Materiały źródłowe

• #1 Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4445438/

  Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. […] The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review. […] The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder that manifests as multiple BCCs, pits of the palms and soles, jaw keratocysts, various other tumors, and developmental abnormalities. […] Subsequently, loss of heterozygosity in the same region was discovered to be important for the pathogenesis of sporadic BCCs. […] Molecular studies revealed the gene to be a human homolog of Drosophila patched. Now called PTCH, the gene encodes a receptor for the Sonic hedgehog (SHH) pathway, a pathway important for patterning and growth during vertebrate development.

• #2 Basal Cell Carcinoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/276624-overview

  Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells (ie, small, round cells found in the lower layer of the epidermis). […] Most of the DNA alterations involved in BCC result from damage caused by exposure to sunlight, but inheritance may be a factor in some cases. […] Although the exact etiology of BCC is unknown, a well-established relationship exists between BCC and the pilosebaceous unit, as tumors are most often discovered on hair-bearing areas. […] Many believe that BCCs arise from pluripotential cells in the basal layer of the epidermis or follicular structures. […] The patched/hedgehog intracellular signaling pathway plays a role in both sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). […] Loss of inhibition of this pathway is associated with human malignancy, including BCC.

• #3

  https://www.nursingcenter.com/journalarticle?Article_ID=5495029&Journal_ID=849729&Issue_ID=5494960

  Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States, with an estimated 4.3 million cases diagnosed each year. […] Although it rarely metastasizes, BCC can cause significant morbidity through local tissue destruction and infiltration into vital underlying organs. […] There are multiple treatment options for BCC, but Mohs micrographic surgery is considered to be the gold standard of therapy. […] For individuals with unresectable or metastatic BCC, new and emerging therapies involving inhibition of the Hedgehog signaling pathway have shown promising results. […] Most genetic mutations associated with BCC involve the Hedgehog (Hh) signaling pathway, which controls for cell growth. The PTCH1 gene is most commonly affected in BCC, followed by sonic hedgehog and smoothened. […] In addition to environmental triggers, several genetic mutations are associated with BCC, although the exact mechanism of carcinogenesis is unclear.

• #4 Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7690754/

  Basal cell carcinoma (BCC) pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. […] Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. […] Aberrant activation of Hedgehog (HH) signaling is the hallmark of BCC pathogenesis. […] The HH pathway is a highly conserved signaling pathway that plays a critical role in embryogenesis, cell differentiation, and cell proliferation. […] Canonical activation of HH pathway occurs through binding of the family of extracellular HH ligands (i.e., sonic hedgehog (SHH), Indian hedgehog (IHH) and desert hedgehog (DHH) in mammals) to the 12-pass transmembrane receptor Patched 1 (PTCH1). […] The outcome of the HH signaling depends on several of cell-specific targets mediating different cellular responses: proliferation and differentiation (Cyclin D1 and D2, E2F1, N-Myc, FOXM1, PDGFR, IGFBP3 and IGFBP6, Hes1, Neogenin), cell survival (BCL-2), self-renewal (Bmi1, Nanog, Sox2), angiogenesis (Vegf, Cyr61), cardiomyogenesis (MEF2C), epithelial-mesenchymal transition (Snail1, Sip1, Elk1, and Msx2), and invasiveness (Osteopontin).

• #5 Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

  https://www.mdpi.com/2227-9059/8/11/449

  Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. […] BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. […] Aberrant activation of Hedgehog (HH) signaling is the hallmark of BCC pathogenesis. […] The HH pathway is a highly conserved signaling pathway that plays a critical role in embryogenesis, cell differentiation, and cell proliferation. […] During embryogenesis, HH signaling orchestrates the morphogenesis of the epidermis and its appendages by signal cross-talk between epithelial and dermal cells.

