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Article ; Online: ATR Inhibitors and Paclitaxel in Melanoma.

Ashworth, Alan

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

2021 Volume 27, Issue 17, Page(s) 4667–4668

Abstract: A phase I study defined a tolerable combination of the ATR inhibitor ceralasertib with paclitaxel and responses were seen in patients with melanoma who had progressed on an immune checkpoint inhibitor. This combination warrants further exploration to ... ...

Abstract	A phase I study defined a tolerable combination of the ATR inhibitor ceralasertib with paclitaxel and responses were seen in patients with melanoma who had progressed on an immune checkpoint inhibitor. This combination warrants further exploration to determine the extent and molecular determinants of clinical activity.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Ataxia Telangiectasia Mutated Proteins ; Humans ; Melanoma/drug therapy ; Paclitaxel/adverse effects ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Protein Kinase Inhibitors ; ATR protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2021-06-25
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-1778
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Article: Biological insights and novel biomarker discovery through deep learning approaches in breast cancer histopathology.

Mandair, Divneet / Reis-Filho, Jorge S / Ashworth, Alan

NPJ breast cancer

2023 Volume 9, Issue 1, Page(s) 21

Abstract: Breast cancer remains a highly prevalent disease with considerable inter- and intra-tumoral heterogeneity complicating prognostication and treatment decisions. The utilization and depth of genomic, transcriptomic and proteomic data for cancer has ... ...

Abstract	Breast cancer remains a highly prevalent disease with considerable inter- and intra-tumoral heterogeneity complicating prognostication and treatment decisions. The utilization and depth of genomic, transcriptomic and proteomic data for cancer has exploded over recent times and the addition of spatial context to this information, by understanding the correlating morphologic and spatial patterns of cells in tissue samples, has created an exciting frontier of research, histo-genomics. At the same time, deep learning (DL), a class of machine learning algorithms employing artificial neural networks, has rapidly progressed in the last decade with a confluence of technical developments - including the advent of modern graphic processing units (GPU), allowing efficient implementation of increasingly complex architectures at scale; advances in the theoretical and practical design of network architectures; and access to larger datasets for training - all leading to sweeping advances in image classification and object detection. In this review, we examine recent developments in the application of DL in breast cancer histology with particular emphasis of those producing biologic insights or novel biomarkers, spanning the extraction of genomic information to the use of stroma to predict cancer recurrence, with the aim of suggesting avenues for further advancing this exciting field.
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2374-4677
ISSN	2374-4677
DOI	10.1038/s41523-023-00518-1
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Article ; Online: Cancer Research in 2030: A unique strategic planning process at a comprehensive cancer center.

Bank, Erin M / Small, Eric J / Ashworth, Alan / Hiatt, Robert A

Preventive oncology & epidemiology

2023 Volume 1, Issue 1, Page(s) 1–9

Abstract: Following the successful renewal of its Cancer Center Support Grant (CCSG), leadership of the UCSF Helen Diller Comprehensive Cancer Center (HDFCCC) began a strategic planning process. The motivation was to think about where cancer research was going in ... ...

Abstract	Following the successful renewal of its Cancer Center Support Grant (CCSG), leadership of the UCSF Helen Diller Comprehensive Cancer Center (HDFCCC) began a strategic planning process. The motivation was to think about where cancer research was going in the future; and with this vision to define a general scientific direction, mission, and priorities. HDFCCC Leadership began discussions about a new strategic plan in early 2018. From these meetings, the theme of "Cancer Research in 2030" arose: that is, what will cancer research look like in 2030? This forward-looking focus was intended to encourage creativity unconfined by a particular institutional structure or grant mechanism. Focusing on the science paved the way for an innovative, actionable, and motivating strategic planning process. Here, we describe the three-phase process, and the various groups involved across the HDFCCC and UCSF. We present the unique framework based on a cells-to-society model and an individual experience perspective, which led to the development of a logic model and ongoing implementation of tactics and tracking progress. We believe that sharing this process and its results will be of value to cancer centers and cancer researchers across the network of NCI comprehensive cancer centers, and cancer research centers in general.
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Journal Article
ISSN	2832-2134
ISSN (online)	2832-2134
DOI	10.1080/28322134.2023.2265563
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Article ; Online: An interview with Pharmacogenomics for the breast cancer special focus issue.

