Papers by Domenico Mastrangelo
Retinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential l... more Retinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so-called “tumor suppressor gene”, the Rb1 gene. The pathogenetic mechanism behind this tumor was first hypothesized by Knudson in 1971 and further confirmed by others who identified the Rb1 gene whose loss or inactivation was claimed to be responsible for the disease. However, after about four decades of continuous research in the field of molecular biology, the evidence behind the role of the Rb1 gene in Rb appears to be seriously flawed in the light of epidemiological, biological, and clinical evidences. This editorial summarizes the inconsistencies on this subject. Nevertheless, the molecular biology establishment still adheres to the biased view of the genetic origin of Rb and other cancers, and hardly any alternative explanations are taken into account. Copyright © 2009 Domenico Mastrangelo et al. This is an open access article distributed u...
Annals of Hematology, 2015
The effect of high doses of intravenous (sodium) ascorbate (ASC) in the treatment of cancer has b... more The effect of high doses of intravenous (sodium) ascorbate (ASC) in the treatment of cancer has been controversial although there is growing evidence that ASC in high (pharmacologic) concentrations induces dose-dependent proapoptotic death of tumor cells, in vitro. Very few data are available on the role of ASC in the treatment of acute myeloid leukemia (AML). Ascorbate behaves as an antioxidant at low (physiologic), and as pro-oxidant at pharmacologic, concentrations, and this may account for the differences reported in different experimental settings, when human myeloid cell lines, such as HL60, were treated with ASC. Considering the myeloid origin of HL60 cells, and previous literature reports showing that some cell lines belonging to the myeloid lineage could be sensitive to the pro-apoptotic effects of high concentrations of ASC, we investigated in more details the effects of high doses (0.5 to 7 mM) of ASC in vitro, on a variety of human myeloid cell lines including the following: HL60, U937, NB4, NB4-R4 (retinoic acid [RA]-resistant), NB4/AsR (ATO-resistant) acute promyelocytic leukemia (APL)-derived cell lines, and K562 as well as on normal CD34+ progenitors derived from human cord blood. Our results indicate that all analyzed cell lines including all-trans retinoic acid (ATRA)-and arsenic trioxide (ATO)-resistant ones are highly sensitive to the cytotoxic, pro-oxidant effects of high doses of ASC, with an average 50 % lethal concentration (LC 50) of 3 mM, depending on cell type, ASC concentration, and time of exposure. Conversely, high doses of ASC neither did exert significant cytotoxic effects nor impaired the differentiation potential in cord blood (CB) CD34+ normal cells. Since plasma ASC concentrations within the millimolar (mM) range can be easily and safely reached by intravenous administration, we conclude that phase I/II clinical trials using high doses of ASC should be designed for patients with advanced/refractory AML and APL.
Medical science monitor : international medical journal of experimental and clinical research, 2008
Retinoblastoma (Rb) is the most common primary malignant intraocular tumour in childhood. The &qu... more Retinoblastoma (Rb) is the most common primary malignant intraocular tumour in childhood. The "two hit" theory, formulated by Knudson in 1971 to explain the variegated clinical expression of the disease, led to the discovery of the so called tumour suppressor genes and the identification of the Rb1 as the prototype of such genes. Mutations of the Rb1 gene are now commonly believed to be the "cause" retinoblastoma, although epidemiological, clinical, and biological evidences argue against it. The Authors have performed a systematic review of available data concerning clinical and diagnostic aspects of retinoblastoma, including molecular genetics. Meta analysis of literature data has been performed in order to validate some of the predictions made by the two hit theory. The following theses are discussed in detail: 1) there is no difference in the age at diagnosis between unilateral and bilateral retinoblastoma; 2) the pathogenetic mechanisms underlying familial, h...
