Cux1^(+)proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics

Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.

Facial basal cell carcinoma:A retrospective study of 67 cases

BACKGROUND Basal cell carcinoma(BCC)is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential.It ideally affects sun-exposed skin of older patients with more propensity for the facial region.AIM To evaluate the different clinicopathological characteristics of the facial BCC and the efficacy and safety of diode laser for the treatment of these lesions.METHODS We retrospectively reviewed facial BCC lesions of<1.5 cm in diameter and subjected them to diode laser ablation during the period from September 2016 to August 2021 at Al-Ramadi Teaching Hospital,Ramadi City,Iraq.Data matching the age,gender,duration,site,and clinical and histological types were registered for every subject.The functional and aesthetic outcomes and complications following diode laser ablation for each patient were also recorded.RESULTS Of 67 patients with facial BCC,there was 65.67%from the age group≥60 years and 58.21%males.The mean duration of the lesions was 5.15±1.836 mo.The most involved location was the nose(29.85%).About half of the cases belong to the noduloulcerative type.Solid histological type comprises 40.3%of the cases,while the least was keratotic(13.4%).Moreover,65.2%of the solid cases were from the age group≤60 years and 38.6%of the adenoid type from the age group>60 years(P value=0.007).Excellent aesthetic and functional outcomes were reported in all cases after 6 mo of follow-up.Few complications were reported after diode laser ablation.CONCLUSION Facial BCC was mostly seen in the elderly and men.The mean duration was 5.15 mo.The nose was the commonest involved site.Noduloulcerative lesions were seen in approximately half of the lesions.The age of the patients determined the histological type of the lesion(solid type was mostly seen in the age group≤60 years,while,adenoid in the age group>60 years).Diode laser ablation showed excellent functional and aesthetic outcomes following a 6-mo follow-up.

Pigmented Basal Cell Carcinoma: A Rare Case Report

Basal cell carcinoma is the most common skin cancer mainly caused by prolonged exposure to ultraviolet rays. It is also known as rodent ulcer or basal cell epithelioma. The main mechanism suggested is prolonged exposure to high intensity ultraviolet rays, which causes DNA damage. Pigmented basal cell carcinoma is a rare variety of basal cell carcinoma. Usually, it presents as pigmented nodular mass over the nose or malar region. Other differential diagnoses of this mass, are malignant melanoma and seborrheic keratosis. Treatment of choice is surgical excision with 2 mm of margins.

Globose basal cells for spinal cord regeneration

Spinal cord injury （SCI） is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells are located intra-craniafly in subventricular zone and hippocampus which are highly invasive sourc- es. The olfactory epithelium is a neurogenic tissue where neurogenesis takes place throughout the adult life by a population of stem/progenitor cells. Easily accessible olfactory neuroepithelial stem/progenitor cells are an attractive cell source for transplantation in SCI. Globose basal cells （GBCs） were isolated from rat olfactory epithelium, characterized by flow cytometry and immunohistochemically. These ceils were further studied for neurosphere formation and neuronal induction. T10 laminectomy was done to create drop-weight SCI in rats. On the 9th day following SCI, 5 × 105 cells were transplanted into injured rat spinal cord. The outcome of transplantation was assessed by the Basso, Beattie and Bresnahan （BBB） locomotor rating scale, motor evoked potential and histological observation. GBCs expressed neural stem cell markers nestin, SOX2, NCAM and also mesenchymal stem cell markers （CD29, CD54, CD90, CD73, CD105）. These cells formed neurosphere, a culture characteristics of NSCs and on induction, differentiated cells expressed neuronal markers ~III tubulin, microtubule-associated protein 2, neuronal nuclei, and neurofilament. GBCs transplanted rats exhibited hindlimb motor recovery as confirmed by BBB score and gastrocnemius muscle electromyography amplitude was increased compared to controls. Green fluorescent protein labelled GBCs survived around the injury epicenter and differentiated into βⅢ tubulin-immunoreactive neuron-like cells. GBCs could be an alternative to NSCs from an accessible source for autologous neurotransplantation after SCI without ethical issues.

