FDA-approved small molecule kinase inhibitors for cancer treatment (2001-2015): Medical indication, structural optimization, and binding mode Part I.

The dysregulation of kinases has emerged as a major class of targets for anticancer drug discovery given its node roles in the etiology of tumorigenesis, progression, invasion, and metastasis of malignancies, which is validated by the FDA approval of 28 small molecule kinase inhibitor (SMKI) drugs for cancer treatment at the end of 2015. While the preclinical and clinical data of these drugs are widely presented, it is highly essential to give an updated review on the medical indications, design principles and binding modes of these anti-tumor SMKIs approved by the FDA to offer insights for the future development of SMKIs with specific efficacy and safety.

Design, synthesis and biological evaluation of sulfonylamidines as potent c-Met inhibitors by enhancing hydrophobic interaction.

The dysregulation of c-Met kinase has emerged as a significant contributing factor for the occurrence, progression, poor clinical outcomes and drug resistance of various human cancers. In our ongoing pursuit to identify promising c-Met inhibitors as potential antitumor agents, a docking study of the previously reported c-Met inhibitor 7 revealed a large unoccupied hydrophobic pocket, which could present an opportunity for further exploration of structure-activity relationships to improve the binding affinity with the allosteric hydrophobic back pocket of c-Met. Herein we performed structure-activity relationship and molecular modeling studies based on lead compound 7. The collective endeavors culminated in the discovery of compound 21j with superior efficacy to 7 and positive control foretinib by increasing the hydrophobic interaction with the hydrophobic back pocket of c-Met active site.

Design, synthesis, and biological evaluation of thiazole/thiadiazole carboxamide scaffold-based derivatives as potential c-Met kinase inhibitors for cancer treatment.

As part of our continuous efforts to discover novel c-Met inhibitors as antitumor agents, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesised, and evaluated for the in vitro activity against c-Met and four human cancer cell lines. After five cycles of optimisation on structure-activity relationship, compound 51am was found to be the most promising inhibitor in both biochemical and cellular assays. Moreover, 51am exhibited potency against several c-Met mutants. Mechanistically, 51am not only induced cell cycle arrest and apoptosis in MKN-45 cells but also inhibited c-Met phosphorylation in the cell and cell-free systems. It also exhibited a good pharmacokinetic profile in BALB/c mice. Furthermore, the binding mode of 51am with both c-Met and VEGFR-2 provided novel insights for the discovery of selective c-Met inhibitors. Taken together, these results indicate that 51am could be an antitumor candidate meriting further development.

Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.

BACKGROUND: Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which causes alveolar bone resorption and tooth loss. Periodontitis treatment goals include prevention of alveolar bone resorption and promotion of periodontal regeneration. We previously found that granulocyte colony-stimulating factor (G-CSF) was involved in periodontitis-related alveolar bone resorption through induction of an immune response and subsequent destruction of periodontal tissue. However, the mechanisms underlying the effects of G-CSF on abnormal bone remodeling have not yet been fully elucidated. Human periodontal ligament stem cells (hPDLSCs) are major modulators of osteogenic differentiation in periodontal tissues. Thus, the aim of this study was to investigated whether G-CSF acts effects on hPDLSC proliferation and osteogenic differentiation, as well as periodontal tissue repair. METHODS: hPDLSCs were cultured and identified by short tandem repeat analysis. The expression patterns and locations of G-CSF receptor (G-CSFR) on hPDLSCs were detected by immunofluorescence analysis. The effects of G-CSF on hPDLSCs in a lipopolysaccharide (LPS)-induced inflammatory microenvironment were investigated. Specifically, Cell-Counting Kit 8 (CCK8) and Alizarin red staining were used to examine hPDLSC proliferation and osteogenic differentiation; reverse transcription-polymerase chain reaction was performed to detect the expression patterns of osteogenesis-related genes (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], and osteocalcin [OCN]) in hPDLSCs; and Western blotting was used to detect the expression patterns of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) of PI3K/Akt signaling pathway. RESULTS: hPDLSCs exhibited a typical spindle-shaped morphology and good clonogenic ability. G-CSFR was mostly localized on the cell surface membrane. Analyses showed that G-CSF inhibited hPDLSC proliferation. Also, in the LPS-induced inflammatory microenvironment, G-CSF inhibited hPDLSC osteogenic differentiation and reduced the expression levels of osteogenesis-related genes. G-CSF increased the protein expression levels of hPDLSC pathway components p-PI3K and p-Akt. CONCLUSIONS: We found that G-CSFR was expressed on hPDLSCs. Furthermore, G-CSF inhibited hPDLSC osteogenic differentiation in vitro in the LPS-induced inflammatory microenvironment.

