Optimized protocols for chromatin immunoprecipitation of exogenously expressed epitope-tagged proteins.

Chromatin immunoprecipitation (ChIP) assay is widely used for investigating the interaction between DNA and DNA-binding proteins such as transcription factors, co-factors, or chromatin-associated proteins. However, a successful ChIP assay largely depends on the quality of a ChIP-grade primary antibody. In cases where specific antibodies are unavailable or with low binding affinity, here, we describe a tailored protocol to achieve robust and reproducible chromatin binding by expressing an exogenous epitope-tagged protein in cells, followed by ChIP assays using a tag-specific antibody. For complete details on the use and execution of this protocol, please refer to Fang et al. (2021)1 and Kidder et al. (2011).2.

Trends in anti-HER2 drugs consumption and influencing factors.

Background: Human epidermal growth factor receptor 2 (HER2) inhibitors have been approved to treat various cancers with HER2 amplification. The Chinese government has made great efforts to improve the availability and affordability of these drugs. This study aimed to analyze the trends in anti-HER2 drug consumptions in Nanjing from 2012 to 2021, and explore influencing factors. Methods: Data about use of anti-HER2 drugs in 2012-2021 were extracted from Jiangsu Medicine Information Institute. Six types of anti-HER2 drugs were included. Drug consumption was expressed as defined daily doses (DDDs) and expenditure. Time series analysis was adopted to find trends in consumption, while interrupted time series was used in analyzing the impact of policy on consumption. The correlation between DDDs and defined daily cost (DDC) was analyzed by Pearson's correlation test. Results: The DDC, DDDs, and expenditure of anti-HER2 drugs changed little from 2012 to 2016. The DDC decreased intermittently, while the DDDs and expenditure of these drugs grew continuously from 2017 to 2021. The anti-HER2 monoclonal antibodies contributed to the majority of total consumption in 2012-2019. The DDDs of anti-HER2 tyrosine kinase inhibitors surpassed the DDDs of monoclonal antibodies in 2020-2021. Trastuzumab was the predominantly prescribed drug in 2012-2019, but the DDDs of pyrotinib surpassed the DDDs of trastuzumab in 2020-2021. The ln value of DDC or self-paid DDC of trastuzumab was negatively correlated with the ln value of its DDDs. The national health insurance coverage (NHIC) and national drug price negotiation policy about anti-HER2 drugs were initiated in 2017. Low-price generics and biosimilar of trastuzumab came into the market in 2020 and 2021, separately. Interrupted time series analysis showed that the DDDs increased significantly after the implementation of NHIC, price negotiation or generic drug replacement. Conclusion: The consumption of anti-HER2 drugs has significantly increased and their DDC has decreased after the implementation of NHIC, price negotiation, or low-price generic drug replacement since 2017. Further efforts are needed to translate the high consumption into clinical benefits.

Consumption and cost trends of EGFR TKIs: influences of reimbursement and national price negotiation.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of EGFR mutation non-small-cell lung cancer. The Chinese government has made great efforts to improve the availability and affordability of these drugs. The aim of this study was to investigate the trends in the consumption and cost of EGFR TKIs in Nanjing, a developed city in China, and evaluate the influence of health insurance coverage and national price negotiation on drug consumption. METHODS: Data about EGFR TKIs applications in 2010-2019 were extracted from Jiangsu Medicine Information Institute. Five types of EGFR TKIs were included. Consumption was expressed in defined daily doses (DDDs) and expenditure. The correlation between defined daily cost (DDC) and DDDs was analyzed by Pearson's correlation test. RESULTS: The DDC, number of DDDs and expenditure of EGFR TKIs changed little from 2010 to 2015. National price negotiation was initiated as a policy and low-price generic gefitinib came into the market in 2016. Three types of EGFR TKIs moved into the coverage of the national health insurance since 2017. Hence, the DDC decreased, and the number of DDDs increased significantly year by year since 2016. The first generation TKIs always made up of comprised the majority of the total consumption. The predominantly prescribed TKIs were gefitinib and icotinib. DDC was negatively correlated with the number of DDDs. The number of DDDs increased significantly after health insurance enrollment, price negotiation and generic drug replacement. CONCLUSION: The consumption of EGFT TKIs has increased and the DDC of EGFR TKIs has decreased since 2016. These trends may be attributed to drug reimbursement, price negotiation and generic drug replacement. Further efforts are needed to translate the high consumption of EGFR TKIs into clinical benefits.

Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study.

Imatinib (IM), a milestone drug used in the field of molecular targeted therapy, has been reported to cause serious adverse liver effects, including liver failure and even death. Immune-mediated injury and mitochondrial dysfunction are involved in drug-induced liver injury. However, the mechanism of IM-induced hepatotoxicity remains unclear and warrants further study. In our study, Sprague Dawley rats were administered IM by gavage with 50 mg/kg body weight (BW) once daily for 10 days. Drug-induced liver injury accompanied by inflammatory infiltration was observed in rats following IM exposure, and the expression of NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins was significantly increased compared with that of the control. HepG2 cells were exposed to 0-100 µM IM for 24 h. The results showed that IM decreased cell viability in a dose-dependent manner. Moreover, IM induced a state of obvious oxidative stress and activation of nuclear factor kappa B (NF-κB) in cells, which resulted in the activation of NLRP3 inflammasomes, including caspase 1 cleavage and IL-1ß release. These results were significantly reduced after the use of the antioxidants N-acetyl-l-cysteine or the NF-κB inhibitor pyrrolidine di-thio-carbamate. Furthermore, NLRP3 knockdown significantly reduced the release of inflammatory cytokines and improved cell viability. In summary, our data demonstrated that oxidative stress and NLRP3 inflammasome activation are involved in the process of IM-induced hepatotoxicity. The results of this study provide a reference for the prevention and treatment of IM-induced hepatotoxicity.

Characteristics of metastasis and survival between male and female breast cancer with different molecular subtypes: A population-based observational study.

OBJECTIVE: Male breast cancer (BC) is a rare disease, having different clinicopathological features and survival outcomes from female patients. The aim of this research was to, combine with molecular subtypes, analyze the metastatic patterns, and prognosis between male and female patients, and to determine whether the gender was the independent prognostic factor for BC. METHODS: Data used in this study were acquired from the SEER database from 2010 to 2016. The clinicopathology features and metastatic patterns were compared by the Chi-square test and Fisher's exact test. Kaplan-Meier method was performed to compare overall survival (OS) and factors correlated with OS were determined by Cox regression models. Competing risk models were used to ascertain factors related to breast cancer-specific death (BCSD). RESULTS: Compared with female BC, the incidence of regional LN (HR 1.849, 95% CI 1.674-2.043, p < 0.001) and distant metastasis (HR 1.421, 95%CI: 1.157-1.744, p < 0.001) was higher in male BC. For regional LN metastasis, hormone receptor (HoR)-/HER2+ subtype occupied the majority in both male (55.56%) and female (36.86%) groups. For distant metastasis, HoR-/HER2- subtype (21.26%), and HoR-/HER2+ (7.67%) were in major in male and female group separately. Male patients shared similar combinations of metastases with female groups as for single-site, bi-site, and tri-site metastasis. Gender was an independent prognostic factor for OS (p < 0.001) but not for BCSD(p = 0.620). In subgroup of patients with HoR+/HER2-(OS: p = 0.003; BCSD: p = 0.606), HoR+/HER2+(OS: p = 0.003; BCSD: p = 0.277), regional LN positive(OS: p = 0.005; BCSD: p = 0.379), or bone metastasis (OS: p = 0.030; BCSD: p = 0.862), the male cohort had poorer OS but similar BCSD with female cohort. CONCLUSIONS: Compared with female patients, male BC had different metastasis patterns and prognostic outcomes, and the affection of breast subtypes on metastasis and survivorship was also different. More attention needs to be paid for specific molecular subtype and more personalized therapeutic strategies should be customized while treating male patients.

ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease, which warrants the critical need to identify new therapeutic targets. We show that Zinc Fingers and Homeoboxes 2 (ZHX2) is amplified or overexpressed in TNBC cell lines and patients. Functionally, depletion of ZHX2 inhibited TNBC cell growth and invasion in vitro, orthotopic tumor growth, and spontaneous lung metastasis in vivo. Mechanistically, ZHX2 bound with hypoxia-inducible factor (HIF) family members and positively regulated HIF1α activity in TNBC. Integrated ChIP-seq and gene expression profiling demonstrated that ZHX2 co-occupied with HIF1α on transcriptionally active promoters marked by H3K4me3 and H3K27ac, thereby promoting gene expression. Among the identified ZHX2 and HIF1α coregulated genes, overexpression of AP2B1, COX20, KDM3A, or PTGES3L could partially rescue TNBC cell growth defect by ZHX2 depletion, suggested that these downstream targets contribute to the oncogenic role of ZHX2 in an accumulative fashion. Furthermore, multiple residues (R491, R581, and R674) on ZHX2 are important in regulating its phenotype, which correspond with their roles on controlling ZHX2 transcriptional activity in TNBC cells. These studies establish that ZHX2 activates oncogenic HIF1α signaling, therefore serving as a potential therapeutic target for TNBC.

RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA.

BACKGROUND: RNPC1 is reported to act as a tumor suppressor by binding and regulating the expression of target genes in various cancers. However, the role of RNPC1 in gastric cancer and the underlying mechanisms are still unclear. METHODS: Gastric cancer cells were stably transfected with lentivirus. Proliferation, migration, invasion, cell cycle in vitro and tumorigenesis in vivo were used to assess the role of RNPC1. Quantitative real-time PCR, western blotting and immunohistochemistry were used to detect the relationship between RNPC1 and aurora kinase B (AURKB). RNA immunoprecipitation (RIP), RNA electrophoretic mobility shift assays (REMSAs), and dual-luciferase reporter assays were used to identify the direct binding sites of RNPC1 with AURKB mRNA. A CCK-8 assay was conducted to confirm the function of AURKB in RNPC1-induced growth promotion. RESULTS: High RNPC1 expression was found in gastric cancer tissues and cell lines and was associated with high TNM stage. RNPC1 overexpression significantly promoted the proliferation, migration, and invasion of gastric cancer cells. Knockdown of RNPC1 could impede gastric cancer tumorigenesis in nude mice. AURKB expression was positively related to RNPC1. RNPC1 directly binds to the 3'-untranslated region (3'-UTR) of AURKB and enhances AURKB mRNA stability. AURKB reversed the proliferation induced by RNPC1 in gastric cancer cells. RNPC1 resulted in mitotic defects, aneuploidy and chromosomal instability in gastric cancer cells, similar to AURKB. CONCLUSION: RNPC1 acts as an oncogene in gastric cancer by influencing cell mitosis by increasing AURKB mRNA stability, which may provide a potential biomarker and a therapeutic target for gastric cancer.

CD8+ T-cell percentage increases in diffuse large B-cell lymphoma patients receiving mannatide combined with standard regimens.

WHAT IS KNOWN AND OBJECTIVE: Suppression of antilymphoma effector cells, mainly T cells, is a key prerequisite for tumorigenesis and resistance in diffuse large B-cell lymphoma (DLBCL). The aim of the study was to determine whether mannatide (MT), an immunomodulator, could enhance the immunological response in DLBCL patients receiving standard regimens. METHODS: Patients with aggressive DLBCL treated with first-line standard regimens were included in this single-centre retrospective study. T-cell subtypes were detected using flow cytometry before and after the first cycle of treatment. Patients in MT group were treated with MT combined with standard first-line regimens, and patients in control group with standard first-line regimens. Chi-square test or Fisher's exact tests were used for categorical variables and independent t-tests for continuous variables. RESULTS AND DISCUSSION: Among the 138 DLBCL patients enrolled in this study, 34 (24.64%) were assigned to the MT group, while 104 (75.36%) patients were included in the control group. There were no significant differences in clinicopathological characteristics and baseline T-cell subtypes between the two groups (p > 0.05). After treatment, CD3+ CD8+ T-cell percentage of MT group was significantly higher than that of control group (p = 0.01), while CD3+ CD4+ T-cell percentage of MT group was significantly lower than that of control group (p < 0.01). Thus, the CD4+ /CD8+ ratio of MT group was significantly lower than that of control group (p = 0.03). In the subgroup of DLBCL patients treated with EPOCH/R-EPOCH, significant differences were also found in post-treatment CD3+ CD8+ T-cell percentage (p < 0.01), CD3+ CD4+ T-cell percentage (p = 0.02) and CD4+ /CD8+ ratio (p = 0.01) between MT and control groups. WHAT IS NEW AND CONCLUSION: CD3+ CD8+ T-cell percentage increased in DLBCL patients receiving MT treatment. Further studies are required to determine the clinical benefits of MT.

