Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Flexible generation of broadly wavelength- and OAM-tunable Laguerre-Gaussian (LG) modes from a random fiber laser.

Broadband wavelength tunable Laguerre-Gaussian (LG) mode with flexibly manipulated topological charge is greatly desired for large-capacity optical communication. However, the operating wavelengths achieved for the current LG modes are significantly restricted either by the emission spectrum of the intracavity gain medium or by the operation wavelengths of mode-conversion or modulation components. Here, broadband wavelength-tunable LG modes with a controllable topological charge are generated based on a random fiber laser (RFL) and a digital micromirror device (DMD). The RFL can produce broadly wavelength-tunable laser emissions spanning from 1044 to 1403 nm with a high spectral purity and an excellent beam quality, benefiting from the cascaded random Raman gain starting from a ytterbium fiber based active gain. A commercially available broadband DMD is then utilized to excite the LG modes with a flexibly tunable topological charge of up to 100 order through the super-pixel wavefront shaping technique. The combination of the RFL and the DMD greatly broadens the operating wavelength region of the LG modes to be achieved, which facilitates the capacity scaling-up in the orbital angular momentum multiplexed optical communication application.

Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm.

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

Nontuberculous Mycobacteria Infection After Autologous Fat Grafting for Cosmetic Breast Augmentation.

BACKGROUND: Autologous fat grafting has been widely applied in cosmetic breast augmentation in recent years. However, nontuberculous mycobacteria infection, as one of the multiple complications described in the literature, has been less well discussed. OBJECTIVE: The aims of the study were to report 5 cases of nontuberculous mycobacteria infection after autologous fat injection for the cosmetic breast augmentation and to explore its causes. METHODS: In this noncomparative, retrospective, and interventional case series, we identified 5 patients with nontuberculous mycobacteria infection. All patients had a history of previous autologous fat injection into the breast for cosmetic purpose, performed in different plastic facilities. RESULTS: Five patients developed nontuberculous mycobacteria infection after autologous fat injection for cosmetic breast augmentation and came to our group for treatment. Grafted fat removal through multiple debridement and long-term intravenous and oral antibiotic therapy were required in our cases. CONCLUSIONS: The number of nontuberculous mycobacteria infection after autologous fat injection into the breast is increasing. Surgeons should be aware of the complication, which rarely manifests during the procedure itself. Strict aseptic principles should be obeyed throughout the surgery.

[Application of antibody drugs in the field of anti-infection].

In recent years, with the rapid development of antibody drugs, the antibody-based therapies have gradually expanded from the cancer and autoimmune diseases to metabolic and infectious diseases and so on. However, the development of antibody-based anti-infective drugs is much slower as there are only two kinds of drugs in the market. This is due to the complex infective mechanism of viruses, bacteria and other pathogens, and the monovalent character of monoclonal antibodies that greatly limit the anti-infection effect of antibody drugs. The development and application of novel technologies, such as recombinant polyclonal antibody technology, will greatly accelerate the development of antibody-based anti-infection drugs. This article will introduce the application and trends in the development of antibody-based drugs in the field of anti-infection therapy.

The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer.

BACKGROUND: Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied. METHODS: The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERß agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis. RESULTS: PPARγ protein and activity were reduced by the over-expression of either ERα or ERß, whereas repression of ERα or ERß increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERß activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERß and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor. CONCLUSIONS: This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERß significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.

Heating tumors with tumor cell-derived nanoparticles to enhance chemoimmunotherapy for colorectal cancer.

Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.

Circ_0003747 promotes thyroid cancer progression by sponging miR-338-3p to upregulate PLCD3 expression.

