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Fulltext Mixed-methods approach to exploring patients' perspectives on the acceptability of a urinary biomarker test in replacing cystoscopy for bladder cancer surveillance

Tan WS, Teo CH, Chan D, Heinrich M, Feber A, Sarpong R, et al.

BJU Int, 2019 09;124(3):408-417.
PMID: 30694612 DOI: 10.1111/bju.14690

OBJECTIVES: To determine the minimal accepted sensitivity (MAS) of a urine biomarker that patients are willing to accept to replace cystoscopy and to assess qualitatively their views and reasons.
PATIENTS AND METHODS: Patients were part of a prospective multicentre observational study recruiting people with bladder cancer for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mixed-methods approach comprising (1) a questionnaire to assess patients' experience with cystoscopy and patients' preference for cystoscopy vs urinary biomarker, and (2) semi-structured interviews to understand patient views, choice and reasons for their preference.
RESULTS: A urine biomarker with an MAS of 90% would be accepted by 75.8% of patients. This was despite a high self-reported prevalence of haematuria (51.0%), dysuria/lower urinary tract symptoms (69.1%) and urinary tract infection requiring antibiotics (25.8%). There was no association between MAS with patient demographics, adverse events experienced, cancer characteristics or distance of patients' home to hospital. The qualitative analysis suggested that patients acknowledge that cystoscopy is invasive, embarrassing and associated with adverse events but are willing to tolerate the procedure because of its high sensitivity. Patients have confidence in cystoscopy and appreciate the visual diagnosis of cancer. Both low- and high-risk patients would consider a biomarker with a reported sensitivity similar to that of cystoscopy.
CONCLUSION: Patients value the high sensitivity of cystoscopy despite the reported discomfort and adverse events experienced after it. The sensitivity of a urinary biomarker must be close to cystoscopy to gain patients' acceptance.

Matched MeSH terms: Biomarkers, Tumor/urine*
Fulltext Identification of O-glycosylated proteins that are aberrantly excreted in the urine of patients with early stage ovarian cancer

Mu AK, Lim BK, Hashim OH, Shuib AS

Int J Mol Sci, 2013 Apr 11;14(4):7923-31.
PMID: 23579955 DOI: 10.3390/ijms14047923

Cancer is known to induce or alter the O-glycosylation of selective proteins that may eventually be excreted in the patients' urine. The present study was performed to identify O-glycosylated proteins that are aberrantly excreted in the urine of patients with early stage ovarian cancer (OCa). These urinary glycoproteins are potential biomarkers for early detection of OCa. In this study, urinary proteins of patients with early stage OCa and age-matched OCa negative women were subjected to two-dimensional gel electrophoresis and detection using a lectin that binds to the O-glycosylated proteins. Our analysis demonstrated significant enhanced expression of clusterin and leucine-rich alpha-2-glycoprotein, but lower levels of kininogen in the urine of the OCa patients compared to the controls. The different altered levels of these urinary glycoproteins were further confirmed using competitive ELISA. Our data are suggestive of the potential use of the aberrantly excreted urinary O-glycosylated proteins as biomarkers for the early detection of OCa, although this requires further validation in a large clinically representative population.

Matched MeSH terms: Biomarkers, Tumor/urine*
Fulltext Structures and binding specificity of galactose- and mannose-binding lectins from champedak: differences from jackfruit lectins

Gabrielsen M, Abdul-Rahman PS, Othman S, Hashim OH, Cogdell RJ

Acta Crystallogr F Struct Biol Commun, 2014 Jun;70(Pt 6):709-16.
PMID: 24915077 DOI: 10.1107/S2053230X14008966

Galactose-binding and mannose-binding lectins from the champedak fruit, which is native to South-east Asia, exhibit useful potential clinical applications. The specificity of the two lectins for their respective ligands allows the detection of potential cancer biomarkers and monitoring of the glycosylated state of proteins in human serum and/or urine. To fully understand and expand the use of these natural proteins, their complete sequences and crystal structures are presented here, together with details of sugar binding.

