Search

Objective This study aimed to investigate the quality of life (QOL) of patients with cleft lip and palate and velopharyngeal insufficiency (VPI) in relation to sex, age, age at initial cleft lip surgery, and age at initial cleft palate surgery. Design This is a cross-sectional study. Setting The study was conducted in a tertiary medical center. Participants The participants were caregivers of 72 patients with cleft lip and palate and VPI aged 4 to 20 years. Main Outcome Measure(s) Participants completed the Chinese version of the caregiver report of the VPI Effects on Life Outcomes (VELO) questionnaire. The Mann–Whitney U test was used to evaluate the patients’ sex, age, age at initial cleft lip repair, and age at initial cleft palate repair in relation to VELO total score and domains. Spearman correlation analysis was completed including all study variables. Associations between the study variables and the VELO total score were tested using a generalized linear mixed model. Results In the univariate analysis, patients’ age and age at initial cleft palate surgery influenced the QOL of patients with VPI. There were no differences in the VELO total score or domains based on sex or age at first cleft lip surgery. In the generalized linear mixed model, patients older than 8 years had higher VELO total scores. Conclusions By caregiver report, the QOL of patients under age 8 years with VPI was lower than older patients. In addition, the caregiver impact domain was higher for parents of children who had their initial cleft palate surgery at age 2 years or younger.

SBF2-AS1 is an oncogenic long non-coding RNA (lncRNA). However, its role and mechanism in hepatocellular carcinoma (HCC) is still not completely clear. The HepG2, Hep3B, Bel-7402 and HL-7702 cell lines were used in our experiments. The CCK-8 kit and EdU staining were applied to detect cell viability and multiplication. The wound healing and Boyden chamber cell migration assays were employed to test the migration ability of cells. The levels of TGF-β1 mRNA, lncRNA SBF2-AS1, and miR-361-5p were assessed by real-time PCR. TGF-β1 protein levels were evaluated by western blotting. The direct interaction between miR-361-5p and TGF-β1 was determined by luciferase reporter assays. A xenograft mouse model (XMM) was established to comprehensively study the effect and mechanisms of lncRNA SBF2-AS1. lncRNA SBF2-AS1 concentration in HCC cells exceeded that in a normal hepatocyte cell line. The downregulation of lncRNA SBF2-AS1 upregulated miR-361-5p levels in HCC cells. And, miR-361-5p negatively regulate TGF-β1 expression in HCC cells. The suppression of miR-361-5p attenuated the influence of lncRNA SBF2-AS1 downregulation on the viability, proliferation, and migration capability of HCC cells. Further, the downregulation of lncRNA SBF2-AS1 inhibited neoplasm growth in an XMM of HCC. Simultaneously, miR-361-5p was upregulated and TGF-β1 was downregulated after lncRNA SBF2-AS1 knocked down. In conclusion, downregulation of lncRNA SBF2-AS1 inhibits HCC proliferation and migration through the regulation of the miR-361-5p/TGF-β1 signaling pathway.

Objectives To investigate the effects of radiation on paracellular pathway of rat submandibular glands (SMGs) and the mechanism of increasing secretion following treatment with pilocarpine. Materials and methods In situ irradiation models of SMGs in Wistar rats were conducted, and the glands were exposed to X-radiation at a single dose of 20 Gy. Pilocarpine was intraperitoneally injected 60 min prior to radiation and continuous 6 days postirradiation for a total of 7 days. Salivary secretion, histological changes, pro-inflammatory cytokines, alterations in tight junctions (TJs), and functional membrane proteins aquaporin-5 (AQP5) and claudin-4 mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks after irradiation. Results Salivary secretion of the irradiated glands was reduced at 1 and 12 weeks. As well, acinar cell numbers, TJ width, and the levels of M3 receptor and AQP5 were decreased. In contrast, tumor necrosis factor-α, interleukin 6, interleukin 1α, and the expression of the TJ protein claudin-4 were significantly increased in irradiated SMGs. Notably, all the alterations were attenuated by pilocarpine treatment. Conclusions Pilocarpine could improve the secretory function of irradiated rat SMGs via reducing inflammation, ameliorating the structural injury of TJs, and attenuating the up-regulation of claudin-4 expression.

