Is ERCC1 a prognostic biomarker for urothelial cancer following radical cystectomy? A long-term analysis.

Introduction: Excision repair cross-complementation 1 protein (ERCC1) plays a vital role in cancer cells enabling DNA repair via nucleotide excision repair. Thus, we hypothesized whether expression of this protein may be utilized as a prognostic marker in patients after radical cystectomy.

Material And Methods: The final analysis involved 123 patients with urothelial bladder carcinoma who underwent radical cystectomy with bilateral lymphadenectomy.

The Tumor Microenvironment-A Metabolic Obstacle to NK Cells' Activity.

NK cells have unique capabilities of recognition and destruction of tumor cells, without the requirement for prior immunization of the host. Maintaining tolerance to healthy cells makes them an attractive therapeutic tool for almost all types of cancer. Unfortunately, metabolic changes associated with malignant transformation and tumor progression lead to immunosuppression within the tumor microenvironment, which in turn limits the efficacy of various immunotherapies.

Inhibition of thioredoxin-dependent HO removal sensitizes malignant B-cells to pharmacological ascorbate.

L-ascorbate (L-ASC) is a widely-known dietary nutrient which holds promising potential in cancer therapy when given parenterally at high doses. The anticancer effects of L-ASC involve its autoxidation and generation of HO, which is selectively toxic to malignant cells. Here we present that thioredoxin antioxidant system plays a key role in the scavenging of extracellularly-generated HO in malignant B-cells.

Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently sensitises these cells to prooxidant agents.

Background: Our previous work has shown peroxiredoxin-1 (PRDX1), one of major antioxidant enzymes, to be a biomarker in human breast cancer. Hereby, we further investigate the role of PRDX1, compared to its close homolog PRDX2, in mammary malignant cells.

Methods: CRISPR/Cas9- or RNAi-based methods were used for genetic targeting PRDX1/2.

Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy.

Lysosomes are conservative organelles with an indispensable role in cellular degradation and the recycling of macromolecules. However, in light of recent findings, it has emerged that the role of lysosomes in cancer cells extends far beyond cellular catabolism and includes a variety of cellular pathways, such as proliferation, metastatic potential, and drug resistance. It has been well described that malignant transformation leads to alterations in lysosomal structure and function, which, paradoxically, renders cancer cells more sensitive to lysosomal destabilization.

Inhibition of autophagy sensitizes cancer cells to Photofrin-based photodynamic therapy.

Background: Accumulating evidence suggest that autophagy plays a pivotal role in various anticancer therapies, including photodynamic therapy (PDT), acting as a pro-death or pro-survival mechanism in a context-dependent manner. Therefore, we aimed to determine the role of autophagy in Photofrin-based PDT.

Methods: In vitro cytotoxic/cytostatic effects of PDT were evaluated with crystal violet cell viability assay.

HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies.

Downregulation of CD20, a molecular target for monoclonal antibodies (mAbs), is a clinical problem leading to decreased efficacy of anti-CD20-based therapeutic regimens. The epigenetic modulation of CD20 coding gene () has been proposed as a mechanism for the reduced therapeutic efficacy of anti-CD20 antibodies and confirmed with nonselective histone deacetylase inhibitors (HDACis). Because the use of pan-HDACis is associated with substantial adverse effects, the identification of particular HDAC isoforms involved in CD20 regulation seems to be of paramount importance.

Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo.

Photodynamic therapy (PDT) exerts direct cytotoxic effects on tumor cells, destroys tumor blood and lymphatic vessels and induces local inflammation. Although PDT triggers the release of immunogenic antigens from tumor cells, the degree of immune stimulation is regimen-dependent. The highest immunogenicity is achieved at sub-lethal doses, which at the same time trigger cytoprotective responses, that include increased expression of glucose-regulated protein 78 (GRP78).

Investigation of cell death mechanisms in human lymphatic endothelial cells undergoing photodynamic therapy.

Background: Photodynamic therapy (PDT) has been shown to induce ablation and functional occlusion of tumor-associated lymphatic vessels. However, direct effects of PDT on lymphatic endothelial cells (LECs) have not been studied so far. The aim of this study was to elucidate molecular mechanisms of cell death induced by PDT in human LECs.

Dimeric peroxiredoxins are druggable targets in human Burkitt lymphoma.

Burkitt lymphoma is a fast-growing tumor derived from germinal center B cells. It is mainly treated with aggressive chemotherapy, therefore novel therapeutic approaches are needed due to treatment toxicity and developing resistance. Disturbance of red-ox homeostasis has recently emerged as an efficient antitumor strategy.