p53-Regulated Long Noncoding RNA PRECSIT Promotes Progression of Cutaneous Squamous Cell Carcinoma via STAT3 Signaling.

Long noncoding RNAs (lncRNAs) have emerged as putative biomarkers and therapeutic targets in cancer. The role of lncRNA LINC00346 in cutaneous squamous carcinoma (cSCC) was examined. The expression of LINC00346 was up-regulated in cSCC cells compared with normal human epidermal keratinocytes. Elevated expression of LINC00346 was noted in tumor cells in cSCC tissue sections in vivo, as compared with cSCC in situ, and actinic keratosis by RNA in situ hybridization; and the expression in seborrheic keratosis and normal skin was very low. Immunohistochemical analysis of cSCC tissue sections and functional assays of cSCC cells in culture showed that LINC00346 expression is down-regulated by p53. Knockdown of LINC00346 inhibited invasion of cSCC cells in culture and suppressed growth of human cSCC xenografts in vivo. Knockdown of LINC00346 inhibited expression of activated STAT3 and resulted in down-regulation of the expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-10, and MMP-13. Based on these observations LINC00346 was named p53 regulated carcinoma-associated STAT3-activating long intergenic non-protein coding transcript (PRECSIT). These results identify PRECSIT as a new p53-regulated lncRNA, which promotes progression of cSCC via STAT3 signaling.

Techniques to Relieve Pain Associated With Botulinum Injections for Palmar and Plantar Hyperhidrosis.

BACKGROUND: Palmar and plantar hyperhidrosis (HH) is a common condition characterized by excessive sweating of the palms and soles. Botulinum neurotoxin (BTX) is a very effective and safe treatment. However, the associated intense injection pain is a major limiting factor deterring patients from selecting this treatment. OBJECTIVE: The aim of this study was to review the numerous techniques used to minimize pain accompanying injections for palmoplantar HH. Additionally, the advantages and limitations of each modality will be discussed. MATERIALS AND METHODS: The authors performed a comprehensive literature search in PubMed/MEDLINE, Embase, Cochrane Central, and Google Scholar on randomized controlled trials, cohort studies, and case series on techniques to relieve pain of BTX injections for treatment of palmar and plantar HH. RESULTS: Current available techniques in reducing botulinum injection with merits and drawbacks are nerve blocks, Bier blocks, cryoanalgesia, needle-free anesthesia, topical anesthetics, and vibration anesthesia. CONCLUSION: Topical anesthesia, ice, and vibration are the safest and most convenient noninvasive available methods to relieve pain associated with botulinum injection. Nerve blocks, Bier block, and needle-free anesthesia provide better anesthesia but are limited by the need for training and equipment.

Management of Primary Focal Hyperhidrosis: An Algorithmic Approach.

Hyperhidrosis (HH) is defined as perspiration beyond the level required to maintain temperature regulation. HH affects nearly 4.8% of the population in the United States. It can have a great impact on patient’s quality of life by disturbing daily activity, performance, confidence, social interactions, and mental health. In the majority of patients with HH (93%), the etiology of excess sweating is idiopathic, which classifies it as primary focal HH. Mild HH may be controlled with topical antiperspirants and lifestyle modifications. Based on the location of involvement, iontophoresis and botulinum toxin may be considered if the patient does not respond to topical therapies. Despite minimizing sweating, chronic use of systemic anticholinergics, in particular oxybutynin, may result in detrimental adverse effects such as dementia. Local surgery, radiofrequency, microwave, and lasers are other potential modalities for HH. Sympathectomy can be a last resort for the treatment of focal HH of the palmar, plantar, axillary, and craniofacial areas after failure of less invasive therapeutic options. In this review, we conducted a comprehensive search in the PubMed electronic database to summarize an algorithmic approach for the treatment of HH. This can help broaden options for managing this difficult disease. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5774.

Transient hypertriglyceridaemia associated with propranolol for treatment of infantile hemangioma.

We present a case of a one-month-old female patient with severe hypertriglyceridaemia as a side effect of treating an ulcerating infantile hemangioma with systemic propranolol. The remarkedly rapid increase in triglyceride returned to normal 96 hours after the discontinuation of the medication, and further follow-up revealed normalisation of the lipid profile. Further research is necessary to unveil the association of systemic propranolol with hypertriglyceridaemia.

The Pinch Stitch: A Pearl for Suturing Wounds Under Tension.

Closing defects under tension in areas such as the scalp and back may be challenging during dermatologic surgery. Different techniques have been advocated to ease the placement of the first deep suture under tension, including the slip-knot stitch, pully stitch, horizontal mattress suture, pulley set-back dermal suture, and tandem pulley stitch.

Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of complement component C3 and complement factor B (CFB) in the growth of cSCC. Analysis of cSCC cell lines (n = 8) and normal human epidermal keratinocytes (n = 11) with real-time quantitative PCR and Western blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell-specific labeling for C3 and CFB in invasive cSCCs (n = 71) and recessive dystrophic epidermolysis bullosa-associated cSCCs (n = 11) than in cSCC in situ (n = 69), actinic keratoses (n = 63), and normal skin (n = 5). Significant up-regulation of C3 and CFB mRNA expression was noted in chemically induced mouse cSCCs, compared to benign papillomas. Knockdown of C3 and CFB expression inhibited migration and proliferation of cSCC cells and resulted in potent inhibition of extracellular signal-regulated kinase 1/2 activation. Knockdown of C3 and CFB markedly inhibited growth of human cSCC xenograft tumors in vivo. These results provide evidence for the roles of C3 and CFB in the development of cSCC and identify them as biomarkers and potential therapeutic targets in this metastatic skin cancer.

Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ.

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, and the prognosis of patients with metastatic disease is poor. There is an emerging need to identify molecular markers for predicting aggressive behaviour of cSCC. Here, we have examined the role of tight junction (TJ) components in the progression of cSCC. The expression pattern of mRNAs for TJ components was determined with RNA sequencing and oligonucleotide array-based expression analysis from cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK, n=5). The expression of CLDN11 was specifically elevated in primary cSCC cell lines (n=5), but low or absent in metastatic cSCC cell lines (n=3) and NHEKs. Claudin-11 was detected in cell-cell contacts of primary cSCC cells in culture by indirect immunofluorescence analysis. Analysis of a large panel of tissue samples from sporadic UV-induced cSCC (n=65), cSCC in situ (n=56), actinic keratoses (n=31), seborrhoeic keratoses (n=7) and normal skin (n=16) by immunohistochemistry showed specific staining for claudin-11 in intercellular junctions of keratinizing tumor cells in well and moderately differentiated cSCCs, whereas no staining for claudin-11 was detected in poorly differentiated tumors. The expression of claudin-11 in cSCC cells was dependent on the activity of p38δ MAPK and knock-down of claudin-11 enhanced cSCC cell invasion. These findings provide evidence for the role of claudin-11 in regulation of cSCC invasion and suggest loss of claudin-11 expression in tumor cells as a biomarker for advanced stage of cSCC.

New perspectives on role of tumor microenvironment in progression of cutaneous squamous cell carcinoma.

Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing worldwide. Solar UV radiation is an important risk factor for cSCC and leads to genetic and epigenetic changes both in epidermal keratinocytes and dermal cells. Tumor cells in cutaneous cSCCs typically harbor several driver gene mutations, but epidermal keratinocytes in sun-exposed normal skin also contain mutations in these same genes. Therefore, alterations in the microenvironment of premalignant lesions are evidently required for their progression to invasive and metastatic cSCC. For example, alterations in the composition of basement membrane and dermal extracellular matrix are early events in cSCC progression. The presence of microbial structures and the influx of inflammatory cells promote the secretion of proteases, which in turn regulate the availability of growth factors, cytokines, and chemokines and thus influence the growth and invasion of cSCC. Together, these observations emphasize the role of the tumor microenvironment in the progression of cSCC and identify it as a novel therapeutic target in cSCC and other malignant tumors. Graphical abstract Tumor-stroma interactions in the progression of cutaneous squamous cell carcinoma (cSCC). Epidermal layer is separated by a well-organized basement membrane (BM) from the dermal layer. UV radiation, other environmental insults, and aging target both epidermal keratinocytes and dermal fibroblasts and lead to genetic and epigenetic changes in these cells. In addition, epidermal keratinocytes in normal sun-exposed skin harbor several mutations in the cSCC driver genes. During transition to premalignant actinic keratosis (AK), the differentiation of keratinocytes is disturbed resulting in a neoplastic epithelium with hyperplastic cells. Expression of proteinases, such as matrix metalloproteinases (MMP) by neoplastic cells and activated stromal fibroblasts and macrophages is induced in AK, and collagen XV and XVIII are lost from the dermal BM. Furthermore, inflammatory cells accumulate at the site of the hyperplastic epithelium. During a later stage of cSCC progression, the number of inflammatory cells increases, and the expression of complement components and inhibitors by tumor cells is induced (CFI complement factor I, CFH complement factor H, FHL-1 Factor H-like protein 1). In addition to MMPs, activated fibroblasts also produce growth factors and promote inflammation, growth, and invasion of tumor cells.

Paring of Skin for Superficially Lodged Foreign Body Removal.

Small foreign bodies superficially embedded in the acral skin can be difficult to remove. Typical treatment includes using forceps and pressure to attempt removal, which is painful and not always successful. Here we present a patient with a prolonged presentation of a superficially embedded foreign body on his finger. The method for extracting the foreign body was successful and painless through the paring of the skin to gently remove the object. This method decreases pain and swelling, making it a more efficient way of extracting small foreign bodies that are lodged in the superficial skin layer. This case report focuses on more efficient and painless removal of superficially lodged foreign body removal in the clinical office setting.