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Editor’s Choice : Cancer Stem Cells: A Review of the Literature and the Implications in Head and Neck Cancer
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Abstract: In the last few decades, stem cells have been the focus of researchers in an effort to understand the molecular pathways involved in tissue regeneration. By studying normal cell interactions, researchers have since identified cancer stem cells and demonstrated their role in tumorigenesis and metastasis. The authors aimed to review the major molecular pathways involved in tumorigenesis, the role of cancer stem cells, and emerging therapies that target these pathways in squamous cell carcinoma of the head and neck. Keywords: Stem cells, cancer stem cells, head and neck, squamous cell carcinoma, hypoxia inducible factor, curcumin, cisplatin.Download Full Article |
Editor’s Choice : TRAP1 is Involved in Cell Cycle Regulated by Retinoblastoma Susceptibility Gene (RB1) in Early Hypoxia and has Variable Expression Patterns in Human Tumors
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Abstract: Tumor necrosis factor receptor associated protein 1(TRAP1) is a member of the Hsp90 family that acts as a molecular chaperon to the tumor suppressor retinoblastoma susceptibility gene (RB1). We have previously demonstrated that TRAP1-positive cells contain a high level of cell proliferating genes, whilst TRAP1-negative cells contain a high level of genes involved in cell cycles and metastases. In this study, we performed a functional analysis of TRAP1 which focused on its regulation within a cell cycle in relation to RB1. Following a heat shock, TRAP1 translocates to the nucleus and chaperonsRB1. When TRAP1 is silenced by siRNA, or prevented from entering the nucleus in hypoxic cells, formation of RB1/E2F1 complexes is impaired and cell cycle activity is promoted by deregulating the G1/S transition. Inhibition of the nuclear translocation of TRAP1 with geldanamycin abrogates its ability to maintain RB1 in a form that associates with E2F1. Restoration of TRAP1 expression reverses these effects. We analysed TRAP1/RB1 expression on 630 tumors by immunohistochemical staining and found TRAP1 lost in some types of cancer, such as non-small cell lung cancer and breast cancer, and the positive correlation of TRAP1 expression in nuclear and cytoplasm with RB1 was observed. Clinico-pathological data showed that breast carcinoma patients lacking nuclear TRAP1 have a shorter disease free survival. Our data suggests that nuclear translocation of TRAP1 is crucial for its function as a chaperon. The loss of TRAP1 expression in certain types of cancer may provide the growth advantage due to the lost control at cell cycle check point. Keywords: TRAP1, RB1, cell cycle, chaperon, hypoxia.Download Full Article |
Editor’s Choice : Molecular Genetic Study of the Allelic State of the Cell Cycle Genes (TP53, BRCA1) and Features of the Regulation of the Cytokine Cascade in Breast Cancer
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Abstract: This article contains the analysis of mutations in genes that regulate the cell cycle (TP53 and BRCA1) and classification relating to tumor suppressor. Shown that the "risk" alleles of these genes may contribute to tumor development, but the activation of the immune system cytokine spectrum of patients can prevent their destructive degeneration. The authors proposed a personalized approach to the study for the prevention of possible proliferative processes. This is confirmed by reversal of "risk" alleles studied genes in tumors in operated patients with cytokine physiologically normal status. Keywords: Breast cancer, tumor suppressor, cytokines, nucleotide substitutions, predisposition.Download Full Article |
Editor’s Choice : Disease–Free Remission Exceeding 37 Years in Patients Treated as Children for Acute Leukemia (AL) with Immunotherapy Using Viable (Cryopreserved) Allogeneic Leukemic Cells
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Abstract: At present time in spite of great achievements in modern chemotherapy of acute leukemia (AL) the issue of eradication of residual leukemic cells (MRD) is still relevant. Since 1971 we included specific immunotherapy in the treatment of children with acute lymphoblastic leukemia in remission using viable cryopreserved allogeneic leukemic cells. 67 children in remission were divided into 2 groups: 27 constituted the control group (only continued standard-for-that-time chemotherapy) and 40 children – the treatment which received immunotherapy in addition to standard chemotherapy. In 3 years all children in the control group relapsed. The median length of remission was 15 months. In the treatment group we observed stabilization of remission only in children over 7 years of age when immunization was initiated after 6 or more months of remission and in children younger than 7 if it was initiated after 1-1,5 years of remission. The median length of remission was 60 months which significantly exceeded (4 times) that parameter in the control group of children. Cytotoxic antibodies against leukemic cells appeared in the serum of effectively immunized children at a higher titer than against donor lymphocytes. Intrathecal administration of this hyperimmune serum to patients with neuroleukemia resistant to chemotherapy led to a sharp decrease in the amount of leukemic cells in the spinal fluid. After 5 years of remission (and 3-5 years of immunotherapy) all treatment in these patients was stopped. Out of 19 patients who received immunotherapy on time, 8 patients (42%) have been in event-free remission for 37 to 41 years (median – 38 years) through the present time and enjoy high quality of life. Our results indicate that immunotherapy initiated during remission period of AL can lead to creation of anti-leukemic immunity with subsequent eradication of MRD and complete recovery. Keywords: Acute leukemia, Immunotherapy, Cryopreserved leukemic cells, Prolongation of remission, Immunological indices.Download Full Article |
