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Background and Objectives: Sweat basil (Ocimum basilicum L.) is an annual herb whose use as vegetable, medicinal and cosmetic plant is increasing all over the world. Arsenic (As) is one of the most important heavy metals, which is considered as one of the most important contaminants of the environment, which is dangerous for plants, animals and humans. The use of 5-ALA (5-Aminilevolunic acid) as plant growth regulator has been introduced as a new soilution to deal with some environmental stresses and to moderate their destructive effects on the growth and developments of plants. This study carried out to investigation the reduction or balancing effects of 5-ALA on hazard effects of As on morphological and physiological properties of basil. Materials and Methods: In this examination basil plant cultivated in two groups of As-contaminated and As-noncontaminated soils. For study of foliar application of 5-ALA in three concentrations (0, 10 and 20 mg/L) on morphological and physiological traits of basil conducted in the greenhouse in form of completely randomized design in four replication carried out. Results: The analysis of results showed that arsenic stress decreased the content of basil morphological properties but the treatment of 5-ALA to some extent improved the content of these properties. Also the physiological properties such as anthocyanin, phenol, flavonoid, proline, soluble sugar, DPPH, MDA, guaicol peroxidase, catalase, ascorbate peroxidase, RWC and ion leakage significantly affected by arsenic contamination and 5-ALA spraying and reaction of these. In the case of photosynthetic pigments (chlorophyll a, chlorophyll b, total chlorophyll and carotenoids) were affected by arsenic contamination and spraying of 5- ALA but the reaction of these factors on these adjectives were not significant. Arsenic stress decreased the basil growth traits (the amounts of leaf number, leaf area, leaf fresh weight, plant height, stem fresh weight and stem dry weight 10.67, 25.47, 26.12, 30.57, 21.98 and 10.34%, respectively) and photosynthetic pigments (the amounts of chlorophyll a, chlorophyll b, total chlorophyll and carotenoid content 31.98, 25.6, 28.83 and 26.43%, respectively) and on other hand electrolyte leakage (217.01%) and MDA (162.31%) content were increased. Actually the spraying of 5-ALA with the increase of proline (251.89%) and antioxidant enzymes (GPX, CAT and APX amounts 48.52, 43.64 and 18.51%, respectively) reduced the negative effects of arsenic stress. Conclusion: According to reduction and inhibition effects of arsenic on growth and development of basil, and effects of 5-ALA decline and adjustment on these factors, it can be said that the use of this component could be as new way to some extend in reduction of dangerous effects of these environment contaminations on plants in the future studies should be considered. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

Salinity, one of the most significant abiotic stress factors restricting plant production, causes the destruction of agricultural lands and reduces productivity. In recent years, the utilization of 5-aminolevulinic acid (5-ALA) applications, which have important effects in terms of avoiding and providing tolerance to factors by impacting the physiology and metabolism of the plants, has been on the agenda. In this research, the impacts of foliar treatments of different levels of 5-ALA (0, 0.3, 0.6 and 0.9 mM) on morphological and physiological traits of 41 B American grapevine rootstocks under salinity stress (NaCl solution starting with 25 mM and reaching 150 mM concentration) were investigated. Salinity stress caused significant decreases in growth parameters, chlorophyll content, RWC and stomatal conductance, and significant increases in leaf temperature, proline and MDA content, physical damage and membrane damage degree. Under salinity stress, 0.9 mM 5-ALA treatments resulted in significant increases in shoot length (14.67 cm), root length (34.50 cm), leaf thickness (0.23 µm) leaf area (31.37 cm2), leaf number (8.67 pieces), chlorophyll content (21.83 SPAD), RWC (80.20%), proline content (0.19 μmol.g-1) and stomatal conductance (78.05 mmol.m-2.s-1); and significant decreases in physical damage degree (1.00 scale degree), membrane injury degree (15.46%) and MDA content (28.20 nmol.g-1) compared to non-ALA treatments. According to the results of this study, 5-ALA can be recommended as an alternative application to provide salinity tolerance in plants in order to reduce the damage caused by salinity stress in agricultural lands.

The review begins with an overview of the fundamental principles/physics underlying light, fluorescence, and other light-matter interactions in biological tissues. It then focuses on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence spectroscopy methods used in neurosurgery (e.g., intensity, time-resolved) and in so doing, describe their specific features (e.g., hardware requirements, main processing methods) as well as their strengths and limitations. Finally, we review current clinical applications and future directions of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence spectroscopy in neurosurgery. [ABSTRACT FROM AUTHOR]

AbstractHuman papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630 ± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450 nm PDT comparing with ALA-635 nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo, immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450 nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635 nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspase-dependent apoptosis pathway. In vivo, ALA-450 nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450 nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases.HighlightsWe combined 5-aminolevulinic acid with 450 nm blue laser using as a novel type of photodynamic therapy.The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibition of the proliferation of End1 and HeLa cells and inducing cell apoptosis in vitro and in vivo.The ALA-450 nm PDT may provide a novel alternative therapeutic option in patients with persistent HPV infection and promote the integration of diagnosis and treatment.

