Downregulation of iASPP Expression Suppresses Proliferation, Invasion and Increases Chemosensitivity to Paclitaxel of Head and Neck Squamous Cell Carcinoma In Vitro.

Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma (HNSCC) and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival of HNSCC. This study investigated the function of iASPP playing in proliferation and invasion of HNSCC in vitro. Methods HNSCC cell line Tu686 transfected with Lentiviral vector-mediated iASPP-specific shRNA and control shRNA were named the shRNA-iASPP group and shRNA-NC group, respectively. The non-infected Tu686 cells were named the CON group. CCK-8 assay, flow cytometry, transwell invasion assay were performed to detect the effects of iASPP inhibition in vitro. Results Our results demonstrated that the proliferation of shRNA-iASPP cells at the time of 72 h (F=32.459, P=0.000), 96 h (F=51.407, P=0.000), 120 h (F=35.125, P=0.000) post-transfection, was significantly lower than that of shRNA-NC cells and CON cells. The apoptosis ratio of shRNA-iASPP cells was 9.42% ± 0.39% (F=299.490, P=0.000), which was significantly higher than that of CON cells (2.80% ± 0.42%) and shRNA-NC cells (3.18% ± 0.28%). The percentage of shRNA-iASPP cells in G0/G1 phase was 74.65% ± 1.09% (F=388.901, P=0.000), which was strikingly increased, compared with that of CON cells (55.19% ± 1.02%) and shRNA-NC cells (54.62% ± 0.88%). The number of invading cells was 56 ± 4 in the shRNA-iASPP group (F=84.965, P=0.000), which decreased significantly, compared with the CON group (111 ± 3) and the shRNA-NC group (105 ± 8). The survival rate of shRNA-iASPP cells administrated with paclitaxel was highly decreased, compared with CON cells and shRNA-NC cells (F=634.841, P=0.000). Conclusion These results suggest iASPP may play an important role in progression and aggressive behavior of HNSCC and may be an efficient chemotherapeutic target for the treatment of HNSCC.

Water-soluble photoluminescent fullerene capped mesoporous silica for pH-responsive drug delivery and bioimaging.

In this paper, a biocompatible and water-soluble fluorescent fullerene (C60-TEG-COOH) coated mesoporous silica nanoparticle (MSN) was successfully fabricated for pH-sensitive drug release and fluorescent cell imaging. The MSN was first reacted with 3-aminopropyltriethoxysilane to obtain an amino-modified MSN, and then the water-soluble C60 with a carboxyl group was used to cover the surface of the MSN through electrostatic interaction with the amino group in PBS solution (pH = 7.4). The release of doxorubicin hydrochloride (DOX) could be triggered under a mild acidic environment (lysosome, pH = 5.0) due to the protonation of C60-TEG-COO-, which induced the dissociation of the C60-TEG-COOH modified MSN (MSN@C60). Furthermore, the uptake of nanoparticles by cells could be tracked because of the green fluorescent property of the C60-modified MSN. In an in vitro study, the prepared materials showed excellent biocompatibility and the DOX-loaded nanocarrier exhibited efficient anticancer ability. This work offered a simple method for designing a simultaneous pH-responsive drug delivery and bioimaging system.

Glucose- and pH-responsive nanogated ensemble based on polymeric network capped mesoporous silica.

In this paper, a glucose and pH-responsive release system based on polymeric network capped mesoporous silica nanoparticles (MSN) has been presented. The poly(acrylic acid) (PAA) brush on MSN was obtained through the surface-initiated atom transfer radical polymerization (SI-ATRP) of t-butyl acrylate and the subsequent hydrolysis of the ester bond. Then the PAA was glycosylated with glucosamine to obtain P(AA-AGA). To block the pore of silica, the P(AA-AGA) chains were cross-linked through the formation of boronate esters between 4,4-(ethylenedicarbamoyl)phenylboronic acid (EPBA) and the hydroxyl groups of P(AA-AGA). The boronate esters disassociated in the presence of glucose or in acidic conditions, which lead to opening of the mesoporous channels and the release of loaded guest molecules. The rate of release could be tuned by varying the pH or the concentration of glucose in the environment. The combination of two stimuli exhibited an obvious enhanced release capacity in mild acidic conditions (pH 6.0).

