Exosomal lncRNA LINC01356 Derived From Brain Metastatic Nonsmall-Cell Lung Cancer Cells Remodels the Blood-Brain Barrier.

Brain metastasis is a severe complication that affects the survival of lung cancer patients. However, the mechanism of brain metastasis in lung cancer remains unclear. In this study, we constructed an in vitro BBB model and found that cells from the high-metastatic nonsmall cell lung cancer (NSCLC) cell line H1299 showed a higher capacity to pass through the blood-brain barrier (BBB), as verified by Transwell assays, than cells from the low-metastatic NSCLC cell line A549. Brain microvascular endothelial cells (BMECs) could internalize H1299-derived exosomes, which remarkably promoted A549 cells across the BBB. The BBB-associated exosomal long noncoding RNA (lncRNA) was selected from the RNA-Seq dataset (GSE126548) and verified by real-time PCR and Transwell assays. LncRNA LINC01356 was significantly upregulated in H1299 cells and exosomes derived from these cells compared to that of A549 cells. Moreover, LINC01356 was also upregulated in serum exosomes of patients with NSCLC with brain metastasis compared with those without metastasis. In addition, BMECs treated with LINC01356-deprived exosomes expressed higher junction proteins than those treated with the control exosomes, and silencing LINC01356 in exosomes derived from H1299 cells could inhibit A549 cells from crossing the BBB. These data might indicate that the exosomal lncRNA LINC01356 derived from brain metastatic NSCLC cells plays a key role in remodeling the BBB system, thereby participating in brain metastasis in lung cancer.

Classification of Pituitary Adenomas Invading the Cavernous Sinus Assisted by Three-Dimensional Multimodal Imaging and Its Clinical Application.

Introduction To help diagnose and evaluate the prognosis of pituitary adenoma with cavernous sinus (CS) invasion and guide endonasal endoscopic surgery (EES) assisted by intraoperative navigation (ION) with three-dimensional multimodal imaging (3D-MMI). We propose a classification of CS invasion based on 3D-MMI. Methods We picked some appropriate cases and reconstructed the 3D-MMI and then classified them into 3 grades according to the stereo relationship among ICA, tumor and CS in 3D-MMI. Then, we applied different strategies according to their grade to remove pituitary adenomas that invaded the CS. Results All 38 patients were divided into 3 grades. Tumors compressing the ICA and CS without CS invasion were divided into grade 1. Tumors encasing the ICA and invading the superior-posterior compartment and/or anterior-inferior compartment but without distinct separation of the ICA and CS lateral wall were deemed as grade 2. Tumors encasing the ICA and filling the lateral compartment of the CS that dissociated the lateral wall from the ICA were deemed as grade 3. The 3D-MMI enabled adequate spatial visualization of the ICA, CS and tumors. All patients were operated on under the guidance of ION with 3D-MMI. Conclusion Classification based on 3D-MMI can better demonstrate the relationships among tumor, ICA and CS in a stereo and multi-angle view, which will have significance in guiding the surgical strategy.

LncRNA PITPNA-AS1 stimulates cell proliferation and suppresses cell apoptosis in glioblastoma via targeting miR-223-3p/EGFR axis and activating PI3K/AKT signaling pathway.

Glioblastoma (GBM) is a kind of malignant primary brain tumor, which is difficult to cure. Continuous researches have underlined that long non-coding RNAs (lncRNAs) get widely involved in the occurrence and progression of tumors, and glioblastoma is included. In this paper, we identified lncRNA PITPNA antisense RNA 1 (PITPNA-AS1) and explored its in-depth regulatory mechanism in glioblastoma cells. Firstly, RT-qPCR examined that PITPNA-AS1 was highly expressed in glioblastoma. Then, PITPNA-AS1 role in glioblastoma was assessed via functional assays. The results demonstrated that depletion of PITPNA-AS1 inhibited the proliferation and promoted the apoptosis of glioblastoma cells. After confirming that PITPNA-AS1 mainly existed in cell cytoplasm, we conducted mechanism assays which disclosed that PITPNA-AS1 sequestered microRNA-223-3p (miR-223-3p) and modulated epidermal growth factor receptor (EGFR) expression, thereby participating in the activation of PI3K/AKT signaling pathway. Eventually, rescue assays validated PITPNA-AS1 sponged miR-223-3p to promote EGFR expression, thus activating PI3K/AKT signaling pathway to accelerate proliferation and inhibit apoptosis of GBM cells. Overall, PITPNA-AS1 played an oncogenic role in glioblastoma which might be developed as a potential biomarker for glioblastoma diagnosis and treatment in the future.[Figure: see text].

