Comparison of Surgical Outcomes for Treatment of Maxillary Sinus Inverted Papilloma: Endoscopic Prelacrimal Recess Approach versus Caldwell-Luc Approach / 대한이비인후과학회지

Background and Objectives@#Endoscopic prelacrimal recess approach (PLRA) was introduced to treat maxillary sinus inverted papilloma (IP) without sacrificing the inferior turbinate and nasolacrimal duct. This study aimed to compare surgical outcomes of prelacrimal recess approach with the conventional Caldwell-Luc approach (CLA) to remove IP of maxillary sinus and to evaluate the usefulness of the PLRA.Subjects and Method We retrospectively reviewed medical records of 51 patients who were treated in our institution for IP of nasal cavity and sinuses between March 2010 and June 2019. Twenty patients had maxillary sinus IP. Sixteen patients underwent endoscopic sinus surgery combined with either CLA (n=8) or PLRA (n=8). Demographic data, surgical technique, site of IP origin, intra- and postoperative complications, duration of follow-up, recurrence rate and pathologic diagnosis were reviewed. @*Results@#IP was the pathologic diagnosis for all 16 cases. Gross total removal was achieved in all cases. The mean follow-up period was 20.1 months in CLA group and 12.5 months in PLRA group. There was one case of massive bleeding during operation requiring transfusion and postoperative ICU care in CLA group. On postoperative follow-up, two patients from the CLA group had recurrence during the follow-up period. One patient had numbness around the gingival area, another patient had transient wound dehiscence, and another had persistent oro-antral fistula. In PLRA group, one patient had periorbital swelling after blowing nose; otherwise, no other patient from the PLRA group developed subjective complaints after surgery. @*Conclusion@#Endoscopic prelacrimal recess approach showed lower complication rates and recurrence rates compared to CLA. PLRA is a safe and effective method for the excision of primary maxillary sinus IP.

Prelacrimal Recess Approach for Maxillary Sinus Inverted Papilloma: Preliminary Study / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Various surgical approaches have been employed for the complete resection of inverted papilloma (IP) of the nose and paranasal sinus. Sacrificing the inferior turbinate (IT) and nasolacrimal duct (NLD) is often unavoidable due to the anatomy of maxillary sinus. However, the prelacrimal recess approach (PLRA) provides a wider entrance to the maxillary sinus without the ablation of NLD and IT. We present seven cases of IP successfully treated by the PLRA. SUBJECTS AND METHOD: We collected data from seven different cases involving patients who underwent resection of IP by means of the PLRA from 2016 to 2017. If the lesion could not be removed first via middle meatal antrostomy (MMA), then PLRA was attempted. The surgical specimens were all confirmed to be IP. RESULTS: Preoperative imaging studies demonstrated that the lesions of IP were located mainly in the maxillary sinus. All of the seven patients had unilateral lesions and all tumors were completely resected via PLRA. The follow-up ranged from 3 to 24 months, during which no recurrence or complications were observed in any of the seven patients. CONCLUSION: PLRA provides an adequate operation field without unfavorable scars. It allows the preservation of sinus structure and function. PLRA is feasible and can be used for the diffuse maxillary sinus IP.

Prelacrimal Recess Approach for Maxillary Sinus Inverted Papilloma: Preliminary Study / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES@#Various surgical approaches have been employed for the complete resection of inverted papilloma (IP) of the nose and paranasal sinus. Sacrificing the inferior turbinate (IT) and nasolacrimal duct (NLD) is often unavoidable due to the anatomy of maxillary sinus. However, the prelacrimal recess approach (PLRA) provides a wider entrance to the maxillary sinus without the ablation of NLD and IT. We present seven cases of IP successfully treated by the PLRA.SUBJECTS AND METHOD: We collected data from seven different cases involving patients who underwent resection of IP by means of the PLRA from 2016 to 2017. If the lesion could not be removed first via middle meatal antrostomy (MMA), then PLRA was attempted. The surgical specimens were all confirmed to be IP.@*RESULTS@#Preoperative imaging studies demonstrated that the lesions of IP were located mainly in the maxillary sinus. All of the seven patients had unilateral lesions and all tumors were completely resected via PLRA. The follow-up ranged from 3 to 24 months, during which no recurrence or complications were observed in any of the seven patients.@*CONCLUSION@#PLRA provides an adequate operation field without unfavorable scars. It allows the preservation of sinus structure and function. PLRA is feasible and can be used for the diffuse maxillary sinus IP.