ObjectiveTo determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes.MethodsThis retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value

Photodynamic therapy (PDT) is a promising cancer treatment that kills cancer cells selectively by stimulating reactive oxygen species generation with photosensitizers exposed to specific light wavelengths. 5-aminolevulinic acid (5-ALA) is a widely used photosensitizer. However, its limited tumour penetration and targeting reduce its therapeutic efficacy. Scholars have investigated nano-delivery techniques to improve 5-ALA administration and efficacy in PDT. This review summarises recent advances in biological host biosynthetic pathways and regulatory mechanisms for 5-ALA production. The review also highlights the potential therapeutic efficacy of various 5-ALA nano-delivery modalities, such as nanoparticles, liposomes, and gels, in treating various cancers. Although promising, 5-ALA nano-delivery methods face challenges that could impair targeting and efficacy. To determine their safety and biocompatibility, extensive preclinical and clinical studies are required. This study highlights the potential of 5-ALA-NDSs to improve PDT for cancer treatment, as well as the need for additional research to overcome barriers and improve medical outcomes. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5- aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450nm PDT comparing with ALA-635nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo, immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspasedependent apoptosis pathway. In vivo, ALA-450nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450nm PDT had an advantage over ALA-635nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases. [ABSTRACT FROM AUTHOR]

The review begins with an overview of the fundamental principles/physics underlying light, fluorescence, and other light-matter interactions in biological tissues. It then focuses on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence spectroscopy methods used in neurosurgery (e.g., intensity, time-resolved) and in so doing, describe their specific features (e.g., hardware requirements, main processing methods) as well as their strengths and limitations. Finally, we review current clinical applications and future directions of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence spectroscopy in neurosurgery.

Objectives: Stereotactic photodynamic therapy (sPDT) using 5-aminolaevulinic acid (5-ALA) as a cytotoxic photosensitizer may be a potentially prospective treatment option for malignant gliomas. Material and Methods: We analyzed data from 10 patients with recurrent malignant gliomas of the brain who were treated with sPDT at the Department of Neurosurgery of the Military-Medical Academy S. M. Kirov, from 2020 to November 2021. Three patients were treated with sPDT again after 3, 7, and 15 months due to relapse. Results: The median age of the patients was 55.5 years, range was 30--60 years, there were six men and four women. At the time of sPDT, 7 (70%) patients with recurrent tumors were diagnosed with glioblastomas (WHO grade IV), and 3 (30%) with anaplastic astrocytomas (WHO grade III). Tumors were without IDH mutation in 7 (70%) patients; MGMT gene expression status was evaluated in tumors in 9 (90%) patients. A 1p/19q co-deletion was not detected in any of the patients. The median tumor volume was 5.85 cm3 (min. 3.2 cm3, max. 22.5 cm3). We have found that the median recurrence-free period after sPDT in patients with anaplastic astrocytomas and glioblastomas was 435 and 195 days, respectively. Conclusion: This result allows to consider sPDT as one of the perspective methods of treatment of patients with recurrent gliomas of high malignancy in cases when repeated open surgical intervention has high risks of new neurological deficit. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiosensitization of glioblastoma is a major ambition to increase the survival of this incurable cancer. Before surgery, oral administration of 5-aminolevulinic acid leads to the accumulation of fluorescent protoporphyrin IX, preferentially in the cancer cells rather than in the normal brain. This property is used to optimize the resection of the tumor under fluorescent light. Protoporphyrin IX may also carry radiosensitization activity. To test this hypothesis, we designed a robust murine preclinical model of glioblastoma with tumors implanted into the brain of mice treated by fractionated radiotherapy, as for humans. Despite the specific accumulation of porphyrins in glioblastoma, there was no radiosensitization. We confirmed these results in in vitro 3D patient-derived spheroids. Radiosensitization by molecules such as porphyrins needs more exploration for application in glioblastoma treatment. Radiosensitization of glioblastoma is a major ambition to increase the survival of this incurable cancer. The 5-aminolevulinic acid (5-ALA) is metabolized by the heme biosynthesis pathway. 5-ALA overload leads to the accumulation of the intermediate fluorescent metabolite protoporphyrin IX (PpIX) with a radiosensitization potential, never tested in a relevant model of glioblastoma. We used a patient-derived tumor cell line grafted orthotopically to create a brain tumor model. We evaluated tumor growth and tumor burden after different regimens of encephalic multifractionated radiation therapy with or without 5-ALA. A fractionation scheme of 5 × 2 Gy three times a week resulted in intermediate survival [48–62 days] compared to 0 Gy (15–24 days), 3 × 2 Gy (41–47 days) and, 5 × 3 Gy (73–83 days). Survival was correlated to tumor growth. Tumor growth and survival were similar after 5 × 2 Gy irradiations, regardless of 5-ALA treatment (RT group (53–67 days), RT+5-ALA group (40–74 days), HR = 1.57, p = 0.24). Spheroid growth and survival were diminished by radiotherapy in vitro, unchanged by 5-ALA pre-treatment, confirming the in vivo results. The analysis of two additional stem-like patient-derived cell lines confirmed the absence of radiosensitization by 5-ALA. Our study shows for the first time that in a preclinical tumor model relevant to human glioblastoma, treated as in clinical routine, 5-ALA administration, although leading to important accumulation of PpIX, does not potentiate radiotherapy. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) with 5‐aminolevulinic acid hydrochloride (ALA) is an established method for the management of AK. PD P 506 A (brand name Alacare®) is an approved medicinal product for the treatment of AK located on scalp and face. It is a self‐adhesive, light‐proof patch loaded with 5‐ALA HCl and was developed for easy handling. AK located on arms, hands or trunk do not respond as well to ALA‐PDT as AK lesions on the head do. It has been reported that occlusion during ALA incubation can improve clinical outcome after ALA‐PDT for AK on hands and arms. We present the results of a first explorative pilot study involving 20 participants with a total of 145 treated (122 evaluable) AK lesions. The trial investigated the conduct of two ALA‐PDTs within 1–2 weeks and involved all severity grades of AK. The model‐based percentage of complete clearance on lesion‐basis was estimated being 78.0% (95%‐CI: [64.6%, 87.3%]), and the by‐participant calculation (patient‐based clearance) led to similar results (78.7% with a 95%‐CI of [67.0%, 90.3%]). The treatment was well tolerated. Local reactions during ALA patch incubation were rare whereas nearly all patients showed the expected reactions during or after the illumination, primarily erythema and pain. The study results indicate that two PD P 506 A‐PDT sessions 1–2 weeks apart are an efficacious treatment for AK on hands and arms. Especially mild but also moderate lesions responded very well to PDT treatment involving ALA incubation under occlusion. [ABSTRACT FROM AUTHOR]

