Navigation-based endoscopic enucleation (NBEE) of large mandibular cystic lesions involving the ramus.

OBJECTIVE: The aim of this study was to present an innovative surgical protocol, navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the mandibular ramus. METHODS: Twelve patients who presented with a large mandibular cystic lesion involving the mandibular ramus were enrolled in this study. Preoperative planning and intraoperative navigation were performed in all 12 patients. RESULTS: All patients in this study were treated with navigation-based endoscopic enucleation successfully. The follow-up period ranged from 7 to 10 months. Bone regenerated was found in all patients postoperatively. Three patients experienced temporary mandibular nerve palsy, and all relieved within 2 months. No pathological bone fracture was found during surgery. CONCLUSIONS: The use of navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the ramus proved to be an effective method for complete and precise enucleation of the cystic lesion that also preserved the surrounding tissue.

Detecting recurrent disease and surgical outcomes in patients with locally advanced tongue cancer after multimodal treatment using ¹8F-FDG-PET/CT.

The purpose of this study was to evaluate the utility of ¹8F-fluorodeoxyglucose positron emission tomography/computed tomography (FPCT) parameters for detecting recurrent disease and the outcomes of salvage surgery in patients with locally advanced oral tongue squamous cell carcinoma (TSCC) after multimodal treatment. In total, 69 patients with locally advanced TSCC were treated with multimodal therapy. All patients underwent whole-body FPCT scans 4-10 months after the initial surgery. The analysis included FPCT parameters, such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Histological examination was used as the reference standard. Patients with recurrent TSCC underwent salvage surgery or surgery plus systemic treatment. This study included 69 patients: 36 in the recurrent TSCC group and 33 in the non-recurrent TSCC group. The SUVmax, MTV, and TLG in the recurrent TSCC group were 11.3 ± 3.6, 28.3 ± 15.6 cm3, and 113.2 ± 46.8 g, respectively; these values were 5.9 ± 3.6, 5.1 ± 2.2 cm3, and 13.4 ± 4.8 g, in the non-recurrent TSCC group respectively. The two groups had significant differences in terms of SUVmax, MTV, and TLG. In the recurrent TSCC group, 91.6 % of patients presented with local, locoregional, and regional disease and underwent salvage surgery plus systemic therapy, whereas 8.4 % had locoregional recurrence with distant metastases alone and underwent surgery plus systemic therapy. The patients were followed up for 12-60 months; 19 and 20 patients in the recurrent and non-recurrent TSCC groups showed no evidence of disease, whereas 11 and 8 were alive with the disease. Local recurrence or distant metastases led to the deaths of six patients in the recurrent TSCC group and five in the non-recurrent TSCC group. No significant differences in survival were observed between the two groups. FPCT parameters can detect the recurrence of locally advanced TSCC after multimodal treatment. Early salvage surgery can improve the treatment outcomes for recurrent TSCC.

Erratum: EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.59331.].

CD79A work as a potential target for the prognosis of patients with OSCC: analysis of immune cell infiltration in oral squamous cell carcinoma based on the CIBERSORTx deconvolution algorithm.

OBJECTIVE: To analyze the abundance of infiltrating tumor immune cells in patients with oral squamous cell carcinoma (OSCC) and to search for potential targets that can predict patient prognosis. METHODS: A total of 400 samples from 210 patients with OSCC were collected using The Cancer Genome Atlas (TCGA) database. CIBERSORTx was used to evaluate the infiltration abundance of tumor immune cells. Potential target genes were searched to predict patient prognosis through case grouping, differential analysis, and enrichment analysis. Surgical excisional tissue sections of patients with oral squamous cell carcinoma admitted to the Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Shantou University Medical College, from 2015 to 2018 were collected and followed up. RESULTS: The CIBERSORTx deconvolution algorithm was used to analyze the infiltration abundance of immune cells in the samples. Cases with a high infiltration abundance of naive and memory B lymphocytes improved the prognosis of OSCC patients. The prognosis of patients with low CD79A expression was significantly better than that of patients with high CD79A expression. CONCLUSION: CD79A can predict the infiltration abundance of B lymphocytes in the tumor microenvironment of patients with OSCC. CD79A is a potential target for predicting the prognosis of patients with OSCC. This study provides novel ideas for the treatment of OSCC and for predicting patient prognosis.

