Types Of Brain Cancer Research Articles

There is currently enough evidence and technology available to warrant taking immediate steps to reduce exposure of consumers to cell‐phone‐related electromagnetic radiation

There is currently enough evidence and technology available to warrant taking immediate steps to reduce exposure of consumers to cell‐phone‐related electromagnetic radiation

Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Carbonic anhydrase isozyme II (CA II) is a cytosolic enzyme that is highly expressed in most organs, including the brain, where it is mainly located in the oligodendrocytes. Recent studies have shown that its expression is induced in the endothelium of neovessels in melanoma and esophageal, renal, and lung cancer. Immunological studies further indicate that CA II represents a major target antigen stimulating an autoantibody response in melanoma patients. These results prompted us to investigate endothelial CA II expression in two types of brain cancer: oligodendrogliomas and astrocytomas. A series of 255 astrocytoma and 71 oligodendroglial tumor specimens was immunostained for CA II. The staining results were correlated with a number of different clinicopathological factors and survival data. CA II showed weak or no expression in low-grade tumors, while grade 3 mixed oligoastrocytoma and glioblastoma multiforme were the most positively stained tumor types. Survival analysis indicated that endothelial CA II staining is significantly associated with a poor prognosis in patients with astrocytomas. About 17% of patients with CA II-negative tumors (weak or no endothelial signal) were still alive at the end of the follow-up period of five years. The presence of CA II in the tumor endothelium suggests that it may play an important functional role in tumor metabolism. From a clinical perspective, the results also open new avenues for selecting tumor types for dendritic cell therapy trials.

Huntingtin Interacting Protein 1 Is a Novel Brain Tumor Marker that Associates with Epidermal Growth Factor Receptor

Huntingtin interacting protein 1 (HIP1) is a multidomain oncoprotein whose expression correlates with increased epidermal growth factor receptor (EGFR) levels in certain tumors. For example, HIP1-transformed fibroblasts and HIP1-positive breast cancers have elevated EGFR protein levels. The combined association of HIP1 with huntingtin, the protein that is mutated in Huntington's disease, and the known overexpression of EGFR in glial brain tumors prompted us to explore HIP1 expression in a group of patients with different types of brain cancer. We report here that HIP1 is overexpressed with high frequency in brain cancers and that this overexpression correlates with EGFR and platelet-derived growth factor beta receptor expression. Furthermore, serum samples from patients with brain cancer contained anti-HIP1 antibodies more frequently than age-matched brain cancer-free controls. Finally, we report that HIP1 physically associates with EGFR and that this association is independent of the lipid, clathrin, and actin interacting domains of HIP1. These findings suggest that HIP1 may up-regulate or maintain EGFR overexpression in primary brain tumors by directly interacting with the receptor. This novel HIP1-EGFR interaction may work with or independent of HIP1 modulation of EGFR degradation via clathrin-mediated membrane trafficking pathways. Further investigation of HIP1 function in brain cancer biology and validation of its use as a prognostic or predictive brain tumor marker are now warranted.

Increased cure rate of glioblastoma using concurrent therapy with radiotherapy and arsenic trioxide

Purpose Patients with glioblastoma multiforme (GBM) do extremely poorly despite aggressive therapy with surgery, radiotherapy (RT), and chemotherapy. In an effort to increase the efficacy of therapy for GBM, we studied the efficacy of arsenic trioxide (ATO) combined with high-dose RT in GBM cells in vitro and GBM xenograft tumors in nude mice. Methods and materials Human glioblastoma cell line SNB75 cells were irradiated in vitro with doses of 0–15 Gy with or without ATO. Clonogenic assays were used to generate radiation survival curves. Intracellular reactive oxygen species and apoptosis induced by ATO and RT were measured. The therapeutic efficacy of ATO alone, local tumor RT alone, and the combined therapy was tested in nude mice bearing established s.c. SNB75 tumors. A single RT dose of 20 Gy was administered locally to tumors. ATO at 10 mg/kg was injected i.p. 10 min after RT for the in vivo experiments. Results Radiation survival curves of GBM SNB75 cells demonstrated that a dose of 0.2 μM ATO increased radiation-induced cell killing by 2 logs at 10 Gy. ATO at 1 μM decreased survival from 4 × 10 −2 after 7 Gy of RT alone to 4 × 10 −5. A time-course experiment demonstrated that the greatest level of cell killing occurred when ATO was administered immediately before or within 2 hours after RT. To test the therapeutic efficacy of this combined treatment regimen in vivo, nude mice with established SNB75 GBM tumors were treated with a single local tumor dose of 20 Gy of RT with or without ATO (10 mg/kg × two doses) administered weekly. Appropriate control groups were included as well. ATO alone did not inhibit tumor growth. RT at 20 Gy alone inhibited tumor growth by 45 days, with regrowth of tumors thereafter. The combination of RT and ATO resulted in complete regression of the tumors in 4 of 5 mice without tumor regrowth for up to 4 months. The fifth mouse in the combined treatment group had a 90% reduction in tumor size without progression during the 4-month follow-up period. Furthermore, ATO alone and in combination with RT did not produce any obvious signs of toxicity. Conclusion These results have demonstrated that ATO increases intracellular levels of reactive oxygen species, induces apoptosis, and enhances the radiation cell killing of GBM cells. RT combined with ATO was an effective treatment for GBM tumors in this preclinical model. These preclinical results are encouraging and provide a rationale for further study of ATO combined with RT for the treatment of GBM and other histologic types of brain cancer using a variety of RT schemes.

High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma.

Temozolomide (SCH 52365; TEMODAL) is an antineoplastic agent with activity against a broad spectrum of murine tumors. This compound is currently marketed in the European Union for the treatment of patients with glioblastoma multiforme and anaplastic astrocytoma, which are serious and aggressive types of brain cancers. It has been postulated that temozolomide exerts its in vivo activity via the decomposition product MTIC, which is believed to alkylate nucleophiles, and in the process is converted to AIC. A high-performance liquid chromatographic (HPLC) method was developed and validated for the analysis of temozolomide in human plasma. The determination of temozolomide involved extraction with ethyl acetate followed by separation on a reversed phase C-18 column and quantification by UV absorbance at 316 nm. The calibration curve was linear over a concentration range of 0.1-20 microg/ml. The limit of quantitation was 0.1 microg/ml, where the coefficient of variation (CV) was 0% and the bias was 10.0%. The method was precise with a coefficient of variation ranging from 2.5 to 6.9% and accurate with a bias ranging from 5.0 to 10.0%. Temozolomide was unstable at 37 degrees C in human plasma with a degradation t1/2 of 15 min; however, it was stable at 4 degrees C for at least 30 min. Temozolomide was stable in acidified human plasma (pH < 4) for at least 24 h at 25 degrees C, and for at least 30 days at -20 degrees C. Moreover, temozolomide was stable in acidified human plasma after being subjected to three freeze thaw cycles. The assay was shown to be specific, accurate, precise, and reliable for use in pharmacokinetic studies.

Single-chain Fv/folate conjugates mediate efficient lysis of folate-receptor-positive tumor cells.

Bispecific antibodies that bind to a tumor antigen and the T cell receptor (TCR) redirect cytotoxic T lymphocytes (CTL) to lyse tumor cells which have escaped normal immune recognition mechanisms. One well-characterized tumor antigen, the folate receptor (FR), is expressed on most ovarian carcinomas and some types of brain cancer. Recently, it was shown that conjugates of folate and anti-TCR antibodies are extremely potent bispecific agents that target tumor cells expressing the high-affinity folate receptor, but not normal cells expressing only the reduced folate carrier protein. In this paper, it is shown that the size of these conjugates can be reduced to the smallest bispecific agent yet described (30 kDa) by attaching folate to a single-chain antibody, scFv, of the anti-TCR antibody KJ16. The scFv/folate conjugates are as effective as IgG/folate conjugates in mediating lysis of FR4 tumor cells by CTL. The optimal folate density was in the range of 5-15 folate molecules per scFv or IgG molecule, which yielded half-maximal lysis values (EC50) of approximately 40 pM (1.2 ng/mL for scFv). Finally, the scFv/folate conjugates could efficiently target tumor cells even in the presence of free folic acid at concentrations that are normally found in serum. Compared to conventional bispecific antibodies, the small size of scFv/folate conjugates may prove advantageous in the ability to penetrate tumors and in reduced immunogenicity.

Descriptive epidemiology of primary cancer of the brain, cranial nerves, and cranial meninges in New Zealand, 1948?88

We used New Zealand data on occurrence of different types of brain cancer to investigate: (i) a possible secular increase which has been seen worldwide and has generated considerable debate; (ii) possibly higher rates among Maori; and (iii) possibly higher risks related to social class and occupation. Data from the NZ Cancer Registry on the 5,684 brain cancers diagnosed among NZ residents from 1948-88 were used to study the pattern of occurrence by gender, age, race, calendar year, social class, occupation, and histology. Age-standardized brain-cancer incidence rates per 100,000 more than doubled over the 41-year period (from 2.9 to 6.9 in males and from 2.1 to 5.1 in females). A strong trend of increasing incidence with increasing social class is seen in males (Ptrend = 0.01). Among Maori, the proportion of all brain cancer that is medulloblastoma is four times that among non-Maori, and the proportion of all brain cancers that lack histologic confirmation is about 40 percent higher. Elevated risks are seen among: dairy farmers (odds ratio [OR] = 3.4, 95 percent confidence interval [CI] = 1.9-6.0); sheep handlers (OR = 2.7, CI = 1.4-5.3); livestock workers (OR = 3.8, CI = 1.7-8.4); and farm managers (OR = 3.2, CI = 1.4-7.2); as well as among electrical engineers (OR = 8.2, CI = 20-34.7); electricians (OR = 4.6, CI = 1.7-12.2); and other electrical workers. Brain cancer rates in NZ have increased steadily since 1948, but this increase has leveled off in the most recent five-year period. Although brain cancer rates are likely to be underestimated among the Maori, an excess of medulloblastoma is evident in this group.