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Background Deep-seated clival varied malignancies represent a surgical challenge because of complex anatomy and surgical procedures posing great risks to adjacent neurovascular structures. To investigate effects of diagnosis and treatment of clival region lesions, review experience of individualized surgical procedures and comprehensive therapy. Methods and Results A total of 56 patients with clival malignancies from July 2007 to December 2018 were included. The patients mainly presented with headache and cranial nerve paresis. After multidisciplinary consultation, radical resection were performed in 45 cases different kinds of surgical approaches including endonasal (15 cases, 33.33% ), intraoral accompanied by intraoral and endonasal combined (7 cases, 15.56%), Derome (8 cases, 17.78%), maxillary swing (9 cases, 20%), and infratemporal (6 cases, 13.33%) approaches were chosen according to clinical and radiographic findings, and biopsies were performed in 11 patients to confirm the pathological diagnosis. The primary pathological finding was chordoma (28 cases, 50%). Total resection was achieved in 21 cases (46.67%), and 17 cases (37.78%) underwent subtotal resection. Besides, partial resection was performed in 7 cases (15.56%). The complications developed in 28 patients, including cranial nerve deficits (13 cases, 23.21%), cerebrospinal fluid leakage (14 cases, 25%), intracranial infection (8 cases, 14.29%), pneumonitis (2 cases, 3.57% ), postoperative hematoma (2 cases, 3.57% ), and mental disorder (1 cases, 1.79% ). Adjuvant chemoradiotherapy was provided by the oncologists depending on the pathological findings. The average follow-up was 59.90 months, but 8 patients (14.29%) were lost. The progression-free survival was achieved in 16 patients (28.57%), whereas the disease progression occurred in 13 patients (23.21%). The mortality was 33.93% (19/56). Conclusions Although malignancies occupy a larger subset of clival tumors, not all are needed to be radically resected. Our preliminary results suggest that multidisciplinary consultation is indispensable to clarify the therapeutic purpose and provide individualized surgical approaches. Postoperative comprehensive therapy may reduce the surgical complications and improve the outcomes of patients. [ABSTRACT FROM AUTHOR]

Objective To review experience of diagnosis, surgical procedures and comprehensive therapeutic strategies for skull base bone tumors. Methods and Results Clinical data of 76 patients with skull base bone tumors were retrospectively analyzed from September 2006 to March 2018. After preoperative assessment, different kinds of surgical approaches including endonasal, intraoral, maxillary swing, craniocervical transjugular, Derome, frontotemporal and infratemporal approaches were chosen according to clinical and radiographic findings. In comparison with 24 patients receiving the endoscopic surgery, other 52 patients were operated on under microscopic visualization. Total resection was achieved in 38 cases, and 22 patients underwent subtotal resection. In addition, 14 cases received partial resection while biopsies were performed in 2 cases to confirm histological findings. Tumor pathology included chordoma (28 cases), osteosarcoma (19 cases), chondrosarcoma (11 cases), fibrous dysplasia (8 cases), giant cell tumor of bone (5 cases), osteoblastoma (3 cases), osteochondroma (1 case), and chondromyxiod fibroma (1 case). Complications included cranial nerve deficits (19 cases), hemiparesis (3 cases), cerebrospinal fluid leakage (12 cases), intracranial infection (8 cases), pneumonitis (4 cases), and wound dehiscence (4 cases). During a 20 to 158 months follow-up, 11 cases were lost and 21 patients died in the study period. The disease-free survival was achieved in 34 cases while 10 patients experienced tumor progression. Conclusions Malignant bone tumors invading the skull base is much more common comparing with the benign lesions. Multidisciplinary consultation may improve diagnostic reliability and clarify the therapeutic purpose. Radical resection using the individualized approaches accompanied by comprehensive therapy should be considered to improve the outcomes of patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficiency of a peptide nucleic acid (PNA) delivery system by using liposome via PNA-DNA hybrids and to test the inhibitive action of antisense PNA on expression of multidrug resistance (MDR) related P-glycoprotein (P-gp) in human neuroblastoma cell line SK-N-SH., Methods: Two antisense PNAs were designed targeting at MDR-1 mRNA and then combined with partially complement DNAs respectively. The hybrids were delivered into cells using cationic liposome. The transfection efficiency, expression of P-gp and MDR-1 mRNA, intracellular adarimycin (ADM) were measured by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and high performance liquid chromatography (HPLC)., Results: Transfection of PNA increased the cell average fluorescence intensity significantly and the extent of increase was dependent on the concentration of PNA. After being transfected by both PNAs, P-gp expression of SK-N-SH cells decreased significantly and the intracellular ADM level was increased by about 3 times. The level of MDR-1 mRNA expression slightly decreased after transfection, but no statistical significance was observed., Conclusions: PNA can be delivered into tumor cells in form of PNA-DNA hybrids by cationic liposome. Properly designed antisense PNA can inhibit MDR related P-gp expression of SK-N-SH cells efficiently and specifically.

Objective: To investigate the effectiveness of phosphorothioate multidrug resistance gene 1 (MDR1) antisense oligodeoxynucleotides (MDR1-AS) suppressing MDR1 expression in multidrug-resistant glioma cell line C6/adr., Methods: The glioma cell line C6/adr served as the tested model in vitro, MDR1-AS (5'-CTCCATCACCACCTC-3'), complementary to the -9- +6 sequence of first exon, was synthesized and phosphorothioate-modified. As control of sequence specificity, MDR1-S (5'-GAGGTGGTGA TGGAG-3') was used. Both antisense and sense oligodeoxynucleotides were transduced to C6/adr cells by lipofectin. The cytotoxity of MDR1-AS was tested using morphological observation and 3- (4,5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide assay. Semi-quantitative reverse transcription polymerase chain reaction was used to monitor the expression levels of the MDR1 mRNA in the different groups. The positive rate of the MDR1 gene product P glycoprotein (P-gp) was determined by flow cytometry assessment., Results: No cytotoxicity of MDR1-AS was observed. The MDR1 mRNA expression level was decreased from 106% to about 30.44% 48 h after MDR1-AS treatment. The P-gp positive rate of MDR1-AS treated C6/adr cells decreased from 100% to 32.77%, with that of C6/adr cells considered as 100%., Conclusions: MDR1-AS can effectively inhibit MDR1 expression in the C6/adr cell line at both the mRNA and protein level, and may be an alternative treatment of drug-resistant gliomas.

Objective: To evaluate the animal model of the multidrug resistant glioma cell line C6/adr for further in vivo studies., Methods: The rat glioma cells C6 and multidrug resistance cells C6/adr were cultured in vitro and implanted into the brain of S-D rats. After implantation, all these animals were examined continually with magnetic resonance imaging (MRI) and histological examination. The growth procedure of intracranial implanted glioma and the survival span of the animal model were evaluated. The statistical analysis was made between the survival data of the two cell lines., Results: The symptoms of intracranial hypertension did not occur until 4 weeks after inoculation. The MRI findings of the implanted glioma in the rat brain were much earlier than the abnormal behavior observed. Pathological results after inoculation demonstrated the MRI findings. The two cell lines had similar growth characteristics and no significant differences in survival times., Conclusion: These results suggest that by means of MRI and histology the growth procedure of the implanted glioma in vivo be successfully observed. All these data will proved to be a useful basis for study of glioma in vivo.

Objective: To establish a drug-resistance cell line of human glioma mediated by MGMT., Methods: Simulated the clinical usage of BCNU to establish a BCNU-resistant human glioma subline by cyclic exposing the U251 parent cells to a constant concentration of BCNU. The resistance index and the expression of MGMT mRNA of U251/BCNU were detected and compared the difference of in vitro proliferation between U251 and U251/BCNU., Results: A subline--U251/BCNU was successfully established in about 4-month culture, which had a stable resistance to BCNU. U251/BCNU cells showed 17-fold higher resistance to BCNU than did U251 cells by MTT assay, while U251/BCNU cells expressed MGMT mRNA. The doubling time of U251 and U251/BCNU had no statistical difference., Conclusion: A drug-resistance cell line of human glioma mediated by MGMT is established, which could provide experimental basis for further studies on the resistance mechanism and reversal methods of glioma chemotherapy.