The latest trends in improving CAR-T cell therapy: from leukemia to solid malignant tumors

CAR-Т cell therapy with the use of cytotoxic lymphocytes with chimeric antigen receptors occupies an important place among modern approaches to the cancer treatment. This therapy has established itself as an effective method of the treatment of CD19+ acute lymphoblastic leukemia. Nevertheless, the recurrences of the illness are not uncommon; the treatment of solid tumors with genetically engineered lymphocytes shows modest results and it is accompanied by the high toxicity. One thing, however, is certain: CAR-Т cell therapy has great potential in the treatment of cancer and further improving of the structure and functions of genetically engineered lymphocytes with chimeric Т cell receptors help greatly increase the efficiency of antitumor treatment.The review includes the current data on the structure of chimeric lymphocytes of different generations and the trends in improving CAR-Т cell therapy. It includes also the fundamental platform for formation of ideology of use CAR-Т cells for the treatment of solid malignant tumors.

The emerging role of circular RNAs in common solid malignant tumors in children

Malignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.

Anlotinib: A Novel Targeted Drug for Bone and Soft Tissue Sarcoma

Bone and soft tissue sarcomas account for approximately 15% of pediatric solid malignant tumors and 1% of adult solid malignant tumors. There are over 50 subtypes of sarcomas, each of which is notably heterogeneous and manifested by remarkable phenotypic and morphological variability. Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) targeting c-kit, platelet-derived growth factor receptors, fibroblast growth factor receptor, and vascular endothelial growth factor receptor. In comparison with the placebo, anlotinib was associated with better overall survival and progression-free survival (PFS) in a phase III trial of patients with advanced non-small cell lung cancer (NSCLC), albeit with cancer progression after two previous lines of treatment. Recently, the National Medical Products Administration approved anlotinib monotherapy as a third-line treatment for patients with advanced NSCLC. Additionally, a phase IIB randomized trial substantiated that anlotinib is associated with a significant longer median PFS in patients with advanced soft tissue sarcoma. Moreover, anlotinib is also effective in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma. Anlotinib has similar tolerability to other TKIs targeting vascular endothelial growth factor receptors and other tyrosine kinase-mediated pathways. However, anlotinib has a notably lower rate of side effects ≥grade 3 relative to sunitinib. This review discussed the remarkable characteristics and major dilemmas of anlotinib as a targeted therapy for sarcomas.

Measurement of plasma fibrinogen and D-dimer in a sample of Iraqi patients with solid malignant tumors

Background: Multifactor affect the pathogenesis of thrombosis in solid malignancy; however, a significant role is attributed to the cancer cells ability to interact with and activate the host hemostatic system. [1] Hemostasis is highly correlated to tumor growth, angiogenesis and metastasis, modulation of these pathways reflects interesting and promising treatment options in the future. [1] Most patients with cancer frequently suffer from chronic compensated DIC and have abnormal laboratory coagulation tests without clinical manifestations of thrombosis, which is a subclinical hypercoagulable state that can be detected by varying degrees of activation of blood clotting. The results of laboratory tests in these patients reflect continuous fibrin formation and lysis during the course of malignancy. [1] Aim of study: To study the effect of solid malignant tumors on blood coagulation via measurements of plasma fibrinogen and D-dimer. Subjects and methods: Thirty patients (9 males and 21 females) attending the oncology consultatory out-patient clinic at Baghdad Teaching Hospital/ Medical City were randomly selected and included in this study. These patients were newly diagnosed as having malignant solid tumors depending on histopathological reports from private and governmental sectors. All the laboratory tests were done at the hematology and biochemistry departments of Teaching Laboratories/ Medical City. Results: Plasma fibrinogen level was significantly higher in patients group rather than control group (3.863 ±0.706) Vs (2.497±0.457 g/L} respectively, (P-value 0.001).The mean value of factor VIII activity was {181% ±58.4)and (99.3% ±11.1)for patient and control groups respectively, the P-Value was significant ( > 0.001 ).D-dimer was negative for all members of control group, for patients group ( 66.7 %) of them showed positive D-dimer and (33.3)were negative for D-dimer ,P-value was significant ( >0.001 ). Conclusions: There was increase in plasma fibrinogen level and positive D-dimer in cancer patients compared to the control group reflecting subclinical thrombophilia and higher risk of VTE in patients with solid tumors due to activation of prothrombotic and fibrinolytic pathways by malignant cells which is vital for the use of primary prophylaxis by anticoagulants.