SignificanceCollagen and lipid are important components of tumor microenvironments (TME) and participates in tumor development and invasion. It has been reported that collagen and lipid can be used as a hallmark to diagnosis and differentiate tumors.AimWe aim to introduce photoacoustic spectral analysis (PASA) method that can provide both the content and structure distribution of endogenous chromophores in biological tissues to characterize the tumor-related features for identifying different types of tumors.ApproachEx vivo human tissues with suspected squamous cell carcinoma (SCC), suspected basal cell carcinoma (BCC), and normal tissue were used in this study. The relative lipid and collagen contents in the TME were assessed based on the PASA parameters and compared with histology. Support vector machine (SVM), one of the simplest machine learning tools, was applied for automatic skin cancer type detection.ResultsThe PASA results showed that the lipid and collagen levels of the tumors were significantly lower than those of the normal tissue, and there was a statistical difference between SCC and BCC (p < 0.05), consistent with the histopathological results. The SVM-based categorization achieved diagnostic accuracies of 91.7% (normal), 93.3% (SCC), and 91.7% (BCC).ConclusionsWe verified the potential use of collagen and lipid in the TME as biomarkers of tumor diversity and achieved accurate tumor classification based on the collagen and lipid content using PASA. The proposed method provides a new way to diagnose tumors.
Port-wine stain (PWS) is a discoloration of human skin caused by a vascular anomaly (i.e., capillary malformation in the skin). In the past years, several techniques have been developed for characterization and treatment evaluation of PWS. However, each of them has some limitations. Optical methods working in the ballistic regime, such as dermoscopy and VISIA, do not have sufficient penetration to cover the entire scale of PWS. High frequency ultrasound, although with better imaging depth, does not offer sufficient contrast to differentiate PWS and normal skin tissue. Therefore, current endpoint clinical assessment for PWS still relies on physicians’ subjective judgement. In this study, photoacoustic (PA) imaging utilizing light emitting diodes (LED) as the light source was adapted to the evaluation of PWS and response to photodynamic therapy (PDT). PA images as well as US images of the targeted skin area before and at different time points after the treatment were acquired. The imaging results from adults and children were also compared. The imaging findings demonstrate that the PWS levels of adult patients are significantly higher than children (p<0.01), which fits well with the knowledge that the vessel malefaction degree develops with patients’ age. The 2-month follow-up study on four children shows that the average PWS level reduced for 33.60%onstrat (p<0.01) as a result of 3-4 times of PDT treatment. This initial clinical trial on patients suggests PA imaging holds potential for quantitative assessment of PWS in clinical settings.
The prodrug 5-aminolevulinic acid (ALA) and its ester derivatives have been used in photodynamic therapy (PDT) in dermatology worldwide. In China, ALA-PDT was first used to treat urethral condylomata acuminata and non-melanoma skin cancers in 1997. A powder formulation of ALA hydrochloride was approved by the Chinese Food and Drug Administration for the treatment of condylomata acuminata in 2007. Large successful experience of treating condylomatas was accumulated compared with Western countries. Meanwhile, numerous clinical studies as well as off-label use of ALAPDT have been carried out in China. To reflect the progress of ALA-PDT in China, several major Chinese and English databases were searched and published data were reviewed in this article.
Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC.
Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined.
Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC.
Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.
Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.
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