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Article ; Online: Crystal Clear: Decoding Isocyanide Intermolecular Interactions through Crystallography.

Chatziorfanou, Eleftheria / Romero, Atilio Reyes / Chouchane, Lotfi / Dömling, Alexander

2024 Volume 89, Issue 2, Page(s) 957–974

Abstract: The isocyanide group is the chameleon among the functional groups in organic chemistry. Unlike other multiatom functional groups, where the electrophilic and nucleophilic moieties are typically separated, isocyanides combine both functionalities in the ... ...

Abstract	The isocyanide group is the chameleon among the functional groups in organic chemistry. Unlike other multiatom functional groups, where the electrophilic and nucleophilic moieties are typically separated, isocyanides combine both functionalities in the terminal carbon. This unique feature can be rationalized using the frontier orbital concept and has significant implications for its intermolecular interactions and the reactivity of the functional group. In this study, we perform a Cambridge Crystallographic Database-supported analysis of isocyanide intramolecular interactions to investigate the intramolecular interactions of isocyanides in the solid state, excluding isocyanide-metal complexes. We discuss examples of different interaction classes, including the isocyanide as a hydrogen bond acceptor (RNC···HX), halogen bonding (RNC···X), and interactions involving the isocyanide and carbon atoms (RNC···C). The latter interaction serves as an intriguing illustration of a Bürgi-Dunitz trajectory and represents a crucial experimental detail in the well-known multicomponent reactions such as the Ugi- and Passerini-type mechanisms. Understanding the spectrum of intramolecular interactions that isocyanides can undergo holds significant implications in fields such as medicinal chemistry, materials science, and asymmetric catalysis.
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	123490-0
ISSN	1520-6904 ; 0022-3263
ISSN (online)	1520-6904
ISSN	0022-3263
DOI	10.1021/acs.joc.3c02038
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Article ; Online: Ethnic and functional differentiation of copy number polymorphisms in Tunisian and HapMap population unveils insights on genome organizational plasticity.

Romdhane, Lilia / Kefi, Sameh / Mezzi, Nessrine / Abassi, Najla / Jmel, Haifa / Romdhane, Safa / Shan, Jingxuan / Chouchane, Lotfi / Abdelhak, Sonia

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4654

Abstract: Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In ... ...

Abstract	Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In this investigation, the "Canary" algorithm was applied to 102 Tunisian samples and 991 individuals from eleven HapMap III populations to genotype 1279 copy number polymorphisms (CNPs). In this present work, we investigate the Tunisian population structure using the CNP makers previously identified among Tunisian. The study revealed that Sub-Saharan African populations exhibited the highest diversity with the highest proportions of allelic CNPs. Among all the African populations, Tunisia showed the least diversity. Individual ancestry proportions computed using STRUCTURE analysis revealed a major European component among Tunisians with lesser contribution from Sub-Saharan Africa and Asia. Population structure analysis indicated the genetic proximity with Europeans and noticeable distance from the Sub-Saharan African and East Asian clusters. Seven genes harbouring Tunisian high-frequent CNPs were identified known to be associated with 9 Mendelian diseases and/or phenotypes. Functional annotation of genes under selection highlighted a noteworthy enrichment of biological processes to receptor pathway and activity as well as glutathione metabolism. Additionally, pathways of potential concern for health such as drug metabolism, infectious diseases and cancers exhibited significant enrichment. The distinctive genetic makeup of the Tunisians might have been influenced by various factors including natural selection and genetic drift, resulting in the development of distinct genetic variations playing roles in specific biological processes. Our research provides a justification for focusing on the exclusive genome organization of this population and uncovers previously overlooked elements of the genome.
MeSH term(s)	Humans ; DNA Copy Number Variations ; HapMap Project ; Genotype ; Genome ; Genetics, Population ; Polymorphism, Single Nucleotide ; North African People
Language	English
Publishing date	2024-02-26
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/s41598-024-54749-8
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Article: Functional Genomic Analysis of Breast Cancer Metastasis: Implications for Diagnosis and Therapy.

Yu, Ziqi / Song, Mei / Chouchane, Lotfi / Ma, Xiaojing

Cancers

2021 Volume 13, Issue 13

Abstract: Breast cancer (BC) is one of the most diagnosed cancers worldwide and is the second cause of cancer related death in women. The most frequent cause of BC-related deaths, like many cancers, is metastasis. However, metastasis is a complicated and poorly ... ...

