phytochlorin and Glioma

To analyze specificity and sensitivity of 5-ALA and chlorin E6 fluorescence-guided navigation in malignant glioma surgery.. Fluorescence-guided navigation was analyzed in 50 patients (2 groups) with high-grade glioma. All patients were treated at the Polenov Russian Neurosurgery Institute. Chlorin E6 1 mg/kg intravenously (Photoditazin) was used as a fluorescence inducer in 25 patients (the 1st group), 5-ALA 20 mg/kg orally (Alasens) - in other 25 patients (the 2nd group). Each group included 10 patients with glioma grade III and 15 patients with glioma grade IV. Both groups were statistically representative (. In patients with glioma grade III, sensitivity of chlorin E6 fluorescence-guided navigation was 83.8%, 5-ALA fluorescence - 82.5%. Specificity was 66.7% and 64.1%, respectively. In patients with glioma grade IV, sensitivity was 87.7% for chlorin E6 and 88.3% for 5-ALA. Specificity was 85.2% and 88.1%, respectively.. Statistical analysis confirmed comparable high efficacy of both agents in surgery of malignant gliomas. Sensitivity and specificity of fluorescence-guided navigation with chlorin E6 and 5-ALA were similar (. Метаболическая навигация в хирургии злокачественных глиом — наиболее эффективный способ, позволяющий различить во время операции границу опухоли, достичь более радикальной резекции и, как следствие, увеличить межрецидивный интервал и продолжительность жизни.. Сравнительный анализ специфичности и чувствительности метода флуоресцентной навигации в хирургии злокачественных глиом с использованием двух различных индукторов флуоресценции.. Проведен сравнительный анализ флуоресцентной навигации у 50 пациентов (2 группы) с глиомой высокой степени анаплазии, находившихся на лечении в отделении нейроонкологии РНХИ им. проф. А.Л. Поленова. У 25 пациентов (1-я группа) в качестве индуктора флуоресценции использовали хлорин Е6 1 мг/кг внутривенно (фотодитазин), другие 25 пациентов (2-я группа) получили 5-аминолевулиновую кислоту (5-АЛА) перорально 20 мг/кг (аласенс). В каждой группе были 10 пациентов с анаплазией глиомы grade III и 15 пациентов с анаплазией grade IV. Обе группы статистически репрезентативны (. Для хирургии глиом grade III чувствительность метода составила 83,8% (хлорин E6), 82,5% (5-АЛА), специфичность — соответственно 66,7% и 64,1%. Для хирургии глиом grade IV чувствительность метода составила 87,7% (хлорин E6), 88,3% (5-АЛА), специфичность — соответственно 85,2% и 88,1%.. Статистический анализ показал сопоставимую высокую эффективность препаратов в хирургии злокачественных глиом. Чувствительность и специфичность метода для флуоресцентных препаратов хлорин E6 и 5-АЛА не показали статистически значимой разницы в достижении результата (

Topics: Aminolevulinic Acid; Brain Neoplasms; Chlorophyllides; Fluorescence; Glioma; Humans; Surgery, Computer-Assisted

