60 research outputs found
Increased RBE of carbon ions in tumor growth inhibition using an in vivo lung adenocarcinoma model
Ein Beitrag zur klinischen Diagnostik des ektopischen ACTH-Syndroms
Es wird über einen Fall von ektopischem ACTH-Syndrom mit Hypercortizismus und hypokaliämischer Alkalose bei einem metastasierten Pankreas-Carcinom berichtet. Das Fehlen einer Differenz zwischen den ACTH-Spiegeln im Plasma aus dem Bulbus cranialis venae jugularis und aus der Vena femoralis unterstützte die Annahme einer nicht hypophysären Herkunft der erhöhten ACTH-Spiegel.A case of ectopic ACTH syndrome is reported presenting with hypercorticism and pronounced hypokalemic alkalosis in a woman aged 55 y. with metastatic cancer of the pancreas. The failure to show a significant difference of plasma ACTH-levels from bulbus superior venae jugularis resp. femoral vein supported the clinical assumption of non pituitary origin of elevated plasma ACTH
Comparison of Two Small‐group Learning Methods in 12th‐grade Physics Classes Focusing on Intrinsic Motivation and Academic Performance
Expression and function of the tumor antigen MAGE-A3 in bladder cancer cell lines
MAGE-A3 is a member of the type I Melanoma Antigen Gene family and is
expressed in various cancers including bladder cancer. MAGE-A3 represents a
candidate antigen as a possible target for cancer immunotherapy. In particular,
MAGE-A3 vaccination protocols are investigated in clinical trials in bladder cancer.
So far, functional studies on MAGE were mainly performed in melanoma cells,
myeloma cells, lung cancer and breast cancer cells whereas the function of
MAGE-A3 in bladder cancer cells is largely unknown.
Here, we analyzed the expression of MAGE-A3 in a panel of human bladder cancer
cell lines and selected appropriate cells for functional studies. Furthermore, we
established potent knockdown of MAGE-A3 by RNA interference and harnessed this
technique for functional analysis of MAGE-A3. MAGE-A3 mRNA levels where
highest in UMUC-3, 5637 and T24 cells whereas no detectable levels were observed
in EJ-28 cells. BFTC-905 and HT-1376 cells exhibited intermediate MAGE-A3
mRNA levels. For further experiments, T24, UMUC-3 and EJ-28 cells were selected
and MAGE-A3 expression was confirmed at protein level by immunocytochemistry.
Potent siRNA knockdown of MAGE-A3 mRNA was validated by RT-PCR exhibiting
down-regulation of MAGE-A3 mRNA by approximately 80 % in T24 and UMUC-3
cells. Evidence of MAGE-A3 knockdown could also be confirmed in a
non-quantitative way by immunocytochemistry. EJ-28 cells that displayed no
detectable MAGE-A3 mRNA abundance were included in these experiments as
control cells.
At the functional level, silencing of MAGE-A3 resulted in significant increased
proliferation, cell count and colony formation in T24 und UMUC-3 cells, whereas
EJ-28 cells were unaffected. Apoptosis was reduced after silencing of MAGE-A3 in
Summary
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T24 cells. In order to get some mechanistic clue for this observation, proteomic array
analysis of cell cycle regulatory and apoptotic proteins was performed in T24 cells
demonstrating increased level of livin and decreased levels of cyclin-dependent kinase
inhibitor p21 and tumor suppressor protein phospho-p53 forms after silencing of
MAGE-A3. Thus, at the functional level we could demonstrate anti-proliferative and
pro-apoptotic effects of MAGE-A3 indicating an anti-oncogenic characteristic. The
anti-proliferative and pro-apoptotic effects of MAGE-A3 were accompanied by
down-regulation of livin and up-regulation of p21 and phospho-p53 forms likely
contributing to or mediating the observed effects.
In sum, we selected suitable bladder cancer cell lines for analysis of MAGE-A3 and
established efficient silencing of MAGE-A3. Interestingly, we revealed an important
so far non-described anti-oncogenic function of MAGE-A3 in bladder cancer cells.
This aspect should be considered when employing immunotherapeutic strategies
targeting MAGE-A3 tumor antigen by antibodies
Electroporation of nucleic acids into prokaryotic and eukaryotic cells by square wave pulses
A novel electroporator is presented that generates adjustable square wave pulses with a maximal pulse strength of 2500 V / 100 A and a pulse length between 0.1 and 15 ms and that efficiently transfects prokaryotic and eukaryotic cells. Various factors influencing DNA transfer into tissue culture cells, embryonic stem cells and E. coli K12 cells were optimized and the respective electrical pulse profiles monitored
Co-regulation of immune checkpoint PD-L1 with interferon-gamma signaling is associated with a survival benefit in renal cell cancer.
Background Programmed death ligand (PD-L1)-based immune checkpoint blockade therapy for metastatic renal cell carcinoma (RCC) achieves significant response rates in a subgroup of patients. The relevance of PD-L1 gene regulation for disease outcome is not clear. Objective To evaluate PD-L1 expression and its dependence on interferon-gamma (IFN-gamma) in RCC cell lines and tissues in relation to disease outcome. Methods and Patients Regulation of PD-L1-mRNA and PD-L1 protein was studied in cell lines from clear cell RCC (ccRCC) and papillary RCC (pRCC) by quantitative RT-PCR and Western-blot analysis. PD-L1-mRNA correlation and gene-set enrichment analysis (GSEA) of the IFN-gamma pathway were conducted with RNA-Seq from ccRCC, pRCC, and skin cutaneous melanoma (SKCM) tissue. In addition, patient overall survival (OS) and disease-free survival (DFS) (cBioPortal for Cancer Genomics) were considered. Results In ccRCC-like cell lines, PD-L1 was induced by canonical IFN-gamma signaling, whereas in a pRCC-like cell line, PD-L1 was refractory towards IFN-gamma signaling. In ccRCC and SKCM tissues, GSEA revealed significant IFN-gamma pathway activation in tissue samples with high PD-L1-mRNA levels. This was not observed in pRCC tissue. ccRCC and SKMC patients with low PD-L1-mRNA levels had significantly shorter OS and DFS than those with high PD-L1-mRNA levels. In pRCC patients, no significant difference in OS and DFS with regard to PD-L1-mRNA tissue levels was obvious. Conclusions The findings suggest that ccRCC and pRCC differ with respect to PD-L1 regulation by IFN-gamma-signaling. High PD-L1-mRNA levels in tumor tissues with a positive IFN-gamma signature favorably affect OS and DFS
Electroporation of nucleic acids into prokaryotic and eucaryotic cells by square wave pulses
Der erythrocyt�re Magnesiumstoffwechsel bei Glykolyseinhibierung durch Natriumfluorid und Monojodacetat
Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro
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