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Article ; Online: The use of cinacalcet for the treatment of calciphylaxis in patients with chronic kidney disease: A comprehensive review.

Deen, Jacqueline / Schaider, Helmut

2019 Volume 60, Issue 3, Page(s) e186–e194

Abstract: Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists so far. In an attempt to avoid surgical intervention with parathyroidectomy, which ... ...

Abstract	Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists so far. In an attempt to avoid surgical intervention with parathyroidectomy, which is of questionable efficacy and carries several risks, a number of noninvasive treatments have been trialled with variable success. These treatments are aimed at modifying risk factors for calciphylaxis, in particular hypercalcaemia, hyperphosphataemia and hyperparathyroidism. The aim of this review was to summarise the available evidence to determine the potential role of cinacalcet in the treatment of calciphylaxis in patients with chronic kidney disease. Demographic, clinical and laboratory data were retrospectively collected from the available English and non-English literature. Overall, there was a very high response rate (partial or complete) of calciphylaxis lesions to both cinacalcet monotherapy and cinacalcet as part of a combination therapy (83.4% and 82.8%, respectively). When examining complete response to treatment specifically, combination therapy with cinacalcet proved more efficacious than monotherapy (62.1% versus 41.7%). There was also an associated rapid reduction of intact parathyroid hormone over a period of 2-33 months in both groups. While there are limitations as to how our data can be interpreted due to the heterogeneity of the methods and follow-up of the included case reports and case series, prompt and consistent therapy including cinacalcet may help improve the disease outcome. Additional research needs to be performed in this area, to further define the optimal use of cinacalcet for the treatment of calciphylaxis.
MeSH term(s)	Calciphylaxis/drug therapy ; Calcium-Regulating Hormones and Agents/therapeutic use ; Cinacalcet/therapeutic use ; Combined Modality Therapy ; Humans ; Renal Insufficiency, Chronic/complications
Chemical Substances	Calcium-Regulating Hormones and Agents ; Cinacalcet (UAZ6V7728S)
Language	English
Publishing date	2019-01-21
Publishing country	Australia
Document type	Journal Article ; Systematic Review
ZDB-ID	138052-7
ISSN	1440-0960 ; 0004-8380
ISSN (online)	1440-0960
ISSN	0004-8380
DOI	10.1111/ajd.12992
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Article ; Online: Distinct HOX Gene Family DNA Methylation Profiles in Histologically Normal Skin Dependent on Dermoscopic Pattern of Adjacent Nevi.

Muse, Meghan E / Schaider, Helmut / Oey, Harald / Soyer, H Peter / Christensen, Brock C / Stark, Mitchell S

The Journal of investigative dermatology

2023 Volume 143, Issue 9, Page(s) 1830–1834.e6

MeSH term(s)	Humans ; Genes, Homeobox ; DNA Methylation ; Nevus/pathology ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Dermoscopy
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.03.1653
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Article: Tumor cell-intrinsic phenotypic plasticity facilitates adaptive cellular reprogramming driving acquired drug resistance.

Hammerlindl, Heinz / Schaider, Helmut

Journal of cell communication and signaling

2017 Volume 12, Issue 1, Page(s) 133–141

Abstract: The enthusiasm about successful novel therapeutic strategies in cancer is often quickly dampened by the development of drug resistance. This is true for targeted therapies using tyrosine kinase inhibitors for EGFR or BRAF mutant cancers, but is also an ... ...

Abstract	The enthusiasm about successful novel therapeutic strategies in cancer is often quickly dampened by the development of drug resistance. This is true for targeted therapies using tyrosine kinase inhibitors for EGFR or BRAF mutant cancers, but is also an increasingly recognized problem for immunotherapies. One of the major obstacles of successful cancer therapy is tumor heterogeneity of genotypic and phenotypic features. Historically, drivers for drug resistance have been suspected and found on the genetic level, with mutations either being pre-existing in a subset of cancer cells or emerging de novo to mediate drug resistance. In contrast to that, our group and others identified a non-mutational adaptive response, resulting in a reversible, drug tolerant, slow cycling phenotype that precedes the emergence of permanent drug resistance and is triggered by prolonged drug exposure. More recently, studies described the importance of initially reversible transcriptional reprogramming for the development of acquired drug resistance, identified factors important for the survival of the slow cycling phenotype and investigated the relationship of mutational and non-mutational resistance mechanisms. However, the connection and relative importance of mutational and adaptive drug resistance in relation to the in vitro models at hand and the clinically observed response patterns remains poorly defined. In this review we focus on adaptive intrinsic phenotypic plasticity in cancer cells that leads to the drug tolerant slow cycling state, which eventually transitions to permanent resistance, and propose a general model based on current literature, to describe the development of acquired drug resistance.
Language	English
Publishing date	2017-11-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2299380-0
ISSN	1873-961X ; 1873-9601
ISSN (online)	1873-961X
ISSN	1873-9601
DOI	10.1007/s12079-017-0435-1
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Article ; Online: Microenvironment-Driven Resistance to BRAF Inhibition Comes of Age.

