Octreotide is a somatostatin analogue that is widely used for cancer therapy and tumor imaging. I... more Octreotide is a somatostatin analogue that is widely used for cancer therapy and tumor imaging. Its efficacy in tumors depends mainly on the expression of the somatostatin receptor type 2 (sst 2). Desensitization and down-regulation of sst 2 after agonist exposure can have important consequences for patients under ongoing octreotide therapy because it may induce temporary tumor unresponsiveness and impair sst 2-based tumor scintigraphy. Therefore, we have investigated the effect of octreotide on sst 2 expression in vitro, as well as in a tumor mouse model. In vitro, short exposure to octreotide induced rapid dose-dependent down-regulation of sst 2 in the rat pancreatic AR4-2J cell line. Within 0.5 h, 80% of sst 2 had disappeared from the cell surface. A total recovery required 24 h and was shown to depend on protein synthesis, but not on new sst 2 mRNA transcription, indicating that sst 2 was probably degraded during the down-regulation process. Similar results were obtained in vivo. On the other hand, long-term continuous release of octreotide for 7 days, as achieved with octreotide-containing osmotic minipumps, caused sst 2 up-regulation in vivo, but not in vitro. Furthermore, this up-regulation of sst 2 in tumor-bearing scid mice was shown to depend on constant exposure of the animals to octreotide, as it was not observed when octreotide was given discontinuously in two s.c. daily injections. These results demonstrate that the continuous release of a small amount of octreotide, which in cancer therapy may be achieved with long-acting release formulations of the peptide, can induce sst 2 up-regulation on cancer cells. This may improve the efficacy of both tumor imaging and long-term octreotide therapy.
Purpose. To investigate the correlation between connective tissue growth factor (CTGF) mRNA expre... more Purpose. To investigate the correlation between connective tissue growth factor (CTGF) mRNA expression and immunohistochemical characteristics of anterior subcapsular cataract (ASC) formation as well as posterior capsule opacification (PCO) development (expression of type I collagen, a-smooth muscle actin and tenascin) under in vivo and under in vitro conditions in human and porcine lens epithelial cells. Methods. CTGF mRNA expression was investigated using in situ hybridization and RT-PCR. Expression of type I collagen, a-smooth muscle actin and tenascin was detected by immunohistochemical staining. Results. CTGF mRNA was expressed in human cataractous plaques of ASC and human PCO membranes, and appeared simultanously with the expression of type I collagen, a-smooth muscle actin and tenascin. Conclusion. The predominant expression of CTGF mRNA in human ASC and human PCO membranes suggests a significant role of CTGF in the pathological course of these ocular disorders.
ChemInform Abstract Gemäss Formelbild wird das Acetat (I) in die gesuchten Verbindungen (III)über... more ChemInform Abstract Gemäss Formelbild wird das Acetat (I) in die gesuchten Verbindungen (III)übergeführt, die Wirkung gegen Leukämiezellen der Maus besitzen. Am wirksamsten ist die Verbindung (IIIa). (UV-spektroskopische Daten).
Die in der vorliegenden Arbeit verwendeten Abkürzungen betreffend Aminosäuren und Peptide entspre... more Die in der vorliegenden Arbeit verwendeten Abkürzungen betreffend Aminosäuren und Peptide entsprechen denjenigen, welche von der IUPAC-IUB Commission on Biochemi¬ cal Nomenclature vorgeschlagen worden sind (Zusammenstellung siehe Wünsch, 1974).
Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated ... more Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.
Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated ... more Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.
Die am Baustein 2 von α‐Melanotropin (Ia) iodierten und markierten Titelverbindungen (Ib) ‐(Id) s... more Die am Baustein 2 von α‐Melanotropin (Ia) iodierten und markierten Titelverbindungen (Ib) ‐(Id) sowie die verwandten Peptide (Ie), (II) und (III) werden synthetisiert.
Octreotide is a somatostatin analogue that is widely used for cancer therapy and tumor imaging. I... more Octreotide is a somatostatin analogue that is widely used for cancer therapy and tumor imaging. Its efficacy in tumors depends mainly on the expression of the somatostatin receptor type 2 (sst 2). Desensitization and down-regulation of sst 2 after agonist exposure can have important consequences for patients under ongoing octreotide therapy because it may induce temporary tumor unresponsiveness and impair sst 2-based tumor scintigraphy. Therefore, we have investigated the effect of octreotide on sst 2 expression in vitro, as well as in a tumor mouse model. In vitro, short exposure to octreotide induced rapid dose-dependent down-regulation of sst 2 in the rat pancreatic AR4-2J cell line. Within 0.5 h, 80% of sst 2 had disappeared from the cell surface. A total recovery required 24 h and was shown to depend on protein synthesis, but not on new sst 2 mRNA transcription, indicating that sst 2 was probably degraded during the down-regulation process. Similar results were obtained in vivo. On the other hand, long-term continuous release of octreotide for 7 days, as achieved with octreotide-containing osmotic minipumps, caused sst 2 up-regulation in vivo, but not in vitro. Furthermore, this up-regulation of sst 2 in tumor-bearing scid mice was shown to depend on constant exposure of the animals to octreotide, as it was not observed when octreotide was given discontinuously in two s.c. daily injections. These results demonstrate that the continuous release of a small amount of octreotide, which in cancer therapy may be achieved with long-acting release formulations of the peptide, can induce sst 2 up-regulation on cancer cells. This may improve the efficacy of both tumor imaging and long-term octreotide therapy.
Purpose. To investigate the correlation between connective tissue growth factor (CTGF) mRNA expre... more Purpose. To investigate the correlation between connective tissue growth factor (CTGF) mRNA expression and immunohistochemical characteristics of anterior subcapsular cataract (ASC) formation as well as posterior capsule opacification (PCO) development (expression of type I collagen, a-smooth muscle actin and tenascin) under in vivo and under in vitro conditions in human and porcine lens epithelial cells. Methods. CTGF mRNA expression was investigated using in situ hybridization and RT-PCR. Expression of type I collagen, a-smooth muscle actin and tenascin was detected by immunohistochemical staining. Results. CTGF mRNA was expressed in human cataractous plaques of ASC and human PCO membranes, and appeared simultanously with the expression of type I collagen, a-smooth muscle actin and tenascin. Conclusion. The predominant expression of CTGF mRNA in human ASC and human PCO membranes suggests a significant role of CTGF in the pathological course of these ocular disorders.
ChemInform Abstract Gemäss Formelbild wird das Acetat (I) in die gesuchten Verbindungen (III)über... more ChemInform Abstract Gemäss Formelbild wird das Acetat (I) in die gesuchten Verbindungen (III)übergeführt, die Wirkung gegen Leukämiezellen der Maus besitzen. Am wirksamsten ist die Verbindung (IIIa). (UV-spektroskopische Daten).
Die in der vorliegenden Arbeit verwendeten Abkürzungen betreffend Aminosäuren und Peptide entspre... more Die in der vorliegenden Arbeit verwendeten Abkürzungen betreffend Aminosäuren und Peptide entsprechen denjenigen, welche von der IUPAC-IUB Commission on Biochemi¬ cal Nomenclature vorgeschlagen worden sind (Zusammenstellung siehe Wünsch, 1974).
Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated ... more Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.
Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated ... more Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.
Die am Baustein 2 von α‐Melanotropin (Ia) iodierten und markierten Titelverbindungen (Ib) ‐(Id) s... more Die am Baustein 2 von α‐Melanotropin (Ia) iodierten und markierten Titelverbindungen (Ib) ‐(Id) sowie die verwandten Peptide (Ie), (II) und (III) werden synthetisiert.
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