DEC2 Serves as Potential Tumor Suppressor in Breast Carcinoma.

BACKGROUND: Identification of new biomarkers can facilitate the development of effective therapeutic strategies in breast cancer (BC). Data from previous studies have revealed that differentiated embryonic chondrocyte gene (DEC) 1 and DEC2 might involve in the progression of various cancer types. We explored the expression profiles and function of DEC1/2 in BC patients in this study. METHODS: The mRNA expression of DEC1/2 in BC patients and cell lines were taken from the Oncomine and Cancer Cell Line Encyclopedia database. The prognostic impacts of DEC1/2 were mined from the bc-GenExMiner and Kaplan-Meier plotter database. The impact of DEC1/2 genomic alterations on patient survival was calculated by cBioPortal. DEC2 protein expressions were confirmed by Western blotting (WB) in 10 pairs of BC samples. In addition, DEC2 sgRNA was constructed to confirm its affection on cell viability, invasion, and colony formation. RESULTS: The DEC1 and DEC2 mRNA levels are both lower in BC tissues than normal tissues. DEC1/2 expression was high in progesterone receptor (PR) positive BC patients (P = 0.0023), but low in human epidermal growth factor receptor 2 (HER2) positive patients (P < 0.0001). Lower DEC2 mRNA level has significant association with more aggressive pathogenic grade (P < 0.0001) and worse overall survival (OS) of BC patients (P = 5.2 × 10-6). Subgroup analysis showed that low DEC2 level was correlated with worse OS in estrogen receptor (ER) positive BC (P = 0.008). DEC2 (P = 0.00029) alteration was significantly correlated with worse OS in BC patients. WB results also confirmed the lower DEC2 protein levels in BC samples than their paired normal tissues. And, DEC2 silencing by sgRNA resulted in a significant increasing in cell viability, invasion, and colony formation. CONCLUSION: DEC2 might serve as a tumor suppressor, and its disfunction may involve in the tumorigenesis and indicate bad clinical outcomes in BC patients.

Microsatellite instability and sensitivity to fluoropyrimidine and oxaliplatin containing first-line chemotherapy in metastatic colorectal cancer.

OBJECTIVES: To examine the effect of microsatellite instability (MSI) on the outcome of fluoropyrimidine and oxaliplatin containing first-line chemotherapy in metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC and treated with fluoropyrimidine/oxaliplatin first-line chemotherapy were included in our study. Demographic data, tumour characteristics, chemotherapy regimens, treatment responses and progression-free survival (PFS) were collected from medical records. The MSI analysis was performed using fluorescence-based PCR, and divided into MSI-high (MSI-H) and MSI-low (MSI-L)/microsatellite stable (MSS). Statistical analysis used Kaplan-Meier method, log-rank test and multivariate Cox model. RESULTS: From 1 January 2015 to 1 May 2016, a total of 192 patients with mCRC were included in our study. Among these, 14 (7.29%) exhibited MSI-H and 178 (92.71%) were MSI-L/MSS. The objective response rate (p=0.79), disease control rate (p=0.22) and PFS (p=0.22) of fluoropyrimidine/oxaliplatin first-line chemotherapy were not significantly different between MSI-H and MSI-L/MSS tumours. But MSI-H tumours had a trend to better disease control rate (71.43% vs 54.49%) and PFS (6.50 m vs 5.40 m) than MSI-L/MSS tumours. Multivariate analysis indicated that MSI was not a predictive factor for PFS (p=0.18). CONCLUSION: The effect of fluoropyrimidine/oxaliplatin first-line chemotherapy was not significantly different between MSI-H and MSI-L/MSS tumours. However, MSI-H tumours tended to have better disease control rate and PFS.

