Cumhur Kaan Yaltirik

Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma

Chordomas are rare tumors of the spine and skull base that are locally destructive and resistant to chemotherapy and radiation therapy, with a poor prognosis and limited therapeutic options. Chordoma patients have a long life expectancy with high mortality from the disease. Cancer stem cells, which are known to exist in chordomas, have extensive proliferative and self-renewal potential and are responsible for maintaining tumor heterogeneity along with chemotherapy and radiotherapy resistance. Leukemia inhibitory factor (LIF) has multiple functions in stem cell biology, the immune response, and cancer, and is potentially a key molecule that allows cancer stem cells to self-renew. The purpose of this study was to determine whether LIF increases the aggressive traits of chordoma cells and leads to a poor prognosis in patients. Chordoma cell lines were treated with LIF, and functional tests were done. Twenty skull base chordoma samples were checked for levels of LIF and a correlation with clinicopathological features. The whole transcriptome microarray was used to observe changes in gene expression. We observed increased migration, invasion, tumorosphere formation, colony formation, epithelial-mesenchymal transition, and chemoresistance accompanied by a dramatic elevation in inflammatory gene networks and pathways in chordomas. The expression of LIF was associated with tumor size and a poorer overall survival. Microarray and quantitative real-time polymerase chain reaction assessments suggest that LIF can facilitate tumor-promoting inflammation. Results indicate that LIF plays a role in maintaining cancer stem cells in chordomas.

Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c

BackgroundAlthough meningioma is a common disease, there is a lack of understanding of the underlying molecular mechanisms behind its initiation and progression. We used combined miRNA-mRNA transcriptome analysis to discover dysregulated genes and networks in meningiomas.MethodsFourteen fresh-frozen meningioma samples and one human meningeal cell line were analyzed by using miRNA and whole transcriptome microarray chips. Data was filtered and analyzed. Candidate miRNAs and mRNAs were selected for validation in fifty-eight patient samples. miRNA and target mRNA relationships were assessed by inhibiting miRNA in meningioma cells. Apoptosis and viability assays were also used as functional tests.ResultsWith the whole transcriptome microarray, 3753 genes were found to be dysregulated, and 891 miRNAs were found to be dysregulated as a result of miRNA microarray. Results were combined and analyzed with bioinformatics tools. Top differential pathways included those of inflammation, cancer, and cellular growth and survival. The oncosupressor PTX3 was constitutively low in meningioma samples. Moreover, PTX3 negatively correlated with miR-29c in our samples. Inhibiting miR-29c upregulated the PTX3 level, induced apoptosis of meningioma cells, and decreased cell viability. CABIN1, miR-29c, TMOD1, PTX3, RPL22, SPARCL1 and RELA were correlated with clinicopathological features in patient samples.ConclusionsOur results present the first integrated mRNA-miRNA analysis in meningiomas. miR-29c-3p and PTX3 are inversely correlated in tissues and meningioma cells, hinting that PTX3 can be regulated by miR-29c-3p. Furthermore, we determined potential clinicopathological markers.

Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes

Although glioblastomas are common, there remains a need to elucidate the underlying mechanisms behind their initiation and progression and identify molecular pathways for improving treatment. In this study, sixteen fresh-frozen glioblastoma samples and seven samples of healthy brain tissues were analyzed with miRNA and whole transcriptome microarray chips. Candidate miRNAs and mRNAs were selected to validate expression in fifty patient samples in total with the criteria of abundance, relevance and prediction scores. miRNA and target mRNA relationships were assessed by inhibiting selected miRNAs in glioblastoma cells. Functional tests have been conducted in order to see the effects of miRNAs on invasion, migration and apoptosis of GBM cells. Analyses were carried out to determine correlations between selected molecules and clinicopathological features. 1332 genes and 319 miRNAs were found to be dysregulated by the microarrays. The results were combined and analyzed with Transcriptome Analysis Console 3 software and the DAVID online database. Primary differential pathways included Ras, HIF-1, MAPK signaling and cell adhesion. OncomiR candidates 21-5p, 92b-3p, 182-5p and 339-5p for glioblastoma negatively correlated with notable mRNA targets both in tissues and in in vitro experiments. miR-21-5p and miR-339-5p significantly affected migration, invasion and apoptosis of GBM cells in vitro. Significant correlations with overall survival, tumor volume, recurrence and age at diagnosis were discovered. In this article we present valuable integrated microarray analysis of glioblastoma samples regarding miRNA and gene-expression levels. Notable biomarkers and miRNA-mRNA interactions have been identified, some of which correlated with clinicopathological features in our cohort.

