BackgroundSo far, glioblastomas cannot be cured by standard therapy and have an extremely poor median survival of about 15 months. The photodynamic therapy (PDT) with next generation photosensitizers, reaching a higher therapeutic depth, might offer a new, adjuvant treatment strategy in brain cancer therapy. Here, we investigated the effect of THPTS-PDT combined with ionizing irradiation (IR) on glioblastoma cells in vitro and in vivo.ResultsTHPTS colocalized to mitochondria and was not found in the nucleus. THPTS (2–20 μg/ml)-PDT significantly reduced the proliferation, metabolic activity and clonogenic survival and induced cell death mainly through apoptosis and autophagy. THPTS-PDT combined with IR decreased the clonogenicity significantly compared to single treatments. THPTS (≤ 300 μg/ml) alone showed no dark toxicity. The maximum therapeutic depth of THPTS-PDT in C6 glioblastomas was 13 mm.Materials and MethodsThree human glioblastoma cell lines (U-87 MG, A-172, DBTRG-05MG) were incubated with THPTS (1–300 μg/ml) 3–24 hours before laser treatment (760 nm, 30 J/cm2). THPTS localization and effects on metabolic activity, proliferation, cell death mechanisms and long-term reproductive survival were assessed. IR was conducted on an X-ray unit (0.813 Gy/min). Results were verified in vivo on a subcutaneous C6 glioblastoma model in Wistar rats.ConclusionsThis study demonstrated efficient THPTS-PDT in glioblastoma cells, in vitro and in vivo. The combinatorial effects of THPTS-PDT and IR are of specific clinical interest as enhanced eradication of infiltrating glioblastoma cells in the tumor surrounding tissue might possibly reduce the commonly occurring local relapses.

Linseed oil (LO) is known for its exceptional nutritional value due to the high content of alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid; its anticarcinogenic effect has been established in several experimental and epidemiological studies. As an adjuvant of chemotherapeutic agents, LO and other ALA-rich vegetable oils have been studied in only a handful of studies at the experimental level. However, the efficacy of antitumoral therapy using doxorubicin (Dox) in combination with ALA and ALA-rich substrates has not yet been investigated. In this work, the antitumor activity of LO in a wide dose range was studied with monotherapy and combined with Dox in animal models with Pliss lymphosarcoma (PLS) and Lewis lung adenocarcinoma (LLC). It was founded the daily oral administration of LO (1, 3, and 10 ml per 1 kg) to rats (PLS) and 6 ml/kg to mice (LLC) for 11–12 days from 7 days after subcutaneous transplantation of tumors has a stable statistically significant effect on the dynamics of tumor growth, reducing the intensity of tumor growth and increasing the frequency of complete tumor regressions (CR) compared with the control. LO showed high antimetastatic activity in the LLC model. Furthermore, LO at a dose of 3 ml/kg potentiates the antitumor effect of Dox in the PLS model, reducing the volume of tumors at the end of treatment by 2.0 times (p = 0.013), the value of the tumor growth index by 1.6 times (p < 0.03) and increasing the frequency of CR 60 days after the start of therapy by 3.5 times (p = 0.019) compared with the use of Dox alone. The combination of Dox and LO or fish oil allows growing efficiency therapy of LLC in comparison with Dox alone, increasing the frequency of CR to 73.68% and 94.4%, respectively, and reducing the frequency of metastasis to zero.

IntroductionCancer is a global health concern, with a significant impact on mortality rates. Despite advancements in targeted antitumor drugs, the development of new therapies remains challenging due to high costs and tumor resistance. The exploration of novel treatment approaches, such as combined chemotherapy, holds promise for improving the effectiveness of existing antitumor agents. Cold atmospheric plasma has demonstrated antineoplastic effects in preclinical studies, but its potential in combination with specific ions for lymphosarcoma treatment has not been investigated.MethodsAn in vivo study was conducted using a Pliss lymphosarcoma rat model to evaluate the antitumor effects of composite cold plasma and controlled ionic therapy. Groups of rats were exposed to composite cold plasma for 3, 7, and 14 days, while the control group received no treatment. Additionally, a combination of chemotherapy with cold plasma therapy was assessed, with doxorubicin hydrochloride administered at a dosage of 5 mg/kg. PERENIO IONIC SHIELD™ emitted a controlled ionic formula during the treatment period.ResultsThe in vivo study demonstrated tumor growth inhibition in groups exposed to composite cold plasma for 3, 7, and 14 days compared to the control group. Furthermore, combining chemotherapy with cold plasma therapy resulted in a threefold reduction in tumor volume. The most significant antitumor effects were observed when doxorubicin hydrochloride at a dosage of 5 mg/kg was combined with 14 days of PERENIO IONIC SHIELD™ ionic therapy.DiscussionThe use of composite cold plasma therapy, in conjunction with a controlled ionic formula emitted by PERENIO IONIC SHIELD™, in the complex treatment of lymphosarcoma in rats showed promising antitumor effects. The combination therapy, particularly when combined with doxorubicin hydrochloride, demonstrated enhanced efficacy. These findings suggest the potential for utilizing cold atmospheric plasma and controlled ions as an adjunctive treatment approach in lymphosarcoma therapy. Further research is warranted to explore the mechanisms underlying these effects and to evaluate the safety and efficacy in human clinical trials.

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