scholarly journals Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Libo Zhang ◽  
Douglass C. Vines ◽  
Deborah A. Scollard ◽  
Trevor McKee ◽  
Teesha Komal ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Expression Profiles ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Xenograft Model ◽  
Tumor Growth Inhibition ◽  
Receptor Imaging ◽  
Expression Levels ◽  
Variable Expression ◽  
Xenograft Models

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.

scholarly journals Resistance to octreotide LAR in acromegalic patients with high SSTR2 expression: analysis of AIP expression

2012 ◽  
Vol 56 (8) ◽  
pp. 501-506 ◽  
Author(s):  
Leandro Kasuki ◽  
Leandro M. Colli ◽  
Paula C. L. Elias ◽  
Margaret de Castro ◽  
Mônica R. Gadelha
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Molecular Data ◽  
Curative Surgery ◽  
Interacting Protein ◽  
Octreotide Lar ◽  
Expression Levels ◽  
Aryl Hydrocarbon

We present here the clinical and molecular data of two patients with acromegaly treated with octreotide LAR after non-curative surgery, and who presented different responses to therapy. Somatostatin receptor type 2 and 5 (SSTR2 and SSTR5), and aryl hydrocarbon receptor-interacting protein (AIP) expression levels were analyzed by qPCR. In both cases, high SSTR2 and low SSTR5 expression levels were detected; however, only one of the patients achieved disease control after octreotide LAR therapy. When we analyzed AIP expression levels of both cases, the patient whose disease was controlled after therapy exhibited AIP expression levels that were two times higher than the patient whose disease was still active. These two cases illustrate that, although the currently available somatostatin analogs bind preferentially to SSTR2, some patients are not responsive to therapy despite high expression of this receptor. This difference could be explained by differences in post-receptor signaling pathways, including the recently described involvement of AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6

Inferior outcome of neuroendocrine tumor patients negative on somatostatin receptor imaging

2020 ◽  
Vol 27 (11) ◽  
pp. 615-624
Author(s):  
Julie Refardt ◽  
Wouter T Zandee ◽  
Tessa Brabander ◽  
Richard A Feelders ◽  
Gaston J H Franssen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Tumor Biology ◽  
Survival Rates ◽  
Receptor Imaging ◽  
Cox Regression Analysis

Sufficient expression of somatostatin receptor (SSTR) in well-differentiated neuroendocrine tumors (NETs) is crucial for treatment with somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) using radiolabeled SSAs. Impaired prognosis has been described for SSTR-negative NET patients; however, studies comparing matched SSTR-positive and -negative subjects who have not received PRRT are missing. This retrospective analysis of two prospectively maintained NET databases aimed to compare matched metastatic grade 1 or 2 SSTR-positive and –negative NET patients. SSTR-negativity was defined as having insufficient tumor uptake on diagnostic SSTR imaging. Patients that underwent PRRT were excluded. Seventy-seven SSTR-negative and 248 SSTR-positive grade 1–2 NET patients were included. Median overall survival rates were significantly lower for SSTR-negative compared to SSTR-positive NET patients (53 months vs 131 months; P < 0.001). To adjust for possible confounding by age, gender, grade and site of origin, 69 SSTR-negative NET patients were propensity score matched to 69 SSTR-positive NET patients. Group characteristics were similar, with the exception of SSTR-negative patients receiving more often chemotherapy and targeted treatment. The inferior survival outcome of SSTR-negative compared to SSTR-positive NET patients persisted with a median overall survival of 38 months vs 131 months (P = 0.012). This relationship upheld when correcting for the main influencing factors of having a higher grade tumor or receiving surgery in a multivariate Cox regression analysis. In conclusion, we showed that propensity score-matched SSTR-negative NET patients continue to have a worse prognosis compared to SSTR-positive NET patients despite receiving more aggressive treatment. Differences in tumor biology likely underlie this survival deficit.

scholarly journals Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors

2010 ◽  
Vol 17 (1) ◽  
pp. R53-R73 ◽  
Author(s):  
Dik J Kwekkeboom ◽  
Boen L Kam ◽  
Martijn van Essen ◽  
Jaap J M Teunissen ◽  
Casper H J van Eijck ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pet Imaging ◽  
Tumor Regression ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Receptor Subtype ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Pet Tracer ◽  
First Choice

Somatostatin receptor imaging (SRI) with [111In-DTPA0]octreotide has proven its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Newer radiolabeled somatostatin analogs which can be used in positron emission tomography (PET) imaging, and which have a higher affinity for the somatostatin receptor, especially receptor subtype-2, have been developed. It would be desirable, however, if one radiolabeled analog became the new standard for PET imaging, because the current application of a multitude of analogs implies a fragmented knowledge on the interpretation of the images that are obtained in clinical practice. In our view, the most likely candidates for such a universal PET tracer for SRI are [68Ga-DOTA0,Tyr3]octreotate or [68Ga-DOTA0,Tyr3]octreotide. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111In-, 90Y-, or 177Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy (PRRT). The results that were obtained with [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the median duration of the therapy response for these radiopharmaceuticals is 30 and 40 months respectively. The patients' self-assessed quality of life increases significantly after treatment with [177Lu-DOTA0,Tyr3]octreotate. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with [177Lu-DOTA0,Tyr3]octreotate. These data compare favorably with the limited number of alternative treatment approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable GEPNETs.

