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Berlin Brandenburg

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  • 1
    Language: English
    In: The Journal of Urology, January 2015, Vol.193(1), pp.331-337
    Description: Classic serum tumor markers (human chorionic gonadotropin, α1-fetoprotein and lactate dehydrogenase) have an important role in managing testicular germ cell tumor. Since only 60% of all patients with testicular germ cell tumor have elevations of these markers, there is a need for new biomarkers with greater sensitivity/specificity. miRNAs are deregulated in cancer and could serve as noninvasive serum biomarkers. We explored the role of serum miRNAs as a novel biomarker in patients with testicular germ cell tumor. Total RNA was isolated from serum. miRNA levels were quantified by quantitative real-time polymerase chain reaction. We assessed the miRNAs miR-302a-3p, 302b-3p, 302c-3p, 367-3p, 371a-3p, 372-3p and 373-3p in a subcohort of 30 patients with testicular germ cell tumor and 18 healthy subjects. Validation was performed in 76 patients treated with inguinal exploration due to suspicion of testicular germ cell tumor, of whom 59 had cancer and 17 had benign disease, and in 84 healthy male subjects. Serum miR-367-3p, 371a-3p, 372-3p and 373-3p levels were significantly increased in patients with testicular germ cell tumor compared to healthy individuals and patients with nonmalignant testicular disease. In particular miR-371a-3p allowed for sensitive (84.7%) and specific (99%) identification of patients with testicular germ cell tumor, thus, outperforming human chorionic gonadotropin or α1-fetoprotein testing. Furthermore, miR-367-3p was increased in nonseminoma compared to seminoma cases. Serum miRNA levels were increased in patients with advanced local stage and metastasis. In 9 patients with localized (clinical stage 1A) testicular germ cell tumor serum miR-371a-3p levels decreased postoperatively, indicating tumor specific release. miR-371a-3p allows for better identification of testicular germ cell tumor than α1-fetoprotein and human chorionic gonadotropin. It could be helpful for clinically managing testicular germ cell tumor, especially for monitoring surveillance therapy and residual disease after chemotherapy.
    Keywords: Testis ; Testicular Germ Cell Tumor ; Tumor Markers ; Biological ; Serum ; Micrornas ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 2
    Language: English
    In: Current Biomarker Findings, Annual, 2014, Vol.4, p.133(5)
    Description: Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in testicular cancer, but they have a limited sensitivity. Ongoing research may lead to the identification of novel biomarkers. Therefore, we review the experimental analyses for nucleic acids, circulating tumor cells, and proteins as potential biomarkers in the serum of testicular germ cell cancer patients. Keywords: biomarker, serum, testicular germ cell cancer
    Keywords: Chorionic Gonadotropins -- Research ; Testicular Cancer -- Genetic Aspects ; Testicular Cancer -- Diagnosis ; Testicular Cancer -- Research ; Tumor Markers -- Usage ; Tumor Markers -- Health Aspects ; Tumor Markers -- Research
    ISSN: 2230-2492
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Current Biomarker Findings, 2014, Vol.4, p.133(5)
    Description: Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in testicular cancer, but they have a limited sensitivity. Ongoing research may lead to the identification of novel biomarkers. Therefore, we review the experimental analyses for nucleic acids, circulating tumor cells, and proteins as potential biomarkers in the serum of testicular germ cell cancer patients. Keywords: biomarker, serum, testicular germ cell cancer
    Keywords: Chorionic Gonadotropins – Research ; Testicular Cancer – Genetic Aspects ; Testicular Cancer – Diagnosis ; Testicular Cancer – Research ; Tumor Markers – Usage ; Tumor Markers – Health Aspects ; Tumor Markers – Research
    ISSN: 2230-2492
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Annals of Diagnostic Pathology, June 2018, Vol.34, pp.18-26
    Description: The mediator complex consists of 33 subunits and plays a central role in transcription. Studies have already described the involvement of individual subunits, especially in carcinogenesis. With regard to the subunit MED30, this has, so far, only been confirmed in gastric and breast carcinoma. The role of MED30 in urological tumours is unknown. First, a database analysis using cBioPortal was performed for the mRNA expression and survival analysis of MED30 in clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC). The immunohistochemical analysis (IHC) against MED30 was performed on tissue microarrays (TMA), with benign, ccRCC, pRCC samples, and ccRCC-metastases. Intensity evaluation was performed using the IRS (Immunoreactive Score). The ccRCC cell lines ACHN and A-498 were used for the functional investigation of proliferation, migration, and invasion after the knockdown of by siRNA. In a database analysis by cBioPortal, it was shown that mRNA overexpression of in the pRCC was significantly associated with a poorer overall survival and progression-free survival. In the IHC, pRCC showed the highest level of MED30 expression, unfortunately without significant results in the survival analysis. The knockdown of resulted in a significant decrease in proliferation, migration, and invasion in ccRCC. In summary, MED30 seems to be involved in the progression of the RCC.
    Keywords: Mediator Complex Subunit Med30 ; Renal Cell Carcinoma ; Proliferation ; Migration ; Medicine ; Biology
    ISSN: 1092-9134
    E-ISSN: 1532-8198
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  • 5
    Language: English
    In: The Journal of Urology, April 2015, Vol.193(4), pp.e860-e860
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2015.02.2469 Byline: Isabella Syring, Niklas Klumper, Zaki Shaikhibrahim, Anne Offermann, Martin Braun, Mario Deng, Diana Bohm, Angela Queisser, Anne von Ma[sz]enhausen, Jorg Ellinger, Stefan C. Muller, Sven Perner Author Affiliation: Bonn, Germany Article Note: (footnote) Source of Funding: none
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 6
    Language: English
    In: Current Biomarker Findings, 09/2014, p.133
    Description: Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in testicular cancer, but they have a limited sensitivity. Ongoing research may lead to the identification of novel biomarkers. Therefore, we review the experimental analyses for nucleic acids, circulating tumor cells, and proteins as potential biomarkers in the serum of testicular germ cell cancer patients.
