ResearchPad - Pharmacology (medical) https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Discovery of Potential Plasma Biomarkers for Tuberculosis in HIV-Infected Patients by Data-Independent Acquisition-Based Quantitative Proteomics]]> https://www.researchpad.co/product?articleinfo=Nfa5d7b87-9f00-4610-a582-184e25b54d5c

Purpose

Tuberculosis (TB) is the leading cause of mortality in individuals infected with human immunodeficiency virus (HIV), yet the methods for detecting Mycobacterium tuberculosis at an early stage remain insensitive or ineffective. This study aimed to discover plasma biomarkers for distinguishing HIV-TB coinfected individuals from HIV individuals without TB (HIV-nonTB).

Patients and Methods

A total of 200 Chinese HIV-positive patients were recruited, 100 each for HIV-nonTB group and HIV-TB group. Plasma proteomic profiles were analyzed for 50 patients each in both groups, using data-independent acquisition (DIA)-mass spectrometry-based proteomics. Differently expressed proteins were revealed with ridge regression analysis. Enzyme-linked immunosorbent assay (ELISA) analyses were performed for further validation in other 100 patients.

Results

DIA-mass spectrometry revealed 13 upregulated and 33 downregulated proteins in the HIV-TB group. AMACR (α-methylacyl-CoA racemase), LDHB (L-lactate dehydrogenase B chain), and RAP1B (Ras-related protein Rap-1b) were selected for building a diagnostic model, for which the receiver operation characteristic curve had under areas of 0.99 and 0.89 testing with proteomics data (sensitivity = 92%, specificity = 100%) and ELISA data (sensitivity = 76%, specificity = 92%), respectively.

Conclusion

The combination of AMACR, LDHB, and RAP1B proteins may serve as a potential marker of TB in HIV-infected patients.

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<![CDATA[ACAT2 Promotes Cell Proliferation and Associates with Malignant Progression in Colorectal Cancer]]> https://www.researchpad.co/product?articleinfo=Nd0c065e5-85fa-40b2-a9c5-f323541897cd

Background and Aims

Colorectal cancer (CRC) is a major disease that threatens human health. It has been reported that the acyl-coenzyme A (CoA): cholesterol acyltransferase 2 (ACAT2) gene can promote the progression of hepatocellular carcinoma, but its function in CRC is still unclear. In this study, we aimed to elucidate the function of ACAT2 in CRC.

Methods

Western blot and qPCR were used to detect the relative level of ACAT2 in CRC tissue and adjacent non-cancerous tissues, and then the association between ACAT2 expression and the clinicopathological features and survival of CRC patients were assessed. The expression of ACAT2 in CT26 and DLD1 cells was down-regulated by siRNA, and the effects of ACAT2 knockdown on cell proliferation were examined. The inhibitory effects of ACAT2 knockdown were further confirmed by tumor growth assays in vivo.

Results

Our data showed that the expression of ACAT2 in CRC tissues was markedly higher than in adjacent non-cancerous tissues. The high expression of ACAT2 was significantly associated with tumor size, lymph node metastasis and clinical stage. The increased expression of ACAT2 was also significantly associated with worse 5-year overall survival of CRC patients. siRNA-mediated ACAT2 knockdown strongly inhibited CT26 and DLD1 cells proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in these cells. Knockdown of ACAT2 expression suppressed the growth of CRC and inhibited the expression of Ki67 in vivo.

Conclusion

Our study demonstrated that ACAT2 played a positive role in regulating the proliferation of CRC and may be useful as a potential biomarker and therapeutic target for this disease.

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<![CDATA[Mitofusin1 Is a Major Mediator in Glucose-Induced Epithelial-to-Mesenchymal Transition in Lung Adenocarcinoma Cells]]> https://www.researchpad.co/product?articleinfo=N740baced-cc25-4460-acf8-d6e46745ed29

Background

Epithelial-to-mesenchymal transition (EMT) has been considered a latent mediator of diverse biological processes in cancer. However, the mechanisms involved in high glucose-associated EMT in lung adenocarcinoma (LAD) have not been fully clarified. In this study, we aimed to investigate whether mitofusin1 (MFN1) is involved in the EMT of LAD cells induced by glucose and to identify the molecular mechanism involved in this process.

