基底细胞癌中肿瘤相关信号通路研究进展

肿瘤的发生、发展、浸润以及转移中均伴随着相关信号通路的信号失调.基底细胞癌是一种最为常见的皮肤恶性肿瘤.大量的研究发现,以Hedgehog信号通路为核心包括wnt、表皮生长因子受体、Notch、转化生长因子β/骨形态发生蛋白、FasL-Fas、P13K-AKT、促分裂原活化蛋白激酶和核因子-κB等多种信号通路的失调在其肿瘤生物学行为中发挥着重要的作用.更为重要的是,基底细胞癌中Hedgehog信号通路在信号传导途径中与包括wnt、表皮生长因子受体、转化生长因子β/骨形态发生蛋白和Notch等信号通路存在着交联机制.这些信号通路的研究对于更加深入地揭示基底细胞癌的肿瘤发生发展机制及寻找更加准确的药物治疗靶点具有重要的意义.

Abstract：

Deregulation of signaling pathways is commonly accompanied with the initiation, development,infiltration and metastasis of many kinds of tumors.Basal cell carcinoma(BCC)is a most common form of skin malignancy.Numerous studies have shown that many signaling pathways including Wnt, epidermal growth factor receptor(EGFR), Notch, transforming growth factor(TGF)β/bone morphogenetic protein(BMP), FasL-Fas, PI3K-AKT, mitogen-activated protein kinase(MAPK), nuclear factor kappa B, etc, play an essential role in the biological behaviors of BCC.Of these signaling pathways, Hedgehog is the core pathway.Most importantly, there are some cross-talks between Hedgehog pathway and Wnt, EGFR, TGFβ/BMP, Notch pathway in the signal transduction in BCC.Researches on these signaling pathways in BCC may contribute to the illumination of pathogenesis of BCC and searches for accurate therapeutic targets.     

Photodynamic therapy with topical aminolevulinic acid

Photodynamic therapy(PDT) is a relatively new therapy in dermatology that uses the topical application of a porphyrin derivative to selectively destroy a cutaneous target. The action is implemented by the application of a specific light frequency. The ability of porphyrin to selectively target tumor tissue has been known since the 1960 s. In the late 1970 s, the underlying mechanism was defined, and Dougherty's discovery of the first chromophore led to the production and commercialization of Photofrin. Many other chromophores that can act as photosensitizers have been studied since then, with aminolevulinic acid currently the most commonly used chromophore in clinical practice. PDT is simple, minimally invasive and can be administered on an outpatient basis. The efficacy of PDT has been proven for actinic keratosis, Bowen's disease and basal cell carcinoma; another of its well-known applications is the treatment of photoaging. Indications for its use are continuously increasing, and promising results are reported for various skin diseases. In this paper we report the mechanism of action of PDT with aminolevulinic acid, the literature concerning the most common diseases treated with PDT and the subsequent level of evidence.     

Does steroid-free immunosuppression improve the outcome in kidney transplant recipients compared to conventional protocols?

Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms of rejection.Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells.Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives.This situation changed with the introduction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile.As a result,the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice.This review aims to evaluate the safety and efficacy of various steroid-minimization approaches(steroid avoidance,early steroid withdrawal,and late steroid withdrawal)in kidney transplant recipients.A meticulous electronic search was conducted through the available data resources like SCOPUS,MEDLINE,and Liverpool University library e-resources.Relevant articles obtained through our search were included.A total number of 90 articles were eligible to be included in this review[34 randomised controlled trials(RCT)and 56 articles of other research modalities].All articles were evaluating the safety and efficacy of various steroidfree approaches in comparison to maintenance steroids.We will cover only the RCT articles in this review.If used in right clinical context,steroid-free protocols proved to be comparable to steroid-based maintenance therapy.The appropriate approach should be tailored individually according to each recipient immunological challenges and clinical condition.     

Cutaneous Manifestations of HIV/AIDS in the Era of Highly Active Antiretroviral Therapy: Evidence from Bangladesh

Objective: Skin diseases are common and striking features of patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and may vary considerably by ethnic and geographic regions and by the influence of highly active antiretroviral therapy (HAART). However, little information exists regarding the cutaneous manifestations of patients with HIV/AIDS in Bangladesh. This study was performed to elucidate the spectrum of cutaneous disorders in patients with HIV/AIDS in the...     

