LIVIVO - Search results -

Search results

Result 1 - 10 of total 27

Search options

Article ; Online: Weight loss and response to chemotherapy in pediatric patients with osteosarcoma.

Peled, Yair / Levin, Dror / Manisterski, Michal / Kollander, Netania / Shukrun, Rachel / Elhasid, Ronit

2024

Abstract: Background: Weight loss and malnutrition are common findings in pediatric oncology patients, but their prognostic significance is controversial. We sought to evaluate the correlation between weight loss and response to neo-adjuvant chemotherapy in ... ...

Abstract	Background: Weight loss and malnutrition are common findings in pediatric oncology patients, but their prognostic significance is controversial. We sought to evaluate the correlation between weight loss and response to neo-adjuvant chemotherapy in pediatric patients with osteosarcoma. Procedure: All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between January 2011 and October 2022 were retrospectively reviewed. Results: Sixty-three patients were suitable for study inclusion. Data on changes in their body weight between the initiation of neo-adjuvant chemotherapy and local therapy (tumor resection) were extracted. Response to chemotherapy was assessed by the percentage of tumor necrosis at the time of surgery. There was a significant direct correlation between a weight loss of 3% and above and good response to chemotherapy as demonstrated by tumor necrosis above 90%. Conclusions: Low caloric intake may imitate a caloric restriction diet that was proven to improve response to therapy in some oncological diseases. Further prospective trials are needed for the establishment of recommended caloric intake during chemotherapy in pediatric patients with osteosarcoma.
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	639358-5
ISSN	1476-5640 ; 0954-3007
ISSN (online)	1476-5640
ISSN	0954-3007
DOI	10.1038/s41430-024-01404-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1045: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Selinexor, a selective inhibitor of nuclear export, inhibits human neutrophil extracellular trap formation

Baron, Szilvia / Rashal, Tami / Vaisman, Dmitry / Elhasid, Ronit / Shukrun, Rachel

Frontiers in pharmacology

2022 Volume 13, Page(s) 1030991

Abstract: Neutrophils are central players in the innate immune system. To protect against invading pathogens, neutrophils can externalize chromatin to create neutrophil extracellular traps (NETs). While NETs are critical to host defense, they also have deleterious ...

Abstract	Neutrophils are central players in the innate immune system. To protect against invading pathogens, neutrophils can externalize chromatin to create neutrophil extracellular traps (NETs). While NETs are critical to host defense, they also have deleterious effects, and dysregulation of NETs formation has been implicated in autoimmune diseases, atherosclerosis and thrombotic conditions, cancer progression and dissemination, and acute respiratory distress syndrome. Here, we report that selinexor, a first-in-class selective inhibitor of nuclear export approved for the treatment of multiple myeloma and diffuse large B-cell lymphoma, markedly suppressed the release of NETs
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.1030991
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Prevalence and management of methotrexate-induced neurotoxicity in pediatric patients with osteosarcoma: a single-center experience.

Peled, Yair / Levin, Dror / Shiran, Shelly / Manisterski, Michal / Shukrun, Rachel / Elhasid, Ronit

International journal of clinical oncology

2022 Volume 27, Issue 8, Page(s) 1372–1378

Abstract: Aims: To determine the incidence, clinical presentation, and outcome of methotrexate (MTX) associated neurotoxicity in pediatric patients treated for osteosarcoma, with the aim of identifying possible risk factors and suggesting recommended treatment ... ...

Abstract	Aims: To determine the incidence, clinical presentation, and outcome of methotrexate (MTX) associated neurotoxicity in pediatric patients treated for osteosarcoma, with the aim of identifying possible risk factors and suggesting recommended treatment for these sequelae. Materials and methods: All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between November 2011 and August 2021 were retrospectively reviewed. All patients were treated according to the EURAMOS AOST0331 protocol, using cisplatin, doxorubicin, and high-dose MTX at a dose of 12 g/m Results: Seventy-eight patients with osteosarcoma were identified (age range 5 to 23 years, 42 males). Seven patients (9%) sustained neurotoxicity following treatment with high-dose MTX. Manifestations of neurotoxicity included among others, generalized seizures, confusion, encephalopathy, dysarthria, and choreiform movements. All but one episode occurred following two sequential cycles of high-dose MTX. All 7 had subacute toxicity, 5-10 days following MTX administration, and 1 had both acute and subacute toxicity. Brain MRI was performed for all patients and demonstrated typical MRI changes attributed to MTX neurotoxicity in 4 of them. Two patients received aminophylline; one patient received dextromethorphan. Patients with normal MRI imaging resumed MTX therapy without any sequels. No risk factors were found for high-dose MTX-related toxicity occurrence. Conclusions: The time of risk of neurotoxicity due to high-dose MTX treatment for osteosarcoma is days 5-10 following two sequential treatment cycles. These findings together with treatment options for these adverse effects should be detailed in the therapeutic protocol of MTX use among pediatric patients with osteosarcoma.
MeSH term(s)	Adolescent ; Adult ; Bone Neoplasms/complications ; Bone Neoplasms/drug therapy ; Child ; Child, Preschool ; Humans ; Male ; Methotrexate/adverse effects ; Neurotoxicity Syndromes/etiology ; Osteosarcoma/drug therapy ; Prevalence ; Retrospective Studies ; Young Adult
Chemical Substances	Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-05-31
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1400227-9
ISSN	1437-7772 ; 1341-9625
ISSN (online)	1437-7772
ISSN	1341-9625
DOI	10.1007/s10147-022-02184-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4828: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Neutrophils extracellular traps formation may serve as a biomarker for disease activity in oligoarticular juvenile idiopathic arthritis: a pilot study.

