Tumor cells tend to behave differently in response to immune selective conditions. Contrary to those in therapeutic antitumor conditions, tumor cells in prophylactic antitumor conditions lose antigen expression for antitumor immune escape. Here, using a CT26/HER2 tumor model, we investigate the underlying mechanism(s). We selected tumor cell variants (CT26/HER2-A1 and -A2) displaying resistance to antitumor protective immunity and loss of HER2 antigen expression. These immune-resistant cells failed to induce Ag-specific IgG and IFN-γ responses while forming tumors at the same rate as CT26/HER2 cells. RT-PCR, qRT-PCR, PCR, Western blot and DNA sequencing analyses demonstrated that HER2 expression was inhibited at the post-transcriptional level in these immune-resistant cells, suggesting that tumor cells may escape antitumor immunity through the post-transcriptional regulation of antigen gene expression. The proteasome and lysosomal protein degradation pathways were not responsible for antigen loss, as determined by an inhibitor assay. Finally, HER2 mRNA was found to be not present in the monosomes and polysomes of CT26/HER2-A2 cells, as opposed to CT26/HER2 cells, suggesting that the translation activity of HER2 mRNAs may be suppressed in these immune-resistant cells. Taken together, our results report a new mechanism by which tumor cells respond to antitumor protective immunity for antitumor immune evasion.
Pretreatment with nicardipine for RSI improved intubation conditions and shortened the onset time of rocuronium and attenuated changes in MAP after intubation. Esmolol may disturb intubation conditions and the onset of action of rocuronium, despite being effective in alleviating responses of HR after RSI.
Fentanyl-induced muscular rigidity has been reported exclusively in patients when large fentanyl dosages were employed in the operating room or in the pediatric intensive care unit. Rigidity and pulmonary edema after analgesic doses of fentanyl had not been reported previously. A 25-year-old man underwent removal of a foreign body and application of an Ilizarov frame of tibia under general anesthesia. The patient received 100 μg of fentanyl during emergence of anesthesia and the procedure of dressing. On arrival to the anesthetic recovery room, the patient presented with muscular rigidity and about 1 hour later, developed pulmonary edema. The notable predisposing factors were rapid injection of fentanyl and history of treatment with antidepressants and haloperidol, modifiers of serotonin and dopamine levels. From this case, we suggest the need for careful observation for the development of muscle rigidity complicating airway management in patients taking antidepressants and antipsychotics, especially after administration of an analgesic dose of fentanyl.
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