TNFalpha has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKbeta, a major downstream kinase in the TNFalpha signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKbeta-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKbeta is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer.

Enhancer of Zeste homolog 2 (EZH2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone H3. Here, we show that Akt phosphorylates EZH2 at serine 21 and suppresses its methyltransferase activity by impeding EZH2 binding to histone H3, which results in a decrease of lysine 27 trimethylation and derepression of silenced genes. Our results imply that Akt regulates the methylation activity, through phosphorylation of EZH2, which may contribute to oncogenesis.

Objective: In this study, we exploited a VGG-16 deep convolutional neural network (DCNN) model to differentiate papillary thyroid carcinoma (PTC) from benign thyroid nodules using cytological images.Methods: A pathology-proven dataset was built from 279 cytological images of thyroid nodules. The images were cropped into fragmented images and divided into a training dataset and a test dataset. VGG-16 and Inception-v3 DCNNs were trained and tested to make differential diagnoses. The characteristics of tumor cell nucleus were quantified as contours, perimeter, area and mean of pixel intensity and compared using independent Student's t-tests.Results: In the test group, the accuracy rates of the VGG-16 model and Inception-v3 on fragmented images were 97.66% and 92.75%, respectively, and the accuracy rates of VGG-16 and Inception-v3 in patients were 95% and 87.5%, respectively. The contours, perimeter, area and mean of pixel intensity of PTC in fragmented images were more than the benign nodules, which were 61.01±17.10 vs 47.00±24.08, p=0.000, 134.99±21.42 vs 62.40±29.15, p=0.000, 1770.89±627.22 vs 1157.27±722.23, p=0.013, 165.84±26.33 vs 132.94±28.73, p=0.000), respectively.Conclusion: In summary, after training with a large dataset, the DCNN VGG-16 model showed great potential in facilitating PTC diagnosis from cytological images. The contours, perimeter, area and mean of pixel intensity of PTC in fragmented images were more than the benign nodules.

Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.

More than half of the subset of "atypical" salivary gland FNAs with histological resection turned out to be malignant tumors; another one-fourth were benign neoplasms. Further, the highly variable ROMs of the "atypical" category amongst different institutions likely reflect the variable practices at each individual institution.

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Genistein is one of the main components of soy-based foods, which are widely known for their many benefits, including anti-cancer, anti-inflammatory, and antioxidant effects. In this study, we investigated the anti-metastasis effects of genistein on B16F10 melanoma cells. Our results showed that genistein strongly inhibited B16F10 cell proliferation and induced apoptosis in time- and concentration-dependent manners. Genistein altered the morphology of B16F10 cells to an elongated shape with slim pseudopodia-like protrusions. Moreover, genistein inhibited the invasion and migration abilities of B16F10 cells in a dose-dependent manner. On one hand, a high concentration of genistein (100 μM) significantly inhibited cell adhesion and migration, as shown by wound healing assays and transwell-migration and invasion assays. Furthermore, the expression levels of p-FAK, p-paxillin, tensin-2, vinculin, and α-actinin were decreased by genistein. As a result, genistein is believed to strongly downregulate the migration and invasion abilities of B16F10 cells via the FAK/paxillin pathway. Moreover, p-p38, p-ERK, and p-JNK levels were also dramatically decreased by treatment with genistein. Finally, genistein significantly decreased the gene expression of FAK, paxillin, vimentin, and epithelial-to-mesenchymal transition-related transcription factor Snail, as shown by real-time PCR (qPCR) analysis. On the other hand, a lower concentration of genistein (12.5 μM) significantly promoted both invasion and migration by activating the FAK/paxillin and MAPK signaling cascades. Taken together, this study showed for the first time that genistein exerts dual functional effects on melanoma cells. Our findings suggest that genistein regulates the FAK/paxillin and MAPK signaling pathways in a highly concentration-dependent manner. Patients with melanoma should therefore be cautious of consuming soy-based foods in their diets.