Establishment of basal cell carcinoma animal model in Chinese tree shrew (Tupaia belangeri chinensis)

Basal cell carcinoma （BCC） is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog （Hh） signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews （Tupaia belangeri chinensis） are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened （Smo） used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lenUviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future

Correlation and Expression of COX-2 and P53 Protein in Basal Cell Carcinoma of Eyelid

The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma （BCC） of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases （aged 28-68 y） at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance （A） and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was sig- nificantly higher than that in paracancerous tissues （P〈0.01）. Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 （r=0.113, P=0.421）. It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.

Curaderm, the Long-Awaited Breakthrough for Basal Cell Carcinoma

Background: Basal cells form a continuous cell layer at the bottom of the epidermis, which is the outermost layer of the skin. Basal cell carcinoma occurs when a mutation occurs in the DNA of a basal cell. The mutation inhibits apoptosis—the programmed cell death mechanism. The cell continues to multiply but does not die, resulting in a change in the skin, such as a growth or sore that will not heal. Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Key words searched for the database of this communication were: Curaderm, BEC 5, cancer, skin cancer, basal cell carcinoma, nonmelanoma skin cancer, solamargine, solasonine and solasodine glycosides. Treatments: Several types of treatments are available to remove or destroy basal cell carcinoma. All currently used treatments are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Development of Curaderm Pharmacotherapy: Curaderm pharmacotherapy discriminates and specifically activates apoptosis at the molecular level in cancer cells but not in normal cells. Accordingly, Curaderm pharmacotherapy for basal cell carcinoma effectively and safely treats virtually all types, sizes and lesion locations. This review describes studies from the inception of Curaderm pharmacotherapy and covers the discovery of the anti-cancer effects, mode of action, preclinical, clinical and field applications with emphasis on efficacy, safety, compliance, tolerance, cost effectiveness and especially cosmetic outcome. In 2018 Curaderm was approved by the European Health Authorities as a Medical Device Class 1 for the indication “Topical Treatment with Keratolytic Action, and Antineoplastic Activity in the Treatment and Healing of Localized Basal Cell Carcinoma of the Skin”.

Basal Cell Carcinoma at Pediatric Age Gorlin-Goltz Syndrome Clinic Experience

The nevoid basal cell carcinoma syndrome is an autosomal dominant inherited disease, associated with PTCH gene mutation. Its presentation is polymorphous, being frequent to appear the clinical triad carcinomas basal cell, odontogenic cysts and skeletal abnormalities. Skin lesions are a very frequent reason for consultation in the paediatric age, being evaluated in most cases in primary care. Sometimes, patients need the intervention of other specialists to deep in a given area. The medical literature shows a fragmented view of the disease, possibly related to the low frequency of appearance of this syndrome, and by the need for intervention of not transversal knowledge specialist, which is why we feel interesting to evaluate the role of specialist who is developing the activity at primary care, with patients who require a multidisciplinary intervention.

Basal cell carcinoma stem cells exhibit osteogenic and chondrogenic differentiation potential

Specific cell subpopulations identified as cancer stem cells(CSCs)can be found in basal cell carcinoma(BCC).Generally,CSCs have a marked trans-differentiation potential that could potentially be used in differentiation therapies.However,there are no studies regarding BCC CSCs multipotency.The aim of the study was to analyze the characteristic of CSCs of BCC with emphasis on their differentiation potential upon specific induction.Specific staining and cell morphology were used for differentiation confirmation,along with the expression analysis of osteogenic(ALP,BSP,Runx2,OCN,BMP2),chondrogenic(COL1 and COL2A1),adipogenic(PPAR-γ)and neurogenic(Nestin and MAP2)markers.BCC CSCs differentiated into osteogenic and chondrogenic lineages,as judged by staining and high expression of specific markers(from 2-to 92-fold higher upon induction).Concomitantly with differentiation,the levels of cancer stem cell markers decreased in the cultures.Adipo-differentiation and neuro-differentiation were unsuccessful.In conclusion,BCC CSCs exhibit the capacity to trans-differentiate,a characteristic that may potentially be useful in the development of new strategies for the treatment of aggressive BCCs.

