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Aging Jun 2024HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature...
HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.
Topics: Humans; Liver Neoplasms; Ubiquitination; Carcinoma, Hepatocellular; Prognosis; Immunotherapy; Gene Expression Regulation, Neoplastic; Tumor Microenvironment; Male; Female; Biomarkers, Tumor; Transcriptome
PubMed: 38870259
DOI: 10.18632/aging.205926 -
Skin Research and Technology : Official... Jun 2024
Topics: Humans; Venous Insufficiency; Skin Neoplasms; Extracellular Matrix; Carcinoma, Basal Cell; Male; Female; Leg; Chronic Disease; Aged; Middle Aged
PubMed: 38867359
DOI: 10.1111/srt.13805 -
Scientific Reports Jun 2024Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The incidence of cSCC is increasing globally and the prognosis of metastatic disease...
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The incidence of cSCC is increasing globally and the prognosis of metastatic disease is poor. Currently there are no specific targeted therapies for advanced or metastatic cSCC. We have previously shown abundant expression of the complement classical pathway C1 complex components, serine proteases C1r and C1s in tumor cells in invasive cSCCs in vivo, whereas the expression of C1r and C1s was lower in cSCCs in situ, actinic keratoses and in normal skin. We have also shown that knockdown of C1s expression results in decreased viability and growth of cSCC cells by promoting apoptosis both in culture and in vivo. Here, we have studied the effect of specific IgG2a mouse monoclonal antibodies TNT003 and TNT005 targeting human C1s in five primary non-metastatic and three metastatic cSCC cell lines that show intracellular expression of C1s and secretion of C1s into the cell culture media. Treatment of cSCC cells with TNT003 and TNT005 significantly inhibited their growth and viability and promoted apoptosis of cSCC cells. These data indicate that TNT003 and TNT005 inhibit cSCC cell growth in culture and warrant further investigation of C1s targeted inhibition in additional in vitro and in vivo models of cSCC.
Topics: Humans; Carcinoma, Squamous Cell; Skin Neoplasms; Cell Proliferation; Cell Line, Tumor; Apoptosis; Animals; Mice; Antibodies, Monoclonal; Cell Survival
PubMed: 38866870
DOI: 10.1038/s41598-024-64088-3 -
Archives of Iranian Medicine Jun 2024Given the significant occurrence of skin cancer in the Middle East and the existing research gap concerning its incidence and trends, this research aimed to study the...
BACKGROUND
Given the significant occurrence of skin cancer in the Middle East and the existing research gap concerning its incidence and trends, this research aimed to study the epidemiology and trend changes of skin cancer in the Golestan province, Northeastern Iran.
METHODS
The Golestan Population-based Cancer Registry's (GPCR's) data bank was utilized to gather information on confirmed skin cancer cases in the province during 2005-2018. We used Poisson regression analysis for comparing incidence rates between groups. values less than 0.05 were considered statistically significant.
RESULTS
Of 1690 patients (mean age: 62.05±15.83 years), most were male (60.1%) and resided in urban areas (61.5%). The age-standardized rate (ASR) of non-melanoma and melanoma skin cancer was 8.49 and 0.56 per 100000 persons-year, respectively. A notably higher ASR for non-melanoma skin cancer (NMSC) was observed in men (ASR: 10.60; 95% CI: 9.91-11.29) (<0.01) and urban residents (ASR: 10.19; 95% CI: 9.52-10.82) (<0.01). There was no significant difference in the ASR of melanoma skin cancer based on gender (=0.24) and place of residence (=0.48). The incidence trend of melanoma (estimated annual percent change [EAPC]: -3.28; 95% CI: -18.54 to 14.83) and NMSC (EAPC: 0.39; 95% CI: -3.99 to 4.97) did not differ significantly.
CONCLUSION
During the 14-year study period, the ASR of both types of skin cancer exhibited a consistent pattern, except for NMSC, which showed higher rates among men and urban residents. This should be taken into consideration when formulating preventive and control strategies in the study area.
Topics: Humans; Iran; Male; Skin Neoplasms; Incidence; Female; Middle Aged; Aged; Adult; Melanoma; Registries; Aged, 80 and over; Sex Distribution; Age Distribution; Young Adult; Urban Population; Adolescent; Carcinoma, Basal Cell
PubMed: 38855798
DOI: 10.34172/aim.28801 -
Cancer Immunology, Immunotherapy : CII Jun 2024Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is...
Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9-29.4) in STS group and 28.3 months (95% CI: 12.7-28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages.
Topics: Humans; Male; Female; Skin Neoplasms; Antibodies, Monoclonal, Humanized; Carcinoma, Squamous Cell; Aged; Retrospective Studies; Middle Aged; Aged, 80 and over; Treatment Outcome; Antineoplastic Agents, Immunological; Adult; Immune Checkpoint Inhibitors
PubMed: 38850335
DOI: 10.1007/s00262-024-03728-z -
Archives of Dermatological Research Jun 2024Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant tumor of the skin. B7 homolog 4 (B7-H4) and B7-H5 (B7 homolog 5) are associated with a...
Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant tumor of the skin. B7 homolog 4 (B7-H4) and B7-H5 (B7 homolog 5) are associated with a variety of tumors. Investigate the potential role of B7-H4 and B7-H5 in regulating the tumorigenesis and progression of CSCC. B7-H4 and B7-H5 transcriptome data were collected from GEO and TCGA databases and subjected to bioinformatical analysis by protein-protein interaction (PPI) network, functional enrichment analysis, immune analysis, and drug-gene interaction prediction analysis. We characterized the expression of B7-H4 and B7-H5 in carcinoma tissues of CSCC patients by immunohistochemistry. Meanwhile, the clinical correlation of B7-H4 and B7-H5 in CSCC was explored by statistical analysis. B7-H4 and B7-H5 genes were under-expressed in CSCC and correlated with tumor staging. According to GO and KEGG Pathway enrichment analysis, B7-H4, and B7-H5 can regulate the proliferation and activation of T cells, lymphocytes, and monocytes, and the expression of cytokines, such as IL-6 and IL-10, in CSCC. B7-H4 and B7-H5 are also jointly involved in the occurrence and development of CSCC via the JAK-STAT and Notch signaling pathways. We found that B7-H4 and B7-H5 proteins were abnormally highly expressed in CSCC tissue and correlated with tumor size and stage. Our findings offer new insights into the pathogenesis of CSCC and suggest that B7-H4 and B7-H5 are novel tissue biomarkers and promising therapeutic targets for CSCC.
Topics: Aged; Female; Humans; Male; Middle Aged; B7 Antigens; Biomarkers, Tumor; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Immunoglobulins; Neoplasm Staging; Protein Interaction Maps; Signal Transduction; Skin Neoplasms; V-Set Domain-Containing T-Cell Activation Inhibitor 1
PubMed: 38850312
DOI: 10.1007/s00403-024-03095-w -
Archives of Dermatological Research Jun 2024Topical tirbanibulin is a highly effective and well tolerated novel treatment option for actinic keratoses (AKs). This study aimed to characterize the mode of action of...
Topical tirbanibulin is a highly effective and well tolerated novel treatment option for actinic keratoses (AKs). This study aimed to characterize the mode of action of tirbanibulin in keratinocytes (NHEK) and cutaneous squamous cell carcinoma (cSCC) cell lines (A431, SCC-12) in vitro. Tirbanibulin significantly reduced proliferation in a dose-dependent manner in all investigated cell lines, inhibited migration, and induced G2/M-cell cycle arrest only in the cSCC cell lines analyzed, and induced apoptosis solely in A431, which showed the highest sensitivity to tirbanibulin. In general, we detected low basal expression of phosphorylated SRC in all cell lines analyzed, therefore, interference with SRC signaling does not appear to be the driving force regarding the observed effects of tirbanibulin. The most prominent tirbanibulin-mediated effect was on β-tubulin-polymerization, which was especially impaired in A431. Additionally, tirbanibulin induced an increase of the proinflammatory cytokines IL-1α, bFGF and VEGF in A431. In conclusion, tirbanibulin mediated anti-tumor effects predominantly in A431, while healthy keratinocytes and more dedifferentiated SCC-12 were less influenced. These effects of tirbanibulin are most likely mediated via dysregulation of β-tubulin-polymerization and may be supported by proinflammatory aspects.
