Research progress on the effect of hyperthermia on vascular endothelial growth factor in tumor microenvironment / 中华放射肿瘤学杂志

Vascular endothelial growth factor (VEGF) plays an important role in promoting tumor vascular growth and changing vascular wall permeability. With the in-depth study of tumor hyperthermia and tumor microenvironment, more and more studies have shown that hyperthermia exerts multiple regulatory effects on VEGF in tumor microenvironment. Combined with current research progress in China and abroad, this article reviews the effect of hyperthermia on VEGF and its related cells and factors in tumor microenvironment, aiming to provide new ideas for the clinical application of tumor hyperthermia combined with immune or targeted therapy.

Effect of hyperthermia on biological behavior of squamous cell carcinoma of the tongue by regulating ferroptosis pathway / 中华放射肿瘤学杂志

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Effect of hyperthermia combined with paclitaxel on proliferation, apoptosis and cycle of human tongue squamous cell carcinoma cell line CAL-27 / 中华放射肿瘤学杂志

Objective:To observe the effect of hyperthermia combined with paclitaxel on the proliferation, apoptosis and cycle of human tongue squamous cell carcinoma cell line CAL-27, and to explore the underlying mechanism.Methods:The working concentration of paclitaxel was determined by CCK-8 assay, and the cultured CAL-27 cells were divided into the control, paclitaxel, 42℃ hyperthermia and combined treatment groups. The ability of cell proliferation was detected by colony formation assay, and the cell cycle and apoptosis were determined by flow cytometry. The expression levels of AKT, p-AKT, Bcl-2 and Bax proteins in each group were measured by Western blot.Results:Compared with the control group, the proliferation was significantly inhibited and the apoptosis of CAL-27 cells was significantly promoted in the combined treatment, hyperthermia and paclitaxel groups (all P<0.05), and the anti-proliferation and apoptosis-promoting effect in the combined treatment group was significantly better than those in the hyperthermia and paclitaxel groups (all P<0.05). Western blot showed that hyperthermia combined with paclitaxel could significantly up-regulate the expression level of Bax protein and significantly down-regulate the expression levels of P-AKT and Bcl-2 in CAL-27 cells (all P<0.05). Conclusions:Hyperthermia combined with paclitaxel can play a synergistic role in inhibiting proliferation and promoting apoptosis of tongue squamous cell carcinoma CAL-27 cells. The mechanism may be related to the inhibition of AKT activation and the activation of Bax/Bcl-2 apoptosis signaling pathway.

Research progress on biological mechanism of tumor hyperthermia / 中华放射肿瘤学杂志

In recent years, tumor hyperthermia has become a hot research topic as an adjuvant therapy to traditional tumor therapy. Hyperthermia can directly induce tumor cell necrosis or apoptosis, or inhibit tumor progression by destroying tumor blood vessels. Meantime, it can also activate the response of immune cells and cytokines in the immune system of the host, thereby regulating the immune state of tumor microenvironment. Multiple combined effects influence the tumor progression. A thorough understanding of the biological mechanism of hyperthermia is beneficial to the development of novel therapeutic methods. In this paper, the biological mechanism of hyperthermia in killing tumors was mainly reviewed.

Hyperthermia combined with chemotherapy induce tongue squamous cell carcinoma cell apoptosis by down-regulating HIF-1α and CYPJ expression / 中华放射肿瘤学杂志

Objective:The investigate the roles and significance of HIF-1α and CYPJ in tongue squamous cell carcinoma cell (TSCC), and further evaluate the regulatory effect of hyperthermia (HT) on HIF-1α and CYPJ in TSCC cells.Methods:Eighty samples of cancer tissues and adjacent normal tissues from TSCC patients were collected. The expression levels of HIF-1α and CYPJ were detected by immunohistochemistry, Western blotting (WB) and fluorescence quantitative PCR, and the relationship between the expression levels of HIF-1α and CYPJ and clinicopathological characteristics was further analyzed. The expression levels of HIF-1α and CYPJ in Cal-27 cells under normoxic and hypoxic conditions for 24 h when combined with HT (42℃), chemotherapy and both were detected by qPCR and WB. Cell migration was detected by cell scratch test and cell apoptosis was measured by flow cytometry.Results:The expression levels of HIF-1α and CYPJ proteins in the tumor tissues of TSCC patients were higher than those in the adjacent normal tissues, which were significantly correlated with tumor size, TNM stage, differentiation degree and lymph node metastasis in TSCC patients (all P<0.05), whereas they were not correlated with gender or age (all P>0.05). The expression levels of HIF-1α and CYPJ in Cal-27 cells were significantly up-regulated in the hypoxic microenvironment (both P<0.05), which were also significantly enhanced by hyperthermia alone (both P<0.05). Compared with hyperthermia or chemotherapy alone, hyperthermia combined with chemotherapy significantly inhibited the expression of HIF-1α and CYPJ, suppressed cell migration and promoted cell apoptosis (all P<0.05). Conclusions:HIF-1α and CYPJ may be potential biomarkers for TSCC tumorigenicity and prognosis. In addition, tumor recurrence after hyperthermia may be due to the role of hyperthermia in triggering HIF-1α expression, which promotes the growth and survival of tumor cells adaptive to hyperthermia treatment by activating the downstream target genes, while hyperthermia combined with chemotherapy may be a promising treatment for TSCC.

