Glioblastoma Multiforme: Sensitivity to Antimicrobial Peptides LL-37 and PG-1, and Their Combination with Chemotherapy for Predicting the Overall Survival of Patients.

Background/Objectives: Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavorable clinical prognosis for affected patients. The objective was to analyze the sensitivity of GBM cells to the antimicrobial peptides (AMPs) cathelicidin (LL-37) and protegrin-1 (PG-1), both alone and in combination with chemotherapy, to predict overall survival (OS) in the patients. Methods: The study was conducted on 27 GBM patients treated in the neurosurgical department of the Almazov Medical Research Centre (Saint Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemotherapy, AMPs, and their combinations on brain tumor cells were assessed by an MTT assay using a 50% inhibitory concentration (IC50). Results: In GBM cells from the patients, LL-37 and PG-1 exhibited strong anticancer effects, surpassing those of chemotherapy drugs. These LL-37 and PG-1 anticancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by experiments on rats with C6 glioma, where the intranasal administration of LL-37 (300 µM) and PG-1 (600 µM) increased the life expectancy of the animals to 69 and 55 days, respectively, compared to 24 days in the control group (HR = 4.139, p = 0.0005; HR = 2.542, p = 0.0759). Conclusions: Additionally, the combination of LL-37 and PG-1 with chemotherapy drugs showed that a high IC50 of LL-37 with cisplatin (cutoff > 800 µM) in GBM cells was associated with increased life expectancy (19 vs. 5 months, HR = 4.708, p = 0.0101) and OS in GBM patients. These combinations could be used in future GBM treatments.

Blood DNA radiosensitivity may be predictive for efficacy of experimental glioma irradiation: an animal study.

OBJECTIVE: An animal study was conducted to evaluate the -association between blood DNA radiosensitivity, assessed by determining the original S-index, and the response of experimental gliomas to irradiation. Possible modifications of the latter after administration of iron-containing water (ICW) were also explored. METHODS: The study was performed on Wistar rats with subcutaneously implanted experimental glioma-35. The tumors were locally X-irradiated with a single 15 Gy dose. ICW (60-63 mg·Fe(2+)/l) was administered in the drinking water for 3 days before treatment. The animals underwent blood sampling for analysis of the DNA concentration and leukocyte count. DNA index was estimated 3 days before irradiation and 24 h thereafter. The S-index was evaluated within 4 h before irradiation. RESULTS: The mean initial S-index in the blood samples of glioma-bearing rats was 0.73 ± 0.05. Addition of ICW in vitro resulted in a significantly increased S-index in half of the samples. In general, the irradiated rats, which had been given pretreatment ICW and demonstrated an in vitro increase of the S-index to >1.0, showed the most marked inhibition of tumor progression and the smallest tumor volume 25 days after irradiation. They also exhibited the lowest rate of lesion growth and the longest survival. CONCLUSION: Determination of the biochemical S-index and evaluation of its changes in vitro caused by ICW may be predictive of the response of experimental glioma to irradiation. Because in vivo administration of ICW was associated with a somewhat better tumor response to treatment, it may be considered as a potential radiosensitizer.

The inhibitory effect of meadowsweet (Filipendula ulmaria) on radiation-induced carcinogenesis in rats.

PURPOSE: To examine the ability of the meadowsweet preparation to inhibit carcinogenesis induced by ionizing radiation in female rats. MATERIALS AND METHODS: The chemical composition of meadowsweet (Filipendula ulmaria) raw material (ethanol and aqueous extracts of meadowsweet flowers) has been studied for the presence of flavonoids, tannins and catechins. Adult female LIO strain rats were subjected to a single whole body γ-irradiation at a dose of 4 Gy in animal experiments. One group of irradiated rats served as control while the other group, starting from the 10th day after irradiation and until the end of the experiment, was given meadowsweet as a decoction of the flowers instead of drinking water. The average daily intake of meadowsweet (dry raw material) was 1 g/kg body weight. Rats were observed for 16 months. RESULTS: The analyzed meadowsweet extracts showed a sufficiently high content of flavonoids and tannins. In irradiated rats after 16 months the overall incidence of tumors was 79.6% (in 82 of 103 rats), the incidence of malignant tumors was 43.7% and the overall tumor multiplicity was 1.48. Most tumors were localized in the mammary gland - 57.3%. In rats that received meadowsweet, the incidence of all malignant tumors and overall multiplicity of tumors were significantly decreased by 1.5 and 1.3 times, respectively. The greatest reduction of many parameters has been identified for breast tumors: the overall incidence was decreased by 1.5 (p = 0.0174) and the overall multiplicity and multiplicity of malignant tumors - by 1.6 (p = 0.0002) and 2.2 (p = 0.0383) times, respectively. CONCLUSIONS: Meadowsweet preparation showed inhibiting activity on radiation carcinogenesis.

Anticarcinogenic activity of alpha-difluoromethylornithine, ginseng, eleutherococcus, and leuzea on radiation-induced carcinogenesis in female rats.

PURPOSE: To carry out a comparative study of inhibition of radiation carcinogenesis using alpha-difluoromethylornithine (DFMO), tinctures of ginseng, eleutherococcus and leuzea in female rats. MATERIALS AND METHODS: Locally bred female LIO-strain rats were subjected to a single whole body γ-irradiation dose of 4 Gy at 12 weeks of age. Modifying drugs were given with drinking water from the 10th day after irradiation until the end of the experiment (for 16 months). RESULTS: Irradiated rats developed tumors 70.0-79.6% (malignant tumors: 43.7-45.0%) with a multiplicity of 1.48-1.75 (malignant: 0.5-0.58), while in unirradiated animals the incidence of all/malignant tumors was 21.9%/7.7% with multiplicity of 0.22/0.08. In exposed rats tumors most often developed in the mammary gland - 57.3%, reproductive and endocrine organs - 27.2%, and other localizations - 29.1%. All drugs, except leuzea, significantly reduced incidence and multiplicity of tumors, overall or at some localizations in irradiated rats. Highest, and practically equal inhibition, was shown by ginseng and DFMO, while eleutherococcus was clearly inferior. Ginseng reduced overall tumor incidence and multiplicity by 1.5 and 2.4 times, malignant tumor incidence and multiplicity - by 2.5 and 2.9 times, respectively. CONCLUSIONS: The ginseng extract is the most promising radiation carcinogenesis inhibitor tested.