amphotericin-b and Brain-Neoplasms

Amphotericin B (AmB) resistance in Candida spp. is very rare. Three cases of fungemia, due to amphotericin B-resistant Candida spp. in pediatric patients after previous neurosurgery for brain tumors, are reported. The Candida strains - one C. guillermondii, one C. lusitaniae, and one C. parapsilosis - showed minimum inhibitory concentrations (MICs) to AmB of 2-4 microg/ml. Two of the three patients had been pretreated with AmB for 5-11 days. All three patients were successfully treated with intravenous fluconazole (6-10 mg/kg per day) for 16-28 days, and all survived. Despite AmB resistance in Candida spp. being very rare, C. lusitaniae, C. guillermondii, and C. parapsilosis isolates in documented infections should be tested for AmB resistance, mainly in patients not responding to therapy with AmB.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Brain Neoplasms; Candida; Candidiasis; Catheterization, Central Venous; Child; Child, Preschool; Craniotomy; Cross Infection; Drug Resistance, Microbial; Equipment Contamination; Fluconazole; Fungemia; Hospitals, Pediatric; Humans; Microbial Sensitivity Tests; Postoperative Complications; Slovakia; Species Specificity; Ventriculoperitoneal Shunt

Topics: Amphotericin B; Antifungal Agents; Brain; Brain Neoplasms; Child, Preschool; Diagnosis, Differential; Female; Humans; Meningitis

The authors report a case of aspergillus granuloma of the brain, in a 28 year old woman, simulating a meningioma. Preoperative diagnosis of aspergilloma is difficult. However, it may be suspected in a patient who has associated pulmonary and paranasal sinus fungal infection. Peroperatively it may be confused with a brain tumour. The lesions usually are in the frontal lobes. Diagnosis can be made only by surgical biopsy with identification of fungal elements. Granuloma induce a good host response, and a high capacity to elaborate antibodies.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Brain Diseases; Brain Neoplasms; Child; Diagnosis, Differential; Female; Flucytosine; Granuloma; Humans; Male; Meningioma; Middle Aged; Olfaction Disorders; 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

Topics: Amphotericin B; Antifungal Agents; Biopsy; Brain; Brain Neoplasms; CD4 Lymphocyte Count; Histoplasma; Histoplasmosis; HIV Infections; Humans; Itraconazole; Magnetic Resonance Imaging; Male; Middle Aged; Polymerase Chain Reaction; Treatment Outcome

Glioblastoma (GBM) is an aggressive brain cancer with a poor prognosis. The use of immune therapies to treat GBM has become a promising avenue of research. It was shown that amphotericin B (Amp B) can stimulate the innate immune system and suppress the growth of brain tumor initiating cells (BTICs). However, it is not feasible to use histopathology to determine immune activation in patients. We developed an MRI technique that can rapidly detect a therapeutic response in animals treated with drugs that stimulate innate immunity. Ultra-small iron oxide nanoparticles (USPIOs) are MRI contrast agents that have been widely used for cell tracking. We hypothesized that the increased monocyte infiltration into brain tumors due to Amp B can be detected using USPIO-MRI, providing an indicator of early drug response.. We implanted human BTICs into severe combined immunodeficient mice and allowed the tumor to establish before treating the animals with either Amp B or vehicle and then imaged them using MRI with USPIO (ferumoxytol) contrast.. After 7 days of treatment, there was a significantly decreased T2* in the tumor of Amp B but not vehicle animals, suggesting that USPIO is carried into the tumor by monocytes. We validated our MRI results with histopathology and confirmed that Amp B-treated animals had significantly higher levels of macrophage/microglia that were colocalized with iron staining in their brain tumor compared with vehicle mice.. USPIO-MRI is a promising method of rapidly assessing the efficacy of anticancer drugs that stimulate innate immunity.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Brain Neoplasms; Cell Tracking; Contrast Media; Dextrans; Disease Models, Animal; Humans; Magnetic Resonance Imaging; Magnetite Nanoparticles; Mice; Mice, SCID; Monocytes; Nanoparticles; Neoplastic Stem Cells; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

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

Topics: Amphotericin B; Antifungal Agents; Brain Diseases; Brain Neoplasms; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Histoplasmosis; Humans; Male; Middle Aged; Pons; Radiography

Topics: Amphotericin B; Antifungal Agents; Brain Neoplasms; Candida; Candida albicans; Candida glabrata; Candidiasis; Caspofungin; Child, Preschool; Drug Resistance, Fungal; Echinocandins; Humans; Immunocompromised Host; Lipopeptides; Male; Neuroectodermal Tumors; Neutropenia; Peptides, Cyclic; Time Factors

We report a patient with a history of prostate cancer and multiple myeloma, with a solitary indolent intracerebral mass lesion without any constitutional symptoms and minimal neurologic symptoms. The radiographic appearance of the lesion was that of a tumor but resection revealed a mycetoma, consistent with Aspergillus. A brief review of the literature discusses the rarity, presentation, diagnosis, and management of primary intracerebral mycetomas.

