-
Scientific Reports Jun 2024Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been...
Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been shown to maintain antitumour efficacy with a reduction in normal tissue toxicity; however, the FLASH effect has been difficult to demonstrate in vitro. The objective to demonstrate the FLASH effect in vitro is challenging, aiming to reveal a differential response between cancer and normal cells to further identify cell molecular mechanisms. New high-intensity petawatt laser-driven accelerators can deliver very high-energy electrons (VHEEs) at dose rates as high as 10 Gy/s in very short pulses (10 s). Here, we present the first in vitro experiments carried out on cancer cells and normal non-transformed cells concurrently exposed to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown on chamber slides were simultaneously irradiated with LPA electrons. A non-uniform dose distribution on the cell cultures was revealed by Gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, which served as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, the greatest proportion of the damaged DNA-containing nuclei was attained by the LPA electrons at a cumulative dose one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, in certain discrete areas, we observed that LPA electron exposure had a different effect on the DNA damage in healthy normal human epidermal melanocyte (NHEM) cells than in A375 melanoma cells; here, the normal cells were less affected by the LPA exposure than cancer cells. This result is the first in vitro demonstration of a differential response of tumour and normal cells exposed to FLASH irradiation and may contribute to the development of new cell culture strategies to explore fundamental understanding of FLASH-induced cell effect.
Topics: Humans; Coculture Techniques; Electrons; Lasers; Cell Line, Tumor; Melanocytes; DNA Damage; Melanoma; DNA Breaks, Double-Stranded
PubMed: 38937505
DOI: 10.1038/s41598-024-65137-7 -
Archives of Dermatological Research Jun 2024
Topics: Humans; Skin Neoplasms; Mohs Surgery; Surgeons; Sunlight; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; Sunscreening Agents; Sunburn
PubMed: 38937379
DOI: 10.1007/s00403-024-03159-x -
In Vivo (Athens, Greece) 2024The objective of this study was to assess the role of iodine (I) plaque brachytherapy in the management of uveal melanoma.
BACKGROUND/AIM
The objective of this study was to assess the role of iodine (I) plaque brachytherapy in the management of uveal melanoma.
PATIENTS AND METHODS
This is a retrospective study of 50 patients (median age 67 years; range=33-86 years) with uveal melanoma, treated with I plaque brachytherapy at the University Hospital of Pisa. Uveal melanoma was diagnosed with A-scan and B-scan standardized echography, fluorescein angiography, indocyanine green-angiography, optical coherence tomography, and/or magnetic resonance imaging. The primary outcomes assessed were local control, overall survival, disease progression, globe preservation, and metastases. Secondary outcomes were acute and late radiation adverse effects.
RESULTS
Inclusion criteria comprised Eastern Cooperative Oncology Group performance status ≤2, life expectancy >6 months, and tumor thickness ≤10 mm and\or diameter ≤20 mm. All the patients were treated with I plaque brachytherapy, with a prescription dose of 85 Gy to the tumor apex. The 5-year rate of local control, progression-free survival, metastasis-free survival, enucleation-free survival, and overall survival were 83.0%, 81.4%, 90.3%, 83.1%, and 92.1% respectively. Twenty-four patients (48.0%) had one or more acute and late toxicities. The most common acute adverse events (CTCAE vs. 5.0) grade 1-3 were conjunctivitis and eye pain (6.0%). Regarding late events, radiation retinopathy grade 1-3 occurred in 18.0% of cases, while grade 1-3 vitreous hemorrhage in 2.5%.
CONCLUSION
I plaque brachytherapy offers an effective and safe approach for selected cases of uveal melanoma, due to the reported satisfactory results in terms of local control, eye conservation and survival.
Topics: Humans; Melanoma; Uveal Neoplasms; Female; Male; Brachytherapy; Middle Aged; Aged; Adult; Iodine Radioisotopes; Aged, 80 and over; Treatment Outcome; Retrospective Studies; Disease Management
PubMed: 38936895
DOI: 10.21873/invivo.13633 -
In Vivo (Athens, Greece) 2024Melanoma, a variant of skin cancer, presents the highest mortality rates among all skin cancers. Despite advancements in targeted therapies, immunotherapies, and tissue...