5-aminolevulinic acid (5-ALA) has been extensively studied for its sustainability and broad-spectrum applications in medical research and theranostics, as well as other areas. It's a precursor of protoporphyrin IX (PpIX), a sustainable endogenous and naturally-existing photosensitizer. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on 5-ALA research has not been reported so far, which would be of major importance to the relevant researchers. In this study, we collected all the research articles published in the last two decades from the Web of Science Core Collection database and employed bibliometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace. A total of 1595 articles were identified. The analysis results showed that China published the largest number of articles, and SBI Pharmaceuticals Co., Ltd. was the most productive institution that sponsored several of the most productive authors. The cluster analysis and burst detections indicated that the improvement of photodynamic efficacy theranostics is the up-to-date key direction in 5-ALA research. Furthermore, we emphatically studied nanotechnology involvement in 5-ALA delivery and theranostics research. We envision that our results will be beneficial for researchers to have a panorama of and deep insights into this area, thus inspiring further exploitations, especially of the nanomaterial-based systems for 5-ALA delivery and theranostic applications. [ABSTRACT FROM AUTHOR]

Background: The use of fluorescein sodium (FS) as a surgical adjunct in glioblastoma resection has shown promise in improving tumor visualization and resection outcomes. This study aimed to evaluate the safety, efficacy, and side effects of FS-aided resection in patients with glioblastoma., Methods: This is a prospective, single-center cohort study conducted at Ibrahim Cardiac Hospital and Research Institute from September 2021 to November 2023. Twelve patients with histologically confirmed glioblastoma underwent FS-guided resection. All participants received an intravenous dose of FS (5 mg/kg body weight) ~30 min before surgery. The study follows a quasi-experimental design, focusing on the outcomes of FS-aided surgery without a control group. Patients were selected based on specific inclusion and exclusion criteria, and all surgeries were performed by a single experienced neurosurgeon. The extent of tumor resection was classified as gross total resection (GTR), near-total resection (NTR), or partial resection (PR)., Results: Gross total resection (GTR) was achieved in 66.6% of patients, near total resection (NTR) in 16.6%, and subtotal resection (STR) in 16.6%. No significant adverse effects were observed except for a single case of postoperative seizure, which was managed without long-term consequences. All patients showed normal liver and kidney function tests postoperatively. The low-dose FS protocol demonstrated both a high rate of GTR and a favorable safety profile, with only minor, transient side effects such as temporary yellow discoloration of the skin, sclera, and urine. No severe or long-term complications related to FS were observed during the follow-up period, which had a median duration of 13.4 months., Conclusion: FS appears to be a safe and effective aid in glioblastoma resection, achieving high rates of GTR with minimal side effects. The findings suggest that FS, particularly at a low dose, is a viable, cost-effective alternative to other fluorescent markers, especially in settings where resource constraints may limit the use of more expensive options like 5-ALA., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aim: The extent of resection seems a solid prognostic factor in patients with high-grade gliomas (HGGs). When administered orally, 5-aminolevulinic acid (5-ALA) is exclusively converted into protoporphyrin IX (PPIX) by malignant cells and detects, identifying contrast-enhancing glial lesions under 400 nm blue light. The authors thoroughly assess the efficacy, accuracy, and safety profile of 5-ALA-guided surgery toward the maximal resection of cranial HGGs. Case Presentation: Thirty consecutive patients with HGG adjacent to the corticospinal tract (CST) met our inclusion criteria in a single-arm retrospective study. Bilateral diffusion tensor imaging (DTI)-derived corticospinal tract (CST) tractography was employed using a 1.5 Tesla magnetic resonance imaging (MRI). Oral 5-ALA was ingested with a dose of 20 mg/kg 4 hours prior to operation and was applied to qualify the margins of the local resection cavity. The clinical and volumetric assessments were postoperatively conducted. The mean preoperative tumor volume on T1 contrast-enhanced MRI and fluid-attenuated inversion recovery (FLAIR) images was 16.8 cm3 and 47.6 cm3, respectively. Complete resection of contrast-enhanced lesions was yielded in 27 of 30 patients (90%). All patients improved postoperatively regarding motor deficits and or seizures. No new permanent neurological deficits were detected in 3 months follow-up. Conclusion: Fluorescence image-guided surgery (FIGS) using 5-ALA increases the extent of resection (EOR) with further surgical risks in eloquent regions when combined with multimodality visualization- functional mapping. It also provides pathological insights to visualize cranial HGGs and identify infiltration of functional fiber tracts. [ABSTRACT FROM AUTHOR]

