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1.
Adv Sci (Weinh) ; : e2400920, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828677

ABSTRACT

Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-ß1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.

2.
Br J Dermatol ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38815138

ABSTRACT

BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma associated with poor prognosis. OBJECTIVES: We aimed to investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: The differences in spatially resolved transcriptome profiles of 9 AAM patients with 29 regions of interest (ROIs) and 11 PAM patients with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b-positive tumor cell areas, we detected 11 upregulated differentially expressed genes (DEGs), including chaperone/ubiquitin-associated DEGs, and 82 downregulated DEGs, including human leukocyte antigen, in AAMs compared with PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signaling, and melanin biosynthesis pathways in S100b-positive ROIs of AAMs compared with those of PAMs. In tumor-associated immune cell areas, the numbers of CD8 T cells (p = 0.044) and M1 macrophages (p = 0.014) were significantly decreased, whereas those of monocytes (p = 0.045) and endothelial cells (p = 0.04) were increased in AAMs compared with those in PAMs. CONCLUSIONS: In conclusion, these findings could widen our understanding of the biological differences between AAMs and PAMs that might result in a different clinical course.

3.
Ann Dermatol ; 36(2): 81-90, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38576246

ABSTRACT

BACKGROUND: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses. OBJECTIVE: This study investigated the impact of mask-wearing habits on facial dermatoses. METHODS: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea. RESULTS: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing. CONCLUSION: Clinical features and factors related to aggravation were different according to the types of facial dermatoses.

4.
Front Psychol ; 15: 1323503, 2024.
Article in English | MEDLINE | ID: mdl-38605846

ABSTRACT

Introduction: Promoting super-leadership is crucial for the sustainable growth of college sport teams, especially as teams are experiencing a noticeable shift towards a more horizontal dynamic, where athletes themselves are emerging as leaders. However, there is a lack of research on the effectiveness of super-leadership and its possible outcomes in the context of collegiate Taekwondo teams. Methods: This study aims to investigate the impact of super-leadership on athletes' self-leadership and exercise commitment and examine the mediating role of self-leadership in this relationship among collegiate Taekwondo athletes in South Korea. A total of 147 survey data were analyzed by structural equation modeling. Results: The findings revealed that super-leadership was found to have a positive impact on both athletes' self-leadership (ß = 0.71, p < 0.001) and exercise commitment (ß = 0.30, p < 0.05). Additionally, the study reveals athletes' self-leadership significantly impacts exercise commitment (ß = 0.34, p < 0.05). Our findings also demonstrate that self-leadership was identified as a partial mediator in the relationship between super-leadership and exercise commitment (∆χ2 = 4.46, p > 0.05). Discussion: Theoretical and practical implications were discussed based on the current study's findings.

5.
J Am Acad Dermatol ; 90(5): 977-985, 2024 May.
Article in English | MEDLINE | ID: mdl-38272394

ABSTRACT

BACKGROUND: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers. OBJECTIVE: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM. METHODS: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data. RESULTS: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion. LIMITATIONS: Single-center, retrospective design. CONCLUSION: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Prognosis , Retrospective Studies , Neutrophils/pathology , Lymphocytes/pathology
6.
J Cosmet Dermatol ; 23(3): 931-937, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38169089

ABSTRACT

BACKGROUND: Prurigo nodularis (PN) is an intensively pruritic skin disease that negatively influences quality of life. Cryosim-1 (Intrinsic IB Spot) is a synthetic, selective transient receptor potential melastatin 8 agonist. AIMS: To investigate the efficacy and safety of cryosim-1 in PN patients. PATIENTS/METHODS: A randomized, double-blinded, placebo-controlled clinical trial including 30 patients was conducted. The numerical rating scale (NRS) of pruritus was evaluated before and 2 h after cryosim-1 application at every visit. RESULTS: At week 8, the mean pruritus NRS before serum application (4.7 ± 0.4 treatment, 6.1 ± 0.5 placebo; p = 0.045) and 2 h after serum application (2.8 ± 0.4 treatment, 4.3 ± 0.5 placebo; p = 0.031) were significantly lower in the treatment group, and the mean NRS for sleep disorder was significantly lower in the treatment group (2.2 ± 0.5 treatment, 4.2 ± 0.8 placebo; p = 0.031). The mean satisfaction scales for pruritus improvement were significantly higher in the treatment group (7.2 ± 0.6) than in the placebo group (4.0 ± 0.9; p = 0.005). There was no difference in TEWL between the two groups, and no adverse reactions were reported. CONCLUSIONS: Cryosim-1 is a safe and effective topical treatment for PN patients.


Subject(s)
Prurigo , TRPM Cation Channels , Humans , Prurigo/drug therapy , Quality of Life , Pruritus/drug therapy , Pruritus/etiology , Administration, Topical , Research Design , TRPM Cation Channels/agonists , Membrane Proteins
7.
J Invest Dermatol ; 144(2): 331-340.e2, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37544586

ABSTRACT

Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.


