ABSTRACT
Objective:To investigate the expression changes at the transcriptional level in normal lung tissues of mice after exposure to heavy ion radiation for different durations at different doses, aiming to provide evidence for exploring sensitive genes of heavy ion radiation, heavy ion radiation effect and the damage mechanism.Methods:Experiments on the temporal kinetics: the whole thorax of mice was irradiated with 14.5Gy carbon-ions and the total RNA of lung tissue was extracted at 3days, 7days, 3 weeks and 24 weeks. In dose-dependent experiment, the total RNA of lung tissue was extracted at 1 week after irradiated with a growing thoracic dose of 0, 7.5, 10.5, 12.5, 14.5, 17.5 and 20Gy. Protein-to-protein interaction (PPI) analysis and gene-ontology biological process enrichment analysis were performed on significant differentially expressed genes (DEGs).Results:A clearly differential expression patterns were observed at 3-day (acute stage), 1-week (subacute stage), 3-week (inflammatory stage) and 24-week (fibrosis stage) following 14.5Gy carbon-ions irradiation. Among those, the 3-day time point was found to be the mostly different from the other time points, whereas the 7-day time point had the highest uniformity with the other time points. Cellular apoptosis was the main type of cell death in normal lung tissues following carbon-ions exposure. The interactive genes of Phlda3, GDF15, Mgmt and Bax were identified as the radiosensitive genes, and Phlda3 was the center ( R=0.76, P<0.001). Conclusion:The findings in this study provide transcriptional insights into the biological mechanism underlying normal lung tissue toxicity induced by carbon-ions.
ABSTRACT
Objective To investigate the radiation induced pulmonary fibrosis with a dose-response mouse model, based on the CT image changes of pulmonary fibrosis.Methods Female C57BL6 mice aged 8-10 weeks were randomly divided into 20 Gy or escalated doses of X-ray whole thoracic irradiation ( WTI) groups. CT scan was performed at different time points before and after radiation. The average lung density and lung volume changes were obtained by three-dimensional segmentation algorithm. After gene chip and pathological validation, the parameters of CT scan were subject to the establishment of logistic regression model. Results At the endpoint of 24 weeks post-irradiation, the lung density in the 20 Gy irradiation group was (-289.81± 12.06) HU, significantly increased compared with (-377.97± 6.24) HU in the control group ( P<0.001) . The lung volume was ( 0.66±0.01) cm3 in the control group, significantly larger than ( 0.44±0.03) cm3 in the irradiated mice ( P<0.001) . The results of quantitative imaging analysis were in accordance with the findings of HE and Mason staining, which were positively correlated with the fibrosis-related biomarkers at the transcriptional level ( all R2=0.75, all P<0.001) . The ED50 for increased lung density was found to be ( 13.64± 0.14) Gy ( R2=0.99, P<0.001) and ( 16.17± 4.36) Gy ( R2=0.89, P<0.001) for decreased lung volume according to the logistic regression model. Conclusions Quantitative CT measurement of lung density and volume are reliable imaging parameters to evaluate the degree of radiation-induced pulmonary fibrosis in mouse models. The dose-response mouse models with pulmonary fibrosis changes can provide experimental basis for comparative analysis of high-dose hypofractioned irradiation-and half-lung irradiation-induced pulmonary fibrosis.
ABSTRACT
Objective To explore the role and mechanism of miR-20a in the radiosensitivity of hepatocellular carcinoma (HCC). Methods The expression level of miR-20a in HCC cell lines and tissue specimens was detected by real-time fluorescent quantitative PCR.HCC cell line stably over-expressing miR-20a was constructed. The effect of miR-20a on HCC cell radiosensitivity was evaluate by cloning assay. The expression levels of Bcl-2,Caspase-3 and γ-H2AX proteins were quantitatively detected by Western blot. The target gene of the downstream regulation of miR-20a was predicted by bioinformatics analysis,which was further verified by dual luciferase reporter assay,real-time fluorescent quantitative PCR and Western blot. HCC cell line stably overexpressing miR-20a was transfected with pCDNA3. 0-PTEN to investigate the changes in the radiosensitivity of cells and to determine whether PTEN is a functional target gene for miR-20a-induced radioresistance of HCC. Results The expression levels of miR-20a was significantly up-regulated in HCC cell line and tissue specimens ( both P< 0. 05). After identical radiotherapy, the cell survival rate,the radioresistance was strengthened ( P< 0. 05),the expression of Bcl-2 was up-regulated, whereas the expression levels of Caspase-3 and γ-H2AX were down-regulated in the LV-miR-20a group compared with those in the blank and control groups ( WT and LV-con groups). Overexpression of PTEN could reverse the miR-20a-induced radioresistance. Conclusion miR-20a is up-regulated in the HCC cell lines and tissue specimens. Overexpression of miR-20a can promote the radioresistance of HCC cells. PTEN is a functional target gene for miR-20a-induced radioresistance of HCC,indicating that miR-20a/ PTEN site may be an effective molecular target associated with clinical radiotherapy for liver cancer.