    Keywords: Biology;
    ISSN: Current Biomarker Findings
    E-ISSN: 2230-2492
    Source: CrossRef
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  • 7
    Language: English
    In: Clinical cancer research : an official journal of the American Association for Cancer Research, 01 April 2017, Vol.23(7), pp.1829-1840
    Description: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities ( = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer ( = 622) stained by immunohistochemistry. The role of and was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq. Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of In primary prostate cancer, was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. , inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion. Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified and to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. .
    Keywords: Cyclin-Dependent Kinase 8 -- Genetics ; Cyclin-Dependent Kinases -- Genetics ; Mediator Complex -- Genetics ; Prostatic Neoplasms -- Genetics
    ISSN: 1078-0432
    E-ISSN: 15573265
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  • 8
    Language: English
    In: Clinical epigenetics, 2015, Vol.7, pp.10
    Description: Long non-coding RNAs (lncRNA) play an important role in carcinogenesis; knowledge on lncRNA expression in renal cell carcinoma is rudimental. As a basis for biomarker development, we aimed to explore the lncRNA expression profile in clear cell renal cell carcinoma (ccRCC) tissue. Microarray experiments were performed to determine the expression of 32,183 lncRNA transcripts belonging to 17,512 lncRNAs in 15 corresponding normal and malignant renal tissues. Validation was performed using quantitative real-time PCR in 55 ccRCC and 52 normal renal specimens. Computational analysis was performed to determine lncRNA-microRNA (MiRTarget2) and lncRNA-protein (catRAPID omics) interactions. We identified 1,308 dysregulated transcripts (expression change 〉2-fold; upregulated: 568, downregulated: 740) in ccRCC tissue. Among these, aberrant expression was validated using PCR: lnc-BMP2-2 (mean expression change: 37-fold), lnc-CPN2-1 (13-fold), lnc-FZD1-2 (9-fold), lnc-ITPR2-3 (15-fold), lnc-SLC30A4-1 (15-fold), and lnc-SPAM1-6 (10-fold) were highly overexpressed in ccRCC, whereas lnc-ACACA-1 (135-fold), lnc-FOXG1-2 (19-fold), lnc-LCP2-2 (2-fold), lnc-RP3-368B9 (19-fold), and lnc-TTC34-3 (314-fold) were downregulated. There was no correlation between lncRNA expression with clinical-pathological parameters. Computational analyses revealed that these lncRNAs are involved in RNA-protein networks related to splicing, binding, transport, localization, and processing of RNA. Small interfering RNA (siRNA)-mediated knockdown of lnc-BMP2-2 and lnc-CPN2-1 did not influence cell proliferation. We identified many novel lncRNA transcripts dysregulated in ccRCC which may be useful for novel diagnostic biomarkers.
    Keywords: Zoology;
    ISSN: 1868-7075
    E-ISSN: 18687083
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  • 9
    Language: English
    In: Diagnostic pathology, 17 September 2015, Vol.10, pp.165
    Description: Testicular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes. Immunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software. In tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis. In conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15 expression in the preinvasive precursor cells, which may provide diagnostic value to distinguish between benign and pre-malignant testicular specimen, and may indicate a role for MED15 in carcinogenesis in TGCT.
    Keywords: Biomarkers, Tumor -- Analysis ; Mediator Complex -- Biosynthesis ; Neoplasms, Germ Cell and Embryonal -- Pathology ; Testicular Neoplasms -- Pathology
    E-ISSN: 1746-1596
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  • 10
    Language: English
    In: Oncology letters, September 2018, Vol.16(3), pp.3013-3021
    Description: The Mediator complex, a multi-subunit protein complex, plays an integral role in regulating transcription. Genetic alterations of the mediator subunit 15 (MED15) in separate tumor entities have been described previously. However, till now, not much is known about the role of MED15 in urothelial bladder cancer (BCa). Using cBioPortal, database analysis was executed for the mRNA expression and survival analysis of MED15 in BCa. Immunohistochemistry (IHC) analysis against MED15 was performed on tissue microarrays with 18 benign, 126 BCa, and 38 metastases samples. The intensity evaluation was performed using a staining intensity score from 0 to 3 and associated with clinicopathological data. The BCa cell lines T24 and TCCSUP were used for the functional investigation. After the knockdown by small interfering (si)RNA, cell proliferation, migration and invasion were investigated. On the mRNA level, only a low number of alterations (2%) was found for MED15 in BCa. Due to the small count of events, there were no significant differences or tendencies in survival. For IHC, MED15 was found to have a higher expression in non-muscle invasive BCa compared with benign and muscle invasive BCa. For survival analysis, no significant differences between samples with or without overexpression of were found. In the functional analysis, proliferation, migration, and invasion were significantly reduced in BCa-cells following the transient siRNA-mediated knockdown. In summary, MED15 appears to play a role in the tumor parameters proliferation, migration, and invasion in BCa, but further investigations are necessary.
    Keywords: Mediator Complex ; Subunit Med15 ; Urothelial Bladder Cancer
    ISSN: 1792-1074
    E-ISSN: 17921082
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