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The Role of CD8+ T-Cells and their Cytokines in the Pathogenesis of Psoriasis. CD8+ T 细胞及其细胞因子在牛皮癣发病机制中的作用。
Iva Volarić, Marijana Vičić, Larisa Prpić-Massari

The important role of CD8+ T-cells in the pathogenesis of psoriasis is well-determined. However, besides type 1 cytokines that were formerly known, it was recently found that these cells secrete type 17 and type 22 cytokines. The majority of IL-17A+CD8+ T-cells in the blood belong to a subset of innate T-cells named mucosa-associated invariant T-cells (MAIT). However, the majority of IL-17A+CD8+ T-cells in psoriatic epidermis are conventional T-cells and are up-regulated in psoriasis. In contrast to Th17 cells that secrete only IL-17, Tc17 cells secrete IFN-ϒ, TNF-α, CCL20, IL-22, and granzyme B as well. The key cytokine is IL-17A, which promotes keratinocyte hyperproliferation and stimulates them to produce other proinflammatory cytokines. These activities initiate and propagate the inflammation and architectural changes in the skin that clinically manifest as psoriatic lesions. However, a relatively novel cell subtype named Tc22 has been discovered in psoriasis that could secrete IL-22 in the absence of IL-17 and IFN-gamma. IL-22 stimulates proliferation and de-differentiation of keratinocytes, subsequently leading to epidermal acanthosis. As the understanding of the pathogenesis of psoriasis increases, the new selective therapies may offer an optimal balance between increased clinical benefit and reduced risk of side-effects.

CD8+ T 细胞在银屑病发病机制中的重要作用已被充分确定。然而,除了以前已知的 1 型细胞因子外,最近还发现这些细胞能分泌 17 型和 22 型细胞因子。血液中的大多数 IL-17A+CD8+ T 细胞属于先天性 T 细胞亚群,被命名为粘膜相关不变性 T 细胞(MAIT)。然而,银屑病表皮中的大多数 IL-17A+CD8+ T 细胞是传统 T 细胞,在银屑病中上调。与只分泌 IL-17 的 Th17 细胞不同,Tc17 细胞也分泌 IFN-ϒ、TNF-α、CCL20、IL-22 和颗粒酶 B。关键的细胞因子是 IL-17A,它能促进角质形成细胞的过度增殖,并刺激它们产生其他促炎细胞因子。这些活动引发并加剧了皮肤的炎症和结构变化,临床上表现为银屑病皮损。然而,在银屑病中发现了一种名为 Tc22 的相对新颖的细胞亚型,它可以在没有 IL-17 和 IFN-gamma 的情况下分泌 IL-22。IL-22 可刺激角朊细胞增殖和去分化,进而导致表皮棘层增生。随着对银屑病发病机理认识的加深,新的选择性疗法可能会在增加临床疗效和降低副作用风险之间实现最佳平衡。
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引用次数: 0
Health Behavior Changes in Cutaneous Melanoma Survivors. 皮肤黑色素瘤幸存者的健康行为变化。
Mirjam Rogl Butina, Igor Švab, Barbara Perić, Igor Bartenjev

Aim of this study was to investigate changes in health behavior of melanoma survivors with emphasis on safe sun behavior (SSB) and skin self-examination (SSE). We also identified factors with significant impact on SSE improvement. We performed a cross-sectional (epidemiological) survey based on a structured questionnaire. 150 patients from three medical institutions were invited and 144 patients responded. Statistical analysis was performed with SPSS version 23.0, with the level of significance set to 0.05. After being diagnosed with cutaneous melanoma, patients significantly improved preventive health behavior: 68.1% showed improvement in SSE, and 91.5% of patients improved SSB. There was statistically significant (P<0.001) improvement in the frequency of skin examination, examination of poorly visible areas (between the toes, genitals), and obtaining help in examination. Use of melanoma images remained scarce. Results for SSB were even better, and statistically significant improvement was recorded in all areas: using higher UV protection filters, wearing sunglasses, headgear, long sleeves, and trousers, and especially in staying in deep shade during hours of heavy UV radiation. The only factor with a positive influence on expected improvement in SSE was female gender. On the other hand, there were two factors that had a negative impact on SSE: patients with melanoma stage 1 and patients who had already self-examined themselves before their melanoma diagnosis. Preventive health behavior improved significantly after diagnosis of cutaneous melanoma. Patients markedly improved SSB and substantially enhanced SSE. We believe that it is reasonable to improve SSE further, encouraging patients by increasing their feeling of self-efficacy.

