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  • 1
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    Abstract 76: Comprehensive genomic profiling as an approach to guide therapeutic planning in pediatric patients with high-risk solid tumors
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 76-76
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 76-76
    Abstract: Despite the great achievements in treating pediatric cancer patients in the last several decades, approximately one fifth of patients remains uncurable using standard therapeutic modalities and require search for innovative therapeutic approaches. Advances in sequencing techniques and bioinformatic data processing enabled identification of wide spectrum of molecular alterations including single nucleotide variants, copy number aberrations, fusion genes or changes in expression and methylation patterns, which could serve as therapeutic targets. Translation of comprehensive molecular profiling into clinical practice is still limited, however, multiple precision oncology initiatives have already explored feasibility of this approach. From September 2016 to December 2020, a total of 160 patients with high-risk solid tumors that were treated or consulted at Department of Pediatric Oncology of University Hospital Brno were subjected to molecular analysis of tumor tissue using whole-exome sequencing, targeted RNA sequencing, whole-transcriptome profiling and array-CGH. In 18 patients, 2 or more biopsies were analyzed due to relapse or progression of the disease. In the cohort, CNS tumors were the most prevalent (41%), followed by sarcomas (33%) and neuroblastoma (9%). All patients were presented at multidisciplinary molecular tumor board, where treatment recommendations were discussed. In 37% of patients (n = 59), therapeutic targets were identified. Most commonly identified targets included BRAF (n = 9), FGFR1 (n = 7), NF1 (n = 6), NRAS (n = 5) and PIK3CA (n = 4), making RAS/MAPK signaling most frequently altered pathway in the subgroup. Single nucleotide variants or small indels accounted for 65% of actionable findings, followed by fusion genes (12%), copy number aberrations (9%), CD274 expression (7%, confirmed by IHC staining for PD-L1 protein), and high tumor mutational burden (7%). Clinically relevant fusions were found in 25% of patients and 20% of identified fusions were targetable. 8 patients were eligible for immunotherapy based on either PD-L1 expression, or high tumor mutational burden ( & gt;10 mut/Mb). Using molecular-based approach in treating high-risk patients represents a promising strategy and helps to understand the complexity of pediatric malignancies though examining tumor biology at multiple levels. Implementing the concept of precision oncology into clinical practice could not only be beneficial in the context of chances for improved survival of high-risk patients, but might also be convenient for other patients, whose successful treatment comes at cost of various secondary complications due to intensive chemotherapy/radiotherapy approaches. Supported by Ministry of Health of the Czech Republic, grant nr. NV19-03-00562, NV19-03-00501, NV19-03-00559 and NU20-03-00240. All rights reserved. Citation Format: Petra Pokorna, Hana Palova, Tina Catela Ivkovic, Sona Adamcova, Michal Kyr, Vojtech Bystry, Robin Jugas, Karolina Trachtova, Dagmar Al Tukmachi, Tomas Merta, Jaroslav Juracek, Jiri Sana, Sona Mejstrikova, Marta Jezova, Peter Mudry, Zdenek Pavelka, Jaroslav Sterba, Ondrej Slaby. Comprehensive genomic profiling as an approach to guide therapeutic planning in pediatric patients with high-risk solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 76.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-76
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
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    Abstract 5256: MiRNA-31-5p expression in glioblastoma tissue and effects of its replacement in glioblastoma cells
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 5256-5256
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 5256-5256
    Abstract: Introduction: Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system of adults. Our previous study has showed significant alterations in expression of microRNAs (miRNAs) in GBM tissue. Some of these miRNAs were also correlated with overall survival, whereas miR-31-5p was the most significant, indicating its tumor suppressive functioning. In this study, miR-31-5p was studied on larger cohort of GBM patients and also in vitro of selected GBM cell lines. Patients, Cell lines and Methods: Expression of miR-31-5p was validated on cohort of 58 GBM patients and 10 samples of non-tumor brain tissue. We have increased expression level of miR-31-5p using transient transfection of specific miRNA mimic in GBM cell lines A172, U87MG, T98MG, and U251. Cell viability and proliferation were analyzed using MTT assay and cell counting, respectively. Cell cycle analyses were performed by flow-cytometry using propidium iodide. Migration and invasion potential were measured by the wound healing assay and transwell invasion