Abstract	Breast cancer (BC) is one of the most diagnosed cancers worldwide and is the second cause of cancer related death in women. The most frequent cause of BC-related deaths, like many cancers, is metastasis. However, metastasis is a complicated and poorly understood process for which there is a shortage of accurate prognostic indicators and effective treatments. With the rapid and ever-evolving development and application of genomic sequencing technologies, many novel molecules were identified that play previously unappreciated and important roles in the various stages of metastasis. In this review, we summarize current advancements in the functional genomic analysis of BC metastasis and discuss about the potential prognostic and therapeutic implications from the recent genomic findings.
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13133276
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Article ; Online: Comprehensive Characterization of Protein Turnover by Comparative SILAC Labeling Analysis in 3T3-L1.

Choi, Sunkyu / Romero, Atilio Reyes / Mashood, Fathima / Goswami, Neha / Chouchane, Lotfi / Schmidt, Frank

Journal of proteome research

2023 Volume 22, Issue 6, Page(s) 1723–1733

Abstract: A balance between the synthesis and degradation of proteins is referred to as protein turnover, which is crucial for cellular protein homeostasis. Proteome-wide analysis of protein turnover in adipocytes, which are well-known for their role in energy ... ...

Abstract	A balance between the synthesis and degradation of proteins is referred to as protein turnover, which is crucial for cellular protein homeostasis. Proteome-wide analysis of protein turnover in adipocytes, which are well-known for their role in energy storage and their link to obesity and metabolism disorders, is yet to be conducted. Thus, with this objective in mind, our investigation utilized a comparative analysis of time-dependent SILAC labeling to assess protein turnover in 3T3-L1 adipocytes, spanning a period of 0 to 144 h. We observed that relatively faster or slower protein half-lives in several protein groups were associated with the PPARγ signaling pathway, energy metabolism, extracellular matrix, ubiquitin-proteasome system, RNA splicing, Golgi complex, and lysosome. It is anticipated that these protein half-life profiles will provide greater clarity on the life cycle of adipocyte proteome and shed light on how they maintain protein homeostasis.
MeSH term(s)	Animals ; Mice ; Proteome/genetics ; Proteome/metabolism ; 3T3-L1 Cells ; Adipocytes/metabolism ; Proteolysis ; Proteasome Endopeptidase Complex/metabolism ; Cell Differentiation
Chemical Substances	Proteome ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.2c00763
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Article ; Online: Targeting UBR5 inhibits postsurgical breast cancer lung metastases by inducing CDC73 and p53 mediated apoptosis.

Yu, Ziqi / Dong, Xue / Song, Mei / Xu, Aizhang / He, Qing / Li, Huilin / Ouyang, Wen / Chouchane, Lotfi / Ma, Xiaojing

International journal of cancer

2023 Volume 154, Issue 4, Page(s) 723–737

Abstract: UBR5 is a HECT domain E3 ubiquitin ligase that is frequently amplified in breast, ovarian and prostate cancers. Heightened UBR5 expression plays a profound role in tumor growth through immune-dependent mechanisms; however, its mode of action in driving ... ...

Abstract	UBR5 is a HECT domain E3 ubiquitin ligase that is frequently amplified in breast, ovarian and prostate cancers. Heightened UBR5 expression plays a profound role in tumor growth through immune-dependent mechanisms; however, its mode of action in driving tumor metastasis has not been definitively delineated. Herein, we used a tetracycline (Tet)-inducible RNAi-mediated expression silencing cell system to investigate how UBR5 enables postsurgical mammary tumor metastatic growth in mouse lungs without the continuous influence of the primary lesion. In vitro, Ubr5 knockdown induces morphological and molecular changes characteristic of epithelial-mesenchymal transition (EMT). In vivo, UBR5 promotes lung metastasis in an E3 ubiquitin ligase-dependent manner. Moreover, doxycycline-induced UBR5 expression knockdown in metastatic cells in the lungs, following removing the primary tumors, resulted in increased apoptosis, decreased proliferation and prolonged survival, whereas silencing the expression of cell division cycle 73 (CDC73), a tumor suppressor and E3 ligase substrate of UBR5, reversed these effects. Transcriptome analyses revealed a prominent role of the p53 pathway in dovitinib-induced apoptosis of tumor cells differentially regulated by UBR5 and CDC73. In human triple-negative breast cancer (TNBC) patient specimens, a strong inverse correlation was observed between UBR5 and CDC73 protein levels, with reduced CDC73 expression at metastatic sites compared to primary lesions. Furthermore, a xenograft model of human TNBC recapitulated the metastatic properties and characteristics of the unique UBR5-CDC73 functional antagonism. This study reveals the novel and critical roles and intricate relationships of UBR5, CDC73 and p53 in postsurgical breast cancer metastasis and indicates the potential of targeting this pathway in cancer therapy.
MeSH term(s)	Animals ; Humans ; Male ; Mice ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Lung Neoplasms/genetics ; Triple Negative Breast Neoplasms/pathology ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	CDC73 protein, human ; Tumor Suppressor Protein p53 ; Tumor Suppressor Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; UBR5 protein, human (EC 2.3.2.26) ; TP53 protein, human
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34769
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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 ; Online: Discovery of new therapeutic targets in ovarian cancer through identifying significantly non-mutated genes.

Al-Farsi, Halema / Al-Azwani, Iman / Malek, Joel A / Chouchane, Lotfi / Rafii, Arash / Halabi, Najeeb M

Journal of translational medicine

2022 Volume 20, Issue 1, Page(s) 244

Abstract: Background: Mutated and non-mutated genes interact to drive cancer growth and metastasis. While research has focused on understanding the impact of mutated genes on cancer biology, understanding non-mutated genes that are essential to tumor development ... ...

Abstract	Background: Mutated and non-mutated genes interact to drive cancer growth and metastasis. While research has focused on understanding the impact of mutated genes on cancer biology, understanding non-mutated genes that are essential to tumor development could lead to new therapeutic strategies. The recent advent of high-throughput whole genome sequencing being applied to many different samples has made it possible to calculate if genes are significantly non-mutated in a specific cancer patient cohort. Methods: We carried out random mutagenesis simulations of the human genome approximating the regions sequenced in the publicly available Cancer Growth Atlas Project for ovarian cancer (TCGA-OV). Simulated mutations were compared to the observed mutations in the TCGA-OV cohort and genes with the largest deviations from simulation were identified. Pathway analysis was performed on the non-mutated genes to better understand their biological function. We then compared gene expression, methylation and copy number distributions of non-mutated and mutated genes in cell lines and patient data from the TCGA-OV project. To directly test if non-mutated genes can affect cell proliferation, we carried out proof-of-concept RNAi silencing experiments of a panel of nine selected non-mutated genes in three ovarian cancer cell lines and one primary ovarian epithelial cell line. Results: We identified a set of genes that were mutated less than expected (non-mutated genes) and mutated more than expected (mutated genes). Pathway analysis revealed that non-mutated genes interact in cancer associated pathways. We found that non-mutated genes are expressed significantly more than mutated genes while also having lower methylation and higher copy number states indicating that they could be functionally important. RNAi silencing of the panel of non-mutated genes resulted in a greater significant reduction of cell viability in the cancer cell lines than in the non-cancer cell line. Finally, as a test case, silencing ANKLE2, a significantly non-mutated gene, affected the morphology, reduced migration, and increased the chemotherapeutic response of SKOV3 cells. Conclusion: We show that we can identify significantly non-mutated genes in a large ovarian cancer cohort that are well-expressed in patient and cell line data and whose RNAi-induced silencing reduces viability in three ovarian cancer cell lines. Targeting non-mutated genes that are important for tumor growth and metastasis is a promising approach to expand cancer therapeutic options.
MeSH term(s)	Base Sequence ; Carcinoma, Ovarian Epithelial/genetics ; Female ; Genome ; Humans ; Mutation/genetics ; Ovarian Neoplasms/genetics
Language	English
Publishing date	2022-05-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-022-03440-5
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Article ; Online: Health influenced by genetics: A first comprehensive analysis of breast cancer high and moderate penetrance susceptibility genes in the Tunisian population.

Boujemaa, Maroua / Mighri, Najah / Chouchane, Lotfi / Boubaker, Mohamed Samir / Abdelhak, Sonia / Boussen, Hamouda / Hamdi, Yosr

PloS one

2022 Volume 17, Issue 3, Page(s) e0265638

Abstract: Significant advances have been made to understand the genetic basis of breast cancer. High, moderate and low penetrance variants have been identified with inter-ethnic variability in mutation frequency and spectrum. Genome wide association studies (GWAS) ...

