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Muscle and Nerve Histology
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
The structural organization of myofibrils is maintained by titin, α-actinin, and nebulin proteins. These proteins are present in the Z-line interacting with other proteins that are associated with varieties of neuromuscular disease. These proteins include telethonin; myozenin; filamin-C; Z-band alternatively spliced, PDZ-motif (ZASP); and four and a half LIM domains protein 1 (FHL1).
Toxicogenomics in Toxicologic Pathology
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Arun R. Pandiri, David E. Malarkey, Mark J. Hoenerhoff
Using single dosing of doxorubicin and two other prototypical cardiotoxins with differing mechanisms of toxicity, isoproterenol and carbofuran, Mori et al. (2010) evaluated the transcriptional response in the hearts of rats in conjunction with histopathology to detect potential genomic biomarkers of cardiotoxicity (Mori et al. 2010). Isoproterenol is a catecholamine that induces acute tachycardia and myocardial infarction (Mikaelian et al. 2008; Mori et al. 2010), while carbofuran is an anti-cholinesterase pesticide (Gupta 1994). Using toxicogenomics to evaluate these different cardiotoxins, the authors identified gene signatures common between the three compounds that were functionally associated with cell proliferation, chemotaxis, regeneration and morphogenesis, correlating with histopathologic findings of myofiber degeneration, edema, infiltration of inflammatory cells, and necrosis. Consistent with other studies, gene expression patterns correlated with the type of histopathologic lesion rather than the type of compound examined, suggesting that despite differing mechanisms of action, the morphologic endpoint of cardiotoxicity is consistent between compounds, illustrating the limited adaptive response of the heart to injury. Consistently up-regulated genes throughout exposure, included genes associated with cardiotoxicity, cardiac infarction, inflammation, dilative or hypertrophic cardiomyopathy, cardiac cytoskeletal proteins, myocarditis, and fibrosis (Spp1, Fhl1, Timp1, Ccl7, Reg3b), providing evidence that the up-regulation of these common genes may be useful in predicting the cardiotoxicity of compounds with unknown cardiotropic effects (Mori et al. 2010).
Chediak−Higashi Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Differential diagnoses for CHS include oculocutaneous albinism (visual impairment, iris/retinal depigmentation, absent or reduced skin and hair pigment, lack of neutropenia, or neurologic abnormalities), Hermansky Pudlak syndrome (HPS; partial oculocutaneous albinism, bleeding diathesis secondary to absent platelet-dense bodies, congenital neutropenia, recurrent infections, developmental delay, balance abnormalities, tremor; general lack of giant intracellular granules in neutrophils; possible presence of giant granules in patients with acute and chronic myeloid leukemia, referred to as pseudo-Chediak−Higashi anomaly), Griscelli syndrome (mild skin hypopigmentation, silvery gray hair, normal platelet function; due to pathogenic variants in MYO5A [GSI, severe neurologic involvement], RAB27A [GSII, immunodeficiency and lymphohistiocytosis], MLPH (GSIII, hypopigmentation]), Cross syndrome (hypopigmentation, ocular defects, and severe developmental delay, lack of infectious component), deficiency of endosomal adaptor p14 (partial albinism, short stature, congenital neutropenia, and lymphoid deficiency, altered azurophilic granule ultrastructure, absent giant inclusions in neutrophils), familial hemophagocytic lymphohistiocytosis (FLH; proliferation and infiltration of hyperactivated macrophages and T-lymphocytes, prolonged fever, cytopenias, hepatosplenomegaly, increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, coma, liver dysfunction, bone marrow hemophagocytosis; autosomal recessive disorder fur to biallelic mutations in FHL1–FLH5), Vici syndrome (cutaneous hypopigmentation, combined immunodeficiency, agenesis of the corpus callosum, bilateral cataracts, cleft lip and palate, cognitive impairment, seizures, and severe respiratory infections) [1,2].
