Gene/Protein
Disease
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Target Concepts:
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Query: UNIPROT:P61278 (
somatostatin
)
22,083
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Somatostatin
(SS) is a 14 amino acid peptide which is secreted by the hypothalamus and the pancreatic islets. It expresses antiproliferative activity in various organ systems, experiments have suggested effects of SS on hematopoietic cells. Here we present investigations regarding the effect of SS and its analog SMS 201-995 (SMS) on the in vitro proliferation of acute lymphoblastic leukemia (ALL; n = 7 cases),
acute myeloid leukemia
(
AML
; n = 21 cases) and chronic lymphocytic leukemia (CLL; n = 2 cases). Both SS and SMS inhibited spontaneous leukemic cell growth in approximately 1/3 of cases (i.e. 7/19). G-CSF stimulated
AML
cells were inhibited by SMS in 11/21 cases.
AML
cell proliferation induced by IL-3 or GM-CSF was suppressed in only 3/21 and 6/21 cases, respectively. In ALL cells, IL-7-induced proliferation was suppressed by SMS in 3/7 cases. The effect of SMS seemed to depend on the type of the hematopoietic growth factor, and on their concentrations. In fact, high concentrations of G-CSF could override SMS blocking completely. Colony formation by normal marrow progenitors and DNA synthesis by HL-60 and T11/65 leukemic cell lines were not affected by SMS. In conclusion,
somatostatin
may act as a negative regulator of the proliferative activity of human leukemia.
...
PMID:Somatostatin and its cyclic octapeptide analog SMS 201-995 as inhibitors of proliferation of human acute lymphoblastic and acute myeloid leukemia. 750 Jun 46
Somatostatin
, a neuropeptide with multiple activities, exerts its function via G-coupled membrane receptors. Five somatostatin receptor subtypes, sst1-5, have been identified. We have recently established that
somatostatin
acts as a chemoattractant on normal hematopoietic progenitor cells. Here, we studied the expression of
somatostatin
receptors (sst) on leukemic cells from 16
AML
patients. Using fluorescent
somatostatin
(Fluo-SS) in flow cytometry, we found that sst are expressed in variable amounts on primary
AML
cells. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis and immunochemistry revealed that only sst subtype 2 is expressed by
AML
cells. Using a two-chamber in vitro migration assay, we show that
AML
cells migrated towards a gradient of octreotide, a stable synthetic analogue of
somatostatin
. The degree of migration correlated with the cell surface density of sst2 as measured by Fluo-SS binding. These findings indicate that
somatostatin
influences trafficking of
AML
cells, which may have implications for the distribution of
AML
cells in the body and for clinical applications of
somatostatin
and analogues thereof in the context of
AML
.
...
PMID:Somatostatin induces migration of acute myeloid leukemia cells via activation of somatostatin receptor subtype 2. 1136 65
Acute myeloid leukemia
(
AML
) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative
AML
targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide
somatostatin
and the photosensitizer ruthenium in
AML
cell lines and primary
AML
patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary
AML
cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34
+
CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with
somatostatin
is efficiently eradicating LSC candidates of patients with
AML
. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting
AML
cells.
...
PMID:Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis. 3194 13