Heshin-Bekenstein, Merav / Baron, Szilvia / Schulert, Grant / Shusterman, Anna / Fidel, Victoria / Ben-Shahar, Yoav / Shukrun, Rachel / Binenbaum, Yoav / Elhasid, Ronit

Arthritis research & therapy

2023 Volume 25, Issue 1, Page(s) 135

Abstract: Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, causing significant morbidity. Despite the dramatic improvement in treatment, many patients do not achieve complete remission, and biomarkers for ... ...

Abstract	Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, causing significant morbidity. Despite the dramatic improvement in treatment, many patients do not achieve complete remission, and biomarkers for subclinical disease, flares, and response to treatment are lacking. Neutrophils and neutrophil extracellular traps (NETs) play key roles in the pathogenesis of autoimmune and inflammatory conditions. In this study, we characterized neutrophil enzyme activity and NETs formation in oligoarticular and polyarticular JIA and explored their association with disease activity. Methods: Neutrophils from 6 healthy controls and 7 patients with oligoarticular and polyarticular JIA were freshly isolated at time of diagnosis and after glucocorticoid intra-articular injection. Enzymatic activity of neutrophil granular enzymes was monitored by colorimetry and PMA-activated NETs formation was assessed using fluorescent microscopy. Results: In this pilot and feasibility study, we revealed that NETs were significantly increased in oligoarticular JIA patients at time of diagnosis compared to healthy controls. Anti-inflammatory treatment using intra-articular steroid injection normalized NETs formation in these patients. Correlation between NETs formation and clinical Juvenile Activity Disease Activity Score-10 (cJADAS-10) was linear and significant (P = 0.007) in oligo but not in poly JIA patients. Conclusions: This is the first study exploring the link of NETs formation with oligo and poly JIA activity. We demonstrated a statistically significant linear correlation between cJADAS-10 and NETs formation in oligo but not in poly JIA patients. Hence, we suggest that NETs may reflect clinical disease activity in JIA, and may serve as a putative biomarker. Further work is needed to validate these initial results and determine the dynamics of NETs formation in JIA.
MeSH term(s)	Child ; Humans ; Arthritis, Juvenile/diagnosis ; Arthritis, Juvenile/drug therapy ; Neutrophils ; Extracellular Traps ; Pilot Projects ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-023-03104-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5490: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment.

Shukrun, Rachel / Baron, Szilvia / Fidel, Victoria / Shusterman, Anna / Sher, Osnat / Kollender, Netanya / Levin, Dror / Peled, Yair / Gortzak, Yair / Ben-Shahar, Yoav / Caspi, Revital / Gordon, Sagi / Manisterski, Michal / Elhasid, Ronit

Cancer science

2023 Volume 115, Issue 1, Page(s) 36–47

Abstract: Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%-80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures ...

Abstract	Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%-80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescence. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared with those with local disease. High NET formation at diagnosis predicted poor response to neoadjuvant chemotherapy, relapse, and death from disease (p < 0.05). NET formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared with pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NET formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.
MeSH term(s)	Humans ; Child ; Sarcoma, Ewing/genetics ; Extracellular Traps ; Neoplasm Recurrence, Local ; Prognosis ; Neutrophils/pathology ; Tumor Microenvironment
Language	English
Publishing date	2023-11-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.15992
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development.