本研究旨在调查黑色素瘤幸存者健康行为的变化,重点是安全晒太阳行为(SSB)和皮肤自我检查(SSE)。我们还确定了对改善 SSE 有重大影响的因素。我们根据结构化问卷进行了横断面(流行病学)调查。我们邀请了来自三家医疗机构的 150 名患者,其中 144 名患者作了回答。统计分析采用 SPSS 23.0 版,显著性水平设为 0.05。确诊为皮肤黑色素瘤后,患者的预防性健康行为明显改善:68.1%的患者改善了SSE,91.5%的患者改善了SSB。在统计意义上(P
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引用次数: 0
Thin Melanoma: A Generic Term Including Four Histological Subtypes of Cutaneous Melanoma. 薄型黑色素瘤:包括四种组织学亚型皮肤黑色素瘤的通用术语。
Luca Roncati, Teresa Pusiol, Francesco Piscioli

Today, the scientific community is focusing on the prognostic significance of different histological subtypes of thin melanoma (1). The current staging system for melanoma of the American Joint Committee on Cancer (AJCC) uses Breslow thickness as the primary attribute: melanomas with up to 1 mm thickness is defined as thin, because they present a good prognosis after surgical excision, with a 10-year survival rate of 85-90% in case of a tumor-free margin ≥1 cm (2). There is a significant interaction between mitotic rate and Breslow depth, so the predictive value of the mitotic rate on sentinel lymph node (SLN) positivity can be dependent on Breslow thickness (3). Cutaneous melanoma generally evolves through three clearly discernible progression stages. At first, transformed melanocytes proliferate above the epidermal basement membrane (the in situ or epidermal radial growth phase); they then invade the papillary dermis (the micro-invasive radial growth phase); and subsequently acquire the capacity to grow as a well-known malignant tumor (the invasive vertical growth phase). More specifically, micro-invasive melanoma is a non-tumorigenic radial growth phase of cutaneous melanoma, which invades the superficial dermis without forming a tumor nodule or papule, in absence of regression (3). In contrast, the micro-invasive radial growth phase of cutaneous melanoma with regression will rarely metastasize and, for this reason, the lesion should be recognized and could also be categorized as a 'micro-invasive radial growth phase of uncertain tumorigenic potential' (4). The early vertical growth phase of tumorigenic melanoma is characterized by the presence of a cell cluster in the dermis that is larger than the largest cluster in the epidermis (5). This feature is typical of tumorigenicity, while the mitogenicity is documented by the observation of mitotic figures in dermal melanoma cells (5,6). The early vertical growth phase and the radial growth phase with regression have a statistical chance of distant metastases (7). Therefore, thin melanoma includes four main histological subtypes, which reflect a specific biological behavior: the in situ epidermal radial growth phase, the non-tumorigenic micro-invasive radial growth phase, the micro-invasive radial growth phase with regression of uncertain tumorigenic potential, and the tumorigenic early vertical growth phase. In conclusion, thin melanoma can be considered a generic term and its subtypes should be histologically distinguished beyond its site of origin (acral versus non-acral) because they have different prognostic relevance.

如今,科学界正在关注薄型黑色素瘤不同组织学亚型的预后意义(1)。美国癌症联合委员会(AJCC)目前的黑色素瘤分期系统以布雷斯罗厚度为主要特征:厚度不超过 1 毫米的黑色素瘤被定义为薄型,因为它们在手术切除后预后良好,无瘤缘≥1 厘米的 10 年生存率为 85%-90%(2)。有丝分裂率和布氏深度之间存在明显的交互作用,因此有丝分裂率对前哨淋巴结(SLN)阳性的预测价值可能取决于布氏厚度(3)。皮肤黑色素瘤一般会经历三个明显的发展阶段。首先,转化的黑色素细胞在表皮基底膜上方增殖(原位或表皮径向生长期);然后侵入乳头状真皮层(微侵袭性径向生长期);随后获得生长为众所周知的恶性肿瘤的能力(侵袭性垂直生长期)。更具体地说,微侵袭性黑色素瘤是皮肤黑色素瘤的非致瘤性径向生长期,它侵袭真皮浅层,不形成肿瘤结节或丘疹,没有消退现象(3)。相比之下,皮肤黑色素瘤的微侵袭径向生长期若有消退,则很少发生转移,因此,这种病变应予以识别,也可归类为 "不确定致瘤潜能的微侵袭径向生长期"(4)。黑色素瘤早期垂直生长期的特点是真皮层出现一个细胞团,该细胞团大于表皮层最大的细胞团(5)。这一特征是典型的致瘤性,而有丝分裂则是通过观察真皮层黑色素瘤细胞的有丝分裂图来证明的(5,6)。据统计,早期的垂直生长期和伴有退行的放射生长期有可能发生远处转移(7)。因此,薄型黑色素瘤包括四个主要的组织学亚型,它们反映了特定的生物学行为:原位表皮径向生长期、非致瘤性微侵袭径向生长期、致瘤潜能不确定的微侵袭径向生长期和致瘤性早期垂直生长期。总之,薄型黑色素瘤可被视为一个通用术语,其亚型应在起源部位(尖锐型与非尖锐型)之外进行组织学区分,因为它们具有不同的预后相关性。
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引用次数: 0
Immunohistochemical Expression of Calponin in Cutaneous Basal Cell Carcinoma. 皮肤基底细胞癌中钙蛋白的免疫组化表达
Vladimír Bartoš, Milada Kullová

