scholarly journals The transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets

2021 ◽  
Vol 4 (7) ◽  
pp. e202000651
Author(s):  
Ivan V Litvinov ◽  
Pingxing Xie ◽  
Scott Gunn ◽  
Denis Sasseville ◽  
Philippe Lefrançois
Keyword(s):  
Sonic Hedgehog ◽  
Basal Cell ◽  
Normal Skin ◽  
Sequencing Data ◽  
Human Malignancy ◽  
Basal Cell Carcinomas ◽  
Common Skin ◽  
Systemic Agents ◽  
Transcriptional Landscape ◽  
Common Malignancy

Basal cell carcinoma (BCC) is the most common skin cancer and human malignancy. Although most BCCs are easily managed, some are aggressive locally, require Mohs micrographic surgery, or can even metastasize. In the latter, resistance to Sonic Hedgehog inhibitors may occur. Despite their frequent occurrence in clinical practice, their transcriptional landscape remains poorly understood. By analyzing BCC RNA sequencing data according to clinically important features (all BCCs versus normal skin, high-risk versus low-risk BCCs based solely on histopathological subtypes with aggressive features, advanced versus non-advanced BCCs, and vismodegib-resistant versus vismodegib-sensitive tumors), we have identified novel differentially regulated genes and new targetable pathways implicated in BCC tumorigenesis. Pathways as diverse as IL-17, TLR, Akt/PI3K, cadherins, integrins, PDGF, and Wnt/β-catenin are promising therapeutic avenues for local and systemic agents in managing this common malignancy, including through drug re-purposing of existing medications. We experimentally validated several of these targets as biomarkers in our patient-derived cohort of primary BCC tumors.

Sonic Hedgehog Pathway Blockade After Surgical Debulk of Large Exophytic Basal Cell Carcinomas

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Paul J. Wirth ◽  
Ryan Hobbs ◽  
Elizabeth Billingsley ◽  
Allison T. Vidimos ◽  
Charlene Lam
Keyword(s):  
Sonic Hedgehog ◽  
Basal Cell ◽  
Hedgehog Pathway ◽  
Sonic Hedgehog Pathway ◽  
Basal Cell Carcinomas

Photodynamic therapy and diagnostic measurements of basal cell carcinomas using esterified and non-esterified δ-aminolevulinic acid

2001 ◽  
Vol 05 (02) ◽  
pp. 147-153 ◽  
Author(s):  
MARCELO SOTO THOMPSON ◽  
LOTTA GUSTAFSSON ◽  
SARA PÅLSSON ◽  
NIELS BENDSOE ◽  
MARIA STENBERG ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Basal Cell ◽  
Aminolevulinic Acid ◽  
Normal Skin ◽  
Continuous Light ◽  
Blood Perfusion ◽  
Surrounding Tissue ◽  
Ir Camera ◽  
Fluorescence Measurements ◽  
Basal Cell Carcinomas

Various optical techniques were used to investigate relevant parameters involved in photodynamic therapy (PDT) of human basal cell carcinomas (BCCs). The aim of the study was to compare the diagnostic and therapeutic outcome when using topically applied methyl-esterified δ-aminolevulinic acid (ALA-ME) and δ-aminolevulinic acid (ALA). A total of 35 pathologically verified BCCs in 14 patients were investigated. A diode laser, emitting continuous light at 633 nm, was used to induce PDT. The diagnostic measurements were performed before, during, and after PDT. Laser-induced fluorescence (LIF) was used to monitor the build-up of the ALA/ALA-ME-induced protoporphyrin IX ( PpIX ). The superficial tissue perfusion was measured with laser-Doppler perfusion imaging (LDPI) and the temperature of the lesion and the surrounding tissue was imaged with an IR-camera. A clear demarcation between the lesion and the normal skin was detected with LIF before the treatment for both PpIX precursors. The fluorescence measurements suggest that PpIX builds up to a higher degree and more selectively in the tumour following ALA-ME as compared to ALA. The LDPI measurements indicate a local transient restriction in blood perfusion immediately post-PDT. The measurement with the IR-camera revealed a temperature rise of about 1–2 °C during the treatment.

Basal Cell Carcinoma in a 12-Year-Old Boy

PEDIATRICS ◽  
1990 ◽  
Vol 86 (3) ◽  
pp. 460-463
Author(s):  
Jody Comstock ◽  
Ronald C. Hansen ◽  
Antoinette Korc
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Ultraviolet B ◽  
Basal Cell Carcinomas ◽  
Common Skin ◽  
The Face ◽  
X Irradiation ◽  
Nevus Sebaceus ◽  
White Adults

Basal cell carcinomas are common skin tumors occurring in white adults that are mainly attributable to ultraviolet-B exposure.1 They grow slowly, invade locally, and rarely metastasize.2 Basal cell carcinomas appear most frequently on the head, neck, and upper extremities. The majority occur on the face and the relative risk for recurrent tumor is high in certain sites, especially the nose.3 It is uncommon to see actinically induced basal cell carcinomas in children. There are well documented associations of basal cell carcinomas in children with the nevoid basal cell carcinoma syndrome, xeroderma pigmentosum, nevus sebaceus of Jadassohn, preceding exposure to x-irradiation, or preceding scar from a burn or trauma.4-10

scholarly journals Cutaneous basal cell carcinoma with endobronchial metastasis

2014 ◽  
Vol 96 (7) ◽  
pp. e20-e21 ◽  
Author(s):  
AH Sadr ◽  
S de Kerviler ◽  
N Kang
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Neck Region ◽  
Rare Tumour ◽  
Head And Neck Region ◽  
Basal Cell Carcinomas ◽  
History Of ◽  
Metastatic Basal Cell Carcinoma ◽  
Common Malignancy

Although basal cell carcinoma is a very common malignancy, metastasis from this tumour is extremely rare. For this reason, many plastic surgeons, dermatologists and physicians dealing with skin malignancies consider this as a locally invasive malignancy. We present a rare case of metastatic basal cell carcinoma manifested as a bronchial tumour. This case highlights the fact that despite basal cell carcinoma’s local invasive potential, the possibility of distant metastasis still exists and clinicians should therefore be cautious about interpreting extracutaneous symptoms. Chest physicians should always consider the possibility of this rare tumour in the lungs in patients with a history of large basal cell carcinomas in the head and neck region.

scholarly journals The Sonic Hedgehog-Induced Type 3 Deiodinase Facilitates Tumorigenesis of Basal Cell Carcinoma by Reducing Gli2 Inactivation

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2077-2088 ◽  
Author(s):  
Cristina Luongo ◽  
Raffaele Ambrosio ◽  
Salvatore Salzano ◽  
Andrzej A. Dlugosz ◽  
Caterina Missero ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Basal Cell ◽  
Molecular Mechanisms ◽  
Shh Pathway ◽  
Iodothyronine Deiodinases ◽  
Basal Cell Carcinomas ◽  
Important Regulator ◽  
Direct Target ◽  
Growth Development ◽  
Type 3

Thyroid hormone (TH) is an important regulator of growth, development, and metabolism. Most of the active TH T3 is generated by peripheral TH metabolism mediated by the iodothyronine deiodinases. Type 3 deiodinase (D3) inactivates T3 via specific deiodination reactions. It is an oncofetal protein frequently expressed in neoplastic tissues and is a direct target of the sonic hedgehog (Shh) pathway in basal cell carcinomas (BCCs). However, the molecular mechanisms triggered by T3 in BCC are still mostly unrevealed. Here, we demonstrate that D3 action is critical in the proliferation and survival of BCC cells. D3 depletion or T3 treatment induce apoptosis of BCC cells and attenuate Shh signaling. This is achieved through a direct impairment of Gli2 protein stability by T3. T3 induces protein kinase A, which in turn destabilizes Gli2 protein via its C-terminal degron. Finally, in a mouse model of BCC, T3-topical treatment significantly reduces tumor growth. These results demonstrate the existence of a previously unrecognized cross talk between TH and Gli2 oncogene, providing functional and mechanistic evidence of the involvement of TH metabolism in Shh-induced cancer. TH-mediated Gli2 inactivation would be beneficial for therapeutically purposes, because the inhibition of Shh-Gli2 signaling is an attractive target for several anticancer drugs, currently in clinical trials.

Metastasizing Auricular Basal Cell Carcinoma

1980 ◽  
Vol 88 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Richard C. Bryarly ◽  
Stephen R. Veach ◽  
Alan D. Kornblut
Keyword(s):  
Skin Cancer ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Basal Cell ◽  
Radical Surgery ◽  
Palliative Therapy ◽  
Basal Cell Carcinomas ◽  
Neck Area ◽  
Common Skin

Basal cell carcinoma represents the most common skin cancer and involves the head and neck area in 80% to 85% of all patients treated. Despite their frequent occurrence, metastatic spread from these tumors is rare. This paper presents a case of a patient who had a metastasizing basal cell carcinoma. Despite control of primary disease by radical surgery and adjunctive irradiation, bony metastasis was found within nine months of therapy. Palliative therapy was given, but the patient died five months later. The pathophysiology of the metastasizing basal cell carcinomas is described, and a rationale for therapy presented.

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