Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.

Isolation, identification, and optimization of conditions for the degradation of four sulfonamide antibiotics and their metabolic pathways in Pseudomonas stutzeri strain DLY-21.

Overuse of sulfonamides in aquaculture and agriculture leads to residual drugs that cause serious pollution of the environment. However, the residues of sulfonamides in the environment are not unique, and the existing microbial degradation technology has a relatively low degradation rate of sulfonamides. Therefore, in this study, a Pseudomonas stutzeri strain (DLY-21) with the ability to degrade four common SAs was screened and isolated from aerobic compost. Under optimal conditions, the DLY-21 strain degraded four sulfonamides simultaneously within 48 h, and the degradation rates were all over 90%, with the average degradation rates of SAs being sulfoxide (SDM) ≈ sulfachloropyridazine (SCP) > sulfa quinoxaline (SQ) > sulfadiazine (SQ). In addition, the main compounds of the strain DLY-21-degrading SAs were identified by LC-MS analysis. On this basis, four detailed reaction pathways for SA degradation were deduced. This is the first report of the use of a P. stutzeri strain to degrade four sulfonamide antibiotics (SQ, SDM, SCP, and SM1), which can improve the removal efficiency of sulfonamide antibiotic pollutants and thus ameliorate environmental pollution. The results showed that DLY-21 had a good degradation effect on four SAs (SQ, SDM, SCP, and SM1).

Hydrochemical and microbial community characteristics and the sources of inorganic nitrogen in groundwater from different aquifers in Zhanjiang, Guangdong Province, China.

Groundwater from different aquifers in the Zhanjiang area suffers from different degrees of nitrogen pollution, which poses a serious threat to the health of urban and rural residents as well as the surrounding aquatic ecological environment. However, neither the water chemistry and microbial community characteristics in different aquifer media nor the sources of inorganic nitrogen pollution have been extensively studied. This study integrated water quality parameters, dual isotopes (δ15N-NO3- and δ18O-NO3-), and 16S rRNA data to clarify the hydrochemical and microbial characteristics of loose rock pore water (LRPW), layered bedrock fissure water (LBFW), and volcanic rock pore fissure water (VRPFW) in the Zhanjiang area and to determine inorganic nitrogen pollution and sources. The results show that the hydrochemistry of groundwater in different aquifers is complex and diverse, which is mainly affected by rock weathering and atmospheric precipitation, and the cation exchange is strong. High NO3- concentration reduces the richness of the microbial community (VRPFW). There are a large number of bacteria related to nitrogen (N) cycle in groundwater and nitrification dominated the N transformation. A quarter of the samples exceeded the relevant inorganic nitrogen index limits specified in the drinking water standard for China. The NO3- content is highest in VRPFW and the NH4+ content is highest in shallow loose rock pore water (SLRPW). In general, NO3-/Cl-, dual isotope (δ15N-NO3- and δ18O-NO3-) data and MixSIAR quantitative results indicate manure and sewage (M&S) and soil organic nitrogen (SON) are the main sources of NO3-. In LRPW, as the depth increases, the contribution rate of M&S gradually decreases, and the contribution rate of SON gradually increases. The results of uncertainty analysis show that the UI90 values of SON and M&S are higher. This study provides a scientific basis for local relevant departments to address inorganic nitrogen pollution in groundwater.

Assessment of rapid initiators and long-lasting nutrients for developing biological permeable reactive barriers to treat mine-contaminated groundwater.

The formation of mine-contaminated groundwater as a result of acidic mine drainage from the oxidation of sulfur-containing minerals entering the groundwater. Biological permeable reactive barrier (Bio-PRB) technology is excellent for the remediation of mine-contaminated groundwater. Usually, the organic substrates utilized in Bio-PRB are a combination of rapid initiators, which are readily bioavailable, and long-lasting nutrients, which are more difficult to degrade. Herein, we investigated the effectiveness of three rapid initiators and three long-lasting nutrients to remove sulfate from simulated mine-contaminated groundwater via simulated column experiments. The rapid initiators comprised crude glycerol, sodium acetate, and industrial syrup (IS), and the long-lasting nutrients included biodiesel emulsified oil, soybean oil emulsified oil, and high-carbon alcohol emulsified oil (HO). Microorganisms were stimulated using IS to create a sulfate reduction system owing to its high total organic carbon content (24.30 g L-1), achieving optimal sulfate removal rate (1.69 mmol dm-3 d-1). The fastest (2.93 mmol dm-3 d-1) and highest (88%) sulfate removal rates were achieved using HO, which is probably associated with the ability of HO to provide the most suitable C/N ratio (111.75) and induce the growth of sulfate-reducing bacteria (SRB) for substrate degradation. Conversely, a high concentration of sulfate reduction products inhibited SRB growth in the HO column. The addition of organic materials promoted SRB growth and various organic substrate-degrading bacteria. Furthermore, the competitive growth of methanogens (86.6%) may be responsible for the decrease in the relative abundance of SRB during the later stages of the experiment in the HO column.

