Precision radiation of immune checkpoint therapy resistant melanoma metastases (PROMMEL study): study protocol for a phase II open-label multicenter trial
Ellen BacklundMuyi YangVitali GrozmanGiuseppe MasucciJohan FalkeniusHanna ErikssonBraslav JovanovicKatarina HammarlundUlf IsacssonCalin RaduEdvard AbelKristin KarlssonRicardo Palanco ZamoraPeter WersällUlrika EdbäckStina L. WickströmEva Darai RamqvistSøren BrageRolf KiesslingKristina ViktorssonBo FranzénRolf LewensohnRoger Olofsson BaggeGustav UllenhagLars NyKarin LindbergHildur Helgadóttir
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Precision radiation of immune checkpoint therapy resistant melanoma metastases (PROMMEL study): study protocol for a phase II open-label multicenter trialKeywords:
Open label
Immune checkpoint
Abstract KCl extracts of Melanoma 14, a human melanoma cell line grown in chemically defined serum‐free medium, inhibited leukocyte migration in 19/36 (53%) patients with malignant melanoma. Only 4/23 (17%) controls with non‐melanoma malignancies and 4/28 (14%) normal subjects with no history of cancer were similarly inhibited. Only 2/27 melanoma patients tested against KCl extracts of normal muscle tissue excised from the donor of Melanoma 14 were significantly inhibited. Patients with Stage I (localized) melanoma and patients with Stage III (generalized) melanoma reacted with roughly equal frequency but the number of patients in each group was too small for meaningful statistical analysis. Leukocytes from the donor of Melanoma 14 were tested in a completely autologous system against extracts of Melanoma 14 tissue culture cells and extracts of autologous muscle and were specifically inhibited by the Melanoma 14 tissue culture extract (Migration Index = 0.67) but not by the extract of normal muscle (Migration Index = 0.96). Only 7/32 (22%) melanoma patients were significantly inhibited by an extract of non‐melanoma tumor. These results suggest that melanoma‐associated antigens are present in soluble extracts of this tumor line. Such extracts could provide a continuing source of standard melanoma‐associated antigens for purification and chemical characterization and for diagnostic and prognostic tests in patients with malignant melanoma.
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Hematology
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Melanoma diagnosis
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Abstract Background Melanoma is an aggressive disease that is rising in incidence. Advanced melanoma is still a life‐threatening disease. CircRNAs are documented to be involved in melanoma progression. But circITCH role in melanoma remains unclear. Methods and Results To explore the functions of circITCH in melanoma, levels of circITCH in melanoma tissues and paracarcinoma normal tissues were detected. To study the roles of circITCH in melanoma in terms of cell proliferation and migration, in vitro and in vivo experiments were performed. Mechanism study was designed to investigate the potential regulatory effect of circITCH in melanoma. Results revealed that circITCH expression was repressed in melanoma versus adjacent normal tissues. Function study showed that circITCH suppressed melanoma cell proliferation and metastasis. The mechanism study showed that circITCH‐sponged miR‐660 to upregulate TFCP2 and suppress melanoma progression. Conclusions The circITCH/miR‐660/TFCP2 axis is involved in melanoma progression hence circITCH can be a diagnostic biomarker as well as a target for treating melanoma.
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The problem of primary multiple malignant tumor (PMMT) of skin melanoma in Ukraine is analyzed. During the period from 2000 to 2006, 16760 cases of skin melanoma have been diagnosed, and in 873 patients from them PMMT has been registered. So, the part of the patients with multiple tumors among all patients with skin melanoma was 5.2%. Most often PMMT appears in the case of skin melanoma of head and neck (6.6 +/- 0.4%). Most commonly skin melanoma is accompanied by other skin malignant neoplasms (40.9 +/- 1.6% of all PMMT cases). Upon malignant skin melanoma, PMMT occurs more often in males (5.7 +/- 0.7%) than in females (4.9 +/- 0.7%). Most often the diagnosis of skin melanoma at PMMT is detected synchronously (48.3 +/- 1.6%), and simultaneous detection of PMMT predominates in all polyneoplasms and in all age groups. The most favourable course of skin melanoma is characteristic for metachronous cancer of II type when melanoma is diagnosed after manifestation of other malignant tumor.
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Surgical oncology
Melanoma diagnosis
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This chapter contains sections titled: Seven features of melanoma Melanoma in situ Thin invasive melanoma Intermediate-thickness melanoma Thick invasive melanoma Hyperpigmented melanoma: brown Hyperpigmented melanoma: black Multicoloured melanoma Hypopigmented melanoma Superficial spreading malignant melanoma Nodular melanoma: pigmented Nodular melanoma: hypopigmented Featureless melanoma Small melanoma Eccentric pigmented melanoma Cutaneous melanoma metastases Negative network Regression in melanoma Melanoma cases Algorithms Algorithms – limitations
Nodular melanoma
Superficial spreading melanoma
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