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Macrophage Response to Simulated Solar Radiation in the Development of Human Malignant Melanoma. 巨噬细胞对模拟太阳辐射在人类恶性黑色素瘤发展中的反应。
Pub Date : 2021-04-01 DOI: 10.46527/2583-6374.119
Sherman Chu, Tatyana A Petukhova, Jeremy S Bordeaux, Thomas S McCormick, Kevin D Cooper

Background: IFN-γ is widely debated regarding its purported anti- or pro-tumorigenic properties. We initiated a pilot study of primary malignant melanoma patients to investigate whether macrophage-derived IFN-γ is produced in humans as proposed in murine melanomagenesis models.

Methods: Biopsy specimens of fresh-frozen primary melanoma tissue were used to quantify co-localization of IFN-γ, macrophages, lymphocytes, and downstream IFN-γ signatures. Additionally, we analyzed simulated solar radiation (SSR) exposed skin in patients with a history of melanoma versus healthy controls to compare the relative magnitude of macrophage infiltration.

Results: Our data identified a subset of tumor infiltrating CD68+ macrophages that co-localized with IFN-γ (Pearson's Correlation = 0.33 ± 0.11) in patients with primary melanoma (Stage 0-III). Additionally, a population of infiltrating CD3+ lymphocytes strongly co-localized with IFN-γ (Pearson's Correlation = 0.57 ± 0.11). Malignant melanoma cells were double positive for downstream IFN-γ response elements, MIG/CXCL9, and phosphorylated STAT-1 (P-STAT-1). Cellular signaling pathways were also observed when we exposed the skin of melanoma patients to SSR. Despite robust CXCL9 expression in the epidermis of SSR-exposed skin of melanoma patients, we observed decreased macrophage infiltration into melanoma patient skin.

Conclusion: Peritumoral macrophages in melanoma patient skin produce IFN-γ and melanocytes appear to exhibit in vivo responsiveness to IFN-γ, such as P-STAT-1 and upregulated CXCL9 expression. However, despite producing CXCL9 in response to SSR, the normal skin of melanoma patients demonstrates a weak leukocyte infiltration. Immune-modulatory studies for the prevention or treatment of human malignant melanoma may need to address complex tissue and melanocyte signaling and crosstalk.

背景:IFN-γ因其抗或促肿瘤特性而被广泛争论。我们启动了一项针对原发性恶性黑色素瘤患者的初步研究,以调查巨噬细胞来源的IFN-γ是否像小鼠黑色素瘤形成模型中提出的那样在人类中产生。方法:使用新鲜冷冻的原发性黑色素瘤组织活检标本来量化IFN-γ、巨噬细胞、淋巴细胞和下游IFN-γ特征的共定位。此外,我们分析了黑色素瘤病史患者与健康对照者的模拟太阳辐射(SSR)暴露皮肤,以比较巨噬细胞浸润的相对大小。结果:我们的数据发现,在原发性黑色素瘤(0-III期)患者中,肿瘤浸润CD68+巨噬细胞与IFN-γ共定位(Pearson’s Correlation = 0.33±0.11)。此外,浸润的CD3+淋巴细胞群体与IFN-γ强烈共定位(Pearson's Correlation = 0.57±0.11)。恶性黑色素瘤细胞对下游IFN-γ反应元件、MIG/CXCL9和磷酸化STAT-1 (P-STAT-1)呈双阳性。当我们将黑色素瘤患者的皮肤暴露于SSR时,也观察到细胞信号通路。尽管CXCL9在ssr暴露的黑色素瘤患者皮肤表皮中表达强劲,但我们观察到巨噬细胞对黑色素瘤患者皮肤的浸润减少。结论:黑色素瘤患者皮肤的瘤周巨噬细胞产生IFN-γ,黑色素细胞似乎对IFN-γ表现出体内反应,如P-STAT-1和上调的CXCL9表达。然而,尽管在SSR反应下产生CXCL9,黑色素瘤患者的正常皮肤显示出微弱的白细胞浸润。预防或治疗人类恶性黑色素瘤的免疫调节研究可能需要解决复杂组织和黑素细胞信号和串扰。
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引用次数: 0
Basal Cell Carcinoma Developed on an Active Lesion of Mucocutaneous Leishmaniasis: A Case Report from Yemen 基底细胞癌在皮肤粘膜利什曼病的活动性病变上发展:也门一例报告
Pub Date : 2018-07-30 DOI: 10.24983/SCITEMED.ACD.2018.00072
Mohamed A Al-Kamel
The author presents a case of BCC developed on an active lesion of mucocutaneous leishmaniasis as one of many cases of skin cancer frequently seen at the Regional Leishmaniasis Control Center (RLCC) clinics in Yemen.
作者提出了一个病例的BCC发展的活跃病变粘膜皮肤利什曼病作为皮肤癌的许多情况下,经常看到在区域利什曼病控制中心(RLCC)诊所在也门。
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引用次数: 1
Rethinking of Small Molecules in Treating Psoriasis 小分子治疗银屑病的再思考
Pub Date : 2017-11-14 DOI: 10.24983/scitemed.acd.2017.00042
Longgui Wang
The author concerns that long-term application of biologics will destroy the natural balance, and argues to rethink about small molecules that can restore immune homeostasis, thereby naturally correcting overproduced proinflammatory cytokines, as a strategy of new drug development against psoriasis and other autoimmune disorders.
作者担心长期使用生物制剂会破坏自然平衡,并主张重新考虑可以恢复免疫稳态的小分子,从而自然地纠正过度产生的促炎细胞因子,作为治疗牛皮癣和其他自身免疫性疾病的新药开发策略。
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引用次数: 0
Alopecia Areata and Severe Psoriasis Successfully Treated with Apremilast 阿普米司特成功治疗斑秃和严重银屑病
Pub Date : 2017-09-27 DOI: 10.24983/SCITEMED.ACD.2017.00033
S. López, C. D. Castro, Pablo Munguía Calzada, P. Segura
This case report shows the effectiveness of Apremilast in refractory ophiasis AA with a rapid and highly scalp-hair regrowth with a cosmetically important response.
本病例报告显示阿普雷米司特治疗难治性AA型蛇癣的有效性,可快速、高度再生头皮毛发,具有重要的美容效果。
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引用次数: 4
Room Temperature Saline-soaked Gauze Assists in Hemostasis Between Mohs Layers 常温盐水浸纱布有助于莫氏层间止血
Pub Date : 2017-08-23 DOI: 10.24983/SCITEMED.ACD.2017.00027
L. Sutton, I. Orengo
leeding between Mohs layers is distressing to the patient and potentially time-consuming for the physician. Electrosurgery is utilized for hemostasis in most Mohs cases. Obtaining complete hemostasis between Mohs layers can be difficult as anticoagulant use by patients is often encountered. We present a simple and cost-effective method to assist in obtaining hemostasis between Mohs layers. Advantages of this method include quick hemostasis that doesn’t require significant electrodesiccation; therefore, saves time for the physician between Mohs layers, less destruction of tissue that may be critical for the reconstruction, and perhaps decreases exposure to smoke from electrosurgery. We have found the use of gauze soaked with room temperature sterile saline and then applied to the wound bed under a pressure bandage can assist in