Visualizing cell-cell communication using synthetic notch activated MRI.

Cell-cell communication plays a fundamental role in multicellular organisms. Cell-based cancer immunotherapies rely on the ability of innate or engineered receptors on immune cells to engage specific antigens on cancer cells to induce tumor kill. To improve the development and translation of these therapies, imaging tools capable of noninvasively and spatiotemporally visualizing immune-cancer cell interactions would be highly valuable. Using the synthetic Notch (SynNotch) system, we engineered T cells that upon interaction with a chosen antigen (CD19) on neighboring cancer cells induce the expression of optical reporter genes and the human-derived, magnetic resonance imaging (MRI) reporter gene organic anion transporting polypeptide 1B3 (OATP1B3). Administration of engineered T cells induced the antigen-dependent expression of all our reporter genes in mice bearing CD19-positive tumors but not CD19-negative tumors. Notably, due to the high spatial resolution and tomographic nature of MRI, contrast-enhanced foci within CD19-positive tumors representing OATP1B3-expressing T cells were clearly visible and their distribution was readily mapped. We then extended this technology onto human natural killer-92 (NK-92) cells, observing similar CD19-dependent reporter activity in tumor-bearing mice. Furthermore, we show that when delivered intravenously, engineered NK-92 cells can be detected via bioluminescence imaging in a systemic cancer model. With continued work, this highly modular imaging strategy could aid in the monitoring of cell therapies in patients and, beyond this, augment our understanding of how different cell populations interact within the body during normal physiology or disease.

A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles.

Early and accurate detection of cancer is essential to optimising patient outcomes. Of particular importance to prostate cancer is the ability to determine the aggressiveness of a primary tumour, which allows for effective management of patient care. In this work, we propose using gene vectors called tumour-activatable minicircles which deliver an exogenously encoded reporter gene into cancer cells, forcing them to produce a unique and sensitive biomarker. These minicircles express a blood reporter protein called secreted embryonic alkaline phosphatase mediated by the tumour-specific survivin promoter, which exhibits activity graded to prostate cancer aggressiveness. Together, these components underlie a detection system where levels of blood reporter are indicative of not only the presence, but also the metastatic potential of a tumour. Our goal was to assess the ability of tumour-activatable minicircles to detect and characterise primary prostate lesions. Our minicircles produced reporter levels related to survivin expression across a range of prostate cancer cell lines. When survivin-driven minicircles were administered intratumourally into mice, reporter levels in blood samples were significantly higher (p < 0.05) in mice carrying prostate tumours of high versus low-aggressiveness. Continued development of this gene-based system could provide clinicians with a powerful tool to evaluate prostate cancer aggressiveness using a sensitive and affordable blood assay.

A synthetic notch (synNotch) system linking intratumoral immune-cancer cell communication to a synthetic blood biomarker assay.

Introduction: Cellular immunotherapy has greatly improved cancer treatment in recent years. For instance, chimeric antigen receptor (CAR) T cell therapy has been proven highly effective in treating hematological malignancies, and many CAR cell designs are being explored for solid tumors. However, many questions remain why responses differ across patients and some tumor types are resistant. Improved and relatively inexpensive ways to monitor these cells could provide some answers. Clinically, blood tests are regularly used to monitor these therapies, but blood signals often do not reflect the activity of immune cells within the tumor(s). Here, using the synthetic Notch (synNotch) receptor that tethers antigen binding to customized transgene expression, we linked intratumoral immune-cancer cell communication to a simple secreted reporter blood test. Specifically, we engineered immune cells with a CD19-targeted synNotch receptor and demonstrated that binding to CD19 on cancer cells in vivo resulted in the production of secreted embryonic alkaline phosphatase (SEAP) at levels that are readily detected in the blood. Methods and Results: Jurkat T cells were engineered via sequential lentiviral transduction of two components: an anti-CD19 synNotch receptor and a synNotch response element encoding SEAP. Co-culture of engineered cells with CD19+, but not CD19-, Nalm6 cells, resulted in significantly elevated SEAP in media. Nod-scid-gamma (NSG) mice were subcutaneously injected with either CD19+ or CD19- Nalm6 cells. Intratumoral injection of engineered T cells (1x107) resulted in significantly elevated blood SEAP activity in mice bearing CD19+ tumors (n = 7), but not CD19- tumors (n = 5). Discussion: Our synNotch reporter system allows for the monitoring of antigen-dependent intratumoral immune-cancer cell interactions through a simple and convenient blood test. Continued development of this system for different target antigens of interest should provide a broadly applicable platform for improved monitoring of many cell-based immunotherapies during their initial development and clinical translation, ultimately improving our understanding of design considerations and patient-specific responses.