Topics: Humans; Carcinoma, Squamous Cell; Keratinocytes; Cell Line, Tumor; Tubulin; Skin Neoplasms; Apoptosis; Cell Proliferation; Cell Movement; Antineoplastic Agents; Polymerization; Keratosis, Actinic; Signal Transduction; Acetamides; Morpholines; Pyridines
PubMed: 38847867
DOI: 10.1007/s00403-024-03032-x -
Skin Health and Disease Jun 2024Actinic keratoses (AK) are pre-malignant skin lesions caused by chronic sun exposure. Progression from an AK to intraepidermal carcinoma (IEC) and a cutaneous squamous...
BACKGROUND
Actinic keratoses (AK) are pre-malignant skin lesions caused by chronic sun exposure. Progression from an AK to intraepidermal carcinoma (IEC) and a cutaneous squamous cell carcinoma (SCC) is well known but the rate of transformation to an invasive SCC is highly variable. Since no definitive biomarkers are available, treatment decisions are made ad hoc.
OBJECTIVES
To fully characterise our AK to SCC progression series, we performed microRNA (miRNA) microarray expression profiling of normal and photodamaged skin, as well as AKs, IEC, and invasive SCCs.
METHODS
The study recruited 27 patients who donated fresh biopsies of normal skin, photodamaged skin, AK, IEC, and SCC ( = 67 specimens). All miRbase (v.21) miRNAs were profiled to identify miRNAs related to SCC progression. miRNAs were validated using qRT-PCR and in vitro phenotypic assays.
RESULTS
There were 234 robustly expressed miRNAs across the tissue collection, which resulted in 20 miRNA that were differentially expressed ((cor) ≤ 0.05 and ≥ 10 fold) between normal skin and SCC. Hierarchical clustering all samples illustrated that AKs, IEC, and SCCs were largely indistinguishable, which confirms the premalignant status of an AK. A panel of miRNAs showed significant dysregulation between normal and photodamaged skin and AK. Importantly, we found miR-34a-5p and miR-31-5p had significant differential expression between AKs and IEC and IEC and SCC respectively. Phenotypic assays determined that the miR-31 duplex had opposing effects on SCC cell lines which suggests that dysregulation of this duplex may be related to the dynamic control of progression of transformed keratinocytes.
CONCLUSIONS
This study confirmed the continuum of AK with IEC and SCC highlighting that miRNA expression plays a role in keratinocyte transformation. Development of our putative miRNA biomarker candidates is warranted to aid in clinical management of patients experiencing high AK load to determine the most appropriate treatment.
PubMed: 38846701
DOI: 10.1002/ski2.360 -
Skin Health and Disease Jun 2024A recent article in the BJD postulated that it may be "Time to reconsider skin cancer-related follow-up visits". In our unit, we too have been seeing too many patient's...
A recent article in the BJD postulated that it may be "Time to reconsider skin cancer-related follow-up visits". In our unit, we too have been seeing too many patient's unnecessarily and we put in place measures to reduce the numbers of outpatient appointments thereby diverting the resources saved into professional development.
PubMed: 38846693
DOI: 10.1002/ski2.364 -
European Journal of Case Reports in... 2024Positron emission tomography (PET) has gained widespread acceptance as a valuable diagnostic tool for cancer. It is rare for a PET/CT scan to overlook the presence of...
UNLABELLED
Positron emission tomography (PET) has gained widespread acceptance as a valuable diagnostic tool for cancer. It is rare for a PET/CT scan to overlook the presence of metastatic disease. Sebaceous carcinoma is an uncommon malignant tumour that typically originates in the skin of the eyelid. In this case report, we present a unique case involving a metastatic sebaceous carcinoma that was not initially detected by a PET/CT scan in an 88-year-old female. Therefore, clinicians must maintain a heightened awareness of sebaceous carcinoma and exercise caution when making decisions solely based on PET scan results. It is crucial to recognise this potential limitation of PET scans in sebaceous carcinoma and consider further diagnostic approaches to ensure timely and accurate detection of sebaceous carcinoma.
LEARNING POINTS
PET scans may miss slow-growing tumours such as sebaceous carcinoma.A high index of suspicion for sebaceous carcinoma is crucial, even with negative PET scans. Additional diagnostic approaches might be necessary for accurate detection.Sebaceous carcinoma is a rare but aggressive cancer. Diagnosis can be challenging due to its varied presentations.
PubMed: 38846664
DOI: 10.12890/2024_004491