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Objective:To investigate the effects of myeloid differentiation protein-2 (MD-2) on paclitaxel resistance cells in triple negative breast cancer (TNBC) through EGFR signaling pathway.Methods:Immunohistochemical method was used to detect the expression of MD-2 in cancer tissue and adjacent tissue of TNBC patients, and the relationship between MD-2 expression and clinicopathological parameters of patients was analyzed. The TNBC paclitaxel-resistant cell line was constructed and MD-2 expression in cells was interfered. Cell invasion was detected by Transwell, and cell apoptosis was detected by flow cytometry. The signaling pathways regulated by MD-2 were screened by transcriptome sequencing and verified by Western blot.Results:The expression of MD-2 was significantly enhanced in cancer tissues relative to adjacent tissues. High expression of MD-2 was closely related to clinical stage, tumor size, tumor recurrence and metastasis ( χ2=4.50, P=0.032; χ2=2.55, P=0.011; χ2=4.40, P=0.036). In cell experiments, compared with normal breast cells, the expression of MD-2 in TNBC cell lines was significantly enhanced. Compared with sh-NC group (100±11.52) (6.81±0.57), knockdown of MD-2 could inhibit the invasion (61.44±6.78) ( t=4.99, P=0.008) but promote apoptosis (15.19±1.06) ( t=12.06, P<0.001) of paclitaxel resistant TNBC cells. Transcriptome sequencing and Western blot results showed that MD-2 mainly affects the biological behavior of TNBC cells by regulating the EGFR signaling pathway. Conclusions:MD-2 promoted TNBC cell invasion and paclitaxel resistance, which may be achieved by affecting the EGFR signaling pathway. MD-2 is expected to become an effective target in TNBC treatment.
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Tumor microenvironments (TMEs) are closely related to tumor resistance. TMEs are divided into cellular components and acellular components. The cellular components include tumor-associated macrophages, tumor-associated fibroblasts, mesenchymal stem cells, etc., which can enhance tumor resistance through recruitment and secretion of a variety of protective cytokines; acellular components such as extracellular matrix, hypoxia and acidification, etc., can mediate drug resistance by constructing physical barriers, affecting tumor cell growth and metabolism. Studying the mechanisms of TME-mediated drug resistance and reshaping TMEs can provide new strategies for anti-tumor therapy.
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Objective To assess the efficacy and safety of mifepristone combined with oral or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of gestation. Methods This was a randomized, multi-center, open clinical trial. A total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either oral misoprostol 400 μg every 3 hours or vaginal misoprostol 400μg every 6 hours for a maximum of 4 doses 36-48 hours later. There were 417 women in oral group with 198 at 8-9 weeks and 219 at 10-16 weeks, while 208 women in vaginal group with 99 at 8-9 weeks and 109 at 10-16 weeks. The outcome measures were the success abortion rate, induction to abortion interval, the amount of bleeding, reoccurrence of menstruation and adverse events. Results Abortion rate was significantly higher in vaginal group [98.1% (202/206)] than that in oral group [94.0%(390/415), P=0.023]; concerning termination of pregnancy at 8-9 weeks and 10-16 weeks respectively, there were no significant differences between oral and vaginal groups (P=0.156, P=0.073). The induction to abortion interval was no significant difference in oral and vaginal group in different gestational weeks ( P=0.238, P=0.273). The average induction to abortion interval was (4.1 ± 6.6) hours and (6.0 ± 4.5) hours respectively in terminating 8-9 weeks and 10-16 weeks of gestation. Concerning the amount of bleeding within 2 hours of placenta expulsion, there was significant difference between oral group [(63±46) ml] and vaginal group [(55 ± 45) ml] in terminating 8-9 weeks of gestation (P=0.047), while there was no significant difference between groups in terminating 10-16 weeks of gestation [oral group (76 ± 52) ml versus vaginal group (76 ± 61) ml, P=0.507]. The reoccurrence of menstruation was about 37 days in both oral and vaginal groups. Two cases of incomplete abortion were serious adverse events (SAE) relating to treatment. The common adverse events (AE) of nausea and vomiting were significantly higher in oral group [57.2% (239/417), 36.3% (151/417)] than those in vaginal group [45.4% (94/208), 26.1% (54/208); P=0.005, 0.011]. Conclusion Oral or vaginal misoprostol combined with mifepristone, is effective and safe for termination of pregnancy between 8 and 16 weeks of gestation.