Materials and Methods

The expression of specific proteins was analysed by Western blotting, immunohistochemistry, co-immunoprecipitation and immunofluorescence analysis. The proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8, bromodeoxyuridine incorporation, wound-healing and transwell assays. Lung tissues of adjacent normal regions and lung tissues from patients with LAD and LAD combined with diabetes mellitus were collected to determine the expression and significance of MFN1.

Results

Here, we showed that the expression of MFN1 was increased in LAD tissues compared with adjacent normal tissues and expression was even higher in lung tissues from patients with LAD combined with diabetes. In the lung cancer cell line A549, increased cell proliferation, invasion and EMT induced by high glucose were inhibited by MFN1 silencing. Mechanistic studies demonstrated that inhibiting autophagy reversed the abnormal EMT triggered by high glucose conditions. In addition, our data provide novel evidence demonstrating that PTEN-induced kinase (Pink) is a potential regulator involved in MFN1-mediated cell autophagy, which eventually leads to high glucose-induced proliferation, invasion and EMT of A549 cells.

Conclusion

Taken together, our data show that MFN1 interacts with Pink to induce the autophagic process and that the abnormal occurrence of autophagy ultimately contributes to glucose-induced pathological EMT in LAD.

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<![CDATA[Dihydroartemisinin Prevents Progression and Metastasis of Head and Neck Squamous Cell Carcinoma by Inhibiting Polarization of Macrophages in Tumor Microenvironment]]> https://www.researchpad.co/product?articleinfo=N2711109f-0f80-479f-aff7-72b2658f3ed0

Background

Polarized M2 macrophages are an important type of tumor-associated macrophage (TAM), with roles in the growth, invasion, and migration of cancer cells in the tumor microenvironment. Dihydroartemisinin (DHA), a traditional Chinese medicine extract, has been shown to inhibit the progression and metastasis of head and neck squamous cell carcinoma (HNSCC); however, the effect of DHA on cancer prevention, and the associated mechanism, has not been investigated in the tumor microenvironment.

Materials and Methods

First, human Thp-1 monocytes were induced and differentiated into M2 macrophages using phorbol 12-myristate 13-acetate (PMA), interleukin-6 (IL-6), and interleukin-4 (IL-4). Induction success was confirmed by cell morphology evaluation, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Then, DHA was applied to interfere with M2 macrophage polarization, and conditioned medium (CM), including conditioned medium from M2 macrophages (M2-CM) and conditioned medium from M2 macrophages with DHA (M2-DHA-CM), was obtained. CM was applied to Fadu or Cal-27 cells, and its effects on cancer invasion, migration, and angiogenesis were evaluated using transwell, wound-healing, and tube formation assays, respectively. Finally, Western blotting was used to evaluate the relationship between signal transducer and activator of transcription 3 (STAT3) signaling pathway activation and M2 macrophage polarization.

Results

Human Thp-1 monocytes were successfully polarized into M2-like TAMs using PMA, IL-6, and IL-4. We found that M2-like TAMs promoted the invasion, migration, and angiogenesis of HNSCC cells; however, DHA significantly inhibited IL-4/IL-6-induced M2 macrophage polarization. Additionally, as DHA induced a decrease in the number of M2-like TAMs, M2-DHA-CM inhibited the induction of invasion, migration, and angiogenesis of Fadu and Cal-27 cells. Finally, DHA inhibited M2 macrophage polarization by blocking STAT3 pathway activation in macrophages.

Conclusion

DHA inhibits the invasion, migration, and angiogenesis of HNSCC by preventing M2 macrophage polarization via blocking STAT3 phosphorylation.

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<![CDATA[The Parkinson’s Disease Death Rate: Carbidopa and Vitamin B6 [Expression of Concern]]]> https://www.researchpad.co/product?articleinfo=N7c6defb2-2a43-4d91-bfde-27abec93ac10 ]]> <![CDATA[An Oncolytic Vaccinia Virus Armed with GM-CSF and IL-24 Double Genes for Cancer Targeted Therapy]]> https://www.researchpad.co/product?articleinfo=Nb48b35f5-1f83-4ab9-9c0f-23e96a7d6974

Purpose

Targeted oncolytic vaccinia virus is an attractive candidate for cancer therapy due to its replication causing lysis of infected tumor cells as well as a delivery vector to overexpress therapeutic transgenes. This study constructed a novel oncolytic vaccinia virus carrying granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-24 (IL-24) double genes to improve efficacy for cancer therapy.

