4016 Background: Challenges persist in the treatment of aEC, particularly for pts with esophageal stenosis and dysphagia, conditions that deteriorate the nutrition status and hinder anti-tumor therapies, leading to dismal prognosis. Building on the promising anti-tumor activity and improvement in dysphagia in a phase II single-arm trial, the phase III DYNA-Esophagus03 trial assessed DVDMS, a novel photosensitizer, -mediated PDT in aEC, comparing to TPC. Methods: Pts with local recurrence or metastasis EC and Stoller dysphagia grade ≥2, stratified by previous treatment lines (1 st vs 2 nd -line), were randomized 2:1 to DVDMS-mediated PDT (PDT delivered 24 hours after 0.2 mg/kg DVDMS injection at a light dose of 102 J/cm² and wavelength of 630±5 nm) or TPC. The primary endpoint was esophageal stenosis overall response rate (es-ORR) assessed by endoscopy at 28 days. A sample size of 186 pts achieved a 90% power to detect an es-ORR increase from 10% to 35% at a 1-side 2.5% level, considering a 30% drop-off rate. Results: As of November 11, 2024, 186 pts were randomly assigned (124 DVDMS-PDT group/62 TPC group). The baseline characteristics were: mean age 67.6 ± 8.7 years, 32.3% distant metastasis, 52.2% grade 3 dysphagia, and 1.1% grade 4. The es-ORR was 51.6% with DVDMS-PDT vs 8.1% with TPC at day 28 (P < 0.0001). At a median follow-up of 8.9 months (mos), the median progression-free survival was 2.8 vs 2.2 mos (HR = 0.61, 95%CI 0.40-0.93; P = 0.0244), respectively. Time to progression was 5.9 vs 3.9 mos (HR = 0.45, 95% CI: 0.25-0.82, P = 0.0056). Median overall survival (OS) was 7.0 vs 6.4 mos (HR = 0.88, 95%CI 0.59-1.32; P = 0.5169), respectively. Considering the high cross-over rate (45.2%), the rank preserving structural failure time-adjusted median OS was 7.0 vs 4.7 mos (HR = 0.64, 95%CI 0.42-0.97; P = 0.0223). The improvement of dysphagia and quality of life are detailed in the Table. Phototoxicity was negative in 64.9% pts in DVDMS-PDT group on day 7, increasing to 91.4% by day 28. Grade ≥3 treatment-emergent adverse events occurred in 38.2% of the DVDMS-PDT group and 49.2% of the TPC group. Six deaths were due to treatment-related adverse events (4.9%) were reported in the DVDMS-PDT group and 5 (8.5%) in the TPC group. Conclusions: DVDMS-PDT significantly improved esophageal stenosis and dysphagia compared to the treatment of physician’s choice in pts with aEC, with prolonged PFS and TTP, potential better OS and a manageable safety profile. Clinical trial information: CTR20221271 . DVDMS-PDT (n=124) TPC (n=62) Reduction at least 1 grade in Stooler's score in 6 mons, % 47.8% 8.6% (P<0.0001) Change in EORTC QLQ-C30 total score -26.7 ± 2.5 -39.8 ± 4.3 Change in dysphagia score 16.0 ± 2.6 24.6 ± 4.3 Change in eating score 16.9 ± 2.4 30.6 ± 4.1 Values are least-squares mean ± standard error unless otherwise noted. Symptom scores were assessed using EORTC QLQ-OES18.

Photodynamic therapy (PDT) for malignant tumors has emerged as a treatment option with unique advantages in preserving patients' appearance and organ function. Four cases illustrate its potential in this area. In cases of facial squamous cell carcinoma and tongue cancer, PDT successfully treated the tumors while preserving the patients' facial aesthetics and tongue function respectively. Conversely, patients with maxillary sinus cancer and another case of tongue cancer faced disfigurement and functional loss due to surgery and radiotherapy. Despite lacking strong evidence-based support to be considered a first-line treatment for these cancers, PDT's ability to preserve patient appearance and organ function when applied promptly after tumor recurrence suggests it may have a pivotal role in certain scenarios. These cases argue that PDT could be ideally suited for situations where preserving patient quality of life is paramount, making it a valuable option in the therapeutic arsenal against malignant tumors.

