Jörg D Hoheisel's research while affiliated with German Cancer Research Center and other places
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Publications (350)
Background: Most of pancreatic cancer patients are diagnosed at late stage due to the inability of early diagnosis for pancreatic ductal adenocarcinoma (PDAC), finally leading to a very high mortality. Therefore the identification of effective biomarkers for the early diagnosis of PDAC has a critical significance for improving the outcome of PDAC p...
Gold compounds have a long history of use as immunosuppressants, but their precise mechanism of action is not completely understood. Using our recently developed liver-on-a-chip platform we now show that gold compounds containing planar N-heterocyclic carbene (NHC) ligands are potent ligands for the aryl hydrocarbon receptor (AHR). Further studies...
Despite recent advances in N6-methyladenosine (m6A) biology, the regulation of crucial RNA processing steps by the RNA methyltransferase-like 3 (METTL3) in glioma stem-like cells (GSCs) remains obscure. An integrated analysis of m6A-RIP (RNA immunoprecipitation) and total RNA-Seq of METTL3-silenced GSCs identified that m6A modification in GSCs is p...
Until recently, whole-proteome microarrays for comprehensive studies of protein interactions were mostly produced by individual cloning and cellular expression of very many open reading frames, followed by protein isolation and purification as well as array production. To overcome this cumbersome process, we have developed a method to generate micr...
Glioblastoma (GBM) is the most aggressive form of adult brain tumors with a poor median survival of less than 15 months. The alkylating agent temozolomide is used for chemotherapy for GBM. Regardless of the rigorous therapeutic regime, almost all cases develop resistance and recur. The mechanisms of the inherent and acquired resistance are less und...
Nanobodies represent the variable binding domain of camelid heavy-chain antibodies and are employed in a rapidly growing range of applications in biotechnology and biomedicine. Their success is based on unique properties including their reported ability to reversibly refold after heat-induced denaturation. This view, however, is contrasted by studi...
Using Chlamydia trachomatis (Ct) as a complex model organism, we describe a method to generate bacterial whole-proteome microarrays using cell-free, on-chip protein expression. Expression constructs were generated by two successive PCRs directly from bacterial genomic DNA. Bacterial proteins expressed on microarrays display antigenic epitopes, ther...
Transcriptional profiling was performed on 452 RNA preparations isolated from various types of pancreatic tissue from tumour patients and healthy donors, with a particular focus on peritumoral samples. Pancreatic ductal adenocarcinomas (PDAC) and cystic tumours were most different in these non-tumorous tissues surrounding them, whereas the actual t...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. With an overall five-year survival rate remaining below 6%, there is an explicit need to search for new molecular targets for therapeutic interventions. We undertook a barcode labelled short-hairpin (shRNA) library screen in pancreatic cancer cells in order to identify...
We are analyzing in detail the molecular communication between the different cell types in the microenvironment of pancreatic ductal adenocarcinomas (PDAC). Also, its regulation is being investigated, looking at aspects such as the kind and mixture of molecules needed for triggering a particular regulative function, and unraveling the inter- and in...
Introduction and aims: Although the overall five-year survival of all patients with cancer stands at 63%, for pancreatic cancer patients, it is a disheartening 8% - a number that remains largely unchanged for three decades. Of the patients diagnosed with pancreatic cancer, about 85% exhibit pancreatic ductal adenocarcinoma (PDAC). Most of these pat...
The CAF1-NOT complex of Trypanosoma brucei, like that of other eukaryotes, contains several NOT proteins (NOT1, NOT3, NOT3/5, NOT10, and NOT11), NOT9/CAF40, and the CAF1 deadenylase, which targets 3' poly(A) tails. Again like other eukaryotes, deadenylation is the first step in the degradation of most trypanosome mRNAs. In animal cells, destruction...
Background:
Variable domains of camelid heavy-chain antibodies, commonly named nanobodies, have high biotechnological potential. In view of their broad range of applications in research, diagnostics and therapy, engineering their stability is of particular interest. One important aspect is the improvement of thermostability, because it can have im...
DNA sequencing has advanced to a state that permits studying the genomes of individual patients as nearly a matter of routine. Towards analysing a tissue’s protein content in a similar manner, we established a method for the production of microarrays that represent full-length proteins as they are encoded in individual specimens, exhibiting the par...
Pancreatic cancer is the currently most lethal malignancy. Toward an accurate diagnosis of the disease in body liquids, we studied the protein composition of the secretomes of 16 primary and established cell lines of pancreatic ductal adenocarcinoma (PDAC). Compared to the secretome of non-tumorous cells, 112 proteins exhibited significantly differ...
