1.Research on LPA and Hippo-YAP signaling pathway in promoting invasion and metastasis of TNBC cell MDA-MB-231
Zhigang FAN ; Hui CAI ; Wanjun LI ; Dong XIAO ; Ming LIANG ; Li WANG ; Yongheng WANG ; Jiansheng WANG
Journal of Medical Postgraduates 2017;30(8):829-833
Objective Triple negative breast cancer(TNBC), a special breast cancer subtype, is lack of effective target therapy.The article aimed to investigate the role of lysophosphatidic acid (LPA) and Hippo Yes-associated protein (Hippo-YAP) signaling pathway in TNBC invasion and metastasis and the mechanisms.Methods The specific small interfering RNA (siRNA) of YAP was synthetized in vitro, and was transfected into MDA-MB-231 cells using liposome transfection.The experiment was divided into YAP-siRNA group, positive control group and blank control group.Each group is provided with 2 parallel holes.Evaluation was made on the effects of each group on Hippo-YAP, the mechanisms and regulation on upstream and downstream molecules of Hippo-YAP pathway.Results In experiment group, YAP content, the capacity of invasion and metastasis after transfection ([0.035±0.005], [2.200±1.000], [3.500±0.800]) significantly decreased compared with positive control group([0.343±0.012], [27.600±5.100], [22.300±5.000]) and blank control group([0.384±0.017], [26.500±4.800], [22.350±6.000]) (P<0.05).YAP expression levels at 60 min, 120 min, and 240 min in experiment group significantly decreased compared with positive control group and blank control group (P<0.05).YAP relative expression levels of 10, 20, 50 μmol/Lwere significantly lower than those of positive control group and blank control group (P<0.05).After respective interference of C3 transferase and Y27623, significant difference was found in the pYAP mRNA contents of experiment group([0.255±0.052], [0.326±0.017]), blank control group([0.048±0.032], [0.534±0.017]) and positive control group([0.052±0.021], [0.528±0.024])(P<0.05).The expression levels of YAP mNA and AREG mNA significantly increased in experiment group([0.176±0.032], [0.263±0.008]) compared with blank control group([0.043±0.013], [0.263±0.008]) and positive control group([0.049±0.025], [0.057±0.043])(P<0.05).Conclusion LPA induces breast cancer invasion and metastasis, which is YAP-dependent, time-dependent and concentration-dependent.LPA-Hippo-YAP singaling pathway may be one of the mechanisms promoting delayed metastasis of TNBC.
2.The study of the relationship between hepatic toxicity in hepatitis B virus markers seropositive cancer patients undergoing chemotherapy
Wei MENG ; Wanjun CAI ; Guofeng SHAO ; Cong WANG ; Long SUN
China Modern Doctor 2015;(13):91-93
Objective To evaluate the relationship between the hepatic toxicity induced by chemotherapy in patients with malignant tumor who test positive for HBV markers. Methods From January 2008 to January 2014, 887 cancer patients were treated by chemotherapy. Among 274 cases of patients were HBV positive (positive group), 613 patients were HBV negative (negative group), the liver function after chemotherapy were compared. Results Positive group patients receiving chemotherapy had higher rate of hepatic toxicity than those in negative group (24.1% vs. 11.3%,P<0.01),the incidence rate of 3-4 grade hepatic toxicity in positive group patients was 11.2%(13/116),more than that in negative group 0.65%(4/613). In the different treatment, there were statistically significant in two groups by TP regimen(paclitaxel+cisplatin), CAF(cyclophosphamide+adriamycin+5-Fluorouracil), CHOP(cyclophosphamide+doxorubicin+oncovin+prednisone)liver function after chemotherapy (P<0.05). In the TP scheme leaded to the incidence of abnor-mal liver function was the highest, the incidence rate in positive group was 36%(18/50),the incidence rate in negative group was 15.8%(19/120). Conclusion HBV infection is associated with higher risk of hepatic toxicity in patients with malignant tumor during chemotherapy(led by TP scheme).
