Pharmacogenomic landscape of VIP genetic variants in Jordanian Arabs and comparison with worldwide populations.

Gene. 2020 Jan 30;:144408

Authors: Al-Eitan LN

Abstract
The pharmacogenomics has lately become a focal field of research that investigates the influence of genetic variations of drug-metabolizing enzymes and their receptors and downstream proteins on the interindividual variability in response to medications and adverse drug reactions. Therefore, it is significantly important to study and analyze the variations in drug response between different ethnic groups and populations. The current study aimed to detect the distribution of the genotype and allele frequencies in several very important pharmacogenetic (VIP) gene polymorphisms in the Jordanian population of Arab descent. This study involved 500 unrelated Jordanian individuals of Arab descent. A total of 65 VIP variants located within 33 candidate genes were randomly selected from the PharmGKB database and genotyped using the MassARRAY (iPLEX GOLD) system. The chi-square test was used to evaluate the significant differences of minor allele and genotype frequencies between the Jordanian and other populations including CHE, ASW, CEU, CHB, CDX, GIH, GBR, JPT, LWK, MXL, TSI, YRI, CAR, and ACB. This study revealed six variants were not in Hardy Weinberg equilibrium (HWE) (P-value > 0.05) and ten SNPs showed monomorphic features. Most of the remaining forty-nine variant frequencies were significantly different from the compared ethnic groups (P-value < 0.05). The results of this study may be helpful to develop safer treatment by applying the concept of personalized medicine based on the profile of VIP pharmacogene variants of the Jordanian population of Arab descent.

PMID: 32007583 [PubMed - as supplied by publisher]

Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease?

Sex Med. 2020 Jan 29;:

Authors: Li D, Li X, Peng E, Liao Z, Tang Z

Abstract
INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases (CVDs) share many common risk factors. ED could be a strong independent predictive factor of CVDs. Furthermore, the treatment of ED had been shown to be beneficial for cardiovascular diseases. However, the association between ED and CVDs has been reported scarcely in the literature.
AIM: To investigate urologists' perception, diagnosis, and treatment of CVDs in patients with ED.
METHODS: The study was conducted as a prospective study from November 2018 through February 2019, including urologists aged 18-64 years. All participants completed a survey of the knowledge of ED via an online questionnaire platform in 7 WeChat groups of urologists. WeChat is the most popular multipurpose messaging and social media in China.
MAIN OUTCOME MEASURE: The main outcomes were the answers that urologists chose or filled.
RESULTS: 449 urologists were included. Most of participants (375, 83.5%) agreed that CVDs are associated with ED. Only 231 participants (51.4%) thought ED was an independent disorder. The awareness of the association between ED and CVDs is significantly higher among male urologists than their female counterparts. Although 378 (83.6%) participants believed that the progression of these 2 diseases was consistent, only 181 (44.9%) would do conjoined assessment of both CVDs and ED. In addition, most urologists only considered conventional treatment, such as psychological intervention (341, 75.4%) and phosphodiesterase type 5 inhibitor (PDE5i) therapy (318, 70.4%) for their patients, whereas 339 urologists (88.3%) claimed that they would treat CVDs in patients with both ED and CVDs. 344 (76.6%) urologists showed some concerns over PDE5is.
CONCLUSION: Urologists' assessment of CVDs in patients with ED was disappointing especially among young and female urologists or those working in underserved areas. Besides, the urologists' treatments of ED were not updated, and their attitudes toward the safety and effectiveness of PDE5is for CVDs were not optimistic. Li D, Li X, Peng A, et al. Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease? Sex Med 2020;XX:XXX-XXX.

PMID: 32007471 [PubMed - as supplied by publisher]

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

pharmacogenomics

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

pharmacogenomics

These pubmed results were generated on 2020/02/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) glucuronidation by non-steroidal anti-inflammatory drugs in human liver microsomes and recombinant UDP-glucuronosyltransferase enzymes.

