HLH-related genes (including AP3B1, FASLG, PRF1, TNFRSF1A, BIRC4, ITK, RAB27A, UNC13D, CASP10
, ITPKC, SH2D1A, CD27, LYST, STX11, FAS, MAGT1 and STXBP2) were detected with high-throughput sequencing.
Rueff, "Genetic susceptibility in acute pancreatitis: genotyping of GSTM1, GSTT1, GSTP1, CASP7, CASP8, CASP9, CASP10
, LTA, TNFRSF1B, and TP53 gene variants," Pancreas, vol.
In this experimental setting, we used, in addition to a pan-caspase inhibitor (Z-VAD-FMK), inhibitors of CASP8 (Z-IETD-FMK), CASP9 (Z-LEHD-FMK), and caspase-10 (CASP10; Z-AEVD-FMK) (R&D Systems, Minneapolis, MN, USA).
Inhibition of the extrinsic pathway by CASP10 and CASP8 inhibitors prevented apoptosis by up to 75% and 60%, respectively, after treatment with viscum and by 50% and 30%, respectively, in viscumTT-treated cells.
For instance, by setting the initial values of FasL, Casp8, granB, and Casp10 to 0 and computing only those equations in blocks B and D of Table 2, we turn off the extrinsic and perforin pathways and hence obtain the apoptosis level contributed by the intrinsic pathway only.
FasL [0,1] FasL * 0 Casp8 [0,1] Casp8 * 0 Casp3 [0,1] Casp3 * 0 Apop 0 Bid [0,1] tBid 0 DNA [0,1] DNAdamage 0 ATR [0,1] ATR * 0 p53 [0,1] p53 * 0 Bax [0,1] BCl2 [0,1] Cytcmit [0,1] Cytc 0 Casp9 [0,1] Casp9 * 0 granB [0,1] granB * 0 Casp10 [0,1] Casp10 * 0 FasL *.Casp8 0 Casp8 *.Casp3 0 ATR *.p53 0 p53 *.Bax 0 Bax.Bak 0 p53 *.BCl2 0 BCl2.Bax 0 Cytc.Casp9 0 Casp9 *.Casp3 0 granB * .Casp10 0 Casp10 *.Casp3 0 Casp8 *.Bid 0 tBid.Bax 0 granB * .Bid 0 All values are in nondimensional form.
Initiator caspases (CASP2, CASP8, CASP9, and CASP10
) cleave inactive pro-forms of effector caspases, thereby activating them.
For example, somatic mutations in CASP3 were found in two of 129 NHL cases  and somatic mutations in CASP10
in 15% of 117 cases .
Rare ALPS patients carrymutations of FASLG coding for FAS-ligand, or CASP10
coding for caspase 10 involved in FAS signaling; a mutation of FASLG is carried also by [MRL.sup.gld/gld] mice showing a disease similar to that displayed by [MRL.sup.lpr/lpr] mice.
Can the results be applied to the local population (CASP10
Kang et al., "Inactivating mutations of CASP10
gene in non-Hodgkin lymphomas," Blood, vol.