Ashworth, Alan

Pharmacogenomics

2012 Volume 13, Issue 6, Page(s) 651–654

MeSH term(s)	BRCA2 Protein ; Breast Neoplasms/genetics ; Breast Neoplasms/therapy ; Female ; Humans ; Pharmacogenetics
Chemical Substances	BRCA2 Protein
Language	English
Publishing date	2012-04-19
Publishing country	England
Document type	Interview
ZDB-ID	2019513-8
ISSN	1744-8042 ; 1462-2416
ISSN (online)	1744-8042
ISSN	1462-2416
DOI	10.2217/pgs.12.32
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Zs.A 5247: Show issues

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Article ; Online: Reducing the Risk of Cardiac Perforation During Placement of Bicaval Veno-Venous Extracorporeal Membrane Oxygenation Cannulae.

Charlesworth, Michael / Ashworth, Alan D

Journal of cardiothoracic and vascular anesthesia

2018 Volume 32, Issue 1, Page(s) e19–e20

MeSH term(s)	Cannula ; Catheters ; Extracorporeal Membrane Oxygenation ; Heart Injuries ; Humans ; Respiratory Insufficiency
Language	English
Publishing date	2018
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1067317-9
ISSN	1532-8422 ; 1053-0770
ISSN (online)	1532-8422
ISSN	1053-0770
DOI	10.1053/j.jvca.2017.09.003
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Zs.A 2203: 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)
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Article: The International Malnutrition Task Force: A model for the future?

Jackson, Alan / Ashworth, Ann / Annan, Reginald A.

Trends in food science & technology. 2022 Sept. 03,

2022

Abstract: The International Malnutrition Task Force (IMTF) of the International Union of Nutritional Sciences was set up as an advocacy and capacity-building initiative in 2005 at a time when malnutrition contributed to 60% of deaths among children under-five, and ...

Abstract	The International Malnutrition Task Force (IMTF) of the International Union of Nutritional Sciences was set up as an advocacy and capacity-building initiative in 2005 at a time when malnutrition contributed to 60% of deaths among children under-five, and when a reduction in under-five mortality by two thirds had been set as Millennium Development Goal 4. By forging partnerships through regional networks of academics, and linking with international agencies and non-governmental organizations, IMTF was able to increase awareness of the urgent need to address the prevention and treatment of child malnutrition. With modest funding, but a common purpose, partners initiated capacity building efforts to reduce high inpatient mortality rates among children admitted with severe malnutrition. In all regions, these initiatives catalysed scaling-up of the WHO 10-step treatment guidelines, resulting in substantial improvements in child survival. Many lessons were learned during this process including the importance of operational research, supervision and teamwork, and political commitment, and the potential of eLearning. By establishing alliances between academics, health professionals, policy makers, and national and international paediatric and nutrition societies through a Task Force, we suggest that similar benefits might accrue in other fields, including childhood cancer and school feeding.
Keywords	advocacy ; childhood ; children ; electronic learning ; food science ; issues and policy ; malnutrition ; models ; mortality ; nutrition ; operations research ; politics ; teams ; technology
Language	English
Dates of publication	2022-0903
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	1049246-x
ISSN	1879-3053 ; 0924-2244
ISSN (online)	1879-3053
ISSN	0924-2244
DOI	10.1016/j.tifs.2022.09.002
Database	NAL-Catalogue (AGRICOLA)

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Z 5184: Show issues

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Article ; Online: Synthetic lethal therapies for cancer: what's next after PARP inhibitors?

Ashworth, Alan / Lord, Christopher J

Nature reviews. Clinical oncology

2018 Volume 15, Issue 9, Page(s) 564–576

Abstract: The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline loss-of-function mutations in either ...

Abstract	The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline loss-of-function mutations in either BRCA1 or BRCA2. Three different PARP inhibitors have now been approved for the treatment of patients with BRCA-mutant ovarian cancer and one for those with BRCA-mutant breast cancer; these agents have also shown promising results in patients with BRCA-mutant prostate cancer. Here, we describe a number of other synthetic lethal interactions that have been discovered in cancer. We discuss some of the underlying principles that might increase the likelihood of clinical efficacy and how new computational and experimental approaches are now facilitating the discovery and validation of synthetic lethal interactions. Finally, we make suggestions on possible future directions and challenges facing researchers in this field.
MeSH term(s)	BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Loss of Function Mutation/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Poly(ADP-ribose) Polymerases/genetics ; Synthetic Lethal Mutations/genetics
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30)
Language	English
Publishing date	2018-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491410-1
ISSN	1759-4782 ; 1759-4774
ISSN (online)	1759-4782
ISSN	1759-4774
DOI	10.1038/s41571-018-0055-6
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Zs.A 6029: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 103: Show issues

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Article ; Online: De novo design of drug-binding proteins with predictable binding energy and specificity.

