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Dentigerous cyst is a developmental odontogenic cyst which originates through alterations of reduced enamel epithelium in an unerupted tooth or a developing tooth bud. These cysts rarely associate with supernumerary teeth. Supernumerary teeth accounts for 5% of all dentigerous cysts. The most common supernumerary teeth are mesiodens. The case study aimed to present a rare case of infected dentigerous cyst on a totally impacted mesiodens. This case report describes a rare case of infected dentigerous cyst associated with mesiodens in a 33 year old female who presented with a slow growing swelling in the palatal. Dentigerous cyst was treated with cyst enucleation with extraction of the mesiodens. Mesiodens should be diagnosed at the earliest possible time and its management should be conducted to prevent development of dentigerous cyst and damage to adjacent teeth and vital structures.

Objective Mandibular fracture is the most common maxillofacial fracture accompanied by complaints of malocclusion and pain. This causes a decrease in the quality of life. Mandibular fracture management can be done with open reduction and internal fixation or intermaxillary fixation. The Oral Health Impact Profile (OHIP 14) and the General Oral Health Assessment Index (GOHAI) were used to evaluate the quality of life after surgical treatment based on the distribution of age, sex, type of neglect, and surgical management. Materials and Methods This research is an analytic study with an analytical observational method with total sampling. The total sample used was 15 patients during the 2006 to 2020 period. The results of this study were scored, and then, the data were processed using the eta test. Results The results of the study based on the OHIP 14 parameters showed the results of each distribution, namely, age: p = 0.154, gender: p = 0.080, neglected type: p = 0.080, and management: p = 0.419. Meanwhile, the GOHAI parameters showed the results of each distribution, namely, age: p = 0.105, gender: p = 0.356, neglected type: p = 0.356, and management p = 0.286. The results of this distribution showed that there was no significant difference between patients' quality of life based on age, sex, neglected type, and treatment using both OHIP 14 and GOHAI parameters. Conclusions The results obtained in this study using characteristics of age, gender, type of fracture, type of neglect, and management did not have a significant effect on the level of patient satisfaction after surgery, using both OHIP 14 and GOHAI questionnaires.

Introduction: Oral Squamous Cell Carcinoma (OSCC) represents approximately 96% of the entire oral cancers. Epithelial-mesenchymal transition (EMT) is a factor contributing to the poor prognosis associated with OSCC. α-mangostin is one of the xanthones which show anti-cancer activities against some types of cancers and can suppress EMT-induced invasion by increasing E-cadherin expression. This study aimed to identify the viability of α-Mangostin to reduce the viable cells of HOC313. Methods: The role of α-mangostin to induce HOC313 cell culture at various concentrations which conducted on two groups: control group using only HOC313 cell line and intervention group comprising HOC313 cell line which added various concentrations. In this present study, cells were treated after reaching the confluency level of 80% in 5x103 cells/well. α-mangostin used had six concentrations: 1.25 µM, 2.5 µM, 3.75 µM, 5 µM, 6.25 µM, and 7.5 µM. Results: Concentration of α-mangostin had a significant effect on cell viability, p-value obtained was at 0.023 (p < 0.05). The Mann-Whitney test was also performed to identify significant differences in cell viability between control cells and all treatment cells were at 2.5 mg/ml and 5 mg/ml with the value p = 0.02 (p < 0.05). The concentrations α-mangostin at 1.25, 2.5, 3.75, 5, 6.25, and 7.5 µM is unable to reduce cell viability of HOC313. Conclusion: Low α-mangostin concentrations possibly result in a biphasic effect which leads to increase the viability cell of HOC313 cell line. Therefore, high α-mangostin concentrations might effectively inhibit cancer cell growth, migration, and invasion.

Objective Canine impaction is a difficult condition to treat, and it usually necessitates a combination of surgical exposure and orthodontic traction or surgical extraction. An accurate assessment of the maxillary canine's position can help determine the severity of the impaction, the difficulty of therapy, and the treatment's prognosis. Materials and Methods A total of 55 impacted canines were studied and selected retrospectively. Difficulty indexes were used to measure the severity of impaction with pretreatment panoramic radiographs. Statistical Analysis Pearson correlation was used to test the validity of the difficulty index modification score. Regression statistical analysis was used to evaluate any correlation between total scoring from each index with surgical treatment. Results The validity test on the variable modification index score showed a valid value (p = 0.000). According to both treatment difficulty and modification index, odontectomy group showed higher mean of total scoring than surgical exposure group. Treatment difficulty and modification index showed a significant correlation with surgical treatment (p = 0.003 and p = 0.001). Conclusions The higher the severity of canine impaction, the greater is the possibility of odontectomy than surgical exposure. Both indexes can consider to be used in determining surgical treatment planning.

