With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To explore the effect of the mucin modulator Talniflumate (Tal) on breast cancer cells and its synergistic effect after combined with the chemotherapy drug paclitaxel (PTX).Methods:The breast cancer cells were cultured in vitro. Lymphocyte proliferation activity assay (MTS) was used to detect the effects of different concentrations of Talniflumate alone and paclitaxel on the survival rate of breast cancer cells. The effects of the above drugs on the apoptosis of breast cancer cells were detected by flow cytometry. Western blot was used to detect the expression of glucosamine transferase (GCNT3) (the target of Talniflumate) in breast cancer cells before and after the treatment with Talniflumate. Transcriptome sequencing clarified the changes in related signaling pathways after treatment with Talniflumate. Results:Talniflumate promoted the apoptosis of breast cancer cells MCF7 and MDA-MB-231 cells in a concentration-dependent manner. The combination of Talniflumate and paclitaxel had a significant synergistic killing effect in MCF7 cells but not MDA-MB-231 cells. Western blot indicated that GCNT3 was highly expressed in MCF7 cells, while almost no expression in MDA-MB-231 cells; Talniflumate could reduce the expression of GCNT3 in MCF7 cells and after combined with paclitaxel, the expression of GCNT3 was downregulated more significantly. Transcriptome sequencing suggested that Talniflumate can regulate the expression of multiple signaling pathways such as TNF, p53, and SNARE.Conclusions:Talniflumate could induce apoptosis of breast cancer cell. Talniflumate combined with paclitaxel has a significant synergistic effect in killing tumor cells in breast cancer cells with high GCNT3 expression such as MCF7. The mechanism of Talniflumate induce apoptosis of breast cancer cells may be related to multiple signaling pathways such as TNF, p53, and SNARE.

Objective:APOBEC3B (A3B) is an important member of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family. The study aims to investigate the relationship between A3B expression and prognosis as well as resistance to cisplatin in non-small cell lung cancer (NSCLC).Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to analysis the A3B mRNA expression in 40 NSCLC tissues; Kaplan Meier plotter was used to analyse the correlation between A3B expression and clinical prognosis; in addition, the knock-down A3B expression cell line in human lung adenocarcinoma cell A549 was constructed; MTS and plate cloning experiment were performed to observe the changes in cell cisplatin sensitivity, and γ-H2AX immunofluorescence was used to quantitate the DNA damage.Results:Compared with adjacent tissues, A3B was highly expressed in NSCLC tissues (27/40). Kaplan Meier plotter analysis showed that A3B expression was positively correlated with NSCLC overall survival (OS) [adenocarcinoma: HR=0.64(0.47-0.86), P=0.002 6; squamous cell carcinoma: HR=0.77(0.59-1.01), P=0.006]. Cell-based studies showed that the knock-down A3B expression contributed to sensitivity to cisplatin in A549 cells. Conclusions:A3B mediates the sensitivity of lung cancer to cisplatin. This effect may partly explain why NSCLC patients with high A3B expression have a better prognosis.

Non-small cell lung cancer (NSCLC) is the histological subtype with highest proportion of lung cancer. Since the discovery of NSCLC driver gene mutations, the drug treatment of NSCLC had evolved from conventional chemotherapy to molecular targeted therapy. Epidermal growth factor receptor (EGFR) was one of the most important driver genes of NSCLC. Three generations of tyrosine kinase inhibitors (TKIs) targeting mutant EGFR had been developed and applied to the clinic, and EGFR-tKIs Targeted therapy had significantly improved the progression-free survival(PFS) and overall survival(OS) of patients with NSCLC. However, most NSCLC patients inevitably developed drug resistance within 10-18 months after receiving targeted therapy with EGFR-TKIs. Great progress had been made on the research of EGFR-TKIs resistance mechanism in recent years. This article intended to briefly review the resistance mechanism of EGFR-TKIs targeted therapy in terms of EGFR secondary mutation, signal bypass activation, cell lineage switching and tumor microenvironment, etc.

