Apatinib Combined With Radiotherapy Enhances Antitumor Effects in an In Vivo Nasopharyngeal Carcinoma Model.

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are highly expressed in nasopharyngeal carcinoma; therefore, blocking the binding of VEGF and VEGFR may be a potential way to treat nasopharyngeal carcinoma. Apatinib inhibits tumor angiogenesis. Previous studies have suggested that treatment with apatinib has an antitumor effect on nasopharyngeal carcinoma. This study will investigate the effect of apatinib combined with radiotherapy. In this study, nude mice injected with CNE-2 nasopharyngeal carcinoma cells were randomly divided into 6 groups. Therapeutic effects were assessed by evaluating tumor inhibition rate, phosphorylation of VEGFR-2, CD31, partial oxygen pressure, and tumor metabolism. We found that the tumor inhibition of mice in the treated groups was better compared to that of the control group. In mice treated with apatinib alone, angiogenesis was prevented, and the tumor tissue partial oxygen pressure was reduced, thereby achieving an antitumor effect. Moreover, the tumor inhibitory effect of combined treatment was stronger than treatment with either apatinib or radiotherapy alone. Compared with monotherapy treatment, combined treatment better resisted angiogenesis. Apatinib combined with radiotherapy to treat nasopharyngeal carcinoma has synergistic effects, which may be related to enhanced antiangiogenesis.

Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma.

BACKGROUND: Conventional chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC) however it increases therapeutic resistance. In contrast, metronomic chemotherapy (MET) is based on frequent drug administration at lower doses, resulting in inhibition of neovascularization and induction of tumor dormancy. This study aims to evaluate the inhibitory effects, adverse events, and potential mechanisms of MET Vinorelbine (NVB) combined with an angiogenesis inhibitor (Endostar). METHODS: Circulating endothelial progenitor cells (CEPs), apoptosis rate, expression of CD31, vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1α) were determined using flow cytometry, western blot analysis, immunofluorescence staining and Enzyme-linked immunosorbent assay (ELISA) analysis. And some animals were also observed using micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) to identify changes by comparing SUVmax values. In addition, white blood cell (WBC) counts and H&E-stained sections of liver, lungs, kidney, and heart were performed in order to monitor toxicity assessments. RESULTS: We found that treatment with MET NVB + Endo was most effective in inhibiting tumor growth, decreasing expression of CD31, VEGF, HIF-1α, and CEPs, and reducing side effects, inducing apoptosis, such as expression of Bcl-2, Bax and caspase-3. Administration with a maximum tolerated dose of NVB combined with Endostar (MTD NVB + Endo) demonstrated similar anti-tumor effects, including changes in glucose metabolism with micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging, however angiogenesis was not inhibited. Compared with either agent alone, the combination of drugs resulted in better anti-tumor effects. CONCLUSION: These results indicated that MET NVB combined with Endo significantly enhanced anti-tumor and anti-angiogenic responses without overt toxicity in a xenograft model of human lung cancer.

Antitumor effects of Endostar(rh-endostatin) combined with gemcitabine in different administration sequences to treat Lewis lung carcinoma.

Background: Endostatin therapy is known to efficiently inhibit angiogenesis and growth of endothelial cells. Nonetheless, the antitumor mechanisms of endostatin combined with chemotherapy remain to be elucidated. Methods: In our study, a Lewis lung carcinoma transplant mouse model was established and treated with the recombinant human [rh]-endostatin, Endostar, combined with gemcitabine at different sequences. 18F-FDG PET/CT imaging was performed to monitor tumor growth, and hypoxia was examined using an oxygen microelectrode. Vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA) levels were detected via immunohistochemistry analysis and cell cycle distributions were analyzed by flow cytometry. Results: Endostar decreased VEGF expression, improved hypoxia, and influenced cell cycle distributions. Simultaneous treatment of Endostar and gemcitabine displayed significantly tumor inhibition, possessed the lowest uptake of FDG, improved oxygen partial pressure, decreased expression of VEGF, and increased pericyte coverage. Cell cycle analysis demonstrated that cells accumulated in the S phase following gemcitabine treatment and G0/G1 arrest occurred following Endostar treatment. An increase of cells in G0/G1 phase was observed following treatment with Endostar and gemcitabine. Conclusions: Our study suggests that the combination therapy of Endostar with gemcitabine simutaneously may optimally enhance their individual antitumor effects.

