Construction and testing of a risk prediction classifier for cardia carcinoma.

OBJECTIVES: This research aimed to construct a prediction model for stages II and III cardia carcinoma (CC), and provide an effective preoperative evaluation tool for clinicians. METHODS: CC mRNA expression matrix was obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. Non-negative matrix factorization was used to cluster data to obtain subgroup information, and weighted gene co-expression network analysis was used to uncover key modules linked to different subgroups. Gene-set enrichment analysis analyzed biological pathways of different subgroups. The related pathways of multiple modules were scrutinized with Kyoto Encyclopedia of Genes and Genomes. Key modules were manually annotated to screen CC-related genes. Subsequently, quantitative real-time polymerase chain reaction assessed CC-related gene expression in fresh tissues and paraffin samples, and Pearson correlation analysis was performed. A classification model was constructed and the predictive ability was evaluated by the receiver operating characteristic curve. RESULTS: CC patients had four subgroups that were associated with brown, turquoise, red, and black modules, respectively. The CC-related modules were mainly associated with abnormal cell metabolism and inflammatory immune pathways. Then, 76 CC-elated genes were identified. Pearson correlation analysis presented that THBS4, COL14A1, DPYSL3, FGF7, and SVIL levels were relatively stable in fresh and paraffin tissues. The area under the curve of 5-gene combined prediction for staging was 0.8571, indicating good prediction ability. CONCLUSIONS: The staging classifier for CC based on THBS4, COL14A1, DPYSL3, FGF7, and SVIL has a good predictive effect, which may provide effective guidance for whether CC patients need emergency surgery.

Axl as a downstream effector of TGF-ß1 via PI3K/Akt-PAK1 signaling pathway promotes tumor invasion and chemoresistance in breast carcinoma.

The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-ß1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-ß1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-ß1 level, tumor differentiation, lymph node metastasis, and clinical stage (p < 0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.

Axl mediates tumor invasion and chemosensitivity through PI3K/Akt signaling pathway and is transcriptionally regulated by slug in breast carcinoma.

The invasion and chemoresistance are crucial causes of morbidity and relapse for cancer patients. Axl is implicated in the modulation of cell invasion, cancer metastasis, and chemosensitivity in human breast carcinoma cell lines. Both breast cancer cell lines and tissues displayed increased expression of Axl, and it over expressed in highly metastatic breast cancer. The altered expression level of Axl was corresponding to the changed invasive phenotype and chemosensitivity of MDA-MB-231 cells both in vitro and in vivo. Further data indicated that experimental inhibition of Axl by RNAi assay inhibited phosphatidylinositol 3-kinase (PI3K)/Akt/GSK3ß signaling pathway, resulted in the decrease of Slug expression, and further suppressed cell invasion properties and chemosensitivity. What is more, after the detection and statistics in human breast cancer specimens, we found the Axl expression was closely correlated with histological grade, lymph node metastasis, and clinical stage (P < 0.01). Taken together, these findings indicate that Axl exerts the role of tumor metastasis and chemosensitivity through activation of the PI3K/Akt/GSK3ß signaling pathway, which is transcriptionally regulated by Slug. Our findings support the possibility that Axl is a novel regulator. It means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.

ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF-κB signaling pathway.

Metastasis of tumor cells is the most deadly attribute of breast cancer patients. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. The objective of this study is to clarify the possible role and mechanism of ST6GalNAcII in the metastasis process of breast carcinoma. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAc II in breast carcinoma cell lines and tissue specimens. PI3K/AKt signaling pathway was also analyzed. The high expression level of ST6GalNAcII was corresponding to invasive phenotype of breast cancer cells both in vitro and in vivo. Further data indicated that manipulation of ST6GalNAcII gene expression led to alter the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Blocking the PI3K/Akt pathway resulted in reduced capacity in invasion of MDA-MB-231 cells. ST6GalNAcII elucidated the unusual properties of invasion in breast cancer cell via modulating the PI3K/AKt signaling pathway.

Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors.

Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.

A preliminary analysis of dental microstructure in Hamipterus (Pterosauria, Pterodactyloidea).

