during the first subculture after establishment and initiation of shoot buds significantly improved the shoot elongation. Single use of GA₃ during the first subculture eliminated the need for prolonged culturing on BAP medium. Further use of GA₃ in the medium was not useful. Shoot culture was established for at least two subcultures without loss of vigor by repeatedly subculturing the original cotyledonary node on shoot multiplication medium followed by shoot elongation medium after each harvest of the newly formed shoots. Thus, from a single cotyledonary node, about 16–18 shoots were obtained in 60 d. Shoots formed in vitro were rooted on full-strength MS medium supplemented with 1.0 μM indole butyric acid (IBA). Plantlets were successfully acclimated, established in soil, and transferred to the nursery.     

Gut dysbiosis promotes the breakdown of oral tolerance mediated through dysfunction of mucosal dendritic cells

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Sentinel lymph node detection by combining nonradioactive techniques with contrast agents: State of the art and prospects

The status of sentinel lymph nodes (SLNs) has a substantial prognostic value because these nodes are the first place where cancer cells accumulate along their spreading route. Routine SLN biopsy (“gold standard”) involves peritumoral injections of radiopharmaceuticals, such as technetium-99m, which has obvious disadvantages. This review examines the methods used as “gold standard” analogs to diagnose SLNs. Nonradioactive preoperative and intraoperative methods of SLN detection are analyzed. Promising photonic tools for SLNs detection are reviewed, including NIR-I/NIR-II fluorescence imaging, photoswitching dyes for SLN detection, in vivo photoacoustic detection, imaging and biopsy of SLNs. Also are discussed methods of SLN detection by magnetic resonance imaging, ultrasonic imaging systems including as combined with photoacoustic imaging, and methods based on the magnetometer-aided detection of superparamagnetic nanoparticles. The advantages and disadvantages of nonradioactive SLN-detection methods are shown. The review concludes with prospects for the use of conservative diagnostic methods in combination with photonic tools.     

Comparison of Monoclonal Antibodies Aua1 and Ber Ep4 With Anti-Cea For Detecting Carcinoma Cells In Serous Effusions and Distinguishing Them From Mesothelial Cells

Commercially available monoclonal antibodies AUA1, BER EP4 and carcinoembryonic antigen (CEA) were applied to cell blocks from 95 serous effusions. AUA1 and BER EP4 were reactive with 89% of effusions known to contain carcinoma cells, and anti-CEA with 71%. They also reacted with cells in two effusions from patients with malignant disease which were regarded as negative on conventional cytological examination of Papanicolaou-stained smears. They were negative in all but one of the benign effusions. Using all three antibodies, 95% of effusions containing carcinoma cells were detected. Use of these antibodies could improve the cytological diagnosis of serous effusions.     

Detection of EBV RNA (EBER-1 and EBER-2) in Malaria Lymph Nodes by In Situ Hybridization

Acute Plasmodium falciparum malaria in African children allows expansion of latent Epstein-Barr virus infection, leading to colonization of lymph nodes by virus-infected lymphoblasts in 60% of cases as demonstrated by in situ hybridization for the detection of EBER-1 and EBER-2 RNA. This probably arises against a background of malaria-induced immunosuppression to EBV and concurrent lymphoid activation. The relevance of the results to the pathogenesis of African endemic Burkitt's lymphoma is discussed.     

Panbiogeographical analysis of the genus Bomarea (Alstroemeriaceae)

Aim  A panbiogeographical analysis of the genus Bomarea was undertaken in order to determine generalized tracks and biogeographical nodes, and to evaluate the current distribution of the genus based on the available tectonic information and the biogeographical regionalization of Latin America.
Location  The Neotropical region from northern Mexico to northern Argentina, and the Nearctic and Andean regions.
Method  A total of 2205 records of 101 species were analysed, representing 95% of the species assigned to Bomarea . Localities were represented on maps and their individual tracks were drawn. Based on their comparison, generalized tracks were detected and mapped. Nodes were identified in the areas where different generalized tracks were superimposed.
Results  Five generalized tracks were recovered. One is located in the Eastern Central America and Western Panamanian Isthmus provinces (Caribbean subregion, Neotropical region), which was supported by three species of Central American distribution. The four remaining generalized tracks were located in South America, in the North Andean Paramo, Cauca and Puna biogeographical provinces. These tracks were supported by species of Bomarea with an Andean distribution. Biogeographical nodes were established in the Central Andean region of Colombia, central Ecuador and central Peru.
Main conclusions  The nodes obtained for Bomarea support a hybrid origin for the Andean region, which presents diverse components from both northern and southern South America. Likewise, the track recovered between Colombia and Ecuador includes Andean and Neotropical areas, providing further support for this hypothesis. The nodes obtained are coherent with vicariant elements evident for Bomarea. Species of three clades proposed for Bomarea are distributed in specific generalized tracks.     

Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics

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