Complete remission of gallbladder neuroendocrine carcinoma with liver metastasis by tislelizumab plus chemotherapy: a case report.

Background: Gallbladder neuroendocrine carcinoma (GB-NEC) is an extremely rare cancer with a poor prognosis in the clinic. Although surgical resection remains the primary and preferred therapeutics, many patients are in a late stage and lose the opportunity for surgery. However, due to the extremely low morbidity, the specific treatment guidelines for GB-NEC have not been established. Case presentation: A 52-year-old woman was admitted to our hospital with the chief complaint of "almost 1 month after palliative surgery for metastatic gallbladder carcinoma." According to the results of pathological findings and imaging manifestations, the patient was diagnosed with GB-NEC with a clinical stage of pT3N1M1 (IVB). The patient then received tislelizumab plus EP chemotherapy (etoposide 100 mg + cisplatin 30 mg, d1-3) every 3 weeks for 8 cycles from 12 November, 2021, followed by maintenance therapy (tislelizumab alone) every 3 weeks until now. The tumor response was evaluated as complete remission since 13 February, 2023. As of the last follow-up, the patient remains alive, with no complaints of discomfort. Conclusions: Gallbladder NEC has no specific symptoms, and the diagnosis is based on pathological and immunohistochemical results. The therapeutic course and efficacy of the case in this study indicates that the application of PD-1 inhibitor might be a feasible therapeutic option for GB-NEC. However, this potential strategy needs validation by further clinical studies in the future.

Study on the Effect of AO-Coupled Constructed Wetlands on Conventional and Trace Organic Pollutant Treatment.

In this study, a pilot-scale integrated process was developed, which combined the integrated biological contact oxidation technology (AO) and the improved constructed wetland technology. The results showed significant removal efficiency for both conventional and trace organic pollutants. The average removal efficiencies for COD, NH4+-N, and TP were 78.52, 85.95, and 49.47%, respectively. For trace organic pollutants, triclocarban, triclosan, and sulfadiazine, the removal efficiencies reached 60.14, 57.42, and 84.29%, respectively. The AO stage played a crucial role in removing trace organic pollutants, achieving removal efficiencies of 37.28, 43.44, and 83.82% for triclocarban, triclosan, and sulfadiazine, respectively. Subsequent treatment using improved constructed wetland technology with coal slag + gravel fillers demonstrated the highest removal efficiency, with average efficiencies of 68.66, 63.38, and 81.32% for triclocarban, triclosan, and sulfadiazine, respectively. Correlation analysis revealed positive correlations between temperature, precipitation, and the removal efficiency of COD, NH4+-N, and TP, while negative correlations were observed with the removal efficiency of triclocarban, triclosan, and sulfadiazine. Furthermore, the influent concentrations of triclocarban and triclosan were significantly negatively correlated with the removal efficiency of COD and TP. The presence of triclocarban and triclosan potentially reduced the microbial diversity and hindered sludge sedimentation performance.

High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression.

Aims: To screen abnormal lncRNAs and diagnostic biomarkers in the progression of hepatocellular carcinoma through high-throughput sequencing and explore the underlying mechanisms of abnormal lncRNAs in the progression of hepatocellular carcinoma. Methods: The transcriptome sequencing was used to analyze the RNA expression profile and identify differentially expressed RNAs. Hub lncRNAs were screened by combining (WGCNA, ceRNA regulatory network, PPI, GO and KEGG analyses, Kaplan-Meier curve analysis, Cox analysis, risk model construction and qPCR). Thereafter, the correlation between the expression of hub lncRNAs and tumor clinicopathological parameters was analyzed, and the hub lncRNAs were analyzed by GSEA. Finally, the effects of hub RNAs on the proliferation, migration and invasion of HepG2 cells were investigated in vitro. Results: Compared with the control group, a total of 610 lncRNAs, 2,593 mRNAs and 26 miRNAs were screened in patients with hepatocellular carcinoma. Through miRNA target prediction and WGCNA, a ceRNA was constructed, comprising 324 nodes and 621 edges. Enrichment analysis showed that mRNAs in ceRNA were involved mainly in cancer development progression. Then, the ZFAS1/miR-150-5p interaction pair was screened out by Kaplan Meier curve analysis, Cox analysis and qPCR analysis. Its expression was related to tumor stage, TNM stage and patient age. ROC curve analysis showed that it has a good predictive value for the risk of hepatocellular carcinoma. GSEA showed that ZFAS1 was also enriched in the regulation of immune response, cell differentiation and proliferation. Loss-of-function experiments revealed that ZFAS1 inhibition could remarkably suppress HepG2 cell proliferation, migration and invasion in vitro. Bioinformatic analysis and luciferase reporter assays revealed that ZFAS1 directly interacted with miR-150-5p. Rescue experiments showed that a miR-150-5p inhibitor reversed the cell proliferation, migration and invasion functions of ZFAS1 knockdown in vitro. Conclusion: ZFAS1 is associated with the malignant status and prognosis of patients with hepatocellular carcinoma, and the ZFAS1/miR-150-5p axis is involved in hepatocellular carcinoma progression.

Utility of a non-target screening method to explore the chlorination of similar sulfonamide antibiotics: Pathways and NCl intermediates.

Sulfonamides (SAs) are ubiquitous antibiotics that are increasingly detected in aquatic environments and can react with free available chlorine to produce transformation products (TPs) during disinfection. However, the TPs generated during chlorination remains poorly understood. Here, a non-target screening method based on the PyHRMS program was used to assess the transformation pathways of five SAs, particularly the transient NCl intermediates, during a simulated chlorination process. We observed 210 TPs during SA chlorination using a non-target screening method based on high-resolution mass spectrometry, and the reaction mechanisms mainly included chlorine substitution, desulfonation, and hydroxylation. Among the TPs, 87 were tentatively proposed to be NCl intermediates as they instantly disappeared after quenching with Na2S2O3. The MS2 spectra of 13 of these potential NCl intermediates were obtained, and all displayed an [M-Cl]+ fragment. A diagnostic fragment ion (DFI) strategy was applied to explore the structural relationship between parent compounds and TPs. Based on the result, five SAs and 101 TPs (if their MS2 spectra were available) could be connected through the same fragments, and this method was also proved effective in a real wastewater treatment plant effluent sample. We believe this novel method can help explore the TPs of organic compounds during chlorination in drinking water plants.

Genomic mutation characteristics and prognosis of biliary tract cancer.

BACKGROUND: The incidence of biliary system cancer is higher in the Chinese population than in the West. The overall prognosis of gallbladder cancer and cholangiocarcinoma is poor, and the current treatment is limited. In order to explore the pathogenesis of biliary tract cancers and potential targeted therapies, we mapped the mutation landscape of biliary tract cancer in the Chinese population and analyzed the molecular mechanism related to prognosis. METHODS: A total of 59 formalin fixed paraffin-embedded (FFPE) tissue samples were obtained from patients with operable biliary tract cancer. We conducted targeted capture sequencing of 620 genes through high-throughput sequencing technology and analyzed the fusion information of 13 genes. RESULTS: Mutations were detected in 88% samples, and the most frequent mutation base was C>T. Genes with higher single nucleotide variations (SNV) and copy number variations (CNV) frequency are TP53, KRAS, ARID1A, VEGFA, cyclin family related genes and cyclin-dependent kinase genes. Actionable mutations were detected in 59.3% samples, and germline mutations were detected in 22% samples. Patients with KRAS mutations, VEGFA pathway mutations and higher tumor mutation burden (TMB) may have poor prognosis. CONCLUSIONS: We explored the mutation characteristics and prognostic mechanism of biliary tract cancers in the Chinese population. This study provides potential evidence for targeted therapy and immunotherapy of biliary tract cancers.

A novel interpolation method to predict soil heavy metals based on a genetic algorithm and neural network model.

To improve the prediction accuracy of soil heavy metals (HMs) by spatial interpolation, a novel interpolation method based on genetic algorithm and neural network model (GANN model), which integrates soil properties and environmental factors, was proposed to predict the soil HM content. Eleven soil HMs (Cu, Pb, Zn, Cd, Ni, Cr, Hg, As, Co, V and Mn) were predicted using the GANN model. The results showed that the model had a good prediction performance with correlation coefficients (R2) varying from 0.7901 to 0.9776. Compared with other traditional interpolation methods, including inverse distance weighting (IDW), ordinary kriging (OK), universal kriging (UK), and spline with barriers interpolation (SBI) methods, the GANN model had a relatively lower root mean square error value, ranging from 0.0497 to 77.43, suggesting that the GANN model might be a more accurate spatial interpolation method and the soil properties together with the environmental geographical factors played key roles in prediction of soil HMs.