• Novel in vitro model of recurrent DFSP established for therapeutic evaluation. • Significant anti-tumor efficacy against DFSP model by 5-ALA PDT. • Inhibition of DFSP cell viability and induction of apoptosis by 5-ALA PDT. • Suppression of DFSP cell migration, invasion, and angiogenic potential by 5-ALA PDT. • Downregulation of key DFSP-related genes COL1A1 and PDGFRB by 5-ALA PDT. Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence. [ABSTRACT FROM AUTHOR]

Background and Aim: The extent of resection seems a solid prognostic factor in patients with high-grade gliomas (HGGs). When administered orally, 5-aminolevulinic acid (5-ALA) is exclusively converted into protoporphyrin IX (PPIX) by malignant cells and detects, identifying contrast-enhancing glial lesions under 400 nm blue light. The authors thoroughly assess the efficacy, accuracy, and safety profile of 5-ALA-guided surgery toward the maximal resection of cranial HGGs. Case Presentation: Thirty consecutive patients with HGG adjacent to the corticospinal tract (CST) met our inclusion criteria in a single-arm retrospective study. Bilateral diffusion tensor imaging (DTI)-derived corticospinal tract (CST) tractography was employed using a 1.5 Tesla magnetic resonance imaging (MRI). Oral 5-ALA was ingested with a dose of 20 mg/kg 4 hours prior to operation and was applied to qualify the margins of the local resection cavity. The clinical and volumetric assessments were postoperatively conducted. The mean preoperative tumor volume on T1 contrast-enhanced MRI and fluid-attenuated inversion recovery (FLAIR) images was 16.8 cm3 and 47.6 cm3, respectively. Complete resection of contrast-enhanced lesions was yielded in 27 of 30 patients (90%). All patients improved postoperatively regarding motor deficits and or seizures. No new permanent neurological deficits were detected in the 3-month follow-up. Conclusion: Fluorescence image-guided surgery (FIGS) using 5-ALA increases the extent of resection (EOR) with further surgical risks in eloquent regions when combined with multimodality visualization- functional mapping. It also provides pathological insights to visualize cranial HGGs and identify infiltration of functional fiber tracts.

5-aminolevulinic acid (5-ALA) has been extensively studied for its sustainability and broad-spectrum applications in medical research and theranostics, as well as other areas. It’s a precursor of protoporphyrin IX (PpIX), a sustainable endogenous and naturally-existing photosensitizer. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on 5-ALA research has not been reported so far, which would be of major importance to the relevant researchers. In this study, we collected all the research articles published in the last two decades from the Web of Science Core Collection database and employed bibliometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace. A total of 1595 articles were identified. The analysis results showed that China published the largest number of articles, and SBI Pharmaceuticals Co., Ltd. was the most productive institution that sponsored several of the most productive authors. The cluster analysis and burst detections indicated that the improvement of photodynamic efficacy theranostics is the up-to-date key direction in 5-ALA research. Furthermore, we emphatically studied nanotechnology involvement in 5-ALA delivery and theranostics research. We envision that our results will be beneficial for researchers to have a panorama of and deep insights into this area, thus inspiring further exploitations, especially of the nanomaterial-based systems for 5-ALA delivery and theranostic applications.

Abstract Background Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors. Methods We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection. Patients were given 20 mg/kg of 5-ALA orally 2 h prior to the surgery. High-powered excitation illumination and a low-pass filter (420, 450, or 500 nm) were used to visualize the fluorescence of protoporphyrin IX (PpIX), the 5-ALA metabolite. We evaluated the relationships between the fluorescence and histopathological findings in both tumoral and peritumoral brain tissue. Results Tumoral PpIX fluorescence was seen in only 5 patients (31%); in the remaining 11 patients (69%), there was no fluorescence in the tumor bulk itself. In 14 patients (86%), vague fluorescence was seen in peritumoral brain tissue, at a thickness of 2–6 mm. The histopathological examination found cancer cell invasion of adjacent brain tissue in 75% of patients (12/16), at a mean ± SD depth of 1.4 ± 1.0 mm (range 0.2–3.4 mm) from the microscopic border of the tumor. There was a moderate correlation between vague fluorescence in adjacent brain tissue and the depth of cancer cell invasion (P = 0.004). Conclusion Peritumoral fluorescence may be a good intraoperative indicator of tumor extent, preceding more complete microscopic gross total resection. Trial registration Institutional Review Board of Osaka Medical College No. 42, registered February 17, 1998, and No. 300, registered April 1, 2008. They were retrospectively registered.

In patients operated for malignant glioma, 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance is useful. However, we occasionally experience instances of non-visible fluorescence despite a histopathological diagnosis of high-grade glioma. We sought to identify factors that influence the intraoperative visualization of gliomas by their 5-ALA-induced fluorescence.

Objective: To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes., Methods: This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant., Results: At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol's iodine) significantly reduced ( p  < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)]., Conclusion: Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Hu, Xu, Jiang, Teng, Xu and Ma.)