Background: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy. Photodynamic therapy (PDT) has shown promise as a treatment option for various skin cancers, including EMPD. This study aims to assess the clinical effectiveness of PDT in treating 15 cases of EMPD. Methods: A retrospective analysis was conducted on 15 patients diagnosed with EMPD in the Oncology Department of Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine from June 2014 to December 2024, all of whom received PDT as part of their treatment. According to the therapeutic regimens, patients were stratified into three cohorts: group A received systemic hematoporphyrin-derivative (HpD) PDT (with or without sequential ALA-PDT); group B underwent surgical excision followed by ALA-PDT as an adjunct; and group C was treated with ALA-PDT alone. Clinical outcomes, including lesion regression, recurrence rates, and adverse events, were evaluated during the follow-up period. Results: The treatment of EMPD with PDT resulted in significant clinical improvement in most patients. Complete remission was achieved in 6 of 15 patients (40 %), partial remission was observed in 7 patients (46.7 %). In Group A, complete response was observed in 2 patients, partial response in 6 patients, and minimal response in 1 patient. All three patients in Group B achieved complete response. Group C had one patient in each category (CR 33 %, PR 33 %, MR 33 %). Treatment response was significantly more favourable in group B, in which all patients achieved a complete response (ordered logistic regression, P = 0.031; Group B vs Group A, OR = 18.0). However, among the six patients who achieved complete remission, four experienced disease recurrence during the subsequent follow-up period. The most common complaint was pain. Local infection and scarring were also observed in a small proportion of patients. Conclusions: PDT shows promising results as a non-invasive treatment option for EMPD, providing a favorable balance between effectiveness and safety. The short-term efficacy of photodynamic therapy is highly encouraging; however, its long-term efficacy remains suboptimal. For patients who are unwilling or unsuitable for surgery, photodynamic therapy is a viable alternative. Although photodynamic therapy can achieve complete remission of lesions in some patients, its cure rate is relatively low, and there is a risk of recurrence. Further studies with larger sample sizes are needed to confirm these findings and investigate long-term outcomes.

Objective To evaluate the long-term and systemic antitumor effects of laser immunotherapy, combining photodynamic therapy (PDT) and glycated chitosan, in an H22 hepatoma model. Methods Tumor inhibition, survival rate, and pathology were compared among control, PDT, and laser immunotherapy (PDT + glycated chitosan) groups (n=12). Mice cured by laser immunotherapy were rechallenged with H22 cells (106 and 5 × 106) to assess immune memory. Additionally, its effect on untreated tumors was investigated in a bilateral tumor model by treating only one side. Results Laser immunotherapy increased the cure rate from 25% (PDT alone) to 50%. Rechallenged mice exhibited delayed tumor onset, with 4 remaining tumor-free. Untreated tumors on the contralateral side also showed inhibition. Conclusion Laser immunotherapy, integrating PDT and an immunoadjuvant, shows promise for cancer treatment, particularly for metastatic tumors.

Patchouli oil (PO), extracted from Pogostemon cablin Benth., a prominent aromatic plant of the Lamiaceae family, has shown considerable protective effects against gastrointestinal infections, particularly those induced by Helicobacter pylori. This study aimed to develop a gastro-floating multi-unit system for PO to enhance its gastric retention and oral bioavailability. Methods: The oil-laden granules were prepared using colloidal silicon dioxide (CSD) for oil adsorption and to provide buoyancy, along with ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) to form a sustained-release matrix. The CSD exhibited favorable characteristics for oil adsorption and floating. Compatibility between PO and CSD was affirmed through DSC thermograms and FTIR spectra. The obtained granules demonstrated a sustained release profile, achieving over 90 % release within 10 h without an initial burst. After oral administration, the granules were observed to remain in the gastric region of rats for over 7 h. The bioavailability of patchouli alcohol from the optimized granules was significantly higher than that from of the PO-loaded powders. The gastro-floating sustained-release granules, based on a CSD/EC/HPMC matrix, offer a simple yet effective strategy to improve the delivery efficacy of PO against Helicobacter pylori infections in the gastric region.

