Predicting article citations using data of 100 top-cited publications in the journal Medicine since 2011: A bibliometric analysis.

BACKGROUND: Publications regarding the 100 top-cited articles in a given discipline are common, but studies reporting the association between article topics and their citations are lacking. Whether or not reviews and original articles have a higher impact factor than case reports is a point for verification in this study. In addition, article topics that can be used for predicting citations have not been analyzed. Thus, this study aims to METHODS:: We searched PubMed Central and downloaded 100 top-cited abstracts in the journal Medicine (Baltimore) since 2011. Four article types and 7 topic categories (denoted by MeSH terms) were extracted from abstracts. Contributors to these 100 top-cited articles were analyzed. Social network analysis and Sankey diagram analysis were performed to identify influential article types and topic categories. MeSH terms were applied to predict the number of article citations. We then examined the prediction power with the correlation coefficients between MeSH weights and article citations. RESULTS: The citation counts for the 100 articles ranged from 24 to 127, with an average of 39.1 citations. The most frequent article types were journal articles (82%) and comparative studies (10%), and the most frequent topics were epidemiology (48%) and blood and immunology (36%). The most productive countries were the United States (24%) and China (23%). The most cited article (PDID = 27258521) with a count of 135 was written by Dr Shang from Shandong Provincial Hospital Affiliated to Shandong University (China) in 2016. MeSH terms were evident in the prediction power of the number of article citations (correlation coefficients  = 0.49, t = 5.62). CONCLUSION: The breakthrough was made by developing dashboards showing the overall concept of the 100 top-cited articles using the Sankey diagram. MeSH terms can be used for predicting article citations. Analyzing the 100 top-cited articles could help future academic pursuits and applications in other academic disciplines.

C2-Ceramide-Induced Rb-Dominant Senescence-Like Phenotype Leads to Human Breast Cancer MCF-7 Escape from p53-Dependent Cell Death.

Ceramide is a sphingolipid which regulates a variety of signaling pathways in eukaryotic cells. Exogenous ceramide has been shown to induce cellular apoptosis. In this study, we observed that exogenous ceramide induced two distinct morphologies of cell fate following C2-ceramide treatment between the two breast cancer cell lines MCF-7 (wild type p53) and MDA-MB-231 (mutant p53) cells. The growth assessment showed that C2-ceramide caused significant growth inhibition and apoptosis in MDA-MB-231 cells through down-regulating the expression of mutant p53 whereas up-regulating the expression of pro-apoptotic Bad, and the proteolytic activation of caspase-3. However, senescence-associated (SA)-ß-galactosidase (ß-gal) was regulated in MCF-7 cells after C2-ceramide treatment. The results of proliferation and apoptosis assays showed that MCF-7 cells were more resistant to C2-ceramide treatment compared to MDA-MB-231 cells. Furthermore, C2-ceramide treatment induced a time-responsive increase in Rb protein, a key regulator of senescence accompanied with the upregulation of both mRNA level and protein level of SA-genes PAI-1 and TGaseII in MCF-7 but not in MDA-MB-231 cells, suggesting that some cancer cells escape apoptosis through modulating senescence-like phenotype. The results of our present study depicted the mechanism of C2-ceramide-resistant breast cancer cells, which might benefit the strategic development of ceramide-based chemotherapeutics against cancer in the future.

Evaluating the optimal radiation dose for definitive chemoradiotherapy for esophageal squamous cell carcinoma: A single institution experience.