ABSTRACT
Objective Tiam1, a member of guanine nucleotide exchange factors, plays an important role in tumor invasion and metastasis.This study aimed to construct Tiam1 truncated recombinant plasmids and induce the expression of GST-tagged human Tiam1 fusion proteins in Escherichia coli (E.coli), followed by purification and identification of the GST-Tiam1 fusion protein.Methods The cDNA fragments of Tiam1 C685, C751 and C1199 were amplified by PCR and cloned into the pGEX-4T-1 vector.After verified by DNA sequencing, the recombinant plasmid was transformed into E.coli BL21 (DE3) competent cells, and the expression of the fusion protein was induced by IPTG.The GST-tagged human Tiam1 fusion proteins were purified with glutathione-agarose resin and indentified by Western blot.Results Three Tiam1 truncated recombinant plasmids were constructed successfully.The recombinant fusion proteins GST-Tiam1 C685, GST-Tiam1 C751, and GST-Tiam1 C1199 were expressed mainly in the form of soluble proteins in the cell lysate supernatant with expected relative molecular weight of 100, 108, and 157 kD.Conclusion The recombinant plasmids expressing the bioactive fusion proteins were constructed successfully, which has prepared the ground for the subsequent studies of the Tiam1 protein.
ABSTRACT
Objective: To study the quality and transdermal properties of matrine microemulsion-based hydrogel (MBH) to provide basis for the development of the preparation.Methods: The stability of MBH was observed at 4 ℃ for 3 months and the changes of particle appearance, viscosity, pH and matrine content were observed.The transdermal permeation of MBH was investigated by a dual chamber permeation and diffusion device with excised mouse skin as the barrier.Taking rabbits as the experimental subjects, the irritation of MBH to the normal skin and damaged skin was investigated.Results: The appearance, viscosity, pH and matrine content of MBH at 4 ℃ in 3 months did not change significantly.In vitro transdermal test showed that MBH had a good penetration rate on mouse skin, and no skin irritation occurred after single or multiple administrations.Conclusion: MBH has good stability and high rate of transdermal penetration without skin irritation, which is a promising drug delivery system of matrine with good application prospects.
ABSTRACT
BACKGROUND:To trace the survival status of transplanted stem cels and the integration with host tissues using non-invasive imaging techniques are the focus of research in recent years. OBJECTIVE:To observe the distribution and migration of superparamagnetic iron oxide (SPIO)-labeled adipose-derived stem cels in the brain of rats with cerebral infarction. METHODS:Rat models of cerebral infarction were established and randomized into SPIO-labeled group and unlabeled group. At 1 day after modeling, the rats in the two groups were given SPIO-labeled adipose-derived stem cel suspension (10 μL) and unlabeled adipose-derived stem cel suspension (10μL) into the brain, respectively. At 1, 7, 14 days after cel transplantation, neurological severity scores were measured, and MRI was used to observe the distribution of SPIO-labeled adipose-derived stem cels. RESULTS AND CONCLUSION:At 7 and 14 days after transplantation, the neurological severity scores in the two groups were significantly lower than those at 1 day after transplantation (P 0.05). At 14 days after transplantation, MRI findings showed low signals in the transplanted region, indicating the cels migrated from the corpus calosum to the lesion. These findings suggest that intracerebral transplantation of adipose-derived stem cels can promote neurological recovery from cerebral infarction in rats, and MRI can be used to visualize the distribution and migration of SPIO-labeled adipose-derived stem cels in the brain.
