Biomedical subjects

Raymond Chen

Publications and source records attributed to Raymond Chen.

6 recordsLinked to original sources

PubMed2026

Viral mimicry escape as a necessary feature of malignant transformation.

Malignant transformation is driven by disruption of pathways regulating proliferation and cell fate, but these same disruptions can create a collateral vulnerability: loss of transcriptional and epigenetic control over transposable elements and other normally silenced genomic regions. Consequently, emerging cancer cells can accumulate transposable element-derived and other endogenous immunogenic nucleic acids capable of triggering antiviral responses, a process termed viral mimicry. Increasing evidence indicates that viral mimicry can eliminate precancerous cells and shape tumour evolution, positioning it as an intrinsic tumour-suppressive mechanism. Here we highlight how cancer-associated changes in DNA methylation, histone modifications, splicing and RNA processing can lead to the presence of immunogenic nucleic acids that can activate viral mimicry pathways. We outline how cancer cells suppress viral mimicry, including compensatory epigenetic repression, RNA editing, nucleic acid decay and dampening of interferon signalling to enable cancer cell growth. Finally, we highlight the evidence suggesting that escaping viral mimicry is a fundamental process for cancer initiation and progression, and suggest that viral mimicry escape is necessary for cancer transformation and a therapeutic target in combination with immunotherapies. By framing viral mimicry escape as a necessary part of cancer transformation, this Review provides a unifying conceptual model for its translational exploitation.

Journal Article↗

PubMed2025

Repeats mimic pathogen-associated patterns across a vast evolutionary landscape.

An emerging hallmark of many human diseases is transcription of typically silenced repetitive DNA containing pathogen-associated molecular patterns (PAMPs). These PAMPs engage the innate immune system via pattern recognition receptors (PRRs)-a phenomenon known as viral mimicry. We propose a statistical physics framework to quantify viral mimicry by measuring "selective forces" that enrich PAMPs compared to a genome-wide reference distribution. We validate our predictions by identifying repeats that bind different PRRs and show potential viral mimics in different repeat families across eukaryotic genomes, suggesting shared mechanisms drive emergence and retention. We propose two non-exclusive evolutionary hypotheses. The first "repeat-centric" hypothesis posits PAMPs are integral to the repeat life cycle and are therefore enriched as they mediate repeat expansion. The second "organism-centric" hypothesis proposes viral mimicry functions as a cell-intrinsic feedback mechanism for sensing and reacting to transcriptional dysregulation, which provides a selective pressure to maintain PAMPs in genomes.

Humans↗

PubMed2006

Suture bicuspidization of the tricuspid valve versus ring annuloplasty for repair of functional tricuspid regurgitation: midterm results of 237 consecutive patients.

OBJECTIVE: Uncorrected functional tricuspid regurgitation has serious long-term morbidity and mortality. We reviewed our experience with tricuspid posterior annular bicuspidization versus ring tricuspid annuloplasty for treatment of functional tricuspid regurgitation. METHODS: From 1999 to 2003, 237 patients underwent tricuspid annuloplasty for functional tricuspid regurgitation as part of their cardiac surgical procedure. Bicuspidization was performed in 157 patients and ring annuloplasty in 80 patients. Preoperatively, 227 (96%) patients had moderate or greater tricuspid regurgitation with a median regurgitation of 3+. Follow-up information was obtained for 234 (99%) patients with a mean follow-up time of 3 years. Postoperative transthoracic echocardiograms were assessed for severity of tricuspid regurgitation. Moderate or greater tricuspid regurgitation was considered significant. Survival and development of recurrent tricuspid regurgitation were evaluated by Kaplan-Meier analysis. Tricuspid regurgitation and risk factors for recurrent regurgitation were identified and analyzed by multivariable ordinal longitudinal methods. RESULTS: At 3 years postoperatively, tricuspid regurgitation in patients treated by bicuspidization annuloplasty was zero to mild in 75%, moderate in 11%, moderate to severe in 6%, and severe in 8% of patients. In those undergoing ring annuloplasty, tricuspid regurgitation was zero to mild in 69%, moderate in 14%, moderate to severe in 7%, and severe in 10%. There was no significant difference between the two groups (P = .18). Risk factors for recurrent tricuspid regurgitation included higher preoperative regurgitation grade, preoperative tricuspid regurgitation without concomitant mitral regurgitation, and higher pulmonary artery systolic pressure. CONCLUSIONS: Bicuspidization annuloplasty and ring annuloplasty were effective at eliminating tricuspid regurgitation at 3 years postoperatively. Bicuspidization annuloplasty is a simple, inexpensive option for addressing functional tricuspid regurgitation. All patients with moderate-to-severe functional tricuspid regurgitation should undergo tricuspid annuloplasty regardless of the technique used.