Efficacy of granulocyte-macrophage colony-stimulating factor combined with metronomic paclitaxel in the treatment of Lewis lung carcinoma transplanted in mice.

Metronomic chemotherapy in combination with immunotherapy is an attractive approach in cancer therapy. The purpose of the present study was to investigate the anti-tumor effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with metronomic paclitaxel (MET PTX) on Lewis lung carcinoma transplanted in mice. In the present study, tumor-bearing mice survival time and tumor growth were monitored. The day after the end of the treatment, white blood cells were counted, and the number and maturation of dendritic cell were determined by flow cytometry. Besides, microvessel density and tumor cell proliferation were determined by immunohistochemistry, while apoptosis was determined by TUNEL (Terminal deoxynucleotidyl transferase-mediated nick end labeling) assay. Micro 18F-FDG PET/CT (18F-Fluorodeoxyglucose positron emission tomography/computed tomography) was used to obtain SUVmax values. White blood cells reduction was not observed in the mice treated with GM-CSF combined with MET PTX. Moreover, GM-CSF combined with MET PTX further reduced proliferation and microvessel density, promoted tumor apoptosis, increased the dendritic cells number and induced their maturation, with concomitant delay in tumor growth and improved survival. Taken together, GM-CSF combined with MET PTX exerted a synergistic anti-tumor effect against lung cancer in a mouse model through an antiangiogenic activity and inducing dendritic cells maturation without exerting pronounced adverse effects. Hence, combined metronomic chemotherapy and immunotherapy could be a potential strategy for the treatment of patients with advanced lung cancer.

The use of peritoneal tissue mobilised with a novel laparoscopic technique to reconstruct a neovagina.

The use of the peritoneum to construct the new lining of the vagina was described 40 years ago. However, the technique required open laparotomy and extensive dissection of the peritoneum and this technical difficulty and morbidities associated with the procedure reduced the acceptance of this technique. Subsequently, outcomes achievable from any neo-vaginoplastic techniques for a vaginal deformity, regardless of the aetiology, have been problematic due to peritoneal reflection at the pelvic floor, lack of ideal tissues to line a neovagina, and cicatricial contracture. The advent of the endoscope renewed interest in using peritoneal tissues in vaginal reconstruction, and peritoneal tissue mobilisation using forceps to grasp the tissue from below has been described. Here, we use a novel device to push a segment of mobilised peritoneum caudally into the vault. We have used this technique successfully in 12 individuals with congenital vaginal agenesis. Under laparoscopic guidance and from the pelvic cavity, a novel instrument was used to push peritoneal tissue down to the introitus, incised, and sutured to the margin of the skin and mucous membrane to form a new introitus. All the new peritoneal linings survived and the diameter, depth, and moisture of the neovaginas allowed for satisfactory sexual intercourse and did not produce unpleasant odour or excessive secretion. Advantages of this operative technique include its simplicity, the reduced possibility of severe complications in the abdominal cavity, the avoidance of severe morbidity in the perineal region, and the production of a functional, hygienic vagina. It is our preferred and recommended method to reconstruct the vagina.

[Laparoscopically assisted neovaginaplasty using peritoneum as vaginal mucous substitute].

OBJECTIVE: To practice a more atraumatic, physiological and aesthetically valued approach of construction for neovagina. METHODS: Laparoscopically using peritoneum as neovagina lining. RESULTS: From March 2005 to September 2006, this technique was adopted to treat 10 patients whose diagnosis was congenital absence of vagina. The ages of the patients were from 19 to 32. The operation lasted average 2.34 hours. And hospitalization was about 20.5 days. Follow-up ranged from 3 - 12 months. No complication occurred. All of the patients was satisfied with their sexual life. CONCLUSIONS: Laparoscopically assisted neovaginaplasty, in which peritoneum was substituted for vaginal mucous membrane, was a kind of ideal approach of vaginal creation.

[Mandibular contour sculpture by osteotomy].

OBJECTIVE: To investigate the method for mandible osteotomy in order to make the mandible of various square face appear harmony. METHODS: According to different types of the mandible, mandible angle osteotomy was performed in combination with mandible edge, mandible half ring osteotomy or chin augmentation. RESULTS: A total of 312 cases have been treated since 1996. In this series, mandible angle and mandible edge osteotomy was performed in 200 cases; only mandible edge osteotomy in 23; mandible half ring osteotomy in 15, chin sharpening in 9, chin augmentation with autogenous bone implantation, in 32. Postoperative follow-up of 150 cases for 1-12 months showed that the satisfactory rate was 97%. CONCLUSION: Integrated mandible osteotomy can make the square face look natural and nice-looking.

[The histological study of the capsules formed around the mammary prosthesis].

OBJECTIVE: To observe and analyze the pathohistological characteristics of capsules which formed around the mammary prosthesis with different contents. And to provide the selective basis for ideal and safe prosthesis in clinical practice. METHODS: 20 specimen of the capsules were taken from 20 cases who receive the operation of prothesis removal for different reasons. HE, Masson and Mallory staining were used to analyse the tissue structure and characteristics under the light microscope. RESULTS: The common structure including the collagen fibers accumulation, inflammatory cells infiltration and the capillary hyperplasia were found in all specimen. A layer of squamous epithelium-like cell was detected in some specimen. The specific characteristics were also found in different capsules formed around different prosthesis. In the capsules around vegetable oil prosthesis, there was excessive collagen fiber accumulation, and the capsules were much thicker. In the PVP (polyvinylpyrolidone) prosthesis capsules, there was severe inflammatory cell infiltration, and the number of eosinophilic granulocyte increased obviously. In the silicone gel and saline prosthesis capsule, the collagen fibers were well-arranged and the inflammatory cells were much less. Synovial metaplasia was detected in two cases. CONCLUSION: 1. The capsules form around the prosthesis in all cases after mammary augmentation. 2. There will be synovial metaplasis in some cases, for vegetable oil prosthesis, the collagen over-accumulated which lead the capsules become thicker and harder. So it is not a kind of ideal mammary prothesis. 4. The severe infiltration of the inflammatory cells especially the large quantity of eosinophilic granulocyte indicate the possibility of the delayed hypersensitive reaction mediated by eosinophilic granulocyte. Cautious attitude should be taken during application.

[Effects of the site and method of liposuction on differentiation of human preadipocytes].

OBJECTIVE: To illustrate the effects of the site and method of liposuction on differentiation of human preadipocytes. METHODS: Forty-two fatty samples were obtained with liposuction, which were then divided into four groups according to operation sites (abdomen, hip or extremity) and the methods (conventional negative-pressure or syringe method). Each sample was treated with collagenase I to release preadipocytes for in vitro culture. Affected by the differentiation-induced agents for 9 days or 28 days, the cultured adipocytes were stained with Nile red and observed under a fluorescent microscope. The differentiation rates were examined with flow cytometric analysis and the quantity of intracytoplasmic lipids was determined with oil red O staining. The results were analyzed with independent samples t-test (Mann-Whitney) using SPSS 10.0. RESULTS: There was no statistical difference in differentiation at the 9th day or 28th day among the preadipocytes obtained from the abdomen, hip or extremity with the negative-pressure method. The preadipocytes from the abdomen differentiated more at the 28th day than the 9th day (P < 0.05), which was not observed in the hip or the extremity. The preadipocytes obtained from the abdomen with the negative-pressure method differentiated more than those with the syringe method (P < 0.05). CONCLUSION: No essential difference was found in preadipocyte differentiation among the liposuction sites, while the abdomen might have some superiority. The negative-pressure method of liposuction is the first option in future research of tissue engineering. The flow cytometric analysis is a convenient way to study preadipocyte differentiation.

[Leg re-contouring by using a new technique of partially removing gastrocnemius].

OBJECTIVE: To evaluate a method to partially remove gastrocnemius for improvement of the contour of the leg. METHODS: Thirteen patients with bulked calf were undergoing the treatment. With a self-designed apparatus, the gastrocnemius was partially removed by placing the device in the muscle through an incision in the popliteal fossa. The follow-ups were carried out for 1-6 months. RESULTS: Thirteen patients were successfully treated by above mentioned technique. The removed amount of muscle was weighted between 11 g and 201 g, averaged 77 g. All of the patients could be able to walk three days after the operation. But, the normal walk had to take 1 month after of the surgery for recovering. The function of the ankle joint was not obviously influenced. CONCLUSION: The above mentioned technique is a safe and effective method for re-contouring the leg.