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Query: UMLS:C1832526 (PCC)
 5,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. MFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.
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PMID:No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblast after alpha particle irradiation. 2350 90

Families of tumor-suppressor genes, such as those involved in homologous recombination or mismatch repair, contain individual genes implicated in hereditary cancer syndromes. Collectively, such groupings establish that inactivating germline changes in genes within pathways related to genomic repair can promote carcinogenesis. The hypoxia pathway, whose activation is associated with aggressive and resistant sporadic tumors, is another pathway in which tumor-suppressor genes have been identified. von Hippel-Lindau disease, some of the hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes, and the syndrome of hereditary leiomyomatosis and renal cell carcinoma are heritable conditions associated with genes involved or associated with the hypoxia pathway. This review links these heritable cancer syndromes to the hypoxia pathway while also comparing the relative aggression and treatment resistance of syndrome-associated tumors to similar, sporadic tumors. The reader will become aware of shared phenotypes (e.g., PGL/PCC, renal cell carcinoma) among these three hypoxia-pathway-associated heritable cancer syndromes as well as the known associations of tumor aggressiveness and treatment resistance within these pathways.
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PMID:Heritable Cancer Syndromes Related to the Hypoxia Pathway. 2704 99

Pancreatic ductal adenocarcinoma (PDAC) cells (PCC) have an exceptional propensity to metastasize early into intratumoral, chemokine-secreting nerves. However, we hypothesized the opposite process, that precancerous pancreatic cells secrete chemokines that chemoattract Schwann cells (SC) of nerves and thus induce ready-to-use routes of dissemination in early carcinogenesis. Here we show a peculiar role for the chemokine CXCL12 secreted in early PDAC and for its receptors CXCR4/CXCR7 on SC in the initiation of neural invasion in the cancer precursor stage and the resulting delay in the onset of PDAC-associated pain. SC exhibited cancer- or hypoxia-induced CXCR4/CXCR7 expression in vivo and in vitro and migrated toward CXCL12-expressing PCC. Glia-specific depletion of CXCR4/CXCR7 in mice abrogated the chemoattraction of SC to PCC. PDAC mice with pancreas-specific CXCL12 depletion exhibited diminished SC chemoattraction to pancreatic intraepithelial neoplasia and increased abdominal hypersensitivity caused by augmented spinal astroglial and microglial activity. In PDAC patients, reduced CXCR4/CXCR7 expression in nerves correlated with increased pain. Mechanistically, upon CXCL12 exposure, SC down-regulated the expression of several pain-associated targets. Therefore, PDAC-derived CXCL12 seems to induce tumor infiltration by SC during early carcinogenesis and to attenuate pain, possibly resulting in delayed diagnosis in PDAC.
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PMID:Early pancreatic cancer lesions suppress pain through CXCL12-mediated chemoattraction of Schwann cells. 2807 10