Cytokines and their effects on maturation,differentiation and migration of dendritic cells

In this review the role of cytokines in the maturation and migration of phenotypically and functionally diverse dendritic cell (DC) subpopulations is discussed and their role in the progress of differentiation from bone marrow progenitors to lymphoid DC is described. GM-CSF is the most important cytokine for the development of functional DC and acts in concert with a varying mixture of other cytokines such as IL-4, IL-1 and TNF-α to direct the development of individual DC subpopulations. Received: 18 July 1996     

Dendritic cells and their role in skin-induced immune responses

This artide gives a brief review on dendritic cells (DC) with regard to their origin, life cyde and functions. The regulation of immune responses by DC functioning as antigen-presenting cells is discussed. Special attention is given to epidermal DC, e.g. Langerhans cells. The perspectives of DC-based therapy are also mentioned.     

Limited reliability of E-cadherin as a specific marker for in vitro-generated Langerhans cells

Langerhans cells (LC) are a unique population of dendritic cells (DC) found in the epidermis where they can be identified by the expression of CD1a, E-cadherin and cytoplasmic Birbeck granules (BG) as their hallmark. Over the past years many techniques have been described to generate LC in vitro from either monocytes or CD34⁺ hematopoietic cell progenitors. Antibodies against Lag and Langerin (two epitopes associated with BG) and E-cadherin (a Ca²⁺-dependent homophilic adhesion molecule) have been used to detect in vitro-generated LC. In this study we investigated whether the expression of E-cadherin on in vitro-generated CD1a⁺ from either CD34⁺ cells or monocytes is able to discriminate LC from other DC. Our results demonstrate that E-cadherin alone is not a reliable marker to specifically identify in vitro-generated LC.     

Indeterminate dendritic cell neoplasm of the skin: A 2‐case report and review of the literature

Indeterminate dendritic cell neoplasm (IDCN) is an exceedingly rare and mostly cutaneous histiocytosis, frequently associated with other hematopoietic malignancies. We report 2 cases of multilesional cutaneous IDCN. A 55‐year‐old male with no associated malignancy and complete response to ultraviolet phototherapy; and a 72‐year‐old male with chronic myelomonocytic leukemia (CMML). Both cases showed histiocytoid cytology, positivity for CD1a and no expression of langerin or BRAF^V600E. With our patients, the literature describes 79 cases of IDCNs, including 65 (82%) with only skin involvement, 7 cases (9%) with involvement of skin and a second site, 5 cases (6%) involving lymph nodes only, 1 splenic lesion and 1 systemic disease. Seventeen cases (22%) were associated with other hematopoietic malignancies, most commonly CMML (6 cases), follicular lymphoma (4 cases) and acute myeloid leukemia (3 cases). All IDCNs associated with myeloid malignancies were limited to the skin, while most cases associated with lymphoma were limited to lymph nodes. Reported responses of cutaneous lesions to ultraviolet phototherapy are encouraging, while systemic chemotherapy is appropriate for clinically aggressive cases and treatment of associated malignancies. Recognition of the clinico‐morphologic spectrum of IDCNs should prevent misdiagnoses and prompt investigation of possible associated neoplasms.     

皮肤Merkel细胞癌伴鳞状细胞癌1例

患者女,76岁。左面颊部肿物1年,明显增大1个月。皮损特点为紫红色球形肿物。皮损组织病理示:表皮见团块状鳞状上皮中-重度异型增生,突破基底膜;真皮全层见形态一致的肿瘤细胞浸润,巢状或片状分布,圆形或卵圆形,胞质少、嗜碱性,核大、散点状分布染色质,核仁明显,可见多数核分裂相。免疫组化:CK20(部分+),P63及CKH(鳞状分化的细胞+),Syn(+),CgA(+),CD56(+),LCA(-),CK7(-),S100(-)。诊断:皮肤Merkel细胞癌伴鳞状细胞癌。     

