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1.
J Med Case Rep ; 11(1): 209, 2017 Jul 27.
Article in English | MEDLINE | ID: mdl-28747219

ABSTRACT

BACKGROUND: The incidence of gemcitabine-induced hemolytic uremic syndrome has already been described in adults. Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic syndrome with different outcomes. One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein. CASE PRESENTATION: We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation. Afterwards he started maintenance chemotherapy with gemcitabine and oxaliplatin. After five courses he presented a progressive clinical worsening, which resulted in a systemic thrombotic microangiopathy. Initially he was treated with rituximab without clinical improvement. Therefore he started therapy with repeated cycles of eculizumab. After seven infusions he showed a gradual improvement and finally a complete remission of gemcitabine-induced hemolytic uremic syndrome. CONCLUSIONS: Eculizumab prevents serious complement-mediated vascular damage for chemotherapy-induced thrombotic microangiopathy in pediatric cases.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Complement Inactivating Agents/administration & dosage , Deoxycytidine/analogs & derivatives , Hemolytic-Uremic Syndrome/drug therapy , Cerebellar Neoplasms/drug therapy , Child, Preschool , Deoxycytidine/adverse effects , Fatal Outcome , Hemolytic-Uremic Syndrome/chemically induced , Hemolytic-Uremic Syndrome/diagnosis , Humans , Male , Medulloblastoma/drug therapy , Gemcitabine
2.
Anticancer Agents Med Chem ; 16(7): 810-5, 2016.
Article in English | MEDLINE | ID: mdl-26584727

ABSTRACT

The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies. The molecular characterization of Breast Cancer Resistance Protein (BCRP/ABCG2), as an ABC transporter conferring multidrug resistance (MDR), has stimulated many studies to investigate its activity on the BBB, its involvement in physiology and CNS diseases and its role in limiting the delivery of drugs in CNS. In this review, we highlight the activity and localization of BCRP on the BBB and the action that this efflux pump has on many conventional drugs or latest generation molecules used for the treatment of CNS tumors and other neurodegenerative diseases.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Blood-Brain Barrier , Central Nervous System Neoplasms/therapy , Neoplasm Proteins/metabolism , Neurodegenerative Diseases/therapy , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/metabolism , Humans , Neurodegenerative Diseases/metabolism , Nootropic Agents/pharmacokinetics , Nootropic Agents/therapeutic use , Tissue Distribution
3.
Am J Cancer Res ; 5(8): 2476-83, 2015.
Article in English | MEDLINE | ID: mdl-26396923

ABSTRACT

Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors.

4.
J Chemother ; 27(3): 128-38, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26058744

ABSTRACT

The aim of this study is to critically summarize the available data on the correlation between vitamin D level and tuberculosis (TB) infection. A literature search covering English language articles published up to 20 October 2014 was conducted in MEDLINE database. Three hundred ninety-seven articles were initially identified, of which 147 studies were initially selected, and other 13 pertinent studies were included. A significant association between low vitamin D levels and susceptibility to TB infection has been found.


Subject(s)
Mycobacterium tuberculosis/pathogenicity , Tuberculosis/complications , Vitamin D Deficiency/prevention & control , Vitamin D/therapeutic use , Humans , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosis
5.
BMC Infect Dis ; 14: 652, 2014 Dec 11.
Article in English | MEDLINE | ID: mdl-25494831

ABSTRACT

BACKGROUND: The aim of this study is to evaluate vitamin D levels in children with latent and active TB compared to healthy controls of the same age and ethnical background. METHODS: A multicenter observational study has been conducted in three tertiary care paediatric centres: Anna Meyer Children's University Hospital, Florence, Italy; Evelina London Children's Hospital, London, United Kingdom and Great Ormond Street Hospital, London, United Kingdom. Vitamin D was considered deficient if the serum level was <25 nmol/L, insufficient between 25 and 50 nmol/L and sufficient for a level >50 nmol/L. RESULTS: The study population included 996 children screened for TB, which have been tested for vitamin D. Forty-four children (4.4%) had active TB, 138 (13.9%) latent TB and 814 (81.7%) were controls. Our study confirmed a high prevalence of hypovitaminosis D in the study population. A multivariate analysis confirmed an increased risk of hypovitaminosis D in children with latent and active TB compared to controls [(P = 0.018; RR = 1.61; 95% CI: 1.086-2.388), (P < 0.0001; RR = 4.587; 95% CI:1.190-9.608)]. CONCLUSIONS: Hypovitaminosis D was significantly associated with TB infection in our study. Further studies are needed to evaluate a possible role of vitamin D in the treatment and prevention of tuberculosis in children.


Subject(s)
Tuberculosis/complications , Vitamin D Deficiency/complications , Vitamin D/blood , Adolescent , Biomarkers/blood , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Prevalence , Prospective Studies , Retrospective Studies , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/epidemiology
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