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The introduction of tyrosine kinase inhibitors (TKI) has resulted in a significant improvement in the treatment of CML patients. However, some CML patients are resistant to imatinib therapy, the initial TKI therapy in the CML. Therefore, it is important to find prognostic markers for resistance. The

Introduction: Even though Istanbul is one of the centers of the world’s fastest-growing tourism and travel sector, there are limited statistics on the knowledge, attitudes, and practices (KAP) of travelers from this region regarding travel-related infectious diseases. This study aimed to determine the passengers’ KAP about contagious diseases and contribute to developing new solutions for the problems people face while traveling abroad. Methods: A questionnaire was administered to 182 Turkish travelers planning on traveling abroad and applied to the Istanbul Travel Health Center and the Istanbul Airport Health Control Center between January and March 2019. Results: The proportion of carrying a vaccination certificate was statistically higher in those who received healthcare services at international terminals (P=0.002), especially those who had yellow fever (P

BACKGROUND Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder that results in a predisposition to the growth of multiple tumors in the central nervous system, the peripheral nervous system, and the skin. The clinical manifestations of neurofibromatosis are associated with loss of neurofibromin expression which causes the upregulation of the RAS pathway. Although neurofibromatosis type 1 can be diagnosed based on the National Institutes of Health criteria, sometimes the diagnosis is difficult, in cases where the characteristic features do not develop. Moreover, other RAS-related disorders may present with significantly overlapping clinical features. AIMS To determine the clinical and molecular genetic characteristics of Turkish patients with neurofibromatosis type 1. STUDY DESIGN Cross-sectional study. METHODS For the genetic analysis of 27 Turkish families clinically diagnosed with NF1 between 1990 and 2019, we used a multi-step process consisting of next-generation sequencing, multiplex ligation-dependent probe amplification, and array-comparative genomic hybridization. RESULTS In this study, we identified 11 novel and 11 previously reported single-nucleotide variants in 22 families. Whole gene deletions were detected by multiplex ligation-dependent probe amplification analysis in 3 families. Of those, array comparative genomic hybridization analysis defined a 17q11.2 deletion in 4 patients from 2 families and 1.2-Mb involving 1 unrelated patient. All patients with a deletion had facial dysmorphism, suggesting a peculiar phenotype in this group. We could not find any pathogenic variant in the 2 families that met the National Institutes of Health criteria. CONCLUSION The novel pathogenic variants identified in this study broaden the spectrum of pathogenic variants in NF1 and provide better clinical characterization of NF1. RNA-seq experiments are recommended in patients who meet the National Institutes of Health diagnostic criteria for NF but have not identified any variants in nextgeneration sequencing, multiplex ligation-dependent probe amplification, or array-comparative genomic hybridization analysis.

Purpose: Plasma Cell Dyscrasias are a heterogeneous group of hematological diseases. The candidate ten genes identified from our transcriptome data are highly valuable and specific. Methods: We investigated the prognostic biomarker status of these genes in Plasma Cell Dyscrasias. Expression levels of ISG20, EEF2, TRIB1, RRBP1, TMED9, KDELR1, DNAJC1, DPP7, COPE and LMAN2 genes were measured via qRT-PCR from bone marrow samples of 38 Multiple Myeloma, 23 MGUS and 16 control groups. Results: According to our results, in the Multiple Myeloma group, all genes were more highly expressed than control and MGUS groups (pDNAJC1 is an important risk factor for MM (pTMED9 gene expression and clinical parameters of urea, Ca, albumin, LDH, and IGA levels (pTMED9gene in our results sheds light on myeloma genesis. Conclusion: This study contributed significantly to the search on prognostic biomarkers for Multiple Myeloma progression from MGUS and for starting early treatment in MGUS.

Heme oxygenase-1 (HMOX-1) is an enzyme that regulates heme degradation. Antiinflammatory, antioxidant, and cytoprotective effects of HMOX-1 were also described. It is encoded by the HMOX1 gene, and biallelic mutations cause HMOX-1 deficiency, which is a rare chronic multisystemic inflammatory disorder. This inflammatory status could lead to the development of secondary AA-type amyloidosis theoretically. Here, we report a 30-year-old male with AA-type renal amyloidosis due to a chronic inflammatory condition of unknown origin. Paternal consanguinity and dysmorphic features raised suspicion of a rare genetic disorder. Clinical exome sequencing (CES) confirmed the HMOX-1 deficiency diagnosis related to homozygous missense G139V mutation. To the best of our knowledge, our patient is the eleventh HMOX-1 deficiency case in the literature. Also, HMOX-1 deficiency-related systemic AA-type amyloidosis has not been reported before.

Loss or decrease of function in runt-related transcription factor 2 encoded by RUNX2 is known to cause a rare autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD). Clinical spectrum and genetic findings in 51 CCD patients from 30 unrelated families are herein presented. In a majority of the patients, facial abnormalities, such as delayed fontanel closure (89%), parietal and frontal bossing (80%), metopic groove (77%), midface hypoplasia (94%), and abnormal mobility of shoulders (90%), were recorded following clinical examination. In approximately one-half of the subjects, wormian bone (51%), short stature (43%), bell-shaped thorax (42%), wide pubic symphysis (50%), hypoplastic iliac wing (59%), and chef's hat sign (44%) presented in available radiological examinations. Scoliosis was identified in 28% of the patients. Investigation of RUNX2 revealed small sequence alterations in 90% and gross deletions in 10% of the patients; collectively, 23 variants including 11 novel changes (c.29_30insT, c.203delAinsCG, c.423 + 2delT, c.443_454delTACCAGATGGGAinsG, c.505C > T, c.594_595delCTinsG, c.636_637insC, c.685 + 5G > A, c.1088G > T, c.1281delC, Exon 6-9 deletion) presented high allelic heterogeneity. Novel c.29_30insT is unique in affecting the P1-driven long isoform of RUNX2, which is expected to disrupt the N-terminal region of RUNX2; this was shown in two unrelated phenotypically discordant patients. The clinical findings highlighted mild intra-familial genotype-phenotype correlation in our CCD cohort.

