A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases.

Background: The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods: Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results: 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion: HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02557490.

Expansion of bilin-based red light sensors in the subaerial desert cyanobacterium Nostoc flagelliforme.

Light is the crucial environmental signal for desiccation-tolerant cyanobacteria to activate photosynthesis and prepare for desiccation at dawn. However, the photobiological characteristics of desert cyanobacteria adaptation to one of the harshest habitats on Earth remain unresolved. In this study, we surveyed the genome of a subaerial desert cyanobacterium Nostoc flagelliforme and identified two phytochromes and seven cyanobacteriochromes (CBCRs) with one or more bilin-binding GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domains. Biochemical and spectroscopic analyses of 69 purified GAF-containing proteins from recombinant phycocyanobilin (PCB), biliverdin or phycoerythrobilin-producing Escherichia coli indicated that nine of these proteins bind chromophores. Further investigation revealed that 11 GAFs form covalent adducts responsive to near-UV and visible light: eight GAFs contained PCB chromophores, three GAFs contained biliverdin chromophores and one contained the PCB isomer, phycoviolobilin. Interestingly, COO91_03972 is the first-ever reported GAF-only CBCR capable of sensing five wavelengths of light. Bioinformatics and biochemical analyses revealed that residue P132 of COO91_03972 is essential for chromophore binding to dual-cysteine CBCRs. Furthermore, the complement of N. flagelliforme CBCRs is enriched in red light sensors. We hypothesize that these sensors are critical for the acclimatization of N. flagelliforme to weak light environments at dawn.

Hepatic Artery Injection of 131I-Metuximab Combined with Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Prospective Nonrandomized, Multicenter Clinical Trial.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors for advanced hepatocellular carcinoma.

Aim: We investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKIs) for advanced hepatocellular carcinoma (HCC). Method: This retrospective study included HCC patients treated with HAIC, TKIs and anti-PD-1 antibodies between May 2019 and November 2020 in our hospital. Primary end points were progression-free survival and safety. Results: Twenty-seven advanced HCC patients were analyzed. The median follow-up was 12.9 months (range: 4.0-24.0 months) and the median progression-free survival was 10.6 months. The objective response rate and disease control rate were 63.0 and 92.6%, respectively. No treatment-related deaths occurred. Conclusion: In patients with advanced HCC, treatment with HAIC, anti-PD-1 antibodies and oral TKIs was effective and safe.

Lay abstract Some tyrosine kinase inhibitors (TKIs) that inhibit tumor vessel growth, such as sorafenib and lenvatinib, have been recommended as first-line treatment for advanced hepatocellular carcinoma (HCC). In hepatic artery infusion chemotherapy, chemotherapeutic drugs can be delivered via a microcatheter to the tumor-supplying artery to increase the local drug concentration, leading to higher local disease control rates and less toxicity than systemic chemotherapy. The combination of anti-PD-1 immunotherapy plus TKIs was shown in a previous study to be a safe and effective treatment for advanced HCC. This study explored the safety and effectiveness of hepatic artery infusion chemotherapy, TKIs and an anti-PD-1 antibody for the treatment of advanced HCC and found that combination therapy is effective, with good tolerability.

Combination Therapy of Chemoembolization and Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Compared with Chemoembolization Alone: A Propensity Score-Matched Analysis.

BACKGROUND: Survival of patients with portal vein tumor thrombosis (PVTT) is extremely poor; transarterial chemoembolization (TACE) is a treatment for patients with HCC and PVTT. Some studies showed that hepatic arterial infusion chemotherapy (HAIC) might improve the survival of HCC with PVTT. There were few researches of combining TACE with HAIC for patients with HCC and PVTT. AIM: This study was aimed at comparing overall survival (OS) and progression-free survival (PFS) following treatment with conventional transarterial chemoembolization plus hepatic arterial infusion chemotherapy (cTACE-HAIC) or conventional transarterial chemoembolization (cTACE) alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHODS: From January 2011 to December 2016, 155 patients with HCC and PVTT who received cTACE-HAIC (cTACE-HAIC group) (n = 86) or cTACE alone (cTACE group) (n = 69) were retrospectively evaluated. Propensity score matching (PSM) reduced the confounding bias and yielded 60 matched patient pairs. The tumors' responses were evaluated using the modified response evaluation criteria in solid tumors (mRECIST). OS and PFS of groups were compared using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models. RESULTS: The median follow-up duration was 93 months (range: 1-93 months). The cTACE-HAIC group's OS (9.0 months) and PFS (6.0 months) were significantly longer than the cTACE group's OS (5.0 months) and PFS (2.0 months) (p = 0.018 and p = 0.045, respectively) in the matched cohort. Multivariate analyses showed that cTACE-HAIC was independently associated with OS (hazard ratio (HR) 0.602, p = 0.010) and PFS (HR 0.66, p = 0.038). The matched groups did not differ regarding grade 3 or 4 adverse events. CONCLUSION: cTACE-HAIC was superior to cTACE alone regarding OS and PFS in patients with HCC and PVTT. Treatment-associated toxicities were generally well tolerated.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have shown promising local benefits for advanced hepatocellular carcinoma (HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC. AIM: To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC. METHODS: In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with (TACE/HAIC + S-1, n = 56) or without (TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate, disease control rate and safety. RESULTS: In total, 115 participants (100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo (0.4-58.6 mo) (95% confidence interval (CI): 3.82 to 6.18) vs 4.4 mo (1.1-54.4 mo) (95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo (0.4-58.6 mo) (95%CI: 6.88 to 9.92) vs 8.3 mo (1.4-54.4 m) (95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups. CONCLUSION: No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.