Questioning the Diagnosis of Recurrent Optic Neuritis Associated with Neuro-Behçet's Disease

No abstract available.

A Case of Bilateral Choanal Atresia without Stenting / 대한이비인후과학회지

Bilateral choanal atresia is a rare disorder characterized by bilateral obstruction of the posterior end of the nasal cavity. It can be present in isolation or associated with multiple disorders such as coloboma, heart defect, choanal atresia, retarded growth, genital hypoplasia, ear abnormalities (CHARGE) syndrome. Because congenital bilateral choanal atresia presents as respiratory distress at birth, immediate diagnosis and adequate treatment is required. Traditionally, using stents was a part of the postoperative treatment to provide a low rate of restenosis but recently it is controversial. Currently nasal endoscopic approach is mainly used with or without stenting. We report a case of CHARGE syndrome with bilateral choanal atresia treated by transnasal endoscopic approach without stenting.

Two Cases of Unilateral Nasoseptal Pedicled Rotational Mucosal Flap and Interpositional Dermal Allograft for Septal Perforations / 대한이비인후과학회지

A nasoseptal perforation is a defect of cartilage, bone, and mucosa of nasal septum, caused by nasal surgery, malignancy, inflammation, or drugs. Although various surgical treatments and procedures are well known, there is no consensus on the procedures due to low success rate (25-90%) and high recurrence rate (12-48%). One of the major factors that affect surgical results is the size of perforation. For large perforations, the surgical success rate is reported to range from 23% to 70%. The authors report two successful cases of repair surgery of nasoseptal perforation, using unilateral pedicled nasoseptal rotational mucosal flap with releasing incision and interpositional dermal allograft. Although larger study populations and long-term follow-up periods are needed, the authors believe that our method is an effective way to minimalize possible inconveniences observed in the cases of comparatively large perforations, or where there is a lack of autografts or donor site defects.

A Child of Palatal Myoclonus Tinnitus Treated with Intraoral Injection of Botulinum Toxin / 대한이비인후과학회지

Palatal myoclonus (palatal tremor) was reported to be presented with a sole symptom of objective pulsating tinnitus and could be controlled by botulinum toxin injection alone. However, there were 3 cases reported in Korea of palatal myoclonus tinnitus controlled with botulinum toxin injection through the dual administration route of the mouth and nasal cavity. We present an 11-year-old boy of essential palatal myoclonus tinnitus, which was controlled by intraoral botulinum toxin injection to the tensor veli palatini muscle alone. Intraoral injection of botulinum toxin to the anatomical location of tensor veli palatini muscle with the guidance of electromyography was effective and safe for the child of objective tinnitus caused by palatal myoclonus.

Early Effect of Barbecue Rotation and Modified Semont Combination in Apogeotropic Horizontal Canal Benign Paroxysmal Positional Vertigo / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) of horizontal canal shows reversible direction changing positional nystagmus and diverse clinical courses because of the frequent clinical presentation of cupulolithiasis. The aim of this study is to find out the early effect of particle repositioning maneuver (PRM) including the barbecue and the modified Semont in single treatment session for the apogeotropic horizontal canal BPPV. SUBJECTS AND METHOD: Thirty-three episodic vertigo patients with direction-changing apogeotropic horizontal nystagmus were enrolled in this study. The patients were initially treated with barbecue rotation and the second PRM was applied 15 minutes after the first PRM. Barbecue rotation was applied when the positional nystagmus was changed its direction to that of geotropic. The modified Semont maneuver or barbecue rotation was randomly applied when nystagmus was not changed. Patients were followed-up 2 or 3 days after the initial visit and the nystagmus was rechecked to determine the single session treatment result. RESULTS: The combination of PRMs in a single treatment session was effective in 23 out of 33 (69.7%) patients. An initial barbecue rotation was effective in 17 patients (51.5%); geotropic nystagmus was obtained in 12, and no nystagmus in 5. Eleven out of 16 (68.8%) patients with persistent apogeotropic nystagmus after initial treatment were successfully treated with the second PRM. There was no statistical difference between the second PRMs of the modified Semont maneuver and barbecue rotation (p=1.000). CONCLUSION: The combination of PRMs including barbecue rotation and the modified Semont maneuver in a single treatment session showed a comparable success rate as the previously reported studies.

