ABSTRACT
Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.
ABSTRACT
Purpose@#Recurrence patterns in rectal cancer patients treated with preoperative chemoradiotherapy (PCRT) are needed to evaluate for establishing tailored surveillance protocol. @*Methods@#This study included 2,215 patients with locally-advanced mid and low rectal cancer treated with radical resection between January 2005 and December 2012. Recurrence was evaluated according to receipt of PCRT; PCRT group (n = 1,258) and no-PCRT group (n = 957). Early recurrence occurred within 1 year of surgery and late recurrence after 3 years. The median follow-up duration was 65.7 ± 29 months. @*Results@#The overall recurrence rate was similar between the PCRT and no-PCRT group (25.8% vs. 24.9%, P = 0.622). The most common initial recurrence site was the lungs in both groups (50.6% vs. 49.6%, P = 0.864), followed by the liver, which was more common in the no-PCRT group (22.5% vs. 33.6%, P = 0.004). Most of the recurrence occurred within 3 years after surgery in both groups (85.3% vs. 85.8%, P = 0.862). Early recurrence was more common in the PCRT group than in the no-PCRT group (43.1% vs. 32.4%, P = 0.020). Recurrence within the first 6 months after surgery was significantly higher in the PCRT group than in the no-PCRT group (18.8% vs. 7.6%, P = 0.003). Lung (n = 27, 44.3%) and liver (n = 22, 36.1%) were the frequent the first relapsed site within 6 months after surgery in PCRT group. @*Conclusion@#Early recurrence within the first 1 year after surgery was more common in patients treated with PCRT. This difference would be considered for surveillance protocols and need to be evaluated in further studies.
ABSTRACT
Purpose@#Recurrence patterns in rectal cancer patients treated with preoperative chemoradiotherapy (PCRT) are needed to evaluate for establishing tailored surveillance protocol. @*Methods@#This study included 2,215 patients with locally-advanced mid and low rectal cancer treated with radical resection between January 2005 and December 2012. Recurrence was evaluated according to receipt of PCRT; PCRT group (n = 1,258) and no-PCRT group (n = 957). Early recurrence occurred within 1 year of surgery and late recurrence after 3 years. The median follow-up duration was 65.7 ± 29 months. @*Results@#The overall recurrence rate was similar between the PCRT and no-PCRT group (25.8% vs. 24.9%, P = 0.622). The most common initial recurrence site was the lungs in both groups (50.6% vs. 49.6%, P = 0.864), followed by the liver, which was more common in the no-PCRT group (22.5% vs. 33.6%, P = 0.004). Most of the recurrence occurred within 3 years after surgery in both groups (85.3% vs. 85.8%, P = 0.862). Early recurrence was more common in the PCRT group than in the no-PCRT group (43.1% vs. 32.4%, P = 0.020). Recurrence within the first 6 months after surgery was significantly higher in the PCRT group than in the no-PCRT group (18.8% vs. 7.6%, P = 0.003). Lung (n = 27, 44.3%) and liver (n = 22, 36.1%) were the frequent the first relapsed site within 6 months after surgery in PCRT group. @*Conclusion@#Early recurrence within the first 1 year after surgery was more common in patients treated with PCRT. This difference would be considered for surveillance protocols and need to be evaluated in further studies.