Abstract	Significant advances have been made to understand the genetic basis of breast cancer. High, moderate and low penetrance variants have been identified with inter-ethnic variability in mutation frequency and spectrum. Genome wide association studies (GWAS) are widely used to identify disease-associated SNPs. Understanding the functional impact of these risk-SNPs will help the translation of GWAS findings into clinical interventions. Here we aim to characterize the genetic patterns of high and moderate penetrance breast cancer susceptibility genes and to assess the functional impact of non-coding SNPs. We analyzed BRCA1/2, PTEN, STK11, TP53, ATM, BRIP1, CHEK2 and PALB2 genotype data obtained from 135 healthy participants genotyped using Affymetrix Genome-Wide Human SNP-Array 6.0. Haplotype analysis was performed using Haploview.V4.2 and PHASE.V2.1. Population structure and genetic differentiation were assessed using principal component analysis (PCA) and fixation index (FST). Functional annotation was performed using In Silico web-based tools including RegulomeDB and VARAdb. Haplotype analysis showed distinct LD patterns with high levels of recombination and haplotype blocks of moderate to small size. Our findings revealed also that the Tunisian population tends to have a mixed origin with European, South Asian and Mexican footprints. Functional annotation allowed the selection of 28 putative regulatory variants. Of special interest were BRCA1_ rs8176318 predicted to alter the binding sites of a tumor suppressor miRNA hsa-miR-149 and PALB2_ rs120963 located in tumorigenesis-associated enhancer and predicted to strongly affect the binding of P53. Significant differences in allele frequencies were observed with populations of African and European ancestries for rs8176318 and rs120963 respectively. Our findings will help to better understand the genetic basis of breast cancer by guiding upcoming genome wide studies in the Tunisian population. Putative functional SNPs may be used to develop an efficient polygenic risk score to predict breast cancer risk leading to better disease prevention and management.
MeSH term(s)	Breast Neoplasms/epidemiology ; Breast Neoplasms/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; MicroRNAs ; Penetrance ; Polymorphism, Single Nucleotide
Chemical Substances	MIRN149 microRNA, human ; MicroRNAs
Language	English
Publishing date	2022-03-25
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.0265638
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Article ; Online: THE FUTURE OF MEDICINE, healthcare innovation through precision medicine: policy case study of Qatar.

Qoronfleh, M Walid / Chouchane, Lotfi / Mifsud, Borbala / Al Emadi, Maryam / Ismail, Said

Life sciences, society and policy

2020 Volume 16, Issue 1, Page(s) 12

Abstract: In 2016, the World Innovation Summit for Health (WISH) published its Forum Report on precision medicine "PRECISION MEDICINE - A GLOBAL ACTION PLAN FOR IMPACT". Healthcare is undergoing a transformation, and it is imperative to leverage new technologies ... ...

Abstract	In 2016, the World Innovation Summit for Health (WISH) published its Forum Report on precision medicine "PRECISION MEDICINE - A GLOBAL ACTION PLAN FOR IMPACT". Healthcare is undergoing a transformation, and it is imperative to leverage new technologies to generate new data and support the advent of precision medicine (PM). Recent scientific breakthroughs and technological advancements have improved our disease knowledge and altered diagnosis and treatment approaches resulting in a more precise, predictive, preventative and personalized health care that is customized for the individual patient. Consequently, the big data revolution has provided an opportunity to apply artificial intelligence and machine learning algorithms to mine such a vast data set. Additionally, personalized medicine promises to revolutionize healthcare, with its key goal of providing the right treatment to the right patient at the right time and dose, and thus the potential of improving quality of life and helping to bring down healthcare costs.This policy briefing will look in detail at the issues surrounding continued development, sustained investment, risk factors, testing and approval of innovations for better strategy and faster process. The paper will serve as a policy bridge that is required to enhance a conscious decision among the powers-that-be in Qatar in order to find a way to harmonize multiple strands of activity and responsibility in the health arena. The end goal will be for Qatar to enhance public awareness and engagement and to integrate effectively the incredible advances in research into healthcare systems, for the benefit of all patients.The PM policy briefing provides concrete recommendations on moving forward with PM initiatives in Qatar and internationally. Equally important, integration of PM within a primary care setting, building a coalition of community champions through awareness and advocacy, finally, communicating PM value, patient engagement/empowerment and education/continued professional development programs of the healthcare workforce.Key recommendations for implementation of precision medicine inside and outside Qatar: 1. Create Community Awareness and PM Education Programs 2. Engage and Empower Patients 3. Communicate PM Value 4. Develop appropriate Infrastructure and Information Management Systems 5. Integrate PM into standard Healthcare System and Ensure Access to Care PM is no longer futuristic. It is here. Implementing PM in routine clinical care does require some investment and infrastructure development. Invariably, cost and lack of expertise are cited as barriers to PM implementation. Equally consequential, are the curriculum and professional development of medical care experts.Policymakers need to lead and coordinate effort among stakeholders and consider cultural and faith perspectives to ensure success. It is essential that policymakers integrate PM approaches into national strategies to improve health and health care for all, and to drive towards the future of medicine precision health.
MeSH term(s)	Health Policy ; Humans ; Precision Medicine ; Qatar
Language	English
Publishing date	2020-11-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2711762-5
ISSN	2195-7819 ; 2195-7819
ISSN (online)	2195-7819
ISSN	2195-7819
DOI	10.1186/s40504-020-00107-1
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Article ; Online: Angiocrine endothelium: from physiology to cancer.

