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Article ; Online: Wnt signaling and colon carcinogenesis: beyond APC.

Najdi, Rani / Holcombe, Randall F / Waterman, Marian L

2011 Volume 10, Page(s) 5

Abstract: Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC) is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a ...

Abstract	Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC) is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a singular event. Here we review how canonical Wnt signaling is modulated by intracellular LEF/TCF composition and location, the action of different Wnt ligands, and the secretion of Wnt inhibitory molecules. We also review the contributions of non-canonical Wnt signaling and other distinct pathways in the tumor micro environment that cross-talk to the canonical Wnt pathway and thereby influence colon cancer progression. These 'non-APC' aspects of Wnt signaling are considered in relation to the development of potential agents for the treatment of patients with colon cancer. Regulatory pathways that influence Wnt signaling highlight how it might be possible to design therapies that target a network of signals beyond that of APC and β-catenin.
Language	English
Publishing date	2011-03-17
Publishing country	India
Document type	Journal Article
ZDB-ID	2098237-9
ISSN	1477-3163 ; 0974-6773
ISSN (online)	1477-3163
ISSN	0974-6773
DOI	10.4103/1477-3163.78111
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Review of the patient-centered communication landscape in multiple myeloma and other hematologic malignancies.

LeBlanc, Thomas W / Baile, Walter F / Eggly, Susan / Bylund, Carma L / Kurtin, Sandra / Khurana, Monica / Najdi, Rani / Blaedel, Julie / Wolf, Jeffrey L / Fonseca, Rafael

Patient education and counseling

2019 Volume 102, Issue 9, Page(s) 1602–1612

Abstract: Objectives: To identify factors limiting and facilitating patient-centered communication (PCC) in the United States hematology-oncology setting, with a focus on multiple myeloma (MM), given the limited attention to PCC and rapid pace of change that has ... ...

Abstract	Objectives: To identify factors limiting and facilitating patient-centered communication (PCC) in the United States hematology-oncology setting, with a focus on multiple myeloma (MM), given the limited attention to PCC and rapid pace of change that has taken place in this setting. Methods: A literature search was performed from 2007 to 2017 to identify published articles and congress abstracts related to clinician-patient communication and treatment decision-making in oncology. Search results were evaluated by year of publication and disease area. A thematic assessment was performed to identify factors limiting and promoting PCC for patients with MM and other hematologic malignancies. Results: Of the 6673 publications initially retrieved, 18 exclusively reported findings in patients with hematologic malignancies and were included in this review. We identified three critical, but modifiable, barriers to PCC in the hematologic malignancy setting, including insufficient information exchange, treatment goal misalignment, and discordant role preferences in treatment decision-making. Factors that enhanced interaction quality included educational programs for clinicians and patients. Conclusions: Patients with MM and other hematologic malignancies experience a distinct set of challenges that may affect PCC. Practice implications: Clinicians have the opportunity to improve patient care by proactively addressing the identified barriers and implementing strategies demonstrated to improve PCC.
MeSH term(s)	Communication ; Decision Making, Shared ; Hematologic Neoplasms/therapy ; Humans ; Multiple Myeloma/therapy ; Patient Education as Topic ; Patient-Centered Care ; Physician-Patient Relations ; United States
Language	English
Publishing date	2019-04-26
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605590-4
ISSN	1873-5134 ; 0738-3991
ISSN (online)	1873-5134
ISSN	0738-3991
DOI	10.1016/j.pec.2019.04.028
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Article ; Online: A randomized controlled clinical trial evaluating the effect of

Najdi, Rania A / Hagras, Magda M / Kamel, Fatemah O / Magadmi, Rania M

African health sciences

2019 Volume 19, Issue 1, Page(s) 1594–1601

Abstract: Background: Herbal medicines long have been used in the management of diabetes mellitus (DM).: Objective: This study was conducted to ascertain if fenugreek compared with glibenclamide had any impacts on controlling blood glucose in patients with ... ...