In recent years, fluorescence navigation has been increasingly used in surgery for gliomas. In most studies, 5-ALA derivatives are used as fluorescence inducers. However, there are few data regarding E6 chlorin for these purposes.. To evaluate an effectiveness and feasibility of fluorescence navigation with chlorin E6 in surgery of brain gliomas.. The study included 30 patients with glial brain tumors grade II-IV. All patients were operated at the Polenov Russian Neurosurgical Institute. We used surgical microscope (Leica OHS-1), D-Light AF System (Karl Storz, Germany), original fluorescence module (St. Petersburg LOMO, developed by G.V. Papayan) and special software RSS Cam - Endo 1.4.313 for visual analysis of fluorescence. Histological examination included hematoxylin-eosin staining of specimens and immunohistochemical studies.. Fluorescence was weak in all patients with Grade II gliomas and strong in almost all patients with Grade III-IV gliomas. Sensitivity of fluorescence diagnosis with chlorin E6 was 72.2% for Grade II gliomas, 83.8% for Grade III gliomas and 87.7% for Grade IV. Specificity of this method was 60% for Grade II gliomas, 66.7% for Grade III gliomas and 85.2% for Grade IV.. Certain method of fluorescence imaging ensured resection of glial brain tumors using chlorin E6. Intensity of tumor fluorescence correlated with glioma malignancy grade. These results indicate that chlorin E6 is an effective photosensitizer for intraoperative fluorescence diagnosis in surgery for glioma.. В последние годы в хирургии глиом все чаще используется флюоресцентная навигация. В большинстве исследований в качестве индуктора флюоресценции применяются производные 5-аминолевулиновой кислоты (5-АЛК). Однако в источниках литературы мало сведений относительно использования препаратов хлорина Е6.. Оценить эффективность и возможность применения флюоресцентной навигации с хлорином Е6 в хирургии глиом разной степени злокачественности.. В исследование включены 30 пациентов с глиальными опухолями разной степени злокачественности (Grade II—IV). Все пациенты оперированы на базе РНХИ им. проф. А.Л. Поленова. Для визуального изучения флюоресценции использовалось оборудование в виде операционного микроскопа OHS-1 («Leica», Германия), установки D-Light AF System («Karl Storz», Германия), флюоресцентного модуля (АО «ЛОМО», Россия, разработка Г.В. Папаяна) и специального программного обеспечения RSS Cam — Endo 1.4.313. Для гистологического изучения биоптатов применяли окраску гематоксилином и эозином и выполняли иммуногистохимическое исследование.. На гистологическом уровне подтверждено, что интенсивность флюоресценции была слабой у всех пациентов с глиомами Grade II и сильной — почти у всех пациентов с глиомами Grade III—IV. Чувствительность метода флюоресцентной диагностики с хлорином Е6 для глиом Grade II составила 72,2%, Grade III — 83,8%, Grade IV — 87,7%. Специфичность метода для глиом Grade II составила 60%, Grade III — 66,7%, Grade IV — 85,2%.. Применение определенной методики флюоресцентной визуализации позволило проводить резекцию глиальных опухолей головного мозга с использованием хлорина Е6, при этом интенсивность флюоресценции опухоли коррелировала со степенью ее злокачественности. Полученные результаты свидетельствуют о том, что хлорин Е6 является эффективным фотосенсибилизатором для интраоперационной флюоресцентной диагностики в хирургии глиом.

Topics: Aminolevulinic Acid; Brain Neoplasms; Chlorophyllides; Fluorescence; Glioma; Humans; Neurosurgical Procedures; Porphyrins

To evaluate the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas based on surgical material morphological and immunohistochemical data.. The surgical material obtained from patients with high-grade (Grade III-IV) anaplastic glioma was examined. Along with histological examination, the proliferation marker Ki-67, the cell cycle transcription factor protein p53, and vascular endothelial growth factor (VEGF) were determined.. A significant direct correlation was found between the expression of Ki-67, p53, and VEGF and the fluorescence intensity of tumor tissues (. The technique of fluorescence navigation using chlorin e6 in comparative morphopathological analysis has confirmed its effectiveness in surgery for malignant gliomas.. Оценить эффективность флуоресцентной навигации с хлорином е6 в хирургии злокачественных глиом на основании данных морфологического и иммуногистохимического исследования операционного материала.. Исследован операционный материал, полученный от пациентов с глиальной опухолью головного мозга высокой степени анаплазии (Grade III—IV). Наряду с гистологическим исследованием определялись маркер пролиферативной активности Ki-67, транскрипционный фактор клеточного цикла белок p53, сосудистый эндотелиальный фактор роста (VEGF).. Установлена достоверная прямая корреляционная связь между показателями экспрессии Ki-67, p53, VEGF и интенсивностью флуоресценции тканей опухоли (. Методика флуоресцентной навигации с использованием хлорина e6 при сравнительном патоморфологическом анализе подтвердила свою эффективность в хирургии злокачественных глиом.

Topics: Brain Neoplasms; Chlorophyllides; Fluorescence; Glioma; Humans; Ki-67 Antigen; Porphyrins; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A

Gliomas are one of the most common types of primary brain tumors. Despite recent advances in the combination of surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy) and supportive therapy in the multimodal treatment of gliomas, the overall prognosis remains poor and the long‑term survival rate is low. Thus, it is crucial to develop a novel glioma management method. Due to its relatively non‑invasive, selective and repeatable characteristics, photodynamic therapy (PDT) has been investigated for glioma therapy in the past decade, exhibiting higher selectivity and lower side effects compared with those of conventional therapy. However, most of the photosensitizers (PSs) are highly hydrophobic, leading to poor water solubility, rapid degradation with clearance in blood circulation and ultimately, low bioavailability. In the present study, hydrophilic polyethylene glycol (PEG)‑chlorin e6 (Ce6) chelated gadolinium ion (Gd3+) nanoparticles (PEG‑Ce6‑Gd NPs) were synthesized via a chelation and self‑assembly process. Initially, the cell cytotoxicity of PEG‑Ce6‑Gd NPs was evaluated with or without laser irradiation. The in vitro study demonstrated the lack of toxicity of PEG‑Ce6‑Gd NPs to tumor cells in the absence of laser irradiation. However, its toxicity was enhanced under laser irradiation. Moreover, the size and weight of brain tumors were significantly decreased in mice with glioma xenografts, which was further confirmed via histological analysis. Subsequently, the results indicated that the PEG‑Ce6‑Gd NPs had a favorable T1‑weighted contrast performance (0.43 mg ml‑1 s‑1) and were observed to have significant contrast enhancement at the tumor site from 0.25 to 1 h post‑injection in vivo. The favorable MRI, as well as the synergetic photodynamic antitumor effect and antineoplastic ability of PEG‑Ce6‑Gd NPs was identified. It was suggested that PEG‑Ce6‑Gd NPs had great potential in the diagnosis and PDT treatment of gliomas, and possibly other cancer types, with prospects of clinical application in the near future.

