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Purpose To apply propensity score matching to evaluate the impact of peripapillary staphylomas (PPS) on vascular and structural characteristics in the myopic eyes. Methods This was a prospective, cross-sectional study. Forty-one control eyes and 41 eyes with PPS were analyzed. The eyes were selected using propensity score matching analysis based on the age and axial length. All subjects underwent ophthalmologic examinations for assessing vessel and structure parameters using swept-source optical coherence tomography (SS-OCT), OCT angiography, color fundus photography, and ocular biometry. Results As compared with control eyes, the eyes with PPS had shallower anterior chamber depth (3.61 ± 0.24 mm vs 3.77 ± 0.24 mm, P = 0.004), higher intraocular pressure (IOP) (16.59 ± 2.88 mmHg vs 14.53 ± 2.45 mmHg, P = 0.002), and higher myopic spherical equivalent (− 11.52 ± 3.22D vs − 9.88 ± 2.20D, P = 0.009). while corneal curvature and lens thickness between the two groups were not statistically different. Compared with control eyes, increased macular deep vessel density, reduced macular choriocapillaris and radial peripapillary capillary, and thinning retinal layer, ganglion cell complex, choroidal layer as well as the superior and inferior peripapillary retinal nerve fiber layer were observed in eyes with PPS, apart from larger disc area, parapapillary atrophy area, and degree of disc rotation. Logistic regression analysis revealed that the IOP (P = 0.046), disc rotation (P = 0.003), and average peripapillary choroidal thickness (P = 0.009) were associated with the presence of PPS. Conclusion Close association of PPS with exacerbation of myopia and anatomical alterations was observed which not only affected the eye posterior segment but also the anterior segments. We further identified significant reductions in the radial peripapillary capillary and macular choroidal perfusion with the increase in macular deep retinal flow blood of myopic eyes with PPS. Higher IOP, thinner peripapillary choroidal thickness, and rotated optic disc were risk factors for the presence of PPS.

High myopia is of worldwide concern due to its high prevalence, and myopia is an independent risk factor for glaucoma. The purpose of this paper is to review the mechanism and clinical manifestations of optic disc tilt and rotation in high myopia and its relationship with glaucoma, to provide clues for monitoring fundus changes in high myopia and the early diagnosis of high myopia with glaucoma.

Background CircRNAs, new non-coding RNA as miRNA sponge, play crucial roles in tumor initiation and development. The present study aimed to identify hsa_circ_0001451 and its related molecules for the progression of gastric cancer. Methods The expression of hsa_circ_0001451 was determined in 66 cases of paired gastric cancer and their adjacent normal gastric tissues by qRT-PCR. The cellular localization of hsa_circ_0001451 was detected with FISH analysis. The biofunction alterations of hsa_circ_0001451 were assessed by its overexpression or knockdown in gastric cancer cell lines. MTS and cloning assay were used to detect cell proliferation. Flow cytometry was used to detect cell cycle. The wound healing and transwell assays were used for cell migration and invasion. Western Blotting was used to detect the expression of a set of genes related proliferation and migration. RNA immunoprecipitation (RIP), biotinylated RNA pull-down and dual luciferase reporter tests were used to detect the interactions of hsa_circ_0001451with mir-197-3p / MT3. The in vivo proliferation and migration ability of hsa_circ_0001451infected cells were determined in zebrafish system. Results Hsa_circ_0001451 was decreased in 66 cases of gastric cancer tissues and cell lines, and significantly related to tumor invasion. The in vitro and in vivo studies indicated that over-expression of hsa_circ_0001451 inhibited the gastric cancer cell proliferation, invasion and migration via suppression of PCNA, CCND1 and BCL-2, and decreased in the S-phase. The results of pull-down, RNA immunoprecipitation and dual-luciferase reporter tests revealed that hsa_circ_0001451 could sponge miR-197-3p, targeting MT3 and affecting the malignancy of gastric cancer cells via regulating EMT related E-cadherin, N-cadherin, MMP7 and VIMENTIN. Conclusion This study revealed that hsa-circ-0001451 inhibited proliferation, invasion and metastasis and modulated EMT of gastric cancer cells via sponging of miR-197-3p and regulatng the downstream MT3. The circ_0001451 / miR-197-3p / MT3 axis are likely to be the biomarkers for prognosis and targets for drug of gastric cancer.

Diabetic gastroparesis (DGP) is a serious and chronic complication of long-standing diabetes mellitus, which brings a heavy burden to individuals and society. Traditional Chinese medicine (TCM) is considered a complementary and alternative therapy for DGP patients. Huanglian (Coptidis Rhizoma, HL) and Banxia (Pinelliae Rhizoma, BX) combined as herb pair have been frequently used in TCM prescriptions, which can effectively treat DGP in China. In this article, a practical application of TCM network pharmacological approach was used for the research on herb pair HL-BX in the treatment of DGP. Firstly, twenty-seven potential active components of HL-BX were screened from the TCMSP database, and their potential targets were also retrieved. Then, the compound-target network and PPI network were constructed from predicted common targets, and several key targets were found based on the degree of the network. Next, GO and KEGG enrichment analyses were conducted to obtain several significantly enriched terms. Finally, the experimental verification was made. The results demonstrated that network pharmacological approach was a powerful means for identifying bioactive ingredients and mechanisms of action for TCM. Network pharmacology provided an effective strategy for TCM modern research.

