Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (lambda>or=600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen ((1)O(2)), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which (1)O(2) contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays.

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A significant proportion of extracellular nucleic acids in plasma circulate highly protected in tumor-specific exosomes, but it is unclear how the release of exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in plasma of 91 colorectal cancer patients to evaluate their potential as a tumor indicator and their repercussions on diagnosis and prognosis. We examined the involvement of TSAP6, a TP53-regulated gene involved in the regulation of vesicular secretion, in levels of circulating exosomes in plasma of colorectal patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell lines. The fraction of exosomes in cancer patients was statistically higher than in healthy controls (mean rank ¼ 53.93 vs. 24.35). High levels of exosomes in plasma of patients correlated with high levels of carcino-embryonic antigen (P ¼ 0.029) and with poorly differentiated tumors (P ¼ 0.039) and tended to have shorter overall survival than patients with low levels (P ¼ 0.056). Release of exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53 was not shown either in tumor samples or in HCT116 cell lines. Although it was not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into the plasma of colorectal cancer patients, the level of circulating exosomes may be used as a tumor indicator, because it correlates with poor prognosis parameters and shorter survival.

Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P < 0.01), MED (P < 0.001) and MPD (P < 0.001). After oral administration of PL, MED increased 2.8 +/- 0.59 times and MPD increased 2.75 +/- 0.5 and 6.8 +/- 1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.

The different clinical forms of leprosy are mainly related to the variety of immunological responses to the infection. Thus, lepromatous leprosy occurs in patients with a poor cell-mediated immunity to Mycobacterium leprae, whereas tuberculoid leprosy is associated with a high resistance to leprosy bacillus. Intermediate forms, including borderline tuberculoid leprosy, borderline lepromatous leprosy, and borderline leprosy, are a continuous and unstable spectrum of the disease. Leprosy reactions are rare and not well-known states that interrupt the usual chronic course and clinical stability of patients with leprosy. They are expressions of immunological perturbations. Attending to the clinical and histopathological manifestations, leprosy reactions may be separated in 2 or 3 different variants: reverse reaction (type I), erythema nodosum leprosum (type II), erythema polymorphous (type II) and Lucio's phenomenon, mainly considered a type II reaction, but sometimes designated type III. Type I leprosy reaction, also named "upgrading reaction," occurs in borderline leprosy states and is associated with a shift toward the tuberculoid pole. Type II reaction usually occurs in lepromatous leprosy, and there are 3 different clinical variants, including erythema nudosum leprosum, erythema polymorphous-like reaction, and Lucio's phenomenon.