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Objective:To investigate the expressions of apoptosis-related factors survivin, p53 and human epidermal growth factor receptor 2 (HER2) in breast cancer tissues and their prognostic value.Methods:A total of 131 patients undergoing radical mastectomy for breast cancer who were admitted to Tangshan Maternal and Child Health Care Hospital from February 2015 to January 2019 were selected as the research subjects. During the operation, the cancer tissues and adjacent tissues (normal tissues >3 cm from the tumor margin) were collected from the patients. Expressions of survivin, p53 and HER2 in cancer tissues and adjacent tissues of patients were detected by using immunohistochemistry. The prognoses of patients were recorded after the follow-up for 3 years; the recurrence, metastasis and death treated as the poor prognosis, the rest prognoses of patients were treated as the good prognosis group. The difference of clinicopathological characteristics between the poor prognosis group and the good prognosis group was compared. Multivariate logistic regression was used to analyze risk factors for prognosis of breast cancer patients. The result of prognosis of breast cancer was taken as the golden standard. The receiver operating characteristic (ROC) curve was used to analyze the value of survivin pasitive, p53 pasitive, HER2 pasitive alone, the combination of both and the combination of the there in the judgement of poor prognosis of breast cancer.Results:The positive expression rates of survivin [49.6% (65/131) vs. 7.6% (10/131)], p53 [60.3% (79/131) vs. 13.0% (17/131)] and HER2 [79.4% (104/131) vs. 16.8% (22/131)] in cancer tissues were higher than those in adjacent tissues (all P<0.001). A total of 131 breast cancer patients were followed up for 3 years without any loss of follow-up, and the follow-up rate was 100%. Within the follow-up for 3 years, there were 15 (11.5%) cases of recurrence, 8 (6.1%) cases of metastasis, and 10 (7.6%) cases of death, the incidence of poor prognosis was 25.2% (33/131); and the remaining 98 cases had good prognosis. The proportions of patients with TNM stage Ⅲ, lymph node metastasis, poorly differentiated histology, tumor diameter ≥3 cm, survivin, p53, and HER2 positive expressions in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). Multivariate logistic regression analysis showed that TNM stage Ⅲ [ OR = 5.323 (95% CI 2.190-12.936)], lymph node metastasis [ OR = 4.773 (95% CI 1.964-11.600)], tumor diameter ≥3 cm [ OR = 3.582(95% CI 1.474-8.706)], positive survivin [ OR = 2.740 (95% CI 1.127-6.659)], positive p53 [ OR = 3.271 (95% CI 1.346-7.949)], and positive HER2 [ OR = 3.873 (95% CI 1.594-9.412)] were independent risk factors for prognosis of breast cancer (all P<0.001). The ROC curve results showed that the area under the curve (AUC) values of survivin positive, p53 positive,HER2 positive, and the combination of any two were more than 0.80 (all P<0.001); the AUC of the combination of the three was 0.944 (95% CI 0.890-0.977) ( P<0.001). Conclusions:The expressions of survivin, p53, and HER2 are highly expressed in breast cancer tissues. The expressions of the three can be used to judge the prognosis of breast cancer patients, and the combination of the three has a higher judgement value.
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BACKGROUND@#Patients with lung cancer are often accompanied by anxiety, which affects postoperative recovery. The aim of this study is to explore the effects of preoperative anxiety on early prognosis in patients after thoracoscopic lung cancer resection.@*METHODS@#A total of 100 patients undergoing thoracoscopic resection of lung cancer were divided into 2 groups by hospital anxiety and depression scale (HADS): 44 in anxiety group (anxiety score>8) and 56 in control group (anxiety score<8). The primary endpoint: length of postoperative hospital stay. The secondary endpoint: length of hospital stay, visual analogue scale (VAS), the incidence of nausea and vomiting as well as postoperative new arrhythmia and the consumption of postoperative analgesic and rescue antiemetic.@*RESULTS@#Compared with the control group, the length of postoperative hospital stay and hospital stay in the anxiety group were both significantly longer [(5.1±2.5) d vs (4.0±1.3) d, P<0.01; (10.9±4.0) d vs (9.1±4.1) d, P<0.05)], the VAS score and the incidence of nausea as well as arrhythmia were significantly increased [(4.7±1.9) vs (2.6±1.8), P<0.001; 40.9% vs 16.1%, P<0.01; 36.4% vs 20.7%, P<0.05], and the consumption of postoperative analgesic and rescue antiemetic were also significantly increased [(72.5±8.9) mL vs (68.2±9.4) mL, P<0.05; (2.1±2.9) mg vs (0.9±1.9) mg, P<0.05].@*CONCLUSIONS@#Preoperative anxiety can affect the early prognosis of patients after thoracoscopic lung cancer resection, prolong hospitalization time, increase the postoperative pain score and the incidence of postoperative nausea and new arrhythmia as well as the consumption of postoperative analgesic and rescue antiemetic.