hemostasis. We use room temperature saline which is most commonly around 20-25°C. We presume the success of this method is due to the saline being cooler than body temperature; therefore, precipitating local vasoconstriction. The saline-weighted gauze might also provide additional pressure. This technique is particularly useful for eyelid lesions where minimizing electrosurgery to improve outcome is critical. Other locations that seem to benefit from this technique are scalp and nose defects. Although we have found success with this method repeatedly, the literature is divergent regarding the temperature of saline to assist in hemostasis. Perhaps contrary to intuition, warm saline opposed to cool or room temperature saline has been associated with reduced bleeding [1]. A recent study in oral surgery compared dressings soaked in room temperature saline compared to saline dressings warmed to 42°C. Significantly reduced bleeding was reported in this split-mouth study with the warmed saline dressings. These findings are aligned with results previously reported in endoscopic sinus surgery and treatment of epistaxis. The use of irrigation with warmed water for epistaxis and minor vessel hemostasis in endoscopic sinus surgery has been reported [2-4]. There is no literature looking at warm soaks on cutaneous versus mucosal surfaces. It has been hypothesized that hypothermia inhibits enzymatic reactions of the coagulation cascade and might impair platelet reactivity [5]. Hypothermia from general anesthesia has been associated with coagulopathy [6]. By increasing the body temperature, this coagulopathy might be nullified and actually reversed. In addition, other mechanisms of action proposed include interstitial edema precipitating compression on blood vessels [7]. Vasodilation of the vessels is also thought to decrease intraluminal pressure that would slow blood flow. Under this theory, the role of vasoconstriction due to hypothermia contributing to hemostasis has yet to be determined and would play a secondary role. The use of cold saline has been supported in various literature. A randomized, control trial during total knee arthro
在莫氏层之间出血对病人来说是痛苦的,对医生来说可能是费时的。大多数莫氏病例采用电手术止血。由于患者经常使用抗凝剂,在莫氏层之间获得完全止血是很困难的。我们提出了一种简单而经济有效的方法来帮助获得莫氏层之间的止血。这种方法的优点包括快速止血,不需要明显的电干燥;因此,节省了医生在莫氏层之间的时间,减少了对重建至关重要的组织的破坏,并且可能减少了电手术产生的烟雾。我们发现使用纱布浸泡室温无菌生理盐水,然后敷在伤口床上压敷绷带可以辅助止血。我们使用室温生理盐水,通常在20-25°C左右。我们认为这种方法的成功是由于盐水比体温低;因此,沉淀局部血管收缩。加了盐的纱布也可能提供额外的压力。这项技术对眼睑病变特别有用,其中最小化电手术以改善结果至关重要。其他受益于这项技术的地方是头皮和鼻子缺陷。虽然我们多次发现这种方法取得了成功,但文献对生理盐水的温度是否有助于止血存在分歧。也许与直觉相反,温盐水相对于冷盐水或室温盐水与出血减少有关[1]。最近的一项口腔外科研究比较了浸泡在室温生理盐水中的敷料和加热到42°C的生理盐水敷料。在这个裂口研究中,温盐水敷料显著减少了出血。这些发现与先前内镜鼻窦手术和鼻出血治疗的结果一致。在鼻窦内窥镜手术中,温水冲洗用于鼻出血和小血管止血已有报道[2-4]。没有文献关注皮肤和粘膜表面的温热浸泡。据推测,低温可抑制凝血级联的酶促反应,并可能损害血小板反应性[5]。全身麻醉后的低温与凝血功能障碍有关[6]。通过提高体温,这种凝血功能可能被消除,甚至被逆转。此外,提出的其他作用机制包括间质水肿对血管的压迫[7]。血管的舒张也被认为可以降低腔内压力,从而减缓血流。根据这一理论,低温引起的血管收缩对止血的作用尚未确定,可能起次要作用。各种文献都支持冷盐水的使用。在全膝关节置换术中,一项随机对照试验比较了常温(21-24℃)下0.5%肾上腺素冷盐水(4℃)与无肾上腺素盐水(无肾上腺素)的冲洗[8]。用冷盐水冲洗的患者术后引流明显减少,血红蛋白下降明显减少[8]。一项涉及接受外部鼻整形的患者的研究是随机的。其中一组患者术中应用冷(2-8℃)盐水浸纱布敷鼻背,术中出血明显少于干纱布压迫组[9]。根据我们的经验,使用无菌盐水浸泡纱布是一种经济有效的方法,以帮助实现莫氏层止血。尽管有证据表明使用温水或生理盐水,但我们的个人经验发现使用室温生理盐水是有益的。进一步的调查可能有助于解释我们的经验和文献中其他人的经验之间的不一致。
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引用次数: 0
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Archives of clinical & experimental dermatology
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