bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microarray gene expression profiling in colorectal (HCT116) and hepatocellular (HepG2) carcinoma cell lines treated withMelicope ptelefolialeaf extract reveals transcriptome profiles exhibiting anticancer activity
Authors: Kabir Mohammad Faujul , Mohd Ali Johari , Haji Hashim Onn 
Published: July 2018

BackgroundWe have previously reported anticancer activities ofMelicope ptelefolia(MP) leaf extracts on four different cancer cell lines. However, the underlying mechanisms of actions have yet to be deciphered. In the present study, the anticancer activity of MP hexane extract (MP-HX) on colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines was characterized through microarray gene expression profiling.MethodsHCT116 and HepG2 cells were treated with MP-HX for 24 hr. Total RNA was extracted from the cells and used for transcriptome profiling using Applied Biosystem GeneChip™ Human Gene 2.0 ST Array. Gene expression data was analysed using an Applied Biosystems Expression Console and Transcriptome Analysis Console software. Pathway enrichment analyses was performed using Ingenuity Pathway Analysis (IPA) software. The microarray data was validated by profiling the expression of 17 genes through quantitative reverse transcription PCR (RT-qPCR).ResultsMP-HX induced differential expression of 1,290 and 1,325 genes in HCT116 and HepG2 cells, respectively (microarray data fold change, MA_FC ≥ ±2.0). The direction of gene expression change for the 17 genes assayed through RT-qPCR agree with the microarray data. In both cell lines, MP-HX modulated the expression of many genes in directions that support antiproliferative activity. IPA software analyses revealed MP-HX modulated canonical pathways, networks and biological processes that are associated with cell cycle, DNA replication, cellular growth and cell proliferation. In both cell lines, upregulation of genes which promote apoptosis, cell cycle arrest and growth inhibition were observed, while genes that are typically overexpressed in diverse human cancers or those that promoted cell cycle progression, DNA replication and cellular proliferation were downregulated. Some of the genes upregulated by MP-HX include pro-apoptotic genes (DDIT3, BBC3, JUN), cell cycle arresting (CDKN1A, CDKN2B), growth arrest/repair (TP53, GADD45A) and metastasis suppression (NDRG1). MP-HX downregulated the expression of genes that could promote anti-apoptotic effect, cell cycle progression, tumor development and progression, which include BIRC5, CCNA2, CCNB1, CCNB2, CCNE2, CDK1/2/6, GINS2, HELLS, MCM2/10 PLK1, RRM2 and SKP2. It is interesting to note that all six top-ranked genes proposed to be cancer-associated (PLK1, MCM2, MCM3, MCM7, MCM10 and SKP2) were downregulated by MP-HX in both cell lines.DiscussionThe present study showed that the anticancer activities of MP-HX are exerted through its actions on genes regulating apoptosis, cell proliferation, DNA replication and cell cycle progression. These findings further project the potential use of MP as a nutraceutical agent for cancer therapeutics.
Mechanical/thermal sensitivity and superficial temperature in the stump of long-term tail-docked dairy cows
Authors: Troncoso Renata J. , Herzberg Daniel E. , Meneses Constanza S. , Müller Heine Y. , Werner Marianne P. , Bustamante Hedie 
Published: July 2018

BackgroundTail docking of dairy cows is a painful procedure that affects animal welfare level. The aims of this study were first to evaluate the response to mechanical and thermal stimulation, and second to determine the superficial temperature of the stump of tail-docked dairy cows.MethodsOne hundred and sixty-four dairy cows were enrolled. From these, 133 cows were assigned to the tail-docked (TD) group and 31 cows were selected as control animals. The following sensory assessments to evaluate pain in tail-docked cows were performed. Sensitivity of the tail region in both groups of animals was evaluated using a portable algometer. Cold and heat sensitivity assessment was performed using a frozen pack (0 °C) and warm water (45 °C), respectively. Pinprick sensitivity was evaluated using a Wartenberg neurological pinwheel. Superficial temperature was evaluated using a thermographic camera. All sensory assessments and superficial temperature were evaluated in the ventral surface of the tail stump (TD) and tail (C).ResultsPressure pain threshold was lower in TD cows (5.97 ± 0.19 kg) compared to control cows (11.75 ± 0.43 kg). Heat and cold sensitivity was higher in the TD cows compared to control cows with 29% and 23% of TD cows responding positively, respectively. Similarly, after pinprick sensitivity test was performed, 93% of TD cows elicited a positive response to stimulation. Tail-docked cows had lower superficial temperature (26.4 ± 0.27 °C) compared to control cows (29.9 ± 0.62 °C).DiscussionPressure pain threshold values in both groups of animals were higher than those previously reported for TD pigs, sows and cows. In contrast, pinprick stimulation evaluates the presence of punctate mechanical hyperalgesia/allodynia, usually related to traumatic nerve injury, and this association may reveal that it is possible that these animals developed a disorder associated to the development of a tail stump neuroma and concurrent neuropathic pain, previously reported in TD lambs, pigs and dogs. Thermal sensitivity showed that TD cows responded positively to heat and cold stimulation. These findings suggest that long-term TD cows could be suffering hyperalgesia/allodynia, which may be indicative of chronic pain. Lower superficial temperature in the stump may be associated to sympathetic fiber sprouting in the distal stump, which can lead to vasoconstriction and lower surface temperatures. Further studies are needed in order to confirm neuroma development and adrenergic sprouting.
Application of Multifunctional Nanomaterials in Radioprotection of Healthy Tissues
Authors: Xie Jiani , Wang Chengyan , Zhao Feng , Gu Zhanjun , Zhao Yuliang 
Published: July 2018

