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SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related tumor markers and serum tumor markers in gastric adenocarcinoma patients.

Oncol Rep. 2017 Jun;37(6):3433-3440

Authors: Bai L, Guo CH, Zhao Y, Gao JG, Li M, Shen C, Guo YM, Duan XY

Abstract
The expression of P53 was previously found by us significantly correlated with maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC) patients. Hence, the aim of this study was to clarify the relationship between SUVmax and the status of the chemotherapy-related tumor marker expression or serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were enrolled in this study. Immunohistochemistry was performed to detect changes of Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients. Then, the relationships between these parameters above were assessed by Spearman correlation analysis. Also, receiver-operating characteristic (ROC) curve was performed to determine the best cut-off value of SUVmax for suggesting chemotherapy resistant tumor markers. Besides, we identified a linear correlation to estimate the equations between SUVmax and the serum tumor markers. Our results showed that higher SUVmax was detected in patients with positive expression of Her-2 and P53, compared with negative groups. The Spearman correlation analysis showed that SUVmax was associated with Her-2 or P53 with the moderate relevant Pearson correlation coefficient. ROC curve analysis showed that the sensitivity and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship between SUVmax and serum tumor markers were analyzed by linear correlation analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to establish an equation for SUVmax by the linear regression models. These results suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her-2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients. However, before PET/CT scanning, serum tumor markers could be used to calculate the SUVmax approximately.

PMID: 28498457 [PubMed - indexed for MEDLINE]

Related Articles

Cariogenic Potential of the commonly Prescribed Pediatric Liquid Medicaments in Kingdom of Saudi Arabia: An in vitro Study.

J Contemp Dent Pract. 2017 Apr 01;18(4):307-311

Authors: Gupta M, Panda S

Abstract
AIM: The aim of this study was to assess the cariogenic potential of the commonly prescribed pediatric liquid medicaments (PLMs) for dental disease in Jazan region, Kingdom of Saudi Arabia.
MATERIALS AND METHODS: Seven most commonly prescribed PLMs were selected by prior questioning the pediatric dentists as well as general dentists in Jazan region. The endogenous pH and sucrose concentrations of the liquid medicaments were assessed. The endogenous pH was assessed by Hanna pH meter instrument. The sucrose concentration was assessed by anthrone reagent method.
RESULTS: All the PLM were acidic. The pH of the PLM ranged from 4.22 to 6.10. All the PLM contained sucrose and its concentration ranged from 5.38 to 11.41 gm% in the samples.
CONCLUSION: In this study, all the PLM were acidic and contained sucrose. Hence, they have cariogenic potential.
CLINICAL SIGNIFICANCE: Parents and dentists are unaware of the hidden sugars and cariogenicity of these medications. Strict oral hygiene instructions are mandatory for the children taking these medications. The use of PLM should also be minimized and parents should seek early dental treatment to restore child's oral health.

PMID: 28349909 [PubMed - indexed for MEDLINE]

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Nor-Binaltorphimine Blocks the Adverse Effects of Morphine after Spinal Cord Injury.

J Neurotrauma. 2017 Mar 15;34(6):1164-1174

Authors: Aceves M, Bancroft EA, Aceves AR, Hook MA

Abstract
Opioids are frequently used for the treatment of pain following spinal cord injury (SCI). Unfortunately, we have shown that morphine administered in the acute phase of SCI results in significant, adverse secondary consequences including compromised locomotor and sensory recovery. Similarly, we showed that selective activation of the κ-opioid receptor (KOR), even at a dose 32-fold lower than morphine, is sufficient to attenuate recovery of locomotor function. In the current study, we tested whether activation of the KOR is necessary to produce morphine's adverse effects using nor-Binaltorphimine (norBNI), a selective KOR antagonist. Rats received a moderate spinal contusion (T12) and 24 h later, baseline locomotor function and nociceptive reactivity were assessed. Rats were then administered norBNI (0, 0.02, 0.08, or 0.32 μmol) followed by morphine (0 or 0.32 μmol). Nociception was reassessed 30 min after drug treatment, and recovery was evaluated for 21 days. The effects of norBNI on morphine-induced attenuation of recovery were dose dependent. At higher doses, norBNI blocked the adverse effects of morphine on locomotor recovery, but analgesia was also significantly decreased. Conversely, at low doses, analgesia was maintained, but the adverse effects on recovery persisted. A moderate dose of norBNI, however, adequately protected against morphine's adverse effects without eliminating its analgesic efficacy. This suggests that activation of the KOR system plays a significant role in the morphine-induced attenuation of recovery. Our research suggests that morphine, and other opioid analgesics, may be contraindicated for the SCI population. Blocking KOR activity may be a viable strategy for improving the safety of clinical opioid use.

PMID: 27736318 [PubMed - indexed for MEDLINE]

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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Funding Opportunity PAR-18-694 from the NIH Guide for Grants and Contracts. This FOA encourages applications that develop, strengthen, and evaluate transdisciplinary approaches, methods, and investigative teams in basic behavioral, social, and/or biobehavioral research to generate fundamental knowledge of the reciprocal linkages between sleep and stress. Stress can result in sleep disruption due to both psychological as well as physiological changes. Sleep disruption can result in physiological changes; however, individuals may not recognize or identify impairment due to sleep disruption. This initiative supports the development of research teams to understand how basic individual, social, biological, and environmental factors interact in a dynamic relationship between sleep patterns and psychosocial stress to influence health, wellness, disease, and/or treatment adherence.

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Funding Opportunity PAR-18-693 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) solicits applications from qualified academic institutions in Puerto Rico whose non-human primate research facilities were damaged by Hurricane Maria. Institutions may request funds to recover, restore, and modernize the physical infrastructure of non-human primate facilities. The rebuilt structures shall comply with the relevant engineering standards applicable to the requirements of the environment, the geographical location, animal welfare and care, and research-related demands. Any request must be justified by the needs of the HIV/AIDS-related NIH-funded research projects that use non-human primates raised, maintained, and housed in these facilities.

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"Rare Diseases"[Mesh] OR "orphan disease"

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22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

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("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

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Managing Bardet-Biedl Syndrome-Now and in the Future.

Front Pediatr. 2018;6:23

Authors: Forsythe E, Kenny J, Bacchelli C, Beales PL

Abstract
Bardet-Biedl syndrome is a rare autosomal recessive multisystem disorder caused by defects in genes encoding for proteins that localize to the primary cilium/basal body complex. Twenty-one disease-causing genes have been identified to date. It is one of the most well-studied conditions in the family of diseases caused by defective cilia collectively known as ciliopathies. In this review, we provide an update on diagnostic developments, clinical features, and progress in the management of Bardet-Biedl syndrome. Advances in diagnostic technologies including exome and whole genome sequencing are expanding the spectrum of patients who are diagnosed with Bardet-Biedl syndrome and increasing the number of cases with diagnostic uncertainty. As a result of the diagnostic developments, a small number of patients with only one or two clinical features of Bardet-Biedl syndrome are being diagnosed. Our understanding of the syndrome-associated renal disease has evolved and is reviewed here. Novel interventions are developing at a rapid pace and are explored in this review including genetic therapeutics such as gene therapy, exon skipping therapy, nonsense suppression therapy, and gene editing. Other non-genetic therapies such as gene repurposing, targeted therapies, and non-pharmacological interventions are also discussed.

PMID: 29487844 [PubMed]

Repurposing the anthelmintic drug niclosamide to combat Helicobacter pylori.