X-Linked Tumor Suppressor Genes Act as Presumed Contributors in the Sex Chromosome-Autosome Crosstalk in Cancers
Published in Cancer Investigation, 2022
Bhanupriya Dhabhai, Amit Sharma, Jarek Maciaczyk, Tikam Chand Dakal
Along with already profoundly investigated sex-related behavior associated factors, the reason for this disproportionality among males and females can partially be explained by 15% X-linked genes that escape from X chromosome inactivation (XCI), a process which equalizes the X-linked gene expression levels in males and females. For instance, X-linked KDM6A gene escapes XCI and is frequently mutated in bladder cancer (5). Similarly, the deletions, mutations, and even down-regulation of FOXP3 (Forkhead box P3, X-linked tumor suppressor) gene have frequently been noticed in breast cancer samples (6). In context of epigenetic, the down-regulation of the FHL1 (Four and a half LIM domains 1) by DNA methylation has been linked to oral cancer (7). Additionally, the (epi) genomic contribution of loci specific (X chromosome) and global LINE-1 (Long interspersed nuclear element-1) repetitive sequence have also been implicated in diverse cancer types (8). Nevertheless, the overall contribution of X chromosome as a disease (cancer) specific determining factor cannot be excluded. In this context, a recent study characterized the difference of mutation clonality between male and female glioblastoma patients and identified clinically relevant sex specific genes and pathways (9). Similarly, the individual potential of autosomal TSGs (genomic counterpart of X-linked TSGs) cannot be excluded either, for instance the pleiotropic effect and shared mutation spectrum of autosomal TSG named as BAP1 (BRCA1 associated protein 1) in multiple human cancers (10,11)
Upregulated miR-410 is linked to poor prognosis in colorectal cancer
Published in British Journal of Biomedical Science, 2020
P Abedi, A Bayat, S Ghasemzadeh, M Raad, H Pashaiefar, M Ahmadvand
MiR-410 has the potential to function as a tumour inducer or a tumour suppressor in various types of cancers [10]. Its oncogenic functions have been reported in retinoblastoma, lung, liver and colorectal cancers where it regulates BAK1, FHL1, CETN3, and BRD7, and functions as a tumour suppressor in pancreatic, bone, gastric and breast cancers by regulating c-MET, AGTR1, and SNAIL [10]. In colorectal cancer, miR-410 is involved in different tumorigenic processes including proliferation, migration, invasion, and apoptosis by regulating FHL1, ITPKB, DKK-1, and Bak1 [11–14]. Furthermore, overexpression of miR-410 was previously reported in colorectal cancer patients and cell lines [11,12,14]. However, there is limited knowledge concerning the clinical implication of miR-410 expression in colorectal cancer. We therefore hypothesized links between the expression of mi-410 in malignant tissue and clinical features, and outcome survival in patients with colorectal cancer.
Complement inhibitor factor H expressed by breast cancer cells differentiates CD14+ human monocytes into immunosuppressive macrophages
Published in OncoImmunology, 2020
Karolina I. Smolag, Christine M. Mueni, Karin Leandersson, Karin Jirström, Catharina Hagerling, Matthias Mörgelin, Paul N. Barlow, Myriam Martin, Anna M. Blom
FH expression was investigated in a breast cancer patient cohort using immunochemistry. Specificity of anti-FH antibodies was verified using paraffin-embedded cell pellets of wild-type (WT) and FH-transfected HEK 293 cells (Figure 7a, Figure S3A, B). In patient tissues FH was expressed at varying levels by epithelial cancer cells, which is consistent with the previously detected expression of FH on mRNA level in breast cancer tissue (www.proteinatlas.org/ENSG00000000971-CFH/pathology/breast+cancer#cbox) and various breast cancer cell lines.37 The FH antiserum used in this study recognizes FH and FH splice variant FH-like protein (FHL1), due to the shared homology between FHL-1 and the seven N-terminal domains of FH. The antiserum also recognizes some of the FH-related proteins (FHRs), due to their homology with the C-terminal region of FH (Figure 7b). However, FHRs were not found in the breast tumors at the mRNA level.38 To further confirm the specificity of our staining for FH, we stained selected breast cancer tissues with MRC-OX24 antibody, which recognizes FH and FHL1 but not FHRs (Figure 7c) and L20/3, which recognizes FH and FHRs but not FHL1 (Figure 7d). Both of these antibodies yielded positive staining, which together with the data on mRNA expression strongly indicates that the protein detected in the tissue was indeed FH and not FHL1 or FHR.