Melanoma, a cancer that arises from melanocytes, is one of the most unresponsive cancers to known therapies and has a tendency to produce early metastases. Several studies showed encouraging results of the efficacy of photodynamic therapy (PDT) in melanoma, in different experimental settings in vitro and in vivo, as well as several clinical reports.AimsOur study focuses on testing the antimelanoma efficacy of several new, synthetic photosensitisers (PS), from two different chemical classes, respectively four porphyrins and six phthalocyanines.MethodsThese PS were tested in terms of cell toxicity and phototoxicity against a radial growth phase melanoma cell line (WM35), in vitro. Cells were exposed to different concentrations of the PS for 24h, washed, then irradiatied with red light (630 nm) 75 mJ/cm2 for the porphyrins and 1 J/cm2 for the phthalocyanines. Viability was measured using the MTS method.ResultsTwo of the synthetic porphyrins, TTP and THNP, were active photosensitizers against WM35 melanoma in vitro. Phthalocyanines were effective in producing a dose dependent PDT-induced decrease in viability in a dose-dependent manner. The most efficient was Indium (III) Phthalocyanine chloride, a metal substituted phthalocyanine.ConclusionsThe most efficient photosensitizers for PDT in melanoma cells were the phthalocyanines in terms of tumor cell photokilling and decreased dark toxicity.

For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour’s favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

Hilar cholangiocarcinoma (hCCA) is a primary liver tumor associated with a dim prognosis. The role of preoperative and palliative biliary drainage has long been debated. The most common techniques are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD); however, recently developed endoscopic ultrasound-assisted methods are gaining more atention. Selecting the best available method in any specific scenario is crucial, yet sometimes challenging. Thus, this review aimed to discuss the available techniques, indications, perks, pitfalls, and timing-related issues in the management of hCCA. In a preoperative setting, PTBD appears to have some advantages: low risk of postprocedural complications (namely cholangitis) and better priming for surgery. For palliative purposes, we propose ERCP/PTBD depending on the experience of the operators, but also on other factors: the level of bilirubin (if very high, rather PTBD), length of the stenosis and the presence of cholangitis (PTBD), ERCP failure, or altered biliary anatomy.

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BackgroundMelanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT) might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine—Gallium phthalocyanine chloride (GaPc) and Metformin was used against melanoma. The study aimed to: (1) find the anti-melanoma efficacy of GaPc-PDT, (2) assess possible beneficial effects of Metformin addition to PDT, (3) uncover some of the mechanisms underlining cell killing and anti-angiogenic effects.MethodsTwo human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting.ResultsGaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF)-κB activation and tumor necrosis factor (TNF)—related apoptosis-inducing ligand (TRAIL) sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT.ConclusionsMetformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects.General significanceCombination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.