Wineberg, Yishay / Kanter, Itamar / Ben-Haim, Nissim / Pode-Shakked, Naomi / Bucris, Efrat / Bar-Lev, Tali Hana / Oriel, Sarit / Reinus, Harel / Yehuda, Yishai / Gershon, Rotem / Shukrun, Rachel / Bar-Lev, Dekel Dov / Urbach, Achia / Dekel, Benjamin / Kalisky, Tomer

Scientific reports

2022 Volume 12, Issue 1, Page(s) 19548

Abstract: Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme-a transient kidney-specific progenitor state-undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various ... ...

Abstract	Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme-a transient kidney-specific progenitor state-undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms' tumor that mimics normal kidney development. While human kidney development has been characterized at the gene expression level, a comprehensive characterization of alternative splicing is lacking. Therefore, in this study, we performed RNA sequencing on cell populations representing early, intermediate, and late developmental stages of the human fetal kidney, as well as three blastemal-predominant Wilms' tumor patient-derived xenografts. Using this newly generated RNAseq data, we identified a set of transcripts that are alternatively spliced between the different developmental stages. Moreover, we found that cells from the earliest developmental stage have a mesenchymal splice-isoform profile that is similar to that of blastemal-predominant Wilms' tumor xenografts. RNA binding motif enrichment analysis suggests that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate alternative mRNA splicing during human kidney development. These findings illuminate new molecular mechanisms involved in human kidney development and pediatric kidney cancer.
MeSH term(s)	Humans ; Child ; Alternative Splicing ; RNA, Messenger/genetics ; Wilms Tumor/genetics ; Wilms Tumor/pathology ; Kidney Neoplasms/pathology ; Kidney/pathology ; Cells, Cultured ; RNA Splicing Factors/genetics ; Repressor Proteins/genetics
Chemical Substances	RNA, Messenger ; RBFOX2 protein, human ; RNA Splicing Factors ; Repressor Proteins
Language	English
Publishing date	2022-11-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-24147-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Targeted therapy aimed at cancer stem cells: Wilms' tumor as an example.

Shukrun, Rachel / Pode Shakked, Naomi / Dekel, Benjamin

Pediatric nephrology (Berlin, Germany)

2013 Volume 29, Issue 5, Page(s) 815–23; quiz 821

Abstract: Wilms' tumor (WT), a common renal pediatric solid tumor, serves as a model for a malignancy formed by renal precursor cells that have failed to differentiate properly. Here we review recent evidence showing that the tumors' heterogeneous cell population ... ...

Abstract	Wilms' tumor (WT), a common renal pediatric solid tumor, serves as a model for a malignancy formed by renal precursor cells that have failed to differentiate properly. Here we review recent evidence showing that the tumors' heterogeneous cell population contains a small fraction of cancer stem cells (CSC) identified by two markers: Neural Cell Adhesion Molecule 1 (NCAM1) expression and Aldehyde dehydrogenase 1 (ALDH1) enzymatic activity. In vivo studies show these CSCs to both self-renew and differentiate to give rise to all tumor components. Similar to other malignancies, the identification of a specific CSC fraction has allowed the examination of a novel targeted therapy, aimed at eradicating the CSC population. The loss of CSCs abolishes the tumor's ability to sustain and propagate, hence, causing tumor degradation with minimal damage to normal tissue.
MeSH term(s)	Aldehyde Dehydrogenase 1 Family ; CD56 Antigen/biosynthesis ; CD56 Antigen/genetics ; Child ; Humans ; Isoenzymes/biosynthesis ; Isoenzymes/genetics ; Kidney Neoplasms/pathology ; Kidney Neoplasms/therapy ; Neoplastic Stem Cells/physiology ; Retinal Dehydrogenase/biosynthesis ; Retinal Dehydrogenase/genetics ; Wilms Tumor/pathology ; Wilms Tumor/therapy
Chemical Substances	CD56 Antigen ; Isoenzymes ; NCAM1 protein, human ; Aldehyde Dehydrogenase 1 Family (EC 1.2.1) ; ALDH1A1 protein, human (EC 1.2.1.36) ; Retinal Dehydrogenase (EC 1.2.1.36)
Language	English
Publishing date	2013-06-13
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-013-2501-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2196: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Genetic Markers Among the Israeli Druze Minority Population With End-Stage Kidney Disease.