The circular RNAs (circRNAs) involved in competitive endogenous RNA (ceRNA) mechanism are critical modulators affecting pathogenesis of thyroid carcinoma (TC). The study's goal was to investigate the effects of circ 0003747 on the biological progression of papillary thyroid cancer (PTC). Normal thyroid cells Nthy-ori3-1 and TC derived cell lines were used in our study. Sanger sequencing and RNase R treatment were utilized for validating the circular structure of circ_0003747. In our work, circ_0003747 was found to be highly expressed in TC cells. Circ_0003747 knockdown reduced TC cell viability, proliferation, migration, and invasion while increasing cell apoptosis. Circ_0003747 targeted and negatively regulated miR-338-3p expression. Besides, miR-338-3p interacted with PLCD3 to repress its expression. Overexpression of miR-338-3p inhibited TC cell progression, and PLCD3 reversed these effects. Furthermore, PLCD3 overexpression reversed the effects of circ_0003747 knockdown on TC cells. Additionally, the knockdown of circ_0003747 remarkably suppressed tumour size and growth, restrained PLCD3 expression and promoted miR-338-3p expression in nude mice. In conclusion, circ_0003747 facilitated the biological progression of TC by modulating the miR-338-3p/PLCD3 axis, and it may be a new target for TC treatment. [Figure: see text]Abbreviations: TC: Thyroid carcinoma; PTC: Papillary thyroid carcinoma; CircRNAs: Circular RNAs; MiRNA: MicroRNA; EMT: Epithelial-mesenchymal transition; HCC: Hepatocellular carcinoma; PLCD3: Phospholipase C Delta 3; CeRNA: Competitive endogenous RNA.

[Protective effect of adipocytes fatty acid binding protein inhibitor on pancreas islet cell against macrophage-mediated cytotoxicity of mice in vitro].

OBJECTIVE: To investigate the potential role of adipocytes fatty acid binding protein (A-FABP)inhibitor to prevent pancreatic islet cells from cytotoxic injury by inflammatory cytokines released from macrophage. METHODS: Co-culture system for RAW264.7 macrophage and MIN6 insulinoma cells was established through transwell combined with A-FABP inhibitor BMS309403 treatment for 48 h. Meanwhile, cultured RAW264.7 and MIN6 respectively were set up as controls. In the inhibitor group, BMS309403 preprocessing (5 µmol/L) was performed 2 h before co-culture. The expression of toll-like receptors(TLR)4 and A-FABP in RAW264.7 macrophages was detected by RT-PCR and Western blotting, interleukin (IL)-1ß and tumor necrosis factor(TNF)-α levels in the supernatant were detected by ELISA, Glucose-stimulated insulin level was detected by insulin radioimmuno-assay kits for the function of islets. RESULTS: (1) The mRNA and protein levels of both TLR4 and A-FABP in RAW264.7 macrophages as well as the concentrations of IL-1ß and TNF-α in the supernatant were significantly higher in co-culture group than in macrophages control group (P < 0.05). (2) Insulin secretion stimulated by high glucose was obviously decreased in co-culture group when compared with insulinoma cells control group [(16.0 ± 2.2) vs (41.1 ± 6.6) ng/ml, P < 0.05]. After the treatment with A-FABP inhibitor, the mRNA and protein levels of both TLR4 and A-FABP as well as the concentrations of IL-1ß and TNF-α in the supernatant were significantly lower than in co-culture control (P < 0.05). However, insulin secretion stimulated by high glucose was significantly enhanced when compared with insulinoma cells control group [(31.4 ± 3.3) vs (16.0 ± 2.2) ng/ml, P < 0.05]. CONCLUSIONS: This study demonstrated that co-culture of macrophage and islet cells can activate inflammation pathway, stimulate inflammatory cytokine release and decrease insulin secretion from islet cells. A-FABP inhibitor can protect islet cells from macrophage-mediated cytotoxicity and preserve its insulin secretory function.

Inflammation-Immunity-Nutrition Score: A Novel Prognostic Score for Patients with Resectable Colorectal Cancer.