Self-immolative polyplexes for DNA delivery.

Nucleic acids have immense potential for the treatment and prevention of a wide range of diseases, but delivery vehicles are needed to assist with their entry into cells. Polycations can reversibly complex with nucleic acids via ionic interactions to form polyplexes and transport them into cells, but they are still hindered by the need to balance cytotoxicity and delivery effectiveness. In this work, we describe a new self-immolative polyglyoxylamide (PGAm) platform designed to address these challenges by complexing nucleic acids via multivalent interactions in the polymeric form and releasing them upon depolymerization. Nine PGAms were synthesized and characterized, with different end-caps and variable cationic pendent groups. The PGAms underwent depolymerization under mildly acidic conditions, with rates dependent on their pendent groups and end-caps. They complexed plasmid DNA, forming cationic nanoparticles, and released it upon depolymerization. Cytotoxicity assays of the PGAms and polyplexes in HEK 293T cells showed a decrease in toxicity following depolymerization, and all samples exhibited much lower toxicity than a commercial non-degradable linear polyethyleneimine (jetPEI) transfection agent. Transfection assays revealed that selected PGAms provided similar levels of reporter gene expression to jetPEI in vitro with a PGAm analogue of poly[2-(dimethylamino)ethyl methacrylate] having particularly interesting activity that was dependent on depolymerization, along with low cytotoxicity. Overall, these results indicate that end-to-end depolymerization of self-immolative polymers can provide a new and promising tool for nucleic acid delivery.

A survivin-driven, tumor-activatable minicircle system for prostate cancer theranostics.

Gene vectors regulated by tumor-specific promoters to express transgenes specifically in cancer cells are an emerging approach for cancer diagnosis and treatment. Minicircles are shortened plasmids stripped of prokaryotic sequences that have potency and safety characteristics beneficial for clinical translation. Previously, we developed minicircles driven by the tumor-specific survivin promoter, which exhibits elevated transcriptional activity in aggressive cancers, to express a secreted reporter for blood-based cancer detection. Here we present the first activatable, cancer theranostic minicircle system featuring a pair of diagnostic and therapeutic minicircles expressing Gaussia luciferase for urine-based cancer detection or cytosine deaminase:uracil phosphoribosyltransferase for gene-directed enzyme prodrug therapy. Diagnostic minicircles revealed urinary reporter output related to cellular survivin levels. Notably, mice with aggressive prostate tumors exhibited significantly higher urine reporter activity than mice with non-aggressive tumors and healthy mice after intratumoral minicircle administration. Therapeutic minicircles displayed specific cytotoxicity in survivin-rich cancer cells and significantly attenuated growth of aggressive orthotopic prostate tumors in mice. Use of these minicircles together creates a theranostic system that can first identify individuals carrying aggressive prostate cancer via a urinary test, followed by stringent control of tumor progression in stratified individuals who carry high-risk prostate lesions.

Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits.

