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ABSTRACT: Expression of placenta growth factor (PlGF) mRNA is shown to correlate with the progression and prognosis of several human cancers. In this study, we assessed whether the PlGF mRNA level in oral squamous cell carcinoma (OSCC) tissue could be used to predict the progression and prognosis of OSCCs in Taiwan.
This study used quantitative real-time reverse transcription-polymerase chain reaction (quantitative RT-PCR) to detect the PlGF mRNA levels in 63 paired OSCC and adjacent normal-looking oral mucosa (non-OSCC) tissues. Threshold cycle (CT) was defined as the PCR cycle number needed to generate a pre-determined amount of DNA (threshold). For a chosen threshold, a smaller starting copy number of mRNA results in a higher CT value. In this study, the relative expression level of tissue PlGF mRNA in each OSCC patients was expressed as -ΔCT = -(OSCC CT - non-OSCC CT). Thus, the higher the -ΔCT, the greater the copy number of PlGF mRNA in tissues.
We found that the higher mean PlGF mRNA -ΔCT value was significantly associated with OSCCs with larger tumor size (p = 0.03), positive lymph node metastasis (p = 0.003), more advanced clinical stages (p = 0.013) or the presence of loco-regional recurrence (p = 0.039). Positive lymph node metastasis (p = 0.019) and PlGF mRNA -ΔCT value >2 (p = 0.016) were identified as two independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, Kaplan-Meier curve showed that OSCC patients with a PlGF mRNA -ΔCT value >2 had a significantly poorer recurrence-free survival than those with a PlGF mRNA -ΔCT value ≤2 (log-rank test, p = 0.017).
The OSCC tissue PlGF mRNA level can be used to predict the progression and prognosis of OSCCs in Taiwan.
Journal of the Formosan Medical Association 05/2013; 112(5):253-8. · 1.13 Impact Factor
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ABSTRACT: OBJECTIVES: Oral squamous cell carcinoma (OSCC) accounts for>90% oral cancer which is a leading cause of cancer death worldwide. Early diagnosis may well offer an opportunity to increase survival to this neoplasm. Micro(mi)RNA-interfered cancer progression is crucial, yet its migration machinery of OSCC is still unknown. To access whether the possible miRNA prognostic markers and underlying mechanisms, we developed a highly migratory TW2.6 MS-10 cells from TW2.6 cells to investigate the issue. MATERIALS AND METHODS: miRNA profiling was performed on TW2.6 and TW2.6 MS-10. Target miRNA was correlated to pathological status in OSCC patients by real-time RT-PCR. A downstream effector was identified using a bioinformatics analysis, and a 3'-untranslated region (UTR) reporter assay was used. RESULTS: An miRNA cluster, miR-17-92, including miR-17, miR-19b, miR-20a, and miR-92a, was found to be significantly down-regulated in TW2.6 MS-10 compared to TW2.6 cells. Overexpression of this cluster decreased the migratory ability of OSCC cell lines. We further demonstrated that miR-17 and miR-20a are the main miRNAs of miR-17-92 cluster which modulate OSCC migration. Clinically, miR-17/20a showed negative correlation with TNM stage and lymphatic metastasis. Through a bioinformatics screening analysis and 3'UTR reporter assay, we confirmed the integrin (ITG) β8 as a direct target of miR-17/20a, and knockdown of ITGβ8 reduced cell migratory capability of OSCC. CONCLUSIONS: miR-17/20a acts as a prognostic predictor of OSCC patients' outcome and a tumor migration suppressor miRNA.
Oral Oncology 04/2013; · 2.86 Impact Factor
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ABSTRACT: BACKGROUND: Expression of Gα12 is found to be associated with cancer cell proliferation, migration, invasion, and metastasis. METHODS: This study used immunohistochemistry to examine the expression of Gα12 protein in 100 specimens of oral squamous cell carcinoma (OSCC), 45 specimens of oral epithelial dysplasia (OED), and 36 specimens of normal oral mucosa (NOM). RESULTS: The mean Gα12 labeling indices (LIs, defined as the percentage of positive cells in total cells) increased significantly from NOM (7 ± 11%) through OED (21 ± 20%) to OSCC samples (53 ± 33%, P < 0.001). The higher mean Gα12 LI was significantly associated with OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.002), or more advanced clinical stages (P = 0.003). Positive lymph node metastasis (P = 0.039) and Gα12 LI > 50% (P = 0.009) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, Kaplan-Meier curve showed that OSCC patients with a Gα12 LI > 50% had a significantly poorer cumulative survival than those with a Gα12 LI ≤ 50% (log-rank test, P = 0.009). CONCLUSIONS: Our results showed a stepwise and significant elevation in Gα12 protein expression from NOM through OED to OSCCs, suggesting that overexpression of Gα12 protein may be an early event in oral carcinogenesis and may play a pivotal role in oral cancer development. Moreover, the Gα12 protein can be a biomarker for prediction of the progression of OSCCs and the prognosis of patients with OSCC in Taiwan.
Journal of Oral Pathology and Medicine 02/2013; · 1.63 Impact Factor
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ABSTRACT: OBJECTIVES: Transforming growth factor β (TGFβ) has been suggested as the main trigger for the increased collagen production and decreased matrix degradation pathways in oral submucous fibrosis (OSF). Connective tissue growth factor (CTGF/CCN2) and cyclooxygenase-2 (COX-2) were found to overexpress in OSF. The aim of this study was to investigate the molecular mechanism underlying the TGFβ-induced CCN2 expressions in human buccal mucosal fibroblasts (BMFs) to identify the potential targets for drug intervention or chemoprevention of OSF. MATERIALS AND METHODS: TGFβ-induced CCN2 expression and its signaling pathways were assessed by Western blot analyses in BMFs. RESULTS: TGFβ1 stimulated CCN2 synthesis in BMFs. Pretreatment with c-Jun NH(2)-terminal kinase (JNK) inhibitor SP600125, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, and activin receptor-like kinase 5 (ALK5) inhibitor SB431542 significantly reduced TGFβ1-induced CCN2 synthesis. Epigallocatechin-3-gallate (EGCG) completely blocked TGFβ1-induced CCN2 synthesis by inhibiting the phosphorylation of JNK and p38 MAPK. Prostaglandin E(2) (PGE(2)) inhibited the TGFβ1-induced CCN2 synthesis in human fetal lung fibroblasts IMR90 but not in BMFs. CONCLUSIONS: The TGFβ1-induced CCN2 synthesis in BMFs could be mediated by the ALK5, JNK, and p38 MAPK pathways. EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in BMFs. CLINICAL RELEVANCE: The exceptional signal transduction pathways of TGFβ1-induced CCN2 production in BMFs contribute to the resistance of PGE(2) downregulation of CCN2 expression; therefore, the CTGF/CCN2 levels are maintained in the OSF tissues in the presence of COX-2. EGCG may serve as a useful agent in controlling OSF.
Clinical Oral Investigations 03/2012; · 2.36 Impact Factor
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ABSTRACT: Background: Connective tissue growth factor (CTGF/CCN2), associated with multiple human fibrotic diseases, is overexpressed in the tissue of gingival overgrowth. Although surgical excision is the current treatment modality for gingival overgrowth, the recurrent rate is high despite proper recall programs. Thrombin plays a key role in wound repair, remodeling, and fibrosis following injury, and exerts pro-fibrotic effects by activating protease-activated receptors (PARs). Curcumin is a natural plant phenolic compound that possesses both anti-inflammatory and anti-oxidant properties. This study investigates the signaling pathway of thrombin-induced CCN2 expression, and curcumin's inhibition of CCN2 expression. Methods: The signaling pathway of thrombin-induced CCN2 expression in human gingival fibroblasts (HGFs) was studied using Western blot analysis. The CCN2 mRNA level was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: Thrombin induced CCN2 expression in HGFs by activating PAR1. Pretreatment with antioxidant N-acetyl-L-cysteine (NAC), apoptosis signal-regulating kinase 1 (ASK1) inhibitor thioredoxin, and c-Jun NH2-terminal kinase (JNK) inhibitor SP600125 significantly reduced thrombin-induced CCN2 expression in HGFs. Curcumin dose-dependently inhibited thrombin-induced CCN2 expression through JNK suppression in HGFs. Conclusions: The results of this study suggest that thrombin-induced CCN2 expression may occur through PAR1, reactive oxygen species (ROS), ASK1, and JNK signaling in HGFs. Curcumin could effectively inhibit CCN2 expression through JNK suppression. These signaling events are important for wound healing and fibrosis. Further research, including animal studies, is required to confirm the inhibiting role of curcumin in the development of gingival overgrowth.
Journal of Periodontology 02/2012; · 2.60 Impact Factor
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ABSTRACT: We recently found that the expression of placenta growth factor (PlGF) in oral squamous cell carcinoma (OSCC) specimens is correlated with the progression and prognosis of OSCC. In this study, serum samples were obtained from 72 OSCC patients before and 3 months after surgical cancer excision and from 30 normal controls. Serum PlGF levels were determined by enzyme-linked immunosorbent assay (ELISA). The mean serum PlGF levels were significantly higher in pre-surgery OSCC patients than in normal controls (19.1±10.7 vs. 10.1±4.5, P<0.001). Serum PlGF levels dropped to near the normal control levels after surgical cancer removal. Higher pre-surgery serum PlGF levels were significantly associated with larger tumor size (P=0.015), positive lymph node metastasis (P=0.001), more advanced clinical stages (P=0.002), and loco-regional recurrence (P=0.037). The serum PlGF level was identified as an independent unfavorable prognosis factor by multivariate Cox regression analyses (P=0.014). Kaplan-Meier curve showed that OSCC patients with a higher serum PlGF level had a significantly poorer cumulative recurrence-free survival than those with a lower serum PlGF level (log-rank test, P=0.009). When we used the serum PlGF level of 19.1 pg/ml (mean normal control value plus 2 standard deviations) as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence was 80%, 56% and 78%, respectively. We conclude that the serum PlGF level may be a valuable biomarker for prediction of therapeutic effect, progression, recurrence and prognosis of OSCC.
Oral Oncology 01/2012; 48(5):424-8. · 2.86 Impact Factor
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ABSTRACT: Src protein overexpression correlates with progression and prognosis of a variety of human cancers.
This study used immunohistochemistry to examine the expression of Src protein in 93 specimens of oral squamous cell carcinoma (OSCC).
We found a significant association of high expression of Src protein (labeling indices >50%) with larger tumor size (p = .017), positive lymph node metastasis (p = .030), more advanced clinical stages (p = .007), and recurrence (p < .001) of OSCC. High expression of Src protein was identified as an independent unfavorable prognosis factor by multivariate Cox regression analysis. The Kaplan-Meier curve showed that patients with OSCC with high expression of Src protein had a significantly poorer cumulative survival than those with low expression of Src protein (log-rank test, p = .00267).
The expression of Src protein is significantly associated with the progression, recurrence, and prognosis of OSCCs in Taiwan.
Head & Neck 11/2011; 34(9):1340-5. · 2.40 Impact Factor
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ABSTRACT: Connective tissue growth factor (CTGF/CCN2) is associated with many human fibrotic disorders and was found to overexpress in oral submucous fibrosis (OSF). OSF is the result of persistent chemical irritation and microtrauma to oral mucosa from areca nut. Microtrauma could lead to the release of thrombin.
Thrombin-induced CCN2 expression and its signaling pathways were assessed by Western blot analyses in human buccal mucosal fibroblasts.
Thrombin stimulated CCN2 synthesis in buccal mucosal fibroblasts via activation of protease-activated receptor-1. Pretreatment with antioxidant N-acetyl-L-cysteine, apoptosis signal-regulating kinase 1 inhibitor thioredoxin, and c-Jun NH(2) -terminal kinase inhibitor SP600125 significantly reduced thrombin-induced CCN2 synthesis. Epigallocatechin-3-gallate completely inhibited thrombin-induced CCN2 synthesis.
Thrombin produced by microtrauma may contribute to the pathogenesis of OSF by up-regulating CCN2 expression. This effect could be mediated by protease-activated receptor-1, reactive oxygen species, apoptosis signal-regulating kinase 1, and c-Jun NH(2) -terminal kinase pathways and prevented by epigallocatechin-3-gallate.
Head & Neck 09/2011; 34(8):1089-94. · 2.40 Impact Factor
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ABSTRACT: T helper 17 (Th17) and regulatory T cells share plasticity in the expression of interleukin (IL)-17 and forkhead box P3 (FOXP3), but their mutual presence in human diseases is unclear.
IL-17 and FOXP3 were analyzed by immunohistostaining and flow cytometry. The cytokine milieu was analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
Oral squamous cell carcinoma expresses high levels of IL-1β, IL-6, and transforming growth factor (TGF)-β. A unique subset of FOXP3(+) IL-17-producing CD4(+) T cells was consistently identified in tumor-infiltrating lymphocytes from advanced stages of cancer, but not in the circulation, at a frequency of 0.5% to 5.5 % of total CD4(+) T and positively correlated with the frequency of IL-17(+)FOXP3(-) T cells. The IL-17(+)FOXP3(+) T cells express CCR6 and suppress the proliferation of autologous CD4(+) CD25(-) responder T-cells in vitro.
The prevalence of IL-17-producing FOXP3(+) CD4(+) tumor infiltrating lymphocytes is increased in oral squamous cell carcinoma.
Head & Neck 09/2011; 33(9):1301-8. · 2.40 Impact Factor
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ABSTRACT: Lovastatin exhibits higher thermal stability and lower degradation rate than simvastatin. However, the amount of research studying a lovastatin delivery device has been far less than similar research on simvastatin. As a consequence, a high lovastatin release rate system has not been developed. We hypothesized that highly efficient release of lovastatin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a short-term release (7 days) could provide an effective delivery system for bone repair. This study optimized the emulsion (o/w) technique in the fabrication process for PLGA nanoparticles, thereby producing the first recorded case of a high release rate (97%) of lovastatin. We also calculated the calibration curve of lovastatin using a UV spectrometer. The results demonstrated that the ALPase activity in human osteoblasts could be significantly stimulated by lovastatin carried in PLGA nanoparticles, but was prominently decreased by free lovastatin with the concentration higher than 4 µg/ml. Animal studies showed that the amount of lovastatin contained in 1 mg PLGA was the optimum dosage. These results suggest the new lovastatin-releasing PLGA delivery device exhibits potential for clinical treatment of bony defects.
Journal of Orthopaedic Research 04/2011; 29(10):1504-10. · 2.81 Impact Factor
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ABSTRACT: J Oral Pathol Med (2011) 40: 699–705Background: Insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3), an oncofetal RNA-binding protein, has been implicated in the enhancement of proliferation and invasion in various cancers. This study aimed to investigate the clinical significance and functional role of IGF2BP3 expression in oral squamous cell carcinoma (OSCC).Methods: IGF2BP3 expression in 93 OSCC patients was investigated using immunohistochemical staining and correlated with clinical parameters and patients’ survival. The effect of IGF2BP3 on cell invasion ability was evaluated by RNA interference in OSCC cell line.Results: High expression of IGF2BP3 in OSCC was significantly correlated with large tumor size and lymph node metastasis. Kaplan-Meier analysis revealed that oral cancer patients with high IGF2BP3 expression had a significantly lower 5-year survival (P = 0.0017). Multivariate analysis of clinical samples demonstrated IGF2BP3 to be an independent prognosis factor (P = 0.003). Moreover, the IGF2BP3 shRNA significantly suppressed the invasion ability of OSCC in vitro, and the knockdown of endogenous IGF2BP3 expression also inhibited tumor formation in vivo.Conclusions: IGF2BP3 enhances cell invasion ability and tumorigenicity in human OSCC in vitro and in vivo. IGF2BP3 is an independent prognostic factor in patients with OSCC. Targeting of IGF2BP3 could potentially suppress the tumor growth and metastasis to improve the outcome of patients with OSCC.
Journal of Oral Pathology and Medicine 02/2011; 40(9):699 - 705. · 1.63 Impact Factor
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ABSTRACT: Cyr61 is associated with growth and progression of many types of tumors and is an independent poor prognostic indicator for oral cancer patients. Areca nut (AN) chewing is the most important etiological factor in the pathogenesis of oral cancer in India and many Southeast Asian countries. Yet, the molecular mechanisms involved in the AN-induced oral cancer remain largely unknown. In this study, we show that arecoline, a main alkaloid found in AN, stimulated Cyr61 synthesis in human gingival epithelial S-G cells. Constitutive overexpression of Cyr61 protein in oral epithelial cells during AN chewing may play a role in the pathogenesis of oral cancer. ERK inhibitor PD98059, N-acetyl-L-cysteine, Rho-associated protein kinase (ROCK) selective inhibitor Y-27632 and a geranylgeranyltransferase inhibitor reduced the arecoline-stimulated levels of Cyr61 protein by ∼31%, 47%, 65% and 100%, respectively. Lovastatin also completely inhibited arecoline-induced Cyr61 synthesis and the inhibition is dose-dependent. Decreased of geranylgeranylated proteins could be the mechanism that lovastatin regulates Cyr61 synthesis and lovastatin could serve as a useful agent in controlling AN-induced oral cancer.
Oral Oncology 02/2011; 47(4):256-61. · 2.86 Impact Factor
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ABSTRACT: Mercury is a well-known neurotoxin but the susceptibility of autonomic nerves to mercury poisoning in vivo has seldom been studied. Our previous studies have shown that the hypoglossal nerve in hamsters contains somatic motor and postganglionic sympathetic fibers. The aim of this study was to investigate the ultrastructural changes in the nervous system following intraneural injection of mercuric chloride into the hypoglossal nerve in hamsters.
Six adult hamsters were used in this study. After anesthesia, the digastric muscle on the right side was removed and the trunk of the hypoglossal nerve was exposed. Two microliters of mercuric chloride aqueous solution was injected into the main trunk of the hypoglossal nerve at the bifurcation. The contralateral hypoglossal nerve was kept intact and used as the normal control. Animals were allowed to survive for 1 or 3 days and were prepared for ammonium sulfide histochemistry and electron microscopy.
Three days after injection of mercuric chloride solution, almost all unmyelinated sympathetic fibers in the hypoglossal nerve trunk were lost, whereas myelinated somatic axons were spared. Although mercury deposition in the myelin sheaths of neuronal processes was observed in the hypoglossal nucleus, the neuronal somas were intact. By contrast, degenerated neuronal processes and mercury deposition in neuronal somas were frequently found in the superior cervical ganglia.
This study demonstrated an undue susceptibility of sympathetic fibers to mercury intoxication. The mechanisms that underlie the selective reaction of sympathetic fibers to mercury warrant further investigation.
Journal of the Formosan Medical Association 02/2011; 110(2):93-9. · 1.13 Impact Factor
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ABSTRACT: Expression of vascular endothelial growth factor (VEGF) correlates with progression and prognosis of several human cancers. The main purposes of this study were to assess expression of VEGF in specimens of oral squamous cell carcinoma (OSCC) and to evaluate the possible influence of VEGF on the progression and prognosis of OSCC in Taiwan.
An immunohistochemical technique was used to examine the expression of VEGF in 100 specimens of OSCC, 66 specimens of oral epithelial dysplasia, and 36 specimens of normal oral mucosa.
We found that the mean labeling indices (Lis) of VEGF increased significantly from normal oral mucosa (13 ± 6%), through mild (22 ± 8%), moderate (24 ± 13%), and severe oral epithelial dysplasia (32 ± 14%), to OSCC samples (50 ± 18%, p < 0.001). The higher mean VEGF LI was significantly related to OSCC with positive lymph node metastasis (p = 0.022) and with more advanced clinical stages (p = 0.046). In addition, positive lymph node metastasis (p = 0.008) and VEGF LI > 40% (p = 0.046) were identified as independent unfavorable prognosis factors for OSCC patients by multivariate analysis with the Cox regression model. Moreover, the Kaplan-Meier curve showed that OSCC patients with a VEGF LI > 40% had a significantly poorer cumulative survival than those with a VEGF LI ≤ 40% (log-rank test, p = 0.016).
We conclude that VEGF may be a biomarker for prediction of the progression and prognosis of OSCC in Taiwan.
Journal of the Formosan Medical Association 01/2011; 110(1):50-7. · 1.13 Impact Factor
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ABSTRACT: 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is being used to treat oral pre-cancerous and cancerous lesions with some encouraging clinical outcomes. However, the exact mechanisms behind the photodynamic treatment are still not fully elucidated.
Flow cytometry, TdT-mediated dUTP nick end labeling assay and Western blot analysis were used to investigate the effects of 5-ALA-PDT on human oral cancer Ca9-22 cells.
We found that 5-ALA-PDT induces apoptosis in Ca9-22 cells. Western blotting showed that 5-ALA-PDT activates both the caspase-8 and caspase-9 pathways, which differed from previous studies conducted in other cell types. Activation of JNK was evident as early as 30 min. The caspases activation was inhibited by JNK inhibitor SP600125. Treatment with NF-κB inhibitor Bay 11-7082 (Bay) completely abrogated ALA-PDT-induced JNK activation. In addition, Bay and SP600125 almost completely abolished ALA-PDT-induced apoptosis.
These results demonstrate significant involvement of caspase-8 and -9 and their upstream NF-κB-JNK pathways in ALA-PDT-induced apoptosis. Future studies on how NF-κB and JNK activity regulate ALA-PDT response should provide a better strategy for the treatment of oral cancer.
Journal of Oral Pathology and Medicine 12/2010; 40(6):483-9. · 1.63 Impact Factor
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ABSTRACT: Cysteine-rich 61 (Cyr61 [CCN1]) has disparate functions in tumorigenesis that are dependent on the cell types. The aim of the study was to investigate its role in the growth of oral squamous cell carcinoma (SCC).
The study used immunohistochemistry to examine Cyr61 expression in 93 oral SCC specimens and assessed the effect of Cyr61 overexpression on proliferation and migration of oral SCC cells in vitro and xenograft growth in severe combined immunodeficient (SCID) mice.
High expression of Cyr61 significantly correlated with large tumor size (p = .009) and advanced tumor stage (p = .036). Multivariate analysis revealed that high Cyr61 (relative risk [RR] 2.44, 95% confidence interval [CI] 1.209-4.95, p = .010) significantly correlated with mortality. Forced expression of Cyr61 stimulated the motility and growth of Ca9-22 cells in vitro and enhanced xenograft growth in SCID mice.
Cyr61 is a positive growth modulator of oral SCC and Cyr61 overexpression is an independent prognostic indicator for patients with oral SCC.
Head & Neck 12/2010; 32(12):1665-73. · 2.40 Impact Factor
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PhD Sang-Heng Kok DDS,
Hao-Hueng Chang DDS, MS, PhD,
Ju-Yi Tsai MS,
DrPH Hsin-Chia Hung DDS,
Chiao-Ying Lin DDS, MS, PhD,
DMSc Chun-Pin Chiang DDS,
Cheing-Meei Liu DDS, PhD Mark Yen-Ping Kuo DDS
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ABSTRACT: Background.Cysteine-rich 61 (Cyr61 [CCN1]) has disparate functions in tumorigenesis that are dependent on the cell types. The aim of the study was to investigate its role in the growth of oral squamous cell carcinoma (SCC).Methods.The study used immunohistochemistry to examine Cyr61 expression in 93 oral SCC specimens and assessed the effect of Cyr61 overexpression on proliferation and migration of oral SCC cells in vitro and xenograft growth in severe combined immunodeficient (SCID) mice.Results.High expression of Cyr61 significantly correlated with large tumor size (p = .009) and advanced tumor stage (p = .036). Multivariate analysis revealed that high Cyr61 (relative risk [RR] 2.44, 95% confidence interval [CI] 1.209–4.95, p = .010) significantly correlated with mortality. Forced expression of Cyr61 stimulated the motility and growth of Ca9-22 cells in vitro and enhanced xenograft growth in SCID mice.Conclusions.Cyr61 is a positive growth modulator of oral SCC and Cyr61 overexpression is an independent prognostic indicator for patients with oral SCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Head & Neck 11/2010; 32(12):1665 - 1673. · 2.40 Impact Factor
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ABSTRACT: Expression of placenta growth factor (PlGF) is found to correlate with the progression and prognosis of several human cancers.
This study used an immunohistochemical technique to examine the expression of PlGF in 100 specimens of oral squamous cell carcinoma (OSCC).
We found that the higher mean PlGF labeling index was significantly associated with OSCCs with positive lymph node metastasis (p = .014) or with more advanced clinical stages (p = .016). Positive lymph node metastasis (p = .008) and PlGF labeling index >40% (p = .010) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, a Kaplan-Meier curve showed that OSCC patients with a PlGF labeling index >40% had a significantly poorer cumulative survival than those with a PlGF labeling index ≤40% (log-rank test, p = .003).
The PlGF labeling index can predict the progression and prognosis of OSCCs in Taiwan.
Head & Neck 10/2010; 32(10):1363-9. · 2.40 Impact Factor
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ABSTRACT: Suberoylanilide hydroxamic acid has been shown to selectively induce tumor apoptosis in cell cultures and animal models in several types of cancers and is about as a promising new class of chemotherapeutic agents. In addition, suberoylanilide hydroxamic acid showed synergistic anticancer activity with radiation, cisplatin, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in some cancers. Here, we report suberoylanilide hydroxamic acid also induced apoptosis in human oral cancer cells. Western blotting showed suberoylanilide hydroxamic acid increased Fas, Fas ligand, DR4, and DR5 protein expression and activated caspase-8 and caspase-9. The apoptosis was almost completely inhibited by caspase-8 inhibitor Z-IETD-FMK and attenuated by caspase-9 inhibitor Z-LEHD-FMK. Human recombinant DR5/Fc chimera protein but not Fas/Fc or DR4/Fc significantly inhibited apoptosis induced by suberoylanilide hydroxamic acid. These results suggest that suberoylanilide hydroxamic acid induces apoptosis mainly through activation of DR5/TRAIL death pathway. Furthermore, subtoxic concentrations of suberoylanilide hydroxamic acid sensitize two TRAIL resistant human oral cancer cells, SAS and Ca9-22, to exogenous recombinant TRAIL-induced apoptosis in a p53-independent manner. Combined treatment of suberoylanilide hydroxamic acid and TRAIL may be used as a new promising therapy for oral cancer.
Molecular Cancer Therapeutics 10/2009; 8(9):2718-25. · 5.23 Impact Factor
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ABSTRACT: Esculetin has been shown to selectively induce tumor apoptosis in several types of cancers and is regarded as a promising chemotherapeutic agent. In this study, we showed that esculetin significantly suppressed the growth of oral cancer SAS cells in a dose-dependent manner. DNA content flow cytometry and TUNEL assay revealed that esculetin induced cell cycle arrest and apoptosis. Western blotting showed esculetin increased DR5 protein expression and activated caspase-8, which differed from previous studies conducted in other cell types. Furthermore, treatment with esculetin significantly increased TRAIL-induced apoptosis in SAS cells and the TRAIL-sensitizing effect was blocked by DR5/Fc chimera protein. Our results indicate that esculetin enhances TRAIL-induced apoptosis primarily through upregulation of DR5. Combination of esculetin and TRAIL may be a novel treatment strategy for oral cancers.
Oral Oncology 09/2009; 45(12):1067-72. · 2.86 Impact Factor
