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.

Endoscopic submucosal tunnel dissection for largesuperficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection(ESD)is a wellestablished treatment for superficial esophageal squamous cell neoplasms(SESCNs)with no risk of lymphatic metastasis.However,for large SESCNs,especially when exceeding two-thirds of the esophageal circumference,conventional ESD is time-consuming and has an increased risk of adverse events.Based on the submucosal tunnel conception,endoscopic submucosal tunnel dissection(ESTD)was first introduced by us to remove large SESCNs,with excellent results.Studies from different centers also reported favorable results.Compared with conventional ESD,ESTD has a more rapid dissection speed and R0 resection rate.Currently in China,ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique,as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria.However,not all patients with SESCNs are candidates for ESTD,and postoperative esophageal strictures should also be taken into consideration,especially for lesions with a circumference greater than three-quarters.In this article,we describe our experience,review the literature of ESTD,and provide detailed information on indications,standard procedures,outcomes,and complications of ESTD.

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.

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,

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients

Introduction: Plasma cell neoplasms are monoclonal proliferations characterized by the secretion of an immunoglobulin product known as component "M" or monoclonal. The World Health Organization (WHO 2008) defines as plasma cell neoplasms the following: plasma cell myeloma, plasmacytoma and those syndromes defined by immunoglobulin deposits and primary amyloidosis, The objective of the present work was to correlate their clinical, morphological and phenotype characteristics in 21 patients. Material and Methods: A 2-year retrospective review was performed of the files of the surgical pathology laboratory and of the hematology service of the General Hospital of Mexico, searching for patients with a diagnosis of plasma cell neoplasm. We analyzed the following variables: age, gender, clinical symptoms, evolution, localization, laboratory tests, morphology, and expression of immunohistochemical markers. Of the 21 patients, 12 (57.1%) corresponded to plasma cell myelomas and 9 (42.8%) were plasmacytomas (seven extraosseous and two solitary bone plasmacytoma);women predominated with 61.4% and age ranged between 22 and 84 years. Mass and epistaxis were observed in the patients with plasmacytomas, and symptoms of medullary compression and anemia were observed in those patients with plasma cell myeloma. The time of symptomatology varied from 3 to 12 months. Laboratory tests revealed that lactate dehydrogenase (LDH), beta 2 microglobulin, C-reactive protein were altered and that hypercalcemia and anemia were present more in the systemic form of the disease. Treatment depended on the clinical staging and laboratory data. Mature forms predominated morphologically. Immunohistochemical stain revealed a constant expression for CD 138, six patients expressed CD 56, and expression of the Kappa and Lambda light chains was while.

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.

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms

AIM: To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS: Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The enblock resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION: Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

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.

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.

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

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”.

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.

A Rare Case of a Large Basal Cell Carcinoma of the Vulva

We present an interesting and unusual case of a 5 cm well-demarcated erosive plaque on the labia minora, extending to the vagina in an 85-year-old woman, causing pain and discomfort for 2 years. The patient was treated several times with topical and systemic anti-fungals without benefit. Histopathology revealed a typical superficial spreading basal cell carcinoma (BCC) and the patient was referred to a gynecologist for surgical excision. Our case is an alert of BCCs arising on the genital area because they are rare and patients usually present with large lesions, as they do not seek medical attention for what they consider simple irritation. Physicians easily misdiagnose these cancers as inflammatory or infectious dermatoses.

Peroxidative Activity in Patients with Skin Basal Cell Carcinoma

Oxidative status assessment is an initial step in tumor related studies. To the best of our knowledge, this is the first study considering oxidative activity of both serum and tissue specimens in human basal cell carcinoma (BCC), which is the most common tumor in the world. Concentration of Malondialdehide (MDA) in human basal cell carcinoma (BCC) and individually matched normal skin tissue were examined with spectrophotometery method. Fresh normal and cancerous skin paired tissue was obtained from 60 patients who underwent curative BCC resection at one center in Tehran (Razi hospital). Serum Concentration of Malondialdehide (MDA) in these patients and 55 normal subjects were also measured. MDA level in cancerous tissue of patients with skin BCC (1.0 ± 0.14 ng/g) was significantly (p = 0.001) higher than normal neighboring skin tissue (0.3 ± 0.07 ng/g). A remarkable (Not significant, P = 0.18) increase was found in the serum MDA level in patients with skin BCC (8.0 ± 2.3 ng/ml) in comparison with the control subjects (7.3 ± 2.9 ng/ml). A significant positive correlation (r = 0.276, p = 0.03) was found between Serum MDA and skin tissue MDA for non-affected skin tissue (normal neighboring skin), whereas no significant correlation (p > 0.05) was found for cancerous tissue. Cut-point of 5.2 ng/ml of serum MDA concentration showed a screening sensitivity of 95%. There is an active oxidative process in BCC lesions. Serum MDA concentration can be used either as a screening test or a predictor for tissue MDA concentration.

Vismodegib Provides a Novel Treatment for Advanced Basal Cell Carcinoma

Objective: To review and evaluate vismodegib, the first US Food and Drug Administration (FDA) approved treatment for locally advanced (laBCC) or metastatic basal cell carcinoma (mBCC) that has recurred after surgery or for patients in which surgery or radiation is not an option. Data Sources: A literature search using PubMed was conducted through January 2013, using the terms vismodegib, GDC-0449, and Erivedge. Additional literature was found through the reference citations of identified articles. Study Selection and Data Extraction: Potential sources were limited to human studies published in English with a priority placed on those focused on laBCC or mBCC. Data Synthesis: Vismodegib is a selective inhibitor of the hedgehog (Hh) pathway approved for the treatment of laBCC or mBCC that has recurred after surgery, or for patients for whom surgery or radiation is contraindicated. Vismodegib inhibits cancer cell growth and survival by binding Smoothened, a transmembrane protein involved in the Hedgehog signal transduction. Vismodegib is administered orally at a dose of 150 mg daily. It is primarily eliminated through the feces unchanged but does have some oxidative metabolites produced from the recombinant cytochrome P450 (CYP) 2C9 and CYP3A4/5. Despite CYP450 involvement, it appears to have very few drug interactions. The most common adverse events reported with vismodegib include muscle spasms, dysgeusia, alopecia, weight loss, fatigue, nausea, anorexia, and diarrhea. FDA approval was based on a single arm phase II study that demonstrated an objective response rate of 30% in mBCC patients and 45% in laBCC patients. Vismodegib was approved by the FDA on January 30, 2012 for use in patients with advanced basal cell carcinoma, and continues to be studied in other patient populations for additional potential uses. Conclusions: Based on a review of current evidence, vismodegib provides an effective and well-tolerated treatment for otherwise untreatable basal cell carcinoma.