Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation. 相似文献
CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease. 相似文献
Prostatitis and male infertility are frequent disorders, and the role of prostatitis in male infertility has been under discussion for more than 30 years. Many researchers have shown relevant links between the two. Although a causal relationship has not been definitely demonstrated, increasing evidence shows that chronic prostatitis has a relevant negative impact on male fertility potential, at least in certain subgroups. In the following review, we focus on the present state of knowledge on the role of chronic prostatitis as an etiologic factor in male infertility. 相似文献
INTRODUCTION: The clinical presentation of morphea varies from localized plaques to generalized eruptions. Its cause remains unknown and medical treatments have often proved unsatisfactory. Studies have previously shown that improvement of hypertrophic scars and fibrotic skin can be achieved with the use of a 585 nm pulsed dye laser (PDL). METHODS: A case of plaque-type morphea was treated with 585 nm pulsed dye laser irradiation at an average fluence of 5.0 J/cm2 at bimonthly time intervals. RESULTS: Marked clinical improvement as evidenced by improved pliability and skin coloration was seen after 4 successive PDL treatments. No side effects or complications were encountered. CONCLUSION: Pulsed dye laser therapy is a viable treatment option for morphea. The mechanism of its effect in this condition remains unknown. 相似文献
Background: Molecular theories of general anesthesia often are divided into two categories: (l) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.
Methods: Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.
Results: Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half. 相似文献
Zusammenfassung Zahlen zur H?ufigkeit von Herztumoren im operativen Krankengut liegen bisher für die Bundesrepublik Deutschland nicht vor.
Um einen entsprechenden überblick für das Jahr 1996 zu erhalten, wurde allen 77 herzchirurgischen Zentren der Bundesrepublik
Deutschland ein standardisierter Fragebogen zugesandt.
Daten von 65 der 77 Herzzentren (=84%) waren schlie?lich verfügbar: 187 Patienten waren wegen Myxomen, lediglich 44 wegen
nichtmyxomat?sen Tumoren, davon 28 wegen malignen prim?ren oder sekund?ren Herztumoren, operiert worden. Im Jahr 1996 waren
somit 0,32% (231/72 763) der Eingriffe mit Herz-Lungen-Maschine (erfa?t 72 763 von insgesamt 87 372) wegen eines Herztumors
vorgenommen worden. Ausgehend von diesen operativen Daten liegt die Inzidenz ausschlie?lich der prim?ren Tumoren des Herzens
zumindest bei 3 Tumoren pro 1 Million Einwohner pro Jahr (253 Tumoren/81,814 Millionen Einwohner). Wenn auch kleine Tumoren
asymptomatisch und unentdeckt bleiben k?nnen, wird heute doch die Mehrzahl prim?rer kardialer Tumoren durch Echokardiographie,
Computer- und Kernspintomographie bereits zu Lebzeiten des Patienten diagnostiziert, und diese Patienten werden in aller Regel
einer Operation zugeführt.
Somit werden gut 0,3% aller Eingriffe mit Herz-Lungen-Maschine in Deutschland wegen Herztumoren durchgeführt, wobei es sich
weit überwiegend um Myxome handelt.
Eingegangen: 23. September 1997, Akzeptiert: 11. Februar 1998 相似文献