ABSTRACT
Objective To investigate the role of individual dental stent on taste protection in the patients with primary nasopharyngeal carcinoma.Methods Firstly,dosimetric evaluation of the tongue under the circumstance of 10 pairs of patient wearing dental stent or not was done.Secondly,a total of 61 patients were randomized into two arms:29 were in the trial arm and 32 in the control arm.The patients wore dental stent during radiotherapy in trial group,but not in control group.The endpoint was taste dysfunction before radiotherapy,every week during radiotherapy till the completion of radiotherapy,and followed up six months after radiotherapy.Results The mean dose of tip of tongue,body of tongue,base of tongue for patient with dental stent or not were (394.43±24.01) cGy,(986.35±77.15) cGy,(4 401.16±179.01) cGy and (677.03± 110.05) cGy,(2 418.19±414.18) cGy,(4 878.67±387.45) cGy (P value were 0.031,0.007 and 0.284,respectively) separately.By the completion of the radiotherapy,there were 9 (31.03 ％) patients suffering from a taste dysfunction in the trial group and 25 (78.13 ％) in the control group (P ＜ 0.001).Conclusions Individual dental stent has a potential tendency to relieve the taste impairment by reducing the irradiation dose of tongue.
ABSTRACT
Objective To investigate the risk factors of radiation-induced oral mucositis (ROM) and to provide evidence for the prevention of ROM. Methods The severity of ROM was observed and recorded in 56 patients with nasopharyngeal carcinoma. The association of the severity of mucositis with age , sex, clinical stage, concurrent chemoradiotherapy, white blood cell count,BMI index, smoking, alcohol intake, and history of diabetes were assessed by using multivariate logistic regression analysis. Results The severity of ROM was significantly associated with a decrease in leucocyte count (P0.05). Conclusions Leukopenia was one of the risk factors for the development of ROM. In clinical pratice,leukopenia should be corrected in patients with bone marrow depression due to radiotherapy in a timely manner.
ABSTRACT
Objective To study the specific killing effect in human carcinoma cells aftercombination treatment of radiation and p53 gene regulated by a radiation-enhanced promoter.Methods Aplasmid pE6 (TATA)-p53 was constructed.After irradiation,the expression of P53 was detected withWestern blot assay,apoptosis was detected by Annexin V-FITC,and cell survival was detected byclonogenic assay then the sensitivity enhancement ratio (SER) was analyzed for HeLa and A549 cells.Results The expression of P53 were increased in the irradiated cells and 6 Gy irradiation triggered thestrongest activity.After p53 transfection,radiation-induced apoptosis was obviously enhanced incomparison with the control group without gene transfection (F =11.018,10.736,P ＜ 0.05).The SER ofp53-promoter was 2.36 for A549 cells and 2.56 for Hela cells.Conclusions The p53-plasmid promotercould induce apoptosis and enhance the radiosensitivity of tumor cells,which may provide a noveltherapeutic strategy for cancer treatment.
ABSTRACT
Objective To analyze the prognostic impact of degree of bone metastasis in patients with nasopharyngeal carcinoma (NPC) after radiochemotherapy.Methods A retrospective analysis was performed on the prognosis of 109 NPC patients who had bone metastases after radiochemotherapy in Nanfang Hospital from June 1997 to December 2007.The Kaplan-Meier method was used to calculate survival rates; the log-rank test was used for univariate prognostic analysis; the Cox regression model was used for multivariate prognostic analysis.Results The 5-year follow-up rate was 97.2％.The 1-,2-,3-,and 5-year overall survival rates for all patients were 67.9％,48.6％,32.9％,and 17.4％,respectively.The 1-,2-,3-,and 5-year survival rates for the 43 patients with not more than 3 bone metastases and the 66 patients with more than 3 bone metastases were 90.7％ vs.53.0％,81.4％ vs.27.3％,72.1％ vs.6.2％,and 34.9％ vs.4.2％,respectively (P=0.000).In the patients with more than 3 bone metastases,the 1-,2-,3-,and 5-year survival rates for those with and without other metastatic sites were 56.5％ vs.72.1％,21.7％ vs.30.2％,3.1％ vs.13.0％,and 0.0％ vs.6.5％,respectively (P=0.866).The multivariate analysis showed that more than 3 bone metastases were an adverse prognostic factor in the patients (P =0.000).Conclusions The number of bone metastases is an important prognostic factor in NPC patients after radiochemotherapy.Patients with not more than 3 bone metastases have better survival than those with more than 3 bone metastases,and aggressive treatment should be considered.In addition,the staging system of NPC needs to be improved.