Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CELLS ; GROWTH ; tumor ; PATHWAYS ; PANCREATIC-CANCER ; EGFR ; antiangiogenic therapy ; MYCOPHENOLIC-ACID ; MAMMALIAN PROTEIN ; AKT/PKB
    Abstract: The mTOR signaling plays an integral role in cellular homeostasis controlling the transition between the catabolic and anabolic states. Originally approved as immunosuppressive agents preventing allograft rejection, inhibitors of mTOR signaling have recently entered the arena of cancer therapy. Using rapamycin derivative (RAD001) as a prototype inhibitor, we aimed to systematically analyze the molecular mechanisms underlying the pleiotropic effects of mTOR signaling. Using proliferation- and clonogenic survival assays, a preferential sensitivity of microvascular endothelial cells (HDMVEC) followed by fibroblasts and U87 gliblastoma to RAD001 treatment was found. In contrast, lung- and prostate tumor cells demonstrated relative resistance against RAD001 treatment. In co-culture with fibroblasts, RAD001 exerted potent antiangiogenic effects by inhibiting endothelial cell tube formation. Further, RAD001 treatment efficiently prevented tumor growth in U87 tumor xenografts. Integrative transcriptome analysis was performed to decipher the molecular mechanism underlying RAD001 -induced anti-tumor and antiangiogenic effects. The predominant expression pattern was downregulation of genes after RAD001 treatment in all three sensitive cell types. Among the RAD001 downregulated genes, a transcriptional network was discovered enriched for genes related to angiogenesis processes and extracellular matrix remodeling, e. g., VEGF, HIF1A, CXCLs, IL6, FN, PAI-1 or NRP1. Of note, key components of PI3K upstream (PDK1) as well as mTORC2 downstream signaling (SGK1, NDRG) were downregulated by RAD001. Decreased expression of IMPDH and 139 common gene targets between mycophenolic acid and RAD001 suggested in part shared mechanisms underlying their antiangiogenic and immunosuppressive effects. In summary, key genetic participants governing anti-tumor and anti-angiogenic effects of mTOR inhibition were identified.
    Type of Publication: Journal article published
    PubMed ID: 23530502
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: While treating a long-term dialysis patient for secondary hyperparathyroidism (SHPT), indications of a synergistic effect between cinacalcet HCI and active vitamin D were observed. After 2.5 years, high initial cinacalcet doses of 180 mg/day could be significantly reduced to only 30 mg/non-dialysis day without losing control over the intact parathyroid hormone. Calcium-phosphorus product improved over time. The combination of cinacalcet and active vitamin D may improve the treatment of SHPT in dialysis patients.
    Type of Publication: Journal article published
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; EXPRESSION ; TUMORS ; p53 ; HPV ; SQUAMOUS-CELL CARCINOMA ; INDIVIDUALS ; p16(INK4A) ; TRANSPLANT RECIPIENTS ; STAPHYLOCOCCUS-AUREUS
    Abstract: BACKGROUND: High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention. METHODS: High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16(INK4a), a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically. RESULTS: The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16(INK4a) expression in most SCC (P〈0.001) and basal cell cancers (P = 0.02), while almost all SCC in situ were p16(INK4a) positive irrespective of HR-HPV presence (P = 0.66). Diffuse p16(INK4a) expression was associated with lack of pRB expression (P = 0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence. CONCLUSION: High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16(INK4a) expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions
    Type of Publication: Journal article published
    PubMed ID: 21427726
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: PROTEINS ; COLORECTAL-CANCER ; CARCINOMAS ; organ transplant recipients
    Type of Publication: Journal article published
    PubMed ID: 22011909
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Chronische Hämodialyse ; Terminale Niereninsuffizienz ; Erworbene Nierenzysten ; Nierentumoren ; Bildgebung ; Key words Maintenance hemodialysis ; Chronic renal failure ; Acquired cystic kidney disease ; Kidney tumors ; Imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The kidneys of patients with chronic renal failure undergoing maintenance hemodialysis may show different variances or complications. Most common are secondarily acquired renal cysts, which may be found in as many as 92% of patients after 8 years of hemodialysis. Single (in 12.5% of patients) or multiple (8.3%) cysts with bleeding are common; additionally, hematuria or ruptured cysts may be found. Bleeding into cysts is more common in patients with autosomal dominant polycystic kidney disease. Due to the decreasing urinary production development of kidney stones is very uncommon, but calcifications in or around cysts can be found in 71% of patients. Kidney tumors occur 41 times more often in patients with chronic renal failure than in patients without kidney disease. We detected tumors in 4.2% of our patients on long-term dialysis. Diagnostic differentiation of the relatively slow growing and fairly late metastasizing malignant tumors from adenomas is not possible. Nevertheless, we screen our patients every 3–4 years. Computed tomography is superior to ultrasonography for this purpose, because ultrasonography lacks the necessary sensitivity in this group of patients.
    Notes: Zusammenfassung An den Nieren von Patienten mit terminaler Niereninsuffizienz unter chronischer Hämodialyse können unterschiedliche Veränderungen oder Komplikationen auftreten. Am häufigsten sind sekundäre, erworbene Nierenzysten, die nach achtjähriger Dialysedauer bei 92% der Patienten gefunden werden. Solitäre (bei 12,5% der Patienten) sowie multipel (8,3%) eingeblutete Nierenzysten sind häufige Befunde, darüber hinaus kann es zu einer Hämaturie oder zur Zystenruptur kommen. Hierbei sind Einblutungen bei Patienten mit familiären Zystennieren häufiger und können dann auch multilokulär auftreten. Konkremente der Nieren sind aufgrund der zunehmenden Oligurie selten, Verkalkungen im Bereich der Nierenzysten und Matrixsteine finden sich allerdings bei ca. 71% der Patienten. Tumoren sind 41fach häufiger als bei Nierengesunden, im eigenen Kollektiv fanden sie sich bei 4,2% der Langzeitdialysepatienten. Differentialdiagnostisch können die relativ langsam wachsenden und spät metastasierenden malignen Tumoren von den häufiger auftretenden Adenomen nicht unterschieden werden. Dennoch führen wir ein regelmäßiges Screening im Abstand von drei bis vier Jahren mittels Computertomographie durch, da die Sonographie bei diesen Patienten nicht ausreichend sensitiv ist.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 444 (2006), S. 122-122 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] “You paid what? I have a chunk of the Berlin Wall at home that's at least as 'artistic' as this,” sputtered Bill. “Did you leave your brain behind when you abandoned physics for finance? Putting a paving stone on a pedestal and calling it a work of art doesn't make it so, Dave. ...
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...