BackgroundThe tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis.MethodsA retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software.ResultsThe study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870).ConclusionsNF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

Ciplukan (Physalis angulata Linn.) is a Solanaceae family species and contains various active compounds with diverse therapeutic potential. The goal of this investigation was to see if the ethyl acetate fraction of ciplukan had an antifibrotic impact on liver fibrosis. The oral administration of 20% carbon tetrachloride (CCl 4 ) twice weekly for 8 weeks was used to cause liver fibrosis. Four weeks following fibrosis induction, ciplukan ethyl acetate fractions of 1.11 mg (CPL-1) and 2.22 mg (CPL-2) were given orally. As a positive control group, vitamin E was used. When compared to the negative control, the ethyl acetate portion of 2.22 mg (CPL-2) lowered serum alanine aminotransaminase levels (83.95 ± 27.675 vs 175.23 ± 5.641, p-value < 0.05). Microscopic histopathological changes based on the better Metavir score (CPL-2 vs. negative control = 1.25 ± 1.893 vs. 3.50 ± 0.577; p-value < 0.05) and Ishak score (CPL-2 vs. negative control = 1.50 ± 1.000 vs. 4.75 ± 0.957 p-value < 0.05) were demonstrated. Overall, in rat liver fibrosis induced by CCl 4 , these findings suggest that the ethyl acetate fraction of ciplukan has an antifibrotic effect.

Objective: This study aimed to investigate the cytotoxicity, anti-proliferation and anti-migration effect of the ethanol extract of Aaptos suberitoides on trastuzumab-resistant HER2+ breast cancer cell line. Methods: Aaptos suberitoides was collected from Tinjil Island, Banten, Indonesia, and was processed with maceration and ethanol extraction. HCC-1954 cells were treated with the ethanol extract and then followed by 3-[4, 5-dimethylthiazol-2-yl] -2.5 diphenyl tetrazolium bromide (MTT) assay to assess cytotoxicity, clonogenic assay and three-dimensional (3D) spheroid assay to evaluate anti-proliferative effect in two-dimensional and 3D model, respectively, and wound healing assay to determine anti-cell migration effect. Four parametric regression was used to analyse the IC 50 . Results: This study revealed that the ethanol extract of Aaptos suberitoides suppressed cell viability in correlation with cell death induction. The IC 50 values of the ethanol extract of Aaptos suberitoides using MTT assay and clonogenic assay were 12.0 ppm and 4.36 ppm, respectively. The extract demonstrated an inhibition effect on spheroid growth. In low concentration, the extract of Aaptos suberitoides inhibited cell migration. Furthermore, MS analysis showed that the most abundant compounds in this extract has molecular weight m/z 229.81 [M+H]+. Conclusion: This study revealed that the ethanol extract of Aaptos suberitoides demonstrates cytotoxicity, anti-proliferation and anti-migration effect as well as inhibition effect on three-dimensional spheroid growth in trastuzumab-resistant HER2+ breast cancer cell line.

Introduction Acral melanoma (AM) has a poor prognosis since it is easily metastatic and resistant to chemo and immunotherapy. Cyclooxygenase-2 (COX-2) is an enzyme that plays a role in the carcinogenesis process. The increased expression of COX-2 has an impact on increasing levels of Myeloid-Derived Suppressor Cell (MDSC), which is a key regulator of immune. The increase in MDSC produces Transforming Growth Factor β1 (TGF-β1), which will suppress Natural Killer (NK) cells and Dendritic Cells (DC) function so that tumor cells are spared from the immune systems and are easier to invade surrounding tissues. Purpose This study aimed to determine the role of COX-2 and TGF-β1 on the depth of invasion on AM. Materials and Methods This study was a cross-sectional observational study on 40 paraffin blocks of AM cases during 2014–2019 in the Department of Pathology Anatomy, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Bandung. The depth of invasion of all samples was measured by dotSlide imaging software and the immunohistochemical staining of COX-2 and TGF-β1 was performed. The association between COX-2 and TGF-β1 expression and AM depth of invasion were analyzed using Mann Whitney. Results The result showed a significant association between COX-2 and TGF-β1 expression and depth of invasion on AM. COX-2 expression had a significant association with TGF-β1 expression (0.0001). Through multivariate analysis, it was found that COX-2 had the greatest association with the depth of invasion (p=0.0001). Conclusion The findings showed that increasing expression of COX-2 in AM is associated with the depth of invasion by increasing TGF-β1 and it might play important roles during the invasion process of AM.