Similar Datasets
Project description:To delineate the role of host ATF4 in the sequence of events leading to tumor growth, we performed transcriptional profiling at the single-cell level (scRNA-seq) in larger (300 mm3) size B16F10 tumors grown in Atf4wt/wt and Atf4D/D mice. We surprisingly detected impaired CAFs activation in Atf4D/D mice, based on the expression levels of Acta2 and Pdgfrb, as one of the most commonly used CAF markers. Among our key findings, we identified the vascular CAFs (vCAFs), a spatially distinct CAF subcluster featured by the highest levels of aSMA and PDGFRb, that were reduced in Atf4D/D mice.
2022-05-10 | GSE159994 | GEO
Project description:To delineate the role of host ATF4 in the sequence of events leading to tumor growth, we performed transcriptional profiling at the single-cell level (scRNA-seq) in smaller (150 mm3) size B16F10 tumors grown in Atf4wt/wt and Atf4D/D mice. Among others, we observed striking differences in gene expression in a cluster that corresponds to CAFs. In this cluster, we identified 148 DE genes, including a significant downregulation of Col1a1 and Col1a2 in the Atf4D/D mice-grown tumors. Notably, the expression levels of aSMA and Pdgfrb were nearly absent in the tumors grown in Atf4D/D mice. Finally, after CAFs subclustering, we identified the vCAFs (vascular CAFs) that are considered essential for vascular development and angiogenesis to be significantly reduced in the Atf4D/D mice.
2022-05-10 | GSE159995 | GEO
Project description:Identify the role of host ATF4 on CAFs in the tumor microenvironment of large size and small size B16F10 tumors
| PRJNA671500 | ENA
Project description:Identify the role of host ATF4 on CAFs in the tumor microenvironment of large size B16F10 tumors
| PRJNA671506 | ENA
Project description:Identify the role of host ATF4 on CAFs in the tumor microenvironment of small size B16F10 tumors
| PRJNA671507 | ENA
Project description:Extracellular vesicles (EV) are secreted by all cell types in a tumor and its microenvironment (TME), playing an essential role in intercellular communication and the establishment of a TME favorable for tumor invasion and metastasis. They encompass a variety of vesicle populations, among them the well-known endosomal-derived small exosomes (Exo), but also larger vesicles (diameter > 100 nm) that are shed directly from the plasma membrane, the so-called microvesicles (MV). Increasing evidence suggests that MV, although biologically different, share the tumor-promoting features of Exo in the TME. Due to their larger size, they can be readily harvested from patients' blood and characterized by routine methods such as conventional flow cytometry, exploiting the plethora of molecules expressed on their surface. In this review, we summarize the current knowledge about the biology and the composition of MV, as well as their role within the TME. We highlight not only the challenges and potential of MV as novel biomarkers for cancer, but also discuss their possible use for therapeutic intervention.
| S-EPMC7432491 | biostudies-literature
Project description:Viruses are obligate parasites that rely heavily on host cellular processes for replication. The small number of proteins typically encoded by a virus is faced with selection pressures that lead to the evolution of distinctive structural properties, allowing each protein to maintain its function under constraints such as small genome size, high mutation rate, and rapidly changing fitness conditions. One common strategy for this evolution is to utilize small building blocks to generate protein oligomers that assemble in multiple ways, thereby diversifying protein function and regulation. In this review, we discuss specific cases that illustrate how oligomerization is used to generate a single defined functional state, to modulate activity via different oligomeric states, or to generate multiple functional forms via different oligomeric states.
| S-EPMC5088105 | biostudies-literature
Project description:Myxoma virus (MV) is a rabbit-specific poxvirus, whose unexpected tropism to human cancer cells has led to studies exploring its potential use in oncolytic therapy. MV infects a wide range of human cancer cells in vitro, in a manner intricately linked to the cellular activation of Akt kinase. MV has also been successfully used for treating human glioma xenografts in immunodeficient mice. This study examines the effectiveness of MV in treating primary and metastatic mouse tumors in immunocompetent C57BL6 mice. We have found that several mouse tumor cell lines, including B16 melanomas, are permissive to MV infection. B16F10 cells were used for assessing MV replication and efficacy in syngeneic primary tumor and metastatic models in vivo. Multiple intratumoral injections of MV resulted in dramatic inhibition of tumor growth. Systemic administration of MV in a lung metastasis model with B16F10LacZ cells was dramatically effective in reducing lung tumor burden. Combination therapy of MV with rapamycin reduced both size and number of lung metastases, and also reduced the induced antiviral neutralizing antibody titres, but did not affect tumor tropism. These results show MV to be a promising virotherapeutic agent in immunocompetent animal tumor models, with good efficacy in combination with rapamycin.
| S-EPMC4376281 | biostudies-literature
Project description:Accumulating data indicates that some cancer treatments can restore anticancer immunosurveillance through the induction of tumor immunogenic cell death (ICD). Nanosecond pulsed electric fields (nsPEF) have been shown to efficiently ablate melanoma tumors. In this study we investigated the mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Our data show that in vitro nsPEF (20-200, 200-ns pulses, 7?kV/cm, 2?Hz) caused a rapid dose-dependent cell death which was not accompanied by caspase activation or PARP cleavage. The lack of nsPEF-induced apoptosis was confirmed in vivo in B16F10 tumors. NsPEF also failed to trigger ICD-linked responses such as necroptosis and autophagy. Our results point at necrosis as the primary mechanism of cell death induced by nsPEF in B16F10 cells. We finally compared the antitumor immunity in animals treated with nsPEF (750, 200-ns, 25?kV/cm, 2?Hz) with animals were tumors were surgically removed. Compared to the naïve group where all animals developed tumors, nsPEF and surgery protected 33% (6/18) and 28.6% (4/14) of the animals, respectively. Our data suggest that, under our experimental conditions, the local ablation by nsPEF restored but did not boost the natural antitumor immunity which stays dormant in the tumor-bearing host.
| S-EPMC6344591 | biostudies-literature
Project description:To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10-10 < P < 5 × 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
| S-EPMC8515199 | biostudies-literature