Tropism of herpes simplex virus type 1 to nonmelanoma skin cancers

Hochberg, Malka; Kunicher, Nikolai; Gilead, Leon; Maly, Alexander; Falk, Haya; Ingber, Arieh; Panet, Amos

doi:10.1111/j.1365-2133.2010.10094.x

Cited by 6 publications

(5 citation statements)

References 54 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protocol can further be extended to measurements of other virally-expressed transgenes including cytrokines. Following infection, tissues can also be embedded in paraffin for further sectioning and staining by immunohistochemical methods, which allows for further refinement of the tissue histology and how it relates to viral infection [10][11][12] .…”

Section: Discussionmentioning

confidence: 99%

<em>Ex Vivo</em> Infection of Live Tissue with Oncolytic Viruses

Diallo

Roy

Abdelbary

et al. 2011

JoVE

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

<em>Ex Vivo</em> Infection of Live Tissue with Oncolytic Viruses

Diallo

Roy

Abdelbary

et al. 2011

JoVE

View full text Add to dashboard Cite

“…81 Likewise, primary cSCC culture conditions, as discussed above, could be adapted to metastatic cSCC ex vivo culture, though existing protocols have very short culture periods that must be extended for meaningful therapeutic screening data. 75,76 HNSCC could also be used for guidance since HNSCC and cSCC demonstrate many genetic similarities, including a predominance of affected tumour suppressor genes, although HNSCC does lack the UV mutational signature characteristic of skin malignancies. 10,83 Regardless of approach, it is critical to consider the physiological and micro-environmental differences that separate a primary cSCC within the skin, the mucosa of a HNSCC tumour, and the lymph nodes of metastatic cSCC.…”

Section: S Hort-term E X Vivo Culture: Que S Ti On S For Me Ta S Tati...mentioning

confidence: 99%

“…Viable culture for up to 4 weeks has been reported for such cultures 81 . Likewise, primary cSCC culture conditions, as discussed above, could be adapted to metastatic cSCC ex vivo culture, though existing protocols have very short culture periods that must be extended for meaningful therapeutic screening data 75,76 . HNSCC could also be used for guidance since HNSCC and cSCC demonstrate many genetic similarities, including a predominance of affected tumour suppressor genes, although HNSCC does lack the UV mutational signature characteristic of skin malignancies 10,83 .…”

Section: Short‐term Ex Vivo Culture: Questions For Metastatic Csccmentioning

confidence: 99%

“…More than a decade ago, 300-500 μm slices of primary cSCC tumours were cultured free-floating in Dulbecco's Modified Eagle Medium (DMEM) supplemented with foetal bovine serum and antibiotics. 75,76 Interestingly, these were not employed for therapeutic screening, but rather for proof-of-concept studies TA B L E 3 Common measures of therapeutic response in short-term ex vivo culture. assessing response to environmental exposures including ultraviolet radiation and Herpes simplex virus type 1.…”

Section: S Hort-term E X Vivo Culture: Que S Ti On S For Me Ta S Tati...mentioning

confidence: 99%

See 1 more Smart Citation

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Conley,

Perry,

Ashford

et al. 2024

Experimental Dermatology

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy worldwide, with most deaths caused by locally advanced and metastatic disease. Treatment of resectable metastases is typically limited to invasive surgery with adjuvant radiotherapy; however, many patients fail to respond and there is minimal data to predict response or propose effective alternatives. Precision medicine could improve this, though genomic biomarkers remain elusive in the high mutational background and genomic complexity of cSCC. A phenotypic approach to precision medicine using patient‐derived ex vivo tumour models is gaining favour for its capacity to directly assess biological responses to therapeutics as a functional, predictive biomarker. However, the use of ex vivo models for guiding therapeutic selection has yet to be employed for metastatic cSCC. This review will therefore evaluate the existing experimental models of metastatic cSCC and discuss how ex vivo methods could overcome the shortcomings of these existing models. Disease‐specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.

show abstract

“…There have been some efforts to translate this methodology to cSCC. However, such efforts were confined to primary cSCC, which can be easily treated via surgical excision [75,76], and require expansion to mcSCC samples to increase their relevance in this challenging to treat disease.…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

PIK Your Poison: The Effects of Combining PI3K and CDK Inhibitors against Metastatic Cutaneous Squamous Cell Carcinoma In Vitro

Perry,

Genenger,

Thind

et al. 2024

Cancers

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (cSCC) is a very common skin malignancy with poor prognosis for patients with locally advanced or metastatic cSCC (mcSCC). PI3K/AKT/mTOR and cell cycle signalling pathways are often dysregulated in mcSCC. A combination drug approach has been theorised to overcome the underwhelming clinical performance of targeted inhibitors as single agents. This study investigates the potential of targeted inhibition of the p110α−subunit of PI3K with PIK-75 or BGT226 (P13Ki), and of CDK1/2/5/9 with dinaciclib (CDKi) as single agents and in combination. The patient−derived mcSCC cell lines, UW-CSCC1 and UW-CSCC2, were used to assess cell viability, migration, cell signalling, cell cycle distribution, and apoptosis. PIK-75, BGT226, and dinaciclib exhibited strong cytotoxic potency as single agents. Notably, the non-malignant HaCaT cell line was unaffected. In 2D cultures, PIK-75 synergistically enhanced the cytotoxic effects of dinaciclib in UW-CSCC2, but not UW-CSCC1. Interestingly, this pattern was reversed in 3D spheroid models. Despite the combination of PIK-75 and dinaciclib resulting in an increase in cell cycle arrest and apoptosis, and reduced cell motility, these differences were largely negligible compared to their single-agent counterpart. The differential responses between the cell lines correlated with driver gene mutation profiles. These findings suggest that personalised medicine approaches targeting PI3K and CDK pathways in combination may yield some benefit for mcSCC, and that more complex 3D models should be considered for drug responsiveness studies in this disease.

show abstract

Tropism of herpes simplex virus type 1 to nonmelanoma skin cancers

Abstract: The results indicated a specific pattern of viral tropism to skin cancer cells that are critical for maintenance of the tumour. This new experimental system should aid in the analysis of new therapeutic modalities, such as oncolytic viruses, for future treatment of these skin tumours.

Cited by 6 publications

References 54 publications

<em>Ex Vivo</em> Infection of Live Tissue with Oncolytic Viruses

<em>Ex Vivo</em> Infection of Live Tissue with Oncolytic Viruses

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

PIK Your Poison: The Effects of Combining PI3K and CDK Inhibitors against Metastatic Cutaneous Squamous Cell Carcinoma In Vitro

Contact Info

Product

Resources

About