Microglial activation and oxidative stress have been linked to the formation of amyloid plaques found in Alzheimer's disease (AD). Epidemiologic and experimental evidence also suggests that cholesterol (CH) contributes to the pathogenesis of AD, particularly the formation of amyloid plaques. We have previously described the development of amyloid-ß (Aß) plaques in New Zealand white rabbits maintained on a 0.125%-0.25% w/w CH diet for extended periods of time (28 months). Here we further characterize this model with combined immunofluorescence and immunohistochemical staining to evaluate markers of immune cell activation. Five out of eight CH-fed rabbits, but not control rabbits, developed extracellular Aß plaques in both the hippocampus and cortex. Significantly (p < 0.05) higher CD11b microglial staining was found in the hippocampus, temporal cortex, and frontal cortex of CH-fed versus control rabbits. In the temporal cortex and parietal cortex, active CD-11b- and ferritin-positive microglia were found in close proximity to Aß plaques. Classification and quantification of activated microglia in the temporal cortex showed that 68±12.9%, 25±7.3%, and 7±2.7% of all microglia had a primed, reactive, and amoeboid phenotype, respectively. Activated microglia also expressed myeloperoxidase which was co-localized to amyloid deposits. Our findings in this dietary-based model lend further support of a role of activated microglia and oxidative stress during the development of AD and strengthens the links between hypercholesterolemia, inflammatory status, and AD.

Preservation of laryngeal function in treatment of hypopharyngeal carcinoma.

OBJECTIVE: To study the surgical technique and results of laryngeal function preservation in treatment of hypopharyngeal carcinoma. METHODS: A retrospective review of 305 patients with malignant neoplasms of the hypopharynx (279 males, 26 females, age ranging from 14 to 77 years) was performed from 1978 to 1996. In the 305 patients (stage I, n = 6; stage II, n = 12; stage III, n = 82; stage IV, n = 205), the sites of origin were pyriform sinus (n = 234), postcricoid (n = 21), posterior pharyngeal wall (n = 35) and superior hypopharynx (n = 15). Of the 305 patients, 206 (67.54%, stage I, n = 6; stage II, n = 12; stage III, n = 65; stage IV, n = 123) were surgically treated with laryngeal function preserved and 99 (32.46%, stage III, n = 17; stage IV, n = 82) had no laryngeal function preserved. All had 55-75 Gy radiotherapy according to their need. RESULTS: A total of 206 patients (67.54%) were surgically treated with laryngeal function preserved, totally (voice, respiration and deglutition) in 139 (67.5%) and partially (voice and deglutition) in 67 (32.5%). 99 patients (32.46%) had no laryngeal function preserved. The overall 5-year survival rate of the 305 patients was 44.8%, which segregated to 83% (stage I), 71% (stage II), 58% (stage III), and 36% (stage IV). The 5-year survival of the laryngeal function preserved group was 48% (n = 66), the rate of complications 28% (n = 58) and the rate of residual tumor 5.8% (n = 12), compared with the no laryngeal function preserved group 37% (n = 20), 31.3% (n = 31), and 6% (n = 6) (P > 0.05). CONCLUSION: Only a small proportion of patients (31/305, 10%) with hypopharyngeal carcinoma who require total laryngectomy and preservation of the laryngeal function is feasible for eradication of tumor and preservation of laryngeal function.

[Surgical approaches of anterior skull base tumors].

OBJECTIVE: Study for surgical approaches on anterior skull base tumors. METHOD: All 37 cases with anterior skull base tumors were surgically treated. Twenty-one cases were treated with anterior craniofacial approaches: Frontal subcranial combined with total maxillectomy in 8 cases or/with orbital exenteration in 5 cases, combined with lateral rhinotomy in 1 cases, combined with naso translocation with medial maxillectomy in 7 cases. Partial or total maxillary swing combined with naso pyramid translocation in 13 cases. Frontonasal, fronto-orbital and midface degloving in one case respectively. RESULT: Of the 27 malignant cases the 3 and 5-year survival rates were 81.9% (22/27) and 62.9% (17/27) respectively, and one tumor free case living well more than 9 years. There were no recurrence in 10 cases with benign tumor. CONCLUSIONS: Various craniofacial approaches except lateral rhinotomy provide directly satisfactory tumor exposure and facilitate enbloc resection of the naso paranasal sinus tumor with intracranial extension. Partial or total maxillary swing combined with naso pyramid translocation is good for tumor involving the skull base without intracranial invasion. The fronto-nasal pyramid translocation is good for removal of the upper part of nasal tumor with intracranial extension on well developed frontal sinus. The fronto orbital approach is proper for removal of fronto-sphenoid tumor and midface degloving may be used in selected cases.