Subject(s)
Lymphoma, Large-Cell, Anaplastic , Mycosis Fungoides , Skin Neoplasms , Humans , Lymphoma, Large-Cell, Anaplastic/genetics , Transcriptome , Ki-1 Antigen/analysis , Mycosis Fungoides/genetics , Mycosis Fungoides/pathology , Skin Neoplasms/pathology , Tumor Microenvironment/genetics
8.
PLoS One ; 18(12): e0294685, 2023.
Article in English | MEDLINE | ID: mdl-38060527

ABSTRACT

BACKGROUND: Emerging evidence has demonstrated that PIWI-interacting RNAs (piRNAs) play important roles in various physiological processes and contribute to cancer progression. Moreover, piRNAs and PIWI protein levels are associated with the prognosis and chemoresistance of various cancers. The limitations of biomarkers challenge early detection and monitoring of chemoresistance and cancer relapse. METHODS: To evaluate the potential of piRNA as a diagnostic biomarker in oncology, we systematically reviewed previous studies on the subject. PubMed, Embase, and Cochrane databases were searched to evaluate the diagnostic relevance of piRNAs in cancer. Eighteen studies (2,352 patients) were included. The quality of each study was evaluated with AMSTAR and QUADAS-2 tool. RESULTS & CONCLUSIONS: The area under the curve (AUC) values of 26 piRNAs in patients with cancer ranged from 0.624 to 0.978, with piR-9491 showing the highest value (0.978). The sensitivity of the total of 21 piRNAs in cancer patients was between 42.86 and 100, with piR-9491 showing the highest sensitivity (100). The specificity of these 21 piRNAs ranged from 60.10 to 96.67 (with piR-018569 showing the highest specificity (96.67)). Their odds ratios were between 1.61 and 44.67, and piR-12488 showed the highest odds ratio (44.67). Generally, the piRNAs in this review showed better sensitivity and AUC values than current clinical diagnostic biomarkers, although current biomarkers appear to be more specific. Reviewed piRNAs showed better diagnostic performance than currently used clinical biomarkers. Notably, piR-823 showed a significant diagnostic performance in four types of cancer (colorectal, esophageal, gastric, and renal cell cancer). However, all 18 studies included in this review were a case-control study. So, further prospective studies are required for their validation.


Subject(s)
Kidney Neoplasms , Piwi-Interacting RNA , Humans , RNA, Small Interfering/metabolism , Case-Control Studies , Neoplasm Recurrence, Local , Biomarkers, Tumor/genetics
9.
Yonsei Med J ; 64(7): 423-432, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37365736

ABSTRACT

PURPOSE: The favorable clinical efficacies of intramuscular injection of autologous blood in patients with atopic dermatitis (AD) and intramuscular injection of autologous serum in patients with chronic urticaria have been demonstrated by randomized clinical trials. In this study, we assessed the clinical effectiveness and safety of the intramuscular injection of autologous serum in patients with AD. MATERIALS AND METHODS: In this randomized, placebo-controlled, and double-blind trial, 23 adolescent and adult patients with moderate-to-severe AD were enrolled. The patients were randomized to receive eight intramuscular injections of 5 mL of autologous serum (n=11) or saline (n=12) over 4 weeks, and were followed up until week 8. Changes in the clinical severity scores of AD assessed by SCORing Atopic Dermatitis (SCORAD), patient-reported Dermatology Life Quality Index (DLQI) score, and incidence of adverse events were assessed from baseline to week 8. RESULTS: One patient in the treatment group and two patients in the placebo group were lost to follow-up before week 8. The intramuscular administration of autologous serum, compared with saline, decreased the SCORAD clinical severity score (-14.8% vs. 10.7%, p=0.006) and improved the DLQI score (-32.6% vs. 19.5%, p=0.01) from baseline to week 8. Serious adverse events were not observed. CONCLUSION: Intramuscular injection of autologous serum may be effective in treating AD. Further studies are needed to evaluate the clinical usefulness of this intervention for AD (KCT0001969).


