Prediction of recurrence risk of estrogen receptor-positive and human epidermal growth factor receptor-2 negative breast cancer using a multi-parameter regression model based on diffusion kurtosis imaging / 中华放射学杂志

Objective:To explore the predictive value of a regression model based on diffusion kurtosis imaging (DKI) parameters for prediction of the recurrence risk in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER-2)-negative early invasive breast cancer.Methods:A retrospective cross-sectional study was designed. The clinicopathological (age, histological grade, Ki-67 level, etc.) and imaging data of 50 patients (50 lesions) with ER-positive, HER-2 negative early invasive breast cancer who underwent treatment at Wuxi People′s Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients were female, aged 29 to 81 years, and underwent pre-operation conventional MRI and DKI examinations. The volume of breast fibroglandular tissue (FGT), background parenchymal enhancement (BPE), and internal enhancement features were recorded; the peak enhancement (PH), peak enhancement rate, time to peak, mean kurtosis (MK), and mean diffusivity (MD) were calculated. Based on the 21-gene recurrence risk scores, patients were divided into low recurrence risk group and medium-high recurrence risk group. Independent sample t test, Mann-Whitney U test, χ2 test were used to compare the differences of various indicators between the two groups. Two logistic models were constructed with age, PH, MD, and MK as independent variables (Pre1), and with Ki-67, age, PH, MD, and MK as independent variables (Pre2), respectively. The efficacy of the models in predicting low recurrence risk in patients was assessed using receiver operating characteristic curve and area under the curve (AUC). Results:There were 25 cases in the low recurrence risk group and 25 cases in the medium-high recurrence risk group. The differences in age, FGT, PH, MD, MK, and Ki-67 between the low recurrence risk group and the medium-high recurrence risk group were statistically significant (all P<0.05), while other indexes showed no statistically significant differences (all P>0.05). The AUC of Pre1 in predicting low recurrence risk of ER-positive, HER-2 negative early invasive breast cancer was 0.87, with a sensitivity of 0.76 and specificity of 0.88. The AUC of Pre2 for predicting the low recurrence risk of ER-positive, HER-2 negative early invasive breast cancer was 0.92, with a sensitivity of 0.84, and specificity of 0.92. Conclusions:A multi-parameter model based on DKI can effectively predict the recurrence risk of ER-positive and HER-2 negative breast cancer. The model with combination of Ki-67 can further improve the predictive efficacy, and help effectively identify patients at low recurrence risk.

X-linked myopathy with excessive autophagy: a case report and literature review / 中华神经科杂志

Objective:To report a case of X-linked myopathy with excessive autophagy (XMEA) and review the literature aiming to analyze the clinical manifestations, muscle imaging, muscle pathology and genetic characteristics of the disease.Methods:The medical history, physical and laboratory examination, muscle imaging and pathology, and genetics of a patient with XMEA who was admitted to QiLu Hospital of Shandong University in June 2018 were retrospectively collected. PubMed, CNKI, and Wanfang Data were searched for relevant literature.Results:This patient was a 40-year-old male who complained of hyper creatine kinase and weakness in his lower extremities for 4 years. Since elementary school, his heels could not touch the ground when squatting and his motor performance was inferior to his peers. Abnormal creatine kinase levels (320-1 167 U/L) were identified several times prior to admission. Magnetic resonance imaging of lower extremities revealed symmetrical fat replacement in bilateral lateral femoral muscles, adductor major and medial head of the gastrocnemius. Muscle biopsy showed intrafibrillar autophagic vacuoles with sarcolemmal features as well as membrane attack complex depositing on the vacuolar membrane; genetic analysis confirmed a hemizygous mutation c. *6A>G in VMA21 gene. Searching the literature, it was found that the onset age of XMEA patients varied from newborns to adulthood. Those XMEA patients with childhood or adulthood-onset mostly exhibited muscle weakness and (or) atrophy in the proximal limbs, with slow progression and normal life expectancy, while those with infant onset were prone to multiple system involvement, rapid disease progression, and high risk of death. Conclusions:XMEA is an extremely rare hereditary autophagic vacuolar myopathy. Although the clinical and prognostic manifestations of XMEA patients vary greatly among different age groups, the muscle pathological changes are relatively consistent, and genetic testing is the main diagnostic method for this disease.

