Orta Anadolu’daki Parkinson Hastalarında Homosistein ve MTHFR Polimorfizmleri Arasındaki İlişkinin Araştırılması ve Tedavi Seçenekleri

Aim In this study, we aimed to investigate the effects of MTHFR C677T and A1298C polymorphisms to homocysteine levels in patients with Parkinson's disease who were treated with levodopa and entekapone. Materials and Methods Plasma homocysteine (hcy), folic acid and vitamin B12 levels and MTHFR (C677T, A1298C) polymorphisms and treatment options were compared in 70 Parkinson's Disease (PD) patients who taking levodopa (n=26), dopamine agonist (n=11) and levodopa and entacapone treatment together (n=33) with 100 controls. Results Although no statistically significant difference was detected, hcy level of the patients was found higher compared to control group (patient 18.29 ± 9.22 µmol /l vs control 15.77 ± 7.58 µmol / l) and hcy level was highest in the patients receiving only levodopa (19.56 ± 10.77 µmol / l). The frequency of TT genotype in the patients was higher compared to the control group (11.4%, 6%). Especially, hcy level for levodopa-receiving patients with 677TT genotype became significantly higher level when compared with other genotypes of levodopareceiving patients (respectively 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59). No statistically significant difference was detected between patients and controls regarding their folic acid and vitamin B12 levels and A1298C polymorphism. Conclusion Finally, both 677TT genotype and levodopa treatment might be jointly contributed to the increasing of the plasma hcy levels in PD patients and entacapone limitedly decreased hcy levels during levodopa treatment. It can be said that results need to be supported with larger sample sized comprehensive studies.Amaç Çalışmamızda levodopa ve entekapon kullanan Parkinson hastalarında MTHFR genindeki C677T ve A1298C polimorfizmlerinin homosistein düzeyine etkilerini araştırmayı amaçladık. Materyal ve Metot 70 Parkinson (PD) hastasında; plazma homosisteini (hcy), folik asit, B12 vitamini seviyeleri, MTHFR (C677T, A1298C) polimorfizmleri ve tedavi seçenekleri karşılaştırıldı. 100 kişilik bir kontrol grubunun yer aldığı çalışmada, 70 hastanın 26’sı levodopa (n=26), 11’i dopamin agonisti (n=11) kullanırken, 33 hasta da levodopa ve entakapon tedavisini birliktealmaktaydı. Bulgular İstatistiki olarak anlamlı bir fark gözlenmese de, hastalardaki homosistein seviyesinin kontrol grubunda yer alanlara göre daha fazla olduğu tespit edildi (hasta 18.29 ± 9.22 µmol /l vs kontrol 15.77 ± 7.58 µmol/ l). Ayrıca homosistein seviyesinin en yüksek olduğu hasta grubunun sadece levodopa kullanan hastalar olduğu görüldü (19.56 ± 10.77 µmol / l). Hastalardaki TT genotipinin sıklığının da kontrol grubunda yer alanlara göre daha fazla olduğu görüldü (%11.4, %6). Özellikle, levodopa kullanan ve 677TT genotipine sahip olan hastalardaki homosistein seviyesi, levodopa kullanan ve diğer genotiplere sahip olan hastalardaki homosistein seviyesine göre anlamlı bir şekilde yüksek (sırasıyla 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59). Hastalar ve kontrol grubu arasında folik asit ve B12 vitamini seviyeleri ile A1298C polimorfizmi açısından anlamlı bir farka rastlanmadı. Sonuç Sonuç olarak; Parkinson hastalarında 677TT genotipinin ve levodopa kullanımının bir arada olmasının plazma homosistein seviyesini artırdığı, ayrıca entakaponun levodopa tedavisi esnasında sınırlı da olsa homosistein seviyesini düşürdüğü gözlemlenmiştir. Ancak sonuçların daha fazla örnek sayısı içeren kapsamlı çalışmalarla desteklenmesinin gerekli olduğu söylenebilir

Investigation of the Association of Homocysteine and MTHFR Polymorphisms and Treatment Options in Parkinson’s Disease in Central Anatolian Region*

AimIn this study, we aimed to investigate the effects of MTHFR C677T and A1298C polymorphisms to homocysteine levels in patients with Parkinson's disease who were treated with levodopa and entekapone.Materials and MethodsPlasma homocysteine (hcy), folic acid and vitamin B12 levels and MTHFR (C677T, A1298C) polymorphisms and treatment options were compared in 70 Parkinson's Disease (PD) patients who taking levodopa (n=26), dopamine agonist (n=11) and levodopa and entacapone treatment together (n=33) with 100 controls.ResultsAlthough no statistically significant difference was detected, hcy level of the patients was found higher compared to control group (patient 18.29 ± 9.22 μmol /l vs control 15.77 ± 7.58 μmol / l) and hcy level was highest in the patients receiving only levodopa (19.56 ± 10.77 μmol / l). The frequency of TT genotype in the patients was higher compared to the control group (11.4%, 6%). Especially, hcy level for levodopa-receiving patients with 677TT genotype became significantly higher level when compared with other genotypes of levodopa-receiving patients (respectively 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59). No statistically significant difference was detected between patients and controls regarding their folic acid and vitamin B12 levels and A1298C polymorphism.ConclusionFinally, both 677TT genotype and levodopa treatment might be jointly contributed to the increasing of the plasma hcy levels in PD patients and entacapone limitedly decreased hcy levels during levodopa treatment. It can be said that results need to be supported with larger sample sized comprehensive studies

Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools

Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups-and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET