1,096 results match your criteria: "Institute of Molecular and Cell Biology IMCB; A*STAR Agency for Science[Affiliation]"

Psychological outcomes in patients with rare cancers: a systematic review and meta-analysis.

EClinicalMedicine

June 2024

Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, 169610, Singapore.

Background: Rare cancers are those that exhibit an incidence of less than six per 100,000 in a year. On average, the five-year relative survival for patients with rare cancers is worse than those with common cancers. The traumatic experience of cancer can be further intensified in patients with rare cancers due to the limited clinical evidence and the lack of empirical evidence for informed decision-making.

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Unlabelled: Encouraged by the observations of significant B7-H3 protein overexpression in many human solid tumors compared to healthy tissues, we directed our focus towards targeting B7-H3 using chimeric antigen receptor (CAR) T cells. We utilized a nanobody as the B7-H3-targeting domain in our CAR construct to circumvent the stability issues associated with single-chain variable fragment-based domains. In efforts to expand patient access to CAR T-cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr virus-specific T cells (EBVST), offering a readily available off-the-shelf treatment.

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FlexStat: combinatory differentially expressed protein extraction.

Bioinform Adv

April 2024

Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.

Motivation: Mass spectrometry-based system proteomics allows identification of dysregulated protein hubs and associated disease-related features. Obtaining differentially expressed proteins (DEPs) is the most important step of downstream bioinformatics analysis. However, the extraction of statistically significant DEPs from datasets with multiple experimental conditions or disease types through currently available tools remains a laborious task.

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Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges.

Cancers (Basel)

April 2024

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Singapore 138673, Singapore.

Article Synopsis
  • Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, responsible for about 90% of liver tumors, and ranks as the second leading cause of cancer deaths globally.
  • Advances in HCC treatment have occurred, but rising incidence and mortality rates remain significant issues, with a shift in causes toward metabolic-associated steatohepatitis (MASH) due to better management of hepatitis B.
  • While early-stage HCC can be treated with promising methods like surgery and ablation for improved survival, most patients are diagnosed at later stages, where newer therapies such as molecular targeted therapy and immune checkpoint inhibitors face challenges, including treatment resistance and lack of effective biomarkers.
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Application of Cas12j for Editing.

Biomolecules

April 2024

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos #07-06, Singapore 138673, Singapore.

In recent years, CRISPR-Cas toolboxes for editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of strains.

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Molecular regulation of myocyte fusion.

Curr Top Dev Biol

April 2024

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Proteos, Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore; Department of Pediatrics, National University of Singapore, Singapore, Singapore. Electronic address:

Myocyte fusion is a pivotal process in the development and regeneration of skeletal muscle. Failure during fusion can lead to a range of developmental as well as pathological consequences. This review aims to comprehensively explore the intricate processes underlying myocyte fusion, from the molecular to tissue scale.

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Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility.

Stem Cell Reports

May 2024

CAAT Europe, University of Konstanz, Konstanz, Germany; In vitro Toxicology and Biomedicine, Department inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.

Cell culture technology has evolved, moving from single-cell and monolayer methods to 3D models like reaggregates, spheroids, and organoids, improved with bioengineering like microfabrication and bioprinting. These advancements, termed microphysiological systems (MPSs), closely replicate tissue environments and human physiology, enhancing research and biomedical uses. However, MPS complexity introduces standardization challenges, impacting reproducibility and trust.

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The circadian clock regulates daily rhythms of numerous physiological activities through tightly coordinated modulation of gene expression and biochemical functions. Circadian disruption is associated with enhanced tumor formation and metastasis via dysregulation of key biological processes and modulation of cancer stem cells (CSCs) and their specialized microenvironment. Here, we review how the circadian clock influences CSCs and their local tumor niches in the context of different stages of tumor metastasis.

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Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption.

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Ghostbuster: A phase retrieval diffraction tomography algorithm for cryo-EM.

Ultramicroscopy

August 2024

NUS Graduate School for Integrative Sciences and Engineering Programme, National University of Singapore, 119077 Singapore, Singapore; Department of Physics, National University of Singapore, 117551 Singapore, Singapore; Department of Biological Sciences, National University of Singapore, 117558 Singapore, Singapore; Center for Bio-Imaging Sciences, National University of Singapore, 117557 Singapore, Singapore. Electronic address:

Ewald sphere curvature correction, which extends beyond the projection approximation, stretches the shallow depth of field in cryo-EM reconstructions of thick particles. Here we show that even for previously assumed thin particles, reconstruction artifacts which we refer to as ghosts can appear. By retrieving the lost phases of the electron exitwaves and accounting for the first Born approximation scattering within the particle, we show that these ghosts can be effectively eliminated.