Highly efficient antibacterial surface grafted with a triclosan-decorated poly(N-hydroxyethylacrylamide) brush.

This work presented a highly efficient antibacterial Ti-surface which was grafted with poly(N-hydroxyethylacrylamide) (PHEAA) brush and further decorated with triclosan (TCS). The modified surfaces were characterized using contact angle measurements, X-ray photoelectron spectroscopy, and attenuated total reflectance Fourier transform infrared. The antibacterial performance of the modified surfaces was evaluated using the Streptococcus mutans and Actinomyces naeslundii attachment test. The Ti surface with PHEAA brush (Ti-PHEAA) was able to resist the adhesion of the bacteria, while the TCS-decorated Ti surface (Ti-TCS) showed the capability of killing the bacteria adhered on the surface. As we coupled the TCS to the PHEAA brush, the surface showed highly efficient antibacterial performance due to the combination of the resistance to the bacteria adhesion and its activity of killing bacteria.

[Resection of parapharyngeal neoplasms via styloid diaphragm approach].

OBJECTIVE: To evaluate the surgical technique and efficacy of the resection of parapharyngeal space neoplasm via styloid diaphragm approach. METHODS: Thirty-three cases underwent the resection of parapharyngeal space tumors via styloid diaphragm approach from Jan 2005 to Jan 2011 were reviewed. Of the cases, 28 were with benign tumors treated by surgery alone, and 5 were malignant tumors treated by surgery plus postoperative radical radiotherapy. RESULTS: The parapharyngeal neoplasms in all cases were completely resected via styloid diaphragm approach. The postoperative follow-up ranged from 13 months to 7 years (median = 4.6 years). No tumor recurrence was found in 30 cases, but 3 cases experienced tumor recurrence, including 1 chondrosarcoma (3 years after surgery and chemoradiotherapy), 1 chordoma and 1 adenoid cystic carcinoma (5 years after surgery and radiotherapy). Severe postoperative complications were not observed, but 2 cases showed mild mouth askew and fully recovered after 3 months, and 1 case was complicated with hoarseness and cough symptoms that disappeared after heteropathy. CONCLUSION: Resection of parapharyngeal neoplasms via styloid diaphragm approach is an ideal surgical technique, with well-exposed surgical field, less tissue injury, and less postoperative complication.

Endoscopic surgery of cavernous sinus tumors originating from the extradura.

In the present study, we explored the effects of various endoscopic approaches in patients with cavernous sinus (CS) tumors. Five endoscopic approaches, including the endoscopic transseptal transsphenoidal approach, extended endoscopic transseptal transsphenoidal approach, extended transnasal transmaxillary approach, extranasal extended maxillary sinus approach, and endoscopic transnasal transpterygoid approach, were selected for the resection of CS tumors from 36 patients. Thirty gross total tumors and 6 subtotal tumors were removed. After a follow-up period of 6 months to 3 years, 30 patients were determined to be recurrence-free, and 2 patients had unchanged residual tumors. One patient with a recurrent pituitary adenoma underwent a second surgery, and 1 patient with chordoma died because of an intracavernous carotid artery rupture 18 months after the operation. Various endoscopic approaches tailored to the origin and extent of the CS tumor were proven efficacious for the maximal and precise removal of CS tumors while avoiding vital structures.

[Expression of HMGB1 protein in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To evaluate the expression of HMGB1 protein in tissue specimens of laryngeal squamous cell carcinoma (LSCC) and adjacent normal mucosa, and explore the correlation of HMGB1 protein expression with clinicopathologic features and prognosis in LSCC. METHODS: Ninty-three cases of LSCC and 5 cases of adjcent mucosal tissue samples were included in this study. Immunohistochemical staining was performed on paraffin-embedded tissue specimens to examine the HMGB1 protein expression. The data were futher correlated with the clinicopathological features and prognosis of the LSCC patients. RESULTS: The positive rates of HMGB1 expression in LSCC specimens was 87.1%, significantly higher than that in the adjcent normal mucosa samples (46.7%, P = 0.001), and its overexpresion was closely correlated with T stage (Chi2 = 10.878, P = 0.004), clinical stage (Chi2 = 21.115, P < 0.01), metastasis (Chi2 = 28.298, P < 0.01) and recurrence (Chi2 = 14. 923, P = 0.001) in patients with LSCC. Patients with HMGB1 overexpression had both poorer disease-free survival and poorer overall survival compared with that in patients with low HMGB1 expression (Chi2 = 13.815, Chi2 = 11.912; Both P < 0.01). Univariate and multivariate Cox regression analyses revealed that HMGBI expression is an independent prognostic factor for patients with LSCC. CONCLUSIONS: The results of this study demonstrate that HMGB1 protein expression is significantly increased in LSCC tissues, and HMGB1 protein overexpression is associated with a poorer prognosis in patients with LSCC. These results suggest that HMGB1 may play a critical role in the initiation and progression of LSCC, implicating HMGB1 may become a valuable marker for the prediction of prognosis in patients with LSCC.

