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Pharmacological Reports : PR Aug 2023Non-steroidal anti-inflammatory drugs have been shown to inhibit the development of induced neoplasms. Our previous research demonstrated that the cytotoxicity of...
BACKGROUND
Non-steroidal anti-inflammatory drugs have been shown to inhibit the development of induced neoplasms. Our previous research demonstrated that the cytotoxicity of sulindac against melanoma cells is comparable to dacarbazine, the drug used in chemotherapy. The aim of this study was to investigate the mechanism of sulindac cytotoxicity on COLO 829 and C32 cell lines.
METHODS
The influence of sundilac on the activity of selected enzymes of the antioxidant system (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of hydrogen peroxide as well as the level of proteins initiating (p53, Bax) and inhibiting (Bcl-2) apoptosis were measured in melanoma cells.
RESULTS
In melanotic melanoma cells, sulindac increased the activity of SOD and the content of HO but decreased the activity of CAT and GPx. The level of p53 and Bax proteins rose but the content of Bcl-2 protein was lowered. Similar results were observed for dacarbazine. In amelanotic melanoma cells, sulindac did not cause an increase in the activity of measured enzymes or any significant changes in the level of apoptotic proteins.
CONCLUSION
The cytotoxic effect of sulindac in the COLO 829 cell line is connected to disturbed redox homeostasis by changing the activity of SOD, CAT, GPx, and level of HO. Sulindac also induces apoptosis by changing the ratio of the pro-apoptotic/anti-apoptotic protein. The presented studies indicate the possibility of developing target therapy against melanotic melanoma using sulindac.
Topics: Apoptosis Regulatory Proteins; Melanoma; Sulindac; Homeostasis; Oxidation-Reduction; Humans; Cell Line, Tumor; Antioxidants; Superoxide Dismutase; Glutathione Peroxidase; Catalase; Hydrogen Peroxide; Signal Transduction
PubMed: 37195561
DOI: 10.1007/s43440-023-00493-1 -
Ugeskrift For Laeger Apr 2023In this case report, a 62-year-old woman was diagnosed with lymph node metastasis from melanoma in the groin. Initially the primary tumour was unknown. The entire skin...
In this case report, a 62-year-old woman was diagnosed with lymph node metastasis from melanoma in the groin. Initially the primary tumour was unknown. The entire skin was examined without any suspicious moles. A PET-CT scan showed an area on the left heel with increased activity. The element surprisingly showed an amelanotic melanoma. Amelanotic melanomas have a significantly worse prognosis compared to pigmented melanomas, presumably because they are detected later and may be very difficult to detect clinically. This case shows the importance of paying attention to unpigmented elements when searching for a primary tumour.
Topics: Female; Humans; Middle Aged; Melanoma, Amelanotic; Positron Emission Tomography Computed Tomography; Skin Neoplasms; Prognosis; Diagnosis, Differential
PubMed: 37114579
DOI: No ID Found -
Cureus Mar 2023Eccrine poroma (EP) is a benign adnexal tumor that is derived from acrosyringium, the intraepidermal eccrine duct of sweat glands. The standard treatment for eccrine...
Eccrine poroma (EP) is a benign adnexal tumor that is derived from acrosyringium, the intraepidermal eccrine duct of sweat glands. The standard treatment for eccrine poroma is complete excision. However, this case report highlights cryotherapy as one of the modalities in treating eccrine poroma. We present a case of a 33-year-old male patient who was a known case of generalized vitiligo since he was nine years old. During our skin checkup before starting him on phototherapy, we found a mass over the palmar aspect of the middle finger of the right hand that started to appear five years ago. The mass gradually increased in size, was painless, has no discharge, and was not associated with a history of trauma or infection. The review of systems was unremarkable. Skin examination revealed an asymptomatic, 2.0 × 1.5 cm-sized, solitary, collarette-encircled, dome-shaped, flesh-colored, non-pigmented, deep-red nodule protrusion from the palmar aspect of the middle finger of the right hand. Poroma was considered as the diagnosis, and a punch skin biopsy was performed to confirm the diagnosis and to roll out pyogenic granuloma, amelanotic melanoma, and porocarcinoma as differential diagnoses. A 3 mm punch skin biopsy was performed under local anesthesia and was found to be histologically consistent with eccrine poroma. Hence, cryosurgery was chosen based on histological favorable features. We used cryospray in a single session of 15 seconds in three applications, with five-second intervals in between (skin frosting recovery). Furthermore, the lesion was completely curative with a single session of cryotherapy. The patient followed up for one year without evidence of recurrence.
