Search results for "Instability"
showing 10 items of 724 documents
Impact of oxygenation status and patient age on DNA content in cancers of the uterine cervix.
2003
Abstract Purpose In carcinomas of the uterine cervix, the tumor oxygenation status has been shown to be a prognostic indicator that is independent of treatment modality. In vitro studies suggest gene amplification and polyploidization to be among the major consequences of hypoxia (with or without consecutive reoxygenation) and to be associated with treatment resistance and tumor progression. This study analyzed whether hypoxia alters net DNA content in uterine cervix cancer cells to the extent that it is identifiable by DNA image cytometry. Methods and materials In 64 patients with primary cervical cancer, tumor oxygenation was assessed polarographically and correlated with cell DNA content…
Hypoxia and anemia: effects on tumor biology and treatment resistance
2004
In locally advanced solid tumors, oxygen (O2) delivery is frequently reduced or even abolished. This is due to abnormalities of the tumor microvasculature, adverse diffusion geometries, and tumor-associated and/or therapy-induced anemia. Up to 50-60% of locally advanced solid tumors may exhibit hypoxic and/or anoxic tissue areas that are heterogeneously distributed within the tumor mass. In approximately 30% of pretreatment patients, a decreased O2 transport capacity of the blood as a result of tumor-associated anemia can greatly contribute to the development of tumor hypoxia. While normal tissues can compensate for this O2 deficiency status by a rise in blood flow rate, locally advanced tu…
Human cytochrome P450 reductase can act as a source of endogenous oxidative DNA damage and genetic instability.
2005
Studies with repair-deficient mice and other experiments suggest that oxidative DNA modifications are generated in all types of cells even under physiological conditions and that this type of endogenous DNA damage contributes to spontaneous cancer incidence. However, the cellular sources of reactive oxygen species that are relevant for nuclear oxidative DNA damage are largely unknown. Here, we report that expression of human NADPH-cytochrome P450 reductase (hOR) in cultured V79 Chinese hamster cells gives rise to elevated basal levels of oxidative purine modifications after depletion of glutathione. Also, the basal levels of micronuclei are increased in the hOR-expressing cells, and again t…
Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
2009
Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA str…
Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
2007
Abstract Background Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form of genome instability in human cancer is chromosome instability (CIN). CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification. Centrosomes control cell division by forming a bipolar mitotic spindle and play an essential role in the maintenance of chromosomal stability. However, whether centrosome amplification could directly cause aneuploidy is not fully established. Also, alterations in genes required for mitotic progression could be involved in CIN. A major candidate is represe…
CENPA overexpression promotes genome instability in pRb-depleted human cells
2009
Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was…
Tumor microenvironmental physiology and its implications for radiation oncology.
2004
Abstract The microenvironmental physiology of tumors is uniquely different from that of normal tissues. It is characterized, inter alia, by O 2 depletion (hypoxia, anoxia), glucose and energy deprivation, high lactate levels, and extracellular acidosis, parameters that are anisotropically distributed within the tumor mass. This hostile microenvironment is largely dictated by the abnormal tumor vasculature and heterogeneous microcirculation. Hypoxia and other hostile microenvironmental parameters are known to directly or indirectly confer resistance to irradiation leading to treatment failure. Hypoxia directly leads to a reduced "fixation" of radiation-induced DNA damage. Indirect mechanisms…
DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts
2001
DNA double-strand breaks (DSBs) are induced by ionizing radiation (IR) and various radiomimetic agents directly, or indirectly as a consequence of DNA repair, recombination and replication of damaged DNA. They are ultimately involved in the generation of chromosomal aberrations and were reported to cause genomic instability, gene amplification and reproductive cell death. To address the question of whether DSBs act as a trigger of apoptosis, we induced DSBs by means of restriction enzyme electroporation and compared the effect with IR in mouse fibroblasts that differ in p53 status [wild-type (+/+) versus p53-deficient (-/-) cells]. We show that (i) electroporation of PVU:II is highly effici…
TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer.
2021
Simple Summary High-grade serous ovarian carcinoma (HGSC) could be analyzed with a molecular stratification defined by different genomic instability signatures associated with specific mutational process and prognostic biomarkers. Immune infiltrate is known to be a robust biomarker in HGSC. We aimed to investigate immune parameters according to genomic instability signatures. We observed that homologous recombination deficiency positive, copy cumber variant signature 7 and TCR (T cells receptor) clonality are good prognostic biomarkers in HGSC. Combining TCR clonality and genomic instability signature or T cell infiltration improved the prognostic value compared to each variable taken alone…
Abnormal mitotic spindle assembly and cytokinesis induced by D-Limonene in cultured mammalian cells
2013
D-Limonene is found widely in citrus and many other plant species; it is a major constituent of many essential oils and is used as a solvent for commercial purposes. With the discovery of its chemotherapeutic properties against cancer, it is important to investigate the biological effects of the exposure to D-Limonene and elucidate its, as yet unknown, mechanism of action. We reported here that D-Limonene is toxic in V79 Chinese hamster cells in a dose-dependent manner. Moreover, to determine the cellular target of D-Limonene, we performed morphological observations and immunocytochemical analysis and we showed that this drug has a direct effect on dividing cells preventing assembly of mito…