• #6 Narrative review: mechanism of ultraviolet radiation-induced basal cell carcinoma – Fan – Frontiers of Oral and Maxillofacial Medicine

  https://fomm.amegroups.org/article/view/55995/html

  Aberrant HH signaling activation is a hallmark of basal cell carcinogenesis. […] A recent study indicated that over 85% of BCCs have defects in the HH signaling pathway. […] Basal cell carcinogenesis is associated with the inactivation of the P53 gene. […] About 50% of BCCs have detectable P53 mutations. […] Basal cell carcinogenesis is the result of the interaction of multiple genetic and environmental factors.

• #7 Basal Cell Carcinoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/276624-overview

  When SHH is present, it binds to PTCH, which then releases and activates SMO. […] Mutated forms of PTCH are unable to bind to SMO, simulating the presence of SHH. […] The same pathway may also be activated via mutations in the SMO gene, which also allows unregulated signaling of tumor growth. […] Most BCCs have abnormalities in either PTCH or SMO genes. […] Some authors even consider defects in the hedgehog pathway to be requirements for BCC development. […] Zhang et al reported that ultraviolet (UV)-specific nucleotide changes in PTCH, as well as the tumor suppressor gene TP53, are implicated in the development of early-onset BCC. […] UV-induced mutations in the TP53 tumor suppressor gene, which resides on band 17p13.1, have been found in some cases of BCC. […] A reduction of bcl-2 proteins is observed in the aggressive, infiltrative type of BCC.

• #8 Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7690754/

  Most components of the HH pathway can function as tumor suppressor or proto-oncogenes, as mutations in their genes promote an oncogenic signaling and are associated with a wide variety of tumors, such as those of the brain, breast, gastrointestinal tract, lung, pancreas, prostate, ovary, and skin, including BCC. […] Loss of one functional copy of tumor suppressor PTCH1 in patients with BCNS (or Gorlin syndrome) predisposes them to BCC development. […] Most sporadic BCC (85%-90%) have loss-of-function mutations in PTCH1, which prevent the repression of HH signaling. […] The gain-of-function mutations in the proto-oncogene SMO, which become resistant to inhibition by PTCH1, can contribute to 10%-20% of sporadic BCC development. […] Although HH pathway dysregulation alone drives BCC formation, a complex genetic network of cancer-related genes and different regulatory pathways contribute to BCC development, supporting a heterogeneous genetic origin, and can underlie the pathogenesis of both slow-growing as well as locally invasive BCCs into a rare metastatic disease.

• #9 Molecular alterations in basal cell carcinoma subtypes | Scientific Reports

  https://www.nature.com/articles/s41598-021-92592-3

  A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. […] The aberrant activation of the Hedgehog (Hh) pathway plays a pivotal role in the pathogenesis of BCC. In physiological condition, the Hh signalling is involved in cell type differentiation and proliferation, adult tissue homeostasis and repair with a fundamental mitogenic and morphogenic role. […] PTCH1 inactivating mutations have been identified in 70-90% of BCCs, while 10-20% of BCC lesions harbour activating mutations in the SMO gene. […] We showed a high prevalence of Hh pathway mutations and a high rate of mutations in CSMD1, NOTCH1 and DPP10 genes, and in TERT and DPH3 promoter regions. […] Interestingly, NOTCH1 and PTCH1 mutations were significantly more frequent in superficial than in nodular BCCs, and CSMD1 mutations occurred along with TP53 changes.

• #10 Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4445438/

  As an inhibitory protein, PTCH allows overactivation of the SHH pathway in the setting of inactivating mutations. […] These findings indicate SMO serves as a proto-oncogene. […] Overexpression of GLI proteins transcription factors activated by SMO in mouse models has been shown to induce BCCs. […] Furthermore, continued SHH signaling has been shown to be required for BCC carcinogenesis because mice engineered to conditionally express GLI-2 show BCC regression when GLI-2 expression is inactivated. […] All of these studies support the concept that overactivation of SHH signaling is necessary and perhaps sufficient for the development of BCCs. […] The TP53 gene is the most commonly mutated tumor suppressor in cancer. Point mutations in the TP53 gene are the second most common genetic alteration in BCCs, occurring in at least 50 percent of cases.