Encephalocraniocutaneous Lipomatosis: Haberland Syndrome

Patient: Male, 11 Final Diagnosis: Haberland syndrome Symptoms: Seizure Medication: — Clinical Procedure: Medical treatment Specialty: Neurosurgery Objective: Rare disease Background: Encephalocraniocutaneous lipomatosis (ECCL) was first announced as a new type of ectomesodermal dysgenesis in 1970 by Haberland and Perou. ECCL was first described in 1970, and approximately 60 cases have been reported since then. The classic triad of ECCL are skin, ocular, and central nervous system involvement, including conditions such as unilateral porencephalic cyst, ipsilateral lipomatous hamartoma of the scalp-eyelids-eye globe, cortical atrophy, cranial asymmetry, developmental delay, seizures, mental retardation, and spasticity of the contralateral limbs. The dermatological hallmark is a hairless fatty tissue nevus of the scalp called nevus psiloliparus. Case Report: An 11-year-old right-handed boy, born at full term, was referred to our clinic. His family had no consanguinity or history of neurocutaneous disease. The patient’s physical examination revealed a large hairless lesion on the right frontoparietal scalp called nevus psiloliparus. Beginning from the birth, a dermolipoma (an uncommon benign tumor) was reported to have occurred on the conjunctiva, mostly ipsilateral in his right eye and present on the ipsilateral side of the neurological abnormalities shown on magnetic resonance imaging and computed tomography. The patient had muscle weakness in left upper and lower extremities. He had a mild form of mental retardation. Conclusions: There is no specific treatment for ECCL. Management of ECCL is usually symptomatic. Surgical correction of a cutaneous lesion can be performed for cosmetic improvement. An early diagnosis of ECCL allows for early symptom treatment and improved patient quality of life.

Thoracic Epidural Hematoma Complicating Vertebroplasty

Patient: Female, 64 Final Diagnosis: Thoracic epidural hematoma Symptoms: Paraplegia Medication: — Clinical Procedure: Thoracal hemilaminectomy Specialty: Neurosurgery Objective: Diagnostic/therapeutic accidents Background: Percutaneous vertebroplasty procedures are commonly used to treat vertebral fractures. These techniques may be associated with major complications. Case Report: We present here a case of a 64-year-old female patient with T9 and T10 acute osteoporotic fractures, treated previously with vertebroplasty for four levels of osteoporotic vertebral fractures. The patient was treated by T9–T10 vertebroplasty. The post-operative neurological examination was normal. Two hours later, she progressively worsened and developed paraplegia. Magnetic resonance imaging (MRI) revealed a hyper-acute epidural hematoma over the T6 to T10 vertebrae. Evacuation of the epidural hematoma completely resolved her motor weakness. Previous literature reports one case with a thoracolumbar epidural hematoma over T11–L2 and another case with a L1 epidural hematoma after vertebroplasty. Conclusions: Percutaneous vertebroplasty is generally a safe procedure but can have rare complications. Epidural hematoma after vertebroplasty is one of the uncommon complications. Before percutaneous vertebroplasty, patients should be informed about these rare complications. Prognosis is very good if early intervention is possible.

Isolated C5 Vertebrae Dislocation with Trauma: An Extremely Rare Case of Isolated C5 Dislocation

Patient: Female, 36 Final Diagnosis: Isolated C5 vertebra dislocation Symptoms: Tetraplegia Medication: — Clinical Procedure: C5 corpectomy and anterior stabilization Specialty: Neurosurgery Objective: Rare disease Background: Total spondylolisthesis, or dislocation of 1 cervical vertebrae, is only caused by high-energy trauma and is usually fatal. Cervical spine fractures and dislocations often cause 3-column structural damage to the cervical spine, injury to the spinal cord, and precipitating alignment of the cervical vertebrae, as well as cervical instability, which are detrimental, show poor prognosis, and are associated with high rates of mortality rate and disability. Case Report: We report an extremely rare case of isolated C5 dislocation caused by falling out of a tree, with sudden tetraplegia. Conclusions: Total spondylolisthesis or dislocation of 1 cervical vertebrae can be surgically treated with anterior approach because it is possible to completely remove the vertebra body, intervertebral disc, and bone fragments, to directly decompress the spinal cord with stabilization.