• Application of combined continuous-pulse irradiation mode for vulvar leukoplakia PDT was investigated for the first time in this study. • Clinical research results indicate strong potential in utilizing such technology towards treatment of pathological vulvar diseases. • The developed treatment protocol is profitable in terms of price and healing effect and allows carrying out theranostics daily in 20 patients. • Selectivity of PDT' impact, absence of adverse reactions, and excellent cosmetic effect are the strengths of the applied approach. Using continuous-pulse irradiation mode application for performing photodynamic therapy sessions to introduce a new method, and conclude results of clinical research focused on vulvar leukoplakia photodynamic therapy efficiency in combination with topical aqueous «Alasens®» solution administration. Seventy patients (average age of 61 years) diagnosed with vulvar leukoplakia disease (2018 ICD-10-CM Diagnosis Code N90.4) were examined. The following values represent doses of combined mode photodynamic therapy session: 12 J/cm2 pulse radiation dose; 3.5 J/cm2 continuous radiation dose. Non-invasive spectroscopic and visual control of drug accumulation in real time was carried out by fluorescence diagnostic method before and after each therapy session. Single-therapy session efficiency was estimated by a fluorescent signal reduction in the pathological region after irradiation, and the direct correlation between photosensitizer photobleaching and disease regression was registered. Photodynamic therapy course included three procedures, with each session applied in 24 -h intervals, and when necessary, an additional course of therapy was applied 60 days afterward. Significant post-treatment results took effect after 2–3 courses with symptom presence reduced or fully regressed depending on the initial severity of the disease. Additionally, side effects and sequelae remained absent in all cases. The result of methods applied during the clinical research period indicate strong potential in utilizing such promising technology to contribute to the possible prevention of malignant transformation and the treatment of vulvar leukoplakia. [ABSTRACT FROM AUTHOR]

Introduction: Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells.Materials/Methods: A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs).Results: PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett's esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs.Conclusion: PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies. [ABSTRACT FROM AUTHOR]

The compound, 5-aminolevulinic acid (5-ALA) is approved for fluorescence-guided resections of malignant gliomas in Europe and other countries for use in adults, but not for children. The application of 5-ALA in children remains an off-label use. Several case reports on fluorescence-guided surgery use in children have been published, yet no prospective study has been conducted. Here we systematically review the reported studies and discuss the usefulness, application, and safety of 5-ALA use in resection of pediatric brain tumors. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630 ± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450 nm PDT comparing with ALA-635 nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo , immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450 nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635 nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspase-dependent apoptosis pathway. In vivo , ALA-450 nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450 nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases.HighlightsWe combined 5-aminolevulinic acid with 450 nm blue laser using as a novel type of photodynamic therapy.The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibition of the proliferation of End1 and HeLa cells and inducing cell apoptosis in vitro and in vivo .The ALA-450 nm PDT may provide a novel alternative therapeutic option in patients with persistent HPV infection and promote the integration of diagnosis and treatment.

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform is one of the most rapidly progressing cerebral tumors and the most aggressive one in our neurosurgical experience. We present the case of a 45 year old patient with very aggressive type of tumor who had come to our service for the following: intense headache, confusion, right hemiparesis installed approximately one month before. IRM scan shows up the presence of a large tumoral mass without a precise border in the left temporal-parietal region which had extended all the way down to the thalamus. The planned intervention used 5-aminolevulinic acid (5-ALA) for the precise removal of the tumor mass, suboptimal because of the risk of lesioning the motor tracts – indicated by the intraoperative electrophysiological monitoring. After surgery the outcome was good with the partial regression of the motor deficit, but only after 3 weeks due to the unexpected tumor growth the neurological status started to decay and even worsened. The patient underwent surgery again with the partial remission of the symptoms although following imagistic controls showed up fast tumor growth once more. He was recommended to oncology service for the beginning of radiotherapy. We consider the evolution and invasion of this tumor in only a 3 weeks period being impressive.

Metastatic melanoma (MM) has a poor prognosis and is attributed to late diagnoses only when metastases has already occurred. Thus, early diagnosis is crucial to improve its overall treatment efficacy. The standard diagnostic tools for MM are incisional biopsies and/or fine needle aspiration biopsies, while standard treatments involve surgery, chemotherapy, or irradiation therapy. The combination of photodynamic diagnosis (PDD) and therapy (PDT) utilizes a photosensitizer (PS) that, when excited by light of a low wavelength, can be used for fluorescent non-destructive diagnosis. However, when the same PS is activated at a higher wavelength of light, it can be cytotoxic and induce tumor destruction. This paper focuses on PS drugs that have been used for PDD as well as PDT treatment of MM. Furthermore, it emphasizes the need for continued investigation into enhanced PS delivery via active biomarkers and passive nanoparticle systems. This should improve PS drug absorption in MM cells and increase effectiveness of combinative photodynamic methods for the enhanced diagnosis and treatment of MM can become a reality.

Purpose: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. Methods: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. Results: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. Conclusion: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful. [ABSTRACT FROM AUTHOR]

Background: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors. Methods: We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection. Patients were given 20 mg/kg of 5-ALA orally 2 h prior to the surgery. High-powered excitation illumination and a low-pass filter (420, 450, or 500 nm) were used to visualize the fluorescence of protoporphyrin IX (PpIX), the 5-ALA metabolite. We evaluated the relationships between the fluorescence and histopathological findings in both tumoral and peritumoral brain tissue. Results: Tumoral PpIX fluorescence was seen in only 5 patients (31%); in the remaining 11 patients (69%), there was no fluorescence in the tumor bulk itself. In 14 patients (86%), vague fluorescence was seen in peritumoral brain tissue, at a thickness of 2-6 mm. The histopathological examination found cancer cell invasion of adjacent brain tissue in 75% of patients (12/16), at a mean ± SD depth of 1.4 ± 1.0 mm (range 0.2-3.4 mm) from the microscopic border of the tumor. There was a moderate correlation between vague fluorescence in adjacent brain tissue and the depth of cancer cell invasion (P=0.004). Conclusion: Peritumoral fluorescence may be a good intraoperative indicator of tumor extent, preceding more complete microscopic gross total resection. [ABSTRACT FROM AUTHOR]

Background. In patients operated for malignant glioma, 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance is useful. However, we occasionally experience instances of non-visible fluorescence despite a histopathological diagnosis of high-grade glioma. We sought to identify factors that influence the intraoperative visualization of gliomas by their 5-ALA-induced fluorescence. Patients and methods. We reviewed data from 60 patients with astrocytic or oligodendroglial tumors who underwent tumor removal under 5-ALA-induced fluorescence guidance between January 2014 and December 2015. Their characteristics, preoperative magnetic resonance imaging (MRI) findings, histological diagnosis, and genetic profile were analyzed and univariate and multivariate statistical analyses were performed. Results. In 42 patients (70%) we intraoperatively observed tumor 5-ALA fluorescence. They were 2 of 8 (25%) patients with World Health Organization (WHO) grade II, 9 of 17 (53%) with grade III, and 31 of 35 (89%) patients with grade IV gliomas. Univariate analysis revealed a statistically significant association between 5-ALA fluorescence and the isocitrate dehydrogenase 1 (IDH1) status, 1p19q loss of heterozygosity (LOH), the MIB-1 labeling index, and the tumor margin, -heterogeneity, and -contrast enhancement on MRI scans (p < 0.001, p = 0.003, p = 0.007, p = 0.046, p = 0.021, and p = 0.002, respectively). Multivariate analysis showed that the IDH1 status was the only independent, statistically significant factor related to 5-ALA fluorescence (p = 0.009). Conclusions. This study identified the IDH1 status as the factor with the most influence on the 5-ALA fluorescence of diffuse gliomas. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform is one of the most rapidly progressing cerebral tumors and the most aggressive one in our neurosurgical experience. We present the case of a 45 year old patient with very aggressive type of tumor who had come to our service for the following: intense headache, confusion, right hemiparesis installed approximately one month before. IRM scan shows up the presence of a large tumoral mass without a precise border in the left temporal-parietal region which had extended all the way down to the thalamus. The planned intervention used 5-aminolevulinic acid (5-ALA) for the precise removal of the tumor mass, suboptimal because of the risk of lesioning the motor tracts - indicated by the intraoperative electrophysiological monitoring. After surgery the outcome was good with the partial regression of the motor deficit, but only after 3 weeks due to the unexpected tumor growth the neurological status started to decay and even worsened. The patient underwent surgery again with the partial remission of the symptoms although following imagistic controls showed up fast tumor growth once more. He was recommended to oncology service for the beginning of radiotherapy. We consider the evolution and invasion of this tumor in only a 3 weeks period being impressive. [ABSTRACT FROM AUTHOR]

There is a growing interest in the physiological roles of reactive oxygen species (ROS) as essential components of molecular mechanisms regulating key cellular processes, including proliferation, differentiation and apoptosis. This interest has fostered the development of new molecular tools to localize and quantify ROS production in cultured cells and in whole living organisms. An equally important but often neglected aspect in the study of ROS biology is the development of accurate procedures to introduce a ROS source in the biological system under study. At present, this experimental requirement is solved in most cases by an external and systemic administration of ROS, usually hydrogen peroxide. We have previously shown that a photodynamic treatment based on the endogenous photosensitizer protoporphyrin IX and further irradiation of the target with adequate light source can be used to transiently switch on an in situ ROS production in human cultured keratinocytes and in mouse skin in vivo . Using this approach we reported that qualitatively low levels of ROS can activate cell proliferation in cultured cells and promote a transient and reversible hyperproliferative response in the skin, particularly, in the hair follicle stem cell niche, promoting physiological responses like acceleration of hair growth and supporting the notion that a local and transient ROS production can regulate stem cell function and tissue homeostasis in a whole organism. Our principal aim here is to provide a detailed description of this experimental methodology as a useful tool to investigate physiological roles for ROS in vivo in different experimental systems. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma (GBM) neurosurgical resection relies on contrast-enhanced MRI-based neuronavigation. However, it is well-known that infiltrating tumor extends beyond contrast enhancement. Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) was evaluated to improve extent of resection (EOR) of GBMs. Preoperative morphological tumor metrics were also assessed.Procedures: Thirty patients from a phase II trial evaluating 5-ALA FGS in newly diagnosed GBM were assessed. Tumors were segmented preoperatively to assess morphological features as well as postoperatively to evaluate EOR and residual tumor volume (RTV).Results: Median EOR and RTV were 94.3 % and 0.821 cm(3), respectively. Preoperative surface area to volume ratio and RTV were significantly associated with overall survival, even when controlling for the known survival confounders.Conclusions: This study supports claims that 5-ALA FGS is helpful at decreasing tumor burden and prolonging survival in GBM. Moreover, morphological indices are shown to impact both resection and patient survival. [ABSTRACT FROM AUTHOR]

