|
1
|
Mora-Lagos B, Reyes ME, Lobos-Gonzalez L, Del Campo M, Buchegger K, Zanella L, Riquelme I, Ili CG, Brebi P. Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival. Biol Res 2025; 58:4. [PMID: 39827154 PMCID: PMC11748569 DOI: 10.1186/s40659-024-00581-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 12/17/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC's most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (3D tumor spheroids), and animal models. RESULTS The combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone. CONCLUSIONS This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.
Collapse
Affiliation(s)
- Bárbara Mora-Lagos
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Temuco, Chile
| | - María Elena Reyes
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Temuco, Chile
| | - Lorena Lobos-Gonzalez
- Centro de Medicina Regenerativa, Facultad de Medicina-Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
- Advanced Center for Chronic Diseases, ACCDiS, Santiago, Chile
- Laboratorio de comunicaciones celulares, Instituto de Ciencias Biomédicas, iCBM, Universidad de Chile, Santiago, Chile
| | - Matías Del Campo
- Centro de Medicina Regenerativa, Facultad de Medicina-Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
- Advanced Center for Chronic Diseases, ACCDiS, Santiago, Chile
| | - Kurt Buchegger
- Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco, Chile
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Biomedical Research Consortium-Chile (BMRC), Santiago, Chile
| | - Louise Zanella
- Doctorado en Ciencias Médicas, Universidad de La Frontera, Temuco, Chile
- Núcleo Milenio de Sociomedicina, Santiago, Chile
| | - Ismael Riquelme
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Temuco, Chile
| | - Carmen Gloria Ili
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
- Biomedical Research Consortium-Chile (BMRC), Santiago, Chile.
| | - Priscilla Brebi
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
- Biomedical Research Consortium-Chile (BMRC), Santiago, Chile.
| |
Collapse
|
|
2
|
Zhang C, Zeng M, Xu Y, Huang B, Shi P, Zhu X, Cao Y. S100A6 mediated epithelial-mesenchymal transition affects chemosensitivity of colorectal cancer to oxaliplatin. Gene 2024; 914:148406. [PMID: 38521111 DOI: 10.1016/j.gene.2024.148406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 03/17/2024] [Accepted: 03/20/2024] [Indexed: 03/25/2024]
Abstract
PURPOSE To investigate the mechanism by which S100 calcium-binding protein A6 (S100A6) affects colorectal cancer (CRC) cells to oxaliplatin (L-OHP) chemotherapy, and to explore new strategies for CRC treatment. METHODS S100A6 expression was assessed in both parental and L-OHP-resistant CRC cells using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA). Lentiviral vectors were utilized to induce the knockdown of S100A6 expression, followed by comprehensive evaluations of cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Additionally, RNA-seq analysis was conducted to identify genes associated with the knockdown of S100A6. RESULTS Elevated S100A6 expression in CRC tissues correlated with an adverse prognosis in patients with CRC. Higher expression of S100A6 was also observed in L-OHP-resistant CRC cells, which showed enhanced proliferation, migration, invasion, and antiapoptotic capabilities. Notably, the knockdown of S100A6 expression resulted in decreased proliferation, increased apoptosis, and suppression of EMT and tumorigenicity in L-OHP-resistant CRC cells. Transcriptome sequencing reveals a noteworthy association between S100A6 and vimentin expression. Application of the EMT agonist, transforming growth factor β (TGF-β), induces EMT in CRC cells. S100A6 expression positively correlates with TGF-β expression. TGF-β facilitated the expression of EMT-related molecules and reduced the chemosensitivity of L-OHP in S100A6-knockdown cells. CONCLUSION In conclusion, the knockdown of S100A6 may overcome the L-OHP resistance of CRC cells by modulating EMT.
Collapse
Affiliation(s)
- Chunying Zhang
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China
| | - Menglu Zeng
- Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynaecology and Paediatrics, Fujian Medical University, Fuzhou, China
| | - Yihan Xu
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China
| | - Bihan Huang
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China
| | - Pengchong Shi
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xianjin Zhu
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Yingping Cao
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
| |
Collapse
|
|
3
|
Gutiérrez Á, Reyes ME, Larronde C, Brebi P, Mora-Lagos B. Targeting CCR3 with antagonist SB 328437 sensitizes 5‑fluorouracil‑resistant gastric cancer cells: Experimental evidence and computational insights. Oncol Lett 2024; 28:296. [PMID: 38737977 PMCID: PMC11082837 DOI: 10.3892/ol.2024.14429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 04/10/2024] [Indexed: 05/14/2024] Open
Abstract
Gastric cancer (GC) ranks fifth globally in cancer diagnoses and third for cancer-related deaths. Chemotherapy with 5-fluorouracil (5-FU), a primary treatment, faces challenges due to the development of chemoresistance. Tumor microenvironment factors, including C-C motif chemokine receptor 3 (CCR3), can contribute to chemoresistance. The present study evaluated the effect of CCR3 receptor inhibition using the antagonist SB 328437 and the molecular dynamics of this interaction on resistance to 5-FU in gastric cancer cells. The 5-FU-resistant AGS cell line (AGS R-5FU) demonstrated notable tolerance to higher concentrations of 5-FU, with a 2.6-fold increase compared with the parental AGS cell line. Furthermore, the mRNA expression levels of thymidylate synthase (TS), a molecular marker for 5-FU resistance, were significantly elevated in AGS R-5FU cells. CCR3 was shown to be expressed at significantly higher levels in these resistant cells. Combining SB 328437 with 5-FU resulted in a significant decrease in cell viability, particularly at higher concentrations of 5-FU. Furthermore, when SB 328437 was combined with 5-FU at a high concentration, the relative mRNA expression levels of CCR3 and TS decreased significantly. Computational analysis of CCR3 demonstrated dynamic conformational changes, especially in extracellular loop 2 region, which indicated potential alterations in ligand recognition. Docking simulations demonstrated that SB 328437 bound to the allosteric site of CCR3, inducing a conformational change in ECL2 and hindering ligand recognition. The present study provides comprehensive information on the molecular and structural aspects of 5-FU resistance and CCR3 modulation, highlighting the potential for therapeutic application of SB 328437 in GC treatment.
Collapse
Affiliation(s)
- Álvaro Gutiérrez
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4810296 Temuco, Chile
- Millennium Institute on Immunology and Immunotherapy, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4810296 Temuco, Chile
| | - María Elena Reyes
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, 4810101 Temuco, Chile
| | - Carolina Larronde
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, 4810101 Temuco, Chile
| | - Priscilla Brebi
- Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4810296 Temuco, Chile
- Millennium Institute on Immunology and Immunotherapy, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4810296 Temuco, Chile
- Biomedical Research Consortium - Chile, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, 4810296 Temuco, Chile
| | - Bárbara Mora-Lagos
- Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, 4810101 Temuco, Chile
| |
Collapse
|
|
4
|
Liu C, Li S, Tang Y. Mechanism of cisplatin resistance in gastric cancer and associated microRNAs. Cancer Chemother Pharmacol 2023; 92:329-340. [PMID: 37535106 DOI: 10.1007/s00280-023-04572-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 07/27/2023] [Indexed: 08/04/2023]
Abstract
Gastric cancer (GC) is a common malignant tumor with high morbidity and mortality rates that seriously affects human health worldwide. Although surgery is currently the preferred clinical treatment for GC, chemotherapy remains the first choice for perioperative treatment, adjuvant therapy, and palliative care for patients with advanced GC. Cisplatin (DDP) is an antineoplastic agent that has been used clinically for decades, and it is the first-line chemotherapy for many solid tumors. However, the therapeutic efficacy of DDP is often limited by resistance and the complexity of its resistance mechanisms, which involve multiple proteins and signaling pathways. It is well documented that a variety of microRNAs (miRNAs) differentially expressed in DDP-resistant GC cells play important roles in regulating or reversing DDP resistance via various pathways. In this review, we first provide an introduction to the cytotoxicity and major resistance mechanisms of DDP in GC and then discuss the role and mechanism of miRNAs in regulating the DDP resistance process in GC cells. This work demonstrates the potential of relevant miRNAs to become diagnostic and prognostic biomarkers for gastric cancer and targets of action to enhance chemosensitivity and provides directions for future research.
