Red mud with other waste materials as artificial soil substitute and its effect on Sinapis alba.

Despite efforts to utilise bauxite residue, the amount of red mud stored in reservoirs is increasing. This paper aims to evaluate the potential of red mud and other sludge waste types as a soil substitute by monitoring plant development. Pot experiments were carried out testing two types of mixtures: dredging sludge from Lake Balaton mixed with garden soil and the sewage sludge and soil blend. These were then treated with red mud (15 and 30% w/w). The plants were under-, while the roots were more developed in the sewage sludge mix than the dredging sludge blend and the control soil. In the sewage amendment, the phosphorous content increased while the calcium content was lower than in the other soil types and the optimum. The metals uptake of the plants was a factor of the red mud quantity. Lead, nickel, titanium and silicon had elevated concentrations parallel to higher red mud content, but only the nickel exceeded the threshold of the Hungarian legislation. Silicon and titanium were beneficial for plant growth, compensating for the potentially toxic effects of lead and nickel. Results suggest that the red mud in a mixture with either sewage sludge or dredging sludge can act as catalysts for the growth rate of test plants, allowing their utilisation as secondary raw materials.

PD-L1 Expression of Lung Cancer Cells, Unlike Infiltrating Immune Cells, Is Stable and Unaffected by Therapy During Brain Metastasis.

BACKGROUND: Approximately 50% of brain metastases originate from non-small-cell lung cancer. The median survival of patients with brain metastases is 1 month without treatment. Novel immunotherapeutic strategies, such as those targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis, are promising in patients with advanced systemic disease but are often preferentially administered to patients with tumors showing PD-L1 positivity. PATIENTS AND METHODS: Surgically resected paired primary lung adenocarcinoma and brain metastasis samples of 61 patients were analyzed. We compared the paired samples regarding the amount of peritumoral and stromal mononuclear infiltration, PD-L1 expression of tumor and immune cells, and PD-1 expression of immune cells. We investigated the effect of radiotherapy, chemotherapy, and steroid therapy on PD-L1 expression in brain metastases. RESULTS: There was significant positive correlation regarding the PD-L1 expression of tumor cells between the paired primary lung adenocarcinoma and brain metastatic samples with the use of different cutoff levels (1%, 5%, 50%). We found no impact of chemotherapy or steroid therapy on the changes of PD-L1 expression of tumor cells between the 2 sites. There is no or only limited concordance of the proportion of PD-1- or PD-L1-positive tumor-associated immune cells between the paired tumor samples, which suggests that brain metastases develop their own immune environment. CONCLUSION: We observed a strong correlation of PD-L1 positive tumor cells between primary lung adenocarcinoma cases and their corresponding brain metastases, which is not significantly influenced by chemotherapy or steroid therapy.

Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts.

BACKGROUND: Poly-ADP ribose polymerase (PARP) inhibitor-based cancer therapy selectively targets cells with deficient homologous recombination repair. Considering their long-term use in maintenance treatment, any potential mutagenic effect of PARP inhibitor treatment could accelerate the development of resistance or harm non-malignant somatic cells. METHODS: We tested the mutagenicity of long-term treatment with the PARP inhibitor niraparib using whole-genome sequencing of cultured cell clones and whole-exome sequencing of patient-derived breast cancer xenografts. RESULTS: We observed no significant increase in the number and alteration in the spectrum of base substitutions, short insertions and deletions and genomic rearrangements upon niraparib treatment of human DLD-1 colon adenocarcinoma cells, wild-type and BRCA1 mutant chicken DT40 lymphoblastoma cells and BRCA1-defective SUM149PT breast carcinoma cells, except for a minor increase in specific deletion classes. We also did not detect any contribution of in vivo niraparib treatment to subclonal mutations arising in breast cancer-derived xenografts. CONCLUSIONS: The results suggest that long-term inhibition of DNA repair with PARP inhibitors has no or only limited mutagenic effect. Mutagenesis due to prolonged use of PARP inhibitors in cancer treatment is therefore not expected to contribute to the genetic evolution of resistance, generate significant immunogenic neoepitopes or induce secondary malignancies.