Topics: Aged; Amphotericin B; Antifungal Agents; Brain Neoplasms; Central Nervous System Fungal Infections; Diagnosis, Differential; Humans; Itraconazole; Magnetic Resonance Imaging; Male; Mitosporic Fungi; Multiple Myeloma; Mycetoma; Neoplasm Metastasis; Prostatic Neoplasms; Treatment Outcome

A 20-year-old man was admitted to our institution complaining of gradually worsening motor weakness in the right extremities. On admission, the radiological examination revealed a mass located in the left parietal region. On April 4, 1988, a left fronto-parietal craniotomy was performed and the tumor was subtotally removed. The pathological findings of the surgical specimen confirmed no specific tumor, but the presence of a small mingled Candida glabrata supported the diagnosis of fungal granuloma. Amphotericin B (AmB) was administered intravenously for the later enlargement of the tumor. MRI 4 weeks after the beginning of this treatment demonstrated the tumor to be prominently decreased in size. At discharge 3 months later, there was no tumor except only a minimal one in the paraventricular region. However, the recurrence of the tumor was discovered again over the next 8 months. AmB was administered as before, but the tumor continued to be enlarged. In May, 1990, surgery was performed again, and the histological diagnosis was germinoma accompanied with considerable granulomatous reaction. Subsequently, local irradiation was given and complete remission was maintained up to the present time 8 months after irradiation. AmB is a polyene antifungal antibiotic, that has also been reported to enhance the response of antitumor drugs to some tumors on the basis of increased tumor cell permeability. Recent investigations revealed that AmB had immunoadjuvant properties mediated through activated lymphocytes and macrophages, which resulted in an increased host resistance against infectious diseases and even tumors in vivo or in vitro studies. We reported a rare case of intracranial germinoma which responded well to AmB probably through its own antitumor effect caused by immunoadjuvant properties. We discussed the possibility of AmB to be used as immunoadjuvant agent or in combination with other antitumor drugs for the effective treatment of some tumors.

Topics: Adult; Amphotericin B; Brain Neoplasms; Dysgerminoma; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Male

We report a rare case of germinoma with granulomatous reaction arising from the corona radiata. This 20-year-old man was admitted to our hospital complaining of progressive motor weakness on the right side. CT demonstrated a poorly demarcated high density area in the left corona radiata, which was heterogeneously enhanced after administration of contrast medium. Moreover, the continuity of the mass to the ventricular wall was confirmed on MRI. At the first operation, subtotal removal of the tumor was performed through a fronto-parietal craniotomy. The diagnosis for the specific neoplasm was not established histologically, but granuloma caused by fungal infection was the most likely cause of the lesion. We tried amphotericin B (AmB), and remission of the tumor was obtained. However, during the following 3 months, the size of the tumor gradually enlarged again. AmB was repeatedly administered, but this time the treatment was ineffective. Six months later, on May 21, 1990, the second operation was performed and histological examination revealed typical germinoma consisting of two-cell pattern. Subsequently, the patient underwent focal irradiation of 33 Gy to the tumor site, and the tumor completely disappeared. As intracranial germinomas are observed to be successfully cured by radiotherapy and/or chemotherapy, choice of the therapeutic management must be carefully determined according to the histological diagnosis, especially in young people. A variety of locations of germinomas and the accompanying granulomatous reactions could create some diagnostic confusion, so great care must be taken in the treatment of much intracranial germinomas.

Topics: Adult; Amphotericin B; Brain Neoplasms; Cerebral Cortex; Combined Modality Therapy; Diagnosis, Differential; Dysgerminoma; Granuloma; Humans; Magnetic Resonance Imaging; Male

Cryptococcus neoformans (Torula histolytica) is an uncommon cause of infection in the central nervous system. We review 15 cases from all over Queensland which have presented in the last 6 years. Computed tomography (CT) studies were abnormal in 73.5%, with mass lesions and hydrocephalus being the commonest findings. Notable findings were: the disproportionate severity of clinical signs and symptoms as compared with the CT findings, which often were either normal or demonstrated only small granulomas without significant mass effect, absence of enhancement in granulomas in two cases and observation of calcification during treatment in one patient.

Topics: Adolescent; Adult; Aged; Amphotericin B; Brain Diseases; Brain Neoplasms; Cryptococcosis; Diagnosis, Differential; Female; Humans; Immune Tolerance; Male; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Tomography, X-Ray Computed; Tuberculosis, Meningeal

Thirty-four consenting patients received VM-26 50-100 mg/m2 I.V. before surgical resection of intracerebral tumor, and drug was measured using a high pressure liquid chromatographic technique. Sufficient tumor for analysis was obtained from 29 patients. Brain metastases (13 patients) had higher concentrations of VM-26 than did gliomas (13 patients). Concentrations were comparable in brain metastases and meningiomas (3 patients). Prolonged (24 h) infusion of VM-26 did not appear to result in higher tumor drug concentrations in 5 patients than did rapid (1 h) infusion in 24 patients. Pretreatment with Amphotericin-B 10 mg/m2 12 h and 1 h before VM-26 did not appear to have any effect on VM-26 uptake into 4 intracerebral tumors, although data were limited, and VM-26 concentrations were very high in 1 metastasis. Pretreatment with oral glycerol 500 mg/kg 18 h, 12 h, 6 h, and immediately before I.V. VM-26 may have resulted in increased penetration of VM-26 into 9 tumors, although confirmation is required. Amphotericin-B, glycerol, and operative conditions did not appear to alter VM-26 plasma pharmacokinetics.