Dose-escalation of oxaliplatin in hemodialysis patient treated with FOLFOX therapy: A case report.

RATIONALE: Oxaliplatin is a key part of the standard treatment for colorectal cancer which is formally contraindicated in patients with severe renal dysfunction. Here, we investigated a safe and efficient dosing schedule of oxaliplatin in folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen by monitoring total and free platinum concentrations in plasma. PATIENT CONCERNS: A 47-year-old female with chronic hemodialysis was diagnosed with left-sided colon cancer and underwent colectomy. One year later, she was presented with omentum metastasis and needed further treatment. DIAGNOSES: The computed tomography (CT) scanning revealed multiple omental nodules. Positron emission tomography-CT (PET-CT) showed increased uptake of the nodules. INTERVENTIONS: The patient was treated with FOLFOX therapy every 3 weeks. The oxaliplatin began with 50 mg/m and gradually increased 85 mg/m as in the standard regimen. A 4-hour dialysis was started 1 hour after the end of oxaliplatin infusion. OUTCOMES: The free platinum concentration time curve showed a biomodel pattern. The Cmax of the 1st peak we observed in our patients at the standard dose is comparable to patients with normal renal function. This patient was treated with FOLFOX for 12 courses. No apparent adverse effect was observed during the treatment. LESSONS: The FOLFOX can be safely administered in hemodialysis patients on a long-term basis. Dose reduction of oxaliplatin is not necessarily needed if hemodialysis is performed soon after the infusion. Further studies are needed to distinguish between active and inactive oxaliplatin products during the 2nd peak of the free platinum concentration curve in this population.

Antitumor pharmacotherapy of colorectal cancer in kidney transplant recipients.

Renal transplantation has become the sole most preferred therapy modality for end-stage renal disease patients. The growing tendency for renal transplants, and prolonged survival of renal recipients, have resulted in a certain number of post-transplant colorectal cancer patients. Antitumor pharmacotherapy in these patients is a dilemma. Substantial impediments such as carcinogenesis of immunosuppressive drugs (ISDs), drug interaction between ISDs and anticancer drugs, and toxicity of anticancer drugs exist. However, experience of antitumor pharmacotherapy in these patients is limited, and the potential risks and benefits have not been reviewed systematically. This review evaluates the potential impediments, summarizes current experience, and provides potential antitumor strategies, including adjuvant, palliative, and subsequent regimens. Moreover, special pharmaceutical care, such as ISDs therapeutic drug monitoring, metabolic enzymes genotype, and drug interaction, are also highlighted.

Consumption trend and prescription pattern of opioid analgesics in China from 2006 to 2015.

OBJECTIVES: To investigate the consumption trend and prescription pattern of opioids in China from 2006 to 2015, and compare the results with those of selected countries and regions, and identify the pain relief level of China. METHODS: Nine different opioid drugs were included in our survey, based on the whole population of China. Consumption of each type of opioid was calculated in grams in reports of the Chinese Food and Drug Administration and the International Narcotics Control Board. Then it was converted to the terms of defined daily doses and morphine equivalents. The correlation between consumption of opioids and gross domestic product, human development index and cancer incidence was analysed by Pearson's correlation test. RESULTS: Defined daily doses increased by 7.89% per year since 2006, and reached 91.05 in 2015. Morphine equivalents increased by 10.57% per year since 2006, and reached 7.24 g in 2015. The average defined daily doses and morphine equivalents were 85.44 and 5.70 g respectively in 2006-2015. Annual defined daily doses of China were lower than the global average. Consumption was related to gross domestic product, but not human development index and cancer incidence. Furthermore, defined daily doses varied greatly in countries with similar gross domestic product or the human development index. Strong opioids or non-intravenous opioids always constituted the majority of opioids, and sustained an increasing tendency in consumption. The predominantly prescribed opioids were fentanyl and morphine. Consumption of oxycodone had a tendency to increase, whereas pethidine tended to decrease. CONCLUSION: Consumption of opioids has shown an increasing tendency and in the meantime the prescription pattern has changed, indicating the progress of pain relief in China, though it remained far lower than the average global level.