AbstractRadiotherapy has been extensively used in clinic for malignant tumors treatment. However, a severe challenge of it is that the ionizing radiation needed to kill tumors inevitably causes damage to surrounding normal tissues. Although some of the molecular radioprotective drugs, such as amifostine, have been used as clinical adjuvants to radio‐protect healthy tissues, their shortcomings such as short systemic circulation time and fast biological clearing from the body largely hinder the sustained bioactivity. Recently, with the rapid development of nanotechnology in the biological field, the multifunctional nanomaterials not only establish powerful drug delivery systems to improve the molecular radioprotective drugs' biological availability, but also open a new route to develop neozoic radioprotective agents because some nanoparticles possess intrinsic radioprotective abilities. Therefore, considering these overwhelming superiorities, this review systematically summarizes the advances in healthy tissue radioprotection applications of multifunctional nanomaterials. Furthermore, this review also points out a perspective of nanomaterial designs for radioprotection applications and discusses the challenges and future outlooks of the nanomaterial‐mediated radioprotection.
N‐Alkylation of Fulleropyrrolidines by Aminomethylation Reaction of Ketones/Arylboronic Acids
Authors: Huang Cheng , Huang Gang , Wang Hui‐Juan , Li Fa‐Bao , Wang Zhen , Huang Yongshun , Liu Li , Liu Chao‐Yang 
Published: July 2018

AbstractN‐alkylation of fulleropyrrolidines in the presence of polyformaldehyde and p‐toluenesulfonic acid was systematically investigated. With the addition of ketones/arylboronic acids, a series of novel N‐alkyl fulleropyrrolidines were formed. Nevertheless, in the absence of ketones/arylboronic acids, scarce N‐methyl fulleropyrrolidines were obtained with the aid of benzyl alcohol. Possible reaction pathways for the formation of N‐alkyl fulleropyrrolidines were proposed to elucidate the above reaction process.magnified image
Extended dosing with CC‐486 (oral azacitidine) in patients with myeloid malignancies
Authors: Savona Michael R. , Kolibaba Kathryn , Conkling Paul , Kingsley Edwin C. , Becerra Carlos , Morris John C. , Rifkin Robert M. , Laille Eric , Kellerman Amy , Ukrainskyj Stacey M. , Dong Qian , Skikne Barry S. 
Published: July 2018

AbstractCC‐486 (oral azacitidine) is an epigenetic modifier in clinical development for treatment of hematological cancers. This study of extended CC‐486 dosing included patients with myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). After a pharmacokinetic assessment period, 31 patients (MDS n = 18, CMML n = 4, and AML n = 9) entered a clinical phase in which they received CC‐486 300 mg once‐daily for 21 days of repeated 28‐day cycles. Median age was 71 years (range: 53‐93); 42% of patients were aged ≥75 years. A total of 5 patients with AML (63%) had prior MDS. Median number of CC‐486 treatment cycles was 4 (range: 1‐32). The most common treatment‐emergent adverse events (TEAEs) were gastrointestinal (84% of patients) and hematologic (81%). Most common grade 3‐4 TEAEs were neutropenia (n = 13, 42%) and anemia (n = 9, 29%). Ten patients experienced grade 4 neutropenia. Infrequently, CC‐486 dose was interrupted or reduced due to gastrointestinal (n = 5, 16%) or hematologic (n = 6, 19%) TEAEs. Overall response rate (complete remission [CR], CR with incomplete hematological recovery [CRi], partial remission [PR], marrow CR) in the MDS/CMML subgroups was 32% and in the AML subgroup (CR/CRi/PR) was 22%. Red blood cell transfusion independence rates in the MDS/CMML and AML subgroups were 33% and 25%, respectively, and 2 MDS/CMML patients attained hematologic improvement as a best response on‐study. No baseline gene mutation was predictive of response/nonresponse. CC‐486 allows flexible dosing and schedules to improve tolerability or response. Neutropenia in early treatment cycles deserves scrutiny and may warrant initiation of prophylactic antibiotics.KEY POINTSThe safety profile of oral CC‐486 was comparable to that of injectable azacitidine; most adverse events were hematological and gastrointestinal.Extended (21‐day/cycle) CC‐486 dosing induced responses in patients with hematological malignancies, many of whom had prior DNMTi failure.
Economic evaluation of smoking cessation in Ontario's regional cancer programs
Authors: Djalalov Sandjar , Masucci Lisa , Isaranuwatchai Wanrudee , Evans William , Peter Alice , Truscott Rebecca , Cameron Erin , Mittmann Nicole , Rabeneck Linda , Chan Kelvin , Hoch Jeffrey S. 
Published: July 2018

AbstractQuitting smoking after a diagnosis of cancer results in greater response to treatment and decreased risk of disease recurrence and second primary cancers. The objective of this study was to evaluate the potential cost‐effectiveness of two smoking cessation approaches: the current basic smoking cessation program consisting of screening for tobacco use, advice, and referral; and a best practice smoking cessation program that includes the current basic program with the addition of pharmacological therapy, counseling, and follow‐up. A Markov model was constructed that followed 65‐year‐old smokers with cancer over a lifetime horizon. Transition probabilities and mortality estimates were obtained from the published literature. Costs were obtained from standard costing sources in Ontario and reports. Probabilistic and deterministic sensitivity analyses were conducted to address parameter uncertainties. For smokers with cancer, the best practice smoking cessation program was more effective and more costly than the basic smoking cessation program. The incremental cost‐effectiveness ratio of the best practice smoking cessation program compared to the basic smoking cessation program was $3367 per QALY gained and $5050 per LY gained for males, and $2050 per QALY gained and $4100 per LY gained for females. Results were most sensitive to the hazard ratio of mortality for former and current smokers, the probability of quitting smoking through participation in the program and smoking‐attributable costs. The study results suggested that a best practice smoking cessation program could be a cost‐effective option. These findings can support and guide implementation of smoking cessation programs.
Effects of thoracic radiotherapy timing and duration on progression‐free survival in limited‐stage small cell lung cancer
Authors: Zhao Shen , Zhou Ting , Ma Shuxiang , Zhao Yuanyuan , Zhan Jianhua , Fang Wenfeng , Yang Yunpeng , Hou Xue , Zhang Zhonghan , Chen Gang , Zhang Yaxiong , Huang Yan , Zhang Li 
Published: July 2018

AbstractConcurrent chemoradiotherapy (CRT) has been recommended and applied widely as the standard treatment for limited‐stage small cell lung cancer (LS‐SCLC). However, controversies remain regarding the optimal timing and treatment duration of thoracic radiotherapy (TRT), and their effects on patient survival. To evaluate prognostic values of TRT timing and duration on progression‐free survival (PFS) in LS‐SCLC and their dependence on TRT fractionation and clinicopathological characteristics, we retrospectively analyzed 197 LS‐SCLC patients receiving CRT from 2000 to 2016 at Sun Yat‐sen University Cancer Center. Based on the optimal cut‐off values of TRT timing and duration generated by Cutoff Finder, patients were divided into early TRT/late TRT group and short TRT/long TRT group respectively. Univariate and multivariate Cox analysis were performed to assess correlations of TRT timing, duration, fractionation, and clinicopathological characteristics with PFS. Univariate analysis revealed that early‐initiated TRT (P = 2.54 × 10−4) and short TRT (P = .001) significantly correlated with longer PFS. Their PFS benefits persisted in patients receiving hyperfractionated TRT and etoposide‐cisplatin (EP) chemotherapy, but were less prominent in those receiving once‐daily TRT and non‐EP chemotherapy. Multivariate analysis further identified early initiated TRT (P = .004) and short TRT (P = .017) as independent prognostic factors for longer PFS in LS‐SCLC. Our study confirmed that early‐initiated TRT and short TRT had positive prognostic roles in LS‐SCLC, especially in patients receiving hyperfractionated TRT and etoposide‐cisplatin chemotherapy. TRT fractionation was not an independent prognostic factor in LS‐SCLC.
Coexpression of CD5 and CD43 predicts worse prognosis in diffuse large B‐cell lymphoma
Authors: Ma Xiao‐bo , Zhong Yan‐ping , Zheng Yan , Jiang Jing , Wang Yin‐ping 
Published: July 2018

