Prophylactic therapy for prevention of surgical site infection after extraction of third molar: An overview of reviews

Background: To compare the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars with different degree of impaction. Material and Methods: Systematic reviews and meta-analyses evaluating the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars were included. An electronic search was performed in PubMed, EMBASE, and the Cochrane Database of Systematic reviews. AMSTAR 2 tool was used to evaluate the confidence in results from the included reviews. Descriptive analyses were performed. Results: Six reviews were included. A significant benefit of different antibiotics to the prevention of site infection after extraction of third molars was reported. Amoxicillin/amoxicillin clavulanic acid could significantly reduce the rate of surgical site infection versus placebo. Chlorhexidine gel could significantly reduce the frequency of alveolar osteitis versus placebo. Conclusions: Based on the limited evidence, there is a significant benefit of prophylactic therapy while the comparative effect of different types of prophylactic regimes are controversial. (AU)

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma.

Pembrolizumab with cisplatin and 5-fluorouracil showed survival benefit but relatively high occurrence of treatment-related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD-L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune-related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment-related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first-line therapy was well tolerable and had potentially favorite efficacy in PD-L1-positive patients with R/M OSCC.

A fast methodology for generating skeletal FEM with detailed human geometric features based on CPD and RBF algorithms.

Due to the significant effects of the human anatomical characteristics on the injury mechanism of passenger in traffic accidents, it is necessary to develop human body FEM (Finite Element Model) with detailed anatomical characteristics. However, traditional development of a human body FEM is an extremely complicated process. In particular, the meshing of human body is a huge and time-consuming project. In this paper, a new fast methodology based on CPD (Coherent Point Drift) and RBF (Radial Basis Function) was proposed to achieve the rapid developing the FEM of human bone with detailed anatomical characteristics. In this methodology, the mesh morphing technology based the RBF was used to generate FEM mesh in the geometry extracted from the target CT (Computed Tomography) data. In order to further improve the accuracy and speed of mesh morphing, the target geometric feature points required in the mesh morphing process were realized via the rapid and automatic generation based on the point-cloud registration technology of the CPD algorithm. Finally, this new methodology was used to generate a 3-year-old ribcage FEM consisting of a total of 27,728 elements with mesh size 3-5 mm based on the THUMS (Total Human Model for Safety) adult model. In the entire process of generating this new ribcage model, it only took about 2.7 s. The average error between the new FEM and target geometries was only about 2.7 mm. This indicated that the new FEM well described the detailed anatomical characteristics of target geometry, thus importantly revealing that the mesh quality of the new FEM was basically similar to that of source FEM.

A functional study of zinc-titanium coatings and exploration of the intrinsic correlation between angiogenesis and osteogenesis.

With the development of implant applications, osseointegration has become a criterion for implant success. A good blood supply is essential for successful osseointegration. To improve the pro-angiogenic ability of the implants, in this experiment we introduced zinc into the titanium coating. The physical morphology, biocompatibility, pro-angiogenic ability, and osteogenic effect of the zinc-containing titanium coatings were investigated. The pro-angiogenic effect of zinc ions was determined, and the intrinsic link between angiogenesis and osteogenesis under the effect of zinc ions was investigated. Zinc-containing titanium coating was prepared using a micro-arc oxidation (MAO) technique. The physical properties of the coating materials were determined by analyzing the microstructure, roughness, hydrophilic properties, constituent elements, and ionic release of the coating. The biocompatibility of the coating materials was examined using apoptosis and proliferation assays of human umbilical vein endothelial cells (HUVECs). The pro-angiogenic function and osteogenic ability of the zinc-containing coating were investigated by CD31 immunofluorescence staining and quantitative polymerase chain reaction (q-PCR) assay. The optimal concentration of zinc ions for pro-angiogenesis was screened by ion assay. Conditioned media (CM) were prepared for the experiments. The intrinsic link between angiogenesis and osteogenesis was determined by q-PCR to detect the expression of genes related to HUVECs and BMSCs after culture in CM. The prepared Zn-containing micro-arc oxide coatings were shown to have good physical properties, stable Zn2+ release ability, and biocompatibility, as well as good angiogenic and osteogenic potential. In addition, ion experiments confirmed that 60 µM Zn2+ exhibited the best angiogenic effect; more importantly, a mutual promotion between angiogenesis and osteogenesis regeneration in the Zn2+ microenvironment was also found. The introduction of Zn2+ improved the implants' functionality and laid the foundation for the clinical application of Zn2+ pro-angiogenesis.