Subject(s)
Dermatitis, Atopic , Humans , Adult , Adolescent , Dermatitis, Atopic/therapy , Injections, Intramuscular , Treatment Outcome , Double-Blind Method , Severity of Illness Index
13.
Anat Cell Biol ; 56(1): 94-108, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-36384888

ABSTRACT

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

14.
Dermatology ; 239(1): 165-173, 2023.
Article in English | MEDLINE | ID: mdl-35878586

ABSTRACT

BACKGROUND: Nail apparatus melanoma (NAM) is a subtype of cutaneous melanoma occurring at nail units and belongs to the acral lentiginous melanoma subgroup. Due to its unique anatomical structure to protect the acral site, mechanical trauma may have a clinicoprognostic impact on NAM. Therefore, we investigated the clinicoprognostic and histopathological characteristics of NAM according to the presence of trauma history prior to melanoma development. METHODS: Clinicopathological and follow-up data of patients with NAM according to trauma history were obtained. RESULTS: We included 87 patients with NAM, 21.8% of whom had a previous trauma history. Trauma-related NAMs were more likely to involve the toenail (p = 0.040), include a high proportion of amelanotic melanomas (p = 0.038) as well as nail bed tumor (p = 0.013), and have a longer time interval between the onset of nail change and confirmed diagnosis (p = 0.012). Moreover, survival analysis revealed that trauma-related NAMs more frequently showed progression in general (p = 0.034) and nodal metastasis (p = 0.047) and had worse prognosis in terms of progression-free survival (p = 0.004). CONCLUSION: In conclusion, NAMs with previous trauma have unique clinicoprognostic characteristics. The specific clinicopathological features of NAMs according to trauma indicate that trauma may play a role in melanoma development.


Subject(s)
Melanoma, Amelanotic , Nail Diseases , Skin Neoplasms , Humans , Skin Neoplasms/pathology , Nails/pathology , Nail Diseases/pathology , Prognosis , Syndrome , Melanoma, Cutaneous Malignant
15.
Yonsei Medical Journal ; : 423-432, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1003228

ABSTRACT

Purpose@#The favorable clinical efficacies of intramuscular injection of autologous blood in patients with atopic dermatitis (AD) and intramuscular injection of autologous serum in patients with chronic urticaria have been demonstrated by randomized clinical trials. In this study, we assessed the clinical effectiveness and safety of the intramuscular injection of autologous serum in patients with AD. @*Materials and Methods@#In this randomized, placebo-controlled, and double-blind trial, 23 adolescent and adult patients with moderate-to-severe AD were enrolled. The patients were randomized to receive eight intramuscular injections of 5 mL of autologous serum (n=11) or saline (n=12) over 4 weeks, and were followed up until week 8. Changes in the clinical severity scores of AD assessed by SCORing Atopic Dermatitis (SCORAD), patient-reported Dermatology Life Quality Index (DLQI) score, and incidence of adverse events were assessed from baseline to week 8. @*Results@#One patient in the treatment group and two patients in the placebo group were lost to follow-up before week 8. The intramuscular administration of autologous serum, compared with saline, decreased the SCORAD clinical severity score (-14.8% vs. 10.7%, p=0.006) and improved the DLQI score (-32.6% vs. 19.5%, p=0.01) from baseline to week 8. Serious adverse events were not observed. @*Conclusion@#Intramuscular injection of autologous serum may be effective in treating AD. Further studies are needed to evaluate the clinical usefulness of this intervention for AD (KCT0001969).

16.
Article in English | WPRIM (Western Pacific) | ID: wpr-999234

ABSTRACT

Purpose@#Dupilumab (a monoclonal antibody to interleukin-4 receptor alpha) is the first biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD). We evaluated the clinical efficacy and compliance of dupilumab therapy for AD in real clinical practice. @*Methods@#Medical records of 132 adolescent and adult patients with AD who received at least one dose of dupilumab were retrospectively analyzed. Clinical efficacy of dupilumab was assessed by either changes in eczema area and severity index (EASI) or changes in the requirement of medications from baseline to weeks 16 and 42. Clinical response was determined by the proportion of patients with decreased EASI scores of at least 75% from baseline at week 16 (EASI–75). Clinical remission was defined as a complete withdrawal of all the medications for AD except dupilumab. @*Results@#Dupilumab was administered for 16 weeks (77.3%) and 42 weeks (63.6%) in 132 patients with AD. In patients who received reimbursement from National Healthcare Insurance of Korea (NHIK) for dupilumab therapy, the compliance of dupilumab therapy was 90.2% and 87.8%, and EASI–75 response rate was 92.5% and 100% at weeks 16 and 42, respectively. In patients who received the dupilumab therapy without NHIK reimbursement (self-payment), the compliance of dupilumab therapy was 71.4% and 52.7%, the clinical remission rate was 44.0% and 64.6%, and the median interval of dupilumab therapy was 4 weeks (range, 2–13 weeks) and 5 weeks (2–15 weeks) at weeks 16 and 42, respectively. @*Conclusion@#Dupilumab therapy may be clinically useful in the aspects of efficacy and compliance in patients with AD.