Introduction Ring chromosomes arise from breakage and fusion at distal regions of short and long arms of the chromosomes. The effect of the ring chromosome on the phenotype may vary widely depending on the amount of the deletion in the chromosomal areas and genes implicated in these regions. Case presentation We present a 35-year-old male patient with infertility and mild intellectual disability (MID) who has de novo ring 13 (r(13)) chromosomes. To determine chromosomal abnormality, we performed karyotype analysis, Y chromosome microdeletion analysis, FISH, and aCGH techniques. Conclusion The patient’s karyotype analysis result was mos46,XY,r(13)(p13q34)[75]/45,XY,-13[14]/46,XY,dic (13;13)[8]/47,XY,r(13), + r(13)[2]/46,XY,tetrac r(13;13;13;13)[1]. FISH analysis supported the findings of the cytogenetic analysis. Y microdeletion analysis showed that the AZF region was intact. On aCGH analysis, we detected a 1.5 megabase deletion at the end of chromosome 13, including the CHAMP1 gene. The loss of the CHAMP1 gene, in particular, may explain our patient's MID, and the other deleted genes at 13q34 may explain our patient's infertility.

Myeloid/lymphoid neoplasm is a rare malignancy with an aggressive course and rapid transformation to acute myeloid leukemia (AML), or less frequently to acute lymphoblastic leukemia (ALL). Cases with t(8;22)(p11;q11) BCR-FGFR1 fusion gene may be misdiagnosed with chronic myeloid leukemia (CML), due to a very similar morphologic and clinical profile. We report a case of 48-year-old woman who complained of weakness and gastric pain. She had splenomegaly, eosinophilia, and elevated white blood cells. Bone marrow (BM) aspiration biopsy was performed with an initial diagnosis of CML. Cytogenetic analysis of the BM showed a 46,XX,t(8;22)(p11.2;q11.2). She was diagnosed with myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1 gene. Throughout the chronic phase, the patient was treated with hydroxurea. Additional chromosomal abnormalities developed during therapy. Owing to the (8;22) clone, our patient did not respond to the treatment and rapidly transformed first to B-ALL and then AML. To the best of our knowledge, this is the first MPN patient with rearrangement of BCR and FGFR1 genes with rapid transformation to B-ALL and then to AML. WOS:000606311500003 Q4

Introduction Coronavirus disease 2019 (COVID-19) has become a serious public health problem for 183 out of 197 countries in the world. Understanding the routes and pathogenesis of the coronavirus is important and it is considered that the studies on host cell receptor Angiotensin Converting Enzyme 2 (ACE2) may be valuable for the treatment and prevention of the disease. Aim To evaluate the possibility of inhibition of SARS-CoV-2 at throat. Methods A comprehensive literature search was conducted. Conclusion In view of the fact that the mouth and nose have higher number of ACE2 expressed cells, they serve as a gateway for the virus to enter. Thus, blocking the gate could be a good choice to reduce or even prevent the transmission. Small interfering RNAs (siRNAs) are double-stranded RNA molecules and could be designed easily and directed against many strains of a virus. Due to their features, siRNAs can provide a potential strategy to interfere with the replication of viral diseases. We think that since oral and nasal epithelial cells are relatively easily accessible it may allow to develop siRNA molecules to inhibit SARS-CoV-2 already at the entry where it continues to replicate for a period (Fig. 1, Ref. 50).

Objectives We aimed to examine the performance of stem cell markers and epithelial-mesenchymal transition (EMT) process in miR-145 transfected EWS cells (TC71, TC106). Methods EWS cells were utilized for functional analysis of mir-145. Proliferation, migration, invasion and soft agar colony assay were performed to observe the alterations in migration behavior of transfected cells. Caspase assay was used to investigate the underlying reasons of proliferative inhibition in cells in whichmiR-145 is overexpressed. QRT-PCR was used to determine the role of miR-145 in EMT transcription markers and mir-145 targeted genes, KLF4, SOX2 and OCT4 expression levels. Results The miR-145 expression has been shown to be down-regulated in EWS. The miR-145 overexpression caused inhibition of proliferation and reduced migration in EWS cells through induction of apoptosis. Mir-145 suppresses EMT capacity and SOX2, KLF4 and OCT4 expression levels. Conclusion This is the first time in the literature we have shown deregulation of miR-145 inhibits EMT process by targeting stem cell properties leading to the inhibition of tumor growth and metastasis in TC71 and TC106 cells. Based on these results, we propose that miR-145, as an important regulator of SOX2, KLF4 and OCT4 carries crucial roles in EWS tumorigenesis and EMT (Tab. 1, Fig. 4, Ref. 26).

