STAT5: From Pathogenesis Mechanism to Therapeutic Approach in Acute Leukemia

2019 ◽  
Vol 51 (4) ◽  
pp. 345-351
Author(s):  
Mohammad Shahjahani ◽  
Amirreza Abroun ◽  
Najmaldin Saki ◽  
Seyed Mohammad Bagher Mohammadi ◽  
Hadi Rezaeeyan
Keyword(s):  
Acute Leukemia ◽  
B Cell Lymphoma ◽  
Leukemic Cells ◽  
Human Telomerase Reverse Transcriptase ◽  
Search Terms ◽  
Pubmed Search ◽  
Materials Used ◽  
Human Telomerase ◽  
Multiple Signaling

Abstract Background Based on the results of multiple studies, multiple signaling pathways is a major cause of resistence to chemotherapy in leukemia cells. Signal transducer and activator of transcription 5 (STAT5) is among these factors; it plays an essential role in proliferation of leukemic cells. Methods We obtained the materials used in our study via PubMed search from 1996 through 2019. The key search terms included “STAT5,” “acute leukemia,” “leukemogenesis,” and “mutation.” Results On activation, STAT5 not only inhibits apoptosis of leukemic cells via activating the B-cell lymphoma 2 (BCL-2) gene but also inhibits resistance to chemotherapy by enhancing human telomerase reverse transcriptase (hTERT) expression and maintaining telomere length in cells. It has also been shown that a number of mutations in the STAT5 gene and in related genes alter the expression of STAT5. Conclusion The identification of STAT5 and the factors activated in its up- or downstream expression, affecting its function, contribute to better treatments such as targeted therapy rather than chemotherapy, improving the quality of life patients.

Effect of hTR Antisense Oligodeoxynucleotides on Telomerase Acitvity and Ciplatin -Sensitivity of Primary Acute Leukemia Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4359-4359
Author(s):  
Yang Xiao
Keyword(s):  
Gel Electrophoresis ◽  
Telomerase Activity ◽  
Leukemic Cells ◽  
Morphological Observation ◽  
Antisense Oligodeoxynucleotide ◽  
Human Telomerase Reverse Transcriptase ◽  
Significant Difference ◽  
Initiator Codon ◽  
Human Telomerase

Abstract BACKGROUND: Between the three key components part of human telomerase, human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) have significant correlation with telomerase activity. The previous study has identified that the telomerase activity of K562 and HL-60 cells was special suppresssed significantly by phosphorothoate antisense oligodeoxynucleotide (ASODN) complementary to the initiator codon of hTR. This study was designed to evalutae the effection of hTR ASODN on telomerase activity and apoptosis of primary acute leukemic cells. To research whether hTR ASODN could enhance apoptosis rates of primary leukemic cells to cisplatin. METHODS: Primary leukemic cells were treated with phosphorothoate ASODN complementary to the initiator codon of hTR in vivo. The changing of telomerase activity was assayed by telomeric repeat amplification protocol(TRAP) and polymerase chain reaction enzyme-linked immunoassay(PCR-ELISA). The survival rates of cells was measured by trypan blue exclusion. Apoptosis was assayed by morphological observation (Giemsa and PI), DNA gel electrophoresis and flow cytometry analysis technology. RESULTS: Primary acute leukemic cells expressed high level of telomerase activity which decreased as the cells treated by hTR ASODN. The telomerase activity was suppresssed significantly by 10umol/L ASODN and the effecttion was most significantly at 72h; Apoptotic bodies of primary leukemic cells were observed easily by fluorescence micrscope when cisplatin was added 48h after ASODN treatment for 24h; Agarose gel electrophoresis of genomic DNA from primary leukemic cells treated with ASODN and cisplatin combination for 72h showed typical DNA ladder; neither did DNA from primary leukemic cells treated with sense oligodeoxynucleotide (SODN) plus cisplatin nor cisplatin alone. In addition, apoptosis rates of primary leukemic cells treated with ASODN for 24h and then with cisplatin for 72h were 41.36±9.28%. There were statistically significant difference in the percentage of apoptotic cells between hTR ASODN plus cisplatin and SODN plus cisplatin (14.51±4.78%) or cisplatin alone group (12.61±2.56)% (P<0.01). CONCLUSIONS: ASODN complementary to the region of hTR could significantly inhibit the telomerase activity of primary acute leukemic cells, and increased the cisplatin-induced apoptosis and enhanced cisplatin-sensitivity in vivo, indicating telomerase may be a new target of treatment to leukemia.

scholarly journals Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1188
Author(s):  
Mot Yee Yik ◽  
Adam Azlan ◽  
Yaashini Rajasegaran ◽  
Aliaa Rosli ◽  
Narazah Mohd Yusoff ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Diagnostic Value ◽  
Telomerase Activity ◽  
Biological Molecules ◽  
Leukemic Cells ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Elevated Expression ◽  
Human Telomerase ◽  
Next Generation Sequencing Ngs

The proliferative capacity and continuous survival of cells are highly dependent on telomerase expression and the maintenance of telomere length. For this reason, elevated expression of telomerase has been identified in virtually all cancers, including leukemias; however, it should be noted that expression of telomerase is sometimes observed later in malignant development. This time point of activation is highly dependent on the type of leukemia and its causative factors. Many recent studies in this field have contributed to the elucidation of the mechanisms by which the various forms of leukemias increase telomerase activity. These include the dysregulation of telomerase reverse transcriptase (TERT) at various levels which include transcriptional, post-transcriptional, and post-translational stages. The pathways and biological molecules involved in these processes are also being deciphered with the advent of enabling technologies such as next-generation sequencing (NGS), ribonucleic acid sequencing (RNA-Seq), liquid chromatography-mass spectrometry (LCMS/MS), and many others. It has also been established that TERT possess diagnostic value as most adult cells do not express high levels of telomerase. Indeed, studies have shown that prognosis is not favorable in patients who have leukemias expressing high levels of telomerase. Recent research has indicated that targeting of this gene is able to control the survival of malignant cells and therefore offers a potential treatment for TERT-dependent leukemias. Here we review the mechanisms of hTERT regulation and deliberate their association in malignant states of leukemic cells. Further, we also cover the clinical implications of this gene including its use in diagnostic, prognostic, and therapeutic discoveries.

scholarly journals Automated identification of leukocyte subsets improves standardization of database-guided expert-supervised diagnostic orientation in acute leukemia: a EuroFlow study

2020 ◽  
Author(s):  
Ludovic Lhermitte ◽  
◽  
Sylvain Barreau ◽  
Daniela Morf ◽  
Paula Fernandez ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Leukemic Cells ◽  
Reference Database ◽  
Similar Data ◽  
Normal Cells ◽  
Adequate Treatment ◽  
Normal Peripheral Blood ◽  
Automated Database

Abstract Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide toward the relevant classification panel and final diagnosis. In this study, we designed and validated an algorithm for automated (database-supported) gating and identification (AGI tool) of cell subsets within samples stained with ALOT. A reference database of normal peripheral blood (PB, n = 41) and bone marrow (BM; n = 45) samples analyzed with the ALOT was constructed, and served as a reference for the AGI tool to automatically identify normal cells. Populations not unequivocally identified as normal cells were labeled as checks and were classified by an expert. Additional normal BM (n = 25) and PB (n = 43) and leukemic samples (n = 109), analyzed in parallel by experts and the AGI tool, were used to evaluate the AGI tool. Analysis of normal PB and BM samples showed low percentages of checks (<3% in PB, <10% in BM), with variations between different laboratories. Manual analysis and AGI analysis of normal and leukemic samples showed high levels of correlation between cell numbers (r2 > 0.95 for all cell types in PB and r2 > 0.75 in BM) and resulted in highly concordant classification of leukemic cells by our previously published automated database-guided expert-supervised orientation tool for immunophenotypic diagnosis and classification of acute leukemia (Compass tool). Similar data were obtained using alternative, commercially available tubes, confirming the robustness of the developed tools. The AGI tool represents an innovative step in minimizing human intervention and requirements in expertise, toward a “sample-in and result-out” approach which may result in more objective and reproducible data analysis and diagnostics. The AGI tool may improve quality of immunophenotyping in individual laboratories, since high percentages of checks in normal samples are an alert on the quality of the internal procedures.