Various Types of Facial-Angular Artery-Based Flaps for Reconstructing Oral and Maxillofacial Defects Following Cancer Ablation.

BACKGROUND: The flap based on the facial-angular vessels (FAVs) has several names and cannot capture the hemodynamics. AIMS: This study was performed to assess the reliability of various types of flaps based on the FAVs for reconstructing oral and maxillofacial defects following cancer ablation. PATIENTS AND METHODS: Forty-three oral and maxillofacial defects were reconstructed with facial-angular artery island flaps (FAAIF, n =14), including V-Y advancement-type and rotation-type flaps based on FAVs and reverse-flow FAAIFs (R-FAAIF, n =29), including ipsilateral, contralateral rotation, full-thickness, and folded types, based on distal FAVs following cancer ablation. The patients (25 males and 18 females) ranged in age from 18 to 82 years. The lesions included basal cell carcinoma ( n =26), squamous cell carcinoma ( n =8), adenoid cystic carcinoma ( n =3), mucoepidermoid carcinoma ( n =3), verrucous carcinoma ( n =2), and nodular melanoma ( n =1). The tumors were classified as clinical stage I to III in 12, 25, and 6 cases, respectively. Lesions were observed in orbital ( n =4), infraorbital ( n =14), glabellar ( n =2), nasal ( n =4), cheek ( n =10), upper lip ( n =3), palate ( n =4), and lower gingival ( n =2) regions. The defects ranged in size from 2.0×2.5 to 5.0×12.0 cm. The skin paddle ranged in size from 1.5×3.0 to 4.0×12.0 cm. RESULTS: There was 1 flap failure, resulting in a flap success rate of 97.7%. Complications, including hematoma, infection, wound dehiscence, and fistula, occurred in 15 (34.9%) patients. Limitations of mouth opening and ectropion occurred in 12 (28.0%) patients. The esthetic outcomes were satisfactory in 36 (83.7%) patients but were not significantly different between the FAAIF and R-FAAIF groups. The patients were followed up for 6 to 60 months. At the time of the last follow-up, 27 (62.8%) patients were alive with no disease, 9 (20.9%) were alive with disease, and 7 (16.3%) had died due to their disease. There was no significant survival difference between the 2 groups. CONCLUSIONS: Various types of FAV-based flaps are valuable reconstructive options for the treatment of oral and maxillofacial defects following clinical stage I-III cancer ablation.

Maxillectomy and Flap Reconstruction of Maxillary Defects After Cancer Ablation Through the Lip-Split Parasymphyseal Mandibulotomy Approach in Patients With Advanced-Stage Maxillary Malignant Tumors.

BACKGROUND: The conventional approach for maxillectomy has some common and serious complications. AIMS: The present study evaluated the outcomes of maxillectomy and flap reconstruction after cancer ablation using the lip-split parasymphyseal mandibulotomy (LPM) approach. METHODS: Twenty-eight patients with malignant tumors, including squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma, underwent maxillectomy through the LPM approach. Brown classes II and III were reconstructed with the facial-submental artery submental island flap, an extensive segmental pectoralis major myocutaneous flap, and a free anterolateral thigh flap with the use of a titanium mesh, respectively. RESULTS: All proximal margin frozen section specimens showed negative surgical margins. Anterolateral thigh flap failure occurred in 1 patient, whereas ophthalmic and mandibulotomy complications developed in 4 and 7 patients, respectively. In all, 84.6% of the patients had satisfactory or excellent lip esthetic results. Of the patients, 57.1% were alive with no evidence of disease, whereas 28.6% were alive with disease and 14.3% died of local recurrence or distant metastasis. No significant survival difference was evident among the squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma groups. CONCLUSIONS: The LPM approach can provide good surgical access, facilitating maxillectomy in advanced-stage malignant tumors with minimal morbidity. Facial-submental artery submental island flap and anterolateral thigh flap or extensive segmental pectoralis major myocutaneous flap with a titanium mesh are ideal techniques for reconstructing Brown classes II and III defects, respectively.

Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling.

BACKGROUND: EGFR is an important signal involved in tumor growth that can induce tumor metastasis and drug resistance. Exploring targets for effective EGFR regulation is an important topic in current research and drug development. Inhibiting EGFR can effectively inhibit the progression and lymph node metastasis of oral squamous cell carcinoma (OSCC) because OSCC is a type of cancer with high EGFR expression. However, the problem of EGFR drug resistance is particularly prominent, and identifying a new target for EGFR regulation could reveal an effective strategy. METHODS: We sequenced wild type or EGFR-resistant OSCC cells and samples from OSCC patients with or without lymph node metastasis to find new targets for EGFR regulation to effectively replace the strategy of directly inhibiting EGFR and exert an antitumor effect. We then investigated the effect of LCN2 on OSCC biological abilities in vitro and in vivo through protein expression regulation. Subsequently, we elucidated the regulatory mechanism of LCN2 through mass spectrometry, protein interaction, immunoblotting, and immunofluorescence analyses. As a proof of concept, a reduction-responsive nanoparticle (NP) platform was engineered for effective LCN2 siRNA (siLCN2) delivery, and a tongue orthotopic xenograft model as well as an EGFR-positive patient-derived xenograft (PDX) model were applied to investigate the curative effect of siLCN2. RESULTS: We identified lipocalin-2 (LCN2), which is upregulated in OSCC metastasis and EGFR resistance. Inhibition of LCN2 expression can effectively inhibit the proliferation and metastasis of OSCC in vitro and in vivo by inhibiting EGFR phosphorylation and downstream signal activation. Mechanistically, LCN2 binds EGFR and enhances the recycling of EGFR, thereby activating the EGFR-MEK-ERK cascade. Inhibition of LCN2 effectively inhibited the activation of EGFR. We translated this finding by systemic delivery of siLCN2 by NPs, which effectively downregulated LCN2 in the tumor tissues, thereby leading to a significant inhibition of the growth and metastasis of xenografts. CONCLUSIONS: This research indicated that targeting LCN2 could be a promising strategy for the treatment of OSCC.

Facial-submental island flap for reconstruction of hemitongue defects in young, middle-aged and elderly patients with early and middle stage oral tongue squamous cell carcinoma.

BACKGROUND: This study evaluated the outcomes of facial-submental artery island flap (FSAIF) for reconstruction of the hemitongue following cancer ablation in patients with early and middle-stage oral tongue squamous cell carcinoma (OTSCC). METHODS: In total, 122 patients with early and middle-stage OTSCC were divided into young, middle-aged, and elderly groups. The Adult Comorbidity Evaluation-27 (ACE-27) index was used to determine the presence of comorbidities. The patients underwent surgical treatment with hemiglossectomy, neck dissection, and hemitongue reconstruction using FSAIF. In addition, stage I (n = 15) and II (n = 69) patients underwent ipsilateral selective neck dissection, whereas those with stage III (n = 38) underwent radical neck dissection. Six patients with T3N1 disease also underwent cobalt-60 adjuvant radiotherapy. RESULTS: Young and elderly patients exhibited significant differences in comorbidities, as assessed by the ACE-27 (p < .05). The skin paddles in the young, middle-aged, and elderly patients were 3 × 9 to 4 × 12 cm, 3 × 11 to 4 × 12, and 3 ×  10 to 5 × 13 cm in size, respectively. FSAIF failure occurred in four patients (success rate: 96.7%). No significant differences were observed in the skin paddle of the flap or rate of flap failure among the age groups (p > .05). Clavien-Dindo grades I, II, IIIa, IIIb, Iva, and IVb were assigned to 7.1, 36.1, 38.5, 9.8, 4.1, and 4.1% of the patients, respectively, with significant differences seen between the young and elderly patients (p < .05). In total, 52.5% of patients could eat normally, whereas 32.8% required a soft diet. Furthermore, 53.3 and 33.6% of patients achieved normal and intelligible speech, respectively. The aesthetic results were rated as excellent and good in 32.8 and 58.2% of patients, respectively. In total, 68.0% of the patients were alive and exhibited no evidence of disease, while 19.7% were alive with active disease. In addition, 12.3% of patients with stage III OTSCC died due to local recurrence or distant metastases. No differences in swallowing, speech, aesthetic, or survival outcomes were observed among the groups. CONCLUSIONS: FSAIF is a simple, safe, and reliable method for reconstructing hemitongue defects following cancer ablation in young, middle-aged, and elderly patients with early and middle-stage OTSCC.