Malignant melanoma is a type of skin cancer with high risk of metastasis. 5-Fluorouracil is commonly used for treatment of skin cancer, however its penetration through the skin is found to be insufficient in some cases. Therefore, we optimized its pharmacokinetics by fabricating 5- Fluorouracil-loaded nanoliposome formulations modified with Poly-L-lysine coating. 5-Fluorouracil-loaded nanoliposome formulations were prepared using dipalmitoylphosphatidylcholine, dicethylphosphate and cholesterol having encapsulation efficiency of 45 +/- 9.61%. The particle size, zeta potential, polydispersity index and encapsulation rate of the prepared formulation was found to be 237.9 +/- 0.986 nm, 41.4 +/- 1.060 mV, 0.233 +/- 0.019 and 88.2 +/- 7.85%, respectively. Surface characterization, molecular structure and thermal property illumination of the formulations were performed alongside stability studies. TheIn-vitrorelease of 5-FU from Lipo-FU6 and PLL-1 formulations was investigated by dialysis membrane method. Within the first 12 hours, the percentage release of 5-FU from Lipo-FU6 and PLL-1 formulations was observed to be 47.17% and 20.84%, respectively. Moreover, the cytotoxicity study on A431 epidermal carcinoma cell lines has revealed that 5-FU-loaded formulations were toxic to cells unlike the 5-FU free formulations. In conclusion, PLL coated nanoliposome formulations showed a potential to be an effective option for further combined drug/gene therapy applications.

Chronic lymphocytic leukemia (CLL) is a neoplasm characterized by excessive accumulation of B lymphocytes in the peripheral blood, bone marrow and lymph nodes. We assessed the expressions of 22 genes in the p53 pathway in 30 CLL patients and 15 healthy subjects by a RT2 Profiler PCR (polymerase chain reaction) Array technique and their relation to cytogenetic aberrations detected by fluorescent in situ hybridization (FISH). Our Student’s t-test results indicated that ATM, ATR, BAX, CASP9, CDK4, CDKN2A, CHEK1, CHEK2, E2F3, MCL1, MDM2, MDM4, PCNA, RB1, P53 and BCL2 genes were statistically significant (p (APAF1, CDKN1A, E2F1, GADD45A, PTEN and PTX3) were not statistically significant. The ATM, ATR, BAX, CASP9, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, MDM4, PCNA, RB1, P53, E2F1, GADD45A and BCL2 genes were found to be upregulated by the 2-ᐃᐃCt (relative fold change in gene expression) method. The highest up-regulation was detected in CDKN2A and BCL2 genes, 10.22- and 8.51-fold, respectively. On the other hand, the PTX3 gene with a fold regulation of 1.84 was found to the highest downregulation. Overall, the CDNK2A BCL2 and PTX3 genes are related to the mechanism of the disease in the p53 pathway and may be an important predictor of the prognosis of the disease. The BCL2 gene may be associated with increased risk of developing CLL. We suggest that the PTX3 gene may be considered as a marker associated with CLL disease. The CDKN2A gene expression seems to play a protective role in CLL.

Anzer honey is well known in Turkey and used for its medicinal properties, especially for pharyngitis, tonsillitis, ulcers and cancer. In this study, we investigated whether Anzer honey, which is shown to have antioxidant, anti-tumoral, and anti-inflammatory properties, has a protective effect against X-ray induced genotoxic damage by cytogenetic methods. Peripheral blood lymphocytes isolated from 20 healthy volunteers were divided into two groups and cultivated by conventional methods. Study group lymphocytes were treated with 10% diluted honey while those in the control group were not. Both groups were exposed to a high dose (2 Gy) X-ray at the 48th hour of culture. Conventional cytogenetic staining and Giemsa banding methods were applied to evaluate chromosomal breakage and ring formation. Micronucleus frequencies were determined by the cytokinesis-block micronucleus (CBMN) assay. Paired sample t test was used to compare groups. Anzer honey, which was analyzed melissopalynologically, was used. Micronucleus frequency was significantly decreased in the study group (CI = 348.75 ± 31, median 326, min. 98, max. 704) compared to the control group (CI = 489.10 ± 27, median 500, min. 216, max. 645) (p = .001). Chromosomal breakage was also significantly decreased in the study group (CI = 118.70 ± 16, median 109, min. 12, max. 316) compared to the control group (CI = 233.60 ± 25, median 225, min. 65, max. 492) (p .0001). This is the first study indicating that genotoxic damage in the peripheral blood lymphocytes of healthy volunteers induced by X-radiation may be prevented or alleviated by adding Anzer honey in vitro. These results encourage further research about the protective effects of honey. RESEARCH HIGHLIGHTS: Anzer honey has a genoprotective effect against radiation-induced genotoxicity, probably by preventing oxidation damage.

Deregulation of miRNA expressions was identified as a novel feature of tumor biology in Ewing sarcoma (EWS). The aim was to evaluate the regulatory role of miR-129-2-3p in EWS cell lines and human EWS tissue samples. EWS cell lines TC-71, TC-106, and CHLA-99 were used in the study and real-time PCR was utilized to investigate the functional role of tumor suppressor mir-129-2-3p and miR-129-2-3p levels in the cells. Proliferation, migration, invasion and apoptosis assays were carried out within the scope of functional in vitro studies. Expression levels of CDK6 and SOX4, which are miR-129-2-3p target genes, were examined. Moreover, the change in expression levels of miR-129-2-3p in EWS tumor tissues was also examined. It was determined that miR-129-2-3p expression markedly diminished in all the studied cell lines. In addition, miR-129-3p was found to decrease in proliferation, migration, invasion and apoptosis assays in all EWS cell lines. CDK6 and SOX4 levels were also decreased in miR-129-2-3p transfected cell lines. It was found that miR-129-2-3p levels were significantly decreased in EWS tumor tissue samples compared to the corresponding adjacent normal tissue samples. In line with the results of our current study, where the possible function of miR‐129-2-3p in EWS cell lines was examined, for the first time in the literature miR-129-2-3p was shown to have low expression level in EWS lines and EWS tumor tissue samples, and to provide a tumor suppressor effect.