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Objective To study the clinical characteristics,pathology,and treatment for papillary carcinoma of the breast.Methods The clinical data of 17 patients of papillary carcinoma of the breast admitted in the First Affiliated Hospital of Wen Zhou Medical College were retrospectively analyzed.Results Papillary carcinoma of the breast accounted for 0.64％ of all breast cancer cases hospitalized during last 10 years.All cases had palpable lumps in the breast.12 cases received modified radical mastectomy,2 cases received simple mastectomy,2 cases underwent breast conservation therapy,1 case underwent simple mastectomy plus sentinel lymph node biopsy.15 patients received postoperative chemotherapy,among those 5 cases also received radiotherapy.During a 32.5-month median follow-up ( 1 month to 8 years),one case with bone metastases died 2 years postoperatively and another one died of multimetastases 7 years later.Conclusions The prognosis of papillary carcinoma of the breast is closely related with its pathology type.For intraductal papillary carcinoma low-traumatic therapy is applicable,while in case of infiltrating papillary carcinoma or invasive micropapillary carcinoma ( IMPC ),more aggressive therapies like that adopted for infiltrating ductal carcinoma are recommended.
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rse effect when compared with tibolone.
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@# ObjectiveTo introduce a method of promoting neural stem cells proliferation.MethodsNeural stem cells were cultured with medium DMEM containing 10% fatal bovine serum for 48 h, then changed medium DMEM/F12 containing epidermal growth factor, basic fibroblast growth factor and B27. Immunohistochemistry was used to identify nestin expression.ResultsNeural stem cells got together fast and formed neurospheres within 48 h and expressed nestin. ConclusionPro-culture with serum can promotes neural stem cell proliferation.
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Objective To investigate the management of research instruments.Methods Scientific and effectual device management and technical training were established.Results The instruments availability and intact conditions including economic efficacy were greatly improved via scientific and effectual management in our neurosurgical institute.Conclusion Scientific standard and systematic management can not only ensure the optimal working conditions of research instruments for research work,but promote the equipment efficacy and increase economic returns.
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<p><b>OBJECTIVE</b>To determine the effects of raloxifene hydrochloride (RLX) on bone mineral density (BMD), bone metabolism markers and serum lipids in healthy postmenopausal women in Beijing.</p><p><b>METHODS</b>A multicenter, randomized, double-blind, placebo-controlled study was conducted in a total of 204 healthy postmenopausal women (age 59.5 +/- 5.0 years and weight 62.8 +/- 8.7 kg) treated with either RLX 60 mg (n = 102) or placebo (n = 102) daily for 12 months. BMD, serum lipids, and bone markers were measured before and after drug administration.</p><p><b>RESULTS</b>Compared with placebo, RLX produced a significant increase in both total lumbar spine and total hip BMD. For the lumbar spine, percentage increase in total BMD was 2.3% with RLX compared with a decrease of 0.1% with placebo (P < 0.001). Corresponding values for total hip BMD were a 2.5% increase for RLX and a 1.1% increase for placebo (P = 0.011). For biochemical markers of bone metabolism, serum osteocalcin and C-telopeptide, percentage decreases were 27.65% and 24.02% in RLX-treated subjects. Corresponding values in placebo were a 10.64% decrease and a 15.75% increase (RLX compared with placebo, both P < 0.001). For total cholesterol and low-density lipoprotein cholesterol levels, percentage decreases were 6.44% and 34.58% in the RLX-treated group. Corresponding values in placebo-treated patients were a 1.44% increase and a 19.07% decrease (RLX compared with placebo, both P < 0.001). No differences were found for high-density lipoprotein cholesterol or triglyceride levels between the two groups. Only 5 subjects discontinued early owing to an adverse event (3 in the RLX group and 2 in the placebo group).</p><p><b>CONCLUSIONS</b>This study confirms that RLX exerts positive effects on the skeleton, increasing BMD and decreasing biochemical markers of bone metabolism, and has a positive effect on the overall serum lipid profile in postmenopausal women in China.</p>
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Aged , Female , Humans , Middle Aged , Biomarkers , Blood , Bone Density , Bone and Bones , Metabolism , China , Estrogen Antagonists , Pharmacology , Lipids , Blood , Postmenopause , Physiology , Raloxifene Hydrochloride , Pharmacology , Selective Estrogen Receptor Modulators , PharmacologyABSTRACT