Background Long non-coding ribonucleic acids (lncRNAs) are a class of non-coding RNAs implicated in the development of many malignancies, including gastric cancer (GC). In this study, we investigated the functions and molecular mechanisms of non-coding RNA activated by deoxyribonucleic acid damage (NORAD) in GC. Methods NORAD expression at the messenger RNA levels was determined by quantitative reverse transcriptase (RT)-polymerase chain reaction assays. Cell proliferation, migration, and invasion were detected by Cell Counting Kit-8 assays, in-vivo tumor formation assays, and Transwell assays. Cell-cycle distribution was detected by a flow cytometry analysis. NORAD location was detected by nucleocytoplasmic fractionation assays. The interaction between NORAD and the microRNA-204-5p (miR-204-5p)/Lysine Methyltransferase 2D (KMT2D) axis was verified by dual-luciferase reporter gene assays and RNA binding protein immunoprecipitation (RIP) assays. Western blot was used to study the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT) signaling pathway. Results NORAD was upregulated in the GC tissues and cell lines. The silencing of NORAD repressed cell proliferation and the Growth 2 (G2)/Mitosis (M) cell-cycle transition in GC. NORAD also regulated KMT2D expression by targeting miR-204-5p and mediated PTEN/PI3K/AKT signaling in GC. Conclusions We found that NORAD acts as an oncogene in GC. Our findings might provide a novel therapeutic target for GC.

Abstract Background: Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs implicated in the development of many malignancies, including gastric cancer (GC). Herein, we investigated the functions and molecular mechanisms of non-coding RNA activated by DNA damage (NORAD) in GC. Methods: NORAD expression at the mRNA levels was determined by qRT-PCR assay. Cell proliferation, migration and invasion was detected by CCK-8 assay, in vivo tumor formation assay and Transwell assay. NORAD location was detected by nucleocytoplasmic fractionation assay. The interaction between NORAD and miR-204-5p/KMT2D axis was verified by dual-luciferase reporter gene assay and RIP assay. Results: NORAD was upregulated in GC tissues and cell lines. NORAD silencing repressed cell proliferation and G2/M cell cycle transition in GC. NORAD could act as a ceRNA of miR-204-5p and regulate KMT2D expression. Conclusions: Our study demonstrated that NORAD played as an oncogene in GC, which might provide a new therapeutic target for the disease.

Gliomas are the most common primary intracranial tumors, which have genetic heterogeneity. It is impossible to accurately evaluate the dynamic evolution of tumor genes and microenvironment only by pathological examination after surgery. As one of the smallest extracellular vesicles secreted by cells, exosomes can be used as potential biomarkers and carriers of intercellular information transmission. It can promote glioma cell proliferation, immune escape and chemoradiotherapy resistance, improve blood oxygen microenvironment, and enhance the ability of invasion and metastasis. The relations of exosomes with glioma occurrence and development are summarized as follows.

OBJECTIVE:To investigate the correlation between FOXP3, CD11c protein expression and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).METHODS:This study included 48 patients with DLBCL who were admitted to Jiujiang No.1 People's Hospital and TCM-Integrated Hospital of Southern Medical University from January 2015 to January 2019. The DLBCL tissues removed during the operation were collected as test specimens. The expression of FOXP3 and CD11c protein were detected by immunohistochemistry. The deadline for postoperative follow-up was December 31, 2019, and the patient's short-term efficacy (complete remission, partial remission) and progression-free survival were recorded.RESULTS:FOXP3 protein was positively expressed in the nucleus, mostly focally or diffusely distributed, the FOXP3+ rate was 54.17% (26/48). While, the CD11c protein was positively expressed on the cell membrane, mostly diffusely distributed, and the CD11c+ rate was 60.47% (29/48). The expression of FOXP3 and CD11c protein was no significant relationship with age, sex, site of involvement, and lactate dehydrogenase level in DLBCL patients, but was a significant relationship with clinical stage and international prognostic index score, the difference was statistically significant (P<0.05). That was, the lower the clinical stage of DLBCL patients and international prognostic index score, the higher the positive expression rate of FOXP3 and CD11c protein (r=0.637, r=0.709). One year after surgery, the total effective rate of DLBCL patients with FOXP3+ or CD11c+ expression was significantly higher than that of patients with FOXP3- or CD11c-,expression (P<0.05). By the end of the follow-up, the median progression-free survival of DLBCL patients with FOXP3+ or CD11c+ expression was significantly longer than that of patients with FOXP3- or CD11c+ expression (P<0.05).CONCLUSION:In some patients with DLBCL, FOXP3 and CD11c expresse positively, and the positive expression rate is related to the clinical stage and international prognostic index score. The positive expression of FOXP3 and CD11c indicate a good prognosis.

BACKGROUND:Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis.METHODS AND ANALYSIS:This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the "PDT once" group, and the "PDT twice" group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively.ETHICS AND DISSEMINATION:The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital.TRIAL REGISTRATION NUMBER:ChiCTR1800014918 .