Potential microRNA panel for the diagnosis and prediction of overall survival of hepatocellular carcinoma with hepatitis B virus infection.

BACKGROUND: In hepatocellular carcinoma (HCC), abnormal expression of multiple microRNAs (miRNAs) has been shown to be involved in the malignant biological behavior of liver cancer. The vast majority of liver cancer cases in China are closely related to hepatitis B virus (HBV) infection, but there are few studies on the changes of miRNA expression in the progression from HBV infection to hepatoma. AIM: To explore the role of miRNAs in the progression of HBV infection to cirrhosis and even to liver cancer. METHODS: We screened differentially expressed miRNAs in 40 HBV cirrhosis, 40 normal and 15 HCC tissues by using a TaqMan Low Density Array and real time quantitative polymerase chain reaction. To evaluate the power of the selected miRNAs to predict disease, we calculated the area under the receiver-operating-characteristic curves. The overall survival of HBV cirrhosis patients was analyzed via Kaplan-Meier analysis. RESULTS: The levels of miR-375, miR-122 and miR-143 were significantly lower in HBV cirrhosis tissues, while miR-224 was significantly higher than in the controls (P < 0.0001). The area under the curves of the receiver-operating-characteristic curve for the 4-miRNA panel was 0.991 (95%CI: 0.974-1). Patients with a lower expression level of miR-224 or higher expression levels of miR-375, miR-122 and miR-143 had longer overall survival. CONCLUSION: The four miRNAs (miR-375, miR-122, miR-143 and miR-224) may be helpful for early diagnosis of HBV infection, HBV cirrhosis, and prediction of its overall survival.

The nickel-catalyzed C3-acylation of 2H-indazoles with aldehydes.

A direct coupling of 2H-indazoles' C3 position and acyl groups has been achieved to produce 3-acyl-2H-indazoles. The Ni(ii)-catalyzed acylation might proceed through a radical pathway for the reaction of 2H-indazoles with either aryl or alkyl aldehydes in the presence of the free radical initiator TBHP and additive PivOH. This method provided a superior approach to fulfil the direct C3-acylation of 2H-indazoles with yields up to 91%. And various substituted 2H-indazoles were well tolerated with this method, enriching the diversity of 2H-indazole derivatives. In comparison with previously reported approaches for the C3-acylation of 2H-indazoles, the developed reaction represents a more convenient and economical method directly using aldehydes as the acylation agents.

Association of handgrip strength with the prevalence of hypertension in a Chinese Han population.

OBJECTIVE: Handgrip strength (HGS) exercise has been reported to reduce blood pressure in both hypertensive and normotensive patients. In this study, we evaluated the association of HGS with hypertension in a Chinese Han Population. METHODS: A total of 11,151 subjects mainly consisting of a rural population were recruited with a multi-stage sampling method in Jurong city, Jiangsu Province, China. Besides hypertension and diabetes, major chronic diseases were excluded. HGS was categorized into tertiles by age and gender. Logistic regression was used to estimate the association of HGS and hypertension with the odds ratio (OR) and 95% confidence interval (CI). RESULTS: From low to high tertiles of HGS, diastolic blood pressure (DBP) was significantly increased (74.52 ± 7.39, 74.70 ± 7.03, and 75.54 ± 7.01 mmHg, respectively; P trend = 0.001), as well as in females (P trend =0.003). The differences in DBP among the tertiles of HGS were still significant in females even after adjusting for covariates (P trend =0.048). No significant differences in systolic blood pressure (SBP) were observed among the tertiles of HGS (P>0.05). Compared to low HGS, high HGS was significantly associated with hypertension after adjustment for age and gender (adjusted OR, 1.19; 95% CI, 1.06-1.34; P =0.004). A stratified analysis showed that the significant association of high HGS and hypertension was also observed with the following factors even after adjusting for age and gender: female gender (adjusted OR, 1.25; 95% CI, 1.08-1.46; P=0.004), ages of 60-69 years (adjusted OR, 1.29; 95% CI, 1.06-1.57; P=0.011), and married (adjusted OR, 1.20; 95% CI, 1.06-1.37; P=0.005). However, no significant associations were found after adjusting for age, gender, smoking status, drinking status, body mass index, physical activity level, glucose, high- and low-density lipoprotein cholesterol, total cholesterol, and triglyceride (P>0.05). CONCLUSION: The findings of the current study suggest that HGS was positively correlated with DBP in a rural population, and high HGS was associated with hypertension in females; however, the association may be modified by smoking status, drinking status, body mass index, physical activity, cholesterol level, and glucose level. Further utilization of HGS exercises to intervene in the development and prognosis of hypertension should be verified in the future.

Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value.

BACKGROUND: Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC). AIM: To understand the mechanism of exosomal microRNA-224 (miR-224) in the development of HCC and evaluate its diagnostic and prognostic value. METHODS: Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis. RESULTS: By targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival. CONCLUSION: Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.

A modified staging of early and intermediate hepatocellular carcinoma based on single tumour >7 cm and multiple tumours beyond up-to-seven criteria.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used staging system for hepatocellular carcinoma (HCC). However, the classifications of early (BCLC-A) and intermediate (BCLC-B) stage HCC remain controversial. AIM: To refine the staging of BCLC-A and -B. METHODS: A total of 986 patients with HCC undergoing liver resection from two institutions formed the training cohort, and 694 from another institution were the validation cohort. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of tumour size in predicting overall survival (OS), and determined the optimised cut-off. Discriminatory performance was evaluated using Harrell's concordance index (C-index). RESULTS: Patients with multiple tumours exceeding Milan criteria but within up-to-seven criteria had similar OS and disease-free survival (DFS) to those with multiple tumours meeting Milan criteria, and were assigned to the modified BCLC-A stage. The area under the ROC curve of tumour size for predicting OS was 0.778, and the diameter of 7 cm was the optimal cut-off to identify patients with single tumours who had higher OS than BCLC-B stage patients. Due to the similar OS, patients with single HCCs >7 cm were assigned to the modified BCLC-B stage. The C-indexes of the modified BCLC classification for OS and DFS were higher compared to the original version. The findings were supported by the validation cohort. CONCLUSIONS: The modified staging of BCLC-A and -B, based on single tumour >7 cm and multiple tumours beyond up-to-seven criteria, could be more accurate to predict the prognosis of HCC patients. Liver resection could benefit patients with resectable multifocal HCCs beyond the Milan criteria.

Effect of primary tumor side on survival outcomes in metastatic colorectal cancer patients after hepatic arterial infusion chemotherapy.

AIM: To analyze the survival data between patients diagnosed with right-sided primary (RSP) tumors and patients diagnosed with left-sided primary (LSP) tumors after hepatic arterial infusion chemotherapy (HAIC) at our center. METHODS: A retrospective analysis of pretreated metastatic colorectal cancer patients who received HAIC from May 2006 to August 2015 was conducted. A Cox proportional hazard regression analysis was used to assess the long-term survival outcomes. The mean and median age of patients was 61 years (range 27-85 years). There were 115 males and 53 females in our study. RESULTS: One hundred sixty-eight patients were enrolled in this study. The overall response rate was 28.9% in LSP patients and 27.3% in RSP patients. The disease control rate was 76.3% in LSP patients and 69.7% in RSP patients. The median overall survival in response to HAIC was 16.3 mo in the LSP arm and 9.3 mo in the RSP arm (P = 0.164). The median progression-free survival was 5.7 mo in the LSP arm and 4.2 mo in the RSP arm (P = 0.851). CONCLUSION: There was no significant difference in survival between LSP patients and RSP patients after HAIC. Further prospective studies are needed to confirm these findings.

UV-B induced biosynthesis of a novel sunscreen compound in solar radiation and desiccation tolerant cyanobacteria.

The small-molecule sunscreen compounds, mycosporine-like amino acids (MAAs), have strong ultraviolet (UV) absorption and can protect cyanobacteria against UV-B damage. However, the molecular mechanism underlying UV-B signaling and MAA chemical diversity remain largely unclear. Here, we identified a five-gene cluster for MAA biosynthesis in the solar radiation and desiccation tolerant cyanobacterium Nostoc flagelliforme. A LuxR family protein OrrA was identified as a positive UV-B responsive regulator binding to the promoter region of this gene cluster. OrrA functions as an activator mediating the UV-B induced MAA biosynthesis. Overexpression of orrA strengthened its UV-B tolerance during desiccation, and enhanced the photosynthetic recovery upon rehydration. Heterologous expression of this gene cluster in Anabaena PCC 7120 produces the same MAA as that in field samples of N. flagelliforme. The MAA structure is assigned as mycosporine-2-(4-deoxygadusolyl-ornithine) with a molecular weight of 756 Da, the structurally unique MAA compound reported to date. This MAA was catalyzed by mysD-mysC2-mysC1 encoding proteins from 4-deoxygadusol, which was synthesized through the catalysis of mysA-mysB products. Thus, we elucidated the transcriptional mechanism for a novel type MAA biosynthesis in solar radiation and desiccation tolerant cyanobacteria, which shed light on the identification of other components for UV-B signaling in cyanobacteria.