Lipoma is a benign, rare, mesenchymal tumor found in the head and neck region, especially in the parotid gland. It thus requires a careful and precise examination to establish a diagnosis. A surgical procedure of the parotid gland is challenging due to the associated risk factor of facial nerve injury. We report a rare case of head and neck region lipoma between the superficial and deep lobe of the parotid gland. A 44-year-old female patient was presented with the chief complaint of a painless lump on the left front ear to the left cheek for about 1 year. There were no complaints of tooth pain before the lump appeared, and there were no lumps in other regions. A fine-needle aspiration biopsy, ultrasonography, and magnetic resonance imaging were all performed to establish the preoperative diagnosis and to plan the correct surgical approach. Lipoma was the initial clinical diagnosis, and a surgical excision with superficial parotidectomy and facialis nerve preservation was performed. Follow-up examinations were conducted to assess any facial nerve injury complications. Conclusion Lipoma rarely grows in the parotid gland. Careful diagnosis should be performed to establish a precise surgery for parotid dissection and facial nerve preservation.

Objective Freeze-dried bovine bone scaffold (FDBB) or decellularized FDBB (dc-FDBB) was developed as an ideal scaffold with osteoinductive properties. This research aims to compare the osteoinductive properties marked by the expression of runt-related transcription factor-2 (RUNX2) and Osterix (OSX) and the osteogenic capacity of these scaffolds imbued with human umbilical cord mesenchymal stem cells (hUCMSCs). Materials and Methods This study was performed in five experimental groups: a negative control group (C-) of hUCMSCs with a normal growth medium, a positive control group (C + ) of hUCMSCs with an osteogenic medium, experimental group 1 (E1) with an FDBB conditioned medium (CM), and experimental group 2 (E2) with a dc-FDBB-CM, and a third experimental group (E3) consisting of a DBBM-CM. Alizarin red staining was performed to qualitatively assess osteoinductive capacity. RUNX2 and OSX expression was quantified using real-time quantification polymerase chain reaction with two replications on day six (D6) and day 12 (D12) as fold changes. Results This experiment revealed that hUCMSCs were positively expressed by CD73, CD90, and CD105 but were not expressed by CD34. Alizarin red staining showed that E1 had the most calcium deposition on D6 and D12, followed by E3 and then E2 The RUNX2 and OSX expression was higher in E1 but this difference was not significant. The OSX expression in E1,E2,E3 was lower on D12 and C+ of OSX had the highest expression. There was a significant difference of fold change measured between all groups (p Conclusion FDBB osteoinduction and osteogenic capacity were higher when compared with DBBM and dc-FDBB.

Aim Demineralized dentin material membrane (DDMM) is a novel bioresorbable guided bone regeneration (GBR) which is derived from the demineralization process of bovine dentin. This material/process could be an alternative to resolve musculoskeletal dysfunction that harms the quality of human life. Purpose To evaluate the cytotoxic effect of DDMM as GBR membrane on MC3T3-E1 osteoblast cell line. Methods Cytotoxic effect was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Osteoblast MC3T3-E1 cell culture was used as a parameter of cell viability after reacting with GBR materials. The absorbance values were examined at each treatment to determine the percentage of cell viability. There were four groups created in the present study: two treatment groups and two control groups. The treatment groups consisted of a DDMM group and a bovine pericardium collagen membrane (BPCM) group. The control groups comprised a group containing cell culture medium as a negative control group and another positive control group that contained cell cultures. Results The results revealed no significant difference in MC3T3-E1 cell viability between the treatment and control groups (p < 0.05). Moreover, as observed in the DDMM group, there was an increase in the number of osteoblast cells. Conclusion DDMM is a suitable alternative biomaterial for GBR as it is non-cytotoxic and could potentially increase the rate of repair of craniofacial defects., Video Abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/-9wbabBPZIo.