[EphA2 promotes angiogenesis and metastasis of head and neck squamous cell carcinoma in vivo].

OBJECTIVE: To investigate the effects of EphA2 on the angiogenesis and cervical lymph node metastasis of squamous cell carcinoma of the head and neck (SCCHN) in vivo. METHODS: EphA2 short hairpin (shRNA) lentiviral particles were used to knockdown the expression of EphA2 in SCCHN cell line M2 with high lymph nodes metastasis rate. Stable clones, obtained by puromycin screening, were assayed by RT-PCR and Western blot to validate the gene silencing efficiency and were used to establish SCCHN metastatic xenograft mouse model. Hematoxylin-eosin staining was applied to identify cervical lymph node metastasis of SCCHN in xenografted tumors. Immunohistochemistry was used to observe microvessel density. Western blot was used to investigate the protein expressions of EphA2 and vascular endothelial, growth factor (VEGF). RESULTS: EphA2 shRNA lentiviral particles efficiently decreased the mRNA and protein expressions of EphA2 in SCCHN cell line M2, which were further successfully utilized to establish SCCHN metastatic xenograft mouse model. Compared with xenografted tumors in control group, xenografted tumors in M2EphA2RNAi(+) group decreased significantly tumor volume [(430.7 ± 190.0) mm(3) (x(-) ± s) vs (1179.0 ± 289.4) mm(3)] and weight [(0.26 ± 0.10) g vs (0.54 ± 0.12) g] (both P < 0.05). More importantly, bilateral cervical lymph node metastasis rate in M2EphA2RNAi(+) was also greatly declined (Mann-Whitney U = 10.0, P < 0.05). Decreased protein expressions of EphA2 and VEGF and microvessel density were observed in M2EphA2RNAi(+) group (t = 26.751, P < 0.01). CONCLUSIONS: Knockdown of EphA2 expression led to the inhibition of tumor growth and metastasis in SCCHN nude mouse model. More importantly, SCCHN angiogenesis was also impeded, which might be associated with the decreased expression of VEGF.

[Correlation of EphA2 protein expression with clinicopathological characteristics and prognosis in laryngeal squamous cell carcinoma].

OBJECTIVE: To evaluate the expression of EphA2 protein in tissue specimens and cell lines of laryngeal squamous cell carcinoma (LSCC), and to further study the correlation of EphA2 protein expression with clinicopathological characteristics and prognosis in LSCC. METHODS: Western blot was applied to assess the EphA2 protein expression in LSCC cell line Hep-2 cells and the head and neck immortalized epithelial cell line NP-69 cells. Immunohistochemical staining was performed on paraffin sections of 88 cases of LSCC specimens and 16 cases of adjcent normal tissue samples to investigate the EphA2 protein expression, and to futher elucidate its correlation with clinicopathological characteristics. RESULTS: Compared with the NP-69 cells, EphA2 expression in LSCC cell line Hep-2 cells was upregulated. The positive rates of EphA2 expression in LSCC and adjcent normal tissues samples were 80.7% and 43.8%, respectively, with a significant difference between the two groups (P < 0.001). EphA2 overexpresion was closely correlated with clinical stage (I + II/III + IV, P = 0.005), metastasis (P = 0.025) and recurrence (P = 0.021) in LSCC. Furthermore, patients with EphA2 overexpression had poorer tumor-free survival and 5-year overall survival compared with that in patients with low EphA2 expression (33.3% vs. 63.2%, P = 0.003; 46.7% vs. 81.6%, P = 0.002). EphA2 expression combined with clinical stage provided a better predictive value in prognosis. Univariate and multivariate Cox regression analysis revealed that EphA2 expression is an independent prognostic factor for patients with LSCC (P = 0.019). CONCLUSIONS: The results of this study demonstrate that EphA2 protein expression is significantly increased in LSCC tissues and cell lines, and EphA2 protein overexpression is associated with tumor recurrence, metastasis and poorer prognosis in LSCC patients. These results suggest that EphA2 may play a critical role in the initiation and progression of LSCC, implicating EphA2 as a valuable marker for the prediction of recurrence, metastasis and prognosis in LSCC.

