Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

Hop-derived Xanthohumol Induces HL-60 Leukemia Cells Death

Background : Acute promyelocytic leukemia (APL) affects both kids and adults, however it is more prevalent in younger population. Although APL has a favorable prognostic, patients that relapse often do not respond positively to additional chemotherapy. Therefore, there is a need to further identify ways to overcome these challenges. Hypothesis: In this study, we examined antileukemic effects of xanthohumol (XN), a prenylated flav onoid derived from hops ( Humulus lupulus L ), on human promyelocytic HL - 60 cells. Materials and Methods : HL - 60 cells were exposed to different concentrations of XN (?M) for 24 h. Cell viability, cell morphology, chromatin condensation, cPARP - 1 level, and caspase - 3 activation, and the expression of p21 WAF1/Cip1 were analyzed. Results : XN reduced HL - 60 cell viability in a dose - dependent manner. XN induced a dose - dependent morphological changes including cell shrinkage and b lebbing , and significantly increased the number of cells with condensed chromatin. XN significantly increased the level of cPARP - 1, active caspase - 3, and the expression of p21WAF/CIP mRNA. Conclusion : These data indicate that XN induces HL - 60 cell death by regula ting cell cycle progression and apoptosis. This study suggests that XN may have antileukemic preventive effects.

Pathological lesions observed in chickens pre-infected with LP H7N1 A/CK/Italy/1279/99 avian influenza and challenged with homologous HP H7N1 A/ostrich/Italy/984/00

Most highly pathogenic avian influenza viruses [AIV] emerge after field passage of non-pathogenic AIVs in birds. The outbreak of low-pathogenic H7N1 avian influenza virus in Italy during 1999-2000 followed by outbreak of highly pathogenic H7N1 avian influenza virus is one example in this regard. This experiment has been designed to investigate the effect of pre-infection of birds with LPAI on subsequent challenge with HPAI virus from the same outbreak. Chickens were inoculated intranasally with LP H7N1 A/CK/ItaIy/1279/99 avian influenza virus at 3 weeks of age and two groups of 10 birds were challenged at 18 and 24 weeks of age with homologous HP H7N1 A/ostrich/Italy/984/00 virus from the same outbreak. The overall mortality of birds was 60%; pre-infected challenged birds died 4-17 days post challenge [PC], while naive birds died 2 days PC. Pre-infected birds showed peritonitis, salpingitis and oophoritis in necropsy and histopathology showed very severe necrosis of the spleen, pancreas, moderate to severe necrosis of the liver and inconsistent degeneration and inflammation of the lung. Necropsy of the control bird showed petechial haemorrhage on the heart, caecal tonsils and the tracheal mucosa

Pathological changes in turkeys experimentally infected with different doses of A/ostrich/Italy/984/2000 H7N1 avian influenza virus

Following experimental inoculation of 3-week-old turkeys with different titres [10[6], 10[4], 10[3], 10[2] and 10[1] egg infectious dose [EID50]] of A/ostrich/Italy/984/2000 H7NI highly pathogenic avian influenza virus [HPAIV], the selected tissues and organs were examined for pathological changes. Tissue samples from different organs that obtained from dead and sacrificed birds were fixed in 10% neutral buffer formaldehyde. Mortality of turkeys which inoculated with different doses of EID50 at different times post inoculation [PI] is as follows: 1] at 48 h PI [HPI]: one, two and four turkeys inoculated with 10[3], 10[4] and 10[6] EID50, respectively 2] at 72 HPI: two, two and one turkeys inoculated with 10[2], 10[3] and 10[6] EID50, respectively 3] at 96 HPI: one and two turkeys inoculated with 10[2] and 10[4] EID50, respectively and 4] at 120 HPI: just one turkey inoculated with 10[4] EID50. Birds inoculated with 10[1] EID50 did not show any mortality. Seven days PI [DPI] the remaining birds were sacrificed. Postmortem examination of birds that died 48 HPI showed very severe hyperaemia and haemorrhage of the lung, slight swelling of kidneys and splenomegaly. Moderate to slight hyperaemia of the lung was observed in the birds sacrificed on day 7. Histopathology showed very severe haemorrhage and vasculitis in the lung, multifocal areas of degeneration and necrosis in the pancreas of birds inoculated with 10[6] EID50. Hyperaemia, haemorrhage, degeneration and vasculitis were also observed in the lung of birds from the other groups; however the severity of lesions correlated positively with the viral dose. The spleen, caecal tonsils and thymus showed extensive necrosis and lymphoid depletion, even in birds inoculated with 10[2] and 10[1] EID50 that were sacrificed 7 DPI, and some repopulation of the spleen was observed 7 DPI. Other organs including the kidneys and adrenal gland showed moderate to slight hyperaemia and necrosis. In conclusion, the lung vascular damage, lymphoid tissue destruction and necrosis were notable even with low viral doses