TSP-A74, a Novel Therapeutic Monoclonal Antibody Against TfR1 for Treatment of Hematologic Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5214-5214
Author(s):  
Lilin Zhang ◽  
Fumiko Nomura ◽  
Youichi Aikawa ◽  
Yukio Sudo ◽  
Kazuhiro Morishita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Growth ◽  
Cell Lymphoma ◽  
Xenograft Model ◽  
Hematologic Malignancies ◽  
Tumor Growth Inhibition ◽  
Xenograft Models ◽  
Complete Tumor

Abstract Transferrin receptor 1(TfR1) is a type II transmembrane glycoprotein regulating the intracellular uptake of iron and is involved in cell growth, proliferation and survival. TfR1 is highly expressed on malignant cells, including those of hematologic malignancies. Therefore, TfR1 may be an attractive target for therapeutic monoclonal antibodies. We generated a panel of fully-human, anti-TfR1 monoclonal antibodies and evaluated the anti-tumor effects of these antibodies both in vitro and in vivo. The results led to the selection of TSP-A74, an antibody with potent in vitro and in vivo anti-tumor activity, for further evaluation in several hematologic malignancy models. First, the efficacy of TSP-A74 was evaluated in acute myeloid leukemia (AML) models. Two AML cell lines, Kasumi-1 and HL-60, were subcutaneously inoculated in severe combined immunodeficiency (SCID) mice. After the tumors were grown to a size of 150 mm3, TSP-A74 was administrated intravenously (IV) once weekly for 4 weeks at doses of 0.4, 2 and 10 mg/kg and 1, 3 and 10 mg/kg for the Kasumi and HL60 xenograft models, respectively. TSP-A74 demonstrated complete tumor regression in these two xenograft models at 10 mg/kg and complete tumor growth suppression in the Kasumi model at 2 mg/kg. Even at the low dose of 1 mg/kg, TSP-A74 demonstrated tumor growth inhibition (TGI) of 60% in the HL60 model. Next, the anti-tumor efficacy of TSP-A74 was assessed in an acute lymphoblastic leukemia (ALL) model. The ALL cell line, CCRF-CEM, was engrafted into SCID mice intravenously. After 3 days, TSP-A74 was administrated IV at a dose of 10 mg/kg once weekly for 4 weeks. The control mice (n=10) rapidly developed leukemia and none survived at 42 days after leukemia cell engraftment. However, 7 of 10 (70%) mice treated with TSP-A74 survived to 179 days after engraftment when the study was terminated. Finally, the efficacy of TSP-A74 was evaluated in non-Hodgkin's lymphoma subcutaneous xenograft models. TSP-A74 produced complete regression of established tumors in the SU-DHL-2 (diffuse large B-cell lymphoma) xenograft model at a dose of 3 mg/kg and tumor growth inhibition of 100 % in the HH (cutaneous T cell lymphoma) xenograft model at a dose of 10 mg/kg. These results indicate that the human anti-TfR1 monoclonal antibody, TSP-A74, could be a new therapeutic candidate for hematologic malignancies. Disclosures Zhang: Perseus Proteomics Inc.: Employment. Nomura:Perseus Proteomics Inc.: Employment. Aikawa:Perseus Proteomics Inc.: Employment. Sudo:Perseus Proteomics Inc.: Employment. Morishita:Perseus Proteomics Inc.: Research Funding.

scholarly journals Immunohistochemical Expression of Somatostatin Receptor Subtypes in a Panel of Neuroendocrine Neoplasias

2019 ◽  
Vol 67 (10) ◽  
pp. 735-743 ◽  
Author(s):  
Satu M. Remes ◽  
Helena L. Leijon ◽  
Tiina J. Vesterinen ◽  
Johanna T. Arola ◽  
Caj H. Haglund
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Membrane Receptors ◽  
Receptor Subtypes ◽  
Receptor Imaging ◽  
Primary Tumors ◽  
Somatostatin Receptor Subtypes ◽  
Negative Controls ◽  
G Protein Coupled