miR-21 regulates the proliferation, invasion and radiosensitivity of cervical cancer HeLa cells by targeting RECK / 中华放射肿瘤学杂志

Objective:To explore the effect of miR-21 on cell proliferation, apoptosis, invasion and radiosensitivity of cervical cancer HeLa cells and unravel the underlying mechanism.Methods:RT-qPCR assay was used to detect the expression levels of miR-21 in cervical cancer tissues and adjacent non-tumor tissues, normal cervical epithelial cells (H8) and cervical cancer cell lines (HeLa, SiHa, ME180). HeLa cell line with inhibition of miR-21 or knockdown of RECK were constructed. CCK-8, Caspase3/7 live cell apoptosis detection, wound healing test, Transwell invasion, clone formation assay, Western blot and immunofluorescence were performed to detect cell viability, apoptosis, migration, invasion, radiosensitivity and related proteins. The dual luciferase assay verified whether miR-21 targeted RECK.Results:MiR-21 level in the cervical cancer tissues was significantly higher than that in its corresponding adjacent non-tumor tissues ( P<0.05). The expression levels of miR-21 in cervical cancer cell lines HeLa, SiHa and ME180 were significantly up-regulated compared with those in normal cervical epithelial cells H8(all P<0.05). MiR-21 knockdown significantly inhibited HeLa cell viability, promoted cell apoptosis, reduced radiation tolerance, down-regulated the expression of Cyclin D 1,Bcl-2, MMP-2 and MMP-9, and up-regulated the expression P21 and Bax proteins (all P<0.05). miR-21 targeted the 3’-UTR of RECK mRNA and negatively regulated the expression of RECK. Silencing RECK reversed the effects of miR-21 knockdown on HeLa cell apoptosis, migration, invasion and radiosensitivity. Conclusions:Inhibiting the expression of miR-21 significantly decreases cell viability, induces cell apoptosis, weakens cell migration and invasion capabilities, and enhances the radiosensitivity of HeLa cells. The potential mechanism is closely related to the targeted up-regulation of RECK.

The role of miR-21 in Endostar combined with X-ray irradiation of cardiac fibroblasts / 中华放射肿瘤学杂志

Objective:To investigate the implication of micro RNA-21(miR-21) in Endostar combined with X-ray irradiation of cardiac fibroblasts (CF).Methods:Rat CFs were used in this experiment and been divided into the blank control group, 10 Gy X-ray irradiation group, Endostar group, 10 Gy X-ray+ Endostar group, 10 Gy X-ray+ Endostar+ NC mimic group (negative control 1), 10 Gy X-ray+ Endostar+ miR-21 mimic group, 10 Gy X-ray+ Endostar+ NC inhibitor group (negative control 2) and 10 Gy X-ray+ Endostar+ miR-21 inhibitor group. The proliferation of CF was determined by Methyl thiazolyl tetrazolium (MTT) assay. The expression level of Collagen Ⅰ protein was analyzed by Western blot. The expression levels of Collagen Ⅰ and miR-21 mRNA were assayed by real-time quantitative polymerase chain reaction (q-PCR).Results:In the 10 Gy X-ray+ Endostar+ miR-21 mimic group, the CF proliferation, Collagen Ⅰ and miR-21 mRNA were increased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group, and negative control group 1 (all P<0.05). In the 10 Gy X-ray+ Endostar+ miR-21 inhibitor group, the CF proliferation and expression levels of Collagen Ⅰ mRNA were decreased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group and negative control group 2(all P<0.05). Conclusions:The CF proliferation and Collagen Ⅰ expression are increased when the expression level of miR-21 gene is simulated. When inhibiting the expression of miR-21 gene, the CF proliferation and Collagen Ⅰ expression are reduced.

