ABSTRACT
OBJECTIVE: To study the effect of metabolic characteristics of the tumor determined by 99mTc-MIBI single-photon emission computed tomography (SPECT) and various molecular genetic features on the outcomes of combination treatment of hemispheric glioblastomas. MATERIAL AND METHODS: This single-center prospective cohort study involved 68 patients aged 25-78 years (38 males and 30 females) with primary glioblastomas. Hypermetylation of the promotor region of the MGMT gene was observed in 24 (42%) out of 57 patients. The IDH1 mutation was revealed in two (3.5%) patients. The catamnestic data were available for 66 out of 68 patients. The first SPECT/CT study was carried out before chemoradiation therapy; the second SPECT/CT study was performed after the chemoradiation therapy. In each study, quantitative measures were calculated for the early (15-30 min after the patient had received a radiopharmaceutical) and late (after 45-60 min) phases. RESULTS: The actuarial survival rates after 12 and 24 months were 69.6 and 29.1%, respectively. The median overall survival rate was 17.5 months (95% CI 12.9-20.3). Favorable prognostic factors for overall survival included the higher uptake index (UI) in the late phase compared to UI in the early phase of the first SPECT/CT study (p=0.0444), dynamics of changes in UI during the second SPECT/CT compared to baseline over 10% (p=0.0436), MGMT hypermethylation (p=0.0003), and duration of the period between surgery and initiation of chemoradiotherapy being <1 month (p=0.0008). No statistically significant correlations were revealed between the absolute UI values in the tumor and its molecular genetic features. CONCLUSION: The 99mTc-MIBI SPECT/CT can be used to predict overall survival and to plan radiation therapy of glioblastoma as it is more readily available at primary healthcare facilities than amino acid PET.
Subject(s)
Brain Neoplasms , Glioblastoma , Technetium Tc 99m Sestamibi , Adult , Aged , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , Female , Glioblastoma/diagnostic imaging , Glioblastoma/metabolism , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Radiopharmaceuticals , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
The technique to detect all possible variants of mutations in 12, 13 and 15 codons of gene KRAS was developed on the basis of the pyrosequencing technology. The analytical characteristics of the developed technique were identified. The limit of detection for mutations G34T, G35A and G38A detected on the cloned control samples consisted 3%. The limit of blank for various mutations consisted from 0.3% to 4.1%. The system was tested on clinical samples. The 7 different types of mutations were identified and detected in quantitative format. No discrepancy of pyrosequencing data with results of sequencing according Sanger was established.
Subject(s)
Codon/genetics , Colorectal Neoplasms/genetics , Point Mutation , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , DNA Mutational Analysis/methods , Female , Humans , Male , Proto-Oncogene Proteins p21(ras)ABSTRACT
Polymerase chain reaction was applied to human genomic DNA using primers corresponding to the rat substance P receptor cDNA. As a result, a fragment of 94 b.p. was isolated identical to the fragment 771-864 of the above-mentioned cDNA, with the exception of the G796----A substitution (Val----Ile in the amino acid sequence). A comparison of the established sequence with the published structures of tachykinin receptors of NK-1, NK-2 and NK-3 types allows its assignment to the substance P receptor (NK-1 tachykinin receptor) gene detected in the human genome.