Abstract	Background: Herbal medicines long have been used in the management of diabetes mellitus (DM). Objective: This study was conducted to ascertain if fenugreek compared with glibenclamide had any impacts on controlling blood glucose in patients with uncontrolled type II DM on conventional therapy. Methods: A total of 12 patients with uncontrolled DM and on metformin were recruited and divided into two groups. Patients in group 1 received 2 g fenugreek per day, whereas those in group 2 received glibenclamide 5 mg once daily. The impacts of fenugreek on the glycemic control and lipid profile were measured before initiation of the regimen and then after 12 weeks. Results: Only 9 of the 12 study participants completed the study. Fenugreek at 2 g/day caused an insignificant drop in fasting blood glucose (P = 0.63), but the fasting insulin level increased significantly (P = 0.04). The ratio of high- to low-density lipoprotein was significantly decreased from before to after treatment (P = 0.006). Fenugreek did not cause any notable adverse impacts on hepatic and renal functions throughout the study. Conclusion: Fenugreek could be used as adjuvant therapy to anti-diabetic drugs to control blood glucose, and further studies are needed.
MeSH term(s)	Adult ; Aged ; Blood Glucose/drug effects ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/drug therapy ; Dose-Response Relationship, Drug ; Female ; Glyburide/chemistry ; Glycated Hemoglobin A/drug effects ; Humans ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Lipids/blood ; Male ; Middle Aged ; Phytotherapy/methods ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Seeds ; Treatment Outcome ; Trigonella/chemistry
Chemical Substances	Blood Glucose ; Glycated Hemoglobin A ; Hypoglycemic Agents ; Lipids ; Plant Extracts ; fenugreek seed meal (68990-15-8) ; Glyburide (SX6K58TVWC)
Language	English
Publishing date	2019-05-23
Publishing country	Uganda
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2240308-5
ISSN	1729-0503 ; 1680-6905
ISSN (online)	1729-0503
ISSN	1680-6905
DOI	10.4314/ahs.v19i1.34
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Article ; Online: Wnt signaling and colon carcinogenesis

Rani Najdi / Randall F Holcombe / Marian L Waterman

Journal of Carcinogenesis, Vol 10, Iss 1, Pp 5-

Beyond APC

2011 Volume 5

Abstract	Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC) is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a singular event. Here we review how canonical Wnt signaling is modulated by intracellular LEF/TCF composition and location, the action of different Wnt ligands, and the secretion of Wnt inhibitory molecules. We also review the contributions of non-canonical Wnt signaling and other distinct pathways in the tumor micro environment that cross-talk to the canonical Wnt pathway and thereby influence colon cancer progression. These ′non-APC′ aspects of Wnt signaling are considered in relation to the development of potential agents for the treatment of patients with colon cancer. Regulatory pathways that influence Wnt signaling highlight how it might be possible to design therapies that target a network of signals beyond that of APC and β-catenin.
Keywords	Adenomatous polyposis coli gene ; colon carcinogenesis ; Wnt signaling ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	570
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Microdevice to capture colon crypts for in vitro studies.

Wang, Yuli / Dhopeshwarkar, Rahul / Najdi, Rani / Waterman, Marian L / Sims, Christopher E / Allbritton, Nancy

Lab on a chip

2010 Volume 10, Issue 12, Page(s) 1596–1603

Abstract: There is a need in biological research for tools designed to manipulate the environment surrounding microscopic regions of tissue. In the current work, a device for the oriented capture of an important and under-studied tissue, the colon crypt, has been ... ...

Abstract	There is a need in biological research for tools designed to manipulate the environment surrounding microscopic regions of tissue. In the current work, a device for the oriented capture of an important and under-studied tissue, the colon crypt, has been designed and tested. The objective of this work is to create a BioMEMs device for biological assays of living colonic crypts. The end goal will be to subject the polarized tissue to user-controlled fluidic microenvironments in a manner that recapitulates the in vivo state. Crypt surrogates, polymeric structures of similar dimensions and shape to isolated colon crypts, were used in the initial design and testing of the device. Successful capture of crypt surrogates was accomplished on a simple device composed of an array of micron-scale capture sites that enabled individual structures to be captured with high efficiency (92+/-3%) in an ordered and properly oriented fashion. The device was then evaluated using colon crypts isolated from a murine animal model. The capture efficiency attained using the fixed biologic sample was 37+/-5% due to the increased variability of the colon crypts compared with the surrogate structures, yet 94+/-3% of the captured crypts were properly oriented. A simple approach to plug the remaining capture sites in the array was performed using inert glass beads. Blockage of unfilled capture sites is an important feature to establish a chemical gradient across the arrayed crypts. A chemical concentration gradient (Cluminal/Cbasal>10) was demonstrated across the arrayed crypts for over 8 h. Finally unfixed colon crypts were demonstrated to be effectively captured by the micromesh array and to remain viable on the capture sites at 5 h after mouse sacrifice. The present study demonstrates the feasibility and potential for rationally microengineered technologies to address the specific needs of the biologic researcher.
MeSH term(s)	Animals ; Colon ; Histocytological Preparation Techniques/instrumentation ; Intestinal Mucosa ; Mice ; Microarray Analysis
Language	English
Publishing date	2010-04-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2056646-3
ISSN	1473-0189 ; 1473-0197
ISSN (online)	1473-0189
ISSN	1473-0197
DOI	10.1039/b927316f
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Article ; Online: A uniform human Wnt expression library reveals a shared secretory pathway and unique signaling activities.

Najdi, Rani / Proffitt, Kyle / Sprowl, Stephanie / Kaur, Simran / Yu, Jia / Covey, Tracy M / Virshup, David M / Waterman, Marian L

Differentiation; research in biological diversity

2012 Volume 84, Issue 2, Page(s) 203–213

Abstract: Wnt ligands are secreted morphogens that control multiple developmental processes during embryogenesis and adult homeostasis. A diverse set of receptors and signals have been linked to individual Wnts, but the lack of tools for comparative analysis has ... ...

Abstract	Wnt ligands are secreted morphogens that control multiple developmental processes during embryogenesis and adult homeostasis. A diverse set of receptors and signals have been linked to individual Wnts, but the lack of tools for comparative analysis has limited the ability to determine which of these signals are general for the entire Wnt family, and which define subsets of differently acting ligands. We have created a versatile Gateway library of clones for all 19 human Wnts. An analysis comparing epitope-tagged and untagged versions of each ligand shows that despite their similar expression at the mRNA level, Wnts exhibit considerable variation in stability, processing and secretion. At least 14 out of the 19 Wnts activate β-catenin-dependent signaling, an activity that is cell type-dependent and tracks with the stabilization of β-catenin and LRP6 phosphorylation. We find that the core Wnt modification and secretion proteins Porcupine (PORCN) and Wntless (WLS) are essential for all Wnts to signal through β-catenin-dependent and independent pathways. This comprehensive toolkit provides critical tools and new insights into human Wnt gene expression and function.
MeSH term(s)	3T3 Cells ; Acyltransferases ; Animals ; Gene Expression Profiling ; Gene Library ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Low Density Lipoprotein Receptor-Related Protein-6/metabolism ; Membrane Proteins/metabolism ; Mice ; Receptors, G-Protein-Coupled/metabolism ; Secretory Pathway ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Wnt Signaling Pathway ; beta Catenin/metabolism
Chemical Substances	Intracellular Signaling Peptides and Proteins ; LRP6 protein, human ; Low Density Lipoprotein Receptor-Related Protein-6 ; Membrane Proteins ; Receptors, G-Protein-Coupled ; WLS protein, human ; Wnt Proteins ; beta Catenin ; Acyltransferases (EC 2.3.-) ; PORCN protein, human (EC 2.3.1.-)
Language	English
Publishing date	2012-07-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	184540-8
ISSN	1432-0436 ; 0301-4681
ISSN (online)	1432-0436
ISSN	0301-4681
DOI	10.1016/j.diff.2012.06.004
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Article: A uniform human Wnt expression library reveals a shared secretory pathway and unique signaling activities

Najdi, Rani / Proffitt, Kyle / Sprowl, Stephanie / Kaur, Simran / Yu, Jia / Covey, Tracy M / Virshup, David M / Waterman, Marian L