Recurrent basal cell carcinoma of lower lid invading the orbit and whole hemiface reconstructed by rectus abdominis free flap

Dear Sir, I am Dong Hyun Ji, from the Department of Ophthalmology of St. Vincent’s Hospital, Suwon, Korea. I write to present a very severely recurrent basal cell carcinoma (BCC) in lower lid invading left orbit and whole hemiface,

Expression of PinX1 and hTERT in basal cell carcinoma and their implications

Objective This study aimed to investigate the expression and significance of PIN2/TERF1 interacting, telomerase inhibitor 1(Pin X1) and human telomerase reverse transcriptase(h TERT) in basal cell carcinoma(BCC). Methods Real-time polymerase chain reaction and immunohistochemistry were performed to quantify the m RNA expressions and integrated optical density(IOD), respectively, of Pin X1 and h TERT in BCC specimens(n = 30), as well as in normal skin specimens(n = 15). Results The m RNA expression level and IOD of Pin X1 in the BCC samples were both significantly lower than those in the control specimens(P < 0.05). Conversely, the m RNA expression level and IOD of h TERT in BCC were both significantly higher than that in the control samples(P < 0.05). The correlation between the expression levels of Pin X1 and h TERT showed no statistical significance(P > 0.05). Conclusion Downregulation of Pin X1 and upregulation of h TERT expression may be associated with the activation and maintenance of telomerases in the induction of BCC.

Vulvar Basal Cell Carcinoma of a 40 Years Old Black Woman: About a Case and Literature Review

Vulva Basal Cell Carcinoma (BCC) is a rare tumor. It usually occurs in Caucasians at an advanced age. We present a case of vulvar BCC in an African patient under 40 years old with HIV infection successfully treated surgically. This presentation is exceptional because of age, race, and the immune status of the patient.

Periocular basal cell carcinoma-current treatment concepts

Basal cell carcinoma(BCC)is by far the most common human skin cancer.In Caucasians,BCCs account for around 90%of periocular malignancies.However,periocular BCCs are usually neglected due to their slow and painless growth,unless presenting complaints,e.g.,large size,bleeding,recurrent infections of the tumor,or secondary symptoms resulting from adjacent structures involvement as epiphora,limited eye globe motility as well as globe displacement.Moreover,although the tumor can usually be cured with local excision,local recurrence can occur in up to 20%of eyelid BCC cases.Recurrent BCCs of the eyelid show a poorer overall prognosis than the primary ones.In addition,the management of advanced diseases,such as orbital or intracranial invasion as well as metastatic lesions,is challenging and often involves a multidisciplinary approach.In this paper,we reviewed the recent research progress of pathogenesis,clinical presentation,and therapeutics of periocular BCCs.We introduced the molecular pathogenesis of BCCs[multi-step ultraviolet(UV)-induced carcinogenesis model,genetic predisposition,and epigenetic changes],clinical classification,and tumor-node-metastasis(TNM)clinically stage of eyelid skin BCCs.We also emphasized the treatment of BCCs,i.e.,surgical resection,oculoplastic reconstruction,and alternative therapies(radiation therapy,systemic therapy,topical therapy,and prophylactic therapy).In the end,we proposed that considering the possible iatrogenic damage to the surface of the eye by surgical excision,the treatment of periocular BCCs is recommended to be performed by or in the presence of an oculoplastic surgeon.

Progress in Diagnosis and Treatment of Basal Cell Carcinoma

Basal cell carcinoma is a common skin carcinogenesis that occurs in the epidermis and the basal layer of the skin.in general,basal cell carcinoma grows slowly,rarely metastasizes,but is locally invasive and destructive.The diagnosis is based on clinical manifestations,but the clinicopathological manifestations are different,and sometimes it is difficult to differentiate from pigmented nevus,malignant melanoma,etc.Therefore,skin biopsy is essential for the diagnosis and assessment of the risk of recurrence.There are many ways to treat basal cell carcinoma.This article reviews the diagnosis and treatment.

High-grade dysplasia,restricted to the basal cell layer involving the entire esophagus

This report presents a case involving a unique observation of a high-grade squamous dysplasia involving the entire esophagus.Dysplastic cells were located exclusively in the basal portion of the esophageal squamous epithelium.The findings were documented using histologic analysis of the step-biopsies from the entire esophagus,histologic examination of the esophagectomy-specimen,immunohistochemicalanalysis,and molecular pathologic analysis of the p53 gene.A minimally invasive total esophagectomy was performed at the Department of Surgery of the University of Cologne,and histologic analysis of the resection specimen confirmed extensive high-grade dysplasia involving the oral resection margin,but no invasive carcinoma.This case does not fit the current World Health Organization(WHO) definition of highgrade squamous cell dysplasia,which requires fullthickness involvement of the squamous epithelium.Thus,the WHO criteria should probably be reconsidered in order to allow for a diagnosis of high-grade dysplasia in cases where dysplastic cells are exclusively located in the basal layer of the esophageal squamous epithelium.