Huocong He,1,*,* Lurong Zhang,1,* Keyu Lin,1,* Zhengrong Huang,2 Yan Zhou,3 Shaojun Lin,4 Ying Su,1 Jianru Pan5 1Laboratory of Radiation Biology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 2Department of Integrative Medicine, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 3Department of Epidemiology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 4Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University, Fuzhou, Fujian, 350014, People’s Republic of China; 5College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian, 350002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huocong HeLaboratory of Radiation Biology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of ChinaEmail hconghe@163.comJianru PanCollege of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian, 350002, People’s Republic of ChinaEmail panjr@fzu.edu.cnBackground: Paraspeckle component 1 (PSPC1) is overexpressed in various cancer and correlated with poor survival in the patients. However, little is known about its expression and role in the progression of nasopharyngeal carcinomas (NPC). The purpose of this study is to examine PSPC1 expression in NPC and explore its role in clinical prognosis of radiation therapy.Methods: The association of PSPC1 expression with clinicopathological features of 109 NPC patients was examined using partial correlation analysis. Cancer tissues were obtained prior to clinical treatment. All cases were diagnosed and pathologically confirmed to be poorly differentiated or undifferentiated NPC without distant metastasis. The patients were then treated with radiation and followed-up. Survival analysis was performed.Results: Partial correlation analysis revealed that the PSPC1 expression in NPC was correlated with N classification, recurrence, prognosis and radiosensitivity in NPC patients, but not with the gender, age, pathohistological pattern, clinical stage, and T classification. The overexpression of PSPC1 was detected in 64 samples (58.72%). Kaplan–Meier survival analysis revealed that the overall survival (OS) was longer in NPC patients with PSPC1 low expression than that in those with PSPC1 high expression. Moreover, patients with the overexpression of PSPC1 had a low progression-free survival and distant metastasis-free survival rate, compared to those who had a low expression of PSPC1. Although not statistically significant, patients with high expression of PSPC1 had a lower locoregional recurrence-free survival rate than those with low expression, and the curves between the two groups was well separated.Conclusion: PSPC1 overexpression was associated with poor prognosis for NPC, which might be a novel useful biomarker to predict the response of NPC to radiation therapy and its clinical outcome.Keywords: nasopharyngeal carcinoma, paraspeckle component 1, PSPC1, clinical prognosis, radiation, overexpression

Objective To investigate the microvasculature and structural characteristics of the eyes of myopic patients and their association with posterior staphyloma (PS). Methods This was a retrospective, case-control study comprising of 106 eyes from 72 individuals. Using 1:1 matching of axial length (AL) of their eyes, patients were allocated into a PS group or no posterior staphyloma (NPS) group. All patients were examined using ultra-widefield fundus imaging, optical coherence tomography angiography, and ocular biometry to acquire microvasculature and microstructure parameters. Results The anterior chamber depth (ACD) of the PS group was significantly different from that of the NPS group (3.56 mm vs 3.76 mm, P < 0.001), as was 1ens thickness (3.72 mm vs 3.57 mm, P = 0.005) and spherical equivalent (SE)(-10.11D vs -8.80D, P = 0.014). The PS group had reduced choriocapillaris flow, subfoveal choroidal thickness (SFCT), and a thinner retinal layer compared with the NPS group. No difference in retinal blood flow between the two groups was observed. The PS group exhibited a smaller disc area (15082.89 vs 17,043.32, P = 0.003) and angle α between temporal retinal arterial vascular arcades (113.29°vs 128.39°, P = 0.003), a larger disc tilt ratio (1.41 vs 1.24, P < 0.001) and parapapillary atrophy (PPA) area (13840.98 vs 8753.86, P = 0.020), compared with the NPS group. Multivariate regression analysis indicated that disc tilt ratio (P = 0.031) and SFCT (P = 0.015) were significant predictors of PS. In addition, PS (P = 0.049), AL (P = 0.003), corneal refractive power (P < 0.001), ACD (P = 0.022), relative lens position (P = 0.045), and disc area (P = 0.011) were significant predictors of SE. Conclusions PS was found to be closely linked to a reduction in choriocapillaris perfusion and anatomical abnormalities including posterior and anterior segments. Furthermore, PS exacerbated the progression of myopia.

Our previous research suggests that 3-deoxyglucosone (3DG), formed in the caramelization course and Maillard reactions in food, is an independent factor for the development of prediabetes. Since the relationship between type 2 diabetes (T2D) and intestinal microbiota is moving from correlation to causality, we investigated the alterations in the composition and function of the intestinal microbiota in 3DG-induced prediabetic rats. Rats were given 50 mg/kg 3DG by intragastric administration for two weeks. Microbial profiling in faeces samples was determined through the 16S rRNA gene sequence. The glucagon-like peptide 2 (GLP-2) and lipopolysaccharide (LPS) levels in plasma and intestinal tissues were measured by ELISA and Limulus test, respectively. 3DG treatment did not significantly change the richness and evenness but affected the composition of intestinal microbiota. At the phylum level, 3DG treatment increased the abundance of nondominant bacteria Proteobacteria but did not cause the change of the dominant bacteria. Meanwhile, the abundance of the Prevotellaceae family and Parasutterela genus and the Alcaligencaeae family and Burkholderiales order and its attachment to the Betaproteobacteria class were overrepresented in the 3DG group. The bacteria of Candidatus Soleaferrea genus, Gelria genus, and Thermoanaerobacteraceae family and its attachment to Thermoanaerobacterales order were apparently more abundant in the control group. In addition, 45 KEGG pathways were altered after two-week intragastric administration of 3DG. Among these KEGG pathways, 13 KEGG pathways were involved in host metabolic function related to amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and metabolism of terpenoids and polyketides. Moreover, the increased LPS levels and the decreased GLP-2 concentration in plasma and intestinal tissues were observed in 3DG-treated rats, together with the impaired fasting glucose and oral glucose tolerance. The alterations in composition and function of the intestinal microbiota were observed in 3DG-treated rats, which provides a possible mechanism linking exogenous 3DG intake to the development of prediabetes.

Lysyl oxidase (LOX) is involved in fibrosis by catalyzing collagen cross-linking. Previous work observed that Triptolide (TPL) alleviated radiation-induced pulmonary fibrosis (RIPF), but it is unknown whether the anti-RIPF effect of TPL is related to LOX. In a mouse model of RIPF, we found that LOX persistently increased in RIPF which was significantly lowered by TPL. Excessive LOX aggravated fibrotic lesions in RIPF, while LOX inhibition mitigated RIPF. Irradiation enhanced the transcription and synthesis of LOX by lung fibroblasts through IKKβ/NFκB activation, and siRNA knockdown IKKβ largely abolished LOX production. By interfering radiation induced IKKβ activation, TPL prevented NFκB nuclear translocation and DNA binding, and potently decreased LOX synthesis. Our results demonstrate that the anti-RIPF effect of TPL is associated with reduction of LOX production which mediated by inhibition of IKKβ/NFκB pathway.