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Elucidating Structural Configuration of Lipid Assemblies for mRNA Delivery Systems.

ACS Nano

April 2024

School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.

The development of mRNA delivery systems utilizing lipid-based assemblies holds immense potential for precise control of gene expression and targeted therapeutic interventions. Despite advancements in lipid-based gene delivery systems, a critical knowledge gap remains in understanding how the biophysical characteristics of lipid assemblies and mRNA complexes influence these systems. Herein, we investigate the biophysical properties of cationic liposomes and their role in shaping mRNA lipoplexes by comparing various fabrication methods.

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Ovarian cancer is the most deadly female gynaecological malignancy in developed countries and new treatments are urgently needed. The luteinising hormone releasing hormone (LHRH) peptide drug conjugate Zoptarelin doxorubicin is one such potential new drug modality that entered clinical trials for treating LHRH receptor-positive gynaecological cancers. However, development stopped after disappointing Phase 3 results in 2017.

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Article Synopsis
  • * Researchers shared strategies for using patient data and cutting-edge techniques to study cancer diversity, resistance to treatments, and potential drug targets.
  • * The conference highlighted innovative methods for tumor inhibition, drug delivery, and improved models for screening cancer vulnerabilities and testing treatments.
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Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Int J Mol Sci

March 2024

Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size.

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A glycolytic metabolite bypasses "two-hit" tumor suppression by BRCA2.

Cell

April 2024

Cancer Science Institute of Singapore, Singapore 117599, Singapore; NUS Centre for Cancer Research (N2CR), National University of Singapore, Singapore 117599, Singapore; MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK; Institute of Molecular and Cell Biology (IMCB), A(∗)STAR, Singapore 138673, Singapore; Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK; Department of Medicine, National University of Singapore, Singapore 119228, Singapore. Electronic address:

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes.

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Engineering cell-free systems by chemoproteomic-assisted phenotypic screening.

RSC Chem Biol

April 2024

Protein and Peptide Engineering and Research Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove Singapore 138648

Phenotypic screening is a valuable tool to both understand and engineer complex biological systems. We demonstrate the functionality of this approach in the development of cell-free protein synthesis (CFPS) technology. Phenotypic screening identified numerous compounds that enhanced protein production in yeast lysate CFPS reactions.

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Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation.

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Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.

Genome Med

March 2024

Laboratory of Systems Biology and Data Analytics, Genome Institute of Singapore (GIS), A*STAR (Agency for Science, Technology and Research), Singapore, 138672, Singapore.

Article Synopsis
  • Type 1 diabetes (T1DM) is an autoimmune disease that destroys insulin-producing cells in the pancreas, and this study aimed to evaluate immune cell changes at the single-cell level for the first time.
  • Researchers analyzed immune cells from 46 T1DM patients and 31 controls, finding significant gene expression alterations in immune cells that were greater than those observed in another autoimmune disease, systemic lupus erythematosus (SLE).
  • The study developed a new metric, the T1DM metagene z-score (TMZ score), which could categorize patients, correlate with existing immune markers, and help inform treatment responses, highlighting the major immune shifts present in T1DM.
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Background: A pancreatic fistula is one of the most devastating complications following a Whipple's procedure. Fistula rates remain high despite various modifications to surgical techniques. We propose the use of a vascularised muscle flap in the primary prevention of pancreatic fistulas.

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Spatial omics techniques and data analysis for cancer immunotherapy applications.

Curr Opin Biotechnol

June 2024

Institute of Molecular Cell Biology (IMCB), Agency of Science, Technology and Research (A⁎STAR), Singapore 169856, Singapore; Bioinformatics Institute (BII), Agency for Science, Technology and Research (A⁎STAR), Singapore 138671, Singapore. Electronic address:

In-depth profiling of cancer cells/tissues is expanding our understanding of the genomic, epigenomic, transcriptomic, and proteomic landscape of cancer. However, the complexity of the cancer microenvironment, particularly its immune regulation, has made it difficult to exploit the potential of cancer immunotherapy. High-throughput spatial omics technologies and analysis pipelines have emerged as powerful tools for tackling this challenge.

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In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire.

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Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells.

Cell Death Dis

March 2024

Laboratory of NF-κB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.

Cellular responses to TNF are inherently heterogeneous within an isogenic cell population and across different cell types. TNF promotes cell survival by activating pro-inflammatory NF-κB and MAPK signalling pathways but may also trigger apoptosis and necroptosis. Following TNF stimulation, the fate of individual cells is governed by the balance of pro-survival and pro-apoptotic signalling pathways.

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