assay, respectively. Finally, potential targets of miR-31-5p were discovered using combination of bioinformatics algorithms for target prediction and GeneChip Human Gene 2.0 ST Array (Affymetrix) whole-genome expression profiling. Results: Down-regulation of miR-31-5p was successfully validated on cohort of 58 GBM patients and 10 samples of non-tumor brain tissue (p & lt;0.001). MiR-31-5p was significantly associated also with progression-free and overall survival of GBM patients. Transient expression of miR-31-5p led to the significant decrease of GBM cell proliferation and viability in A172, U87MG, T98G, and U251 cell lines (t-test; p & lt; 0.05) due to the cell cycle arrest in G1 phase. Moreover, transfected A172 and U251 cells had a lower migration and invasiveness potential in comparison with control cells (t-test; p & lt; 0.05). Finally, analysis of global gene expression profiles together with predicted mRNA targets revealed several interesting targets of miR-31-5p, which are involved in crucial signaling pathways of GBM. Conclusion: Taken together, our data suggest that miR-31-5p is not only powerful diagnostic marker as showed previously but seems to be promising therapeutic target in GBM patients. This work was supported by grants of Internal Grant Agency of the Czech Ministry of Health no. NT13514-4/2012, NT/13860-4/2012, NT/13549-4/2012, NT/13547-4/2012; and project “CEITEC - Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068). Citation Format: Jiri Sana, Andrej Besse, Jakub Ondracek, Marek Vecera, Pavel Fadrus, Leos Kren, Hana Mlcochova, Robert Illiev, Jitka Mlcochova, Petra Vychytilova, Renata Hezova, Jaroslav Juracek, Ondrej Slaby. MiRNA-31-5p expression in glioblastoma tissue and effects of its replacement in glioblastoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5256. doi:10.1158/1538-7445.AM2015-5256
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-5256
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 3
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    Abstract 1959: Global microRNA expression analysis of Sox-2 positive and negative glioblastoma cells
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1959-1959
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1959-1959
    Abstract: Introduction: Glioblastoma multiforme (GBM) is the most frequent intracranial malignity of astrocytic origin in adults. This tumor is characterized by infaust prognosis, which is primarily caused by resistance to the therapy and early relapses relate to the presence of glioblastoma stem cells (GSCs). These cells form neurospheres in vitro and express markers of stemness such as Sox-2, Oct-4, and nestin. Targeting of GSCs could be a novel promising therapeutic approach leading to the overcome of therapy resistance and better prognosis of GBM patients. One of the approaches how to successfully regulate GSC is a targeted regulation of microRNAs (miRNAs). These small non-coding RNA molecules post-transcriptionally regulate an expression of more than 2/3 of all human genes that are also involved in stem cell associated signaling pathways. Moreover, deregulated expression of some miRNAs has been observed in many cancers including GBM. Cell lines and Methods: We have prepared eleven Sox-2 positive and negative paired primary GBM cell lines, which have been cultured under DMEM/F12 medium supplemented with bFGF, EGF, and B12 supplement and DMEM medium supplemented with 10% FBS, respectively. The global miRNA expression analysis was performed using GeneChip miRNA 4.0 Array (Affymetrix). Targeted regulation of miRNA levels have been carried out by the transient transfection of specific anti-miRNAs or miRNA mimics in GSC cell lines NCH 601 acquired from Interdisciplinary Center For Neurosciences (Heidelberg, Germany). The sphere formation assay was analyzed using IncuCyte ZOOM instrument (Essen BioScience). Sox-2 and nestin expressions were analyzed on both protein and transcriptional levels using combination of PAGE with Western blotting and real-time PCR, respectively. Results: Analysis of Sox-2 positive and negative paired GBM cell lines revealed 29 differentially expressed miRNAs, from which miR-93-3p, miR-95-5p, miR-106b-5p, miR-22-3p, and miR-3195 showed high significance (adjust. P value & lt; 0.05) and association with both Sox-2 (Spearman R; p & lt; 0.002) and nestin (Spearman R; p & lt; 0.02) expressions. MiR-22-3p and miR-3195 showed lower expression whereas other miRNAs higher expression in Sox-2 positive GBM cells. The in vitro analyses also suggest that miR-22-3p and miR-106b-5p affect the sphere formation potential and Sox-2 expression in GSC cells. Conclusion: Taken together, our data suggest that miR-22-3p and miR-106b-5p are probably involved in GSC biology and, thus, should be promising molecular targets to overcome GBM therapeutic resistance. This work was supported by Ministry of Health of the Czech Republic, grant nr. 15-33158A, 15-34553A, 15-31627A and 15-34678A. All rights reserved. Citation Format: Jiri Sana, Marek Vecera, Romana Butova, Pavel Fadrus, Leos Kren, Jaroslav Juracek, Robert Illiev, Jitka Mlcochova, Zuzana Ozanova, Petra Vychytilova, Ondrej Slaby. Global microRNA expression analysis of Sox-2 positive and negative glioblastoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1959.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-1959
