Table of Content

  

10 January 2018
Volume 56 Issue 1

Focused updates of American Society of Clinical Oncology Guideline on the use of multigene tests in clinical practice for breast cancer

LIU Yinhua, ZHAO Jingyi, XIN Ling

Journal of Shandong University (Health Sciences). 2018, 56(1):  1-5.  doi:10.6040/j.issn.1671-7554.0.2017.1074

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In recent years, multigene tests have been recommended to guide decisions on the need of adjuvant chemotherapy for patients with early-stage breast cancer. The comprehensive strategy of early-stage breast cancer has come into an era, when both anatomic tumor burden and multigene test results should be taken into consideration to gain a better understanding of tumor biology and personalized treatment, in order to minimize toxic effects. In July 2017, the Journal of Clinical Oncology(JCO)published the new version of the clinical practice guideline of American Society of Clinical 山 东 大 学 学 报 (医 学 版)56卷1期 -刘荫华,等.美国临床肿瘤学会多基因检测临床实践指南更新及临床意义 \=-Oncology(ASCO)on the use of biomarkers to guide therapeutic decision for breast cancer. The guideline provided criteria of clinical utility for different patient groups, and focused on the recommendation of MammaPrint^®with evidence of high quality, leading to reasonable decision-making for clinicians to avoid overtreatment.

Review of neoadjuvant therapy for breast cancer at the St.Gallen conference

SHI Aiping, XU Gege, XIE Xinpeng

Journal of Shandong University (Health Sciences). 2018, 56(1):  6-11.  doi:10.6040/j.issn.1671-7554.0.2017.899

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Neoadjuvant therapy is the standard treatment for local advanced breast cancer. Some inoperable breast cancer can be operated and some patients who should not undergo breast conservative surgery can keep their breast after neoadjuvant therapy. Nowadays, based on new evidences, there are new missons in neoadjuvant therapy, such as screening out sensitive drugs for the patients who may acquire pathological complete reaction in order to gain survival benefits and 山 东 大 学 学 报 (医 学 版)56卷1期 -石爱平,等.St.Gallen会议乳腺癌新辅助治疗回顾 \=-avoiding axillary dissection for some patients who are clinically nodes positive at diagnosis and downstage. The new progress of neoadjuvant therapy at St. Gallen conference will be reviewed in the paper.

Current perspectives of neoadjuvant therapy for breast cancer in 2017

CHEN Bo, ZHANG Lei

Journal of Shandong University (Health Sciences). 2018, 56(1):  12-16.  doi:10.6040/j.issn.1671-7554.0.2017.896

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Neoadjuvant therapy is critical for treatment in patients with breast cancer, including chemotherapy, endocrine therapy, targeted therapy and so on. The response of tumor tissue, especially pathological complete response(PCR)has been proposed as a surrogate endpoint for prediction of long-term clinical benefit.The neoadjuvant therapy also provides information of tumor response and improves further therapeutic strategies. Recently, substantial developments have been made in neoadjuvant therapy with important clinical trials, and our concept of neoadjuvant therapy is also changing. This review showed the current perspectives in neoadjuvant therapy in 2017.

Treatment of early breast cancer: more or less? Study from the 2017 American Society of Clinical Oncology Annual Meeting

WANG Shu, PENG Yuan

Journal of Shandong University (Health Sciences). 2018, 56(1):  17-21.  doi:10.6040/j.issn.1671-7554.0.2017.897

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The treatment of breast cancer is moving forward to precision medicine. American Society of Clinical Oncology Meeting went deep into a full discussion on the addition and subtraction of breast cancer treatment in 2017. The results of many clinical trials were updated in the treatment of early breast cancer, from the traditional surgery, chemo- 山 东 大 学 学 报 (医 学 版)56卷1期 -王殊,等.从2017年美国临床肿瘤学会大会报告看早期乳腺癌治疗加减法 \=-therapy and endocrine therapy, to anti-HER2 therapy and the finding of new therapeutic targets. The meeting gave us a new sight on finding the effective, less injured and economic treatment for the patients with early breast cancer.