The optimal radiation dose for definitive chemoradiotherapy in inoperable esophageal squamous cell carcinoma (ESCC) has been long debated. In this study, we evaluated the effect of doses greater than the conventional radiation dose (50.4 Gy) on tumor control, tumor response, overall survival (OS), and disease-free survival (DFS).The database of patients diagnosed with inoperable ESCC from 2007 to 2015 was obtained from the cancer registry of Chi-Mei Medical Center. All categorical variables were compared using Chi-squared test. The risk of OS and DFS were estimated using Cox proportional hazards regression, and Kaplan-Meier plots presented the trend of OS and DFS with log-rank tests used to compare differences. All significance levels were set at P < .05.A total of 84 patients were retrospectively analyzed, with 42 (50%) receiving >50.4 Gy and 42 (50%) receiving ≤50.4 Gy (50%) concurrently with chemotherapy. Univariate and multivariate analysis revealed no significant differences between higher dose and conventional dose in OS (P = .21) and DFS (P = .26). Further dose analysis of <50, 50 to 50.4, 51 to 60, and >60 Gy showed no significant differences in OS or DFS. Higher doses conveyed no significant benefit on the failure pattern, either local regional failure or distant failure (P = .42). Major prognostic factors associated with better OS on multivariate analysis were stages I and II patients (P = .03) and radiation technique using arc therapy (P = .04). No acute toxicity of grade III or higher was recorded.The results of our study show that providing higher than conventional radiation doses concurrent with chemotherapy for inoperable ESCC does not impact OS or DSF, nor does it improve locoregional failure or distant failure. Although tumor response might be improved by radiation doses >50.4 Gy, the impact on OS and DFS remain to be studied.

Exogenous C8-Ceramide Induces Apoptosis by Overproduction of ROS and the Switch of Superoxide Dismutases SOD1 to SOD2 in Human Lung Cancer Cells.

Ceramides, abundant sphingolipids on the cell membrane, can act as signaling molecules to regulate cellular functions including cell viability. Exogenous ceramide has been shown to exert potent anti-proliferative effects against cancer cells, but little is known about how it affects reactive oxygen species (ROS) in lung cancer cells. In this study, we investigated the effect of N-octanoyl-D-erythro-sphingosine (C8-ceramide) on human non-small-cell lung cancer H1299 cells. Flow cytometry-based assays indicated that C8-ceramide increased the level of endogenous ROS in H1299 cells. Interestingly, the ratio of superoxide dismutases (SODs) SOD1 and SOD2 seem to be regulated by C8-ceramide treatment. Furthermore, the accumulation of cell cycle G1 phase and apoptotic populations in C8-ceramide-treated H1299 cells was observed. The results of the Western blot showed that C8-ceramide causes a dramatically increased protein level of cyclin D1, a critical regulator of cell cycle G1/S transition. These results suggest that C8-ceramide acts as a potent chemotherapeutic agent and may increase the endogenous ROS level by regulating the switch of SOD1 and SOD2, causing the anti-proliferation, and consequently triggering the apoptosis of NSCLC H1299 cells. Accordingly, our works may give a promising strategy for lung cancer treatment in the future.

The age-adjusted Charlson comorbidity index is a better predictor of survival in operated lung cancer patients than the Charlson and Elixhauser comorbidity indices.

OBJECTIVES: To compare the prognostic performance between different comorbidity assessments of survival in patients with operated lung cancer. METHODS: A total of 4508 lung cancer patients treated by surgery between 2003 and 2012 were identified through Taiwan's National Health Insurance Research Database. Information on pre-existing comorbidities prior to the cancer diagnosis was obtained and adapted to the Charlson comorbidity index, age-adjusted Charlson comorbidity index (ACCI) and Elixhauser comorbidity index scores. The influence on survival was analysed using a Cox proportional hazard model. The discriminatory ability of the comorbidity indices were evaluated using Akaike information criterion and Harrell's C-statistic. RESULTS: The mean age of the study cohort was 64.95 ± 11.15 years, and 56.28% of the patients were male. The median follow-up time was 2.59 years, and the 3-year overall survival was 73.94%. Among these patients, 2134 (47.3%) patients received adjuvant therapy. The Charlson comorbidity index and ACCI scores correlated well with survival and higher scores were associated with an increased 3-year mortality risk (hazard ratio = 1.21, 95% confidence interval = 1.03-1.42 and hazard ratio = 1.43, 95% confidence interval = 1.08-1.90, respectively) in multivariate analysis. The ACCI scores provided better discriminatory ability with a smaller Akaike information criterion and greater Harrell's C-statistic for 3-year overall survival compared to the Charlson comorbidity index or Elixhauser comorbidity index scores. CONCLUSIONS: The operated lung cancer patients with severe comorbidities were associated with worse survival. The ACCI appears to be a more appropriate prognostic indicator and should be considered for use in clinical practice.