Neuroendocrine neoplasias (NENs) are known to express somatostatin receptors (SSTRs) 1–5, which are G-protein-coupled cell membrane receptors. Somatostatin receptor imaging and therapy utilizes the SSTR expression. Synthetic somatostatin analogs with radioligands are used to detect primary tumors, metastases, and recurrent disease. Receptor analogs are also used for treating NENs. Furthermore, commercially available SSTR antibodies can be used for the immunohistochemical (IHC) detection of SSTRs. We investigated different SSTR antibody clones applying diverse IHC protocol settings to identify reliable clones and feasible protocols for NENs. A tissue microarray including NENs from 12 different primary sites were stained. Only UMB clones were able to localize SSTR on the cell membranes of NENs. SSTR2 (UMB1) emerged as the most common subtype followed by SSTR5 (UMB4) and SSTR1 (UMB7). SSTR3 (UMB5) expression was mainly cytoplasmic. Yet, SSTR4 expression was weak and located primarily in the cytoplasm. Thus, appropriate IHC protocols, including proper positive and negative controls, represent requirements for high-quality NEN diagnostics and for planning personalized therapy.

scholarly journals Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayank Patel ◽  
Isabel Tena ◽  
Abhishek Jha ◽  
David Taieb ◽  
Karel Pacak
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Rare Condition ◽  
Receptor Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Well Differentiated ◽  
Succinate Dehydrogenase Subunit B

Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.

Combined activity of the cancer metabolism inhibitor MPC-8640 and 5-fluorouracil in xenograft models.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13581-e13581
Author(s):  
Vijay R. Baichwal ◽  
Chad Bradford ◽  
J. Scott Patton ◽  
Leslie Reeves ◽  
Lynn DeMie ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Cancer Metabolism ◽  
Tumor Regression ◽  
Single Agent ◽  
Xenograft Model ◽  
Tumor Growth Inhibition ◽  
Tumoricidal Activity ◽  
Xenograft Models ◽  
Carcinoma Xenograft

e13581 Background: Nicotinamide (Nam) phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in NAD biosynthesis from Nam. Nampt inhibition causes NAD depletion, inhibition of ATP synthesis and cell death. MPI-0487316 is a selective Nampt inhibitor with potent tumoricidal activity against cancer cell lines of diverse origin. MPC-8640, an orally bioavailable prodrug of MPI-0487316, induces regressions in xenograft models. Combining Nampt inhibitors with 5-fluorouracil (5-FU) results in synergistic tumoricidal activity in cells. We have explored the combination of MPC-8640 with 5-FU in a colon carcinoma xenograft model. Methods: In vitro studies were done in HCT-116 human colon carcinoma cells. Cell viability was measured by determining ATP levels. Xenograft studies were done with cells implanted subcutaneously into athymic mice (nu/nu). MPC-8640 was dosed orally at 12 to 48 mg/kg daily on Days 1-7 and 15-21. 5-FU was dosed intraperitoneally, weekly at 100 mg/kg. Results: MPI-0487316 showed synergistic tumoricidal activity in vitro with 5-FU. In xenograft studies, the prodrug MPC-8640, at 12, 24 and 36 mg/kg, resulted in tumor growth inhibition (TGI) of 64%, 98% and 91%, respectively, at the end of dosing on Day 22 and tumor regression of 5%, when dosed at 48 mg/kg. In the 36 and 48 mg/kg group, 20% and 10% of the mice, respectively, had no detectable tumors by the end of the study on Day 42. In another study, mice were given 5-FU or MPC-8640 as single agents or in combination. Combining 5-FU with MPC-8640 at 24 mg/kg resulted in 45% tumor regression on Day 21 compared to TGI of 88% and 78% for MPC-8640 or 5-FU, respectively, dosed as single agents. Similarly, combining 5-FU and MPC-8640 at 32 mg/kg resulted in 83% tumor regression on Day 21 compared to TGI of 86% and 78% for MPC-8640 and 5-FU, respectively, dosed as single agents. The combinations of 5-FU and MPC-8640 were well-tolerated with <10% change in median body weight. Conclusions: A combination of MPC-8640 with 5-FU causes tumor regression in a colon carcinoma xenograft model and is more effective than either agent dosed alone. Thus, MPC-8640 may have potential for treating cancers as a single agent or in combination with antimetabolites.

