Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA)-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

Abstract Purpose: For malignant brain tumor surgery, photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) is useful for maximal removal of the tumor. Although it has the advantage of identifying the presence or absence of residual tumors during surgery, there are variations in positive rates, and the classification is limited, based on visual inspection such as Stummer’s classification (strong, vague, none). We analyzed the luminance of positive findings using software Image J for brain tumor surgery using 5-ALA, and we report the results. Materials and Methods: From April 2018 to March 2021, 31 patients with suspected malignant glioma before surgery were included. Intraoperative 5-ALA positive findings were analyzed by software Image J (Wayne Rasband: NIH), the luminance was measured with a histogram, and compared the maximum luminance titer. Results: Among the positive cases, the average maximum luminance value for malignant glioma was 101 (50–168), which consisted of 11 cases of Glioblastoma, 1 case of Oligodendroglioma, and 1 case of anaplastic astrocytoma. The average maximum brightness of metastatic brain tumors is lower than that of malignant gliomas, even if they are visually strong, 83.5 (28–121). Conclusions: Even if it is visually strong in the conventional Stummer classification, it may be possible to classify in detail by analyzing luminance with Image J. In addition, more objective index is necessary to classify the vague findings.

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Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2012.06.003 ◽

2013 ◽

Vol 10 (1) ◽

pp. 42-50 ◽

Cited By ~ 34

Author(s):

Wei Sun ◽

Yoshinaga Kajimoto ◽

Hiroto Inoue ◽

Shin-Ichi Miyatake ◽

Toshihisa Ishikawa ◽

...

Keyword(s):

Photodynamic Therapy ◽

Brain Tumor ◽

Tumor Cells ◽

Aminolevulinic Acid ◽

Malignant Brain Tumor ◽

Brain Tumor Cells

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Singlet oxygen model evaluation of interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor

Journal of Biomedical Optics ◽

10.1117/1.jbo.25.6.063803 ◽

2019 ◽

Vol 25 (06) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Atsuki Izumoto ◽

Takahiro Nishimura ◽

Hisanao Hazama ◽

Naokado Ikeda ◽

Yoshinaga Kajimoto ◽

...

Keyword(s):

Photodynamic Therapy ◽

Brain Tumor ◽

Singlet Oxygen ◽

Model Evaluation ◽

Aminolevulinic Acid ◽

Malignant Brain Tumor ◽

Interstitial Photodynamic Therapy

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Photodynamic Diagnosis for Malignant Pleural Diseases Using 5-Aminolevulinic Acid and Autofluorescence Imaging System

Nihon Kikan Shokudoka Gakkai Kaiho ◽

10.2468/jbes.70.176 ◽

2019 ◽

Vol 70 (2) ◽

pp. 176-176

Author(s):

M. Kitada ◽

Y. Ohsaki ◽

S. Yasuda ◽

N. Takahashi ◽

S. Okazaki ◽

...

Keyword(s):

Aminolevulinic Acid ◽

Imaging System ◽

Photodynamic Diagnosis ◽

Autofluorescence Imaging ◽

Pleural Diseases

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Faculty Opinions recommendation of Photodynamic diagnosis using 5-aminolevulinic acid for the detection of positive surgical margins during radical prostatectomy in patients with carcinoma of the prostate: a multicentre, prospective, phase 2 trial of a diagnostic procedure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7708957.8028056 ◽

2011 ◽

Author(s):

Yoshihiko Hirao ◽

Kiyohide Fujimoto

Keyword(s):

Radical Prostatectomy ◽

Diagnostic Procedure ◽

Aminolevulinic Acid ◽

Surgical Margins ◽

Photodynamic Diagnosis ◽

Phase 2 ◽

Positive Surgical Margins ◽

Carcinoma Of The Prostate ◽

Phase 2 Trial ◽

Prospective Phase

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Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

Reproduction ◽

10.1530/rep-13-0007 ◽

2013 ◽

Vol 146 (2) ◽

pp. 119-133 ◽

Cited By ~ 29

Author(s):

Barbara Ambruosi ◽

Gianluca Accogli ◽

Cécile Douet ◽

Sylvie Canepa ◽

Géraldine Pascal ◽

...