Objective To investigate the effect and mechanism of miR-23b on the proliferation and migration of triple negative breast cancer (TNBC) cells.Methods Real time polymerase chain reaction (PCR) was used to detect the expression of miR-23b in triple negative breast cancer tissues.MDA-MB-231/miR-23b,BT549/miR-23b cell lines are constructed.Proliferation assay,scaling healing experiment and Transwell migration assay were used to detect the effect of miR-23b on the proliferation and migration of triple negative breast cancer cells.Dual-luciferase reporter gene assay was employed to examine the interactions between miR-23b and forkhead box C2 (FOXC2).Real time PCR and Western blot were performed to detect the effect of miR-23b on the expression of FOXC2.Results The expression level of miR-23b in triple negative breast cancer tissues was significantly less than that in adjacent normal tissues.miR-23b could reduced the proliferation and migration of triple negative breast cancer cells.Dual-luciferase assay confirmed that miR-23b could regulate the expression and activity of FOXC2.The expression of FOXC2 in mRNA and protein level was inhibited by miR-23b.Conclusions miR-23b can inhibit the expression of FOXC2 and affect the proliferation and migration of triple negative breast cancer cells.

Objective To explore the role and mechanism of long non-coding RNA (lncRNA)RP11-316M1.12 in breast cancer cells.Methods Bioinformatics analysis was performed to varify RP11-316M1.12 expression pattern in breast cancer tissues and normal tissues.Quantitative real time polymerase chain reaction (qRT-PCR) assay was used to check the expression level of RP11-316M1.12 in breast cancer cells and tissues.Further,the correlationship between RP11-316M1.12 expression and clinical paremeters of breast cancer was analysed according to RP11-316M1.12 level.RP11-316M1.12 was overexpressed in MCF-7 cells,and RP11-316M1.12 was knocked down in MDA-MB-231 cells.Transwell method was used to detect the invasive ability of these cells.Western blot was used to detect the expression of epithelialmesenchymal transition (EMT) markers in these cells.Results Gene Expression Profiling Interactive Analysis (GEPIA) database suggested that RP11-316M1.12 was highly expressed in breast cancer tissues than that in normal tissues.The similar results were got in 65 cases of breast cancer tissues and 23 cases of normal tissues by qRT-PCR assay.Meanwhile,we found that RP11-316M1.12 was enhanced in breast cancer cells than that in normal epithelial cell and RP11-316M1.12 expression is related to TNM stage and distant metastasis in breast cancer.Transwell assay demonstrated that RP11-316M1.12 significantly enhanced breast cancer cells invasion.Mechanismly,over expression of RP11-316M1.12 can remakably downregulated E-cadherin,enhanced ZEB1 and Vimentin expression in these cells.Conclusions RP11-316M1.12 was enhanced in breast cancer,and RP1 1-316M1.12 could accelerate invasion of breast cancer cells.

Objective To explore the role of insulin-like growth factor-2/insulin-like growth factor1 receptor/insulin receptor substrate-1 (IGF2/IGF1R/IRS1) signal pathway inducing the chemoresistance of epidermal growth factor receptor 2 (ErbB2) positive breast cancer cells to Herceptin.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay were used to determine the expression levels of IGF2,IGF1 R,and IRS1.The direct targets of miR-126 were validated by dual-luciferase reporter gene assay.In SKBR3/pool2 cells,IGF1 R activity was reduced by an inhibitor of IGF1 R,and IRS1 was knocked-down by shRNAs.Furthermore,3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to evaluate the sensitivity of these treated cells to Herceptin.Results IGF2,IGF1 R,and IRS1 were significantly higher expressed in SKBR3/pool2 cell compared to that in SKBR3 cell.Western blot assay showed that IGF2/IGF1R/IRS1 was activated in SKBR3/pool2 cells.Bioinformatics analysis combined with luciferase activity suggested that miR-126 directly targeted IRS1.MTS results demonstrated that the chemosensitivity to Herceptin of SKBR3/ pool2 cells with inhibitor of IGF1R or shRNAs targeting IRS1 or overexpressing miR-126 was significantly reduced.Conclusions IGF2/IGF1R/IRS1 signal pathway confers to the chemoresistance of ErbB2 positive breast cancer cells to Herceptin.