In this study, it was aimed to develop drug eluting biodegradable and biocompatible bone supportive fibers and films, which can locally be applicable on the infected bone defect area for osteomyelitis treatment. For this purpose, vancomycin (Vm) loaded gelatin (G) microspheres were prepared and dispersed into poly(e-caprolactone) (PCL) solution and then the suspension was processed as films and fibers by solvent casting and wet spinning techniques, respectively. The mean particle size distribution and morphology of Vm loaded G microspheres were characterized by laser diffraction method and scanning electron microscopy, respectively. In vitro Vm release profiles and release kinetics from microsphere, fiber and film formulations were investigated. In vitro biodegradation properties of fiber and film formulations were examined in both hydrolytic and enzymatic media during 25 days period. The cytotoxicity of Vm eluting films and fibers were tested on L929 cells by MTT assay. Presence of PCL in film and fiber formulations retarded the release of Vm from microspheres and provided long term sustained release. Vm eluting films and fibers exhibited strong antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis.

The alpha-actinin (ACTN) genes are important structural components of the sarcomere. Sarcopenia is a common geriatric syndrome characterized by morbidity and mortality. Our study aimed to examine the relationship between the ACTN3 R577X gene and sarcopenia in community-dwelling Turkish adults. We designed a cross-sectional study among the patients aged ≥ 65 years admitted to the geriatric outpatient clinic. We recorded the general characteristics of the patients. We used the Jamar hand dynamometer to evaluate handgrip strength. Body composition was estimated using bioimpedance analysis. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People2 criteria with population-specific cutoffs. We performed analyses of low muscle mass (LMM) with skeletal muscle mass index adjusted for body mass index [SMMI(BMI)]. We further categorized the SMMI(BMI) cutoffs into tenths. The analyzes were performed according to the 90th percentile SMMI(BMI) cutoffs. Peripheral blood samples were collected to determine the ACTN3 genotypes. 197 participants were included [mean age: 76.3 ± 6.1 years, 151 (76.6%) women]. The proportions of the ACTN3 genotypes were as follows: RX (45.1%) > RR (31%) > XX (23.9%). The significant difference between genotypes was found only for low SMMI(BMI) according to the 90th percentile (p = 0.025). In multivariate analysis, only gender (female) was independently associated with LMM. We did not find any association between ACTN3 R577X gene polymorphism and probable sarcopenia, confirmed sarcopenia and LMM. Besides, much more research is needed to reveal how ethnicity affects the muscles of older adults with ACTN3 R577X gene polymorphism.

The blood–brain barrier (BBB) is a control mechanism that limits the diffusion of many substances to the central nervous system (CNS). In this study, we designed an in-vitro 3-dimensional BBB system to obtain a fast and reliable model to mimic drug delivery characteristics of the CNS. A support membrane of polycaprolactone nanofiber surfaces was prepared using electrospinning. After confirming the fiber morphology and size, endothelial cells (HUVEC) and glial cells were cultured on either side of this membrane. The model’s similarity to in vivo physiology was tested with a home-designed transmembrane resistance (TR) device, with positive and negative control molecules. Finally, 2 doses of methotrexate (MTX), a chemotherapy agent, were applied to the model, and its permeability through the model was determined indirectly by a vitality test on the MCF-7 cell line. Nicotine, the positive control, completed its penetration through the model almost instantly, while albumin, the negative control, was blocked significantly even after 2 days. MTX reached a deadly threshold 24 h after application. The TR value of the model was promising, being around 260 ohm.cm2. The provided model proposes a disposable and reliable tool for investigating drug permeability through the BBB and has the potential to reduce the number of animal experiments. © TÜBİTAK., Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, This project was supported by TÜBİTAK (The Scientific and Technological Research Council of Turkey) by the 2209-A program. We would like to thank EBİLTEM (Ege University Science and Technology Application and Research Center), Ege University Bioengineering Department Biomaterials and 3D Biointerphases Laboratories, and colleagues for supporting this project. We also thank Ege University Faculty of Medicine Oncology Department and Prof. Dr. Ayfer Haydaroğlu for providing MTX and Prof. Dr. Gülperi Öktem for providing C6 glial cells.

To investigate the effect of several chelating solutions on transforming growth factor (TGF-β) release from dentine discs and their subsequent impact on cellular behaviour.Human dentine discs were prepared with a standardized diameter and disinfected using 1.5% NaOCl for 5 min. The dentine discs were then exposed to 17% ethylenediaminetetraacetic acid (EDTA), 1% phytic acid (IP6), 9% etidronic acid (HEDP) or distilled water (DW). The release of transforming growth factor (TGF-β) was quantified using ELISA. The proliferation of dental pulp stem cells (DPSCs) on the conditioned dentine discs was analysed using an MTT assay, and the cell morphology was observed by SEM. Migration of DPSCs towards the conditioned dentine discs was measured using a Transwell assay. Data for cell proliferation and migration were analysed using two-way analysis of variance with a Bonferroni post hoc test; a Kruskal-Wallis test was used for analysing TGF-β release.Both HEDP and IP6 treatment triggered TGF-β release and cell migration. The greatest TGF-β release was observed after HEDP treatment as compared with EDTA and DW but there was no significant difference between the groups. In terms of cell migration, HEDP was more effective than EDTA (P 0.05) whilst IP6 was similar to EDTA. Cell proliferation significantly increased with time after EDTA, DW and IP6 treatment (P 0.05), whereas HEDP treatment did not induce cell proliferation (P 0.05).IP6 and HEDP were effective chelating agents on TGF-β release, and cell migration was as effective as EDTA.