Collapse
Affiliation(s)
- Changqing Liu
- Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute of Hengyang Medical School, University of South China, 28 Changsheng Road, Hengyang, 421001, Hunan Province, People's Republic of China
| | - Shan Li
- Department of Pathology, People's Hospital of Shaoyang County, Hengyang, Hunan Province, People's Republic of China
| | - Yunlian Tang
- Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute of Hengyang Medical School, University of South China, 28 Changsheng Road, Hengyang, 421001, Hunan Province, People's Republic of China.
| |
Collapse
|
|
5
|
Riquelme I, Pérez-Moreno P, Mora-Lagos B, Ili C, Brebi P, Roa JC. Long Non-Coding RNAs (lncRNAs) as Regulators of the PI3K/AKT/mTOR Pathway in Gastric Carcinoma. Int J Mol Sci 2023; 24:ijms24076294. [PMID: 37047267 PMCID: PMC10094576 DOI: 10.3390/ijms24076294] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Gastric cancer (GC) represents ~10% of the global cancer-related deaths, increasingly affecting the younger population in active stages of life. The high mortality of GC is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not guide the patient management adequately, thereby new and more reliable biomarkers and therapeutic targets are still needed for this disease. RNA-seq technology has allowed the discovery of new types of RNA transcripts including long non-coding RNAs (lncRNAs), which are able to regulate the gene/protein expression of many signaling pathways (e.g., the PI3K/AKT/mTOR pathway) in cancer cells by diverse molecular mechanisms. In addition, these lncRNAs might also be proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in GC. This review describes important topics about some lncRNAs that have been described as regulators of the PI3K/AKT/mTOR signaling pathway, and hence, their potential oncogenic role in the development of this malignancy.
Collapse
Affiliation(s)
- Ismael Riquelme
- Institute of Biomedical Sciences, Faculty of Health Sciences, Universidad Autónoma de Chile, Temuco 4810101, Chile
- Correspondence: (I.R.); (J.C.R.); Tel.: +56-95923-6933 (I.R.); +56-22354-1061 (J.C.R.)
| | - Pablo Pérez-Moreno
- Millennium Institute on Immunology and Immunotherapy (MIII), Center for Cancer Prevention and Control (CECAN), Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8380000, Chile
| | - Bárbara Mora-Lagos
- Institute of Biomedical Sciences, Faculty of Health Sciences, Universidad Autónoma de Chile, Temuco 4810101, Chile
| | - Carmen Ili
- Millennium Institute on Immunology and Immunotherapy (MIII), Laboratory of Integrative Biology (LIBi), Center for Excellence in Translational Medicine—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile
| | - Priscilla Brebi
- Millennium Institute on Immunology and Immunotherapy (MIII), Laboratory of Integrative Biology (LIBi), Center for Excellence in Translational Medicine—Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile
| | - Juan Carlos Roa
- Millennium Institute on Immunology and Immunotherapy (MIII), Center for Cancer Prevention and Control (CECAN), Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8380000, Chile
- Correspondence: (I.R.); (J.C.R.); Tel.: +56-95923-6933 (I.R.); +56-22354-1061 (J.C.R.)
| |
Collapse
|
|
6
|
Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. Histochem Cell Biol 2022; 159:431-437. [PMID: 36536187 DOI: 10.1007/s00418-022-02172-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/07/2022] [Indexed: 12/23/2022]
Abstract
Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in therapy resistance are still insufficient. We analyzed SERPINA1 mRNA expression in three different multidrug-resistant (MDR) cell lines-U87-TxR, NCI-H460/R, and DLD1-TxR-and in U87 cells grown in alginate microfibers as a 3D cellular model of glioblastoma. Expression of IL-6 as a major modulator of SERPINA1 was also analyzed. Additionally, AAT protein expression in MDR cells was analyzed by immunofluorescence. SERPINA1 gene expression and AAT protein expression were significantly upregulated in all the tested MDR cell lines compared with their sensitive counterparts. Moreover, SERPINA1 was significantly upregulated in 3D models of glioblastoma, previously found to have upregulated drug-resistance-related gene expression compared with 2D cells. With the exception of NCI-H460/R, in all cell lines as well as in a 3D model of U87 cells, increase in SERPINA1 expression correlated with the increase in IL-6 expression. Our results indicate that AAT could be utilized as a biomarker of therapy resistance in cancer; however, further studies are needed to elucidate the mechanisms driving AAT upregulation in therapy resistance and its biological significance in this process.