Medical and Pediatric Oncology, 2002
Medical and Pediatric Oncology, 2002
Ophthalmic Paediatrics and Genetics, 1991
In an attempt to verify some of the current conflicting results concerning the impact of relevant... more In an attempt to verify some of the current conflicting results concerning the impact of relevant prognostic factors in the retinoblastoma therapy, the authors took into consideration, for statistical analysis, the series of 459 cases included in the Italian Registry for retrospective study of retinoblastoma. Although this series appears large enough, problems related to the continuously changing approaches to the disease and the consequent lack of standardization often make it difficult to draw significant conclusions. Hence, while historical (retrospective) analysis often allows the manipulation of a great number of data, particularly in the case of relatively rare diseases, prospective randomized controlled trials are strongly recommended to standardize definitely the relevant prognostic criteria. These and other problems related to retrospective analysis are discussed in detail.
Journal of Neuro-Oncology, 2009
The purpose of this study was to describe the growth pattern of congenital malignant teratoid med... more The purpose of this study was to describe the growth pattern of congenital malignant teratoid medulloepithelioma of the ciliary body by reporting clinical and imaging findings with pathological correlation. An 11-month-old little girl presented with a whitish-pink iris mass in the right eye resulting from a small ciliary body mass consistent with medulloepithelioma at both clinical and computed tomography (CT) findings. At CT, the lesion showed heterogeneous attenuation, without intraocular calcifications. Eleven months later, clinical and ultrabiomicroscopy showed a clear enlargement of the mass, which invaded the pupil. At magnetic resonance imaging (MRI), the lesion showed T1-weighted hyperintensity and T2-weighted slight hypointensity when compared to the vitreous and a notch in the anterolateral aspect of the ipsilateral lens. After intravenous gadolinium administration, the lesion showed intense homogeneous enhancement, and there was leakage of gadolinium in the anterior chamber, resulting from impairment of blood-aqueous barrier. Biopsy revealed a malignant teratoid medulloepithelioma. The eye was then enucleated, and histology confirmed the diagnosis. Systemic chemotherapy and radiotherapy were not performed, since there was no extraocular extension. The 57-month clinical and MRI follow-up did not show disease relapse. This uncommon case displays the natural history of congenital malignant teratoid medulloepithelioma of the ciliary body. While the tumour might have been successfully treated by local excision at diagnosis, the delay in surgical treatment led to tumour overgrowth with consequent need for enucleation. The most important prognostic feature is extraocular extension, which carries a risk of local recurrence, eventually resulting in intracranial extension and/or lymphatic spread.
Journal of Cataract and Refractive Surgery, 1990
International Ophthalmology, 2014
This case report highlights the usefulness of Ultrasound Biomicroscopy (UBM) in a case of retinob... more This case report highlights the usefulness of Ultrasound Biomicroscopy (UBM) in a case of retinoblastoma which showed massive anterior chamber involvement after treatment with intra-arterial chemotherapy. UBM was used to document tumour pseudohypopion, cells in the aqueous humor, implanted clusters of cells on the corneal endothelium, iris nodules, lens capsule deposits and ciliary body invasion. The UBM data, compared with the histopathologic analysis, performed on eye tissue, after enucleation of the affected eye, revealed a significant concordance. UBM may represent an important diagnostic tool in retinoblastoma, when the decision about enucleation of the eye must be made in the absence of histopathologic data.
Experimental Eye Research, 1992
... 2. Shields CL，Meadows AT，Leahey AM，Shields JA.Continuing challenges in the management of Rb w... more ... 2. Shields CL，Meadows AT，Leahey AM，Shields JA.Continuing challenges in the management of Rb with chemotherapy.Retina，2004，24(6)：849-862. 3. Knudson AG：The genetics of childhood cancer.Cancer，1975，3(Suppl)：1022-1026. ...
American Journal of Ophthalmology, 2005
Medical science monitor : international medical journal of experimental and clinical research, 2007
According to the western medical establishment, homeopathy is both "unscientific" and &... more According to the western medical establishment, homeopathy is both "unscientific" and "implausible". A short overview of its history and the methods it uses, however, easily reveals that homeopathy is a true science, fully grounded on the scientific method and on principles, such as, among others, the Arndt-Schultz law, hormesis, and epitaxy, whose plausibility has been clearly and definitely demonstrated in a number of scientific publications and reports. Through a review of the scientific literature, an explanation of the basic principles of homeopathy is proposed based on arguments and evidence of mainstream science to demonstrate that, in spite of the claims of conventional medicine, homeopathy is both scientific and plausible and that there is no reasonable justification for its rejection by the western medical establishment. Hopefully, this hurdle will be overcome by opening academic institutions to homeopathy to enlarge the horizons of medical practice, re...