Background Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated. Aims To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology. Study design Cell study. Methods Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools. Results In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file. Conclusion EEF1G, ITM2C, FTL, CLPTM1L, and CYBA are identified as possible candidate genes associated with myelomagenesis.

Aim: Familial Mediterranean Fever (FMF) is the most frequent and historically the oldest autosomal recessive autoinflammatory disorder. No pathogen or auto-antibody has been shown to be associated with FMF. The disorder manifests with bouts of fever and abdominal pain, which are called “attacks”. In the present study, we aimed to find the most frequent mutations in the MEFV gene in the Turkish population. Methods: Thousand eight hundred and forty patients with an initial diagnosis of FMF were enrolled in the study. DNA was extracted from the peripheral blood according to the kit protocol. Twenty-two target sequences of the MEFV gene were amplified with polimeraze chain reaction and sequenced with the pyrosequencing method. Results: When the patients were divided into two groups according to age, the mean age of 866 patients was 8.5±7.5 years in

Neurite outgrowth and elongation of neural cells is the most important subject that is considered in nerve tissue engineering. In this regard, aligned nanofibers have taken much attention in terms of providing guidance for newly outgrown neurites. The main objective of this study was to fabricate aligned polyurethane nanofibers by electrospinning process and decorate them with gold nanoparticles to further investigate the synergistic effects of nanotopography, biological nerve growth factor (NGF) and electrical stimulations on neurite outgrowth and elongation of pheochromocytoma (PC-12) model cells. In this regard, smooth and uniform aligned polyurethane nanofibers with the average diameter of 519 ± 56 nm were fabricated and decorated with the gold nanoparticles with the average diameter of ∼50 nm. PC-12 cells were cultured on the various nanofiber surfaces inside the bio-mimetic bioreactor system and exposed either to NGF alone or combination of NGF and electrical stimulation. It was found that 50 ng/mL NGF concentration is an optimal value for the stimulation of neurite outgrowth. After 4 days of culture under 100 mV, 10 ms electrical stimulation in 1 h/day period it was found that the gold nanoparticle decorated aligned polyurethane nanofibers increased the neurite outgrowth and elongation more with the combinational NGF and electrical stimulation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1604-1613, 2018.

Background Oral white sponge nevus (WSN) is a rare autosomal dominant benign condition, characterized by asymptomatic spongy white plaques. Mutations in Keratin 4 (KRT4) and 13 (KRT13) have been shown to cause WSN. Familial cases are uncommon due to irregular penetrance. Thus, the aim of the study was: a) to demonstrate the clinical and histopathological features of a three-generation Turkish family with oral WSN b) to determine whether KRT4 or KRT13 gene mutation was the molecular basis of WSN. Material and Methods Out of twenty members of the family ten were available for assessment. Venous blood samples from six affected and five unaffected members and 48 healthy controls were obtained for genetic mutational analysis. Polymerase chain reaction was used to amplify all exons within KRT4 and KRT13 genes. These products were sequenced and the data was examined for mutations and polymorphisms. Results Varying presentation and severity of clinical features were observed. Analysis of the KRT13 gene revealed the sequence variant Y118D as the disease-causing mutation. One patient revealed several previously unreported polymorphisms including a novel mutation in exon 1 of the KRT13 gene and a heterozygous deletion in exon 1 of KRT4. This deletion in the KRT4 gene was found to be a common polymorphism reflecting a high allele frequency of 31.25% in the Turkish population. Conclusions Oral WSN may manifest variable clinical features. The novel mutation found in the KRT13 gene is believed to add evidence for a mutational hotspot in the mucosal keratins. Molecular genetic analysis is required to establish correct diagnosis and appropriate genetic consultation. Key words:White sponge nevus, leukokeratosis, oral mucosa, keratins, mutation.

Variant Philadelphia (Ph) translocations involving chromosome 7 are rarely seen in Chronic Myeloid Leukemia (CML) patients. It is aimed to contribute new cases to the literature by reviewing the cases in our archive and shed light into the understanding of the role of chromosome 7 in CML. This study was carried out in 237 newly diagnosed CML patients with variant Ph translocations. Among the patients, those with variant Ph translocation involving chromosome 7 were evaluated in terms of clinical and genetic characteristics. Chromosome analysis was performed on 24 and 48 h of bone marrow cultures. FISH analysis was performed with BCR-ABL1 dual color dual fusion translocation probes. BCR-ABL1 transcript levels were analysed by QRT-PCR and results were reported as BCR-ABL1/ABL1 (BCR-ABL1 (IS) %) according to international scale. Four of the patients had variant Ph translocations including chromosome 7. The karyotypes were 46,XX,t(7;9;22)(p13;q34;q11); 46,XX,t(7;9;22)(p21;q34;q11); 46,XX,t(7;9;22)(q22;q34;q11) and 46,XY,t(7;9;22)(q22;q34;q11). The breakpoints demonstrated by cytogenetic analysis were confirmed by FISH analysis. Monitoring by QRT-PCR showed that patients with variant Ph translocation including 7p13 and 7p21 had a dramatic decrease in BCR-ABL1 levels resulting in complete hematological, complete cytogenetic and deep molecular responses. Despite achieving complete hematological, complete cytogenetic response in two patients with variant Philadelphia translocation, including 7q22, no major molecular response was achieved and both patients are still in the warning category. Response to tyrosine kinase inhibitor therapy may be associated with both the variant translocation mechanism and new gene interactions that occur due to the breakpoints of additional chromosomes involved in translocation.