Objective: To explore the clinical efficacy of HiPorfin photodynamic therapy for advanced esophageal cancer and evaluate its impact on survival. Methods: Retrospective analysis of 32 patients with advanced obstructive esophageal cancer at our institution from September 2013 to December 2016. HiPorfin was infused as the photosensitizer at a dose of 5 mg/kg, and after 48 hours, 630-nm laser irradiation was subsequently performed through an optical fiber that passed through the biopsy channel of a flexible endoscope. Results: The effectiveness rate was 78.1% (25/32), and the significant efficacy rate was 56.3% (18/32). The dysphagia score decreased from 3.43 ± 0.73 to 1.79 ± 0.53 (P < .05). There was no grade 3 or more toxicity. The median overall survival was estimated to be 16 months. Univariate analysis showed higher overall survival with a Karnofsky Performance Status score ≥80 compared with a Karnofsky Performance Status score <80 (hazard ratio: 2.626; 95% CI: 1.091-6.322; P = .024). Overall survival was higher in patients who had received radiation therapy than in patients who did not receive radiation therapy (hazard ratio: 3.574; 95% CI: 1.501-8.510; P = .002). Conclusion: Photodynamic therapy is an effective method for advanced esophageal cancer. The side effects are mild, and the short-term effect is good, especially in the relief of dysphagia. Photodynamic therapy can prolong the survival of patients with advanced esophageal cancer, and the Karnofsky Performance Status score and previous radiation therapy have a significant effect on the overall survival.

This study was aimed to evaluate the potential function of circ-0001946 in the progression of colorectal cancer (CRC) and the related regulatory mechanism. First, the expression levels of circRNA_0001946 and microRNA-135a-5p (miR-135a-5p) in normal and CRC tissues were measured by quantitative real-time polymerase chain reaction (RT-qPCR). In addition, cell proliferation was assessed by the Cell Counting Kit-8 (CCK-8) assay, cell migration and invasion were evaluated by Transwell assays, and the cell cycle patterns were determined by flow cytometry. The relationship between the expression levels of circ_0001946 and miR-135a-5p was determined by dual-luciferase reporter assays. Our data showed that the expression of circ_0001946 was upregulated in CRC tissues, which was negatively correlated with tumor size, histologic grade, lymphatic metastasis, and TMN stage, and patients with circ_0001946 overexpression were more likely to have a poor prognosis. In addition, in vitro experiments showed that silencing circ_0001946 inhibited the epithelial-mesenchymal transition (EMT) pathway and markedly suppressed CRC cell growth, migration, and invasion. Furthermore, we discovered that the transfection of miR-135a-5p mimics could reverse the antitumor effects of circRNA_0001946 downregulation. To summarize, this study revealed that circRNA_0001946 might act as a tumor promoter by activating the miR-135a-5p/EMT axis and may be a promising treatment target for CRC.

光动力治疗是近些年不断兴起的肿瘤治疗手段,将光敏剂注射到体内后,光敏剂能特异性聚集在肿瘤组织中,再予以特定波长的光照射肿瘤部位,使光敏剂产生光动力学反应,使肿瘤细胞器损伤、肿瘤细胞凋亡及坏死、肿瘤微循环障碍、机体肿瘤免疫等作用机制杀死肿瘤细胞.近年来,作为光动力疗法的关键因素,新的光敏剂及光源不断被探索并应用于临床,关于光动力治疗恶性肿瘤的临床研究日益增多,尤其是头颈部恶性肿瘤.随着新型光敏剂如金丝桃素及相关光源投入使用以及将光动力技术与其他治疗手段相结合后,光动力治疗效果主要观察指标"生存时间"较既往有所延长,相关不良反应如日光性皮炎、药物过敏反应等有所减少,且其在保存重要器官功能完整和美容功能上令人满意.本文对近年来光动力治疗在头颈部恶性肿瘤的临床应用做一综述,重点阐述光动力治疗鼻咽癌、鼻窦癌、喉癌、口腔癌、面部皮肤恶性肿瘤等头颈部常见恶性肿瘤时所体现的疗效好、完整保存重要器官功能、美容及副作用小的优越性,以了解近些年光动力技术对头颈部恶性肿瘤疗效的发展,及表达需进一步研发性能更优的光敏剂和光源、寻找光动力疗法结合其他治疗手段的需求.