The Role of Bcl-2, CD10 and CD34 Expression in Differentiation between Basal Cell Carcinoma and Trichoepithelioma

Background: Basal cell carcinoma (BCC) and trichoepithelioma (TE) have some similarities clinically and histologically. The aim of this work is to evaluate the role of Bcl-2, CD10 and CD34 in differentiation between BCC and TE. Methods: The immunohistochemical expression of Bcl-2, CD10 and CD34 was evaluated in 20 BCCs and 12 TEs in a retrospective study. The localization of these markers in tumor and stromal cells was determined and comparison between BCC and TE was done. Immunohistochemistry for Bcl-2, CD10 and CD34 was performed on sections obtained from formalin-fixed, paraffin-embedded blocks. Bcl-2, CD10 and CD34 immunoreactivity in the stromal and/or tumor cells was determined as follows: negative (0);1+ (10% - 50% positive cells);and 2+ (>50% positive cells). Results: In BCC (20 cases), the expression of Bcl-2 in stromal cells showed (0) immunoreactivity in 8 cases (40%), (1+) immunoreactivity in 7 cases (35%), and (2+) immunoreactivity in 5 cases (25%). Tumoral cells showed diffuse positivity in 20 out of 20 cases (100%), (1+) immunoreactivity in 5 cases (25%) and (2+) immunoreactivity in 15 cases (75%). On the other hand, the expression of Bcl2 in TE, 4 cases showed positive stromal cells out of 12 (33.33%), (1+) immunoreactivity in 2 cases (16.6%) and (2+) immunoreactivity in 2 cases (16.6%), and 8 cases showed no immunoreactivity. Tumoral cells showed positivity in 12 out of 12 cases (100%), (1+) immunoreactivity in 5 cases (41.6%), (2+) immunoreactivity in 7 cases (58.3%). In BCC cases, the expression of CD10 was noted in stromal cells in 8 out of 20 cases (40%), 5 cases showed positivity in stromal and basaloid cells and 3 cases showed positivity in stromal cells only, and 12 cases showed no immunoreactivity (60%). Tumor cells showed positivity in 11 cases out of 20 (55%), (1+) immunoreactivity in 6 cases (30%), (2+) in 5 cases (25%), and 9 cases showed no immunoreactivity (45%). On the other hand, the expression of CD10 in TE 7 cases showed positive stromal cells out of 12 (58.33%), (1+) immunoreactivity in 5 cases (41.6%) and (2+) in 2 cases (16.6%), and 5 cases showed no immunoreactivity (41.66%). Tumor cells showed positivity in 5 cases out of 12 (41.66%), (1+) immunoreactivity in 4 cases (33.33%) and (2+) in 1 case (8.3%), and 7 cases showed no immunoreactivity (58.33%). In BCC cases, the expression of CD34 was noted in stromal cells in14 cases out of 20 cases (70%), (1+) immunoreactivity in 10 cases (50%) and (2+) in 4 cases (20%), and 6 cases showed no immunoreactivity (30%). On the other hand, the expression of CD34 in TE, 10 cases showed positive stromal cells out of 12 (83.33%), (1+) immunoreactivity in 6 cases (50%) and (2+) in 4 cases (33.33%), and 2 cases showed no immunoreactivity (16.6%). Tumor cells showed no immunoreactivity for CD 34 in both BCC and trichoepithelioma, (100%) negative tumor cells. Significant difference of tumor\stromal cells immunoreactivity for Bcl-2 and CD34 in both BCC and TE but it was insignificant for CD10. Conclusion: We conclude that Bcl-2 CD10, CD34 are useful markers in the differential diagnosis of BCC versus TE.