The Integrated Surgical Strategy for Removal of Inverted Papilloma Involving the Maxillary Sinus According to the Site of Tumor Origin / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The objective of this study is to determine the appropriate surgical approach for the resection of inverted papilloma (IP) involving the maxillary sinus (MS) according to the site of tumor origin in the MS. SUBJECTS AND METHOD: Twenty-six patients who underwent surgery from January 2002 to April 2008 for IP originating from the MS were reviewed retrospectively in regard to the type of integrated surgical approach, site of tumor origin in the MS and the follow-up clinical results. RESULTS: Ten cases (38.4%) originated from medial wall of the MS; of these, four EES (endonasal endoscopic surgery), two EMM (endoscopic medial maxillectomy), two EES+CP (canine puncture), and two EES+CLA (Caldwell-Luc's approach) were performed. EES+CP procedure were performed in all three cases (11.5%) of the anterior wall origin. One case (3.8%) that originated from the posterolateral wall was removed by EES+CLA. Four cases (15.3%) originated from the medial-posterolateral wall. Two EES, and one each of EMM and EES+CLA were performed. Three cases (11.5%) originated from the superior-posterolateral wall, of which two cases were removed by EES and the other by EES+CLO (Caldwell-Luc's operation). Two cases of inferior-anterior wall and inferior-posterolateral wall were removed by EES+CLO and EES+CLA, respectively. EES+CLO were performed for three cases of the whole wall origin (11.5%). Two recurrent cases were found in each of EES and EES+CLO. CONCLUSION: IP originated from the MS were successfully managed by EES alone or EES combined with other approaches such as CP, CLA, CLO and EMM. These integrated approaches need to be applied in a gradual manner from less severe to more aggressive cases.

Clinically Related Factors and Features of Central Compartment Neck Lymph Nodes in Thyroid Micropapillary Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Despite the overall excellent prognosis for patients with thyroid papillary microcarcinoma (PMC), PMC is associated with central compartment lymph node metastasis. The aim of this study is to evaluate the effect of clinical and pathological factors affecting the central compartment lymph node metastasis in thyroid PMC. SUBJECTS AND METHOD: We undertook a retrospective study of 161 patients treated between January, 2003 and June, 2007 for papillary thyroid microcarcinoma by total thyroidectomy and central compartment neck dissection (n=161) with or without comprehensive lateral neck dissection. Following factors were included to analyze the relationship of tumor size and central compartment lymph node metastasis; sex, age, extracapsular extension, lymphovascular tumor emboli, multifocality, bilaterality, AMES risk group, lateral cervical lymph node involvement. RESULTS: In 109 of 161 patients (67.7%), tumor size between 5-10 mm was significantly related with extracapsular extension (p=0.027) and also with the AMES high risk group (p=0.007). In 75 of 161 patients (46.6%), central compartment lymph node metastasis were found. By univariate analysis, tumor multifocality, bilaterality, and lateral lymph node involvement were related with central compartment lymph node metastasis. But on multivariate analysis, tumor bilaterality (p=0.008) and lateral lymph node involvement (p=0.018) were significantly related with central compartment lymph node metastasis. CONCLUSION: Prophylactic neck dissection of central compartment lymph nodes in PMC should be recommended as a routine procedure particularly for patients with tumor bilaterality and metastatic lymph nodes in the lateral neck.

Retraction: Comparison of As2O3 and As4O6 in the Detection of SiHa Cervical Cancer Cell Growth Inhibition Pathway / Journal of the Korean Cancer Association, 대한암학회지

No abstract available.

Application of experion(TM) assay system for discovery of ovarian cancer serum biomarkers / 대한산부인과학회지

OBJECTIVE: The discovery of new biomarkers for ovarian cancer is clearly necessary for the detection and monitoring of the disease. Experion(TM) automated electrophoresis system can be employed in the identification of differentially expressed proteins in cancer cells. The objective of this study was to discover potential diagnostic serological biomarkers for ovarian cancer. METHODS: We performed protein expression difference analyses for 14 healthy women and 28 ovarian cancer patients with stage I, III and IV using Experion(TM) system. And then we checked the protein expression as silver staining after loading at 8~16% gradient gel for comparison with Experion(TM) gel image. The candidate biomarkers were purified and determined using MALDI-TOF mass spectrometer. RESULTS: The distinctive polypeptide peaks were detected at 115.40, 15.96, 14.8, 11.66, and 10.69 kDa and these five peaks were identified as ceruloplasmin, hemoglobin beta chain, hemoglobin sigma chain, serum amyloid A4, and amyloid related serum protein SAA, respectively. These proteins were significantly different between the sera of normal healthy women and ovarian cancer patients. CONCLUSIONS: Five proteins were found to be significantly different between the sera of normal healthy women and ovarian cancer patients. In addition, Experion(TM) assay system can provide high performance for analysis of ovarian cancer-related proteins by increasing the throughput while maintaining a high level of accuracy.