HPV Enhances HNSCC Chemosensitization by Inhibiting SERPINB3 Expression to Disrupt the Fanconi Anemia Pathway.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck, and the prognosis of patients is poor due to chemotherapeutic resistance. Interestingly, patients with HNSCC induced by human papillomavirus (HPV) infection are more sensitive to chemotherapy and display a better prognosis than HPV-negative patients. The biological relevance of HPV infection and the mechanism underlying chemosensitivity to cisplatin remain unknown. Herein, SERPINB3 is identified as an important target for regulation of cisplatin sensitivity by HPV-E6/E7 in HNSCC. Downregulation of SERPINB3 inhibits cisplatin-induced DNA damage repair and enhances the cytotoxicity of cisplatin. In detail, decreasing SERPINB3 expression reduces the USP1-mediated deubiquitination of FANCD2-FANCI in the Fanconi anemia pathway, thereby interfering with cisplatin-induced DNA interstrand crosslinks repair and further contributing to HNSCC cell apoptosis. To translate this finding, pH-responsive nanoparticles are used to deliver SERPINB3 small interfering RNA in combination with cisplatin, and this treatment successfully reverses cisplatin chemotherapeutic resistance in a patient-derived xenograft model from HPV-negative HNSCC. Taken together, these findings suggest that targeting SERPINB3 based on HPV-positive HNSCC is a potential strategy to overcome cisplatin resistance in HPV-negative HNSCC and improves the prognosis of this disease.

RPS3 Promotes the Metastasis and Cisplatin Resistance of Adenoid Cystic Carcinoma.

Background: Adenoid cystic carcinoma (ACC) is a malignant tumor in salivary gland tissue, that is characterized by strong invasiveness and lung metastasis, leading to poor survival rates. RPS3 is been reported to be associated with the biological functions of tumor cells. This study explored the regulatory effect of RPS3 in ACC to provide new therapeutic targets for ACC therapy. Methods: We reviewed the clinical and pathologic data of 73 ACC patients. The expression of RPS3 was examined in ACC by immunohistochemistry. Transwell, wound healing, half-maximal inhibitory concentration (IC50) and other experiments were used to determine the regulatory effect of RPS3 on ACC functions. Coimmunoprecipitation and mass spectrometry analysis were used to detect the binding proteins of RPS3, mechanisms by which RPS3/STAT1/NF-kB signaling regulates ACC behavior were assessed using western blotting (WB), qPCR, etc. To explore the regulatory effect of RPS3 on ACC in vivo, we constructed nude mouse sciatic nerve infiltration model and a lung metastasis model for studies. Results: High RPS3 expression was associated with metastasis and a poor prognosis in ACC patients. Inhibition of RPS3 expression reduced ACC migration, invasion and cisplatin resistance, and overexpression of RPS3 promoted ACC migration, invasion and cisplatin resistance. Further experiments revealed that RPS3 can activate the STAT1/NF-kB signaling pathway and regulate ACC behavior through binding to STAT1. The incidence of sciatic nerve infiltration and lung metastasis in nude mice after RPS3 knockdown was lower than that of the control group in vivo. Conclusion: RPS3 is highly expressed and associated with the prognosis and survival of ACC patients. The RPS3/STAT1/NF-kB pathway may play an important regulatory role in ACC migration, invasion and chemoresistance. As a new therapeutic target of ACC, its clinical application value is worthy of attention and further exploration.

Progression and postoperative complications of osteoradionecrosis of the jaw: a 20-year retrospective study of 124 non-nasopharyngeal cancer cases and meta-analysis.