• #11 Understanding the Molecular Genetics of Basal Cell Carcinoma

  https://www.mdpi.com/1422-0067/18/11/2485

  Beyond HH signaling, other tumor suppressor genes and proto-oncogenes have been implicated in the pathogenesis of BCC, including the TP53 tumor suppressor gene and members of the RAS proto-oncogene family. […] In a recent study including 293 BCC tumors, the driver pivotal role of PTCH1, TP53, and SMO has been confirmed; however, 85% of BCC also harbored additional driver mutations in other cancer-related genes, such as MYCN, PPP6C, PTPN14, STK19, and LATS1. […] Finally, emerging reports have identified somatic mutations within regulatory sequences as the promoters of the telomerase reverse transcriptase (TERT) gene and of the diphthamide biosynthesis 3 (DPH3) gene. […] Of note, the mutational pattern of genes involved in BCC tumorigenesis is consistent with UV-induced DNA damage, since genes harbor “UV signature” mutations. […] The transformation of the keratinocytes occurs when these mutations affect the function of multiple oncogenes, tumor-suppressor genes and important housekeeping genes, leading to an unregulated cell cycle.

• #12 Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4445438/

  Mutations in the CDKN2A locus and in members of the ras gene family (H-ras, K-ras, and N-ras) also have been identified in a smaller number of sporadic BCCs. […] The identity of the cell of origin for BCC remains controversial because of conflicting evidence. […] A recent study using cell fate tracking showed that X-ray-induced BCCs in PTCH (+/-) mice originate from keratin 15-expressing stem cells of the follicular bulge. […] However, conditional loss of p53 also produced BCCs from basal keratinocytes of the interfollicular epidermis in addition to enhancing development of BCCs from the bulge. […] These data indicate that depending on the circumstances, BCCs may arise from basal keratinocytes of the interfollicular epidermis or of the hair follicle. Further research is needed to clarify what those circumstances are.

• #13 Genetic factors underlying basal cell carcinoma risk: a narrative review – Ju – Frontiers of Oral and Maxillofacial Medicine

  https://fomm.amegroups.org/article/view/57361/html

  A genetic analysis study of 293 BCCs concluded that gene mutations of eighty-five percent cases were related to the HH pathway (PTCH1 73%, or SMO 20%, and SUFU 8 %) and TP53 (61%). […] The up-regulation of N-Myc and Hippo-YAP pathway target genes (MYCN, PTPN14, and LATS1) shows the potential relevance in BCC tumorigenesis and progression.

• #14 Narrative review: mechanism of ultraviolet radiation-induced basal cell carcinoma – Fan – Frontiers of Oral and Maxillofacial Medicine

  https://fomm.amegroups.org/article/view/55995/html

  Basal cell carcinoma (BCC) is the most widespread malignant skin cancer and also the most common cancer in adults. […] Among many risk factors, ultraviolet radiation (UVR) is the essential factor in forming BCC. […] This review summarizes the potential mechanisms underlying BCC development due to UVR. UVB can be directly absorbed by DNA and induce skin cancer through intracellular signaling leading to DNA damage and altered gene expression. […] UVA radiation generates reactive oxygen species (ROS), which causes skin cancer through secondary damage to DNA and usually requires long-term cumulative exposure. […] As a result, mutations in proto-oncogenes and suppressor genes may occur, leading to tumor formation. […] UVR damages DNA, and its repair system alters the immune system and leads to progressive genetic alterations and tumor formation, genetic alterations, and tumor formation.