BackgroundImpaction of third molars is often found in dental practice. Since reported in history on the discovery of the mandible bone 13.000–15.000 BC, research on dental impaction continues to grow. In the modern population, the highest prevalence is found in the impaction of mandibular third molars. There is a limited study regarding the impact pattern of mandibular third molars.ObjectiveTo investigate the impact pattern of mandibular third molars in populations in Surabaya and the surrounding area in East Java, Indonesia.MethodsA retrospective, cross-sectional study was conducted to investigate the impact patterns of mandibular third molars from the medical record data of patients at the Maxillofacial Oral Surgery Clinic of the Dental Hospital of Universitas Airlangga from July 2017-June 2019. Data were processed by age group, sex, angulation type, level position, complaint, indication was performed odontectomy and analyzed using chi-square significance of p-value ≤ 0.05.Results1057 cases of impacted third molar teeth with a prevalence of 72%. The highest group was found aged 20–24 years (42.5%) female (60.7%), mesioangular angulation type (41.9%), level of impacted IIA impacted teeth (66.9%), local pain complaint (86.3%), and pericoronitis as an indication for odontectomy (56.3%). There is a significant difference between sex and age with angulation of impacted tooth (p ConclusionImpaction of mandibular third molars was found in the young age group, most characteristics in women, mesioangular angulation, level IIA position with the complaint of local pain around impacted teeth and pericoronitis as an indication of odontectomy. Trial Registration: Number 694/HRECC.FODM/X/2019.

Objective The objective of this study was to determine the characteristics of demineralized dentin material sponge (DDMS). Material and Methods An observational study was conducted on DDMS and BPCM. Fourier transform infrared (FTIR) test was performed to determine the characterizations of the materials. Scanning electron microscope-electron dispersive X-ray spectroscopy (SEM-EDX) test was performed to observe the elements contained in the materials. Results The infrared spectrum of the DDMS and BPCM functional groups showed the same pattern in each variation, and no significant differences were found. According to SEM analysis, the cavities that make up the membrane were spotted on the surface. Besides, according to the SEM-EDX analysis, DDMS contained chlorine, carbon, and calcium, while BPCM contained carbon, oxygen, and sulfur. Conclusion DDMS has the potential to be a biomaterial for bone tissue engineering in terms of the characteristics. DDMS had a structure that almost resembles BPCM as seen from the results of the FTIR graph between DDMS and BPCM. The morphological structure of the two materials in the SEM test appeared to have porosity with various sizes.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and the presence of restricted interests and repetitive behaviours. Comorbidities following ASD, such as seizure, intellectual disability, and sensory impairment worsen patients’ ability to care for themselves. We present the case of a 22-year-old man with autism, intellectual disability and visual impairment who had recurrent pain in his upper and lower left posterior teeth that had cavities. On the first visit, the patient was observed and had panoramic x-ray. Clinical examination could not be done properly due to lack of patient cooperation. Restoration, pulp capping, tooth extraction, and odontectomy were planned under general anaesthesia.

The low-affinity nerve growth factor receptor p75 is a stratified epithelial stem/progenitor marker of human epithelia. We found OM-1, a human squamous cell carcinoma (SCC) cell line, showed distinct cells with p75 cluster, especially located at the center of a growing colony in a monolayer culture. A cell with p75 cluster was surrounded by cytokeratin 14- and cytokeratin 13-expressing cells that settled at the outer margin of the colony. OM-1 cells were also capable of forming tumor spheres in a cell suspension culture, an ability which was attenuated by the inhibition of p75-signaling. Intriguingly, we also found a p75-negative cell population from a growing culture of OM-1 that re-committed to become p75-clustering cells. These results indicated the possibility that SCC with epithelial multi-layering capacity can exploit the p75-dependent stratified epithelial progenitor property for the cancer stemness., Highlights • Squamous cell carcinoma cell line OM-1 maintained cell population with p75 cluster in the cell. • Single cell-derived OM-1 colonies with the cell at centre maintained hierarchical stratified epithelial linages. • OM-1 cells have p75-dependent epithelial progenitor and stemness properties.