This prospectively designed study aimed to investigate the association between sleep duration and overweight in a cohort of Chinese adolescents. A school-based cohort study with a 2-year follow-up was conducted among Chinese adolescents in Ningbo region (China). For the baseline study, 1901 school-aged Chinese children aged 12–13 years were recruited. Finally, 1510 adolescents were successfully reinterviewed in October 2018. Participants were asked to complete a self-administered questionnaire, and their heights and weights were directly measured. Overweight adolescents had shorter sleep duration or later bedtimes than non-overweight children in baseline (P

Objective: Incomplete radiofrequency ablation (ICR) has been proposed as a major cause of recurrence in the treatment of hepaticmetastatic tumors. We tried to determine the mechanisms of this progression in colorectal cancer (CRC) liver metastasis (CRLMs) Methods: We have established a mouse model of radiofrequency ablation (RFA) therapy to demonstrate increased risk ofrecurrence of CRLMs with ICR. Here we focused on heat shock-induced CRC malignancy. Sub-lethal heat shock (HS) in CRC celllines provoked cell growth, invasion, and tumor initiation in vitro and in vivo. Results: We found that Fra-1, which lies downstream of PKCα-ERK1/2 signaling, was significantly increased by HS compared withthe untreated CRC cells. Silencing Fra-1 reversed the tumor promoting effects of HS. Furthermore, proliferation and tumorinitiation inducer c-Myc, together with tumor invasion inducer matrix-metalloprotase 1 (MMP-1) expression were up-regulatedby AP-1/Fra-1 induced genes transcription. Conclusions: Our study demonstrated that ICR generated HS induces CRC malignancy by targeting Fra-1, which could be apotential prognostic marker and a promising therapeutic strategy to prevent disease recurrence after radiofrequency ablationtreatment. Cite this article as: Zhang Z, Zhang Y, Zhang L, Pei Y, Wu Y, Liang H, et al.Incomplete radiofrequency ablation provokes colorectal cancer livermetastases through heat shock response by PKCα/Fra-1 pathway. Cancer BiolMed. 2019; 16: 542-55. doi: 10.20892/j.issn.2095-3941.2018.0407

In the present study, we intend to assess the function of Sema3A in osteointegration of titanium implants both in vivo and in vitro. Briefly, Sema3A was transfected in HBMSCs cells to detect its effect on osteogenesis. Subsequently, an in vivo rabbit model was established. Eighteen female rabbits were randomly assigned into three groups (n=6), and rabbits in the two treatment groups (OVX groups) were subjected to bilateral ovariectomy, while those in the control group were treated with sham operation. Twelve weeks later, we first examined expression levels of Sema3A in rabbits of the three groups. Titanium implants were implanted in rabbit proximal tibia. Specifically, rabbits in sham group were implanted with Matrigel, while the remaining in the OVX experimental group (OVX+Sema3A group) and OVX group were implanted with Matrigel containing Sema3A adeno-associated virus or empty vector, respectively. Histomorphometry results uncovered that rabbits in the OVX+Sema3A group had a significantly higher BIC compared with those of the OVX group on the 12th week of post-implantation. And compared with the OVX group, the maximum push-out force increased by 89.4%, and the stiffness increased by 39.4%, the toughness increased by 63.8% in the OVX+Sema3A group at 12 weeks. Sema3A has a positive effect on promoting early osseointegration of titanium implants in osteoporotic rabbits. Our research found that Sema3A can improve the osteogenic ability of bone marrow stem cells and promotes osseointegration during osteoporosis.

To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20 Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12 weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12 weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

Background. Corydalis Rhizoma(CR) showed a high efficacy for coronary heart disease (CHD). However, the interaction between the active ingredients of CR and the targets of CHD has not been unequivocally explained in previous researches. To study the active components and potential targets of Corydalis Rhizoma and to determine the mechanism underlying the exact effect of Corydalis Rhizoma on coronary heart disease, a method of network pharmacology was used. Materials and Methods. The active components of CR and targets corresponding to each component were scanned out from Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and target genes of CHD were searched on GeneCards database and Online Mendelian Inheritance in Man(OMIM) database. The active components and common targets of CR and CHD were used to build the “CR-CHD” network through Cytoscape (version 3.2.1) software as well as protein-protein interaction(PPI) network on String database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was executed by clusterProfiler(version 3.8) and DOSE(version 3.6) package on R platform. Results. 49 active ingredients and 394 relevant targets of CR and the 7173 CHD-related genes were retrieved. 40 common genes were selected for subsequent analysis. Crucial biological processes and pathways were obtained and analyzed, including DNA-binding transcription activator activity, RNA polymerase II-specific, RNA polymerase II transcription factor binding, kinase regulator activity, ubiquitin-like protein ligase binding, fluid shear stress and atherosclerosis, TNF signaling pathway, apoptosis, MAPK signaling pathway and PI3K-Akt signaling pathway. Conclusions. Overall, CR could alleviate CHD through the mechanisms predicted by network pharmacology, laying the foundation for future development of new drugs from traditional Chinese medicine on CHD.