• #15

  https://www.czytelniamedyczna.pl/3184,basal-cell-carcinoma-current-views-part-i-epidemiology-pathogenesis-clinical-fea.html

  Solar radiation (UV) can be divided into three parts depending on the wavelength: UVA (wavelength of 320-400 nm), UVB (wavelength of 280-320 nm) and UVC (wavelength of 200-280 nm). […] Long-term UVB actions lead to the formation of mutagenic photoproducts that damage DNA chains in skin cells. […] Apart from damage to DNA of skin cells UV radiation also causes mutations in a suppressor gene of the p-53 protein. […] The presence of a mutation in the p-53 gene is found in 60-100% of cases of skin cancer. […] The significance of solar radiation in BCC pathogenesis is emphasised by the fact that this neoplasm is found on the skin areas with the most exposure to sunlight, such as the head and neck (85% of all lesions, including 30% within the nose). […] The pharmacological immunosuppression combined with UVB radiation that additionally reduces the number of Langerhans cells (immune properties) leads to increased immunosuppression in the skin and increases the risk of neoplasm.

• #16 Narrative review: mechanism of ultraviolet radiation-induced basal cell carcinoma – Fan – Frontiers of Oral and Maxillofacial Medicine

  https://fomm.amegroups.org/article/view/55995/html

  This review highlights UVR damages DNA and its repair mechanisms, suppression the immune system, causes progressive gene mutations, and ultimately leads to tumor formation. […] UV-induced skin carcinogenesis is a complex and sequential biological process caused by different wavelengths of UV light. UVB can be absorbed directly by DNA, leading to DNA damage and altered gene expression through intracellular signal transduction, which can induce skin cancer. […] Cells could repair damaged DNA, but DNA repair may go wrong due to genetic or environmental factors. […] Therefore, the mutation of proto-oncogenes and suppressor genes may occur, leading to the formation of tumors. […] UVR-induced immunosuppression plays a crucial role in skin carcinogenesis. […] UVR production such as CPDs has been reported to cause immunosuppression.

• #17 Basal-cell carcinoma – Wikipedia

  https://en.wikipedia.org/wiki/Basal-cell_carcinoma

  Basal-cell carcinoma (BCC), also known as basal-cell cancer, basalioma or rodent ulcer, is the most common type of skin cancer. It is thought to develop from the folliculosebaceousapocrine germinative cells known as trichoblasts. Overexposure to the sun leads to the formation of thymine dimers, a form of DNA damage. There is, therefore, cumulative DNA damage leading to mutations. Studies of the role of DNA repair in susceptibility to sunlight-induced basal cell carcinoma indicated that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population. In a small proportion of cases, basal-cell carcinoma also develops as a result of basal-cell nevus syndrome, or Gorlin Syndrome, which is also characterized by keratocystic odontogenic tumors of the jaw, palmar or plantar pits, calcification of the falx cerebri and rib abnormalities. The cause of this syndrome is a mutation in the PTCH1 tumor suppressor gene located in chromosome 9q22.3, which inhibits the hedgehog signaling pathway. A mutation in the SMO gene, which is also on the hedgehog pathway, also causes basal-cell carcinoma. […] Basal-cell carcinoma is named after the basal cells that populate the lowest layer of the epidermis due to the histological appearance of the cancer cells under the microscope. Nevertheless, not all basal-cell carcinomas actually originate within the basal layer.

• #18

  https://scholarsjournal.net/index.php/ijier/article/view/2226

  Basal cell carcinoma is the most common malignant neoplasm in humans, with low mortality, high morbidity, and exposure to solar radiation (UVB and UVA) is the most critical risk factor. […] Ultraviolet B rays generate mutagenic photoproducts in DNA and mutations in important genes regulating cellular functions, such as the tumor suppressor gene TP53. […] Ultraviolet A rays generate cytotoxic and mutagenic free radicals, potentiating the effects of UVB rays. […] There is current evidence to support the role of inflammatory biomarkers related to tumorigenesis of basal cell carcinoma.

• #19 Basal cell carcinoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Basal_cell_carcinoma_pathophysiology

  The majority of mutations in sporadic basal cell carcinoma and basal cell nevus syndrome(BCNS) patients occur in PTCH1 gene, a protein that inhibits smoothened gene (SMO). […] Loss of PTCH1 results in the failure of Smoothened inhibition, subsequently leading to increases in GLI1 levels, changes in transcription, and subsequent tumorigenesis. […] Gain-of-function smoothened(SMO) mutations also leads to increased GLI1 levels and tumorigenesis. […] Cumulative DNA damage caused by chronic sunlight exposure results in DNA mutations that predispose to the development of basal cell carcinoma. […] While DNA repair eliminates most UV-induced damage, not all cross-links are excised, which eventually results in mutations. […] Apart from the mutagenesis, sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells.

• #20 Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

  https://www.mdpi.com/2227-9059/8/11/449

  Loss of one functional copy of tumor suppressor PTCH1 in patients with BCNS (or Gorlin syndrome) predisposes them to BCC development. […] Most sporadic BCC (85%–90%) have loss-of-function mutations in PTCH1, which prevent the repression of HH signaling. […] The gain-of-function mutations in the proto-oncogene SMO, which become resistant to inhibition by PTCH1, can contribute to 10–20% of sporadic BCC development. […] Although HH pathway dysregulation alone drives BCC formation, a complex genetic network of cancer-related genes and different regulatory pathways contribute to BCC development, supporting a heterogeneous genetic origin, and can underlie the pathogenesis of both slow-growing as well as locally invasive BCCs into a rare metastatic disease.

• #21 Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

  https://ouci.dntb.gov.ua/en/works/4r5kn1Y7/

  Activation of Hedgehog (Hh) signaling pathway appears to be a key driver of BCC development. […] Activation of the Wnt pathway is also observed in BCCs. […] Recent studies have identified insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a direct target of the Wnt/β-catenin signaling, as the factor that binds to GLI1 mRNA and upregulates its levels and activities.

• #22 Vascular patterns in basal cell carcinoma: Dermoscopic, confocal and histopathological perspectives (Review)

  https://www.spandidos-publications.com/10.3892/ol.2019.10070

  Basal cell carcinoma (BCC) is the most prevalent skin cancer in the Caucasian population. […] As vascular formation and angiogenesis are indicators of tumor development and progression, the presence of blood vessels, their morphology and architecture are important markers in skin lesions, providing critical information towards pathogenesis and diagnosis. […] Vascular structures play a substantial role in the pathogenesis of malignant skin tumors. Hence, investigation of vascular structures in skin lesions using non-invasive techniques such as dermoscopy and reflectance confocal microscopy (RCM) and evaluation of their morphology and architectural arrangement on histopathological examination could provide valuable clues for the diagnosis and prognosis of BCC. […] Expression of VEGF, the main proangiogenic factor, has been found increased in BCCs when compared to normal skin, although to a lesser degree than in cutaneous SCC.

• #23 Vascular patterns in basal cell carcinoma: Dermoscopic, confocal and histopathological perspectives (Review)

  https://www.spandidos-publications.com/10.3892/ol.2019.10070

  There is sufficient evidence suggesting that angiogenesis is crucial for the metastasis of vascular tumors. […] BCCs ability of local invasion but rarely metastasis may be connected to its microvasculature, suggesting that histopathological and immunohistochemical studies of microvessels counts and angiogenic factors expression could provide a more detailed account of the vascular mechanisms supporting its evolution. […] The angiogenic phenotype sets the boundary line between hyperplasia and neoplasia, and that even though vascular patterns vary significantly in solid tumors, there is a certain relationship between tumor growth and the degree of vascularization. […] The term angiogenic switch refers to the predominance of proangiogenic factors, resulting in formation of new blood vessels.

• #24 Vascular patterns in basal cell carcinoma: Dermoscopic, confocal and histopathological perspectives (Review)

  https://www.spandidos-publications.com/10.3892/ol.2019.10070

  Studies attempting to predict tumor behavior by quantifying MVD face a number of obstacles. […] The absence of a proven correlation between vascular density and depth of invasion in BCCs is consistent with the existing concept of a stromal angiogenic switch that precedes the onset of invasive behavior. […] The forming picture shows that the angiogenic response takes place in the peritumoral stroma, at the edge of these tumors.

• #25 Basal cell carcinoma: biology, morphology and clinical implications | Modern Pathology

  https://www.nature.com/articles/3800512

  Perturbation of the SHH pathway, which is the rule in heredofamilial BCC, appears to be frequently operative in the sporadic BCC as well. Mutations of SMOH or PTCH were detected in 12 of 31 sporadic BCCs in one study; the same group of researchers showed mutations in this pathway in two-thirds of sporadic BCCs in a subsequent study. An additional or alternate pathway of tumorigenesis appears to be at play in the remainder. […] The expression of bcl-2, an inner mitochondrial membrane protein that inhibits apoptosis, has been demonstrated in BCCs of sporadic type. By semiquantitative analysis, preferential overexpression of bcl-2 has been shown in the indolent-growth forms of BCC (ie superficial and nodular BCC). In our proposed scheme, immortalization of progenitor epithelia of the hair follicle and the interfollicular epidermis by bcl-2 predisposes to subsequent mutagenic hits from UV light. In particular, enhanced expression of p53 occurs in the absence of concomitant up regulation of p21 expression, suggesting that mutagenesis of p53 appears preferentially in the aggressive growth vs the indolent growth variants of BCC.

• #26 Basal cell carcinoma: biology, morphology and clinical implications | Modern Pathology

  https://www.nature.com/articles/3800512

  BCCs express p53 protein and do so in a preferential fashion in aggressive growth variants. Mutations of p53 have been documented in up to 40% of studied BCCs; 72% of the mutations bear the signature of UV light induction. The aggressive growth variants of sporadic BCC are associated with stromal fibroplasia and overexpression of what is likely mutant p53. It is this stromal response to tumor which makes the aggressive growth BCC less amenable to local therapy and control. […] The interaction between tumor and stroma, as demonstrated in many neoplastic systems, is critical to lesional pathogenesis. Loss of basement membrane material around individual tumor cell nests occurs with progression from indolent to aggressive growth neoplasms. The working hypothesis is that activation of matrix metalloproteinases in the process of transformation results in the digestion of basal lamina around tumor nests, promoting the elaboration and/or release of proplastic cytokines and their subsequent availability to the rapidly proliferating aggressive growth neoplasms. […] In our hands, the indolent growth variants are found widely distributed on both sun-exposed and sun-protected skin, while the aggressive growth variants such as infiltrative and morpheaform BCC are more frequent in sun-exposed skin.

• #27 Basal cell carcinoma: biology, morphology and clinical implications | Modern Pathology

  https://www.nature.com/articles/3800512

  The nevoid BCC syndrome or Gorlin-Goltz syndrome is inherited as an autosomal dominant trait with a minority of cases representing sporadic mutations. Typically expressed in young adulthood, the syndrome comprises multiple basal cell cancers and other anomalies as described below. It is now recognized that for most patients the abnormality represents a mutation in the human homologue of the PTCH. A tumor suppressor gene, PTCH is sited on chromosome 9 q22q31. The PTCH gene product functions as a transmembrane receptor for the Sonic hedgehog (shh) protein; when binding of the wild-type protein occurs, the inhibition by PTCH of a second seven-span transmembrane protein termed Smoothened (smo) is downregulated. The inhibition of smo is held to be relieved by mutations of PTCH or SMO that eventuate in cell proliferation.

• #28 Basal cell carcinoma: biology, morphology and clinical implications | Modern Pathology

  https://www.nature.com/articles/3800512

  BCC is held to derive from basaloid epithelia located in the follicular bulges, in the anagen hair bulbs and the follicular matrix cells, and in specific basaloid cells of the interfollicular epidermis. The cells of origin are held to be pluripotent progenitor epithelia in adults or epithelial germ cells in the case of those neoplasms arising in childhood (ie linear basal cell nevi). BCCs manifest a keratin profile similar to that of the lower part of the hair follicle and that is therefore distinct from that of the adjacent epidermal basal layer epithelia. In particular, and held to reflect their derivation from basaloid epithelia, BCCs express keratins type 5, 6 and 14 and also alpha 2 and beta 1 integrins in a fashion that does not correlate well to tumor subtype. The expression of CD10 supports derivation from the folliculo-sebaceous unit. Key to our understanding of the pathogenesis of BCC has been the unraveling of the molecular basis of the nevoid BCC syndrome.

• #29 Modern understanding of the pathogenesis of basal cell skin cancer – Saytburkhanov – Vestnik dermatologii i venerologii

  https://journal-vniispk.ru/0042-4609/article/view/117568

  The incidence of basal cell skin cancer is increasing worldwide. The initiation and progression of basal cell skin cancer is due to the interaction of environmental factors and the patient’s genetic characteristics. Aberrant activation of the transmission of the Hedgehog signaling pathway is the main pathogenetic pathway of carcinogenesis. […] Since basal cell skin cancer is manifested by significant variability of morphological structure, aggressiveness and response to treatment, the disclosure of the molecular genetics of pathogenesis will become the basis for developing new approaches and increasing the effectiveness of treatment, as well as overcoming tumor resistance to treatment.

• #30 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Basal-Cell-Carcinoma-Pathophysiology.aspx

  Basal cell carcinoma is highly localized and does not usually spread. However, as this type of cancer can still invade and destroy surrounding tissue, it is considered a malignant form of cancer. […] A rare hereditary disorder called basal-cell nevus syndrome (BCNS) raises the risk of developing basal cell carcinoma. Also known of as Gorlin syndrome, BCNS is associated with mutations of genes located at human chromosome 9q22. A tumor suppressor gene PTCH1 has also been identified. If mutations occur in this gene, cell signalling pathways may fail to prevent cancerous growth of the cell. […] According to researchers, basal cell cancers are also genetically stable which prevents further DNA mutation leading to metastasis.

• #31 What Are Basal and Squamous Cell Skin Cancers? | Types of Skin Cancer | American Cancer Society

  https://www.cancer.org/cancer/types/basal-and-squamous-cell-skin-cancer/about/what-is-basal-and-squamous-cell.html

  Basal cell carcinoma (BCC, also called basal cell skin cancer, or just basal cell cancer) is most common type of skin cancer. About 8 out of 10 skin cancers are basal cell carcinomas. […] These cancers start in the basal cell layer, which is the lower part of the epidermis. […] BCCs usually develop on sun-exposed areas, especially the face, head, neck, and arms. They tend to grow slowly. Its very rare for a basal cell cancer to spread to other parts of the body. But if BCC is left untreated, it can grow into nearby areas and invade the bone or other tissues beneath the skin. […] If not removed completely, BCC can come back (recur) in the same place on the skin. People who have had basal cell skin cancers are also more likely to get new ones in other places.

• #32 Ionizing Radiation Exposure and Basal Cell Carcinoma Pathogenesis

  https://bioone.org/journals/radiation-research/volume-185/issue-3/RR4284.S1/Ionizing-Radiation-Exposure-and-Basal-Cell-Carcinoma-Pathogenesis/10.1667/RR4284.S1.full

  Ionizing Radiation Exposure and Basal Cell Carcinoma Pathogenesis […] BCC, the most common type of human cancer, is driven by the aberrant activation of hedgehog (Hh) signaling. […] Ptch, a tumor suppressor gene of Hh signaling pathway, and Smoothened play a key role in the development of radiation-induced BCCs in animal models. […] Epidemiological studies provide evidence that humans exposed to radiation as observed among the long-term, large scale cohorts of atomic bomb survivors, bone marrow transplant recipients, patients with tinea capitis and radiologic workers enhances risk of BCCs. […] The mechanism underlying these observations remains undefined. Understanding interactions between radiation-induced signaling pathways and those which drive BCC development may be important in unraveling the mechanism associated with this enhanced risk. […] Recent studies showed that Vismodegib, a Smoothened inhibitor, is effective in treating radiation-induced BCCs in humans, suggesting that common strategies are required for the intervention of BCCs development irrespective of their etiology.

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