Methods: A comparative cross-sectional study involving 86 Malay premature babies (ROP = 41 and non-ROP = 45) was performed from September 2012 to December 2014. Mutation analyses in (FEVR)-causing genes (NDP, FZD4, LRP5, and TSPAN12) were performed using DNA from premature babies using polymerase chain reaction (PCR) and direct sequencing. Sequencing results were confirmed with PCR-Restriction Fragment Length Polymorphism (RFLP).
Results: We found variants of FZD4, LRP5, and TSPAN12 in this study. One patient from each group showed a non-synonymous alteration in FZD4, c.502C>T (p.P168S). A synonymous variant of LRP5 [c.3357G>A (p.V1119V)] was found in 30 ROP and 28 non-ROP patients. Two variants of TSPAN12, c.765G>T (p.P255P) and c.*39C>T (3'UTR), were also recorded (29 and 21 in ROP, 33 and 26 in non-ROP, respectively). Gestational age and birth weight were found to be significantly associated with ROP (P value < 0.001 and 0.001, respectively).
Conclusion: Analysis of data obtained from the ROP Malay population will enhance our understanding of these FEVR-causing gene variants. The c.3357G>A (p.V1119V) variant of LRP5, and c.765G>T (p.P255P) and c.*39C>T variants of TSPAN12 could be common polymorphisms in the Malay ethnic group; however, this requires further elucidation. Future studies using larger groups and higher numbers of advanced cases are necessary to evaluate the relationship between FEVR-causing gene variants and the risk of ROP susceptibility in Malaysian infants.
METHODS: A total of 50 patients with pathologically confirmed brain tumors (13 LGGs, 20 HGGs, and 17 meningiomas) were enrolled in this study. mtDNA was detected by using polymerase chain reaction (PCR) technique and later confirmed via Sanger DNA sequencing.
RESULTS: Overall, mtDNA was observed in 16 (32%) patients and it was significantly correlated with the type of tumor group and sex, being more common in the HGG group and in male patients.
CONCLUSION: The prevalence of mtDNA in Malaysian glioma and meningioma cases has been described for the first time and it was, indeed, comparable with previously published studies. This study provides initial insights into mtDNA in brain tumor and these findings can serve as new data for the global mitochondrial DNA mutations database.
METHODS: Brain tumor tissues and corresponding blood specimens were obtained from 45 patients. The ND3 10398A>G alteration at target codon 114 was detected using the PCR-RFLP analysis and later was confirmed by DNA sequencing.
RESULTS: Twenty-six (57.8%) patients showed ND3 10398A>G mutation in their tumor specimens, in which 26.9% of these mutations were heterozygous mutations. ND3 10398A>G mutation was not significantly correlated with age, gender, and histological tumor grade, however was found more frequently in intra-axial than in extra-axial tumors (62.5% vs. 46.2%, p<0.01).
CONCLUSION: For the first time, we have been able to describe the occurrence of ND3 10398A>G mutations in a Malaysian brain tumor population. It can be concluded that mitochondrial ND3 10398A>G alteration is frequently present in brain tumors among Malaysian population and it shows an impact on the intra-axial tumors.
PURPOSE AND METHOD: The present study was undertaken to explore the cytotoxicity and anticancer effects of DOXY and AZI on human GBM U87 cells via 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), Hoechst, Annexin V-FITC/PI, and clonogenic assays. CompuSyn software was used to determine the combination index (CI) for DOXY+AZI.
RESULT: Individual treatment with DOXY and AZI decreased U87 cell viability in dose- and time-dependent, and quantitatively comparable to TMZ. Nevertheless, combinations of both antibiotics evidenced antagonistic behaviour in U87 cells. Increased apoptotic event was also observed with the individual treatment of DOXY and AZI. Furthermore, the proliferative and clonogenic capability of 21-day survived U87 cells was completely terminated by DOXY and AZI, but not TMZ.
CONCLUSION: The antiproliferative and apoptosis-inducing activity exhibited by both antibiotics against U87 cells demonstrates their potential as a likely alternative to combat GBM. It would be interesting to find out more about their molecular players and cytotoxic effects in different types of GBM cells, including glioma stem cells (GSCs).
Materials and Methods: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds.
Results: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions.
Conclusion: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.