Concerns and perspectives for multigene tests of breast cancer: opportunities and challenges

YU Zhigang, WANG Fei

Journal of Shandong University (Health Sciences). 2018, 56(1):  22-26.  doi:10.6040/j.issn.1671-7554.0.2017.1036

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Both Oncotype DX^® and MammaPrint^® have been recommended by American Society of Clinical Onco-logy(ASCO)to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. However, based on current evidence, multigene tests are still regarded supplementary to traditional clinical pathological examinations, and confined to specific patients. Besides, there are still clinical challenges concerning multigene tests: slow concordance of risk assignment by different tests, inaccurate prediction of late recurrences and poor prediction of drug-specific or regimen-specific benefits. In the future, multi-omics characteristic spectrum based on high-throughput technology platforms, innovative prediction models based on interdisciplinary research, and dynamic risk monitoring based on repetitive tests, will offer new opportunities and directions for multigene tests of breast cancer.

Advances of endocrine therapy for hormone-receptor-positive breast cancer

LING Rui, ZHANG Juliang

Journal of Shandong University (Health Sciences). 2018, 56(1):  27-31.  doi:10.6040/j.issn.1671-7554.0.2017.898

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Endocrine therapy is the mainstay treatment for hormone-receptor-positive breast cancer. Based on new evid-ences collected from clinical trials, new strategies have been available and have improved the long-term outcomes of patients, including longer endocrine treatment of early breast cancer, combined use of ovarian suppression, and so on. In parallel with expanding knowledge about the resistance mechanisms to endocrine therapy, new agents for hormone receptor-positive metastatic breast cancer continue to appear. The selective estrogen-receptor degrader, fulvestrant, and new endocrine-target combinations provide significant and clinically meaningful improvements in outcomes. This review will explore the current and investigational approaches to endocrine therapy for hormone-receptor-positive breast cancer.

Correlation between breast and axillary pathologic complete response after neoadjuvant chemotherapy

ZHU Jiujun, JIAO Dechuang, QIAO Jianghua, WANG Lina, MA Youzhao, YANG Yue, LU Zhenduo, LIU Zhenzhen

Journal of Shandong University (Health Sciences). 2018, 56(1):  32-37.  doi:10.6040/j.issn.1671-7554.0.2017.1094

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Objective To investigate the risk and significance of axillary metastasis in patients who achieved breast pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC). Methods The clinical data of 701 breast cancer cases treated with NAC during 5th March 2014 and 21st July 2017 were retrospectively analyzed. The relationship of axillary pCR(apCR)with clinicopathological characteristics and breast pCR(bpCR)was calculated using χ2 test. The correlation between the variables and apCR was analyzed with multivariate binary logistic regression. Results Lymph node staging, estrogen receptor(ER)and HER2 were independent predictors for apCR. Among bpCR patients who were HER2 positive and cN0, 93% had no nodal metastasis(14/15), and 6 of 7 cases had an apCR in basal-like, cN0 group. The aPCR rate in the cN1 group were 67%. Among Luminal A&B groups, 3 and 17(60%, 40%)patients with cN0 disease, while 8 and 20(47%, 27%)patients with cN1 disease had an apCR. Compared with patients with bpCR, those without bpCR had 4.53 times higher risk of positive nodal metastases. Conclusion The nodal status is highly correlated with bpCR after neoadjuvant chemotherapy. Patients with cN0/1 who are HER2 positive and BL subtype patients with cN0 have low risk of nodal metastases if they achieve bpCR after neoadjuvant chemotherapy.

Effect and mechanism of magnesium isoglycyrrhizinate on the biological behavior of breast cancer cell lines

LI Yi, PENG Jing, ZHANG Lei, LU Jingsong

Journal of Shandong University (Health Sciences). 2018, 56(1):  38-44.  doi:10.6040/j.issn.1671-7554.0.2017.1038

