ABSTRACT
OBJECTIVE： To observe the efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase （ALK） positive advanced lung adenocarcinoma. METHODS： From Aug. 2015 to May 2017， 72 patients with ALK positive advanced lung adenocarcinoma were selected from our hospital. According to the simple random method， the patients were divided into control group and observation group， with 36 patients in each group. The control group was given Pemetrexed disodium for injection 500 mg/m2，d1， ivgtt+ Cisplatin for injection 75 mg/m2，d1-3，ivgtt； Dexamethasone acetate tablets 0.75 mg were given orally one day before administration， once in the morning and again in the evening； 7 days before administration， Folic acid tablets 0.4 mg were given orally till 21 days after the last administration of cisplatin； Vitamin B12 1 mg injection was injected intramuscularly every 3 weeks after intramuscular injection of cisplatin. Isotonic Glucose injection 100 g was intravenously dripped 1 day before medication； on the day of chemotherapy， isotonic Sodium chloride injection or Glucose injection was infused intravenously for 3 000-3 500 mL； at the same time， Potassium chloride injection 0.5 g， Mannitol injection 50 g， Furosemide injection 20 mg were given to ensure daily urine volume of 2 000-3 000 mL； a treatment course lasted for 21 d， and there were 2 courses in total. Observation group was additionally given Crizotinib capsules 250 mg orally， once at 7：00 in the morning and evening， swallowing whole capsule， not chewed or dissolved， for 42 days. The clinical efficacies， survival quality and the occurrence of toxic reaction were observed in 2 groups. RESULTS： Total response rate （61.11％） and stable rate of survival quality （83.33％） in observation group were significantly higher than those （27.78％， 44.44％） of control group （P＜0.05）； incidence of grade Ⅰ-Ⅳ myelosuppression， gastrointestinal reaction， abnormal liver function， peripheral neuritis and alopecia in observation group were significantly lower than those of control group； incidence of grade Ⅰ-Ⅳ visual effect in observation group was significantly higher than control group（P＜0.05）. There was no statistical significance in the incidence of edema between 2 groups（P＞0.05）. CONCLUSIONS： Based on routine chemotherapy， additional application of crizotinib can significantly improve therapeutic efficacy of patients with advanced ALK positive lung adenocarcinoma， and effectively improve survival quality of patients without increasing the occurrence of toxic reaction of other tissues or organs， but the incidence of toxic reaction is in high level relatively.
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Objective To investigate the effects of RNA interference technique silencing MTDH on proliferation,metastasis and invasion of human breast cancer cell MDA-MB-231.Methods The MTDH miRNA was transfected into Human breast cancer cell MDA-MB-231 by means of lipofectamine 2000.The silencing efficiency of MTDH was examined by RT-PCR and western blot.The influence of MDA-MB-231 cell proliferation,metastasis and invasion ability from inhibition MTDH gene was conducted by using MTT assay,scratch experiments,and Transwell assay.Results MTDH miRNA effectively inhibited MTDH mRNA and protein levels.The best inhibition rate were 79.41％ and 80.56％ (P ＜ 0.05).With miRNA interferring cells,the ability of cells proliferation was decreased (P ＜ 0.05),and cells invasive and metastasis were depressed (P ＜ 0.05).Conclusion MTDH expression is obviously suppressed after transfected by MTDH miRNA in MDA-MB-231 cells.The inhibition of MTDH expression from microRNA leads to significant suppression of proliferation,invasion and metastasis of breast cancer cell MDA-MB-231.
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Objective To explore the expressions of Smad4 and estrogen receptor (ER) and their interrelation,and the relationship with the clinicopathological features of breast cancer.Methods The immunohistochemical SP method was used to detect the expressions of Smad4 and ER in 50 case of invasive cancer,12 cases of carcinoma in situ and 15 cases of normal breast tissues.The differences in different clinical stages,differentiation degrees and nodal metastases were analyzed.The correlation between Smad4 and ER was explored.Results The positive expression rate of Smad4 in invasive cancer was 52.00％,which lower than that in normal breast tissue (93.33％),with a significant difference (x2 =8.329,P =0.004),positive expression rates of ER were 60.00％ and 40.00％ respectively,with no significant difference (x2 =1.868,P =0.172).The positive expression rates of Smad4 in carcinoma in situ and invasive cancer were 75.00％ and 52.00％ respectively,with no significant difference (x2 =2.082,P =0.149).The positive expression rates of ER were 58.33％ and 60.00％ respectively,with no significant difference (x2 =0.011,P =0.916).The positive expression of Smad4 was related to the TNM stage (x2 =6.392,P =0.011) and the lymph node metastasis (x2 =6.738,P =0.009),but it was not associated with the histologic grade (x2 =0.542,P =0.462).The positive expression of ER was related to the lymph node metastasis (x2 =4.133,P =0.042) and histologic grade (x2 =5.357,P =0.021),but it was not associated with the TNM stage (x2 =1.159,P =0.282).There was positive correlation between Smad4 and ER in breast cancer tissue (r =0.263,P =0.032).Conclusion Smad4 is expressed at lower level in breast cancer than in normal breast tissue.The expressions of Smad4 and ER are related to the different clinicopathological features of breast cancer with positive correlation.