This review article briefly described the interaction and inner link between chemotherapy tolerance and metastasis of breast cancer.The common pathways of occurrence of drug resistance and metastasis were analyzed with formation and outcome of breast cancer epithelial-mesenchymal transition (EMT) and with enrichment and function of breast cancer stem cells.The chemotherapy which play positive role in clinical practice was pointed out that may cause negative effects by changing tumor microenvironment.Those evidences show that the theory on tumor microenvironment will help to formulate the research strategies for preventing and reversing resistance of breast cancer to drug and metastasis.

Objective To investigate the effect of histone deacetylase inhibitor on Her2 positive breast cancer cell line BT474 and SKBR3 in apoptosis and metastasis.Methods Histone deacetylase inhibitor MS-275,suberoylanilide hydroxamic acid (SAHA)(4 μmol/L,and 50 μmol/iL,respectively) treated the cell lines BT474 and SKBR3 cells.Flow cytometer examined the apoptosis ratio.Transwell tested their metastatic activity.Western blot assay was performed to detect the associated proteins.Results SAHA and MS-275 inhibited the cell survival.The BT474 cell survival was (39 ± 11) ％,(54 ± 8) ％,and the SKBR3 survival was (62 ± 6) ％,(71 ± 9) ％,according to the fluorescence-activated cell sorting (FACS) result.SAHA and MS-275 induced the BT474 cell apoptosis 8.46± 0.28 (P ＜0.01),4.15 ± 0.71 (P ＜0.01) fold change,respectively;and upregulated the SKBR3 cell apoptosis ratio 5.51 ± 1.24 (P ＜0.01),4.04 ±0.69 (P ＜0.01) fold.The Transwell result showed that SAHA,MS-275 inhibited the Transwell ability of BT474 from the control 184.7 ± 18.8 to 104.3 ± 7.1,131.3 ±9.1 per view,and the SKBR3 from control 60 ± 16.7 per view to 14.3 ± 6.5,34.3 ± 8.7 per view.The Western blot result showed that SAHA,MS-275 inhibited the protein level of vimentin,Her2,β-catenin,histone deacetylase inhibitor (HDACi),and upregulated the acetylation level of histone 3.The E-caherin protein was regulated in BT474 and SKBR3 cells.Conclusions MS-275,SAHA can induce BT474 and SKBR3 apoptosis significantly,also inhibit their metastatic activity.

] Objective To explore the role and mechanisms of FGF2 in chemo?resistance in breast cancer. Methods The inhibitors for different signal pathway were used to treat two drug?resistant breast cancer cell lines MCF?7/5?Fu and T47D/5?Fu established in our lab. MTS assay was used to determine chemo?sensitivity and Hoechst stain was used to measure apoptosis. Protein activation and FGF2 protein level in cell culture medium were detected by western blot and ELISA respectively. Results Akt inhibitor MK?2206 (20 nM) and mTOR inhibitor AZD8055 (2 nM) significantly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel, but ERK1/2 inhibitor SCH772984 showed no significant effect. Compared to parent cell lines MCF?7 and T47D, p?Akt and p?S6K (represented as mTORactivity) levels were obviously up?regulated in MCF?7/5?Fu and T47D/5?Fu cell lines, and so do the FGF2 mRNA level and FGF2 protein level from culture medium. Moreover, FGFR inhibitor AZD4547 (4 nM) markedly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel and down?regulated activation of FGFR?Akt?mTOR signal pathway. In agreement, FGF2 protein (10ng/ml) enhanced the chemo?resistance of MCF?7 and T47D cell lines to 5?Fu and paclitaxel and up?regulated activation of FGFR?Akt?mTOR signal pathway. Conclusion Activation of FGF2?FGFR?Akt?mTOR signal pathway promoted chemo?resistance of breast cancer cells.