Publications by authors named "Martin B Lee"

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls.

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Peritoneal dialysis (PD) is the only well-established home-based dialysis therapy in Singapore. As it is a home-based modality, PD should be considered as a preferred mode of kidney replacement therapy (KRT) for patients with kidney failure during this COVID-19 pandemic as it avoids frequent visits to hospitals and/or satellite dialysis centres. The highly infectious nature of this virus has led to the implementation of the Disease Outbreak Response System Condition orange status in Singapore since early February 2020.

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Aim: The COVID-19 pandemic poses unprecedented operational challenges to nephrology divisions in every country as they cope with COVID-19-related kidney disease in addition to regular patient care. Although general approaches have been proposed, there is a lack of practical guidance for nephrology division response in a hospital facing a surge of cases. Here, we describe the specific measures that our division has taken in the hope that our experience in Singapore may be helpful to others.

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We report a rare case of carbapenemase-producing enterobacte-riaceae peritonitis in a patient undergoing automated peritoneal dialysis (APD). The PD catheter had to be removed as the patient remained unwell despite antibiotics. Antimicrobial resistance in PD peritonitis is a concern in this era of multi-drug resistant bacteria.

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The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena in both tumor responses and toxicities. We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments.

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Cancer is one of the most studied areas of human biology over the past century. Despite having attracted much attention, hype, and investments, the search to find a cure for cancer remains an uphill battle. Recent discoveries that challenged the central dogma of molecular biology not only further increase the complexity but also demonstrate how various types of noncoding RNAs such as microRNA and long noncoding RNA, as well as their related processes such as RNA editing, are important in regulating gene expression.

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Myths in peritoneal dialysis.

Curr Opin Nephrol Hypertens

November 2016

Purpose Of Review: To clarify misconceptions about the feasibility and risks of peritoneal dialysis that unnecessarily limit peritoneal dialysis uptake or continuation in patients for whom peritoneal dialysis is the preferred dialysis modality. The inappropriate choice of haemodialysis as a result of these misconceptions contributes to low peritoneal dialysis penetrance, increases transfer from peritoneal dialysis to haemodialysis, increases expenditure on haemodialysis and compromises quality of life for these patients.

Recent Findings: Peritoneal dialysis is an excellent renal replacement modality that is simple, cost-effective and provides comparable clinical outcomes to conventional in-centre haemodialysis.

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Meprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprin β. More importantly, OS-9 interacts with the hypoxia inducible factor-1α (HIF-1α) and the prolyl-hydroxylase, proteins which mediate the cell's response to hypoxia.

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In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups.

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The embryonic pattern of global DNA methylation is first established in the inner cell mass (ICM) of the mouse blastocyst. The methyl donor S-adenosylmethionine (SAM) is produced in most cells through the folate cycle, but only a few cell types generate SAM from betaine (N,N,N-trimethylglycine) via betaine-homocysteine methyltransferase (BHMT), which is expressed in the mouse ICM. Here, mean ICM cell numbers decreased from 18-19 in controls to 11-13 when the folate cycle was inhibited by the antifolate methotrexate and to 12-14 when BHMT expression was knocked down by antisense morpholinos.

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Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB.

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Background: Cancer cells can employ telomerase or the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. Cancer cells that use the ALT pathway exhibit distinct phenotypes such as heterogeneous telomeres and specialised Promyelocytic leukaemia (PML) nuclear foci called APBs. In our study, we used wild-type PML and a PML mutant, in which the coiled-coil domain is deleted (PML C/C-), to investigate how these proteins can affect telomere maintenance pathways in cancer cells that use either the telomerase or ALT pathway.

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Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO) dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1) cell cycle arrest in fibroblast cells.

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Methyltransferases are an important group of enzymes with diverse roles that include epigenetic gene regulation. The universal donor of methyl groups for methyltransferases is S-adenosylmethionine (AdoMet), which in most cells is synthesized using methyl groups carried by a derivative of folic acid. Another mechanism for AdoMet synthesis uses betaine as the methyl donor via the enzyme betaine-homocysteine methyltransferase (BHMT, EC 2.

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Betaine (N,N,N-trimethylglycine) added to culture media is known to substantially improve the development of preimplantation mouse embryos in vitro, and to be imported into 1-cell embryos by a transporter that also accepts proline. Here, we found that the betaine/proline transporter is active in preimplantation mouse embryos only for a short period of development, between the 1- and 2-cell stages. Betaine/proline transport was activated after fertilization, beginning approximately 4 hours post-egg activation and reaching a maximum by approximately 10 hours.

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Background: Methylamines have many metabolic roles and there is an increasing demand for their measurement. Glycine betaine is an important osmolyte, and a reservoir for methyl groups. Proline betaine and trigonelline are important dietary betaines.

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Article Synopsis
  • The study reveals that orphan nuclear receptors, specifically SF-1 and liver receptor homolog 1, are regulated by SUMO modification, which suppresses their activity.
  • Mutating certain lysine residues or introducing SUMO isopeptidase SENP1 significantly boosts the activity of these receptors, suggesting that SUMO modification is crucial in regulating their function.
  • The findings indicate that direct interaction between sumoylated SF-1 and the DEAD-box protein DP103 plays a key role in this repression, involving specific E3-SUMO ligase candidates that enhance this SUMOylation process.
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Objective: To determine whether daily dimethylglycine supplementation affects plasma homocysteine concentrations.

Design And Methods: A randomized, blinded, crossover design was used. Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days.

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Betaine-homocysteine methyltransferase (BHMT) activity can be measured directly and kinetically by (1)H-nuclear magnetic resonance spectroscopy. The disappearance of substrates and the formation of products are monitored simultaneously. Alternative substrates, separately and when mixed with glycine betaine, can also be monitored.

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Glycine betaine supplementation lowers homocysteine levels in homocystinuria and in chronic renal failure patients through methylation catalysed by betaine-homocysteine methyltransferase (BHMT). The aim of this study was to determine the effect of glycine betaine analogues on homocysteine metabolism in Lewis rats. Glycine betaine, proline betaine, trigonelline, dimethylsulfoniopropionate (DMSP) or dimethylthetin (1.

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The ventromedial hypothalamic nucleus (VMN) is known to mediate autonomic responses in feeding and reproductive behaviors. To date, the most definitive molecular marker for the VMN is the orphan nuclear receptor steroidogenic factor-1 (SF-1). However, it is unclear whether SF-1 functions in the VMN as it does in peripheral endocrine organ development where loss of SF-1 results in organ agenesis due to apoptosis.

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