Effect of hTERT Antisense on Cisplatin Sensitivity of Acute Lymphoblastic Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4358-4358
Author(s):  
Wenyu Li ◽  
Yuan Zhang
Keyword(s):  
Leukemic Cells ◽  
Morphological Observation ◽  
Blue Dye ◽  
Double Staining ◽  
Hoechst 33258 ◽  
Human Telomerase Reverse Transcriptase ◽  
Cisplatin Sensitivity ◽  
Staining Techniques ◽  
Induced Apoptosis ◽  
Human Telomerase

Abstract AIM: To investigate the effect of human telomerase reverse transcriptase(hTERT) antisense phosphorothioate oligodeoxynucleotide(AS PS-ODN) on enhancing cisplatin sensitivity in acute lymphoblastic leukemic cells. METHODS: The expression levels of hTERT protein were detected by immunofluorescence using fluoresce isothiocyanate(FITC) lable. Cell surviving fraction was determined using the trypan blue dye exclusion assay. Apoptosis was detected by morphological observation and flow cytomertric cell cycle analysis. RESULTS: The expression of hTERT protein was inhibited after treated by hTERT AS PS-ODN. Treatment with cisplatin after 24h of exposure to AS PS-ODN had significantly reduced the number of viable ALL cells. However, there was no difference on ALL cells survival between sense oligodeoxynucleotide(S PS-ODN)/CDDP combination and CDDP treated cells alone. In morphological observation of apoptotic cells using Hoechst 33258 and PI double staining techniques, cells displayed classic apoptotic changes treated with CDDP or CDDP combined with hTERT AS PS-ODN or S PS-ODN at 48h. Apoptotic rates of cells added CDDP and AS PS-ODN were higher than that of cells added CDDP only(P<0.05). Apoptotic rates of cells added CDDP and S PS-ODN were similar with that of cells added CDDP only(P>0.05). CONCLUSION: hTERT AS-ODN inhibited the expression of hTERT protein and increased the CDDP induced apoptosis in primer acute lymphoblastic leukemic cells.

CUIDADOS BUCAIS EM PACIENTES VENTILADOS MECANICAMENTE: CONHECIMENTO DE ENFERMEIROS DE UM HOSPITAL ESCOLA

2018 ◽  
Vol 8 (4) ◽  
Author(s):  
Gérsica Sampaio Silva ◽  
Fernanda Alves Ferreira Gonçalves ◽  
Bárbara Ribeiro Miquelin Bueno ◽  
Georlucya Kátia Da Silva Ferreira ◽  
Ludmila Pinheiro Da Silva ◽  
...  
Keyword(s):  
Oral Hygiene ◽  
Oral Care ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Mechanically Ventilated ◽  
Mechanically Ventilated Patients ◽  
Complicating Factors ◽  
Materials Used ◽  
Ventilated Patients

Objetivo: Avaliar o conhecimento acerca dos cuidados bucais realizados por enfermeiros a pacientes ventilados mecanicamente. Método: Estudo transversal, realizado em um hospital escola de Goiânia/Goiás. A coleta de dados deu-se por meio de questionário estruturado. Resultados: Os enfermeiros conhecem as medidas recomendadas sobre higiene bucal. Os fatores dificultadores encontrados foram a falta de pessoal (21,7%), falta de tempo (16,7%) e trabalhos burocráticos (15%). Contudo ainda existem lacunas no que se refere a produtos e materiais utilizados na higiene bucal. Conclusão: As Lacunas e os fatores dificultadores sinalizados nesse estudo merecem reflexão, como forma de avaliar a qualidade do cuidado oferecido.Descritores: Biofilme; Higiene Bucal; Cuidados de enfermagem.ORAL CARE IN MECHANICALLY VENTILATED PATIENTS: KNOWLEDGE OF NURSES FROM A SCHOOL HOSPITALObjective: To evaluate the knowledge about oral care performed by nurses in mechanically ventilated patients. Methods: a cross-sectional study, conducted in a teaching hospital of Goiania/Goias. The data collection was performed by means of a structured questionnaire. Results: The nurses know the measures recommended on oral hygiene. The complicating factors found were the lack of personnel (21.7%), lack of time (16.7%) and work on tape (15%). However there are still gaps in relation to products and materials used in oral hygiene. Conclusion: The gaps and the factors complicating factors indicated in this study deserve consideration, as a means of evaluating the quality of care offered.Keywords: Biofilm; Oral hygiene; Nursing care.CUIDADO ORAL EN PACIENTES CON VENTILACIÓN MECÁNICA: EL CONOCIMIENTO DE LAS ENFERMERAS DEL HOSPITAL ESCUELAObjetivo: Evaluar el conocimiento sobre el cuidado bucal realizadas por enfermeras en pacientes ventilados mecánicamente. Métodos: Estudio transversal, realizado en un hospital de Goiania y Goias. La recolección de datos se realizó por medio de un cuestionario estructurado. Resultados: Las enfermeras saben las medidas recomendadas en la higiene bucal. Los factores encontrados fueron la falta de personal (21,7%), la falta de tiempo (16,7%) y trabajar en la cinta (15%). Sin embargo todavía hay lagunas en relación con los productos y los materiales utilizados en la higiene bucal. Conclusión: Las brechas y los factores factores indicados en este estudio merecen consideración, como medio de evaluar la calidad de la atención ofrecida.Palabras clave: Biofilme; Higiene Bucal; Atención de Enfermería.