Collapse
|
|
7
|
A novel adenine-based diruthenium(III) complex: Synthesis, crystal structure, electrochemical properties and evaluation of the anticancer activity. J Inorg Biochem 2022; 232:111812. [DOI: 10.1016/j.jinorgbio.2022.111812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/10/2022] [Accepted: 03/31/2022] [Indexed: 12/22/2022]
|
|
8
|
Jiang X, Zhang W, Li L, Xie S. Integrated Transcriptomic Analysis Revealed Hub Genes and Pathways Involved in Sorafenib Resistance in Hepatocellular Carcinoma. Pathol Oncol Res 2021; 27:1609985. [PMID: 34737677 PMCID: PMC8560649 DOI: 10.3389/pore.2021.1609985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/28/2021] [Indexed: 12/31/2022]
Abstract
Hepatocellular carcinoma (HCC), a high mortality malignancy, has become a worldwide public health concern. Acquired resistance to the multikinase inhibitor sorafenib challenges its clinical efficacy and the survival benefits it provides to patients with advanced HCC. This study aimed to identify critical genes and pathways associated with sorafenib resistance in HCC using integrated bioinformatics analysis. Differentially expressed genes (DEGs) were identified using four HCC gene expression profiles (including 34 sorafenib-resistant and 29 sorafenib-sensitive samples) based on the robust rank aggregation method and R software. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING), and small molecules reversing sorafenib resistance were searched for using the connectivity map (CMAP) database. Pearson correlation and survival analyses of hub genes were performed using cBioPortal and Gene Expression Profiling and Interactive Analysis (GEPIA). Finally, the expression levels of hub genes in sorafenib-resistant HCC cells were verified using quantitative polymerase chain reaction (q-PCR). A total of 165 integrated DEGs (66 upregulated and 99 downregulated in sorafenib resistant samples compared sorafenib sensitive ones) primarily enriched in negative regulation of endopeptidase activity, extracellular exosome, and protease binding were identified. Some pathways were commonly shared between the integrated DEGs. Seven promising therapeutic agents and 13 hub genes were identified. These findings provide a strategy and theoretical basis for overcoming sorafenib resistance in HCC patients.
Collapse
Affiliation(s)
- Xili Jiang
- Department of Radiology, The Second People's Hospital of Hunan Province/Brain Hospital of Hunan Province, Changsha, China
| | - Wei Zhang
- Department of Radiology, The Second People's Hospital of Hunan Province/Brain Hospital of Hunan Province, Changsha, China
| | - Lifeng Li
- Department of Radiology, Changsha Central Hospital, Changsha, China
| | - Shucai Xie
- Department of Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
9
|
Ramos A, Sadeghi S, Tabatabaeian H. Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them. Int J Mol Sci 2021; 22:9451. [PMID: 34502361 PMCID: PMC8430957 DOI: 10.3390/ijms22179451] [Citation(s) in RCA: 141] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/28/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023] Open
Abstract
With nearly 10 million deaths, cancer is the leading cause of mortality worldwide. Along with major key parameters that control cancer treatment management, such as diagnosis, resistance to the classical and new chemotherapeutic reagents continues to be a significant problem. Intrinsic or acquired chemoresistance leads to cancer recurrence in many cases that eventually causes failure in the successful treatment and death of cancer patients. Various determinants, including tumor heterogeneity and tumor microenvironment, could cause chemoresistance through a diverse range of mechanisms. In this review, we summarize the key determinants and the underlying mechanisms by which chemoresistance appears. We then describe which strategies have been implemented and studied to combat such a lethal phenomenon in the management of cancer treatment, with emphasis on the need to improve the early diagnosis of cancer complemented by combination therapy.
Collapse
Affiliation(s)
- Alisha Ramos
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore;
| | - Samira Sadeghi
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore;
- Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore
| | - Hossein Tabatabaeian
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| |
Collapse
|