Calponin is an actin filament-associated protein significantly involved in the regulation of the cellular motility. Some data have indicated that overproduction of calponin in basal cell carcinoma (BCC) of the skin may be responsible for local tumor invasiveness and more aggressive biological behavior. We studied the immunohistochemical expression of calponin in a set of cutaneous BCCs, in order to clarify whether the presence of calponin in cancer cells may be a predictor of invasive tumor growth. The study group consisted of 37 primary BCCs categorized into a non-infiltrative subgroup (5 superficial, 16 nodular subtypes) and infiltrative subgroup (9 nodular-infiltrative, 7 infiltrative subtypes). A specific monoclonal antibody against calponin was used for staining. Expression of calponin in tumor tissue was found in 72.9% (27/37) of the cases, though staining intensity was relatively weak. In superficial, nodular, nodular-infiltrative, and infiltrative BCC subtypes, calponin positivity was found in 80% (4/5), 75% (12/16), 66.7% (6/9), and 71.5% (5/7), respectively. We did not confirm a significant correlation between expression of calponin and given, non-infiltrative, and infiltrative BCC subgroups. Furthermore, we found seven BCCs (18.9%) with striking immunoreactivity for calponin in adjacent peritumorous stroma. There was a significant association between stromal immunoreactivity for calponin and tumor growth histomorphology being positive only in BCCs with infiltrative growth features. Our study has shown that neoplastic cells in cutaneous BCC commonly produce calponin regardless of histological subtype. Expression of calponin in tumor tissue was not associated with the aggressive tumor phenotype. However, since some BCCs with infiltrative growth patterns strongly expressed calponin in peritumorous stroma, this finding could more reliably reflect the biological behavior of cancer and should be better explained in the future.

钙调蛋白是一种肌动蛋白丝相关蛋白,在细胞运动调节中发挥着重要作用。一些数据表明,皮肤基底细胞癌(BCC)中钙蛋白的过度生成可能是造成局部肿瘤侵袭性和更具侵袭性生物学行为的原因。我们研究了一组皮肤基底细胞癌(BCC)中钙蛋白的免疫组化表达,以明确癌细胞中钙蛋白的存在是否可预测肿瘤的侵袭性生长。研究组由 37 例原发性 BCC 组成,分为非浸润亚组(5 例浅表亚型、16 例结节亚型)和浸润亚组(9 例结节浸润亚型、7 例浸润亚型)。染色使用的是针对钙调蛋白的特异性单克隆抗体。72.9%的病例(27/37)发现肿瘤组织中有钙蛋白表达,但染色强度相对较弱。在表皮型、结节型、结节浸润型和浸润型 BCC 亚型中,钙蛋白阳性率分别为 80%(4/5)、75%(12/16)、66.7%(6/9)和 71.5%(5/7)。我们没有证实钙蛋白的表达与给定、非浸润和浸润性 BCC 亚组之间存在明显的相关性。此外,我们还发现有 7 例 BCC(18.9%)的邻近瘤周基质对钙蛋白有明显的免疫反应。钙蛋白的基质免疫反应与肿瘤生长组织形态学之间存在明显的关联,只有具有浸润性生长特征的 BCC 才会出现阳性反应。我们的研究表明,皮肤 BCC 中的肿瘤细胞通常会产生钙调素,而与组织学亚型无关。钙蛋白在肿瘤组织中的表达与侵袭性肿瘤表型无关。然而,由于一些具有浸润性生长模式的 BCC 在瘤周基质中强烈表达钙调蛋白,因此这一发现可以更可靠地反映癌症的生物学行为,并在未来得到更好的解释。
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引用次数: 0
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Acta dermatovenerologica Croatica : ADC
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