Topics: Animals; Brain; Brain Neoplasms; Cell Line, Tumor; Chlorophyllides; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; Gadolinium; Glioma; Humans; Magnetic Resonance Imaging, Interventional; Mice; Multifunctional Nanoparticles; Photochemotherapy; Photosensitizing Agents; Polyethylene Glycols; Porphyrins; Rats

Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors.. ACHL: Angiopep-2-modified liposomes loaded with Ce6 and hydroxychloroquine; ACL: Angiopep-2-modified liposomes loaded with Ce6; BBB: blood brain barrier; Ce6: chlorin e6; CHL: liposomes loaded with Ce6 and hydroxychloroquine; CL: liposomes loaded with Ce6; CNS: central nervous system; DDS: drug delivery system; EB: Evans blue; FUS: focused ultrasound; HCQ: hydroxychloroquine; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MBs: microbubbles; MTG: MitoTracker Green; MTR: MitoTracker Red; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS: phosphate-buffered saline; PDI: polydispersity index; PINK1: PTEN induced kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; SDT: sonodynamic therapy; SQSTM1: sequestome 1; TA: terephthalic acid; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling; US: ultrasound; UTMD: ultrasound-targeted microbubble destruction.

Topics: Animals; Brain Neoplasms; Cell Death; Cell Line, Tumor; Cell Survival; Chlorophyllides; Drug Delivery Systems; Endocytosis; Female; Glioma; Low Density Lipoprotein Receptor-Related Protein-1; Mice; Mice, Inbred C57BL; Microbubbles; Mitochondria; Mitophagy; Nanoparticles; NIH 3T3 Cells; p38 Mitogen-Activated Protein Kinases; Particle Size; Peptides, Cyclic; Porphyrins; Protein Kinases; Reactive Oxygen Species; Signal Transduction; Somatostatin; Tissue Distribution; Ubiquitin-Protein Ligases; Ultrasonic Therapy

The aim of this study was to investigate the low-power density sonication, sonodynamic therapy (SDT) with Photolon and combination of SDT and photodynamic therapy (PDT) with Photolon for the ablation of glioma C6 tumor model in rats.. The study was performed on 50 rats bearing glioma C6. The tumors were sonicated with/without prior intravenous injection of photosensitizer (PS) Photolon (2.5 mg/kg b.w). Sonication was performed with 0.4; 0.7 and 1.0 W/cm² power density at 1 MHz frequency for 10 min, 2.0 h after Photolon administration using BTL-5710 Sono (BTL Industries Limited, Great Britain). PDT was carried out 2.5 h after Photolon administration using diode laser with 661 nm wavelength (IMAF-AXICON, Minsk, Republic of Belarus) at doses of 50 and 100 J/cm² with 0,17 W/cm² fluence rate. Assessment of tumor response was performed by vital staining with Evans blue and pathologic examination.. The maximal tumor necrosis area that underwent sonication (1 MHz; 0.7 W/cm²; 10 min.) followed by PDT at a dose of 100 J/cm² was 100%.. This is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models.

Topics: Animals; Brain Neoplasms; Chlorophyllides; Combined Modality Therapy; Disease Models, Animal; Glioma; Photochemotherapy; Photosensitizing Agents; Porphyrins; Povidone; Protoporphyrins; Rats; Sonication; Ultrasonic Therapy

To evaluate the impact of Photolon on cytostatic and cytotoxic effects of therapeutic range ultrasound in C6 glioma cells.. C6 glioma cells in suspension or monolayer cell culture were exposed to ultrasound (880 kHz, 0.2-0.7 W/cm2) in the presence or absence of Photolon at the concentration of 1 μg/ml in the culture medium, and then cell viability was evaluated.. Photolon increased the cytotoxic effect of ultrasound by 1.5-2.3-fold but had no effect on its cytostatic activity.. Photolon produces a pronounced sonosensitizing effect on glioma C6 cells and is a promising drug for sonodynamic treatment of malignant tumors.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cell Survival; Chlorophyllides; Glioma; Porphyrins; Povidone; Protoporphyrins; Rats; Tumor Cells, Cultured; Ultrasonic Therapy