3.Synergistic effect of sarcopenia and osteoporosis on spinal osteoporotic fracture in patients with rheumatoid arthritis
Cong WANG ; Shengqian XU ; Yuechen XU ; Keming CHEN ; Yuzhu TENG ; Wanjun LI ; Mu LI ; Jing CAI
Chinese Journal of Rheumatology 2020;24(3):192-197
Objective:To investigate the synergistic effect of sarcopenia and osteoporosis on the occurrence of spinal osteoporotic fracture (OPF) in patients with rheumatoid arthritis (RA).Methods:A total of 389 hospitalized RA patients and 156 age and sex-matched normal subjects (control group) were recruited. Dual energy X-ray absorptiometry (DEXA) method was used to measure bone mineral density (BMD) of lumbar spine and hip, and bioelectrical impedance method was applied to determine skeletal muscle mass of limbs. X-ray examination of spin was conducted and spinal OPF was diagnosed according to semi-quality method. Student's t test was used for comparison of measurement date between the two groups, χ2 test was used for comparison of intergroup rates, and Logistic Regression(Backward LR) method was used for multivariate Regression analysis of binomial classification data. Results:BMD of all test sites in RA patients was significantly lower than that in the control group ( P<0.01). The incidence of total OP in RA group was significantly higher than that in the control group [(32.9% vs 12.8%), χ2=22.706, P<0.01]. A total of 84 patients with RA developed spinal OPF, with an incidence of 21.6% which was higher than that in the control group [(3.8%), χ2=25.439, P<0.01]. The incidence of sarcopenia in RA was 54.8%, significantly higher than that in the control group [(9.6%), χ2=93.241, P<0.01]. The incidence of sarcopenia combined with osteoporosis in RA group (28.5%) was significantly higher than that in the control group [(5.8%), χ2=118.110, P<0.01]. Comparison of the incidence of spinal OPF in RA patients among groups with different bone mass (normal bone mass, osteopenia, osteoporosis) showed that the incidence of spinal OPF among these groups was statistically different ( χ2=43.373, P<0.01), and the incidence of spinal OPF increased along with the decrease of bone mass ( χ2=43.003, P<0.01). The incidence of spinal OPF in RA patients with sarcopenia (27.2%, 58/213) was significantly higher than that in RA patients without sarcopenia [(14.8%, 26/176), χ2=8.833, P=0.003]. All participants were divided into three groups: group 1=no OP and sarcopenia, group 2=with sarcopenia or OP, group 3=both sarcopenia and OP. Difference of incidence of spine OPF in RA patients among three groups was statistically significant ( χ2=33.832, P<0.01), and the incidence of spinal OPF raised gradually in group 1 and 3, ( χ2=37.164, P<0.01). Incidences of sarcopenia, OP and spinal OPF in RA treated with glucocorticoid (GC) were higher than those in RA without GC ( P<0.05, P<0.01). Results of logistic regression showed advanced age[ OR(95% CI)=1.069(1.038, 1.101), P<0.01], usage of GC [ OR(95% CI)=3.169(1.679, 5.984), P<0.01] and sarcopenia combined with OP [ OR(95% CI)=2.113(1.430, 3.124), P<0.01] were risk factors for spinal OPF in RA patients. Conclusion:Incidences of sarcopenia, OP and spinal OPF in RA patients are higher than that in normal controls. Sarcopenia and OP have a synergistic effect on spinal OPF in RA patients.
4. Application of pegylated recombinant human granulocyte colony-stimulating factor to prevent chemotherapy-induced neutropenia in patients with lymphoma: a prospective, multicenter, open-label clinical trial
Huiqiang HUANG ; Bing BAI ; Yuhuan GAO ; Dehui ZOU ; Shanhua ZOU ; Huo TAN ; Yongping SONG ; Zhenyu LI ; Jie JIN ; Wei LI ; Hang SU ; Yuping GONG ; Meizuo ZHONG ; Yuerong SHUANG ; Jun ZHU ; Jinqiao ZHANG ; Zhen CAI ; Qingliang TENG ; Wanjun SUN ; Yu YANG ; Zhongjun XIA ; Hailin CHEN ; Luoming HUA ; Yangyi BAO ; Ning WU
Chinese Journal of Hematology 2017;38(10):825-830
Objective:
To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma.
Methods:
This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed.
Results:
①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) .
Conclusion
During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.