BACKGROUND/AIM
Melanoma, a variant of skin cancer, presents the highest mortality rates among all skin cancers. Despite advancements in targeted therapies, immunotherapies, and tissue culture techniques, the absence of an effective early treatment model remains a challenge. This study investigated the impact of dabrafenib on both 2D and 3D cell culture models with distinct molecular profiles.
MATERIALS AND METHODS
We developed a high-throughput workflow enabling drug screening on spheroids. Our approach involved cultivating 2D and 3D cultures derived from normal melanocytes and metastatic melanoma cells, treating them with dabrafenib and conducting viability, aggregation, migration, cell cycle, and apoptosis assays.
RESULTS
Dabrafenib exerted multifaceted influences, particularly on migration at concentrations of 10 and 25 μM. It induced a decrease in cell viability, impeded cellular adhesion to the matrix, inhibited cellular aggregation and spheroid formation, arrested the cell cycle in the G phase, and induced apoptosis.
CONCLUSION
These results confirm the therapeutic potential of dabrafenib in treating melanoma with the BRAF V600E mutation and that 3D models are validated models to study the potential of new molecules for therapeutic purposes. Furthermore, our study underscores the relevance of 3D models in simulating physiological in vivo microenvironments, providing insights into varied treatment responses between normal and tumor cells.
Topics: Oximes; Humans; Imidazoles; Melanoma; Proto-Oncogene Proteins B-raf; Cell Line, Tumor; Apoptosis; Cell Movement; Spheroids, Cellular; Cell Survival; Cell Culture Techniques; Protein Kinase Inhibitors; Cell Cycle; Antineoplastic Agents; Cell Proliferation; Cell Culture Techniques, Three Dimensional; Drug Screening Assays, Antitumor
PubMed: 38936891
DOI: 10.21873/invivo.13608 -
The Lancet. Oncology Jul 2024
Topics: Humans; Rectal Neoplasms; Exanthema; Male; Leg; Middle Aged
PubMed: 38936391
DOI: 10.1016/S1470-2045(24)00273-0 -
Archives of Dermatological Research Jun 2024Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN)... (Review)
Review
Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN) guidelines designate poorly differentiated tumors as "very high risk". Despite its clear prognostic implications, there is no standardized grading system for CSCC differentiation in common use today. CSCC differentiation is graded inconsistently by both dermatopathologists and Mohs surgeons, and reliability studies have demonstrated suboptimal inter- and intra-rater reliability in both of these groups. The absence of a standardized and reliable grading system has impeded the use of differentiation in CSCC staging, despite its apparent correlation with disease outcomes. We performed a comprehensive review of the literature summarizing historical CSCC differentiation grading systems, as well as grading systems in non-cutaneous head and neck SCC as a point of reference. Relevant articles were identified by searching Embase and PubMed, as well as by reviewing reference lists for additional articles and histology textbook excerpts. CSCC grading systems that were identified and summarized include the historical Broders system, the World Health Organization system, the College of American Pathologists' system, and a system described by a 2023 Delphi consensus panel of dermatopathologists.
Topics: Humans; Skin Neoplasms; Carcinoma, Squamous Cell; Neoplasm Grading; Prognosis; Cell Differentiation; Reproducibility of Results; Neoplasm Staging; Skin; Mohs Surgery
PubMed: 38935165
DOI: 10.1007/s00403-024-03184-w -
Indian Journal of Dental Research :... Jan 2024Melanoma is the ninth most prevalent and the second most lethal tumour. The aetiology and pathogenesis remain uncertain. It occurs in elderly people, over the fifth...
Melanoma is the ninth most prevalent and the second most lethal tumour. The aetiology and pathogenesis remain uncertain. It occurs in elderly people, over the fifth decade, and is predominant in males. Clinically, they present as an asymptomatic macular or nodular growth. The prognosis is impacted by the size of the tumour and distant metastases. Patients with distant metastases have a 5-year survival rate of less than 30%, constituting metastasis as the major cause of melanoma-related fatality. Currently, the mainstay of treatment for metastatic melanoma is immunotherapy due to the inoperable state, radioresistant nature of the tumour and high chances of cytotoxicity in chemotherapy. A senile male patient, who was diagnosed with oral malignant melanoma of the maxillary buccopalatal gingiva with distant metastasis to the liver and the prostate, is reported here. Although metastasis to the liver is common among malignant melanomas, in this case metastasis to the prostate gland highlights the rarity.
