Role of 18F-FDG PET Scans in Patients with Helicobacter pylori-Infected Gastric Low-Grade MALT Lymphoma

BACKGROUND/AIMS: Endoscopic ultrasound (EUS) plays a crucial role in the assessment and treatment of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma; however, interobserver variation, inadequate accuracy in judging the depth of tumor invasion, and histological heterogeneity of the tumor can limit its role. Thus, we have assessed the role of (18)F-FDG PET scans in the management of Helicobacter pylori-infected gastric MALT lymphoma. METHODS: Eighteen patients with H. pylori-infected low-grade gastric MALT lymphoma underwent an (18)F-FDG PET scan prior to receiving H. pylori eradication therapy. We analyzed these patients' clinicopathologic data and measured the baseline and change in the metabolic activity of the tumor using standardized uptake values (SUVs). RESULTS: Two patients failed to achieve complete remission of the low-grade gastric MALT lymphoma after successful H. pylori eradication. The baseline SUVs were significantly higher in these patients compared to successfully treated patients, 13.35±0.07 vs 2.98±0.93, respectively (n=2 vs n=16, p<0.001). The reduction in the SUV was significantly greater in the complete remission patients compared to treatment failure patients (p=0.018). CONCLUSIONS: A high SUV at baseline (18)F-FDG PET and a lower reduction in the SUV within 3 months after eradication therapy are associated with treatment failure in H. pylori-positive low-grade gastric MALT lymphoma patients undergoing eradication treatment.ope

Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies

IntroductionMost human mammary epithelial cells (HMEC) cultured from histologically normal breast tissues enter a senescent state termed stasis after 5 to 20 population doublings. These senescent cells display increased size, contain senescence associated beta-galactosidase activity, and express cyclin-dependent kinase inhibitor, p16INK4A (CDKN2A; p16). However, HMEC grown in a serum-free medium, spontaneously yield, at low frequency, variant (v) HMEC that are capable of long-term growth and are susceptible to genomic instability. We investigated whether ionizing radiation, which increases breast cancer risk in women, affects the rate of vHMEC outgrowth.MethodsPre-stasis HMEC cultures were exposed to 5 to 200 cGy of sparsely (X- or gamma-rays) or densely (1 GeV/amu 56Fe) ionizing radiation. Proliferation (bromodeoxyuridine incorporation), senescence (senescence-associated beta-galactosidase activity), and p16 expression were assayed in subcultured irradiated or unirradiated populations four to six weeks following radiation exposure, when patches of vHMEC became apparent. Long-term growth potential and p16 promoter methylation in subsequent passages were also monitored. Agent-based modeling, incorporating a simple set of rules and underlying assumptions, was used to simulate vHMEC outgrowth and evaluate mechanistic hypotheses.ResultsCultures derived from irradiated cells contained significantly more vHMEC, lacking senescence associated beta-galactosidase or p16 expression, than cultures derived from unirradiated cells. As expected, post-stasis vHMEC cultures derived from both unirradiated and irradiated cells exhibited more extensive methylation of the p16 gene than pre-stasis HMEC cultures. However, the extent of methylation of individual CpG sites in vHMEC samples did not correlate with passage number or treatment. Exposure to sparsely or densely ionizing radiation elicited similar increases in the numbers of vHMEC compared to unirradiated controls. Agent-based modeling indicated that radiation-induced premature senescence of normal HMEC most likely accelerated vHMEC outgrowth through alleviation of spatial constraints. Subsequent experiments using defined co-cultures of vHMEC and senescent cells supported this mechanism.ConclusionsOur studies indicate that ionizing radiation can promote the outgrowth of epigenetically altered cells with pre-malignant potential

Neurocytotoxic effects of iron-ions on the developing brain measured in vivo using medaka (Oryzias latipes), a vertebrate model

Purpose: Exposure to heavy-ion radiation is considered a critical health risk on long-term space missions. The developing central nervous system (CNS) is a highly radiosensitive tissue; however, the biological effects of heavy-ion radiation, which are greater than those of low-linear energy transfer (LET) radiation, are not well studied, especially in vivo in intact organisms. Here, we examined the effects of iron-ions on the developing CNS using vertebrate organism, fish embryos of medaka (Oryzias latipes)

Heavy Ion Carcinogenesis and Human Space Exploration

Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets