FKBP11 promotes cell proliferation and tumorigenesis via p53-related pathways in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the causes of cancer-related death worldwide. The abnormal proliferation ability of OSCC has become one of the major reasons for its poor prognosis. FK-506 binding protein 11 (FKBP11) is abnormally expressed in malignant tumors and affects many biological processes. The purpose of this study is to investigate the effect of FKBP11 on cell proliferation in OSCC and explore the possible regulatory mechanism. The expression of FKBP11 was detected by western blotting (WB) and/or real-time PCR in OSCC and paracancerous normal tissues in tongue squamous cell carcinoma (TSCC) cell lines, revealing high expression in OSCC and CAL-27 cells. Furthermore, FKBP11 knockdown inhibited the proliferation of CAL-27 cells by CCK-8 and colony formation assays. G2/M arrest and induction of apoptosis were observed using flow cytometry, Hoechst 33258 and Calcein-AM/PI staining, accompanied by changes in some cell cycle- and apoptosis-related proteins, including CDK1, Cyclin B1, p21, p27, p53, Bax, Bcl-2 and Caspase-3. Additionally, the expression of these proteins can be reversed by the use of pifithrin-α (PFT-α), a p53 inhibitor. An in vivo xenograft model further confirmed that FKBP11 enhanced OSCC progression. In conclusion, FKBP11 could promote cell proliferation by regulating G2/M phase and apoptosis via the p53/p21/p27 and p53/Bcl-2/Bax pathways, respectively, which suggests that it may be a new candidate target for the treatment of OSCC.

Validation of the "obturator functioning scale" for Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy.

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

EFFECT OF YISHENJIANPI RECIPE ON SEMEN QUALITY AND SPERM MITOCHONDRIA IN MICE WITH OLIGOASTHENOZOOSPERMIA INDUCED BY TRIPTERYGIUM GLYCOSIDES.

BACKGROUND: Kidney tonifying - spleen strengthening method being one of the modalities for treatment of astheno-oligozoospermia is currently commonly used in the clinical setting. To investigate the mechanism of YiShenJianPi (YSJP) Recipe, used in Traditional Chinese Medicine to benefit "the kidney" and strengthen "the spleen". MATERIALS AND METHODS: Oligoasthenozoospermia, male BALB/c mice were randomly divided into normal control, disease model, positive control, low-dosage and high-dosage groups. Oligoasthenozoospermia was induced by tripterygium glucosides intragastric administration before treatment started. Through using computer-aided sperm analysis to test the changes in sperm quality, utilizing flow cytometry to test the percentage of sperm with normal mitochondrial transmembrane potential (JC-1 + %), utilizing X-ray microscopy to observe epididymal sperm ultra-microstructure placing special emphasis and photographing the differences in mitochondria of the flagellum region. RESULTS: Compared with DM, sperm quality of the treated mice was significantly better (P<0.05, respectively). Compared with PC, the LD group had significantly better quality sperms, while the parameters in the HD group were numerically better. Compared with NC, all other groups had significantly lower percentage of sperms with normal mitochondrial membrane potential. In PC, LD and HD groups, the percentage of sperms with normal mitochondrial membrane potential was significantly higher than that of D. The 9+9+2 mitochondrial sheath structure was complete in NC but damaged in DM. In the treatment groups, this structure was fairly clear. CONCLUSION: YSJP improved semen quality with oligoasthenozoospermia by improving sperm mitochondrial membrane potential and restoring sperm mitochondrial ultrastructure.

[A pilot study on hypoxia of squamous cell carcinoma in oral cavity].

OBJECTIVE: To examine the extent of hypoxia in oral squamous cell carcinoma and investigate the factors related to the hypoxia. METHODS: An animal model of oral squamous cell carcinoma was established and single photon emission computed tomography (SPECT) with 99mTc-HL91 used to detect the hypoxia extent of the oral squamous cell carcinoma. The expression of hypoxia inducible factor 1 alpha (HIF-1alpha) was examined by immunohistochemical staining in 42 cases of formalin-fixed paraffin-embed squamous cell carcinoma. RESULTS: The uptake of 99mTc-HL91 in the tumor tissue was higher than that in normal tissue and had linear relation with the tumor size (P < 0.05). There was no HIF-1alpha expression in the normal oral mucosa. The expression of HIF-1alpha was high in oral mucosa carcinoma and closely related to the differentiation degree of tumor and metastasis of lymph node (P < 0.05). CONCLUSIONS: Tumor tissue had broad hypoxic region. HIF-1alpha highly expressed in oral squamous cell carcinoma and may play an important role in carcinogenesis and aggression.

[Expression of integrin-beta1 in oral leukoplakia and early invasive carcinoma and its relationship with cell proliferation].

OBJECTIVE: To investigate the expression and significance of integrin-beta1 in oral leukoplakia and early invasive carcinoma. METHODS: The expression of integrin-beta1 and Ki-67 was examined in 12 normal oral mucosa, 10 simple hyperplasia, 24 epithelial dysplasia and 14 early invasive carcinoma by immunohistochemistry. RESULTS: In normal and simple hyperplasia epithelium, integrin-beta1 was mostly expressed in the basal cell membrane, and Ki-67 in the nuclei of basal and the parabasal layers. In dysplasia epithelium and early invasive carcinoma, integrin-beta1 showed membrane staining and Ki-67 showed nuclear staining in dysplastic basal cells, sprinkle cells and SCC cells. Integrin-beta1 and Ki-67 were overexpressed in 7 and 10 of 24 dysplasia cases and in 8 of 14 early invasive carcinoma cases respectively. There was a significant difference in integrin-beta1 and Ki-67 expression among the four groups (chi2 = 10.651, P = 0.014; chi2 = 14.831, P = 0.002), in integrin-beta1 expression among normal oral mucosa, simple hyperplasia and early invasive carcinoma (P = 0.008, P = 0.013) and in Ki-67 expression among normal oral mucosa and dysplasia, early invasive carcinoma (P = 0.026, P = 0.001), and among simple hyperplasia and early invasive carcinoma (P = 0.005). A significant correlation between integrin-beta1 and Ki-67 (R = 0.442, P < 0.01) was found. CONCLUSIONS: Integrin-beta1 showed increased staining in dysplasia epithelium cells and SCC cells, and may correlate to the proliferation of the dysplasia cells.