Background. Deproteinized bovine bone mineral (DBBM) particle is the commonly used bone graft substitute in implant surgery which is mainly osteoconductive and has very slow degradation. Demineralized freeze-dried bovine bone xenograft (DFDBBX) particle is being developed as a novel xenogeneic bone filler. Objectives. The study aimed to analyze osteogenic activity and bone-forming capacity of DFDBBX particles compared to DBBM particles in alveolar bone defects in rabbit mandibles models. Material and Methods. This study investigated bone defects whether filled with DBBM particles or DFDBBX particles or left unfilled in 30 rabbit mandibles. Specimens were processed for histology, immunohistochemistry, and micro-CT scanning. Statistical difference was set at a p value < 0.05. Results. The quantitative assessment showed a significantly lower number of osteoclasts and a higher number of osteoblasts in the DFDBBX group compared to the DBBM group in 2 and 4 weeks ( p < 0.05 ). Immunostaining analyses showed significantly higher expression of RUNX2, collagen type I, alkaline phosphatase, and osteocalcin in the DFDBBX group compared to the DBBM group in 2 and 4 weeks. Bone healing score in the DFDBBX group was comparable to the DBBM group. Micro-CT presented no significant difference in the volume percentage of the mineralized tissue in the DBBM and DFDBBX groups in spite of the different healing patterns in both groups. Conclusion. DFDBBX particles induced higher osteoblastic activities than DBBM particles at the early stage of healing. Meanwhile, the capacity of bone formation in DFDBBX particles was comparable with DBBM particles at the later stage of healing. Considering the limitation of this study, the results presented DFDBBX particles as potential bone filler candidates.

Cleft lip/palate (CL/P) is one of the most common birth defects in humans. Haploinsufficiency in genesBone Morphogenetic Protein (BMP) 2 is thought to play an important role in the incidence of CL/P. Thisstudy aimed to identify changes in the nucleotide (Single Nucleotide Polymorphism/SNP) BMP 2 rs235768A>T gene in CL/P patient in Indonesia. Seventy samples of DNA that were successfully amplified andrestricted consisted of patient and control samples with the three of which were used for sequencing. Basedon the analysis using restriction enzymes and Finch TV and Bioedit software programs, this study identifieda change from nucleotide A to nucleotide T which is a mutation missense (Serine-Arginine/TCA-TCT).Based on the results of the Fisher’s exact test, there was difference in genotype frequency between the CL/Pgroup and the control. Meanwhile, there was no difference in allele frequencies between the two groups. Theallele frequency T has a higher value than the frequency of the allele A.

The most common symptoms of Williams-Beuren syndrome (WBS) are heart defects and unusual facial features. The objective of this case report was to highlight the preparation of comprehensive dental care for this syndrome. A seven-year-old boy came with multiple dental caries as a chief complaint. Parents reported a history of corrected tetralogy of Fallot (ToF) three years ago. The routine medical check-up was carried out annually. Based on the typical signs and symptoms, a diagnosis of William-Beuren Syndrome was made. Comprehensive dental care under general anesthesia on a patient with a history of heart defect and multiple dental caries was the best choice and exhibits a high success rate. Extraction treatment was carried out to avoid the risk of endocarditis infection, restoration to prevent the progressivity of caries, and space maintainers to restore function and aesthetics.

A solitary fibrous tumour (SFT) is a rare spindle-cell neoplasm of mesenchymal origin usually located in the pleura. It has been recently described as occurring in various head and neck sites, including the oral cavity. The purpose of this article is to report a case of SFT originating in the buccal space and extending into the infratemporal space treated by means of transoral approach surgery. A 25-year-old female patient reported to the Department of Oral and Maxillofacial Surgery, Universitas Airlangga Hospital, chiefly complaining of a painless lump in the left cheek which had been present for nine months. The diagnosis was arrived at on the basis of a combination of clinical investigation, imaging studies and histopathological examination (biopsy). The surgical approach involved transoral incision through the buccal mucosa. An SFT of buccal space may extend to nearby structures producing the anatomical challenge of removal through a transoral approach. Excisional biopsy involving a transoral approach is, nevertheless, considered appropriate because it produces an attractive aesthetic appearance, reduces morbidity from nerve/ vascular/ gland injury and promotes more effective healing. Key words:Solitary fibrous tumor, buccal space, infratemporal space, transoral approach.

Background. Bovine pericardium collagen membrane (BPCM) had been widely used in guided bone regeneration (GBR) whose manufacturing process usually required chemical cross-linking to prolong its biodegradation. However, cross-linking of collagen fibrils was associated with poorer tissue integration and delayed vascular invasion. Objective. This study evaluated the potential of bovine cortical bone collagen membrane for GBR by evaluating its antigenicity potential, cytotoxicity, immune and tissue response, and biodegradation behaviors. Material and Methods. Antigenicity potential of demineralized freeze-dried bovine cortical bone membrane (DFDBCBM) was done with histology-based anticellularity evaluation, while cytotoxicity was analyzed using MTT Assay. Evaluation of immune response, tissue response, and biodegradation was done by randomly implanting DFDBCBM and BPCM in rat’s subcutaneous dorsum. Samples were collected at 2, 5, and 7 days and 7, 14, 21, and 28 days for biocompatibility and tissue response-biodegradation study, respectively. Result. DFDBCBM, histologically, showed no retained cells; however, it showed some level of in vitro cytotoxicity. In vivo study exhibited increased immune response to DFDBCBM in early healing phase; however, normal tissue response and degradation rate were observed up to 4 weeks after DFDBCBM implantation. Conclusion. Demineralized freeze-dried bovine cortical bone membrane showed potential for clinical application; however, it needs to be optimized in its biocompatibility to fulfill all requirements for GBR membrane.

Dentigerous cysts are cysts of the epithelial lining of the jaws derived from the dental follicle of unerupted teeth. These cysts are often found during routine radiographic examination along with unerupted teeth. Dentigerous cysts are usually asymptomatic unless the size becomes large, thus causing swelling. This case report describes the management of dentigerous cyst in the upper left canine region with canine impaction to the orbital floor. Dentigerous cyst was treated with cyst enucleation but the impacted canine was not taken because of the magnitude of risk that can occur which was a disruption to the eye muscle. Conclusion. Treatment of dentigerous cysts can be performed by enucleation technique and management related the impacted tooth at the orbital floor needs a further evaluation consideration.

Background. Implant placement in defective anterior maxilla poses a great challenge regarding functional and aesthetic outcomes. Therefore, it requires predictable alveolar ridge augmentation. Deproteinized bovine bone mineral (DBBM) particle has commonly been used for bone grafting. However, it is associated with low resorption rates which potentially compromise the outcome of horizontal augmentation in conjunction with implant placement. Aims. This study is aimed at evaluating the stability of tissue augmented with DBBM particle associated with implant placement in the anterior maxilla. Materials and Methods. The inclusive criteria consist of patients being treated with guided bone regeneration (GBR) incorporating the use of DBBM particles with either a simultaneous or staged approach. The parameters analyzed include the implant survival rate, post-GBR clinical stability based on tissue resorption level, and the tissue stability between simultaneous and staged approaches. Statistical analysis using Mann-Whitney test is performed with significance determined at p value < 0.05. Results. Seventeen patients with 23 implant placements satisfy the criteria for this study. Simultaneous approach is adopted in 18 (78.3%) implants and a staged approach in 5 (21.7%) implants. The implant survival rate is 100%. The evaluation of horizontal tissue stability reveals a low resorption level in 19 (82.6%) implants, while moderate and high resorption levels are found in 3 (13.0%) and 1 (4.3%) implants, respectively. The statistical analysis shows that the simultaneous approach produces significantly (p=0.005) lower resorption level compared to the staged approach. Conclusion. Horizontal ridge augmentation using DBBM particles associated with implant placement in the anterior maxilla produces good clinical stability. The stability appears to be higher in the simultaneous approach compared to the staged approach.

Background: An odontectomy constitutes a common surgical procedure performed by oral and maxillofacial surgeons on a daily basis. The anesthesia procedure required during this form of operation may involve the administering of a general anesthesia which, while a safe procedure when performed by an anesthesiologist, still involves an element of risk and should only be undertaken with appropriate safeguards. Various measures, not only anxiety control-based, are suggested in this article. Purpose: The purpose of this study was to report considerations factors, other than anxiety, as indications in performing odontectomy conducted under a general anesthesia at Universitas Airlangga Hospital, Surabaya, Indonesia. Cases: Four cases of patients who had undergone an odontectomy under a general anesthetic are reported here. Case management: The four cases of management involved odontectomies conducted under a general anesthetic for a variety of reasons with contrasting outcomes. The treatment of the four patients was based on an anatomical approach and previously ineffective pain control due to greater trauma. One of the patients also suffered from schizophrenia that produced comorbidity requiring holistic observation. This individual required intricate surgery whose performance was challenging under a local anesthetic. None of our other patients suffered from serious complications related either to surgery or the administering of a general anesthetic. Conclusion: In conclusion, important factors relating to an odontectomy performed under a general anesthetic on four patients in Universitas Airlangga Hospital, Surabaya included: anxiety, anatomical approach, adequate pain control, comorbidity of systemic medical conditions and the potential need for surgical procedures difficult to perform under a local anesthetic.

We found that high galectin-1 (Gal-1) mRNA levels were associated with invasive squamous cell carcinoma (SCC) cells that expressed Snail, an epithelial-to-mesenchymal transition (EMT) regulator. Both Gal-1 overexpression and soluble Gal-1 treatment accelerated invasion and collective cell migration, along with activation of cdc42 and Rac. Soluble Gal-1 activated c-Jun N-terminal kinase to increase expression levels of integrins α2 and β5, which were essential for Gal-1 dependent collective cell migration and invasiveness. Soluble Gal-1 also increased the incidence of EMT in Snail-expressing SCC cells; these were a minor population with an EMT phenotype under growing conditions. Our findings indicate that soluble Gal-1 promotes invasiveness through enhancing collective cell migration and increasing the incidence of EMT.

In this study, we found that wounding of a confluent monolayer of squamous cell carcinoma (SCC) cells induced epithelial-mesenchymal transition (EMT) specifically at the edge of the wound. This process required the combined stimulation of TGFβ, TNFα, and PDGF-D. Such a combined cytokine treatment of confluent monolayers of the cells upregulated the expression levels of Snail and Slug via PI3K. The PI3K downstream effector, AKT, was dispensable for the upregulation of Snail and Slug, but essential for enabling EMT in response to upregulation of Snail and Slug.

We found a linear correlation between the Prostaglandin E 2 (PGE 2 ) amount and the NR4A2 expression in oral squamous cell carcinoma (SCC) tissues through a statistical analysis among 41 clinical cases. In SCC cell lines, PGE 2 receptor (EP) ligation by exogenous PGE 2 promoted the NR4A2 expression in the cAMP/protein kinase A (PKA)-dependent manner. The process required a nature of SCC cell represented by constitutive activated epidermal growth factor receptor (EGFR) family. Targeted inactivation of the EGFRs interfered the PGE 2 -dependent NR4A2 expression. The PGE 2 -dependent NR4A2 induction is essential for the resistance to anti-cancer drug-induced apoptosis especially in SCC cells which showed constitutive EGFRs activity via autocrine epiregulin, a ligand for EGFRs. Conversely, SCC cells which lack epiregulin expression in their nature could gain the ability to promote the NR4A2 expression in response to PGE 2 and attain the resistance to anti-cancer drug-induced apoptosis under the existence of exogenous epiregulin. These findings suggest that susceptibility of SCC to anti-cancer drug could be compromised when PGE 2 was delivered in the microenvironment of SCC cells supported by constitutive EGFR family activities as their nature.

We previously identified genes associated with Snail-mediated squamous cell carcinoma (SCC) invasiveness, in which we observed significant elevation of Cyr61 expression. In this study, SCC cell lines overexpressing Cyr61 exhibited constitutive activation of Rho A and upregulated invasiveness without the disruption of homophilic cell attachment. Humoral Cyr61 enhanced further production of endogenous Cyr61 by SCC cells, which stimulated collective cell migration and the development of an invasive tumor nest. We propose a Cyr61-dependent model for the development of invasive SCC nest, whereby a subset of tumor cells that highly produce Cyr61 may direct other tumor cells to undergo collective cell migration, resulting in a formation of primary SCC mass.

We found a linear correlation between the Prostaglandin E(2) (PGE(2)) amount and the NR4A2 expression in oral squamous cell carcinoma (SCC) tissues through a statistical analysis among 41 clinical cases. In SCC cell lines, PGE(2) receptor (EP) ligation by exogenous PGE(2) promoted the NR4A2 expression in the cAMP/protein kinase A (PKA)-dependent manner. The process required a nature of SCC cell represented by constitutive activated epidermal growth factor receptor (EGFR) family. Targeted inactivation of the EGFRs interfered the PGE(2)-dependent NR4A2 expression. The PGE(2)-dependent NR4A2 induction is essential for the resistance to anti-cancer drug-induced apoptosis especially in SCC cells which showed constitutive EGFRs activity via autocrine epiregulin, a ligand for EGFRs. Conversely, SCC cells which lack epiregulin expression in their nature could gain the ability to promote the NR4A2 expression in response to PGE(2) and attain the resistance to anti-cancer drug-induced apoptosis under the existence of exogenous epiregulin. These findings suggest that susceptibility of SCC to anti-cancer drug could be compromised when PGE(2) was delivered in the microenvironment of SCC cells supported by constitutive EGFR family activities as their nature.