PURPOSE: This study was designed to investigate the prognostic value of the combination of high-sensitivity C-reactive protein, lymphocyte, and albumin in patients with resectable colorectal cancer. PATIENTS AND METHODS: Seven-hundred-and-nineteen patients who underwent colorectal cancer resection in Hubei Cancer Hospital were included. Inflammation-Immunity-Nutrition score (0-6) was constructed based on preoperative high-sensitivity C-reactive protein, lymphocyte, and albumin. Time-dependent receiver operating characteristic curve, decision curve, Kaplan-Meier survival curve, Cox regression, and C-index were conducted to detect the prognostic values of inflammation-immunity-nutrition score. The prognostic values of inflammation-immunity-nutrition score in different subgroups by sex, location of tumor, pathologic stage, and KRAS mutation were also explored. The prognostic performance of inflammation-immunity-nutrition score was further compared with that of other traditional prognostic indicators. RESULTS: The median follow-up time was 40 months. High inflammation-immunity-nutrition score (>2 scores) presented worse survival, with the adjusted hazard ratios (95% confidence intervals) of 3.106 (2.202-4.380) for overall survival and 2.105 (1.604-2.764) for disease-free survival. Besides, the associations of high inflammation-immunity-nutrition score with overall survival were even stronger in cases with wild type KRAS, with the adjusted hazard ratios (95% confidence intervals) of 4.018 (2.355-6.854). Considering the AUCs, C-indices, and hazard ratios estimates, inflammation-immunity-nutrition score presented better prognostic performance than high-sensitivity modified Glasgow prognostic score, high-sensitivity C-reactive protein to albumin ratio, prognostic nutrition index, carcinoembryonic antigen, and carbohydrate antigen 19-9 for overall survival. CONCLUSION: Inflammation-immunity-nutrition score might serve as a powerful prognostic score in patients with colorectal cancer for overall survival, particularly in patients with wild type KRAS.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

NF-κB-Activated miR-574 Promotes Multiple Malignant and Metastatic Phenotypes by Targeting BNIP3 in Thyroid Carcinoma.

Thyroid cancer is the most common endocrine malignancy, and miR-574 is significantly upregulated in thyroid cancer. However, the role and underlying mechanism of miR-574 in thyroid cancer development are poorly understood. In this study, we showed that NF-κB/p65 signaling pathway was activated and miR-574 was upregulated in thyroid cancer cells. p65 directly bound to the promoter of miR-574 and activated miR-574 transcription. Functionally, miR-574 inhibited apoptosis, promoted proliferation and migration of thyroid cancer cells, and stimulated thyroid cancer-induced tube formation of endothelial cells. On the molecular level, miR-574 inhibited the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) by binding to 3'-UTR of BNIP3. miR-574 also downregulated the expression of apoptosis-inducing factor (AIF), while elevated the levels of MMP2, MMP9, and VEGFA. In vivo, miR-574 promoted xenograft growth, which was associated with reduced apoptosis and enhanced angiogenesis. NF-κB/miR-574 signaling presents multiple oncogenic activities on thyroid cancer development by directly regulating the BNIP3/AIF pathway. Therefore, targeting NF-κB/miR-574 signaling may reduce the aggressiveness of thyroid cancer. IMPLICATIONS: miR-574, directly regulated by NF-κB/p65, promotes tumorigenesis of thyroid cancer via inhibiting BNIP3/AIF pathway.

MicroRNA-574-5p directly targets FOXN3 to mediate thyroid cancer progression via Wnt/ß-catenin signaling pathway.

OBJECTIVE: Thyroid cancer is the most common endocrine tumor. A large number of thyroid cancer-related miRNAs have been studied and identified. However, the detailed roles of miR-574-5p in thyroid cancer remain poorly understood. This work mainly aimed to investigate the role of miR-574-5p/FOXN3 axis and its mechanism in the thyroid cancer progression. METHODS: MiR-574-5p, FOXN3, Wnt/ß-catenin pathway, and apoptosis-related markers were measured by quantitative real-time PCR (qRT-PCR) and western blotting analysis, respectively. Luciferase reporter assay was employed to validate the direct targeting of FOXN3 by miR-574-5p. MTT, flow cytometry, wound healing and transwell experiments were applied to analyze the functions of FOXN3 and miR-574-5p in thyroid cancer cells. RESULTS: Knockdown of miR-574-5p up-regulated FOXN3 expression and miR-574-5p directly targeted FOXN3 in thyroid cancer cells. Biological function experiments showed that knockdown of miR-574-5p inhibited proliferation, migration, invasion and promoted apoptosis of thyroid cancer cells. The activation of Wnt/ß-catenin pathway was suppressed by MiR-574-5p silencing. FOXN3 silencing reversed the effects of miR-574-5p inhibitor on FOXN3 level and Wnt/ß-catenin singling pathway, also reversed the effects on cell migration, proliferation, invasion and apoptosis. CONCLUSION: The miR-574-5p/FOXN3 axis is a novel molecular mechanism that promotes thyroid cancer progression, suggesting their potential for clinical therapy of thyroid cancer.

