Kuo-Chou Chiu

Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma

BACKGROUND This study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). METHODS Condition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects on macrophage (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-κB were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues. RESULTS THP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-κB diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues. CONCLUSION Axl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-κB pathway.

Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-κB signaling

Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-α and attenuated M2-related cytokines IL-8, IL-10, and TGF-β expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages. Conversely, M1 inducing cytokine IFN-γ was upper-regulated in cancer cells. Additionally, through increasing AMPK and p65 phosphorylation, metformin treatment activated AMPK-NF-κB signaling of cancer cells that participate in regulating M1 and M2 inducing cytokines expression. Moreover, Compound C, an AMPK inhibitor, significantly increased IL-4, IL-10, and IL-13 expression while BAY-117082, an NF-κB inhibitor, decreased expression. In metformin-treated tumor tissue, the percentage of M2-like macrophages decreased while M1-like macrophages increased. These findings suggest that metformin activates cancer AMPK-NF-κB signaling, a pathway involved in regulating M1/M2 expression and inducing genes for macrophage polarization to anti-tumor phenotype.

γ-Synuclein Expression Is a Malignant Index in Oral Squamous Cell Carcinoma

Dysregulation of γ-synuclein (SNCG) has been reported in many cancers; however, its role in cancer development is still controversial. Here, we examined the potential involvement of DNA methylation in regulating SNCG and its role in oral squamous cell carcinoma (OSCC). We used 8 OSCC cell lines to investigate SNCG methylation and expression. SNCG methylation was examination by methylation-specific polymerase chain reaction and bisulfate sequencing. Cells showing a high degree of SNCG methylation were treated with 5-aza (methylation inhibitor), and changes in their methylation and expression profiles were analyzed. Functional effects of SNCG in OSCC were examined by its overexpression and knockdown. Additionally, methylation and expression of SNCG in OSCC tissues were investigated and correlated with clinicopathologic features. All OSCC cells showed detectable SNCG expression at the mRNA and protein levels. Methylation-specific polymerase chain reaction and bisulfate sequencing revealed high SNCG expression in SCC25 cells with the unmethylated allele, and their 15 CpG islands were unmethylated. The methylated allele was detected only in OEC-M1 cells exhibiting low SNCG expression, and their CpG islands were partially methylated. 5-aza treatment in OEC-M1 cells attenuated methylation and restored SNCG expression. SNCG overexpression increased colony forming, migration, and invasion abilities in OEC-M1 cells. Silencing SNCG in SCC25 cells suppressed these behaviors. All 25 tumor-adjacent normal tissues were negative for SNCG immunostaining. SNCG upregulation was frequently observed in dysplastic and OSCC tissues. Positive SNCG expression was found in 45% (37 of 82) OSCC tissues. Positive SNCG expression in OSCC significantly correlated with cancer staging and lymph node metastasis. However, SNCG methylation did not correlate with its expression and clinicopathologic variables in OSCC tissues. DNA methylation may participate in regulating SNCG expression in some OSCC cells. SNCG upregulation could be involved in OSCC progression.

The association of betel quid, alcohol, and cigarettes with salivary gland tumor—A case–control study

Background/purpose Salivary gland tumor (SGT) is a rare disease with a largely unknown etiology. The risks of betel quid chewing, alcohol drinking, and cigarette smoking have been well documented in oral cancer but not in SGT. We aimed to investigate the independent and combined effects of betel quid chewing, cigarette smoking, and alcohol consumption on the incidence of SGT. Materials and methods We conducted a case–control study of 1845 patients aged 35–65 years, including 239 patients with pathologically proven SGT and 1606 controls from the health examination clinics of the same hospital during 2005–2014 to examine the association of these three risk factors with SGT in Taiwan. Adjusted odds ratio (aOR) and their 95% confidence interval for the association of risk factors to SGT were analyzed. Results After adjusting for covariates, aOR of cigarette smoking, alcohol drinking, and betel quid chewing were 2.50, 1.27, and 3.38, respectively for SGT. The significantly increased risk for SGT was observed in cigarette smoking (P < 0.001). Cigarette smoking was also found to increase risks in subgroups of SGT (aOR = 5.24, 2.41, 2.63, and 2.04 in minor, major, benign, and malignant SGT, respectively). Conclusion Our study provided the first evidence to show the independent and combined impact of betel quid chewing with cigarette smoking and alcohol drinking on the SGT, and support the concept that cigarette smoking may associate with SGT carcinogenesis.