[Endoscopic posterior septectomy for patients with nasopharyngeal tumor].

OBJECTIVE: To explore the techniques, advantages and disadvantages, indications and cautions of a surgical approach for the resection of nasopharyngeal tumor. METHODS: Ten cases with nasopharyngeal tumors were recruited in this study, of them, 3 cases with residual nasopharyngeal carcinoma after chemoradiotherapy, 2 cases with cavernous angioma, 2 cases with benign mixed tumor, 1 malignant mixed tumor, 1 adenoid cystic carcinoma, and 1 chordoma. All patients underwent endoscopic resection of posteroinferior quarter part of nasal septum, and then the removal of nasopharyngeal tumors through bilateral transnasal approach. RESULTS: Total resection of the tumor was achieved for all cases without severe surgical complications. All cases with benign tumors, with following-up of 6-18 months, showed no recurrence. Of 6 cases with malignant tumors, with following-up of 12-48 months, 5 cases showed no recurrence, and 1 case was suspected to relapse one year postoperatively, but not with any lesion enlargement after another 6 month follow-up. CONCLUSIONS: Posteroinferior quarter part of nasal septectomy is preferred for endoscopic resection of nasopharyngeal tumors because it can provide a panoramic view on nasopharyngeal cavity and tumors, thus, facilitating the removal of nasopharyngeal tumors.

[Tumor-targeted human telomerase reverse transcriptase promoter/tk gene therapy against human nasopharyngeal carcinoma cells in vitro].

OBJECTIVE: To investigate the targeted killing effect of human telomerase reverse transcriptase promoter (hTERTp)/tk gene on human nasopharyngeal carcinoma (NPC) cells. METHODS: The recombinant plasmid hTERTp/tk/pGL3 was transfected into human NPC HNE1 cells and the expressions of TK and telomerase were investigated. The targeted killing effect induced by hTERTp/tk on HNE1 cells was assessed using RT-PCR and MTT assay. RESULTS: TK gene expression was detected in HNE1 cells transfected by hTERTp/tk/pGL3, and the cells showed reduced telomerase and hTERT expression as compared with the control cells. hTERTp/tk/pGL3 resulted in target killing of HNE1 cells but not of the normal control cells. The tumor cell-killing effect of hTERTp/tk/pGL3 was slightly milder than that of the positive control CMV/tk/pGL3 that produced nonselective cell killing. CONCLUSION: hTERTp/tk, a tumor-specific expression system, allows targeted tumor cell killing and reduces the activity of telomerase in NPC cells in vitro.

[Clinical study on mometasone furoate nasal spray in the treatment of non-allergic rhinitis].

OBJECTIVE: To evaluate the outcome of mometasone furoate nasal spray (MFNS) used for 3 months on non-allergic rhinitis (NAR). METHODS: In this multicenter study, NAR patients were enrolled from eight hospitals and received MFNS 200 microgram once daily for 3 months. The patients were followed-up for three times (at baseline, month 1 and month 3) to record the symptom scores and nasal endoscopic appearances. At the same time, the adverse events frequency was recorded and analyzed. RESULTS: A total of 188 NAR cases were enrolled in the study. The total nasal symptom score assessment descended significantly at month 1 (1.70 ± 0.75) and month 3 (0.95 ± 0.79) visits versus at baseline (2.67 ± 0.68, Z value were from -11.603 to -10.491, all P < 0.01). The individual symptoms, including nasal stuffiness, nasal discharge, nasal stuffiness-related dizziness or headache, hyposmia, sleep quality, daily life activity, work or study efficiency, mental status, and whole body fatigue, also showed less scores at month 1 and month 3 visits versus at baseline (Z value were from -11.313 to -6.802, all P < 0.01). At the same time, nasal mucosal appearances assessed by endoscopy had lower scores at month 1 (1.40 ± 0.62) and month 3 (0.75 ± 0.71) visits versus at baseline (2.27 ± 0.73, Z value were from -11.484 to -10.002, all P < 0.01). Additionally, adverse events were only observed in 5.3% cases with light rhinorrhagia and nasal dryness. No other side effect was found. CONCLUSIONS: A 3-months administration of intranasal mometasone can effectively and safely improve NAR patients' clinical symptom and nasal mucosal appearances.

Differential gene expression profiling of laryngeal squamous cell carcinoma by laser capture microdissection and complementary DNA microarrays.

BACKGROUND AND AIMS: Genetic alteration associated with initiation and progression of laryngeal squamous cell carcinoma (LSCC) is largely unknown. The aim of this study was to identify genetic changes associated with the disease pathogenesis and pinpoint genes whose expression is impacted by these genetic alterations. METHODS: Tumor cells were collected from eight matched pairs of specimens of glottic carcinoma of the larynx and histologically normal epithelium tissues adjacent to the carcinoma by laser capture microdissection (LCM). RNAs prepared from these cells were used for genome-wide transcriptome analysis by probing 16 cDNA microarrays. Real-time quantitative RT-PCR and immunohistochemistry of tissue microarrays were used to validate a group of the differentially expressed genes identified by the cDNA microarrays. RESULTS: Hierarchical cluster analysis of the expressed genes showed that 2351 genes were differentially expressed and could distinguish cancerous and noncancerous samples. We also found 761 differentially expressed genes that were consistently different between early stage and later stage specimens. Furthermore, abnormal expression of some relevant genes such as MMP12, HMGA2, and TIMP4 were validated by real-time quantitative RT-PCR and immunohistochemistry. Analysis of gene ontology and pathway distributions then highlighted genes that may be critically important to laryngeal carcinogenesis. CONCLUSIONS: Our results suggest that using LCM plus DNA microarray analysis may facilitate the identification of clinical molecular markers for disease and novel potential therapeutic targets for LSCC.

[Global gene expression profiling of laryngeal squamous cell carcinoma by laser capture microdissection and complementary DNA microarrays].

OBJECTIVE: To examine the gene expression profile of laryngeal squamous cell carcinoma (LSCC) by combination of laser capture microdissection (LCM) and microarray and to identify genetic changes in disease pathogenesis. METHODS: The study analysed 8 matched pairs of specimens of glottic carcinoma of larynx and histologically normal epithelium tissues adjacent to the carcinoma preserved in the RNA later reagent. A genome-wide transcriptome analysis was performed by probing 16 cDNA microarrays with fluorescent-labeled amplified RNA derived from laser capture microdissected cells. Real-time quantitative (RT-PCR) of tissue microarray was used to validate the reliability of cDNA microarrays. RESULTS: Significant analysis of microarray (SAM) software and hierarchical cluster analysis of the expressed genes showed that 2351 genes was significantly expressed respectively according to different analysis method (false discover rate = 0.63%). A selected set of MMP12, KRT16, RARB, PRB1 genes was identified to be consistent with array data by RT-PCR. CONCLUSIONS: The analysis of gene ontology and pathway distributions futher highlighted genes that may be critically important to laryngeal carcinogenesis. The results strongly suggest that this new approach may facilitate the identification of clinical molecular markers of disease and novel potential therapeutic targets for LSCC.

[Prevention and management of complications of endoscopic surgery for nasal-skull base neoplasms].

OBJECTIVE: To analyze the surgical complications of endoscopic nasal-skull base surgery. The secondary objective was to propose the preliminary strategies for prevention and treatment of complications. METHODS: One hundred and thirty two patients with nasal-skull base tumors undergoing endoscopic or endoscope-assisted surgery were included in this study. Surgical approaches included endoscopic endonasal transethmoidal approaches, endoscopic endonasal transseptal transsphenoidal approach, extended endoscopic endonasal transseptal transsphenoidal approach, endoscopic transmaxillary posttrial wall approach, extended endoscopic transmaxillary posttrial wall approach, endoscopic nasal lateral wall dissection, maxillary osteotomy approach and endoscopic transoropharyngeal approach. These approaches were selectively used to resect the tumors in the area of nasal-skull base. RESULTS: The total resection of the tumors was obtained in 104 patients (104/132, 78.8%), with 29.5% (39/132) incidence of complications, including profuse bleeding, nerve injury, cerebrospinal fluid leakage, diabetes insipidus, electrolyte imbalance, hyperglycemia, and psychological disturbance. No catastrophic complications, sequelae and operative mortality encountered. Four months to 8 years' follow up (median 3.0 years) indicated that recurrence rate of the benign tumor was 9% (9/100) without died case, and 3-year and 5-year survival rates of the malignant tumor were 75.0% and 55.6%, respectively. CONCLUSIONS: Strategies proved to be effective in reduction of the overall incidence of the complications, especially in minimizing the catastrophic complications and sequelae. The strategies were as follows: first, according to original site, extension and characteristics of the tumor, designing appropriate endoscopic approaches for the treatment of skull base tumor; second, recognizing reliable surgical access points and safe plane of the dissection; third, predicting surgical risks preoperatively and proposing the corresponding plan to avoid these risks; fourth, acquainted with the endoscopic skills and familiarized the skull base structures; lastly, ensuring the correct management of the interdisciplinary problems with close collaboration with the interdisciplinary medical personnels.

[A preliminary study of endoscopic transoral trans-posteriorwall pharynx resection of hypo-clivus chordoma].

OBJECTIVE: To introduce a endoscopic surgical approach for hypo-clivus chordoma, and to explore the clinical value of the endoscopic resection of hypo-clivus chordoma. METHODS: Three hypo-clivus chordoma were resected by endoscopic transoral tans-posteriorwall pharynx approach. RESULTS: The MR image showed that total removal of the tumor was achieved in 2 patients and subtotal resection was received in one patient. No severe postoperative complications and sequelae occurred. In 6 months to 2 years' follow-up, the MRI showed that 2 patients had no residue tumor, and one patient died due to recurrence of the tumor 1 year after operation. CONCLUSION: The endoscopic transoral tans-posteriorwall pharynx approach might be valuable in the treatment of the hypo-clivus chordoma. The use of the endoscope allows for direct access to the hypo-clivus lesions while minimizing the chances of surrounding anatomic structure injury. In addition, this approach has the advantages of quick recovery, avoidance of catastrophic complications and sequelae. Especially, various angle view of the endoscope provides a panoramic view of the hypo-clivus, thus exposing and resecting hide lesion which can not be exposed by other approaches. This approach might facilitate complete resection of the chordoma with maximal preservation of normal tissues.

[Surgical approaches for different stages of nasopharyngeal angiofibromas].

OBJECTIVE: To explore the optical surgical approaches for the resection of early and advanced stage of nasopharyngeal angiofibromas. METHODS: Twenty two male patients aged 9 - 30 years (median 16 years) hospitalized in Xiangya Hospital from June 2003 to July 2006 with nasopharyngeal angiofibroma were recruited. Five operative approaches were selected according classification of juvenile nasopharyngeal angiofibroma described by Fisch. Six cases with stage I nasopharyngeal angiofibroma underwent endoscopic transnasal surgery. Six cases with stage II and 2 cases with stage III underwent endoscopic endonasal middle meatal transmaxillary-antrum approach. Three cases with stage III and 2 cases with stage IV underwent endoscopic endonasal middle and inferior meatal approach with extended transmaxillary-antrum resection. One case with stage IV underwent microscopic preauricula infratemporal fossa approaches combined with endoscopic endonasal middle and inferior meatal transantral approach. Two cases with stage IV underwent nasomaxillary osteotomy approach. RESULTS: After surgery, CT scan or MR image showed that total removal of the tumor was achieved in 21 patients. One patient who received subtotal resection were performed by second endoscopic surgery and obtained total resection. No postoperative complications have been encountered in all treated patients. Nine months to 3 years follow up indicated that no cases recurred after surgery. CONCLUSIONS: Appropriate surgical approach should be selected according to the clinical classification and whether the tumor has extended into whole nasal cavity, lateral fossa infratemporalis, intracranial or not. Such approaches might better facilitate the complete removal of nasopharyngeal angiofibromas and reduce the surgery-related injury.

Resection of extensive sellar tumors with extended endoscopic transseptal transsphenoidal approach.

