High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea.

Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors.

Evidence for the genesis of WHO grade II glioma in an asymptomatic young adult using repeated MRIs.

As the natural course of WHO grade II glioma (G2G) during their initial silent period is unknown, the G2G genesis and their "date of birth" are a matter of debate. Here, a left temporo-insular G2G was discovered incidentally in a 31-year-old man in 2009 (MRI performed for a Chiari malformation). The mean tumor diameter increased from 29 (April 2009) to 31 mm (October 2009) before surgery. Since we recently demonstrated that the growth rate is constant during the initial silent period in G2G, the extrapolation backward in time leads to date the glioma birth in 2002. This observation is in agreement with an MRI performed in 1997, where no signal abnormality was detected. To our knowledge, this is the first report demonstrating that the tumorigenesis of a G2G occurs during the young adult period. In addition, estimation of the date of birth may serve as a reproducible "starting point" when analyzing survivals in series of G2G.

Association between malaria incidence and all cancer mortality in fifty U.S. States and the District of Columbia.

BACKGROUND: There is a relationship between malaria in the United States and brain tumor incidence, seen in data on malaria outbreaks in 2004 from the Centers for Disease Control and Prevention and reports of brain tumor incidence by state from 19 US states. METHODS: In the present study, data from 50 US states and the District of Columbia on malaria outbreaks in 1994, compiled by the Centers for Disease Control and Prevention, was analyzed in relation to state by state all cancer mortality data, 1950-94, from the National Cancer Institute. RESULTS: There was a significant association of malaria incidence with all cancer mortality in 50 US states and the District of Columbia. The association was independent of state population size, percentage black population by state, and median population age. CONCLUSION: The association between malaria and cancer mortality can be possibly explained by the well established ability of Plasmodium to induce suppression of the immune system. A second explanation may be that the anopheles mosquito, the vector of malaria, transmits an obscure virus that initially causes only a mild transitory illness but much later predisposes to cancer.

Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition.

Inhibition of hypoxia inducible factor-1 (HIF-1) is an attractive therapeutic strategy to target the tumor microenvironment. However, HIF-1 inhibitors may have limited activity as single agents and combination therapies may be required. We tested the hypothesis that HIF-1 inhibition in a hypoxic-stressed tumor microenvironment, which could be generated by administration of antiangiogenic agents, may result in a more pronounced therapeutic effect. The activity of bevacizumab, either alone or in combination with the HIF-1alpha inhibitor topotecan, was evaluated in U251-HRE xenografts. Tumor tissue was collected at the end of treatment and changes in tumor oxygenation, angiogenesis, proliferation, apoptosis, HIF-1alpha levels, HIF-1 target genes, and DNA damage were evaluated. Bevacizumab decreased microvessel-density and increased intratumor-hypoxia, but did not induce apoptosis. Moreover, bevacizumab alone caused a significant increase of HIF-1-dependent gene expression in tumor tissue. Addition of a low dose of daily topotecan to bevacizumab significantly inhibited tumor growth, relative to mice treated with topotecan or bevacizumab alone (P < 0.01). The addition of topotecan to bevacizumab was also associated with profound inhibition of HIF-1 transcriptional activity, significant inhibition of proliferation, and induction of apoptosis. Importantly, DNA damage induced by topotecan alone was not augmented by addition of bevacizumab, suggesting that increased cytotoxic activity did not account for the increased antitumor effects observed. These results strongly suggest that combination of anti-vascular endothelial growth factor antibodies with HIF-1 inhibitors is an attractive therapeutic strategy targeting in the hypoxic tumor microenvironment.

Microfilariae of Wuchereria bancrofti in cyst fluid of tumors of the brain: a report of three cases.

Microfilariae of various nematodes, including Loa loa, Dirofilariae, and Onchocerca volvulus, have been identified in the central nervous system (CNS). The CNS, however, is a rare site for the isolation of microfilariae of Wuchereria bancrofti. To the best of our knowledge, the presence of microfilariae of W. bancrofti in tumor cyst fluids or cerebrospinal fluid has not been reported to date. We report three cases in which microfilariae were identified in the cyst fluid of tumors of the brain. Cyst fluid aspirated from space-occupying lesions in the thalamus and C6-D1 spinal segments in a 46-yr-old man and a 35-yr-old man, respectively, showed numerous microfilariae of W. bancrofti, along with fragments of tumor suggestive of glioma. In the third case, in a 12-yr-old boy, the fluid from the space-occupying lesion in the third ventricle showed microfilariae in a necrotic dirty background with a few squames and cholesteral crystals. Histopathologic examination of the tumor showed an anaplastic astrocytoma and a low-grade astrocytoma in the first two cases, respectively, and a craniopharyngioma in the third case. No microfilariae were identified on the histology sections.

