Establishment of Human Lung Adenocarcinoma Radioresistant Cell Lines and the Mechanism of Radioresistance / 中国肺癌杂志

BACKGROUND@#Radiotherapy is one of the most common treatments for lung cancer, and about 40%-50% of patients after radiotherapy will appear uncontrolled or recurrence in the case of local tumors. Radioresistance is the predominant cause of local therapeutic failure. Nevertheless, the lack of in vitro radioresistance models is an influential factor obstructing the study of its mechanism. Therefore, the establishment of radioresistant cell lines, H1975DR and H1299DR, was beneficial to explore the mechanism of radioresistance in lung adenocarcinoma.@*METHODS@#The radioresistant cell lines of H1975DR and H1299DR were obtained from H1975 and H1299 cells irradiated with equal doses of X-rays; Clonogenic assays were performed to compare the clone-forming ability of H1975 vs H1975DR cells, H1299 vs H1299DR cells, then fitting cell survival curve by linear quadratic model; The comet assay was employed to examine DNA damage repair and calculate the percentage of DNA tails; The optical microscopy, CCK-8, flow cytometry, Transwell invasion assays were used to compare biological characteristics such as cell morphology, cell proliferation, apoptosis level, cycle distribution, cell migration and invasion; Western blot was carried out to measure the protein expression of DNA damage repair factors, such as DNA-PKcs, 53BP1, RAD51, and p-ATM.@*RESULTS@#After five months of continuous irradiation and stable culture, radioresistant cell lines H1975DR and H1299DR were obtained. The cell proliferation activity, clone formation ability and DNA damage repair ability of the two radioresistant cell lines were significantly improved under X-ray irradiation. The proportion of the G2/M phase was markedly decreased and the proportion of the G0/G1 phase was increased. Cell migration and invasion ability were significantly enhanced. Relative expression levels of p-DNA-PKcs (Ser2056), 53BP1 in the nonhomologous end-joining (NHEJ) repair pathway and p-ATM (Ser1981), RAD51 in the homologous recombination (HR) repair pathway were higher than those in H1975 and H1299.@*CONCLUSIONS@#H1975 and H1299 cell lines can be able to differentiate into lung adenocarcinoma radioresistant cell lines H1975DR and H1299DR by equal dose fractional irradiation, which provided an in vitro cytological model for the study of radiotherapy resistance mechanism of lung cancer patients.

Advances in Predictive Research of Immune Checkpoint Inhibitors-related Adverse Events / 中国肺癌杂志

The era of tumor treatment has been revolutionized by the advent of immune checkpoint inhibitors. However, while immunotherapy benefits patients, it can also lead to immune-related adverse events that may affect multiple organs and systems throughout the body, potentially even posing a life-threatening risk. The diverse clinical manifestations and onset times of these adverse events further complicate their prediction and diagnosis. The purpose of this paper is to review the clinical characteristics and predicted biomarkers of adverse events related to inhibitors at immune checkpoints, in order to help clinicians evaluate drug risks and early warn adverse events.
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Research progress on tumor hyperthermia / 中华放射肿瘤学杂志

In recent years, increasing evidence has shown that hyperthermia is safe, effective and causes low toxicity. Hyperthermia can exert synergistic effect with other treatments, such as radiotherapy and chemotherapy. It has become an important adjuvant anti-tumor treatment secondary to surgery, chemotherapy, radiotherapy and biological treatment. Hyperthermia can improve the efficacy of radiotherapy and chemotherapy by directly inhibiting tumor cells and heat-induced radiosensitizing effect. Hence, hyperthermia is gradually applied in the multimodality treatment of tumors. In this article, we intend to review the research progress on the application of tumor hyperthermia in conventional radiotherapy, chemotherapy, immunotherapy and new biomaterials.

Research Progress in CircRNA and Radiotherapy Resistance of Non-small Cell Lung Cancer / 中国肺癌杂志

As the main type of lung cancer, non-small cell lung cancer (NSCLC) is a common cancer which is characterized by low 5-year survival rate and worse prognosis. Nowadays, some studies show that the low survival rate and worse prognosis are due to the resistance to radiotherapy caused by circRNA. Therefore, to find out the relationship between circRNA and radiotherapy resistance of NSCLC was imoprtant. According to research the relevant literatures, the relationship between circRNA and radiotherapy resistance of NSCLC was explored. CircRNA plays an important role in the invasion, metastasis, proliferation and treatment resistance of NSCLC. The radiation resistance of tumor cells induced by circRNA has become a crucial problem in radiotherapy. CircRNA plays an important role in the radiotherapy resistance of NSCLC.
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Pathological and Molecular Features of Lung Micropapillary Adenocarcinoma / 中国肺癌杂志