[The relationship between cyclin D1 and hypopharyngeal carcinoma].

OBJECTIVE: To study the relation ship between Cyclin expression and the biological behavior in 53 cases of hypopharyngeal squamous cell carcinoma. METHOD: Immunohistochemical (sp). method was used to detect the expression of cyclin D in 53 cases of hypopharyngeal squamous cell carcinoma and 11 cases of normal adjacent epithelium. RESULT: Positive expression for Cyclin D1 in hypopharyngeal squamous cell carcinoma was found in nuclear. The expression of cyclin D1 in the tumorous cell was significant hig her than in normal epithelium. Cyclin D1 expression was related to T grade and primary site, which correlation coefficient were 0.345 and -0.386 respectively. The highest positive rate of Cyclin D1 expression was in pyriform sinus. CONCLUSION: Cyclin D1 expression was related to T grade and primary site positively.

[Surgical approaches for sinonasal tumors with intracranial extension].

OBJECTIVE: To investigate the surgical approaches for sinonasal tumors with intracranial extension. METHODS: Seventeen patients with intracranial invasion tumors were treated surgically by maxillectomy combined with frontal or infratemporal approaches in 11 cases, including squamous cell carcinoma 8 cases, papillocarcinoma 2 cases and meningioma 1 case. Nasofrontal bone translocation in 1 case which was a meningioma case, craniofacial approaches in 5 cases, including squamous cell carcinoma 4 cases and esthesioneuroblastoma 1 csae. RESULTS: One of two meningioma cases with cavernous sinus invasion was incompletely resected, another case was resected en bloc. In malignant group, ten cases were treated by nasomaxillectomy combined with frontal or infratemporal approaches. One patient died 1 year after operation, 7 cases survived for over 3 years, and 5 for over 5 years. Five cases were treated by craniofacial approach, among them, one patient died 6 months after operation, 4 cases survived for over 3 years, and 2 for over 5 years. All patients healed smoothly. CONCLUSIONS: Maxillary nasopyramid translocation combined with frontocranial or infratemporal approach is available for en bloc removal of sinonasal tumors with intracranial extension. The nasofrontal bone translocation is available for removal of tumors with limited intracranial extension and well developed frontal sinus. Cranioanterolateral facial approach is suitable for nasocranial tumors with facial bone involvement.

[Preservation of laryngeal function in surgical treatment of posterior hypopharyngeal wall cancer].

OBJECTIVE: To explore the feasibility and the related surgical techniques of laryngeal function preservation in surgical treatment of posterior hypopharyngeal wall cancer. METHOD: Thirty-five cases with posterior hypopharyngeal wall cancer were treated surgically. The methods of removing tumor and repairing surgical defects were depended on the extension of lesions. The laryngeal and pharyngeal function were rebuild by normal tissue preserved with lesions entirely removed. Twenty-seven cases were surgically treated with laryngeal functions preserved and eight cases total laryngectomy. The most of the cases received postoperative radiotherapy. RESULT: The overall 3 and 5-year survival rates were 45.7% and 28.6%, respectively. 45.7% patients having laryngeal functions (voice, respiration and deglutition) completely restored and 31.4% partially restored(voice and deglutition). Among the died patients, nine cases died from cervical lymph node metastasis, ten cases died from local recurrence, twa cases died from lung metastasis, one cases died from cervical massive haemorrhage, twa cases died from hear disease and one died from ambiguous reason. CONCLUSION: The preservative surgery is feasible for the selected posterior hypopharyngeal wall cancer cases. Choosing and following what is optimum from multiple feasible surgical methods is a prerequisite for improving the quality of life of the cases.

[Surgical approaches to the skull base neoplasms].