皮肤细胞DNA光损伤后反应机制研究进展

紫外线可引起皮肤细胞DNA损伤,诱发皮肤肿瘤和光老化.DNA损伤类型包括:DNA单链断裂、链间交联、核苷酸碱基修饰等.细胞拥有DNA损伤后反应机制以维持基因组稳定,如细胞周期监控点、DNA修复和细胞早衰等.细胞周期监控系统检测到染色体结构异常时将引起细胞周期停滞并启动修复进程;而在检测到无法修复的损伤时则会诱使细胞衰老.因此皮肤光老化也是一种预防肿瘤发生的防御机制,ATR-Chk1信号通路在其中起着关键的调控作用.

Abstract：

Ultraviolet radiation can induce DNA damage in skin cells, cause skin tumors and accelerate skin photoaging. UV-induced DNA damage in skin cells includes DNA single strand breaks, DNA interstrand cross-links and nucleotide base modifications. Skin cells could exert DNA damage responses, such as cell cycle checkpoints, DNA repair and premature senescence to prevent genomic instability. When cell cycle checkpoint systems sense the abnormal chromosomal DNA structures, they execute cell cycle arrest and DNA repair process will be initiated. Cellular senescence is also executed by checkpoint responses when unrepairble and extensive chromosomal abnormalities are detected. So skin photoaging is thought to be one of the major mechanisms against skin carcinogenesis. ATR-Chk1 signaling pathway plays a key role in the regulation of DNA damage response process.     

Spa-1和Ki-67在乳房外Paget病肿瘤组织中的表达

目的 探讨Spa-1在乳房外Paget病发生和转移中可能的作用.方法 取17例原位乳房外Paget病和12例侵袭性乳房外Paget病患者皮损及9例正常人皮肤组织,用免疫组化分别检测Spa-1和Ki-67的表达.结果 Spa-1在胞质中显色,Ki-67在胞核中显色.Spa-1和Ki-67仅少量表达于正常人皮肤基底层,在乳房外Paget病肿瘤组织中的表达明显高于正常人皮肤(P<0.01).Spa-1在侵袭性乳房外Paget病肿瘤组织中表达明显高于原位乳房外Paget病(P<0.01).乳房外Paget病肿瘤组织中Spa-1的表达与Ki-67的表达呈正相关.结论 Spa-1在乳房外Paget病的发生发展中可能起作用.

Abstract：

Objective To investigate the potential role of Spa-1 in the development and metastasis of EMPD.Methods Tissue specimens were resected from 17 patients with primary EMPD,12 patients with invasive EMPD and 9 normal human controls.Immunohistochemistry was performed to measure the expression of spa-1 and Ki-67.Results Positive staining was observed for Spa-1 in cytoplasm,and for Ki-67 in cell nuclei.Spa-1 and Ki-67 were weakly expressed in the basal layer of normal skin.The expression of Spa-1 and Ki-67 in EMPD tissue were statistically higher than those in the normal control tissue (both P<0.01).Increased expression of Spa-1 was noted in invasive EMPD tissue compared with in situ EMPD tissue.The expression of Spa-1 was positively correlated with that of Ki-67 in the tissue of EMPD.Conclusion Spa-1 may play a certain role in the initiation and progression of EMPD.     

树突细胞相关C型凝集素-1受体介导的抗白念珠菌免疫作用及机制

树突细胞相关c型凝集素-1是一种主要的C型凝集素样受体,存在于多种细胞和组织中.它能够特异性识别白念珠菌细胞壁主要成分β-葡聚糖,进而诱导机体产生固有免疫反应和适应性免疫反应.其可单独或与其他模式识别受体相互协同完成上述过程.白念珠菌β-葡聚糖的暴露、树突细胞相关C型凝集素-1表达水平等因素可影响机体免疫效应的强度,对其进行调控将为自念珠菌感染预防和治疗提供一个新的方向.

Abstract：

Dectin-1, a principal C-type lectin pattern-recognition receptor, exists in various types of cells and tissues. It can specifically recognize β-glucans, which are the major cell wall component of Candida albicans, and then trigger the innate and adaptive immune responses in hosts. Dectin-1 can independently, as well as collaboratively with other pattern recognition receptors, induce above mentioned processes. The intensity of immune responses in hosts is modulated by multiple factors such as the exposure of β-glucans on Candida albicans and the expression level of Dectin-1, and this modulation may provide a new direction for the prevention and therapy of Candida albicans infection.     