AMPK inhibitor BML-275 induces neuroprotection through decreasing cyt c and AIF expression after transient brain ischemia.

Stroke is a major public health problem with an imperative need for a more effective and tolerated therapy. Neuroprotective therapy may be an effective therapeutic intervention for stroke. The morbidity and mortality of stroke-induced secondary brain injury is mainly caused by neuronal apoptosis, which can be executed in a caspase-dependent or apoptosis inducing factor (AIF)-dependent manner. As apoptosis is an energy-dependent process with a relative time delay, abnormal energy metabolism could be a significant and fundamental pathophysiological basis of stroke. To our knowledge, convincible evidences that AMPK inhibition exerts neuroprotection in cerebral ischemia injury via anti-apoptosis remain to be investigated. Accordingly, the aims of this study were to investigate the protective effects of AMPK inhibitor BML-275 on cerebral ischemic/reperfusion (I/R) injury and to elucidate the underlying mechanisms. Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) in male C57BL/6 mice. The therapeutic effects of BML-275 were evaluated by infarct sizes, neurological scores and the proportion of apoptotic neurons after 24 h of reperfusion. The cell apoptosis markers cyt c and AIF were also evaluated. The results showed that intraperitoneally administration of BML-275 alleviate the cerebral infarction, neurological deficit and neuronal apoptosis induced by MCAO. BML-275 simultaneously induces anti-apoptosis and decreases the expression of cyt c and AIF. This study supports the hypothesis that anti-apoptosis is one of potential neuroprotective strategies for the treatment of stroke.

An inverse association of Helicobacter pylori infection with oral squamous cell carcinoma.

BACKGROUND: Few studies have focused on the relationship between Helicobacter pylori (H. pylori) infection and oral diseases. In this study, we explored the correlation between H. pylori infection and oral squamous cell carcinoma (OSCC). METHODS: A total of 68 patients with OSCC and 104 age- and sex- matched healthy control subjects were retrospectively enrolled in this study. The H. pylori immunoglobin (Ig) G antibodies in serum were detected by enzyme-linked immunosorbent assay (ELISA) method to assess the status of H. pylori infection of our study sample. Polymerase chain reaction (PCR) was also employed using H. pylori genus-specific 16S rRNA primers in fasting blood, and OSCC specimens were analyzed by histochemical stain of each enrolled subject. The strength of correlation between H. pylori and the development of OSCC was estimated by Spearman's correlation coefficient. RESULTS: According to the three methods for detecting prevalence of H. pylori infection in the patients with OSCC, it was statistically lower than that in the healthy controls (35.3% vs. 54.8%, P = 0.012). An inverse correlation was observed between H. pylori infection and OSCC development (Spearman's correlation coefficient = -0.191, P = 0.012). In stratification analysis, we also found a statistical association between H. pylori infection and OSCC in the subpopulation with age ≥ 60 years (P = 0.037). CONCLUSION: Our findings suggested that H. pylori infection may be negatively related to OSCC. A reverse association of H. pylori infection with OSCC risk in the subpopulation with age ≥ 60 years was also found.

Influence of microbial community structure of seed sludge on the properties of aerobic nitrifying granules.

In order to evaluate the influence of microbial community structure of seed sludge on the properties of aerobic nitrifying granules, these granules were cultivated with different seed sludge, and the variation of microbial community and dominant bacterial groups that impact the nitrogen removal efficiency of the aerobic nitrifying granules were analyzed and identified using 16s rDNA sequence and denaturing gradient gel electrophoresis (DGGE) profiles. The results presented here demonstrated that the influence of the community structure of seed sludge on the properties of aerobic nitrifying granules was remarkable, and the granules cultivated by activated sludge from a beer wastewater treatment plant showed better performance, with a stable sludge volume index (SVI) value of 20mL/g, high extracellular polymeric substance (EPS) content of 183.3mg/L, high NH4(+)-N removal rate of 89.42% and abundant microbial population with 10 dominant bacterial groups. This indicated that activated sludge with abundant communities is suitable for use as seed sludge in culturing aerobic nitrifying granules.

[Determination of bisphenols in sediment by accelerated solvent extraction and solid-phase extraction purification coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Bisphenols are endocrine disruptors that are characterized with bioaccumulation, persistence, and estrogenic activity. Even low contents of bisphenols can exert adverse effects on human health and the ecological environment. Herein, a method combining accelerated solvent extraction and solid-phase extraction purification with ultra performance liquid chromatography-tandem mass spectrometry was developed for the accurate detection of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), and bisphenol AP (BPAP) in sediments. The mass spectrometric parameters of the seven bisphenols were optimized, and the response values, separation effects, and chromatographic peak shapes of the target compounds were compared under three different mobile phase conditions. The sediment samples were pretreated by accelerated solvent extraction, and orthogonal tests were used to optimize the extraction solvent, extraction temperature, and cycle number. The results showed that the use of 0.05% (v/v) ammonia and acetonitrile as the mobile phase for gradient elution could rapidly separate the seven bisphenols on an Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm). The gradient program was as follows: 0-2 min, 60%A; 2-6 min, 60%A-40%A; 6-6.5 min, 40%A; 6.5-7 min, 40%A-60%A; 7-8 min, 60%A. Orthogonal experiments indicated that the optimal extraction conditions were as follows: extraction solvent of acetonitrile, extraction temperature of 100 ℃, and cycle number of three. The seven bisphenols showed good linearity in the range of 1.0-200 µg/L, with correlation coefficients (r2) greater than 0.999, and the limits of detection were 0.01-0.3 ng/g. The recoveries for the seven bisphenols ranged from 74.9% to 102.8% at three spiking levels (2.0, 10, 20 ng/g), with relative standard deviations ranging from 6.2% to 10.3%. The established method was applied to detect the seven bisphenols in sediment samples collected from Luoma Lake and its inflow rivers. BPA, BPB, BPF, BPS, and BPAF were detected in the sediments of the lake, and BPA, BPF, and BPS were detected in the sediments of its inflow rivers. The detection frequency of BPA and BPF was 100%, and the contents of these bisphenols in the sediment were 11.9-38.0 ng/g and 11.0-27.3 ng/g, respectively. The developed method is simple, rapid with high accuracy and precision, and is suitable for the determination of the seven bisphenols in sediment.

Efficacy and risk factors of traditional denture restoration versus biofunctional complete denture restoration system.

OBJECTIVE: This study was designed to determine the efficacy of a traditional complete denture and a biofunctional prosthetic system of a complete denture, and risk factors affecting their efficacy. METHODS: A retrospective analysis was performed on 95 patients with total dentition loss admitted to our hospital from January 2015 to June 2022. Among them, 45 patients who received traditional dentures were assigned to a control group, and the other 50 who received a biofunctional prosthetic system with complete dentures were assigned to an observation group. The clinical efficacy was compared between the two groups before and after treatment, and the masticatory function indexes and comfort scores of the two groups were also compared. Logistics regression analysis was conducted to analyze the risk factors affecting the efficacy of patients. RESULTS: The observation group showed a higher total effective rate than the control group (P<0.05). After treatment, the observation group showed notably higher masticatory efficiency and absorbance of masticatory substances than the control group (P<0.05). In addition, the denture tenderness point in the observation group was notably lower than that in the control group (P<0.05). After treatment, the observation group had notably higher scores in General Comfort Questionnaire than the control group (P<0.05). Moreover, according to Logistics regression analysis, older age, dentition loss caused by tooth defect, smoking history and traditional denture restoration were independent risk factors for ineffective treatment. CONCLUSION: The biofunctional prosthetic system of complete dentures can better improve the masticatory function and enhance the comfort of patients with total dentition loss, and with good efficacy.

Polydopamine surface-modified hyperbranched polymeric nanoparticles for synergistic chemo/photothermal therapy of oral cancer.

