Project description:Transcriptomic profiling of normal mouse tissue and blood following 177Lu irradiation Total RNA was isolated from fresh-frozen tissue samples
Project description:Transcriptomic profiling of normal mouse kidney cortex and medulla following 177Lu irradiation Total RNA was isolated from fresh-frozen tissue samples
Project description:Transcriptomic profiling of normal mouse kidney cortex and medulla following 177Lu irradiation Total RNA was isolated from fresh-frozen tissue samples
Project description:The radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In vitro and preclinical in vivo studies have shown that irradiation can up-regulate the expression of somatostatin receptors and thereby give an increased uptake of 177Lu-octreotate. The cellular processes that underlie positive treatment response to 177Lu-octreotate are otherwise largely unknown. Genome-wide analysis of tumor cell responses in this successful mouse model offers a venue to identify critical treatment parameters and to optimize clinical effectiveness of 177Lu-octreotate therapy. Combining 177Lu-octreotate with other anti-tumor agents has also been proposed as a strategy for optimization. Some studies have shown synergistic effects in tumor cell killing and volume reduction The hedgehog signaling pathway is involved in embryonic development and tissue regeneration and can be/is abnormally activated in various cancers. Inhibition of the hedgehog signaling pathway has yielded promising therapeutic effects on NE tumors and may potentially enhance the effects of 177Lu-octreotate treatment in patients.
Project description:The radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In xenografted tumors, the human stromal components have been replaced with mouse stroma, which may have an impact in the treatment response of the xenografts.
Project description:This work aimed to examine the regulation of apoptosis-related genes in GOT1 tumors one and seven days after administration of 177Lu-octreotate with and without A1M and of A1M alone. At study start, 22 adult female Balb/c GOT1 tumor-bearing mice were divided into four groups of six animals that received 30 MBq 177Lu-octreotate or 5 mg/kg A1M, or co-treatment with both 177Lu-octreotate and A1M by i.v. injection. Also, a control group was sham-treated with saline. Half of the animals in each treatment and control group were terminated by cardiac puncture one-day post-injection (1 dpi), and the remaining animals were terminated at 7dpi. Tumor tissues were dissected at the time of termination, snap-frozen in liquid nitrogen and stored at -80°C.
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Experiment Overall Design: Obtained tumors were established as xenografts in nude mice. RNA were purified from each xenograft, normalized by concentration and three samples of RNA from each group were pooled for hybridization with each array. Three arrays were used for each group.
