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Article ; Online: A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients.

Lee, Valerie / Parkinson, Rose / Zahurak, Marianna / Cope, Leslie / Cercek, Andrea / Verheul, Henk / Gootjes, Elske / Lenz, Heinz Josef / Iqbal, Syma / Jones, Peter / Baylin, Stephen / Rami, Vandna / Ahuja, Nita / El Khoueiry, Anthony / Azad, Nilofer S

International journal of cancer

2024 Volume 154, Issue 10, Page(s) 1794–1801

Abstract: ... 102 (Arm B) on a 28-day cycle. Between January 15, 2016 and October 24, 2018, 104 pts were randomized ... at four international sites, with 96 pts undergoing treatment, 62 in Arm A and 34 in Arm B. Median overall ... survival was 7.15 months for Arm A and 7.66 months for Arm B (HR 0.93, 95% CI: 0.58-1.47, P = .75 ...

Abstract	DNA methyltransferase inhibitors (DNMTi) have demonstrated benefit in reversing resistance to systemic therapies for several cancer types. In a phase II trial of guadecitabine and irinotecan compared to regorafenib or TAS-102 in pts with advanced mCRC refractory to irinotecan. Patients with mCRC refractory to irinotecan were randomized 2:1 to guadecitabine and irinotecan (Arm A) vs standard of care regorafenib or TAS-102 (Arm B) on a 28-day cycle. Between January 15, 2016 and October 24, 2018, 104 pts were randomized at four international sites, with 96 pts undergoing treatment, 62 in Arm A and 34 in Arm B. Median overall survival was 7.15 months for Arm A and 7.66 months for Arm B (HR 0.93, 95% CI: 0.58-1.47, P = .75). The Kaplan-Meier rates of progression free survival at 4 months were 32% in Arm A and 26% in Arm B. Common ≥Grade 3 treatment related adverse events in Arm A were neutropenia (42%), anemia (18%), diarrhea (11%), compared to Arm B pts with neutropenia (12%), anemia (12%). Guadecitabine and irinotecan had similar OS compared to standard of care TAS-102 or regorafenib, with evidence of target modulation. Clinical trial information: NCT01896856.
MeSH term(s)	Humans ; Irinotecan/therapeutic use ; Colorectal Neoplasms/pathology ; Treatment Outcome ; Colonic Neoplasms/drug therapy ; Rectal Neoplasms/drug therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neutropenia ; Anemia/drug therapy ; Thymine ; Trifluridine ; Azacitidine/analogs & derivatives ; Phenylurea Compounds ; Drug Combinations ; Pyrrolidines ; Pyridines
Chemical Substances	Irinotecan (7673326042) ; trifluridine tipiracil drug combination ; guadecitabine (2KT4YN1DP7) ; regorafenib (24T2A1DOYB) ; Thymine (QR26YLT7LT) ; Trifluridine (RMW9V5RW38) ; Azacitidine (M801H13NRU) ; Phenylurea Compounds ; Drug Combinations ; Pyrrolidines ; Pyridines
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase II ; Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34845
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Zs.A 478: 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 576: Show issues

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Article: "APUD" cells: fact and fiction.

Baylin, S B

Trends in endocrinology and metabolism: TEM

2008 Volume 1, Issue 4, Page(s) 198–204

Abstract: Pearse's "APUD" cell theory helps define the ontogeny and differentiation programs of small polypeptide hormone-secreting cells of diverse tissue origins. Cells with such features may arise through one of multiple related pathways of epithelial cell ... ...

Abstract	Pearse's "APUD" cell theory helps define the ontogeny and differentiation programs of small polypeptide hormone-secreting cells of diverse tissue origins. Cells with such features may arise through one of multiple related pathways of epithelial cell differentiation ongoing in tissues of all embryonic lineages.
Language	English
Publishing date	2008-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/1043-2760(90)90053-6
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Zs.A 2999: Show issues

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Article ; Online: Associations of bacterial enteropathogens with systemic inflammation, iron deficiency, and anemia in preschool-age children in southern Ghana.

Lambrecht, Nathalie J / Bridges, Dave / Wilson, Mark L / Adu, Bright / Eisenberg, Joseph N S / Folson, Gloria / Baylin, Ana / Jones, Andrew D

PloS one

2022 Volume 17, Issue 7, Page(s) e0271099

Abstract: Anemia remains a pervasive public health problem among preschool-age children in Ghana. Recent analyses have found that anemia in Ghanaian children, particularly in Southern regions, is largely attributable to infectious causes, rather than nutritional ... ...