水通道蛋白-3与皮肤研究进展

Aquaporins (AQPs) are a group of membrane transport proteins involved in the transport ofwater across cell membranes. AQP3, the most abundant aquaporin subset in human skin, is permeable notonly to water but also to small solutes such as glycerol. It has been reported that AQP3-knockout mice havereduced stratum corneum water content, elasticity and impaired wound healing. AQP3 has been revealed to berelated to cell proliferation and migration, and involved in the initiation, progression and metastasis of tumors.In addition, AQP3 expression is associated with the pathogenesis of inflammatory cutaneous diseases such asatopic dermatitis and erythema toxicum neonatorum. AQP3 expression can be modulated by multiple factorssuch as retinoic acid and tumor necrosis factor α, and this modulation may provide a new clue for the therapyof related skin diseases.     

Cutaneous Manifestations and Treatment Advances of Adult T-Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe th...     

人乳头瘤病毒感染对朗格汉斯细胞影响机制的研究进展

人乳头瘤病毒感染时,皮肤朗格汉斯细胞的数量、形态、分布及功能发生一系列改变,尤其功能受损被认为与导致人乳头瘤病毒逃逸宿主免疫、造成持续感染有关.研究提示,人乳头瘤病毒感染时某些细胞因子或蛋白酶等,如前列腺素E2及其主要限速酶、巨噬细胞炎性蛋白3α、转化生长因子-β、上皮细胞钙黏素、胰岛蛋白、肿瘤坏死凶子相关的凋亡诱导配体等的异常表达可能影响朗格汉斯细胞功能活化.但确切机制有待进一步研究证实.

Abstract：

The infection of human hosts with human papillomavirus (HPV) can lead to a series of changes in the number, morphology, distribution and function of cutaneous Langerhans cells. In particular, the functional impairment of Langerhans cells is considered to be associated with the escape of HPV from host immunity and persitent HPV infection. Studies have suggested that the abnormal expression of some cytokines or proteases, such as prostaglandin E2 and its major rate-limiting enzyme, macrophage inflammatory protein 3 alpha, transforming growth factor-beta, E-cadherin, langerin/CD207, tumor necrosis factor-related apoptosisinducing ligand, may affect the activation and function of Langerhans cells. Further studies are required to explore the exact mechanisms.     

Vaccinations in kidney transplant recipients: Clearing the muddy waters

Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant.Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.     

黑素与新生隐球菌

黑素的产生与多种微生物的毒力相关.新生隐球菌主要通过酚氧化酶(漆酶)合成黑素,黑素主要通过抵抗宿主微生物杀伤机制和影响宿主免疫应答来致病.主要就新生隐球菌黑素的微观结构、生物合成,漆酶的分子调节,黑素与新生隐球菌毒力的关系,黑化对真菌生存的影响及与抗真菌治疗的关系等方面进行概述,以期通过对黑素特征的理解为抗真菌药物的开发和对疾病的治疗策略选择提供帮助.

Abstract：

The production of melanin is associated with the virulence of various microorganisms.Cryptococcus neoformans produces melanin mainly via phenoloxidase(laccase)pathway.Melanin contributes to virulence likely by reducing the susceptibility of melanized fungi to host defense mechanisms and affecting immune responses in infected hosts.This review mainly focuses on the microstructure and biosynthesis of Cryptococcus neoformans melanin, molecular regulation of laecase, relationship between melanin and Cryptococcus neoformans virulence, effects of melanization on the survival of fungi, relationship between melanization and antifungal treatment, ete, which may facilitate the design and development of antifungal agents and strategies.     

Malignant melanoma in the pediatric population

Controversial pigmented lesions in children are a problem for pathologist, clinicians and families that are confronted with this dilemma. Some skin lesions in this population defy diagnosis with pathologists split between a benign diagnosis and a cancer diagnosis. Three cases of controversial pigmented lesions in the pediatric population are presented. Three patients underwent radical resection of the controversial pigmented lesion, intra-operative lymphatic mapping and sentinel lymph node(SLN) biopsy. Due to the low morbidity of the SLN procedure a case is made to perform lymphatic mapping in this clinical scenario. If the SLNs are negative, not much is lost except for the scar and this becomes another line of evidence that perhaps the original lesion was benign. If the SLN shows metastatic cells, then the original skin lesion must be malignant and the patient is offered stage Ⅲ recommendations that would include complete node dissections and adjuvant Interferon therapy. This strategy provides for adequate treatment of the worse-case scenario, that the skin lesion is malignant. The cost to the patient is a low morbidity procedure, the SLN biopsy.     

Role of β2-microglobulin in uremic patients may be greater than originally suspected

The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.