amphotericin-b and Glioma

Mucormycosis and aspergillosis are two opportunistic fungal infections, which can evolve into life-threatening complications. They generally affect patients with relevant risk factors such as immunocompromisation or long-term use of antibiotics or corticosteroids. Treatment usually combines medical and surgical approaches, often including extended necrosectomies, although the prognosis of generalized fungal infections is very poor. In this paper, we present the case of a 17-year-old girl affected by combined aspergillosis and mucormycosis, following treatment of a recurrent glioma. The patient was hospitalized for a suspected cellulitis of the right hemi-face, involving frontal maxillary area and the upper airways and was immediately put on intravenous antibiotic therapies; after performing nasal septum and maxillary biopsies, concomitant mucormycosis and aspergillosis were diagnosed and antimycotic therapy with liposomal B-amphotericin was administered. After evaluation by the oral surgeon and otolaryngologist, surgical cranio-facial necrosectomy was suggested, but refused by the parents of the patient. The girl died only few days later, due to a respiratory arrest. Awareness of this pathology with prompt diagnosis and early treatment may improve the outcome of these infections and reduce the mortality.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Brain; Coinfection; Facial Dermatoses; Fatal Outcome; Female; Glioma; Histocytochemistry; Humans; Magnetic Resonance Imaging; Maxilla; Microscopy; Mucormycosis; Recurrence; Stomatitis; Tomography, X-Ray Computed

Topics: Amphotericin B; Anti-Infective Agents; Biopsy; Brain Neoplasms; Central Nervous System Infections; Diagnosis, Differential; Diplopia; Face; Female; Gait Disorders, Neurologic; Glioma; Humans; Immunocompetence; Infections; Magnetic Resonance Imaging; Middle Aged; Neurosurgical Procedures; Paresthesia; Prototheca; Taste Disorders; Tetracycline

Brain tumor initiating cells (BTICs) contribute to the genesis and recurrence of gliomas. We examined whether the microglia and macrophages that are abundant in gliomas alter BTIC growth. We found that microglia derived from non-glioma human subjects markedly mitigated the sphere-forming capacity of glioma patient-derived BTICs in culture by inducing the expression of genes that control cell cycle arrest and differentiation. This sphere-reducing effect was mimicked by macrophages, but not by neurons or astrocytes. Using a drug screen, we validated amphotericin B (AmpB) as an activator of monocytoid cells and found that AmpB enhanced the microglial reduction of BTIC spheres. In mice harboring intracranial mouse or patient-derived BTICs, daily systemic treatment with non-toxic doses of AmpB substantially prolonged life. Notably, microglia and monocytes cultured from glioma patients were inefficient at reducing the sphere-forming capacity of autologous BTICs, but this was rectified by AmpB. These results provide new insights into the treatment of gliomas.

Topics: AC133 Antigen; Amphotericin B; Analysis of Variance; Animals; Annexin A5; Antigens, CD; Antineoplastic Agents; Brain Neoplasms; Bromodeoxyuridine; Calcium-Binding Proteins; Cell Cycle; Cell Differentiation; Chemokine CCL2; Coculture Techniques; Culture Media, Conditioned; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Flow Cytometry; Gene Expression Profiling; Glioma; Glycoproteins; Humans; Interleukin-1; Kaplan-Meier Estimate; Macrophages; Magnetic Resonance Imaging; Mice; Microfilament Proteins; Microglia; Neoplasm Transplantation; Nerve Tissue Proteins; Nitric Oxide Synthase Type II; Oligonucleotide Array Sequence Analysis; Peptides; Receptors, CCR2; RNA, Messenger; RNA, Small Interfering; Time Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Topics: Amphotericin B; Animals; Antineoplastic Agents; Brain Neoplasms; Glioma; Humans; Macrophages; Microglia; Tumor Cells, Cultured

Topics: Amphotericin B; Animals; Antineoplastic Agents; Brain Neoplasms; Glioma; Humans; Macrophages; Microglia; Tumor Cells, Cultured

We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections.. A 73-year-old man with a history of glioblastoma multiforme (GBM), on dexamethasone and status post radiation therapy and two cycles of temozolamide, presented with decreased level of consciousness for 24 h and was found to have cerebrospinal fluid (CSF) and blood cultures positive for Cryptococcus neoformans. A 33-year-old man with a history of anaplastic astrocytoma, on dexamethasone and status post radiation therapy, four cycles of temozolomide and two cycles of Lomustine (CCNU), presented with headache, dizziness and photophobia and was found to have CSF and blood cultures positive for Cryptococcus neoformans.. Both patients were treated with an initial regimen of amphotericin B and flucytosine for a minimum of two weeks and switched to fluconazole for 6 months to 1 year of treatment.. Patients with high-grade glioma treated with long-term corticosteroid therapy and chemotherapy are at increased risk of developing opportunistic infections. The two patients reported here developed cryptococcal meningitis and sepsis. Prophylactic regimens with either fluconazole or itraconazole currently exist that effectively decrease the incidence of both cryptococcal infections. Further investigations into the risk:benefit ratio of primary prophylactic therapy in this patient population may prove beneficial.

Topics: Adult; Aged; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents, Alkylating; Brain Neoplasms; Cerebrospinal Fluid; Cryptococcus neoformans; Dacarbazine; Dexamethasone; Fatal Outcome; Fluconazole; Flucytosine; Glioma; Humans; Immunosuppression Therapy; Lomustine; Male; Meningitis, Cryptococcal; Opportunistic Infections; Temozolomide; Treatment Outcome

In an attempt to modify the cytotoxicity of cisplatin, amphotericin B (AmB) was given as pretreatment to BDIX rats with intracerebral BT4C glioma implants. Ten animals given AmB 5 mg/kg i.p. followed by cisplatin 5 mg/kg i.p. displayed massive haematuria within 24 h after treatment and died a few days later. The antitumoral effect could not, therefore, be evaluated. Histopathological examination of the kidneys showed extensive tubular necrosis. No signs of apoptotic cell death were found using in situ end labelling with biotin-labelled nucleotides or with DNA integrity analysis in agarose gel electrophoresis. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the distribution of cisplatin in brain tumour, normal brain and kidney. Addition of AmB to cisplatin caused increased adduct formation in kidneys, particularly in tubular cells. It seems plausible that the nephrotoxicity, at least in part, was mediated by increased levels of cisplatin-DNA adducts. Pretreatment with AmB did not have any obvious effect on the formation of adducts in the cerebral cortex. The adduct levels in the tumours from animals pretreated with AmB were not significantly increased compared with those treated with cisplatin only. Thus, addition of AmB to cisplatin caused excessive nephrotoxicity suggesting a decrease in the therapeutic ratio of cisplatin.

Topics: Amphotericin B; Animals; Antineoplastic Agents; Apoptosis; Cisplatin; DNA Adducts; DNA, Neoplasm; Drug Interactions; Glioma; Kidney Tubular Necrosis, Acute; Neoplasm Transplantation; Rats; Rats, Inbred Strains

Topics: Amphotericin B; Animals; Cell Line; Concanavalin A; Glioma; Mice; Models, Biological; Neuroblastoma; Rats; Receptors, Concanavalin A; Receptors, Mitogen; Ricin