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Introduction In children with hepatocellular carcinoma (pHCC) overall survival is poor. In adult HCC several antitumor properties are described in in vitro models for the use of curcumin (CUR). Methods Hepatoma cell lines (HuH6, HepT1, HepG2, HC-AFW1) were treated with CUR or, and Cisplatin (PDDT), cultures were either kept in the dark or exposed to blue light (PDT; 480 nm, 300W, 10 seconds), MTT-tests were performed. ROS production was measured. Reduction of cancer stem cells (CSC) was investigated with FACS analyses. Orthotopic growth of the pediatric hepatocellular carcinoma cell line HC-AWF1 in NSG mice was induced. By the increase serum alpha fetoprotein AFP >5 U/mL mice were treated with micellar CUR, PDDT, or CUR PDDT and compared to controls. Curcuminoid levels in serum and organ lysates as well as AFP serum levels were investigated. Results In all cell lines IC50 were significantly lower after blue light exposure than after CUR alone (p < 0.001). Blue light exposure resulted in significant ROS production in all cell lines. CUR alone reduced HEK-6D6 positive CSC not as effectively as CDDP alone or as curcumin with PDT. Serum CUR decreased from 3513.89 ± 2791.84 nmol/L two hours after administration to 769.74 ± 448.61 nmol/L after five hours. CUR concentrations significantly differed between organs (p=0.000), highest concentrations were observed in the lungs 11.33 ± 9.17 nmol/Kg, lowest in the brain 0.16 ± 0.24 nmol/Kg. The concentrations in the tumor tissue (2.57 ± 1.49 nmol/Kg) were higher than in the liver (1.77 ± 1.50 nmol/Kg). Combination therapy significantly reduced AFP concentrations compared to control group (week 3: 1.04 ± 0.67 vs. 2.73 ± 0.64, p = 0.004; week 4: 2.05 ± 1.01 vs. 3.35 ± 0.43, respectively, p = 0.02). Conclusion These data prove the potential of micellar curcumin as a complementary agent in pediatric oncology to enhance the overall survival of patients with pediatric liver tumors. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Isolated Tubulitis, Borderline Changes, and Isolated Arteritis suspicious for histologic T cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR)., Methods: In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with Isolated Tubulitis (i0, t1-3, v0; n=101), Borderline Changes (according to Banff 2022, v0; n=9), Isolated Arteritis (no borderline, v1; n=37), No Inflammation (i0, t0, v0; n=67) and a Positive Control Cohort (hTCMR, n=27; Mixed histologic Rejection, n=8; both according to Banff 2022; total n=35). The first three groups were summarized as TCMR-Suspicion (n=147). Subcategorization included the presence and absence of microvascular inflammation (MVI; g+ptc≥2). Molecular rejection rates and differentiation were investigated., Results: Molecular rejection rates were 37/147 cases (25.2%; 32 with MVI) in TCMR-Suspicion, 6/67 (9%; 4 with MVI) in No Inflammation and 30/35 (85.7%; 19 with MVI) in the Positive Control Cohort. Molecular antibody-mediated rejection (mAMR) was present in 39/73 (53.4%) of cases. The presence of donor-specific antibodies (DSA) at the time of the biopsy was high (127/249, 51%). Only 3 mAMR/TCMR and no pure mTCMR cases were detected in TCMR-Suspicion and No Inflammation, compared to 12 mAMR/TCMR and 10 mTCMR cases in the Positive Control Cohort (p<0.001). Even though the TCMR-specific molecular (Classifier) score differentiated between TCMR-Suspicion and No Inflammation (p=0.005), rejection phenotype scores (R2 and R3) did not (p=0.157 and 0.121)., Conclusions: MMDx did not identify pure mTCMR among Isolated Tubulitis, Borderline Changes, or Isolated Arteritis, likely due to low sensitivity for TCMR-lesions. However, it identified mAMR or mAMR/TCMR, especially in cases with MVI. Subthreshold findings remain to be further studied., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background/aim: Curcumin (CUM) is a promising agent in complementary oncology. The present study analyzed the photoactive properties of curcumin on pediatric epithelial liver tumor cell lines., Materials and Methods: Hepatoblastoma cell lines (HuH6, HepT1) and hepatocellular carcinoma cell lines (HepG2, HC-AFW1) were treated with curcumin and exposed to blue light (phototherapy, 480 nm, 300 W). Cell viability (MTT tests), cellular oxidative stress (production of reactive oxygen species (ROS)) and cellular uptake/degradation of curcumin were analyzed., Results: Significant loss of viability resulted from 24-48 h incubation with curcumin. With photodynamic therapy (PDT), even short time incubation (1 h) with curcumin resulted in significantly lower half maximal inhibitory concentration (IC50) (p<0.001, two-way ANOVA). Significant ROS production was observed with PDT and curcumin., Conclusion: Phototherapy strongly enhances the anticancer properties of curcumin in pediatric solid liver tumors in vitro., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.