Yik Yuen Gan

New stimuli-responsive copolymers of N-acryloyl-N′-alkyl piperazine and methyl methacrylate and their hydrogels

Water-soluble copolymers of N-acryloyl-N′-alkylpiperazine (alkyl: methyl, ethyl) with methyl methacrylate were synthesized and the lower critical solution temperatures (LCSTs) of the copolymers which depend on the compositions and pH of the aqueous solutions are described. The effects of cationic surfactants and simple inorganic salts on the LCSTs are also reported. The influences of pH and temperature on the swelling of the ionizable and thermosensitive hydrogels are studied.

The effect of photodynamic therapy on tumor angiogenesis

Photodynamic therapy (PDT), the activation of a photosensitive drug in tumor tissue with light of specific wavelength, has been used effectively to treat certain solid tumors. Though therapeutic responses are encouraging, PDT-mediated oxidative stress can act as an angiogenic switch that ultimately leads to neovascularization and tumor recurrence. This article explores the effect of PDT on angiogenesis in different tumor models. Overexpression of proangiogenic vascular endothelial growth factor, cyclooxygenase-2 and matrix metalloproteases has often been reported post-illumination. Recent clinical studies have demonstrated that inhibiting angiogenesis after chemotherapy and radiotherapy is an attractive and valuable approach to cancer treatment. In this review, we report the effective therapeutic strategy of combining angiogenesis inhibitors with PDT to control and treat tumors.

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

BackgroundPhotodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period.ResultsOur results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux.ConclusionThe combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors.

The 27-bp VNTR Polymorphism in Intron 4 of the Human eNOS Gene in Healthy Singaporean Chinese, Indians, and Malays

Human endothelial nitric oxide synthase (eNOS) is one isoform of the nitric oxide synthases that are responsible for nitric oxide synthesis from l-arginine. The gene encoding eNOS contains a 27-bp VNTR polymorphism in intron 4. We report here for the first time the presence of a novel allele 3, which was absent in all other populations studied to date, in 1.7% each of Singaporean Indians and Malays. We also detected the presence of a novel genotype 3/5 in 3.4% each of Singaporean Indians and Malays. Allele 6, which was absent in Han Chinese from northern China and Taiwan and was also absent in Indians from the Indian subcontinent, was found in 2.1% of Singaporean Chinese and in 0.3% of Singaporean Indians.

Hardy–Weinberg Disequilibrium of the IL-18 C−607A SNP Suggesting Selective Advantage of Heterozygotes

Interleukin-18 (IL-18) plays a key role in autoimmune, inflammatory, and infectious diseases. The IL-18 gene contains a C to A single nucleotide polymorphism (SNP) at position −607 (C−607A) within the promoter region, which was found to affect the promoter activity and subsequently the protein level of IL-18. We investigated this SNP in a group of healthy Singaporeans and found that CA was the most common genotype and the C allele was more prevalent than the A allele, which was not always the case in other ethnic groups. In addition, Singaporean Chinese were significantly different from Singaporean Indians in both allelic and genotypic distributions. Furthermore, significant deviations from Hardy–Weinberg equilibrium of this SNP were found in all three ethnic groups studied (Chinese, Indians, and Malays) and also in other published literature, suggesting that heterozygotes of this IL-18 C−607A SNP may have certain selective advantages.

Coating of polystyrene thin film on glass for protein immobilization in optical biosensor applications

Immobilizing protein on glass surfaces is typically more difficult and less efficient than on plastic surfaces. Proteins are readily adsorbed on plastic surfaces in a single step. To simplify protein immobilization efficiency on glass surfaces and enhance its efficiency, styrylsilane and polystyrene were coated on glass to serve as protein binding substrates.

Author's reply to comment on ''The effect of photodynamic therapy on tumor angiogenesis. Cellular and Molecular Life Sciences, 66, 2275-2283''

The comments by Nowak-Slieinska et al. are an extensionof our review article. We agree with the authors that vas-cular normalization is an important event that decides theoutcome of anti-angiogenesis therapies. As reported byJain RK et al. [1], antiangiogenic agents can normalize theabnormal structure and function of tumor vasculature tomake it more efficient for oxygen and drug delivery.Therefore, induction of vascular normalization caused byanti-angiogenic agents provides a novel means of effectivedelivery of chemotherapeutic drugs. Our report was basedon the effective use of anti-angiogenesis therapy toimprove therapeutic efficacy of PDT. The authors agreethat the use of anti-angiogenesis agents before PDT toinduce vascular normalization and increase the homoge-nous effect of oxygen-dependent PDT is an interestinghypothesis that is worth pursuing.Reference

Combination of angiogenesis inhibitors increases the anti-tumor efficacy of photodynamic therapy in a human bladder tumor xenograft model

Photodynamic therapy (PDT) is a standard treatment for various malignant and non-malignant conditions. Though therapeutic responses are encouraging, recurrences have been noted, as one of the limitations of PDT is treatment-induced hypoxia that triggers angiogenesis. The present study evaluates the use of angiogenic inhibitors Avastin, that targets vascular endothelial growth factor (VEGF) and Erbitux that targets epidermal growth factor receptor (EGFR) with PDT in an in vivo bladder carcinoma xenograft. Tumor bearing mice were assigned to 6 different categories: control, PDT only, Avastin + Erbitux, PDT + Avastin, PDT + Erbitux and PDT + Avastin and Erbitux. Treated and control tumors were monitored for recurrence for up to 90 days. VEGF and EGFR expression was detected in the tumor tissue. Migratory assay was performed to establish the inhibitory effect of the angiogenesis agents. Using confocal laser endomicroscopy, the tumor microvasculature was assessed. Tumors treated with the combination therapy of PDT + inhibitors showed significantly greater response compared to control and PDT only treated group. Combination therapy treated tumors also showed the most post-treatment damage with reduced tumor vasculature. These results demonstrate that the combination of PDT with inhibitors that target different angiogenesis pathways can improve tumor control.

Studies of photoluminescence of p-phenylenevinylene oligomer and its polymer blends

Abstract A p-phenylenevinylene oligomer, 1,4-bis(3′-methyl-6′-octyloxystyryl)benzene was synthesized using Wittig’s reaction. The oligomer was isomerized to all trans structure by refluxing in toluene with a catalytic amount of iodine. The oligomer was characterized by using 1H NMR, UV–VIS, differential scanning calorimetry and fluorescence techniques. Polymer blends of the oligomer with PMMA and two short conjugation length polymers were studied for their photoluminescence (PL) properties. The blends with short conjugation length polymers showed significant increase in PL intensity, suggesting the occurrence of excitonic migration from oligomer to these polymers.