A large basal cell adenoma extending to the ipsilateral skull base and mastoid in the right parotid gland: A case report

BACKGROUND Basal cell adenoma (BCA) is a rare benign tumour that has unique histological characteristics and primarily arises in the parotid glands. According to published reports, nearby tissue destruction by BCA seems impossible. CASE SUMMARY We presented a case of a 54-year-old woman with a mass in the deep lobe of the right parotid gland involving the ipsilateral skull base and mastoid. The patient exhibited gradual right facial swelling but no other obvious symptoms. Combined resection of the total right parotid gland and partial skull base excision were performed. The biopsy conducted before the surgery and sections cut from intraoperatively obtained tissues were not definitive for identifying the character of the neoplasm. A final diagnosis of tubular BCA without malignant elements was established based on postoperative pathology results and immunohistochemical analysis. The tumour did not recur during the 12-mo follow-up period. CONCLUSION A diagnosis of BCA can only be established based on a histopathological examination after an excisional biopsy, and tubular BCA should carefully be considered as a destructive type.

Nevoid basal cell carcinoma: Case report

Nevoid basal cell carcinoma, known as Gorlin Goltz Syndrome, is a rare hereditary condition, characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. In this report, we discuss a case of a patient with Gorlin Goltz Syndrome, who was 16 years old when first admitted for an initial appointment. The patient was diagnosed, treated and followed up for 7 years to present day. This syndrome is associated with a broad spectrum of anomalies and neoplasms as basal cell carcinomas, odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. It affects multiple organ systems, which include skeletal, teeth, jaw, skin, eyes, reproductive organs, and neural system. All the features however, are rarely observed in a single patient. The following paper presents the significance of early diagnosis of Gorlin Goltz Syndrome and the importance of a multidisciplinary approach in providing proper treatment for the patient.

Basal Cell Carcinoma: Experience in a Teaching Hospital, Calabar-South Nigeria

Background: Basal cell carcinoma (BCC) is the commonest malignancy among Caucasians in Europe, North America, and Australia. This study attempted to identify the prevalence, risk factors, and outcome of management of this problem in our region. Methods: All the patients with histologic diagnosis of BCC presenting to the University of Calabar Teaching Hospital, Calabar during the study period January 2000 to December 2009 were evaluated. Results: One hundred and fifty two patients (136 blacks, 16 albinos) were afflicted with skin malignancy, squamous cell carcinoma and BCC totaled 70 [SCC – 62, BCC – 8], and malignant melanoma (MM) – 16. Of the 8 patients, (3 males and 5 females, mean age 43 years, range 21-65 years) observed with BCC lesions, 2 (25%) were darkly pigmented and 6 (75%) were albinos. Most of the albinos who presented 3 decades before the darkly pigmented ranged in age from 21-60 years (mean 35.7 years). The lesions afflicted the head and neck region, 9 (82%), while 2 (18%) were observed on the upper limb. All the patients had excision with satisfactory results during the period of follow up that ranged from 6 months to 3 years (mean 13 months). Conclusion: BCC is an uncommon lesion in our region. Albinism and solar radiation were identified risk factors. Most of the albinos presented 3 decades earlier than the darkly pigmented. Early institution of preventive measures, early diagnosis, and treatment would result in better outcome.

Basal Cell Hyperplasia Observed at Biopsy Specimens after HIFU Therapy: Implication of Stemness for Organ Regeneration

Prostatic basal cell is thought to play a pivotal role in hyperplastic change or carcinogenesis of prostate by their proliferation and stem cell transformation. We investigated stem cell transformation of basal cell hyperplasia observed at biopsy specimens after High Intensity Focused Ultrasound (HIFU) therapy for early stage prostate cancer. Patients and Methods: Basal cell hyperplasia was observed at biopsy specimens in two patients after HIFU therapy. Of these patients, one showed cancer recurrence. Specimens were studied with usual HE, and immunohistochemical studies for prostate specific antigen (PSA), stem cell markers such as CD44, CD117 (c-kit), CD133 and Vimentin. Results: Both basal cell hyperplasia cases indicated PSA (-), CD44 (++), CD117 (-), Vimentin (-) and one specimen showed CD133 (++). Basal cell hyperplasia was presumed to appear during the regeneration process of normal prostate tissue after HIFU therapy, when basal cell proliferated and transformed to acinal cells through epithelial to mesenchymal transition.