Differentiation. 2012 Sept., v. 84, no. 2

2012

Abstract	Wnt ligands are secreted morphogens that control multiple developmental processes during embryogenesis and adult homeostasis. A diverse set of receptors and signals have been linked to individual Wnts, but the lack of tools for comparative analysis has limited the ability to determine which of these signals are general for the entire Wnt family, and which define subsets of differently acting ligands. We have created a versatile Gateway library of clones for all 19 human Wnts. An analysis comparing epitope-tagged and untagged versions of each ligand shows that despite their similar expression at the mRNA level, Wnts exhibit considerable variation in stability, processing and secretion. At least 14 out of the 19 Wnts activate β-catenin-dependent signaling, an activity that is cell type-dependent and tracks with the stabilization of β-catenin and LRP6 phosphorylation. We find that the core Wnt modification and secretion proteins Porcupine (PORCN) and Wntless (WLS) are essential for all Wnts to signal through β-catenin-dependent and independent pathways. This comprehensive toolkit provides critical tools and new insights into human Wnt gene expression and function.
Keywords	adults ; embryogenesis ; gene expression ; homeostasis ; humans ; messenger RNA ; molecular cloning ; phosphorylation ; receptors ; secretion
Language	English
Dates of publication	2012-09
Size	p. 203-213.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	184540-8
ISSN	1432-0436 ; 0301-4681
ISSN (online)	1432-0436
ISSN	0301-4681
DOI	10.1016/j.diff.2012.06.004
Database	NAL-Catalogue (AGRICOLA)

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Article: Ty3 capsid mutations reveal early and late functions of the amino-terminal domain.

Larsen, Liza S Z / Zhang, Min / Beliakova-Bethell, Nadejda / Bilanchone, Virginia / Lamsa, Anne / Nagashima, Kunio / Najdi, Rani / Kosaka, Kathryn / Kovacevic, Vuk / Cheng, Jianlin / Baldi, Pierre / Hatfield, G Wesley / Sandmeyer, Suzanne

Journal of virology

2007 Volume 81, Issue 13, Page(s) 6957–6972

Abstract: The Ty3 retrotransposon assembles into 50-nm virus-like particles that occur in large intracellular clusters in the case of wild-type (wt) Ty3. Within these particles, maturation of the Gag3 and Gag3-Pol3 polyproteins by Ty3 protease produces the ... ...

Abstract	The Ty3 retrotransposon assembles into 50-nm virus-like particles that occur in large intracellular clusters in the case of wild-type (wt) Ty3. Within these particles, maturation of the Gag3 and Gag3-Pol3 polyproteins by Ty3 protease produces the structural proteins capsid (CA), spacer, and nucleocapsid. Secondary and tertiary structure predictions showed that, like retroviral CA, Ty3 CA contains a large amount of helical structure arranged in amino-terminal and carboxyl-terminal bundles. Twenty-six mutants in which alanines were substituted for native residues were used to study CA subdomain functions. Transposition was measured, and particle morphogenesis and localization were characterized by analysis of protein processing, cDNA production, genomic RNA protection, and sedimentation and by fluorescence and electron microscopy. These measures defined five groups of mutants. Proteins from each group could be sedimented in a large complex. Mutations in the amino-terminal domain reduced the formation of fluorescent Ty3 protein foci. In at least one major homology region mutant, Ty3 protein concentrated in foci but no wt clusters of particles were observed. One mutation in the carboxyl-terminal domain shifted assembly from spherical particles to long filaments. Two mutants formed foci separate from P bodies, the proposed sites of assembly, and formed defective particles. P-body association was therefore found to be not necessary for assembly but correlated with the production of functional particles. One mutation in the amino terminus blocked transposition after cDNA synthesis. Our data suggest that Ty3 proteins are concentrated first, assembly associated with P bodies occurs, and particle morphogenesis concludes with a post-reverse transcription, CA-dependent step. Particle formation was generally resistant to localized substitutions, possibly indicating that multiple domains are involved.
MeSH term(s)	Amino Acid Substitution ; Capsid/metabolism ; DNA Polymerase III ; DNA, Complementary/biosynthesis ; DNA, Complementary/genetics ; Gene Products, gag/genetics ; Gene Products, gag/metabolism ; Inclusion Bodies/genetics ; Inclusion Bodies/metabolism ; Inclusion Bodies/ultrastructure ; Mutation, Missense ; Protein Structure, Secondary ; Protein Structure, Tertiary/genetics ; Retroelements/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae/ultrastructure ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	DNA, Complementary ; Gene Products, gag ; POL3 protein, S cerevisiae ; Retroelements ; Saccharomyces cerevisiae Proteins ; DNA Polymerase III (EC 2.7.7.-)
Language	English
Publishing date	2007-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02207-06
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