The CRISPR/Cas9 system is a recently developed genome editing technique. In this study, we used a modified CRISPR system, which employs the fusion of inactive Cas9 (dCas9) and the FokI endonuclease (FokI-dCas9) to correct the most common variant (allele frequency 21.4%) in the phenylalanine hydroxylase (PAH) gene - c.1222C>T (p.Arg408Trp) - as an a...
Many diagnostic and therapeutic concepts require antibodies of high specificity. Recombinant binder libraries and related selection approaches allow the efficient isolation of antibodies against almost every target of interest. Nevertheless, it cannot be guaranteed that selected antibodies perform well and interact specifically enough with analytes...
Background & aims:
Incidence of and mortality from pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, are almost equivalent, so better treatments are needed. We studied gene expression profiles of PDACs and the functions of genes with altered expression to identify new therapeutic targets.
Methods:
We performed m...
Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialize...
In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were...
Significance:
Changes in platelet concentrate (PC) supernatants during storage have been so far only poorly addressed and high abundant proteins burden the identification of quantitative changes in the secretome. We applied a high-throughput antibody microarray allowing for the sensitive quantification of 673 extracellular factors. PCs account for...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasis-associated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter me...
Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed stron...
Control of gene expression at the post-transcriptional level is essential in all organisms, and RNA-binding proteins play critical roles from mRNA synthesis to decay. To fully understand this process, it is necessary to identify the complete set of RNA-binding proteins and the functional consequences of the protein-mRNA interactions. Here, we provi...
The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera f...
Introduction:
Pancreatic ductal adenocarcinoma (PDAC) is by far the most common type of pancreatic cancer. It constitutes about 90% of tumors of the exocrine pancreas. The aggressive nature of PDAC along with its poor diagnostic markers contributes to a high lethality of this disease. Studies from other cancer entities implicate the role of viruses...
Meaningful profiling of pancreatic cancer samples is particularly challenging due to their complex cellular composition. Beyond tumor cells, surgical biopsies contain desmoplastic stroma with infiltrating inflammatory cells, adjacent normal parenchyma, and "non-pancreatic tissues". The risk of misinterpretation rises when the heterogeneous cancer t...
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures i...
To identify miRNAs whose expression are differentially regulated during trypanosome infections a microarray targeting more than 600 rat miRNA was used to analyze the miRNA expression profiles between uninfected rats and animals infected by Trypanosoma congolense and Trypanosoma brucei s.l. The potential targets of dysregulated miRNAs as well as the...
After the establishment of DNA/RNA sequencing as a means of clinical diagnosis, the analysis of the proteome is next in line. As a matter of fact, proteome-based diagnostics is bound to be even more informative, since proteins are directly involved in the actual cellular processes that are responsible for disease. However, the structural variation...
Identification of a single molecular trait that is determinant of common malignancies may serve as a powerful diagnostic supplement to cancer type-specific markers. Here, we report a DNA methylation mark that is characteristic of seven studied malignancies, namely cancers of lung, breast, prostate, pancreas, colorectum, glioblastoma and B cell chro...
BackgroundmiRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists.Methods
We evaluated genome-wide circulating profil...
GISTs have distinct gene expression patterns according to localisation, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA ex...
Stroke induces a profound neuroinflammatory reaction that leads to secondary cerebral tissue injury. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that is endogenously produced by immune cells and limits this inflammatory reaction. Previously, therapeutic administration of IL-10 has been shown to be neuroprotective in experimental stro...
About 70% of newly diagnosed cases of bladder cancer are low-stage, low-grade, non muscle-invasive. Standard treatment is transurethral resection. About 60% of the tumours will recur, however, and in part progress to become invasive. Therefore, surveillance cystoscopy is performed after resection. However, in the USA and Europe alone, about 54,000...
In trypanosomatids, gene expression is regulated mainly by post-transcriptional mechanisms, which affect mRNA processing, translation and degradation. Currently, our understanding of factors that regulate either mRNA stability or translation is rather limited. We know that often, the regulators are proteins that bind to the 3'-untranslated region;...
Exchange of molecules via exosomes is a means of eukaryotic intercellular communication, especially within tumour microenvironments. However, no data are available on alterations of exosomal molecular cargo by environmental cues (eg, pharmacological treatments). To approach this issue, we compared the abundance of 754 miRNAs and 741 cancer-related...