Consumption trends and prescription patterns of opioids from 2011 to 2016: a survey in a Chinese city.

OBJECTIVE: Opioid consumption in China has been very less and has varied widely since 1995. The representatively high level of consumption in Mainland China has never been reported. Our aim was to describe the consumption trends and prescription patterns of opioids in Nanjing, a highly developed city of Mainland China, and compare the results with selected worldwide regions. METHODS: Application data of opioids in 2011-2016 were extracted from the Jiangsu Medicine Information Institute. Six opioids were included. Consumption was expressed in terms of defined daily doses (DDDs), morphine equivalents (MEs) and expenditure. The correlation between consumption of opioids and gross domestic product (GDP), Human Development Index (HDI) and cancer incidence was analysed by Pearson's correlation test. RESULTS: DDDs, expenditure and MEs of opioids were, respectively, 256.04, $599.24 and 13.07 g in 2011, and increased to 361.27, $1041.79 and 18.09 g in 2016. DDDs in Nanjing were 2.80-fold that in Mainland China, 1.42-fold that in East and South-East Asia, but only equivalent to 8.89% of the worldwide average level. From 2011 to 2016, the consumption had a linear correlation with GDP, HDI and cancer incidence (p<0.05). However, DDDs varied greatly in countries with similar GDP or HDI. Within 45 Asian countries, the GDP only contributed to 10.47% of change in DDDs, while the HDI contributed to 20.32%. Consumption of non-intravenous opioids or strong opioids always comprised majority of the total consumption. The opioids prescribed predominantly were fentanyl, oxycodone and morphine. Fentanyl and oxycodone account for most of the increase in consumption. CONCLUSION: Opioid consumption has increased >40% from 2011 to 2016, with consumption of fentanyl and oxycodone accounting for most of that increase. The consumption in Nanjing was higher than the average Chinese level, but lower than the global average. An increase in pain control services might be needed, but this need should be highly regulated.

Clinical and economic impact of pharmacist interventions on sampled outpatient prescriptions in a Chinese teaching hospital.

BACKGROUND: Limited studies have evaluated the effectiveness of pharmacist interventions on outpatient prescription. The goal of this study was to evaluate the clinical and economic impacts of pharmacist interventions on randomly sampled outpatient prescriptions. METHOD: Outpatient prescriptions of our hospital were sampled automatically and reviewed by pharmacists since 2011. Pharmacists intervened in inappropriate prescriptions (IPs) real-timely, and summarized and analyzed the information monthly. Cost-benefit analysis was performed to estimate the economic benefit of the pharmacist intervention. RESULTS: From 2011 to 2016, pharmacists reviewed 101,271 prescriptions and intervened in 5155 prescriptions. With the interventions of pharmacists, the number of IPs decreased from 1845 to 238, while the inappropriate percentage decreased from 12.60 to 1.22%. The inappropriate rates of different departments and the types decreased annually. IPs were mainly from the Department of Medicine and Department of Surgery and category 1 (Non-indicated medications) in all years. The benefit-to-cost ratios of pharmacist interventions were always more than 1. In the same years, the benefit-to-cost ratios in public payments were higher than those with insurance and self-payment. CONCLUSION: This form of pharmacist intervention constitutes a method that showed positive clinical and economic benefits and is worth expanding in large hospitals. Pharmacists should pay more attention on prescriptions in department of surgery or prescriptions with public payments.

Chemotherapy in patient with colon cancer after renal transplantation: A case report with literature review.