Lu, Lei / Gou, Xuxu / Tan, Sophia K / Mann, Samuel I / Yang, Hyunjun / Zhong, Xiaofang / Gazgalis, Dimitrios / Valdiviezo, Jesús / Jo, Hyunil / Wu, Yibing / Diolaiti, Morgan E / Ashworth, Alan / Polizzi, Nicholas F / DeGrado, William F

Science (New York, N.Y.)

2024 Volume 384, Issue 6691, Page(s) 106–112

Abstract: The de novo design of small molecule-binding proteins has seen exciting recent progress; however, high-affinity binding and tunable specificity typically require laborious screening and optimization after computational design. We developed a ... ...

Abstract	The de novo design of small molecule-binding proteins has seen exciting recent progress; however, high-affinity binding and tunable specificity typically require laborious screening and optimization after computational design. We developed a computational procedure to design a protein that recognizes a common pharmacophore in a series of poly(ADP-ribose) polymerase-1 inhibitors. One of three designed proteins bound different inhibitors with affinities ranging from <5 nM to low micromolar. X-ray crystal structures confirmed the accuracy of the designed protein-drug interactions. Molecular dynamics simulations informed the role of water in binding. Binding free energy calculations performed directly on the designed models were in excellent agreement with the experimentally measured affinities. We conclude that de novo design of high-affinity small molecule-binding proteins with tuned interaction energies is feasible entirely from computation.
MeSH term(s)	Binding Sites ; Drug Design/methods ; Ligands ; Molecular Dynamics Simulation ; Poly(ADP-ribose) Polymerase Inhibitors/chemistry ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Protein Binding ; Proteins/chemistry ; Humans
Chemical Substances	Ligands ; Poly(ADP-ribose) Polymerase Inhibitors ; Proteins
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adl5364
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Zs.A 27: 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)
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Article ; Online: Is the Invisibility of Dementia a Super-Power or a Curse? A Reflection on the SUNshiners' Questionnaire into the Public Understanding of Dementia as an Invisible Disability: A User-Led Research Project.

Tingley, Danielle / Ashworth, Rosalie / Torres Sanchez, Dalia / Mac Mahon, Grace Hayes / Kusel, Yvette / Rae, Brigitta Maria / Shorthouse, Tracey / Bartley, Alan / Howell, Gabrielle / Hurley, Joanne

International journal of environmental research and public health

2024 Volume 21, Issue 4

Abstract: The SUNshiners group includes people in the early stages of dementia with an interest in dementia activism and research. The group found that despite the growing awareness of invisible disabilities, there is very limited research into the pros and cons ... ...

Abstract	The SUNshiners group includes people in the early stages of dementia with an interest in dementia activism and research. The group found that despite the growing awareness of invisible disabilities, there is very limited research into the pros and cons of the invisibility of dementia. Our paper explores the SUNshiners research which stemmed from varied individual experiences of disclosing diagnoses. The group designed and developed a short survey to explore what the public knew about dementia and what they thought about the invisibility of dementia. A mixture of open- and closed-ended questions were used to gain meaningful data. A total of 347 people completed the survey (315 online and 32 paper-based), which was then co-analysed. The findings suggest that the majority of the public felt that the invisibility of dementia was negative; that knowing someone had dementia when first meeting them would be beneficial; that people living with dementia should maintain the right to vote; and that people living with dementia do not automatically require a consistent, regular carer. Common themes from the open-ended answers included capacity, severity of dementia, and access to support. The findings support the disclosure of dementia diagnosis; however, more action is needed to tackle stigmatised views, particularly as the SUNshiners felt that people do not have enough dementia education to support a positive disclosure experience. They shared their experiences of the group and the project's benefits, but also the losses they have faced. Our paper aims to be as accessible as possible.
MeSH term(s)	Humans ; Dementia/psychology ; Surveys and Questionnaires ; Female ; Male ; Aged ; Middle Aged ; Adult ; Disabled Persons/psychology ; Aged, 80 and over ; Young Adult ; Health Knowledge, Attitudes, Practice
Language	English
Publishing date	2024-04-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph21040466
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Article ; Online: PARP inhibitors: Synthetic lethality in the clinic.

Lord, Christopher J / Ashworth, Alan

Science (New York, N.Y.)

2017 Volume 355, Issue 6330, Page(s) 1152–1158

Abstract: PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry ... ...

Abstract	PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Protocols ; BRCA2 Protein/genetics ; Clinical Trials as Topic ; DNA Damage/genetics ; DNA Repair/genetics ; Germ-Line Mutation ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/chemistry ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Synthetic Lethal Mutations ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	Antineoplastic Agents ; BRCA2 Protein ; BRCA2 protein, human ; Poly(ADP-ribose) Polymerase Inhibitors ; BRAP protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2017-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aam7344
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Zs.A 27: 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)
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