Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism / 生物医学工程学杂志

Oncogene StarD4 had the function of promoting proliferation and metastasis of triple-negative breast cancer (TNBC), but its clinical value and molecular mechanism are unknown. This paper found that StarD4 was highly expressed in cancer tissues of TNBC patients, and higher expression level of StarD4 in TNBC patient resulted in poorer prognosis. Based on transcriptomics of MDA-MB-231 cell model, the results of bioinformatics analysis showed that down-regulated expression level of StarD4 led to overall downregulation of cholesterol-relative genes and significant enrichment of cancer mechanism and pathway. Further analysis and investigation verified that StarD4 might cross-promote the protein stability of receptor ITGA5 through the cholesterol pathway to enhance TNBC progression, which provides guidance for clinical application of TNBC diagnosis and treatment.

Value of supraclavicular region radiotherapy on patients with pT1-2N1M0 breast cancer after mastectomy / 中南大学学报(医学版)

To evaluate the potential clinical benefit on radiotherapy to supraclavicular region on patients pT1-2N1M0 breast cancer with after mastectomy.
 Methods: A total of 923 patients with pT1-2N1M0 treated by radiotherapy (RT) to chest wall plus supraclavicular region (supraclavicular RT group, SCRT) or RT to chest wall only (non-supraclavicular RT, NSCRT) were retrospectively analyzed. Supraclavicular fossae recurrence (SCFR) rate and overall survival (OS) rate were analyzed by Kaplan-Meier method. The risk factors for SCFR were evaluated by univariate and multivariate analysis.
 Results: In the following-up period (medium time: 108 months; range from 6 to 179 months), the 5-year and 10-year SCFR in the NSCRT group and the SCRT group were 3.5% and 1.5% (P=0.052), 7% and 2.6% (P=0.001), and the 5-year and 10-year OS were 81.5% and 87.3% (P=0.023), 67.9% and 78.4% (P=0.001), respectively. Univariate analysis showed that risk factors associated with SCFR were age <35 years (P=0.016), T2 stage (P=0.018), 3 axillary lymph nodes (P=0.006), progesterone receptor negative (P=0.038), and human epidermal growth factor receptor-2 positive (P=0.01). Multivariate analysis further demonstrated that T2 stage and age<35, with 3 positive axillary lymph nodes were SCFR-independent prognostic factors. Analysis was conducted by grouping patients with any two of the three items as a high-risk group and patients without or with only one of the three conditions as a low-risk group. RT in the supraclavicular region significantly reduced the 10-year SCFR in the high-risk group (NSCRT, 30.2%; SCRT, 4.5%, P<0.001). However, this benefit was not obvious in the low-risk group (NSCRT, 4%; SCRT, 1.8%, P=0.063).
 Conclusion: RT in supraclavicular region should be recommended to pT1-2N1M0 breast cancer patients with two of the three items (<35 years, T2 stage diseases, and 3 axillary lymph node metastasis). High-risk patients need SCRT; whereas the low-risk patients do not need.

p53 gene mutations of familial breast cancer and early-onset breast cancer in part population of southern China / 中南大学学报(医学版)

Objective:To investigate the site and characteristic ofp53 gene mutations in familial or early-onset breast cancer patients in part population of southern China.Methods:A total of 150 patients with familial and early-onset breast cancer in parts population of southern China were enrolled.Genomic DNA was isolated from each peripheral blood sample,and the entire coding sequence and exon and intron splicing region of p53 gene were amplificated by PCR in the 150 patients.The mutation analysis were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by DNA sequence analysis.Results:In the 150 patients with familial and early-onset breast cancer,6 mutations including one novel pathogenic mutation 869_888 ins20 (insert mutation) and 5 previously reported pathogenic mutations (deletion mutation 643_660de118 and 4 missense mutation 91G＞A,215C＞G,537T＞G,743G＞A) were identified in p53 gene encoding region in 9 patients of breast cancer.Moreover,one same sense mutation 141G＞A in exon 4,one 16 bases deletion in intron 3,and 9 single nucleotide polymorphisms in p53 gene introns were also identified.The total mutation frequency ofp53 gene in 150 patients with familial breast cancer and early-onset breast cancer from part population of southern China was 6.00％,and the mutation frequency of familial breast cancer and early-onset breast cancer was 6.81％ and 6.25％,respectively.Conclusion:The total mutation frequency ofp53 gene in 150 patients with familial breast cancer and early-onset breast cancer from partpopulation of southern China is higher than the frequency previously reported.The pathogenicity of the novel mutations (insert mutation) 869_888ins20 will be confirmed by function analysis in the future study.The deletion mutation 643_660de118 enriches the p53 gene mutation database among Chinese population,which is probably the specific mutation of breast cancer in Chinese population.