Inhibition of Inflammatory Response and Promotion of Osteogenic Activity of Zinc-Doped Micro-Arc Titanium Oxide Coatings.

An early and sustained immune response can lead to chronic inflammation after the implant is placed in the body. The implantable materials with immunomodulatory effects can reduce the body's immune response and promote the formation of ideal osseointegration between the implants and bone tissue. In this study, zinc-coated titanium micro-arc oxide coating was prepared on titanium surface by micro-arc oxidation. The physical properties, anti-inflammation, and osteogenesis of the material were evaluated. We have physically characterized the surface structure of the coatings by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and atomic force microscopy (AFM) and detected the release of Zn2+ from the coating surface by inductively coupled optical plasma emission spectrometry (ICP-OES). The BMSCs were inoculated on the surface of the coating, and the biocompatibility of the coating was evaluated by CCK-8 analysis and living and dead cell staining. The osteogenic effect of the layer on BMSCs was evaluated by alkaline phosphatase (ALP) assays, osteocalcin (OCN) immunofluorescence, and quantitative polymerase chain reaction (q-PCR). The survival status of RAW264.7 on the coating surface and the mRNA expression of the associated proinflammatory markers, tumor necrosis factor-α (TNF-α), cluster of differentiation 86 (CD86), and inducible nitric oxide (INOS) were detected by CCK-8 analysis and q-PCR. In parallel, the cell counting kit-8 (CCK-8) analysis and q-PCR screened and evaluated the effective concentration of Zn2+ anti-inflammatory in vitro. The results show that the coating has good physical characterization, and Zn is uniformly bound to the surface of titanium and shows stable release and good biocompatibility to BMSCs, downregulating the expression of inflammation-related genes promoting the bone formation of BMSCs. We have successfully prepared zinc-coated micro-arc titanium oxide coating on the titanium surface, which has good osteogenesis and great anti-inflammatory potential and provides a new way for osseointegration in the implant.

A novel intronic circular RNA, circGNG7, inhibits head and neck squamous cell carcinoma progression by blocking the phosphorylation of heat shock protein 27 at Ser78 and Ser82.

BACKGROUND: There is increasing evidence that circular RNAs (circRNAs) play a significant role in pathological processes including tumorigenesis. In contrast to exonic circRNAs, which are the most frequently reported circRNAs in cancer so far, the studies of intronic circRNAs have been greatly lagged behind. Here, we aimed to investigate the regulatory role of intronic circRNAs in head and neck squamous cell carcinoma (HNSCC). METHODS: We conducted whole-transcriptome sequencing with four pairs of primary tumor tissues and adjacent normal tissues from HNSCC patients. Then, we characterized circGNG7 expression in HNSCC tissues and cell lines and explored its association with the prognosis of HNSCC patients. We also identified interactions between circGNG7 and functional proteins, which alter downstream signaling that regulate HNSCC progression. RESULTS: In this study, we identified a new intronic circRNA, circGNG7, and validated its functional roles in HNSCC progression. CircGNG7 was predominately localized to the cytoplasm, and its expression was downregulated in both HNSCC tissues andCAL27, CAL33, SCC4, SCC9, HN6, and HN30 cells. Low expression of circGNG7 was significantly correlated with poor prognosis in HNSCC patients. Consistent with this finding, overexpression of circGNG7 strongly inhibited tumor cell proliferation, colony formation, in vitro migration, and in vivo tumor growth. Mechanistically, the expression of circGNG7 in HNSCC cells was regulated by the transcription factor SMAD family member 4 (SMAD4). Importantly, we discovered that circGNG7 could bind to serine residues 78 and 82 of the functional heat shock protein 27 (HSP27), occupying its phosphorylation sites and hindering its phosphorylation, which reduced HSP27-JNK/P38 mitogen-activated protein kinase (MAPK) oncogenic signaling. Downregulation of circGNG7 expression in HNSCC increased HSP27-JNK/P38 MAPK signaling and promoted tumor progression. CONCLUSIONS: Our results revealed that a new intronic circRNA, circGNG7, functions as a strong tumor suppressor and that circGNG7/HSP27-JNK/P38 MAPK signaling is a novel mechanism by which HNSCC progression can be controlled.

Proximal-type epithelioid sarcoma in the maxillary sinus: an unusual presentation.