Pretreatment of a matrix metalloproteases inhibitor and aprotinin attenuated the development of acute pancreatitis-induced lung injury in rat model.

OBJECTIVE: Acute lung injury (ALI) is one of the most common extra-pancreatic complications of acute pancreatitis. In this study, we examined the protective effect of protease inhibitor aprotinin and a matrix metalloproteinase inhibitor (MMPi) on pulmonary inflammation in rats with severe pancreatitis-associated ALI. METHOD: A rat model of acute pancreatitis (AP) was established by injecting sodium glycodeoxycholate (GDOC) into the pancreatic duct. Pharmacological interventions included pretreatment with a protease inhibitor aprotinin (10mg/kg) and a matrix metalloproteinase inhibitor (MMPi, 100g/kg). The extent of pancreatic and lung injury and systemic inflammation was assessed by examinations of blood, bronchoalveolar lavage (BAL), and lung tissue. Pancreatic or lung tissue edema was evaluated by tissue water content. Pulmonary arterial pressure and alveolar-capillary membrane permeability were evaluated post-injury via a catheter inserted into the pulmonary artery in an isolated, perfused lung model. RESULTS: Pre-treatment with aprotinin or MMPi significantly decreased amylase and lactate dehydrogenase (LDH), and the wet/dry weight ratio of the lung and pancreas in AP rats. Compared to the GDOC alone group, administration of aprotinin or MMPi prevented pancreatitis-induced IL-6 increases in the lung. Similarly, treatment with aprotinin or MMPi significantly decreased the accumulation of white blood cells, oxygen radicals, nitrite/nitrates in both blood and BAL, and markedly reduced lung permeability. CONCLUSION: Pretreatment with either aprotinin or MMPi attenuated the systemic inflammation and reduced the severity of lung and pancreas injuries. In short, our study demonstrated that inhibition of protease may be therapeutic to pulmonary inflammation in this GDOC-induced AP model.

Dual roles of extracellular signal-regulated kinase (ERK) in quinoline compound BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer cells.

BACKGROUND: 2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinoline-11-one (BPIQ), is a synthetic quinoline analog. A previous study showed the anti-cancer potential of BPIQ through modulating mitochondrial-mediated apoptosis. However, the effect of BPIQ on cell migration, an index of cancer metastasis, has not yet been examined. Furthermore, among signal pathways involved in stresses, the members of the mitogen-activated protein kinase (MAPK) family are crucial for regulating the survival and migration of cells. In this study, the aim was to explore further the role of MAPK members, including JNK, p38 and extracellular signal-regulated kinase (ERK) in BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer (NSCLC) cells. METHODS: Western Blot assay was performed for detecting the activation of MAPK members in NSCLC H1299 cells following BPIQ administration. Cellular proliferation was determined using a trypan blue exclusion assay. Cellular apoptosis was detected using flow cytometer-based Annexin V/propidium iodide dual staining. Cellular migration was determined using wound-healing assay and Boyden's chamber assay. Zymography assay was performed for examining MMP-2 and -9 activities. The assessment of MAPK inhibition was performed for further validating the role of JNK, p38, and ERK in BPIQ-induced growth inhibition, apoptosis, and migration of NSCLC cells. RESULTS: Western Blot assay showed that BPIQ treatment upregulates the phosphorylated levels of both MAPK proteins JNK and ERK. However, only ERK inhibitor rescues BPIQ-induced growth inhibition of NSCLC H1299 cells. The results of Annexin V assay further confirmed the pro-apoptotic role of ERK in BPIQ-induced cell death of H1299 cells. The results of wound healing and Boyden chamber assays showed that sub-IC50 (sub-lethal) concentrations of BPIQ cause a significant inhibition of migration in H1299 cells accompanied with downregulating the activity of MMP-2 and -9, the motility index of cancer cells. Inhibition of ERK significantly enhances BPIQ-induced anti-migration of H1299 cells. CONCLUSIONS: Our results suggest ERK may play dual roles in BPIQ-induced apoptosis and anti-migration, and it would be worthwhile further developing strategies for treating chemoresistant lung cancers through modulating ERK activity.

9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11H-indeno[1, 2-c]quinolin-11-one (BPIQ), A Quinoline Derivative Inhibits Human Hepatocellular Carcinoma Cells by Inducing ER Stress and Apoptosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading cancers in the world, including Taiwan. The chemoresistance of advanced HCC frequently results in the poor prognosis of patients. Previous studies demonstrated the quinoline derivative, 9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11Hindeno[ 1,2-c]quinolin-11-one (BPIQ) exerts the inhibitory potential against several cancer cells, including liver cancer cells. OBJECTIVE: We further investigated the anti-HCC effects of BPIQ, including apoptosis and the modulation of ER stress. METHODS: Both trypan blue exclusion assay and colony formation assay were performed to examine whether BPIQ affects the growth of HCC cell lines Ha22T and Huh7. Flow cytometry-based assay was performed for determining the cell cycle distribution and apoptosis. Western blot assay was conducted for detecting the changes in apoptosis- and endoplasmic reticulum (ER) stress-associated proteins. RESULTS: BPIQ inhibits cell growth and induces the apoptosis of both Ha22T and Huh7 cell lines significantly. The level of γH2AX, an endogenous DNA damage biomarker was dramatically increased suggesting the involvement of DNA damage pathway in BPIQ-induced apoptosis. Further, BPIQ down-regulates the pro-survival proteins, survivin, XIAP and cyclin D1. BPIQ also may regulate ER stress response through modulating the levels of ER stress-related proteins Glucose-regulated protein of 78 kD (GRP78), Inositol-requiring kinase-1α (IREα), C/EBP homologous protein (Chop) and calnexin. CONCLUSIONS: The anti-HCC effect of BPIQ may occur through down-regulating pro-survival proteins, and the modulation of ER stress may contribute to the BPIQ-induced apoptosis of HCC cells. The chemotherapeutic or chemopreventive applications of BPIQ for HCC treatment will be worthy of further investigation in future.

A Quinone-Containing Compound Enhances Camptothecin-Induced Apoptosis of Lung Cancer Through Modulating Endogenous ROS and ERK Signaling.

The natural compound camptothecin (CPT) derivatives have widely been used for anti-cancer treatments, including lung cancer. However, many chemoresistant cancer cells often develop a relatively higher threshold for inducing apoptosis, causing a limited efficacy of anti-cancer drugs. Likewise, lung cancer cells acquire chemoresistance against CPT analogs, such as irinotecan and topotecan, finally resulting in an unsatisfied outcome and poor prognosis of lung cancer patients. TFPP is a quinone-containing compound as a candidate for CPT-based combination chemotherapy. In this study, we examined the effect of TFPP and CPT cotreatment on non-small cell lung cancer (NSCLC) cells. Cell proliferation and flow cytometry-based Annexin-V/PI staining assays demonstrated the synergistic effect of TFPP on CPT-induced apoptosis in both NSCLC A549 and H1299 cells. The results of CPT and TFPP cotreatment cause the regulation of the ERK-Bim axis and the activation of mitochondrial-mediated caspase cascade, including caspase-9 and caspase-3. Besides, TFPP significantly enhanced CPT-induced endogenous reactive oxygen species (ROS) in the two NSCLC cells. In contrast, the treatment of N-acetyl-L-cysteine (NAC), an ROS scavenger, rescues the apoptosis of NSCLC cells induced by TFPP and CPT cotreatment, suggesting that the synergistic effect of TFPP on CPT-induced anti-NSCLC cells is through upregulating ROS production. Consequently, our results suggest that TFPP sensitizes NSCLC towards CPT-based chemotherapy may act through decreasing the apoptosis-initiating threshold. Therefore, TFPP may be a promising chemosensitizer for lung cancer treatment, and the underlying mechanism warrants further.