Browsing by Author "Vargel, I."

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Open Access
Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma
(Wiley-Blackwell Publishing Ltd., 2015) Bozdogan, O.; Yulug, I. G.; Vargel, I.; Cavusoglu, T.; Karabulut, A. A.; Karahan, G.; Sayar, N.
Background: Basal cell carcinomas (BCCs) are common malignant skin tumors. Despite having a significant invasion capacity, they metastasize only rarely. Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs. Methods: A total of 96 BCC and 10 normal skin samples were included for the immunohistochemical study. Eleven frozen BCC samples were also studied by quantitative real time polymerase chain reaction (qRT-PCR) to detect the gene expression profile. Results: NM23-H1 was strongly and diffusely expressed in all types of BCC. Significant cytoplasmic expression of NDRG1 and E-cadherin was also detected. However, AKAP12 and CD82/KAI1 expression was significantly decreased. The expressions of the other proteins were somewhere between the two extremes. Similarly, qRT-PCR analysis showed down-regulation of AKAP12 and up-regulation of NM23-H1 and NDRG1 in BCC. Morphologically aggressive BCCs showed significantly higher cytoplasmic NDRG1 expression scores and lower CD82/KAI1 scores than non-aggressive BCCs. Conclusion: The relatively preserved levels of NM23-H1, NDRG1, and E-cadherin proteins may have a positive effect on the non-metastasizing features of these tumors.
Open Access
Focused RF hyperthermia using magnetic fluids
(WILEY, 2009-04-27) Tasci, T. O.; Vargel, I.; Arat, A.; Guzel, E.; Korkusuz, P.; Atalar, Ergin
Heat therapies such as hyperthermia and thermoablation are very promising approaches in the treatment of cancer. Compared with available hyperthermia modalities, magnetic fluid hyperthermia (MFH) yields better results in uniform heating of the deeply situated tumors. In this approach, fluid consisting of superparamagnetic particles (magnetic fluid) is delivered to the tumor. An alternating (ac) magnetic field is then used to heat the particles and the corresponding tumor, thereby ablating it. However, one of the most serious shortcomings of this technique is the unwanted heating of the healthy tissues. This results from the magnetic fluid diffusion from the tumor to the surrounding tissues or from incorrect localization of the fluids in the target tumor area. In this study, the authors demonstrated that by depositing appropriate static (dc) magnetic field gradients on the alternating (ac) magnetic fields, focused heating of the magnetic particles can be achieved. A focused hyperthermia system was implemented by using two types of coils: dc and ac coils. The ac coil generated the alternating magnetic field responsible for the heating of the magnetic particles; the dc coil was used to superimpose a static magnetic field gradient on the alternating magnetic field. In this way, focused heating of the particles was obtained in the regions where the static field was dominated by the alternating magnetic field. In vitro experiments showed that as the magnitude of the dc solenoid currents was increased from 0 to 1.8 A, the specific absorption rate (SAR) of the superparamagnetic particles 2 cm apart from the ac solenoid center decreased by a factor of 4.5, while the SAR of the particles at the center was unchanged. This demonstrates that the hyperthermia system is capable of precisely focusing the heat at the center. Additionally, with this approach, shifting of the heat focus can be achieved by applying different amounts of currents to individual dc solenoids. In vivo experiments were performed with adult rats, where magnetic fluids were injected percutaneously into the tails (with homogeneous fluid distribution inside the tails). Histological examination showed that, as we increased the dc solenoid current from 0.5 to 1.8 A, the total burned volume decreased from 1.6 to 0.2 cm3 verifying the focusing capability of the system. The authors believe that the studies conducted in this work show that MFH can be a much more effective method with better heat localization and focusing abilities.
Open Access
Metastasis suppressor proteins in cutaneous squamous cell carcinoma
(Elsevier, 2016-07) Bozdogan, O.; Vargel, I.; Cavusoglu, T.; Karabulut, A. A.; Karahan, G.; Sayar, N.; Atasoy, P.; Yulug, I. G.
Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.
Open Access
Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene
(BMJ Group, 2008) Kaplan, Y.; Vargel, I.; Kansu, T.; Akin, B.; Rohmann, E.; Kamaci, S.; Uz, E.; Ozcelik, T.; Wollnik, B.; Akarsu, N. A.
Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females.