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Biomedical subjects

Chun-Pin Chiang

Publications and source records attributed to Chun-Pin Chiang.

At least 19 recordsLinked to original sources

Establishment and characterization of a tumorigenic cell line from areca quid and tobacco smoke-associated buccal carcinoma.

A cell line, TW2.6, has been established from the surgically resected specimen of an untreated primary squamous cell carcinoma of the buccal mucosa from a 48-year-old man who was an areca quid chewer and tobacco smoker. TW2.6 cells exhibited morphological features of keratinocytes and replicated rapidly in culture with a doubling time of 24h. The karyotype showed human chromosomes with high hyperdiploidy and complex rearrangements. Western blotting showed pronounced expression of p53 and moderate expression of p21(CIP1). The baseline expressions of p27(KIP1) and p16(INK4a) were barely detectable. Low levels of Bax and Fas were found in TW2.6 cells but Bcl-2 expression was more readily observed. Mutational analysis of p53 gene revealed an A-->G transition at the second base of codon 220, resulting in amino acid substitution from tyrosine to cysteine in the protein. Functional analysis showed that TW2.6 was unable to activate the p53-specific PUMA promoter. Lipofectamine 2000 and calcium phosphate precipitation technique offer good transfection efficiencies for TW2.6 cells and may be used in future transfection experiments. A xenograft-SCID mouse tumor model was established for TW2.6. Histological examination demonstrated that the engrafted tumors maintained the morphological features of a squamous cell carcinoma. It is thought that the establishment of tumorigenic TW2.6 cell line provides a valuable model for AQ and tobacco smoke-associated buccal carcinoma.

Areca↗

Expression of human telomerase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan.

This study used an immunohistochemical technique to examine the expression of human telomerase reverse transcriptase (hTERT) protein in 82 specimens of OSCC, 116 specimens of oral epithelial dysplasia (OED), and 21 specimens of normal oral mucosa (NOM). The cytoplasmic and nuclear hTERT staining intensity (SI; 0, no staining; 1, weak; 2, moderate; 3, strong), labeling indices (LIs, defined as the percentage of positive cells in total cells), and labeling scores (LSs, defined as LI x SI) in OSCC, OED, and NOM samples were calculated and compared among groups. The correlation between the cytoplasmic or nuclear hTERT LS in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. The mean cytoplasmic hTERT LSs increased significantly from NOM (87+/-17%) through OED (95+/-18%) to OSCC samples (114+/-33%, p=0.000). The mean nuclear hTERT LSs also increased from NOM (80+/-14%) to OED (91+/-20%) and then decreased to OSCC samples (86+/-35%) with no statistically significant difference among the 3 groups. A significant correlation was found between the higher mean cytoplasmic hTERT LSs and OSCCs occurring in male patients (p=0.023), with larger tumor sizes (T3 and T4, p=0.048), with more advanced clinical stages (stages 3 and 4, p=0.033), or from patients with areca quid chewing (p= 0.029), cigarette smoking (p=0.027), or alcohol drinking habit (p=0.025). In addition, OSCC patients with nuclear hTERT LSs greater than 100% were prone to have a higher recurrence rate (p=0.044) and a lower 5-year survival rate (p=0.011). Our results indicate that the increased expression of hTERT protein is an early event in oral carcinogenesis and hTERT may be a biomarker for OSCCs. Measuring the amount of cytoplasmic or nuclear expression of hTERT in OSCC samples may predict the oral cancer progression, recurrence, and prognosis in Taiwan.

Adult↗

Carcinoma and dysplasia in oral leukoplakias in Taiwan: prevalence and risk factors.

