Stories
A Genomic-augmented Multivariate Prognostic Model for the Survival of Natural-killer/T-cell Lymphoma Patients from an International Cohort (Am J Hematol, Jun 2022)
August 15, 2022
With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients.
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A Degradative to Secretory Autophagy Switch Mediates Mitochondria Clearance in the Absence of the mATG8-conjugation Machinery (Nat Commun., Jun 2022)
August 15, 2022
PINK1-Parkin mediated mitophagy, a selective form of autophagy, represents one of the most important mechanisms in mitochondrial quality control (MQC) via the clearance of damaged mitochondria.
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SETDB1 Acts as a Topological Accessory to Cohesin via an H3K9me3-independent, Genomic Shunt for Regulating Cell Fates (Nucleic Acids Res, Jul 2022)
August 10, 2022
SETDB1 is a key regulator of lineage-specific genes and endogenous retroviral elements (ERVs) through its deposition of repressive H3K9me3 mark.
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Congratulations to the Graduating Class of 2022!
August 10, 2022
CSI Singapore would like to extend its heartiest congratulations to the graduates of the PhD Graduate Program in Cancer Biology!
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Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities (Gut, Jul 2022)
August 5, 2022
According to GLOBOCAN, gastric cancer (GC) is a significant cause of cancer mortality worldwide, with over 700,000 deaths attributable to it annually. Mesenchymal-subtype gastric cancer (Mes-GC) is a particularly aggressive subtype associated with poor clinical prognosis and chemoresistance. However, few effective treatment options are currently available. Existing regimens consist of “one-size-fits-all” approaches such as surgery […]
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[Review] Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis (J Clin Oncol, June 2022)
July 25, 2022
The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM).
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Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid (ACS Nano., June 2022)
July 25, 2022
Bioorthogonal catalysis (BC) generates chemical reactions not present in normal physiology for the purpose of disease treatment. Because BC catalytically produces the desired therapy only at the site of disease, it holds the promise of site-specific treatment with little or no systemic exposure or side effects.
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Identification of Mechanism of Cancer-cell-specific Reactivation of hTERT Offers Therapeutic Opportunities for Blocking Telomerase Specifically in Human Colorectal Cancer (Nucleic Acids Res., June 2022)
July 22, 2022
Transcriptional reactivation of hTERT is the limiting step in tumorigenesis. While mutations in hTERT promoter present in 19% of cancers are recognized as key drivers of hTERT reactivation, mechanisms by which wildtype hTERT (WT-hTERT) promoter is reactivated, in majority of human cancers, remain unknown.
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Pan-cancer Pervasive Upregulation of 3’UTR Splicing Drives Tumorigenesis (Nat. Cell Biol., May 22)
July 7, 2022
Most mammalian genes generate messenger RNAs (mRNAs) that consist of central protein-coding regions flanked by variable untranslated regions (UTRs). These UTRs, while not directly involved in protein production, nevertheless harbour many regulatory sequences and structures, and play important roles in post-transcriptional regulation, ensuring correct gene expression and function. Changes to these UTRs can be pathogenic, […]
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Congratulations to Ms. Xu Jingru, a CSI PhD student on receiving the Materials Research Society (MRS) 2022 NM05 Symposium Best Student Oral Presentation Award!
June 14, 2022
Held in Honolulu, Hawaii between May 8 – 13, Ms. Xu Jingru presented at the NM05 Symposium, which focuses on discussions relating to the recent advances of nanodiamond in quantum sensing, diagnostic, biomedical and other novel applications.
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Hepatocellular Carcinoma Organoid Co-cultures Mimic Angiocrine Crosstalk to Generate Inflammatory Tumor Microenvironment (Biomaterials, May 22)
June 13, 2022
Despite approvals of several therapeutics to treat advanced HCC in the past few years, the impact of anti-angiogenic treatment on HCC patient overall survival remains limited. This suggests there may be alternative, perfusion-independent roles of endothelial cells that support tumor progression.
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Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer (Cancer Res, May 22)
June 13, 2022
Mutations in the DNA mismatch repair gene MSH2 are causative of microsatellite instability (MSI) in multiple cancers. Here, we discovered that besides its well-established role in DNA repair, MSH2 exerts a novel epigenomic function in gastric cancer (GC).
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Demethylation and Up-regulation of an Oncogene After Hypomethylating Therapy (N Engl J Med, May 22)
June 13, 2022
Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated.
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“Cancer fishing”: CSI Singapore Researchers Discover New Mechanisms of Cancer using Zebrafish and Single-cell Sequencing Technology
May 27, 2022
Utilising a novel zebrafish cancer model, A/Prof. Takaomi Sanda and his team have been able to study the mechanism of cancer and elucidate tissue-specific oncogenicity. One such breakthrough would be the analysis of the oncogenicity of IRF4, an oncogene that is specifically expressed and regulates gene transcription in several types of mature lymphomas.
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CSI Principal Investigator and Senior Research Scientist Receive Awards at the Asian Fund for Cancer Research’s (AFCR) 2021 BRACE Award Venture Competition
May 5, 2022
Congratulations to A/Prof. Edward Kai-Hua Chow and Dr. Bee Hui Liu, who have recently won awards at the Asian Fund for Cancer Research’s (AFCR) 2021 BRACE Award Venture Competition, a first-of-its-kind program for early-stage oncology technology companies focused on Asian-prevalent cancers.
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Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Post-Menopausal Women with Hormone Receptor Positive Breast Cancer (Clin Cancer Res, Apr 22)
May 5, 2022
RET is an estrogen response gene with preclinical studies demonstrating cross talk between RET and estrogen receptor (ER) pathways. We investigate the role of lenvatinib, a multi-kinase inhibitor with potent activity against RET, in patients with metastatic breast cancer.
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Non-Coding RNA LEVER Sequestration of PRC2 Can Mediate Long Range Gene Regulation (Commun Biol, Apr 22)
May 5, 2022
Polycomb Repressive Complex 2 (PRC2) is an epigenetic regulator required for gene silencing during development. Although PRC2 is a well-established RNA-binding complex, the biological function of PRC2-RNA interaction has been controversial. Here, we study the gene-regulatory role of the inhibitory PRC2-RNA interactions. We report a nuclear long non-coding RNA, LEVER, which mapped 236 kb upstream of the ?-globin cluster as confirmed by Nanopore sequencing.
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Multilayered Control of Splicing Regulatory Networks by DAP3 Leads to Widespread Alternative Splicing Changes in Cancer. (Nat Commun, Apr 22)
May 5, 2022
The dynamic regulation of alternative splicing requires coordinated participation of multiple RNA binding proteins (RBPs). Aberrant splicing caused by dysregulation of splicing regulatory RBPs is implicated in numerous cancers. Here, we reveal a frequently overexpressed cancer-associated protein, DAP3, as a splicing regulatory RBP in cancer.
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CSI Singapore Researchers Uncover Role of ADARs and its Implications in Cancer Development
May 4, 2022
In a novel step forward, A/Prof. Polly Chen and her team embarked on a study to better understand the role of crosstalk between RNA editing machinery (ADAR proteins) and circRNA biogenesis machinery in cancer. Findings from this interesting study will provide new insights that can contribute to the development of effective therapeutic approaches utilizing ADARs-regulated circRNAs, given their high stability and diverse functions.
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PLK1 Inhibition Selectively Induces Apoptosis in ARID1A Deficient Cells Through Uncoupling of Oxygen Consumption from ATP Production. (Oncogene, Mar 22)
April 6, 2022
Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition.
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