Non-melanoma Skin Cancer Treated by Contact High-dose-rate Radiotherapy (Brachytherapy): A Mono-institutional Series and Literature Review

Tagliaferri, Luca; Ciardo, Francesco Giuseppe; Fionda, Bruno; Casà, Calogero; Stefani, Alessandro; Lancellotta, Valentina; Placidi, E.; Macchia, G.; Capocchiano, Nikola Dino; Morganti, Alessio Giuseppe; Kovács, György; Bussu, Francesco; Peris, Ketty; Valentini, Vincenzo

doi:10.21873/invivo.12505

Cited by 19 publications

(18 citation statements)

References 41 publications

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“…Generally, melanoma, as well as non-melanoma skin cancers are usually treated with surgery followed by immunotherapy or radiotherapy. High-dose rate radiotherapy was shown recently to be effective for treatment of non-melanoma skin cancer [59]. Peri-induction radiotherapy induces tumor cell death in the central hypoxic segment of tumor [60], stimulates anti-tumor immunity and regulates the tumor microenvironment by T cell activation [61,62].…”

Section: Discussionmentioning

confidence: 99%

Mambalgin-2 Inhibits Growth, Migration, and Invasion of Metastatic Melanoma Cells by Targeting the Channels Containing an ASIC1a Subunit Whose Up-Regulation Correlates with Poor Survival Prognosis

et al. 2021

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Melanoma is an aggressive cancer characterized by the acidification of the extracellular environment. Here, we showed for the first time that extracellular media acidification increases proliferation, migration, and invasion of patient-derived metastatic melanoma cells and up-regulates cell-surface expression of acid-sensitive channels containing the ASIC1a, α-ENaC, and γ-ENaC subunits. No influence of media acidification on these processes was found in normal keratinocytes. To control metastatic melanoma progression associated with the ASIC1a up-regulation, we proposed the ASIC1a inhibitor, - mambalgin-2 from Dendpoaspis polylepis venom. Recombinant analog of mambalgin-2 cancelled acidification-induced proliferation, migration, and invasion of metastatic melanoma cells, promoted apoptosis, and down-regulated cell-surface expression of prooncogenic factors CD44 and Frizzled 4 and phosphorylation of transcription factor SNAI. Confocal microscopy and affinity purification revealed that mambalgin-2 interacts with heterotrimeric ASIC1a/α-ENaC/γ-ENaC channels on the surface of metastatic melanoma cells. Using the mutant variant of mambalgin-2 with reduced activity toward ASIC1a, we confirmed that the principal molecular target of mambalgin-2 in melanoma cells is the ASIC1a subunit. Bioinformatic analysis confirmed up-regulation of the ASIC1 expression as a marker of poor survival prognosis for patients with metastatic melanoma. Thus, targeting ASIC1a by drugs such as mambalgin-2 could be a promising strategy for metastatic melanoma treatment.

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Section: Discussionmentioning

confidence: 99%

Mambalgin-2 Inhibits Growth, Migration, and Invasion of Metastatic Melanoma Cells by Targeting the Channels Containing an ASIC1a Subunit Whose Up-Regulation Correlates with Poor Survival Prognosis

et al. 2021

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“…Management of NMSC is based on early diagnosis and treatment, as well as monitoring of recurrences [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study

Giovannacci

Meleti

Garbarino

et al. 2021

Cancers

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Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions (“cases”; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400–430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis (p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs.

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“…Apart from normal skin measurements, Skin Contact Capacitive Imaging can also be used for measuring diseased skin. Combined with the advances of Artificial Intelligence, which has already been used for skin classification [9] and decision supporting in radiotherapy [37], it is possible to develop a skin capacitive image classification system to identify different types of skin diseases, such as neoplastic lesions [38]. With the 50 µm spatial resolution, it is also possible to detect skin diseases at an early stage.…”

Section: Discussionmentioning

confidence: 99%

Skin Characterizations by Using Contact Capacitive Imaging and High-Resolution Ultrasound Imaging with Machine Learning Algorithms

et al. 2021

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We present our latest research on skin characterizations by using Contact Capacitive Imaging and High-Resolution Ultrasound Imaging with Machine Learning algorithms. Contact Capacitive Imaging is a novel imaging technology based on the dielectric constant measurement principle, with which we have studied the skin water content of different skin sites and performed image classification by using pre-trained Deep Learning Neural Networks through Transfer Learning. The results show lips and nose have the lowest water content, whilst cheek, eye corner and under-eye have the highest water content. The classification yields up to 83.8% accuracy. High-Resolution Ultrasound Imaging is a state-of-the-art ultrasound technology, and can produce high-resolution images of the skin and superficial soft tissue to a vertical resolution of about 40 microns, with which we have studied the thickness of different skin layers, such as stratum corneum, epidermis and dermis, around different locations on the face and around different body parts. The results show the chin has the highest stratum corneum thickness, and the arm has the lowest stratum corneum thickness. We have also developed two feature-based image classification methods which yield promising results. The outcomes of this study could provide valuable guidelines for cosmetic/medical research, and methods developed in this study can also be extended for studying damaged skin or skin diseases. The combination of Contact Capacitive Imaging and High-Resolution Ultrasound Imaging could be a powerful tool for skin studies.

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Non-melanoma Skin Cancer Treated by Contact High-dose-rate Radiotherapy (Brachytherapy): A Mono-institutional Series and Literature Review

Cited by 19 publications

References 41 publications

Mambalgin-2 Inhibits Growth, Migration, and Invasion of Metastatic Melanoma Cells by Targeting the Channels Containing an ASIC1a Subunit Whose Up-Regulation Correlates with Poor Survival Prognosis

Mambalgin-2 Inhibits Growth, Migration, and Invasion of Metastatic Melanoma Cells by Targeting the Channels Containing an ASIC1a Subunit Whose Up-Regulation Correlates with Poor Survival Prognosis

Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study

Skin Characterizations by Using Contact Capacitive Imaging and High-Resolution Ultrasound Imaging with Machine Learning Algorithms

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