A novel drug delivery system for the treatment of oral cancer was developed using a facile polydopamine (PDA)-based surface modification and a binding mechanism linking folic acid-targeting ligands. The system was able to achieve the following objectives: loading of chemotherapeutic agents, active targeting, pH responsiveness, and prolonged in vivo blood circulation. DOX-loaded polymeric nanoparticles (DOX/H20-PLA@PDA NPs) were functionalized with amino-poly (ethylene glycol)-folic acid (H2N-PEG-FA) after coating them with PDA to form the targeting combination, DOX/H20-PLA@PDA-PEG-FA NPs. The novel NPs exhibited drug delivery characteristics similar to DOX/H20-PLA@ PDA NPs. Meanwhile, the incorporated H2N-PEG-FA contributed to active targeting, as illustrated in cellular uptake assays and animal studies. In vitro cytotoxicity and in vivo anti-tumor studies have shown that the novel nanoplatforms exhibit extremely effective therapeutic effects. In conclusion, the multifunctional PDA-modified H20-PLA@PDA-PEG-FA NPs offer a promising chemotherapeutic strategy to improve the treatment of oral cancer.

Occurrence, distribution, and risk assessment of bisphenol analogues in Luoma Lake and its inflow rivers in Jiangsu Province, China.

Bisphenol analogs (BPs) are widely used in industrial and commercial products and have been detected in surface water, sediment, sewage, and sludge. The presence of BPs in the natural environment poses threats to the aquatic ecosystem and human health. The concentration, distribution, seasonal variation, and risk assessment of BPA and BPA structural analogs including BPB, BPF, BPS, BPZ, BPAF, and BPAP in surface water and sediment during dry season and flood season in Luoma Lake and its inflow rivers in Jiangsu Province, China, were investigated in this study. The detection frequency of BPA and BPF was 100%. Although the use of BPA is restricted, BPA is still the dominant BPs in surface water and sediment. The concentration of BPs in surface water during flood season was higher than that in dry season. The concentrations of BPs in Fangting River, Zhongyun River, and Bulao River were higher than those in Luoma Lake. The average concentrations of BPs in surface water were in the order of BPA > BPF> BPS> BPB > BPZ > BPAF> BPAP. Compared with other studies, the concentration of BPs in Luoma Lake was moderate. There is no significant spatial distribution and difference in seasonal variation of BPs concentration in sediment (p > 0.05). Compared with other studies, the contamination of BPs in sediment of Luoma Lake was relatively low. Risk quotient (RQ) was used to evaluate the ecological risk of BPs in water environment, and the 17ß estradiol equivalent (EEQ) method was used to estimate the estrogenic activity of BPs. The risk assessment showed no high ecological risk (RQ < 1.0) and estrogenic risk (EEQ < 1.0 ng/L) in dry season and flood season. The estimated RQ and EEQt indicated that the ecological and human health impacts were negligible in the short term.

Integrative Analysis of DNA Methylation Data and Transcriptome Data Identified a DNA Methylation-Dysregulated Four-LncRNA Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma.

Increasing evidence has demonstrated the crosstalk between DNA epigenetic alterations and aberrant expression of long non-coding RNAs (lncRNAs) during carcinogenesis. However, epigenetically dysregulated lncRNAs and their functional and clinical roles in Head and Neck Squamous Cell Carcinoma (HNSCC) are still not explored. In this study, we performed an integrative analysis of DNA methylation data and transcriptome data and identified a DNA methylation-dysregulated four-lncRNA signature (DNAMeFourLncSig) from 596 DNA methylation-dysregulated lncRNAs using a machine-learning-based feature selection method, which classified the patients of the discovery cohort into two risk groups with significantly different survival including overall survival, disease-specific survival, and progression-free survival. Then the DNAMeFourLncSig was implemented to another two HNSCC patient cohorts and showed similar prognostic values in both. Results from multivariable Cox regression analysis revealed that the DNAMeFourLncSig might be an independent prognostic factor. Furthermore, the DNAMeFourLncSig was substantially correlated with the complete response rate of chemotherapy and may predict chemotherapy response. Functional in silico analysis found that DNAMeFourLncSig-related mRNAs were mainly enriched in cell differentiation, tissue development and immune-related pathways. Overall, our study will improve our understanding of underlying transcriptional and epigenetic mechanisms in HNSCC carcinogenesis and provided a new potential biomarker for the prognosis of patients with HNSCC.

Double-edged effects of interferons on the regulation of cancer-immunity cycle.

Interferons (IFNs) are a large family of pleiotropic cytokines that regulate both innate and adaptive immunity and show anti-cancer effects in various cancer types. Moreover, it was revealed that IFN signaling plays critical roles in the success of cancer therapy strategies, thereby enhancing their therapeutic effects. However, IFNs have minimal or even adverse effects on cancer eradication, and mediate cancer immune escape in some instances. Thus, IFNs have a double-edged effect on the cancer immune response. Recent studies suggest that IFNs regulate each step of the cancer immunity-cycle, consisting of cancer antigen release, presentation of antigens and activation of T cells, trafficking and infiltration of effector T cells into the tumor microenvironment, and recognition and killing of cancer cells, which contributes to our understanding of the mechanisms of IFNs in regulating cancer immunity. In this review, we focus on IFNs and cancer immunity and elaborate on the roles of IFNs in regulating the cancer-immunity cycle.

Charge-reversal nanomedicine based on black phosphorus for the development of A Novel photothermal therapy of oral cancer.

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor. With excellent photothermal properties of polydopamine (PDA) modified black phosphorus nanosheets (BP NSs) as basal material, then used polyacrylamide hydrochloride-dimethylmaleic acid (PAH-DMMA) charge reversal system for further surface modification, which can be negatively charged at blood circulation, and become a positive surface charge in the tumor site weakly acidic conditions due to the breaking of dimethylmaleic amide. Therefore, the uptake of oral cancer cells was enhanced and the therapeutic effect was improved. It can be proved that this nanomedicine has excellent photothermal properties and tumor enrichment ability, as well as a good killing effect on oral cancer cells through in vitro cytotoxicity test and in vivo photothermal test, which may become a very promising new model of oral cancer treatment.

Study on the application of oral digital design in aesthetic restoration of anterior teeth of cleft lip/palate patients.

OBJECTIVES: A study was conducted to investigate the clinical effects of oral digital design on the aesthetic restoration of anterior teeth of cleft lip/palate patients. METHODS: Nine adult cleft lip/palate patients who need aesthetic restoration of anterior teeth were recruited. Digital information of patients' dental arches, the surrounding soft tissue and face were captured by digital camera and scanner. The aesthetic analysis and design were conducted using keynote and 3shape software and were demonstrated to the patients. The optimized treatment plan was ensured by communicating with the patients. Digital wax-up models were exported and printed into resin diagnostic models, which were then utilized in the treatment process to guide the doctors and the technicians in tooth preparation and in making the final restorations, respectively. The adhesive procedure was completed after satisfactory try-in. Aesthetics assessment was conducted in accordance with the anterior esthetic evaluation form. The scores of patient's satisfaction were recorded on a questionnaire containing six items of aesthetic index and doctor-patient communication. Patients were interviewed and examined after 1, 3, 6, and 12 months, respectively, and the clinical effects of restorations were evaluated. RESULTS: All nine patients had satisfactory clinical results. The aesthetic defects of the patients were effectively addressed. All treatments met the requirements of the preoperative digital designs. The patients' scores were all above 90 on the satisfaction scale. At 12 months after the operation, the clinical effects of restorations of all cases achieved A class in each evaluation indicator. CONCLUSIONS: For cleft lip/palate patients with esthetic defect in the anterior teeth, the digital design plays an important role in optimizing the treatment plan and guides the whole treatment process. This design can help clinicians achieve predictable satisfactory aesthetic results.

Mussel-Inspired Polydopamine: The Bridge for Targeting Drug Delivery System and Synergistic Cancer Treatment.

Polydopamine (PDA), a mussel-inspired molecule, has been recognized as attractive in cancer therapy due to a number of inherent advantages, such as good biocompatibility, outstanding drug-loading capacity, degradability, superior photothermal conversion efficiency, and low tissue toxicity. Furthermore, due to its strong adhesive property, PDA is able to functionalize various nanomaterials, facilitating the construction of a PDA-based multifunctional platform for targeted or synergistic therapy. Herein, recent PDA research, including targeted drug delivery, single-mode therapy, and diverse synergistic therapies against cancer, are summarized and discussed. For synergistic therapy, advanced developments are highlighted, such as photothermal/radiotherapy, chemo-/photothermal/gene therapy, photothermal/immune therapy, and photothermal/photodynamic/immune therapy. Finally, the challenges and promise of PDA for biomedical applications in the future are discussed.

