216 results match your criteria: "National Cancer Center Singapore[Affiliation]"

Introduction: To investigate the efficacy and safety of proton-beam irradiation (PBI) combined with intravitreal conbercept (IVC) injection for refractory or recurrent polypoidal choroidal vasculopathy (PCV).

Methods: A prospective interventional clinical trial included 12 patients with refractory PCV (defined as persistent exudation or fluid after six consecutive injections at monthly intervals and/or photodynamic therapy) or recurrent PCV (defined as new exudative signs after six monthly injections and/or photodynamic therapy) treated between January 2019 and September 2020. Every patient underwent single PBI (14 GyE) with concomitant IVC (0.

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Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBM ) and tumor core (GBM ) cells from the brains of 6 highly invasive patient-derived orthotopic models is described.

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Introduction: As many as 30% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BMs) over the course of their illness. Here, we quantitatively compare the efficacy of the various emerging regimens for NSCLC BMs without a definitive targetable epidermal growth factor receptor mutation/ALK rearrangement.

Methods: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.

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Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT): A subspecialty surgical oncological care model for advanced malignancies requiring complex procedures.

Asian J Surg

January 2022

Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Center Singapore, Singapore; Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore; SingHealth Duke-NUS Oncology Academic Medical Program, Duke-NUS Medical School, Singapore. Electronic address:

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Background: The occurrence of cardiovascular events is a major cause of death in patients with cancer. Small studies have documented a connection between specific brain alterations and autonomic cardiac dysfunctions, possibly resulting in a worse prognosis. We aimed to refine the knowledge of fatal cardiac events in patients with brain metastasis (BM).

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Purpose: The therapeutic landscape of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents and their combinations with endocrine therapies. In this scenario, optimizing treatment selection and sequencing is daunting for clinicians. The purpose of this review is to provide evidence-based answers to key clinical questions on treatment selection and sequencing for the management of HR + HER2 - mBC.

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Context: There are few international studies about the continuous use of sedatives (CUS) in the last days of life.

Objectives: We aim to describe the experiences and opinions regarding CUS of physicians caring for terminally ill patients in seven countries.

Methods: Questionnaire study about practices and experiences with CUS in the last days of life among physicians caring for terminally ill patients in Belgium (n = 175), Germany (n = 546), Italy (n = 214), Japan (n = 513), the Netherlands (n = 829), United Kingdom (n = 114) and Singapore (n = 21).

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Impact of Dying Neonates on Doctors' and Nurses' Personhood: A Systematic Scoping Review.

J Pain Symptom Manage

January 2022

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Supportive and Palliative Care, National Cancer Center Singapore, Singapore, Singapore; Division of Cancer Education, National Cancer Center Singapore, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore; Palliative Care Institute Liverpool, Academic Palliative & End of Life Care Center, University of Liverpool, Cancer Research Center, University of Liverpool, Liverpool, United Kingdom; Center of Biomedical Ethics, National University of Singapore, Singapore, Singapore; PalC, The Palliative Care Center for Excellence in Research and Education, Singapore, Singapore. Electronic address:

Context: Caring for dying neonates is distressing for healthcare professionals (HCP)s. Yet, the extent of these effects is poorly understood, compromising support of HCPs. To better understand and support HCPs, a systematic scoping review (SSR) of prevailing data is proposed.

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Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma.

Immunity

August 2021

Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Singapore 138648, Singapore; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA. Electronic address:

Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8 T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens.

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Purpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in -mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in -negative resistance.

Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic -mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M) and -negative (T790M) disease.

Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M tumors, orthogonally validated using multiplex IHC.

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Purpose: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center.

Patients And Methods: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore.

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Background: CGM097 inhibits the p53-HDM2 interaction leading to downstream p53 activation. Preclinical in vivo studies support clinical exploration while providing preliminary evidence for dosing regimens. This first-in-human phase I study aimed at assessing the safety, MTD, PK/PD and preliminary antitumor activity of CGM097 in advanced solid tumour patients (NCT01760525).

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Simultaneous Screening of the FRAXA and FRAXE Loci for Rapid Detection of FMR1 CGG and/or AFF2 CCG Repeat Expansions by Triplet-Primed PCR.

J Mol Diagn

August 2021

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore; Department of Laboratory Medicine, National University Hospital, Singapore; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Moderate to hyper-expansion of trinucleotide repeats at the FRAXA and FRAXE fragile sites, with or without concurrent hypermethylation, has been associated with intellectual disability and other conditions. Unlike molecular diagnosis of FMR1 CGG repeat expansions in FRAXA, current detection of AFF2 CCG repeat expansions in FRAXE relies on low-throughput and otherwise inefficient techniques combining Southern blot analysis and PCR. A novel triplet-primed PCR assay was developed for simultaneous screening for trinucleotide repeat expansions at the FRAXA and FRAXE fragile sites, and was validated using archived clinical samples of known FMR1 and AFF2 genotypes.