Objective To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. Methods The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0 g/50 mL) was performed 180–240 min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. Results Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20 mg/kg/body. Conclusions ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20 mg/kg/body in the present study. [ABSTRACT FROM AUTHOR]

Treatment of patients with high-grade glioma (HGG) should begin with thorough evaluation by a specialized multidisciplinary team to determine whether or not the patient is appropriate for surgery, chemotherapy and radiotherapy. Particular attention should be paid to the performance status and neurological function. Surgery is the first step in therapeutic intervention. Patients undergo either biopsy, debulking surgery or maximal resection depending on the anatomical location of the tumour and the patient's clinical condition. Extent of resection has a prognostic value. In patients who are 'fit for surgery', the aim is to remove all contrast-enhancing tumour without causing neurological deficit. If microsurgical resection is not feasible, then a biopsy, either open or stereotactic, should be performed to confirm high-grade glioma diagnosis and to perform molecular genetic analyses (MGMT methylation status, loss of heterozygosity in 1p/19q, IDH1 status) as this has treatment implications. Over the past decade, much glioma research has focussed on novel surgical approaches to improve long-term outcomes. The evidence to support the benefit of maximizing extent of resection is growing. Advances in neurosurgical techniques allow safer, more aggressive surgery to maximize tumour resection whilst minimizing neurological deficit. Surgical adjuncts including advanced neuronavigation, intraoperative magnetic resonance imaging, high-frequency ultrasonography, fluorescence-guided microsurgery using intraoperative fluorescence, functional mapping of motor and language pathways, and locally delivered therapies are extending the armamentarium of the neurosurgeon to provide patients with the best outcome. Operating on elderly patients and those with recurrent disease, although controversial, is becoming more common due to emerging neurosurgical approaches. Here, we discuss the emerging surgical techniques and comment on the future of HGG surgery. [ABSTRACT FROM AUTHOR]

Highlights: [•] We invent a novel and effective photosensitizer chlorophyllin e4 with cheaper synthesis cost. [•] We examine autophagic changes of the bladder cancer cells in response to e4-PDT. [•] Autophagy inhibition could enhance the photodynamic effects of chlorophyllin e4. [Copyright &y& Elsevier]

Objective. Radiodynamic therapy (RDT) uses high-energy photon beams instead of visible/near-infrared light to treat deep-seated tumors that photodynamic therapy cannot achieve due to the low penetration depth of laser beams. The purpose of this study is to investigate the therapeutic effect of RDT with 15 MV photon beams combined with 5-aminolevulinic acid (5-ALA) using a mouse model. Approach. A subcutaneous C57BL/6 mouse model of KP1 small-cell lung cancer cell line was used. The tumors (N = 120) were randomized into four groups to observe individual and synergistic effects of 5-ALA and radiation treatment: control (untreated, N = 42), radiation treatment (RT) only (N = 20), 5-ALA only (N = 20), and RDT (N = 38). For the RT only and RDT groups, 4 Gy in a single fraction was delivered to the tumors using 15 MV photons. For the 5-ALA only and RDT groups, 5-ALA was injected at a dose of 100 mg kg -1 by tail-vein 4 h prior to RT. The tumor response was assessed by monitoring tumor growth using 1.5 T MR, maximum standardized uptake value (SUV max ) and total lesion glycolysis (TLG) using [ 18 F]FDG PET/CT, and animal survival. Main results. RDT achieved a statistically significant delay in tumor growth by 52.1%, 48.1%, and 57.9% 7 days post-treatment compared to 5-ALA only, RT only, and control group ( P <  0.001), respectively. There were no significant differences in tumor growth between 5-ALA only and RT only groups. An additional 38.5%-40.9% decrease in tumor growth was observed, showing a synergistic effect with RDT. Furthermore, RDT significantly decreased [ 18 F]FDG uptakes in SUV max and TLG 7 days post-treatment by 47.4% and 66.5% ( P <  0.001), respectively. RDT mice survived the longest of all treatment groups. Significance. RDT with 15 MV photons and 5-ALA resulted in greater tumor control compared to the control and other treatment groups. A significant synergistic effect was also observed with RDT. These preliminary results demonstrate an effective cancer treatment modality., (© 2022 IOP Publishing Ltd.)

Abstract: Melanoma, occurring as a rapidly progressive skin cancer, is resistant to current chemo- and radiotherapy, especially after metastases to distant organs has taken place. Most chemotherapeutic drugs exert their cytotoxic effect by inducing apoptosis, which, however, is often deficient in cancer cells. Thus, it is appropriate to attempt the targeting of alternative pathways, which regulate cellular viability. Recent studies of autophagy, a well-conserved cellular catabolic process, promise to improve the therapeutic outcome in melanoma patients. Although a dual role for autophagy in cancer therapy has been reported, both protecting against and promoting cell death, the potential for using autophagy in cancer therapy seems to be promising. Here, we review the recent literature on the role of autophagy in melanoma with respect to the expression of autophagic markers, the involvement of autophagy in chemo- and immunotherapy, as well as the role of autophagy in hypoxia and altered metabolic pathways employed for melanoma therapy. [Copyright &y& Elsevier]