Synthetic lethality is an appealing technique for selectively targeting cancer cells which have acquired molecular changes that distinguish them from normal cells. High-throughput RNAi-based screens have been successfully used to identify synthetic lethal pathways with well-characterized tumor suppressors and oncogenes. The recent identification of...
Genome sequencing has led to the identification of many proteins, which had not been recognized before. In consequence, the basic set of human proteins is generally known. Far less information, however, exists about protein-protein interactions, which are required and responsible for cellular activities and their control. Many protein isoforms that...
Abstract
The quest for a better understanding of organisms, and the human body in particular, at a comprehensive
level has stimulated the development of techniques and processes that permit the analysis and assessment of
biomedical information at high throughput. This has had substantial impact, not only by merely gathering knowledge
but also by...
The gold standard for determining the tumorigenic potential of human cancer cells is a xenotransplantation into immunodeficient mice. Higher tumorigenicity of cells is associated with earlier tumor onset. Here, we used xenotransplantation to assess the tumorigenic potential of human breast cancer cells following RNA interference-mediated inhibition...
In this study, plasma samples from a multicentric case-control study on lymphoma were analyzed for the identification of proteins useful for diagnosis.
The protein content in the plasma of 100 patients suffering from the three most common B-cell lymphomas and 100 control samples was studied with antibody microarrays composed of 810 antibodies that...
Breast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well as chemoresistance. Consequently, great efforts have been made to understand the molecular mechanisms underlying cancer stem cell maintenance. In order to study these rare cells in-vitro, they are typically enriched via mammosphere culture....
Pancreatic stellate cells are key mediators in chronic pancreatitis and play a central role in the development of pancreatic
fibrosis, stromal formation, and progression of pancreatic cancer. This study was aimed at investigating molecular changes
at the level of the proteome that are associated with the activation of pancreatic stellate cells by p...
Pancreatic cancer is one of the leading cancer-related causes of death in the western world with an urgent need for new treatment strategies. Recently, hyperforin and nemorosone have been described as promising anti-cancer lead compounds. While hyperforin has been thoroughly investigated in vitro and in vivo, in vivo data for nemorosone are still m...
Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II) and without (stage I) brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from per...
mRNAs with significantly altered abundance in sleeping sickness patients. Sheet 1: Results for individual patients are shown, with a corresponding result for pooled controls. Sheet 2: Annotations from GeneCARD for the regulated genes.
(XLSX)
Predicted targets of the miRNAs that were significantly changed in sleeping sickness samples. Only mRNAs that also showed a change in expression are included.
(XLS)
Chemotherapy of advanced pancreatic cancer has mainly been gemcitabine-based for the past fifteen years, with only limited effect. Recently, combination therapy that also targets checkpoint kinase 1 (CHK1) has become an attractive option. The central role of CHK1 in many DNA damage response pathways, however, may result in undesired cytotoxicity in...
Histomorphological examination of pancreatic tumor tissue sections with Hematoxylin and Eosin stains. Representative photomicrographs of three sections with low, medium and high tumor contents are shown.
(TIF)
Clinico-pathological details and tumor mutational status of all pancreatic cancer patients.
(DOC)
KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only...
Kaplan-Meier survival curves showing difference in overall survival in exocrine cancer patients with and without mutations. (A) Median survival of patients with KRAS mutations was 17 months against 30 months for patients without mutations in the gene. (B) Median survival of patients with KRAS codon 12 GGT>GAT (G12D) mutations was 16 months against...
Mutation frequency by clinic pathology and effect on survival of pancreatic cancer patients.
(DOC)
Representative SSCP of KRAS codon 12 and codon 61 in pancreatic tumors. (A) The lanes 1–4 contain amplified fragments of exon 2 (codon 12) and lanes 5–6 contain amplified fragments of exon 3 (codon 61) from tumor DNA samples. The shifted bands seen in lane 1 contain GGT>GAT (G12D) mutation, lane 2 contains GGT>CGT (G12R), lane 3 contains GGT>GTT (G...
Primer sequences and SSCP conditions for detection of mutations in the KRAS and CDKN2A genes.
(DOC)
There is strong epidemiologic evidence indicating that common genetic variability could be implicated in pancreatic cancer risk and, to date, various loci have been proposed. In particular, there is increasing evidence of the involvement of ABO gene variability and pancreatic cancer risk. In a large multicentric study of 1,028 pancreatic ductal ade...
Dilated cardiomyopathies (DCM) show remarkable variability in their age of onset, phenotypic presentation, and clinical course. Hence, disease mechanisms must exist that modify the occurrence and progression of DCM, either by genetic or epigenetic factors that may interact with environmental stimuli. In the present study, we examined genome-wide ca...