Research status of hyperthermia and energy metabolism of tumor cells in hypoxic microenvironment / 中华放射肿瘤学杂志

Metabolic reprogramming is a malignancy hallmark, which refers to the ability of cancer cells to alter metabolic and nutrient acquisition modes in order to support the energy demands for accomplishing the rapid growth, dissemination, metastasis and obtain the "building blocks" needed to maintain cell division. When solid tumors are exposed to low pH, low oxygen and tumor microenvironment with nutrient deficiencies, the hypoxia-inducible factor-1 can be activated, which mediates the remodeling of metabolic patterns in tumor cells, namely, energy is obtained by circulating intracellular components (removing substrates such as proteins and lipid) or by utilizing adaptive metabolic reprogramming (such as glycolysis, autophagy and lipid metabolism, etc.). As a treatment scheme based on local heating of tumors, hyperthermia has a variety of anticancer mechanisms and can be used in combination with radiotherapy, chemotherapy and biological immune therapy. In this review, we briefly discussed the metabolic remodeling model mediated by hypoxia-inducible factor 1 in a hypoxia microenvironment, described the possible regulatory mechanism of hyperthermia on hypoxia-inducible factor-1 and prospected the application of hyperthermia in oral and maxillofacial tumors.

Effect of hyperthermia on immune cells and immune-related cytokines in tumor immune microenvironment / 中华放射肿瘤学杂志

With the in-depth study of tumor hyperthermia and tumor immune microenvironment (TIME), the role of hyperthermia in TIME has captivated increasing attention from scholars in recent years. Based upon recent research progress at home and abroad, the effect and mechanism of hyperthermia on several major immune cells and immune-related cytokines in the TIME were reviewed in this article. Comprehensive and deep understanding of the regulation of hyperthermia on the TIME could provide new ideas and methods for tumor treatment.

Postoperative complications and survival analysis of 1 118 cases of open splenectomy and azygoportal disconnection in the treatment of portal hypertension / 中华外科杂志

Objective@#To analyze the recent postoperative and long-term postoperative complications of open-splenectomy and disconnection in patients with portal hypertension.@*Methods@#There were 1 118 cases with portal hypertension who underwent open splenectomy and azygoportal disconnection from April 2010 to September 2015 at Department of Surgery, People′s Liberation Army 302 Hospital. Retrospective case investigation and telephone follow-up were conducted in October 2016. All patients had history of upper gastrointestinal bleeding before operation. Short-term complications after surgery were recorded including secondary laparotomy of postoperative abdominal hemostasis, severe infection, intake disorders, liver insufficiency, postoperative portal vein thrombosis and perioperative mortality. Long-term data including postoperative upper gastrointestinal rebleeding, postoperative survival rate and incidence of postoperative malignancy were recorded, too. GraphPad Prism 5 software for data survival analysis and charting.@*Results@#Postoperative short-term complications in 1 118 patients included secondary laparotomy of postoperative abdominal hemostasis(1.8%, 21/1 118), severe infection(2.9%, 32/1 118), intake disorders(1.0%, 11/1 118), liver dysfunction (1.6%, 18/1 118), postoperative portal vein thrombosis(47.1%, 526/1 118)and perioperative mortality(0.5%, 5/1 118). After phone call following-up, 942 patients′ long-term data were completed including 1, 3, 5 years postoperative upper gastrointestinal rebleeding rate(4.4%, 12.1%, 17.2%), 1, 3, 5-year postoperative survival rate(97.0%, 93.5%, 90.3%); the incidence of postoperative malignant tumors in 1, 3 and 5 years were 1.7%, 4.4% and 6.2%.@*Conclusions@#Reasonable choosing of surgical indications and timing, proper performing the surgery process, effective conducting perioperative management of portal hypertension are directly related to the patient′s short-term prognosis after portal hypertension. Surgical intervention can reduce the rates of patients with upper gastrointestinal rebleeding, improve survival, and do not increase the incidence of malignant tumors.

Postoperative portal vein thrombosis and the liver function after splenectomy and pericardial devascularization / 中华肝胆外科杂志

Objective To study the impact of splenectomy and pericardial devascularization on the occurrence and development of portal vein thrombosis and the liver function in patients with cirrhosis complicated by portal hypertension.Methods 29 patients with cirrhosis and portal hypertension who underwent splenectomy and pericardial devascularization in the 302 Hospital of PLA from December 2012 to June 2013 were retrospectively studied.The incidences of PVT before and after operation were monitored.The liver function was assessed using the Child-Pugh classification.Results 29 patients with cirrhosis and portal hypertension underwent splenectomy and pericardial devascularization.The incidences of PVT in the preoperative period,12 days,3 months,6 months after operation were 10.3％,89.7％,51.7％,24.1％,respectively.The Child-Pugh scores in the preoperative period,12 days,3 months,6 months after operation were (5.2 ± 0.4),(5.6 ± 0.7),(5.2 ± 0.7),(5.3 ± 0.7),respectively.Conclusions The incidences of postoperative PVT increased after operation,but it decreased on long-term follow-up after operation.The liver function did not change.

Expressions of NMDAR2 and GLAST in supraoptic nucleus and hippocampal gyrus under sleep deprivation in young rats / 医学研究生学报

Objective: To observe the expressions of NMDAR2 and GLAST in the hippocampal gyrus and supraoptic nucleus(SON) under sleep deprivation in young rats.Methods: The changes in expressions of NMDAR2 and GLAST in SON and hippocampal gyrus under sleep deprivation in younger rats were observed by immunohistochemistry method. Results:The expressions of NMDAR2 and GLAST in SON and the hippocampal gyrus were significantly increased on the 3rd day of sleep deprivation,even more sigificantly on the 5th day,decreased gradually on 7th day,and became similar to those of control group on the 14th day.Conclusion: Sleep deprivation can affect the expressions of NMDAR2 and GLAST in the hippocampal gyrus and supraoptic nucleus,but the effect diminisshes gradually with prolonged time,which may be associated with self-regulation and self-protection of the central nervous system.

EFFECT OF LIVER TRANSPLANTATION ON GASTRIC MUCOSAL LESIONS AND ITS SIGNIFICANCE / 解放军医学杂志

To observe the effect of liver transplantation on gastric mucosa lesions and the changes in plasma superoxide dismutase(SOD),malondialdehyde(MDA),interleukin 1(IL 1) and prostaglandin(PG) between before and after liver transplantation, a hepatic cirrhosis model was established in rats by subcutaneous injection of 40% carbon tetrachloride. Rat liver transplantation was made with the two cuff technique. By immunohistochemical method,we observed the effect of liver transplantation on rat gastric mucosa lesions. Using chemical method the changes in plasma SOD, MDA,IL 1 and PG between before and after liver transplantation were observed.The results showed that gastric mucosal lesions alleviated significantly after liver transplantation in rats with liver cirrhosis,and lesion index decreased gradually.The plasma levels of SOD decreased,MDA increased,and the plasma levels of IL 1, PGE 2 increased gradually after liver transplantation. Therefore, liver transplantation can improve gastric mucosal lesion, and this effect may be connected with its action on oxygen radicals, PG and IL 1.

Changes of the levels of tumor necrosis factor and interleukin-8 in the blood and gastric mucosa and their mRNA expression after liver ischemia- reperfusion / 中国普通外科杂志

Objective To investigate the changes of the levels of TNF and IL 8 in blood and in gastric mucosa and their mRNA expression after liver ischemia reperfusion (I/R). Methods 130 rats were randomly divided into 3 groups: (1) sham operation group(control group, n=10);(2)liver ischemia reperfusion group (n=60), including ischemia for 20min and 40min, and reperfusion for 1h, 24h and 72h respectively; (3) liver I/R rats treated with famotidine group (n=60). ALT and AST were detected after operation, pathomorphological changes of gastric mucosa were studied by light microscope and transmission electronic microscope, the concentrations of TNF and IL 8 in blood and gastric mucosa were measured by radioimmunoassay (RIA), TNF mRNA and IL 8 mRNA were detected by in situ hybridization. Results After liver I/R,inflammatory damage appeared in gastric mucosa, TNF and IL 8 concertrations increased significantly(P

Sleep deprivation leads to the electric activity in NTS and the expression of NMDAR2 and GLAST in hippocampal gyrus in young rats / 解放军医学杂志

Objective To observe the effect of electric activity in the nucleus of solitary tract and the expression of NMDAR2 and GLAST in the zone of hippocampal gyrus after sleep deprivation in younger rats, in order to provide some theoretical basis for clinical therapeutie strategy. Methods Synchronous experiment was conducted with electrophysiological method. The changes in electric-activity of nucleus of solitary tract (NTS) were determined. Immunohistochemical method was employed to detected the expression of NMDAR2 and Glast in the zone of hippocampal gyrus in younger rats with sleep deprivation. Results The electric activity in nucleus of solitary tract (NTS) increased gradually along with sleep deprivation for 3 days, and the electric activity was much increased on the 7th day of sleep deprivation. In the second week of sleep deprivation, the electric activity in NTS was restrained. In the zone of hippocampal gyrus, the expression of both NMDAR2 and GLAST was increased significantly with 3-day sleep deprivation, and on the 5th day, the expression was much increased, while on the 7th day the expression decreased gradually. However, the expression of both NMDAR2 and GLAST in the zone of hippocampal gyrus in the second week of sleep deprivation was similar to that of the control group. Conclusion Sleep deprivation can exert a marked influence on the electric activity of the nucleus of solitary tract (NTS), and may interfere with the ability of study and memory in younger rats.