Combination of Gas Plasma and Radiotherapy Has Immunostimulatory Potential and Additive Toxicity in Murine Melanoma Cells in Vitro.
- 作者列表："Pasqual-Melo G","Sagwal SK","Freund E","Gandhirajan RK","Frey B","von Woedtke T","Gaipl U","Bekeschus S
:Despite continuous advances in therapy, malignant melanoma is still among the deadliest types of cancer. At the same time, owing to its high plasticity and immunogenicity, melanoma is regarded as a model tumor entity when testing new treatment approaches. Cold physical plasma is a novel anticancer tool that utilizes a plethora of reactive oxygen species (ROS) being deposited on the target cells and tissues. To test whether plasma treatment would enhance the toxicity of an established antitumor therapy, ionizing radiation, we combined both physical treatment modalities targeting B16F10 murine melanoma cell in vitro. Repeated rather than single radiotherapy, in combination with gas plasma-introduced ROS, induced apoptosis and cell cycle arrest in an additive fashion. In tendency, gas plasma treatment sensitized the cells to subsequent radiotherapy rather than the other way around. This was concomitant with increased levels of TNFα, IL6, and GM-CSF in supernatants. Murine JAWS dendritic cells cultured in these supernatants showed an increased expression of cell surface activation markers, such as MHCII and CD83. For PD-L1 and PD-L2, increased expression was observed. Our results are the first to suggest an additive therapeutic effect of gas plasma and radiotherapy, and translational tumor models are needed to develop this concept further.
: 尽管治疗不断进步，恶性黑色素瘤仍然是最致命的癌症之一。同时，由于其高度的可塑性和免疫原性，黑色素瘤在测试新的治疗方法时被视为模型肿瘤实体。冷物理血浆是一种新型的抗癌工具，利用大量的活性氧 (ROS) 沉积在靶细胞和组织上。为了测试血浆治疗是否会增强已建立的抗肿瘤疗法电离辐射的毒性，我们在体外结合了两种靶向 B16F10 鼠黑色素瘤细胞的物理治疗方式。重复而不是单次放疗，结合气体血浆引入 ROS，以相加的方式诱导细胞凋亡和细胞周期阻滞。趋向于气体等离子体处理使细胞对随后的放疗敏感，而不是相反。这伴随着上清液中 tnf α 、 IL6 和 GM-CSF 水平的增加。在这些上清液中培养的鼠颌骨树突状细胞显示细胞表面活化标记物的表达增加，如 MHCII 和 cd83。对于 PD-L1 和 PD-L2，观察到表达增加。我们的结果首次提出了气体血浆和放疗的相加治疗效果，需要翻译肿瘤模型来进一步发展这一概念。
METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.
METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.