Lung micropapillary adenocarcinoma is characterized by frequent metastasis, lymph node infiltration, high recurrence rate and low overall survival rate as a high-grade lung adenocarcinoma. Special oncogenic pathway is activated and immune microenvironment is established in this subtype of tumor. This article reviews the Pathological phenomena and molecular features of micropapillary adenocarcinoma studied in recent years, aiming to deepen the understanding of micropapillary lesions and lay the foundation for formulating specific treatment strategies.
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Research Advances and Obstacles of CT-based Radiomics in Diagnosis and Treatment of Lung Cancer / 中国肺癌杂志

Radiomics, a technology based on multimodal medical image processing and analysis, is able to extract automatically and analyze massive data from computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT) via high-performance computer algorithm in order to pursue early diagnosis of disease, benign and malignant tumor discrimination, dynamic evaluation of disease treatment, and individualized precision therapy. To date, many studies demonstrate that radiomics not only has great potential in early diagnosis of lung cancer and prediction of genotype, treatment efficacy, as well as prognosis but also is based on imaging methods that are noninvasive, inexpensive, and repeatable. It does demonstrate precious values in guiding the clinical diagnosis and treatment of lung cancer, especially in the personalized and precise treatments and researches of lung cancer. However, the consistency and reproducibility of radiomics and the selection of robust characteristics still warrant further researches.
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Study on the correlation between acute radionuclitidis and improved body mass index in intensity-modulated radiation therapy after cervical cancer surgery / 中华放射肿瘤学杂志

Objective To investigate the relationship between the body mass index (BMI)/body mass index improved (BMIIMPd) and the dose of the small intestine as well as the acute radiation colitis in the intensity-modulated radiation therapy after cervical cancer surgery.Methods Thirty-nine cervical cancer patients underwent postoperative adjuvant radiotherapy.All patients received Philips large bore CT scan for enhanced CT scan,target delineation and organ at risk.All patients were treated with a single arc 10 MV VMAT plan.The correlation between the radiation dose of the small intestine and the acute radiation enteritis and BMI/BMIIMPd was analyzed.Results The BMI was calculated as (22.23±2.80) kg/m2,BMIIMPd was (21.49±3.95) kg/m2,the small intestine volume VSI was (1 155.71 ± 419.33)cc3.The volume of the small intestine received more than 10 Gy (V10_SI) VMAT was (66.50± 27.01) ％,and the equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) were (4 098.87± 184.93) cGy and (7.98±8.73)％.One way ANOVA demonstrated that under the VMAT technology,the BMIIMPd,V30,V40,EUD (or=50) and NTCP in the small intestine were the influencing factors of the occurrence of acute radiation enteritis.Conclusions If the improved BMIIMPd is utilized to distinguish the BMI,the high dose area of the small intestine will be larger and the incidence of acute radiation enteritis will be higher for patients with BMIIMPd between 10.1 and 16.9(normal and thin).Conventional BMI cannot be utilized as a basis for the prediction of the incidence of acute radiation enteritis in patients with cervical carcinoma.

Microwave Hyperthermia Combined with Gemcitabine Inhibits Proliferation and Induces Apoptosis of Human Lung Squamous Carcinoma Cells / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the highest morbidity and mortality in the world and it is very important to find an effective anti-tumor method. Microwave hyperthermia, a new treatment technology, has been getting more and more attention. This study was designed to investigate the effects of microwave hyperthermia combined with gemcitabine on the proliferation and apoptosis of human lung squamous cell carcinoma (NCI-H1703 and NCI-H2170) in vitro.@*METHODS@#The proliferation of cells treated with microwave hyperthermia, the effect of gemcitabine on cell proliferation and the proliferation of cells treated with different methods of microwave hyperthermia and gemcitabine were detected by CCK-8 assay. Colony formation assay was used to measure the colony formation of human lung squamous cell carcinoma cells. Flow cytometry assay was used to detect the total apoptosis rates of the treated cells. Caspase-3, Caspase-8 activity assay was used to detect the activity of Caspase-3, Caspase-8 enzyme in each group of cells. CCK-8 assay was used to detect the effect of control group, AC-DEVD (Caspase-3 inhibitor) group, thermalization combined group, and thermal AC-DEVD combined group on cell proliferation. The levels of p53, Caspase-3, Cleaved-Caspase-3, PARP, Bax and BCL-2 protein expression were detected using Western blot assay.@*RESULTS@#Our results demonstrated that microwave hyperthermia inhibited the proliferation of lung squamous cell carcinoma. The IC₅₀ values of gemcitabine for the two cells were 8.89 μmol/L and 44.18 μmol/L, respectively. The first chemotherapy after microwave hyperthermia has synergistic effect on the two lung squamous cell carcinoma cells and can significantly inhibit the cell clone formation (P0.05). Furthermore, Western blot analysis showed that microwave hyperthermia combined with gemcitabine could up-regulate the p53, Caspase-3, Cleaved-Caspase-3, Cleaved-PARP and Bax protein expression.@*CONCLUSIONS@#Microwave hyperthermia combined with gemcitabine remarkably inhibit the proliferation and induce apoptosis of human lung squamous cell carcinoma in vitro. This effect may be associated with the activation of p53, cleavage of PARP protein, and induced the Caspase-3 dependent apoptosis.

