In 2010, Choi et al. [ 31] identified two secondary mutations (C1156Y and L1196M) within the kinase domain of ALK fusion protein, which confer marked crizotinib resistance.
Increase HO-1 expression in chemical HC plays an effective role to counteract oxidative damage and to control inflammation and confers marked resistance to apoptosis [ 10].
Considering that increase HO-1 expression in chemical HC plays an effective role to counteract oxidative damage and to control inflammation and confers marked resistance to apoptosis [ 10], we studied HO-1 expression by immnunohistochemical analysis in the liver of animals under a protocol of carcinogen withdrawal.
In contrast, a single mutation of P32del conferred marked resistance to NS5A inhibitors.
Preclinical studies have demonstrated that a deficiency in any one of the more than 30 genes involved in the nucleotide excision repair (NER) pathway confers marked hypersensitivity to cisplatin[9].
Direct support for this proposition comes from the observation that over-expression of PGC-1α in mouse skeletal muscle confers marked resistance to muscle atrophy following hindlimb unweighting [52], [53].
Overexpression of ABCC1 and ABCC2 in human ovarian cancer cells conferred marked resistance to chemotherapeutics, such as methotrexate [ 55].
Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors, PF-02341066 and a 2,4-pyrimidinediamine derivative (PDD) [ 15].
Ectopic expression of miR-29 alone in young sympathetic neurons confers marked resistance to multiple apoptotic stimuli including NGF deprivation, DNA damage, and endoplasmic reticulum stress.
Cellular over expression of heme oxygenase-1 (HO-1), the anti-inflammatory and anti-oxidative stress protein that catalyzes heme degradation producing biliverdin, iron and CO, up-regulates p21cip1/waf1, diminishes cell growth proliferation and confers marked resistance to apoptosis.
Interestingly, the base substitutions conferring marked ASP-RNAi appeared to be largely present in the region of guide siRNAs, corresponding to the seed region of microRNAs.