Análise de custo-efetividade de um painel genético no câncer de mama precoce na saúde suplementar brasileira / Cost-effectiveness analysis of a genetic panel in early breast cancer in Brazilian supplementary health

Objetivo: Avaliar o custo-efetividade do uso de um painel genético de 21 genes em pacientes adultas diagnosticadas com câncer de mama em estádio inicial em uma operadora de saúde com mais de 500.000 vidas. Métodos: Foi utilizada uma coorte prospectiva seguida de um estudo de custo-efetividade entre os pacientes que utilizaram Oncotype DX® em 2020. Calcularam-se as despesas totais de cada esquema de quimioterapia (QT), somando-se os custos dos produtos e taxas de infusão. Resultados: Das 35 pacientes que utilizaram o teste de 21 genes no período avaliado, 60% (n = 21) não necessitaram de QT. Quando aplicadas simulações, houve custo evitado de R$ -1.945.448,88 (custos incrementais potenciais de R$ -6.488.207,56 até R$ 443.485,26, dependendo do esquema de QT escolhido). Conclusão: A inserção do teste de 21 genes na jornada do tratamento de câncer de mama na saúde suplementar evidenciou significativa relevância, pois contribuiu com o uso adequado da terapêutica, garantindo a sustentabilidade do sistema de saúde. Apresentando-se como uma opção custo-efetiva para a maioria dos esquemas de QT em comparação com a sua não utilização no tratamento, para a saúde suplementar brasileira

Objective: To evaluate the cost-effectiveness of the use of a genetic panel of 21 genes in adult patients diagnosed with early stage breast cancer in a healthcare provider with more than 500,000 lives. Methods: A prospective cohort study was conducted, followed by cost-effectiveness, among patients who used Oncotype DX® , in 2020. The total costs of each chemotherapy scheme (QT) were calculated, adding the costs of the products and infusion fees. Results: Of the 35 patients who used 21 gene tests in the evaluation period, 60% (n = 21) did not require QT. When simulations were applied, there was an avoided cost of R$ -1.945.448,88 (Potentials incremental costs from -R$ 6.488.207,56 to +R$ 443.485,26, depending on the chosen QT scheme). Conclusion: The insertion of 21-Gene recurrence score in the breast cancer treatment journey in supplementary health showed significant relevance, as it contributes to the appropriate use of therapy, guaranteeing the sustainability of the health system. Presenting itself as a cost-effective option for most QT schemes compared to not being used in treatment, for Brazilian supplementary health System

Prognostic value of the 21-gene recurrence score in ER-positive, HER2-negative, node-positive breast cancer was similar in node-negative diseases: a single-center study of 800 patients / 医学前沿

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER

Prognosis analysis and 21-gene recurrence score according to TAILORx standard in hormone receptor positive early-stage breast cancer / 中华普通外科杂志

Objective To explore the association of 21 gene recurrence score (RS)according to TAILORx standard and prognosis of hormone receptor (HR) positive,axillary lymph node negative breast cancer.Methods The clinicopathologic data of 558 early breast cancer patients who underwent 21 gene RS testing from May 2012 to Jan 2017 were retrospectively analyzed.RS was subgrouped according to TAILORx standard.Estimates of relapse free survival(RFS) were made from the Kaplan-Meier curves.Results In 558 patients,RS≤10,RS 11-25 and RS≥26 groups accounted for 23.1％,63.6％ and 13.3％.After a median follow-up of 38 months,the recurrence ratesin RS ≤ 10,RS 11-25 and RS ≥ 26 groups were 3.3 ％,4.5％ and 5.4％,respectively.Kaplan-Meier RFS curve showed no significant difference between the 3 groups(P =0.788).The recurrence ratesin RS ≤ 15 group(3.0％) was significantly lower than that in RS≥ 16 group(5.9％)(P =0.041).Conclusions A significant association exists between RS and breast cancer prognosis.It is rational not to give chemotherapy to RS ＜ 18 low risk patients according to classical standard.

