Genetic Drivers of Ileal Neuroendocrine Tumors

Carpizo, Darren R.; Harris, Chris

doi:10.3390/cancers13205070

Cited by 7 publications

(5 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study SSTR2 expression was high in all tumors. Although this animal model has some limitations when it comes to experimental planning, we preferred to make the present study in the GOT1 model, since it is the only transplantable human NET cell line with retained SSTR expression and neuroendocrine properties that is known to us 13 , 14 , 43 . This choice, however, limited the number of animals that could be included in the study, together with problems to receive the radiopharmaceutical for preclinical research at the time of experiment.…”

Section: Discussionmentioning

confidence: 99%

Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors

Rassol

Andersson

Pettersson

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the 177Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of 177Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq 177Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7 days. Gene expression analysis of apoptosis-related genes in GOT1 tissue was performed with RT-PCR. In general, similar expression patterns of pro- and anti-apoptotic genes were found after 177Lu-octreotate exposure with or without co-administration of A1M. The highest regulated genes in both irradiated groups compared to untreated controls were FAS and TNFSFRS10B. Administration of A1M alone only resulted in significantly regulated genes after 7 days. Co-administration of A1M did not negatively affect the transcriptional apoptotic response of 177Lu-octreotate in GOT1 tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors

Rassol

Andersson

Pettersson

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Alternatively, this phenomenon may be explained by lack of chromogranin A expression during mitoses. The tumour cells in NETs are phenotypically very similar to the normal NE cell of origin, which probably reflects the low mutation rate in these tumours [27,28]. In contrast to other epithelial cells, normal NE cells do not adhere to each other, possibly due to reduced expression of adherence molecules.…”

Section: Neuroendocrine Cellsmentioning

confidence: 90%

Time to Classify Tumours of the Stomach and the Kidneys According to Cell of Origin

Mjønes

2021

IJMS

View full text Add to dashboard Cite

Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type.

show abstract

“…A probable explanation for the non-responding mouse in the present study could be a difference in SSTR expression in the tumor in that individual mouse, a fact that was also demonstrated by the immunohistochemical analyses. The GOT1 tumor model is unique, since it is probably the only small-intestinal NET cell line that could be transplanted to nude mice with preserved neuroendocrine features and receptor expression [ 34 , 39 , 40 ]. Since GOT1 cell proliferation is slow, most GOT1 animal studies are performed in the model based on serial transplantation of small tissue pieces from one tumor to several younger mice, which was the case in the present study.…”

Section: Discussionmentioning

confidence: 99%

Hyperfractionated Treatment with 177Lu-Octreotate Increases Tumor Response in Human Small-Intestine Neuroendocrine GOT1 Tumor Model

Elvborn

Shubbar

Forssell-Aronsson

2022

Cancers

View full text Add to dashboard Cite

Radionuclide treatment of patients with neuroendocrine tumors has advanced in the last decades with favorable results using 177Lu-octreotate. However, the gap between the high cure rate in animal studies vs. patient studies indicates a potential to increase the curation of patients. The aim of this study was to investigate the tumor response for different fractionation schemes with 177Lu-octreotate. BALB/c mice bearing a human small-intestine neuroendocrine GOT1 tumor were either mock treated with saline or injected intravenously with a total of 30–120 MBq of 177Lu-octreotate: 1 × 30, 2 × 15, 1 × 60, 2 × 30, 1 × 120, 2 × 60, or 3 × 40 MBq. The tumor volume was measured twice per week until the end of the experiment. The mean tumor volume for mice that received 2 × 15 = 30 and 1 × 30 MBq 177Lu-octreotate was reduced by 61% and 52%, respectively. The mean tumor volume was reduced by 91% and 44% for mice that received 2 × 30 = 60 and 1 × 60 MBq 177Lu-octreotate, respectively. After 120 MBq 177Lu-octreotate, given as 1–3 fractions, the mean tumor volume was reduced by 91–97%. Multiple fractions resulted in delayed regrowth and prolonged overall survival by 20–25% for the 120 MBq groups and by 45% for lower total activities, relative to one fraction. The results indicate that fractionation and hyperfractionation of 177Lu-octreotate are beneficial for tumor reduction and prolongs the time to regrowth.

show abstract

Genetic Drivers of Ileal Neuroendocrine Tumors

Cited by 7 publications

References 118 publications

Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors

Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors

Time to Classify Tumours of the Stomach and the Kidneys According to Cell of Origin

Hyperfractionated Treatment with 177Lu-Octreotate Increases Tumor Response in Human Small-Intestine Neuroendocrine GOT1 Tumor Model

Contact Info

Product

Resources

About