Coleythrane9757

Most of patients (80%) with detected MYC aberrations were previously untreated, suggesting that these lesions might occur early in the course of the disease. The MYC aberrations were found mutually exclusive with high risk TP53 and SF3B1 mutations, while one case was identified, where MYC amplification and NOTCH1 mutation coincided simultaneously. Regarding clinical outcome, the MYC aberrations were associated with a shorter time to first treatment (3 vs 25 months, p = 0.008) as well as reduced overall survival (60 vs 139 months). CONCLUSION Our data suggest that MYC aberrations might be an early event in IR-related CLL and contribute to aggressive disease development in the absence of high risk TP53 and SF3B1 mutations.AIM To describe incidence of malignant germ cell neoplasms (GCNs) in Ukraine and assess the medical care to patients with GCNs and its efficacy. MATERIALS AND METHODS Records on 6495 males and 1038 females with malignant GCNs diagnosed in 2000-2013 extracted from the database of National Cancer Registry of Ukraine have been analyzed using methods of descriptive epidemiology and survival evaluation. RESULTS In Ukraine, GCNs covered 79.1% of testicular cancers and 48.9% of ovarian cancers in patients aged 0-19 years, while their proportions in total cancer incidence did not exceed 0.7% in males and 0.1% in females. Most of GCNs in males (75.9%) were diagnosed at the reproductive age (20-49) and in females 72.2% of GCNs were diagnosed at the age of 0-44 years. Female gonadal GCNs were divided by germinomatous and nongerminomatous as 49.3% vs 50.7% while in males this proportion was 65.3% vs 34.7%. Age-specific incidence of genital GCNs in Ukraine reached peak values in males aged 25-39 years and in females aged that in countries in transition. Further research and analysis are impossible without due registration of both the diagnosis and the treatment undertaken as well as close follow-up of patients' life status.AIM Aberrant Sonic hedgehog (Shh) pathway signaling has been described in small cell lung cancer (SCLC), as well discrepancies, when analyzing expression of pathway components in SCLC cell lines vs tumor biopsies. Shh key component GLI1 was evaluated in advanced SCLC and data correlated with patient survival. MATERIALS AND METHODS GLI1 expression was analyzed by quantitative real-time polymerase chain reaction in pre-treatment fresh frozen tumor biopsies of 12 advanced SCLC patients and mRNA level of GLI1 was compared in short-term vs long-term survivor's samples (stratified by median survival, independent samples t-test). RESULTS Expression of GLI1 mRNA was significantly higher in long-term (> 9.6 months, n = 6) survivor's biopsies than in short-term (≤ 9.6 months, n = 6) survivors (p = 0.0196, 95% CI 0.000016 to 0.000147, two-tailed independent samples t-test). CONCLUSION High GLI1 mRNA expression in SCLC was found to be positive prognostic marker associated with longer survival. Further research is needed for validation of these results due to the small number of patients in the study.Placental-like alkaline phosphatase (PLAP) is expressed by many tumors and can be detected in sera of patients with various cancers. Its aberrant expression has been considered to be potentially useful as tumor marker. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The expression of various forms of AP in cells of chronic myeloid leukemia (CML) has not yet been studied. AIM To analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E. MATERIALS AND METHODS RNA extracted from leukemic cells was converted to cDNA and real-time reverse transcription polymerase chain reaction was performed using SYBR Green protocol with primers to tissue non-specific alkaline phosphatase (TNAP), intestinal alkaline phosphatase and CCAAT-enhancer-binding proteins alpha (C/EBPα). To analyze the modulation of expression of APs and C/EBPα, CML cells were incubated with 100 µM vitamin E. RESULTS We have observed the aberrant expression of mRNA intestinal alkaline phosphatase in CML cells that upon sequencing demonstrated the significant alignment with PLAP sequence while no gene homology with tissue placental alkaline phosphatase (PAP) was revealed. Vitamin E decreases mRNA PLAP expression and increases mRNA TNAP expression. Moreover, along with down-regulation of aberrant PLAP and up-regulation of TNAP, vitamin E increases C/EBPα mRNA expression. CONCLUSION The loss of TNAP in CML may contribute to pathogenesis of this disease. buy Ferrostatin-1 PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the potential role of vitamin E as the inducer of differentiation potential of leukemic cells in CML.Tumor cell metabolism is considered one of the hallmarks of cancer. This concept is exploited in the development of new ways of anticancer therapy based on the use of substances capable of changing drastically bioenergetic metabolism of tumor cells. Among them, sodium dichloroace-tate (DCA), an inhibitor of pyruvate dehydrogenase kinase, and metformin (MTF), an antidiabetic hypoglycemic drug, an inhibitor of the mitochondrial respiratory chain (complex I), both have been long used in clinical non-oncological practice, and presently are considered promising candidates in oncology. AIM To study the capability of MTF to enhance the antitumor action of DCA against Lewis lung carcinoma cells in vitro. MATERIALS AND METHODS LLC/R9, a low metastatic variant of Lewis lung carcinoma cells, was used. Effects of 30 mM DCA in combination with 2 mM MTF on cell survival, cell cycle distribution, apoptosis, mitochondrial potential, intracellular ATP level, glucose consumption, and lactate production rates were determined inF enhanced the cytotoxic/cytostatic action of DCA against LLC/R9 cells in vitro, which points on their possible synergistic antitumor action in vivo.AIM To assess oxidative stress and structural changes of the serum albumin in rats with transplanted Walker-256 carcinosarcoma (W256) strains with varying sensitivity to doxorubicin (Dox). MATERIALS AND METHODS The study was performed on female Wistar rats with transplanted W256. On the 9th day after tumor cell transplantation an analysis of peripheral blood, oxidative stress parameters, and structural changes of serum albumin of experimental animals was performed. RESULTS On the 9th day after W256 transplantation a significant increase in the leukocyte counts was observed in the groups of animals with the Dox-resistant and parental (Dox-sensitive) W256 tumors compared with the group of the intact animals up to 14.24 ± 1.92 • 103/μl and 9.78 ± 1.03 • 103/μl, vs 8.92 ± 1.04 • 103/μl, respectively, due to the increase of granulocyte and monocyte counts. The number of lymphocytes was within the normal range. The level of hemoglobin and the erythrocyte counts were also within normal limits, but hematocrit in both groups of animals with tumors somewhat increased against the background of 1.