Prostaglandins Leukot Essent Fatty Acids. 2020 Jan 18;153:102055

Authors: Jarrar YB, Kim DH, Lee SJ, Shin JG

Abstract
20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite which is known to increase platelet aggregation and cardiovascular risk. In this study, nine non-steroidal anti-inflammatory drugs (NSAIDs) selected by chemical structures were screened to determine their effects on the glucuronidation of 20-HETE using human liver microsomes (HLMs). Then, the combined effects of the selected NSAID and genetic polymorphisms in UDP-glucuronosyltransferase (UGT) were investigated. Among the tested NSAIDs, diclofenac was the strongest inhibitor of 20-HETE glucuronidation with an IC50 value of 3.5 μM. Celecoxib, naproxen, mefenamic acid, ibuprofen, and indomethacin showed modest inhibition with IC50 values of 77, 91, 190, 208, and 220 μM, respectively, while acetylsalicylic acid, rofecoxib, and meloxicam did not inhibit 20-HETE glucuronidation. Glucuronidation of 20-HETE by UGT2B7 and UGT1A9 recombinant enzymes was significantly inhibited by indomethacin, mefanemic acid, diclofenac, ibuprofen, naproxen, and celecoxib (P < 0.001). In addition, diclofenac exhibited a competitive inhibition mechanism with the Km value of 20-HETE glucuronidation increasing from 23.5 μM to 62 μM in the presence of 3.5 μM diclofenac. Diclofenac further decreased 20-HETE glucuronidation in HLMs carrying UGT2B7*2 alleles compared with the wild-type HLMs. The results from this study would be useful in understanding the alteration of 20-HETE levels in relation to NSAID and UGT genetic polymorphisms.

PMID: 31999978 [PubMed - as supplied by publisher]

Effect of high-dose rifampicin on efavirenz pharmacokinetics: drug-drug interaction randomized trial.

J Antimicrob Chemother. 2020 Jan 30;:

Authors: Atwine D, Baudin E, Gelé T, Muyindike W, Mworozi K, Kyohairwe R, Kananura K, Orikiriza P, Nyehangane D, K T Nanjebe D, Furlan V, Verstuyft C, Barrail-Tran A, Taburet AM, Bonnet M, ANRS 12292 Rifavirenz study group

Abstract
BACKGROUND: High-dose rifampicin is considered to shorten anti-TB treatment duration but its effect on antiretroviral metabolism is unknown.
OBJECTIVES: To assess the effect of doubling the rifampicin dose (to 20 mg/kg/day, R20) on efavirenz pharmacokinetics (PK) in HIV/TB coinfected patients.
METHODS: Open-label Phase 2 drug-drug interaction randomized trial. Pulmonary TB, ART-naive adults were randomized to R20 and either efavirenz 600 mg (EFV600) or 800 mg (EFV800), or rifampicin 10 mg/kg/day (R10) and EFV600 with a 1:1:1 ratio. Patients were first started on TB treatment and 2-4 weeks later started on ART. They were switched to R10 and EFV600 after 8 weeks. Full PK sampling was done 4 weeks (on rifampicin) and 24 weeks (off rifampicin) after ART initiation. Transaminases, plasma HIV-1 RNA and sputum cultures were monitored. The efavirenz geometric mean ratio (GMR) of AUC at 4 and 24 weeks after ART initiation within the same patient was calculated in each arm and its 90% CI was compared with a preset range (0.70-1.43).
RESULTS: Of 98 enrolled patients (32 in the R20EFV600 arm, 33 in the R20EFV800 arm and 33 in the R10EFV600 arm), 87 had full PK sampling. For the R20EFV600, R20EFV800 and R10EFV600 arms, GMRs of efavirenz AUC were 0.87 (90% CI: 0.75-1.00), 1.12 (90% CI: 0.96-1.30) and 0.96 (90% CI: 0.84-1.10). Twelve weeks after ART initiation, 78.6%, 77.4% and 72.4% of patients had HIV-1 RNA below 100 copies/mL and 85.7%, 86.7% and 80.0% had Week 8 culture conversion, respectively. Two patients per arm experienced a severe increase in transaminases.
CONCLUSIONS: Doubling the rifampicin dose had a small effect on efavirenz concentrations and was well tolerated.

PMID: 31999314 [PubMed - as supplied by publisher]

The Current State of MicroRNAs as Restenosis Biomarkers.