Inhibition of cellular proliferation by knockdown of MARCH6 gene expression in breast cancer cells / 中南大学学报(医学版)

To investigate effects of MARCH6 gene knockdown on MCF-7 cell proliferation and cell cycle.
 Methods: 293T cells were transfected with MARCH6 shRNA lentivirus. Fluorescence microscope was used to observe and verify the transfection efficiency. The initial effect of the MARCH6 gene knockdown in MCF-7 cells was observed via fluorescence microscope. Real-time PCR and Western blot were used to detect the expression of MARCH6. MTT and BrdU assay were used to examine cell proliferation, and staining flow cytometry was used to analyze cycle distribution of MCF-7 cells.
 Results: MARCH6 shRNA lentivirus was successfully transfected and about 80% of the cells expressed green fluorescent in comparison of the control. About 90% of the cells showed green fluorescence. The mRNA and protein in MCF-7 cells were transcription and expression of protein was significantly decreased after the transfection of MARCH6 shRNA lentivirus accompanied by a decrease in MCF-7 cell proliferation (P<0.01). Flow cytometry showed that the cell cycles were inhibited at the G1 phase and the proliferation index was significantly reduced.
 Conclusion: Knockdown of MARCH6 gene by RNA interference inhibits the proliferation of MCF-7 cells, suggesting that the expression of MARCH6 promotes proliferation of breast cancer cells through regulation of the cell cycle.

A study of stability training and reliability of bladder filling before radiotherapy for pelvic tumors / 中华放射肿瘤学杂志

Objective To explore the reliability of patients' sensation of the need to urinate,and to investigate the optimal volume and duration of bladder filling and training method for the stability of bladder filling. Methods From 2014 to 2015,Fifty patients with pelvic tumor were divided into group A and group B,according to whether they had the history of diseases or surgery in the pelvis or urinary system. Both groups received training of the sensation of the need to urinate. The training required patients to drink a fixed volume of water every time they emptied the bladder. The bladder capacity was measured by a bladder scanner ( BladderScan BVI 9400) ,and a rating scale of the sensation of the need to urinate was completed at 30 min,45 min,1 h,and over 1 h when the patient sensed the limit for bladder capacity. The optimal volume and duration of bladder filling or optimal frequency for the training were explored. The paired t-test method was performed for the difference between the predictive value and the measured value,Pearson method was performed for correlation between the sensation of the need to urinate and the measured value. Results In the A and B groups,there was no significant difference between the predicted value and measured value ( A:predicted value and measured value P=0. 777,B:predicted value and measured value P=0. 061) ,suggesting that the measured value could be used to reflect the predictive value. Compared with group B,group A had a higher correlation between the sensation of the need to urinate and the measured value ( rA=0. 812, rB=0. 762).The correlation between the predictive value and the measured value became the highest at 45 min and 1 h ( r=0. 858 and 0. 916) ,and the corresponding bladder filling volume and score of the sensation of the need to urinate were 330-450 ml and 4-6,respectively. The correlation between the predictive value and the measured value increased with the frequency of the training ( r2=0. 914, r3=0. 917, r4=0. 930, r5=0. 951,r6=0. 962) . Conclusions Before radiotherapy,patients with pelvic tumor should received at least 4-6 rounds of the training of bladder filling. Patients should drink 800-1 400 ml of water every time they empty the bladder,and the optimal bladder filling volume and the reliable and stable sensation of the need to urinate will be achieved after 45 min-1 h. For the patients with the history of urinary system diseases or pelvic surgery,the bladder filling volume needs to be measured using a bladder scanner ( BladderScan BVI 9400) during the training before radiotherapy.

Effect of CDK2-AP1 gene over-expression on proliferation and cell cycle regulation of breast cancer cell line MCF-7 / 中南大学学报(医学版)

OBJECTIVE@#To over-express cyclin-dependent kinase 2-associated protein 1 (CDK2-AP1) gene, and investigate its effect on the proliferation and cell cycle regulation in breast cancer cell line MCF-7.@*METHODS@#CDK2-AP1 gene coding region was cloned into lentivirus vector. Lentivirus particles were infected into MCF-7 cells to upregulate the expression of CDK2-AP1 gene. The expression level of CDK2-AP1 was detected at both mRNA and protein levels by real-time PCR and Western blot. MTT assay, colony formatting assay, and flow cytometry were performed to detect the change of proliferation and cell cycle in MCF-7 cells. We examined the expression of cell cycle associated genes (CDK2, CDK4, P16Ink4A, and P21Cip1/Waf1) followed by CDK2-AP1 over-expression by Western blot.@*RESULTS@#CDK2-AP1 gene was up-regulated significantly at both mRNA (6.94 folds) and protein level. MTT based growth curve, colony formatting assay and flow cytometry showed that CDK2-AP1 over-expression lentivirus inhibited the proliferation of MCF-7 cells with statistical difference (P<0.05). In addition, with CDK2-AP1 over-expression, MCF-7 cells were arrested in G1 phase accompanied by apoptosis. Western blot showed that the expression level of P21Cip1/Waf1 and P16 Ink4A was upregulated, while the expression level of CDK2 and CDK4, members of the CDK family, was downregulated.@*CONCLUSION@#CDK2-AP1 gene plays a cancer suppressor role in breast cancer. Its function includes inhibiting the proliferation of MCF-7 cells and arresting the cell cycle in G1 phase.

Efficacy and safety of 3-dimensional conformal radiotherapy combined with temozolomide for glioma / 中南大学学报(医学版)

OBJECTIVE@#To study the efficacy and safety of 3-dimensional conformal radiotherapy combined with temozolomide (TMZ) for gliomas.@*METHODS@#A total of 78 patients with pathologically confirmed glioma ( from September 2005 to March 2007) were postoperatively divided into 3 groups: a chemotherapy group (n=24), a radiotherapy group (n=25), and a comprehensive therapy group(n=29). The patients received temozolomide alone,3-dimensional conformal radiotherapy alone,3-dimensional conformal radiotherapy combined with temozolomide in the chemotherapy group,the radiotherapy group and the comprehensive therapy group respectively. The survival rate, progression-free survival, overall survival time and adverse reactions were observed.@*RESULTS@#The 3-year survival rate in the comprehensive therapy group was significantly higher than that in the other two groups. The 3-year survival rates were 20.83%, 20.00%, and 41.38% in the chemotherapy group, the radiotherapy group and the comprehensive therapy group respectively. The progression-free survival time was 17.68,17.94, and 23.29 months and the average overall survival time was 20.28, 21.54, and 25.75 months in the chemotherapy group, the radiotherapy group and the comprehensive therapy group, respectively.The adverse reactions were mild and tolerable.@*CONCLUSION@#Three-dimensional conformal radiotherapy combined with temozolomide is more effective for gliomas than the simple 3-dimensional conformal radiotherapy and the temozolomide chemotherapy alone.

Dosimetric verification and clinical efficacy of intensity modulated radiotherapy in nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVE@#To investigate dosimetric characteristics and to evaluate the clinical efficacy of intensity modulated radiotherapy (IMRT) as compared with conventional radiotherapy in nasopharyngeal carcinoma (NPC).@*METHODS@#Forty-seven NPC patients who accepted IMRT served as the IMRT group, and conventional radiotherapy plan was also made for each patient in this group using the treatment planning system. Dosiological evaluation of the 2 radiotherapy plans was made through dose volume histogram, 95% target volume dose (V(95)) and normal tissue complication probability. Another 47 patients who underwent conventional radiotherapy (CRT) at the same period formed the control group. The therapeutic effect as well as the acutes and late toxicities of normal tissues in the 2 groups were observed.@*RESULTS@#V(95) of the IMRT was more than 96% (96.83%-99.99%) for each target area, obviously superior to CRT in the sub-clinical target area. The radiation dose of normal tissues such as the brainstem and the spinal cord in the IMRT was much less than that in the CRT. Consistant with this, the part and complete remission rate, the 3-year loco-regional progress free survival rate, and overall survival rate in the IMRT group were all higher than those in the CRT group. For most patients in the IMRT group, the grade of acute toxicities was much lower than that in the CRT group. Patients in the IMRT group showed no more than grade 3 xerostomia, while in the CRT group still 21% of the patients suffered grade 3 or higher xerostomia a year later.@*CONCLUSION@#Compared with CRT, IMRT can improve the target volume dose and decrease the dose of surrounding tissues, resulting in higher control rate and fewer side effects.