17.
Article in English | WPRIM (Western Pacific) | ID: wpr-968079

ABSTRACT

Background@#Adiponectin is an adipose-derived hormone that plays a role in various metabolic diseases. We previously demonstrated that adiponectin inhibits melanin synthesis through adenosine monophosphate-activated protein kinase (AMPK) activation in melanocytes. However, melanocytes can be affected by neighboring keratinocytes, and the effect of adiponectin on these functional units has not been investigated. @*Objective@#We investigated the effect of adiponectin on melanogenesis in co-cultured models of normal human melanocytes (NHMs), normal human keratinocytes (NHKs), and human dermal fibroblasts (HDFs), and the effect of adiponectin on melanin content in human skin tissues. @*Methods@#Quantitative real-time polymerase chain reaction (qPCR) was performed for tyrosinase and microphthalmia-associated transcription factor (MITF). The degree of phosphorylation of AMPK, cAMP response element binding protein (CREB), and AKT was evaluated by western blot assay, and Fontana-Masson staining was performed on cultured human skin tissues. @*Results@#Adiponectin decreased the melanin content in the co-culture models of NHMs with NHKs, NHMs with HDFs, and NHMs with both NHKs and HDFs. qPCR revealed that both tyrosinase and MITF were decreased after adiponectin treatment in the co-culture system. Following adiponectin treatment, AMPK was activated in all cell groups; however, the phosphorylation of CREB was decreased in HDFs and NHKs. The phosphorylation of AKT was decreased in only NHMs. In the experiment with human skin tissues cultured ex vivo, the densitometric analysis of Fontana-Masson staining revealed that adiponectin treatment reduced the melanin level of ultraviolet-irradiated human skin tissues. @*Conclusion@#Adiponectin inhibited melanogenesis in both co-culture models and human skin tissues ex vivo.

18.
Article in English | WPRIM (Western Pacific) | ID: wpr-968066

ABSTRACT

Background@#Upadacitinib is an oral Janus kinase1 (JAK1)-selective inhibitor, which showed a quick and significant effect on patients with atopic dermatitis in several phase 3 clinical studies. Although, an increasing number of studies have reported data on the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis, no studies have yet been published in Korea. @*Objective@#We assessed the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis in Korean patients. @*Methods@#A total of 17 patients with atopic dermatitis who received 15 mg of oral upadacitinib everyday for 16 weeks, were included in this retrospective single-center study. Based on electronic medical records, the clinical characteristics, Eczema Area and Severity Index (EASI) score, and adverse events were investigated. @*Results@#The mean EASI score was significantly reduced at 4 weeks of upadacitinib treatment (8.81±9.00) and gradually reduced at week 8 (5.70±7.38), week 12 (4.55±6.23), and week 16 (4.58±6.74) (p<0.001). At week 16, 61.54%, 30.77%, and 15.38% of patients achieved EASI 75, EASI 90, and EASI 100 responses, respectively. There was no statistically significant difference between EASI 75 and EASI 90 by age or gender at week 16 (p>0.05). A total of 13 people (76.5%) had adverse events, of which acne was the most common. In all patients, the symptoms were mild and self-limited, and no patient discontinued treatment. @*Conclusion@#Upadacitinib was effective and safe for Korean patients with atopic dermatitis in real-world clinical practice.

19.
Anatomy & Cell Biology ; : 94-108, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-966182

ABSTRACT

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer.Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

20.
Australas J Dermatol ; 63(4): e297-e304, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36066015

ABSTRACT

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare fibrohistiocytic tumour of unknown pathogenesis with intermediate malignant potential. Although trauma has been hypothesized as a predisposing factor for DFSP development, clinicopathological characteristics of trauma-related DFSP have not been investigated. OBJECTIVE: This study investigated the differences between trauma-associated DFSP and trauma-unrelated DFSP. METHODS: Patients histopathologically diagnosed with DFSP from January 2000 to December 2019 at the Dermatology Department were included. Clinical, histopathological, prognostic features and trauma history were analysed. RESULTS: We recruited 141 patients with DFSP (mean age, 36.1 years; male: female, 1:1.01). Recurrence and systemic metastasis were observed in 15.6% and 2.8% of patients, respectively. Older patients were likely to develop DFSP at the trauma sites more frequently on the face and lower legs. The active-growing lesions were more frequently associated with trauma-related DFSP. Multivariable logistic regression revealed that age at diagnosis (OR: 1.031; 95% CI: 1.004-1.059; p = 0.024) and tumour growth (OR: 3.336; 95% CI: 1.162-9.578, p = 0.025) were significantly associated with trauma-related DFSPs. CONCLUSIONS: The age at diagnosis, lesion location and tumour growth were associated with DFSPs in this study. Analysis of DFSP with trauma history provides a deeper understanding of long-term trauma effects on sarcoma development.


Subject(s)
Dermatofibrosarcoma , Skin Neoplasms , Humans , Male , Female , Adult , Dermatofibrosarcoma/pathology , Neoplasm Recurrence, Local , Prognosis , Skin Neoplasms/pathology , Republic of Korea/epidemiology
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