Adult↗

PubMed2004

Automated peak tracking for comprehensive impurity profiling in orthogonal liquid chromatographic separation using mass spectrometric detection.

The presence and quantity of impurities in pharmaceutical drugs can have a significant impact on their quality and safety. With the continuous pressure for increased industry productivity, there is urgent need for a systematic and comprehensive drug impurity profiling strategy. We report here our development of the fully automated Comprehensive Orthogonal Method Evaluation Technology (COMET) system. The system includes five columns, seven orthogonal HPLC methods, and hyphenated UV-MS detections, which provides automated generic impurities screening for any drug sample. An automated MS peak tracking approach by program-based mass spectral interpretation is devised to unambiguously track impurities among all orthogonal HPLC methods. The program passes electro-spray ionization mass spectra (ESI-MS) through four sequential decision-making mass ion tests and determines molecular weights for every peak. The system reduces the time required to obtain impurity profile from weeks to days, while the automated MS peak tracking takes only minutes to interpret all MS spectral data of interest. Up-to-date, impurity contents of 56 in-development drug candidate samples have all been successfully illustrated by COMET, which contained more than 500 chemical entities. The program is able to track more than 80% of the compounds automatically with majority of the failure due to insufficient ionization for some impurities by ESI. This system is well suited for efficient drug development and ensuring the quality and safety of drug products.

Algorithms↗

PubMedDate not supplied

Development and validation of a cost-effective, efficient, and robust liquid chromatographic method for the simultaneous determination of the acetyl and succinoyl content in hydroxypropyl methylcellulose acetate succinate polymer.

A reversed-phase liquid chromatographic method was developed and validated for the determination of the content of free acetic acid, free succinic acid, acetyl substituents, and succinoyl substituents in hydroxypropyl methylcellulose acetate succinate (HPMCAS; Chemical Abstracts Service Registry No. 71138-97-1) polymer. This single new method gave accurate and precise measurement of both acetyl and succinoyl substituents, which had previously required 3 Japanese Pharmaceutical Excipients (JPE) methods to accomplish. Consequently, analysis time and turnaround time are decreased significantly. Furthermore, this method can also separate and determine the free acetic and succinic acids in HPMCAS polymer, a task that the corresponding JPE method cannot achieve. The values for accuracy (average recovery from 12 standard samples) were 99.9% for acetic acid and 99.8% for succinic acid. The values for injection precision (relative standard deviation [RSD]) were 0.11% for acetic acid and 0.28% for succinic acid. The values for intermediate precision (RSD) were 1.25% for determination of the acetyl content at the 8.78% (w/w) level and 1.33% for determination of the succinoyl content at the 10.9% (w/w) level. The values for intermediate precision (RSD) were 5.98% for determination of free acetic acid at the 0.12% (w/w) level and 5.13% for determination of free succinic acid at the 0.029% (w/w) level. The method was proven to be robust with respect to variation in the pH of the mobile phase, the concentration of potassium dihydrogen phosphate, and the flow rate. The method is well suited for quality control in today's fast-paced pharmaceutical laboratories.

Acetates↗

PubMedDate not supplied

Alternative liquid chromatographic method for determination of the methoxyl and 2-hydroxypropoxyl content in cellulose ether derivatives.

An alternative liquid chromatographic (LC) method was developed and validated for the simultaneous determination of methoxyl and 2-hydroxypropoxyl substituents in hypromellose and hypromellose acetate succinate. The method uses the hydriodic acid cleavage reaction, catalyzed by adipic acid, of the substituted methoxyl and 2-hydroxypropoxyl groups, which are quantitatively converted to iodomethane and 2-iodopropane. The iodomethane and 2-iodopropane are extracted into xylene, the extract is diluted with methanol, and the analytes are separated and assayed by gradient elution using a reversed-phase C18 column. The method is selective and sensitive and has good linearity with values of 0.999 for R2 and 0.25% for the gamma-intercept bias from 1.39 to 5.55 mg/mL for iodomethane, and 0.999 for R2 and 0.52% for the gamma-intercept bias from 0.184 to 0.735 mg/mL for 2-iodopropane. The relative standard precisions for this LC method were found to be +/- 2.3% for determining methoxyl at the 23.1% (w/w) level, and +/- 3.5% for determining 2-hydroxypropoxyl at the 6.7% (w/w) level. Compared with the current gas chromatographic (GC) compendial (JPE) method, the LC assay method has equal or better precision. It was found that both the standard and sample solutions have limited stability (8 h) after preparation. This limited stability has not been reported previously in the literature and may have an impact on the reported accuracy/precision of the literature data for the GC method. The LC method was proven to be robust with respect to variation in derivatization time and temperature, flow rate, and column temperature. It is well suited for the quality control needed in today's fast-paced pharmaceutical laboratories.

Adipates↗