Based on about a decade of technical developments in analysing the human proteome with antibody microarrays and experience in performing such analyses, now there are the means at hand for detailed and simultaneously global investigations of this kind. Many technical aspects have been dealt with of both the microarray format itself - such as overcom...
Expression and overlap of CD44/CD24/ESA/CD133 in JoPaca-1. A. Expression of putative stem cell markers CD44, CD24, ESA, and CD133 was determined by FACS using the respective antibodies conjugated to fluorescent dyes: Phycoerythrin-Cy7 to anti CD44, FITC to anti-CD24, APC to anti-ESA, and phycoerythrin to anti-CD133. Depicted here are two-dimensiona...
Most commonly observed mutations in pancreatic cancer listed for BxPC-3 and JoPaca-1. Listed here are non-synonymous coding mutations of the top-17 mutated genes for pancreatic cancer (according to the COSMIC database) as well as BRCA1/2, PALLD and PALB2 (OMIM database) for BxPC-3 and JoPaca-1. Mutated bases are shown beneath each cell line with th...
Selected SNPs from genome wide association studies in pancreatic cancer listed for BxPC-3 and JoPaca-1. The table lists significant non-coding variations for PDAC and their degree of mutation in the cell lines BxPC-3 and JoPaca-1. Mutations were selected from genome wide association studies up to January 2012. Sources can be identified by the first...
FACS histograms of CD133 content in JoPaca-1. The content of CD133+ cells in JoPaca-1 was determined in increasing passages. Histograms are shown of cells stained with phycoerythrin-conjugated CD133-antibody (blue) and unstained cells (red) determined by FACS.
(TIF)
Chromosomal aberrations observed in the karyograms of 26 JoPaca-1 cells. Listed here are all observed aberrations and their prevalence in 26 karyograms. “t” marks translocations and “i” stands for inversions.
(DOCX)
Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequisite for acquiring drug resistance and reoccurrence...
FACS contour plots of cell lines with low CD133 content. The CD133+ content of established pancreatic cell lines was measured by FACS. Depicted here are contour plots of unstained cells (red) and cells stained with phycoerythrin-conjugated CD133-antibody (blue). Outliers of the contour are shown as dots and were include in the analysis. The gate fo...
Sanger sequencing of KRAS codon 12. Electropherograms are presented for codons 11, 12, and 13 of the KRAS locus of JoPaca-1 parental cells and three JoPaca-1 subclones as well as four established cell lines. Sanger sequencing of JoPaca-1 parental cells detected both mutated (dT) and wildtype (dG) basepairs at the second position of codon 12, wherea...
DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast spec...
Table S2. The optimal GLS models found for each of the examined genes by a stepwise backward reduction of the full model described in Material and Methods.
Table S1. Demographic and clinical characteristics of CLL patients and healthy donors.
Background
The Wnt/β-catenin signalling is aberrantly activated in primary B cell chronic lymphocytic leukaemia (CLL). Epigenetic silencing of pathway inhibitor genes may be a mechanism for its activation. In this study, we investigated systematically and quantitatively the methylation status of 12 Wnt/β-catenin pathway inhibitor genes – CDH1, DACT...
Aims Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to anatomical localisation and genotype, with potential impact on biological aggressiveness. DNA methylation of CpG dinucleotides in the promoter region of genes is an important mechanism for regulation of gene expression. We performed a large-scale analys...
Citations
... The activation and induction of fibrogenesis of PSC was triggered by the addition of TNF-α and as described previously [35]. In brief, PSCs were maintained in IMDM supplemented with heat-inactivated fetal bovine serum (10%), penicillin (50 units/ml), and streptomycin (50 μg/ ml) at 37°C and 5% CO 2 . ...
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... Strategies that enable VHHs to cross the blood-brain barrier have recently shown promise. These findings have driven tremendous growth in the use of VHHs for treating central nervous system diseases (44)(45)(46). A limiting factor for the clinical use of VHH domains is that the hydrodynamic radius of VHHs falls below the kidney's glomerular filtration limit, which can contribute to rapid renal clearance and a weak pharmacokinetic (PK) profile, considerably affecting their therapeutic effectiveness. ...
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... Some studies have suggested that overexpression of METTL3 profoundly inhibited the proliferation, tumorigenicity and migration ability of glioma [144,145], breast cancer [146] or bladder cancer cells [147] by altering the mRNA expression of genes or proteins. Paradoxically, other studies have shown that by silencing METTL3 [148][149][150][151][152][153] or WTAP (only in glioma) [154], similar cell growth and aggressiveness inhibition was achieved (Fig. 4). ...