Shlomovitz, Omer / Atias-Varon, Danit / Yagel, Dina / Barel, Ortal / Shasha-Lavsky, Hadas / Skorecki, Karl / Eliyahu, Aviva / Bathish, Younes / Frajewicki, Victor / Kushnir, Daniel / Zaid, Rinat / Paperna, Tamar / Ofir, Ayala / Tchirkov, Marina / Hassan, Kamal / Kruzel, Etty / Khazim, Khaled / Geron, Ronit / Weisman, Irit /

Hanut, Anaam / Nakhoul, Farid / Kenig-Kozlovsky, Yael / Refael, Gery / Antebi, Alon / Storch, Shimon / Leiba, Marcel / Kagan, Maayan / Shukrun, Rachel / Rechavi, Gidi / Dekel, Benjamin / Ben Moshe, Yishay / Weiss, Karin / Assady, Suheir / Vivante, Asaf

American journal of kidney diseases : the official journal of the National Kidney Foundation

2023 Volume 83, Issue 2, Page(s) 183–195

Abstract: Rationale & objective: Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease (CKD). However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. ... ...

Abstract	Rationale & objective: Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease (CKD). However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. This study characterized the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD). Study design: A national-multicenter cross-sectional study of Israeli Druze patients (an Arabic-speaking Near-Eastern transnational population isolate) who are receiving maintenance dialysis for ESKD. All study participants underwent exome sequencing. Setting & participants: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period. Predictors: Demographics and clinical characteristics of kidney disease. Outcome: Genetic markers. Analytical approach: Whole-exome sequencing and the relationship of markers to clinical phenotypes. Results: We identified genetic etiologies in 17 of 94 participants (18%). None had a previous molecular diagnosis. A novel, population-specific, WDR19 homozygous pathogenic variant (p.Cys293Tyr) was the most common genetic finding. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, and monogenic forms of noncommunicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in fewer than half of the participants. Limitations: This study was limited to Druze individuals, so its generalizability may be limited. Conclusions: Exome sequencing identified a genetic diagnosis in approximately 18% of Druze individuals with ESKD. These results support conducting genetic analyses in minority populations with high rates of CKD and for whom phenotypic disease specificity may be low. Plain-language summary: Chronic kidney disease (CKD) affects many people worldwide and has multiple genetic causes. However, there is limited information on the prevalence of genetic etiologies, especially among minority populations. Our national-multicenter study focused on Israeli Druze patients. Using exome-sequencing, we identified previously undetected genetic causes in nearly 20% of patients, including a new and population-specific WDR19 homozygous pathogenic variant. This mutation has not been previously described; it is extremely rare globally but is common among the Druze, which highlights the importance of studying minority populations with high rates of CKD. Our findings provide insights into the genetic basis of end-stage kidney disease in the Israeli Druze, expand the WDR19 phenotypic spectrum, and emphasize the potential value of genetic testing in such populations.
MeSH term(s)	Adult ; Humans ; Minority Groups ; Israel/epidemiology ; Genetic Markers ; Cross-Sectional Studies ; Kidney Failure, Chronic/epidemiology ; Kidney Failure, Chronic/genetics ; Kidney Failure, Chronic/therapy ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/diagnosis ; Health Disparate Minority and Vulnerable Populations
Chemical Substances	Genetic Markers
Language	English
Publishing date	2023-09-15
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2023.06.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 468: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Novel homozygous ENPP1 mutation causes generalized arterial calcifications of infancy, thrombocytopenia, and cardiovascular and central nervous system syndrome.

Staretz-Chacham, Orna / Shukrun, Rachel / Barel, Ortal / Pode-Shakked, Ben / Pleniceanu, Oren / Anikster, Yair / Shalva, Nechama / Ferreira, Carlos R / Ben-Haim Kadosh, Admit / Richardson, Justin / Mane, Shrikant M / Hildebrandt, Friedhelm / Vivante, Asaf

American journal of medical genetics. Part A

2019 Volume 179, Issue 10, Page(s) 2112–2118

Abstract: Generalized arterial calcifications of infancy (GACI) is caused by mutations in ENPP1. Other ENPP1-related phenotypes include pseudoxanthoma elasticum, hypophosphatemic rickets, and Cole disease. We studied four children from two Bedouin consanguineous ... ...