Clear cell renal cell carcinoma (ccRCC) is a highly aggressive disease and ∼30% of the patients are diagnosed at the metastatic stage. Even with new targeted therapies, the average progression-free...

Rationale: Accumulating evidence supports the importance of radiation therapy in the induction of antitumor immunity. Small extracellular vesicles (sEVs) play essential roles in tumor antigen loading and delivery. However, the role of sEVs in radiation-induced antitumor immunity remains unclear. It is therefore important to determine the role and regulatory mechanisms of sEVs in radiation-induced immunity. Methods: Tumor cells were irradiated (8 Gy), and sEVs were purified via ultracentrifugation. Primary tumor and experimental lung metastasis models were established in mice to evaluate antitumor immunity triggered by immunization with sEVs. Proteomic and bioinformatic analyses were performed to identify altered cargos in sEVs induced by radiation. Peptides derived from up-regulated proteins in sEVs were designed and synthesized as vaccines according to major histocompatibility complex (MHC) I binding and immunogenicity. Results: Here, we demonstrated that sEVs derived from irradiated tumor cells could trigger antitumor immunity against primary tumor and experimental lung metastasis by enhancing CD8+ and CD4+ T cell infiltration. Radiation may also enrich sEVs with tumor antigens and heat-shock proteins. Furthermore, CUB domain-containing protein 1 (CDCP1) derived from radiation-induced sEVs was identified as a novel tumor-associated antigen and developed as a peptide vaccine that may generate antitumor immune responses. Conclusions: Our results demonstrate that the use of sEVs secreted by irradiated tumor cells constitutes an efficient approach for tumor antigen delivery and presentation and highlight the role of sEVs in radiation-triggered antitumor immunity.

The clinical value of Decoy receptor 3 (DcR3) in severe burn is investigated. Ten patients with severe burns were monitored for DcR3, PCT, CRP, IL6, SOFA score, white blood cell (WBC), and platelet. The correlations were analyzed. DcR3 increased on day 1. The nonsurvivors had a steady high level of DcR3 while the survivors had a relatively low level of DcR3. The peak magnitude of DcR3 was high in five nonsurvivors and low in five survivors without overlap. Three patients had a continuously increasing DcR3 level and then died. In the other two nonsurvivors, DcR3 reached the peak and then decreased before death. DcR3 correlated well with PCT (ρ = 0.4469, P < .0001), less with CRP, platelet, IL6, SOFA score and WBC (ρ = 0.4369, 0.4078, 0.3995, 0.2631, 0.1504, respectively, all P < .001). To explore the mechanisms, the HaCaT or THP-1 cells were stimulated by the plasma of burn patients, 45°C, LPS or stimulators of TLRs or NOD2 (PGN, CL264, MDP, iE-DAP, Gardiquimod), and their DcR3 was increased, which could be reduced by GDC-0941 or BEZ235 (inhibitors of PI3K and mTOR). The levels of DcR3 appeared to be a useful biomarker for monitoring the clinical severity and a predictor of mortality of severe burns.

Background: Active immunotherapy is an effective, long-lasting, cheap and safe way to suppress the progression of cancer, however, the key issue is to find the appropriate tumor vaccines. Oncoproteins are up-regulated under various stresses, such as radiation, chemodrugs, targeted drugs, hypoxia, malnutrition and so on to promote the cell growth, suppress apoptosis and alter the micro-environment for survival locally and remotely. Oncoproteins and their immunogenic domain could well serve as tumor vaccines to prime the host active anti-tumor immunity, which might enhance the immune (such as anti-PD-1) modulators given exogenously on effective stage. Methods: Proteomics and bio-information analysis were performed to identify potential tumor associated antigens (TAAs) induced by 8 Gy irradiation (IR). Then, peptides derived from CD151 were designed and synthesized according to MHC I binding and immunogenicity. Cell killing assay, flow cytometer, immunohistochemistry staining, and in vivo bioluminescence imaging were applied to assessed active anti-tumor immunity triggered by CD151 peptides in H22 hepatoma primary tumor and experimental 4T1 breast cancer lung metastasis model. Results: We utilized 8 Gy irradiation as therapeutic stress to up-regulate a panel of oncoproteins, and identified CD151 as a TAA according to proteomics and bio-information analysis. Two CD151 peptides were synthesized as "tumor vaccine" to immunize the mice, which triggered active anti-cancer immunity against both the primary growth of H22 hepatoma and the lung metastasis of 4T1 breast cancer in two mouse model via activation of CD8+IFNγ+ lymphocytes and their targeted cytotoxicity as well as reduction of negative regulator of MDSC cells. The survival of mice with lung metastases in CD151 peptide immunized group was also prolonged. Conclusions: The stress-upregulated oncoproteins defined by proteomics and bio-information on 8 Gy irradiated tumor cells are the good candidates for designing immunogenic peptides as tumor vaccines. Anti-tumor active immunity primed by peptides from tetraspanin oncoprotein CD151 could exert effective, long-lasting, cheap and safe way to suppress the progression of cancer. Funding: The project was funded in part by the grants of Fujian Province Natural Science Foundation (2017J01260); the Key Clinical Specialty Discipline Construction Program of Fujian; the National Clinical Key Specialty Construction Program; Fujian Engineering Research Center of Cancer precision Diagnosis and Immunotherapy; Science&Technology Program of Fujian Province, China (#2018Y2003). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: Animal experiments were approved by Fujian Medical University Institutional Animal Ethical Committee (FJMU IACUC #2018-075). The applicable institutional guidelines for the care and use of animals were followed.

3-Deoxyglucosone (3DG) is derived from D-glucose during food processing and storage and under physiological conditions. We reported that glucagon-like peptide-1 (GLP-1) secretion in response to an oral glucose load in vivo and high-glucose stimulation in vitro was decreased by acute 3DG administration. In this study, we determined the acute effect of 3DG on GLP-1 secretion under basal conditions and investigated the possible mechanisms. Normal fasting rats were given a single acute intragastric administration of 50 mg/kg 3DG. Plasma basal GLP-1 levels and duodenum 3DG content and sweet taste receptor expression were measured. STC-1 cells were acutely exposed to 3DG (80, 300, and 1000 ng/ml) for 1 h under basal conditions (5.6 mM glucose), and GLP-1 secretion, intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and molecular expression of STR signaling pathway were measured. Under the fasted state, plasma GLP-1 levels, duodenum 3DG content, and duodenum STR expression were elevated in 3DG-treated rats. GLP-1 secretion was increased in 3DG-treated cells under either 5.6 mM glucose or glucose-free conditions. 3DG-induced acute GLP-1 secretion from STC-1 cells under 5.6 mM glucose was inhibited in the presence of the STR inhibitor lactisole, which was consistent with the observation under glucose-free conditions. Moreover, acute exposure to 3DG increased the protein expression of TAS1R2 and TAS1R3 under either 5.6 mM glucose or glucose-free conditions, with affecting other components of STR signaling pathway, including the upregulation of transient receptor potential channel type M5 TRPM5 and the increment of intracellular Ca2+ concentration. In summary, the glucose-free condition was used to first demonstrate the involvement of STR in 3DG-induced acute GLP-1 secretion. These results first showed that acute 3DG administration induces basal GLP-1 secretion in part through upregulation of STR expression.

Context: Sodium glucose co-transporter 1 (SGLT1) triggers low glucose-induced glucagon-like peptide-1 (GLP-1) secretion. We reported that a two-week administration of 3-deoxyglucosone (3DG), an independent factor associated with the development of pre-diabetes, reduces basal GLP-1 secretion in rats. Objective: This study investigated the effects of 3DG on GLP-1 secretion and SGLT1 pathway under low-glucose conditions in STC-1 cells. Methods: STC-1 cells were incubated with phloridzin or 3DG at 5.6 mM glucose. SGLT1 expression (by western blotting), GLP-1 and cyclic adenosine monophosphate (cAMP) levels (by ELISA), and intracellular Ca2+ concentration (by Fluo-3/AM) were measured. Results: Phloridzin inhibited GLP-1 secretion. SGLT1 protein expression in STC-1 cells cultured in 5.6 mM glucose is higher than that in 25 mM glucose. Exposure to 3DG for 6 h reduced GLP-1 secretion, SGLT1 protein expression, and intracellular concentrations of cAMP and Ca2+. Conclusions: 3DG reduces low glucose-induced GLP-1 secretion in part through reduction of SGLT1 expression.

Maintenance of glucose homeostasis is reciprocally regulated by insulin and glucagon-like peptide-1 (GLP-1). We previously reported that GLP-1 secretion in response to an oral glucose load was impaired following an administration of 3-deoxyglucosone (3DG), an independent factor associated with the development of pre-diabetes. Here we investigated the effects of 3DG on insulin signaling and insulin-induced GLP-1 secretion under high-glucose conditions in the enteroendocrine L cell line STC-1. STC-1 cells were exposed to 3DG (80, 300, and 1000 ng/ml) in the presence of 10−7 M insulin and 25 mM glucose. GLP-1 secretion was determined by ELISA, glucose uptake was monitored with 2-NBDG (2-(N(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose), glucose consumption was detected by glucoseoxidase, and protein expression of insulin signaling molecules was examined by western blot. Results showed a decrease in insulin-induced GLP-1 secretion and insulin receptor phosphorylation after 3DG treatment. Concomitantly, 3DG treatment inhibited insulin-induced phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway activation. In the presence, but not absence, of insulin, 3DG treatment decreased insulin-stimulated glucose consumption. Inhibition of PI3K with Wortmannin attenuated insulin-induced increment in glucose transporter 2 (GLUT2) expression and 2-NBDG uptake. Accordingly, insulin-induced increase in GLUT2 expression and 2-NBGD uptake was significantly inhibited by 3DG treatment. 3DG-mediated reduction in GLUT2 expression contributes to the attenuation of insulin-induced GLP-1 secretion under high-glucose conditions in part through the insulin-PI3K/Akt/GLUT2 pathway in STC-1 cells. We conclude that 3DG interferes with insulin signaling and attenuates insulin action on glucose-induced GLP-1 secretion in STC-1 cells.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a key negative immunoregulatory molecule with characteristics of gene polymorphisms. Genetically predisposed CTLA-4 alteration in humans was associated with gastric cancer (GC) development. To explore the association of CTLA-4 polymorphism with susceptibility of noncardiac GC (NCGC), 490 NCGC patients and 1476 control individuals were studied. Four CTLA-4 polymorphisms were genotyped with SNPscan genotyping assays and the haplotypes were constructed with SHESIS software. Frequencies of the CTLA-4 haplotypes were estimated using an expectation-maximization algorithm. The CTLA-4 polymorphism genotype distribution and allele frequencies were not significantly different between the NCGC patients and the control subjects. The CTLA-4 haplotypes did not exhibit a significantly increased risk for NCGC patients. Adjusting status of age, sex, smoking status, alcohol use, and body mass index could not moderate any of the relationships. Data suggested that CTLA-4 polymorphisms (rs3087243, rs16840252, rs733618, and rs231775) were not significantly associated with the risk of NCGC in this Chinese population studied.

Radioresistance is an important factor for unsatisfactory prognosis in Nasopharyngeal carcinoma (NPC) patients. Ubiquitous mitochondrial creatine kinase (CKMT1) is always associated with malignancy in a variety of cancers. However, its significance in NPC progression and radiosensitivity remains unclear. The present study focused on investigating the effects of CKMT1 on NPC cell radiosensitivity.CKMT1 was overexpressed in NPC cell line CNE-1 or knocked out in CNE-2. Biological changes were detected after cells exposing to different doses of X-ray to determine the role of CKMT1 on NPC cell radiosensitivity.CKMT1 promotes proliferation and migration in NPC cell lines CNE-1 and CNE-2. Overexpression of CKMT1 in CNE-1 cells enhanced colony formation rates, reduced G2/M phase cell cycle arrest, lowered apoptosis rate and c-PARP level, and elevated STAT3 phosphorylation level after radiation treatment. While knocking out CKMT1 using the CRISPR/Cas9 system in CNE-2 cells lowered colony formation rates, increased G2/M phase cell cycle arrest, apoptosis rates, and c-PARP levels, and decreased STAT3 phosphorylation in response to radiation treatment.NPC cells with higher CKMT1 exhibited lower radiosensitivity through promoting phosphorylation of STAT3. Our findings suggest that CKMT1 may be an alternative radiotherapeutic target in NPC therapy.