Abstract	Anemia remains a pervasive public health problem among preschool-age children in Ghana. Recent analyses have found that anemia in Ghanaian children, particularly in Southern regions, is largely attributable to infectious causes, rather than nutritional factors. Infections with enteropathogens can reduce iron absorption and increase systemic inflammation, but few studies have examined direct links between enteropathogens and anemia. This study investigated associations between detection of individual bacterial enteropathogens and systemic inflammation, iron deficiency, and anemia among 6- to 59-month-old children in Greater Accra, Ghana. Serum samples were analyzed from a cross-sectional sample of 262 children for concentrations of hemoglobin (Hb), biomarkers of systemic inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)], and biomarkers of iron status [serum ferritin (SF) and serum transferrin receptor (sTfR)]. Stool samples were analyzed for ten bacterial enteropathogens using qPCR. We estimated associations between presence of each enteropathogen and elevated systemic inflammation (CRP > 5 mg/L and AGP > 1 g/L), iron deficiency (SF < 12 μg/L and sTfR > 8.3 mg/L) and anemia (Hb < 110 g/L). Enteropathogens were detected in 87% of children's stool despite a low prevalence of diarrhea (6.5%). Almost half (46%) of children had anemia while one-quarter (24%) had iron deficiency (low SF). Despite finding no associations with illness symptoms, Campylobacter jejuni/coli detection was strongly associated with elevated CRP [Odds Ratio (95% CI): 3.49 (1.45, 8.41)] and elevated AGP [4.27 (1.85, 9.84)]. Of the pathogens examined, only enteroinvasive Escherichia coli/Shigella spp. (EIEC/Shigella) was associated with iron deficiency, and enteroaggregative Escherichia coli (EAEC) [1.69 (1.01, 2.84)] and EIEC/Shigella [2.34 (1.15, 4.76)] were associated with anemia. These results suggest that certain enteroinvasive pathogenic bacteria may contribute to child anemia. Reducing exposure to enteropathogens through improved water, sanitation, and hygiene practices may help reduce the burden of anemia in young Ghanaian children.
MeSH term(s)	Anemia/epidemiology ; Anemia, Iron-Deficiency/complications ; Anemia, Iron-Deficiency/epidemiology ; Bacteria/metabolism ; Biomarkers ; C-Reactive Protein/metabolism ; Child ; Child, Preschool ; Cross-Sectional Studies ; Ferritins ; Ghana/epidemiology ; Hemoglobins/metabolism ; Humans ; Infant ; Inflammation ; Iron/metabolism ; Iron Deficiencies
Chemical Substances	Biomarkers ; Hemoglobins ; C-Reactive Protein (9007-41-4) ; Ferritins (9007-73-2) ; Iron (E1UOL152H7)
Language	English
Publishing date	2022-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0271099
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Article ; Online: Tissue-location-specific transcription programs drive tumor dependencies in colon cancer.

Yang, Lijing / Tu, Lei / Bisht, Shilpa / Mao, Yiqing / Petkovich, Daniel / Thursby, Sara-Jayne / Liang, Jinxiao / Patel, Nibedita / Yen, Ray-Whay Chiu / Largent, Tina / Zahnow, Cynthia / Brock, Malcolm / Gabrielson, Kathy / Salimian, Kevan J / Baylin, Stephen B / Easwaran, Hariharan

Nature communications

2024 Volume 15, Issue 1, Page(s) 1384

Abstract: Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with ... ...

Abstract	Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAF
MeSH term(s)	Humans ; Mice ; Animals ; Proto-Oncogene Proteins B-raf/genetics ; CDX2 Transcription Factor/genetics ; Colonic Neoplasms/genetics ; Colonic Neoplasms/pathology ; DNA-Binding Proteins ; Transcription Factors/genetics ; Homeodomain Proteins/genetics
Chemical Substances	Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; CDX2 Transcription Factor ; DNA-Binding Proteins ; Transcription Factors ; Homeodomain Proteins
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45605-4
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Article ; Online: Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers.

Bhandari, Yuba R / Krishna, Vinod / Powers, Rachael / Parmar, Sehej / Thursby, Sara-Jayne / Gupta, Ekta / Kulak, Ozlem / Gokare, Prashanth / Reumers, Joke / Van Wesenbeeck, Liesbeth / Bachman, Kurtis E / Baylin, Stephen B / Easwaran, Hariharan

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 31, Page(s) e2301536120

Abstract: Colorectal cancers (CRCs) form a heterogenous group classified into epigenetic and transcriptional subtypes. The basis for the epigenetic subtypes, exemplified by varying degrees of promoter DNA hypermethylation, and its relation to the transcriptional ... ...

Abstract	Colorectal cancers (CRCs) form a heterogenous group classified into epigenetic and transcriptional subtypes. The basis for the epigenetic subtypes, exemplified by varying degrees of promoter DNA hypermethylation, and its relation to the transcriptional subtypes is not well understood. We link cancer-specific transcription factor (TF) expression alterations to methylation alterations near TF-binding sites at promoter and enhancer regions in CRCs and their premalignant precursor lesions to provide mechanistic insights into the origins and evolution of the CRC molecular subtypes. A gradient of TF expression changes forms a basis for the subtypes of abnormal DNA methylation, termed CpG-island promoter DNA methylation phenotypes (CIMPs), in CRCs and other cancers. CIMP is tightly correlated with cancer-specific hypermethylation at enhancers, which we term CpG-enhancer methylation phenotype (CEMP). Coordinated promoter and enhancer methylation appears to be driven by downregulation of TFs with common binding sites at the hypermethylated enhancers and promoters. The altered expression of TFs related to hypermethylator subtypes occurs early during CRC development, detectable in premalignant adenomas. TF-based profiling further identifies patients with worse overall survival. Importantly, altered expression of these TFs discriminates the transcriptome-based consensus molecular subtypes (CMS), thus providing a common basis for CIMP and CMS subtypes.
MeSH term(s)	Humans ; Transcription Factors ; Gene Expression Regulation ; DNA Methylation ; Precancerous Conditions ; Colorectal Neoplasms ; Epigenesis, Genetic
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2301536120
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Zs.A 1148: Show issues

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Article ; Online: Phase I Clinical Trial of DNA Methyltransferase Inhibitor Decitabine and PARP Inhibitor Talazoparib Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia.

Baer, Maria R / Kogan, Aksinija A / Bentzen, Søren M / Mi, Tian / Lapidus, Rena G / Duong, Vu H / Emadi, Ashkan / Niyongere, Sandrine / O'Connell, Casey L / Youngblood, Benjamin A / Baylin, Stephen B / Rassool, Feyruz V

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 28, Issue 7, Page(s) 1313–1322

Abstract: ... 25 patients, including 22 previously treated with DNMTi(s)] to a recommended phase II dose ...

Abstract	Purpose: Patients with acute myeloid leukemia (AML) unfit for, or resistant to, intensive chemotherapy are often treated with DNA methyltransferase inhibitors (DNMTi). Novel combinations may increase efficacy. In addition to demethylating CpG island gene promoter regions, DNMTis enhance PARP1 recruitment and tight binding to chromatin, preventing PARP-mediated DNA repair, downregulating homologous recombination (HR) DNA repair, and sensitizing cells to PARP inhibitor (PARPi). We previously demonstrated DNMTi and PARPi combination efficacy in AML in vitro and in vivo. Here, we report a phase I clinical trial combining the DNMTi decitabine and the PARPi talazoparib in relapsed/refractory AML. Patients and methods: Decitabine and talazoparib doses were escalated using a 3 + 3 design. Pharmacodynamic studies were performed on cycle 1 days 1 (pretreatment), 5 and 8 blood blasts. Results: Doses were escalated in seven cohorts [25 patients, including 22 previously treated with DNMTi(s)] to a recommended phase II dose combination of decitabine 20 mg/m2 intravenously daily for 5 or 10 days and talazoparib 1 mg orally daily for 28 days, in 28-day cycles. Grade 3-5 events included fever in 19 patients and lung infections in 15, attributed to AML. Responses included complete remission with incomplete count recovery in two patients (8%) and hematologic improvement in three. Pharmacodynamic studies showed the expected DNA demethylation, increased PARP trapping in chromatin, increased γH2AX foci, and decreased HR activity in responders. γH2AX foci increased significantly with increasing talazoparib doses combined with 20 mg/m2 decitabine. Conclusions: Decitabine/talazoparib combination was well tolerated. Expected pharmacodynamic effects occurred, especially in responders.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; DNA ; Decitabine/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Methyltransferases ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Chemical Substances	Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors ; Decitabine (776B62CQ27) ; DNA (9007-49-2) ; talazoparib (9QHX048FRV) ; Methyltransferases (EC 2.1.1.-) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-3729
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Zs.A 4223: Show issues

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Article ; Online: Associations between livestock ownership and lower odds of anaemia among children 6-59 months old are not mediated by animal-source food consumption in Ghana.

Lambrecht, Nathalie J / Wilson, Mark L / Baylin, Ana / Folson, Gloria / Naabah, Samuel / Eisenberg, Joseph N S / Adu, Bright / Jones, Andrew D

Maternal & child nutrition

2021 Volume 17, Issue 3, Page(s) e13163

Abstract: Livestock ownership may mitigate anaemia among young children by providing access to animal-source foods (ASFs) yet exacerbate anaemia by exposing children to animal-source pathogens. This study aimed to assess the association between household livestock ...

Abstract	Livestock ownership may mitigate anaemia among young children by providing access to animal-source foods (ASFs) yet exacerbate anaemia by exposing children to animal-source pathogens. This study aimed to assess the association between household livestock ownership and child anaemia and examine whether this relationship is mediated by child ASF consumption or by child morbidity and inflammation. We conducted a cross-sectional study of 470 children aged 6-59 months in Greater Accra, Ghana. Child blood samples were analysed for haemoglobin concentration, iron status biomarkers and inflammatory biomarkers. Caregivers were asked about the child's frequency of ASF consumption in the past 3 months. Livestock ownership was categorized into five typologies to distinguish households by the number and combinations of species owned. In adjusted logistic regression, children from households in Type 5, owning cattle, small livestock (goats, sheep or pigs) and poultry, had lower odds of anaemia compared with those in Type 1, owning no livestock (OR [95% CI]: 0.32 [0.14, 0.71]). Although children from households that owned poultry were more likely to consume chicken meat, and children from households with cattle were more likely to drink cow's milk, consumption of these ASFs did not mediate the observed association between livestock ownership and child anaemia. There were no associations between livestock ownership and children's symptoms of illness or inflammation. Further research is needed to understand how ownership of certain livestock species, or a greater diversity of livestock species, may be associated with the risk of child anaemia, including the role of dietary and income-based pathways.
MeSH term(s)	Anemia/epidemiology ; Animals ; Cattle ; Child ; Child, Preschool ; Cross-Sectional Studies ; Ghana/epidemiology ; Humans ; Infant ; Livestock ; Ownership ; Sheep ; Swine
Language	English
Publishing date	2021-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175105-5
ISSN	1740-8709 ; 1740-8695
ISSN (online)	1740-8709
ISSN	1740-8695
DOI	10.1111/mcn.13163
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Article ; Online: Ruminant-Related Risk Factors are Associated with Shiga Toxin-Producing Escherichia coli Infection in Children in Southern Ghana.

Lambrecht, Nathalie J / Wilson, Mark L / Bridges, Dave / Eisenberg, Joseph N S / Adu, Bright / Baylin, Ana / Folson, Gloria / Jones, Andrew D

The American journal of tropical medicine and hygiene

2021 Volume 106, Issue 2, Page(s) 513–522

Abstract: Livestock can provide benefits to low-income households, yet may expose children to zoonotic enteropathogens that cause illness and negative long-term health outcomes. The aim of this cross-sectional study was to determine whether livestock-related risk ... ...

Abstract	Livestock can provide benefits to low-income households, yet may expose children to zoonotic enteropathogens that cause illness and negative long-term health outcomes. The aim of this cross-sectional study was to determine whether livestock-related risk factors, including animal ownership, exposure to animal feces, and consumption of animal-source foods, were associated with bacterial zoonotic enteropathogen infections in children 6-59 months old in Greater Accra, Ghana. Stool samples from 259 children and 156 household chickens were analyzed for atypical enteropathogenic Escherichia coli (aEPEC), Campylobacter jejuni/coli (C. jejuni/coli), Salmonella, and Shiga toxin-producing Escherichia coli (STEC) using quantitative polymerase chain reaction (qPCR). aEPEC, C. jejuni/coli, STEC, and Salmonella were detected in 45.6%, 11.6%, 4.3%, and 0.8% of children's stool samples, respectively. In adjusted logistic regression models, household ownership of goats or sheep was associated with STEC detection in children (odds ratio [95% confidence interval]: 4.30 [1.32, 14.08]), as were positive detection of STEC in chicken feces (7.85 [2.54, 24.30]) and frequent consumption of fresh cow's milk (3.03 [1.75, 5.24]). No livestock-related risk factors were associated with aEPEC or C. jejuni/coli infection in children. Our findings suggest that ruminant ownership in southern Ghana may expose children to STEC through household fecal contamination and foodborne routes. The lack of association between livestock risk factors and the more commonly detected pathogens, aEPEC and C. jejuni/coli, warrants further research, particularly to help explain how animal-keeping and sanitation practices affect transmission of fecal pathogens that were highly prevalent in chicken feces.
MeSH term(s)	Animals ; Campylobacter Infections/diagnosis ; Campylobacter Infections/epidemiology ; Campylobacter Infections/microbiology ; Campylobacter jejuni/growth & development ; Campylobacter jejuni/pathogenicity ; Cattle ; Chickens/microbiology ; Child, Preschool ; Cross-Sectional Studies ; Enteropathogenic Escherichia coli/growth & development ; Enteropathogenic Escherichia coli/pathogenicity ; Escherichia coli Infections/diagnosis ; Escherichia coli Infections/epidemiology ; Escherichia coli Infections/microbiology ; Feces/microbiology ; Ghana ; Goats ; Humans ; Infant ; Livestock/microbiology ; Logistic Models ; Milk/microbiology ; Ruminants/microbiology ; Salmonella/growth & development ; Salmonella/pathogenicity ; Salmonella Infections/diagnosis ; Salmonella Infections/epidemiology ; Salmonella Infections/microbiology ; Sheep ; Shiga-Toxigenic Escherichia coli/growth & development ; Shiga-Toxigenic Escherichia coli/pathogenicity
Language	English
Publishing date	2021-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.21-0550
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Ud II Zs.61: Show issues