Comparison of radiobiological models for evaluation of radiotherapy treatment planning of breast cancer / 中华放射肿瘤学杂志

Objective To find an appropriate r3diobiological model for analyzing the biological effect of the radiotherapy for breast cancer by comparing different results computed by various types of radiobiological models. Methods DVHs database simulating breast conserving radiotherapy was set up,based on clinical DVHs data of the heart.the lung and PTV of 22 patients with early breast cancer given conventional tangential radiotherapy.Two models assessing NTCP of radiation pneumonitis and cardiac mortality and four models assessing TCP were compared by analyzing the effects of the parameters and DVH database input methods on the results. Results When mean irradiation dose of the whole lung was 30 Gy.the incidence of radiation pneumonitis was 32%and 54%predicted by NTCP-RSM model and NTCP-Lyman model,respectively.When 1%cardiac mortality of radiation was assumed,28 Gy and 40 Gy isodose should cover the heart assessed by the two models.The mean TCP were 21.1%.80.8%.38.4%and 41.0%when assessed by LQ-Poisson-TCP,Zaider-TCP,Poisson-TCP and Logit-TCP models,respectively.Setting various differential DVH(dDVH)bins had very few effect on the NTCP/TCP results in a certain model.Adopting physical dose or LQED2 affected the results with greater resu]ts for physical dose.Variation in α or β value,tumor cell density and D50 had significant effect upon TCP results in LQ-Poisson-TCP(P:0.000). Conclusions NTCP-Lyman model is better for predicting the incidence of radiation pneumonitis while NTCP-RSM model is better for predicting radiation-induced cardiac mortality.LQ-Poisson-TCP is the best TCP model for clinical application.Parameters selected for model can significantly affect the results.It is imporrant to understand the distinct characteristics of different models.

Post-operative radiotherapy for renal cell carcinoma: reterospective analysis of 90 patients / 中华放射肿瘤学杂志

Objective To evaluate the efficacy of post-operative radiotherapy and prognosis of renal cell carcinoma(RCC). Methods Between 1981 and 1998 , 90 s uch patients with disease limited to the kidney underwent nephrectomy at our ins titution. According to TNM classification(UICC,1997) the pathological stage was: Ⅰin 27 patients(30%),Ⅱ in 18 (20%), Ⅲ in 35(38.9%), and Ⅳ in 10(11.1%).Post - operative irradiation, with a median dose of 50?Gy in 25 fractions over 5 weeks w as given to 52 patients in 3～5weeks after surgery, using AP-PA opposing portal s or oblique portals. Results The 5- and 10-year survival rates in the irradiate d patients(S+Rt) were 75% and 60%,respectively, but in the non-irradiated patien t s(S) 50% and 40%, respectively.This difference is statistically significant. 5- y ear survival rates by TNM stage in the two groups were as follows: stageⅠ:S 67 %,S+Rt 100%;stageⅡ: S 55%,S+Rt 71%;stageⅢ: S 47%,S+Rt 65% (P=0 .010);stageⅣ: S 0%, S+Rt 43%.Diseases recurred locally in a total of 12 patients: 3 had tumo r b ed recurrence and 6 had regional lymph node recurrence and 3 had both. Local rec urrence in S was 29% and that of S+R was 2% (P=0.001). and local recurrence by T NM stage:Ⅲ were 33% and 5%, respectively. One patient developed radiation-indu c ed small bowel obstruction which necessitated surgical intervention, but no pat i ent died from radiotherapy-induced complications. By multivariate analysis: per f ormance status, symptomatic presentation, lymph node involvement, post-operativ e radiation and post-operative residual were all independent predictors of overa l l survival in the RCC patients. Conclusions In renal cell carcinoma, radiothera py is beneficial in reducing the locoregional recurrence. Radiotherapy has a sup prisingly positive effect on both local control and survival in TNM stage Ⅲ pat ients. Performance status, symptomatic presentation, lymph node involvement, pos t-operative radiation and post-operative residual are prognostic indicators of RCC. TNM staging is superior to Robson staging in predictive values .