Abstract. Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric population. In 35% of cases, RMS develops in the head and neck (H&N) region, and only combined therapy is recognized as a curative treatment. However, recent advances in skull base and reconstructive surgery, along with microsurgery and endoscopic surgery, have strengthened the role of surgery as an important part of RMS treatment. In the present study, 36 pediatric RMS cases (24 males and 12 females) were analyzed after surgical treatment. The average age at diagnosis was 7 years. In total, 67% of tumors were localized in the parameningeal region. Alveolar RMS was the most common histopathological type. A total of 16 patients were treated due to disease recurrence or a previous non-radical surgical procedure, while 19 cases had inductive chemotherapy and/or radiotherapy preceding surgical treatment due to locally advanced disease. In 1 case, only diagnostic biopsy was performed. It is recommended that the management of H&N RMS is interdisciplinary from the beginning. Extensive surgical dissection in the H&N region for RMS may result in severe cosmetic defects and functional impairment; thus, these risks should be considered during treatment planning, and the surgical approach should be based on the individual characteristics of each patient.

Our report supports statement that TKI treatment of dialyzed patients is safe and effective. ccRCC increases risk of developing renal insufficiency as well as end-stage renal disease that require dialysis. Introduction of multitargeted receptor kinase inhibitors (TKIs), including sunitinib, sorafenib and pazopanib significantly expanded life time expectancy of metastatic renal clear cell carcinoma. The advance also applies to patients with ccRCC and end-stage renal disease who undergo dialyses.

Abstract. Carbohydrate metabolism disorders increase the risk of carcinogenesis. Diabetes mellitus alters numerous physiological processes that may encourage cancer growth. However, treating impaired glucose homeostasis may actually promote neoplasia; maintaining proper glucose plasma concentrations reduces metabolic stresses, however, certain medications may themselves result in oncogenic effects. A number of previous studies have demonstrated that metformin reduces the cancer risk. However, the use of sulfonylurea derivatives correlates with an increased risk of developing a malignancy. Another form of treatment, insulin therapy, involves using various forms of insulin that differ in pharmacodynamics, pharmacokinetics and efficacy. Previous studies have indicated that certain insulin variants also affect the cancer risk. The results from analyses that address the safety of long-lasting insulin types raise the most concern regarding the increased risk of malignancy. Rapid development of novel diabetic medications and their widespread use carries the risk of potentially increased rates of cancer, unnoticeable in limited, randomized, controlled trials. In the present review, the results of clinical and epidemiological studies are evaluated to assess the safety of anti-hyperglycemic medications and their effect on cancer risk and outcomes.

The introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack of official guidelines and the exclusion of patients with reduced kidney function from the clinical trials of recently approved drugs complicate the issue even further. Early detection and correct management of renal toxic effects are crucial to preserve kidney function and ensure the optimal administration of life-prolonging therapies. This review presents detailed information on the renal toxicities of three groups of drugs commonly used in renal cell carcinoma treatment: tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and immune checkpoint inhibitors. We outline the incidence and underlying mechanisms of renal adverse effects with a focus on patients on renal replacement therapy, as well as present suggestions for their management.

39 40 41 42 43 Running title: Novel mutations in TOP2A in gliomas 44 45 46 47 48 High grade gliomas (HGGs) are aggressive, primary brain tumors with poor clinical outcomes. 49To better understand glioma pathobiology and find potential therapeutic susceptibilities, we 50 designed a custom-panel 664 cancer-and epigenetics-related genes and employed targeted 51 next generation sequencing to study the genomic landscape of somatic and germline variants in 52 182 glioma samples of different malignancy grades. Besides known alterations in TP53, IDH1, 53 ATRX, EGFR genes, we found several novel variants that can be potential drivers in gliomas. In 54 four patients from the Polish glioma cohort, we identified a novel recurrent mutation in the 55 TOP2A gene coding for Topoisomerase 2A in glioblastomas (GBM, WHO grade IV gliomas). 56The mutation results in a substitution of glutamic acid (E) 948 to glutamine (Q) of TOP2 A and 57we predicted this E948Q substitution may affect DNA binding and a TOP2A enzymatic activity. 58Topoisomerases are enzymes that control the higher order DNA structure by introducing 59 transient breaks and rejoining DNA strands. Using recombinant proteins we demonstrated 60 stronger DNA binding and DNA supercoil relaxation activities of the variant proteins. 61 Glioblastoma (GBM) patients with the mutated TOP2A had shorter overall survival than wild 62 type TOP2A GBM patients. Computational analyses of transcriptomic data showed that the 63 GBM samples with the mutated TOP2A have different transcriptomic patterns suggesting higher 64 transcriptomic activity. The results suggest that TOP2A E948Q variant strongly binds to DNA 65 and is more active in comparison to the wild-type protein. Altogether, our findings suggest that 66 the E948Q substitution leads to gain of function by TOP2A. 67 68 69 4