Purpose: We evaluated the effectiveness of photodynamic therapy using Radachlorin® in patients with high grade, nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy who refused radical cystectomy. Materials and Methods: Between July 2009 and December 2011 photodynamic therapy was performed in 22 men and 12 women. Radachlorin (0.5 to 0.6 mg/kg) was injected intravenously 2 to 3 hours before photodynamic therapy. After complete transurethral resection, a diffuser using a 22Fr cystoscope was placed in the bladder for irradiation with a 662 nm laser. Output beam power was adjusted to 1.8 W and the light dose was 15 J/cm2. Photodynamic therapy was performed for 16 to 30 minutes. Recurrence after photodynamic therapy was followed by regular cystoscopy at 1, 2 and 3 months, and at 3-month intervals thereafter for up to 2.8 years. Efficacy was assessed by cystoscopy, cytology and histology, and defined as the number of patients who were tumor free after initial photodynamic therapy. Results: Mean ± SD patient age was 62.94 ± 8.71 years. Average followup was 26.74 ± 6.34 months (median 28.12). As the primary efficacy outcome, the recurrence-free rate was 90.9% at 12 months, 64.4% at 24 months and 60.1% at 30 months. As the secondary efficacy outcome, there was no statistical difference in mass size, carcinoma in situ, number of previous bacillus Calmette-Guérin administrations, number of transurethral bladder resections or tumor multiplicity on Kaplan-Meier analysis (each p >0.05). No evidence of severe adverse effects was detected after photodynamic therapy. Conclusions: Photodynamic therapy with Radachlorin is a safe, effective treatment for nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy in select patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Since the ATP-binding cassette transporter ABCG2 plays a physiologically significant role of porphyrin efflux from living cells, the expression of ABCG2 may influences the efficacy of photodynamic therapy (PDT). In this study, we evaluated the effect of gefitinib, a potent ABCG2 inhibitor, on 5-aminolevulinic acid (5-ALA)-PDT in brain tumor cell lines in vitro. Materials and methods: Four human glioma cell lines (U87MG, U118MG, A172, and T98G) and a malignant meningioma cell line (IOMM-Lee) were incubated with gefitinib (0.01–1.0μM) before incubation with 5-ALA (1mM). The effects gefitinib on intracellular protoporphyrin IX (PpIX), mRNA and protein expression of ABCG2, and PDT were evaluated, in vitro. Results: At concentrations of 0.1μM or higher, gefitinib enhanced intracellular levels of PpIX in a dose-dependent manner in all those cell lines. Gefitinib decreased mRNA and plasma membrane protein expression of ABCG2, and efficiently enhanced the effect of 5-ALA-PDT in malignant brain tumor cells. Conclusion: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect. [Copyright &y& Elsevier]

Abstract: Objective: Diffuse gliomas may harbor anaplastic foci which affect prognosis and determine adjuvant therapies. Such foci are not always detected by contrast-enhancement on MRI. Recently, other modalities have been introduced, such as FET-PET for pre-diagnostic imaging and 5-aminolevulinic derived tumor fluorescence for intraoperative identification of malignant glioma tissue. The relationship between these modalities and their value for guiding biopsies during resection has not yet been elucidated in the group of diffuse gliomas. Methods: FET-PET was performed in 30 consecutive patients with intracerebral lesions suggestive of diffuse gliomas on MRI with or without areas of contrast-enhancement. Prior to surgery patients were given 5-ALA at a dose of 20mg/kg body weight. Areas of FET uptake with a lesion/brain ratio of 1.6 or more were considered indicators of tumor. FET-PET data were corregistered with MRI data before surgery in order to obtain neuronavigated biopsies during resection, which were collected from FET positive and negative areas, analyzed for tumor fluorescence and correlated to contrast-enhancement on MRI. Results: 13 of 30 tumors were diagnosed as gliomas WHO Grade II, 15 as gliomas WHO Grade III and 2 as gliomas WHO Grade IV. The mean lesion/brain tissue ratio of FET uptake was significantly greater for high-grade than for low-grade gliomas (averages SD 2.323±0.754 vs. 1.453±0.538 p =0.0014). A match of FET-pos/ALA-pos biopsies was found in 70.6% (12/17) of high-grade gliomas (WHO Grade III/IV) but only in 7.7% (1/13) of low grade gliomas. Gd-neg/FET-neg/ALA-neg biopsies yielded a low-grade tumor in 46.2% (6/13). A mismatch between FET uptake and 5-ALA (FET-pos/ALA-neg) was found in 46.2% (6/13) of the low-grade and in 17.6% (3/17) of the high-grade tumors. The combination of FET-PET- and 5-ALA-positivity yielded a sensitivity for identifying high-grade glioma foci of 70.5% and a specificity of 92.3%. Conclusions: In low grade gliomas 5-ALA fluorescence is the exception and FET PET is more sensitive. High grade areas in diffuse gliomas with anaplastic foci usually fluoresce, if they are FET PET positive. As a result, FET PET appears valuable for pre-operative identification of anaplastic foci and hot spots are strongly predictive for ALA-derived fluorescence, which highlight anaplastic foci during resection. [Copyright &y& Elsevier]

Purpose: The aim of the study was to compare presurgical F-fluoroethyl- L-tyrosine (F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. Methods: F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for F-FET or Gd and checked for 5-ALA fluorescence. F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive. Results: Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III ( n = 19) or IV ( n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on F-FET PET. Conclusion: There are differences between F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. [ABSTRACT FROM AUTHOR]