OBJECTIVE: To discuss the best surgical approach to the skull base neoplasms. METHODS: Retrospective analysis the 79 skull base neoplasms cases treated with surgical resection in Qilu hospital of Shandong university from 1992 to 2002. Eleven surgical approaches including midfacial degloving, frontal coronal discission, nasal eversion, maxillary swing, partial maxillary resection, total resection of orbit, mandibular swing, combination of front, temple, preauricular, post aureum, neck, and transoral approaches were used to resect the tumor which involved fossae pterygopalatine, paranasal sinuses, nasopharynx, antero, meso and posterobasilar region, lobi frontalis and lobi temporalis of cerebrum. RESULTS: Seventy-nine skull base neoplasms were totally removed and no one died from the operation. Although 5 cases complicated with cerebrospinal fluid leak and all recovered within 1 week, no serious cranium-cerebrum complication occurred. In 29 patients with benign tumor including 11 cases of meningioma, 3 cases of chondroma, 1 case of hemangio-meningioma, 1 case of cavernous hemangioma, 2 cases of osteodysplasia fibromas, 9 cases of neurofibroma, 1 case of glomus jugular tumor, 1 case of neurilemmoma, 19 have survived over 5 years and the longest one has survived over 8 years. For 50 patients with malignant tumor including 3 cases of well-differentiated squamous cell carcinoma, 17 cases of moderately differentiated squamous cell carcinoma, 11 cases of poorly differentiated squamous cell carcinoma, 1 case of undifferentiated carcinoma, 2 cases of chondrosarcoma, 5 cases of canceration of papilloma, 2 cases of adenocarcinoma, 1 case of esthesioneuroblastoma, 2 cases of malignant fibrohistiocytoma, 1 case of fibrosarcoma, 2 cases of malignant mixed tumour, 3 cases of sarcoma survival rates of 3 and 5 years were 59.2% (29/49), 38.5% (10/26) respectively. CONCLUSION: In order to resect the tumor completely and reduce the complication and malformation as far as possible, different surgical approaches must be designed according to the pathological changes characters and involved area,and the surgeon should select the shortest approach, avoid to damage the important neurovascular structure, and resect the tumor through the natural anatomy space by the shelter incision.

[Preservation of laryngeal function in surgical treatment of pyriform sinus carcinoma].

OBJECTIVE: To explore the feasibility and the related surgical techniques of laryngeal function preservation in surgical treatment of pyriform sinus cancer. METHODS: Two hundred and thirty cases (stage I, 6; stage II, 10; stage III, 91; stage IV, 123) with pyriform sinus cancer were treated surgically from 1978 to 1996 in the Department of Otorhinolaryngology of Qilu Hospital of Shandong University. The methods of removing tumor and repairing surgical defects were depended on the extension of lesions. The laryngeal and pharyngeal functions were rebuilt by normal tissue preserved with lesions entirely removed. One hundred and fifty-eight cases were surgically treated with laryngeal functions preserved and 72 cases total laryngectomy. The most of the cases received postoperative radiotherapy. RESULTS: The overall 3 and 5 year survival rates were 67.4% (155/230) and 48.3% (111/230) respectively. For stage I, the survival rate was 5/6; stage 11, 70.0% (7/10); stage III, 57.1% (52/91) and stage IV, 38.2% (47/123); the 3 and 5 year survival rates in functionally preserved group were 67.7% (107/158) and 50.0% (79/158), while in none functional group were 66.7% (48/72) and 43.1% (31/72), respectively. 75.3% (119/158) patients have laryngeal functions (voice,respiration and deglutition) completely restored and 24.7% (39/ 158) partially restored(voice and deglutition). CONCLUSIONS: The preservative surgery is feasible for the selected pyriform sinus cancer cases. Choosing and following optimum surgical methods is a prerequisite for improving the quality of life of the cases.

[Surgical treatment of postcricoid carcinoma].

