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In our previous study, a liver-targeting peptide CSP I-plus modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed and showed potent antiangiogenic capability and could specifically bind to human hepatocellular carcinoma cells to make a direct inhibition in vitro. In this study, the biological activities of rES-CSP in vivo were evaluated by subcutaneous and orthotopic xenograft nude mice model of human hepatocellular carcinoma cells HepG2. We found that rES-CSP significantly decreased tumor volume to 54.9% in the nude mice with subcutaneous xenograft compared with the control. In orthotopic xenograft model, rES-CSP not only decreased tumor volume (to 39.6% compared with the control) and tumor weight, it also increased its biodistribution in the liver tissue and hepatoma tissue. Moreover, lower microvessel density (MVD) and higher apoptotic index (AI) were also observed in the tumor tissues. It had no significant side-effects on the heart, liver, spleen, lung and kidney of mice. Results indicated CSP I-plus modified Endostar may be a potential candidate for a targeting therapy on hepatocellular carcinoma.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Endostatinas/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/efectos de los fármacos , Proteínas Recombinantes/farmacología , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Endostatinas/química , Femenino , Células Hep G2 , Humanos , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Microvasos/efectos de los fármacos , Microvasos/metabolismo , Microvasos/patología , Proteínas Protozoarias/química , Proteínas Protozoarias/farmacología , Distribución Aleatoria , Proteínas Recombinantes/química , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective To investigate the clinical and pathological characteristics of atypical polypoid adenomyoma (APA) for improvement of the diagnosis, different diagnosis and treatment of the disease. Methods The clinical data, pathological characteristics, and the follow-up information were retrospectively analyzed in 27 cases of APA admitted in Peking Univeristy People′s Hospital from 2007 to 2016. Results The median age was 42.6 years old (range 25-60 years old). Fifteen patients were nullipara, 2 patients were postmenopausal. The most common presenting symptom was abnormal uterine bleeding (81%,22/27). Leisions were obtained by using hysteroscopy in 23 cases, hysterectomy 3 cases and dilatation and curettage 1 case. Fertility preserving treatments were performed in 10 patients who had strong desire for fertility, among which 1 case progressed into endometrial carcinoma. Among 15 patients underwent hysterectomy and (or) bilateral salpingo-oophorectomy, 9 cases of them had endometrial atypical hyperplasia. Endometrial carcinoma along with APA were found in three patients, 2 cases of them underwent hysterectomy and bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the other one received medication for fertility preservation. Follow up information were available in 24 cases(89%,24/27)with a median follow up of 46 months (range 4-108 months), 1 case recurred and 1 case progressed into endometrial carcinoma. One case died of other malignancy, while the other patients were alive. Conclusions APA is a rare uterine neoplasm mixed with epithelial and mesenchymal component. It occurs mostly in childbearing-age women and its diagnosis is dependent on pathology. Although it′s clinical course is benign, there is risk of co-existance of endometrial carcinoma and endometrial atypical hyperplasia. For those who has desire of fertility, the treatment strategy is completely removed the lesion and closely followed up. For those who do not desire to preserve fertility, hysterectomy may be an option.
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To obtain sufficient purified and active fusion protein-hepatocyte-targeting peptide-human endostatin (HTP-rES), we studied the growth curve and the optimal induction timing of BL21/pET21b-HTP-rES. Different conditions of pH value, induction time, induction concentration and induction temperature were optimized by univariate analysis. After washing, refolding and purifying, the activity of fusion protein was identified by flow cytometry and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT). Results show that the logarithmic growth phase of BL21/pET21b-HTP-rES was from 1.5 h to 3.5 h, the optimum expression conditions were pH 8.0, 0.06 mmol/L IPTG, at 42 ℃ for 5 h. The purity of inclusion bodies was up to 60% after washing. The purity of target protein was more than 95% after refolding and purification. Our findings provide the foundation for further biological activity and drug development.
Asunto(s)
Humanos , Sistemas de Liberación de Medicamentos , Endostatinas , Farmacología , Escherichia coli , Hepatocitos , Cuerpos de Inclusión , Péptidos , Farmacología , Proteínas Recombinantes de FusiónRESUMEN
Objective To investigate the clinicopathologic characteristics of premalignant and malignant endometrial polyps (EP) in premenopausal and postmenopausal women.Methods A retrospective analysis was conducted in 42 cases of premalignant and malignant EP from 1993 to 2012.Polyps were classified into premenopausal (group A,10 cases) and menopausal (group B,32 cases),including 26 cases of endometrioid adenocarcinoma,4 of clear cell carcinoma,9 of serous adenocarcinoma,and 3 of atypical hyperplasia.Results The prevalence rate of premalignant and malignant EP was 1.42% (42/2 965),the prevalence rate of malignancy in postmenopausal and postmenopausal women was 0.48% (10/2 064) and 3.55% (32/901),respectively.The mean size of EP was (1.6 ± 0.8) cm,abnormal uterine bleeding was positive in 90% (38/42) of cases.The EP pathological diagnosis showed all were endometrioid adenocarcinoma in group A,while there were 4 of clear cell carcinoma,9 of serous adenocarcinoma in group B.The mean size of EP was (1.1 ± 0.6) and (1.7 ± 0.9) cm in group A and B respectively (P <0.05).According to immunohistochemistry,all cases of group A were ER positive,but 41% (11/27) of group B were ER negative (P =0.059).The PR positive rate was 8/9 and 56% (15/27) in group A and B,respectively (P =0.169).Conclusions The risk of the EP malignancy rate is higher,while ER,PR positive rate are lower in postmenopausal womcn.Postmenopausal EP,especially accompanied by abnormal uterine bleeding and large polyps should be removed as soon as possible.
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Objective To investigate the clinical feature, risk factors and prognosis of bone metastasis from uterine carcinomas. Methods Eight cases of bone metastasis of uterine carcinomas in our hospital from Mar 2001 to Jun 2005 were studied retrospectively. These eight women, aged 35 to 74, suffered from cervical cancer (5/8) and endometrial carcinoma (3/8) respectively. Results (1) The interval between diagnosis of primary carcinoma and detection of bone metastases was within 2 years. The average interval was 5.3 months in patients with poorly differentiated tumor, and 21 months in the other patients. (2) Specific pathology type and poorly differentiated carcinomas may be risk factors of bone metastasis. (3) Three patients did not receive therapy of bone metastasis, and died within 6 months. In the other five patients, four are still alive. Conclusions The interval between diagnosis of uterine carcinoma and detection of bone metastases is within two years. The most common sites are pelvic bone and vertebrae. Specific pathology type and poorly differentiated carcinomas may be risk factors of bone metastasis. The prognosis of bone metastasis of uterine carcinomas is poor. Treatment of bone metastasis is primarily palliative and may prolong survival.