Clinical Significance in Expression of p53, Bcl-2, PCNA and VEGF in Head and Neck Squamous Cell Carcinoma: Relationships with Cisplatin Chemosensitivity and Prognosis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Many researchers have attempted to correlate tumor marker expression with the response of chemoradiotherapy and prognosis of head and neck cancer. But no clear markers are available that can predict responses to treatment or survival in head and neck cancer. This study investigates the relationship between tumor marker expressions and prognosis. SUBJECTS AND METHOD: Thirty-eight patients who received cisplatin and 5-fluorouracil (5-FU) chemotherapy for the treatment of head and neck cancer were enrolled in this study. Author evaluated the relationship between the response of chemotherapy and the immunohistochemical expression of p53, Bcl-2, VEGF, PCNA. The relationship between survival and tumor marker expression was evaluated in twenty five patients who received chemotherapy and radiotherapy. RESULTS: Expression rates of p53, Bcl-2, VEGF, PCNA were 65%, 26%, 26%, 68%, respectively. Of the markers examined, while the expression of p53 was associated with chemosensitivity (p=0.02), other markers was not associated with chemosensitivity (p>0.05). The recurrent rate was 52%. T stage seemed to be associated with recurrence (p=0.07), tumor markers and other clinical parameters were not associated with recurrence (p>0.05). Five year survival rate was 60%. The primary site of tumor seemed to be associated with the overall survival rate of (p=0.07). Any other clinical characteristics and tumor markers were not associated with survival. CONCLUSION: The expression of p53 may be a clinically useful predictor of chemosensitivity in this group of patients. Further studies using a larger group is needed to establish the relationship between tumor markers and prognosis of head neck cancer.

Genomic gain and loss of cervical cancer using BAC Chip / 대한산부인과학회지

OBJECTIVE: Cervical cancer has long been linked to the sexually transmitted human papillomavirus (HPV), and the oncoproteins E6 and E7 disrupt the functions of tumour suppressor genes, resulting in genetic alteration. It was shown that loss of heterozygosity at 6p is a common genetic alteration in cervical cancer. However, the molecular genetics of cancer have only recently been understood, and for the development of cervical cancer additional genetic alterations in host cell genes are required. The present study has identified the differential changes of the cervical cancer-associated genetic alterations by a genome-wide array based comparative genomic hybridization (array-CGH). METHODS: We analyzed 15 cases of cervical cancer from St. Mary's hospital of The paraffin-fixed tissue samples were microdissected under microscope and DNA was extracted by the procedures of proteinase K digestion and chloroform extraction. Array-based CGH and genomic PCR were carried out with statistical analyses such as hierarchical clustering and Gene Ontology. The BAC array used in this study consisted of 1,440 human BACs, the space among the clones were approximately 2.08 megabase (Macrogen, Seoul, Korea). RESULTS: All of 15 cases of cervical cancer showed specific gains and losses. The analysis limit of average gains and losses was 53%. A significant positive correlation was found between 1p36.32, 3p14.2, 3q27.1, 7p21.1, 8q24.3 and 11q13.1 changes through the cervical carcinogenesis. The high-level of gain regions, BAC clones encoded GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA and RPS6KA4 genes. Frequently gained BAC clones encoded genes were PRSS8, FUS, COL18A1, PCOLN3, MAFG and ASPSCR1. The genes encoded by frequently lost BAC clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B and NR3C2. Also, hierarchical clustering of the expression data readily distinguished genomic alterations in cervical cancer. A subset of cellular processes from each gene was clustered by Gene Ontology database. CONCLUSION: Using Array-CGH, genomic alterations related to cervical cancer were identified to determine whether induction of chromosomal imbalances occurs prior to carcinogenesis. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes present in the gained or lost clones.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer. MATERIALS AND METHODS: Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software(TM). The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. RESULTS: A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. CONCLUSION: 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC.

Proteomic analyses of cervical cancer tissues by two-dimensional gel electrophoresis and mass spectrometry / 대한산부인과학회지

OBJECTIVE: Comparison of protein expressions by two-dimensional gel electrophoresis (2-DE) in normal cervix and squamous cell carcinoma tissues in Korean women. METHODS: Normal cervix and squamous cell carcinoma tissues were solubilized with 2-DE buffer and the first dimension of PROTEAN IEF CELL, isoelectric focusing (IEF), was performed using pH3-10 linear IPG strips of 17 cm. And then running 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and sliver stain. Scanned image was analyzed using PDQuest 2-D softwareTM. Protein spot spectrum was identified by assisted laser desorption/ionization-time of fighting (MALDI-TOF) and the protein mass spectrum identifications were performed by searching protein databases of Swiss-prot/TrEMBL, Mascot and MS-FIT. RESULTS: We found 9 up-regulation proteins (Alpha enolase, Keratin 19 type I, Keratin 20 type I, Keratin 13 type I, beta-actin, Aflatoxin B1 aldehyde reductase 1, Annexin A2, Squamous cell carcinoma antigen 2, unknown), 7 down-reguation proteins (Annexin 1, Myosin regulatory light chain 2, 14-3-3 protein epsilon, Heat shock 27 kDa protein, Hypothetical protein (DKFZP434C1715), Tumor necrosis factor receptor superfamily member 13B, Smoth muscle protein 22-alpha) and 6 up and down-regulation proteins (Tropomyosin 1, Tropomyosin 2, Tropomyosin 3, Serine (or cysteine) proteinase inhibitor, Phosphatidylinositol transfer protein alpha isoform, Src homology 3 domain-containing protein HIP-55) between normal cervix and squamous cell carcinoma cell tissues. CONCLUSION: 2-DE offers total protein expressions between normal cervix and squamous cell carcinoma cell tissues, and searching of differently expressed protein for the diagnostic markers of squamous cell carcinoma tissue.

Two Cases of Metachronous Squamous Cell Carcinoma Involving Both Maxillary Sinuses / 대한이비인후과학회지

Malignant tumors of the nasal cavities and paranasal sinuses are uncommon, comprising less than one percent of all tumors. Although multiple primary carcinoma of the aerodigestive tract are commonly reported, metachronous squamous cell carcinomas of both maxillary sinuses are extremely rare. The incidence of metachronous maxillary carcinoma involving both sinuses is 1.2-1.4 percent of all patients with maxillary carcinoma. Here we present two cases of metachronous squamous cell carcinoma involving both maxillary sinuses, which are the first reported cases in Korea. A 74-year-old female and 56-year-old male had right maxillary cancer. They had additional carcinoma developed in the contralateral maxillary sinus after 6 years and 12 years, respectively. Although the possibility is rare, metachronous tumors of the contralateral maxillary sinus can occur. An early dianosis and appropriate treatment of the secondary lesion is critical.

Expression Profiling of the Cellular Processes in Uterine Leiomyomas: Omic Approaches and IGF-2 Association with Leiomyosarcomas / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study utilized both cDNA microarray and 2D protein gel electrophoresis technology to investigate the multiple interactions of the genes and proteins involved in the pathophysiology of uterine leiomyomas. Also, Gene Ontology (GO) analysis was used to systematically characterize the global expression profiles, which were found to correlate with the leiomyosarcomas. MATERIALS AND METHODS: The uterine leiomyoma biopsies were obtained from patients in the Department of Obstetrics and Gynecology, The Catholic University of Korea. Differentially expressed transcriptome and proteome, in 6 paired leiomyoma and normal myometrium, were profiled. The total RNAs from the leiomyoma and normal myometrium were labeled with Cy5 and Cy3. All specimens were punch-biopsy-obtained, and frozen in liquid nitrogen. RESULTS: Screening of up to 17, 000 genes identified 71 that were either up-regulated or down-regulated (21 and 50, respectively). The gene expression profiles were classified into 420 mutually dependent functional sets, resulting in 611 cellular processes, according to the gene ontology. Also, the protein analysis, using 2D gel electrophoresis, identified 33 proteins (17 up-regulated and 16 down-regulated) with more than 500 total spots, which were classified into 302 cellular processes. Of these functional profilings, transcriptomes and proteoms down- regulations were shown in the cell adhesion, cell motility, organogenesis, enzyme regulator, structural molecule activity and responses to external stimulus functional activities, which are supposed to play important roles in the pathophysiology. In contrast, up-regulation was only shown in the nucleic acid binding activity. The CDKN2A, ADH1A, DCX, IGF2, CRABP2 and KIF5C were found to increase the reliability of this study, and correlate with the leiomyosarcomas. CONCLUSION: Potentially significant pathogenetic cellular processes showed that down-regulated functional profiling has an important impact on the discovery of the pathogenic pathways in leiomyomas and leiomyosarcomas. GO analysis can also overcome the complexity of the expression profiles of cDNA microarrays and 2D protein analyses, via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at cellular process levels.

Comparison of As2O3 and As4O6 in the Detection of SiHa Cervical Cancer Cell Growth Inhibition Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: An arsenical compound, As2O3, has been reported to be effective for treating acute leukemia and inducing apoptosis in many different tumor cells. In this study, the ability of As4O6 to suppress cell growth and induce gene expression patterns was tested using a cDNA microarray in HPV16 immortalized cervical carcinoma cells, SiHa cells, along with As2O3. MATERIALS AND METHODS: A novel arsenical compound, As4O6, was designed and its ability to induce cell growth inhibition as well as gene expression profiles along with As2O3 in HPV16 infected SiHa cervical cancer cells was compared. Both As2O3 and As4O6 induced apoptosis in SiHa cells, as determined by DNA ladder formation. To further compare the gene expression profiles between these two drugs, a 384 cDNA microarray system was employed. Also, the gene expression profiles were classified into the Gene Ontology (GO) to investigate apoptosis-related cellular processes. RESULTS: As4O6 was more effective i suppressing the growth of SiHa cells in vitro compared to As2O3. In the case of treatment with As2O3, 41 genes were up- or down- regulated at least 2 fold compared to non-treatment. However, 65 genes were up- or down-regulated by As4O6 treatment. In particular, 27 genes were commonly regulated by both arsenic compounds. Also, the GO analysis indicated that down-regulation of cell-regulatory functions, such as cell cycle, protein kinase activity and DNA repair, induced anti-tumor effect. CONCLUSION: These data support that As4O6 could be more effective than As2O3 in inhibiting the growth of HPV16 infected cervical cancer cells. This appears to be mediated through a unique, but overlapping regulatory mechanism(s), suggesting that the regulated genes and cellular processes could be further used as a new potential drug approach for treating cervical cancer in clinical settings.

Identification of Gene Expression and Gene Ontology Classification by Differential Display RT-PCR in Human Cervical Squamous Cell Carcinoma / 대한산부인과학회잡지

OBJECTIVE: The molecular pathology of cervical cancer associated with human papillomavirus infection is presently unclear. In an effort to clarify the multiple interactions of a number of genes involved in cervical carcinogenesis, the gene expression profiles and pathogenic cellular processes between human cervical squamous cell carcinoma and normal cervix were investigated by mRNA differential display and the Gene Ontology analysis. METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The squamous cell carcinoma tissue samples of 3 patients invasive cancer stage II (1), IV (2) were investigated by mRNA differential display. As a control, we used a common reference that was mixed with equal amount of RNA obtained from 17 normal cervix to obtain variation- independent control. Also, we constructed hierarchical functional structures using gene ontology. Then, the specific function groups were correlated with differential gene expression profiles. In addition, specific gene expression patterns in several tissue samples were investigated by using DDRT-PCR analysis. RESULTS: Differentially expressed 191 genes were identified in tumor samples. Of these genes, 128 were up-regulated and 63 were down-regulated above 1.5-fold. The gene expression profiles were classified into 46 mutually dependent function sets and organized into sub-function sets depending on the cervical cancer pathway, suggesting the potentially significant genes of unknown function affected by carcinogenesis pathway. The genes related to metabolism, signal transduction, and chaperon activity were significantly up-regulated. In contrast, significant down-regulations were shown in nucleic acid binding activity, tumor suppressor and structural activity. Reliable gene expression data shows the validation of profiling method for studying the cervical cancer-specific pathway. CONCLUSION: The specific functions assigned to each expressed gene were correlated with gene ontology for the establishment of a powerful cervical carcinogenesis pathway. The results suggest that the differentially regulated cellular process profiles have an important impact on discovery of pathogenic pathway in human cervical squamous cell carcinoma and provide the potentially significant genes of unknown function. Also, the gene ontology analysis can overcome the complexity of the expression profiles of mRNA differential display via a cellular process level approach. Thereby, a valuable prognostic candidate gene with real relevance to disease-specific pathogenesis can be found at the cellular process levels.