A Series of 62 Skull Base Chordomas in Pediatric and Adolescent Patients: Clinical Characteristics, Treatments, and Outcomes.

BACKGROUND: Skull base chordomas in pediatric and adolescent patients are rare and challenging for surgeons. OBJECTIVE: Well-specified diagnosis and treatment are of great value for the long-term control of chordoma. This study summarizes well-followed pediatric and adolescent chordoma (PAC) patients treated in a single Asian center. METHODS: PAC patients were enrolled. Data collected included clinical presentation, tumor volume, texture, surgical approach, pathology, complications, adjuvant radiotherapy (RT), and long-term outcomes. RESULTS: Sixty-two patients were identified from a total of 516 skull base chordoma patients (12%). Diplopia was the most prominent complaint (30%). The craniocervical junction area was the most common location (41.8%) and had the highest proportion of large tumors. The gross total resection (GTR) rate was 20.3%. The GTR rate was lowest for tumors located in the craniocervical junction area. Thirty-eight cases experienced surgical complications. Of note, there was a significant difference in the complication rate between endoscopic approaches (22.7%) and open approaches (57.9%) (P = 0.005). The mean follow-up was 66.5 months. The GTR group showed better survival compared with the non-GTR group (P = 0.043). Metastases were found in two cases. No significant difference in the overall survival (OS) time was found between the group with RT and the group without RT (P = 0.559). CONCLUSIONS: A higher proportion of PAC patients than previously reported exist in the population in Asia, and the metastatic rate is lower. GTR predicts excellent long-term control of the disease. RT should be considered on an individual basis.

Surgical Outcomes of Cavernous Sinus Syndrome in Pituitary Adenomas.

OBJECTIVE: The type of pituitary adenoma with a manifestation that includes cavernous sinus syndrome is rare. Based on the clinical data of 70 patients, this study investigated the pathogenesis, imaging characteristics, and prognostic factors of pituitary adenoma with cavernous sinus syndrome. METHODS: We conducted a retrospective analysis of the characteristics of patients with pituitary adenoma with cavernous sinus syndrome who received surgical treatment. The patients were classified into different prognosis groups according to the time required for them to recover from the cavernous sinus syndrome. Univariate analyses were conducted for the correlations between the prognosis and factors. RESULTS: Of the 3598 cases of pituitary adenomas, 70 (1.95%) presented cavernous sinus syndrome. Of the patients, 55.7% recovered within 2 weeks of surgery, 24.3% recovered from 2 weeks to 1 year after surgery, and 20% had not returned to normal after more than 1 year after surgery. Univariate analyses showed that shorter disease duration (P < 0.001), lower Knosp grade (P = 0.045), a transsphenoidal approach (P < 0.001), and associated pituitary apoplexy (P = 0.012) were predictive factors of early postoperative recovery. CONCLUSIONS: The prognosis of cavernous sinus syndrome differs depending on the mechanism of the syndrome. There was no significant difference in the prognosis between patients with total pituitary adenoma resection and subtotal resection. Timely surgery within 100 days of symptom occurrence, Knosp grade 0-2, and associated pituitary apoplexy are predictive factors of good prognosis.

Rosette-Forming Glioneuronal Tumor Originating From the Spinal Cord: Report of 2 Cases and Literature Review.

Rosette-forming glioneuronal tumor (RGNT) is a recently recognized and rarely encountered tumor occurring in the fourth ventricle. RGNT was first described as a new entity for the distinct clinicopathologic features by Komori et.al. in 2002. Histologically, it is composed of 2 distinct features: a glial component, resembling pilocytic astrocytoma, and a neurocytic component forming neurocytic rosettes and/or perivascular rosettes. We report 2 extremely rare cases of RGNT arising from the spinal cord, which were misdiagnosed as ependymoma and astrocytoma preoperatively. Symptoms included dissociated sensory disturbances and episodic pain and fatigue of 2 years' duration in case 1, as well as motor disturbance for 2 months' duration in case 2. Magnetic resonance imaging (MRI) revealed these masses in the thoracolumbar (T7-L1) and cervicothoracic (C3-C7) spinal cord. The solid component appeared hypointense in T1-weighted MRI sequences, hyperintense in the T2-weighted MRI sequences, and heterogeneous in MRI images enhanced with gadolinium contrast medium in both cases. Gross total resection was performed via a median laminectomy. Postoperative pathological examination confirmed the diagnosis of RGNT. In addition, extensive analysis of genetic mutations was performed to explore the relationship with glioma, including telomerase reverse transcriptase promoter, isocitrate dehydrogenase 1/2, BRAF-V600E, and O(6)-methylguanine-DNA methyltransferase promoter. No radiotherapy or chemotherapy were performed in these two cases. As of the latest follow-up, both patients had a good prognosis. Given the widely varying clinical characteristics of, prognosis of, and treatments for spinal tumors, differential diagnosis is of great importance before surgery. Consideration of the tumor location and the patient's age and sex, in combination with the imaging features, may be the best approach to narrowing the differential diagnosis. Surgery is the preferred treatment for RGNT. We do not recommend to implement adjuvant radiotherapy and chemotherapy in these patients except the invasive or recurrent tumors. Further examination and routine follow-up should be recommended to estimate the long-term prognosis.

