Antitumor Effect of Sclerostin against Osteosarcoma

Various risk factors and causative genes of osteosarcoma have been reported in the literature; however, its etiology remains largely unknown. Bone formation is a shared phenomenon in all types of osteosarcomas, and sclerostin is an extracellular soluble factor secreted by osteocytes that prevents bone formation by inhibiting the Wnt signaling pathway. We aimed to investigate the antitumor effect of sclerostin against osteosarcoma. Osteosarcoma model mice were prepared by transplantation into the dorsal region of C3H/He and BALB/c-nu/nu mice using osteosarcoma cell lines LM8 (murine) and 143B (human), respectively. Cell proliferations were evaluated by using alamarBlue and scratch assays. The migratory ability of the cells was evaluated using a migration assay. Sclerostin was injected intraperitoneally for 7 days to examine the suppression of tumor size and extension of survival. The administration of sclerostin to osteosarcoma cells significantly inhibited the growth and migratory ability of osteosarcoma cells. Kaplan–Meier curves and survival data demonstrated that sclerostin significantly inhibited tumor growth and improved survival. Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. Osteosarcoma model mice inhibited tumor growth and prolonged survival periods by the administration of sclerostin. The effect of existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.ArticleCancers 13(23) : 6015(2021)journal articl

Quantitative Analysis of Viral Load per Haploid Genome Revealed the Different Biological Features of Merkel Cell Polyomavirus Infection in Skin Tumor

Merkel cell polyomavirus (MCPyV) has recently been identified in Merkel cell carcinoma (MCC), an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR) and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9) and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen’s disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]). In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%), BCC (1 case; 2%), and AK (3 cases; 6%). We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119–42.8) and AK (0.02–0.07) groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662). Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4) demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC), but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection

Domino C–F Bond Activation of the CF₃ Group: Synthesis of Fluorinated Dibenzo[<i>a</i>,<i>c</i>][7]annulenes from 2‑(Trifluoromethyl)-1-alkenes and 2,2′-Diceriobiaryls

The construction of ring-fluorinated seven-membered carbocycles was readily achieved via the domino S_N2′-type/S_NV reaction between 2-(trifluoromethyl)-1-alkenes and 1,4-carbodianions. The S_N2′-type reaction of 2-(trifluoromethyl)-1-alkenes with 2,2′-diceriobiaryls generated the intermediary 1,1-difluoro-1-alkenes bearing a monoceriobiaryl moiety, which in turn underwent intramolecular S_NV reaction to afford fluorinated 5<i>H</i>-dibenzo­[<i>a</i>,<i>c</i>]­[7]­annulenes

Domino C–F Bond Activation of the CF₃ Group: Synthesis of Fluorinated Dibenzo[<i>a</i>,<i>c</i>][7]annulenes from 2‑(Trifluoromethyl)-1-alkenes and 2,2′-Diceriobiaryls

The construction of ring-fluorinated seven-membered carbocycles was readily achieved via the domino S_N2′-type/S_NV reaction between 2-(trifluoromethyl)-1-alkenes and 1,4-carbodianions. The S_N2′-type reaction of 2-(trifluoromethyl)-1-alkenes with 2,2′-diceriobiaryls generated the intermediary 1,1-difluoro-1-alkenes bearing a monoceriobiaryl moiety, which in turn underwent intramolecular S_NV reaction to afford fluorinated 5<i>H</i>-dibenzo­[<i>a</i>,<i>c</i>]­[7]­annulenes

Polymerase chain reaction (PCR) amplification of the Merkel cell polyomavirus in the skin tumors.

<p>Six MCPyV gene fragments were detected in Merkel cell carcinoma, basal cell carcinoma (BCC), and actinic keratosis (AK). Cases involving synchronous or metachronous metastases are marked with an asterisk. Specific PCR fragments, including large T (LT)2, VP1, and VP2, were not amplified constantly in AK cases 2 and 3 (see text). To clarify, we replaced this part with a picture of successful amplification in another trial. Abbreviations: BCC, basal cell carcinoma; AK, actinic keratosis; 293T, polyomavirus SV40 T antigen-positive 293 cells. The lower panel indicates the single PCR proliferation band of the CDC25 gene.</p