Summary:Despite new antifungal treatment strategies, invasive aspergillosis (IA) remains a principal cause of infectious mortality after bone marrow transplantation (BMT). We reviewed the medical records of 93 allogeneic and 149 autologous transplant recipients during a 20 month period, with attention to cases of proven or probable IA. No autologous transplant recipient developed IA, whereas IA was seen in 15.1% of allogeneic recipients (including two of five patients with a prior history of IA despite prophylaxis), for an overall incidence of 5.8%. The median time to occurrence was 92 days post transplant, with no de novo cases developing prior to engraftment. Survival 100 days from diagnosis was 29%. Risk factors for the development of IA included у21 days of corticosteroid therapy of у1 mg/kg/day and post-transplant cytomegalovirus (CMV) infection. These two risk factors were statistically linked. Our data illustrate a shift toward a later occurrence of posttransplant IA, suggesting a need for close, prolonged surveillance in the outpatient environment. The contributory role of protracted corticosteroid use is also highlighted. These data have important implications in an era of alternate donor transplants and more intense immunosuppression. Established strategies implementing newer, less toxic antifungal agents as prophylaxis in high-risk patients are needed. sources and more profound immunosuppression, including T cell depletion techniques, which weaken host defenses in the post-engraftment period. The time of onset in autologous transplant recipients is typically during the preengraftment period, whereas later infections are often also seen in allogeneic recipients. 6 Specific knowledge of the usual time of onset and identifiable risk factors for IA is essential to the development of more effective prevention strategies and the application of new therapeutic techniques. Previously identified risk factors include age, 3,7 unrelated donor, 3,4 transplant outside of a laminar air flow room, 5 low cell dose, 7 recipient CMV seropositivity, 7 persistent or prolonged neutropenia, 5,8 early corticosteroid use for acute graft-versus-host disease (GVHD) prophylaxis, 9 high-grade acute GVHD, 1,3,4 chronic GVHD 4,8 and graft rejection. 10 Decreased risk for IA has been ascribed to housing patients in a high-efficiency particulate air (HEPA) filtered environment. 11 To our knowledge, no data exist comparing the risk for IA using different sources of harvested stem cells (peripheral blood vs bone marrow). Furthermore, the need exists for more data regarding the role of GVHD, as well as duration and dose of corticosteroids as predisposing factors for infection.In this study, we reviewed the current epidemiology of IA in the Bone Marrow Transplant Unit at the University of Florida with specific attention to the time of onset and survival. These findings were compared to those reported in a similar epidemiologic study done at this institution between 1981 and 1985. 11 Such a comparison can illustrate the effects of new tr...

Objectives Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer. Methods ECC-1 and Ishikawa cells were treated with low glucose (1mM), normal glucose (5mM) and high glucose (25mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated. Results Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-Cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways. Conclusions Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer.

Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Thus, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species (ROS) and expression of endoplasmic reticulum (ER) stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.