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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    Abstract 237: Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 237-237
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 237-237
    Abstract: Introduction: Piwi-interacting RNAs (piRNAs) consists a newly discovered class of non-coding RNA. PiRNAs were first identified in the germ cells of various animal species. They bind to Piwi proteins which are a subfamily of Argonaut proteins. In humans were identified four Ago genes and four Piwi genes. Human Piwi genes include PIWIL1, PIWIL2, PIWIL3 and PIWIL4. Recent studies suggest that deregulated expression of Piwi proteins is common to many types of tumors and also correlate with clinicopathologic features and worse prognosis in patients with breast, cervical, ovarian, colorectal and other cancers. PiRNAs are short single-stranded RNAs with 26-31 nucleotides in length. They are involved in silencing of transposable elements and it is assumed that also participate in sequence-specific chromatin modifications. The differential expression of piRNAs was found in gastric and breast cancer. In our pilot study we analyzed expression of Piwi genes and piR-651, which was previously found to be deregulated in various types of tumors. Patients and Methods: In our study, we have used the tumor tissue and the paired renal parenchyma tissue of 56 patients with renal cell carcinoma (RCC). From the tissue was isolated total RNA and by RT-qPCR were examined the expression of Piwi genes and piR-651. For the analysis of circulating piR-651, blood serum samples of 75 patients with RCC and 75 age, gender-matched healthy donors were used. We have compared expression levels of the studied genes in tumor and non-tumor tissues, serum samples, and also correlated them with clinicopathologic features of RCC patients (stage, grade, RFS, OS). Results: We found a significant down-regulation of PIWIL1 (p & lt;0,0001) and piR-651 (p & lt;0,0001) expression levels in tumor tissue when compared to paired renal parenchyma samples. The expression levels of PIWIL2, PIWIL3 and PIWIL4 were not significantly deregulated in tumor tissue. Interestingly, levels of PIWIL2 and PIWIL4 correlated significantly with the stage (p = 0,002 and p = 0,003, resp.) and grade (p = 0.007 and p & lt;0.0001, resp.) of RCC. We found also a correlation between higher levels of PIWIL1 and overall survival (p & lt;0.05). We have observed significantly decreased expression levels of piR-651 in blood serum samples of RCC patients when compared to healthy donors and accordingly to ROC analysis we were able to distinguish blood serum of RCC patients and control subjects with the sensitivity of 77.33% and a specificity of 72.37%. Expression levels of serum piR-651 were not in correlation with the stage and grade of RCC. Conclusion: Accordingly to our pilot data expression of Piwi genes is altered in tumor tissue and is correlated to selected clinicopathologic features of RCC. We also suggest the potential of piR-651 in blood serum as novel non-invasive diagnostic biomarker in RCC. Acknowledgments: IGA MZCR No: NT/13860-4/2012, NT/13549-4/2012, NT/13547-4/2012, NT/13514-4/2012 Citation Format: Robert Iliev, Petra Vychytilova-Faltejskova, Jaroslav Juracek, Hana Mlcochova, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby. Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 237. doi:10.1158/1538-7445.AM2015-237
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-237
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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    Genome‐wide identification of urinary cell‐free micro RNA s for non‐invasive detection of bladder cancer
    Wiley ; 2018
    In:  Journal of Cellular and Molecular Medicine Vol. 22, No. 3 ( 2018-03), p. 2033-2038
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 3 ( 2018-03), p. 2033-2038
    Abstract: Urinary micro RNA s (mi RNA s) are emerging as clinically useful tool for early and non‐invasive detection of various types of cancer including bladder cancer ( BCA ). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary mi RNA s were obtained using Affymetrix mi RNA microarrays (2578 mi RNA s) and candidate mi RNA s further validated in independent cohorts using qRT ‐ PCR . Whole‐genome profiling identified 76 mi RNA s with significantly different concentrations in urine of BCA compared to controls ( P   〈  0.01). In the training and independent validation phase of the study, miR‐31‐5p, miR‐93‐5p and miR‐191‐5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls ( P   〈  0.01). We further established 2‐mi RNA ‐based urinary DxScore (miR‐93‐5p, miR‐31‐5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post‐operatively. In conclusion, we identified and independently validated cell‐free urinary mi RNA s as promising biomarkers enabling non‐invasive detection of BCA .