Epithelioid sarcoma (ES) is a rare histological type of soft tissue sarcoma presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Recently, a more aggressive, so called 'proximal-type' ES has been described. The literature is limited on the clinical features and management of ES originating in the head and neck area. We here report a case of 16-year-old female who initially presented with progressive swelling and pain in the left cheek. On physical and radiographic examination, a malignant neoplasm was found in the left maxillary sinus with bony invasion. The definite diagnosis of proximal-type ES was based on the pathological and immunohistochemical characteristics. A subtotal maxillectomy with wide margins was performed on this patient. The patient survived uneventfully for three years. This is the first report of a proximal-type ES found in the maxillary sinus.

EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy.

Rationale: The oncogenesis of head and neck squamous cell carcinoma (HNSCC) is believed to result from oncogene activation and tumor suppressor inactivation. Here, we identified a new oncogenic role for the EREG gene in HNSCC. Methods: The TCGA database and immunohistochemistry assay were used to analyze expression of EREG in HNSCC tissues. Immunoblotting was performed to identify the EGFR-mediated pathways altered by EREG. The role of EREG in oncogenesis was investigated in vivo and in vitro. Results: Upregulated EREG expression predicted a poor prognosis and triggered HNSCC oncogenic transformation by activating the epidermal growth factor receptor (EGFR) signaling pathway. We also demonstrated the direct association of EREG with EGFR and that this binding required EGFR domains I and III and the N57 residue of EREG. Moreover, EREG overexpression was shown to promote HNSCC oncogenesis by inducing C-Myc expression, and the pharmacological inhibition of C-Myc rescued EREG-promoted HNSCC oncogenesis. Unlike other EGFR ligands, EREG could mimic EGFR mutations by sustaining the activation of the EGFR-Erk pathway, and high EREG expression was positively associated with the response to treatment with the EGFR inhibitor erlotinib. Furthermore, knockdown of EREG decreased sensitivity to erlotinib treatment in vitro and in vivo. Conclusions: These results identify the EREG-EGFR-C-Myc pathway as a crucial axis that drives HNSCC oncogenesis and show that EREG expression could be a predictive functional marker of sensitivity to erlotinib therapy in HNSCC.

MOF-derived novel porous Fe3O4@C nanocomposites as smart nanomedical platforms for combined cancer therapy: magnetic-triggered synergistic hyperthermia and chemotherapy.

Multifunctional nanomedical platforms have broad prospects in imaging-guided combination therapy in cancer precision medicine. In this work, metal-organic framework (MOF)-derived novel porous Fe3O4@C nanocomposites were developed as an intelligent cancer nanomedical platform for combined cancer therapy with MRI-guided magnetic-triggered hyperthermia and chemotherapy functions. The magnetic behavior, porous character and good surface modification endowed this smart nanoplatform with favorable biocompatibility, high-efficiency MRI imaging, magnetic-triggered on-demand DOX release function, and synergistic therapy of magnetic hyperthermia and chemotherapy, which proposed an all-in-one platform for cancer therapy. Additionally, in vivo animal experiments verified the significant suppression of malignant tumor growth with negligible side effects, which were attributed to the consecutive 13 day synergistic therapy of magnetic hyperthermia and chemotherapy in one. To be specific, Fe3O4@C-PVP@DOX significantly decreases the volume (2.5 to 0.44 of tumor volume ratio) and weight (0.49 g to 0.10 g) of tumors after magnetic-triggered hyperthermia and chemotherapy treatments. Moreover, no big difference of body weight and associated damage was observed among all major organs. Therefore, owing to its high-efficiency combined therapy of magnetic-triggered hyperthermia and chemotherapy, this smart nanoplatform holds great potential application in the precise treatments of clinical cancer.

Validation of Gene Profiles for Analysis of Regional Lymphatic Metastases in Head and Neck Squamous Cell Carcinoma.

The progress of Head and Neck Squamous Cell Carcinoma (HNSCC) is dependent on both cancer stem cells (CSCs) and immune suppression. This study was designed to evaluate the distribution of CSCs and the characteristic immune suppression status in HNSCC primary tumors and lymph nodes. A total of 303 lymph nodes from 25 patients, as well as tumor and adjacent normal tissue samples, were evaluated by a quantitative PCR assay of the markers of CSCs and the characteristic immune suppression. Expressions of selected genes in The Cancer Genome Atlas (TCGA) datasets were also analyzed. In the primary tumors, we found that expressions of CSCs markers (ALDH1L1, PECAM1, PROM1) were down-regulated, while immune suppression markers FOXP3, CD47, EGFR, SOX2, and TGFB1 were up-regulated significantly when compared to that in adjacent normal tissues. In the lymph nodes, expressions of both CSCs, and immune suppression markers were upregulated significantly compared with that in primary tumors. The mRNA expression of selected CSCs and immune suppression markers exhibited the highest expression in the level II of metastasis, then declined in the level III and remained constant at a reduced value in levels IV and V of metastases. These results reveal a comprehensive understanding of the unique genetic characteristics associated with metastatic loci and potential routes of lymphatic dissemination of HNSCC, which helps to explain why the level II has a high incidence of lymph node metastasis, and why skip metastasis straight to the level IV or level V is rarely found in the clinic.

TLR4 activation leads to anti-EGFR therapy resistance in head and neck squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and related to cancer progression. The resistance to anti-EGFR therapy remains a major clinical problem in HNSCC. In this study, we found that TOLL-like receptor 4 (TLR4) was highly expressed in 50% of EGFR overexpressed HNSCC biopsies, which correlated to worse prognosis in patients. In HNSCC cell lines, activation of TLR4 reversed cetuximab-induced the inhibition of proliferation, migration and invasion. LPS induced of TLR4 signaling was potentiated under cetuximab treatment, showing increased activation of downstream NF-κB and MAPK pathways. Accordingly, cetuximab treatment also increased expression of TNF-α, COX2, and other molecules involved in TLR4 induced tumor inflammation. Mechanistically, we found inhibition of EGFR by cetuximab led to decreased phosphorylation of Src and sequentially Src-medicated activation of Cbl-b. This inhibited Cbl-b-mediated degradation of the key TLR4 adaptor protein MyD88 and activated TLR4 signaling. TLR4 or MyD88 overexpressed CAL27 and SCC4 cells grew faster and were more resistant to cetuximab and gefitinib both in vitro and in vivo. Out study delineates a crosstalk between EGFR and TLR4 pathways and identified TLR4 as a potential biomarker as well as a therapeutic target in overcoming the resistance to anti-EGFR therapy of HNSCC.

A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma.

BACKGROUND: Interferon alpha (IFNα) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains largely unknown. METHODS: Differentially expressed lncRNAs were screened under IFNα stimulation using lncRNA sequencing. The role and mechanism of lncRNA in immunosuppression were investigated in HNSCC in vitro and in vivo. RESULTS: We identified a novel IFNα-induced upregulated lncRNA, lncMX1-215, in HNSCC. LncMX1-215 was primarily located in the cell nucleus. Ectopic expression of lncMX1-215 markedly inhibited expression of the IFNα-induced, immunosuppression-related molecules programmed cell death 1 ligand 1 (PD-L1) and galectin-9, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. Binding sites for H3K27 acetylation were found on PD-L1 and galectin-9 promoters. Mechanistically, we found that lncMX1-215 directly interacted with GCN5, a known H3K27 acetylase, to interrupt its binding to H3K27 acetylation. Clinically, negative correlations between lncMX1-215 and PD-L1 and galectin-9 expression were observed. Finally, overexpression of lncMX1-215 suppressed HNSCC proliferation and metastasis capacity in vitro and in vivo. CONCLUSIONS: Our results suggest that lncMX1-215 negatively regulates immunosuppression by interrupting GCN5/H3K27ac binding in HNSCC, thus providing novel insights into immune checkpoint blockade treatment.

Enhanced corrosion resistance and bioactivity of Mg alloy modified by Zn-doped nanowhisker hydroxyapatite coatings.

In this work, Zn is doped into a hydroxyapatite coating on the surface of ZK60 magnesium alloys using a one-pot hydrothermal method to obtain a corrosion-resistant implant with abilities of osteogenic differentiation and bacterial inhibition. With the addition of Zn, the morphology changes with a nanowhisker structure appearing on the coating. Electrochemical measurements show that the nanowhisker hydroxyapatite coating provides a high corrosion resistance. Compared with hydroxyapatite coating, the nanowhisker coating not only effectively inhibits bacteria, but also promotes the adhesion and differentiation of rat bone marrow mesenchymal stem cells at appropriate Zn concentrations. In conclusion, a novel nanowhisker structure prepared by a single variable Zn doping can significantly improve the corrosion resistance and biological activity of hydroxyapatite coatings.

Altered expression of TIM-3, LAG-3, IDO, PD-L1, and CTLA-4 during nimotuzumab therapy correlates with responses and prognosis of oral squamous cell carcinoma patients.

BACKGROUND: Since the inhibitory immune checkpoint receptors have been described to benefit the OSCC patients clinically, it is unknown that whether their expression in tumor immune microenvironment (TME) can determine the clinical outcome in response to nimotuzumab therapy. METHODS: We examined the expression patterns of immune checkpoint receptors (including TIM-3, LAG-3, PD-L1, and CTLA-4) and an immunoregulatory enzyme called IDO in 36 OSCC patients during nimotuzumab therapy by immunohistochemistry. Then, we divided the recruited patients into clinical responders and non-responders according to computed tomography (CT) scan and analyzed the relationship between the immunological parameters and clinical outcome. RESULTS: We observed that nimotuzumab therapy significantly increased the expression of TIM-3, LAG-3, IDO, PD-L1, and CTLA-4 in the TME, and the expression of LAG-3 and PD-L1 before nimotuzumab therapy was inversely correlated with the overall survival. In clinical non-responders, we found the expression of TIM-3, LAG-3, IDO, PD-L1, and CTLA-4 was significantly increased during nimotuzumab therapy, and the expression of TIM-3, LAG-3, IDO, PD-L1, and CTLA-4 before nimotuzumab therapy was negatively correlated with the overall survival. However, in clinical responders, neither of those showed significant. CONCLUSIONS: It suggests that these immune checkpoint receptors and IDO could be considered as biomarkers to reflect immune status in the tumor microenvironment during nimotuzumab therapy. Blockade of these immune checkpoint receptors might enhance nimotuzumab-based cancer immunotherapy, thus potentially improving clinical outcomes of OSCC patients.

Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma.

Despite multiple antitumor activities, interferon-alpha (IFNα) therapy alone is less effective in solid tumors. Autophagy has been reported to play a key role in tumor chemoresistance. Therefore, it is meaningful to explore whether autophagy can be activated by IFNα in head and neck squamous cell carcinoma (HNSCC) and serve as a potential target to improve efficacy of IFNα therapy. In this study, we report that IFNα not only exhibits anti-proliferation activity and induces apoptosis, but also activates autophagy in HNSCC cells. Moreover, silencing autophagy-related protein 5 (ATG5) and signal transducer and activator of transcription 1 (STAT1) suppresses autophagy flux. Furthermore, IFNα and autophagy inhibitors (hydroxychloroquine and wortmannin) show clear synergistic effects on inhibiting growth and promoting apoptosis in HNSCC cells and xenograft models. Our findings indicate that IFNα-induced autophagy plays a cytoprotective role and blocking autophagy flux promotes IFNα-mediated apoptosis in HNSCC. These results suggest that the combination of IFNα and autophagy inhibitors represents a novel strategy for HNSCC treatment.

Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma.

BACKGROUND: An immunosuppressive microenvironment is critical for cancer initiation and progression. Whether interferon alpha (IFNα) can suppress immune and cancer cells and its involved mechanism still remain largely elusive. METHODS: We examine the expression of interferon alpha/beta receptor-1 (IFNAR1), CD8, CD56 and programmed death ligand 1 (PDL1) in head and neck squamous cell carcinomas (HNSCC). The effect of IFNα on PDL1 and programmed cell death protein 1 (PD1) expression in tumour cells and immune cells was detected in vitro and in vivo. RESULTS: Overexpression of IFNAR1, MX1 and signal transducer and activator of transcription 1 (Stat1) indicated the endogenous IFNα activation in tumour microenvironment, which correlated with immunosuppression status in HNSCC patients. Moreover, IFNα transcriptionally activated the expression of PDL1 through p-Stat1 (Tyr701) and promoted PD1 expression in immune cells through IFNAR1. The inhibition of IFNα signalling enhanced the cytotoxic activity of nature killer cells. At lastastly, we confirmed the upregulation of PDL1 and PD1 in response to IFNα treatment in both xenograft tumour models and patient-derived xenograft models. CONCLUSIONS: Our findings demonstrate that IFNα-induced PDL1 and PD1 expression is a new mechanism of immunosuppression in HNSCC, suggesting that blocking IFNα signalling may enhance the efficacy of immune checkpoint blockade.

Retracted: Effects of Nano-Hydroxyapatite/Polyetheretherketone-Coated, Sandblasted, Large-Grit, and Acid-Etched Implants on Inflammatory Cytokines and Osseointegration in a Peri-Implantitis Model in Beagle Dogs.