二期梅毒患者外周血Th1/Th2及Tc1/Tc2的研究

目的探讨CD4+T细胞(Th细胞)和CD8+T细胞(Tc细胞)亚群在梅毒发病机理中的作用及其相互关系。方法采用流式细胞术检测经三色荧光抗体染色的二期梅毒患者外周血CD4+/IFN-γ+(Th1),CD4+1/IL-4+(Th2),CD4+/IFN-γ+/IL-4+(Tho),CD8+/IFN-γ+(Tc1),CD8+/IL-4+(Tc2),CD8+/IFN-γ+/IL-4+(Tc0)细胞含量。结果梅毒组Th1细胞含量、Th1/Th2,Tc1/Tc2比值均明显低于正常对照组(P<0.01),而Tc0和Tc2细胞含量显著高于正常对照组,其他细胞两组间无显著性差异(P>0.05)。结论二期梅毒患者Th1/Th2及Tc1/Tc2比值失衡,可能是机体不能完全清除梅毒螺旋体造成其潜伏体内形成长期感染的重要因素之一。     

内皮细胞生长因子促进细胞增殖的研究

用高效液相色谱分析技术获得纯化内皮细胞生长因子 ( ECGF) ,体外培养发现 ECGF能提高人脐静脉内皮细胞及 L92 9成纤维细胞的分裂增殖能力     

CD_4~+T淋巴细胞与寻常型天疱疮相关性研究进展

寻常型天疱疮(PV)是一种危及生命的自身免疫性大疱性皮肤黏膜病,以往认为PV的发生与体液免疫有关,目前认为,除了B细胞的功能异常产生致病性抗体外,T细胞所介导的细胞免疫异常介导了PV患者出现病理性免疫应答。现就CD4+T淋巴细胞在寻常型天疱疮发病中的研究进展作一综述。     

Isolation and culture of human primary keratinocytes—a methods review

Keratinocyte culture is a necessary and widely used tool in a variety of experimental dermatological and biomedical studies. Literature search has revealed a variety of different protocols of human primary keratinocyte isolation and culture. Therefore, the aim of this paper was to review and summarize current trends in human primary keratinocyte culture techniques. We present data on the most popular and effective methods of human keratinocyte isolation and cultivation obtained from screening of 945 papers published during the last 10 years.     

Granulomas en dermatopatología: principales entidades. Parte I

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.     

Histogenesis of pure and combined Merkel cell carcinomas: An immunohistochemical study of 14 cases

The histogenesis of Merkel cell carcinoma (MCC) has remained unresolved. Moreover, one of the questions is whether pure MCC and combined MCC represent the same histogenesis and entity. The existence of combined MCC suggests that MCC likely arise from pluripotent stem cells. Merkel cells (MC) localize within the bulge area, which is populated by hair follicle stem cells. We used hair follicle stem cell markers to investigate whether MCC share certain characteristics of these stem cells. Fourteen MCC specimens were examined histologically and immunohistochemically. There were six pure MCC and eight combined MCC. In six combined MCC, both MCC components and squamous components at least focally shared the expression of one or more of cytokeratin (CK)15, CK19 and CD200, which are hair follicle stem cell markers. On the other hand, four cases of pure MCC showed partially distinct CK19 expression, but did not show CK15 and/or CD200 expression. There was a distinct difference between pure MCC and combined MCC on the expression of hair follicle stem cell markers. The normal skin expressed CK15, CK19 and CD200 in the bulge area, whereas CK15 and CD200 were absent in the MC‐rich glabrous skin and touch domes. The results led us to hypothesize that combined MCC originate from the hair follicle stem cells. We postulate that combined MCC undergo multidirectional differentiation into squamous, glandular, mesenchymal and Merkel cells. Further investigation is warranted to confirm the histogenesis of pure MCC and combined MCC.     

