The expression levels of miR-365 vary in different malignancies. Herein, we found that miR-365 was overexpressed in both cells and clinical specimens of cutaneous squamous cell carcinoma (SCC). We demonstrated that the HaCaTpre-miR-365-2 cell line, which overexpressed miR-365, could induce subcutaneous tumors in vivo. Antagomir-365, an anti-miR-365 oligonucleotide, inhibited cutaneous tumor formation in vivo, along with G1 phase arrest and apoptosis of cancer cells. These findings suggest that miR-365 may act as an onco-miR in cutaneous SCC both in vitro and in vivo. The present study provides valuable insight into the role of miR-365 in cutaneous SCC formation, which can help develop new drug and miR-365 target-based therapies for cutaneous SCC.
Background
Biomarkers based on detecting prostate cancer-specific transcripts are associated with inferior outcomes, but their validation in a clinical context is lacking.
Objective
To determine whether detecting prostate cancer enhanced transcripts in whole blood using an analytically valid assay has prognostic significance relative to circulating tumor cell (CTC) enumeration.
Design, Setting, and Participants
The predictive value for overall survival of the detection in whole blood by reverse transcription real-time polymerase chain reaction (RT-PCR) of KLK3, KLK2, HOXB13, GRHL2, and FOXA1 was studied in 97 men with metastatic castration-resistant prostate cancer (mCRPC).
Intervention
2.5ml of blood was collected in PAXgene tubes for total RNA extraction and 7.5 ml for CTC enumeration from patients with progressive mCRPC.
Outcome Measurements and Statistical Analysis
Prostate cancer enriched genes were detected using a sensitive RT-PCR assay in whole blood from patients with mCRPC. Analytical validity of the assay was established in a clinical laboratory environment. The frequency of detecting transcripts was compared to CTC enumeration using CellSearch® in an independent data set and survival associations were explored by concordance probability estimate (CPE).
Results and Limitations
Two or more genes were detected by PCR in 53% (51 of 97, 95% CI 43–63%) of patients, and unfavorable CTC counts (≥5cells) were seen in 46% (45 of 97, 95% CI 36–56%). Importantly, transcripts were detectable in 11 of 52 patients with favorable CTC counts (21%, 95% CI 8–35%). Transcript detection predicted overall survival in a proportional hazards model. Significantly, the predictive accuracy of RT-PCR detection in combination with CTC enumeration had a CPE of 0.752 (SE=0.038), although limited by the number of patients.
Conclusions
This validated RT-PCR assay detecting prostate-specific RNA in whole blood is prognostic for survival, and may assess patient risk complimentary with CellSearch CTC enumeration. Its clinical utility is being prospectively explored.
Cathepsins are involved in regulatory mechanisms in human skin, but their role in photoaged skin remains unknown. This study investigates the role of cathepsin B, D, K, and G in skin photoaging in vivo and in vitro. Cathepsin-induced changes in skin as a result of chronic UV irradiation were detected by immunohistochemistry methods. Protein cathepsin expressions in UVA-induced premature senescence in fibroblasts in vitro were detected by Western blot technique. Cathepsin mRNA expression in photoaged skin and fibroblasts was detected by real-time reverse transcription-polymerase chain reaction. Immunohistochemistry and Western blot show lower protein expression of cathepsin B, D, and K in photoaged skin and fibroblasts, while cathepsin G was higher. The mRNA expression of cathepsin B, D, and K of the photoaged skin in vivo decreased to 20 ± 0.5, 25 ± 1.6 and 22 ± 0.8%, while cathepsin G mRNA increased to 2.24 ± 0.09 times that of control. In photoaged fibroblasts, cathepsin B, D, and K mRNA was downregulated to 64 ± 2.9, 24 ± 2.1 and 9 ± 0.5% while cathepsin G mRNA was upregulated to 1.42 ± 0.06 times that of control fibroblasts. These experiments suggest that cathepsin B, D, K, and G may act as biomarkers in photoaged human skin.
Facial skin physiology showed seasonal variations in China. The reasons for the changes may refer to seasonal changes in temperature, humidity, and UV radiation.
Sunscreen protection is not related in one uniform way to the amount of product applied to human skin. Consumers may achieve an even lower than expected sunburn protection from high SPF products than from low SPF sunscreens.
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