The article is withdrawn by the authors request.

Long non-coding RNA ANRIL promotes tumorgenesis through regulation of FGFR1 expression by sponging miR-125a-3p in head and neck squamous cell carcinoma.

ANRIL (CDKN2B antisense RNA 1, CDKN2B-AS1) is involved in the progression of various cancers. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we found that ANRIL expression was upregulated in HNSCC and correlated with tumor progression. Further functional analysis showed that knockdown of ANRIL significantly inhibited proliferation in vivo and in vitro. ANRIL functioned as a ceRNA (competing endogenous RNAs) for miR-125a-3p and upregulated FGFR1 (fibroblast growth factor receptor-1), which could promote tumor growth. Moreover, we confirmed that ANRIL promoted HNSCC activity via FGFR1 with a FGFR1 inhibitor in vivo and in vitro. Thus, it could be concluded that ANRIL promoted the progression of HNSCC via miR-125a-3p/FGFR1/MAPK signaling, which might provide a new target for the diagnosis and treatment of HNSCC.

Altered expression pattern of circular RNAs in metastatic oral mucosal melanoma.

Circular RNAs (circRNAs) are known to be associated with carcinogenesis, and can serve as potential biomarkers for cancer diagnosis and therapeutic implications. However, little is known about their expression patterns in oral mucosal melanoma (OMM), an extremely rare cancer that is distinct from cutaneous melanoma for its clinical course and prognosis. To investigate circRNAs expression profile in OMM, we performed a circRNAs microarray to analyze 6 primary OMM samples with lymph nodes dissemination, and constructed a genome-wide circRNA profile. Our results revealed that 90 circRNAs were significantly dysregulated in the metastatic OMM tissues when compared to the paired adjacent tissues. Among them, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0008042 were significantly upregulated in primary tumor and metastatic lymph nodes compared to paired adjacent normal tissues and non-metastatic lymph nodes, whereas the expression of hsa_circ_0000869 and hsa_circ_0000853 were downregulated relatively. Gene Ontology (GO) and pathway analyses of differentially expressed circRNAs indicated that these identified circRNAs might play important roles in protein modification, protein binding and cellular metabolism in metastatic OMM. Functions of several selected circRNA were also identified. In addition, by using bioinformatics predictions, we further demonstrated that hsa_circ_0005320, hsa_circ_0067531 and hsa_circ_0000869 could serve as competing endogenous RNA (ceRNA), which might regulate tumorigenesis and metastatic of OMM by binding to specific microRNAs. Our results not only suggested that circRNAs might play critical roles in metastasis of OMM, but also provided critical information of circRNAs in regulating OMM progression. The findings would help us to develop potential biomarkers for clinical diagnosis and design therapeutic strategies for OMM.

Ultrasound hyperthermia enhances chemo-sensitivity in oral squamous cell carcinoma by TRIF-mediated pathway.

BACKGROUND: Hyperthermia is currently used as an alternative to surgery or in combination with chemotherapy and/or radiation therapy in the treatment of oral squamous cell carcinoma. However, little has been known about the change in chemo-sensitivity after hyperthermia and the mechanism underlie it in oral squamous cell carcinoma. METHODS: The aim of this study was to explore the influence of chemo-sensitivity of CAL-27 and SCC-4 cells by histoculture drug response assay after the animal model treated by the ultrasound hyperthermia. Then, we conducted a microarray between xenograft after hyperthermia at 42°C for 45 minutes and that with no treatment. We further confirmed the expression of TRIF in hyperthermia by immunohistochemistry, RT-PCR and Western blot. RESULTS: The chemo-sensitivity to five kinds of drugs demonstrated ultrasound hyperthermia performed in 42°C for 45 minutes would reach the highest inhibition rate in CAL-27 and SCC-4 cells. The microarray dataset revealed that 847 mRNA were upregulated and 1031 were downregulated. GO and pathway analyses indicated that they play an important role in translational initiation, nucleoplasm, and poly (A) RNA binding in the hyperthermia process. We further confirmed the expression of TRIF was downregulated in hyperthermia along with inactivation of NF-κB pathway. CONCLUSIONS: The experiments confirms the rationality of synchronous combination of hyperthermia and chemotherapy and may provide a better treatment that the use of sensitivity testing in such cases may lead to individualized, more effective therapy.