Prognosis analysis and 21-gene recurrence score according to TAILORx standard in hormone receptor positive early-stage breast cancer / 中华普通外科杂志

Objective@#To explore the association of 21 gene recurrence score(RS)according to TAILORx standard and prognosis of hormone receptor(HR) positive, axillary lymph node negative breast cancer.@*Methods@#The clinicopathologic data of 558 early breast cancer patients who underwent 21 gene RS testing from May 2012 to Jan 2017 were retrospectively analyzed. RS was subgrouped according to TAILORx standard.Estimates of relapse free survival(RFS) were made from the Kaplan-Meier curves.@*Results@#In 558 patients, RS≤10, RS 11-25 and RS≥26 groups accounted for 23.1%, 63.6% and 13.3%.After a median follow-up of 38 months, the recurrence ratesin RS≤10, RS 11-25 and RS≥26 groups were 3.3%, 4.5% and 5.4%, respectively. Kaplan-Meier RFS curve showed no significant difference between the 3 groups(P=0.788). The recurrence ratesin RS≤15 group(3.0%) was significantly lower than that in RS≥16 group(5.9%)(P=0.041).@*Conclusions@#A significant association exists between RS and breast cancer prognosis.It is rational not to give chemotherapy to RS<18 low risk patients according to classical standard.

Impact of the 21-gene recurrence score assay in clinical treatment and prognosis analysis for patients with hormone receptor positive early-stage breast cancer / 中华肿瘤杂志

Objective@#To explore the association between the 21-gene recurrence score (RS) and clinicopathologic characteristics as well as prognosis in patients with axillary lymph node negative, hormone receptor (HR) positive breast cancer.@*Methods@#The clinicopathologic data of 439 early breast cancer patients who underwent 21 gene RS testing was retrospectively analyzed. According to the 21 gene RS, the patients were divided into low risk (295 cases), intermediate risk (111 cases) and high-risk (33 cases) group. The relationship between the 21 gene RS and clinicopathological characteristics, treatment, recurrence and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for relapse free survival (RFS).@*Results@#Tumor grade, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 index were significantly different among the 3 risk cohorts (P<0.001 for all). After a median follow-up of 32 months, the recurrence rate in low risk group (3.7%) was significantly lower than that in the intermediate-high risk group (9.0%), the locoregional recurrence (LRR) rate of low, intermediate and high risk group was 2.4%, 6.3% and 9.1%; and the distant metastasis (DM) rate in low risk group was 1.4% and 2.1% in the intermediate-high risk group. Univariate analysis showed RS, ER status and endocrine therapy were prognostic factors for RFS (P<0.05 for all). Multivariate analysis showed that RS was an independent significant predictor for RFS (P=0.04).@*Conclusions@#The 21-gene RS is related to tumor grade, ER, PR and Ki-67 index. RS is an independent risk factor for RFS in patients with hormone receptor positive early-stage breast cancer.

Effect of miR-3619-5p on proliferation of human bladder cancer cell lines EJ and T24 / 中华泌尿外科杂志

Objective To study the effects of a synthetic miR3619-5p mimics on bladder carcinoma cell lines of EJ and T24 in vitro.Methods EJ and T24 cells were cultured in vitro and treated with three different processing:negative control group(tinfection with dsControl),positive control group(infection with dsP21-322) and the experimental group(infection with miR-3619-5p)during October 2015 to March 2016.Real-time fluorescent quantitative PCR (qPCR) was performed to detect the expression of p21 mRNA,cell cycle protein D1 (CyclinD1) and cell cycle-dependent kinase (CDK4 and CDK6) mRNA.Western Blot method was conducted to evaluate the expression of p21,CyclinD1 and CDK4 and CDK6 proteins;the change of cell cycle was displayed by flow cytometric analysis.Colony formation assay was used to test the ability of single cancer cell clone proliferation.Cell proliferation assay(MTS) was implemented to observed the inhibitive effect of cell proliferative potential.Results qPCR results showed that miR-3619-5p upregulated p21 mRNA expression (P ＜ 0.05),while the expression of CyclinD1,CDK4 and CDK6 were a little lower(P ＜ 0.05) in EJ and T24cells,respectively.Western Blot analysis testified that the expressions of p21,CyclinD1,CDK4 and CDK6 were difference among groups.Flow cytometry displayed that,the G0/ G1 phase increased significantly after transfected with miR-3619-5p and dsP21-322,compared with dsControl group(P ＜ 0.05),indicating that the cell cycle block in G0/G1 phase.Cell colony formation assay certified that the colony formation rates were less in the groups of miR-3619-5p and dsP21-322 than in that of dsControl group(P ＜ 0.05).Cell proliferation assay demonstrated that,cell proliferation ability decreased obviously when transfected with miR-3619-5p and dsP21-322 (P ＜0.05),compared with dsControl group.Conclusions miR-3619-5p could up-regulate the expression of p21 by RNA activation pathway and remarkably induced cell cycle arrest in G0/G1 phase,inhibiting the proliferation of bladder cancer cells.