Topics: Humans; Male; Melanoma; Prostatic Neoplasms; Mouth Neoplasms; Liver Neoplasms; Gingival Neoplasms; Aged
PubMed: 38934760
DOI: 10.4103/ijdr.ijdr_376_23 -
Melanoma Research Aug 2024
Topics: Humans; Melanoma; Retrospective Studies; Skin Neoplasms; Male; Female; Prognosis; Middle Aged; Adult; Aged; Asian People; China; Young Adult; Aged, 80 and over; Adolescent; East Asian People
PubMed: 38934062
DOI: 10.1097/CMR.0000000000000976 -
Melanoma Research Aug 2024A standard metric for melanoma detection is the number needed to biopsy (NNB). This metric has been used to evaluate practicing dermatologists, dermatology advanced...
A standard metric for melanoma detection is the number needed to biopsy (NNB). This metric has been used to evaluate practicing dermatologists, dermatology advanced practice professionals, and primary care providers. This metric, however, has rarely been applied to residency clinics. We aimed to determine the NNB at the University of Colorado residency clinics. Moreover, we sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on NNB. This study is a retrospective analysis of biopsies performed from 2016 to 2022 at the Denver Health Medical Center and the Rocky Mountain Regional Veteran Affairs dermatology clinics. Differential diagnosis at the time of biopsy was searched for keywords including melanoma, melanoma in situ, and lentigo maligna. Skin biopsies that included re-excisions were excluded. The NNB was subsequently generated by dividing the number of biopsied lesions with suspected melanoma by the number of histologically confirmed melanomas. The data was further separated by pre-COVID-19 (2016-February 2020), COVID-19 shutdown period (March 2020-July 2020), and post-COVID-19 (March 2020-present). Demographic data, including age, sex, race, and Fitzpatrick type, were collected. There were 2230 biopsies with suspected melanoma in the differential diagnosis at both clinic sites from 2016 to 2022. Of these, 362 were histologically confirmed melanoma. Total NNB was 6.16. The pre-COVID-19 NNB was 5.86, and the post-COVID-19 NNB was 6.91. Residency clinics have NNB similar to published values of practicing dermatologists. Furthermore, within these clinics, the impact of the COVID-19 pandemic was appreciated by a relative, although statistically insignificant, increase in NNB.
Topics: Humans; Melanoma; Skin Neoplasms; COVID-19; Retrospective Studies; Biopsy; Dermatology; Female; Male; Melanoma, Cutaneous Malignant; Middle Aged; SARS-CoV-2
PubMed: 38934061
DOI: 10.1097/CMR.0000000000000979 -
Melanoma Research Aug 2024Gender disparity in melanoma is a complex issue where sex hormones could be engaged. Differences in genetic variations are important in understanding the mechanisms of...
Gender disparity in melanoma is a complex issue where sex hormones could be engaged. Differences in genetic variations are important in understanding the mechanisms of sex disparity in melanoma. Post-transcriptional regulation of prostaglandin-endoperoxide synthase (PTGS2) mRNA occurs through a complex interplay of specific trans-acting RNA-binding proteins and microRNAs. MiR-146a is a key player in melanoma, modulating immune responses and tumor microenvironment (TME). Polymorphisms in PTGS2 gene rs20415G
C have been associated with an increased risk of melanoma. Epistasis between polymorphisms rs20415G C was investigated by genotyping 453 melanoma patients and 382 control individuals. The effects of testosterone and 17β-estradiol were analyzed in keratinocytes and two melanoma cell lines. The rs2910164GG showed a higher risk in the presence of the genotype rs20417CC in the male population. Testosterone and 17β-estradiol act differently on PTGS2 and miR-146a expression, depending on the cell type. Testosterone augments PTGS2 gene expression in keratinocytes and miR-146a in melanoma cells. While 17β-estradiol only increases miR-146a expression in HaCaT cells. The present study indicates a sex-specific relation between miR-146a and PTGS2 polymorphisms with melanoma cancer risk. Testosterone and 17β-estradiol act differently on the expression of PTGS2 and miR-146a depending on the skin cell type. Topics: Humans; Melanoma; MicroRNAs; Cyclooxygenase 2; Male; Female; Skin Neoplasms; Risk Factors; Middle Aged; Gonadal Steroid Hormones; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Adult; Sex Factors; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Estradiol; Aged
PubMed: 38934060
DOI: 10.1097/CMR.0000000000000978