Methods

Vaccinia virus co-expressing GM-CSF and IL-24 based on Chinese Guang9 strain (VG9-GMCSF-IL24) was constructed with disruption of the viral thymidine kinase (TK) gene. The cytotoxicity of VG9-GMCSF-IL24 in various cell lines was assessed by MTT. The synergistic antitumor effect of VG9-GMCSF-IL24 in vivo was assessed on multiple tumor models.

Results

In vitro cytotoxicity assay showed that VG9-GMCSF-IL24 exerted a strongly cytotoxic effect on cancer cells, but with no significant cytotoxicity to normal cells. Significant tumor growth inhibition and prolonged survival were observed in different tumor models treated with VG9-GMCSF-IL24. Additionally, systemic and specific antitumoral immunity was investigated in vivo, and enhanced antitumor immunity was observed in VG9-GMCSF-IL24-treated mice.

Conclusion

Our results indicated that VG9-mediated GM-CSF and IL-24 co-expression performed cooperative and overlapping antitumor effect. As a novel and effective therapeutic strategy for cancer, the combination of oncolysis and immunotherapy with vaccinia virus carrying one or more immunostimulatory genes may have a satisfactory clinical application prospect.

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<![CDATA[Genomic and Phenotypic Diversity of Listeria monocytogenes Causing Pregnancy-Associated Listeriosis from Zhejiang Province, China, 2016–2018]]> https://www.researchpad.co/product?articleinfo=Nd50c7e99-53bc-478b-a9bc-d840a2e290a5

Introduction

There are few investigations describing the pregnancy-associated listeriosis in China, and the molecular characteristics of Listeria monocytogenes causing such infections remain largely unknown. We aim to investigate the phenotypic and genomic profiles of pregnancy-associated L. monocytogenes isolates and their association with isolates recovered from human and non-human in China.

Materials and Methods

In this study, we conducted a 3-year surveillance of listeriosis in a women’s hospital in Zhejiang province, using whole genome sequencing and bioinformatics tools.

Results

From 2016 to 2018, we identified 13 clinical L. monocytogenes isolates. Among these pregnancy-associated isolates, we found seven sequence types (STs), with the prevalent STs of ST87 and ST7. Serotyping divided the strains into four serotypes, including serotype 1/2a, 1/2b, 3a, and 4b. Antimicrobial resistance testing showed that all the isolates were susceptible to 10 antibiotics. Comparative genomics analysis clearly classified our genome collection into four distinct evolutionary lineages with most isolates grouping into lineages I and II. Interestingly, we found three pairs of isolates with high identity, although no evident epidemiological association was observed.

Conclusion

This study reports for the first time the surveillance of pregnancy-associated listeriosis in Zhejiang province, China, which indicates that the infection rate is low in this region. Our findings provide insight into the evolution and genetic diversity of pregnancy-associated L. monocytogenes from Zhejiang province. Additional investigations involving more human and non-human isolates with a “one health” strategy are needed for prediction of the listeriosis risk associated with a typical prevalent clone in Zhejiang province, such as ST87.

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<![CDATA[A Vaccine Against Group B Streptococcus: Recent Advances]]> https://www.researchpad.co/product?articleinfo=N88ff99ec-00ee-497f-bcc2-4853da710b46

Abstract

Group B streptococcus (GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharide – protein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible.

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<![CDATA[ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer]]> https://www.researchpad.co/product?articleinfo=Ncb66c365-b2c3-4781-a0c7-b342816abb03

Introduction

Breast cancer is a common malignancy in females worldwide. In this study, we investigated the role of activating transcription factor 3 (ATF3) and ADP-ribosylation factor like-4 (ARL4) in human breast cancer, and the associated mechanisms.

Materials and Methods

We measured ATF3 and ATL4C expressions in 15 paired breast cancer tissues using qRT-PCR, Western blotting and IHC. Cell growth, migration and invasion were tested in ATF3 or ARL4C overexpression breast cancer cells. TCGA database analysis was done to identify the correlation between ATF3 and ARL4C. We evaluated the binding of ATF3 to ARL4C promoter sequences and the effect of hypermethylation and demethylation of ATF3. A meta-analysis was done to investigate the relationship between the expression of ATF3 and/or ARL4C and the poor prognoses.