AbstractBoth CD5 and CD43 are expressed on the surface of B lymphocytes of definite phase and associated with the adverse outcome in diffuse large B‐cell lymphoma (DLBCL). However, the relationship between CD5 and CD43 expression and the prognostic value of CD5/CD43 coexpression in DLBCL are unknown. We herein determined the correlation between CD5 and CD43 expression, as separate factors or in combination, with the clinicopathological features and survival of 200 patients with DLBCL receiving standard chemotherapy with or without rituximab. Among these DLBCL patients, CD5 expression, CD43 expression, and CD5/CD43 coexpression were detected in 18 (9%), 57 (27%), and 10 (5%) patients, respectively, and all were positively correlated with advanced age and nongerminal cell type. CD5‐positive and CD43‐positive DLBCL patients had poorer event‐free survival (EFS, P < 0.001) and overall survival (OS, P < 0.001) than CD5‐negative and CD43‐negative patients, respectively. CD5/CD43 coexpression was correlated with a significantly worse prognosis than CD5 or CD43 expression alone. Univariate analysis showed that CD5 expression, CD43 expression, and CD5/CD43 coexpression were all adverse prognostic factors for DLBCL patient survival, and CD5/CD43 coexpression was associated with a greater relative risk for recurrence and death than either CD5 or CD43 expression alone. Multivariate analysis demonstrated that CD5/CD43 coexpression was an independent prognostic factor for EFS (P < 0.001) and OS (P < 0.001) in DLBCL. In conclusion, our data indicate that DLBCL patients with CD5/CD43 coexpression represent a specific subgroup with a significantly worse prognosis than those expressing either marker alone.
Cancer of unknown primary—Epidemiological trends and relevance of comprehensive genomic profiling
Authors: Binder Carmen , Matthes Katarina Luise , Korol Dimitri , Rohrmann Sabine , Moch Holger 
Published: July 2018

AbstractBackgroundCancer of unknown primary (CUP) is a distinct clinicopathological entity with poor prognosis, frequently resistant to chemotherapy. Comprehensive genomic profiling (CGP) by next‐generation sequencing potentially identifies novel treatment options for CUP patients. The objective of this study was to determine incidence and survival trends and to discuss the value of CGP in CUP patients.MethodsAge‐standardized incidence rates (ASR) per 100 000 were calculated for 2935 CUP patients from 1981 to 2014 using cancer registry data of the canton of Zurich, Switzerland. Kaplan–Meier survival curves were estimated for sex, age, and histological groups. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR). A literature review was conducted to assess the current use of CGP in CUP patients.ResultsASR of CUP increased from 10.3 to 17.6 between 1981 and 1997 and decreased to 5.8/100 000 in 2014. Mean overall survival remained stable. Mortality was significantly lower for patients with squamous cell carcinoma (HR 0.48 [95% CI, 0.41‐0.57]) and neuroendocrine carcinoma (0.75 [0.63‐0.88]) and higher for unclassified neoplasms (1.25 [1.13‐1.66]) compared to adenocarcinomas. The literature review identified 10 studies using CGP of CUP tissue. Clinically relevant mutations were identified in up to 85% of CUP patients, of which 13%‐64% may benefit from currently available drugs.ConclusionsCUP incidence decreased probably due to improved diagnostics, but mortality did not improve over the last 34 years. CGP testing may help to identify molecular signatures in CUP patients and enable targeted treatment.
Chemical Constituents from Chloranthus anhuiensis and Their Cytotoxic Activities
Authors: Zhu Hui‐Lin , Qu Wei , Zhang Jie , Guo Er‐Yan , Du Tao , Liu Wen‐Yuan , Cao Wen‐Yuan , Feng Feng , Xu Jian 
Published: July 2018

