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Mar 2024 DOI 10.14302/issn.2572-3030.jcgb-24-4970
Melanoma treatment has improved significantly with the development of immune checkpoint inhibition (ICI), which has greatly enhanced the survival rates of patients with metastatic melanoma. However, a significant number of patients do not respond well to ICI treatment and experience progression. This highlights the critical need for practical means to track melanoma patients' response to ICI. To address this issue, the patterns of circulating miRNAs were studied in liquid biopsies of melanoma patients. These miRNAs have the potential to provide essential information regarding the cancer stage, progression, and the presence of PD-L1 in tumor tissue. A sophisticated flow cytometric test was used to measure up to 63 different miRNAs at once. The study identified a combination of nine miRNAs that are capable of distinguishing between different stages of melanoma, particularly stage IV. Additionally, five miRNAs were pinpointed which are downregulated in patients who do not respond to ICI treatment. Furthermore, two miRNAs were found that correlate to the level of PD-L1 in tumor tissue, and low levels of miR-150-5p were linked to poorer overall survival. These findings suggest that circulating miRNAs could serve as valuable markers to predict the effectiveness of ICI, provide insights into the cancer's stage and PD-L1 status, and ultimately help physicians make better treatment decisions in the future. However, further research is needed to confirm these findings and establish their clinical usefulness.
Mar 2022 DOI 10.14302/issn.2641-5518.jcci-22-4097
Malignant melanoma the most common malignancies associated with GI involvement. They usually manifest clinically at an advanced stage of neoplasm. Surgery is also recommended for palliative treatment of GIT metastases. A case of a 67-year-old male diagnosed with malignant melanoma for 7 months had burning epigastric pain and bloatedness. Esophagogastroduodenoscopy showed multiple flat lesions. Biopsy findings were consistent with malignant melanoma. Malignant melanoma has an early tendency to metastasize and has a high mortality rate due to its complications. In patients with malignant melanoma since Gastrointestinal involvement is now being documented as part of metastatic work up esophagogastroduodenoscopy is suggested as an important tool in the treatment and patient’s +outcome. Although metastases to the stomach is rare, it is essential to be thorough and include an upper endoscopy to rule out metastatic disease, especially in symptomatic patients.
Mar 2020 DOI 10.14302/issn.2471-2175.jdrt-20-3274
Pharmacodynamic modeling of sunscreens was performed using a new concept of Skin UV Index (SUI) on the exposed skin as a parameter to evaluate the potential effectiveness of sunscreens against sun damage. The SUI predicts the UV heat intensity on the skin surface in terms of the solar UV Index at the time of the study and is calculated by solar UV Index/sunscreen’s SPF. SUI numbers for sunscreen with SPF ranging from 2 to 100 under a solar UV Index of 10 was used for illustration. Based on guidelines from WHO, Australia and New Zealand, sunscreens yielding SUI < 3 are assumed to be effective against sun damage such as sunburn and melanoma. Based on the above assumption, sunscreens with SPF > 4 were found to be effective when sunscreens were evenly applied at 2 mg/cm2. Review of numerous studies suggests that missing applications may represent a major, seemingly unavoidable, SPF-independent factor causing unintended sunburns for sunbathers in the US and other countries with a temperate climate. This might in turn become a major factor for causing exponential increase in melanoma incidence rates observed in the last few decades. For example, in an SPF 30 sunscreen study all 25 participants suffered unintended sunburns after one week of sunbathing. Also, a mean missing application of 20% of the total exposed area and a mean missing of about 50% of the time were reported in two separate studies. Simulations were also performed with under-applications of 50% and 75%. The present simulations may provide a rationale of why routine use of a low SPF 8 sunscreen was reported to be effective against melanoma in a 2018 Australian study. Based on model simulations it is proposed that in the US, SPF 8 sunscreen and SPF 2 to 6 sunscreen may be adequate for routine, unintentional use for sun-sensitive populations and non-sun-sensitive populations, respectively.
Feb 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2581
We report the case of a 75 year-old female with past history of ampullary adenocarcinoma presenting with a rapidly enlarging breast mass, initially misclassified on fine needle aspiration as a probable sarcoma, which was ultimately diagnosed as melanoma on resection in the absence of a known cutaneous primary lesion. Next-generation sequencing (NGS) of the tumor revealed a mutation in the Smoothened oncogene (SMO) of unknown significance and wild-type BRAF. To our knowledge, SMO mutation in melanoma of any site has not been previously reported, though the effectiveness of SMO inhibitors has been studied in both in vivo and in vitro models of melanoma. Currently, these inhibitors have not been studied in SMO mutant melanoma. The patient declined further therapy after resection due to multiple comorbidities. She expired two years after presenting with the breast mass from complications of high grade urothelial carcinoma.
Nov 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1760
Metastatic melanoma is a very deadly type of skin cancer with poor prognosis and low 5-year survival rates. Until recently, patients with metastatic melanoma had very few treatment options, which only included dacarbazine and aldesleukin. In 2011, the first checkpoint blocker, ipilimumab was approved for the treatment of unresectable metastatic melanoma but its success was eclipsed by low response rates and high incidence of adverse events. Later in 2014, anti-PD-1 antibodies, nivolumab and pembrolizumab were approved for the treatment of metastatic melanoma. With comparatively high response rates and manageable safety profile, PD-1 blockers were remarkably successful in the treatment of melanoma and also other cancer subtypes such as non-small cell lung cancer and metastatic urothelial carcinoma. This article highlights the success of anti-PD-1 antibodies, discusses the mechanism of PD-1:PD-L1/2 pathway, responses of melanoma patients to PD-1 blockers and the research on improving response rates to PD-1 blockers.
Apr 2017 DOI 10.14302/issn.2372-6601.jhor-17-1463
Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells. In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment. In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.
Nov 2016 DOI 10.14302/issn.2574-4526.jddd-16-1322
Summary Primary malignant melanoma arising from the parotid gland is extremely rare and only sporadic cases have been described. This entity is characterized by delayed diagnosis, poor prognosis and controversial pathogenesis. We report a case of primary malignant melanoma of the parotid gland in a 54-year-old man. The initial diagnosis, made by fine needle aspiration cytology, was malignant tumor without precision. Radical parotidectomy was performed. Diagnosis of primary melanoma of the parotid gland was confirmed by immunochemical analysis revealing positive staining for S-100, HBA-45 and Melan A. Computed Tomography and whole-body 18F-FDGPET/CT image were made to evaluate metabolic and morphologic characteristics of the primary melanoma, to identify potential systemic metastasis at early stage and to exclude primary melanoma elsewhere in the body. The clinical, pathological, immunohistochemical and the role of combined FDG PET/CT features of this lesion are discussed compared to a literature review.
Jan 2022 DOI 10.14302/issn.2372-6601.jhor-22-4061
Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.