BACKGROUND: To assess the contributing risk factors for the progression of, and the postoperative poor prognosis associated with, osteoradionecrosis of jaw (ORNJ) following non-nasopharyngeal cancer treatment in head and neck. METHODS: A retrospective study of 124 non-nasopharyngeal carcinoma patients in head and neck treated at one institution between 2001 and 2020 was conducted. A cumulative meta-analysis was conducted according to PRISMA protocol and the electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. After assessing surgery with jaw lesions as a risk factor for the occurrence of ORNJ, 124 cases were categorized into two groups according to the "BS" classification, after which jaw lesions, chemotherapy, flap reconstruction and onset time of ORNJ were analyzed through the chi-square test and t-test to demonstrate the potential association between them and the progression of ORNJ. Postoperative outcomes of wound healing, occlusal disorders, and nerve injury were statistically analyzed. RESULTS: With the statistically significant results of the meta-analysis (odds ratio = 3.07, 95% CI: 1.84-5.13, p < 0.0001), the chi-square test and t-test were used to validate our hypotheses and identified that surgery with jaw lesions could aggravate the progression and accelerate the appearance of ORNJ. Patients who underwent chemotherapy tended to suffer from severe-to-advanced osteonecrosis but did not shorten the onset time of ORNJ. Flap reconstruction presented obvious advantages in wound healing (p < 0.001) and disordered occlusion (p < 0.005). The mean onset time of ORNJ in non-nasopharyngeal cancer patients (4.5 years) was less than that in patients with nasopharyngeal cancer (NPC) (6.8 years). CONCLUSIONS: Iatrogenic jaw lesions are evaluated as a significant risk factor in the occurrence and progression of ORNJ in non-nasopharyngeal carcinoma patients who tend to have more severe and earlier osteonecrosis after radiotherapy than NPC patients. Flap reconstruction is a better choice for protecting the remaining bone tissue and reducing postoperative complications of ORNJ.

Trichosanthin inhibits cell growth and metastasis by promoting pyroptosis in non-small cell lung cancer.

Background: A number of studies have demonstrated that trichosanthin (TCS) can induce apoptosis in numerous types of tumor cell lines. However, whether TCS can induce pyroptosis has not yet been reported. This study aimed to investigate the role of TCS and its inhibitory effect on tumor growth by modulating pyroptosis in non-small cell lung cancer (NSCLC). Methods: Effects of different concentrations of TCS on the cell viability, proliferation, migration and invasion of NSCLC were detected by Cell Counting Kit-8 (CCK-8), colony formation, migration, and invasion assays. Immunofluorescence was used to detect the effect of TCS on the expression of pyroptosis marker protein gasdermin-D (GSDMD)-N in A549 cells. A tumor xenograft animal model was established by injecting A549 cells into nude mice. Results: In the present study, we found that TCS significantly inhibited the proliferation, migration, and invasion of A549 cells in a concentration-dependent manner. In addition, TCS at a high concentration (40 µg/mL) significantly promoted the expression of pyroptosis-related proteins [GSDMD-N, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and GSDMD], which showed an inhibitory effect on the pyroptosis of A549 cells. Additionally, we found that necrosulfonamide (NSA) significantly reversed the inhibitory effect of high concentrations of TCS on the pyroptosis of A549 cells. The in vivo experiments showed that TCS effectively reduced the tumor volume and inhibited the expression of Ki-67, whereas it increased the expression of GSDMD-N. Conclusions: Taken together, these results indicated that TCS could inhibit the progression of NSCLC by promoting pyroptosis. These findings provide further information on the possible underlying mechanism of TCS in the treatment of NSCLC.

GSDMD enhances cisplatin-induced apoptosis by promoting the phosphorylation of eIF2α and activating the ER-stress response.