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Objective To explore the role of σ1 receptor (σ1R) in the clinical prognosis of cervical cancer,and provide a theoretical basis for σ1R targeted molecular therapy through observing the inhibition of synthetic σ1R-specific ligand compounds on the growth of cervical cancer cells. Methods (1) Immunohistochemical or immunocytochemistry staining were respectively used to detect the expression and localization of σ1R protein.(2)The Cancer Genome Atlas (TCGA) data set was used to validate our results. (3)Two series of 4 novel σ1R ligand compounds were synthesized by altering the N-terminal substituents on the piperidine ring of the prezamicol analogue, named as 14a, 14e, 15c and 15f. Methyl thiazolyl-tetrazolium (MTT) assay was detect the anti-proliferative effect of the four compounds on HeLa and SiHa cells. Compound 14a with potent inhibitory activity and the highest specificity of σ1R was selected for further experiments. Scratch test was observed the migration effect of compound 14a on HeLa and SiHa cells. Flow cytometry was determined cell cycles and apoptosis. Results (1) Immunostaining of σ1R protein was located in the cytoplasm and nucleus of cervical epithelium. The expression of cervical squamous cell carcinoma (SCC) was significantly higher than those of high-grade squamous intraepithelial lesion (HSIL) or normal cervical tissues. There was no significant difference in the expression of σ1R between HSIL and normal cervical tissues. σ1R expression in cervical adenocarcinoma (AC) was higher than that in SCC (P=0.020). The nuclear expression rate of σ1R in AC (10/18) was higher than that of SCC (27.1%, 19/70; P=0.024). The median overall survival (MOS) of σ1R-positive SCC patients was lower than that of σ1R-negative patients [(45.8±3.1) vs (51.7±2.9) months, P=0.045]. MOS of the patients with σ1R nuclear positive SCC was lower than that of non-nuclear staining [(38.9±3.8) vs (48.7±2.1) months, P=0.022]. MOS of the patients with σ1R nuclear positive AC was lower than that of non-nuclear staining [(35.0± 6.3) vs (44.2±4.2) months, P=0.034]. (2) Analysis of TCGA data showed that σ1R expression of in SCC was correlated with age (P=0.005). σ1R expression in AC was significantly associated with advanced stage, lymphnode metastasis and vascular invasion (all P<0.05). MOS of AC patients with σ1R overexpression was significantly lower than that of the patients with low expression (P=0.034). There was no significant difference in the MOS of different expression of σ1R mRNA in SCC patients(P=0.930). (3) MTT assay showed that these four compounds could suppressed the growth of HeLa and SiHa cells in time- and dose-dependent manner. The growth inhibition rates of HeLa and SiHa cells at 48 hours treated by combination of different concentrations of nedaplatin (NDP) with compound 14a (6 μmol/L) were significantly higher than those treated by NDP alone. Compound 14a (30 μmol/L) significantly inhibited the migration (both P<0.01) and induced the apoptosis of HeLa or SiHa cells (both P<0.01). Conclusions σ1R is over-expressed in cervical cancer and HSIL. σ1R nuclear expression is an important marker of AC. σ1R over-expression, especially σ1R nuclear expression is associated with the poor prognosis of cervical cancer. Our study is mostly consistent with cervical cancer data of TCGA. These results suggest that the novel synthetic prezamicol analogues 14a for σ1R could inhibit the growth of cervical cancer cells and cell migration through inducing apoptosis and arresting cell cycle in G0/G1 period, enhance NDP-induced cytotoxicity.
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Objective To investigate the effect of transcutaneous electric acupoint stimulation (TEAS)of Hegu-Neiguan-Houxi-Zhigou for preventing postoperative nausea and vomiting (PONV) in patients undergoing thoracoscopic lobectomy.Methods Sixty-four ASA physical status Ⅰ-Ⅲ pa-tients,aged 18-75 years,scheduled for elective thoracoscopic lobectomy were enrolled.Patients were randomly allocated into two groups (n =32):TEAS group (group E)and sham TEAS group (group C).TEAS at Hegu,Neiguan,Houxi and Zhigou was applied to patients before,during and after sur-gery in group E.The frequency was 2/100 Hz and the intensity was 2 times the threshold of sensation before and after surgery,and 30 mA during surgery.While sham TEAS with the intensity of sensory threshold was given to patients before and after surgery in group C.Patients in both groups received sufentanil,propofol and rocuronium for induction of anesthesia.Target controlled infusion of propofol and remifentanil was administered for maintenance of anesthesia.Patient-controlled intravenous anal-gesia (PCIA)was applied in both groups.No antiemetic was given to patients before and during sur-gery.Frequency of nausea or vomiting and any use of antiemetic for remediation were recorded after surgery.The postoperative Visual Analogue Scale (VAS)score and analgesic dosage were also docu-mented.Results Compared to group C,the incidence of nausea immediately after surgery,6 h after surgery,24 h after surgery and 48 h after surgery were significantly lower in group E.The incidence of vomiting 24 h after surgery was significantly lower in group E.The VAS score 6h and 24 h after surgery were significantly lower in group E.The analgesic dosage 48 h after surgery were reduced in group E.There were no significant differences regarding the use of antiemetic for remediation between the two groups.Conclusion TEAS at Hegu-Neiguan-Houxi-Zhigou is effective for preventing PONV in patients undergoing thoracoscopic lobectomy.
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Objective To compare the risk of tumor invasion and metastasis under paravertebral block (PVB) combined with general anesthesia versus general anesthesia in the patients undergoing radical resection for lung cancer performed via video-assisted thoracoscope in terms of plasma concentrations of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9).Methods Forty ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 30-64 yr,with body mass index of 18-25 kg/m2,scheduled for elective radical resection for lung cancer performed via video-assisted thoracoscope,were randomly divided into 2 groups (n =20 each) using a random number table:general anesthesia group (group G) and PVB combined with general anesthesia (group PG).PVB of T4-7 was performed successfully with local injection of 0.375％ ropivacaine 5 ml before induction of anesthesia.Double-lumen endotracheal tube was placed after induction of anesthesia,and the patients were mechanically ventilated.Anesthesia was maintained with inhalation of sevoflurane (end-tidal concentration 1％-2％),and intravenous infusion of remifentanil 0.2-0.3 μg · kg-1 · min-1,and intermittent intravenous boluses of atracurium.Before anesthesia and at 24 h after surgery,the venous blood samples were collected for measurement of plasma concentrations of VEGF and MMP-9.Results The plasma VEGF and MMP-9 concentrations were significantly lower after surgery in group PG than in group G.Conclusion PVB combined with general anesthesia significantly decreases the risk of tumor invasion and metastasis in the patients undergoing radical lung cancer resection performed via video-assisted thoracoscope in comparison to general anesthesia.
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Objective To compare the efficacy of oxycodone versus sufentanil for intravenous analgesia after radical resection of pulmonary carcinoma performed via video-assisted thoracoscope.Methods One hundred fifty-four patients of both sexes, aged 18-64 yr, with body mass index of 18-25 kg/m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , scheduled for elective radical resection of pulmonary carcinoma performed via video-assisted thoracoscope, were randomly divided into either sufentanil group (group S, n=76) or oxycodone group (group O, n =78) using a random number table.The 2 groups received combined intravenous-inhalational anesthesia.When postoperative visual analogue scale (VAS) score ≥ 4, sufentanil 5 μg or oxycodone 2 mg was injected intravenously, and the administration was repeated when necessary until VAS score ≤ 3.Patient-controlled intravenous analgesia (PCIA) was then used for postoperative analgesia (lasting for 48 h).PCIA solution contained tropisetron 20 mg and sufentanil 200 μg in 100 ml of normal saline in group S.PCIA solution contained tropisetron 20 mg and oxycodone 50 mg in 100 ml of normal saline in group O.The PCIA pump was set up to deliver a 2 ml bolus dose with a 10 min lockout interval and background infusion at a rate of 1 ml/h.VAS score was maintained ≤3.When VAS scores ≥4, morphine 10 mg injected intramuscularly was used as rescue analgesic.The requirement for rescue analgesic, level of patient's satisfaction with analgesia,and analgesia-related adverse events were recorded.Results The incidence of nausea and vomiting was significantly lower in group O than in group S (P＜0.05).There was no significant difference in the requirement for rescue analgesic, level of patient's satisfaction, and incidence of dizziness and over-sedation between the two groups (P＞0.05).No patients developed respiratory depression and pruritus in the two groups.Conclusion Compared with sufentanil, oxycodone can produce similar analgesic efficacy when used for PCIA after radical resection of pulmonary carcinoma performed via video-assisted thoracoscope, with lower incidence of nausea and vomiting.