PubMed: 37095806
DOI: 10.7759/cureus.36563 -
Clinical, Cosmetic and Investigational... 2023Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively...
BACKGROUND
Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described.
PURPOSE
To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure.
METHODS
We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq).
RESULTS
The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability.
CONCLUSION
Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.
PubMed: 37077860
DOI: 10.2147/CCID.S404381 -
NMC Case Report Journal 2023Melanoma carries a high risk of brain metastasis. A small subset of metastatic melanomas, known as amelanotic melanomas, does not present black coloration, reflecting a...
Melanoma carries a high risk of brain metastasis. A small subset of metastatic melanomas, known as amelanotic melanomas, does not present black coloration, reflecting a lack of melanin pigmentation. Here, we report a case of B-Raf proto-oncogene (BRAF) V600E mutation associated with a metastatic brain tumor caused by the amelanotic melanoma. A 60-year-old man was transferred to our department following acute onsets of left upper limb paralysis and convulsion. In the brain imaging, multiple lesions in the right frontal lobe and left basal ganglia were detected, and the presence of an enlarged left axillary lymph node was revealed. Consequently, we removed the right frontal lesion and performed a biopsy of the left axillary lymph node. Histological analysis of both specimens indicated an amelanotic melanoma, and genetic testing revealed a BRAF V600E mutation. The residual intracranial lesions were treated with stereotactic radiotherapy and molecular-targeted therapy, with dabrafenib and trametinib as the systemic treatment. Based on the Response Evaluation Criteria in Solid Tumors, we determined that the patient achieved complete remission (CR) under uninterrupted molecular-targeted therapy over a period of 10 months. After the temporary withdrawal of dabrafenib and trametinib to avoid hepatic dysfunction, a new intracranial lesion appeared. CR of this lesion was achieved following reinstatement of the two drugs. These results suggest that, under limited conditions, molecular-targeted therapy can produce a sustained response against the intracranial metastasis of melanoma, and the therapy with reduced dose is still effective against a recurrent case after cessation of the therapy due to the toxicity.
PubMed: 37065875
DOI: 10.2176/jns-nmc.2022-0227 -
Cancers Mar 2023Although the histopathological diagnosis of cutaneous melanocytic lesions is fairly accurate and reliable among experienced surgical pathologists, it is not perfect in...
Although the histopathological diagnosis of cutaneous melanocytic lesions is fairly accurate and reliable among experienced surgical pathologists, it is not perfect in every case (especially melanoma). Microscopic examination-clinicopathological correlation is the gold standard for the definitive diagnosis of melanoma. Pathologists may encounter diagnostic controversies when melanoma closely mimics Spitz's nevus or blue nevus, exhibits amelanotic histopathology, or is in situ. It would be beneficial if diagnosing cutaneous melanocytic lesions can be automated by using deep learning, particularly when assisting surgical pathologists with their workloads. In this preliminary study, we investigated the application of deep learning for classifying cutaneous melanoma in whole-slide images (WSIs). We trained models via weakly supervised learning using a dataset of 66 WSIs (33 melanomas and 33 non-melanomas). We evaluated the models on a test set of 90 WSIs (40 melanomas and 50 non-melanomas), achieving ROC-AUC at 0.821 for the WSI level and 0.936 for the tile level by the best model.