Abstract	Generalized arterial calcifications of infancy (GACI) is caused by mutations in ENPP1. Other ENPP1-related phenotypes include pseudoxanthoma elasticum, hypophosphatemic rickets, and Cole disease. We studied four children from two Bedouin consanguineous families who presented with severe clinical phenotype including thrombocytopenia, hypoglycemia, hepatic, and neurologic manifestations. Initial working diagnosis included congenital infection; however, patients remained without a definitive diagnosis despite extensive workup. Consequently, we investigated a potential genetic etiology. Whole exome sequencing (WES) was performed for affected children and their parents. Following the identification of a novel mutation in the ENPP1 gene, we characterized this novel multisystemic presentation and revised relevant imaging studies. Using WES, we identified a novel homozygous mutation (c.556G > C; p.Gly186Arg) in ENPP1 which affects a highly conserved protein domain (somatomedin B2). ENPP1-associated genetic diseases exhibit phenotypic heterogeneity depending on mutation type and location. Follow-up clinical characterization of these families allowed us to revise and detect new features of systemic calcifications, which established the diagnosis of GACI, expanding the phenotypic spectrum associated with ENPP1 mutations. Our findings demonstrate that this novel ENPP1 founder mutation can cause a fatal multisystemic phenotype, mimicking severe congenital infection. This also represents the first reported mutation affecting the SMB2 domain, associated with GACI.
MeSH term(s)	Base Sequence ; Cardiovascular Abnormalities/complications ; Cardiovascular Abnormalities/diagnostic imaging ; Cardiovascular Abnormalities/genetics ; Central Nervous System/abnormalities ; Central Nervous System/diagnostic imaging ; Fatal Outcome ; Female ; Genetic Predisposition to Disease ; Homozygote ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation/genetics ; Pedigree ; Phenotype ; Phosphoric Diester Hydrolases/genetics ; Pregnancy ; Pyrophosphatases/genetics ; Syndrome ; Thrombocytopenia/complications ; Thrombocytopenia/genetics ; Vascular Calcification/complications ; Vascular Calcification/diagnostic imaging ; Vascular Calcification/genetics
Chemical Substances	Phosphoric Diester Hydrolases (EC 3.1.4.-) ; ectonucleotide pyrophosphatase phosphodiesterase 1 (EC 3.1.4.1) ; Pyrophosphatases (EC 3.6.1.-)
Language	English
Publishing date	2019-08-24
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1493479-6
ISSN	1552-4833 ; 1552-4825
ISSN (online)	1552-4833
ISSN	1552-4825
DOI	10.1002/ajmg.a.61334
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: HTLV-1 Tax oncoprotein inhibits the estrogen-induced-ER α-Mediated BRCA1 expression by interaction with CBP/p300 cofactors.

Shukrun, Meital / Jabareen, Azhar / Abou-Kandil, Ammar / Chamias, Rachel / Aboud, Mordechai / Huleihel, Mahmoud

PloS one

2014 Volume 9, Issue 2, Page(s) e89390

Abstract: BRCA1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor and regulated by certain recruited transcriptional co-activators. Interference with BRCA1 expression and/or functions leads to high risk ...

Abstract	BRCA1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor and regulated by certain recruited transcriptional co-activators. Interference with BRCA1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Another multifunctional protein, HTLV-1Tax oncoprotein, is widely regarded as crucial for developing adult T-cell leukemia and other clinical disorders. Tax profile reveals that it can antagonize BRCA1 expression and/or functionality. Therefore, we hypothesize that Tax expression in breast cells can sensitize them to malignant transformation by environmental carcinogens. Here we examined Tax effect on BRCA1 expression by testing its influence on E2-induced expression of BRCA1 promoter-driven luciferase reporter (BRCA1-Luc). We found that E2 strongly stimulated this reporter expression by liganding to ERα, which consequently associated with BRCA1 promoter, while ERα concomitantly recruited CBP/p300 to this complex for co-operative enhancement of BRCA1 expression. Introducing Tax into these cells strongly blocked this E2-ERα-mediated activation of BRCA1 expression. We noted, also, that Tax exerted this inhibition by binding to CBP/p300 without releasing them from their complex with ERα. Chip assay revealed that the binding of Tax to the CBP/p300-ERα complex, prevented its link to AP1 site. Interestingly, we noted that elevating the intracellular pool of CBP or p300 to excessive levels dramatically reduced the Tax-mediated inhibition of BRCA1 expression. Exploring the mechanism of this reduction revealed that the excessive co-factors were sufficient to bind separately the free Tax molecules, thus lowering their amount in the CBP/p300-ERα complex and relieving, thereby, the inhibition of BRCA1 expression.
MeSH term(s)	BRCA1 Protein/genetics ; BRCA1 Protein/metabolism ; CREB-Binding Protein/genetics ; CREB-Binding Protein/metabolism ; Cell Line, Tumor ; Epithelial Cells/metabolism ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Gene Products, tax/genetics ; Gene Products, tax/metabolism ; Human T-lymphotropic virus 1/metabolism ; Humans ; p300-CBP Transcription Factors/genetics ; p300-CBP Transcription Factors/metabolism
Chemical Substances	BRCA1 Protein ; Estrogen Receptor alpha ; Gene Products, tax ; CREB-Binding Protein (EC 2.3.1.48) ; p300-CBP Transcription Factors (EC 2.3.1.48)
Language	English
Publishing date	2014-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0089390
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED