Photodynamic therapy with Verteporfin in subfoveal choroidal metastasis of breast carcinoma (a controlled case)

A 55-year old woman with growing unilateral subfoveal choroidal metastasis of breast carcinoma was treated by photodynamic therapy (PDT) with verteporfin. Best corrected visual acuity remained stable during the whole follow-up of 6 months. Tumor flattened from 2.2 mm to 0 mm on ultrasound one month after the therapy. PDT with verteporfin appears to be the best tolerated method for palliative treatment of growing subfoveal choroidal metastasis of the breast carcinoma.     

New therapies for the treatment of age-related macular degeneration]

Age-related macular degeneration has a natural progression from the precursors (the drusen) towards atrophic or neovascular complications. Choroidal neovascularization is undoubtedly the aspect of the disease that benefits most from new therapeutical approaches. Destructive photocoagulation based on fluorescein angiography has demonstrated since 20 years its efficiency on choroidal neovascularization. The same approach based on indocyanine green (ICG) angiography would increase the number of patients available to therapy. Very recently photodynamic therapy has demonstrated its efficiency to stabilize visual acuity at least at two years in patients with choroidal new vessels predominantly well defined. Other treatment developments are considered, such as refinement of photocoagulation techniques or of surgery. Until now, none has demonstrated its efficiency although they raise justified hopes. The future approaches rely upon the progress of the research both in physiopathology of the disease and on the angiogenic process requiring a constant interaction with all thematics of research. Finally, palliative treatments will be required before heading up to a preventive treatment.     

Strategies for treating oesophageal diseases with stem cells

There is a wide range of oesophageal diseases, the most general of which are inflammation, injury and tumours, and treatment methods are constantly being developed and updated. With an increasingly comprehensive understanding of stem cells and their characteristics of multilineage differentiation, self-renewal and homing as well as the combination of stem cells with regenerative medicine, tissue engineering and gene therapy, stem cells are playing an important role in the treatment of a variety of diseases. Mesenchymal stem cells have many advantages and are most commonly applied; however, most of these applications have been in experimental studies, with few related clinical trials for comparison. Therefore, the methods, positive significance and limitations of stem cells in the treatment of oesophageal diseases remain incompletely understood. Thus, the purpose of this paper is to review the current literature and summarize the efficacy of stem cells in the treatment of oesophageal diseases, including oesophageal ulceration, acute radiation-induced oesophageal injury, corrosive oesophageal injury, oesophageal stricture formation after endoscopic submucosal dissection and oesophageal reconstruction, as well as gene therapy for oesophageal cancer.     

Oesophageal cancer in Africa

Oesophageal cancer, the eighth most frequent cancer in the world occurs as two main subtypes, squamous cell carcinoma (more prevalent in developing countries) and adenocarcinoma (more common in developed countries). Certain populations of central, eastern, and southern Africa display very high frequencies of oesophageal squamous cell carcinoma, presenting a serious health burden to the continent. Most patients are diagnosed at a late stage because of the asymptomatic development of the disease, with associated poor prognosis. A better understanding of the aetiological agents and molecular mechanisms involved in the development of oesophageal squamous cell carcinoma may offer opportunities to reduce exposure to environmental risk factors and also allow early diagnosis or predict response to therapy. Epidemiologic studies have identified smoking, alcohol consumption, diets poor in fresh fruit and vegetables, consumption of foods contaminated with Fusarium verticillioides, and HPV infection as risk factors associated with the development of this disease in Africa. Although we have an incomplete understanding of the molecular events involved in the development of oesophageal squamous cell carcinoma, advances have been made that suggest lines of future exploration. South African patients with oesophageal squamous cell carcinoma display a lower incidence of point mutations in the p53 gene than described elsewhere, suggesting that the profile of aetiological agents may be different than described for other high-risk areas for oesophageal cancer. Recent studies suggest that RARbeta and COX II is frequently downregulated and upregulated, respectively, in oesophageal squamous cell carcinomas. These results suggest potential therapeutic opportunities that can be exploited to combat the high incidence of this disease in Africa.     

藻红蛋白光敏剂研究进展

光动力学治疗法作为一种新的肿瘤治疗方法,近年来发展十分迅速。从红藻中提取的藻红蛋白可以作为光动力学治疗法的一种新的光敏剂。本概述了我国红藻藻红蛋白资源概况、光疗法和光敏剂作用机理及其研究发展历史与现状,重点阐述了藻红蛋白光敏剂的应用现状、前景和发展趋势,并认为藻红蛋白是光动力学治疗法中一种非常有前景的光敏剂。藻红蛋白在490nm有吸收光谱,而发射光谱位于560nm;藻红蛋白能特异性地聚集在肿瘤细胞周围,吸收周围环境光能并传递给氧分子,使氧分子转化为具有强氧化性的多线态氧,从而可以大量杀死肿瘤细胞。     

MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: potential biomarkers and therapeutic targets

MicroRNAs are a class of small, non‐coding RNAs that can negatively regulate protein‐coding genes, and are associated with almost all known physiological and pathological processes, especially cancer. The number of studies documenting miRNA expression patterns in malignancy continues to expand rapidly, with continuously gained critical information regarding how aberrantly expressed miRNAs may contribute to carcinogenesis. miRNAs can influence cancer pathogenesis, playing a potential role as either oncogenes or tumour suppressors. Recently, several miRNAs have been reported to exert different regulatory functions in oesophageal cancer – the carcinoma typically arising from the epithelial lining of the oesophagus. These miRNAs also have potential clinical applications towards developing biomarkers or targets for possible use in diagnosis or therapy in oesophageal cancer. In this review, we have summarized the two (oncogenic or tumour suppressive) roles of miRNAs here, and their applications as potential biomarkers or therapeutic targets, which may illuminate future treatment for oesophageal cancer.     

光学成像技术在体研究肿瘤的光动力效应

光动力疗法 (PDT) 已发展成为一种较成熟的肿瘤治疗方法, PDT 诱导的血管损伤是杀死肿瘤的重要机制之一 . 为了在活体肿瘤模型上实时监测 PDT 导致的血管损伤效应,使用稳定高表达绿色荧光蛋白 (GFP) 的人涎腺腺样囊性癌细胞株 (ACC-M-GFP) ,建立了基于鸡胚尿囊膜 (CAM) 的肿瘤模型 . 应用荧光成像技术对肿瘤的生长位置、大小,以及治疗区域进行方便精确的定位;利用激光散斑成像技术,实时监测 CAM 上肿瘤周围血管的血液动力学参数 . 发现不同光动力剂量所导致的血管损伤有显著不同 . 结果表明,荧光标记的鸡胚尿囊膜肿瘤模型为研究 PDT 导致的血管损伤效应提供了良好的实验模型,激光散斑成像技术适用于实时监测 PDT 过程中血管结构、血流速度的变化,由此得出血液灌注率可用以评估 PDT 对肿瘤周围血管的损伤效应 .     

Current trends in photodynamic therapy of neoplasms and non-neoplastic diseases

The photodynamic therapy of tumors is a modern therapeutic modality for organ-preserving treatment of oncological diseases. The method is based on selective laser irradiation of tumor tissues previously sensitized by tumorotropic dyes. During the last decades, photodynamic therapy has become worldwide known as a proper approach to the treatment of the patients with malignant tumors of various locations and a number of nontumoral diseases. The characteristics of modern photosensitizers and light sources for photodynamic therapy and their clinical applications are reviewed.     

Photodynamic Therapy Using Systemic Administration of 5-Aminolevulinic Acid and a 410-nm Wavelength Light-Emitting Diode for Methicillin-Resistant Staphylococcus aureus-Infected Ulcers in Mice

Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.     

The outcome of 5-ALA-mediated photodynamic treatment in melanoma cells is influenced by vitamin C and heme oxygenase-1

Photodynamic therapy (PDT) is an important clinical approach for cancer treatment. It involves the administration of a photosensitizer, followed by its activation with light and induction of cell death. The underlying mechanism is an increased production of reactive oxygen species (ROS) leading to oxidative stress, which is followed by cell death. However, effectiveness of PDT is limited due to an initiation of endogenous rescue response systems like heme oxygenase-1 (HO-1) in tumor cells. In recent years, consuming of antioxidant supplements has become widespread, but the effect of exogenously applied antioxidants on cancer therapy outcome remains unclear. Thus, this study was aimed to investigate if exogenous antioxidants might decrease ROS-induced cytotoxicity in photodynamic treatment. Lycopene, β-carotene, vitamin C, N-acetylcysteine, trolox, and N-tert-butyl-α-phenylnitrone in different doses were administered to human melanoma cells prior exposure to photodynamic treatment. Supplementation with vitamin C resulted in a significant decrease of the cell death rate, whereas the other tested antioxidants had no effect on cell viability and oxidative stress markers. The simultaneous application of vitamin C with the HO-1 activity inhibitor zinc protoporphyrine IX (ZnPPIX) caused a considerable decrease of photodynamic treatment-induced cytotoxicity compared to ZnPPIX alone. It can be summarized that exogenously applied antioxidants do not have a leading role in the protective response against photodynamic treatment. However, further studies are necessary to investigate more antioxidants and other substances, which might affect the outcome of photodynamic treatment in cancer therapy.     