OBJECTIVE: To explore the surgical techniques in surgical treatment of postcricoid carcinoma. METHODS: Twenty-one cases with postcricoid carcinoma were treated surgically. The TNM stage were as follows: T3NOM0 5 cases, T3N1M0 1 case, T3N2M0 2 cases, T4NOM0 7 cases, T4N1M0 4 cases, T4N2M0 1 case, T4N3M0 1 case. The laryngeal and pharyngeal functions were rebuilt by the remaining tissue when the lesions entirely removed. Ten cases were surgically treated with laryngeal functions preserved and 11 cases with total laryngectomy. Eight cases were received unilateral neck dissection, and 3 cases were received bilateral neck dissection. All the cases received postoperative radiotherapy. RESULTS: The follow-up interval varied from 60 to 276 months with average interval 96 months. Four cases died of cervical metastasis,3 died of local recurrence, 1 died of cardiopulmonary failure, 2 died of unknown reasons. The overall 3 and 5 year survival rates were 61.9% (13/21) and 52.4% (11/21), respectively. Among 10 cases having laryngeal functions partially restored (voice and deglutition), the postoperative complications included 5 cases of pharyngeal fistula, 3 hypopharyngeal stenosis and 1 severe aspiration. CONCLUSIONS: The preservative surgery is feasible for the selected cases with postcricoid carcinoma. The laryngeal function can be partially restored with lesions entirely removed. The patients can gain satisfied survival rate and quality of life.

[Clinical study of combined approach of tympanoplasty and mastoidectomy with close technique].

OBJECTIVE: To improve the surgery results and living quality of patients following the operation of the combined approach of tympanoplasty and mastoidectomy with close technique. METHODS: The clinical data and following-up results of 49 patients treated with combined approach of tympanoplasty and mastoidectomy with close technique and 82 patients treated with open mastoidectomy with tympanoplasty were retrospective analyzed. RESULTS: In the group treated with combined approach tympanoplasty, all patients got dry ear in 20 days and 31 patients' hearing level enhanced over 15 dB after the operation; but in the group treated with open mastoidectomy with tympanoplasty, only 13 patients got dry ear in 20 days and no patients' hearing level enhance over 15 dB after the operation. Although the recurrence rates between two groups were not significant difference, the patients of former group not only took a shorter recovery time and got a better hearing recovery, but also kept a normal external auditory meatus, at the same time, they need not to clear scab at fixed period all life long. CONCLUSIONS: When performed on carefully selected patients, combined approach tympanoplasty was a feasible surgical method to improve the surgery results and living quality of patients following the operation, however, the advanced equipment and perfect operation skill are necessary.

[Reconstructing or pulling down tongue-base in surgical treatment of laryngeal cancer].

BACKGROUND & OBJECTIVE: The surgical treatment of laryngeal cancer, especially for the supraglottic cancer, usually involve the management of tongue-base, which is important in the rebuilding laryngeal function. There was no simple and effective method to repair tongue-base previously, which was removed for the greater part when invaded by advanced laryngeal cancer. As a result, many cases could not regain the satisfactory laryngeal function. And only several published reports focused on the efficacy of rebuilding laryngeal function by means of tongue-base flap. In order to develop a simple and reliable method to rebuild the laryngeal function, the management of tongue base in surgical treatment of laryngeal cancer was explored. METHODS: After the laryngeal carcinoma or the involved tongue-base was removed, according to the extent of surgical defect, sternohyoid myofascial flap was used to reconstruct the tongue-base, or the tongue-base was selected to rebuild the laryngeal function when greater part of it was preserved. RESULTS: Out of the 32 cases with partial laryngectomy, 26 cases were decannulated with a decannulation rate of 81.3%, all the cases regained speaking functions except 4 cases undergone total laryngectomy. All the cases resumed normal diet, none presented complication of accidental aspiration. The 3-year and 5-year survival rates were 81.3% and 65.6%, respectively. CONCLUSION: Reconstructing or pulling down the tongue-base is highly effective in rebuilding satisfactory laryngeal function, which is easily and simply performed with less damage and complications, appropriate for surgical treatment of laryngeal cancer.

[Combined frontal-preauricular-cervical approach for resection of huge transcranial lateral skull base tumors].