Menon, Dinoop Ravindran / Schaider, Helmut

The Journal of investigative dermatology

2015 Volume 135, Issue 12, Page(s) 2923–2925

Abstract: Increasingly comprehensive observations indicate that the tumor microenvironment contributes to drug resistance toward small molecule inhibitors. Fedorenko et al. describe a role for fibroblasts in creating a favorable niche for melanoma cell survival if ...

Abstract	Increasingly comprehensive observations indicate that the tumor microenvironment contributes to drug resistance toward small molecule inhibitors. Fedorenko et al. describe a role for fibroblasts in creating a favorable niche for melanoma cell survival if treated with the BRAF inhibitor vemurafenib. TGF-β released by vemurafenib-treated melanoma cells stimulated fibroblasts for increased α-smooth muscle actin, neuregulin (NRG), and fibronectin expression. Off-target effects of vemurafenib led to paradoxical secretion of hepatocyte growth factor (HGF) by fibroblasts. Combined inhibition of BRAF/MET/HER kinases was insufficient to reverse the protective effect of the fibroblasts, whereas reversal was achieved by combined BRAF/PI3K inhibition. A thorough understanding of the complex spatiotemporal interactions in tumor microenvironments holds promise for improved targeting using combination therapies in patients with melanoma.
MeSH term(s)	Humans ; Melanoma/drug therapy ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors
Chemical Substances	Protein Kinase Inhibitors ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2015-12
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1038/jid.2015.373
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Article ; Online: Emerging roles of H3K9me3, SETDB1 and SETDB2 in therapy-induced cellular reprogramming.

Torrano, Joachim / Al Emran, Abdullah / Hammerlindl, Heinz / Schaider, Helmut

Clinical epigenetics

2019 Volume 11, Issue 1, Page(s) 43

Abstract: Background: A multitude of recent studies has observed common epigenetic changes develop in tumour cells of multiple lineages following exposure to stresses such as hypoxia, chemotherapeutics, immunotherapy or targeted therapies. A significant increase ... ...

Abstract	Background: A multitude of recent studies has observed common epigenetic changes develop in tumour cells of multiple lineages following exposure to stresses such as hypoxia, chemotherapeutics, immunotherapy or targeted therapies. A significant increase in the transcriptionally repressive mark trimethylated H3K9 (H3K9me3) is becoming associated with treatment-resistant phenotypes suggesting upstream mechanisms may be a good target for therapy. We have reported that the increase in H3K9me3 is derived from the methyltransferases SETDB1 and SETDB2 following treatment in melanoma, lung, breast and colorectal cancer cell lines, as well as melanoma patient data. Other groups have observed a number of characteristics such as epigenetic remodelling, increased interferon signalling, cell cycle inhibition and apoptotic resistance that have also been reported by us suggesting these independent studies are investigating similar or identical phenomena. Main body: Firstly, this review introduces reports of therapy-induced reprogramming in cancer populations with highly similar slow-cycling phenotypes that suggest a role for both IFN signalling and epigenetic remodelling in the acquisition of drug tolerance. We then describe plausible connections between the type 1 IFN pathway, slow-cycling phenotypes and these epigenetic mechanisms before reviewing recent evidence on the roles of SETDB1 and SETDB2, alongside their product H3K9me3, in treatment-induced reprogramming and promotion of drug resistance. The potential mechanisms for the activation of SETDB1 and SETDB2 and how they might arise in treatment is also discussed mechanistically, with a focus on their putative induction by inflammatory signalling. Moreover, we theorise their timely role in attenuating inflammation after their activation in order to promote a more resilient phenotype through homeostatic coordination of H3K9me3. We also examine the relatively uncharacterized functions of SETDB2 with some comparison to the more well-known qualities of SETDB1. Finally, an emerging overall mechanism for the epigenetic maintenance of this transient phenotype is outlined by summarising the collective literature herein. Conclusion: A number of converging phenotypes outline a stress-responsive mechanism for SETDB1 and SETDB2 activation and subsequent increased survival, providing novel insights into epigenetic biology. A clearer understanding of how SETDB1/2-mediated transcriptional reprogramming can subvert treatment responses will be invaluable in improving length and efficacy of modern therapies.
MeSH term(s)	Animals ; Cellular Reprogramming ; Drug Resistance, Neoplasm ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/metabolism ; Humans ; Interferon Type I/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Phenotype ; Signal Transduction
Chemical Substances	Histones ; Interferon Type I ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; SETDB1 protein, human (EC 2.1.1.43) ; SETDB2 protein, human (EC 2.1.1.43)
Language	English
Publishing date	2019-03-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-019-0644-y
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Article ; Online: Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer.