Combined effects of radiotherapy and photodynamic therapy on an in vitro human prostate model

Human prostate cancer cells were evaluated for growth after photodynamic therapy, radiotherapy, and combined treatment. Indocyanine green was tested as a photosensitizer and radiosensitizer. Two human cell lines were used: PC-3 derived from prostate carcinoma, and EPN derived from normal prostate tissue. The light source used for the photoactivation experiments was a diode laser peaked at 805 nm. The light dose incident on cells was 108 J/cm(2). Ionizing radiation was produced by a linear accelerator, and the dose was 2, 4 and 6 Gy. Cytotoxicity was evaluated by measuring the colony forming ability of cells. Our results show that indocyanine green induces cell death by photoactivation, but it does not act as a radiosensitizer if used with ionizing radiation. The combined treatment of photodynamic therapy and radiotherapy produces an additive effect which does not depend on the sequence of the two treatments. Combined treatments could be more useful since they allow the reduction of the ionizing radiation dose to obtain the same effect as one obtainable by radiotherapy alone.     

Comprehensive treatment of malignant mesothelioma patients after the failure of systemic chemotherapy

Malignant mesothelioma (MM) is an aggressive neoplasm usually arising from the mesothelial surfaces of the pleural or peritoneal cavity. Currently, no standard therapy is available. The most commonly used therapy is cytoreductive surgery combined with systematic chemotherapy, but the median overall survival (OS) is less than 12 months; moreover, treatments are lacking for patients in whom chemotherapy has failed and/or who cannot withstand surgery. We investigated multiple minimally invasive therapies (cryosurgery, photodynamic therapy and intracavity chemotherapy) for the treatment of MM patients in whom systemic chemotherapy had failed. Twenty-seven patients were divided into comprehensive (combination of the three therapies) and palliative (intracavity chemotherapy only) treatment groups. The OS of patients who received comprehensive treatment was significantly longer than that of those who received palliative treatment (median OS: 64 vs. 9 months, P < 0.001). This interesting result was not associated with treatment timing, but was closely associated with repeated treatments.     

Effect of curcumin-nanoemulsion associated with photodynamic therapy in breast adenocarcinoma cell line

Curcumin, a natural compound has several antineoplastic activities and is a promising natural photosensitizer used in photodynamic therapy. However, its low solubility in physiological medium limit the clinical use of curcumin. This study aimed to analyze the action of curcumin-nanoemulsion, a new and well-designed Drug Delivery System (DDS+) molecule, used as a photosensitizing agent in photodynamic therapy in an in vitro breast cancer model, MCF-7 cells. The empty nanoemulsion fulfils all necessary requirements to be an excellent DDS. Furthermore, the use of curcumin-nanoemulsion in photodynamic therapy resulted in a high phototoxic effect after activation at 440?nm, decreasing to <10% viable tumor cells after two irradiations and increasing the reactive oxygen species (ROS) production. The use of curcumin-nanoemulsion associated with photodynamic therapy resulted in an increase in the levels of caspase 3/7 activity for the studied MCF-7 cell model, indicating that this therapy triggers a cascade of events that lead to cell death, such as cellular apoptosis. In conclusion, curcumin-nanoemulsion proved to be efficient as a photosensitizing agent, had phototoxic effects, significantly decreased the proliferation of MCF-7 cells and stimulating the ROS production in combination with photodynamic therapy, so, this formulation has a great potential for use in treatment of breast cancer.     

光动力技术治疗胃癌的进展及展望

近年来应用光动力技术治疗胃癌取得了可喜的进步,它对各个时期的胃癌均有比较满意的临床效果。本文通过对国内外近年来用光动力技术治疗胃癌方面的文献进行综述,系统阐述光动力运用于胃癌治疗这一项技术的原理、机制,光敏剂、光源及临床效果等方面,并总结了这项技术在治疗胃癌方面的优点和相关问题。     

Comprehensive treatment of malignant mesothelioma patients after the failure of systemic chemotherapy

Malignant mesothelioma (MM) is an aggressive neoplasm usually arising from the mesothelial surfaces of the pleural or peritoneal cavity. Currently, no standard therapy is available. The most commonly used therapy is cytoreductive surgery combined with systematic chemotherapy, but the median overall survival (OS) is less than 12 months; moreover, treatments are lacking for patients in whom chemotherapy has failed and/or who cannot withstand surgery. We investigated multiple minimally invasive therapies (cryosurgery, photodynamic therapy and intracavity chemotherapy) for the treatment of MM patients in whom systemic chemotherapy had failed. Twenty-seven patients were divided into comprehensive (combination of the three therapies) and palliative (intracavity chemotherapy only) treatment groups. The OS of patients who received comprehensive treatment was significantly longer than that of those who received palliative treatment (median OS: 64 vs. 9 months, P < 0.001). This interesting result was not associated with treatment timing, but was closely associated with repeated treatments.     

Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

Photodynamic molecules represent an alternative approach for cancer therapy for their property (i) to be photo-reactive; (ii) to be not-toxic for target cells in absence of light; (iii) to accumulate specifically into tumour tissues; (iv) to be activable by a light beam only at the tumour site and (v) to exert cytotoxic activity against tumour cells. However, to date their clinical use is limited by the side effects elicited by systemic administration. Extracellular vesicles are endogenous nanosized-carriers that have been recently introduced as a natural delivery system for therapeutic molecules. We have recently shown the ability of human exosomes to deliver photodynamic molecules. Therefore, this review focussed on extracellular vesicles as a novel strategy for the delivery of photodynamic molecules at cancer sites. This completely new approach may enhance the delivery and decrease the toxicity of photodynamic molecules, therefore, represent the future for photodynamic therapy for cancer treatment.     

New approach to the adoptive immunotherapy of Walker-256 carcinosarcoma with activated macrophages combined with photodynamic therapy

Experiments were performed on five batches of Wistar inbred rats with Walker-256 carcinoma receiving sole (PDT, MAK) or combined therapy (PDT + MAK-A; PDT + MAK-B); the control batch (HBSS) consisted of animals with untreated tumors. The results were as follows: a) the sole treatment (PDT, MAK) gave survival rates between 37.7 and 47.5%, b) the "combined" therapy in five doses increased significantly (70.8%) the survival rate of tumor bearing rate as well as the rate of complete regression (82.1%). The cell-mediated immunity test and histopathological as well as the electron microscopy observations were in full agreement with the results above. Summing up, these results demonstrate that "combined" photodynamic therapy with intra- and peritumoral MAK infusion stimulated cell-mediated antitumoral activity, increased survival rates and reduces incidence of Walker-256 carcinoma in rat model.     

Hypericin as a potential phototherapeutic agent in superficial transitional cell carcinoma of the bladder.

Photodynamic therapy (PDT) involves the local or systemic administration of a photosensitizing drug that, upon light irradiation and presence of oxygen, results in tissue damage such as tumor destruction. Hypericin, a hydroxylated phenanthroperylenequinone, is obtained from Hypericum perforatum plants. Hypericin exhibits a high fluorescence quantum yield, and its presence in the tissue can easily be visualized. Interestingly, when instilled into the human bladders, hypericin selectively accumulates in the bladder carcinoma lesions, with the specificity and sensitivity of detecting CIS reaching up to 98.5 and 93%, respectively. Due to this selective accumulation of hypericin in bladder carcinoma lesions, the compound is now used as a fluorescent diagnostic tool for superficial bladder cancer. However, hypericin is also a photosensitizer with a potent photocytotoxic activity. Taken together, these data indicate that hypericin could be used for whole bladder wall PDT of superficial bladder tumors. This review focuses on the more recent in vitro and in vivo evaluation of hypericin as a photodynamic agent in the treatment of superficial transitional cell carcinoma (TCC) bladder tumors.     

Lactose esters: synthesis and biotechnological applications

Biodegradable nonionic sugar esters-based surfactants have been gaining more and more attention in recent years due to their chemical plasticity that enables the various applications of these molecules. In this review, various synthesis methods and biotechnological implications of lactose esters (LEs) uses are considered. Several chemical and enzymatic approaches are described for the synthesis of LEs, together with their applications, i.e. function in detergents formulation and as additives that not only stabilize food products but also protect food from undesired microbial contamination. Further, this article discusses medical applications of LEs in cancer treatment, especially their uses as biosensors, halogenated anticancer drugs, and photosensitizing agents for photodynamic therapy of cancer and photodynamic inactivation of microorganisms.     

Oesophageal cancer treatment in North East Thames region, 1981: medical audit using Hospital Activity Analysis data.

Figures from the Hospital Activity Analysis in the North East Thames region in 1981 were used to perform a medical audit on oesophageal cancer treatment. Four hundred and forty four patients were admitted with this diagnosis; 80 had been intubated without a thoracotomy or laparotomy, and 73 had had surgery (two thirds radical and one third palliative) with an overall operative mortality of 33%. Fifty five patients had had radiotherapy and 179 patients had no recorded operation or investigation. One hundred and seventy seven different consultants had looked after all these inpatients, most being general surgeons. Only five consultants had looked after 10 or more patients each year. From a calculated estimate of a total 286 patients in the region, 28% had palliative intubation and 25% had surgery; 20% of all the patients had radiotherapy either as a radical or palliative treatment, the remainder having no recorded therapeutic procedure. One hundred and eighty seven patients (66% of the calculated total) died in hospital. Investigation and treatment do not seem to be limited by lack of money, but money is being wasted by admitting patients for terminal care into acute hospital beds. It would be more humane for these patients to die at home or in a hospice if they wished.