Preclinical in vitro and in vivo study of UD-017, a novel highly selective and orally available CDK7 inhibitor, in a variety of cancers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14086-e14086 ◽  
Author(s):  
Kazuhiro Onuma ◽  
Yasuhiro Aga ◽  
Sayaka Ogi ◽  
Takashi Matsushita ◽  
Hidetoshi Sunamoto ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Xenograft Model ◽  
Antitumor Efficacy ◽  
Expression Levels ◽  
Oncogenic Driver ◽  
Xenograft Models

e14086 Background: Cyclin dependent kinase 7 (CDK7) modulates mRNA transcription and some oncogenes are reported to be sensitive to inhibition of transcription in certain cancer cells. CDK7 inhibitors have been considered as an intriguing approach to treat cancers that depend on transcriptional regulation of their oncogenes. We synthesized a novel highly selective CDK7 inhibitor, UD-017, and found that the compound showed antitumor potency in a variety of cancers in vitro and in vivo. We therefore explored underlying mechanisms especially focusing on an oncogenic driver, c-Myc. Methods: We examined CDK7 selectivity of UD-017 against the other CDKs and kinases. We evaluated an antiproliferative activity of UD-017 in over 200 multiple types of cancer cell lines including patients-derived cancer cells. We then investigated the correlation between c-Myc expression levels and an antiproliferative activity of UD-017 in cancer cells. Antitumor efficacy of UD-017 was assessed in multiple types of cancer xenograft models and patients-derived xenograft model. We determined whether an intratumoral c-Myc expression levels correlated with in vivo antitumor efficacy of UD-017 in xenograft models. Results: UD-017 inhibited CDK7 enzyme (IC50= 16 nM) highly selectively among the CDKs (over 300-fold) and almost mono-specifically in a panel of 313 kinases assay. In a cellular antiproliferative panel assay, UD-017 broadly inhibited the proliferation of a variety of cancer cells and c-Myc expression levels showed the good correlation with antiproliferative activity. UD-017 showed favorable PK profile and good oral absorbability and showed the potent antitumor activity in multiple types of cancer xenograft models in mice. In correlation with the PK, UD-017 reduced the intratumoral c-Myc mRNA levels time-dependently after dosing of UD-017 in the colorectal cancer xenograft model. Conclusions: We identified a highly selective and orally available CDK7 inhibitor that showed the broad in vitro and in vivo antitumor activity in a variety of cancers, modulating c-Myc as an oncogenic driver. These data support the rationale for further advancing towards clinical development.

scholarly journals Multicenter Analysis of Presacral Neuroendocrine Neoplasms—Clinicopathological Characterization and Treatment Outcomes of a Rare Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Sami Matrood ◽  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Sebastian Krug ◽  
Harald Lahner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Outcomes ◽  
Rare Disease ◽  
Median Overall Survival ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Receptor Imaging ◽  
Presacral Space

Background and AimsNeuroendocrine neoplasms (NENs) of the presacral space are an extremely rare disease entity with largely unknown outcome and no established standard of care treatment. Therefore, we wanted to analyze clinical presentation, histopathological findings, treatment outcomes, and prognosis in a multicentric patient cohort.MethodsWe searched local databases of six German NEN centers for patients with presacral NEN. Retrospective descriptive analyses of age, sex, stage at diagnosis, symptoms, grade, immunohistochemical investigations, biomarkers, treatment, and treatment outcome were performed. Kaplan–Meier analysis was used to determine median overall survival.ResultsWe identified 17 patients (11 female, 6 male) with a median age of 50 years (range, 35–66) at diagnosis. Twelve cases presented initially with distant metastases including bone metastases in nine cases. On pathological review the majority of patients had well-differentiated G2 tumors. Immunohistochemical profile resembled rectal NENs. All but one patient had non-functioning tumors. Somatostatin receptor imaging was positive in 14 of 15 investigated cases. Eight patients were treated surgically including palliative resections; 14 patients received somatostatin analogs with limited efficacy. With 14 PRRTs completed, 79% showed clinical benefit, whereas only one patient with neuroendocrine carcinoma (NEC) responded to chemotherapy. Treatment with everolimus in three patients was not successful, whereas cabozantinib resulted in a disease stabilization in a heavily pretreated patient. During a median observation period of 44.5 months, 6 patients died. Median overall survival was not reached.ConclusionPresacral NEN are histopathologically similar to rectal NENs. Presacral NEN should be considered as possible primary in NEN of unknown primary. The majority of tumors is non-functioning and somatostatin receptor positive. PRRT demonstrated promising activity; tyrosine kinase inhibitors warrant further investigations. Further molecular characterization and prospective evaluation of this rare tumor entity are needed.

NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas

2021 ◽  
Vol 56 (2) ◽  
pp. 133-139
Author(s):  
Secil Ak Aksoy ◽  
Melis Mutlu ◽  
Rabia Nur Balcin ◽  
Mevlut Ozgur Taskapilioglu ◽  
Cagla Tekin ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Pediatric Brain Tumors ◽  
Normal Brain ◽  
Diffuse Glioma ◽  
Expression Levels ◽  
Treatment Models ◽  
New Treatment

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression ­profiles of microRNA (miRNA) and long noncoding RNA ­(LncRNA) in POGs. Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

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