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Objective To explore the effects and mechanism of magnesium isoglycyrrhizinate on the biological behavior of breast cancer. Methods Breast cell lines MDA-MB-231 and MCF-7 were treated with different concentrations(0, 50, 500 μmol/L)of magnesium isoglycyrrhizinate. Cell proliferation, migration and death were detected by CCK-8 assay, wound healing test, and LDH-cytotoxicity assay kit. Effect of magnesium isoglycyrrhizinate on the expressions of Bax, Bcl-2, Caspase-3, Caspase-9, HSP70 and HSP90 in breast cancer cells were examined by Western blotting. Results After treated with different concentrations of magnesium isoglycyrrhizinate, cell proliferation and migration abilities were inhibited in breast cancer cells, while autophagy and apoptosis increased. The inhibitory effects of platinum on cell migration were enhanced by the combination usage with magnesium isoglycyrrhizinate. Expression of HSP90 was reduced and Bax was promoted in MDA-MB-231 cell line. Expression of HSP70 was reduced in MCF-7 cell line. Conclusion Magnesium isoglycyrrhizinate inhibits the malignant phenotype of human breast cancer cell lines and has the synergic antitumor effect combined with platinum. The mechanism of magnesium isoglycyrrhizinate on MCF-7 and MDA-MB-231 cell lines are different.

Efficacy and safety of single-agent domestic docetaxel in the treatment of advanced breast cancer

LÜ Huimin, ZHANG Mengwei, NIU Limin, ZENG Huiai, YAN Min

Journal of Shandong University (Health Sciences). 2018, 56(1):  45-49.  doi:10.6040/j.issn.1671-7554.0.2017.1025

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Objective To observe the efficacy and toxicities of domestic docetaxel single-agent chemotherapy in the treatment of advanced breast cancer. Methods A total of 141 patients with advanced breast cancer treated with domestic docetaxel were reviewed every 2 cycles of treatment. The objective response rate(ORR), time to progress(TTP), time to treatment failure(TTF), toxicity and adverse responses were evaluated. The effects of dexamethasone dosage on the safety of chemotherapy were observed. Results The median number of treatment was 6(1~14)cycles. Of all 141 cases, none were complete remission(CR), 62 were partial remission(PR), 61 were stable disease(SD), and 18 were progression disease(PD). The ORR was 43.0%(62/141), clinical benefit rate(CBR)was 51.8 %(73/141), disease control rate(DCR)was 87.2%(123/141), TTP was 6.5(5.8~7.2)months, and TTF was 4.0(3.9~4.1)months. The grade 3~4 adverse reactions included neutropenia(72.3%), abdominal pain and diarrhea(2.8%)and oral mucositis(4.3%), which were relieved after symptomatic treatment. Reducing the dosage of dexamethasone did not increase adverse reactions. Conclusion Single-agent domestic docetaxel showed good efficacy and safety for patients with advanced breast cancer. The dosage of dexamethasone can be reduced for those who could not tolerate adverse reactions caused by corticosteroid.

Precise sentinel lymph node biopsy in breast cancer guided by preoperative ultrasound combined with intraoperative lymphatic drainage

CHEN Sisi, LI Xiaoyan, JIANG Liyu, KONG Xiaoli, MA Tingting, YANG Qifeng

Journal of Shandong University (Health Sciences). 2018, 56(1):  50-56.  doi:10.6040/j.issn.1671-7554.0.2017.1115

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Objective Sentinel lymph node biopsy(SLNB)was monitored during the complete surgical procedures to achieve accurate treatment and to determine its clinical value. Methods Axillary lymph nodes were assessed by ultrasound before operation. The lymph nodes near breast which were abnormally enlarged were marked. Intraoperatively, the lymph vessels and nodes were stained with both methylene blue and indocyanine green(ICG). After the true sentinel lymph nodes(trSLNs), para-SLNs(paSLNs)and post-SLNs(poSLNs)were accurately distinguished, the trSLNs were resected for biopsy. Results The evaluation of 126 cases of breast cancer revealed that the coincidence rate of preoperative ultrasound diagnosis was 78.8%. The SLNB specificity, sensitivity, and false negative rate(FNR)were 100%, 88.1% and 11.9%, respectively. The false negative of multifocal tumor was statistically significant(P=0.009), while preoperative assessment of lymph node status and paSLN metastasis were not statistically significant. Conclusion Preoperative ultrasound localization combined with intraoperative drainage guided SLNB can cause few trauma and low false negative rate. Multifocal tumor is a risk factor of false negative.