International Ophthalmology Clinics, 1993
European Journal of Ophthalmology, 2006
Leukocoria and strabismus are the most frequent presenting signs of retinoblastoma (RB) (1). Rare... more Leukocoria and strabismus are the most frequent presenting signs of retinoblastoma (RB) (1). Rare and atypical signs of RB include hypopyon, hyphema, retinal detachment, heterochromia, pain, buphthalmos, orbital cellulitis, proptosis, endophthalmitis, and phthisis bulbi (1-3). Unusual clinical signs of RB, which are commonly observed in older children (4), cause delay in diagnosis, resulting in poor prognosis. In unilateral phthisis, the diagnosis of RB is difficult, while the very rare combination of one phthisical eye and one buphthalmic eye has been reported as a presenting feature in bilateral RB (5). We report two girls with RB presenting with phthisis bulbi and contralateral buphthalmos and review the literature on the topic. PATIENTS AND METHODS The medical records of 321 RB were reviewed. A total of 111 patients had bilateral RB, 2 of them presenting with simultaneous phthisis bulbi and buphthalmos. Both patients underwent bilateral enucleation. Clinical reports, imaging studies, and histopathology were reviewed in each case and the data are critically analyzed. Case 1 A 30-month-old girl was referred to our center in 1987 for buphthalmos of the left eye and phthisis bulbi of the right eye. The left preauricular lymph node was enlarged. Examination under anesthesia (EUA) showed a phthisical right eye with a completely distorted anterior chamber and a thickened, opaque cornea measuring 6 mm in diameter. The left eye showed buphthalmos, with a hazy
Myeloid Leukemia, 2018
Vitamin C (ascorbic acid) is an essential nutrient with a number of beneficial effects on the hum... more Vitamin C (ascorbic acid) is an essential nutrient with a number of beneficial effects on the human body. Although the majority of mammals can synthesize their own Vitamin C, humans and a few other species, do not produce it and depend on dietary sources for their Vitamin C supply. Among its many effects on cell function and metabolism, Vitamin C has shown, in vitro, a powerful anticancer effect against a number of human tumor cell lines, including myeloid leukemia. There are many different mechanistic explanations for the anticancer/anti-leukemic effects of Vitamin C and the aim of the present review is to illustrate these mechanisms, showing the results of some preliminary in vitro investigations, and outlining their potential clinical relevance.
Journal of Integrative Oncology, 2016
The anticancer properties of Vitamin C (ascorbic acid o sodium ascorbate) are known since at leas... more The anticancer properties of Vitamin C (ascorbic acid o sodium ascorbate) are known since at least four decades, However, being a cheap and "natural" product, Vitamin C is not patentable and therefore has never been developed as an anticancer molecule. Recent in vitro investigations have confirmed the extraordinary antitumor properties of high doses of Vitamin C (sodium ascorbate), particularly when administered by the intravenous route, and phase I/II randomized, controlled clinical trials have been started to verify its anticancer properties in vivo. Unfortunately, the controlled clinical trials performed so far, do not confirm the extraordinary results obtained with Vitamin C (sodium ascorbate) in vitro. However, this may depend on a number of different factors, such as the pharmaceutical preparation (Sodium ascorbate may be more suitable than buffered ascorbic acid), the schedule of administration (slow infusion better than rapid infusion), tumor tissue oxygenation (Cancer tissue oxygenation is lower that oxygenation of tumor cell lines, in vitro), etc., which deserve further in depth investigation. Even with these limitations, Vitamin C (sodium ascorbate) in high doses, administered by intravenous route, beyond being extremely effective in vitro, against a number of human tumor cell lines, is safe, has minimal contraindications, improves the quality of life of patients, and is highly selective for cancer cells. The Authors discuss these important aspects and suggest possible solutions to improve the in vivo anticancer effects of Vitamin C (sodium ascorbate).
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Papers by Domenico Mastrangelo