OBJECTIVES: The issue of existence of malignancy within oral leukoplakia has seldom been addressed in Taiwan. The aims of this study were to investigate the prevalence of carcinoma and dysplasia within oral leukoplakia at the time of clinical diagnosis and to identify the associated risk factors in Taiwan. STUDY DESIGN: The prevalence rate of malignancy and dysplasia in 1046 oral leukoplakias at a university hospital was calculated. Univariate and multivariate analyses by the Mantel-Haenszel method and multiple logistic regression model were performed to examine risk factors associated with the presence of carcinoma and dysplasia within the lesions. RESULTS: The prevalence rate of carcinoma was 12.9%. The relative risks for the presence of malignancy in leukoplakias on the tongue/floor of mouth and with nonhomogeneous appearance were 2.72- and 28.13-fold by multivariate logistic regression analysis, when compared with those on buccal mucosa and lesions having homogeneous surface (both P < .05). In contrast, patients who both smoked and chewed betel quid had a significantly lower risk for carcinoma than the abstainers (P < .05). A synergistic effect between the 2 major risk factors of clinical appearance and lesion site was evident. Nonhomogeneous leukoplakia on tongue/floor of mouth had a 43.10-fold higher risk compared to homogeneous lesions located on buccal mucosa or other sites (P < .05). However, homogeneous leukoplakia in buccal mucosa or other sites of the oral cavity still had the possibility of having carcinoma within the lesion. The prevalence of dysplasia was 45.6% among the noncancerous leukoplakias with risk factors similar to those for carcinoma. CONCLUSIONS: Our results demonstrate that some leukoplakias contain a malignant component. Lesions with certain features are more prone to carcinoma, but no clinical attributes can bring certitude. Therefore, all oral leukoplakias should be submitted to microscopic analysis before any definite treatment or long-term follow-up.

Adult↗

Levamisole can modulate the serum tumor necrosis factor-alpha level in patients with recurrent aphthous ulcerations.

BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor necrosis factor (TNF)-alpha is an important inflammatory mediator and a critical cytokine for adequate host defense. Our previous studies have shown that 14-43% and 59-63% of patients in the ulcerative stage of major, minor or herpetiform RAU have significantly higher than normal serum levels of interleukin (IL)-6 and IL-8, respectively. In this study, we examined whether RAU patients in the ulcerative stage had a significantly higher than normal serum level of TNF-alpha and assessed whether treatment with levamisole can modulate serum TNF-alpha levels in RAU patients. METHODS: This study used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of TNF-alpha in 146 patients with RAU, nine patients with traumatic ulcers (TU), and 54 normal control subjects. Fifty-five RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml were treated with levamisole for 0.5-4 months and their serum TNF-alpha levels were measured after treatment. RESULTS: We found that 29% (42 of 146) RAU patients as well as 39% (24 of 61) major type, 20% (14 of 69) minor type, and 25% (four of 16) herpetiform type RAU patients had a serum level of TNF-alpha greater than the upper normal limit of 7.4 pg/ml. The mean serum level of TNF-alpha in patients with RAU (9.1 +/- 1.0 pg/ml, P < 0.001), major type RAU (11.6 +/- 1.9 pg/ml, P < 0.001), minor type RAU (6.9 +/- 0.9 pg/ml, P < 0.005), or herpetiform type RAU (9.6 +/- 2.7 pg/ml, P < 0.001) was higher than that (3.8 +/- 0.2 pg/ml) in normal control subjects. The mean serum TNF-alpha level was significantly higher in patients with major type RAU than in patients with minor type RAU (P < 0.05) and was significantly higher in major type RAU patients in the exacerbation stage than in the post-exacerbation stage (P < 0.05). In 55 RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml, treatment with levamisole for a period of 0.5-4 months could significantly reduce the serum TNF-alpha level from 16.4 +/- 1.9 to 5.8 +/- 0.6 pg/ml (P < 0.001). CONCLUSIONS: We conclude that a significantly higher than normal serum level of TNF-alpha can be detected in 20-39% of patients in the ulcerative stage of major, minor or herpetiform RAU. The serum TNF-alpha level may be associated with the severity and the stage of RAU. Levamisole can modulate serum TNF-alpha levels in RAU patients.

Adjuvants, Immunologic↗

Extensive maxillary sequestration resulting from mucormycosis.

Mucormycosis is an invasive and potentially lethal infection caused primarily by fungi of the order mucorales. An ulcer or extraction in the mouth can be the port of fungal invasion, particularly when the patient is immunocompromised. Early recognition and aggressive treatment have reduced the mortality and morbidity. We present a case of oral mucormycosis with extensive maxillary osteonecrosis that is of interest because the patient ignored the initial warning signs and was rescued from the fulminating stage by thorough debridement and medical treatment.

Follow-Up Studies↗

Univariate and multivariate analysis of prognostic significance of betel quid chewing in squamous cell carcinoma of buccal mucosa in Taiwan.

BACKGROUND AND OBJECTIVES: While betel quid (BQ) chewing is clearly the most avoidable risk factor of squamous cell carcinoma of buccal mucosa (BMSCC), little is known about the influence of this habit on the prognosis of BMSCC. METHODS: We surveyed 280 patients with BMSCC who were treated during an 8-year period in a cohort study to assess the independent predictive value of pretreatment BQ chewing habit on the prognosis by univariate and multivariate analysis. RESULTS: We found by univariate analysis that sex, age, clinical stage, smoking, and BQ chewing significantly affected the patients' prognosis and only age, clinical stage, and BQ chewing had significant influence on prognosis by multivariate analysis (P < 0.05). Further analysis revealed that the prognostic effect of BQ chewing changed in a dose- and time-dependent manner. The risk of death was 31.4-fold higher in heavy user (duration >30 years, daily consumption >30 quids, age of start <20 years old) when compared to those who chewed BQ to a milder degree (duration <10 years, daily consumption <15 quids, age of start > or =20 years old ) (P < 0.001). CONCLUSIONS: Pretreatment BQ chewing habit worsens the prognosis of BMSCC in Taiwan. BQ chewing is a prognostic indicator that can be used in conjunction with clinical staging to help plan the treatment for the patients.

Adult↗

Norcantharidin-induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio.

Norcantharidin (NCTD), the demethylated analogue of cantharidin, has been used to treat human cancers in China since 1984. It was recently found to be capable of inducing apoptosis in human colon carcinoma, hepatoma and glioblastoma cells by way of an elusive mechanism. In this study, we demonstrated that NCTD also induces apoptosis in human oral cancer cell lines SAS (p53 wild-type phenotype) and Ca9-22 (p53 mutant) as evidenced by nuclear condensation, TUNEL labeling, DNA fragmentation and cleavage of PARP. Apoptosis induced by NCTD was both dose- and time-dependent. We found NCTD did not induce Fas and FasL, implying that it activated other apoptosis pathways. Our data showed that NCTD caused accumulation of cytosolic cytochrome c and activation of caspase-9, suggesting that apoptosis occurred via the mitochondria mediated pathway. NCTD enhanced the expression of Bax in SAS cells consistent with their p53 status. Moreover, we showed that NCTD downregulated the expression of Bcl-2 in Ca9-22 and Bcl-XL in SAS. Our results suggest that NCTD-induced apoptosis in oral cancer cells may be mediated by an increase in the ratios of proapoptotic to antiapoptotic proteins. Since oral cancer cells with mutant p53 or elevated Bcl-XL levels showed resistance to multiple chemotherapeutic agents, NCTD may overcome the chemoresistance of these cells and provide potential new avenues for treatment.

Apoptosis↗

Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues.

BACKGROUND AND OBJECTIVES: Time-resolved autofluorescence spectroscopy has been used for effectively distinguishing normal tissues from precancers and cancers in various organs. The aim of this study was to find out the possibility of using time-resolved autofluorescence spectroscopy to differentiate normal oral mucosa (NOM) from oral premalignant lesions including verrucous hyperplasia (VH), epithelial hyperplasia (EH), and epithelial dysplasia (ED). STUDY DESIGN/MATERIALS AND METHODS: Time-resolved autofluorescence spectra at 633 nm under 410-nm excitation were recorded for 15 VH, 9 EH, 14 ED, and 38 NOM samples. The two-component lifetimes of the obtained curves were calculated, and a Fisher's discriminant analysis (FDA) was employed for distinguishing these tissue samples. RESULTS: After two-component lifetimes for all samples being calculated, a two-dimensional scatter plot was developed, in which 76 oral tissue samples were separated into three groups by FDA. With a leave-one-out method, the FDA algorithm gave an accuracy rate of 93% for ED, of 75% for VH and EH, and of 100% for NOM samples. In addition, all oral premalignant lesions (including VH, EH, and ED) could be distinguished from NOM samples by this FDA algorithm. CONCLUSIONS: We conclude that time-resolved autofluorescence spectroscopy at 633 nm under 410-nm excitation, based on two-component lifetime calculation and FDA, is a very sensitive technique for in vivo diagnosis of oral premalignant lesions. .

Adult↗

Successful treatment of oral verrucous hyperplasia and oral leukoplakia with topical 5-aminolevulinic acid-mediated photodynamic therapy.