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the association of MnSOD single nucleotide polymorphisms (SNPs) with the susceptibility to nasopharyngeal carcinoma (NPC) in Cantonese.</p><p><b>METHODS</b>A total of 105 Cantonese NPC patients and 136 age-matched healthy controls were enrolled in this study. Genotyping of the SNP Ala-9Val of MnSOD gene was performed by PCR and direct sequencing of the PCR products.</p><p><b>RESULTS</b>The allele frequency of Ala in Cantonese was 19.1%. The frequencies of Val/Val, Val/Ala, and Ala/Ala genotypes were 83.8%, 14.3%, and 1.9% in NPC patients and 80.9%, 16.9%, and 2.2% in healthy individuals, respectively. No significant differences were found in the allele or genotype frequencies between NPC patients and controls. Ala/Val genotype was shown to be significantly less frequent in patients with a positive lymph node status, but the allele Ala was not correlated to lymph node involvement. No significant differences were found in the allele and genotype frequencies in patients with different tumor sizes, metastatic statuses, clinical statuses and histological types.</p><p><b>CONCLUSION</b>MnSOD Ala-9Val polymorphism can be region- and race-related, and it is not correlated to the genetic susceptibility of NPC in Cantonese.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Carcinoma , Case-Control Studies , China , Epidemiology , Gene Frequency , Genetic Predisposition to Disease , Genotype , Nasopharyngeal Neoplasms , Epidemiology , Genetics , Polymorphism, Single Nucleotide , Superoxide Dismutase , GeneticsABSTRACT
The target organs of the most common complications in thoracic radiotherapy mainly contain esophagus,lung and cardiovascular system.Studies of influences such as the related physical dose factors and combined chemotherapy and so on,susceptible biomarks,protective factors,become the study focus,which provide the light for clinical prevention and therapy.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effects of Pseudomonas aeruginosa vaccine (PA-MSHA) on the proliferation of human nasopharyngeal cancer cells and explore the possible mechanism.</p><p><b>METHODS</b>MTT assay was used to determine the cell growth of human nasopharyngeal cancer cell line 5-8F and 6-10B in vitro treated with the vaccine. The cell cycle distribution of the cells was detected by flow cytometry, and the expression levels of apoptosis and cycle-related proteins were evaluated by Western blotting.</p><p><b>RESULTS</b>PA-MSHA treatment significantly suppressed the proliferation of 5-8F and 6-10B cells in a time- and concentration-dependent manner compared with the control group (P<0.05). The cells with PA-MSHA treatment exhibited a decreased percentage of cells entering S phase and a corresponding increase in G(1) phase cells in FACS analysis. The expression of cyclin D(1), CDK4, and CDK6 was significantly up-regulated, Bax protein up-regulated, and the anti-apoptosis protein Bcl-2 down-regulated in PA-MSHA-treated cells.</p><p><b>CONCLUSION</b>PA-MSHA can suppress the proliferation of nasopharyngeal carcinoma cell in vitro by affecting the cell cycle and promoting cell apoptosis.</p>
Subject(s)
Humans , Apoptosis , Cancer Vaccines , Allergy and Immunology , Cell Line, Tumor , Cell Proliferation , Nasopharyngeal Neoplasms , Pathology , Pseudomonas aeruginosa , Allergy and ImmunologyABSTRACT
Objective To investigate the radiosensitivity of silencing N-Ras by RNA interference in hepatoma carcinoma cell MHCC-97.Methods N-Ras RNA interference (RNAi) vector was constructed by using pcDNA 6.2-GW/EmGFP-mir plamid.The RNAi effect was detected by RT-PCR,Western bolt,immunohistochemisty and MTT method.Survival curve for each cell line were obtained by measuring the clone forming abilities of irradiated cell populations.Results After silencing the N-Ras by RNAi,The expression level of N-Ras mRNA,N-Ras protein,immunohistochemisty were decreased 96.9% ±0.159%(t=40.377,P＜0.05),89.8%±0.012% (t=31.595,P＜0.05),90%,respectively,and The survival of hepatoma carcinoma cell MHCC-97 line were inhibited 21.9% (F = 4.63,P < 0.05).Which have significant difference in statistics.The SER of hepatoma carcinoma cell MHCC-97 line after interference was 1.15.Conclusions RNAi targeting silence N-Ras may increase the radiosensitivity of hepatoma carcinoma cell MHCC-97 line.