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.2018.22.issue-3
    DOI: 10.1111/jcmm.13487
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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    Abstract 521: Dynamic measurements of circulating microRNAs reflect different biological effects of radiofrequency ablation and transarterial chemoembolisation in liver cancer patients
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 521-521
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 521-521
    Abstract: Introduction: The majority of primary or metastatic liver tumors are unresectable (because of tumor size, location, poor performance status or multifocality), therefore other therapeutic modalities as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) are applied. RFA is a localized thermal treatment technique designed to produce tumor destruction by heating tumor tissue, while TACE combines cytotoxic effect of particle based tumor ischemia and locoregional chemotherapy. Both methods cause characteristic changes in liver tissue (inflammation, hypoxia, elevated temperature, tissue destruction) accompanied by targeted systemic secretion of microRNA into the bloodstream. Since RFA and TACE differ in the dynamics with which they affects the tumor tissue, we aimed to investigate whether the expression level of circulating microRNAs related to hypoxia (miR-21 and miR-210), liver injury (miR-122) and epithelial-mesenchymal transition (miR-200a) could reflect such changes. Material and methods: This study consisted of 14 patients diagnosed with primary hepatocellular carcinoma (HCC) (median age 73; TACE) and 20 patients diagnosed with liver metastases of colorectal cancer (median age 63; 17 patients - RFA, 3 patients - TACE). RFA was performed using the rf/mw generator (AngioDynamics). For TACE drug eluting beads (Biocompatibles Ltd.) loaded with irinotecan for mCRC patients and doxorubicin for HCC patients were used. The concentrations of miRNA were determined for all patients in series of blood plasma from 4 time points (before intervention, immediately after intervention, 24 hours after intervention, 1 week after intervention) using miRNA-specific TaqMan assays and qRT-PCR method. Results: In RFA cases we observed significant increase of investigated miRNA concentrations immediately after intervention (miR-122, FC = 15, P = 0.0002; miR-200a, FC = 1.9, P = 0.015). In TACE we observed delayed increase in circulating miRNA concentrations at time point 24 hours after intervention (miR-21, FC = 10.4, P & lt; 0.0001; miR-210, FC = 9.0, P = 0.03; miR-122, FC = 27, P = 0.0004; miR-200a, FC = 4.0, P = 0.0098). In both methods, the initial increase was followed by a steady decline of miRNA levels. Identified dynamic changes in circulating miRNA levels were in accordance with the nature of RFA and TACE biologic effects. In selected cases, we observed specific dynamic miRNA patterns to be linked to the course of the disease (e.g. necessity of additional intervention). Conclusions: Our preliminary data indicates potential usage of circulating miRNAs for monitoring of the systemic effects of RFA and TACE therapy and their ability to reflect efficacy of intervention procedures. This work was supported by Ministry of Health of the Czech Republic, grant nr. 15-33158A, 15-34553A, 15-31627A, 16-31314A, and 15-34678A. Citation Format: Jaroslav Juracek, Tomas Andrasina, Barbora Cechova, Petra Vesela, Jan Zavadil, Tana Machackova, Jiri Sana, Marek Vecera, Natalia Gablo, Marek Svoboda, Nahum Goldberg, Ondrej Slaby. Dynamic measurements of circulating microRNAs reflect different biological effects of radiofrequency ablation and transarterial chemoembolisation in liver cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 521.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-521
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    Abstract 5409: Deep sequencing of circulating microRNAs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5409-5409
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5409-5409