Front Genet. 2019;10:1247

Authors: Varela N, Lanas F, Salazar LA, Zambrano T

Abstract
In-stent restenosis corresponds to the diameter reduction of coronary vessels following percutaneous coronary intervention (PCI), an invasive procedure in which a stent is deployed into the coronary arteries, producing profuse neointimal hyperplasia. The reasons for this process to occur still lack a clear answer, which is partly why it remains as a clinically significant problem. As a consequence, there is a vigorous need to identify useful non-invasive biomarkers to differentiate and follow-up subjects at risk of developing restenosis, and due to their extraordinary stability in several bodily fluids, microRNA research has received extensive attention to accomplish this task. This review depicts the current understanding, diagnostic potential and clinical challenges of microRNA molecules as possible blood-based restenosis biomarkers.

PMID: 31998354 [PubMed]

Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells.

J Mol Med (Berl). 2020 Jan 29;:

Authors: Montoro-García S, Alburquerque-González B, Bernabé-García Á, Bernabé-García M, Rodrigues PC, den-Haan H, Luque I, Nicolás FJ, Pérez-Sánchez H, Cayuela ML, Salo T, Conesa-Zamora P

Abstract
Tumor invasion and metastasis involve processes in which actin cytoskeleton rearrangement induced by Fascin1 plays a crucial role. Indeed, Fascin1 has been found overexpressed in tumors with worse prognosis. Migrastatin and its analogues target Fascin1 and inhibit its activity. However, there is need for novel and smaller Fascin1 inhibitors. The aim of this study was to assess the effect of compound G2 in colorectal cancer cell lines and compare it to migrastatin in in vitro and in vivo assays. Molecular modeling, actin-bundling, cell viability, inmunofluorescence, migration, and invasion assays were carried out in order to test anti-migratory and anti-invasive properties of compound G2. In addition, the in vivo effect of compound G2 was evaluated in a zebrafish model of invasion. HCT-116 cells exhibited the highest Fascin1 expression from eight tested colorectal cancer cell lines. Compound G2 showed important inhibitory effects on actin bundling, filopodia formation, migration, and invasion in different cell lines. Moreover, compound G2 treatment resulted in significant reduction of invasion of DLD-1 overexpressing Fascin1 and HCT-116 in zebrafish larvae xenografts; this effect being less evident in Fascin1 known-down HCT-116 cells. This study proves, for the first time, the in vitro and in vivo anti-tumoral activity of compound G2 on colorectal cancer cells and guides to design improved compound G2-based Fascin1 inhibitors. KEY MESSAGES: • Fascin is crucial for tumor invasion and metastasis and is overexpressed in bad prognostic tumors. • Several adverse tumors overexpress Fascin1 and lack targeted therapy. • Anti-fascin G2 is for the first time evaluated in colorectal carcinoma and compared with migrastatin. • Filopodia formation, migration activity, and invasion in vitro and in vivo assays were performed. • G2 blocks actin structures, migration, and invasion of colorectal cancer cells as fascin-dependent.

PMID: 31996952 [PubMed - as supplied by publisher]

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.

Acta Neuropathol Commun. 2020 Jan 29;8(1):5

Authors: Orme T, Hernandez D, Ross OA, Kun-Rodrigues C, Darwent L, Shepherd CE, Parkkinen L, Ansorge O, Clark L, Honig LS, Marder K, Lemstra A, Rogaeva E, St George-Hyslop P, Londos E, Zetterberg H, Morgan K, Troakes C, Al-Sarraj S, Lashley T, Holton J, Compta Y, Van Deerlin V, Trojanowski JQ, Serrano GE, Beach TG, Lesage S, Galasko D, Masliah E, Santana I, Pastor P, Tienari PJ, Myllykangas L, Oinas M, Revesz T, Lees A, Boeve BF, Petersen RC, Ferman TJ, Escott-Price V, Graff-Radford N, Cairns NJ, Morris JC, Pickering-Brown S, Mann D, Halliday G, Stone DJ, Dickson DW, Hardy J, Singleton A, Guerreiro R, Bras J

Abstract
Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease.

PMID: 31996268 [PubMed - in process]

Regulatory SNP rs5743417 impairs constitutive expression of human β-defensin 1 and has high frequency in Africans and Afro-Americans.