Tooth-associated and non-tooth-associated Idiopathic Osteoscleroses in Taiwan

Idiopathic osteoscleroses (IOSs) are common lesions of the jaw bone. The present study was undertaken to survey the incidence of jaw bone IOSs in a Taiwanese population and the relationship between IOS types and their distributions in the mandible. Panoramic radiographs and clinical information for 3269 patients were examined to identify IOSs, which were classified as either tooth-associated (TA) or non-tooth-associated (NTA) lesions. Statistic analyses were performed using Chi-square test. In a total, 208 IOS lesions were identified in 197 patients. There were 113 (54.3%) TA and 95 (45.7%) NTA IOS lesions. The age and gender distributions were similar for both IOS groups (p=0.844 and 0.985, respectively). The most-common site was the first molar region (23.9%) for TA IOSs and the first premolar region (24.2%) for NTA IOSs. The association between both types of IOS and the regional distribution in the mandible was significant (p＜0.05). Conclusions: In the Taiwanese population, the relatively prevalent location for TA and NTA IOSs is the mandibular premolar region.

Condensing Osteitis- Literature Review and Three Case Reports

硬化性骨炎是一種常見因慢性牙髓組織發炎與刺激而引起的骨性重建與增生病灶．臨床上通常可能沒有症狀，但可以經由例行Ｘ光檢查發現。臨床上，這樣的病灶很容易被誤診是其他顎骨內的放射性不透射病灶。本文選取了三個確診為硬化性骨炎的臨床病例，討論其臨床表徵及與其他顎骨內相關放射線不透過病灶的鑑別診斷方法。

Treating Lower Jaw Protruding with Internal Derangement of Temporomandibular Joints by Bilateral Modified Condylotomy-A Case Report

Condylotomy serves as surgical modality for various temporomandibular joint (TMJ) disorders. The modified condylotomy consists of an intraoral vertical ramus osteotomy (IVRO), in which the condyle segment is supposed to displace inferiorly. This technique provides more intra-capsular space for a better disc-condyle relationship, hence improves associated symptoms of internal derangement of TMJ. We present a 24-year-old female with mandibular prognathism and bilateral internal derangement of TMJ, Wilkes stage I-II, whose clicking sounds diminish after bilateral intraoral vertical ramus osteotomy.

Use of Intra-operative Ultrasonography to Detect Deep Foreign Bodies in Severe Facial Trauma-A Case Report

Traumas involving foreign bodies in the soft tissues are a frequent problem in human medical practice. In such cases, detection of the foreign body is an important aspect of retrieval, and plain film radiography is necessary to identify its location and characteristics. Depending on its characteristics, magnetic resonance imaging (MRI), computed tomography (CT), or ultrasonography is used to identify its exact location. Herein we present a case of penetration injury to the facial region, with residual radiolucent and radiopaque foreign bodies, and describe the use of ultrasonography in the management of foreign bodies in soft tissues in this case. This case report describes an alternative option for the detection of foreign bodies, and emphasizes the importance of performing intra-operative ultrasound examinations on patients with injuries, which may reduce the possibility of lawsuits following clinical surgery.

Frequency and Distribution of Idiopathic Osteosclerosis in Diabetic Patients - a Pilot Study in Taiwan

Background: Idiopathic osteosclerosis (IOS) refers to lesions of the jaw bone. The present study was undertaken to determine the prevalence of IOS in a group of diabetes mellitus (DM) patients by radiographic evaluation and to investigate the relationship between the findings in relation to age, gender, and localization. Methods: Panoramic radiographs and clinical information for 832 DM patients were examined to identify IOS. Statistical analyses were performed using chisquare test. Results: In total, 60 IOS lesions were identified in 48 patients. The prevalence of IOS in DM patients was 5.8%. All the IOS lesions were detected in the mandible. Twenty-six IOS lesions were associated with root apex and 34 lesions were not associated with tooth. IOS occurred more commonly in the fourth (25.0%) and fifth (28.3%) decades of DM patients. In addition, 27 (53.3%) and 21 (35%) IOS lesions were observed in the premolar and molar area of mandible, respectively. Conclusions: In DM patients, the frequency of IOS is similar to that in the general population and the relatively prevalent location for IOS is the mandibular premolar region. IOS lesions can arise at any age without sex predilection. Additionally, our findings support the theory that IOS is a variation of normal bone development unrelated to a local stimulant.