RATIONALE: Experience of pharmacotherapy in posttransplantation colorectal cancer (CRC) patients is inadequate. PATIENT CONCERNS: A Chinese man had right renal transplantation and began immunosuppressive treatment at the age of 31 in 2009. He was diagnosed with colon cancer and underwent anterior resection in 2014. He was diagnosed with metastatic colon carcinoma by abdomen computed tomography (CT) and positron emission tomography-computed tomography in April 2017. DIAGNOSIS: Metastatic colon carcinoma in posttransplantation patient. INTERVENTIONS: Three cycles of FLOFOX (5-fluorouracil and leucovorin and oxaliplatin) chemotherapy were given since April 2017. OUTCOMES: Plasma concentrations of immunosuppressant and kidney function were within normal during the chemotherapy. Abdomen CT revealed the progress of colon cancer at the end of the third course of chemotherapy. LESSONS: A few cases about monochemotherapy of posttransplantation CRC have been reported, whereas experience of doublet chemotherapy was currently unavailable. We shared the experience of FOLFOX in a patient with posttransplantation colon cancer. Neither of incompatibility with immunosuppressant nor serious adverse drug reaction was observed. It provides evidence for the pharmacotherapy of posttransplantation CRC.

A Case of Capecitabine-induced Hyperammonemia in a Patient with Colon Cancer.

BACKGROUND: Hyperammonemia is an infrequent adverse drug reaction (ADR) of chemotherapy. A few cases of 5-fluorouracil (5-FU) related hyperammonemia have been reported. However, hyperammonemia induced by capecitabine, an oral prodrug of 5-FU, has not been reported till date. CASE REPORT: A patient with colon cancer was treated with CapeOx (oxaliplatin 200mg, day 1; capecitabine 1.5g bid, days 1-14). On the fifth day of first cycle chemotherapy, she developed hyperammonemia (245 µmol/L) and psychiatric symptoms. The serum 5-FU level (3.2µg/L) was lower than normal. When the patient recovered with drug treatment, capecitabine was restarted at a lower dose (1g bid). Hyperammonemia (98µmol/L) and psychiatric symptoms reappeared after three days. Serum 5-FU remained at a low level (4.6µg/L). This case highlighted the possibility of hyperammonemia induced by capecitabine. Case reports such as these would make physicians more aware of rare ADR and what to be done in such case.

The role of statin therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia, and AF is associated with relatively higher all-cause mortality in both men and women. However, there are limited treatment options for AF. Statins are hypothesized to have a benefit against arrhythmias in addition to well-established secondary prevention benefit for atherosclerotic coronary artery disease, yet the data are inconsistent WHAT THIS STUDY ADDS: Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. The benefit of statin therapy seemed more markedly in secondary prevention than primary prevention. These results provided some evidence for the benefit of statins beyond their lipid-lowering activity AIMS: The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF. METHODS: Meta-analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed. RESULTS: Twenty studies with 23,577 patients were included in the analysis. Seven studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and two studies investigated mixed populations of patients. The incidence or recurrence of AF occurred in 1543 patients. Overall, statin therapy was significantly associated with a decreased risk of AF compared with control (odds ratio 0.49, 95% confidence interval 0.37-0.65; P < 0.00001). A beneficial effect was found in the atorvastatin subgroup and the simvastatin subgroup, but not in the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34, 95% confidence interval 0.18-0.64; P < 0.0008) than in primary prevention (odds ratio 0.54, 95% confidence interval 0.40-0.74; P < 0.0001). CONCLUSIONS: Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient populations and surgery types. The benefit of statin therapy seemed more pronounced in secondary than in primary prevention.

Effect of prostaglandin E1 on TNF-induced vascular inflammation in human umbilical vein endothelial cells.

Prostaglandin E1 (PGE1) is a member of the prostaglandins and has a variety of cardiovascular protective effects. Increasing attention has been paid to the anti-inflammation activity of PGE1, but little direct evidence has been found. We investigated the effects of PGE1 on cell adhesion and inflammation and the mechanisms responsible for this activity in tumor necrosis factor (TNF)-treated human umbilical vein endothelial cells. Results demonstrated that pretreatment with PGE1 decreased the adhesion between vascular endothelial cells and monocytes, reduced the expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in vascular endothelial cells. In addition, PGE1 suppressed TNF-induced NF-kappaB activation and production of reactive oxygen species. We concluded that PGE1 suppressed the vascular inflammatory process, which might be closely related to the inhibition of reactive oxygen species and NF-kappaB activation in human umbilical vein endothelial cells.

WITHDRAWN: Prostaglandin E1 attenuate hydrogen peroxide-induced stress injury in human umbilical vein endothelial cells.

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