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Objective To provide the theoretical supportting for targeted heparanase (HPA) inhibition of cervical cancer through observing the anti-proliferative effect of the HPA inhibitor on HeLa cell line of cervical cancer. Methods The two series of 13 kinds of novel HPA inhibitors were synthesized and optimized. Heparan degrading enzyme assay kit was used to test the effect of the inhibitors on the inhibition of HPA enzyme activity. Methyl thiazolyl tetrazolium (MTT) method and scratch test were used to observe the anti-proliferative and the migration effect of the inhibitors on HeLa cells. Flow cytometry was performed to determine the cell cycles and apoptosis. The expression of HPA was evaluated by reverse transcription (RT)-PCR, western blot and immunocytochemistry. Results All tested inhibitors could inhibit the activity of HPA enzyme [the range of 50% inhibiting concentration (IC50) values from 4.47 to 47.19 μmol/L] and the growth of HeLa cells (the range of IC50 values from 48.16 to 96.64μmol/L). Among them, No.16 compound exhibits the strongest inhibition against the growth of HeLa, which could arrest the cell into G0/G1 and G2/M phases. The rate of cell apoptosis in the group treated with 50μmol/L No.16 for 48 hours [(11.9±1.2)%] was significantly higher than that [(6.6 ± 1.8)%] in untreated group (P=0.013). Real time PCR and western blot showed that expression levels of HPA mRNA (1.23±0.46) and protein (0.46±0.31) significantly decreased in the treated group as compared with the levels of HPA mRNA (3.43 ± 0.45) and protein (1.30 ± 0.58) in the untreated group (both P<0.05). Immunocytochemistry also showed that the treatment of No.16 significantly reduced the average optical density (0.39 ± 0.04) of HPA immuostaining signal compared with that in the control group (0.50 ± 0.09; P=0.026). Conclusion Novel 1,3-O,N spiroheterocyclic HPA inhibitors could inhibit the proliferation of HeLa cells,inhibit the HPA enzyme activity in different degree, and down-regulate the expression of HPA protein.
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ObjectiveTo determine the correlation of real-time contrast-enhanced ultrasonography (CEUS) patterns and quantitative parameters with microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression of breast tumors.Methods One hundred and five patients with 128 breast lesions(62 benign,66 malignant) underwent CEUS examination.CEUS patterns were analyzed and parameters were obtained by time-intensity curve analysis software.Immunohistochemical staining using anti-factor CD34 was performed to evaluated the MVD and VEGF expression was detected.Results All CEUS patternsweresignificantlyassociatedwithMVDandVEGFexpressionexceptboundary characteristics( P ＜ 0.05).The enhancement parameters showed that the time to peak was significantly faster in malignant tumors than that in benign lesions,and the peak intensity and area under the curve were significantly higher in malignant tumors than those in benign lesions( P ＜0.05).The time to peak,the peak intensity,area under the time-intensity curve were statistically correlated with MVD (P ＜0.05),the highest correlation was between the area and MVD( r =0.81,P ＜0.001).Only the area under the timeintensity curve was significantly associated with VEGF expression (P ＜ 0.05).Conclusions CEUS patterns and parameters of breast lesions are closely correlated with MVD,which can be used to evaluated the angiogenesis in breast tumors.
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Objective To study the expression of estrogen receptor beta in the lung tissue of mice treaded with B[a]p alone or combined with estrogen (17 ?-estradiol, E2) in female Kunming strain mice and to explore the effect of estrogen in the lung cancer of mice induced by benzo[a]pyrene (B[a]P). Methods One hundred and twenty-five female Kunming mice were randomly divided into 5 groups: normal control group was group 1 ;group 2 was treated with subcutaneous injection of estrogen ( 900 ?g/kg); group 3 was given B[a]P(75 ?mol/kg) by gavage;the last two groups were given the same dosage of B[a]P (75 ?mol/kg)plus two different dosage of estrogen: 900 ?g/kg and 300 ?g/kg. After 8 weeks,there was a recovery period of 8 weeks. Then, the lung tissue was obtained by surgical resection. The expression of estrogen receptor-? gene and estrogen receptor-? protein of the lung tissue was detected by real-time PCR and Western blotting technology respectively. Results The expression of estrogen receptor-? protein and estrogen receptor-? gene in the B[a]P group and the B[a]P plus low dosage estrogen group was significantly higher than the normal group (P