Home page News Related Researches 2020-2029

Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development

Published on Friday, 03 September 2021

Abstract

Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas.

In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas.

Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas.

MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth.

Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy.

These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules.

Download the complete article

About his publication.

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Variable Part - Omega 3 Essential/Unsaturated Fatty Acids. From 1.5 grams up to 3.0 grams per day orally);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);