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Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019 Page 21 of 24

29. The Di Bella method’s biological multi-therapy has improved the objective response,
expectation and quality of life of brain malignancies: Statistical evaluation at seven years

Giuseppe Di Bella, Roberta Scanferlato

Giuseppe Di Bella Foundation, Bologna, Italy

The interaction between growth hormone (GH) and prolactin receptor (PRL) acts on physiological and
neoplastic growth, which uses these factors on multiple physiological measures, with dose-dependent
relationship. From a review of the literature, GH and growth hormone receptor (GHR) overexpression in
tumors is constant. In more than a thousand cases published on www.pubmed.gov by Giuseppe and Luigi
Di Bella of various neoplasms, an improvement in the objective response, quality of life, and survival was
documented, compared to conventional oncological protocols, inhibiting GH and GF correlated through
somatostatin and analogs in the context of biological multi-therapy “Metodo Di Bella” (MDB).

Rationale-Mechanism of action of therapy. The Di Bella Foundation has been treating and monitoring for
nine years several cerebral neoplasms including oligodendrogliomas 2° and 3°, astrocytomas, glioblastomas
3°, anaplastic gliomas 2° and 3°, and anaplastic oligoastrocytomas.

• Somatostatin 3 mg - subcutaneous (every night - 12 h infusion)
• Slow Octreotide 20 mg intramuscular release (every three weeks)
• Conjugated Melatonin (Melatonin 12%, Adenosine 51%, and Glycine 37%) 100 mg (daily-oral)
• Retinoid solution - 8 mL oral (three times a day) (ATRA 0.5 g, Axeroftole Palm. 0.5 g, Beta Carotene 2 g,
and Alpha Tocopherol Acet. 1000 g)
• Vit. D3, 1.25; OH-Tachysterol, 10-12 drops (three times a day - oral)
• Tetracosactide Acetate 0.25 mg intramuscular (three times a week)
• Cabergoline 0.5 mg (½ cps) - oral (twice a week)
• Bromocriptine 2.5 mg (½ cps) - oral (twice a day)
• Temozolamide (20 mg/morning and evening) daily metronomic administration (morning and evening)
Hydroxyurea 500 mg at midday meal
• Ac. Slow release valproic 500 mg morning and evening
• Calcium Levofolinate capsules 22 mg per day
• Vit. C 2 gr (2 times a day)

Somatostatin + Octreotide with antiproliferative function and receptor saturation are interactive with
dopamine 2 receptor (D2R) agonist prolactin inhibitors, whose PRLR receptor is co-expressed with
GHR on cytosolic membranes. MDB multi-therapy with inhibition of GH-PRL proliferative axis and
GH-dependent growth factors (IGF1-FGF-VEGF-EGF) with anti-proliferative effect have increased life
expectancy, on average over six years, in the mentioned neoplasms.

The myelotoxicity of the metronomic use of Temozolamide-Hydroxyurea is contained by the
myeloprotective properties of melatonin and retinoid solution, which, with vitamins D3 and C, exert a
differentiating synergism, with antioxidant and immunomodulating activities; instead, with somatostatin
and prolactin inhibitors, they exert a cytostatic effect. For the still reduced survival of malignant brain
tumors (Glioblastoma, 15 months), we consider useful this biological multi-therapy of synergistic
and factorially interactive molecules, singularly managed by non-toxic antitumor activity, which act
centripetally on the myriad biological reactions of the tumoral life, bringing back to normal the vital
reactions deviated due to cancer.