Photodynamic therapy (PDT) has emerged as a capable therapeutic modality for the treatment of cancer. PDT is a targeted cancer therapy that reportedly leads to tumor cell apoptosis and/or necrosis by facilitating the secretion of certain pro-inflammatory cytokines and expression of multiple apoptotic mediators in the tumor microenvironment. In addition, PDT also triggers oxidative stress that directs tumor cell killing and activation of inflammatory responses. However, the cellular and molecular mechanisms underlying the role of PDT in facilitating tumor cell apoptosis remain ambiguous. Here, we investigated the ability of PDT in association with hypericin (HY) to induce tumor cell apoptosis by facilitating the induction of reactive oxygen species (ROS) and secretion of Th1/Th2/Th17 cytokines in human hepatocellular liver carcinoma cell line (HepG2) cells. To discover if any apoptotic mediators were implicated in the enhancement of cell death of HY-PDT-treated tumor cells, selected gene profiling in response to HY-PDT treatment was implemented. Experimental results showed that interleukin (IL)-6 was significantly increased in all HY-PDT-treated cells, especially in 1 μg/ml HY-PDT, resulting in cell death. In addition, quantitative real-time PCR analysis revealed that the expression of apoptotic genes, such as BH3-interacting-domain death agonist (BID), cytochrome complex (CYT-C) and caspases (CASP3, 6, 7, 8 and 9) was remarkably higher in HY-PDT-treated HepG2 cells than the untreated HepG2 cells, entailing that tumor destruction of immune-mediated cell death occurs only in PDT-treated tumor cells. Hence, we showed that HY-PDT treatment induces apoptosis in HepG2 cells by facilitating cytotoxic ROS, and potentially recruits IL-6 and apoptosis mediators, providing additional hints for the existence of alternative mechanisms of anti-tumor immunity in hepatocellular carcinoma, which contribute to long-term suppression of tumor growth following PDT.
Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent.
Gold nanoparticles (AuNPs) have undergone significant research for their use in the treatment of cancer. Numerous researchers have established their potent antitumor properties, which have greatly impacted the treatment of cancer. AuNPs have been used in four primary anticancer treatment modalities, namely radiation, photothermal therapy, photodynamic therapy, and chemotherapy. However, the ability of AuNPs to destroy cancer is lacking and can even harm healthy cells without the right direction to transport them to the tumor microenvironment. Consequently, a suitable targeting technique is needed. Based on the distinct features of the human tumor microenvironment, this review discusses four different targeting strategies that target the four key features of the tumor microenvironment, including abnormal vasculature, overexpression of specific receptors, an acidic microenvironment, and a hypoxic microenvironment, to direct surface-functionalized AuNPs to the tumor microenvironment and increase antitumor efficacies. In addition, some current completed or ongoing clinical trials of AuNPs will also be discussed below to further reinforce the concept of using AuNPs in anticancer therapy.
This study aimed to review the risk factors and clinical outcomes of patients undergoing pars planar vitrectomy (PPV) for breakthrough bleeding (BTB) from age related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). We performed a retrospective review of medical records of 346 patients operated by the vitreoretinal unit at Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia from January 2008 - June 2011. We found eight eyes of 8 patients with AMD/IPCV-related BTB who underwent PPV. Mean age of patients was 64.4 years (range 41-80 years) with 5 males. Five were Chinese. Duration of symptoms ranged from days to months. Four patients were on anti-coagulants. Two had history of prior photodynamic therapy. There were five cases of PCV, of which three were macular in location. All three cases of AMD were macular. Intraoperative intravitreal ranibizumab injection was given in three cases and two had combined vitrectomy and cataract extraction. All cases reported improvement in visual acuity with four cases achieving 6/60 or better post operatively including two cases of extramacular PCV achieving 6/9 vision. Mean follow-up was 60 weeks. Postoperative complications included retinal tear and detachment in one case, reattached on reoperation. Six patients had a history of hypertension including one individual with stroke. Our small series indicates a predominance of Chinese individuals with BTB. Usage of anticoagulants and hypertension may be a predisposing factor. Better visual prognosis occurs with extramacular lesions which tend to be of PCV type.
Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides the skin, genital mucosa, scalp and nails. An immune mediated pathogenesis is recognized in lichen planus although the exact etiology is unknown. The disease most commonly affects middle-aged females. Oral lichenoid reactions (OLR) which are considered variants of OLP, may be regarded as a disease by itself or as an exacerbation of an existing OLP, by the presence of medication (lichenoid drug reactions) or dental materials (contact hypersensitivity). OLP usually presents as white striations (Wickham's striae), white papules, white plaque, erythema, erosions or blisters. Diagnosis of OLP is established either by clinical examination only or by clinical examination with histopathologic confirmation. Direct immunofluorescence examination is only used as an adjunct to the above method of diagnosis and to rule out specific autoimmune diseases such as pemphigus and pemphigoid. Histopathologic features of OLP and OLR are similar with suggestions of certain discriminatory features by some authors. Topical corticosteroids are the treatment of choice for OLP although several other medications have been studied including retinoids, tacrolimus, cyclosporine and photodynamic therapy. Certain OLP undergo malignant transformation and the exact incidence and mechanisms are still controversial. In this paper, etiopathogenesis, diagnosis, management and malignant transformation of OLP and OLR have been reviewed.
We report a case of optic disc drusen (ODD) associated with peripapillary polypoidal choroidal vasculopathy (PCV). A 62-year-old Malay lady presented with both eye ODD and the left eye associated with peripapillary subretinal hemorrhage. Ultrasound B-scan and red-free photography confirmed the optic nerve head drusen findings bilaterally. Optical coherence tomography (OCT) of the left eye showed sharply elevated peripapillary pigment epithelial detachment with subretinal fluid. The presence of peripapillary polyps with branching vascular network in indocyanine green angiography of the left eye further confirmed the diagnosis of PCV and excluded choroidal neovascularization (CNV) secondary to ODD. Subsequently, the patient was treated with a combination of verteporfin photodynamic therapy with three monthly intravitreal ranibizumab injections. Three months after the combined treatment, OCT showed completely resolved subretinal fluid. ODD can cause compression of the subretinal vessels at the optic disc that results in retinal ischemia and release of vascular endothelial growth factor, which may trigger the development of CNV or PCV. The rarity of this combination makes it interesting to study more cases of ODD with PCV. Importantly, a thorough evaluation in distinguishing the PCV from the CNV that mimics it is crucial for early detection and prompt intervention. In this case, indocyanine green angiography (ICGA) is the diagnostic method to differentiate the PCV from CNV secondary to ODD.