Reactive oxygen species (ROS) play an essential role in regulating various physiological functions of living organisms. The intrinsic biochemical properties of ROS, which underlie the mechanisms ne...

Reactive Oxygen Species (ROS)-Based Nanomedicine.

Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC.

An essential role for Hedgehog (Hh) signaling in human cancer has been established beyond doubt. At present, targeting Hh signaling has mainly been investigated with SMO inhibitors. Unfortunately, resistance against currently used SMO inhibitors has already been observed in basal cell carcinoma (BCC) patients. Therefore, the use of Hh inhibitors targeting the signaling cascade more downstream of SMO could represent a more promising strategy. Furthermore, besides the classical canonical way of Hh signaling activation, non-canonical activation of the GLI transcription factors by multiple important signaling pathways (e.g. MAPK, PI3K, TGFβ) has also been described, pinpointing the importance of targeting the transcription factors GLI1/2. The most promising agent in this context is probably the GLI1/2 inhibitor GANT61 which has been investigated preclinically in numerous tumor types in the last few years. In this review, the emerging role of Hh signaling in cancer is critically evaluated focusing on the potential of targeting Hh signaling more downstream of SMO, i.e. at the level of the GLI transcription factors. Furthermore, the working mechanism and therapeutic potential of the most extensively studied GLI inhibitor in human cancer, i.e. GANT61, is discussed in detail. In conclusion, GANT61 appears to be highly effective against human cancer cells and in xenograft mouse models, targeting almost all of the classical hallmarks of cancer and could hence represent a promising treatment option for human cancer.

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Targeting the Hedgehog signaling pathway in cancer: beyond Smoothened

The challenge of targeting cancer stem cells to halt metastasis.

Two dimensional semiconductors for ultrasound-mediated cancer therapy: the case of black phosphorus nanosheets

The aim of this study was to investigate sonic hedgehog (SHH) signaling pathway components (Shh and Gli-1), E-cadherin, and MMP-9 expression in human oral squamous cell carcinoma (OSCC) and to evaluate their role in prognosis. Expression of Shh, Gli-1, and MMP-9 was significantly upregulated in 74 OSCC samples compared with non-cancerous tissue samples (Shh IOD: 162.44 ± 29.35 and 608.82 ± 170.99; Gli-1 IOD: 203.50 ± 71.57 and 831.11 ± 242.352; MMP-9 IOD: 196.69 ± 64.48 and 721.64 ± 197.99 in non-cancerous and tumor tissues, respectively, P < 0.01), whereas E-cadherin expression was downregulated (E-cadherin IOD: 1,006.19 ± 230.42 and 442.20 ± 156.11; in non-cancerous and tumor tissues, respectively, P < 0.01). Highly expressed proteins were associated with lymph node metastasis; moreover, overexpression of Gli-1 was related to tumor recurrence and cancer clinical staging. Spearman’s analysis indicated that the expression of Gli-1 and MMP-9 was positively correlated, whereas expression of Shh/Gli-1 and E-cadherin was negatively correlated. Kaplan–Meier results revealed that patients with low Shh, Gli-1, and MMP-9 expression survived longer than those with high expression. In contrast, low E-cadherin expression was associated with poor prognosis (P < 0.01). In conclusions, transcription factor Gli-1 of the SHH signaling pathway may be an important mediator of invasion and metastasis of OSCC through induced expression of MMP-9 and E-cadherin and may serve as a new prognostic marker.

Sonic hedgehog signaling may promote invasion and metastasis of oral squamous cell carcinoma by activating MMP-9 and E-cadherin expression

Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3-4 times more cell apoptosis compared to sonocation alone. PpIX-SDT caused cell membrane damage prior to mitochondria damage and upregulated the expression of Fas and Fas L, while the effect was suppressed if cells were pre-treated with p53 inhibitor. Additionally, we examined the SDT-induced cell apoptosis in two cell lines with different p53 status. The increases of p53 expression and apoptosis rate in wild-type p53 SAS cells were found in the SDT group, while p53-mutated HSC-3 cells did not show such increase. Our data suggest that PpIX-SDT suppress the proliferation of SAS cells via arresting cell cycle at G2/M phase and activating the extrinsic Fas-mediated membrane receptor pathway to induce apoptosis, which is regulated by p53.

/pdf/antiproliferative-and-apoptosis-inducing-effect-of-exo-533k8bah35.pdf

Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor related to high mortality and is still lacking a satisfactory cure. Tumor metastasis is currently a major challenge of cancer treatment, which is highly related to angiogenesis. The vascular endothelial growth factor (VEGF)/VEGFR signaling pathway is thus becoming an attractive therapeutic target. Moreover, chemotherapy combined with gene therapy shows great synergistic potential in cancer treatment with the promise of nanomaterials. In this work, a formulation containing 5-FU and siRNA against the VEGF/VEGFR signaling pathway into N-acetyl-galactosamine (GalNAc)-modified nanocarriers is established. The targeting ability, biocompatibility and pH-responsive degradation capacity ensure the efficient transport of therapeutics by the formulation of 5-FU/siRNA@GalNAc-pDMA to HCC cells. The nano-construct integrated with gene/chemotherapy exhibits significant anti-metastatic HCC activity against C5WN1 liver cancer cells with tumorigenicity and pulmonary metastasis in the C5WN1-induced tumor-bearing mouse model with a tumor inhibition rate of 96%, which is promising for future metastatic HCC treatment.

/pdf/inhibition-of-metastatic-hepatocarcinoma-by-combined-2kcjxo5h.pdf

Inhibition of Metastatic Hepatocarcinoma by Combined Chemotherapy with Silencing VEGF/VEGFR2 Genes through a GalNAc-Modified Integrated Therapeutic System

Nian Liu

Papers

Sonic hedgehog signaling may promote invasion and metastasis of oral squamous cell carcinoma by activating MMP-9 and E-cadherin expression

Antiproliferative and Apoptosis-inducing Effect of exo-Protoporphyrin IX based Sonodynamic Therapy on Human Oral Squamous Cell Carcinoma.

Inhibition of Metastatic Hepatocarcinoma by Combined Chemotherapy with Silencing VEGF/VEGFR2 Genes through a GalNAc-Modified Integrated Therapeutic System