Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n = 90) were assigned in equal numbers to receive 0, 100 or 200 mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P < 0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P < 0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P < 0.002) and the numbers tended to decrease linearly (P < 0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P < 0.05). Moreover tumor length decreased (P < 0.02) and tumor length tended to decrease linearly (P < 0.03) as supplemental lycopene increased from 0 to 200 mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.
by
Sean Stowell;
C. Maridith Arthur;
Kathryn R. Girard-Pierce;
Harold C. Sullivan;
Manjula Santhanakrishnan;
Prabitha Natarajan;
Seema R. Patel;
Christopher A. Tormey;
James Zimring;
Jeanne Hendrickson
Alloantibodies against red blood cell (RBC) antigens, which may be generated following exposure to foreign antigens on transfused RBCs or on fetal RBCs during pregnancy, can be clinically significant from the standpoint of morbidity and mortality.1 In the transfusion setting, RBC alloantibodies can lead to premature clearance of transfused RBCs, resulting in hemolytic transfusion reactions and even death in severe cases. In the pregnancy setting, these antibodies can cause hemolytic disease of the fetus and newborn (HDFN). With the exception of RhIg, which is primarily utilized to prevent Rh(D) alloimmunization in pregnancy, no antigen specific targeted therapies exist to prevent RBC alloimmunization.
Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.