Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short telomeres have been linked to cancer risk, yet other evidence supports them being tumor suppressive. Here, we report cancer outcomes in individuals with germline mutations in telomerase and other telomere-maintenance genes. Among 180 individuals evaluated in a hospital-based setting, 12.8% had cancer. Solid tumors were rare (2.8%); nearly all were young male DKC1 mutation carriers, and they were generally resectable with good short-term outcomes. Myelodysplastic syndrome (MDS) was most common, followed by acute myeloid leukemia (AML); they accounted for 75% of cancers. Age over 50 years was the biggest risk factor, and MDS/AML usually manifested with marrow hypoplasia and monosomy 7, but the somatic mutation landscape was indistinct from unselected patients. One- and 2-year survival were 61% and 39%, respectively, and two-thirds of MDS/AML patients died of pulmonary fibrosis and/or hepatopulmonary syndrome. In one-half of the cases, MDS/AML patients showed a recurrent peripheral blood pattern of acquired, granulocyte-specific telomere shortening. This attrition was absent in age-matched mutation carriers who did not have MDS/AML. We tested whether adult short telomere patients without MDS/AML also had evidence of clonal hematopoiesis of indeterminate potential-related mutations and found that 30% were affected. These patients also primarily suffered morbidity from pulmonary fibrosis during follow-up. Our data show that the Mendelian short telomere syndromes are associated with a relatively narrow cancer spectrum, primarily MDS and AML. They suggest that short telomere length is sufficient to drive premature age-related clonal hematopoiesis in these inherited disorders.
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PMID:Cancer spectrum and outcomes in the Mendelian short telomere syndromes. 3207 14

Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair. Studies have shown that BMSCs gather at the injured tissue site after granulocyte-colony stimulating factor (G-CSF) administration. In this study, we first investigated whether G-CSF could promote BMSC homing to damaged lung tissue induced by bleomycin (BLM) and then investigated whether SDF-1/CXCR4 chemotaxis might be involved in this process. Next, we further studied the potential inhibitory effect of G-CSF administration in mice with lung fibrosis induced by bleomycin. We examined both the antifibrotic effects of G-CSF in mice with bleomycin-induced pulmonary fibrosis in vivo and its effects on the proliferation, differentiation and chemotactic movement of cells in vitro. Flow cytometry, real-time PCR, transwell and Cell Counting Kit-8 (CCK-8) assays were used in this study. The results showed that both preventative and therapeutic G-CSF administration could significantly inhibit bleomycin-induced pulmonary fibrosis. G-CSF enhanced BMSC migration to lung tissues, but this effect could be alleviated by AMD3100, which blocked the SDF-1/CXCR4 axis. We also found that BMSCs could inhibit fibroblast proliferation and transdifferentiation into myofibroblasts through paracrine actions. In conclusion, G-CSF exerted antifibrotic effects in bleomycin-induced lung fibrosis, in part by promoting BMSC homing to injured lung tissues via SDF-1/CXCR4 chemotaxis.
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PMID:G-CSF Inhibits Pulmonary Fibrosis by Promoting BMSC Homing to the Lungs via SDF-1/CXCR4 Chemotaxis. 3260 21


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