LncRNA TBX5-AS1 Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer.

PURPOSE: Long non-coding RNAs (lncRNAs) have been reported to play important roles in tumor biology. In this study, we aimed to investigate the effects of T-box transcription factor 5 antisense RNA 1 (TBX5-AS1) on aggressive phenotypes of non-small cell lung cancer (NSCLC) cells and explore its regulatory pathway. METHODS: The expression of TBX5-AS1 in tissues, plasma, and cells was determined by qRT-PCR. Cell viability, proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, wound-healing, Transwell, and flow cytometry assay, respectively. Western blot analysis was performed to measure the expression of apoptosis-related proteins. Besides, transfected cells were exposed to PI3K activator (740Y-P) to verify the regulatory pathway. RESULTS: TBX5-AS1 expression was down-regulated in NSCLC tissues, plasma, and cells, and associated with lymph node metastasis and histological grade. Overexpression of TBX5-AS1 inhibited cell viability, colony formation, migration, and invasion, while it promoted apoptosis. Conversely, knockdown of TBX5-AS1 showed the completely opposite results. Additionally, western blot showed that the phosphorylation of PI3K and AKT was stimulated by TBX5-AS1 knockdown and suppressed by TBX5-AS1 overexpression. The addition of 740Y-P in transfected cells reversed the TBX5-AS1-induced inhibition of PI3K and AKT phosphorylation and effects on aggressive phenotypes of NSCLC cells. CONCLUSION: The study confirmed the down-regulation of TBX5-AS1 in patients with NSCLC and its association with the progression. We innovatively proposed a possible model of TBX5-AS1-mediated gene regulation in NSCLC progression that TBX5-AS1 inhibited the aggressive phenotypes of NSCLC cells through inactivating the PI3K/AKT pathway. This finding provided a novel insight into NSCLC pathogenesis.

Susceptibility and Resistance Mechanisms During Photodynamic Therapy of Melanoma.

Melanoma is the most aggressive malignant skin tumor and arises from melanocytes. The resistance of melanoma cells to various treatments results in rapid tumor growth and high mortality. As a local therapeutic modality, photodynamic therapy has been successfully applied for clinical treatment of skin diseases. Photodynamic therapy is a relatively new treatment method for various types of malignant tumors in humans and, compared to conventional treatment methods, has fewer side effects, and is more accurate and non-invasive. Although several in vivo and in vitro studies have shown encouraging results regarding the potential benefits of photodynamic therapy as an adjuvant treatment for melanoma, its clinical application remains limited owing to its relative inefficiency. This review article discusses the use of photodynamic therapy in melanoma treatment as well as the latest progress made in deciphering the mechanism of tolerance. Lastly, potential targets are identified that may improve photodynamic therapy against melanoma cells.

Increased expression of cyclooxygenase-2 and increased infiltration of regulatory T cells in tumors of patients with hepatocellular carcinoma.

BACKGROUND: Studies on Cox-2 and Foxp3+ regulatory T cells (Treg) in hepatocellular carcinoma (HCC) showed that Treg suppress local immune response in a Cox-2-dependent fashion. AIMS: To investigate Cox-2 expression, Foxp3+ Treg infiltration and CD4+ T cell frequency in HCC tumors. METHODS: Tumors and the corresponding nontumor hepatitis B virus-related liver tissues from 40 HCC patients with hepatitis B virus infection, plus 10 liver samples from patients with hemangioma as controls, were assessed for Cox-2 expression, Foxp3+ Treg and total CD4+ T cell numbers using immunohistochemistry. Serum TGF-beta1 was assessed by ELISA. RESULTS: Reduced Cox-2 expression, increased Treg and increased CD4+ T cells were shown in tumor as compared with nontumor tissues. Moreover, of 40 tumor tissues, 23 that expressed Cox-2 showed increased Foxp3+ Treg and reduced CD4+ T cells compared with the remaining 17 that did not express Cox-2. Correlation analyses showed that within tumors Treg infiltration correlated positively with Cox-2 expression, and that Treg infiltration or Cox-2 expression correlated negatively with CD4+ T cells. Additionally, serum TGF-beta1 was higher in HCC patients than in controls. CONCLUSION: Within tumors, Cox-2 expression, Treg infiltration and CD4+ T cell frequency were increased, and the Cox-2 expression correlated positively with Treg infiltration and negatively with CD4+ T cell frequency.

Overexpression of Raf-1 kinase inhibitor protein inhibits cell invasion and migration in lung cancer cells through suppressing epithelial-mesenchymal transition.

BACKGROUND: Raf-1 kinase inhibitor protein (RKIP) is a small evolutionary conserved protein that was associated with the Raf-MEK-ERK pathway. However, whether RKIP would alter the invasion and metastasis of non-small cell lung cancer (NSCLC) and play the role through suppressing epithelial-mesenchymal transition (EMT) remains to be explored. METHODS: A549 cells were transfected with RKIP-GV141 plasmid for overexpression of RKIP. Colony formation assay and MTT assay were performed to measure the effects of RKIP on the proliferation and cell viability assay of A549 cells. Transwell, Migration Assay and wound healing assay were performed to analyze the effects of RKIP on the invasion and metastasis of A549 cells. E-cadherin and vimentin were measured by Western blot to conform RKIP affects invasion and metastasis of NSCLC via inhibiting EMT. RESULTS: RKIP is downregulated in NSCLC tissues compared to adjacent normal lung tissues by IHC. Decreased expression of RKIP contributes to poor prognosis in lung adenocarcinoma patients. Age and pTNM stage were independent prognostic factors for adenocarcinoma patients. Overexpression of RKIP reduces the cell viability and limits the proliferation, invasion, and migration of A549 cells in vitro. Wound healing assay showed the degressive ability of metastasis. High expression of E-cadherin and low expression of vimentin indicated that RKIP affects invasion and metastasis of NSCLC via inhibiting EMT. CONCLUSIONS: RKIP is decreased in NSCLC tissues. Overexpression of RKIP in A549 cells would decrease the cellular proliferation, viability, invasion ability, and metastasis ability probably via inhibiting EMT through upregulating E-cadherin expression and downregulating vimentin expression.

Survival and analysis of prognostic factors for hepatoblastoma: based on SEER database.

BACKGROUND: The goal of this study is to assess the newest survival of hepatoblastoma (HB) and the risk factors which impacted on survival by using the Surveillance, Epidemiology and End Results (SEER) database, also calculate the incidence of HB in recent years. METHODS: We calculate age-adjusted incidence of HB by using SEER 21 registries. Age, sex, race, tumor size, macrovascular involvement, multifocal tumor, distant metastasis, the way of treatment, and the survival were collected for survival and analysis of prognostic factors in SEER 18 registries. Survival curves, according to different factors, were obtained by Kaplan-Meier estimates. Multivariable Cox regression models were also built. RESULTS: The overall age-adjusted incidence of HB was 0.19 patients per 100,000 children with a statistically significant increase per year. Overall survival (OS) at 1-, 3- and 5-year for all patients were 89.3%, 84.6%, and 81.9%, respectively. Multivariate analysis showed tumor size >5 cm [hazard ratio (HR), 8.271; 95% confidence interval (CI), 1.134-60.310], multiple tumors (HR, 2.578; 95% CI, 1.424-4.668) and no-surgery treatment (HR, 7.520; 95% CI, 4.121-13.724) were independent indicators of poor prognosis. Only the age ≥2-year-old (HR, 3.240; 95% CI, 1.433-7.326) and multiple tumors (HR, 2.395; 95% CI, 1.057-5.430) were the risk factors for the surgical treatment group. CONCLUSIONS: The survival of patients with HB has been greatly improved in the recent years, and at the same time, due to the application of better chemotherapy, we should re-evaluate the traditional risk indicators of prognosis in order to better apply to the clinical.

Zebrafish Xenograft Model of Human Lung Cancer for Evaluating Osimertinib Resistance.

About half of NSCLC patients with EGFR mutation had secondary mutation T790M after treatment with a first-generation tyrosine kinase inhibitor (TKI), Gefitinib. The third-generation of EGFR-TKI Osimertinib is suitable for patients with EGFR mutation and T790M mutation. However, drug screening for NSCLC patients after the emergence of acquired resistance has become a difficult problem for clinicians. In this study, we established drug-resistant cell lines of Gefitinib and Osimertinib to evaluate cell proliferation in vitro. And we investigated the inhibitory effect of different drug concentration gradients on cancer cells. Zebrafish with high homology to human genes were selected as xenotransplantation models to compare the effects of different concentrations of Osimertinib on the proliferation and angiogenesis of zebrafish tumors after transplantation of different lung cancer cell lines. It was confirmed that Osimertinib could inhibit the proliferation of tumor cells with EGFR mutation and T790M resistance mutation in zebrafish, which was consistent with the clinical research conclusion.

Correlation between expression of cyclooxygenase-2 and the presence of CD4+ infiltrating T-lymphocyte in human primary hepatocellular carcinoma.

BACKGROUND/AIMS: Recent studies have found that Cyclooxygenase-2(Cox-2) is frequently inappropriately expressed in primary hepatocellular carcinoma (HCC), suggesting that abnormal Cox-2 expression plays an important role in hepatocarcinogenesis. But it remains controversial in these reports. Moreover, there are only a few studies on the correlation between Cox-2 and infiltrating immunocytes in the tumor-microenvironment. CD4+ tumor-infiltrating lymphocytes (TIL) and infiltrating immunocytes around the tumor are closely correlated to the development of the tumor, but so far no reports are available showing the relationship among Cox-2, CD4+ TIL of tumor and CD4+ infiltrating T-lymphocytes of adjoining non-tumorous (ANT) tissues in tumor-microenvironment. This study is designed to appropriately select and collect patients' specimens to better reflect Cox-2 expression in human HCC, and also to stress the correlation among Cox-2, CD4+ TIL and CD4+ infiltrating T-lymphocytes in the tumor-microenvironment. METHODOLOGY: Tumor tissue, and its matched ANT tissue removed less than 1 cm from the solid tumor border, were obtained from 25 HCC patients all of whom came from Hunan province, China, and were infected with hepatitis B virus (HBV). Normal liver tissues of 10 hemangiomas were collected as controls. Both Cox-2 expression and the number of CD4+ TIL and CD4+ infiltrating T-lymphocyte were detected by immunohistochemistry, and data were analyzed closely with patients' clinical figures so as to investigate the correlation between the 3 elements. RESULTS: In 25 HCC patients, remarkably higher Cox-2 expression in both tumor and ANT tissues was observed compared with normal liver tissues (p < 0.001). The percentage of Cox-2 positive cells was, remarkably, higher in ANT tissues than in tumors (p < 0.001). Similarly the distribution of CD4+ T cells was significantly higher in ANT tissue than in tumor tissue (p < 0.0001), and also significantly higher in tumor tissue than in normal tissue (p < 0.0001). Importantly, in the group of patients with Cox-2-expressing tumors, the number of CD4+ infiltrating T-lymphocyte in ANT tissues was 79.4(+)9.92/hpf, which is obviously lower (p = 0.019) than that of the group with non-Cox-2-expressing tumors with the number of CD4+ infiltrating T-lymphocyte in ANT tissues at 118.13(+)12.47/hpf. Cox-2 expression of tumors showed a significant negative correlation with number of CD4+ infiltrating T cells of ANT tissues (r = 0.499, p = 0.024). The number of CD4+ TILs are lower in Cox-2-expressing tumors than in non-Cox-2-expressing tumors, but there was not statistical significance (p = 0.057). CONCLUSIONS: Taken together we suggest in the tumor-microenvironment of HCC the expression of Cox-2 may inhibit the number CD4+ infiltrating T-lymphocyte in ANT tissues. As a result, Cox-2 overexpression may contribute to both suppression of local immune responses and enhancement of metastatic potential in human HCC.