Effect of bevacizumab on the expression of fibrosis-related inflammatory mediators in ARPE-19 cells.

AIM: To investigate the effect of anti-vascular epithelial growth factor (VEGF) agents on the expression of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions, and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS: Human retinal pigment epithelial (RPE) cells were incubated under normoxic and hypoxic conditions. For hypoxia treatment, CoCl2 at 200 µmol/L was added to the media. ARPE-19 cells were treated as following: 1) control group: no treatment; 2) bevacizumab group: bevacizumab at 0.25 mg/mL was added to the media; 3) hypoxia group: CoCl2 at 200 µmol/L was added to the media; 4) hypoxia+bevacizumab group: CoCl2 at 200 µmol/L and bevacizumab at 0.25 mg/mL were added to the media. The expression of interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)-α were evaluated using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at 6, 12, 24 and 48h. RESULTS: Both mRNA and protein levels of IL-1ß, IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point, and TNF-α gene and protein expression was only significantly higher only at 24 and 48h (P<0.05). Under hypoxic conditions, bevacizumab significantly increased the expression of IL-1ß, IL-6, IL-8 and TNF-α at 6, 12, 24 and 48h (P<0.05). IL-1ß, IL-8 and TNF-α peaked at 24h and IL-6 peaked at 12h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION: Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under both normoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after anti-VEGF therapy, and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.

Therapeutic effects of adenovirus-mediated CD and NIS expression combined with Na131I/5-FC on human thyroid cancer.

Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na131I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na131I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na131I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na131I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na131I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.

Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction.

Risk burdens of modifiable risk factors incorporating lipoprotein (a) (Lp(a)) and low serum albumin (LSA) concentrations for first incident acute myocardial infarction (AMI) haven't been studied previously. Cross-sectional study of 1552 cases and 6125 controls was performed for identifying the association of risk factors with first incident AMI and their corresponding population attributable risks (PARs). Modifiable risk factors incorporating LSA and Lp(a) accounted for up to 92% of PAR for first incident AMI. Effects of these risk factors were different in different sexes across different age categories. Overall, smoking and LSA were the 2 strongest risk factors, together accounting for 64% of PAR for first incident AMI. After multivariable adjustment, Lp(a) and LSA accounted for 19% and 41%, respectively, and together for more than a half (54%) of PAR for first incident AMI. Modifiable risk factors incorporating LSA and Lp(a) have accounted for an overwhelmingly large proportion of the risk of first incident AMI, indicating most first incident AMI is preventable. The knowledge of risk burdens for first incident AMI incorporating Lp (a) and LSA may be beneficial for further reducing first incident AMI from a new angle.

Comparison of Safety and Efficacy of Different Models of Target Vessel Regional Chemotherapy for Gastric Cancer with Liver Metastases.

BACKGROUND/AIMS: We previously demonstrated the safety and efficacy of low-dose, short-interval target vessel regional chemotherapy (TVRC(LDSI)) delivered through the hepatic artery with transarterial embolization (TAE) in patients with advanced gastric cancer (AGC). The present study aimed to compare the efficacy of TAE + TVRC(LDSI) with that of standard TAE + TVRC in AGC patients with liver metastases who failed to respond to first- or second-line systemic chemotherapy. METHODS: This study recruited a total of 58 GC patients with liver metastases after failure of first- or second-line systemic chemotherapy. Twenty-eight patients were assigned to the TAE + TVRC(LDSI) group and 30 patients to the TAE + TVRC group. The primary end point was overall survival (OS(TVRC)), which was defined as the time from the initiation of TVRC until the last follow-up or death. RESULTS: OS(TVRC), time to progression (TTP) until appearance of intra- and extrahepatic metastases, and overall TTP and treatment periods in the TAE + TVRC(LDSI) group were all significantly longer than in the TAE + TVRC group (all p < 0.001). CONCLUSION: TAE + TVRC(LDSI) had a higher efficacy and safety, which was reflected by OS rates, progression-free survival rates, longer duration of treatment and milder side effects compared to standard TAE + TVRC.