Ravindran Menon, Dinoop / Hammerlindl, Heinz / Torrano, Joachim / Schaider, Helmut / Fujita, Mayumi

Theranostics

2020 Volume 10, Issue 14, Page(s) 6261–6277

Abstract: Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic ... ...

Abstract	Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic process involving phenotypic plasticity and tumor heterogeneity in the evolution of acquired drug resistance. Chronic stress after drug treatment induces intrinsic cellular reprogramming and cancer stemness through a slow-cycling persister state, which subsequently drives cancer progression. Both epigenetic and metabolic mechanisms play an important role in this dynamic process. In this review, we discuss how epigenetic and metabolic reprogramming leads to stress-induced phenotypic plasticity and acquired drug resistance, and how the two reprogramming mechanisms crosstalk with each other.
MeSH term(s)	Animals ; Cell Plasticity/physiology ; Cellular Reprogramming/physiology ; Drug Resistance, Neoplasm ; Epigenesis, Genetic ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Stem Cells/pathology ; Stress, Physiological
Language	English
Publishing date	2020-05-15
Publishing country	Australia
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.42523
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Article ; Online: Skin cancer excisions and histopathology outcomes when following a contemporary population-based cohort longitudinally with 3D total-body photography.

Soyer, H Peter / O'Hara, Montana / V Silva, Carina / Horsham, Caitlin / Jayasinghe, Dilki / Sanjida, Saira / Schaider, Helmut / Aitken, Joanne / Sturm, Richard A / Prow, Tarl / Menzies, Scott W / Janda, Monika

Skin health and disease

2023 Volume 3, Issue 2, Page(s) e216

Abstract: Background: Skin cancer represents a significant health burden across the globe and early detection is critical to improve health outcomes. Three-dimensional (3D) total-body photography is a new and emerging technology which can support clinicians when ... ...

Abstract	Background: Skin cancer represents a significant health burden across the globe and early detection is critical to improve health outcomes. Three-dimensional (3D) total-body photography is a new and emerging technology which can support clinicians when they monitor people's skin over time. Objectives: The aim of this study was to improve our understanding of the epidemiology and natural history of melanocytic naevi in adults, and their relationship with melanoma and other skin cancers. Methods: Mind Your Moles was a 3-year prospective, population-based cohort study which ran from December 2016 to February 2020. Participants visited the Princess Alexandra Hospital every 6 months for 3 years to undergo both a clinical skin examination and 3D total-body photography. Results: A total of 1213 skin screening imaging sessions were completed. Fifty-six percent of participants ( Conclusions: 3D total-body imaging results in diagnosis of a high number of keratinocyte cancers (KCs) and their precursors in the general population.
Language	English
Publishing date	2023-01-22
Publishing country	England
Document type	Journal Article
ISSN	2690-442X
ISSN (online)	2690-442X
DOI	10.1002/ski2.216
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Article ; Online: The Experience of 3D Total-Body Photography to Monitor Nevi: Results From an Australian General Population-Based Cohort Study.

Horsham, Caitlin / O'Hara, Montana / Sanjida, Saira / Ma, Samantha / Jayasinghe, Dilki / Green, Adele C / Schaider, Helmut / Aitken, Joanne F / Sturm, Richard A / Prow, Tarl / Soyer, H Peter / Janda, Monika

JMIR dermatology

2022 Volume 5, Issue 2, Page(s) e37034

Abstract: Background: Digital 3D total-body photography of the skin surface is an emerging imaging modality that can facilitate the identification of new and changing nevi.: Objective: We aimed to describe the experiences of study participants drawn from the ... ...