Three hiherto unknown phenylpropanoid compounds, namely (7S,8R)‐1‐(1‐ethoxy‐2‐hydroxypropyl)‐2‐methoxy‐3,4‐(methylenedioxy)benzene (1), (7S,8S)‐1‐(1‐ethoxy‐2‐hydroxypropyl)‐2‐methoxy‐3,4‐(methylenedioxy)benzene (2), and (7S,8R)‐1‐(1‐methoxy‐2‐hydroxypropyl)‐2‐methoxy‐3,4‐(methylenedioxy)benzene (3), along with 12 known compounds (4 – 15) were obtained from the extract of whole plant of Chloranthus anhuiensis. Among them, 7 and 13 were obtained from nature for the first time. The structures of these natural compounds were characterized by extensive spectroscopic analysis and calculated electronic circular dichroism (ECD) data. Furthermore, their cytotoxic and neuroprotective activities were evaluated using MDA‐MB‐231, 4T1, HepG2, and PC12 cell lines. Compounds 8 and 13 exhibited moderate cytotoxic activities against MDA‐MB‐231 cell line with the IC50 values of 39.7 and 25.8 μm, respectively. And all the isolated compounds have no neuroprotective activities.
Identification of a BRCA2 mutation in a Turkish family with early‐onset breast cancer
Authors: Celik Elifnaz , Ermis Tekkus Kubra , Akcay Izzet Mehmet , Alkurt Sal Gizem , Ezberci Fikret , Dinler Doganay Gizem , Doganay Levent 
Published: July 2018

Key Clinical MessageWe used a multi‐gene panel testing to identify the germline variants in a mother‐daughter pair with early‐onset breast cancer, and detected one pathogenic protein‐truncating variant in BRCA2. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.
Heterocyclization and Spirocyclization Processes Based on Domino Reactions of N‐Tosylhydrazones and Boronic Acids Involving Intramolecular Allylborylations of Nitriles
Authors: Plaza Manuel , Parisotto Stefano , Valdés Carlos 
Published: July 2018

AbstractPolycyclic molecules featuring all‐carbon quaternary bridgehead centers were synthesized through domino cyclizations between N‐tosylhydrazones and boronic acids. Variations of the general cascade have been applied for the preparation of 3‐quinuclidinones and related alkaloid‐like scaffolds through transannular heterocyclizations. Moreover, the employment of 3‐cyanopropyl and 4‐cyanobutylboronic acids and α,β‐unsaturated N‐tosylhydrazones led to spirocycles through unprecedented formal [n+1] cyclizations, including the stereoselective spirocyclization of the Hajos–Parrish ketone. The common feature of all the new reactions described is the creation of an all‐carbon quaternary center by formation of two Csp3−C bonds on the hydrazonic carbon atom. DFT‐based calculations suggested the occurrence of cascade processes, which involve a diazo compound carboborylation followed by a 1,3‐borotropic rearrangement on an intermediate allylboronic acid and a novel bora‐aza‐ene cyclization.
Non‐coronary predictors of elevated high‐sensitive cardiac troponin T (hs‐cTnT) levels in an unselected emergency patient cohort
Authors: Berger Manfred , Emir Meryem , Brünnler Tanja , Rockmann Felix , Lehmann Ralf 
Published: July 2018

BackgroundAim of this study was to evaluate the predictors of hs‐cTnT in a non‐ACS patient cohort admitted to the emergency department.HypothesisAtrial fibrillation and hypertension may not always be sufficient for elevation for hs‐cTnT.MethodsWe performed a retrospective, single center study encompassing in total 1003 patients. Individuals were retrospectively divided in ACS‐ and non‐ACS patients by two independent investigators reviewing the medical records. In order to identify predictors of hs‐cTnT elevation hazard ratios were calculated for age, gender, vital signs, cardiovascular risk factors, LVEF, serum levels of CRP, hemoglobin, and creatinine. Elevation of hs‐cTnT was defined by exceeding 14 ng/L (upper reference limit [URL]).ResultsAbout 987 patients were included while 25 patients were excluded because of missing data. 307 patients (31.4%) met the current guideline requirements of diagnosing an ACS, whereas 671 patients (68.6%) were hospitalized with excluded ACS. In the multivariate analysis age, anemia, CRP, creatinine, and reduced systolic left ventricular ejection fraction were independent predictors of elevated troponin T levels in the non‐ACS group. However, hypertensive systolic blood pressure, atrial fibrillation and tachycardia were not predictive for Troponin T elevation in non‐ACS patients in this multivariate analysis.ConclusionsIn an unselected, non‐ACS patient cohort age, chronic renal failure, inflammatory state, and reduced left ventricular systolic function were associated with hs‐cTnT levels above the upper reference limit. Rather, often supposed predictors as atrial fibrillation, hypertension, and tachycardia cannot sufficiently explain increased hs‐cTnT in our study. Hence, further studies are needed to assess whether isolated hypertension, tachycardia, or atrial fibrillation sufficiently explain elevated hs‐cTnT.