Mechanism of biochar functional groups in the catalytic reduction of tetrachloroethylene by sulfides.

In recent years, biochar has become of considerable interest for environmental applications, it can be used as a catalyst for sulfides reduction of perchloroethylene, but the crucial role of biochar properties played in catalyzing dechlorination remained ambiguous investigation. To pinpoint the critical functional groups, the modified biochars were respectively produced by HNO3, KOH and H2O2 with similar dimensional structures but different functional groups. Combined with the adsorption and catalytic results of different biochars, the acid-modified biochar had the best catalytic performance (99.9% removal) due to the outstanding specific surface area and ample functional groups. According to characterization and DFT results, carboxyl and pyridine nitrogen exhibited a positive correlation with the catalytic rate, indicating that their contribution to catalytic performance. Customizing biochar with specific functional groups removed depth demonstrated that the carboxyl was essential component. Further, alkaline condition was conducive to catalytic reduction, while tetrachloroethylene cannot be reduced under acidic conditions, because HS- and S2- mainly existed in alkaline environment and the sulfur-containing nucleophilic structure formed with biochar was more stable under this condition. Overall, this study opens new perspectives for in situ remediation by biochar in chlorinated olefin polluted anoxic environment and promotes our insight of modifying for biochar catalyst design.

Ultrafiltration concentrated biogas slurry can reduce the organic pollution of groundwater in fertigation.

Biogas slurry has the problems of having a low concentration, having a large production volume, and containing many small-molecule organic pollutants. During the fertigation process of biogas slurry, many small-molecule organic pollutants may pose potential pollution risks to groundwater. In this study, the ultrafiltration membrane technology was used to separate small-molecule organics in the biogas slurry to prepare ultrafiltration concentrated biogas slurry (UCBS). To research the impact of UCBS and raw biogas slurry (RBS) on the small-molecule organic pollution of groundwater, a laboratory soil column simulation leaching device was used to conduct leaching experiments with 4 types of UCBS and RBS in acric ferralsols and hydragric anthrosols for two quarters (8 fertilization periods). The results of the study show that both UCBS and RBS caused nitrate pollution to groundwater. UCBS has a lower risk of organic pollution to groundwater than RBS. Irrigating UCBS in hydragric anthrosols has a higher risk of organic pollution of groundwater than that in acric ferralsols. Analysis of the molecular weight distribution of dissolved organic matter (DOM) in the leaching solution showed that the organic pollutants were mainly small molecules <10 kDa. According to 3D excitation-emission matrix (3D-EEM) analysis, the main organic pollutants in the leaching solution were fulvic acid, microbial protein metabolites and humic acid organic compounds. The research results show that the pretreatment of biogas slurry by ultrafiltration can reduce the risk of small-molecule organic pollution of groundwater in land application, which can provide a new scientific basis to standardize biogas slurry land application technical guidelines and reduce groundwater pollution.

Potential for phytoremediation of nonylphenol from sewage sludge.

Nonylphenol (NP) is considered a major contaminant that must be removed to enable safe and environmentally friendly land application of sewage sludge. Phytoremediation is a technology in which plants are used to remove and/or stabilize organic and inorganic contaminants present in the soil, municipal wastewater, and sewage sludge. In this study, a 391-d large pot experiment was conducted to remove NP from sewage sludge by phytoremediation using Zea mays L. 'Yunshi-5', Lolium perenne L., and co-cropping of the two plants. The fate of NP in the soil under the sewage sludge was assessed at the same time. At the end of the experiment, the NP levels in sludge from the various treatments were as follows: control (38.60%) > L. perenne (31.27%) > Z. mays (16.25%) > co-cropping (15.28%). Degradation followed an availability-adjusted first-order kinetics with a decreasing order of half-lives as follows: control (88.2 d) > L. perenne (87.3 d) > co-cropping (66.2 d) > Z. mays (59.1 d). The results indicated that Z. mays and co-cropping could both degrade NP. The concentrations of NP in tissues of different plants differed significantly. The mean bioconcentration factors for Z. mays and L. perenne were 0.16 and 3.69, respectively. Direct removal of NP from sewage sludge by plant uptake was negligible, as was downward movement of NP in the system. Moreover, NP was not detected in soils in any treatments at harvest.

Clinical and molecular characteristics of Chinese non-small cell lung cancer patients with ERBB2 transmembrane domain mutations.

Transmembrane domain (TMD) mutations of ERBB2 have previously been reported in lung cancer patients in addition to well-studied kinase domain (KD) mutations, which may stabilize ERBB2 heterodimerization with other EGFR family members and favor a kinase active conformation. However, the frequency and clinical significance of ERBB2 TMD mutations in Chinese population is unknown. We prospectively analyzed the next-generation sequencing data of 34 368 Chinese lung cancer patients with different sample types, including tumor tissue, plasma, cerebrospinal fluid, and pleural effusion. Patients' clinical characteristics and treatment history were retrieved from the database for further evaluation. Our findings show that ERBB2 V659/G660 mutations were detected at a frequency of 0.13% (45/34 368), of which the most frequent was V659D/E (88.9%), with a trend in nonsmokers and male. Moreover, 18% of patients (8/45) showed EGFR and/or ERBB2 amplification, whereas nine patients presented EGFR L858R or exon19 deletion. Interestingly, novel ERBB3 TMD mutation I646R was found coexisting in three patients with ERBB2 V659D and one patient with ERBB2 G660D, which might influence its heterodimerization with ERBB2 and further activate ERBB2. Four ERBB2 TMD mutation-positive patients received afatinib monotherapy or combination therapy, but showed variable responses. One patient with V659E responded well to ERBB2 inhibitor lapatinib plus capecitabine as well as subsequent afatinib treatment upon progression. Our study provides valuable insights into the distribution of ERBB2 TMD mutations by employing the largest Asian lung cancer cohort thus far. Patients with ERBB2 TMD mutations who received afatinib, a pan-ERBB inhibitor, demonstrated mixed responses, posing the urgent need to develop more effective therapeutic strategy for patients who carry ERBB2 TMD mutations.

Changes and Clinical Significance of Detailed Peripheral Lymphocyte Subsets in Evaluating the Immunity for Cancer Patients.

OBJECTIVE: The evaluation of lymphocyte subsets is widely regarded as an important factor for monitoring tumor progression and response to therapy. This study was designed to establish a comprehensive and detailed assessment of peripheral lymphocyte subsets with a multi-parametric flow cytometry assay for response prediction and prognosis evaluation of cancer patients. METHODS: Peripheral blood samples collected from 40 cancer patients and 23 age- and sex-matched healthy volunteers were tested for 29 lymphocyte subsets by flow cytometry. The univariate analysis was applied to establish the reference interval of healthy samples, and the ratio and proportion of 29 lymphocyte subsets between patient samples and healthy controls were compared to evaluate their clinical significance by Mann-Whitney U-test model. RESULTS: The reference ranges of 29 lymphocyte subsets were established with a normal distribution and no significant differences were observed between genders. Compared with healthy control group, lower proportion and ratio of specific parameters, such as Naïve Th cells (p<0.01), Naïve Tc cells (p<0.01), CM (central memory) Tc cells (p<0.01), Naïve T cells/Memory T cells (p<0.001), Naïve T cells/EM (effector memory) T cells (p<0.001) and Naive Th cells/Memory Th cells (p< 0.001), and higher proportion and ratio of EM Th cells (p<0.001), EM Tc cells (p<0.01), effector Tc cells (p<0.05), EM Th cells/CM Th cells (p<0.01) and EM Tc cells/CM Tc cells (p<0.01), as well as Breg (p<0.001), B cells (p<0.05) and CD16-NK cells (p<0.001) were found in cancer cohorts. CONCLUSION: This study suggests that the changes in certain lymphocyte subsets might be helpful to evaluate the immunity of cancer patients, and holds great potential for clinical application.

Prognostic factors for operable biliary tract cancer: serum levels of lactate dehydrogenase, a strong association with survival.

