Surgical Management of Temporomandibular Joint Ankylosis with Mersilene Mesh Interpositional Arthroplasty: A Case Series Study.

Ankylosis of the temporomandibular joint (TMJ) is one of the most prevalent TMJ disorders in patients who have experienced trauma. Due to the high risk of recurrence, gap arthroplasty without interpositional material has been gradually discontinued as a treatment for TMJ ankylosis. After arthroplasty surgery, various interposition materials have been used to prevent a recurrence. Reporting on the effectiveness of TMJ bony ankylosis treatment using Mersilene mesh interpositional arthroplasty is the purpose of this study.This was a retrospective study carried out on five patients of TMJ ankylosis. All patients were treated through a Mersilene mesh interpositional arthroplasty procedure from January 2016 to April 2022 in Dr. Soetomo General Hospital and Universitas Airlangga General Hospital and evaluated 3 months postoperatively for the functional stability of TMJ. The result is preoperative mouth opening ranged between 0.7 and 13 mm. The patients achieved the interincisal opening between 27 and 40 mm postoperatively and had no complications for 3 months. In conclusion, Mersilene mesh interpositional arthroplasty is a very effective surgical treatment for TMJ bony ankylosis to achieve maximum mouth opening and avoid recurrences. The prevention of ankylosis recurrence necessitates thorough rehabilitation.

Effect of α-Mangostin on Interleukin-11 and Runt-related Transcription Factor-2 Gene Expression on Cell Line Osteoblast Cultures Induced with Lipopolysaccharide.

Background: Loss of permanent teeth after tooth extraction without replacement of missing teeth can result in impaired masticatory, esthetic, phonetic functions, and impaired balance of the masticatory organ in the mouth. Therefore, a method is needed to inhibit the alveolar bone resorption process so that the dimensions of the tooth socket can be maintained vertically or horizontally until the time of implant placement, which is called the socket preservation procedure. α-mangostin is known to have a potential anti-inflammatory effect and most likely can be used as a potential therapeutic agent to inhibit bone resorption caused by posttooth extraction inflammatory processes. Aims: The aim of the study was to determine the effect on the inflammatory process and osteogenesis on osteoblast cell line culture by induction with lipopolysaccharide (LPS) and α-mangostin. Materials and Methods: This was an in vitro laboratory experimental study on mouse osteoblast cell line culture. The treatment was given with LPS, α-mangostin, and combination on osteogenic medium, using the same concentration for all concentrates. The sample will then be processed and analyzed using the real-time polymerase chain reaction. Results: The highest interleukin-11 (IL-11) gene expression was found in α-mangostin treatment, but there was no significant difference in IL-11 expression between the study groups. The highest runt-related transcription factor-2 (RUNX-2) gene expression was found in a group that received induction with LPS and α-mangostin, and from these results, it was found that there was a significant difference in RUNX-2 expression between the study groups. Conclusions: LPS and α-mangostin can increase osteogenesis in osteoblast cell culture in the osteogenic medium.

Quality of Life Evaluation of Postsurgical Mandibular Fracture Patients with Oral Health Impact Profile 14 and General Oral Health Assessment Index Parameters.

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.

Lipoma in Parotid Gland: A Rare Case Report.

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.

Osteoinductive and Osteogenic Capacity of Freeze-Dried Bovine Bone Compared to Deproteinized Bovine Bone Mineral Scaffold in Human Umbilical Cord Mesenchymal Stem Cell Culture: An In Vitro Study.

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 < 0.05), and there was no significant difference between any of the groups treated with OSX and RUNX2 on D6 and D12. CONCLUSION: FDBB osteoinduction and osteogenic capacity were higher when compared with DBBM and dc-FDBB.

Dexamethasone resets stable association of nuclear Snail with LSD1 concomitant with transition from EMT to partial EMT.

Cancer cells utilize epithelial to mesenchymal transition (EMT) during invasion and metastasis. This program has intermediate cell states with retained epithelial and gained mesenchymal features together, referred to as partial EMT. Histone demethylase LSD1 forms a complex with the EMT master transcription factor Snail to modify histone marks and regulate target gene expression. However, little is known about the formation of this complex during the Snail-dependent transition between partial EMT and EMT. Here we visualized the nuclear complex of Snail and LSD1 as foci signals using proximity ligation assay. We demonstrated that the nuclear foci numbers varied with the transition of exogenous Snail-dependent partial EMT to EMT. Furthermore, we found that long exposure to dexamethasone could revert exogenous Snail-dependent EMT to partial EMT. In this reversion, the nuclear foci numbers also returned to previous levels. Therefore, we concluded that Snail might select partial EMT or EMT by altering its association with LSD1.

The Characteristics of Demineralized Dentin Material Sponge as Guided Bone Regeneration Based on the FTIR and SEM-EDX Tests.

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.

Decision-Making Criteria of Odontectomy or Surgical Exposure in Impacted Maxillary Canine Based on Treatment Difficulty Index Modification.

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.

Postoperative Complications of Impacted Mandibular Third Molar Extraction Related to Patient's Age and Surgical Difficulty Level: A Cross-Sectional Retrospective Study.

Mandibular third molar surgical extraction, either partially erupted or fully impacted, is the most common surgical procedure in oral and maxillofacial surgery (OMFS). However, this procedure can be associated with many postoperative complications including persistent pain, swelling, trismus, and paresthesia due to nerve injury. This study aimed to identify the correlation of postoperative complications with patient's age, sex, and surgical difficulty level. This study was a cross-sectional retrospective and single-center research conducted on patients with a history of mandibular third molar surgical extraction in the period between 2017 and 2019 at Dental and Oral Hospital Universitas Airlangga, Surabaya, Indonesia. The researchers assessed the factors of age, sex, and surgical difficulty level regarding postoperative complications on the first day of the surgery and after one week on the 7th day of it. Among 916 respondents, the majority of the sample was females (59%) and the dominant age group (60.9%) was the age group of 21-30 years while the dominant surgical difficulty level was shown by the advanced cases group (77%). The statistical analysis showed that there was a significant correlation between surgical difficulty level and postoperative complications including pain, trismus, and paresthesia on the first-day assessment. On the other hand, age was significantly related to complications like pain, swelling, and trismus on the first-week assessment. Age and surgical difficulty level were the most common risk factors of the mandibular third molar extraction postoperative complications. Dentists should take into consideration that older patients (≥51 years) and patients with complex surgical level are more vulnerable to severe postoperative complications.

Analyses of Bone Regeneration Capacity of Freeze-Dried Bovine Bone and Combined Deproteinized-Demineralized Bovine Bone Particles in Mandibular Defects: The Potential Application of Biological Forms of Bovine-Bone Filler.

OBJECTIVE: This study aimed to evaluate bone regeneration capacity of FDBX granules compared to composite DBBM/DFDBX granules for filling of bone defect in rabbit mandible. MATERIAL AND METHODS: Critical size defects were created in 45 rabbits' mandible. The defect in the control group is left untreated, while in other groups the defects were filled with FDBX granules and composite DBBM/DFDBX granules, respectively. Specimens were collected at 2, 4, and 8 weeks for histology and immunohistochemical analyses. Significant difference is set at p-value < 0.05. RESULTS: The osteoblast-osteoclast quantification, osteoblast expression of Runx2, alkaline phosphatase, collagen-I, and osteocalcin, and osteoclast expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in FDBX groups were statistically comparable (p > 0.05) with the composite group, while OPG/RANKL ratio, bone healing scores, and trabecular area were significantly higher (p < 0.05) in the composite compared to FDBX group. CONCLUSION: Composite DBBM/DFDBX granules, within the limitation of this study, has better bone forming capacity than FDBX granules for filling of bone defects in the mandible.

In vitro Cell Proliferation Assay of Demineralized Dentin Material Membrane in Osteoblastic MC3T3-E1 Cells.

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.

In Vivo Analyses of Osteogenic Activity and Bone Regeneration Capacity of Demineralized Freeze-Dried Bovine Bone Xenograft: A Potential Candidate for Alveolar Bone Fillers.

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.

The squamous cell carcinoma cell line OM-1 retains both p75-dependent stratified epithelial progenitor potential and cancer stem cell properties.

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.

Transoral surgical approach to solitary fibrous tumors in buccal space with infratemporal tumor extension: A case report.

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.

Stability of Tissue Augmented with Deproteinized Bovine Bone Mineral Particles Associated with Implant Placement in Anterior Maxilla.

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.

Demineralized Freeze-Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane.

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.

Autocrine galectin-1 promotes collective cell migration of squamous cell carcinoma cells through up-regulation of distinct integrins.

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 ß5, 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.

AKT primes snail-induced EMT concomitantly with the collective migration of squamous cell carcinoma cells.

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 TGFß, 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.

Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma.

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.

PGE2 targets squamous cell carcinoma cell with the activated epidermal growth factor receptor family for survival against 5-fluorouracil through NR4A2 induction.

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.