Liver cancer is one of the most common malignant tumors with no available satisfactory treatment. The aim of the present study was to investigate the anti-tumor effect of an irradiated hepatocellular carcinoma (HCC) whole-cell vaccine and its underlying mechanisms. Hepa1-6 and H22 HCC cell lines were irradiated in preparation for whole-cell vaccine production. Subsequently, two HCC tumor-bearing mouse models were created by injecting these Hepa1-6 and H22 cells into the abdominal skin of C57BL/6 and ICR mice, respectively. The mice were immunized with the corresponding whole-cell vaccine the next day, and then once a week until the end of the experimental period. Tumor growth, blood T helper (Th)9 cells and plasma interleukin (IL)-9 levels were monitored during the immunization period. Th9 cells were also induced by in vitro co-culture of the whole-cell vaccine with lymphocytes from the spleen and lymph nodes of the corresponding mice. Alterations of gene expression in transcription factor (TF) were determined by reverse transcription-quantitative PCR, and Th9 cells were detected using flow cytometry. The whole-cell vaccine effectively suppressed HCC tumor growth, as indicated by slower tumor growth and a smaller tumor size in the immunized group compared with the control. The percentage of blood Th9 cells and the concentration of plasma IL-9 were significantly increased in the immunized group. The whole-cell vaccine also induced Th9 cell differentiation and upregulated the expression of TFs PU.1, interferon regulatory factor 4 and basic leucine zipper transcriptional factor ATF-like. These results suggest that the irradiated HCC whole-cell vaccine inhibited tumor growth by increasing Th9 cell numbers in HCC mice.

Circular RNA (CircRNA) is related to tumor development. Nevertheless, the regulation and function of hsa_circ_0006692 and its interactions with miR-205-5p and CDK19 in the development of non-small-cell lung cancer (NSCLC) were un-explored. The correlations of expression levels of hsa_circ_0006692 in NSCLC specimens and cells with pathological characteristics were studied. The interactions of hsa_circ_0006692 with miR-205-5p and CDK19 were assessed with real-time PCR, RNA-binding protein immunoprecipitation (RIP), luciferase reporter, RNA pull-down, and fluorescence in situ hybridization (FISH). The roles of hsa_circ_0006692 on cell growth, invasion, and migration in vitro and metastasis in vivo were evaluated. Hsa_circ_0006692 was over-expressed in 60 cases of NSCLC specimens and cells, which was positively correlated with TNM stage, tumor size, and invasion of the lung basal layer. The results of the in vitro and in vivo studies revealed that the over-expression of hsa_circ_0006692 facilitated NSCLC cell growth, migration, and invasion, cell cycle arrest at the S phase, and the activation of BCL-2, CCND1, and PCNA. The results of the dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that hsa_circ_0006692 sponged miR-205-5p, which targeted CDK19 and facilitated the malignant behaviors of lung cancer cells. Hsa_circ_0006692 modulated EMT of lung cancer cells via the stimulation of CDH1, CDH2, VIMENTIN, and MMP7. This study revealed that hsa_circ_0006692 promoted NSCLC progression via enhancing cell growth, invasion, and metastasis through sponging mir-205-5p, up-regulating the downstream oncogene CDK19 and modulating EMT of lung cancer cells. The circ-0006692/mir-205-5p/CDK19 axis might serve as a prognosis biomarker and target for drugs aimed against NSCLC.

Cancer patients who initially benefit from Erlotinib, a drug targeting EGFR path, eventually develop resistance to the drug. The underlying mechanism is largely unknown. This study investigated the role of ARL4C in Erlotinib resistance development of NSCLC. qRT-PCR and Western blotting were performed to analyze the expression of mRNA and protein of ARL4C in two NSCLC cell lines (HCC827 and PC-9). Several assays (MTS, colony formation, transwell migration, luciferase reporter, and chromatin-immunoprecipitation) were used to explore the role of ARL4C in biofunctional changes of Erlotinib-resistant cells and their associations with Jak2/Stat 5/β-catenin signaling. Results demonstrated that (1) long-term use of Erlotinib resulted in downregulation of ARL4C; (2) overexpression of ARL4C could regain the sensitivity to Erlotinib in the drug-resistant HCC827/ER cells, while downregulation of ARL4C increased HCC827, and PC-9 cells' resistance to the drug; (3) Erlotinib-induced downregulation of ARL4C resulted in phosphorylation of Jak2/Stat5 and upregulation of β-catenin and their related molecules Axin2, CD44, Ccnd1, Lgr-5, and MMP7, which promoted the malignant behaviors of Erlotinib-resistant cells; (4) chromatin immunoprecipitation and luciferase reporter assay revealed that Stat5 could bind to β-catenin promoter to upregulate molecules to maintain the malignant behaviors, which might count for how Erlotinib-resistant cell survived while EGFR path was blocked; (5) the expression of ARL4C was not associated with known EGFR gene mutations in both Erlotinib-resistant cells and NSCLC tissues. Our data suggest that Erlotinib resistance of NSCLCs is associated with downregulation of ARL4C via affecting Jak/Stat/β-catenin signaling. ARL4C could serve as a biomarker to predict the effectiveness of TKI targeting therapy and a potential therapeutic target for overcoming Erlotinib resistance in NSCLC.

The tumor immunological microenvironment in hepatocellular carcinoma (HCC) is the T-helper (Th) 2 dominant inhibition state. Improving the immunosuppressive tumor microenvironment represents an important strategy for HCC treatment. TSLP-OX40L pathway is a target to improve Th2 immunosuppression. Yupingfeng granule (YPF) is clinically used to effectively improve the immune status of HCC. In this study, YPF increased the percentage of mature dendritic cells (DCs) and decreased levels of TSLP, TSLPR, and OX40L in tumor and adjacent tissues of the orthotopic-HCC mice model. This occurs together with the decreased levels of Th2 cytokines and increased levels of Th1 cytokines and Th1/Th2 ratio. In vitro experiment showed that YPF not only increased the percentage of mature DCs and stimulated IL-12 secretion in DCs but also reduced the positive rate of OX40L expression, decreased the proportion of CD4+ IL-13+ T cells, increased levels of Th1 cytokines, and decreased levels of Th2 cytokines from TSLP-treated DCs. In summary, these findings demonstrated that YPF promoted the maturation of DCs, decreased OX40L in TSLP-induced DCs, and improved the immunosuppressive state of Th2 in HCC microenvironment. Our results suggest that the mechanism underlying the improving effect of YPF on the immunosuppression is related to the DC-mediated TSLP-OX40L pathway.

3-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an independent factor for the development of prediabetes and suggest that intestine could be its novel target tissue. The present study investigated whether exogenous 3DG increases intestinal permeability by triggering carbonyl and oxidative stress, thus contributing to β-cell dysfunction. Rats were administered 3DG for two weeks by gastric gavage. Then levels of insulin, ROS, MDA, SOD, NLRP3, TNF-α and IL-1β in blood plasma as well as the ROS level and content of TNF-α and IL-1β in pancreas were assessed. Also, the expression of E-cadherin and ZO-1 as well as levels of 3DG, protein carbonylation, ROS, TNF-α and IL-1β in colon were determined. The 3DG-treated rats showed an elevation in systemic oxidative stress (ROS, MDA and SOD) and in inflammation (TNF-α and IL-1β), decreased plasma insulin level 15 min after the glucose load, and increased levels of TNF-α, IL-1β and ROS in pancreatic tissue. In colon tissues of the 3DG-treated rats, decreased E-cadherin expression and increased ROS production as well as an elevation of TNF-α and IL-1β levels were observed. Interestingly, elevation of colon protein carbonylation was observed in the 3DG-treated rats that displayed 3DG deposition in colon tissues. We revealed for the first time that 3DG deposition in colon triggers carbonyl and oxidative stress and, as a consequence, impairs gut permeability. The enhanced intestinal permeability caused by 3DG deposition in colon results in systemic and pancreatic oxidative stress and inflammatory process, contributing to the development of β-cell dysfunction.

Osthole has been demonstrated to have antitumor activity. Previous studies by our group indicated that osthole effectively inhibited tumor growth in hepatocellular carcinoma (HCC) through the induction of apoptosis and enhancement of antitumor immune responses in mice. The importance of angiogenesis in the proliferation, invasion and metastasis of tumor cells in HCC is well established. The present study aimed to investigate the effects of osthole on angiogenesis in an orthotopic mouse model of HCC. Orthotopic HCC in mice was established, and osthole at 61, 122 and 244 mg/kg was administered intraperitoneally once daily to the tumor-bearing mice for 14 consecutive days. Immunohistochemistry was performed to analyze the microvessel density (MVD) of tissues, and the level of vascular endothelial growth factor (VEGF) was measured by ELISA. The protein levels of nuclear factor-κB (NF-κB) p65 and IκB-α were also detected by western blotting. MVD was positively correlated with tumor weight in the orthotopic mouse model of HCC. Osthole administration significantly decreased MVD in tumor and adjacent tissues, and inhibited tumor growth. Furthermore, osthole downregulated the expression of VEGF and NF-κB p65, and upregulated IκB-α expression in tumor and adjacent tissues. To the best of our knowledge, the results of the present study demonstrated for the first time that osthole inhibits angiogenesis in an orthotopic mouse model of HCC, which may be one of the mechanisms underlying the anti-HCC activity of osthole, which in turn may be mediated by the NF-κB/VEGF signaling pathway. Therefore, osthole, a potential angiogenesis inhibitor and immune system enhancer, may be a promising lead compound for the treatment of HCC.

There is a high incidence of nasopharyngeal carcinoma (NPC), malignant head and neck tumors, in southern China. Radioresistance is the main cause affecting the efficacy of NPC treatments. The POLG gene particularly plays an important role in radiation-induced damage repair. In this study, the authors established RNAi CNE-1 and CNE-2 knockdown in two NPC cell lines to observe whether this gene affects the radiosensitivity of NPC cells.Four short hairpin RNA (shRNA) expression plasmids targeting POLG gene were constructed and transfected into the NPC cell lines CNE-1 and CNE-2. Screening was performed to evaluate the stable expression of cloned cells, which were named CNE-1/POLG-shRNA1, CNE-1/POLG-shRNA2, CNE-2/POLG-shRNA1, and CNE-2/POLG-shRNA2. The negative controls CNE-1/Neg-shRNA and CNE-2/Neg-shRNA were additionally used. The MTT method, flow cytometry, clone formation analysis, cell migration, and other experimental methods were employed to verify changes in the radiosensitivity of the NPC cells.Fluorescent quantitative PCR and Western blot confirmed the downregulation of the PLOG gene through diminished PLOG messenger RNA and protein levels. Consequently, the authors report the stable knockdown of the POLG gene in an NPC model. Dose-dependent radiation exposure of POLG inhibited NPC cell growth and increased apoptosis compared with control cells (p 0.01), as demonstrated through colony formation assay and flow cytometry. Functional assays indicated that knockdown of the POLG in CNE-1 and CNE-2 cells remarkably reduced cell viability and proliferation. Specifically, POLG knockdown led to G1 phase arrest and apoptosis.Overall, the authors conclude that POLG downregulation alters the radiosensitivity of NPC cells, indicating that the gene is likely involved in conferring the radiation response of the cells. In addition, findings in this study suggest a novel role for POLG as a potential predictive marker for NPC radiotherapy efficiency. POLG gene can be used as a potential clinical target to effectively improve the radiosensitivity of NPC.