BACKGROUND: Biliary tract cancers (BTCs) are uncommon but fatal, with a low 5-year survival rate after surgical resection. This study was designed to investigate the prognostic factors for operable BTC. METHODS: Baseline demographics at diagnosis were retrospectively evaluated in 341 BTC patients undergoing radical surgery at The First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2015. The association between prognostic factors and overall survival (OS) was determined by multivariate analysis using the Cox proportional hazards regression model. RESULTS: Our study showed that 341 patients were included in the analysis, of which 166 (48.7%) were males and 175 (51.3%) were females. Older age, depth of tumor invasion, positive surgical margin, lower hemoglobin, and higher lactic dehydrogenase (LDH) were associated with significantly worse OS using multivariate analysis. In the entire cohort, the estimate of median OS in patients with LDH <271 U/L was 36.291 months (95% CI; 30.989-41.594 months), and 30.736 months (95% CI; 19.154-42.318 months) in patients with LDH ≥271 U/L (adjusted HR-1.505, 95% CI; 1.009-2.245, P = 0.045). Moreover, it was investigated whether serum LDH retained its significance as a prognostic marker in BTC subgroups separately. The results showed that LDH was prognostic in patients with distal bile duct (DBD) carcinoma undergoing radical surgery (HR-2.452, 95% CI; 1.167-5.152, P = 0.018). However, there were no statistical differences between LDH and OS in multivariate analysis in the other three individual subgroups except for DBD carcinoma. This may be due to the limited number of patients in the study, indicating that a greater number of patients may be required for statistical significance. CONCLUSION: Older age, depth of tumor invasion, positive surgical margin status, lower hemoglobin levels, and elevated serum LDH level are associated with poor survival in operable BTC patients. Serum LDH level is a cost-effective prognostic biomarker in patients with operable BTC and especially DBD carcinoma.

Long-term remission of hormone receptor-positive/HER2-positive metastatic breast cancer due to combined treatment with everolimus/trastuzumab/exemestane: A case report.

The present case report describes a postmenopausal patient with hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer, who experienced progression of disease in bilateral lungs, lymph nodes and the liver under previous endocrine therapy and trastuzumab. Following the failure of two lines of endocrine-based treatment, the patient was administered the combined treatment of everolimus, trastuzumab and exemestane following surgical resection of the liver metastasis. A durable partial remission was achieved, which has continued for >27 months. This prominent clinical outcome in this patient demonstrates that the combined administration of endocrine therapy, trastuzumab and everolimus is clinically effective, and may induce long-term remission in patients with HR+/HER2+ metastatic breast cancer.

The association analysis of hOGG1 genetic variants and gastric cancer risk in a Chinese population.

Human 8-oxoguanine DNA glycosylase (hOGG1) is known to play an important role in the prevention of carcinogenesis, including gastric cancer (GC). We performed a case-control study to investigate whether single nucleotide polymorphisms (SNPs) of hOGG1 are associated with GC risk in a Chinese population. Two potential functional tagSNPs (rs159153 and rs1052133) and a previously reported risk SNP (rs125701) were genotyped in 1,275 GC patients and 1,436 controls. We found that SNP rs125701 G > A was significantly associated with the increased GC risk [adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.05-1.79 in additive model]. Besides, the functional studies demonstrated that the minor A allele of rs125701 significantly reduced the transcriptional activity of hOGG1 promoter and enhanced the methylation level of CpG site of cg15357639. In conclusion, our results suggested that the SNP rs125701 in hOGG1 promoter was associated with the elevated GC risk, which could act as a new potential biomarker for GC susceptibility. Further functional verification of rs125701 in GC pathogenesis is warranted.

Mouse double minute 2 (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal transition in breast cancer cells in vitro and in vivo.

The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers. In this study, we investigated the role of MDM2 in epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms in breast cancer cells in vitro and in vivo. The results showed that up-regulation of MDM2 in MCF-7 cells altered the cell morphology to a mesenchymal phenotype. Knockdown of MDM2 in MDA-MB-231 cells altered the cell morphology to the epithelial phenotype. In addition, overexpression of MDM2 increased the expression of N-cadherin and Vimentin and decreased the expression of E-cadherin, at both the mRNA and protein levels, in vitro and in vivo. Conversely, down-regulation of MDM2 decreased the expression of N-cadherin and Vimentin, and increased the expression of E-cadherin in vitro. Furthermore, MDM2 up-regulated both the mRNA and protein expression of Snail in vitro and in vivo. Knockdown of Snail almost abolished MDM2 induced EMT in vitro. Finally, we found that MDM2 expression correlated with EMT markers and Snail: Snail expression was inversely associated with E-cadherin in human breast cancer samples. Our findings demonstrated that MDM2 induces EMT by enhancing Snail expression in vitro and in vivo. Thus, MDM2 may be a potential target for therapy against human metastatic breast cancer.

Residual veterinary antibiotics in pig excreta after oral administration of sulfonamides.

Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection.