The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance... more The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance (MDR) observed before and after the treatment. For this reason in MM cases an early resistance to treatment can be developed or the disease can relapsed in early period. Yet, there has been no improved drug resistance against proteazom inhibitor Bortezomib (Bor), which is used alone or with other chemotherapeutic agents in resistant or relapsed MM cases. In this study, bortezomib resistant human MM cell lines; RPMI-8226, secreting lambda light chain, and ARH-77, secreting IgG, were developed and responsible resistance mechanisms were investigated. For this purpose, by exposing to the cells to sequentially gradual doses of Bor in vitro conditions, resistant cell lines were acquired throughout one year. The IC50 values for Bor were determined after 48 hour incubation by MTT cytotoxicity assay (IC50:1,16nM for RPMI-8226 and IC80:0,6nM for ARH-77) against wild type cells. Throughout one yea...
Amaç: Histon deasetilazların değişmiş ifadesi hematolojik maligniteler için kanser tedavisinde he... more Amaç: Histon deasetilazların değişmiş ifadesi hematolojik maligniteler için kanser tedavisinde hedef olabilecek niteliktedir. HDAC mutasyonları ve anormal ifade seviyeleri çeşitli kanser tiplerinde ve özellikle hematolojik malignitelerde sıklıkla görülmekte olduğu, çocukluk çağı lösemi örneklerinde HDAC2, HDAC3, HDAC6, HDAC7 ve HDAC8 gen ifadelerinin sağlıklı çocuk kemik iliği örneklerine göre önemli derece yüksek olduğu rapor edilmiştir. Gereç ve Yöntem: Çalışmamızda 6 HDAC geninin gen ifade profilini çocukluk çağı akut lösemisinde kantitatif Real Time PCR yöntemi kullanılması ile tedavinin farklı zamanlarında belirlenmesi gerçekleştirilmiştir. Bulgular: Çalışmamız sonucunda çocukluk çağı lösemi örneklerinde HDAC genleri ifade seviyelerinin birbirine göre farklılık gösterdiği gözlenmiştir. Çalışmamızda; tedavi öncesinde, kontrol örneklerinin ifadelenme seviyelerine göre; HDAC2 ve HDAC9 ifadelenme seviyelerinin düşük, HDAC 4 ve HDAC 8 eşit seviyede ve son olarak HDAC 5 ve HDAC7 yüks...
There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's... more There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's were located on the exon 4 (CD 47), exon 6 (CD 213) and intron 6 (A-G). CD 47 (C-T) was not present. CD 213 (G) occurred very rarely with a frequency of 0.0114. The frequency of the Int 6 A/G a alteration was found to be 0.70 for "G". The heterozygosity rate was 32.72%.
Introduction and Aim Glanzmann’s thrombasthenia (GT) is an inherited disorder of platelet aggrega... more Introduction and Aim Glanzmann’s thrombasthenia (GT) is an inherited disorder of platelet aggregation, resulting from defective glycoprotein IIb/IIIa on platelet surface. Bernard Soulier Syndrome (BSS) is also an inherited disorder of platelet adhesion and associated with defective glycoprotein Ib-V-IX on platelet surface. Both of these disorders usually present with mucocutaneous bleedings. We aimed to evaluate the clinical and genetic characteristics of the patients diagnosed as BSS and GT in department of pediatric hematology of Meram Faculty of Medicine, retrospectively. Method Seven patients diagnosed with BSS and 20 patients diagnosed with GT were enrolled to the study. Medical records of patients were reviewed retrospectively. Glycoprotein IIb gen rearrangement was investigated in genetic department of Ankara University Medical School, Turkey. Mutational analysis for BSS was performed in Medicina Interna ed Oncologia Medica, Italy. The correlation between clinical outcome and genotyping was investigated. Results Of 20 patients of GT, 8 were male and 12 were female. Of 7 patients of BSS, all of them were female. Glycoprotein IIB gene rearrangement was detected in 7 patient of GT. 5 of 7 were newly described mutations in published literature. Mutations in GpIBB and GpIBA gene were detected in 7 patients with BSS. No correlation was observed among the clinical and genotype characteristics of patients both with GT and BSS. The most common patterns of bleeding were epistaxis and gum bleeding. Life threatening bleeding was seen in 5 of GT patients (4 gastrointestinal bleeding, 1 mediastinal hematoma) and 2 of BSS patients (1 splenic rupture and 1 gastrointestinal bleeding). No patients had died due to major bleedings. One patient with GT experienced spontaneous duodenal intramural bleeding resulting duodenal obstruction. One patient with BSS experienced spontaneous mediastinal hematoma. Although the BSS, it is interesting that the patient was able to control of mediastinal hematoma. Further investigations revealed the patient has prothrombotic mutation (heterozygous FV Leiden). Conclusion The most common bleeding pattern in patients with thrombocyte dysfunction is mucocutaneous bleeding. Some patients may suffer from life-threatening bleedings. Our study contributes to the literature because of five newly described mutations in GT patients. It may be hypothesed that the presence of prothrombotic mutation in patients with thrombocyte dysfunction may reduce the severity of bleedings. Disclosures: No relevant conflicts of interest to declare.
Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi
Amaç: Bu çalışmanın amacı, Dr. Nuriye Peker’in “Zavallı Çocuklar” başlıklı kitabının, sosyal pedi... more Amaç: Bu çalışmanın amacı, Dr. Nuriye Peker’in “Zavallı Çocuklar” başlıklı kitabının, sosyal pedi-atrinin ülkemizdeki gelişim sürecindeki yerini karşılaştırmalı olarak incelemektir. Yöntem: Öncelikle Dr. Peker’in tıp eğitimi ve onun sosyal pediatriye yönelmesinde etkili olan unsur ve kişiler incelenmiştir. Akabinde “Zavallı Çocuklar” kitabı, içerik, söylem ve metodolojik açıdan analiz edilmiş, daha sonra kitapta yer alan sosyal pediatriye ilişkin yaklaşımların dönemin ulusal ve uluslararası mevzuatında nasıl yer aldığı irdelenmiştir. Son olarak, “Zavallı Çocuklar” kitap içeriği, 1968 yılında ülkemiz basılmış olan ilk sosyal pediatri ders kitabının yazarı olan Dr. Sabiha Özgür’ün tanımladığı ‘gelişmekte olan ülkelerde sosyal pediatrinin dört ana hedefi’ kapsamında tartışılmıştır. Bulgular: “Zavallı Çocuklar” kitabının yazıldığı dönemde ülkemizde ve dünyada etkin olan ‘nature-nurture’ tartışmasında ‘nature’ kavramının ön planda olduğu göz önünde bulundurulursa, Dr. Peker’in çocuk ile ...
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It ... more B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis (IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A), specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide varia...
Introduction: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by ... more Introduction: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels <1.5 g/L. Objective: In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. Methods: We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the FGB gene using the DNA isolated from the peripheral blood samples of patients and controls. Results and Conclusion: We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same pati...
The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance... more The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance (MDR) observed before and after the treatment. For this reason in MM cases an early resistance to treatment can be developed or the disease can relapsed in early period. Yet, there has been no improved drug resistance against proteazom inhibitor Bortezomib (Bor), which is used alone or with other chemotherapeutic agents in resistant or relapsed MM cases. In this study, bortezomib resistant human MM cell lines; RPMI-8226, secreting lambda light chain, and ARH-77, secreting IgG, were developed and responsible resistance mechanisms were investigated. For this purpose, by exposing to the cells to sequentially gradual doses of Bor in vitro conditions, resistant cell lines were acquired throughout one year. The IC50 values for Bor were determined after 48 hour incubation by MTT cytotoxicity assay (IC50:1,16nM for RPMI-8226 and IC80:0,6nM for ARH-77) against wild type cells. Throughout one yea...
Amaç: Histon deasetilazların değişmiş ifadesi hematolojik maligniteler için kanser tedavisinde he... more Amaç: Histon deasetilazların değişmiş ifadesi hematolojik maligniteler için kanser tedavisinde hedef olabilecek niteliktedir. HDAC mutasyonları ve anormal ifade seviyeleri çeşitli kanser tiplerinde ve özellikle hematolojik malignitelerde sıklıkla görülmekte olduğu, çocukluk çağı lösemi örneklerinde HDAC2, HDAC3, HDAC6, HDAC7 ve HDAC8 gen ifadelerinin sağlıklı çocuk kemik iliği örneklerine göre önemli derece yüksek olduğu rapor edilmiştir. Gereç ve Yöntem: Çalışmamızda 6 HDAC geninin gen ifade profilini çocukluk çağı akut lösemisinde kantitatif Real Time PCR yöntemi kullanılması ile tedavinin farklı zamanlarında belirlenmesi gerçekleştirilmiştir. Bulgular: Çalışmamız sonucunda çocukluk çağı lösemi örneklerinde HDAC genleri ifade seviyelerinin birbirine göre farklılık gösterdiği gözlenmiştir. Çalışmamızda; tedavi öncesinde, kontrol örneklerinin ifadelenme seviyelerine göre; HDAC2 ve HDAC9 ifadelenme seviyelerinin düşük, HDAC 4 ve HDAC 8 eşit seviyede ve son olarak HDAC 5 ve HDAC7 yüks...
