TRAIL (tumor-necrosis factor related apoptosis-inducing ligand, CD253) and its death receptors TRAIL-R1 and TRAIL-R2 selectively trigger the apoptotic cell death in tumor cells. For that reason, TRAIL has been extensively studied as a target of cancer therapy. In spite of the promising preclinical observations, the TRAIL–based therapies in humans have certain limitations. The two main therapeutic approaches are based on either an administration of TRAIL-receptor (TRAIL-R) agonists or a recombinant TRAIL. These approaches, however, seem to elicit a limited therapeutic efficacy, and only a few drugs have entered the phase II clinical trials. To deliver TRAIL-based therapies with higher anti-tumor potential several novel TRAIL-derivates and modifications have been designed. These novel drugs are, however, mostly preclinical, and many problems continue to be unraveled. We have reviewed the current status of all TRAIL-based monotherapies and combination therapies that have reached phase II and phase III clinical trials in humans. We have also aimed to introduce all novel approaches of TRAIL utilization in cancer treatment and discussed the most promising drugs which are likely to enter clinical trials in humans. To date, different strategies were introduced in order to activate anti-tumor immune responses with the aim of achieving the highest efficacy and minimal toxicity.In this review, we discuss the most promising TRAIL-based clinical trials and their therapeutic strategies.

The receptor for advanced glycation end products (RAGE) and its ligands are involved in the pathogenesis of cancer. Glyoxalase I (GLO1) is an enzyme which detoxifies advanced glycation end product (AGE) precursors. The aim of the study was to find out the relationship between four polymorphisms (single nucleotide polymorphism, SNP) of the RAGE gene (AGER) and one SNP of the GLO1 gene and clear cell renal cancer (ccRCC). All polymorphisms (rs1800625 RAGE -429T/C, rs1800624 -374T/A, rs3134940 2184A/G, rs2070600 557G/A (G82S), and GLO1 rs4746 419A/C(E111A)) were determined by PCR-RFLP in 214 patients with ccRCC. A group of 154 healthy subjects was used as control. We found significant differences in the allelic and genotype frequencies of GLO1 E111A (419A/C) SNP between patients and controls-higher frequency of the C allele in ccRCC-58.6 vs. 44.5% in controls, OR (95% CI) 1.77 (1.32-2.38), p = 0.0002 (corrected p = 0.001); OR (95% CI) CC vs. AA 2.76 (1.5-4.80), p = 0.0004 (corrected p = 0.002); and AC+CC vs. AA 2.03 (1.23-3.30), p = 0.0034 (corrected p = 0.017). High aggressiveness of the tumor (grade 4) was associated with the presence of C allele RAGE -429T/C SNP (original p = 0.001, corrected p = 0.005) and G allele RAGE 2184A/G SNP (p < 0.001 and p < 0.005), and for genotypes RAGE -429CC (original p = 0.008, corrected p = 0.04) and RAGE 2184GG SNP (original p = 0.005, corrected p = 0.025). Our results demonstrate the link of E111A GLO1 SNP to the presence of the tumor and the connection of RAGE -429T/C and 2184A/G SNPs with the aggressiveness of the tumor. Further studies are required, especially with respect to potential therapeutic implications.

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Abstract. Background: Insufficient specificity and invasiveness of currently used diagnostic methods raises the need for new markers of urological tumors. The aim of this study was to find a link between the urinary excretion of amino acids and the presence of urological tumors. Materials and Methods: Using ion-exchange chromatography, we tested urine samples of patients with prostate cancer (n=30), urinary bladder cancer (n=28), renal cell carcinoma (n=16) and healthy volunteers (control group; n=21). Results:In each category, we found a group of amino acids which differed in concentration compared to the control group. These differences were most significant in sarcosine in patients with prostate cancer; leucine, phenylalanine and arginine in those with bladder cancer; and sarcosine, glutamic acid, glycine, tyrosine and arginine in the those with renal cell carcinoma. Conclusion: Results of our research imply a possible connection between the occurrence of specific types of amino acids in the urine and the presence of urological tumors.The incidence of urological malignancies including cancer of the prostate, bladder and kidney is relatively high. Prostate cancer is the second most common malignancy in the United States among men aside from non-melanoma skin cancer, with estimated 172,000 diagnoses and 28,000 deaths in 2014 (1).Bladder cancer is the 11th most commonly diagnosed cancer in the world and 14th leading cause of cancer death (2), while renal cell carcinoma represents 2-3% of all cancer and in most European countries, its incidence is still rising (3).Despite the frequency of these types of cancer, reliable biomarkers still need to be discovered. Many possible biomarkers of prostate cancer have been tested, including prostate cancer antigen 3 (4), alpha-methyl coenzyme A racemase (5), transmembrane protease, serine 2 (TMPRSS2)-ERG, ETS transcription factor (ERG) translocation (6), urinary prostate-specific antigen (PSA) (7) or urinary thiosulfate (8). However, the only routinely used marker is serum PSA, which still causes many controversies due to the non-specificity of its elevation (9).For patients with renal tumors, early diagnosis is crucial, nevertheless the majority of renal masses are detected incidentally during the investigation of unrelated problems. Numerous molecular markers have been tested such as carbonic anhydrase IX (CaIX) (10), vascular endothelial growth factor (VEGF) (11), hypoxia-inducible factor (HIF) (12), Ki67, p53, phosphatase and tensin homolog (PTEN) and others (13), however none of these has been recommended for routine practice.Bladder cancer is associated with the need for lifelong surveillance by cystoscopy and urine cytology (14) and the highest cost from diagnosis to death among all cancer types (15). Currently tested markers include DNA, RNA, miRNA and protein markers. However, none are routinely used in daily clinical practice.Urine represents an attractive biological material for testing due to the non-invasiveness of its collection, its relative stability during ...

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