Reisinger et al., pp. 1603–1608 Epstein-Barr Virus (EBV) preferentially infects B cells and is associated with benign and malignant diseases. In this study, Reisinger et al. established a means of visualizing the genomic organization of the virus in infected cells. Using a technique based on dynamic molecular combing (DMC), DNA from Burkitt's lymphoma cell lines, Daudi and Namalwa—which have episomal and integrated EBV DNA, respectively—were probed with EBV-specific DNA probes and visualized using fluorescence in situ hybridization (FISH). When the authors examined the Namalwa DNA, all 54 FISH signals displayed a split terminal repeat (TR) sequence pattern, which strongly suggests that the virus has been integrated in these cells. On the other hand, when Daudi cells were subjected to the same DNA probes, all 59 hybridization patterns visualized displayed a single—unsplit—TR signal, which is the hallmark of episomal expression. This technique seems to unambiguously distinguish between episomal and integrated forms of EBV DNA. Importantly it could be used to further investigate how EBV DNA is habored in various diseases and whether integrated forms are associated with oncogenic consequences. Cohen et al., pp. 1609–1617 Heparanase is the main enzyme that cleaves heparin sulfate, an abundant polysaccharide in the extracellular matrix (ECM). Its activity has been demonstrated in a host of malignancies, and is known to be important in metastasis and tumor angiogenesis. Previous studies have shown that heparanase expression in breast cancer patients correlates with the metastatic potential of the tumor. In this report, Cohen et al. investigated the role of the enzyme in primary breast cancer progression. To do this, they stably (and mock) transfected a breast cancer cell line, MCF-7, with human heparanase (H-hpa) cDNA and injected these cells into the mammary pads of nude mice. Tumor growth after 30 days—as monitored by MRI—showed that heparanase expression accelerated MCF-7 tumor growth in vivo. Not only that, but the resultant tumors' volume and mass were 7 times greater in the H-hpa fashioned tumors than in the mock transfected ones. Futhermore, ex vivo the H-hpa-expressing MCF-7 tumors had a higher mitotic activity and proliferation rate and lower apoptotic potential. This study clearly shows that heparanase both affects primary breast cancer growth and offers insight into why cells expressing this enzyme might have a survival advantage. Bak et al., pp. 1618–1622 DNA adducts—complexes that form when a chemical binds to DNA—have been shown to be necessary but insufficient for tumorigenesis. Human carcinogens have been isolated in such adducts. Using a Danish population cohort comprising over 50,000 people with no previous cancer diagnosis, the authors investigated whether levels of bulky DNA adducts in white blood cells (WBC) are a reliable risk indicator of lung cancer. Using 32P-postlabeling, Bak et al. analyzed WBC bulky DNA in 245 study participants who developed lung cancer and 255 healthy controls randomly selected and stratified by age, sex and duration of smoking. Current smokers with high—above the median—levels of bulky adducts had a higher risk (1.61 95% CI 1.04-2.49) of lung cancer than those with adduct levels below the median. In comparison with previous studies, Bak and colleagues' comprehensive study is population based and investigates adducts prior to cancer diagnosis. Their findings indicate a weak association between bulky DNA adducts in WBC risk and lung cancer risk. Davidson et al., pp. 1623–1627 Circadian rhythms are known to be important for biological processes as fundamental as cell division. Recent data suggest that disruption of circadian rhythmicity can affect tumor growth in rodents. In this report, Davidson et al. investigated whether circadian rhythms were distinct in hepatocellular carcinoma cells (HCC) compared to healthy liver tissue and whether these processes could be disrupted by experimental restricted feeding (RF) or jet-lag. Rats transgenic for a luciferase reporter gene driven by core circadian clock gene, Period 1, were chemically induced to develop HCC and exposed to different restricted feeding patterns—including night-time and ad libitum feeds (n=18)—or experimental jet-lag (n=20). The authors then explanted the hepatomas and normal liver tissue and measured Period 1 activity with bioluminescence. Restricted feeding—both day or night—altered Period 1 expression in both malignant and healthy cells. Interestingly, the HCC cells were much less sensitive to this effect: peak Period 1 expression in HCC in day-fed vs. night-fed groups differed by 6.3 hours, whereas in healthy liver it differed by over 11 hours. This differential circadian rhythmicity found between cancerous and healthy tissue could be exploited to use restricted feeding to target cancer cells with chemotherapy when the tumors cells are in a mitotic phase and healthy cells not.
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May 20, 2023
Haiyan Yu + 10
Open Access