BACKGROUND AND OBJECTIVES: Our recent studies showed that a new topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) protocol using a light-emitting diode (LED) light source is an effective and successful treatment modality for five cases of oral verrucous hyperplasia (OVH) and one case of verrucous carcinoma. In this study, we treated eight OVH lesions with the same topical ALA-PDT protocol to further confirm the efficacy of this protocol on OVH lesions. In addition, our recent study demonstrated an unsatisfactory clinical outcome for 24 oral leukoplakia (OL) lesions treated once a week by the same topical ALA-PDT protocol. Therefore, in this study 24 OL lesions were treated twice a week by the same protocol to compare whether the twice-a-week treatment modality could result in a better clinical outcome than the once-a-week treatment modality. STUDY DESIGN/MATERIALS AND METHODS: In this study, 8 OVH and 24 OL lesions were treated by the same topical ALA-PDT once a week and twice a week, respectively. RESULTS: All the former eight OVH lesions treated once a week showed complete response (CR) after 2-5 (mean, 3.8) treatments of ALA-PDT. The latter 24 OL lesions treated twice a week demonstrated CR in 8, partial response (PR) in 16, and no response in none. The present 24 OL lesions treated twice a week had a significantly better clinical outcome than the previous 24 OL lesions treated once a week (P = 0.000, chi-square test). CONCLUSIONS: We conclude that complete regression of OVH lesions can be achieved by less than six treatments of topical ALA-PDT once a week. Although the response of OL lesions to the topical ALA-PDT is not as good as the response of OVH lesions to the same therapy, all OL lesions can have at least PR after eight treatments with the topical ALA-PDT twice a week. In addition, OL lesions treated twice a week have a significantly better clinical outcome than OL lesions treated once a week.

Administration, Topical↗

Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan.

Survivin, a recently characterized novel member of the inhibitor of apoptosis (IAP) family, is not detectable in most differentiated normal adult tissues but is expressed in a wide range of cancer tissues. Its expression in cancer has been correlated with poor prognosis, cancer progression and drug resistance. We immunohistochemically examined the expression of survivin in 62 cases of oral epithelial dysplasia (ED) and 96 cases of oral squamous cell carcinoma (SCC). Cytoplasmic survivin staining was detected in 60 of the 62 (97%) ED specimens and 94 of the 96 (98%) SCC specimens but not in adjacent normal oral mucosal tissues. The labeling index (LI) for survivin protein significantly increased from ED (32.3+/-16.3%) to SCC samples (49.4+/-28.5%) (p<0.001). In addition, the mean LI for ED cases with further malignant transformation into SCC (45.6+/-8.8%) was higher than those without malignant transformation (30.1+/-16.3%) (p=0.008). No significant correlation was found between the survivin expression and the patients' age, sex, oral habit, cancer location, or STNM status in SCC cases. Kaplan-Meier curves showed oral SCC patients with high survivin expression (LI>25%), advanced stage, larger tumor size, or positive lymph node metastasis had significantly shorter overall survival (p=0.014, 0.012, 0.005 and 0.011, respectively by log-rank test) than others. The associations remained significant after adjusting for age. These results indicate that survivin protein expression may be an important early event in oral carcinogenesis and predicts unfavorable prognosis for oral SCC. Furthermore, the unique expression of survivin in cancer cells but not in most normal adult tissues suggests that modulation of survivin protein expression may provide a novel strategy for the therapy of oral SCC.

Adult↗

Higher expressions of p53 and proliferating cell nuclear antigen (PCNA) in atrophic oral lichen planus and patients with areca quid chewing.

OBJECTIVE: The aim of the study was to examine the expressions of p53 and proliferating cell nuclear antigen (PCNA) in oral lichen planus (OLP) in relation to its clinical behavior and the patients' oral habits. STUDY DESIGN: Immunohistochemical study was carried out to investigate the expressions of p53 and PCNA in 56 OLP specimens. The results were correlated with the clinical behavior of the disease and the patients' oral habits. The expression rates were further compared with those of normal oral mucosa (NOM), epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinoma (SCC). RESULTS: The staining rate of p53 (28.6%) and PCNA labeling index (LI) (27.6 +/- 8.8%) in OLP were similar to those in EH ( P = .868, .074, respectively), but higher than those of NOM and lower than those of ED and SCC (all P < .05). In OLP, no significant correlations were found between p53 or PCNA expression and the patients' age, gender, lesion duration, location, size, number of site, presence of pain, presence of local irritant, and the habits of alcohol drinking and cigarette smoking (all P > .05). In addition, the mean PCNA LI of p53+ cases was close to that of p53- cases (P = .38). However, the staining rate of p53 in OLP was higher in areca quid (AQ) chewers compared to abstainers (P = .001), and the mean PCNA LI in atrophic cases was higher than that in hypertrophic cases (P = .029). Interestingly, the staining rate of p53 and mean PCNA LI were significantly increased in AQ chewers with atrophic OLP (100%, 36.7% +/- 9.0%, respectively), which were similar to those in ED and SCC (all P > .05). CONCLUSIONS: Although this study could not confirm the precancerous nature of OLP by the relatively low p53 and PCNA expression, the results do suggest that atrophic form OLP and patients with AQ chewing habit may have a higher disease activity in view of higher expression rates of p53 and PCNA in the lesions.