Objective To evaluate the effectiveness and safety of triptorelin in the treatment of uterine leiomyoma. Methods A multi-center, prospective, randomly controlled clinical trial was carried out from Dec. 2002 to Mar. 2004 in three university hospitals. A total of 125 qualified patients with uterine leiomyoma were randomly divided into either triptorelin group (63 cases) treated with 3.75 mg triptorelin injected intramuscularly or leuprorelin group (62 cases) treated with 3.75 mg leuprorelin injected subcutaneously. Both drugs were injected every 28 days for a total of 3 months. Results All 125 patients finished the trial. The uterine volumes were similar before treatment between the triptorelin group and the leuprorelin group and were decreased significantly after drug therapy (P0.05).) The volumes of the largest leiomyoma decreased significantly after drug therapy (P0.05). Patients with serum level of 17?-estradiol 0.05). Dysmenorrhea, noncyclic pelvic pain and pressure-like symptoms were relieved quickly and remarkably in both groups after treatment. The rates of adverse event occurred in 71% of patients in both groups. The main side effects included flare-up effects and hypoestrogenic symptoms. Nine patients in the triptorelin group and 6 in the leuprorelin group received add-back therapy with tibolone 1.25-2.50 mg/d because of remarkable climacteric-like symptoms. Conclusion Treatment of uterine leiomyoma with triptorelin for 3 months is both effective and safe in Chinese women.
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Objective To investigate the role of angiogenesis and expression of vascular endothelial growth factor (VEGF) in the pathophysiology of adenomyosis of the uterus. Methods The study included 32 patients with histologically proven adenomyosis and 30 patients with asymptomatic leiomyoma of the uterus. Immunohistochemical staining was used to detect VEGF expression in different parts of the uterus. A computerized morphometric study on the VEGF expression was performed. Results The VEGF H-Score of glandular cells in the endometrium of adenomyosis uterus [proliferative phase (9.6?1.4), secretory phase (11.7?1.6)] was much higher than that of leiomyoma uterus [proliferative phase (8.3?1.7),secretory phase (10.2?1.5)] (P0.05). The VEGF H-Score of myometrium around the ectopic lesions [proliferative phase (9.5?1.3), secretory phase (8.7?1.3)] was higher than that of normal myometrium [proliferative phase (4.8?1.9), secretory phase (4.5?1.4)] (P
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0 05). For the average blood loss at 2 hour postpartum, it was 129 7 ml, 133 9 ml, 168 5 ml and 178 2 ml for group Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively, while the total blood loss for the 4 groups was 243 3 ml, 242 9 ml, 308 1 ml, and 314 8 ml respectively. The average blood loss of group Ⅰ and Ⅱ was significantly less than group Ⅲ and Ⅳ ( P 0 05). The occurrences of postpartum hemorrhage (blood lose ≥400 ml) were 6 4%, 13 3%, 20 7% and 25 3% for group Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. There was no major adverse effects appeared. Conclusions Transamin is efficient and safe in reducing the postpartum blood loss. 1 0 g of Transamin has the best efficacy, and 0.5g of Transamin followed.
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Objective To investigate the levels of interleukin-1?,interleukin-6,tumor necro- sis factor-? in preterm labor with intraamniotic infection(IAI).Methods Plasma and amniotic fluid were sampled from 30 women with preterm labor(Group A),31 women with term labor(Group B) and 46 women without labor but after 37 weeks(Group C).Interleukin-6 in blood,interleukin-1?, interleukin-6 and tumor necrosis factor-? in amniotic fluid were examined.IAI were diagnosed accord- ing to clinical criteria or bacterial culture or pathology.Results 1.The levels of IL-6 in blood in Group A were higher than in Group Band C(46.34 vs 20.53,6.67pg/ml,P
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Objective To investigate the variation of cytokines IL-4, IL-1? and TNF-? before and after the onset of pregnancy induced hypertension (PIH) and to discuss the role of cytokine in the pathogenesis of PIH. Method A prospective cohort study of 550 pregnant women were followed. Plasma drawn from 25 women who developed moderate and severe PIH and 30 controls at 12~16 and 32~36 gestational weeks were analyzed. The concentrations of IL-4, IL-1? and TNF-? were analyzed using ELISA method. Results (1)In the second trimester, the plasma level of TNF-? in PIH group was significantly higher than control group(27.66 ng/L vs 17.80 ng/L, P