Application of 16S rDNA gene sequencing in the detection of pathogens in non-puerperal mastitis

ZHOU Fei, LIU Lu, LIU Liyuan, WANG Fei, YU Lixiang, XIANG Yujuan, MA Zhongbing, YU Zhigang

Journal of Shandong University (Health Sciences). 2018, 56(1):  57-61.  doi:10.6040/j.issn.1671-7554.0.2017.418

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Objective To investigate the application value of 16S rDNA gene sequencing in detecting pathogens in patients with non-puerperal mastitis. Methods A total of 33 samples of non-puerperal mastitis were collected. Traditional bacteria microscopy examination, microbial culture and identification were conducted. Meanwhile, the DNA was extracted for PCR amplification and 16S rDNA gene sequencing analysis. Results Bacterial staining group: 17 samples were collected for Gram staining, 41.18%(7/17)of which were Gram positive, and 35.29%(6/17)were Gram negative. Microbial culture group: 5 pus samples were incubated, 1 of which was positive with 2 types of bacteria. 16S rDNA sequencing group: all 33 cases were positive, 39.39%(13/33)of which were mixed bacterial infections, 27.27%(9/33)were Pseudomous, 6.06%(2/33)were kroppenstedtii. corynebacterium, 6.06%(2/33)were faecium. Enterococci, 3.03%(1/33)were Bacillus firmus, 3.03%(1/33)were Sporosarcina, 3.03%(1/33)were Staphylococcus aureus, and 12.12%(4/33)were uncultured bacterium clone. Conclusion The application of 16S rDNA sequencing technique to detect pathogens in non-puerperal mastitis is safe, simple, highly sensitive and strongly distinctive. It may provide guidance for the rational use of antibiotics.

Effects and mechanisms of hepatoma-derived growth factor on the proliferation of prostate cancer cells

YANG Feilong, ZHOU Zunlin, REN Juchao, YAN Lei, LIU Hainan, ZHANG Wenhua, YU Nengwang, LI Dawei, XU Zhonghua

Journal of Shandong University (Health Sciences). 2018, 56(1):  62-69.  doi:10.6040/j.issn.1671-7554.0.2017.379

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Objective To study the effect and mechanism of human hepatoma-derived growth factor(hHDGF)on the proliferation of prostate cancer cells. Methods Lentivirus vector was constructed according to the target sequence of hHDGF gene, which was then packaged into lentivirus particles and purified to transfect prostate cancer cells DU145 and LNCaP. The cells were divided into two groups separately: (1) Control group, which was treated by lentivirus with the insignificant sequence; (2) Experimental group, which was treated by the lentivirus with the target sequence. Relative mRNA expression of hHDGF was evaluated by quantitative real-time polymerase chain reaction(qRT-PCR). CCK-8 assay and colony formation assay were performed to measure cell proliferation ability. Relative expressions of hHDGF, phosphatidylinositol 3-kinase(PI3K), phospho-serine/threonine protein kinase(P-AKT)and phosphorylated mammalian 山 东 大 学 学 报 (医 学 版)56卷1期 -杨飞龙,等.肝癌衍生生长因子对前列腺癌细胞增殖的影响及其机制 \=-target of rapamycin(P-mTOR)proteins were detected by Western blotting. Results Lentivirus vector was successfully constructed, packaged and stably transfected into prostate cancer cells. qRT-PCR and Western blotting revealed that the mRNA and protein expression of hHDGF in experimental group were both downregulated(P<0.05). CCK-8 assay and colony formation assay indicated that cell proliferation of experimental group was inhibited(P<0.05). Western blotting revealed that relative protein expression of PI3K, P-AKT and P-mTOR were all downregulated(P<0.05). Conclusion Cell proliferation of proatate cancer is inhibited by the downregulation of hHDGF expression, which may be related with the inhibition of PI3K-AKT-mTOR signaling way.