Aim: To explore the expression and biological function of long intergenic non-protein coding RNA 1089 (LINC01089) in gastric cancer (GC) progression and its underlying mechanism. Methods: LINC01089 and microRNA-27a-3p (miR-27a-3p) expressions were detected with the quantitative real-time polymerase chain reaction (RT-qPCR). Cell proliferation, migration and invasion were evaluated by Cell Counting Kit-8 (CCK-8) and Transwell assay. Epithelial-mesenchymal transition (EMT)-related proteins were also measured by Western blot. The relationship between LINC01089 and miR-27a-3p was revealed by a bioinformatics analysis and dual-luciferase reporter assay. Results: LINC01089 was significantly down-regulated in GC tissues, as well as GC cell lines. GC patients with lower LINC01089 expression were more likely to have poor outcomes. Overexpression of LINC01089 significantly suppressed GC cells growth, migration and invasion and forbade the EMT process. LINC01089 was directly targeted at miR-27a-3p. The transfection of miR-27a-3p mimics reversed the inhibitory effects on proliferative and metastatic abilities of GC cells with LINC01089 overexpression. Conclusion: LINC01089 inhibits cell proliferation and metastasis in GC by targeting miR27a-3p/EMT axis, which should be considered as a promising therapeutic target.

Metastases and recurrence of cancer are the main causes of failure and death. Induction of a long-term tumor specific immunity seems to be a great strategy to deal with this challenge. Laser immunotherapy (LIT), using immunomodulatory techniques in combination with photodynamic therapy (PDT), so as to enhance an already robust immune response, has been proposed and investigated by numerous researchers. In our study, mice bearing EMT6 breast tumors and 4T1 metastatic breast tumors were addressed in various permutations of the different components in LIT. The survival rates and the tumor growth curve of EMT6 breast tumors bearing mice were analyzed. We compared the level of inflammatory reaction, cell apoptosis and activated immune cells infiltration of local tumors. We validated the systemic effect of LIT through the 4T1 metastatic breast tumors bearing mice. The results not only proved that concomitant with Glycated chitosan (GC) can improve the effect of inhibiting the tumor growth, improving survival, enhancing local inflammatory reaction and attracting acted immune cells to tumor by photodynamic therapy with Photofrin, but also intuitively proved the systemic effect and long-term effect of LIT.

BACKGROUND Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat colon cancer. Despite impressive initial clinical responses, drug resistance has dramatically compromised the effectiveness of DOX. However, the underlying mechanisms of chemotherapeutic resistance in colon cancer remain poorly understood. MATERIAL AND METHODS In this study, we compared the expression of miR-222-3p in DOX-resistant colon cancer cells (LoVo/ADR) with the corresponding DOX-sensitive parental cells (LoVo/S) using quantitative real-time PCR. In addition, miR-222-3p inhibitors were infected into LoVo/ADR cell lines and the effects of this treatment were assessed. The Cell Counting Kit 8 assay was employed to verify the sensitivity of colon cancer cell lines to DOX. EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, and in vivo subcutaneous tumorigenesis were used to assess cell proliferation and apoptosis. Transwell and wound healing assays were used to investigate cell migration after adding DOX. Additionally, the expression of forkhead box protein P2 (FOXP2), P-glycoprotein (P-gp) and caspase pathway-associated markers was assessed by western blotting. RESULTS Our results showed that miR-222-3p was upregulated in LoVo/ADR compared with the expression in LoVo/S cells. Additionally, downregulation of miR-222-3p in LoVo/ADR cells increased their sensitivity to DOX, reduced P-gp expression, and activated the caspase pathway. However, the downregulation of FOXP2 could efficiently reverse the effect of miR-222-3p inhibitors on LoVo/ADR cells. CONCLUSIONS Taken together, our results showed that miR-222-3p induced DOX resistance via suppressing FOXP2, upregulating P-gp, and inhibiting the caspase pathway.

The objective of this study was to hydrophobically modify fenugreek gum (FG) and to further evaluate the potential application of the obtained derivative in liver-targeted drug delivery system. Stearic acid (C18) was conjugated with FG (FG-C18) by a simple esterification reaction. The obtained FG-C18 was then characterized on its chemical structure by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The self-assembled nanomicelles (NMs) of FG-C18 in water were prepared by an ultrasonication method. The average diameter and zeta potential of FG-C18 NMs were 196.70 ± 6.12 nm and -31.79 ± 1.58 mV, respectively. FG-C18 NMs appeared as spherical particles under transmission electron microscopy and possessed a critical micellar concentration of 0.042 mg/ml by pyrene fluorescence probe method. A low toxicity of FG-C18 was revealed on both HepG2 and MCF-7 cells at 0.1-100 mg/ml. Haemolysis of FG-C18 was less than 5%. Cellular uptake of coumarin-6 into HepG2 cells was enhanced by treating with C6-loaded FG-C18 NMs compared to free coumarin-6. These results suggest that FG-C18 have a potential application for a liver targeted drug delivery.

Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related tumor. The role of EBV-encoding miR-BART22 is still unclear in NPC. This study aimed to identify the detailed mechanisms by which EBV-miR-BART22 functions as a tumor-promoting factor and evaluate the action of cinobufotalin in treating EBV-miR-BART22-overexpressing NPC cells. Methods: Using real-time PCR, western blotting, immunohistochemistry, and In situ hybridization, we detected the expression of miR-BART22 and MAP2K4 in tissues and cells, as well as evaluated their clinical relevance in NPC patients. The effects of miR-BART22 on cell metastasis, stemness and DDP chemoresistance were examined by sphere formation assay, side population analysis, transwell, boyden, in vivo xenograft tumor mouse model et al. Western blotting, immunofluorescence staining, luciferase reporter assay, ChIP, EMSA and Co-IP assay et al. were performed to explore the detailed molecular mechanism of EBV-miR-BART22 in NPC. Finally, we estimated the effects and molecular basis of Cinobufotalin on EBV-miR-BART22-overexpressing NPC cells in vitro and in vivo assays. Findings: We observed that EBV-miR-BART22 not only promoted tumor stemness and metastasis, but also enhanced the resistance to Cisplatin (DDP) in vitro and in vivo. Mechanistic analysis indicated that EBV-miR-BART22 directly targeted the MAP2K4 and upregulated non-muscle myosin heavy chain IIA (MYH9) expression by PI3K/AKT/c-Jun-induced transcription. Further, MYH9 interacted with glycogen synthase 3 beta(GSK3 beta) protein and induced its ubiquitin degradation by activating PI3K/AKT/c-Jun-induced ubiquitin transcription and the latter combined with increased TRAF6 E3 ligase, which further bound to GSK3 beta protein. Reductions in the GSK3 beta protein thus promoted beta-catenin expression and nuclear translocation, which induced tumor stemness and the epithelial-to-mesenchymal transition (EMT) signals. Furthermore, we observed that cinobufotalin, a new chemically synthesized compound, significantly suppressed EBV-miR-BART22-induced DDP chemoresistance by upregulating MAP2K4 to suppress MYH9/GSK3 beta/beta-catenin and its downstream tumor stemness and EMT signals in NPC. Finally, clinical data revealed that increased miR-BART22 and reduced MAP2K4 expression caused the poor prognoses of NPC patients. Interpretation: Our study provides a novel mechanism that cinobufotalin reversed the DDP chemoresistance and EMT induced by EBV-miR-BART22 in NPC. (C) 2019 The Authors. Published by Elsevier B.V.

光动力疗法(photodynamic therapy,PDT)是一种联合利用光敏剂、光和氧,通过光动力反应选择性地治疗肿瘤的局部靶向疗法.光敏剂、激光和氧是光动力疗法的三个重要元素,本文主要从PDT的三要素及PDT后肿瘤复发进展的原因进行了综述.

FAM83A is part of an 8-member protein family of unknown function and is reported to be a cancer-promoting and treatment-resistance factor in several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Analysis of the Cancer Genome Atlas (TCGA) showed that FAM83A mRNA expression is upregulated in HCC, as are the protein expression levels in both HCC cell lines and tissues. Clinical data have demonstrated that high FAM83A expression is positively correlated with poor progression-free survival time, thus suggesting its cancer-promoting potential. Functional analyses showed that FAM83A overexpression promoted HCC cell migration and invasion in vitro and suppressed sorafenib sensitivity. Inhibiting FAM83A reversed these results. A pulmonary metastasis model further confirmed that FAM83A promoted HCC cell metastasis in vivo. Mechanistic analyses indicated that FAM83A activated the PI3K/AKT signaling pathway, its downstream c-JUN protein, and epithelial-to-mesenchymal transition (EMT)-related protein levels, including downregulation of E-cadherin and upregulation of Vimentin and N-cadherin. Interestingly, c-JUN induced FAM83A expression by directly binding to its promoter region and thus forming a positive-feedback loop for FAM83A/PI3K/AKT/c-JUN. In conclusion, we demonstrated that FAM83A, as a cancer-metastasis promoter, accelerates migration, invasion and metastasis by activating the PI3K/AKT/c-JUN pathway and inducing its self-expression via feedback, thus forming a FAM83A/PI3K/AKT/c-JUN positive-feedback loop to activate EMT signaling and finally promote HCC migration, invasion and metastasis.