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Atypical teratoid rhabdoid tumor (ATRT) is an aggressive embryonal brain tumor among infants and young children. Two challenges exist for preclinical testing in ATRT. First, genetically quiet, ATRT is a difficult tumor to target molecularly.

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Background: Resection of parotid carcinomas involving the parapharyngeal space is challenging. How this affects tumor margin control, recurrence, and survival is unclear.

Methods: Patients who underwent resection of parotid carcinomas between 1985 and 2015 at Memorial Sloan Kettering Cancer Center were evaluated for the impact of parapharyngeal extension (PPE) on margin status, local recurrence-free probability (LRFP), and disease-specific survival (DSS).

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DNA hypermethylation in a promoter region causes gene silencing via epigenetic changes. We have previously reported that early B cell factor 1 (EBF1) was down-regulated in cholangiocarcinoma (CCA) tissues and related to tumor progression. Thus, we hypothesized that the DNA hypermethylation of EBF1 promoter would suppress EBF1 expression in CCA and induce its progression.

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Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood.

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Article Synopsis
  • Breast fibroepithelial lesions include common benign tumors like fibroadenomas (FAs) and rarer phyllodes tumors (PTs), with this study analyzing 262 conventional FAs, 45 cellular FAs, and 321 benign PTs using a 16 gene panel.
  • It was found that benign PTs had more mutations and cancer driver gene alterations compared to FAs, specifically noting significant mutations in genes like MED12 and TERT promoter.
  • The study suggests that genetic sequencing can help improve diagnoses of these lesions by identifying specific mutations, with TERT promoter changes being particularly useful for distinguishing between FAs and benign PTs.
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Rapid Molecular Screen of Spinocerebellar Ataxia Types 1, 2, and 3 by Triplet-Primed PCR and Melting Curve Analysis.

J Mol Diagn

May 2021

Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Laboratory Medicine, National University Hospital, Singapore. Electronic address:

The autosomal dominantly inherited spinocerebellar ataxias (SCAs) can be caused by dynamic mutations of short tandem repeats within various genes. Because of the significant clinical overlap among the various SCA types, molecular screening of multiple genetic loci by fluorescent PCR and capillary electrophoresis is necessary to identify the causative repeat expansion. We describe a simple, rapid, and inexpensive strategy to screen for CAG repeat expansion mutations at the ATXN1, ATXN2, and ATXN3 loci using melting curve analysis of triplet-primed PCR products.

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Comprehensive understanding of aberrant splicing in gastric cancer is lacking. We RNA-sequenced 19 gastric tumor-normal pairs and identified 118 high-confidence tumor-associated (TA) alternative splicing events (ASEs) based on high-coverage sequencing and stringent filtering, and also identified 8 differentially expressed splicing factors (SFs). The TA ASEs occurred in genes primarily involved in cytoskeletal organization.

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Objective: To evaluate the cost-effectiveness of olaparib as a maintenance treatment versus routine surveillance (RS) in patients with mutated (m) advanced ovarian cancer (OC) following response to first-line platinum-based chemotherapy in Singapore.

Methods: A 4-health state partitioned survival model was developed to simulate the lifetime (50 years) incremental cost-effectiveness ratio (ICER) of olaparib versus RS from a healthcare payer perspective. Progression-free survival, time to second disease progression, and overall survival were estimated using SOLO-1 data and extrapolated beyond the trial period using parametric survival models.

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Reply to Colorectal cancer and COVID-19: Do we need to raise awareness and vigilance?

Cancer

March 2021

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, China.

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Background And Purpose: Post-operative spine stereotactic body radiation therapy (SBRT) represents a significant challenge as there are many restrictions on beam geometry to avoid metal hardware as it surrounds the target volume. In this study, an international multi-institutional end-to-end test using an in-house spine phantom was developed and executed. The aim was to evaluate the impact of titanium spine hardware on planned and delivered dose for post-operative spine SBRT.

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Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy.

Cell Mol Gastroenterol Hepatol

March 2022

Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background & Aims: Hepatocellular carcinoma (HCC) arises in a cirrhotic, pro-angiogenic microenvironment. Inhibiting angiogenesis is a key mode of action of multikinase inhibitors and current non-cirrhotic models are unable to predict treatment response. We present a novel mouse cirrhotic model of xenotransplant that predicts the natural biology of HCC and allows personalized therapy.

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