The endoscope has recently been used to extensive sellar lesions, but the extended areas of the lesions and operative techniques vary from each study. Here we present our experience with extended endoscopic transseptal transsphenoidal (EETT) approach to 16 patients with extensive sellar lesion and evaluate the feasibility of EETT in different extensive sellar tumor resection. Sixteen patients with extensive sellar lesion were operated by EETT approach in this study. The approach included unilateral posterior septum mucosa resection, posterior septectomy, extended ethmoidectomy and sphenoidoctomy, four tumoral circumferences (bilateral, superior, inferior aspects) isolated and subsequently tumoral removal from outside to inside of the tumors obtained. This surgical procedure is satisfactory for sellar lesion with different juxtasellar extension. After surgery, CT scan and MR image showed that total removal of the tumor was achieved in 10 patients. Six patients who received subtotal resection were treated with postoperative radiation therapy or gamma knife surgery. Two patients developed postoperative cerebrospinal fluid leak that was successfully managed by conservative treatment within 6 days after surgery. No other new postoperative endocrinological or neurological defects occurred. Six months to 5 years follow up indicated that all 16 patients with the visual disturbances and 4 patients with endocrine impairments have recovered or improved. One patient with malignant meningioma died due to recurrence of the tumor 2 years postoperation. Another one patient with malignant inverted papilloma recurred 1 year postoperation and underwent operation and radiation therapy again. The EETT approach might better facilitate the removal of different extensive sellar lesions with maximal preservation of important anatomical structures and nasal function.

[Combining FCU/5-FU suicide gene/prodrug system and radiation in treating nasopharyngeal carcinoma: an experimental study].

OBJECTIVE: To explore the in vitro, in situ and in vivo killing effects to CNE-2 cells of human nasopharyngeal carcinoma (NPC) by FCU/5-FC system combined with gamma irradiation for predicting the treatment effect on NPC. METHODS: Plasmid pcDNA3.1(-)CMVe.Egr-1. FCU was introduced into CNE-2 cells by electroporation. The transfected cells were selected by G418 (600 microg/ml) for 14 days to yield cells expressing FCU stably. The FCU protein in transfected CNE-2 cells was tested by Western blotting. In vitro response of FCU-expressing CNE-2 cells to 5-FC or gamma irradiation, alone or in combination was detected by MTT assay. Furthermore, A NPC model was employed by inoculating CNE-2 cells in the right flank of nude mice for in situ gene therapy, and after 12 days of inoculation, those rats were randomized to seven groups, then the suppression of NPC growth in model was observed after giving different treatments. Finally, FCU-expressing CNE-2 cells were inoculating in the right flank of nude mice to generate NPC xenografts for in vivo gene therapy, and after 5-day of implantation, those rats were randomized to seven groups, then the delaying of tumour growth was observed in xenografts treated with different conditions. RESULTS: A anticipated relative molecular quality 42,000 protein was obtained from total protein of FCU-expressing CNE-2 cells. The growth of FCU-positive CNE-2 cells were inhibited by 5-FC or gamma irradiation, alone or in combination, but cells treated with both 5-FC and gamma irradiation resulted in enhanced cell killing when compared with cells treated with gamma irradiation or 5-FC alone. In vitro study showed that the relative survival rates of FCU-expressing CNE-2 cells treated with gamma irradiation were 15.85% - 97.88%, while that of gamma irradiation + 5-FC (100 microg/ml) group were 6.58% - 50.00%, and there was a significant difference (P < 0.01). The MTT results also demonstrated that the relative survival rate has a striking different (P < 0.01) between 5-FC group (12.11% - 99.51%) and 5-FC + gamma irradiation (1.0 Gy) group (2.37% - 35.87%). Not only in situ but also in vivo, potent growth inhibition on the explanted NPC tumours was observed in mice treated with 5-FC or gamma irradiation, alone or in combination, among which interference of both 5-FC and gamma irradiation leaded to most distinct suppression of tumour growth. Tumour volumes in groups interfered by 5-FC and or gamma irradiation were extinctly different with the control group and PBS treatment group (P < 0.05). CONCLUSION: CNE-2 cells or nasopharyngeal carcinoma venograph could be killed by FCU/5-FC suicide gene prodrug system or gamma irradiation, and there is a synergistic therapeutic effect on NPC between FCU/5-FC and gamma irradiation.