Aim To investigate the proliferation and differentiation potential of human dental pulp stem cells (DPSCs) in a three-dimensional culture model (TDM) by incorporation of VEGF and BMP-2. Methodology TDM was established using fibrin gel (fg) as a soft tissue matrix and demineralized dentine disc (dd) as a hard tissue matrix. DPSCs and vascular endothelial growth factor (VEGF) were encapsulated in fibrin gel (fg-VEGF) and then inserted into bone morphogenetic protein (BMP-2) coated demineralized dentine discs (dd-BMP-2). DPSCs were incubated for 28 days in various fg/dd combinations in the absence or presence of VEGF and BMP-2. Proliferation and morphology of DPSCs in fibrin gel were analysed using MTT and Live&Dead assays. Release profiles of VEGF and BMP-2 from fibrin gel and dentine discs were quantified using ELISA, and the expressions of angiogenic and odontogenic differentiation markers were determined with RT-qPCR analysis. Data were analysed statistically using Wilcoxon signed rank tests, Kruskal-Wallis tests with Mann Whitney U tests and Bonferroni adjustment. The level of significance was set at p

The major focus of this study was to prepare poly(lactic-co-glycolic) acid (PLGA) microspheres containing atorvastatin calcium (ATR) in combination with alpha-lipoic acid (ALA). PLGA microspheres will maintain dual-release for providing neuroprotective effects for peripheral nerve injury. For this purpose, micro spheres were prepared by spray dryer with different drug:polymer ratios. Microsphere formulations were evaluated for particle size distribution, preparation and encapsulation efficiency, surface morphology, in-vitro release and dose dependent cytotoxicity test with L-929 and B-35 cells. TGA, DSC and FTIR analysis were performed for the investigation of physicochemical properties of the PLGA microspheres. Encapsulation efficiencies were calculated as > 70% for ALA and > 62% for ATR. FTIR results indicated that there was no interaction between the polymer and the active ingredients. A novel analytical method has been developed and fully validated, which would allow for quantification of ATR and ALA simultaneously. Release profiles showed that ALA is released within the first 17 h and ATR release lasted for 17 days. Finally, results showed that there was no any toxicity associated with ALA and ATR containing PLGA formulations on both B-35 and L-929 cells. It was concluded that PLGA formulations with dual effects are promising systems for the treatment of peripheral nerve injury. (C) 2017 Elsevier B.V. All rights reserved.

İnfertilite tüm dünyada çiftlerin yaklaşık %15’ini etkileyen önemli bir sağlık sorunudur. İnfertilite hem erkek hem de kadın kaynaklı faktörler ile ortaya çıkabilir. Vakaların yaklaşık %40’ında tiyoloji belirsizdir. Dengeli resiprokal translokasyonlar, insanlarda en yaygın olarak karşılaşılan yapısal kromozom anomalileridir ve infertilite ile yakından ilişkilidir. Dengeli resiprokal translokasyonlar çoğunlukla taşıyıcıların fenotipini etkilemez ancak kromozomal olarak dengesiz gamet oluşturma yönünden bu kişiler anlamlı şekilde artmış riske sahiptir. 6p21.3 kromozomal bölgesi infertilite ile ilişkili birçok geni barındırmaktadır. 6p21.3 bölgesini içine alan dengeli resiprokal translokasyonlar genellikle infertilite ile ilişkilendirilmiştir. Bu çalışmada bilim dalımıza infertilite nedeni ile refere edilen çiftten yapılan karyotip analizi sonucunda erkekte tespit ettiğimiz t(1;6)(p13p21.3) dengeli resiprokal translokasyonun infertiliteyle ilişkisi üzerinde durulmuştur.

Three-dimensional (3D) cancer tumor models are becoming vital approaches for high-throughput drug screening, drug targeting, development of novel theranostic systems, and personalized medicine. Yet, it is becoming more evident that the tumor progression and metastasis is fueled by a subpopulation of stem-like cells within the tumor that are also called cancer stem cells (CSCs). This study aimed to develop a tumoroid model using CSCs. For this purpose CD133(+) cells were isolated from SaOS-2 osteosarcoma cell line with magnetic-activated cell sorting. To evaluate tumoroid formation ability, the cells were incubated in different cell numbers in agar gels produced by 3D Petri Dish (R) method. Subsequently, CD133(+) cells and CD133(-) cells were co-cultured to investigate CD133(+) cell localization in tumoroids. the characterization of tumoroids was performed using Live&Dead staining, immunohistochemistry, and quantitative polymerase chain reaction analysis. the results showed that, CD133(+), CD133(-) and SaOS-2 cells were all able to form 3D tumoroids regardless of the initial cell number, but, while 72 hr were needed for CD133(+) cells to self-assemble, 24 hr were enough for CD133(-) and SaOS-2 cells. CD133(+) cells were located within tumoroids randomly with high cell viability. Finally, when compared to two-dimensional (2D) cultures, there were 5.88, 4.14, 6.95, and 1.68-fold higher messenger RNA expressions for Sox2, OCT3/4, Nanog, and Nestin, respectively, in CD133(+) cells that were cultured within 3D tumoroids, showing longer maintenance of stem cell phenotype in 3D, that can allow more relevant screening and targeting efficiency in pharmaceutical testing. It was concluded that CSC-based tumoroids are propitious as 3D tumor models to fill the gap between conventional 2D in vitro culture and in vivo animal experiments for cancer research., Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [113M243]; Ege University Scientific Research Projects Coordination UnitEge University [13-FBE-011], Scientific and Technological Research Council of Turkey, Grant/Award Number: 113M243; Ege University Scientific Research Projects Coordination Unit, Grant/Award Number: 13-FBE-011

