Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells—Literature Review

Glial tumors are one of the most common lesions of the central nervous system. Despite the implementation of appropriate treatment, the prognosis is not successful. As shown in the literature, maximal tumor resection is a key element in improving therapeutic outcome. One of the methods to achieve it is the use of fluorescent intraoperative navigation with 5-aminolevulinic acid. Unfortunately, often the level of fluorescence emitted is not satisfactory, resulting in difficulties in the course of surgery. This article summarizes currently available knowledge regarding differences in the level of emitted fluorescence. It may depend on both the histological type and the genetic profile of the tumor, which is reflected in the activity and expression of enzymes involved in the intracellular metabolism of fluorescent dyes, such as PBGD, FECH, UROS, and ALAS. The transport of 5-aminolevulinic acid and its metabolites across the blood–brain barrier and cell membranes mediated by transporters, such as ABCB6 and ABCG2, is also important. Accompanying therapies, such as antiepileptic drugs or steroids, also have an impact on light emission by tumor cells. Accurate determination of the factors influencing the fluorescence of 5-aminolevulinic acid-treated cells may contribute to the improvement of fluorescence navigation in patients with highly malignant gliomas.

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Response of cultured human glioblastomas to radiation and BCNU chemotherapy

Journal of Neurosurgery ◽

10.3171/jns.1974.41.3.0339 ◽

1974 ◽

Vol 41 (3) ◽

pp. 339-349 ◽

Cited By ~ 20

Author(s):

John Mealey ◽

Tsu T. Chen ◽

Robert Shupe

Keyword(s):

Ionizing Radiation ◽

Tumor Cells ◽

Mammalian Cells ◽

Radiation Treatment ◽

Malignant Gliomas ◽

Cell Loss ◽

Response To Treatment ◽

Glial Tumor ◽

Content Type ◽

Effects Of Radiation

✓Individual and combined effects of ionizing radiation and chemotherapy with 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) on glial tumor cells were assessed in cultures derived from human glioblastomas. Drug and radiation exposures were performed on cell monolayers in 0.02 ml wells of microtest plates. Response to treatment was determined from serial observations on surviving populations in the original wells and comparisons with matched control cultures. Chemosensitivity was more variable than radiosensitivity in cell lines derived from five different glioblastomas: BCNU caused growth inhibition of 4% to 85% in doses of 8 µg/ml for 3 days compared to a 40% to 73% reduction after 400 rads of radiation. These findings were all significant statistically. Single doses above 600 to 800 rads appeared lethal, causing widespread loss of cells or transformation into giant forms that did not multiply. The doseresponse curves after BCNU and radiation treatment of cultured glial tumor cells were exponential, demonstrating that both modalities affected a constant fraction of the exposed cell populations according to dose. The observations on radiosensitivity of human glial tumor cells conformed to the generally known responses of cultured normal and neoplastic mammalian cells to ionizing radiation. BCNU in the higher doses tested acted as a possible radiosensitizing agent to potentiate the lethal effects of radiation since an increased rate of cell loss was demonstrated in glioma cultures exposed to this drug and radiation compared to those treated only by irradiation. These results in a controlled experimental environment support the concept that a combination of BCNU and radiation therapy should increase the time of survival of patients with malignant gliomas.

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Sonodynamic Therapy for Gliomas. Perspectives and Prospects of Selective Sonosensitization of Glioma Cells

Cells ◽

10.3390/cells8111428 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1428 ◽

Cited By ~ 6

Author(s):

Krzysztof Bilmin ◽

Tamara Kujawska ◽

Paweł Grieb

Keyword(s):

Aminolevulinic Acid ◽

Malignant Gliomas ◽

Tumor Resection ◽

Cerebral Stroke ◽

Efficacy And Safety ◽

Sonodynamic Therapy ◽

Current Review ◽

The Central Nervous System ◽

The Difference ◽

Routine Therapy

Malignant glial tumors (gliomas) are the second (after cerebral stroke) cause of death from diseases of the central nervous system. The current routine therapy, involving a combination of tumor resection, radio-, and chemo-therapy, only modestly improves survival. Sonodynamic therapy (SDT) has been broadly defined as a synergistic effect of sonication applied in combination with substances referred to as “sonosensitizers”. The current review focuses on the possibility of the use of tumor-seeking sonosensitizers, in particular 5-aminolevulinic acid, to control recurring gliomas. In this application, SDT employs a principle similar to that of the more widely-known photodynamic therapy of superficially located cancers, the difference being the use of ultrasound instead of light to deliver the energy necessary to eliminate the sensitized malignant cells. The ability of ultrasound to penetrate brain tissues makes it possible to reach deeply localized intracranial tumors such as gliomas. The major potential advantage of this variant of SDT is its relative non-invasiveness and possibility of repeated application. Until now, there have been no clinical data regarding the efficacy and safety of such treatment for malignant gliomas, but the preclinical data are encouraging.

