Genetic factors affecting intraoperative 5-aminolevulinic acid-induced fluorescence of diffuse gliomas

Saito, Kiyotaka; Hirai, Toshinori; Takeshima, Hideo; Kadota, Yoshihito; Yamashita, Shinji; Ivanova, Asya; Yokogami, Kiyotaka

doi:10.1515/raon-2017-0019

Cited by 24 publications

(18 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the vast majority of glioblastomas shows strong PpIX‐fluorescence, a dependence on MGMT‐status as a determining single factor can be excluded. While an in vitro study found stronger PpIX fluorescence in cells harboring IDH‐1 mutation, clinical experience seems to point in the opposite direction, finding non‐fluorescent gliomas predominantly in the IDH mutated subgroup . It may be worth mentioning that the rate of contrast enhancement in MRI among the IDH mutant gliomas is also lower than with IDH wild‐type ones , suggesting that this effect may be caused by differences in BBB deficiency.…”

Section: ‐Ala—fundamentalsmentioning

confidence: 97%

5‐ALA in the management of malignant glioma

Stepp¹,

2018

View full text Add to dashboard Cite

Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients. Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience. Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT). Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018.

show abstract

Section: ‐Ala—fundamentalsmentioning

confidence: 97%

5‐ALA in the management of malignant glioma

Stepp¹,

2018

View full text Add to dashboard Cite

show abstract

“…Analysis was as previously described. 15 TERT mutations were confirmed by direct sequencing. A fragment of the TERT promoter was amplified with a primer (5′-GTCCTGCCCCTTCACCTT-3′ [forward], 5′-GCACCTCGCGGTAGTGG-3′ [reverse]) that contained the C228T and C250T mutation sites.…”

Section: Analysis Of Idh1 and Tert Mutationsmentioning

confidence: 99%

MGMT promoter methylation in patients with glioblastoma: is methylation-sensitive high-resolution melting superior to methylation-sensitive polymerase chain reaction assay?

Yamashita¹,

Yokogami²,

Matsumoto³

et al. 2019

Journal of Neurosurgery

Self Cite

View full text Add to dashboard Cite

OBJECTIVE The methylation status of the O6-methylguanine-DNA methyltransferase ( MGMT) gene promoter is a prognostic factor in adults with glioblastoma (GBM); it also yields information that is useful for clinical decision-making in elderly GBM patients. While pyrosequencing is the gold standard for the evaluation of the methylation status of MGMT, methylation-sensitive polymerase chain reaction (MS-PCR) assay continues to be used widely. Although MS-PCR results exhibited a good correlation with the prognosis of patients with GBM treated under the Stupp protocol, interpretation of the bands is based on subjective judgment, and the assay cannot be used to analyze heterogeneously methylated samples. We assessed whether methylation-sensitive high-resolution melting (MS-HRM) is an alternative to MS-PCR. METHODS The authors prepared 3 primer sets that covered CpG 72-89 for MS-HRM analysis to determine the methylation levels of 6 human glioma cell lines. The results were validated by bisulfite sequencing of cloned alleles. The authors also subjected surgical samples from 75 GBM patients treated with temozolomide (TMZ) to MS-HRM to assess the MGMT methylation status and compared the findings with MS-PCR results using receiver operating characteristic (ROC), univariate, and multivariate analyses. RESULTS There was a strong correlation between the methylation levels of the 6 glioma cell lines evaluated by MS-HRM and by bisulfite sequencing; with primers 1 and 2, the correlation was significant (r = 0.959 and r = 0.960, respectively, p < 0.01). Based on log-rank analysis, MS-HRM was significantly better than MS-PCR for predicting progression-free survival (PFS) and overall survival (OS) based on the methylation status of the MGMT promoter (PFS predicted by MS-HRM and MS-PCR = 0.00023 and 0.0035, respectively; OS = 0.00019 and 0.00028, respectively). ROC analysis showed that the area under the curve was larger with MS-HRM than with MS-PCR (PFS: 0.723 vs 0.635; OS: 0.716 vs 0.695). Based on multivariate Cox regression analysis, MS-HRM was significantly better than MS-PCR for predicting the treatment outcome (MS-HRM vs MS-PCR: PFS, p = 0.001 vs 0.207; OS, p = 0.013 vs 0.135). CONCLUSIONS The authors' findings show that MS-HRM is superior to MS-PCR for the detection of MGMT promoter methylation. They suggest MS-HRM as an alternative to MS-PCR for assessing the prognosis of patients with GBM.

show abstract

“…Stummer et al . 8 reported that progression-free survival (PFS) was prolonged when ALA-PDD was used during glioblastoma surgery, and 5-ALA has already been approved as a diagnostic drug for grade III and IV glioma in Europe, Japan and the USA 9,10 . Recently, 5-ALA was also approved as a diagnostic agent for nonmuscle invasive bladder cancer in Japan 11 .…”

Section: Introductionmentioning

confidence: 99%

Mechanistic study of PpIX accumulation using the JFCR39 cell panel revealed a role for dynamin 2-mediated exocytosis

Kitajima

Ishii

Kohda

et al. 2019

Sci Rep

View full text Add to dashboard Cite

5-aminolevulinic acid (5-ALA) has recently been employed for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various types of cancer because hyperproliferating tumor cells do not utilize oxidative phosphorylation and do not efficiently produce heme; instead, they accumulate protoporphyrin IX (PpIX), which is a precursor of heme that is activated by violet light irradiation that results in the production of red fluorescence and singlet oxygen. The efficiencies of ALA-PDD and ALA-PDT depend on the efficient cellular uptake of 5-ALA and the inefficient excretion of PpIX. We employed the JFCR39 cell panel to determine whether tumor cells originating from different tissues can produce and accumulate PpIX. We also investigated cellular factors/molecules involved in PpIX excretion by tumor cells with the JFCR39 cell panel. Unexpectedly, the expression levels of ABCG2, which has been considered to play a major role in PpIX extracellular transport, did not show a strong correlation with PpIX excretion levels in the JFCR39 cell panel, although an ABCG2 inhibitor significantly increased intracellular PpIX accumulation in several tumor cell lines. In contrast, the expression levels of dynamin 2, which is a cell membrane-associated molecule involved in exocytosis, were correlated with the PpIX excretion levels. Moreover, inhibitors of dynamin significantly suppressed PpIX excretion and increased the intracellular levels of PpIX. This is the first report demonstrating the causal relationship between dynamin 2 expression and PpIX excretion in tumor cells.

show abstract

Genetic factors affecting intraoperative 5-aminolevulinic acid-induced fluorescence of diffuse gliomas

Cited by 24 publications

References 38 publications

5‐ALA in the management of malignant glioma

5‐ALA in the management of malignant glioma

MGMT promoter methylation in patients with glioblastoma: is methylation-sensitive high-resolution melting superior to methylation-sensitive polymerase chain reaction assay?

Mechanistic study of PpIX accumulation using the JFCR39 cell panel revealed a role for dynamin 2-mediated exocytosis

Contact Info

Product

Resources

About