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... Furthermore, a number of miRNAs which suppress proliferation, invasion, and migration of cancer cells, were downregulated due to promoter hypermethylation in different types of cancer. Among these miRNAs are let-7a, miR-9, miR-34b/c, miR-338-3p, miR-596, miR-125a-5p, miR-375, miR-27b-3p, miR-495-3p, miR-490-3p and miR-124a in gastric cancer [87][88][89][90][91][92][93][94][95][96][97], let-7a, miR-9, miR-124 s, miR-125a-5p, miR-192, miR-615-5p, miR-1247, miR-142-3p, miR-148a, miR-132, miR-200, miR-152, miR-17 and miR-92 in pancreatic cancer [98][99][100][101][102][103][104][105][106][107][108][109], miR-9, let-7a, miR-191, miR-203, miR-335, miR-137, miR-142, miR-148a, miR-375, miR-195, miR-183, miR-497, miR-124, miR-125, miR-378, miR-639 in HCC [110][111][112][113][114][115][116][117][118][119][120], and let-7a, miR-107, miR-203a, miR-1258, miR − 9, miR-107, miR-124-3p, miR-125b-5p, miR-127-5p, miR-129-5p, miR-130b, miR-132-3p, miR-137, miR-148a-3p, miR-339-3p, miR-375, miR-34a, miR-203a, miR-34b/c, miR-191-5p, miR-193a-5p, miR-193a-3p, miR-196, miR-508-3p, miR-424/503 cluster in ovarian cancer [121][122][123][124][125][126][127][128][129][130][131][132]. It has been shown by numerous studies that there is a significant change in the expression profile of the miRNA not just in tumor samples but also in the blood and urine of patients with bladder neoplasm [133,134]. ...
Reference: MicroRNA: A signature for cancer progression
... GIST is the second common gastrointestinal tumor showing variable clinical outcomes because of complicated molecular alteration [21]. The involvement of DNA methylation has been found in GIST [22]. In the current study, we explored the role of EZH2-mediated PAX8 methylation in GIST, and found it a facilitator for GIST progression via downregulation of Wnt4. ...
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... Although autophagy can prevent tumour cell proliferation in early tumorigenesis steps [55], it seems to act as a pro-tumour player in later stages of tumour formation [4]. Moreover, CSCs represent a particular cell population that has higher basal autophagy levels than other cancer cells, as they use it as a way to proceed to quiescence in order to survive under drastic conditions within the tumour core [56,57]. Wolf et al. [57] thus showed that inhibiting ATG4A expression led to a decrease of the CSC-like phenotype in breast cancer tumours in vivo, suggesting its importance in maintenance of CSCs. ...
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... The fabrication of protein microarrays was performed applying the multiple spotting technique, an approach that uses DNA templates to synthesize proteins directly on microarray slides [17,37]. The protein microarrays were spotted on epoxysilane coated slides (SCHOTT Nexterion AG, Jena, Germany) using a microarray non-contact printer, the Nanoplotter 2 (GeSIM, Radeberg, Germany) following the protocol described by Hufnagel et al. [38]. The protein microarrays manufacture process is outlined in Figure 5. ...
... It does not appear to bind any of the eIF4G candidates and was found to migrate with the heavy polysomal complexes in sucrose gradients, thus could be associated with the stabilization of polysomes in Leishmania. Genome-wide tethering assay in Trypanosoma brucei classified LeishIF4E-2 as a putative translation repressor [18], but in Leishmania its role still remains elusive [19]. ...
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... This technique can be applied for the simultaneous detection of multiple proteins, and has the advantage of high-throughput applicability. 25 We accordingly used this advanced antibody array detection chip technology to identify protein markers associated with sperm apoptosis and sperm damage, and showed that Fas/Fasl, Bcl-2/Bax, caspase-3, caspase-8, p53, p21, TNF-α, TNF-β, sTNF-R1, and sTNF-R2 were all significantly upregulated in line with increasing BMI in men. Interestingly, livin, which was upregulated in the overweight group, was significantly downregulated in the obese group. ...
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... IET covers the most detrimental malignancies including pancreatic ductal adenocarcinoma (PDAC), breast cancer 2 , and ovarian cancer 3 . The 5-year overall survival rate of IET, take PDAC as an example, is around 5% 4,5 . Emerging advances in immunotherapy including immune-checkpoint blockade (ICB) have shown promise in melanoma, lung cancer and urothelial carcinoma 6 . ...
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