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.

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.

Comparative Analysis of Ki-67 Protein as a Proliferative Expression Index in Cutaneous Basal and Squamous Cell Carcinoma in Federal Medical Centre Umuahia, Nigeria

Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.

Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate

The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate （TmLRP）. TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 （CK14）, CK5, CK18, synaptophysin （Syn）, chromogranin A （CgA）, uroplakin, transforming growth factor-β1 （TGF-β1）, and TGF-β type Ⅱ receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type Ⅱ receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.

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.

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.

The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment

The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.

Unique Clinical Features of Curaderm when Treating Skin Cancers

Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.

Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)?

Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.

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

THE EXPRESSION OF C－erbB－1 AND C－erbB－2ONCOGENES IN BASAL CELL CARCINOMA ANDSQUAMOUS CELL CARCINOMA OF SKIN

The expression of c-erbB-1 and c-erbB-2 oncogenes were investigated by immunohistochemistry using monoclonal antibodies to c-erbB-2 and c-erbB-2 protein in 43 cases of basal cell carcinoma (BCC) and 26 cases of squamous cell carcinoma (SCC). We found that the expression of c-erbB-1 oncogene in all BCC increased by different degrees and the expression of c-erbB-2 oncogene in BCC was significantly reduced or lost when compared to that in normal epidermal cells. Furthermore, apparent negative and positive rela-tionships were observed respectively between the tumor differentiation and the expression of cerbB-1 and c-erbB-2 oncogenes in SCC. It is suggested that the abnormal expression of c-erbB-1 and c-erbB-2 oncogenes in BCC and SCC may play a role in the development of skin tumors. The pattern of the c-erbB-1 and c-erbB-2 oncogenes expression in SCC may assist in distinguishing the biological behavior and prognosis of SCC.

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.

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.

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.

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.