Sci Rep. 2018 Feb 27;8(1):3701

Authors: Tharmalingam N, Port J, Castillo D, Mylonakis E

Abstract
There is an urgent need to discover novel antimicrobial therapies. Drug repurposing can reduce the time and cost risk associated with drug development. We report the inhibitory effects of anthelmintic drugs (niclosamide, oxyclozanide, closantel, rafoxanide) against Helicobacter pylori strain 60190 and pursued further characterization of niclosamide against H. pylori. The MIC of niclosamide against H. pylori was 0.25 μg/mL. Niclosamide was stable in acidic pH and demonstrated partial synergy with metronidazole and proton pump inhibitors, such as omeprazole and pantoprazole. Niclosamide administration at 1 × MIC concentration, eliminated 3-log10 CFU of H. pylori adhesion/invasion to AGS cells. Interestingly, no resistance developed even after exposure of H. pylori bacteria to niclosamide for 30 days. The cytotoxic assay demonstrated that niclosamide is not hemolytic and has an IC50 of 4 μg/mL in hepatic and gastric cell lines. Niclosamide administration decreased transmembrane pH as determined by DiSC3(5) assay indicating that the mechanism of action of the anti-H. pylori activity of niclosamide was the disruption of H. pylori proton motive force. Niclosamide was effective in the Galleria mellonella-H. pylori infection model (p = 0.0001) and it can be develop further to combat H. pylori infection. However, results need to be confirmed with other H. pylori and clinical strains.

PMID: 29487357 [PubMed - in process]

S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.

Cell Rep. 2018 Feb 27;22(9):2431-2441

Authors: Cohen TS, Boland ML, Boland BB, Takahashi V, Tovchigrechko A, Lee Y, Wilde AD, Mazaitis MJ, Jones-Nelson O, Tkaczyk C, Raja R, Stover CK, Sellman BR

Abstract
Clinical severity of Staphylococcus aureus respiratory infection correlates with alpha toxin (AT) expression. AT activates the NLRP3 inflammasome; deletion of Nlrp3, or AT neutralization, protects mice from lethal S. aureus pneumonia. We tested the hypothesis that this protection is not due to a reduction in inflammasome-dependent cytokines (IL-1β/IL-18) but increased bactericidal function of macrophages. In vivo, neutralization of AT or NLRP3 improved bacterial clearance and survival, while blocking IL-1β/IL-18 did not. Primary human monocytes were used in vitro to determine the mechanism through which NLRP3 alters bacterial killing. In cells treated with small interfering RNA (siRNA) targeting NLRP3 or infected with AT-null S. aureus, mitochondria co-localize with bacterial-containing phagosomes. Mitochondrial engagement activates caspase-1, a process dependent on complex II of the electron transport chain, near the phagosome, promoting its acidification. These data demonstrate a mechanism utilized by S. aureus to sequester itself from antimicrobial processes within the cell.

PMID: 29490278 [PubMed - in process]

Allelic variant in the glucagon-like peptide 1 receptor gene associated with greater effect of liraglutide and exenatide on gastric emptying: A pilot pharmacogenetics study.

Neurogastroenterol Motil. 2018 Feb 28;:

Authors: Chedid V, Vijayvargiya P, Carlson P, Van Malderen K, Acosta A, Zinsmeister A, Camilleri M

Abstract
BACKGROUND: Weight loss in response to the long-acting GLP-1 receptor (GLP1R) analog, liraglutide, is correlated with delay in gastric-emptying (GE). The aim of this pilot study was to assess whether specific genetic variants in GLP1R or TCF7L2 are associated with delayed GE and weight loss in obese patients treated with liraglutide or the short-acting GLP-1 agonist, exenatide.
METHODS: We evaluated in obese individuals the associations of genetic variations of GLP1R (rs6923761) and TCF7L2 (rs7903146) on GE T1/2 and weight from two trials that evaluated separately exenatide, 5 μg BID for 30 days, or liraglutide, 3 mg daily for 5 weeks. Data were analyzed using the dominant genetic model and intention-to-treat analysis.
KEY RESULTS: There was a significant correlation between changes in weight and GE T1/2 (rs  = -.382, P = .004). GLP1R rs6923761 minor allele A (AA_AG) carriers who received either exenatide or liraglutide had greater delay in GE T1/2 relative to baseline (117.9 ± 27.5 [SEM] minutes and 128.9 ± 38.32 minutes) compared to GG genotype (95.8 ± 30.4 minutes and 61.4 ± 21.4 minutes, respectively; P = .11). There was a non-significant difference in weight loss based on GLP1R rs6923761 genotype after 5 weeks of treatment. There were no significant correlations with TCF7L2 (rs7903146) genotype.
CONCLUSIONS & INFERENCES: The minor A allele of GLP1R (rs6923761) is associated with greater delay in GE T1/2 in response to liraglutide and exenatide. These studies provide data to plan pharmacogenetics testing of the hypothesis that GLP1R (rs6923761) influences weight loss in response to GLP1R agonists.

PMID: 29488276 [PubMed - as supplied by publisher]

Managing Bardet-Biedl Syndrome-Now and in the Future.

Front Pediatr. 2018;6:23

Authors: Forsythe E, Kenny J, Bacchelli C, Beales PL

Abstract
Bardet-Biedl syndrome is a rare autosomal recessive multisystem disorder caused by defects in genes encoding for proteins that localize to the primary cilium/basal body complex. Twenty-one disease-causing genes have been identified to date. It is one of the most well-studied conditions in the family of diseases caused by defective cilia collectively known as ciliopathies. In this review, we provide an update on diagnostic developments, clinical features, and progress in the management of Bardet-Biedl syndrome. Advances in diagnostic technologies including exome and whole genome sequencing are expanding the spectrum of patients who are diagnosed with Bardet-Biedl syndrome and increasing the number of cases with diagnostic uncertainty. As a result of the diagnostic developments, a small number of patients with only one or two clinical features of Bardet-Biedl syndrome are being diagnosed. Our understanding of the syndrome-associated renal disease has evolved and is reviewed here. Novel interventions are developing at a rapid pace and are explored in this review including genetic therapeutics such as gene therapy, exon skipping therapy, nonsense suppression therapy, and gene editing. Other non-genetic therapies such as gene repurposing, targeted therapies, and non-pharmacological interventions are also discussed.

PMID: 29487844 [PubMed]

DPYD and UGT1A1 genotyping to predict adverse events during first-line FOLFIRI or FOLFOXIRI plus bevacizumab in metastatic colorectal cancer.

Oncotarget. 2018 Jan 30;9(8):7859-7866

Authors: Cremolini C, Del Re M, Antoniotti C, Lonardi S, Bergamo F, Loupakis F, Borelli B, Marmorino F, Citi V, Cortesi E, Moretto R, Ronzoni M, Tomasello G, Zaniboni A, Racca P, Buonadonna A, Allegrini G, Ricci V, Di Donato S, Zagonel V, Boni L, Falcone A, Danesi R

Abstract
Our study addresses the issue of the clinical reliability of three candidate DPYD and one UGT single nucleotide polymorphisms in predicting 5-fluorouracil- and irinotecan-related adverse events. To this purpose, we took advantage of a large cohort of metastatic colorectal cancer patients treated with first-line 5-fluorouracil- and irinotecan-based chemotherapy regimens (i.e., FOLFIRI or FOLFOXIRI) plus bevacizumab in the randomized clinical trial TRIBE by GONO (clinicaltrials.gov: NCT00719797), in which adverse events were carefully and prospectively collected at each treatment cycle. Here we show that patients bearing DPYD c.1905+1G/A and c.2846A/T genotypes, together with UGT1A1*28 variant carriers, have an increased risk of experiencing clinically relevant toxicities, including hematological AEs and stomatitis. No carrier of the DPYD c.1679T>G minor allele was identified. Present results support the preemptive screening of mentioned DPYD and UGT1A1 variants to identify patients at risk of clinically relevant 5-fluoruracil- and irinotecan-related AEs, in order to improve treatments' safety through a "genotype-guided" approach.

PMID: 29487697 [PubMed]

Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine.

Front Genet. 2018;9:40

Authors: Howard JT, Ashwell MS, Baynes RE, Brooks JD, Yeatts JL, Maltecca C

Abstract
In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs (n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study.

PMID: 29487615 [PubMed]

[Dihydropyrimidine dehydrogenase (DPD) deficiency screening and securing of fluoropyrimidine-based chemotherapies: Update and recommendations of the French GPCO-Unicancer and RNPGx networks].

Bull Cancer. 2018 Feb 24;:

Authors: Loriot MA, Ciccolini J, Thomas F, Barin-Le-Guellec C, Royer B, Milano G, Picard N, Becquemont L, Verstuyft C, Narjoz C, Schmitt A, Bobin-Dubigeon C, Harle A, Paci A, Poinsignon V, Quaranta S, Evrard A, Hennart B, Broly F, Fonrose X, Lafay-Chebassier C, Wozny AS, Masskouri F, Boyer JC, Etienne-Grimaldi MC

Abstract
Fluoropyrimidines (FU) are still the most prescribed anticancer drugs for the treatment of solid cancers. However, fluoropyrimidines cause severe toxicities in 10 to 40% of patients and toxic deaths in 0.2 to 0.8% of patients, resulting in a real public health problem. The main origin of FU-related toxicities is a deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme of 5-FU catabolism. DPD deficiency may be identified through pharmacogenetics testing including phenotyping (direct or indirect measurement of enzyme activity) or genotyping (detection of inactivating polymorphisms on the DPYD gene). Approximately 3 to 15% of patients exhibit a partial deficiency and 0.1 to 0.5% a complete DPD deficiency. Currently, there is no regulatory obligation for DPD deficiency screening in patients scheduled to receive a fluoropyrimidine-based chemotherapy. Based on the levels of evidence from the literature data and considering current French practices, the Group of Clinical Pharmacology in Oncology (GPCO)-UNICANCER and the French Network of Pharmacogenetics (RNPGx) recommend the following: (1) to screen DPD deficiency before initiating any chemotherapy containing 5-FU or capecitabine; (2) to perform DPD phenotyping by measuring plasma uracil (U) concentrations (possibly associated with dihydrouracil/U ratio), and DPYD genotyping (variants *2A, *13, p.D949V, HapB3); (3) to reduce the initial FU dose (first cycle) according to DPD status, if needed, and further, to consider increasing the dose at subsequent cycles according to treatment tolerance. In France, 17 public laboratories currently undertake routine screening of DPD deficiency.

PMID: 29486921 [PubMed - as supplied by publisher]

Concentration of 8-isoprostanes in the exhaled breath condensate as a marker of oxidative stress in patients with type 1 diabetes.

Adv Respir Med. 2018;86(1):3-6

Authors: Pękala-Wojciechowska A, Poznański M, Szyszow K, Antczak A

Abstract
INTRODUCTION: Type 1 diabetes is an insulin deficiency-based chronic disease. It leads to the development of hyperglycaemia, which plays a key role in the initiation and progression of tissue damage in patients with diabetes. This mostly results from oxidative stress, whose increased severity is observed in this group of patients. Increased levels of 8-isoprostanes are seen in many inflammatory diseases, including asthma, COPD and cystic fibrosis. These diseases demonstrated the usefulness of the exhaled breath condensate (EBC) for extracting material for markers of oxidative stress, including 8-isoprostanes. The purpose of this study was to assess the severity of oxidative stress measured with 8-isoprostane concentrations in the exhaled breath condensate in healthy subjects and in patients with type 1 diabetes with and without vascular complications.
MATERIAL AND METHODS: 33 patients assigned to the control group, type 1 diabetes without complications group and type 1 diabetes group with advanced complications were included in the study. Retinopathy, nephropathy or neuropathy have been reported as a criterion distinguishing between complicated and uncomplicated diabetes. EBC was obtained for each subject. 8-isoprostane concentrations were determined in serum and EBC by ELISA.
RESULTS AND CONCLUSIONS: Mean (± SD) blood levels of 8-isoprostane in patients with type 1 diabetes mellitus without complications and those with type 1 diabetes with advanced complications were significantly higher compared to the control group (178.17 [135.73] vs. 183.34 [200.41] vs. 47.13 [25.20] pg/ml; p < 0.05). The mean (± SD) concentration of 8-isoprostane in EBC was lower in diabetic patients with type 1 diabetes with advanced complications than in patients with type 1 diabetes without advanced complications and in the control group (8.32 [4.60] vs. 19.13 [22.35] vs. 28.17 [35.11] pg/ml; p < 0.05). Measurement of 8-isoprostanes in the EBC in patients with type 1 diabetes does not appear to be a good diagnostic tool for monitoring the activity of oxidative stress in these patients.

PMID: 29490415 [PubMed - in process]