    Abstract: Introduction: Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy (CHRT) with fluoropyrimidines followed by radical surgical resection. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers of response to CHRT in rectal cancer patients. Materials and Methods: In prospective one-center study, 48 patients diagnosed with rectal cancer who underwent neoadjuvant chemoradiotherapy followed by surgical treatment were included. Blood plasma samples were collected before the neoadjuvant chemoradiotherapy (in 24 cases) and after the therapy at the time of clinical restaging (in 48 cases). Total RNA was isolated from 72 blood plasma samples of 48 patients. cDNA libraries were prepared using CleanTaq Small RNA Library Prep Kit (TriLink BioTechnologies). The final sequencing analyses were performed by Next 500/550 High Output v2 Kit - 75 cycles using the NextSeq 500 instrument (both Illumina). For miRNA mapping and analysis, an online tool Chimira was used. Obtained data were statistically evaluated using the Bioconductor edgeR and DESeq2 package. Results: When miRNA profiles of samples collected before and after therapy were compared, 10 miRNAs showed higher levels and of 2 miRNAs lower levels in pre-treatment specimens (P & lt;0.05). Samples collected at the time of clinical restaging were divided into groups accordingly to tumor regression grade (Dworak score) evaluated after surgical resection of the tumor. Pre-treatment miRNA profiles of patients from CHRT responsive group (Dworak 3+4) and non-responsive group (Dworak 1+2) were compared and 4 miRNAs were upregulated and 4 miRNAs were downregulated in patients with good response to CHRT. Finally, samples collected after the therapy, at the time of clinical restaging, were divided into groups accordingly to the nodal metastatic involvement and 10 miRNAs were identified to be significantly deregulated between groups (P & lt;0.025). Conclusion: Our findings suggest that circulating miRNAs could serve as potential predictive biomarkers of the response to neoadjuvant CHRT in rectal cancer. This work was supported by Ministry of Health of the Czech Republic, grant nr.15-33158A, 15-34553A, 15-31627A, 15-34678A, 16-31314A, 16-31765A and by grant of Czech Grant Agency nr. 16-18257S. Citation Format: Tana Machackova, Dominika Brchnelova, Zdenek Kala, Vladimir Prochazka, Tomas Grolich, Lukas Fiala, Beata Hemmelova, Jaroslav Juracek, Marek Vecera, Jiri Sana, Natalia Gablo, Parwez Ahmad, Marek Svoboda, Ondrej Slaby. Deep sequencing of circulating microRNAs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5409.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-5409
    RVK:
    XA 36000
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    Abstract 1953: MiRNA and piRNA expression profiles in renal cell carcinoma tissue detected by next generation sequencing
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1953-1953
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1953-1953
    Abstract: MicroRNAs (miRNAs) are the class of small non-coding RNAs, about 21-25 nucleotides in length, that play an important role in regulation of transcription. They affect gene expression at post-transcriptional levels through binding to complementary mRNAs and mediate their degradation in RISC complex. Piwi-interacting RNAs (piRNAs) is newly discovered class of non-coding RNA. PiRNAs are short single-stranded RNAs with 26-31 nucleotides in length. They are involved in silencing of transposable elements and it is assumed that also participate in sequence-specific chromatin modifications. It was repeatedly shown that piRNAs are present also in somatic cells and are dysregulated in kidney, bladder, gastric, breast, pancreatic and liver cancers. According to small non-coding RNA databases there are about 2600 mature miRNAs and more than 24 000 piRNAs in humans. There were extensive studies aiming to discover miRNAs and to analyze their functions. However, there are only few published studies of miRNA and piRNA profiles in renal cell carcinoma (RCC) using next generation sequencing (NGS) technology. In our study we used the tumor tissue and the paired adjacent non-tumor renal parenchyma of 12 patients (8 males and 4 females) with RCC treated in Masaryk Memorial Cancer Institute (Brno, Czech Republic). RNA was isolated with mirVana™ miRNA Isolation Kit. For preparing RNA library was used TruSeq Small RNA Sample Preparation Kit from Illumina and then the miSeq sequencing technology was employed to