The toothed members of Pterosauria display an extremely wide range of tooth morphologies that supported a variety of feeding habits. Histological studies on the teeth of different pterosaur clades are potentially valuable in understanding the development of their tooth diversity. In this study, we used histological sections and scanning electron microscopy to describe and interpret the tooth microstructure of Hamipterus (Pterodactyloidea). Our analysis is based on seven teeth of Hamipterus (six isolated and one from a skull) from the Lower Cretaceous collected in Hami, China. Our results show that the enamel on the tooth crown is thin (~25 µm) in Hamipterus and covers only approximately half of the tooth crown. This thin enamel of the Hamipterus tooth makes it vulnerable and often becomes damaged during taphonomic and diagenetic processes. The radicular pulp inside the conical-shaped root shows a spindle space with a small foramen at the bottom, while the coronal pulp shows a small tunnel (100-140 µm in diameter). We estimate that the small teeth of Hamipterus likely took approximately 80 days to form. Furthermore, the tooth has Andresen lines, which represent 7-15 days period. For stable articulation of the tooth in the alveolus, the thick cellular cementum is concentrated on the lingual side of the root. The acellular cementum (~40 µm thick) layer runs from the root to the partial tooth crown.

Effect of Radical Surgery for Advanced Adenocarcinoma of Esophagogastric Junction on Perioperative Cellular Cell Immunity.

Background: To investigate the perioperative peripheral blood levels of CD4+CD25+ regulatory T cells, programed cell death 1 (PD-1), and lymphocyte activation gene 3 (LAG-3) in patients with advanced Siewert type II adenocarcinoma of esophagogastric junction (AEG). Methods: Patients (n = 102) with advanced Siewert type II AEG underwent open total gastrectomy/proximal gastrectomy with a transhiatal resection of the distal esophagus and lymphadenectomy of the lower mediastinum and the abdominal D2 compartment. Flow cytometry was used to detect CD4+CD25+ T cells, PD-1 and LAG-3 expression on both CD4+ and CD8+ T cells in the peripheral blood of the Siewert type II AEG patients prior to surgery and on postoperative day (POD) 1, 3, 7, and 9. Results: The proportion of CD4+CD25+ T cells rapidly decreased on POD 1, then gradually increased and peaked at POD 7. The proportion of CD4+PD-1+ T cells significantly increased after surgery, reaching a maximum on POD 1, and remained significantly elevated on POD 3 compared to the preoperative day. The proportion of CD8+ PD-1+ and CD4+LAG-3+ T cells gradually increased after surgery and reached a peak at POD 7. The change in proportion of CD8+LAG-3+ T cells in the peripheral venous blood lymphocytes after surgery was not statistically significant. Conclusion: The change in the CD4+PD-1+ T lymphocyte ratio may likely reflect the cellular immunity status of the perioperative period.

The origin of Rhinocerotoidea and phylogeny of Ceratomorpha (Mammalia, Perissodactyla).

Rhinoceroses have been considered to have originated from tapiroids in the middle Eocene; however, the transition remains controversial, and the first unequivocal rhinocerotoids appeared about 4 Ma later than the earliest tapiroids of the Early Eocene. Here we describe 5 genera and 6 new species of rhinoceroses recently discovered from the early Eocene to the early middle Eocene deposits of the Erlian Basin of Inner Mongolia, China. These new materials represent the earliest members of rhinocerotoids, forstercooperiids, and/or hyrachyids, and bridge the evolutionary gap between the early Eocene ceratomorphs and middle Eocene rhinocerotoids. The phylogenetic analyses using parsimony and Bayesian inference methods support their affinities with rhinocerotoids, and also illuminate the phylogenetic relationships and biogeography of Ceratomorpha, although some discrepancies are present between the two criteria. The nearly contemporary occurrence of various rhinocerotoids indicates that the divergence of different rhinocerotoid groups occurred no later than the late early Eocene, which is soon after the split between the rhinocerotoids and the tapiroids in the early early Eocene. However, the Bayesian tip-dating estimate suggests that the divergence of different ceratomorph groups occurred in the middle Paleocene.