scholarly journals Expression of 58-kD Microspherule Protein (MSP58) is Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients

2016 ◽  
Vol 38 (2) ◽  
pp. 635-645 ◽  
Author(s):  
Wei Lin ◽  
Shu-hui Dai ◽  
Tao Chen ◽  
Nobuyuki Kawai ◽  
Keisuke Miyake ◽  
...  

Background/Aims: The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation. Methods: In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas. Results: The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). The IRS of MSP58 in the tumor showed a highly significant positive correlation with corresponding FLT uptake value (r = 0.61, P < 0.001). The correlation between MSP58 expression and glioma malignancy was also confirmed by immunofluorescence, RT-PCR and western blot analysis. FLT uptake value also exhibited a highly significant positive correlation with the Ki-67 index (r = 0.59, P < 0.001). Kaplan-Meier analysis revealed that MSP58 expression has a significant prognostic ability for the overall survival time similar to that found in the uptake value of FLT-PET. Conclusion: These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy.

2019 ◽  
Vol 12 (5) ◽  
pp. e218979 ◽  
Author(s):  
Kalevi Kairemo ◽  
Vivek Subbiah

Primary cardiac angiosarcoma, the most common primary cardiac sarcoma has an incidence ranging from 0.001% to 0.028% in autopsy reports with around 200 cases reported in literature. Since a diagnosis of cardiac angiosarcoma portends a poor prognosis, it is vital to ascertain the precise extent of the lesions for follow-up. Imaging with positron emission tomography (PET) tracer 2-deoxy-2-[18F]-fluoro-D-glucose in cardiac angiosarcoma is challenging as myocardium takes up glucose and delineation of tumour becomes difficult. Cell proliferation rate in normal cardiac muscular tissue is low whereas cardiac tumours display a higher proliferation rate. This aspect could be exploited by use of 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (18F-FLT PET/CT] in cardiac tumours where the cell proliferation could be measured. Herein, we imaged an index case of cardiac angiosarcoma using18F-FLT PET/CT and report the findings.


2013 ◽  
Vol 12 (5) ◽  
pp. 452-457 ◽  
Author(s):  
George A. Alexiou ◽  
George Vartholomatos ◽  
Kalliopi Stefanaki ◽  
Amalia Patereli ◽  
Lefkothea Dova ◽  
...  

Object Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis. Methods The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed. Results Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer15) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer82), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer15) and Ki-67 index (r = −0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076). Conclusions A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23100-e23100
Author(s):  
Xue Meng ◽  
Xiaoli Zhang ◽  
Xindong Sun ◽  
Jinming Yu

e23100 Background: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumor subvolumes for selecting dose escalation in radiation therapy. The aim of this study was to monitor tumor cell proliferation and repopulation during fractionated radiotherapy and investigated the spatial concordance of tumor cell proliferation and repopulation with 18F-FLT tracer uptake. Methods: Mice bearing A549 xenograft tumors were assigned to 5 different irradiated groups (3f/6d, 6f/12d, 9f/18d, 12f/24d and 18f/36d) with 2 Gy/fractions and non-irradiated group. Serial 18F-FLT micro PET scans were performed at different time points, the maximum of standard uptake value (SUVmax) were measured to detect the feasible time of tumor repopulation during irradiation. Ex vivo images of the spatial pattern of intratumor 18F-FLT uptake and Ki-67 labeling index (LI) were obtained from thin tumor tissue sections. A layer-by-layer comparison between SUVmax and Ki-67 LI results, including the thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation, were conducted to evaluate the spatial imaging pathology correlation. Results: The SUVmax were observed decreases in the 3f/6d group (P = 0.000), compared to these for non-irradiated tumors. However, it was significantly increased in the 6f/12d later, and then gradually reduced with treatment time prolonged again after 6f/12d group. Proliferation changes on pathology imaging at 6f/12d were also confirmed. Significant correlations were found between the SUVmax and Ki-67 LI of all ROIs in each in vitro tumor of cell proliferation group (Ps < 0.001). Similar results were also found in each tumor of accelerated repopulation group (Ps < 0.001). Furthermore, both of the mean ORRs were more than 50% in all layer of the tumor cell proliferation and accelerated groups. Regions of high-intensity 18F-FLT uptake in the autoradiographs exhibited prominent staining for Ki-67. Conclusions: 18F-FLT PET may be a promising imaging surrogate of tumor proliferative response to fractionated radiotherapy and might help make adaptive radiation oncology treatment plan.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2537-2537 ◽  
Author(s):  
G. A. McArthur ◽  
R. M. Hicks ◽  
D. R. Shalinsky ◽  
D. Binns ◽  
C. O’Kane ◽  
...  