The effect of microwave radiation on the permeability change of blood brain barrier / 中华放射肿瘤学杂志

Microwave radiation plays an important role in the diagnosis and treatment of malignant tumors. Whether microwave radiation can improve the effect of chemotherapy on intracranial carcinoma through improving the permeability of blood brain barrier is a hot topic at present. Blood-brain barrier permeability can be increased by microwave radiation though thermal effect and non thermal effect,and the mechanism may be related to the regulation of vascular endothelial growth factor,Occludin,aquaporin 4 and adhesion molecule-1.However, there are still questions on the physical parameters, include temperature, microwave frequency,specific absorption rate and exposure time.

Research progress on biomarkers in predicting radiosensitivity of non-small cell lung cancer / 中华放射肿瘤学杂志

Radiotherapy is a critical approach for the comprehensive treatment of non-small cell lung cancer.Deep understanding of the individualized radiosensitivity of lung cancer patients plays a pivotal role in the selection of radiotherapy dosage and regime and establishment of comprehensive therapeutic strategies.Currently,multiple researchers have identified a variety of biomarkers in predicting the radiosensitivity of lung cancer patients.In this article,research progress on the biomarkers in predicting radiosensitivity of non-small cell lung cancer was reviewed.

Clinical value of lung equivalent uniform dose in predicting VMAT-induced radiation pneumonitis / 中华放射肿瘤学杂志

Objective To investigate the clinical effect of lung equivalent uniform dose (LEUD)-based predictive model for radiation pneumonitis (RP) induced by volumetric modulated arc therapy (VMAT) and to determine the optimal a value.Methods A total of 65 patients with primary lung cancer who received VMAT from July 2015 to February 2016 were divided into RP group and non-RP group according to the presence or absence of RP after radiotherapy.Their dose-volume histogram (DVH) data and other data were obtained and analyzed by the self-compiled numerical analysis program.The LEUD values in the two groups were calculated at a=[-50, 50], and then the a value was identified when the relative difference of LEUD between the two groups was maximal.The paired t test was used for analyzing the differences in V5, V20, V30, minimum lethal dose (MLD), and LEUD (aoptimal) between the two groups.A Pearson correlation analysis was used to determine the correlation of Vdose and LEUD (aoptimal) with RP.The logistic regression method was used to establish the predictive model of RP.Results The maximum relative difference in LEUD between RP group and non-RP group was obtained at a=0.3(627.94 cGy vs.510.23 cGy, relative difference[R]=23.07%).R decreased slowly at t=[-50,-5], increased sharply at t=[-5, 0], and reached the maximum value at a=0.3.After a rapid decrease at a=[0.3, 4], R decreased slowly at a=[4, 50].The correlation analysis of the traditional physical volume dose threshold also showed that the LEUD (at a=0.3) was correlated with V5, V10, V20, and MLD (r=0.929, P<0.05).Conclusions For patients receiving VMAT for thoracic cancer, LEUD (at a=0.3) can distinguish between patients with and without RP.Therefore, LEUD is recommended to be<510 cGy.A combination of LEUD and conventional physical dose has a good clinical predictive value for RP under non-uniform irradiation.

Advances in radiotherapy combined with EGFR-TKIs for non-small cell lung cancer / 中国肿瘤临床

Lung cancer is the main cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer cases, but only 25%-30% of initially diagnosed patients have the option of radical surgery because of the lack of effective measures for early diagnosis. For locally advanced and advanced NSCLC, radiotherapy alone or comprehensive treatment with chemoradiotherapy is the main treatment method; however, the curative effect is unsatisfactory. Recently, increasing evidence sug-gests that targeted drugs, such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), combined with radiotherapy/chemoradiotherapy represent a promising treatment modality for NSCLC. This review will discuss the research status of EGFR-TKIs and radiotherapy for locally advanced and advanced NSCLC.