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NCMP-13. LEPTOMENINGEAL DISEASE FOLLOWING RESECTION OF INTRAVENTRICULAR MELANOMA METASTASIS DIAGNOSED THROUGH CIRCULATING TUMOR CELLS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.524 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii125-ii125

Author(s):

Christopher Wang ◽

Melissa Limia ◽

Peter Forsyth ◽

James Liu

Keyword(s):

Early Intervention ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Surgical Resection ◽

Tumor Resection ◽

Leptomeningeal Disease ◽

Melanoma Metastasis ◽

Tumor Seeding ◽

Csf Analysis ◽

Dismal Prognosis

Abstract Leptomeningeal disease in the setting of malignant melanoma metastatic to the brain provides a dismal prognosis. The relationship between intraventricular metastatic tumor seeding following surgical resection and development of leptomeningeal disease (LMD) is not completely clear, although there appears to be correlation. While the mechanisms that drive the development of LMD is not well understood, monitoring of cerebrospinal fluid (CSF) for circulating tumor cells (CTCs) in high risk patients may allow for early intervention for LMD prior to radiographical diagnosis. This report describes a patient with metastatic melanoma who developed ventricular trapping from an intraventricular melanoma metastasis. The patient underwent endoscopic assisted resection of the tumor. Due to concern for leptomeningeal seeding given the location of the tumor and use of surgical resection, CSF analysis was performed. CTC count was increased shortly after surgical resection along with cytology that was suspicious for malignancy. Due to the increase in CTCs, the patient was treated for LMD with whole brain radiation therapy and intrathecal pembrolizumab. Subsequent CSF analysis revealed clearing of malignant cells in the CSF. The patient developed symptoms consistent with LMD approximately 9 months after the surgery and died 21 months after resection of his brain metastasis. This case illustrates a rare occurrence of an intraventricular melanoma metastasis, and the use of CTC presence within the CSF to diagnose LMD for early intervention. This emphasizes that the risk of developing LMD must be considered with intraventricular metastasis or ventricular exposure during tumor resection, and that CTCs may be an effective factor to monitor for early development of disease with possible prolonged survival benefit.

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Regulation of adenylate cyclase from glial tumor cells by calcium and a calcium-binding protein.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)33265-9 ◽

1976 ◽

Vol 251 (15) ◽

pp. 4744-4750 ◽

Cited By ~ 3

Author(s):

M A Brostrom ◽

C O Brostrom ◽

B M Breckenridge ◽

D J Wolff

Keyword(s):

Adenylate Cyclase ◽

Tumor Cells ◽

Calcium Binding ◽

Binding Protein ◽

Calcium Binding Protein ◽

Glial Tumor

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A poor prognostic metastatic nongestational choriocarcinoma of the ovary: a case report and the literature review

Journal of Ovarian Research ◽

10.1186/s13048-021-00810-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Kimihiro Nishino ◽

Eiko Yamamoto ◽

Yoshiki Ikeda ◽

Kaoru Niimi ◽

Toshimichi Yamamoto ◽

...

Keyword(s):

Tumor Cells ◽

Tumor Resection ◽

Left Lung ◽

Str Analysis ◽

Case Presentation ◽

Gestational Choriocarcinoma ◽

Mucosal Cells ◽

Malignant Germ Cell Tumor ◽

Brain Tumor Resection ◽

Short Tandem

Abstract Background Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. Case presentation A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. Conclusion Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

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Therapy and regeneration-combined bone cements for minimally invasive treatment of neoplastic bone defects

Journal of Materials Chemistry B ◽

10.1039/d1tb00703c ◽

2021 ◽

Author(s):

Yu Qu ◽

Hui Zhuang ◽

Meng Zhang ◽

Yufeng Wang ◽

Dong Zhai ◽

...

Keyword(s):

Calcium Phosphate ◽

Minimally Invasive ◽

Tumor Cells ◽

Bone Tumor ◽

Tumor Resection ◽

Bone Defects ◽

Bone Cements ◽

Invasive Treatment ◽

Calcium Phosphate Cements ◽

Bone Tumor Resection

Although calcium phosphate cements (CPC) have been clinically used to repair bone defects caused by bone tumor resection, traditional CPC cannot kill the remaining tumor cells after surgery and prevent...

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Adenosine 3′,5′-Monophosphate in Glial Tumor Cells

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)44062-3 ◽

1973 ◽

Vol 248 (8) ◽

pp. 2699-2704

Author(s):

Joan P. Schwartz ◽

N. Ronald Morris ◽

Bruce McL. Breckenridge

Keyword(s):

Tumor Cells ◽

Glial Tumor

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EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

Neuro-Oncology ◽

10.1093/neuonc/noz175.400 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi97-vi97

Author(s):

Satoshi Suehiro ◽

Takanori Ohnishi ◽

Akihiro Inoue ◽

Daisuke Yamashita ◽

Masahiro Nishikawa ◽

...

Keyword(s):

Tumor Cells ◽

Malignant Gliomas ◽

Glioma Cells ◽

High Intensity Focused Ultrasound ◽

Control Group ◽

Normal Brain ◽

Sonodynamic Therapy ◽

Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

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