Poly(glycerol sebacate) (PGS) was discovered in the previous decade and is a promising bioelastomer with tuneable mechanical, biodegradable and biocompatible properties. Despite of these superiorities, PGS possesses solubility and processability disadvantages. To overcome these drawbacks of PGS, blends could be formed with a polymer which is soluble in a common solvent with PGS prepolymer, having a melting temperature above the crosslinking temperature and which can be removed from the structure after crosslinking. In this study, PGS fibers were fabricated for the first time using pressurized gyration as scaffolds. Fibers were obtained through blending the synthesized PGS prepolymer with poly(vinyl alcohol) (PVA) to overcome solubility/melting drawbacks of crosslinked PGS polymer. Obtained fiber diameters have a narrow size distribution which did not change after thermal crosslinking. After the washing procedure, ∼25% decrease in the average fiber diameter was observed due to the PVA removal. Resulting PGS fibers were characterized in terms of chemical structure, morphology, and cell viability. Fibroblast cell adhesion and spreading on three-dimensional fiber networks were determined by microscopy. PGS fibers supported cell adhesion and proliferation. After 7 days of cell-PGS fiber interactions, cell proliferation and spreading increased without any toxicity.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

Infertility is an important health problem affecting 15% of couples worldwide. Intellectual disability (ID) is characterized with significant impairment of intellectual function, adaptive daily life skills and social skills. Insertion is a rare chromosomal rearrangement causing infertility and ID. Here, we report a 39-year-old man presenting with primary infertility and mild ID. The patient’s spermiogram was consistent with azoospermia. Conventional cytogenetic analysis showed a novel inversion/insertion type of chromosomal aberration involving chromosomes 18 and 2: 46, XY, inv ins(18;2)(q11.2;q13q22). We carried out the array comparative genomic hybridization analysis to confirm the cytogenetic findings. Y micro-deletion analysis demonstrated that the AZF region as intact. We suggest that the novel insertion found in this case [46, XY, inv ins(18;2)(q11.2;q13q22)] may have caused infertility and mild ID in our patient. To the best of our knowledge, this chromosomal insertion has not previously been reported.

Neurite outgrowth and elongation of neural cells is the most important subject that is considered in nerve tissue engineering. In this regard, aligned nanofibers have taken much attention in terms of providing guidance for newly outgrown neurites. The main objective of this study was to fabricate aligned polyurethane nanofibers by electrospinning process and decorate them with gold nanoparticles to further investigate the synergistic effects of nanotopography, biological nerve growth factor (NGF) and electrical stimulations on neurite outgrowth and elongation of pheochromocytoma (PC-12) model cells. In this regard, smooth and uniform aligned polyurethane nanofibers with the average diameter of 519 ± 56 nm were fabricated and decorated with the gold nanoparticles with the average diameter of ∼50 nm. PC-12 cells were cultured on the various nanofiber surfaces inside the bio-mimetic bioreactor system and exposed either to NGF alone or combination of NGF and electrical stimulation. It was found that 50 ng/mL NGF concentration is an optimal value for the stimulation of neurite outgrowth. After 4 days of culture under 100 mV, 10 ms electrical stimulation in 1 h/day period it was found that the gold nanoparticle decorated aligned polyurethane nanofibers increased the neurite outgrowth and elongation more with the combinational NGF and electrical stimulation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1604-1613, 2018.

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3–p22.3, 5q13–q22, and 11p15) have been mapped to autosomes and one gene ( SOS1 ) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor ( REST ) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.

The control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications.

Background: The process of development of bladder cancer features alteration of normal biological conditions caused by changes in molecular pathways. Removing control over regulation of these pathways could lead to changes in signal transduction and abnormal regulation of genes. During tumor formation and progression, genes regulate critical cellular processes, involved in cell cycling, growth and death. Here we evaluated the expression and prognostic importance of FGFR1, HRAS, CCND1, CCND3, STAT3 and FAS genes. Methods: Tumor tissues of 44 patients diagnosed with bladder cancer were investigated for changes in expression levels of FGFR1, HRAS, CCND1, CCND3, FAS and STAT3 genes by the RT-PCR method. Signal transduction pathways and expression of individual genes related to these pathways were analyzed using the “One Sample Test”. Results: There were statistically significant changes in the expression levels of HRAS, CCND1, CCND3 and STAT3, but not FGFR1 and FAS genes. Examination of associations with age, gender, smoking, chemotherapy, tumor grade and tumor growth pattern using the “Independent Samples Test”, showed importance relations between the CCND1 gene and cigarette smoking and sex. Conclusion: Over-expression of HRAS, CCND1, CCND3 and STAT3 genes may play roles in bladder cancer development and progression, while cigarette smoking is significantly associated with CCND1 gene expression and consequently concluded to be contributing to the development of bladder cancer.

Background: In oral and maxillofacial surgery, synthetic bone grafts are most widely used as bone substitutes, due to the limited sources of autologous bone. The aim of this study was to examine the influence of three different synthetic bone grafts (Cerasorb, Fortoss and Perioglass) on sisters chromatide exchanges (SCEs) in peripheral lymphocytes. Materials and Methods: Peripheral blood samples taken from 68 patients (45 females and 23 males), who underwent oral surgery procedures, such as apical resection, cyst enucleation or periodontal curretage, were obtained for SCE a day before and two months after the surgeries. A control group included 30 patients, while the study group was made of the patients who underwent bone grafting with Cerasorb ® (11 patients), Fortoss ® VITAL (10 patients) or Perioglass ® (17 patients). Results: Comparing with the results of the study group before and after the treatment, it was concluded that the results were statistically significant (p = 0.001). In the Perioglass ® subgroup, a greater statistical significance (p = 0.003) was noted, than that in either the Cerasorb ® (p = 0.620) or Fortoss ® (p = 0.210) subgroups, in which there was no statistical significance. Conclusions: Although further investigations may be necessary, our results suggest that the synthetic bone grafts might have an influence on SCE in peripheral lymphocytes.