Effects of proteasome inhibitor bortezomib combined with cisplatin on proliferation of human cervical cancer cells

DING Changkuan, Jason Chen

Journal of Shandong University (Health Sciences). 2018, 56(1):  70-75.  doi:10.6040/j.issn.1671-7554.0.2017.138

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Objective To investigate the effects of proteasome inhibitor bortezomib(BTZ), cisplatin(CIS)and their combination on proliferation of cervical cancer cells and to explore the mechanisms involved. Methods Hela cells were divided into four groups: normal control group(NC group), BTZ group, CIS group and C&B group. Cell Counting Kit-8(CCK-8)was used to examine HeLa cell proliferation after treatment. Western blotting was used to investigate the expression of p53 protein and Rb protein in the treated cells. Flow cytometry was used to observe apoptosis ratio after treatment. Results The inhibitory effect on the proliferation of HeLa cells in the C&B group was higher compared with the other groups. Western blotting analysis showed that the expression of p53 protein in CIS group was higher than that in NC group and C&B group(P<0.05), but had no obvious difference in BTZ group. Compared with that in other three groups, the expression of Rb protein in BTZ group was higher(P<0.05), and no obvious change was observed among these three groups. Flow cytometry demonstrated a synergistic effect of BTZ and CIS on HeLa cell apoptosis. Conclusion CIS may inhibit the proliferation of HeLa cells via regulating the expression of p53; BTZ may inhibit the proliferation of HeLa cells via regulating the expression of Rb; BTZ could enhance the inhibitory effects of CIS on HeLa cells.

Effects of sympathetic signals on orthodontic root resorption in rats

WANG Qianqian, WANG Xuxia, QIAO Qingfang, WANG Yingzi, YANG Panpan, ZHANG Jun

Journal of Shandong University (Health Sciences). 2018, 56(1):  76-80.  doi:10.6040/j.issn.1671-7554.0.2017.580

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Objective To explore the effects of sympathetic signals on root resorption in rats during orthodontic tooth movement. Methods Models of orthodontic tooth movement were established in 36 male 8-week old specific pathogen free(SPF)SD rats, which were randomly divided into 3 groups: propranolol(PRO)group, isoprenaline(ISO)group, and control group. The rats in the 3 groups were intraperitoneally injected with PRO［20 mg/(kg·d)］, ISO［5 mg/(kg·d)］ and isometric 0.9% saline, respectively, and were executed with force once every 7 days. After 14 days, the rats were sacrificed. The maxillae and first molars were separated. The root resorption was observed with hematoxylin-eosin(HE)staining.The volume of the mesial root of the first molars were measured with MicroCT. The differences among the 3 groups were compared using the SPSS 19.0 software. Results The results of HE staining showed that root resorption pits appeared in all 3 groups. The depth and scope of root resorption pits were the most serious in the ISO group, followed by the control and PRO groups. The results of MicroCT showed that the volume of mesial root of the first molars in the PRO group was larger than that in the control group(P<0.01), while the volume in the ISO group was obviously smaller than that in the control group(P<0.05). Conclusion Sympathetic signals can influence the root resorption during orthodontic tooth movement. The activation of signals promotes root resorption while the suppression of signals inhibits resorption.

Relationship between adipocyte β3 adrenergic receptor expression level and adiposity in adults

CAO Wenyue, PU Ying, LIU Zhao, GUO Feng, YU Jing, YIN Xiao

Journal of Shandong University (Health Sciences). 2018, 56(1):  81-85.  doi:10.6040/j.issn.1671-7554.0.2017.750

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Objective To detect relationship between adipocyte β3AR expression and adiposity in adults, and to explore the potential therapeutic target for obesity. Methods A total of 42 adipose tissues were collected from the patients who accepted abdominal operation and divided into overweight group(25≤BMI<30)and normal weight group(BMI<25). β3AR expressions in mRNA and protein levels were detected by qRT-PCR and Western blotting. Results The β3AR mRNA of mature adipocyte(t=2.594, P=0.013), β3AR protein level of mature adipocyte(t=2.760, P=0.010)and preadipocyte(t=2.442, P=0.023)in overweight group were lower than that in normal weight group. There was negative correlation between β3AR mRNA expression and BMI(r=-0.406, P=0.008). Conclusion The down-regulation of adipocyte β3AR expression in overweight group may play an important role in development of obesity.