Regulation And Effect Of Telomerase And Telomeric Length In Stem Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Basak Celtikci ◽  
Gulnihal Kulaksiz Erkmen ◽  
Zeliha Gunnur Dikmen
Keyword(s):  
Telomere Length ◽  
Somatic Cells ◽  
Telomere Maintenance ◽  
The Other ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Telomere Shortening ◽  
Maintenance Mechanism ◽  
Associated Diseases ◽  
Human Telomerase

: Telomeres are the protective end caps of eukaryotic chromosomes and they decide the proliferative lifespan of somatic cells, as the guardians of the cell replication. Telomere length in leucocytes reflects telomere length in other somatic cells. Leucocyte telomere length can be a biomarker of human ageing. The risk of diseases, which are associated with reduced cell proliferation and tissue degeneration, including aging or aging-associated diseases, such as dyskeratosis congenita, cardiovascular diseases, pulmonary fibrosis and aplastic anemia, are correlated with an increase in short telomeres. On the other hand, the risk of diseases, which are associated with increased proliferative growth, including major cancers, is correlated with long telomeres. In most of the cancers, a telomere maintenance mechanism during DNA replication is essential. The reactivation of the functional ribonucleoprotein holoenzyme complex [telomerase] starts the cascade from normal and premalignant somatic cells to advanced malignant cells. Telomerase is overexpressed during the development of cancer and embryonic stem cells, through controlling genome integrity, cancer formation and stemness. Cancer cells have mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis, and halting cell division by critically short telomeres. Modulation of the human telomerase reverse transcriptase is the ratelimiting step for the production of functional telomerase and the telomere maintenance. Human telomerase reverse transcriptase promoter promotes its gene expression only in tumor cells, but not in normal cells. Some cancers activate an alternative lengthening of telomeres maintenance mechanism via DNA recombination to unshorten their telomeres. Not only heritability but also oxidative stress, inflammation, environmental factors, and therapeutic interventions have an effect on telomere shortening, explaining the variability in telomere length across individuals. There have been a large number of publications, which correlate human diseases with progressive telomere shortening. Telomere length of an individual at birth is also important to follow up telomere shortening, and it can be used as biomarkers for healthy aging. On the other hand, understanding of cellular stress factors, which affect stem cell behavior, will be useful in regeneration or treatment in cancer and age-associated diseases. In this review, we will understand the connection between stem cell and telomere biology, cancer, and aging-associated diseases. This connection may be useful for discovering novel drug targets and improve outcomes for patients having cancer and aging-associated diseases.

EVALUATION OF TRIBOTECHNICAL PROPERTIES OF THE COATING OBTAINED BY ELECTRIC SPARK HARDENING

2020 ◽  
Vol 4 (141) ◽  
pp. 157-163
Author(s):  
IL’YA ROMANOV ◽  
◽  
ROMAN ZADOROZHNIY
Keyword(s):  
Wear Resistance ◽  
Reference Sample ◽  
Optical Microscope ◽  
Research Purpose ◽  
Tribotechnical Properties ◽  
Uncoated Surface ◽  
Before And After ◽  
Materials Used ◽  
Friction Track

When applying coatings using various methods on the surfaces of moving parts that work in joints, it is important to make sure that the coatings are strong and wear-resistant in order to return them to their original resource. All existing hardening technologies and materials used to perform coatings have their own characteristics, therefore, the quality of the resulting coatings can be judged only after specific tests. (Research purpose) The research purpose is in evaluating the properties of the coating obtained by the method of electric spark hardening, and its ability to resist friction and mechanical wear. (Materials and methods) Authors conducted tests on the basis of the "Nano-Center" center for collective use. A coating was applied on the BIG-4M unit with a VK-8 hard alloy electrode, tribological properties were evaluated on a CSM Instruments TRB-S-DE-0000 tribometer, the width of the friction track was measured after the test using an inverted OLYMPUS gx51 optical microscope, and samples were weighed before and after the test on a VLR-200 analytical balance. Conducted research in accordance with GOST 23.224-86 and RD 50-662-88 guidelines. (Results and discussion) The article presents performed tests on the run-in and wear resistance of the coating. The samples were worked on with a step-by-step increase in the load. During the tests, the friction force was drawed on the diagram. Authors compared the results with the reference sample, an uncoated surface. (Conclusions) The resulting coating has better run-in and wear resistance compared to the standard, and the increase in wear resistance in dry friction conditions is very significant.