Matched MeSH terms: Biomarkers, Tumor/urine
Fulltext Detection of differential levels of proteins in the urine of patients with endometrial cancer: analysis using two-dimensional gel electrophoresis and o-glycan binding lectin

Mu AK, Lim BK, Hashim OH, Shuib AS

Int J Mol Sci, 2012;13(8):9489-501.
PMID: 22949810 DOI: 10.3390/ijms13089489

Cancers can cause some proteins to be aberrantly excreted or released in the urine, which can be used as biomarkers. To screen for potential biomarkers for endometrial cancer (ECa), the urinary proteins from patients who were newly diagnosed with early stage ECa and untreated controls were separated using two-dimensional gel electrophoresis (2-DE) and followed by image analysis. The altered levels of zinc alpha-2 glycoprotein, alpha 1-acid glycoprotein, and CD59 were detected in the patients compared to the controls. In addition, the urine of the ECa patients was also found to contain relatively lower levels of a fragment of nebulin when the 2-DE separated urinary proteins were probed using champedak galactose binding (CGB) lectin. The different levels of the nebulin fragment were further validated by subjecting the urinary protein samples to CGB lectin affinity chromatography and analysis of the bound fractions by LC-MS/MS. Our data is suggestive of the potential use of the differentially expressed urinary proteins as biomarkers for ECa although this requires further extensive validation on clinically representative populations.

Matched MeSH terms: Biomarkers, Tumor/urine*
Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment

Jayapalan JJ, Ng KL, Shuib AS, Razack AH, Hashim OH

Electrophoresis, 2013 Jun;34(11):1663-9.
PMID: 23417432 DOI: 10.1002/elps.201200583

The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.

Matched MeSH terms: Biomarkers, Tumor/urine*
Determination of α-ketoglutaric and pyruvic acids in urine as potential biomarkers for diabetic II and liver cancer

Makahleh A, Ben-Hander GM, Saad B

Bioanalysis, 2015;7(6):713-23.
PMID: 25871588 DOI: 10.4155/bio.14.307

BACKGROUND: A simple and sensitive hollow fiber-liquid phase microextraction with in situ derivatization method was developed for the determination of α-ketoglutaric (α-KG) and pyruvic acids (PA) in small-volume urine samples. 2,4,6-trichloro phenyl hydrazine was used as derivatization agent.
RESULTS: Under the optimum extraction conditions, enrichment factors of 742 and 400 for α-KG and PA, respectively, were achieved. Calibration curves were linear over the range 1 to 1000 ng/ml (r(2) ≥ 0.998). Detection and quantitation limits were 0.03 and 0.02, and 0.10 and 0.05 ng/ml for α-KG and PA, respectively.
CONCLUSION: The concentrations in diabetic II and liver cancer samples were significantly lower than those from healthy people, showing their potential as biomarkers for these diseases.

Matched MeSH terms: Biomarkers, Tumor/urine*
Fulltext Exacerbation of colon carcinogenesis by Blastocystis sp

Kumarasamy V, Kuppusamy UR, Jayalakshmi P, Samudi C, Ragavan ND, Kumar S

PLoS One, 2017;12(8):e0183097.
PMID: 28859095 DOI: 10.1371/journal.pone.0183097

Colorectal cancer (CRC) is one the most commonly diagnosed cancers worldwide and the number is increasing every year. Despite advances in screening programs, CRC remains as the second leading cause of cancer deaths in the United States. Oxidative stress plays an important role in the molecular mechanisms of colorectal cancer (CRC) and has been shown to be associated with Blastocystis sp., a common intestinal microorganism. In the present study, we aimed to identify a role for Blastocystis sp. in exacerbating carcinogenesis using in vivo rat model. Methylene blue staining was used to identify colonic aberrant crypt foci (ACF) and adenomas formation in infected rats whilst elevation of oxidative stress biomarker levels in the urine and serum samples were evaluated using biochemical assays. Histological changes of the intestinal mucosa were observed and a significant number of ACF was found in Blastocystis sp. infected AOM-rats compared to the AOM-controls. High levels of urinary oxidative indices including advanced oxidative protein products (AOPP) and hydrogen peroxide were observed in Blastocystis sp. infected AOM-rats compared to the uninfected AOM-rats. Our study provides evidence that Blastocystis sp. has a significant role in enhancing AOM-induced carcinogenesis by resulting damage to the intestinal epithelium and promoting oxidative damage in Blastocystis sp. infected rats.

Matched MeSH terms: Biomarkers, Tumor/urine