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis (n = 134), SIRS (n = 60) and normal adults (n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1–2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis (rs = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1–2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

Circulating tumor cells (CTCs) represent the key step of cancer cell dissemination. The alteration of CTCs correlates with the treatment outcome and prognosis. To enrich and identify CTCs from billions of blood cells renders a very challenging task, which triggers development of several methods, including lysis of RBC plus negative or positive enrichment using antibodies, and filter membrane or spiral microfluidics to capture CTCs. To compare the advantages of different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells transfected with both green fluorescent protein (GFP) and luciferase to trace CTCs in the experimental lung metastasis model. Three methods were used to detect CTCs at the same time: bioluminescence assay, smearing method, and membrane filter method. The in vivo alive mouse imaging was used to dynamically monitor the growth of lung metastases. The sensitivity and accuracy of three detection methods were compared side-by-side. Our results showed that 1) the sensitivity of bioluminescence assay was the highest, but there was no information of CTC morphology; 2) the smearing method and membrane filter method could observe the detail of CTC morphology, such as in single or in cluster, while their sensitivity was lower than bioluminescence assay; 3) A dynamic observation at a 7-day intervals, the lung metastatic cancer grew at a log speed, while CTCs were increased at a low speed. This might be due to the activated immune cells eliminating the CTCs at a speed much faster than CTCs were generated. This comparison of three CTC detection methods in mouse model suggests that bioluminescence assay could be used in quantitative study of the effect of certain agent on the suppression of CTCs, while GFP-based morphological assays could be used to study the dissemination mechanism of CTCs. The combination of both bioluminescence assay and GFP-based assay would generate more information for quantity and quality of CTCs.

// Chun Chen 1, * , Shanmin Yang 2, * , Mei Zhang 2 , Zhenhuan Zhang 2 , Steven B. Zhang 2 , Bing Wu 3 , Jinsheng Hong 3 , Weijian Zhang 3 , Jianhua Lin 3 , Paul Okunieff 2 and Lurong Zhang 2, 3 1 Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China 2 Department of Radiation Oncology, University of Florida, Gainesville 32610, Florida, USA 3 Fujian Platform for Medical Research at First Affiliated Hospital, Fujian Key Lab of Individualized Active Immunotherapy and Key Laboratory of Radiation Biology of Fujian Province Universities, Fuzhou 350005, China * These authors contributed equally to this work Correspondence to: Chun Chen, email: chenchun-0428@163.com Lurong Zhang, email: lz8506@163.com Keywords: Triptolide, radiotherapy, pneumonitis, alveolar macrophage, inflammative molecules Received: January 09, 2017 Accepted: March 14, 2017 Published: March 22, 2017 ABSTRACT Ionizing radiation-induced pulmonary injury is a major limitation of radiotherapy for thoracic tumors. We have demonstrated that triptolide (TPL) could alleviate IR-induced pneumonia and pulmonary fibrosis. In this study, we explored the underlying mechanism by which TPL mitigates the effects of radiotoxicity. The results showed that: (1) Alveolar macrophages (AMs) were the primary inflammatory cells infiltrating irradiated lung tissues and were maintained at a high level for at least 17 days, which TPL could reduce by inhibiting of the production of macrophage inflammatory protein-2 (MIP-2) and its receptor CXCR2. (2) Stimulated by the co-cultured irradiated lung epithelium, AMs produced a panel of inflammative molecules (IMs), such as cytokines (TNF-α, IL-6, IL-1α, IL-1β) and chemokines (MIP-2, MCP-1, LIX). TPL-treated AMs could reduce the production of these IMs. Meanwhile, AMs isolated from irradiated lung tissue secreted significantly high levels of IMs, which could be dramatically reduced by TPL. (3) TPL suppressed the phagocytosis of AMs as well as ROS production. Our results indicate that TPL mitigates radiation-induced pulmonary inflammation through the inhibition of the infiltration, IM secretion, and phagocytosis of AMs.

β‑cell dysfunction is the primary cause of type 2 diabetes mellitus (T2DM). 1,2‑dicarbonyl compounds, such as 3‑deoxyglucosone (3DG) have been reported to increase the risk of T2DM. Abnormal elevation of plasma 3DG may impair β‑cell function and thereby, it is linked to T2DM. Previous findings suggest that exogenous 3DG may serve an important role in the development of pre‑diabetes. In the present study, the authors examine whether exogenous 3DG induces impaired glucose regulation in mice by decreasing β‑cell function involving of accumulation of plasma 3DG. At two weeks following administration of 3DG, fasting blood glucose (FBG) levels, oral glucose tolerance (by a glucose meter) and plasma levels of 3DG (by HPLC) and insulin (by radioimmunoassay) were measured. Glucose‑stimulated insulin secretion in cultured pancreas islets and INS‑1 cells was measured by radioimmunoassay. Western blotting was used to examine the expression of the key molecules of the insulin‑PI3K signaling pathway. 3DG treatment increased FBG and fasting blood insulin levels, reduced oral glucose tolerance in conjunction with decreased ∆Ins30‑0/∆G30‑0. In 3DG‑treated mice, an increase in the plasma 3DG level was observed, which was most likely the mechanism for decreased β‑cell function. This idea was further supported by these results that non‑cytotoxic 3DG concentration obviously decreased glucose‑stimulated insulin secretion in cultured pancreas islets and INS‑1 cells exposure to high glucose (25.5 mM). 3DG decreased the expression of GLUT2 and phosphorylation of IRS‑1, PI3K‑p85 and Akt in high glucose‑induced INS‑1 cells. To the best of the authors' knowledge, the present study is the first to demonstrate that exogenous 3DG induced normal mice to develop IGR, resulting from β‑cell dysfunction. Exogenous 3DG administration increased plasma 3DG levels, which participates in inducing β‑cell dysfunction, at least in part, through impairing IRS‑1/PI3K/GLUT2 signaling.

Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%-3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5Gy or 10Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9-/- mice. TLR9 agonist ODN1826 stimulation in vitro for 5h induced more B10 cells to express cytoplasmic IL-10 in sub-TBI WT mice than in TLR9-/- mice. Prolonged ODN1826 stimulation (48h) induced additional spleen CD19hiCD5+CD1dhi B cells to express IL-10. TLR9-dependent signaling molecules, MyD88, TRAF6 and IRF8 are involved in sub-TBI induced Breg/B10 cells development and expansion. Furthermore, using a mouse model for multiple sclerosis, we show here that sub-TBI induced Breg/B10 cells dramatically inhibit disease onset and severity when transferred into mice with established experimental autoimmune encephalomyelitis (EAE). Adoptively transferred sub-TBI induced Breg cells significantly suppress inflammatory T cell responses of TH17 and TH1 types in EAE mice. In conclusion, sub-TBI can drive Breg/B10 cell development and expansion, which could be used as a novel tool for suppressing undesirable immunity. The ex vivo expansion and reinfusion of autologous Breg/B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.

Summary Sepsis, a life‐threatening systemic infection, requires quick treatment. Gram‐negative bacteria (GNB) are the major causative pathogens and their endotoxin can be a surrogate biomarker for diagnosis. We explored a fast identification of GNB by first culturing blood to increase endotoxin levels and then detecting endotoxin by Tachypleus amebocyte lysate (TAL) with kinetic turbidimetric assay (KT‐TAL). Heating samples could significantly increase the endotoxin released from GNB; speed and time of centrifugation, and sample dilution could affect the endotoxin results. At a high GNB load, endotoxin was detected 3 h after culture, 6.5 h earlier than the BD BACTEC blood culture system detecting GNB. At a low GNB load, endotoxin was detected at 9 h after culture, 13 h earlier than by the BD BACTEC system. In a sepsis patient with Acinetobacter baumannii, we detected endotoxin at 12 h after culture, while the BD BACTEC system needed 28.5 h for detection, allowing physicians an earlier decision on appropriate treatment.

Tumor antigen-induced lymphocyte transformation (LT) represents the antitumor cellular immunity, which might correlate with the cancer treatment outcome. Currently, there is no LT assay (LTA) routinely used in clinic. To establish a sensitive and convenient procedure for LTA, the same samples were used to simultaneously perform three assays: 5-ethynyl-2'-deoxyuridine (EdU) assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and carboxyfluorescein succinimidyl ester (CFSE) assay, and then the three results were compared. Several conditions were optimized: the LT harvest time, sources of lymphocytes (blood, lymph nodes, or spleen), the added amount of stimulatory tumor antigen and

Glucose triggers glucagon-like peptide (GLP)-1 secretion from L cells involving several glucose sensors including sodium-glucose transporter (SGLT)1, glucose transporter (GLUT)2, and sweet taste receptors (STRs). This study investigated the effects of different glucose concentrations on GLP-1 secretion, intracellular concentrations of Ca2+ and cAMP, glucose uptake, and protein levels of SGLT1, GLUT2, and STRs in STC-1 cells. Low glucose (5.6 mM) increased GLP-1 secretion, intracellular Ca2+ concentration, and SGLT1 protein level compared with glucose-free group. GLP-1 secretion and intracellular Ca2+ concentration triggered by low glucose were inhibited by the SGLT1 inhibitor. GLP-1 secretion or intracellular Ca2+ concentration in high-glucose (25, 100, 200 mM) groups was significantly higher than that of low-glucose group. Elevation of cAMP level was observed in concentration-dependent manner, and decreased glucose uptake was observed in 100 or 200 mM glucose group. High glucose increased protein levels of STRs and GLUT2 in comparison to low-glucose group. GLP-1 secretion and intracellular levels of Ca2+ and cAMP triggered by high glucose were inhibited in the presence of the GLUT2 or STR inhibitor. These results suggest that SGLT1 is dominantly responsible for GLP-1 secretion triggered by low glucose, and that STRs and GLUT2 are involved in GLP-1 secretion induced by high glucose.

Mingqiu Chen,1–4 Pingping Liu,5 Yuangui Chen,6 Zhiwei Chen,7 Minmin Shen,5 Xiaohong Liu,5 Xiqing Li,5 Yu Lin,1 Rongqiang Yang,8 Wei Ni,8 Xin Zhou,8 Lurong Zhang,1 Ye Tian,3,4 Junqiang Chen11Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China; 2Fujian Provincial Platform for Medical Laboratory Research of First Affiliated Hospital, Fujian, China; 3The Second Affiliated Hospital of Soochow University, Jiangsu, China; 4Institute of Radiotherapy & Oncology, Soochow University, Jiangsu, China; 5Fujian Medical University Cancer Hospital, Fujian, China; 6Department of Radiation Oncology, Fujian Medical University Union Hospital, Fujian, China; 7Fuzhou Center for Disease Control and Prevention, Fuzhou, Fujian, China; 8Cancer and Genetics Research Complex, Department Molecular Genetics and Microbiology, College Medicine, University of Florida, Gainesville, FL, USAPurpose: The primary tumor regression patterns of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT) were investigated to determine an optimal surveillance scheme.Method: The clinical data and radiology images of patients before CRT, at completion of CRT and every 1–3 months for the subsequent 12months or until disease progression were retrospectively reviewed to define the patterns of primary tumor regression after CRT. Survival rates were analyzed statistically in order to determine an optimal surveillance scheme.Results: A total of 82 patients were enrolled in the present study for analysis. At the first surveillance visit date at the end of CRT, a total of 21 patients achieved complete response (early-CR), 29 patients reached incomplete response (IR), 25 patients maintained stable disease (SD) and 7 patients encountered progression of disease (PD). During subsequent surveillance, a total of 14 IR patients regressed continuously to CR (later-CR), 15 patients maintained IR (early-IR) and 9 SD patients gradually regressed to IR (later-IR). At full tumor regression (FTR), a total of 21, 14, 15, 9, 16 and 7 patients were defined as early-CR, later-CR, early-IR, later-IR, SD and PD, respectively. The median FTR time for later-CR and later-IR was 7.5 and 7weeks, respectively. The 3-year overall survival rate of the early-CR group was 85.7% (P