2537 Background: Strategies to monitor molecular & cellular responses to novel cell cycle targeting agents are vital to provide proof of their mechanism & biological activity. In developing biomarkers for the novel chk1 inhibitor, PF-477736, we demonstrated that gemcitabine chemotherapy induced a significant increase, or flare, in uptake of the PET tracer, 3’-deoxy-3’flurothymidine (FLT), into tumor xenografts 24 h after dosing (Proc ASCO 24:A3045, 2006). We postulated that an early flare in FLT may also occur following gemcitabine therapy in human tumors. Methods: Eligible patients had at least 1 malignant lesion identified by CT scan outside of a previous radiation field. Patients received a baseline FLT-PET scan day-1 to -4 relative to 1st dose of gemcitabine at 1,000 mg/m2, and a post dose FLT- PET scan 22–26 h after gemcitabine. Endpoints were FLT uptake as assessed by: SUV; a qualitative scoring system; and tumor-to-background (T:B) ratios using liver, mediastinum and bone marrow as references. Results: Six of 8 planned patients with 14 index lesions have been accrued in this pilot study. 4/6 patients demonstrated increased uptake of FLT as defined by >50% increase in SUV or T:B ratio in at least 1 lesion. Analysing all index lesions showed an increase in FLT-uptake post gemcitabine as assessed by a 4 point qualitative scoring system from 1.6±0.2 to 2.7±0.1 (p=0.01) or T:B 1.1±0.2 to 2.0±0.3 (p<0.01) using liver as a reference. Interestingly in contrast to increased uptake in tumors, uptake of FLT in bone marrow was reduced from an SUV of 6.4±0.6 to 3.4±0.7 (p<0.01) following gemcitabine. Conclusion: Following treatment with gemcitabine there was an early flare in uptake of FLT into many tumors. In contrast, uptake in bone marrow was reduced. FLT-PET appears to be a promising tool to monitor the cell cycle response of both tumor and bone marrow to cytotoxic chemotherapy. No significant financial relationships to disclose.


2021 ◽  
Vol 8 ◽  
Author(s):  
Taesik Yun ◽  
Yoonhoi Koo ◽  
Hakhyun Kim ◽  
Wonguk Lee ◽  
Soochong Kim ◽  
...  

A 15.5-year-old, neutered, male, domestic shorthair cat was presented with neurologic dysfunctions. At presentation, an obtunded mental status and vestibular ataxia were identified. On neurologic examination, postural reactions were decreased-to-absent in all four limbs, and pupillary light reflexes showed bilaterally delayed results. Magnetic resonance imaging was performed, and a demarcated lesion was identified in the third ventricle. The cat was tentatively diagnosed with a brain tumor, which was suspected to be a meningioma. The cat was treated with hydroxyurea and prednisolone. Mental status was considered more alert, and ataxia improved following treatment. On the 106th day after the commencement of treatment, a 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan was performed. On the PET images, a hypermetabolic region was found in the lesion. The average standardized uptake value of FDG was 2.47, and the tumor-to-normal-tissue ratio was 1.25. The cat died 408 days following the commencement of treatment, and a grade 1 meningioma was confirmed by postmortem histopathology. Immunohistochemistry for Ki-67 and p53 was performed. The labeling indices of Ki-67 and p53 were 2.56 and 0%, respectively. This case shows that chemotherapy with hydroxyurea and prednisolone may be considered in the treatment of feline meningiomas. Furthermore, this is the first case describing the application of FDG-PET to visualize a naturally occurring meningioma in a cat.


2016 ◽  
Vol 185 (1) ◽  
pp. 31-38 ◽  
Author(s):  
John A. Cieslak ◽  
Zita A. Sibenaller ◽  
Susan A. Walsh ◽  
Laura L. Boles Ponto ◽  
Juan Du ◽  
...  

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