Mu-Kuan Chen - Academia.edu (original) (raw)

Papers by Mu-Kuan Chen

BioMed Research International, 2014

Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia miltiorrhiza Bunge,... more Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose) polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer.

BioMed research international, 2014

Objective. Using the Hörmann technique of hyoid suspension in sleep apnea surgery, a steel wire i... more Objective. Using the Hörmann technique of hyoid suspension in sleep apnea surgery, a steel wire is placed through the thyroid cartilage and slung around the hyoid bone. However, we experienced thyroid cartilage fracture by steel wire traction. A modification is presented to avoid thyroid cartilage fracture.

Vaccine, 1999

Commercial in¯uenza vaccines generate serum antibody, but not local IgA. In¯uenza vaccines that i... more Commercial in¯uenza vaccines generate serum antibody, but not local IgA. In¯uenza vaccines that induce both serum and secretory antibody are more likely to protect against infection and disease progression. The adjuvants MF59 and LT-K63 were tested intramuscularly and intranasally with subunit HA. In naive mice, intranasal adjuvant eect was more apparent when included with the ®rst than second immunization. In previously infected mice, intranasal adjuvants had little eect on serum antibodies and were most eective for nasal antibodies after the second immunization. Overall, both adjuvants enhanced anti-HA IgA and IgG by intranasal vaccination whereas, by intramuscular vaccination, they only enhanced serum IgG. #

The Laryngoscope, 2013

This study built a simple prediction system by three-dimensional (3D) Doppler ultrasonography to ... more This study built a simple prediction system by three-dimensional (3D) Doppler ultrasonography to evaluate the metastases of cervical lymph nodes and the preoperative initial stage of head and neck cancer. Retrospective review of cervical lymph node ultrasound features and prospective nodal staging of head and neck cancer. One hundred thirty-nine suspicious cervical lymph nodes, receiving 3D Doppler ultrasonography, were used to establish a predictive model. Then nodal metastasis was initially staged from 27 patients with head and neck cancer by this model. The prediction system was constructed by major (internal matting, vascularity pattern) and minor (age ≥ 40 years, short/long ratio ≥ 0.5) sign categories. Cervical lymph node was regarded as metastasis with the presence of one major and any of the other factors. The predictive model resulted in sensitivity of 91.9%, specificity of 88.2%, and accuracy of 89.2%. Then we evaluated the initial staging of patients with head and neck cancer by this model, and the rate of correct N staging was 92.6%. According to this prediction system, 3D Doppler ultrasonography definitely provides a rapid and reliable method for initial staging of head and neck cancer.

Oral Oncology, 2011

s u m m a r y Substantial epidemiological data suggest a role for environmental factors (for exam... more s u m m a r y Substantial epidemiological data suggest a role for environmental factors (for example, the use of alcohol, betel quid (BQ), and cigarettes) in the occurrence of oral squamous cell carcinoma (OSCC), but the evidence for the genes involved has been inconsistent. This study was to investigate the role of CYP26B1, together with the use of alcohol, BQ, and cigarettes, on BQ-related OSCC. The association study (247 OSCC cases and 338 controls) was conducted to examine the possible interplay between CYP26B1 polymorphisms and alcohol, BQ, and cigarettes use. Additional gene expression was evaluated between OSCC tissue and adjacent normal tissue. The genetic polymorphism AA of CYP26B1 appeared to correlate with the risk of OSCC (OR = 2.26; 95% CI, 1.35-3.80). Chewing BQ multiplicatively interacted with CYP26B1 AA to increase the OSCC risk (aOR = 70.04; 95% CI, 13.62-360.11). The independent risk of OSCC was observed among BQ chewers with CYP26B1 AA, and compared with chewers with the CYP26B1 CC genotype (stratified aOR = 2.88; 95% CI, 1.07-7.74). Increased expression of CYP26B1 was observed in tumor tissue compared with adjacent normal tissue. The CYP26B1 gene plays a novel role in the BQ dependent pathogenesis of OSCC. nut extract; qRT-PCR, quantitative reverse transcriptase-polymerase chain reaction; SD, standard deviation; SDS, sodium dodecyl sulfate; HGF, human gingival fibroblast; aOR, adjusted odds ratio; CI, 95% confidence interval; IPB, inflorescence of Piper betel Linn.; PBL, Piper betel leaf; RA, retinoic acid.

Journal of Surgical Oncology, 2010

Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is t... more Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. Genetic polymorphism has been reported as a factor for increased susceptibility of HCC. Glutathione-S-transferases theta (GSTT1) and micro (GSTM1) play essential roles in detoxification of ingested xenobiotics and modulation of the susceptibility of gene-related cancer. The aim of this study was to estimate the relationships between these two gene polymorphisms and HCC risk and clinicopathological status in Taiwanese. Polymerase chain reaction (PCR) was used to determine gene polymorphisms of 102 patients with HCC and 386 healthy controls. Both gene polymorphisms were not associated with the clinical pathological status of HCC and serum levels of liver-related clinical pathological markers. While no relationship between GSTM1 gene polymorphism and HCC susceptibility was found, individuals of age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;56 years old with GSTT1 present genotype have a risk of 2.77-fold (95% CI: 1.09-7.09) for HCC compared to that with null variant, after adjustment for other confounders. GSTT1 and GSTM1 null genotypes do not associate with increased risk of HCC.

Journal of Biological Chemistry, 2010

Oral squamous cell carcinoma (SCC) has a striking tendency to migrate and metastasize. Cyclooxyge... more Oral squamous cell carcinoma (SCC) has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. However, the effects of COX-2 on human oral cancer cells are largely unknown. We found that over-expression of COX-2 or exogenous PGE 2 increased migration and intercellular adhesion molecule-1 (ICAM)-1 expression in human oral cancer cells. Using pharmacological inhibitors, activators, and genetic inhibition of EP receptors, we discovered that the EP1 receptor, but not other PGE receptors, is involved in PGE 2 -mediated cell migration and ICAM-1 expression. PGE 2 -mediated migration and ICAM-1 up-regulation were attenuated by inhibitors of protein kinase C (PKC) , and c-Src. Activation of the PKC , c-Src, and AP-1 signaling pathway occurred after PGE 2 treatment. PGE 2 -induced expression of ICAM-1 and migration activity were inhibited by a specific inhibitor, siRNA, and mutants of PKC , c-Src, and AP-1. In addition, migration-prone sublines demonstrated that cells with increased migration ability had higher expression of COX-2 and ICAM-1. Taken together, these results indicate that the PGE 2 and EP1 interaction enhanced migration of oral cancer cells through an increase in ICAM-1 production.

Head & Neck, 2009

Background. The aim of this study was to estimate the relationship of glutathione S-transferases ... more Background. The aim of this study was to estimate the relationship of glutathione S-transferases (GST)P1, GSTA1, GSTM1, and GSTT1 gene polymorphisms to oral cancer risk.

Carcinogenesis, 2011

Oral cancer is the fourth common male cancer and causally associated with environmental carcinoge... more Oral cancer is the fourth common male cancer and causally associated with environmental carcinogens in Taiwan. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has a significant effect on tumorigenesis by limiting angiogenesis and invasion of tumors through the extracellular matrix. RECK downregulation has been confirmed in many human cancers and associated with lymph node metastasis clinically. In the present hospital-based case-controlled study, the demographic, RECK genotype and clinicopathologic data from 341 male oral cancer patients and 415 cancer-free controls were investigated. We found that RECK rs10814325, rs16932912, rs11788747 or rs10972727 polymorphisms were not associated with oral cancer susceptibility. Among 488 smokers, RECK polymorphisms carriers with betel quid chewing have a 7.62-fold [95% confidence interval (CI), 2.96-19.64] to 25.33-fold (95% CI, 9.57-67.02) risk to have oral cancer compared with RECK wild-type carrier without betel quid chewing. Among 352 betel quid chewers, RECK polymorphisms carriers with smoking have a 6.68-fold (95% CI, 1.21-36.93) to 18.57-fold (95% CI, 3.80-90.80) risk to have oral cancer compared with those who carried wild-type without smoking. In 263 betel quid chewing oral cancer patients, RECK rs10814325 polymorphism have a 2.26-fold (95% CI, 1.19-4.29) risk to have neck lymph node metastasis compared with RECK wild-type carrier. These results support that gene-environment interactions between the RECK polymorphisms, smoking and betel quid may alter oral cancer susceptibility and metastasis.

BMC Complementary and Alternative Medicine, 2013

Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown a... more Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

Archives of Otolaryngology - Head and Neck Surgery, 1987

American journal of cancer research, 2015

Oral squamous cell carcinoma (OSCC), which is malignant tumors in oral cavity, is the fourth most... more Oral squamous cell carcinoma (OSCC), which is malignant tumors in oral cavity, is the fourth most common male cancer in Taiwan. EZH2 plays a key role in transcriptional repression through chromatin remodeling and in cancer development. Although the EZH2 expression in OSCC is highly correlated with tumorigenesis, it has not been determined if specific EZH2 genetic variants are associated with OSCC risk. The aim of this study was to investigate the relationship between genetic polymorphisms of EZH2 and susceptibility to OSCC in Taiwan. Here, four SNPs of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by a real-time PCR genotyping in 576 patients with oral cancer and 552 cancer-free controls. After adjusting for other co-variants, we found that carrying CC genotype at EZH2 rs6950683 and rs3757441 had a lower risk of developing OSCC than did wild-type carriers. The CCCA or CCTA haplotype among the four EZH2 sites was also associated with a reduced risk of OSCC. Fur...