Multiple primary triple cancer of the thyroid breast and lung and 21-gene expression detection: A case report / 肿瘤

Objective: To discuss the clinical and pathological features and the diagnosis and therapy of multiple primary triple cancers of thyroid, breast and lung. Methods: The medical records of a case of multiple primary triple cancers of thyroid, breast and lung were reviewed retrospectively, and the clinicopathological features as well as the diagnosis and therapy were analyzed. Results: Multiple primary triple cancers of this case were performed with surgical operation. Because this case had lymph node-negative and estrogen receptor-positive early-stage breast cancer, the 21-gene detection was performed, and the recurrence score showed low risk, so the case didn't need chemotherapy treatment. Conclusion: The principle of treatment and the prognosis of multiple primary cancers are similar to those of single cancer, and the treatment options for patients with early-stage breast cancer with estrogen receptor-positive and lymph node-negative may refer to the 21-gene recurrence score system.

Effect of 21-gene recurrence score on chemotherapy decisions for patients with estrogen receptor-positive, epidermal growth factor receptor 2-negative and lymph node-negative early stage-breast cancer / 中华肿瘤杂志

Objective@#To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer.@*Methods@#One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed.@*Results@#After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy.@*Conclusion@#Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer.

Clinical utility study of 21-gene assay in 927 Chinese patients with early breast cancer / 中华肿瘤杂志

Objective@#To investigate the distribution patterns of 21-gene assay and its influencing factors in Chinese patients with early breast cancer.@*Methods@#Nine hundred and twenty-seven early breast cancer patients were retrospectively recruited from January 2009 to December 2015 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The 21-gene reverse transcriptase-polymerase chain reaction(RT-PCR) assay were conducted in paraffin-embedded tumor tissues to calculate the Recurrence Score(RS). Immunohistochemistry(IHC) assay was used to measure the expression levels of estrogen receptor(ER), progesterone receptor(PR) and Ki-67. Concordances of RT-PCR and IHC results were assessed. Correlations of RS and classical clinicopathological factors were evaluated, and logistic regression were applied to determine independent predictive factors for RS.@*Results@#The median RS of 927 patients was 23(range: 0~90), and the proportions of patients categorized as having a low, intermediate, or high risk were 26.5%, 47.7% and 25.8%, respectively. The distribution of RS varied significantly according to different tumor grade, T stage, PR status, Ki-67 index and molecular subtypes(P<0.05 for all). Grade, PR status and Ki-67 index were independent predictive factors for RS. ER, PR status and Ki-67 index showed significantly correlation between RT-PCR and IHC assays, and the concordance rates for ER and PR status were 98.7% and 87.8%, respectively.@*Conclusions@#RS significantly correlated with tumor grade, T stage, PR status, Ki-67 index and subtypes. Grade, PR status and Ki-67 index can independently predict RS. Remarkable concordances of ER, PR status and Ki-67 index are found between RT-PCR and IHC assays.

The application of Oncotype DX 21-gene assay in early-stage ER positive breast cancer / 中国癌症杂志

Several multi-gene assays have been developed to predict the risk of recurrence in patients with early-stage, estrogen receptor (ER) positive breast cancer. Among them, Oncotype DX 21-gene assay is widely applied among node-negative patients because of its unique prediction of therapeutic benefit. Although many retrospective stud-ies have proved its prognostic and predictive value in node-positive population, evidence from large prospective clinical trials remains insufficient. When combined with clinicopathological variables, the assay has been shown to impact adjuvant treatment decision making in a cost-effective manner. This article reviewed the available clinical evidence for the prognostic and predictive value, unique advantages, the effect on treatment decision making, cost-effectiveness and contradictories of 21-gene assay in early-stage luminal breast cancer patients.

Validation of the silencing site of rhesus monkey P21 gene in COS-7 cells / 中国实验动物学报

Objective To screen the effective silencing targets of P21 gene at the cellular level in rhesus monkey . Methods To detect the expression of P21 gene in COS-7 cells ( derived from the kidney of African green monkey , Cerco-pithecus aethiops).Four small hairpin RNA (shRNA) sequences targeting rhesus monkey P21 gene were designed and in-serted into lentivirus-based gene silencing constructs FUGW-TDT.The vectors were transfected into COS-7 cells respective-ly.The suppression of P21 mRNA was detected by real-time PCR, and the expression of P21 protein was detected by West-ern blot assay .Results Four gene-silencing sequences were screened that lied in 541-561 bp, 542-562 bp, 215-239 bp, and 624-648 bp of the rhesus monkey P21 mRNA.Their silencing rate was (91.82 ±3.21)%, (82.47 ±2.48)%, (81.31 ±2.69 )% and ( 87.35 ±4.59 )%, and the protein expression was ( 11.97 ±0.70 )%, ( 20.22 ±0.65 )%, ( 23.21 ± 0.63)%and (14.42 ±0.86)%, respectively.Conclusions Four effective silencing target sequences are screened at cel-lular level , which can be used in gene silencing research of rhesus monkeys .

Prediction of breast cancer and prognosis by 21-gene oncotype Dx / 中华内分泌外科杂志

Objective To study the prognostic and predictive significance of 21-gene assay ( oncotype DX)in breast cancer.Methods Real-time quantitative PCR(RT-QPCR)was used to detect 21 gene expression in breast cancer tissues (100 cases)and recurrence score(RS)was calculated.Results Among the 100 cases, 52 cases had low RS , 22 cases had middle RS , and 26 cases had high RS .The recurrence rate of five years was 1.92%,4.55%and 15.38%respectively.21 gene expression had nothing to do with patients'age, tumor size, histological grade , lymph node metastasis state , ER expression , or PR expression .It was associated with HER 2 expression .Conclusions 21 genes is a good prediction factor in breast cancer and its prognosis .

Polymorphism at P21 codon 31 and dinucleotide polymorphism of P73 gene and susceptibility to bladder cancer in individuals from North India.

BACKGROUND AND AIM: p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 expression in response to deoxyribonucleic acid damage leading to cell cycle arrest at G1 checkpoint. In the present study, we are targeting p21 codon 31 and p73 gene variants of G4C14‑to‑A4T14 (Exon 2) polymorphism for bladder cancer (BC) risk in North Indians. MATERIALS AND METHODS: The above gene variants of P21 and P73 were assessed in the case‑control study comprising of 200 BC cases and 200 healthy controls of the same age, gender and similar ethnicity. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method and PCR‑based confronting two‑pair primers (PCR with CTPP). RESULTS: The variant genotype of p73Exon 2 polymorphism showed significant risk for BC (p = 0.014). While combining with heterozygous genotype, variant genotype of p73Exon2 showed a significant association with BC risk (p = 0.010). While in case of p21 codon31 showed no significant association for BC risk at genotypic level. Significant association between p73Exon2 polymorphism and smoking was observed for BC risk. Furthermore, gene combination analysis revealed that AT/AT‑Ser/Ser is associated with risk for BC. Variant genotype of P73Exon2 was associated with reduced risk of recurrence (p = 0.039) in superficial BC patients receiving Bacillus Calmette‑Guerin treatment thus showing least survival (log rank = 0.029). CONCLUSION: Our study provided evidence that the p73 G4C14 > A4T14 (Exon2) polymorphisms were associated with higher risk of BC in North Indian population.