GSDMD is the key effector of pyroptosis, but its non-pyroptosis-related functions have seldom been reported. Here, we report that GSDMD is overexpressed in different types of tumours, including head and neck squamous-cell carcinoma, and it promotes the sensitivity of tumour cells to cisplatin. Unexpectedly, the enhanced cisplatin sensitivity is mediated by apoptosis but not pyroptosis, the well-known function of GSDMD. Furthermore, we found that GSDMD can activate the unfolded protein response by promoting the phosphorylation of eIF2α. Mechanistically, we demonstrated that GSDMD can directly bind to eIF2α and enhance the interaction between eIF2α and its upstream kinase PERK, leading to eIF2α phosphorylation. Consequently, the protein levels of ATF-4 were upregulated, downstream apoptosis-related proteins such as CHOP were activated, and apoptosis was induced. Remarkably, activation of endoplasmic-reticulum (ER) stress induced by GSDMD promotes cell apoptosis during cisplatin chemotherapy, thereby increasing the treatment sensitivity of tumours. Therefore, for the first time, our work reveals an unreported nonpyroptotic function of the classic pyroptosis protein GSDMD: it promotes cell apoptosis during cisplatin chemotherapy by inducing eIF2α phosphorylation and ER stress, which are related to the drug sensitivity of tumours. Our study also indicated that GSDMD might serve as a biomarker for cisplatin sensitivity.

Application of an L-shaped anterolateral thigh flap in reconstruction after hemiglossectomy.

OBJECTIVE: Tongue defect reconstruction is one of the key components of tongue cancer surgery. In this study, we used an L-shaped flap design adopted as a simple and efficient method to repair tongue defects after hemiglossectomy. Furthermore, we evaluated and contrasted the clinical effects of two methods, the L-shaped and traditional methods. STUDY DESIGN: Fifteen patients in the L-shaped group and 20 patients in the traditional group were evaluated and compared in terms of postoperative complications, dysphagia, language function and appearance satisfaction. RESULTS: The results (Table 1) showed that there were 2 cases of donor area invalid traumas, and 2 patients had scar hyperplasia in the traditional group. The degree of global and functional dysphagia of the L-shaped group (2.60 ± 0.29 and 11.47 ± 1.38) was lower than that of the traditional group (3.55 ± 0.29 and 15.75 ± 1.22) (P < 0.05). In the language evaluation, the traditional group (3.20 ± 0.26) had lower scores than the L-shaped group (4.13 ± 0.30) (P < 0.05). CONCLUSION: The L-shaped ALTP flap is a simple and efficient modification of ALTP, that can be used for half-tongue repair after radical operations for tongue cancer. It has better performance in the recovery of dysphagia and language function than the traditional ALTP flap.

Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth.

Deregulated store-operated calcium entry (SOCE) mediated by aberrant STIM1-ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1ß, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1ß, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca2+ signaling. At the molecular level, the 31-residue insertion destabilizes STIM1ß by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1ß depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant-specific tumor-promoting role of STIM1ß that can be potentially targeted for glioblastoma intervention.

Nucleus-specific RNAi nanoplatform for targeted regulation of nuclear lncRNA function and effective cancer therapy.

In the context of cancer therapy, a recently identified therapeutic target is represented by the essential subtype of RNA transcripts - the long noncoding RNAs (lncRNA). While this is the case, it is especially difficult to successfully regulate the expression of this subtype in vivo, particularly due to the protection granted by the nuclear envelope of nuclear lncRNAs. This study documents the development of a nucleus-specific RNA interference (RNAi) nanoparticle (NP) platform for the targeted regulation of the nuclear lncRNA function, in order to effectuate successful cancer therapy. An NTPA (nucleus-targeting peptide amphiphile) and an endosomal pH-responsive polymer make up the novel RNAi nanoplatform in development, which is capable of complexing siRNA. The nanoplatform is capable of accumulating greatly in the tumor tissues and being internalized by tumor cells, following intravenous administration. The exposed complexes of the NTPA/siRNA may conveniently escape from the endosome with the pH-triggered NP disassociation, following which it can target the nucleus by specifically interacting with the importin α/ß heterodimer. In orthotopic and subcutaneous xenograft tumor models, this would result in a notable suppression of the expression of nuclear lncNEAT2 as well as greatly impede the growth of tumors in liver cancer.

Outcomes of patients with mucoepidermoid carcinoma of minor salivary gland in palate undergoing radical resection followed by submental flap reconstruction.

