The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs

Anthony, Catherine T.; Hughey, S. H.; Lyons, John; Weiss, Sean; Hornick, Conrad A.; Drouant, George J.; Fuselier, Joseph A.; Coy, David H.; Murphy, William A.; Woltering, Eugene A.

doi:10.1016/j.jss.2003.06.002

Cited by 7 publications

(4 citation statements)

References 17 publications

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“…The present data strongly suggest that the specific pattern of internalized sst 2 receptors should also be considered as an additional reliable criterion for specific sst 2 expression when it is confirmed that the patient has been on octreotide therapy immediately before or during surgery. Sst 2 receptor desensitization and escape from octreotide treatment, in particular in gastro-enteropancreatic neuroendocrine tumors (29,30) has been an important clinical observation that has been repeatedly debated in the past (31)(32)(33)(34)(35). In addition, preoperative management of secreting neuroendocrine tumors is still a challenge.…”

Section: Discussionmentioning

confidence: 99%

Internalized Somatostatin Receptor Subtype 2 in Neuroendocrine Tumors of Octreotide-Treated Patients

Reubi

Waser

Cescato

et al. 2010

The Journal of Clinical Endocrinology &Amp; Metabolism

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Section: Discussionmentioning

confidence: 99%

Internalized Somatostatin Receptor Subtype 2 in Neuroendocrine Tumors of Octreotide-Treated Patients

Reubi

Waser

Cescato

et al. 2010

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…The analyses were done using GraphPad Prism 4.0 (San Diego, LA). For further internalization [29], cells were then re-suspended and incubated in HBSS (pH4, acetic acid) on ice for 10 min, washed with cold PBS and then re-counted for radioactivity. Due to the radioactivity of membrane-bound receptors being released by the acid wash, the remaining radioactivity represents the internalized peptide.…”

Section: Methodsmentioning

confidence: 99%

Targeted Chemotherapy Using a Cytotoxic Somatostatin Conjugate to Inhibit Tumor Growth and Metastasis in Nude Mice

Sun

Mackey

Luo

et al. 2008

Clinical medicine. Oncology

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Abstract:The major problems of traditional chemotherapy are non-selectivity and non-specifi city, resulting in severe toxic side effects. Peptides are a new-generation of drug-delivery vector to increase effi cacy of this therapy and avoid the resulting damage. The cytotoxic somatostatin (SST) conjugate JF-10-81 was developed by coupling camptothecin (CPT) to the N-terminus of a SST analog (JF-07-69) using an activated carbamate linker. This conjugate selectively targets somatostatin receptor subtype 2 (SSTR2) and also retains high binding affi nity and rapid internalization as well as anti-proliferative activity towards various tumor cells. JF-10-81 was tested for its inhibitory activity against the growth of human tumors which included neuroblastoma (IMR32), pancreatic cancer (CFPAC-1), leukemia (MOLT-4), pancreatic carcinoid (BON) and prostate cancer (PC-3). Both SSTR2 mRNAs and proteins were detected in all these tumor cell lines. The conjugate displayed potent in vivo inhibitory activity, although some of the potency measured in in vitro experiments was lost. JF-10-81 was found to signifi cantly inhibit growth of these SSTR-positive tumors, resulting in 87% tumor reduction in neuroblastoma IMR32 and 97% in leukemia MOLT-4 bearing animals, even inducing regression of CFPAC-1 tumors. SSTR-overexpressing BON tumors were unfortunately relatively CPT-insensitive in vitro, however, JF-10-81 again exhibited in vivo potency presumably by specifi cally increasing CPT concentrations inside the tumor cells so that the inhibition rate for JF-10-81 was 85%. Also, JF-10-81 was used to treat highly invasive PC-3 tumors where s.c. injections inhibited both tumor growth (almost 60% reduction) and tumor metastasis (over 70%). This conjugate demonstrated its broad and excellent anti-tumor activity by targeting SSTR2-specifi c tumor tissues, supporting that short peptides and their analogs may be applied as ideal drugdelivery carriers to improve the traditional chemotherapy.

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“…A human placental vein angiogenesis model (HPVAM) was used in all the tests. Tissue preparation followed previously published methods (Jung et al, 2002;Woltering, 2003;Anthony et al, 2004;Hornick et al, 2003;Siegrist et al, 2003). Discarded human placentas were obtained anonymously with prior approval from the LSUHSC Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

Gallic acid is partially responsible for the antiangiogenic activities ofRubus leaf extract

et al. 2006

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An aqueous extract of leaves from Rubus suavissimus S. Lee (Rosaceae) or sweet leaf tea was tested for antiangiogenic activity in a human tissue-based fibrin-thrombin clot angiogenesis assay. Further fractionation of this crude extract was performed and the antiangiogenic effect of individual fractions was assessed. The extract was also tested for its oral bioavailability by using the serum of normal rats gavaged with the extract in the assay. At a 0.1% w/v concentration, the extract inhibited initiation of the angiogenic response and subsequent neovessel growth from samples that had already initiated an angiogenic response. Two subfractions of the extract showed significant inhibition of angiogenesis at 0.1% w/w. Gallic acid was elucidated as one of the active angiogenesis inhibitors in one fraction. A 1 mm concentration of gallic acid totally inhibited angiogenesis. In the form of leaf extract, a one-tenth concentration produced the same total inhibition as pure gallic acid. The 10-fold difference in potency suggests the presence of other active compounds contributing to the overall antiangiogenic effect of the extract. The oral absorption of this extract was tested by using serum from rats given the extract orally (gavage) in the angiogenesis assay system. The serum of rats orally administered the sweet leaf tea extract at doses of 0.1% w/w and 0.3% w/w did not significantly inhibit angiogenesis. However, the serum of rats injected intraperitoneally at a dose of 0.1% w/w caused a 41% inhibition of angiogenesis compared with saline injected controls. These preliminary results warrant further bioassay directed identification of other responsible compounds.

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The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs

Cited by 7 publications

References 17 publications

Internalized Somatostatin Receptor Subtype 2 in Neuroendocrine Tumors of Octreotide-Treated Patients

Internalized Somatostatin Receptor Subtype 2 in Neuroendocrine Tumors of Octreotide-Treated Patients

Targeted Chemotherapy Using a Cytotoxic Somatostatin Conjugate to Inhibit Tumor Growth and Metastasis in Nude Mice

Gallic acid is partially responsible for the antiangiogenic activities ofRubus leaf extract

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