[Impact assessment on enamel remineralization after orthodontic treatment with casein phosphopeptide calcium phosphate complex].

PURPOSE: To compare the effect on enamel demineralization following fluoride rinse or casein phosphopeptide calcium phosphate complex (CPP-ACP) after fixed appliance orthodontic treatment. METHODS: The study population consisted of 21 post-orthodontic patients (13 females, 8 males, 84 affected teeth) with white spot lesions (WSL). They were divided into 3 groups with 28 affected teeth in each group. Participants in the control group were brushed with fluoride toothpaste twice a day. Participants in the fluoride group were instructed to rinse the mouth with 20mL 0.01% sodium fluoride rinse in addition to brushing twice a day. Participants in CPP-ACP group were instructed to use tooth moss after brushing their teeth twice a day for 6 months. SPSS 17.0 software package was used to analyze the data. RESULTS: Within 6 months after orthodontic treatment, white spot lesions areas of the three groups caused by enamel demineralization were all reduced in different degrees, and the differences of success rate were significant among three groups (P<0.05). CPP-ACP group achieved the highest success rate (51%) than the other group, the fluoride group (44%) and the control group (42%). CONCLUSIONS: Brushing teeth, fluoride rinse and CPP-ACP have certain effect on remineralization of demineralized teeth in 6 months after orthodontic treatment. Compared with brushing and fluoride rinse, CPP-ACP can reduce the area of enamel demineralization more effectively.

[Effect of HBXIP on biological function and PI3K/Akt signaling pathway of adenoid cystic carcinoma cell line ACC-M].

PURPOSE: To study the effect of hepatitis B virus X protein binding protein (HBXIP) on proliferation, migration and invasion of adenoid cystic carcinoma cell line ACC-M, and the possible mechanism of PI3K/Akt signaling pathway. METHODS: HBXIP plasmid was transfected into ACC-M. The cells were divided into experimental group (transfected with plasmid pEGFP-N1-HBXIP) control group (non-transfected group) and blank control group (vector group, pEGFP-N1). RT-PCR was used to detect the expression HBXIP in ACC-M; MTT assay, transwell chamber experiments and scratches over the proliferation of HBXIP were utilized individually to evaluate the influence of HBXIP on ACC-M expression, migration and invasion; Western blotting was used to detect the protein expression of Akt, p-Akt, PI3K, p-PI3K and S100A4 after overexpression of HBXIP. Statistical analysis was performed using SPSS 18.0 software package. RESULTS: MTT results showed that the number of surviving cells of experimental group was significantly higher than the control group (P<0.05); Scratch test results showed that the cell mobility of the experimental group was significantly higher than the control group (P<0.01); Transwell chamber experiments showed that the number of cell invasion of the experimental group was significantly higher than the control group (P<0.01); Western blotting results showed that compared with the control group, the expression of p-Akt, p-PI3K and S100A4 in the experimental group with overexpressed HBXIP was relatively increased. CONCLUSIONS: Overexpression of HBXIP gene promotes ACC-M proliferation, invasion and migration. Further, ACC-M proliferation, invasion and migration may be promoted by increased Akt, PI3K phosphorylation and S100A4 protein expression.

[DNA repair gene polymorphisms in ERCC4 rs6498486 and ERCC5 rs751402 and risk of salivary gland tumors].

PURPOSE: To investigate the association between ERCC4 and ERCC5 polymorphisms and risk of salivary gland tumors. METHODS: Case-control study was carried out in 133 cases of histologically confirmed salivary gland tumors and 142 age and gender matched healthy control cases. Polymorphisms of ERCC4 rs6498486 and ERCC5 rs751402 were detected by PCR-RFLP. Multiple factors logistic regression analysis was conducted to investigate the association between gene polymorphisms and risk of salivary gland tumors using SPSS 18.0 software package. RESULTS: The genotype distribution of each polymorphism was found to be of Hardy-Weinberg equilibrium in the study. ERCC5 rs751402 TT genotype was associated with risk of salivary gland tumors (TT vs. CC+CT: OR=0.45, 95% CI: 0.21-0.98, P=0.046). No significant association was found in ERCC4 rs6498486. CONCLUSIONS: The results suggest that ERCC5 rs751402 polymorphism may be associated with risk of salivary gland tumors.