Int J Immunogenet. 2020 Jan 29;:

Authors: Cruz Díaz LA, Gutiérrez Ortega A, Chávez Álvarez RDC, Velarde Félix JS, Prado Montes de Oca E

Abstract
The prediction of regulatory single nucleotide polymorphisms (rSNPs) in proximal promoters of disease-related genes could be a useful tool for personalized medicine in both patient stratification and customized therapy. Using our previously reported method of rSNPs prediction (currently a software called SNPClinic v.1.0) as well as with PredictSNP tool, we performed in silico prediction of regulatory SNPs in the antimicrobial peptide human β-defensin 1 gene in three human cell lines from 1,000 Genomes Project (1kGP), namely A549 (epithelial cell line), HL-60 (neutrophils) and TH 1 (lymphocytes). These predictions were run in a proximal pseudo-promoter comprising all common alleles on each polymorphic site according to the 1,000 Genomes Project data (1kGP: ALL). Plasmid vectors containing either the major or the minor allele of a putative rSNP rs5743417 (categorized as regulatory by SNPClinic and confirmed by PredictSNP) and a non-rSNP negative control were transfected to lung A549 human epithelial cell line. We assessed functionality of rSNPs by qPCR using the Pfaffl method. In A549 cells, minor allele of the SNP rs5743417 G→A showed a significant reduction in gene expression, diminishing DEFB1 transcription by 33% when compared with the G major allele (p-value = .03). SNP rs5743417 minor allele has high frequency in Gambians (8%, 1kGP population: GWD) and Afro-Americans (3.3%, 1kGP population: ASW). This SNP alters three transcription factors binding sites (TFBSs) comprising SREBP2 (sterols and haematopoietic pathways), CREB1 (cAMP, insulin and TNF pathways) and JUND (apoptosis, senescence and stress pathways) in the proximal promoter of DEFB1. Further in silico analysis reveals that this SNP also overlaps with GS1-24F4.2, a lincRNA gene complementary to the X Kell blood group related 5 (XKR5) mRNA. The potential clinical impact of the altered constitutive expression of DEFB1 caused by rSNP rs5743417 in DEFB1-associated diseases as tuberculosis, COPD, asthma, cystic fibrosis and cancer in African and Afro-American populations deserves further research.

PMID: 31994826 [PubMed - as supplied by publisher]

ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization.

Eur Arch Psychiatry Clin Neurosci. 2020 Jan 28;:

Authors: Scotti-Muzzi E, Chile T, Moreno R, Pastorello BF, da Costa Leite C, Henning A, Otaduy MCG, Vallada H, Soeiro-de-Souza MG

Abstract
Bipolar disorder (BD) is characterized by unstable mood states ranging from mania to depression. Although there is some evidence that mood instability may result from an imbalance between excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, few proton magnetic resonance spectroscopy (1H-MRS) studies have measured these two neurometabolites simultaneously in BD. The enzyme glutamic acid decarboxylase (GAD1) catalyzes the decarboxylation of glutamate (Glu) to GABA, and its single nucleotide polymorphisms (SNPs) might influence Glu/GABA ratio. Thus, we investigated Glu/GABA ratio in the dorsal anterior cingulate cortex (dACC) of euthymic BD type I patients and healthy controls (HC), and assessed the influence of both mood stabilizers and GAD1 SNPs on this ratio. Eighty-eight subjects (50 euthymic BD type I patients and 38 HC) underwent 3T 1H-MRS in the dACC (2 × 2 × 4.5 cm3) using a two-dimensional JPRESS sequence and all subjects were genotyped for 4 SNPs in the GAD1 gene. BD patients had lower dACC Glu/GABA ratio compared to HC, where this was influenced by anticonvulsant and antipsychotic medications, but not lithium. The presence of GAD1 rs1978340 allele A was associated with higher Glu/GABA ratio in BD, while patients without this allele taking mood stabilizers had a lower Glu/GABA ratio. The lowering of dACC Glu/GABA could be one explanation for the mood stabilizing action of anticonvulsants and antipsychotics in BD type I euthymia. Therefore, this putative role of Glu/GABA ratio and the influence of GAD1 genotype interacting with mood stabilization medication should be confirmed by further studies involving larger samples and other mood states.ClincalTrials.gov registration: NCT01237158.

PMID: 31993746 [PubMed - as supplied by publisher]

Emerging role of long non-coding RNAs in cancer precision medicine.

Mol Cell Oncol. 2020;7(1):1684130

Authors: Nath A, Huang RS

Abstract
A vast majority of the human genome encodes long non-coding RNAs (lncRNAs) as compared to protein-coding genes (PCGs). But most efforts to determine biomarkers of anticancer drug response have focused entirely on PCGs. Comprehensive investigation of lncRNAs and drug response demonstrates that lncRNAs are indeed crucial biomarkers of drug response.

PMID: 31993497 [PubMed]

Long-noncoding RNAs (lncRNAs) in drug metabolism and disposition, implications in cancer chemo-resistance.

Acta Pharm Sin B. 2020 Jan;10(1):105-112

Authors: Wang Y, Fang Z, Hong M, Yang D, Xie W

Abstract
Drug metabolism is an orchestrated process in which drugs are metabolized and disposed through a series of specialized enzymes and transporters. Alterations in the expression and/or activity of these enzymes and transporters can affect the bioavailability (pharmacokinetics, or PK) and therapeutic efficacy (pharmacodynamics, or PD) of drugs. Recent studies have suggested that the long non-coding RNAs (lncRNAs) are highly relevant to drug metabolism and drug resistance, including chemo-resistance in cancers, through the regulation of drug metabolism and disposition related genes. This review summarizes the regulation of enzymes, transporters, or regulatory proteins involved in drug metabolism by lncRNAs, with a particular emphasis on drug metabolism and chemo-resistance in cancer patients. The perspective strategies to integrate multi-dimensional pharmacogenomics data for future in-depth analysis of drug metabolism related lncRNAs are also proposed. Understanding the role of lncRNAs in drug metabolism will not only facilitate the identification of novel regulatory mechanisms, but also enable the discovery of lncRNA-based biomarkers and drug targets to personalize and improve the therapeutic outcome of patients, including cancer patients.

PMID: 31993309 [PubMed]

Editorial of Special Issue on Drug Metabolism and Disposition in Diseases.

Acta Pharm Sin B. 2020 Jan;10(1):2

Authors: Xie W

PMID: 31993303 [PubMed]

Identifying chemogenetic interactions from CRISPR screens with drugZ.

Genome Med. 2019 08 22;11(1):52

Authors: Colic M, Wang G, Zimmermann M, Mascall K, McLaughlin M, Bertolet L, Lenoir WF, Moffat J, Angers S, Durocher D, Hart T

Abstract
BACKGROUND: Chemogenetic profiling enables the identification of gene mutations that enhance or suppress the activity of chemical compounds. This knowledge provides insights into drug mechanism of action, genetic vulnerabilities, and resistance mechanisms, all of which may help stratify patient populations and improve drug efficacy. CRISPR-based screening enables sensitive detection of drug-gene interactions directly in human cells, but until recently has primarily been used to screen only for resistance mechanisms.
RESULTS: We present drugZ, an algorithm for identifying both synergistic and suppressor chemogenetic interactions from CRISPR screens. DrugZ identifies synthetic lethal interactions between PARP inhibitors and both known and novel members of the DNA damage repair pathway, confirms KEAP1 loss as a resistance factor for ERK inhibitors in oncogenic KRAS backgrounds, and defines the genetic context for temozolomide activity.
CONCLUSIONS: DrugZ is an open-source Python software for the analysis of genome-scale drug modifier screens. The software accurately identifies genetic perturbations that enhance or suppress drug activity. Interestingly, analysis of new and previously published data reveals tumor suppressor genes are drug-agnostic resistance genes in drug modifier screens. The software is available at github.com/hart-lab/drugz .

PMID: 31439014 [PubMed - indexed for MEDLINE]

White pepper-derived ratiometric carbon dots for highly selective detection and imaging of coenzyme A.

Food Chem. 2020 Jan 09;315:126171

Authors: Long R, Guo Y, Xie L, Shi S, Xu J, Tong C, Lin Q, Li T

Abstract
A new-style white pepper derived dual-emission carbon dots (CDs) with a quantum yield of 10.4% was designed and facile constructed with one-pot solvothermal method. The green emission (520 nm) had an efficient and special "turn-on" fluorescence sensing of coenzyme A (CoA) with the aid of Cu2+, while red emission (668 nm) barely changed and worked as reference. In the concentration range (0-150 µM), relative fluorescence intensity ratios (F520/F668) showed excellent linear correlation with concentrations of CoA, and detection limit was as low as 8.75 nm. Moreover, the strategy has been successfully applied for label-free detection of CoA in real pig liver samples with good recoveries (93.3-108.0%). Notably, the synthesized CDs had durable fluorescence, low cytotoxicity, and good biocompatibility for cellular imaging, which demonstrated wide and promising applicability for biosensing and bioimaging in the future.

PMID: 31991253 [PubMed - as supplied by publisher]

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs: A case report.

World J Gastroenterol. 2020 Jan 21;26(3):366-374

Authors: Nam NH, Taura K, Kanai M, Fukuyama K, Uza N, Maeda H, Yutaka Y, Chen-Yoshikawa TF, Muto M, Uemoto S

Abstract
BACKGROUND: Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct (IPNB), distant metastasis remains unexplained especially in cases of carcinoma in situ. In the present study, we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.
CASE SUMMARY: A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma. Laboratory tests on admission reported a mild elevation of alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin in serum. Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct (CBD) extending to the left hepatic duct. Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern. Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis. Therefore, a diagnosis of IPNB cT1N0M0 was established. Left hepatectomy with bile duct reconstruction was performed. Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement. The patient was monitored carefully by regular examinations. However, at 32 mo after the operation, a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level. Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated. In addition to histopathological results, a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.
CONCLUSION: This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

PMID: 31988595 [PubMed - in process]

Prognostic role of SCAMP family in acute myeloid leukemia.

Pharmacogenomics J. 2020 Jan 28;:

Authors: Qian T, Cheng Z, Quan L, Zeng T, Cui L, Liu Y, Si C, Huang W, Dai Y, Chen J, Liu L, Jiao Y, Deng C, Pang Y, Ye X, Shi J, Fu L

Abstract
Acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem or progenitor cells characterized by abnormal proliferation of primary and immature myeloid cells in bone marrow and peripheral blood. Gene mutation and expression profiles can be used as prognosis predictors for different prognostic subgroups. Secretory carrier-associated membrane proteins (SCAMPs) are a multigenic family with five members and act as cell surface vectors in the post-Golgi recycling pathways in mammals. Nevertheless, the prognostic and clinical influence of SCAMP family has hardly ever been illustrated in AML. In our study, expression patterns of SCAMP family (SCAMP1-5) were analyzed in 155 AML patients which were extracted from the Cancer Genome Atlas database. In chemotherapy, only subgroup, higher SCAMP1 level was significantly associated with longer EFS and OS (all P = 0.002), and SCAMP1 was confirmed to be an independent favorable factor in un-transplanted patients by Multivariate analysis (all P < 0.05). Nevertheless, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment subgroup, none of the SCAMP genes had any effect on the clinical survival. Our study found that high expression level of SCAMP1 is a favorable prognostic factor in AML, but allo-HSCT may neutralize its prognostic effect.

PMID: 31988488 [PubMed - as supplied by publisher]

RASA1 loss in a BRAF-mutated Langerhans cell sarcoma: a mechanism of resistance to BRAF inhibitor.

Ann Oncol. 2019 Jul;30(7):1170-1172

Authors: Jouenne F, Reger de Moura C, Lorillon G, Meignin V, Dumaz N, Lebbe C, Mourah S, Tazi A

PMID: 31987385 [PubMed - in process]

Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue.

Ann Oncol. 2019 Dec;30(12):2015

Authors: Ciavarella S, Vegliante MC, Fabbri M, De Summa S, Melle F, Motta G, De Iuliis V, Opinto G, Enjuanes A, Rega S, Gulino A, Agostinelli C, Scattone A, Tommasi S, Mangia A, Mele F, Simone G, Zito AF, Ingravallo G, Vitolo U, Chiappella A, Tarella C, Gianni AM, Rambaldi A, Zinzani PL, Casadei B, Derenzini E, Loseto G, Pileri A, Tabanelli V, Fiori S, Rivas-Delgado A, López-Guillermo A, Venesio T, Sapino A, Campo E, Tripodo C, Guarini A, Pileri SA

PMID: 31987310 [PubMed - in process]