Summary Objective Previous epidemiology studies have demonstrated that short sleep duration may be associated with the development of obesity, although the effects remain controversial. This study aimed to assess epidemiologic evidence systematically on the relation between sleep duration and obesity in children. Design and methods We searched the Medline, Cochrane Library, EMBASE and Science Citation Index databases and reference lists of the included articles. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a random-effects model. Results Fifty cohorts from thirteen studies were included in the pooled analysis. They included 35,540 participants from around the world. In children/adolescents the pooled OR was 1.71 (1.36–2.14; I 2 = 91.3%), the positive association was consistent after omitting any of the studies. In subgroup analyses, the results indicated that the heterogeneity of effect may due to differences in geographical location, cut-off for short sleep duration and definition of obesity/overweight. The publication bias tests indicated a no evidence of publication bias. Conclusion This meta-analysis provides evidence that short sleep duration in children is associated with a significantly increased risk of obesity. Enough sleep duration is potentially important for the prevention of obesity among children.

Background The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. Methods From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. Results Eighty nine TACE procedures (1.35 ± 0.67; 1–4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), “typical tumor enhancement” (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. Conclusions The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

Objective Previous meta-analyses have demonstrated that lifestyle modification can reduce the blood glucose levels in patients with type 2 diabetes, although the effects of changes in the blood glucose level on impaired glucose tolerance (IGT) remain controversial. This review therefore aimed to determine the efficacy of lifestyle interventions in adults with IGT. Methods We searched the Medline, Cochrane Library, EMBASE and Science Citation Index databases and reference lists of the included articles. Two independent reviewers extracted the data and assessed the quality of the included studies; a total of nine randomized controlled trials met the inclusion criteria. In addition, we tested for trial heterogeneity and calculated the pooled effects size using the random effects model. Results The overall interventions were associated with a decline in the 2-hour plasma glucose levels [standardized mean differences (SMD) -0.56; 95% confidence interval (CI), -1.01 to -0.10; I(2), 96.6%]. Moreover, dietary intervention (SMD -0.53; 95% CI -0.77 to -0.28) and physical intervention (SMD -0.42; 95% CI -0.63 to -0.20) were each associated with a decline in the 2-hour plasma glucose levels compared with that observed in the control participants. The overall interventions were associated with a decline in the fasting plasma glucose (FPG) levels (SMD -0.27; 95% CI -0.38 to -0.15; I(2) = 47.1%). In addition, physical intervention (SMD -0.25; 95% CI -0.44 to -0.05) and combined dietary and physical intervention were each associated with a decreased FPG level (SMD -0.28; 95% CI -0.44 to -0.12) compared with that observed in the control participants. Conclusion Lifestyle modification based on physical or dietary interventions or both is associated with improvements in the 2-hour plasma glucose and FPG levels in IGT patients.

Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cell lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3' UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.

Minocycline, a semisynthetic tetracycline, is a highly lipophilic molecule capable of infiltrating tissues and blood. Previous studies have revealed the functions and mechanisms of minocycline in anti-inflammation, protection of the nervous system and certain tumors. The role of minocycline has never been investigated in hepatocellular carcinoma (HCC). The functions of minocycline on HCC cells were investigated using immunohistochemical staining and western blotting. Minocycline was applied to L02, HepG2 and Huh7 cells, and the growth characteristics were studied. Cisplatin was administered in combination with minocycline in this study. Cell cycle and apoptosis analyses were employed to investigate the mechanisms underlying the growth regulation associated with minocycline and(or) cisplatin. Minocycline caused S phase cell cycle arrest and an increase in the apoptotic rate associated with upregulation of p27, cleaved-caspase8, cleaved-caspase3 and cleaved-PRAP-1. Low dose of cisplatin promoted cell cycle arrest and apoptosis, whereas minocycline was mainly associated with upregulation of cleaved-PARP-1. The combination of cisplatin and minocycline increased the rate and extent of cell cycle arrest and increased the apoptosis rate caused by minocycline. A novel mechanism was revealed. Minocycline functions as an antitumor drug in HCC by regulating p27, caspase-3 and PARP-1. Cisplatin enhanced minocycline's effect on PARP-1.

Background We aimed to investigate the correlations between ACE2 polymorphisms and type 2 diabetes mellitus (T2DM) combined with cerebral stroke (CS). Methods A total of 346 patients treated or hospitalized in our hospital were enrolled, including 181 cases without cerebrovascular complications (T2DM group) and 165 cases combined with CS (T2DM + CS group); 284 healthy individuals were selected as the control group. PCR-RFLP and ELISA were used to analyze ACE2 G8790A polymorphisms and serum ACE2 levels, respectively. Results Significant differences were observed in the genotype/allele frequency of ACE2 G8790A between the T2DM + CS and control groups, and the T2DM and T2DM + CS groups, and in the genotype frequency of ACE2 G8790A between the T2DM and the control groups. The A allele may increase the risk of T2DM combined with CS. The AA genotype may also increase the risk of T2DM combined with CS (OR = 3.733, 95%CI = 2.069-6.738; OR = 3.597, 95%CI = 1.884-6.867). Serum ACE2 levels showed statistically significant differences among the groups. Systolic pressure and diastolic pressure were protective factors of T2DM combined with CS. Conclusion The ACE2 G8790A polymorphism in T2DM patients was correlated with CS, and the A allele might be a risk factor of T2DM combined with CS.

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.

Transforming growth factor (TGF)-β induces cell growth arrest in well-differentiated hepatocellular carcinoma (HCC) while hepatitis B virus X protein (HBx) minimizes the tumor suppression of TGF-β signaling in early chronic hepatitis B. However, how to reverse the oncogenic effect of HBx and sustain the tumor-suppressive action of TGF-β has yet to be investigated. The present study examined the effect of TGF-β and a c-Jun N-terminal kinase (JNK) inhibitor on cell growth in HCC cells with forced expression of HBx. It was found that HBx promoted cell growth via activation of the JNK/pSMAD3L pathway and inhibition of the transforming growth factor-beta type I receptor (TβRI)/pSMAD3C pathway. pSMAD3L/SMAD4 and pSMAD3C/SMAD4 complexes antagonized each other to regulate c-Myc expression. In the absence of HBx, TGF-β induced cell growth arrest through activation of the TβRI/pSMAD3C pathway in well-differentiated HCC cells. In the presence of HBx, TGF-β had no effect on cell growth. JNK inhibitor SP600125 significantly reversed the oncogenic action of HBx and favored TGF-β to regain the ability to inhibit the cell growth in HBx-expressing well-differentiated HCC cells. In conclusion, targeting JNK signaling favors TGF-β to block HBx-induced cell growth promotion in well-differentiated HCC cells. As an adjunct to anti-viral therapy, the combination of TGF-β and inhibition of JNK signaling is a potential therapy for HBV-infected HCC.

Transcriptional intermediary factor 1 gamma (TIF1γ) may play either a potential tumor-suppressor or -promoter role in cancer. Here we report on a critical role of TIF1γ in the progression of hepatocellular carcinoma (HCC). Reduced expression of TIF1γ was detected in HCC, especially in advanced HCC tissues, compared to adjacent noncancerous tissues. HCC patients with low TIF1γ expression had shorter overall survival times and higher recurrence rates than those with high TIF1γ expression. Reduced TIF1γ expression was an independent and significant risk factor for recurrence and survival after curative resection. In HCC cells, TIF1γ played a dual role: It promoted tumor growth in early-stage HCC, but not in advanced-stage HCC, whereas it inhibited invasion and metastasis in both early- and advanced-stage HCC. Mechanistically, we confirmed that TIF1γ inhibited transforming growth factor-β/ Drosophila mothers against decapentaplegic protein (TGF-β/Smad) signaling through monoubiquitination of Smad4 and suppressed the formation of Smad2/3/4 complex in HCC cells. TGF-β-inducing cytostasis and metastasis were both inhibited by TIF1γ in HCC. We further proved that TIF1γ suppressed cyotstasis-related TGF-β/Smad downstream c-myc down-regulation, as well as p21/cip1 and p15/ink4b up-regulation in early-stage HCC. Meanwhile, TGF-β inducible epithelial-mesenchymal transition and TGF-β/Smad downstream metastatic cascades, including phosphatase and tensin homolog deleted on chromosome ten down-regulation, chemokine (CXC motif) receptor 4 and matrix metalloproteinase 1 induction, and epidermal growth factor receptor– and protein kinase B–signaling transactivation, were inhibited by TIF1γ. In addition, we found that the down-regulation of TIF1γ in HCC was caused by hypermethylation of CpG islands in the TIF1γ promoter, and demonstrated that the combination of TIF1γ and phosphorylated Smad2 was a more powerful predictor of poor prognosis. Conclusion: TIF1γ regulates tumor growth and metastasis through inhibition of TGF-β/Smad signaling and may serve as a novel prognostic biomarker in HCC. (Hepatology 2014;60:1620–1636)

Transforming growth factor β (TGF-β)/Smad signaling is involved in colorectal carcinoma (CRC) development and progression. The frequent loss of SMAD4 is associated with liver metastasis and poor prognosis of CRC, but the underlying mechanism remains elusive. This study aimed to elucidate the role of Smad-independent TGF-β signaling in CRC metastasis. Immunohistochemistry showed that Smad4 level was negatively correlated with TNM stage and phospho-ERK level in human CRCs and liver metastasis samples. Knockdown of Smad4 in CT26 and HCT116 cells activated ERK pathway, altered the expression of MMP2 and COX-2, promoted cell motility, migration, and invasion in vitro, enhanced metastasis, and shortened the survival of metastatic tumor-bearing mice. MEK inhibitor U0126 and GSK1120212 inhibited the motility, migration, and invasion of Smad4 knockdown cells, inhibited metastasis, and prolonged the survival of metastatic tumor-bearing mice. Furthermore, MEK inhibitor could reverse the changes of phospho-ERK, MMP2, and COX-2 levels. In conclusion, our results indicate that ERK pathway plays a key oncogenic role in CRC with SMAD4 inactivation mutations, and implicate ERK as a potential therapeutic target for CRC liver metastasis.

Even now, radiofrequency ablation (RFA) is accepted as a curative therapy for colorectal cancer liver metastasis (CRLMs). Accumulating data have shown that incomplete radiofrequency ablation (ICR) associates with increase of tumor recurrence and more aggressive malignant phenotype. We determined the mechanisms of this progression, including effectively predict biologic behaviors.We established a mouse model highly mimicking the process of RFA treatment. Functional studies were performed in vitro and in vivo. Our xenograft model unveiled ICR increases the risk in CRLMs recurrence. Here we focused on the heat shock (HS)-induced CRC malignance. Sublethal HS in CRC cell lines provoked cell growth, invasion, and tumor initiation in vitro. Consistently, the xenograft mouse model also confirmed the effects of HS in promoting tumor growth. With Western blot analysis, we found that Fra-1, which is a typical down-stream of the transcription factor ERK1/2, was significantly increased by heat shock stimuli compared with the untreated CRC cells. Furthermore, we demonstrated that silence of Fra-1 in HS treated cells could abolish the effects of HS in promoting malignant phenotype. Significantly, proliferation markers (Ki67, c-Myc, CyclinD1, CDK2), stem cell markers (Sox-2, Sox-9, Oct3/4, Lgr5) and invasion related MMP1 were up-regulated in the HS treated cells and in xenograft model. Taken together, this study established a novel mouse model to study the effect of ICR in CRLM. HS induces CRC proliferation and metastasis by targeting Fra-1, which is a potential prognostic marker and a promising therapeutic strategy for CRC recurrence after RFA treatment. Citation Format: Zhan-Guo Zhang, Wan-Guang Zhang, Yan-Hui Wu, Hui-Fang Liang, Bi-Xiang Zhang, Xiao-Ping Chen. Incomplete RFA-generated heat shock response provokes colorectal cancer liver metastases (CRLMs) recurrence by inducing cancer cell stemness and invasion. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B47.