OBJECTIVE: To search into the appropriate approach for surgical treatment of the huge lateral skull base tumors. METHODS: The combined frontal-preauricular-cervical approach was used in two cases with huge transcranial lateral skull base tumors occupying the parapharngeal space, infratemporal fossa and middle cranial fossa. To acquire a wide surgical exposure, the flaps of orbital-zygomatic bone and the skull bone were removed, and then the mandibula was dislocated inferiorly. RESULTS: The tumors in the two cases were resected completely. The postoperative conditions of the patients were good. No cerebral spinal fluid leakage and other intracranial complications or facial morbidity were found. The occlusion was not interfered. CONCLUSION: The combined frontal-preauricular-cervical approach may provide a potential way for the surgical treatment of the large transcranial neoplasms occupying the parapharngeal space and infratemporal fossa and the middle cranial base.

[Surgical approaches to the skull and near skull base neoplasms].

OBJECTIVE: To seek for the best surgical approaches to the skull and near-skull base neoplasms. METHOD: 161 patients with skull or near-skull base tumors were surgically treated. The surgical approaches were craniofacial approach in 6 cases, total maxillectomy or/with orbital exenteration in 5 cases, lateral rhinotomy in 7 cases, frontorbital approach in 1 cases, maxillary swing or extended maxillary swing approach in 21 cases, mandibular swing approach in 30 cases, cervical approach in 48 cases, postaurical large C incision approach in 19 cases, transparotid approach in 8 cases, transoral approach in 6 cases, temporofrontal approach in 8 cases, subtemporal preauricular approach in 2 cases. RESULT: Of the 98 benign tumors cases, 2 recurred postoperatively. Of the 63 malignant tumors, 1 case had cerebrospinal fluid leakage and died of intracranial infection 1.5 months postoperatively. In the follow up period, the longest one survival was over 8 years, and 10 over 5 years, 19 over 3 years, 16 over 2 years, 16 over 1 year. Survival rates of 3 and 5 years were 59.18% and 38.46% respectively. CONCLUSION: According to the site, range and pathology of the skull base neoplasmas, surgical approaches were designed and selected rationally and the effects better.

[Expression of MDM2 and p27 in hypopharyngeal carcinoma and their clinical significance].

OBJECTIVE: To explore the relationship between the expression of MDM2 and p27 in hypopharyngeal carcinoma and clinicopathological parameters and their clinical significance. METHOD: The expression of MDM2 and p27 in 59 hypopharyngeal carcinoma were detected by S-P immunohistochemical technique. RESULT: The high-expression rates of MDM2 and p27 were 66.1% and 33.9%, respectively, and the low-expression rates of them were 33.9% and 66.1%, respectively. The expression of MDM2 was unrelated to p27 (P > 0.05). The lymph node metastasis in high-expression group of MDM2 was significantly higher than that in low-expression group (P < 0.01). The expression rate of p27 was significantly different among the four T groups and degree of differentiation, respectively (P < 0.05). The survival rate was significantly higher in high-expression rate group of MDM2 than that in low-expression rate group (P < 0.01), while the survival rate was significantly lower in high-expression rate group of p27 than that in low-expression rate group (P < 0.05). CONCLUSION: The expression of MDM2 and p27 may be involved in carcinogenesis and progression in hypopharyngeal carcinoma. Combined detecting of MDM2 and p27 may predict its prognosis better in hypopharyngeal carcinoma.

[Preservative surgery of T3 glottic cancer: 75 cases report].

OBJECTIVE: To explore the methods of surgery and evaluate the long-term results of preservative surgery for T3 glottic cancer. METHOD: Seventy-five cases with T3 glottic cancer were treated surgically from 1989 to 1999. The lesions were removed entirely, the epiglottis, bi-pedicled myoperichondral flap, platysma myocutaneous flap, sternohyoid myofascial flap, platysma myofascial flap, thyroid perichondral flap were utilized to restore the defects of larynx and reconstruct the laryngeal functions. RESULT: The 3- and 5-year survival rates were 83.2% and 73.6% in all cases, 82.7% had all laryngeal functions (voice, respiration and deglutition) restored and 17.3% partially restored(voice and deglutition). CONCLUSION: Preservative surgery can be carried out for T3 glottic cancer with the lesions entirely removed. Choosing and following what is optimum from multiple feasible surgical methods is a prerequisite for better laryngeal functions.