Association of Craniovertebral Junction Anomalies, Klippel-Feil Syndrome, Ruptured Dermoid Cyst and Mirror Movement in One Patient: A Unique Case and Literature Review.

The Klippel-Feil syndrome (KFS) has been reported to be associated with intracranial neoplasms, most frequently epidermoid or dermoid cysts. To our knowledge, however, patients who present with a posterior fossa dermoid cyst (DC) and KFS are extremely rare with only 24 previously reported cases in the English literature worldwide. Therefore, we present the first report of a patient with a craniocervical ruptured DC accompanied by craniovertebral junction (CVJ) anomalies, KFS and mirror movement. Meanwhile, a literature review of KFS accompanying with posterior fossa DC discusses these conditions from the embryological, anatomical, clinical and therapeutic perspectives. Additionally, the combination of CVJ anomalies, KFS and DC may represent a new syndrome that has previously gone unnoticed.

Diagnosis and microsurgical treatment of chondromas and chondrosarcomas of the cranial base.

Chondromas and chondrosarcomas of the cranial base are rare neoplastic diseases. The aim of the present study was to evaluate the diagnosis and microsurgical treatment of these difficult cranial base tumors. A total of 19 patients who underwent microsurgery were pathologically diagnosed with cranial base chondromas or chondrosarcomas and their clinical data was reviewed. The chondromas and chondrosarcomas of the cranial base in the present study commonly originated in the sphenopetrosal, sphenoclival or petroclival junctions, and the majority were located in the parasellar region of the middle cranial base extradurally. The most frequent symptoms were headaches and cranial nerve palsy, and the Karnofsky performance score (KPS), assessed pre-operatively, averaged at 87.1. A frontotemporal or preauricular subtemporal-infratemporal approach was used in 11 cases, a tempo-occipital transtentorial or presigmoid supratentorial-infratentorial approach was employed in six further cases, and the far-lateral or retrosigmoid approach was applied in the remaining two cases. A total or near-total tumor removal was secured in 13 cases, while a subtotal removal was obtained in another five and a partial removal was achieved in one case. The most common post-operative complications included cranial nerve palsy and cerebrospinal fluid leakage, but there were no post-operative fatalities. A total of 15 patients were followed up for a mean of 67.2 months (range, 5-140 months), and 13 (76.5%) of these patients were living normal lives (KPS, 80-90). There were two patients with recurrent tumors. The neuroradiological examinations and the presenting symptoms and signs allow the pre-operative diagnosis to be presumed for the majority of cranial base chondromas or chondrosarcomas. Surgical resection is the key treatment for these tumors, and this treatment is known to improve the survival rates.

Diagnosis and management of adult intracranial neurenteric cysts.

BACKGROUND: Intracranial neurenteric cysts are rare, benign lesions of the central nervous system. OBJECTIVE: To analyze our experience with these lesions and conduct a review of the literature with the aim of identifying a rational approach to diagnosis and management. METHODS: Seven patients underwent surgical treatment for intracranial neurenteric cysts from July 2000 to December 2008. The general strategy was to perform complete resection whenever possible. The clinical, radiological, operative, and pathological findings of the patients were reviewed retrospectively. RESULTS: This series included 3 women and 4 men. The age of hospitalized patients ranged from 19 to 55 years, with an average age of 34 years. Headache and dizziness were the most common chief symptoms. The imaging spectrum for these lesions is broad, leading to several preoperative misdiagnoses. All 7 lesions were resected by a far lateral transcondylar or retrosigmoid approach. Total tumor resection was achieved in 3 patients. Four patients presented transient fever postoperatively. All patients were healthy and showed no signs of tumor recurrence at their latest follow-up. CONCLUSION: Intracranial neurenteric cysts ventral to the brainstem are rare lesions occurring in young adults. These lesions should be considered in the differential diagnosis for intracranial extra-axial cystic lesions anterior to the brainstem. Total surgical resection seems to be the most effective therapeutic method, although radical resection at the risk of impairing the brainstem is not recommended. This benign lesion has a favorable overall prognosis.