Pasquier, Jennifer / Ghiabi, Pegah / Chouchane, Lotfi / Razzouk, Kais / Rafii, Shahin / Rafii, Arash

Journal of translational medicine

2020 Volume 18, Issue 1, Page(s) 52

Abstract: The concept of cancer as a cell-autonomous disease has been challenged by the wealth of knowledge gathered in the past decades on the importance of tumor microenvironment (TM) in cancer progression and metastasis. The significance of endothelial cells ( ... ...

Abstract	The concept of cancer as a cell-autonomous disease has been challenged by the wealth of knowledge gathered in the past decades on the importance of tumor microenvironment (TM) in cancer progression and metastasis. The significance of endothelial cells (ECs) in this scenario was initially attributed to their role in vasculogenesis and angiogenesis that is critical for tumor initiation and growth. Nevertheless, the identification of endothelial-derived angiocrine factors illustrated an alternative non-angiogenic function of ECs contributing to both physiological and pathological tissue development. Gene expression profiling studies have demonstrated distinctive expression patterns in tumor-associated endothelial cells that imply a bilateral crosstalk between tumor and its endothelium. Recently, some of the molecular determinants of this reciprocal interaction have been identified which are considered as potential targets for developing novel anti-angiocrine therapeutic strategies.
MeSH term(s)	Endothelial Cells ; Endothelium ; Humans ; Neoplasms/genetics ; Neovascularization, Pathologic ; Tumor Microenvironment
Language	English
Publishing date	2020-02-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-020-02244-9
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Article: Breast Reconstruction Combining Lipofilling and Prepectoral Prosthesis after Radiotherapy.

Razzouk, Kais / Fitoussi, Alfred / Al Khori, Noor / Pasquier, Jennifer / Chouchane, Lotfi / Tabrizi, Arash Rafii

Plastic and reconstructive surgery. Global open

2020 Volume 8, Issue 5, Page(s) e2659

Abstract: Prosthetic reconstruction in previously irradiated breasts has been associated with a higher risk of complications. Here we describe the surgical and cosmetic outcome of our breast reconstruction process based on primary fat grafting combined with ... ...

Abstract	Prosthetic reconstruction in previously irradiated breasts has been associated with a higher risk of complications. Here we describe the surgical and cosmetic outcome of our breast reconstruction process based on primary fat grafting combined with prosthetic placement. Methods: In this multicenter retrospective study, 136 patients who underwent mastectomy and external chest wall radiotherapy between 2014 and 2018 were benefited from chest wall lipofilling and silicone implant placement were chosen. Patients were assessed for skin trophicity, thickness, and mobility and were allowed to undergo several lipofilling sessions before implant placement, if required. No patient had >3 lipofilling sessions. Cosmetic outcome was evaluated by the patient, surgeon, and nurse, using a Likert-type ordinal scale. Results: We included 136 patients: 79 patients (58%) received only 1 session of lipofilling before implant placement, 33 (24.6%) had 2 sessions, and 24 (17.4%) had 3 sessions. The volume of the third lipofilling was significantly higher and the volume of the prosthesis of these patients was significantly lower than those of patients undergoing 1 or 2 lipofillings. Reconstruction failure rate was 2.2% (3 patients had explantation); however, all benefited from prosthesis reconstruction a year after the initial procedures. The average satisfaction score was 4.7 out of 5 as evaluated by patients, 4.8 out of 5 by surgeons, and 4.8 out of 5 by nurses. Conclusions: Primary lipofilling combined with prosthesis placement after radiotherapy is a reconstructive method that yields a satisfactory cosmetic outcome with a low complication rate. Such minimally invasive breast reconstruction approach can be an alternative to flap-based reconstruction.
Language	English
Publishing date	2020-05-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2851682-5
ISSN	2169-7574 ; 2169-7574
ISSN (online)	2169-7574
ISSN	2169-7574
DOI	10.1097/GOX.0000000000002659
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