detect small RNAs. In our 12 paired samples of tumor tissue and the paired adjacent non-tumor renal parenchyma we detected 283 miRNAs with over 1 read in at least 7 samples. Expression levels of 55 miRNAs were significantly different expressed (p & lt; 0.05) in tumor tissue and adjacent non-tumor parenchyma. Among miRNAs with the most significantly altered expression (p & lt; 0.01) were for example, miR-129, miR-138, miR-142, miR-149, miR-154, miR-155, miR-200b, miR-210, miR-218, miR-340, miR-584, miR-885, miR-891a, miR-1270, miR-3690 and miR-7641. After analyzing piRNA sequences we found 440 piRNAs with over 1 read in at least 7 samples. From these piRNAs were 38 piRNAs significantly deregulated (p & lt;0.01) in RCC tissue, whereas the most significantly different expression levels were determined in piR-1207, piR-2107, piR-2155, piR-12487, piR-12488, piR-21508, piR-23230, piR-26525, piR-26527and piR-28131. In our pilot study we found altered expression patterns of miRNAs and piRNAs in tumor tissue of RCC and paired adjacent non-tumor renal parenchyma. For the first time, we have described piRNAs expression profile in RCC tissue by NGS approach. This work was supported by Ministry of Health of the Czech Republic, grant nr. 15-33158A, 15-34553A, 15-31627A and 15-34678A. All rights reserved. Citation Format: Robert Iliev, Petra Faltejskova-Vychytilova, Zuzana Ozanova, Silvia Rybecka, Jaroslav Juracek, Jitka Mlcochova, Lenka Radova, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Ondrej Slaby. MiRNA and piRNA expression profiles in renal cell carcinoma tissue detected by next generation sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1953.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-1953
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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    Abstract 5406: Predictive value of tumor microRNAs in head and neck cancer patients treated with intensity-modulated radiation therapy
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5406-5406
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    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5406-5406
    Abstract: Introduction: Head and neck cancers are the sixth most common cancers worldwide mainly represented by the squamous cell carcinoma (HNSCC). Very important treatment modality in HNSCC is radiotherapy (RT). Closed as well as ongoing clinical trials are evaluating especially potential for reduced-dose RT in less aggressive radiosensitive HNSCC defined by human papillomavirus (HPV) positivity, with promise of less acute and late toxicity. To this end, variety of different biomarkers with promising predictive value is currently investigated in HNSCC. MicroRNAs (miRNAs) are short endogenous RNAs that post-transcriptionally modulate gene expression and their deregulated expression has been observed in many cancers including HNSCC. Specific expression patterns of miRNAs have been also shown to predict prognosis and therapeutic response in HNSCC. Aim of our study was to identify tumor tissue miRNAs enabling of predict locoregional control (LRC) in HNSCC patients who underwent intensity-modulated RT. Materials and methods: We have analyzed global miRNA expression profiles in 43 FFPE tumor biopsies collected from HNSCC patients treated with intensity-modulated radiation therapy, who were divided into two groups according to their LRC as follows: short LRC [n = 22; median 5.1 months (min 1.3, max 18.6)] vs. long LRC [n = 21; 60.4 (46.8, 98.8)] . This analysis has been performed using the hybridization Affymetrix GeneChip miRNA 4.0 array. Validation of miRNA candidates was performed in independent cohort of 64 HNSCC patients. MiRNA determination was carried out by RT qPCR technology using the miRNA-specific RT stem-loop primers according to the Taq-Man MicroRNA Assay protocol (Thermo Fisher Scientific). Results: We identified 24 miRNAs with significantly different expression between both examined groups (p & lt; 0.05; average log(Fold Change) = 0.42). Based on pre-defined critera, 12 miRNAs were selected for independent validation, from which miR-421 and miR-1228 were differentially expressed between groups of patients with short and long LRC. Moreover, risk-score based on combination of these 2 miRNAs expression and CD44 status enabled to predict 3-years LRC with 82% sensitivity and 82% specificity (AUC = 0.798). Conclusion: Our results suggest that miR-421 and miR-1228 are promising predictive biomarkers in HNSCC patients treated with intensity-modulated RT. This work was supported by Ministry of Health of the Czech Republic, grant nr. 15-34553A, 15-33158A, 15-31627A, 15-34678A, 16-31314A and 16-31765A. Citation Format: Parwez Ahmad, Jiri Sana, Marek Vecera, Jaroslav Juracek, Tana Machackova, Natalia Anna Gablo, Marek Svoboda, Marketa Hermanova, Marek Slavik, Pavel Slampa, Pavel Smilek, Ondrej Slaby. Predictive value of tumor microRNAs in head and neck cancer patients treated with intensity-modulated radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5406.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-5406
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    Abstract 4976: Small RNA sequencing of preoperative blood plasma identifies microRNA signature enabling to find pancreatic cancer patients who will not benefit from surgical resection
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4976-4976
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4976-4976
    Abstract: Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer, associated with limited treatment options and high mortality rates. Radical resection remains the most effective curative approach for patients in early stage of disease. However, there is a high risk of surgical morbidity/mortality, and therefore development of prognostic assays to identify those patients who will not benefit from surgical resection, present important unmet medical need. miRNAs are small, non-coding RNAs, that post-transcriptionally regulate gene expression. miRNAs are frequently deregulated under pathological conditions including PDAC and therefore present promising candidates for new prognostic biomarkers in PDAC. Materials and methods: We analyzed preoperative plasma samples obtained from 45 PDAC patients who underwent radical tumor resection. Patients were divided into two prognostic groups: 23 patients with poor prognosis (median overall survival (OS) = 10 months) and 22 patients with good prognosis (median OS = 25 months). cDNA libraries were prepared using CleanTaq Small RNA Library Prep Kit (TriLink). The sequencing analysis were performed by Next 500/550 High Output v2 Kit - 75 cycles using the NextSeq 500 instrument (both Illumina). For miRNA mapping and analysis, an online tool Chimira was used. Obtained data were statistically evaluated using the Bioconductor edgeR and DESeq2 package. Results: When miRNA expression profiles of the patients from good and poor prognostic group were compared, 41 miRNAs were identified to have significantly different plasma levels between the two groups (P & lt;0.05). Out of these miRNAs, 33 were found to have significantly higher levels in plasma samples of patients with poor prognosis (e.g. mir-376a-3p, mir-6763-5p, mir-885-3p, mir-1258, mir-192-5p, mir-6751-5p, mir-891a-5p, mir-3178, mir-3173-3p, mir-378g, mir-4453, mir-6764-5p, mir-556-5p, mir-6836-5p, mir-6516-5p), and 8 miRNAs have lower levels (mir-885-3p, mir-192-5p, mir-3178, mir-8072, mir-378d, mir-99a-5p, mir-30a-5p, mir-1976) compared to those with good prognosis. Conclusion: Our findings suggest, that there is a blood plasma miRNAs signature associated with the prognosis of PDAC patients, and after independent validation, miRNAs from this signature may allow for a prognostic stratification of PDAC patients. This work was supported by Ministry of Health of the Czech Republic, grant nr.15-33158A, 15-34553A, 15-31627A, 15-34678A, 16-31314A, 16-31765A and by grant of Czech Grant Agency nr. 16-18257S. Citation Format: Natalia Gablo, Vladimir Prochazka, Tana Machackova, Eva Vencovska, Zdenek Kala, Jiri Sana, Parwez Ahmad, Jaroslav Juracek, Marek Vecera, Marek Svoboda, Ondrej Slaby. Small RNA sequencing of preoperative blood plasma identifies microRNA signature enabling to find pancreatic cancer patients who will not benefit from surgical resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4976.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-4976
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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