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Vienna, Austria

Tang C.-H.,China Medical University at Taichung | Keng Y.-T.,China Medical University at Taichung | Liu J.-F.,Central Laboratory
Cancer Letters | Year: 2012

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. High mobility group box chromosomal protein 1 (HMGB)-1 is a widely studied, ubiquitous nuclear protein that is present in eukaryotic cells, and plays a crucial role in inflammatory response. However, the effects of HMGB-1 on human chondrosarcoma cells are largely unknown. In this study, we found that HMGB-1 increased the migration and the expression of α5β1 integrin in human chondrosarcoma cells. Transfection of cells with receptor for advanced glycation end products (RAGE) receptor siRNA reduced HMGB-1-induced cell migration and integrin expression. Activations of phosphatidylinositol 3-kinase (PI3K), Akt, and AP-1 pathways after HMGB-1 treatment were demonstrated, and HMGB-1-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and AP-1 cascades. Taken together, our results indicated that HMGB-1 enhances the migration of chondrosarcoma cells by increasing α5β1 integrin expression through the RAGE receptor/PI3K/Akt/c-Jun/AP-1 signal transduction pathway. © 2012 Elsevier Ireland Ltd.

Hou C.-H.,National Taiwan University Hospital | Lin F.-L.,Sijhih Cathay General Hospital | Hou S.-M.,Shin Kong Wu Ho Su Memorial Hospital | Liu J.-F.,Central Laboratory
Molecular Cancer | Year: 2015

Background: Osteosarcoma is the most common primary malignant tumor in children and young adults, and its treatment requires effective therapeutic approaches because of a high mortality rate for lung metastasis. Epithelial to mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining the invasive and metastatic behavior during cancer progression. The cysteine-rich angiogenic inducer 61 (Cyr61) gene, a member of the CCN gene family, is responsible for the secretion of Cyr61, a matrix-associated protein that is involved in several cellular functions. A previous study showed that Cyr61 expression is related to osteosarcoma progression. In addition, Cyr61 could promote cell migration and metastasis in osteosarcoma. However, discussions on the molecular mechanism involved in Cyr61-regulated metastasis in osteosarcoma is poorly discussed. Results: We determined that the expression level of Cyr61 induced cell migration ability in osteosarcoma cells. The Cyr61 protein promoted the mesenchymal transition of osteosarcoma cells by upregulating mesenchymal markers (TWIST-1 and N-cadherin) and inhibiting the epithelial marker (E-cadherin). Moreover, the Cyr61-induced cell migration was mediated by EMT. The Cyr61 protein elicited a signaling cascade that included αvβ5 integrin, Raf-1, mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and Elk-1. The reagent or gene knockdown of these signaling proteins could inhibit Cyr61-promoted EMT in osteosarcoma. Finally, the knockdown of Cyr61 expression obviously inhibited cell migration and repressed mesenchymal phenotypes, reducing lung metastasis. Conclusion: Our results indicate that Cyr61 promotes the EMT of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves αvβ5 integrin, Raf-1, MEK, ERK, and Elk-1. © 2014 Hou et al.; licensee BioMed Central Ltd.

To investigate the possibility of applying multiplex ligation-dependent probe amplification (MLPA) to the detection of azoospermia factor (AZF) microdeletion on the Y chromosome in infertile men with azoospermia or severe oligozoospermia. DNA samples were obtained from 147 azoospermia or severe oligozoospermia patients and 154 normal controls. After denatured at 95 degrees C, the samples were hybridized to the specific probes designed for the AZF region. With the ligase, the hybrid products were amplified by a pair of universal primers labeled with FAM fluorescence, and then separated by capillary electrophoresis for data analysis. Meanwhile all the samples were subjected to multiplex-PCR (mPCR) analysis for sequence-tagged sites (STS) in the AZF region. STS deletion was detected in 22 (15.0%) of the 147 patients but not in the normal controls. By MLPA, 40 (27.2%) of the patients were found with specific probe omission in the AZF region, as compared with 20 cases in the control group. Compared with mPCR, MLPA has a better sensitivity in detecting AZF microdeletions, and it provides more precise genetic information on the AZF regions, which may contribute to in-depth exploration into the etiological mechanism of impaired spermatogenesis.

Minder E.I.,Central Laboratory
Expert Opinion on Investigational Drugs | Year: 2010

Importance of the field: Afamelanotide, an α-melanocyte stimulating hormone (MSH) agonistic analog is a first-in-class therapeutic. Its application to protoporphyria (PP), a disease associated with absolute sunlight-intolerance is discussed. Areas covered in this review: The genetics and existing therapy of the inherited disease PP comprising both erythropoietic protoporphyria and X-linked dominant protoporphyria. The physiological and pharmacological actions of α-MSH and afamelanotide including receptor-mediated intracellular signaling and effects of receptor polymorphisms. Adverse effects and safety issues. What the reader will gain: The clinical severity and the necessity for an effective therapy for the rare disease PP are illustrated by a short, up-to-date portrait. A condensed description of clinically important aspects of α-MSH signaling, physiological, pharmacological and safety issues of afamelanotide applied to humans and the rational for its potential efficacy in PP are given. The different trials of afamelanotide in PP and their most recent results are discussed. Take home message: Although early, results of the first trials of afamelanotide for PP are promising and the risksafety profile appears favorable today. We expect afamelanotide and analogs thereof to be a prospective therapeutic tool in light-related skin diseases, and in future this drug class might prove effectiveness in other medical conditions. © 2010 Informa UK, Ltd.

Al-Anazi K.A.,King Khalid University | Al-Jasser A.M.,Central Laboratory
Frontiers in Oncology | Year: 2014

Stenotrophomonas maltophilia (S. maltophilia) is a globally emerging Gram-negative bacillus that is widely spread in environment and hospital equipment. Recently, the incidence of infections caused by this organism has increased, particularly in patients with hematological malignancy and in recipients of hematopoietic stem cell transplantation having neutropenia, mucositis, diarrhea, central venous catheters or graft versus host disease and receiving intensive cytotoxic chemotherapy, immunosuppressive therapy or broad-spectrum antibiotics. The spectrum of infections in hematopoietic stem cell transplantation recipients includes: pneumonia, urinary tract and surgical site infection, peritonitis, bacteremia, septic shock and infection of indwelling medical devices. The organism exhibits intrinsic resistance to many classes of antibiotics including carbapenems, aminoglycosides, most of the third generation cephalosporins and other ß-lactams. Despite the increasingly reported drug resistance, trimethoprim-sulfamethoxazole is still the drug of choice However, the organism is still susceptible to: ticarcillin-clavulanic acid, tigecycline, fluoroquinolones, polymyxin-B and rifampicin. Genetic factors play a significant role not only in evolution of drug resistance but also in virulence of the organism. The outcome of patients having S. maltophilia infections can be improved by: using various combinations of novel therapeutic agents and aerosolized aminoglycosides or colistin, prompt administration of in-vitro active antibiotics, removal of possible sources of infection such as infected indwelling intravacular catheters and application of strict infection control measures. © 2014 Al-anazi and Al-jasser.

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