Background: Microwave ablation (MWA) is widely used to treat unresectable primary and secondary malignancies of the liver, and a limited number of studies indicate that ablation can cause not only necrosis at the in situ site but also an immunoreaction of the whole body. This study aimed to investigate the effects of MWA on cytokines in patients who underwent MWA for a hepatic malignancy. Methods: Patients admitted to the Oncology Department in the First Affiliated Hospital of Soochow University between June 2015 and February 2019 were selected. Peripheral blood was collected from patients with a hepatic malignancy treated with MWA. The levels of cytokines (IL-2, IFN-γ, TNF-α, IL-12 p40, IL-12 p70, IL-4, IL-6, IL-8, IL-10, and vascular endothelial growth factor (VEGF)) were detected with a Milliplex® MAP Kit. The comparison times were as follows: before ablation, 24 h after ablation, 15 days after ablation, and 30 days after ablation. Data were analyzed using a paired sample t-tests and Spearman’s correlation analysis. Results: A total of 43 patients with hepatic malignancies were assessed. There were significant differences in IL-2, IL-12 p40, IL-12 p70, IL-1β, IL-8, and TNF-α at 24 h after MWA. Significant increases (> 2-fold vs. before ablation) were observed in IL-2, IL-1β, IL-6, IL-8, IL-10, and TNF-α after MWA. Elevated IL-2 and IL-6 levels after ablation were positively correlated with energy output during the MWA procedure. Conclusions: WA treatment for hepatic malignancies can alter the serum levels of several cytokines such as IL-2 and IL-6.

Background: Hepatocellular carcinoma (HCC) is the fourth most common malignant tumor in China. Temozolomide (TMZ) is a common chemotherapy drug which can effectively kill HCC cells in vitro. However, it is possible that HCC cells possess intrinsic resistance to TMZ. A key mechanism of TMZ resistance is the overexpression of O6-methylguanine-DNA methyltransferase (MGMT). Studies have shown that MAPK may be related to MGMT expression, U0126 is a highly selective inhibitor of MEK1 and MEK2, which were crucial molecule in cascade of mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway. Sorafenib was another widely applicated target drug in HCC which could inhibit multiple kinases including MAPK/ERK. This research was aimed to investigate the efficacy of MAPK/ERK inhibitor U0126 and sorafenib combine with TMZ in the treatment of HCC. Methods: In HCC cells, MAPK/ERK signaling pathway was blocked by U0126 and sorafenib. The effect of blocking MAPK/ERK signaling pathway on TMZ-induced cytotoxicity was evaluated by MTT assay, flow cytometry and TUNEL assay. DNA damage protein and the expression of MGMT were detected by Western-blot. After the downregulation of MAPK/ERK signaling pathway, MGMT mRNA expression and the protein expression of MGMT were quantified by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence assay, respectively. HepG2 cells were transfected with an MGMT over expression plasmid. After transfection, the effect of U0126 on TMZ-induced cytotoxicity was evaluated by MTT and Western-Blot in MGMT OE cells. The influence of Sorafenib on TMZ-induced cytotoxicity to HCC cells was also detected by MTT assay. Results: U0126 can enhance the chemosensitivity of HCC cells to TMZ. At the same time, we also found that U0126 increases the damage to DNA caused by TMZ in HepG2 cells. Moreover, the results from RT-qPCR and Western blot showed that U0126 downregulated MGMT mRNA and MGMT protein expression via blocking MAPK/ERK pathway. Furthermore, after transfection with an MGMT expression plasmid, overexpression of MGMT restored U0126-induced chemosensitivity to TMZ in HCC cells. Sorafenib can also increase the chemosensitivity of HCC cells to TMZ. Conclusions: Our studies suggest great clinical potential for the utilization of combined U0126 and TMZ in patients with advanced HCC.

Background: Bone is among the most common metastasis sites in patients with advanced cancer. Approximately two-thirds of bone metastasis results in pain, the majority of which is moderate to unbearable pain, which seriously affects the quality of life of patients. With the development of ablation techniques, microwave ablation (MWA) has great potential to eliminate the pain caused by bone metastasis. This study aimed to evaluate the efficacy and safety of image-guided (computed tomography-guided) percutaneous MWA for metastatic osseous pain. Methods: This is a retrospective study involving 18 patients with cancer-related pain caused by osseous or soft tissue metastasis in the First Affiliated Hospital of Soochow University from June 2015 to October 2020. All patients (14 men and 4 women; mean age 60.2 years) underwent image-guided percutaneous palliative MWA. A paired-sample t-test was used to compare the changes in Numeric Rating Scale (NRS) score and dosage of morphine preoperatively and postoperatively (at 24 h, 3 days, and 14 days after MWA). In addition, we assessed the level of pain relief according to the patients’ subjective feelings. Results: The paired-samples t-test showed that the NRS score (6.83±0.92 vs. 1.67±0.97, P<0.05) and dosage of morphine (85.56±17.23 vs. 32.78±4.61, P<0.05) were significantly decreased at 3 days after MWA. At 14 days after MWA, the NRS score (6.83±0.92 vs. 0.94±0.87, P<0.05) and dosage of morphine (85.56±17.23 vs. 10.56±8.73, P<0.05) were also markedly decreased. Moreover, according to the patients’ subjective feeling, 88.89% patients had pain relief postoperatively, while the remaining patients had no progress. Conclusions: Image-guided (Computed Tomography-guided) percutaneous MWA can effectively relieve pain, thus improving the quality of life in patients with osseous metastasis. MWA is a feasible, safe, and effective treatment for pain caused by bone metastasis.

Metastasis is one of the biggest challenges in the management of Esophageal Squamous Cell Carcinoma (ESCC), of which molecular mechanisms remain elusive. The present study aimed to explore the roles and underlying mechanisms of Transmembrane protein 26 (TMEM26) in ESCC. TMEM26 expressions in tumorous and adjacent tissues from patients with ESCC and in normal esophageal epithelial and ESCC cell lines were detected by immunostaining and western blotting, respectively. The Epithelial-Mesenchymal Transition (EMT), a critical process during metastasis, was investigated by wound healing and Transwell assays, and EMT-related proteins were examined after the TMEM26 alteration in ESCC cell lines. NF-κB signaling activation and Tight Junction (TJ) protein expression were analyzed by western blotting and immunofluorescence, respectively. In vivo verification was performed on the liver metastatic murine model. Compared with non-cancerous esophageal tissues and cells, the TMEM26 expression level was higher in ESCC samples and cell lines, where the plasma membrane localization of TMEM26 was observed. The EMT-related processes of ESCC cells were suppressed by RNAi depletion of TMEM26 but aggravated by TMEM26 overexpression. Mechanistically, TMEM26 promoted NF-κB signaling to accelerate EMT in ESCC cells. The plasma membrane presentation and assembly of TJ proteins were impaired by TMEM26. Overall, TMEM26 acts as a critical determinant for EMT in ESCC cells by disrupting TJ formation and promoting NF-κB signaling, which may be a potential therapeutic target for treating metastatic ESCC.

Radiotherapy (RT) is a primary modality in clinical cancer treatment. However, its ability to induce tumor cell apoptosis offers limited activation of anti

Tumorigenesis is closely related to defects in DNA damage response (DDR), which plays an important role in maintaining genomic integrity. The DDR process i