OBJECTIVE: To investigate the outcomes of patients with mucoepidermoid carcinoma of the palate undergoing pedicled facial-submental artery island flap (FSIF) reconstruction following resection. PATIENTS AND METHODS: 41 patients with early stage disease and 9 patients with advanced-stage disease underwent radical excision and neck dissection. 37 IIb, 4 class IIa and 9 IIIb maxillary defects were reconstructed with FSIF, folded FSIF or folded FSIF with titanium mesh respectively. The skin paddles were 3 × 8 to 5 × 15 cm and 3 × 8 to 5 × 14 cm, respectively. 5 patients with high grade disease were treated with cobalt 60 adjuvant radiotherapy after operation. RESULTS: One flap failure occurred, yielding a success rate of 98.0% in the reconstruction of palate II and III defects with FSIF or titanium mesh. The patients were seen for follow-up for 16-60 months postoperative. 76.0% patients alive with no disease (AND); 14.0% patients alive with disease (AD) and 10.0% died of disease (DD). Rates of AND, AD and DD differed significantly according to histopathologic grade and TNM stage (P < 0.001); rates of AND, AD and DD differed obviously according to necrosis of the tumors lymph node metastasis, and tumour cell anaplasia and treatment (P < 0.05). CONCLUSIONS: Radical resection with wide safety margins of normal tissues including neck dissection is the mainstay of treatment modality. The patients with high grade disease should be treated with postoperative radiotherapy. The FSIF is a reliable and safe method for repairing Brown class II maxillary defects.

Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety.

Chimeric antigen receptor (CAR) T cell-based immunotherapy, approved by the US Food and Drug Administration, has shown curative potential in patients with haematological malignancies. However, owing to the lack of control over the location and duration of the anti-tumour immune response, CAR T cell therapy still faces safety challenges arising from cytokine release syndrome and on-target, off-tumour toxicity. Herein, we present the design of light-switchable CAR (designated LiCAR) T cells that allow real-time phototunable activation of therapeutic T cells to precisely induce tumour cell killing. When coupled with imaging-guided, surgically removable upconversion nanoplates that have enhanced near-infrared-to-blue upconversion luminescence as miniature deep-tissue photon transducers, LiCAR T cells enable both spatial and temporal control over T cell-mediated anti-tumour therapeutic activity in vivo with greatly mitigated side effects. Our nano-optogenetic immunomodulation platform not only provides a unique approach to interrogate CAR-mediated anti-tumour immunity, but also sets the stage for developing precision medicine to deliver personalized anticancer therapy.

EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway.

Background: Malignant proliferation and cervical lymphatic metastasis restrict the prognosis of oral squamous cell carcinoma (OSCC). Erythropoietin-producing human hepatocellular B4 (EPHB4) regulates a series of tumour functions involving tumourigenesis, cancer cell attachment and metastasis. However, the mechanism of EphB4 regulating the malignant progression of OSCC has not been fully elucidated. Methods: EPHB4 expression was analysed in 65 OSCC samples and adjacent noncancerous tissues through immunohistochemistry (IHC). siRNA and overexpression plasmids were transfected into OSCC cells to modify EPHB4 expression, and then, regulatory functions were explored in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry were applied to detect proteins interacting with EPHB4. Subsequently, protein stability assays and NF-κB pathway inhibition assays were used to verify the regulation of EPHB4, high-mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) activation. Results: EPHB4 was found to be highly expressed in OSCC tissues, which was related to tumour stage and lymphatic metastasis and resulted in a poor prognosis. Cellular experiments and mouse tongue xenograft models further confirmed that high EPHB4 expression promoted the proliferation and metastasis of OSCC tumours. Mechanistically, co-IP and mass spectrometry studies indicated that EPHB4 could bind to HMGB1 and maintain HMGB1 stability. Downregulation of HMGB1 inhibited the proliferation and metastasis of OSCC cells and inhibited NF-κB phosphorylation activation but did not affect EPHB4 expression. Conclusion: This study revealed the mechanism by which EPHB4 promotes the proliferation and metastasis of OSCC by activating the HMGB1-mediated NF-κB signalling pathway, which can be exploited as a novel marker or therapeutic target to control metastasis and improve the survival rate of OSCC.