Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review

<p>Abstract</p> <p>Background</p> <p>Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease.</p> <p>Methods</p> <p>Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale.</p> <p>Results</p> <p>21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses.</p> <p>Conclusions</p> <p>Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.</p

Identification of thioredoxin reductase 1-regulated genes using small interference RNA and cDNA microarray

Thioredoxin reductase 1 (TrxR1) is a cytosolic enzyme that plays a central role in controlling cellular redox homeostasis. TrxR1 can transduce regulatory redox signals through NADPH-dependent reduction of thioredoxin (Trx), which is able to reduce a broad spectrum of target enzymes and regulate the activity of several transcription factors (e.g., p53 and NF-kappaB). The TrxR1/Trx system is involved in every step of cancer biology, ranging from transformation and progression to invasion, metastasis and resistance to therapy. TrxR1 was also recently identified as one key enzyme involved in cell death induced by interferon-beta (IFN-beta)/all-trans retinoic acid (ATRA) anti-cancer treatment. Our study employed small interference RNA (siRNA) and microarray techniques to investigate the effect of TrxR1 silencing on gene expression in HepG2 cells. We also investigated TrxR1-mediated cell response to IFN-beta/ATRA treatment. We identified TrxR1-dependent genes with functions related to several cellular processes such as apoptosis (SOX4), ubiquitination (Ubiquitin D, F-box protein 25), organization of cytoskeletal/extracellular matrix (Keratin 19, Fibronectin 1) and transport (Cystine/Glutamate transporter). We also investigated the effect of TrxR1 siRNA on the protein profile using surface enhanced laser desorption ionization time-of-flight (SELDI-TOF) technology. Profiles confirmed significant involvement of TrxR1 in cell response to IFN-beta/ATRA

Design and synthesis of H2S-donor hybrids: A new treatment for Alzheimer's disease?

Hydrogen sulphide (H2S) is an endogenous gasotransmitter, largely known as a pleiotropic mediator endowed with antioxidant, anti-inflammatory, pro-autophagic, and neuroprotective properties. Moreover, a strong relationship between H2S and aging has been recently identified and consistently, a significant decline of H2S levels has been observed in patients affected by Alzheimer's disease (AD). On this basis, the use of H2S-donors could represent an exciting and intriguing strategy to be pursued for the treatment of neurodegenerative diseases (NDDs). In this work, we designed a small series of multitarget molecules combining the rivastigmine-scaffold, a well-established drug already approved for AD, with sulforaphane (SFN) and erucin (ERN), two natural products deriving from the enzymatic hydrolysis of glucosinolates contained in broccoli and rocket, respectively, endowed both with antioxidant and neuroprotective effects. Notably, all new synthetized hybrids exhibit a H2S-donor profile in&nbsp;vitro and elicit protective effects in a model of LPS-induced microglia inflammation. Moreover, a decrease in NO production has been observed in LPS-stimulated cells pre-treated with the compounds. Finally, the compounds showed neuroprotective and antioxidant activities in human neuronal cells. The most interesting compounds have been further investigated to elucidate the possible mechanism of action