Research on the geometric difference between different ITV generation methods in non-small cell lung cancer treated with stereotactic radiotherapy / 中华放射肿瘤学杂志

Objective To study the geometric difference between six different ITV generation methods from 4DCT for patients with non?small cell lung cancer ( NSCLC) treated with stereotactic ablative radiotherapy technique ( SABR) . Methods Between Dec. 2013 and Mar. 2014,16 patients were enrolled in this retrospective study. All patients underwent imaging with 4DCT scans. The MI and DI index were evaluated between six ITV generation methods:combining GTV from all 10 respiratory phases ( ITV10 );combining GTV from four respiratory phases, including two extreme phases ( 0% and 50%) plus two intermediate phases ( 20% and 70%) ( ITVYeo ) which was proposed by Seung?Gu Yeo of Soonchunhyang University;combining GTV from two extreme phases ( ITVEI+EE ) . And combining GTV from five odd phases (10%,30%,50%,70%,90%)(ITVodd).Accordingly the ITVEVEN which was combined from the remaining five even phases (20%,40%,60%,80%,0%),and ITVAVG,ITVMIP were contoured from two reconstructed 4DCT sequences,finally,a method which was not sensitive to the tumor volume and motion characteristic was selected for clinical use. Data were compared using a variance analysis followed by Student?Newman?Keulsa test both in same group or between groups. At the same time, the volume and the three dimensional movements of the tumor, the relativity of MI and DI were analyzed by Multi?parameter regression analysis. Results The mean (range) tumor motion (RLR,RAP,RCC,and R3D) are 3. 5 mm (1. 4?8. 4 mm),4. 5 mm (1. 1?8. 6 mm),9. 5 mm (0?10 mm),12. 3 mm (2. 5?55. 3 mm) respectively. The IGTVx volume are Underestimated by 25. 7%,35. 6%,17. 9%,12. 8%,3. 6%,4. 8%( P=0. 000) respectively. The MI index comparisons between six ITV generation methods and ITV10 showed statistical significance:0. 69,0. 62,0. 80, 0. 86,0. 93,0. 91 ( P=0. 006 ) . The DI index showed no statistical significance:0. 98, 0. 98, 0. 97, 0. 97, 0. 99,0. 98(P=0. 130).The tumor size and motion amplitude were certified not the independent factors for the MI index of ITVodd and ITVEVEN . Conclusions IGTVODD/EVEN based on odd or even 4DCT phases is not sensitive to the tumor size or motion characteristic and is proved to have a good marching with ITV10 meanwhile maintaining a reasonable contouring efficiency,it can be recommend to the institutions which was not equipped with the deformable registration systems.

Experimental gait study based on the plantar pressure test for the young people / 生物医学工程学杂志

Based on force sensing resistor (FSR) sensor, we designed insoles for pressure measurement, which were stable and reliable with a simple structure, and easy to wear and to do outdoor experiments with. So the insoles could be used for gait detection system. The hardware includes plantar pressure sensor array, signal conditioning unit and main circuit unit. The software has the function of data acquisition, signal processing, feature extraction and classification function. We collected 27 groups of gait data of a healthy person based on this system to analyze the data and study pressure distribution under various gait features, i.e., walking on the flat ground, uphill, downhill, up the stairs, and down the stairs. These five gait patterns for pattern recognition and classification by K-nearest neighbors (KNN) recognition algorithm reached up to 90% accuracy. This preliminarily verified the usefulness of the system.

Expression of caudal related homeodomain transcription 2 in colon cancer and its relationship with metas-tasis / 中华内分泌外科杂志

Objective To study the expression of caudal related homeodomain transcription 2 ( CDX2 ) protein in human colon cancer , and study the relationship between protein expression and colon cancer metasta -sis.Methods With immunohistochemical technique in peroxidase notation , pathological specimens of 80 cases of colon cancer were selected , including 47 cases of distal metastasis , and 33 cases without cancer metastasis . CDX2 protein expression in cancer tissue and the related data were statistically analyzed .Results Patients'sex, age and location of colon tumors had no statistical relation with CDX 2 protein expression(P>0.05).CDX2 pro-tein was statistically different in well-differentiated(100.00%), moderately-differentiated(80.00%), and poor-ly-differentiated(33.33%) tumor tissues.The difference had statistical significance (P<0.05), The expression of CDX2 protein reduced with the reduction in the degree of colorectal adenocarcinoma differentiation , rs =0.217, indicating that CDX2 protein expression was positively correlated with the malignant degree of colon canc -er.Positive CDX2 protein expression was significantly lower in metastatic colon cancer tissues (72.3%) than in non-metastatic tissues ( 90.9%) , and the difference had statistical significance .Lymph node metastasis could down regulate CDX2 protein expression in colorectal cancer .Conclusion CDX2 protein is positively correlated with the differentiation degree of colon cancer and distal metastasis can down regulate CDX 2 protein expression .

Research Progress in the mechanism of histone deacetylase inhibitors as radiosensitizers / 国际肿瘤学杂志

One leading research target of modern tumor radiotherapy is to increase radiosensitization of tumor and improve curative effect of radiotherapy.Histone deacetylase inhibitors are epigenetic drugs that can play a part in radiosensitization through means of induction of apoptosis,inhibition of repair of DNA doublestrand breaks,cell cycle arrest,improvement of tumor cell hypoxia and increase of reactive oxygen species.There is an urgent need to develop biomarkers based on these pathways,which can promote clinically individualized treatment.

GPRC5A and lung cancer / 国际肿瘤学杂志

The G protein-coupled receptor family C,member 5,group A (GPRC5A) gene is known as retinoic acid-induced gene,which is mainly distributed in lung tissue.The expression of GPRC5A in lung cancer is significantly decreased compared with normal lung.GPRC5A leads to lung cancer through knockout mice,which is proven to be a suppressor gene of lung cancer.GPRC5A may be a novel biomarker for the diagnosis of lung cancer and a new target for the treatment of lung cancer.

Serum miRNA: a new marker of cancer diagnosis / 国际肿瘤学杂志

Dysfunction of microRNA (miRNA) is associated with occurrence and development of tumor.MiRNA are very stable in blood serum,significantly tumor-related and tissue-specific.The detection of serum miRNA is convenient,little-invasive and fast,and then serum miRNA can be used as a new biomarker for tumor diagnosis.

The effects of a rotating magnetic field in the prevention and treatment of irradiation-induced esophagitis / 中华物理医学与康复杂志

Objective To observe the effect of a rotating magnetic field in preventing and treating irradiation-induced esophagitis in rats. Methods Forty female Wistar rats were randomized into 5 groups:a non-irradiated control group,an irradiation group,an amifostine treatment group ( amifostine group ),a 90 min magnetic field treatment group (90 min magnetic group) and a 120 min magnetic field treatment group ( 120 min magnetic group),with 8 rats in each group.The esophaguses of all rats except those in the control group were exposed to a single irradiation with 6 MV X-rays from a linear accelerator at a dosage of 43 Gy.Four rats in each group were randomly chosen to be observed 1 and 2 weeks after the irradiation.Blood cytokines were detected in their arterial blood.Any pathological changes of the esophagus were observed with HE staining under a light microscope at the same time. Results Irradiation-induced esophagitis was observed in the irradiation group 7 days after irradiation,with obvious exfoliation and necrosis of the esophagal epithelium mucosae.The submucosa were hyperaemic and dropsical with abundant inflammatory cell infiltration.The pathological changes of the esophagus were similar at 7 and 14 days after irradiation.However,the irradiation-induced esophagitis of rats in the amifostine group,the 90 min magnetic group and the 120 min magnetic group were relatively slighter and the blood leucocytes and neutrophis in those 3 groups were significantly lower than those in the irradiation group,while a tendency toward repair of the mucosa of the esophagus was detected.Serum TNF-α,IL-1 and IL-6 in the 90 min magnetic group and 120 min magnetic group were significantly lower than those in the irradiation group. Conclusions Both a rotating magnetic field and amifostine can help prevent and treat irradiation-induced esophagitis.Their therapeutic efficacy is similar.Exposure to a rotating magnetic field could inhibit the expression of inflammatory factors,and thus lessen the inflammatory reaction of acute irradiation-induced esophagitis.

Application of hypofractionated conformal radiotherapy in non-small cell lung cancer / 国际肿瘤学杂志

Hypofractionated conformal radiotherapy is capable to deliver much higher doses to the cancer than is possible with standard techniques. Recently there is data suggesting that the early stage nonsmall cell lung cancer ( NSCLC) which is not suitable to surgery is likely to benefit from this regimen, with low lung toxicity. Manyphase Ⅰ-Ⅱ studies showed that the patients with locally advanced NSCLC are well-tolerated to hypofractionated conformal radiotherapy. The model of radio-physic and relative clinical studies suggest that hy-pofractionation would not increase the risk of radiation pneumonitis compared to standard therapy.