PubMed: 36980793
DOI: 10.3390/cancers15061907 -
Cancers Mar 2023To improve the diagnostic accuracy and optimal management of pediatric melanomas.
PURPOSE
To improve the diagnostic accuracy and optimal management of pediatric melanomas.
METHODS
We conducted a retrospective descriptive, multicenter study of the epidemiological, clinical, and dermoscopic characteristics of histopathologically proven melanomas diagnosed in patients less than 18 years old. Data on sociodemographic variables, clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, and outcome were collected from the databases of three Italian dermatology units. We performed a clinical evaluation of the morphological characteristics of each assessed melanoma, using both classic ABCDE criteria and the modified ABCDE algorithm for pediatric melanoma to evaluate which of the two algorithms best suited our series.
RESULTS
The study population consisted of 39 patients with a histologically confirmed diagnosis of pediatric melanoma. Comparing classic ABCDE criteria with the modified ABCDE algorithm for pediatric melanomas, the modified pediatric ABCDE algorithm was less sensitive than the conventional criteria. Dermoscopically, the most frequent finding was the presence of irregular streaks/pseudopods (74.4%). When evaluating the total number of different suspicious dermoscopy criteria per lesion, 64.1% of the lesion assessments recognized two dermoscopic characteristics, 20.5% identified three, and 15.4% documented four or more assessments.
CONCLUSIONS
Contrary to what has always been described in the literature, from a clinical point of view, about 95% of our cases presented in a pigmented and non-amelanotic form, and these data must be underlined in the various prevention campaigns where pediatric melanoma is currently associated with a more frequently amelanotic form. All the pediatric melanomas analyzed presented at least two dermoscopic criteria of melanoma, suggesting that this could be a key for the dermoscopic diagnosis of suspected pediatric melanoma, making it possible to reach an early diagnosis even in this age group.
PubMed: 36980721
DOI: 10.3390/cancers15061835 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Ulcer; Skin Neoplasms; Melanoma, Amelanotic; Melanoma, Cutaneous Malignant
PubMed: 36922334
DOI: 10.1016/j.abd.2021.08.015 -
Molecular Biology Reports May 2023Melanoma is an aggressive type of cancer that can metastasize to numerous other organs. TGFβ is one of the key signaling pathways in melanoma progression. Previous...
BACKGROUND
Melanoma is an aggressive type of cancer that can metastasize to numerous other organs. TGFβ is one of the key signaling pathways in melanoma progression. Previous studies on various types of cancer have shown that both: polyphenols and a static magnetic field (SMF) can be potential chemopreventive/therapeutic agents. Therefore, the aim of the study was to evaluate the effect of a SMF and selected polyphenols on the transcriptional activity of TGFβ genes in melanoma cells.
METHODS AND RESULTS
Experiments were performed on the C32 cell line treated with caffeic or chlorogenic acids, and with simultaneous exposure to a moderate-strength SMF. The RT-qPCR method was used to determine the mRNA level of genes encoding the TGFβ isoforms and their receptors. The concentration of the TGFβ1 and TGFβ2 proteins were also measured in the cell culture supernates. The first response of C32 melanoma cells to both factors is the reduction of TGFβ levels. Then, mRNA level of these molecules returned to values close to pre-treatment level by the end of experiment.
CONCLUSION
Our study results demonstrate the potential of polyphenols and a moderate-strength SMF to support cancer therapy by altering TGFβ expression, which is a very promising topic for the diagnosis and treatment of melanoma.
Topics: Humans; Transforming Growth Factor beta; Melanoma, Amelanotic; Transforming Growth Factor beta1; Skin Neoplasms; RNA, Messenger; Protein Isoforms; Receptors, Transforming Growth Factor beta; Melanoma, Cutaneous Malignant
PubMed: 36899279
DOI: 10.1007/s11033-023-08336-1