scholarly journals Analysis of Quality of Backyard Compost and Its Potential Utilization as a Circular Bio-Waste Source

2021 ◽  
Vol 11 (10) ◽  
pp. 4392
Author(s):  
Apolka Ujj ◽  
Kinga Percsi ◽  
Andras Beres ◽  
Laszlo Aleksza ◽  
Fernanda Ramos Diaz ◽  
...  
Keyword(s):  
Crop Production ◽  
Basic Education ◽  
Raw Materials ◽  
Nutrient Content ◽  
Quality Analysis ◽  
Weed Seed ◽  
Quality Properties ◽  
Seed Dispersion ◽  
Materials Used

The use and quality analysis of household compost have become very important issues in recent years due to the increasing interest in local food production and safe, self-produced food. The phenomenon was further exacerbated by the COVID-19 pandemic quarantine period, which gave new impetus to the growth of small home gardens. However, the knowledge associated with making high-quality compost is often lacking in home gardeners. Therefore, the objective of this research was to find answers to the following questions: can the quality of backyard compost be considered safe in terms of toxicity and nutrient content? Can weed seed dispersion affect the usability of backyard compost? In general, can the circulation of organic matter be increased with the spread of home composting? In this study, 16 different house composts were analysed for stability, weed seed contamination, toxic elements, and nutrient content using analysis of variance. The results of the research showed that the quality properties of the composts (including their weed seed dispersion effect) were greatly influenced by the different techniques and raw materials used. The toxicity levels, as well as the content of macro and microelements, were within the parameters of safe-quality compost. The specific macronutrient (Ca, Mg) and micronutrient (Fe, Mn) contents of the tested composts have a similar and, in some cases, more favorable nutrient supply capacity in crop production than the frequently-used cow manure-based composts. With a plan of basic education on composting, there is potential to encourage farmyard composting.

A Novel Peptide Derived from Ginger Induces Apoptosis through the Modulation of p53, BAX, and BCL2 Expression in Leukemic Cell Lines

Planta Medica ◽  
2021 ◽  
Author(s):  
Chawalit Chatupheeraphat ◽  
Sittiruk Roytrakul ◽  
Narumon Phaonakrop ◽  
Kamolchanok Deesrisak ◽  
Sucheewin Krobthong ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Raji Cell ◽  
Leukemic Cell ◽  
B Cell Lymphoma ◽  
Leukemic Cells ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Peptide Fraction

AbstractDespite the efficacy of chemotherapy, the adverse effects of chemotherapeutic drugs are considered a limitation of leukemia treatment. Therefore, a chemotherapy drug with minimal side effects is currently needed. One interesting molecule for this purpose is a bioactive peptide isolated from plants since it has less toxicity to normal cells. In this study, we extracted protein from the Zingiber officinale rhizome and performed purification to acquire the peptide fraction with the highest cytotoxicity using ultrafiltration, reverse-phase chromatography, and off-gel fractionation to get the peptide fraction that contained the highest cytotoxicity. Finally, a novel antileukemic peptide, P2 (sequence: RALGWSCL), was identified from the highest cytotoxicity fraction. The P2 peptide reduced the cell viability of NB4, MOLT4, and Raji cell lines without an effect on the normal peripheral blood mononuclear cells. The combination of P2 and daunorubicin significantly decreased leukemic cell viability when compared to treatment with either P2 or daunorubicin alone. In addition, leukemic cells treated with P2 demonstrated increased apoptosis and upregulation of caspase 3, 8, and 9 gene expression. Moreover, we also examined the effects of P2 on p53, which is the key regulator of apoptosis. Our results showed that treatment of leukemic cells with P2 led to the upregulation of p53 and Bcl-2-associated X protein, and the downregulation of B-cell lymphoma 2, indicating that p53 is involved in apoptosis induction by P2. The results of this study are anticipated to be useful for the development of P2 as an alternative drug for the treatment of leukemia.

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