Expression of FAP in Oral Leukoplakia and Oral Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments. RESULTS: Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001). CONCLUSIONS: Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.

Nano-drug delivery system targeting FAP for the combined treatment of oral leukoplakia.

Oral leukoplakia (OLK) has received much attention due to its potential risk of malignant transformation. Studies have shown that when drug therapy is combined with photothermal therapy (PTT), not only can the cytotoxicity of the drug be enhanced, but also the heat energy can be used to kill the lesion cells, so we can combine drug therapy with PTT to enhance the therapeutic effect on OLK. However, with certain drawbacks due to its lack of targeting, fibroblast activating protein (FAP) has become an attractive target for OLK combination therapy. In this study, we used NGO-PEG loaded with FAP-targeting peptide (F-TP) and celecoxib (CXB) to construct a nano-drug delivery system CGPF for targeting OLK with high FAP expression and confirmed the biocompatibility and therapeutic efficacy of CGPF by in vitro and in vivo experiments. Overall, the novel nano-drug delivery system CGPF proposed in this study showed a very significant potential for the combination therapy of OLK.

pH-responsive graphene oxide loaded with targeted peptide and anticancer drug for OSCC therapy.

Oral squamous cell carcinoma (OSCC) is the most common type of cancer occurring in the oral and maxillofacial regions. Despite of the advances in the diagnosis and treatment, the overall 5-year survival rate has remained about 40%-50% in the past decades. Various nanotechnology-based carrier systems have been investigated for their potentials in the OSCC treatment. However, because of the lack of active targeting of tumors, their application is limited. Studies have shown that gastrin-releasing peptide receptors (GRPRs) are overexpressed on many human cancers, including head and neck squamous cell carcinoma. Herein, we aimed to develop a GRPR-targeted nano-graphene oxide (NGO) nanoprobe drug delivery system for OSCC therapy. DOX@NGO-BBN-AF750 was synthesized by the non-covalent bonding method to couple carboxylated NGO with BBN-AF750 (bombesin antagonist peptides conjugated to Alexa Fluor 750) and DOX (doxorubicin) through π-π and hydrogen bonding. Internalization and antitumor activities were carried out in human HSC-3 cancer cells. The tumor pH microenvironment was simulated to study the release of antitumor drug DOX from the DOX@NGO-ant BBN-AF750 complex under different pH conditions. DOX@NGO-BBN-AF750 showed internalization into HSC-3 cells. The IC50 (50% inhibitory concentration) was 5 µg/ml for DOX@NGO-BBN-AF750 in HSC-3 cells. Furthermore, DOX@NGO-BBN-AF750 showed a pH-sensitive drug release rate, and a dose-dependent and pH-responsive cytotoxicity in HSC-3 cells. DOX@NGO-BBN-AF750 presents the characteristics ensuring a slow release of DOX from the nanoprobe, thereby protecting the drug from degradation and prolonging the half-life of the drug. This report provides a versatile strategy to achieving targeted and imaging-guided therapy of OSCC.

Determination of the longitudinal validity and minimally important difference of the 8-item Parkinson's Disease Questionnaire (PDQ-8).

The aim of our study was to assess the longitudinal validity of the 8-item Parkinson's Disease Questionnaire (PDQ-8) in terms of responsiveness and test-retest reliability and to determine the minimally important difference (MID) for PDQ-8 using the anchor-based approach in Asians with Parkinson's disease (PD). A consecutive sample of PD patients attending a tertiary neuroscience clinic in Singapore completed the English or Chinese version of PDQ-8 twice during two different clinic visits. During the second visit, patients were also asked to rate their changes in health in general, PD severity, and overall impact of PD since at the time of their first visit 1 year ago using a 5-point response scale. A total of 96 patients participated in the study. For patients who reported changed conditions in the second visit, responsiveness measured by Cohen's effect size, standardized response mean, and Guyatt's responsiveness index ranged from 0.21 to 0.68. The intraclass correlation coefficient values calculated using patients reporting no change in health or PD status ranged from 0.64 to 0.76. The mean changed PDQ-8 summary index score in patients who reported that their health or PD status worsened only "a little bit" ranged from 5.8 to 7.4 points. Our current results show that PDQ-8 is a longitudinally reliable and responsive measure for assessing the health-related quality of life in patients with PD. The MID of the PDQ-8 estimated in the study will further support the use of this instrument in both clinical research and practice.