Immunohistochemical localization of proliferating cell nuclear antigen/cyclin in human skin

Summary Expression of proliferating cell nuclear antigen/cyclin (PCNA/cyclin) in skin tissue specimens and cultured keratinocytes was studied using a monospecific antibody, obtained from a patient with systemic lupus erythematosus, and a monoclonal antibody. Indirect immunofluorescent staining revealed that cultured keratinocytes obtained from human foreskins expressed PCNA/cyclin as variable nuclear patterns in 15–30% of the cells. In normal human skin tissue specimens, PCNA/cyclin was demonstrated in only a few basal cells. Interestingly, PCNA/cyclin was expressed strongly in almost all the cells of the lowest layer of the epidermis adjacent to squamous cell carcinomas, whereas the tumor aggregates themselves had no positive staining. In contrast, no such characteristic staining was demonstrated in specimens of basal cell carcinoma. The staining pattern of PCNA/cyclin was different from that of Ki-67 in the skin tissue specimens. Our results suggest that PCNA/cyclin could be a useful marker of cell proliferation.     

Usefulness of ulceration and hyperkeratosis as clinical predictors of Merkel cell polyomavirus‐negative and combined Merkel cell carcinoma: A retrospective study

Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin that is associated with Merkel cell polyomavirus (MCPyV). The clinical appearance and demographic characteristics of this tumor have been described using the mnemonic AEIOU: asymptomatic, expanding rapidly, immune suppression, older than 50 years, and ultraviolet‐exposed fair skin. In addition, MCC can be categorized based on morphology as pure MCC or combined MCC that exhibits neuroendocrine and other phenotypic elements. There is limited information regarding the clinical characteristics and prognosis of combined MCC. This retrospective study aimed to identify factors, such as ulceration or hyperkeratosis, that could predict MCPyV status and morphological variants. Twenty patients with MCC were divided into groups based on MCPyV status and morphology: MCPyV‐positive or MCPyV‐negative MCC and pure or combined MCC. The patients’ MCPyV status was immunohistochemically determined using the CM2B4 antibody to the MCPyV large T‐antigen. The patients’ clinicopathological characteristics were evaluated to identify predictors of MCPyV‐negative MCC and combined MCC. The presence of ulceration/hyperkeratosis predicted the presence of MCPyV‐negative MCC (80% of cases) and combined MCC (50% of cases). None of the 10 patients with MCPyV‐positive MCC had ulceration/hyperkeratosis. The clinical presence of ulceration/hyperkeratosis may help guide the diagnosis of MCPyV‐negative MCC and combined MCC.     

A previously undescribed variant of cutaneous clear‐cell squamous cell carcinoma with psammomatous calcification and intratumoral giant cell granulomas

Cutaneous clear‐cell squamous cell carcinoma (ccSCC) is a rare variant of SCC composed of clear cells that lack cytoplasmic glycogen or evidence of tricholemmal keratinization. We report a previously undescribed variant of ccSCC with psammomatous calcification and intratumoral giant cell granulomas. The differential diagnosis with trichilemmal carcinoma is outlined according to the criteria of the fourth edition of World Health Organization (WHO) classification. Our findings outline that psammomatous calcification may occur inside the keratinous pearls of the neoplastic lobules triggering an intratumoral giant cell granulomatous reaction. The prognostic significance of this histopathological presentation is unknown but the potential for formation of psammoma bodies in cSCC should be considered to avoid diagnostic pitfalls.     

Merkel细胞癌合并原位鳞状细胞癌一例并文献复习

Merkel细胞癌是一种罕见的、具有高度侵袭性的皮肤神经内分泌癌,好发于老年人的日光暴露部位,尤其是头颈部(41%～50%),其次是四肢(32%～38%)。Merkel细胞癌可与鳞状细胞癌、鲍温病、基底细胞癌等皮肤肿瘤合并发生。我们报道一例发生在非光暴露部位的Merkel细胞癌合并原位鳞状细胞癌,并对相关文献进行复习。     

新的喜树碱类化合物-喜树异碱抑制鳞癌细胞增殖及对其细胞周期影响的实验研究

目的观察一种新的喜树碱类化合物--喜树异碱对鳞癌Tca8113细胞的增殖抑制作用及对其细胞周期的影响.方法四甲基偶氮唑盐(MTT)法检测喜树异碱对细胞增殖的抑制作用及有效浓度范围;流式细胞仪检测分析喜树异碱对Tca8113细胞周期的影响.结果喜树异碱在试验浓度内对Tca8113细胞的增殖有明显抑制作用,且可将Tca8113细胞阻滞于S期,并表现出一定的时间和剂量依赖性.结论提示该新的喜树碱类化合物可能具有抗肿瘤作用,其机制可能与抑制细胞增殖并影响细胞周期有关.     