Results

Our results showed that ATF3 and ARL4C were decreased in breast cancer specimens at both mRNA and protein levels. Restoration of ATF3 or ARL4C reduced breast cancer tumorigenesis, evidenced by decreased cell growth, migration and invasion. The expression of ATF3 was positively correlated with ARL4C in breast cancer specimens, and ATF3 was shown to bind to the ARL4C promoter sequences. Furthermore, the expression of ATF3 was negatively regulated by hypermethylation, and demethylation of ATF3 stimulated ATF3 expression, which further promoted ARL4C transcription. Finally, a meta-analysis showed that patients with breast cancer with lower expression levels of ATF3 and/or ARL4C had worse prognoses.

Conclusion

Our results suggest that the ATF3/ARL4C axis may be a prospective biomarker for diagnosis and determination of prognosis, and a potential target for breast cancer treatment.

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<![CDATA[Phosphoproteomics Reveals Key Regulatory Kinases and Modulated Pathways Associated with Ovarian Cancer Tumors]]> https://www.researchpad.co/product?articleinfo=N6e54be71-efea-4456-a8e5-42ce660ba5f7

Background

Ovarian cancer (OC) is the seventh most common cancer worldwide for women. However, there are no sufficient diagnostic methods and few treatment options available due to poor understanding of its pathogenic mechanisms.

Methods

To comprehensively analyze the phosphoproteomic characterization for OC, we took advantage of a quantitative global phosphoproteomics method, titanium(IV) immobilized metal affinity chromatography (Ti4+-IMAC) coupled to nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) on ovarian tissue samples obtained from five OC patients and five matched controls.

Results

A total of 722 phosphorylated sites corresponding to 534 proteins were significantly different (fold change ≥ 2, p < 0.01) between OC patients and the controls. Among them, 83 transcription factors mainly consisted of transcription cofactors, zf-C2H2, and chromatin remodeling factors and 29 kinases were included. Further functional analysis suggested significantly biological processes were highly enriched and involved in the pathogenesis of OC, especially fructose and mannose metabolism. Moreover, the regulatory roles of modulated pathways, including MAPK, ErbB, and GnRH signaling pathways were also identified as critical processes involved in OC. The results here highlighted key phosphorylated proteins, particularly kinases, and the corresponding cancer-related metabolic and signal pathways that played important roles in the development of OC. Additionally, the expression levels of two kinases, phosphorylated CDK (T14) and phosphorylated PRKCQ (S695), were validated by Western blot analysis in the other group of ovarian tissue samples.

Conclusion

Altogether, our data not only provided novel insights into the potential biomarkers and therapy options for OC but also extended our knowledge on its pathophysiological mechanism.

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<![CDATA[Impact of Hyaluronic Acid-Containing Artificial Tear Products on Reepithelialization in an In Vivo Corneal Wound Model]]> https://www.researchpad.co/product?articleinfo=5b59a5ed463d7e789700d0e2

Abstract

Purpose: To evaluate the effect of 6 commercially available hyaluronic acid (HA)-containing topical artificial tear products on corneal reepithelialization following injury, in an in vivo mouse model.

Methods: Ninety-six C57Bl/6 mice (16 per treatment group; male to female ratio, 1:1 per group) were anesthetized. Epithelial debridement was performed on 1 cornea per animal, and the debrided eye was imaged. A 30 μL masked test solution containing 1 of 6 artificial tear products was instilled, immediately on debridement, and subsequently, every 2 h, for a total of 4 administrations. At 24 h post debridement, corneas were stained with fluorescein and imaged to calculate corneal healing rate (number of fluorescein-negative corneas).

Results: All 6 artificial tear products used in this study permitted the initial process of corneal wound healing. However, the corneal reepithelialization rate after 24 h was higher with Hydroxypropyl guar (HPG)/HA (53.33%) compared with other HA-containing artificial tear products [HA1 (12.5%), HA2 (26.67%), HA3 (31.25%), HA4 (6.25%), and HA5 (43.75%)]. The average area and percentage area of reepithelialization after 24 h were also higher with HPG/HA compared with other treatment groups.

Conclusions: Percentage of eyes with complete corneal reepithelialization 24 h post debridement was highest with HPG/HA compared with other HA-containing artificial tear products tested. The results of this study provide additional evidence on the potential benefits of HPG/HA in the management of dry eye and its role in the rapid restoration of a healthy ocular epithelium. However, further studies are required to confirm the effects on human corneal wounds.

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<![CDATA[A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population]]> https://www.researchpad.co/product?articleinfo=5b59793f463d7e5ce270da2e

Purpose

Medicine acceptability, which is of the utmost importance for vulnerable patients’ adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population.

Methods

An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model’s reliability.

Results

A three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients’ ability to swallow, we have highlighted the tool’s efficacy in demonstrating the impact of user features on medicine acceptability.

Conclusions

This multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions.

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<![CDATA[Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin]]> https://www.researchpad.co/product?articleinfo=5b589f4b463d7e4d042bbfdb

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

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<![CDATA[Role of presurgical targeted molecular therapy in renal cell carcinoma with an inferior vena cava tumor thrombus]]> https://www.researchpad.co/product?articleinfo=5b58a06e463d7e4d042bbfe0

Purpose

The clinical benefit of targeted molecular therapy (TMT) in renal cell carcinoma (RCC) with an inferior vena cava (IVC) tumor thrombus remains controversial. The aim of this study was to investigate the effects of presurgical TMT on the heights and levels of IVC thrombi, and to assess its impact on surgical strategy.

Patients and methods

We retrospectively reviewed data from 18 patients with RCC involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy. The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging. Clinicopathological factors were also evaluated to assess their association with TMT efficacy.

Results

The tumor thrombus levels before TMT were stage I in 1 patient (5.6%), II in 12 patients (66.7%), III in 4 patients (22.2%), and IV in 1 patient (5.6%). After a median of two treatment cycles (range: 1–3), the thrombus height decreased measurably in 11 patients (61.1%) with an average shrinkage of 17.7%. The thrombus height remained stable in five patients (27.8%) and was enlarged in two (11.1%). Downstaging of the thrombus level occurred in four patients (22.2%); the surgical strategy was modified in three patients (16.7%) to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy. Furthermore, a higher neutrophil count tended to be associated with a worse clinical TMT-associated outcome (P=0.056).

Conclusion

Our data suggest a limited influence of presurgical TMT with a positive benefit in RCC patients with level III and IV thrombus. Thrombus-level regression may potentially alter the surgical strategy, especially robotic surgery. However, our findings require validation with additional prospective investigations.

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<![CDATA[Negative Mood-Induced Alcohol-Seeking Is Greater in Young Adults Who Report Depression Symptoms, Drinking to Cope, and Subjective Reactivity]]> https://www.researchpad.co/product?articleinfo=5b5890c8463d7e4bbcb756e3

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18–25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence.

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<![CDATA[Open adrenalectomy versus laparoscopic adrenalectomy for adrenocortical carcinoma: a retrospective comparative study on short-term oncologic prognosis]]> https://www.researchpad.co/product?articleinfo=5bfb917cd5eed0c484af9666

Purpose

Open adrenalectomy (OA) remains the gold standard of surgical therapy for adrenocortical carcinoma, while the role of laparoscopic approach is controversial. We aim to explore the influence of surgical approaches on the oncologic prognosis of adrenocortical carcinoma by comparing the short-term outcomes of patients undergoing OA with those undergoing laparoscopic adrenalectomy (LA).

Patients and methods

We retrospectively analyzed the baseline characteristics, perioperative data and short-term prognosis of 42 patients diagnosed with stage I–III adrenocortical carcinoma, receiving OA (n=22) and LA (n=20) as primary therapy. The primary end point was the first recurrence.

Results

OA group had larger mean maximum diameter of tumor (10.1±3.6 versus 6.3±2.2 cm) and lesser benefits in operative time, bleeding loss and postoperative hospital stay than laparoscopic group. Mean disease-free survival (DFS) of OA was 44.8±35.1 months, which was longer than 17.5±10.4 months of LA, and the rate of 2-year DFS after primary surgery in the open group was higher than in the laparoscopic group (61.1% versus 21.4%, respectively). Rates of 1- and 3-year DFS showed no significant difference. All patients undergoing LA (11/11) showed local recurrent lesions at the first time of recurrence, while 5 of 13 patients undergoing OA did not show local recurrence (P=0.03).

Conclusion

OA for adrenocortical carcinoma is superior to laparoscopic approach in terms of DFS and rate of 2-year DFS, in spite of the larger maximum diameter of tumors and lesser benefit during perioperation. After LA, patients are more likely to show local recurrent lesions at the first time of relapse.

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<![CDATA[Upregulated long non-coding RNAs demonstrate promising efficacy for breast cancer detection: a meta-analysis]]> https://www.researchpad.co/product?articleinfo=5b4c57b4463d7e09f8ec4a78

Purpose

Focusing on the latest literature, dysregulated long non-coding RNAs (lncRNAs) have been extensively explored in breast cancer (BC) research. The purpose of this meta-analysis is to synthesize the evidence on the diagnostic performance of abnormally expressed lncRNAs for BC.

Materials and methods

Relevant studies were searched in multiple electronic databases. The Quality Assessment of Diagnosis Accuracy Studies II criteria were applied to assess the quality of included studies. The bivariate meta-analysis model was applied to synthesize the diagnostic parameters using Stata 12.0 software. Publication bias was judged in terms of the Deek’s funnel plot asymmetry test.

Results

We included 10 eligible studies, which comprised 835 BC patients and 725 paired controls for this meta-analysis. The pooled sensitivity, specificity, diagnostic odds ratio, likelihood ratio positive, likelihood ratio negative, and area under the curve (AUC) of upregulated lncRNA expression signature in confirming BC were 0.79 (95% CI: 0.70–0.85), 0.80 (95% CI: 0.73–0.85), 14.61 (95% CI: 10.91–19.55), 3.90 (95% CI: 3.03–5.02), 0.27 (95% CI: 0.20–0.36), and 0.86, respectively. Stratified analyses yielded a sensitivity of 0.83 (95% CI: 0.80–0.86) for serum-based analysis, which was higher than plasma-based analysis, whereas plasma-based analysis revealed a greater specificity of 0.88 (95% CI: 0.85–0.91). Moreover, lncRNA-homeotic genes (HOX) transcript antisense RNA showed a pooled specificity of 0.89 (95% CI: 0.84–0.93) and AUC of 0.86, which were superior to performances by lncRNA-metastasis-associated lung adenocarcinoma transcript-1 and -H19 in diagnosing BC. Notably, the analysis based on cancer subtypes demonstrated that lncRNA expression signature could distinguish triple-negative BC (lacks estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression) from non-triple-negative BC, with an AUC of 0.85.

Conclusion

Upregulated lncRNAs reveal an immense potential as novel non-invasive biomarker(s) that could complement BC diagnosis.

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<![CDATA[Correction to: Afatinib in advanced NSCLC: a profile of its use]]> https://www.researchpad.co/product?articleinfo=5b4c32ae463d7e05c0737e96 ]]> <![CDATA[Vascular endothelial growth factor suppresses dendritic cells function of human prostate cancer]]> https://www.researchpad.co/product?articleinfo=5bfacad6d5eed0c4847cbe8d

Purpose

Prostate cancer (PCa) patients often have dendritic cell (DC) function defects, but the mechanism is not clear. The aim of this study was to detect the effect of vascular endothelial growth factor (VEGF) in mature DCs.

Patients and methods

In this study, we chose 30 PCa patients, 10 prostatic intraepithelial neoplasia (PIN) patients and 30 benign prostatic hyperplasia (BPH) patients, and compared the composition of peripheral blood T cells, the composition and function of local dendritic cells in prostate tissue, and the density of local VEGF.

Results

The results showed that the numbers of total DCs, mature and functional DCs, and CD4+ T cells were inhibited in PCa, and the inhibitory effect was enhanced with increased malignancy. In addition, the infiltration density of VEGF-positive cells was increased in PCa, and this increase was associated with an increased malignant degree of PCa. The inhibition of tumor immunity in patients with PCa is achieved by inhibiting the function of dendritic cells.

Conclusion

VEGF plays an important role in the inhibition of the maturation and function of dendritic cells, and this inhibition is gradually increased with an increasing malignant degree of PCa.

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<![CDATA[Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate]]> https://www.researchpad.co/product?articleinfo=5b4bfc96463d7e022037ff80

Background

SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404.

Objective

The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Methods

Participants aged 6–17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant.

Results

All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, − 6.6%; SWM total between-search errors, − 22.8%; SST stop signal reaction time, –18.9%), and at the last on-treatment assessment (DMS median reaction time, − 6.5%; SWM total between-search errors, − 32.6%; SST stop signal reaction time, − 25.7%).

Conclusions

Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required.

ClinicalTrials.gov identifier

NCT01328756.

Electronic supplementary material

The online version of this article (10.1007/s40263-017-0487-z) contains supplementary material, which is available to authorized users.

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