BACKGROUND Metal alloys utilized in the management of jaw fractures may exert genotoxic effects. Our purpose was to compare the genotoxicity of intermaxillary fixation devices containing nickel and chromium to that of titanium miniplates utilized in treatment of jaw fractures through the analysis of sister chromatid exchange. METHODS In this prospective study, in a total of 28 non-smoker patients (10 females, 18 males; mean age 33.43±10.76; range 15 to 60 years) with jaw fractures, 14 were treated with intermaxillary fixation by administration of nickel-chromium wire and arch bar and 14 with titanium miniplates to investigate the genotoxicity of different metal alloys. The outcome variable was the frequency of sister chromatide exchange in peripheral lymphoctyes, determined through the analysis of venous blood samples obtained preoperatively and 4 to 6 weeks postoperatively. RESULTS The frequency of the average sister chromatid exchange was found to be significantly higher in patients treated with the nickel-chromium intermaxillary fixation devices than those treated by titanium miniplates (1.29±0.29 vs. 0.46±0.39, p

Polymorphisms of the x-ray repair cross-complementing group 1 (XRCC1) gene have been reported to be associated with various forms of cancer. We evaluated the possible effects of the Arg194Trp and the Arg399Gln polymorphisms on the risk for chronic lymphocytic leukemia (CLL) in 73 patients and 50 controls. We also analyzed their relation to frequency of sister chromatid exchange (SCE). With respect to codon 194, the allelic frequency of the Arg194Trp polymorphism did not significantly differ between the 2 groups. The proportion of individuals carrying the Arg194Trp polymorphism was not different in the 2 groups. With respect to codon 399, the proportion of the individuals carrying the Arg399Gln allele (90% vs 62%; p=0.000; odds ratio [OR], 5.779; 95% confidence interval [CI], 2.2-15.183) and the allelic frequency of the Arg399Gln polymorphism (56% vs 36%; p=0.002; OR, 2.278; 95% CI, 1.350-3.843) was significantly higher in the patient group. The frequency of the Arg/Gln genotype was significantly higher in the patient group (68.50% vs 52%; p=0.049; OR, 2.007; 95% CI, 0.955-4.217). The mean SCE frequency in the patient group was significantly higher (9.2±4 vs 7.5±2; p=0.02). When different compound genotypes were compared, the coexistence of Arg/Arg genotype in codon 194 with Arg/Arg genotype in codon 399 was significantly more frequent in the control group (30% vs 9%; p=0.004; OR, 0.247; 95% CI, 0.092-0.664). Within the patient group, SCE frequency did not differ between patients with various genotypes. The Arg399Gln polymorphism may be etiologically associated with CLL; however, it does not seem to increase SCE frequency.

Oligodontia is the agenesis of 6 or more teeth, excluding third molars. The etiology of congenital absence of teeth is believed to be rooted in heredity or developmental anomalies. The absence of teeth in patients can cause aesthetic, functional, and psychological problems, particularly if the anterior region is involved. This case report describes the multidisciplinary treatment approach toward a patient 17 years of age with non-syndromic oligodontia, with absence of 11 permanent teeth. Genetic counseling revealed non-syndromic, autosomal-recessive-linked oligodontia. The objectives of the first phase of therapy were pre-prosthetic orthodontic space opening for proper positioning of the missing teeth and correction of inter-maxillary relations, as a prerequisite for proper prosthetic restoration. The second phase of therapy was prosthetic restoration of the missing teeth and provision of occlusion with full-mouth porcelain fused to metal crowns and bridges after increasing occlusal vertical dimension by 2 mm. (Eur J Dent 2012;6:218-226)

Item does not contain fulltext Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere. 01 juli 2010

Hereditary Gingival Fibromatosis (HGF) is a rare, benign disorder characterized by slowly progressive fibrous overgrowth of the gingiva. HGF occurs in several forms as a Mendelian trait (usually as an autosomal dominant condition), in malformation syndromes, in chromosomal abnormality syndromes and side effect of several pharmacological agents. Except Son of sevenless-1 (SOS1) gene mutation, molecular basis of HGF is unclear. Here, we reported the cytogenetic and SOS1 gene mutation analysis in a Turkish family with 7 affected members through three generations, whose features are consistent with the diagnosis of autosomal dominant, isolated hereditary gingival fibromatosis. To the best of our knowledge this is the first large Turkish family with hereditary gingival fibromatosis. In this study, we excluded the chromosomal abnormalities and the mutation in SOS1 gene at this family.

Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients.

Loss of heterozygosity (LOH) in a chromosomal location indicates the presence of an inactivated tumor suppressor gene (TSG). Inactivation of TSG has a functional role in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Based on the recent evidences of a putative TSG on chromosome 14, we examined LOH on chromosome 14q using eight polymorphic microsatellite markers in 50 cases of HNSCCs. Three regions were detected to have a high LOH rate which included 14q21.2-22.3 (42.5%), 14q31 (55%), and 14q32.1 (37%). The correlation between LOH and clinicopathological findings was investigated through statistical analyses. A strong correlation was observed between the highest LOH marker and the overall and disease-free survival. The results suggest that the distal part of chromosome 14 may host a TSG that may lead to the development and/or progression of HNSCCs. Several genes such as CHES1, BMP4, SAV, and PNN have arisen as candidate tumor suppressors in the region.