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Jan 8, 2015

In humans, fucosyltransferase-2 (FUT2) plays an important role in α1,2- linkage of fucose and par... more In humans, fucosyltransferase-2 (FUT2) plays an important role in α1,2- linkage of fucose and participates in complex cellular processes such as fertilization, embryogenesis, and immune responses. However, little information is available concerning the FUT2 expression in tumorigenesis. The aim of this work was to investigate the combined effect of FUT2 gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinic pathological characteristics of oral cancer. Four SNPs of the FUT2 gene (rs281377, rs1047781, rs601338, and rs602662) from 1200 non-cancer controls and 700 oral squamous cell carcinoma (OSCC) patients were analyzed by real-time polymerase chain reaction (PCR). The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of OSCC, and the impact of these SNPs on the susceptibility and clinic pathological characteristics of OSCC. After adjusting for other covariant, we observed that betel quid chewi...

Medicine, 2015

Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental ... more Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental carcinogens. Tissue inhibitor of metalloproteinase-3 (TIMP3), a member of the TIMP family, is the only protein that binds to the extracellular matrix for suppressing cancer cell growth, angiogenesis, migration, and invasion. The association of TIMP3 polymorphism with oral cancer susceptibility, however, has not yet been reported. In this study, 1947 participants-1200 healthy male controls and 747 male patients with oral cancer-were recruited. Allelic discrimination of TIMP3 -1296 T > C (rs9619311), TIMP3 C > T (rs9862), and TIMP3 C > T (rs11547635) polymorphisms were assessed through real-time polymerase chain reaction. The authors discovered that individuals carrying the polymorphic rs9862 allele are more susceptible to oral cancer [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.2-1.9; adjusted OR (AOR), 1.6; 95% CI, 1.2-2.1] after adjustment for betel quid chewing, alco...

PloS one, 2015

PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 ... more PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-...

Oncotarget, 2014

Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular ho... more Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer.

Ear, nose, & throat journal, 2015

Olfactory neuroblastoma is rare. We conducted a retrospective study to review our experience with... more Olfactory neuroblastoma is rare. We conducted a retrospective study to review our experience with minimally invasive resection of olfactory neuroblastomas via a transnasal endoscopic technique, including an analysis of surgical outcomes. Our series included 5 patients-3 men and 2 women, aged 29 to 75 years (mean: 48). Surgical outcomes were evaluated on the basis of each patient's preoperative Dulguerov classification and postoperative evaluation on computed tomography and magnetic resonance imaging. One patient was treated with surgery alone, 3 with surgery plus radiotherapy, and 1 with surgery, radiotherapy, and chemotherapy. During follow-up of 18 to 115 months, all 5 patients remained alive and disease-free. We found that endoscopic resection of olfactory neuroblastoma is a feasible and effective procedure, even in patients with more aggressive stages of disease. We also believe that the Dulguerov classification is more useful than other classifications for clinical manageme...

Auris, nasus, larynx, 2014

This paper aims to present the case of a 43-year-old woman diagnosed with a rare condition of men... more This paper aims to present the case of a 43-year-old woman diagnosed with a rare condition of meningoencephalocele that arose from a meningioma, and treated with endoscope-assisted transnasal tumor extirpation and repair of the skull base defect with tensor fascia lata flap. Endoscope-assisted operation is a viable and minimally invasive alternative to traditional craniotomy. With improved endoscopic equipment and operative technique, we can perform more reliable surgery and provide better quality of life for these patients.

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Jan 16, 2015

The myeloid zinc finger 1 (MZF1) is a zinc finger transcription factor which regulates myeloid di... more The myeloid zinc finger 1 (MZF1) is a zinc finger transcription factor which regulates myeloid differentiation and oncogenesis. However, little information is available concerning the MZF1 expression in oral squamous cell carcinoma (OSCC) and its correlation with patients' prognosis. We detected the expression of MZF1 in 274 patients with OSCC using tissue microarrays (TMAs) and evaluated the associations between nuclear MZF1 expression and the clinical parameters of OSCC patients. We found that nuclear MZF1 expression was present in 190/274 (69.3 %) cases, and loss of nuclear expression of MZF1 was associated with more advanced clinical stages (p = 0.011) and larger tumor size (p = 0.002), but not associated with positive lymph node metastasis and distal metastasis. Importantly, tongue squamous cell carcinomas (SCC) patients with negative nuclear MZF1 expression had significantly worse overall survival rates (log-rank test, p = 0.028). In conclusion, our results revealed that t...

Oral oncology, Jan 13, 2015

Extensive research supports the administration of herbal medicines or natural foods during cancer... more Extensive research supports the administration of herbal medicines or natural foods during cancer therapy. Pterostilbene, a naturally occurring phytoalexin, has various pharmacological activities, including antioxidant activity, cancer prevention activity, and cytotoxicity to many cancers. However, the effect of pterostilbene on the autophagy of tumor cells has not been clarified. In this study, the unique effects of pterostilbene on the autophagy of human oral cancer cells were investigated. The results of this study showed that pterostilbene effectively inhibited the growth of human oral cancer cells by inducing cell cycle arrest and apoptosis. In addition, the formation of acidic vesicular organelles and LC3-II production also demonstrated that pterostilbene induced autophagy. Administering 3-methylamphetamine (3-MA) and bafilomycin A1 (BafA1) exerted differing effects on the pterostilbene-induced death of human oral cancer cells. Pterostilbene-induced autophagy was triggered by ...