Synergic effect of human IL-21 gene transfer combined with γ-ray irradiation on the growth of cervical carcinoma HeLa cells / 中华放射医学与防护杂志

Objective To study the combined effect of interleukin-21 gene transfer and ionizing radiation on the growth of cervical carcinoma HeLa cells.Methods Previously constructed Ad-IL-21 gene was amplified by infecting 293A cells and the titer was measured by TCID50 method. HeLa cells were transfected with Ad-1L-21 and then irradiated with 6 Gy 137Cs γ-rays.The cells were divided into 5 groups,including blank control,Ad-LaeZ group,Ad-IL-21 group,radiation group and Ad-IL-21 combined with radiation group (combination group).The cell growth,cell cycle,apoptosis,and the expressions of IL-21 gene and protein in HeLa cells were detected.Results Ad-IL-21 was successfully amplified and the titer of Ad-11.-21 was 9 × 1010 pfu/ml.Compared with Ad-IL-21 group and radiation group,the cell growth of combination group was significantly inhibited at 96 h after transfection ( F =85.26,72.98,P ＜ 0.05 ).The cells in combination group were arrested in G1 phase and decreased at S phase( F =36.69,34.83,P ＜ 0.05),while the cellular apoptosis increased markedly ( F =28.23,25.57,P ＜ O.05 ). The gene expression of 1L-21 in the combination group was 1.54- and 2.43-fold of Ad-IL-21 group and blank control group,respectively (F=22.31,36.65, P ＜ 0.05 ), while the protein expression of IL-21 in the combination group was 1.62-fold and 2.31-fold of Ad-IL-21 group and blank control group,respectively ( F =27.36,35.86,P ＜ 0.05 ).Conclusions Ad-IL-21 gene transfection combined with radiation has synergic effect on the inhibition of cervical carcinoma cell growth.

A case with 21-hydroxylase deficiency combined with adrenal adenoma and testicular adrenal rest tumors / 中华内分泌代谢杂志

Objective To investigate the clinical and genetic characteristics in a male patient with 21hydroxylase deficiency combined with adrenal and testicular tumors.Methods Clinical features and laboratory data were collected from the patient.Testicular biopsy was performed.The CYP21 gene was sequenced for mutations.Results The patient presented left adrenal and testicular enlargements.The laboratory examinations showed that plasma ACTH,androstenedione,testosterone,progesterone,and 17-hydroxyprogesterone were markedly elevated.CT scan revealed that the right adrenal gland being resected and the left adrenal with nodular enlargement.Furthermore,testicular biopsy showed a prominent peritubular fibrosis with increased number of peritubular fibroblasts,tubular hyalinisation,and calcification.Sequencing analysis showed a A>G homozygous mutation at intron 2.Conclusion Patients with untreated 21-hydroxylage deficiency may.have adrenal adenomas and(or)testicular adrenal rest tumor simultaneously.

Effects of ionizing radiation on expression of P21 protein in Jurkat cell line and p21 gene in thymocytes and splenocytes of mice / 中华放射医学与防护杂志

Objective To investigate the effects of ionizing radiation on the expression of P21 protein in Jurkat cell line and p21 gene in thymocytes and splenocytes of mice.Methods Flow cytometry (FCM)was used to analyze the expression of P21 protein in Jurkat cells at 12 and 24 h after irradiation to 0,0.5,1.0,2.0,4.0,and 6.0 Gy.Real-time PCR was used to detect the expression of p21 gene in thymocytes and splenocytes of mice at4 and 24 h after irradiation to 0,0.5,1.0,2.0,4.0,and 6.0 Gy.Multi-staining was used to analyze the micronucleus rates of Rct in bone marrow.Results The expressions of P21 protein were increased in a dose-dependent manner during 0.5-4.0 Gy(t=-24.23--3.96,P<0.05),but decreased at 6.0 Gy at 12 and 24 h post-irradiation(t=-11.19,-14.50,P<0.05).The expressions of p2 1 gene in both thymocytes and splenocytes of mice were increased in dose-dependent manner in the range of 0-6.0 Gy(including 6.0 Gy)(t=-29.96-8.80,P<0.05),and reached to the peak at 6.0 Gy at 4 and 24 h post-irradiation(t=-11.84--3.42,P<0.05),except thymocytes at 4 h and 1.0 Gy post-irradiation(t=-3.42,P>0.05).Conclusions The expressions of P21 protein and p21 gene could be increased by X-ray irradiation.which shows good dosedependent manners in certain range of dose.