Keyword(s):

Brain Tumor ◽

Western Blot ◽

Immunohistochemical Analysis ◽

Fertilization Rate ◽

Malignant Brain Tumor ◽

Estrus Cycle ◽

Immunofluorescence Analysis ◽

Oviductal Fluid ◽

Porcine Spermatozoa

Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and subsequent embryonic development. The aim of this study was to evaluate the effect of oviductal fluid and the possible involvement of deleted in malignant brain tumor 1 (DMBT1) on IVF in porcine and equine species that represent divergent IVF models. We first performed IVF after pre-incubation of oocytes with or without oviductal fluid supplemented or not with antibodies directed against DMBT1. We showed that oviductal fluid induces an increase in the monospermic fertilization rate and that this effect is canceled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase in the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization process. The presence of DMBT1 in the oviduct at different stages of the estrus cycle was shown by western blot and confirmed by immunohistochemical analysis of ampulla and isthmus regions. The presence of DMBT1 in cumulus–oocyte complexes was shown by western blot analysis, and the localization of DMBT1 in the zona pellucida and cytoplasm of equine and porcine oocytes was observed using immunofluorescence analysis and confocal microscopy. Moreover, we showed an interaction between DMBT1 and porcine spermatozoa using surface plasmon resonance studies. Finally, a bioinformatic and phylogenetic analysis allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.

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The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

International Journal of Molecular Sciences ◽

10.3390/ijms22052250 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2250

Author(s):

Evita Athanasiou ◽

Antonios N. Gargalionis ◽

Fotini Boufidou ◽

Athanassios Tsakris

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Comprehensive Evaluation ◽

Tumor Development ◽

Scientific Data ◽

Malignant Brain Tumor ◽

Direct Role ◽

Tumor Pathology ◽

Human Herpesviruses

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

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Preanesthetic severe postural hypotension following 5-aminolevulinic acid pretreatment in patients for photodynamic diagnosis-assisted urological surgery

JA Clinical Reports ◽

10.1186/s40981-019-0295-1 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Tohru Shiratori ◽

Kunihisa Hotta ◽

Masaaki Satoh ◽

Chiaki Kiuchi ◽

Noriyuki Ogawa ◽

...

Keyword(s):

Postural Hypotension ◽

Aminolevulinic Acid ◽

Vital Signs ◽

Photodynamic Diagnosis ◽

Careful Monitoring ◽

High Concentration ◽

Acid Pretreatment ◽

Case Presentation ◽

Severe Hypotension ◽

Prolonged Hypotension

Abstract Background 5-Aminolevulinic acid (5-ALA) is utilized for photodynamic diagnosis-assisted (PDD) surgery. However, it has been associated with vasodilation, hence, occasional hypotension. Case presentation We encountered two patients who had severe postural hypotension following 5-ALA pretreatment prior to an operation. They were scheduled for urological PDD surgery, but upon standing to walk to the operation room, they felt sick because of severe hypotension. One of them underwent the surgery after recovery, but the other surgery was canceled due to a prolonged hypotension that lasted for more than a day. Conclusions Severe postural hypotension may develop as a result of the high concentration of porphyrin precursors, which may affect the nervous system. Severe postural hypotension may be due to 5-ALA-induced autonomic dysfunction as well as vasodilative action of 5-ALA. These observations suggest that in addition to the careful monitoring of patients’ vital signs, standing should be avoided following 5-ALA pretreatment.

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MS-1 Surgical strategy for brain tumor based on molecular and functional connectomics profiles

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.008 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii2-ii2

Author(s):

Tatsuya Abe

Keyword(s):

Overall Survival ◽

Brain Tumor ◽

Standard Procedure ◽

Awake Craniotomy ◽

Surgical Strategy ◽

Neurological Deficits ◽

Cortical Mapping ◽

Photodynamic Diagnosis ◽

Tumor Surgery ◽

Brain Tumor Surgery

Abstract It is reported that the development of new perioperative motor deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. The maximum safe resection without any neurological deficits is required to improve overall survival in patients with brain tumor. Surgery is performed with various modalities, such as neuro-monitoring, photodynamic diagnosis, neuro-navigation, awake craniotomy, intraoperative MRI, and so on. Above all, awake craniotomy technique is now the standard procedure to achieve the maximum safe resection in patients with brain tumor. It is well known that before any treatment, gliomas generate globally (and not only focally) altered functional connectomics profiles, with various patterns of neural reorganization allowing different levels of cognitive compensation. Therefore, perioperative cortical mapping and elucidation of functional network, neuroplasticity and reorganization are important for brain tumor surgery. On the other hand, recent studies have proposed several gene signatures as biomarkers for different grades of gliomas from various perspectives. Then, we aimed to identify these biomarkers in pre-operative and/or intra-operative periods, using liquid biopsy, immunostaining and various PCR methods including rapid genotyping assay. In this presentation, we would like to demonstrate our surgical strategy based on molecular and functional connectomics profiles.

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