ABSTRACT
Objective To explore the relationship between severe(≥grade 3 ) radiation pneumonitis (RP) and dose-volume histogram (DVH) parameters for non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3-DCRT). Methods Ninety-four patients with NSCLC treated with 3-DCRT were retrospectively analyzed. Clinical parameters were analyzed. DVH parameters analyzed were V20, V30, V40,mean lung dose (MLD),normal tissue complication probability(NTCP) ,and total dose. Results Age,sex, Karnofsky scored, performance status, forced expiratory volume in 1 second,presence of weight loss, preexisting lung disease, history of thoracic surgery, and history of chemotherapy were not associated with the risk of severe RP(P>0.05). However,in univariate analyses, V20, V30, V40, MID and NTCP were associated with severe RP(P<0.01). In multivariate analysis, MID and V30 were variable associated with severe RP(P<0.01). The severe RP was 0 when MLD < 10 Gy and 21%(8/39) when MLD between 10 Gy and 20 Gy but 35%(7/20) when MLD > 20 Gy,it was 0 when V30 < 25% and 12%(4/33) when V30 between 25% and 35% but 38%(11/29) when V30 >35%. Conclusion MLD and V30 are significant predictive factors for severe RP and they should be limited to ≤20 Gy and ≤ 35% in order to reduce severe RP.
ABSTRACT
Objective:To study the clinical features and prognostic factors of brain injury after radiothera-py for nasopharyngeal carcinoma(NPC).Methods:From January 1998 to June 2006,49 NPC patients with Dost-radiation brain injury in our hospital were analyzed retrospectively.Results:The incidence of post-radia-tion brain injury after single-pass radiotherapy and re-course radiotherapy was 2.31%and 9.64%.respectively ,(P＜0.05).The median latency period was 50.5 months for single-pass radiotherapy and 25.5 months for re-course radiotherapy.Fourty-nine patients suffered from radiation injury in the brain.The lesions were locat-ed in the temporal lobe in 37 patients(75.5%),in the pens in 9 patients(18.4%)and in mixed position in 3 pa-tients(6.1%).The symptoms and signs of the patients could be alleviated by therapy, but the quality of life was not improved.Conclusion:Radiation brain injury in NPC patients after radiotherapy is related to field de-sign.The incidence of radiation brain injury in the temporal lobe is the highest.Compared with single-pass ra-diotherapy, re-course radiotherapy leads to higher incidence of brain injury and shorter latency period.
ABSTRACT
This article introduces a new educational model-Ability Standard Teaching Mode,which emphasizes that students should participate in teaching and promotes the students to change their thinking style from memory and imitation style to thought and creativity style.
ABSTRACT
There are many difficulties in studying Radiation & Oncology.We improve the teaching effect by selecting the proper teaching content,optimizing the teaching mode,cultivating idea of multidisciplinary tumor management and clinical teaching.
ABSTRACT
Objective To analyse the ultrastructural and metabolic changes of brain injury after single-fraction high-dose radiation in rabbits by means of proton 1-hydrogen) magnetic resonance spectroscopy ~1H MRS) ,in order to provide the basic theory for early detection of radiation-induced brain injury.Methods Experimental model of single-fraction high-dose radiation-injured brain was established in 40 rabbits , which were randomly divided into 4 groups and underwent 10, 15, 20 Gy and 30 Gy radiation , respectively. Proton MRS in a clinical MR imager was used to ascertain the amount of whole-brain N-acetylaspartic acid NAA), lactic acid Lac), choline Cho), creatine Cr) before and within 8 weeks after focused single-fraction high-dose irradiation therapy. Metabolic maps of NAA, Lac, Cho and Cr were created from MRS data set. Detection of irradiation injury among the tested models was assessed by receiver operating characteristic analysis and by quantitative signal intensity changes. The peak values of NAA , Lac , Cho and Cr on MRS before and after radiation were measured. Histopathology and electron microscope were used to ascertain changes of the ultrastructural organization in the irradiated area.the results were compared and statisti-cally analyzed. Results Initially MRS was found a slightly decrease. Until obviously change was detected, statistical significance variation of MRS occurred. A significant decrease in~1H MRS occurred at the early stage of brain injury induced by single-fraction high-dose irradiation.Conclusion ~1H MRS may be regarded as a noninvasive and sensitive means for the detection of early radiation-induced brain injury.
ABSTRACT
Objective To evaluate the efficacy of transcatheter arterial chemoembolization (TACE) combined with hypofractionated 3 dimensional conformal radiotherapy for hepatocellular carcinoma (HCC). Methods During May 1998 and Dec. 1999, 81 unresectable HCC patients were divided into two groups. Forty one patients in group A were treated with TACE and hypofractionated 3 dimensional conformal radiotherapy and 40 patients in group B were treated with TACE alone. Acute effects were analyzed and survival rates were assessed from the date of the beginning of treatment using the Kaplan Meier method. The survival rates of two groups were compared using Log rank. The Cox proportional hazards model was used to analyze the prognostic factors in group A. Results The objective response rate in group A was higher than that in group B (85.4% vs. 65.0% , P