There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's... more There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's were located on the exon 4 (CD 47), exon 6 (CD 213) and intron 6 (A-G). CD 47 (C-T) was not present. CD 213 (G) occurred very rarely with a frequency of 0.0114. The frequency of the Int 6 A/G a alteration was found to be 0.70 for "G". The heterozygosity rate was 32.72%.
Introduction and Aim Glanzmann’s thrombasthenia (GT) is an inherited disorder of platelet aggrega... more Introduction and Aim Glanzmann’s thrombasthenia (GT) is an inherited disorder of platelet aggregation, resulting from defective glycoprotein IIb/IIIa on platelet surface. Bernard Soulier Syndrome (BSS) is also an inherited disorder of platelet adhesion and associated with defective glycoprotein Ib-V-IX on platelet surface. Both of these disorders usually present with mucocutaneous bleedings. We aimed to evaluate the clinical and genetic characteristics of the patients diagnosed as BSS and GT in department of pediatric hematology of Meram Faculty of Medicine, retrospectively. Method Seven patients diagnosed with BSS and 20 patients diagnosed with GT were enrolled to the study. Medical records of patients were reviewed retrospectively. Glycoprotein IIb gen rearrangement was investigated in genetic department of Ankara University Medical School, Turkey. Mutational analysis for BSS was performed in Medicina Interna ed Oncologia Medica, Italy. The correlation between clinical outcome and genotyping was investigated. Results Of 20 patients of GT, 8 were male and 12 were female. Of 7 patients of BSS, all of them were female. Glycoprotein IIB gene rearrangement was detected in 7 patient of GT. 5 of 7 were newly described mutations in published literature. Mutations in GpIBB and GpIBA gene were detected in 7 patients with BSS. No correlation was observed among the clinical and genotype characteristics of patients both with GT and BSS. The most common patterns of bleeding were epistaxis and gum bleeding. Life threatening bleeding was seen in 5 of GT patients (4 gastrointestinal bleeding, 1 mediastinal hematoma) and 2 of BSS patients (1 splenic rupture and 1 gastrointestinal bleeding). No patients had died due to major bleedings. One patient with GT experienced spontaneous duodenal intramural bleeding resulting duodenal obstruction. One patient with BSS experienced spontaneous mediastinal hematoma. Although the BSS, it is interesting that the patient was able to control of mediastinal hematoma. Further investigations revealed the patient has prothrombotic mutation (heterozygous FV Leiden). Conclusion The most common bleeding pattern in patients with thrombocyte dysfunction is mucocutaneous bleeding. Some patients may suffer from life-threatening bleedings. Our study contributes to the literature because of five newly described mutations in GT patients. It may be hypothesed that the presence of prothrombotic mutation in patients with thrombocyte dysfunction may reduce the severity of bleedings. Disclosures: No relevant conflicts of interest to declare.
Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi
Amaç: Bu çalışmanın amacı, Dr. Nuriye Peker’in “Zavallı Çocuklar” başlıklı kitabının, sosyal pedi... more Amaç: Bu çalışmanın amacı, Dr. Nuriye Peker’in “Zavallı Çocuklar” başlıklı kitabının, sosyal pedi-atrinin ülkemizdeki gelişim sürecindeki yerini karşılaştırmalı olarak incelemektir. Yöntem: Öncelikle Dr. Peker’in tıp eğitimi ve onun sosyal pediatriye yönelmesinde etkili olan unsur ve kişiler incelenmiştir. Akabinde “Zavallı Çocuklar” kitabı, içerik, söylem ve metodolojik açıdan analiz edilmiş, daha sonra kitapta yer alan sosyal pediatriye ilişkin yaklaşımların dönemin ulusal ve uluslararası mevzuatında nasıl yer aldığı irdelenmiştir. Son olarak, “Zavallı Çocuklar” kitap içeriği, 1968 yılında ülkemiz basılmış olan ilk sosyal pediatri ders kitabının yazarı olan Dr. Sabiha Özgür’ün tanımladığı ‘gelişmekte olan ülkelerde sosyal pediatrinin dört ana hedefi’ kapsamında tartışılmıştır. Bulgular: “Zavallı Çocuklar” kitabının yazıldığı dönemde ülkemizde ve dünyada etkin olan ‘nature-nurture’ tartışmasında ‘nature’ kavramının ön planda olduğu göz önünde bulundurulursa, Dr. Peker’in çocuk ile ...
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It ... more B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis (IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A), specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide varia...
Introduction: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by ... more Introduction: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels <1.5 g/L. Objective: In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. Methods: We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the FGB gene using the DNA isolated from the peripheral blood samples of patients and controls. Results and Conclusion: We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same pati...
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