Hedgehog family proteins are important morphogens which mediate the development of embryo as well as the carcinogenesis in adults. Inappropriate activation of Hedgehog signaling pathway contributes to numerous human cancers. The Hedgehog signaling pathway is considered to be involved in the molecular mechanism of the invasion and metastasis of the tumors, and to facilitate the metastasis of tumors through signaling pathways interaction. It is suggested that a potential therapeutic strategy pharmacologically targeting Hedgehog-dependent tumors may be developed.

Objective To review our single institutional 10-year experience in complex chest wall reconstruction and identify a working algorithm based on our retrospective analysis.Methods A retrospective analysis of 87 patients who underwent chest wallreconstruction in our department from January 2005 to December 2015.Fifty female patients and 37 male patients who underwent the above procedure were reviewed retrospectively.The median age of the patients is 52.3 years (24-75years).Histologic diagnosis including squamous-cell carcinoma (n =10),soft tissue sarcoma(n =22),chondrosarcomas(n =13) and metastasis from breast cancer(n =42).Type of skeletal defect including partial ribs/sternum defects in 19 cases,soft tissue defects alone in 33 cases,complicated composite chest wall defects involving multiple layers(soft tissue,ribs/sternum,and intrathoracic organs) in 35 cases.Sole methylmethacrylate/polypropylene mesh was used for small sized rib defects in 26cases.Methylmethacrylate/polypropylene mesh sandwich prostheses was used in 28 cases with extensive skeletal reconstruction after partial sternectomy and rib resection.The chest wall defects were repaired with pedicled internal mammary artery perforator flap(3 cases),pedicled deep superior epigastric artery perforator flap(4 cases),pedicled pectoralis major flap(8 cases),free anterolateral thigh perforator flap(9 cases),free deep inferior epigastric artery perforator flap(17 cases),pedicled lateral thoracic flap(5 cases),pedicled latissimus dorsi flap(17 cases),pedicled rectus abdominis flap(15 cases),free deep inferior epigastric artery perforator flap combined with pedicled rectus abdominis flap (4 cases),pedicled bipaddled latissimus dorsi flap(5 cases).11 cases with extensive full-thickness defects of the chest wall,the skeletal reconstruction was achieved with prosthetic sandwich and then covered with the omental flap,further free flaps were harvested for skin and soft tissue repairing.Results 1 case with pedicled rectus abdominis flap partial necrosis was noted,free anterolateral thigh flap was used for repairmen after further revision.1 case with edicled bipaddled latissimus dorsi flap,necrosis of the distal 1/4 part of one paddle was noted,healed with dressing therapy,no secondary skin grafting was required.Postoperative venous congestion occurred in 2 cases with deep inferior epigastric artery flap transplantation,in which both skin flaps exhibited venous crisis within 24 h after surgery.The reexploration procedures were successful in both cases and the flaps survived totally.All other flaps survived.The mean follow-up was 31 months,ranged from 9 to 72 months.No tumour extirpation was noted,functional and appearance results were satisfied.Conclusion According to the size and location of chest wall defect,different pedicled and free flaps should be chosen to achieve optimal outcome.Free flaps are efficient for large complex chest defects reconstruction.

Adult ; Female ; Humans ; Myxoma ; diagnosis ; pathology ; surgery ; Vulvar Neoplasms ; diagnosis ; pathology ; surgery

We constructed prokaryotic expression vectors for different domains of TACE gene and expressed the fusion proteins, so as to explore their effects on the proliferation, adhesion and invasion potential of tumor cells in vitro. The total RNA was isolated from THP1 cell. TACE cDNA was amplified by RT-PCR and subcloned into pMD18-T vector to construct pMD-18T-TACE vector. The different cDNA fragment of TACE were amplified from plasmid pMD-18T-TACE and then cloned into pET-28a( + ) to construct expression vector pET28a( + )- 300, pET28a( + )-T800, and pET28a( + )-T1300, which respectively transformed into E. coli BL21 (DE3). The expression of His-tagged fusion proteins were induced with IPTG and purified through BBST NTA resin. The proliferation ability was examined by MTT assay. The adhesive and invasive ability were examined by plated adhesion model and Transwell assay. The protein pET28a( + )-T300 and pET28a( + )-T1300 can reduce the proliferation, adhesion and invasion ability of human lung carcinoma cell A549 in vitro, but otherwise the protein pET28a( + )-T800 had not shown the inhibitive function. The fusion protein of disintegrin domain of TACE have the similar biological function to other disintegrins, which can be used for further research on function of TACE in inflammation and tumor.
ADAM Proteins ; biosynthesis ; genetics ; pharmacology ; ADAM17 Protein ; Adenocarcinoma ; pathology ; Cell Adhesion ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Humans ; Lung Neoplasms ; pathology ; Neoplasm Invasiveness ; Prokaryotic Cells ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.