Showing papers by "Cezary Szczylik published in 2020"
01 Oct 2020
TL;DR: For an actively treated patient with cancer, cancer remains the main life-threatening disease during the COVID-19 pandemic and the need for more attentive psychological care should be provided especially to female patients, patients with breast cancer, those under 65 years of age and treated with curative intention, as these factors are associated with a higher level of anxiety.
Abstract: Background Life-threatening diseases have a negative impact on emotional well-being and psychosocial functioning. This study aimed to assess the relationship between the level of anxiety caused by a neoplasm and the threat of coronavirus infection among patients with cancer actively treated with systemic therapy during the COVID-19 pandemic. Additionally, we searched for clinical factors associated with a higher level of anxiety. Methods In this multicentre, prospective, non-interventional study conducted in Poland, we enrolled 306 actively treated patients with cancer and collected their clinical data, including age, gender, cancer type and treatment intention. The fear/anxiety of SARS-CoV-2 were rated in Fear of COVID-19 Scale (SRA-FCV-19S) and Numerical Anxiety Scale (SRA-NAS). The fear and anxiety associated with cancer (CRA) were rated with the NAS (CRA-NAS). Results The mean level of SRA-FCV-19S was 18.5±7.44, which was correlated with the SRA-NAS (r=0.741, p 65 years (6.73±2.96 vs 5.66±3.24; p=0.007). Conclusions For an actively treated patient with cancer, cancer remains the main life-threatening disease during the COVID-19 pandemic. The need for more attentive psychological care should be provided especially to female patients, patients with breast cancer, those under 65 years of age and treated with curative intention, as these factors are associated with a higher level of anxiety.
84 citations
TL;DR: This review focuses on the effects of hypoxia in the microenvironment and its consequences on tumor treatments, and opens the way to innovative combined treatments to the advantage of immunotherapy outcome in ovarian cancers.
Abstract: Hypoxia, a common factor ruling the microenvironment composition, leads to tumor progression. In this hypoxic context, cytokines and cells cooperate to favor cancer development and metastasis. Tumor hypoxia is heterogeneously distributed. Oxygen gradients depend on the vicinity, functionality of blood vessels, and oxygen ability to diffuse into surrounding tissues. Thus, the vasculature state modulates the microenvironment of the tumor cells. Cells sense and react to small variations in oxygen tension, which explains the lack of tumor cells' unicity in their reaction to drugs. Ovarian cancers are highly hypoxia-dependent, ascites worsening the access to oxygen, in their reactions to both chemotherapy and new immunotherapy. Consequently, hypoxia affects the results of immunotherapy, and is thus, crucial for the design of treatments. Controlling key immunosuppressive factors and receptors, as well as immune checkpoint molecule expression on tumor, immune and stromal cells, hypoxia induces immunosuppression. Consequently, new approaches to alleviate hypoxia in the tumor microenvironment bring promises for ovarian cancer immunotherapeutic strategies. This review focuses on the effects of hypoxia in the microenvironment and its consequences on tumor treatments. This opens the way to innovative combined treatments to the advantage of immunotherapy outcome in ovarian cancers.
17 citations
TL;DR: Implantation of CD44−/CD105− cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors, characterized by low uptake of [18F]FDG, while CD105+ and CD44+ tumors expresses Nanog and Oct-4, whileCD44− tumors additionally expressed endothelial cell marker - CD31.
Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. Prognosis for ccRCC is generally poor since it is largely resistant to chemo- and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/TICs isolated from established RCC cell lines - basic ccRCC research model - has never been investigated in vivo. CD105+, CD105-, CD44+ and CD44- as well as CD44-/CD105- CD44+/CD105+ and CD44-/CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into NOD SCID mice and tumor growth was monitored with MRI and PET/CT. Tumor growth was observed after implantation of CD105+, CD44+, CD44-, CD44-/CD105+ and CD44-/CD105- but not CD105- or CD44+/CD105+. Implantation of CD44-/CD105- cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44- tumors expresses Nanog and Oct-4, while CD44- tumors additionally expressed endothelial cell marker - CD31.
14 citations
TL;DR: A novel recurrent mutation in the TOP2A gene coding for Topoisomerase 2A in glioblastomas (GBM, WHO grade IV gliomas) is identified and it is suggested that the E948Q substitution leads to gain of function by TOP2a.
Abstract: High grade gliomas (HGGs) are aggressive, primary brain tumors with poor clinical outcomes To better understand glioma pathobiology and find potential therapeutic susceptibilities, we designed a custom-panel 664 cancer- and epigenetics-related genes and employed targeted next generation sequencing to study the genomic landscape of somatic and germline variants in 182 glioma samples of different malignancy grades Besides known alterations in TP53, IDH1, ATRX, EGFR genes, we found several novel variants that can be potential drivers in gliomas In four patients from the Polish glioma cohort, we identified a novel recurrent mutation in the TOP2A gene coding for Topoisomerase 2A in glioblastomas (GBM, WHO grade IV gliomas) The mutation results in a substitution of glutamic acid (E) 948 to glutamine (Q) of TOP2 A and we predicted this E948Q substitution may affect DNA binding and a TOP2A enzymatic activity Topoisomerases are enzymes that control the higher order DNA structure by introducing transient breaks and rejoining DNA strands Using recombinant proteins we demonstrated stronger DNA binding and DNA supercoil relaxation activities of the variant proteins Glioblastoma (GBM) patients with the mutated TOP2A had shorter overall survival than wild type TOP2A GBM patients Computational analyses of transcriptomic data showed that the GBM samples with the mutated TOP2A have different transcriptomic patterns suggesting higher transcriptomic activity The results suggest that TOP2A E948Q variant strongly binds to DNA and is more active in comparison to the wild-type protein Altogether, our findings suggest that the E948Q substitution leads to gain of function by TOP2A
4 citations