Possible association between Taenia solium cysticercosis and cancer: increased frequency of DNA damage in peripheral lymphocytes from neurocysticercosis patients.

Helminths, particularly some Schistosoma species, have been associated with cancer in humans. Neurocysticercosis, produced by cysticerci of the helminth Taenia solium, has been associated with the emergence of brain tumours and haematological malignancies. Local tumours, such as glioblastoma, could be explained by the induction of DNA damage in cells surrounding the cysticercus and chronically exposed to an inflammatory host response. However, systemic effects such as haematological malignancies are not easy to understand. The present work was conducted in Mexico to find out whether DNA damage arises in peripheral lymphocytes in patients with neurocysticercosis. We utilized a highly sensitive technique to analyse chromosomal aberrations, in-situ hybridization with probes against chromosomes 1, 2 and 4, and in addition the blocked-cytokinesis technique was used to determine the formation of micronuclei, a peculiar form of DNA damage. The study was made in lymphocytes from 8 patients before and after the administration of praziquantel, 1 of the 2 drugs used for neurocysticercosis treatment. The frequencies of chromosome aberrations and micronuclei in peripheral blood lymphocytes were higher in the infected patients as compared to those observed both in healthy donors and in the group of patients after praziquantel therapy. Our results suggest that chromosome aberrations induced in peripheral cells during neurocysticercosis could be associated with the development of haematological neoplasias.

Colchicine decreases the infection by Toxoplasma gondii in cultured glial cells.

Addition of colchicine (2.5 x 10(-8)-1.25 x 10(-6) M) to cultures of glial cells infected with Toxoplasma gondii decreased the number of parasites up to 80% (P < 0.05) in comparison with controls. Our results indicate that colchicine could interfere with the infectious, or replicative mechanisms, or both, of Toxoplasma and place it as a candidate in the search for additional antitoxoplasmic therapy for those cases where the parasitic load is massive. Further studies in vivo must be made to confirm this finding and provide support for therapeutic trials.

Anti-parasitic effector mechanisms in human brain tumor cells: role of interferon-gamma and tumor necrosis factor-alpha.

Toxoplasma gondii, an obligate intracellular parasite, is able to replicate in human brain cells. We recently showed that interferon (IFN)-gamma-activated cells from glioblastoma line 86HG39 were able to restrict Toxoplasma growth. The effector mechanism responsible for this toxoplasmostatic effect was shown by us to be the IFN-gamma-mediated activation of indolamine 2,3-dioxygenase (IDO), resulting in the degradation of the essential amino acid tryptophan. In contrast, glioblastoma 87HG31 was unable to restrict Toxoplasma growth after IFN-gamma activation, and IFN-gamma-mediated IDO activation was weak. We observed that tumor necrosis factor (TNF)-alpha alone is unable to activate IDO or to induce toxoplasmostasis in any glioblastoma cell line tested. Interestingly, we found that TNF-alpha and IFN-gamma were synergistic in the activation of IDO in glioblastoma cells 87HG31, 86HG39 and U373MG and in native astrocytes. This was shown by the measurement of enzyme activity as well as by the detection of IDO mRNA in TNF-alpha + IFN-gamma activated cells. This IDO activity results in a strong toxoplasmostatic effect mediated by glioblastoma cells activated simultaneously by both cytokines. Antibodies directed against TNF-alpha or IFN-gamma were able to inhibit IDO activity as well as the induction of toxoplasmostasis in glioblastoma cells stimulated with both cytokines. Furthermore, it was found that the addition of L-tryptophan to the culture medium completely blocks the antiparasitic effect. We therefore conclude that both TNF-alpha and IFN-gamma may be involved in the defense against cerebral toxoplasmosis by inducing IDO activity as an antiparasitic effector mechanism in brain cells.

[Supportive therapy in brain tumors in children]. / Terapia di supporto nei tumori cerebrali infantili.

Recent advances in brain tumors therapy in infancy may be attributed not only to surgical, chemical and physical therapies improvement, but also to a more complete and accurated assistance to the neoplastic child. The constant support of an up-to-date and specialized laboratory and nursing staff may reduce the most common compliances of the neoplastic disease course and therapy. Neoplastic child with his family is facing a terrible stress, often with incumbent death risks. So a psychologic help is advisable for the whole family, and the best feeling is requested for the physicians. Supportive therapy must provide prevention and correction of the most common compliances of tumoral conditions, i.e. infections and hemorrhages . A correct and specific antibiotic therapy is absolutely necessary, but sometime is not sufficient. The introduction of hemoderivatives let us to spare the side effects of excessive whole blood transfusions, while the defective component may be selectively provided. Granulocyte transfusion recently introduced, may be the clue to the resolution of an overcoming infection.