Abstract	Background: Digital 3D total-body photography of the skin surface is an emerging imaging modality that can facilitate the identification of new and changing nevi. Objective: We aimed to describe the experiences of study participants drawn from the general population who were provided 3D total-body photography and dermoscopy for the monitoring of nevi. Methods: A population-based prospective study of adults aged 20-70 years from South East Queensland, Australia was conducted. Participants underwent 3D total-body photography and dermoscopy every 6 months over a 3-year period. Participants were asked to provide closed and open-ended feedback on their 3D total-body photography and dermoscopy experience (eg, comfort, trust, intended future use, and willingness to pay) at the halfway study time point (18 months) and final study time point (36 months). We assessed changes in participants' reported experience of 3D total-body photography, and patient characteristics associated with patient experience at the end of the study (36 months) were analyzed. Results: A total of 149 participants completed the surveys at both the 18- and 36-month time points (median age 55, range 23-70 years; n=94, 63.1% were male). At the 18-month time point, most participants (n=103, 69.1%) stated they completely trusted 3D total-body imaging for the diagnosis and monitoring of their nevi, and this did not change at the 36-month (n=104, 69.8%) time point. The majority of participants reported that they were very comfortable or comfortable with the technology at both the 18- (n=138, 92.6%) and 36-month (n=140, 94%) time points, respectively; albeit, the number of participants reporting that they were very comfortable reduced significantly between the 18- and 36-month time points, from 71.1% (n=106) to 61.1% (n=91; P=.01). Almost all participants (n=140, 94%) would consider using this technology if it were to become commercially available, and this did not change during the two study time points. Half of the participants (n=74) cited barriers to participating in 3D total-body photography, including trust in the ability of this technology to detect and monitor suspicious lesions, digital privacy, cost, and travel requirements. Conclusions: The majority of participants expressed positive attitudes toward 3D total-body photography for the monitoring of their moles. Half of the participants identified potential barriers to uptake.
Language	English
Publishing date	2022-06-20
Publishing country	Canada
Document type	Journal Article
ISSN	2562-0959
ISSN (online)	2562-0959
DOI	10.2196/37034
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Article: In-Depth Characterisation of Real-World Advanced Melanoma Patients Receiving Immunotherapies and/or Targeted Therapies: A Case Series.

Sanjida, Saira / Betz-Stablein, Brigid / Atkinson, Victoria / Janda, Monika / Barsoum, Ramez / Edwards, Harrison Aljian / Chiu, Frank / Tran, My Co / Soyer, H Peter / Schaider, Helmut

Cancers

2022 Volume 14, Issue 11

Abstract: Immunotherapies and targeted therapies have shown significant benefits for melanoma survival in the clinical trial setting. Much less is known about the characteristics and associated outcomes of those receiving such therapies in real-world settings. ... ...

Abstract	Immunotherapies and targeted therapies have shown significant benefits for melanoma survival in the clinical trial setting. Much less is known about the characteristics and associated outcomes of those receiving such therapies in real-world settings. This study describes the characteristics of patients with advanced melanoma receiving immuno- and/or targeted therapies in a real-world setting. This prospective cohort study enrolled participants aged >18 years, diagnosed with advanced melanoma and currently undergoing immuno- and/or targeted therapies outside a clinical trial for follow-up with three-dimensional (3D) total-body imaging. Participants (n = 41) had a mean age of 62 years (range 29−86), 26 (63%) were male and the majority (n = 26, 63%) had ≥2 comorbidities. After a median of 39 months (range 1−52) follow-up, 59% (n = 24/41) of participants were alive. Despite multiple co-morbidities, the survival of participants with advanced melanoma treated using immuno- and/or targeted therapies was similar or better in our real-world setting compared to those treated in clinical trials using similar therapies. Larger studies powered to evaluate phenotypic and socio-economic characteristics, as well as specific comorbidities associated with survival in a real-world setting, are required to help determine those who will most benefit from immuno- and/or targeted therapies.
Language	English
Publishing date	2022-06-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14112801
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Article ; Online: Chemoprevention of cutaneous squamous cell carcinoma and its precursors in solid organ transplant recipients using topical sirolimus: A randomized, double-blind, placebo-controlled pilot trial.

Chong, Sharene / Wong, Ho Yi / Althabteh, Ahmad / Cox, Charlotte / Stevenson, Paul H / Brown, Susan / Griffin, Anthony / Isbel, Nicole / Siller, Gregory / Soyer, H Peter / Schaider, Helmut / Roy, Edwige / Campbell, Scott / Green, Adele C / Khosrotehrani, Kiarash

Journal of the American Academy of Dermatology

2022 Volume 87, Issue 5, Page(s) 1163–1166

MeSH term(s)	Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/prevention & control ; Chemoprevention ; Double-Blind Method ; Humans ; Organ Transplantation/adverse effects ; Pilot Projects ; Sirolimus/adverse effects ; Skin Neoplasms/drug therapy ; Skin Neoplasms/prevention & control ; Transplant Recipients
Chemical Substances	Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	603641-7
ISSN	1097-6787 ; 0190-9622
ISSN (online)	1097-6787
ISSN	0190-9622
DOI	10.1016/j.jaad.2022.02.039
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