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Article ; Online: Role of nuclear architecture in epigenetic alterations in cancer.

Easwaran, H P / Baylin, S B

Cold Spring Harbor symposia on quantitative biology

2011 Volume 75, Page(s) 507–515

Abstract: It is widely accepted that cancer results from an array of epigenetic and genetic alterations, particularly aberrant epigenetic patterns that are a hallmark of every cancer type studied. Another well-known feature of cancer cells is the array of ... ...

Abstract	It is widely accepted that cancer results from an array of epigenetic and genetic alterations, particularly aberrant epigenetic patterns that are a hallmark of every cancer type studied. Another well-known feature of cancer cells is the array of abnormalities in their nuclear structure. Although it is known that nuclear structure has an important role in the regulation of gene expression, we know little about the direct relationship between nuclear structural alterations and aberrant epigenetic patterns in cancer. Here, we discuss some of the recent studies from our lab and others to understand the relationship between alterations of nuclear architecture and aberrant epigenetic patterns in cancer cells. Although the precise relationship remains elusive, we suggest that changes in nuclear structure and composition could alter long-range genomic interactions and cause global epigenetic changes during tumorigenesis. We emphasize the need for further studies to elucidate the direct relationship between nuclear structure alterations and aberrant epigenetic patterns in cancers.
MeSH term(s)	Animals ; Cell Nucleus/chemistry ; Cell Nucleus/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; Models, Genetic ; Neoplasms/genetics ; Neoplasms/pathology ; Nuclear Proteins/metabolism
Chemical Substances	Nuclear Proteins
Language	English
Publishing date	2011-03-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1943-4456 ; 0091-7451
ISSN (online)	1943-4456
ISSN	0091-7451
DOI	10.1101/sqb.2010.75.031
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Article ; Online: Cancer-like epigenetic derangements of human pluripotent stem cells and their impact on applications in regeneration and repair.

Huo, Jeffrey S / Baylin, Stephen B / Zambidis, Elias T

Current opinion in genetics & development

2014 Volume 28, Page(s) 43–49

Abstract: A growing body of work has raised concern that many human pluripotent stem cell (hPSC) lines possess tumorigenic potential following differentiation to clinically relevant lineages. In this review, we highlight recent work characterizing the spectrum of ... ...

Abstract	A growing body of work has raised concern that many human pluripotent stem cell (hPSC) lines possess tumorigenic potential following differentiation to clinically relevant lineages. In this review, we highlight recent work characterizing the spectrum of cancer-like epigenetic derangements in human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) that are associated with reprogramming errors or prolonged culture that may contribute to such tumorigenicity. These aberrations include cancer-like promoter DNA hypermethylation and histone marks associated with pluripotency, as well as aberrant X-chromosome regulation. We also feature recent work that suggests optimized high-fidelity reprogramming derivation methods can minimize cancer-associated epigenetic aberrations in hPSC, and thus ultimately improve the ultimate clinical utility of hiPSC in regenerative medicine.
MeSH term(s)	Animals ; Cell Differentiation ; Epigenomics ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Pluripotent Stem Cells/pathology ; Regenerative Medicine ; Wound Healing
Language	English
Publishing date	2014-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1077312-5
ISSN	1879-0380 ; 0959-437X
ISSN (online)	1879-0380
ISSN	0959-437X
DOI	10.1016/j.gde.2014.09.008
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