Adolescent↗

The chinese herbal medicine Tien-Hsien liquid inhibits cell growth and induces apoptosis in a wide variety of human cancer cells.

OBJECTIVE: Tien-Hsien liquid (THL) is a commercially available Chinese herbal mixture that has been used as an anticancer dietary supplement for more than 10 years. We recently showed that THL has strong immunomodulatory effects on peripheral blood mononuclear cells (PBMC) and T cells. To investigate the antitumor activity of THL further, we sought to test whether THL could induce apoptosis in various human cancer cell lines based on the fact that THL contains several components with tumor killing functions. DESIGN: The growth inhibitory effect of THL on human cervical carcinoma C-33A cells, human lung carcinoma H1299 cells, and human PBMC was assessed by counting viable cells using the trypan blue dye exclusion method. The apoptosis-inducing activity of THL in H1299 cells was assessed by analyzing the cells with four assays: (1) Hoechst 33258 nuclear DNA staining; (2) the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay; (3) the nucleosomal DNA fragment ladder assay; and (4) the sub-G1 cell analysis. The activities of caspase-8, -9, and -3 in H1299 cells treated with or without THL were also measured to elucidate the possible mechanism underlying THL apoptosis-inducing effect. Finally, the apoptotic effect of THL on fifteen human cancer cell lines and normal human cells were analyzed by the TUNEL assay. RESULTS: THL could induce apoptosis in all human cancer cell lines tested but not in normal human cells. THL treatment of H1299 cancer cells resulted in activation of caspase-8, -9, and -3 and the inhibitors of these caspases could partially block THL-induced apoptosis. CONCLUSIONS: THL has been used by numerous patients with cancer for many years with no known adverse effect. Our present study showing that THL had a broad-range tumor killing function has provided a molecular basis underlying THL therapeutic activity. Furthermore, because THL had apoptotic effects only on cancer cells but not on normal cells, this selectivity suggests that THL could be a potential cancer therapeutic agent.

Antineoplastic Agents↗

Successful treatment of an extensive verrucous carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy.

Our recent study found that a new topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) protocol composed of multiple 3-min fractionated irradiations with a light emitting diode (LED) red light at 635 +/- 5 nm for a total of 1000 s (fluence rate: 100 mW/cm(2); light exposure dose: 100 J/cm(2)) after topical application of 20% ALA for 1.5 or 2 h can be used successfully for the treatment of oral verrucous hyperplasia. In this case report, we tested the efficacy of this new treatment protocol of ALA-PDT for an extraoral verrucous carcinoma (VC) lesion at the right mouth angle and an intraoral VC lesion at the right buccal mucosa of a 56-year-old male areca quid chewer and smoker. The extraoral tumor was cleared after six treatments of topical ALA-PDT and the intraoral tumor showed complete regression after 22 treatments of topical ALA-PDT. No recurrence of the VC lesion was found after a follow-up period of 6 months. We suggest that PDT using a topical application of 20% ALA followed by multiple 3-min fractionated irradiations with an LED red light is also an effective and successful treatment modality for VC.

Administration, Topical↗

HMB-45 may be a more sensitive maker than S-100 or Melan-A for immunohistochemical diagnosis of primary oral and nasal mucosal melanomas.

BACKGROUND: Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three. METHODS: This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers. RESULTS: Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 +/- 43%) was significantly lower than that of HMB-45 (83 +/- 28%, P = 0.0065) or of S-100 (79 +/- 33%, P = 0.0237). CONCLUSIONS: Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.

Adult↗

"Tien-Hsien liquid" can modulate antigen-stimulated cytokine production by T-cells isolated from patients with recurrent aphthous ulcerations.

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. Our previous study found that THL can modulate the antigen-stimulated proliferative response of peripheral blood mononuclear cells and T-cells isolated from RAU patients. In this study, we further tested whether THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. To achieve this goal, T-cells isolated from 19 RAU patients were incubated with phytohemagglutinin (PHA), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. The levels of interleukin (IL)-2, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-6, or IL-10 in the supernatants of T-cell cultures were measured by cytokine enzyme-linked immunosorbent assay (ELISA) kits. We found that THL significantly increased the PHA- or TT-stimulated TNF-alpha, IL-6, and IL-10 production by T-cells isolated from RAU patients. However, THL could also significantly decrease the TT-stimulated IL-2 production, the GtfD-stimulated IL-2, TNF-alpha, IL-6 and IL-10 production, and the S. mutans-stimulated IFN-gamma, TNF-alpha, and IL-10 production by T-cells isolated from RAU patients. These results indicate that THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. Because RAU is probably a Thl-mediated disease with elevated levels of IL-2, IFN-gamma, TNF-alpha and IL-6 in either the patient's sera or oral lesions and these increased levels of cytokines can be reduced by THL, we suggest that THL may be a potential immunoceutical agent for treatment of RAU.

Adult↗

Community-based multiple screening model: design, implementation, and analysis of 42,387 participants.

BACKGROUND: Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow-up. METHODS: An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS: A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38-1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS: The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease.

Adult↗

Photodynamic Therapy of oral dysplasia with topical 5-aminolevulinic acid and light-emitting diode array.

BACKGROUND AND OBJECTIVES: In Taiwan, more than two million people have the betel quid (BQ) chewing habit which is a risk factor related to premalignant lesion and squamous cell carcinoma of oral cavity. We developed a light-emitting diode (LED) array combined with topical 5-aminolevulinic acid (ALA) for photodynamic therapy (PDT) and evaluated its effectiveness for the treatment of oral lesions. STUDY DESIGN/MATERIALS AND METHODS: We compared the ALA-PDT effect of the homemade LED array to that of a commercial light source on cultured Ca9-22 human gingival carcinoma cells and the DMBA-induced hamster buccal pouch carcinoma model. Furthermore, we treated several patients having an oral lesion using a topical ALA delivery system and the LED array. RESULTS: The LED array light source was as effective as the commercial light source for ALA-PDT in cultured Ca9-22 cells with LD(50) of 4.5 and 4.3 J/cm(2), respectively, using an MTT assay. This light source was also effective in the DMBA-induced hamster buccal pouch carcinoma model, and in the patients of oral leukoplakia. CONCLUSIONS: ALA-PDT is effective for premalignant lesions such as mucosal dysplasia and carcinoma in situ of oral cavity. Good results could be obtained by using the homemade LED array as light source. The LED array has the advantages of low cost, high reliability, and portability. It is safe, convenient and easy to use for the treatment of oral dysplasia.

Administration, Topical↗

Successful treatment of oral verrucous hyperplasia with topical 5-aminolevulinic acid-mediated photodynamic therapy.

Previous studies have shown a selective accumulation of 5-aminolevulinic acid (ALA)-derived protoporphrin IX (PpIX) in oral premalignant and malignant tissues. This provides a biologic rationale for the clinical use of ALA-mediated PDT (ALA-PDT) for oral premalignant and malignant lesions. In this study, five patients with oral verrucous hyperplasia (OVH) were treated with a new protocol of ALA-PDT composed of multiple 3-min irradiations with a light emitting diode (LED) red light at 635+/-5 nm separated with several 3-min rests for a total of 1000 s (fluence rate, 100 mW/cm(2); light exposure dose, 100 J/cm(2)) after topical application of 20% ALA for 1.5 or 2 h. Topical ALA-PDT was repeated once a week until the complete regression of the lesion. Complete regression of all OVH lesions was observed after 1-3 treatments (average, 2 treatments) of topical ALA-PDT. At an average follow-up of 5.6 months (range, 3-11 months), all the five OVH patients were free of tumor recurrence. We conclude that topical ALA-PDT with fractionated irradiations by an LED red light at 635+/-5 nm is an effective and successful treatment modality for OVH.

Adult↗