The Merkel cell — a member of the APUD cell system?

Summary Merkel cells of sinus hair follicles of nude mice were investigated by fluorescence and electron microscopy following pretreatment with amine precursors (L-Dopa, L-5-Hydroxytryptophan) and monoaminoxidaseinhibitors (Marsilid, Harmaline). Neither in control animals nor in pretreated animals any evidence for an involvement of Merkel cells in monoamine metabolism could be found. Therefore, the hypothesis that Merkel cells might share the most constant cytochemical characteristics of the cells of the APUD series, i.e., to take up amine precursors, should definitely be left.Following Harmaline treatment, however, Merkel cells were found fluorescent; cytophotometric analysis of the fluorescence emission spectra of formaldehyde-treated and untreated tissue ascertained that this fluorescence was due merely to a specific Harmaline fluorescence. The significance of Harmaline uptake in Merkel cells, most probably in the Merkel cell granules, is discussed.     

Do inflammatory pathways drive melanomagenesis?

Inflammatory pathways serve to protect the host and promote tissue healing/repair; however, over‐activation or dysregulation can be pathological with unintended consequences including malignant progression. A correlation between inflammation and cancer has been well established, and anti‐inflammatory medications have been shown to be chemopreventive in certain malignancies. Data are now becoming available that outline an inflammatory pathway that may have a critical role in melanomagenesis. ATP‐regulated membrane channels/receptors P2X7 and PANX1 have been directly implicated in melanoma tumor growth. Among other potential effects, opening of the P2X7/PANX1 channel results in activation of the NALP3 inflammasome, which in turn leads to caspase‐1 activation and increased levels of activated IL‐1β. Elevated levels of caspase‐1 and IL‐1β have been correlated with melanoma progression, and inhibitors of the inflammasome, caspase and IL‐1β activity have all been shown to inhibit melanoma growth. Among many other potential actions, IL‐1β increases cyclooxygenase‐2 expression leading to local increases in inflammatory mediators such as prostaglandin E2 (PGE2). Anti‐inflammatory medications targeting the end of this pathway have had positive results for certain cancers but overall remain mixed for melanoma. A better understanding of the pathways and appropriate intervention points may help direct future therapies. In this viewpoint, we will review data and attempt to model an inflammatory pathway that may be critical for melanomagenesis and propose future directions for exploration.     

Hematopoietic stem cell transplantation for cutaneous T‐cell lymphoma: Summary of 11 cases from two facilities in Japan and Brazil

Some patients with cutaneous T‐cell lymphoma (CTCL) show a miserable clinical course and the only option that can induce long‐term remission for advanced CTCL may be hematopoietic stem cell transplantation (HSCT). So far, studies on HSCT for CTCL patients have been limited. In this study, we summarized 11 cases with CTCL treated with HSCT, including nine cases in Japan and two cases in Brazil. The patients were five cases with mycosis fungoides (MF), two cases with Sézary syndrome (SS), three cases with anaplastic large cell lymphoma, and one case with primary cutaneous peripheral T‐cell lymphoma, not otherwise specified (PTL‐NOS). Currently, seven out of 11 cases are alive (at 13–108 months after transplantation) and four died at 15 days to 14 months after transplantation. When focusing on the eight patients who received allogeneic HSCT for MF/SS and PTL‐NOS, all four patients at 45 years old or under are alive at present. One case showed relapse in the skin. On the other hand, one out of the other four patients at over 45 years old survived. Engraftment failure was seen in one case and all the other three cases experienced relapse. Although this is only a case series with a small number, our study has suggested that we should be careful about age when treating patients with MF/SS by allogeneic HSCT.