Topics: Amphotericin B; Astrocytoma; Brain Neoplasms; Glycerol; Humans; Kinetics; Meningioma; Podophyllotoxin; Teniposide

The permeability of the blood-brain barrier (BBB) to methotrexate, Na+, and Cl- was studied in rats treated with the membrane-active antifungal agent amphotericin B. Enhancement of brain uptake of methotrexate was expected as amphotericin B increases the permeability of lipid membranes, including tumor cell membranes. However, amphotericin B had no effect of the BBB permeability to methotrexate, Na+, and Cl-. This may have been because the amphotericin B acted only on the luminal and not on the abluminal brain capillary membrane, leaving the BBB intact.

Topics: Amphotericin B; Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Chlorides; Drug Therapy, Combination; Male; Methotrexate; Rats; Rats, Inbred Strains; Sodium

We assayed the femoral marrows of individual AKR mice for leukemia colony-units (LCFU) after treatment with amphotericin B (AmB) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with BCNU alone. No differences between the groups were noted in the first 7 days after treatment. All the mice treated with BCNU alone were dead by day 8, and all the survivors among the animals receiving AmB and BCNU retained high levels of LCFU for 2 more days; these LCFU were subsequently rejected by the host. By day 12, LCFU were undetectable. Histologic examination of organs from the same mice on day 5 showed fewer leukemia cells in the mice treated with the combination of agents. In all treatment groups, mice dying of leukemia early (by day 9) had systemic leukemia and most had central nervous system (CNS) involvement. All animals dying between days 10 and 14 had CNS leukemia, but few had systemic leukemia; at later times, though few animals died, they invariably had CNS leukemia without systemic involvement.

Topics: Amphotericin B; Animals; Bone Marrow; Brain Neoplasms; Carmustine; Cell Division; Clone Cells; Drug Therapy, Combination; Female; Leukemia, Experimental; Mice; Mice, Inbred AKR; Time Factors

The membrane-active polyene, amphotericin B (AMB) has been shown to enhance or potentiate the effects of various chemotherapeutic agents against tumor cells in tissue culture. Because of the need to increase the efficacy of the nitrosoureas in brain-tumor chemotherapy, we have studied the effect of the nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), with or without AMB pretreatment. The intraperitoneal administration of 25 mg/kg of AMB 24 hours before 5, 10, 20 or 30 mg/kg of intraperitoneal CCNU did not result in a significant improvement in survival. The failure of intraperitoneal AMB to potentiate the effect of CCNU was likely a failure in drug delivery, since AMB crosses the blood-brain barrier very poorly. To circumvent the drug-delivery problem, AMB was administered intracerebrally directly into the tumor-bearing hemisphere. With 0.5 mg/kg of intracerebral AMB administered 24 hours before 10 mg/kg CCNU was given intraperitoneally, the life-span was significantly increased over the control group. The same dose of CCNU alone did not significantly increase survival. When 0.2, 0.5, or 1.0 mg/kg AMB was administered intracerebrally 24 hours before 20 mg/kg of interaperitoneal CCNU, survival was significantly increased over those groups receiving the same dose of CCNU alone. It is concluded that direct intracerebral administration of AMB enhances or potentiates the therapeutic effect of CCNU in this brain-tumor model.

Topics: Amphotericin B; Animals; Brain Neoplasms; Drug Synergism; Female; Lomustine; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Nitrosourea Compounds; Transplantation, Homologous

Topics: Amphotericin B; Animals; Bone Marrow Cells; Brain Neoplasms; Carmustine; Cell Survival; Clone Cells; Drug Synergism; Drug Therapy, Combination; Female; Kinetics; Leukemia, Experimental; Mice; Mice, Inbred AKR; Neoplasm Metastasis; Paralysis; Spinal Cord Neoplasms; Spleen; Subarachnoid Space

Topics: Adolescent; Adult; Aged; Amphotericin B; Astrocytoma; Brain Neoplasms; Female; Humans; Male; Middle Aged

Topics: Amphotericin B; Astrocytoma; Brain Neoplasms; Brain Stem; Candidiasis; Child; Female; Humans; Spinal Cord Neoplasms

Topics: Amphotericin B; Astrocytoma; Brain Neoplasms; Brain Stem; Child; Female; Humans

Topics: Amphotericin B; Astrocytoma; Brain Neoplasms; Brain Stem; Child; Female; Humans

Topics: Adolescent; Adult; Amphotericin B; Brain Abscess; Brain Neoplasms; Cerebral Ventriculography; Chronic Disease; Coccidioidomycosis; Complement Fixation Tests; Diagnosis, Differential; Female; Humans; Male; Meningitis; Skin Tests

Topics: Amphotericin B; Brain Neoplasms; Cerebral Cortex; Diagnosis, Differential; Drug Therapy; Histoplasmosis; Humans