Efficacy and safety of perioperative intravenous iron sucrose therapy in elderly patients with femoral intertrochanteric fracture

LIN Jinxiu, SUN Dongsheng, ZHENG Xiao, FU Kaifeng, LI Ye, YIN Dechao

Journal of Shandong University (Health Sciences). 2018, 56(1):  86-89.  doi:10.6040/j.issn.1671-7554.0.2017.785

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Objective To evaluate the efficacy and safety of perioperative intravenous iron sucrose therapy in elderly patients with femoral intertrochanteric fracture. Methods A total of 81 patients with femoral intertrochanteric fracture(≥65 years)treated with proximal femoral nail anti-rotation(PFNA)were divided into two groups: treatment group(n=41), and control group(n=40). The treatment group received 200mg iron sucrose onceadayfor3 consecutive days after admission, while the control group did not receive any iron treatment. The blood transfusion rate, hemoglobin(HB),serum ferritin, complication rate and healing were compared between the two groups. Results The transfusion rate in the treatment group and control group was 48.8% vs 52.5%, with no significant difference between the two groups(P>0.05). The HB of 7, 30, 90 days postoperatively in the treatment group and control group were(95.2±10.5)vs(90.1±12.1),(118.9±13.6)vs(109.8±12.8), and(125.5±14.9)vs(118.6±12.3)g/L. There were significant differences between the two groups(P<0.05). The serum ferritin in both groups was higher than normal before surgery, and markedly increased after operation, especially in the treatment group. There were no significant differences in complication rate and fracture healing between the two groups(P>0.05). Conclusion Perioperative intravenous iron sucrose can increase HB and improve anemia in elderly patients with femoral intertrochanteric fracture, but it cannot reduce transfusion rate.

Effects of temperature on hemorrhagic fever with renal syndrome based on the distributed lag non-linear models in Qingdao City

XU Qinqin, LI Runzi, LIU Yafei, SUN Yuanying, ZHENG Zhaolei, WANG Peizhu, WANG Zhiqiang, LI Xiujun

Journal of Shandong University (Health Sciences). 2018, 56(1):  90-96.  doi:10.6040/j.issn.1671-7554.0.2017.597

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Objective To investigate the effects of temperature on the onset risk of hemorrhagic fever with renal syndrome(HFRS)in Qingdao City. Methods The daily HFRS cases and meteorological variables in Qingdao City were collected from 1st January 2007 to 31st December 2013. Distributed lag non-linear models were used to analyze the exposure-response relationships between HFRS onset risk and daily mean temperature, maximum temperature and minimum temperature, respectively. Results With the reference temperature of 0 ℃, when the daily mean temperature, maximum temperature and minimum temperature were low(<0 ℃), they had an immediate effect on HFRS onset risk. With the increase of temperature and lag days, the onset risk of HFRS was higher at about 20 days lag, and RR values were 1.06(95% CI: 1.02-1.11), 1.05(95% CI: 1.00-1.10)and 1.07(95% CI: 1.03-1.12), respectively. On the whole, the highest onset risk of HFRS occurred with CRR values being 5.71(95% CI: 1.74-18.76)at mean temperature -8.8 ℃, 4.19(95% CI: 1.62-10.83)at maximum temperature -6.4 ℃, and 4.72(95% CI: 1.19-18.65)at minimum temperature -11.1 ℃. With the increase of temperature(>0 ℃), CRR values firstly increased, then decreased, and the lowest value occurred at the highest temperature. In addition, when the mean temperature ranged in 10 ℃ and 20 ℃, maximum temperature was <0 ℃ and minimum temperature was <20 ℃, HFRS had the greater onset risks(all P<0.05). 山 东 大 学 学 报 (医 学 版)56卷1期 -许勤勤,等.基于分布滞后非线性模型的青岛市温度与肾综合征出血热的剂量反应关系 \=- Conclusion The effects of temperature variables on the onset risks of HFRS are consistent and lagged. The risk of HFRS is greatest at the lowest temperature.