Friends or foes: The mononuclear phagocyte system in ischemic stroke.

Ischemic stroke (IS) is a major cause of disability and death in adults, and the immune response plays an indispensable role in its pathological process. After the onset of IS, an inflammatory storm, with the infiltration and mobilization of the mononuclear phagocyte system (MPS), is triggered in the brain. Microglia are rapidly activated in situ, followed by waves of circulating monocytes into the ischemic area. Activated microglia and monocytes/macrophages are mainly distributed in the peri-infarct area. These cells have similar morphology and functions, such as secreting cytokines and phagocytosis. Previously, the presence of the MPS was considered a marker of an exacerbated inflammatory response that contributes to brain damage. However, recent studies have suggested a rather complicated role of the MPS in IS. Here, we reviewed articles focusing on various functions of the MPS among different phases of IS, including recruitment, polarization, phagocytosis, angiogenesis, and interaction with other types of cells. Moreover, due to the characteristics of the MPS, we also noted clinical research addressing alterations in the MPS as potential biomarkers for IS patients for the purposes of predicting prognosis and developing novel therapeutic strategies.

Significant response to apatinib monotherapy in heavily pretreated advanced HER2-positive breast cancer: a case report and literature review.

Although HER2-targeted therapy has been shown to prolong the survival of patients with HER2-positive breast cancer, most patients eventually progress due to drug resistance. Novel treatment options are urgently needed to overcome resistance to HER2-targeted therapy. The VEGF/VEGFR (Vascular endothelial growth factor and its receptors) pathway is essential in tumor angiogenesis, which may be a promising target in HER2-positive breast cancer providing a rationale for the use of tyrosine kinase inhibitors (TKIs) targeting VEGFR. Here, we present a case of a heavily pretreated advanced breast cancer patient who did not respond to HER2-targeted therapy and developed resistance to multiple lines of HER2-targeted treatment. The patient was treated with apatinib at a dose of 500 mg daily, and obtained partial remission (PR) with a progression-free-stage (PFS) of 6 months. Our case indicates that apatinib might have anti-tumor activity in patients with HER2-positive breast cancer with HER2-targeted resistance. This case is of value which may provide new insights into strategies for HER2-targeted therapy resistance options in the clinic.

[Analysis of postoperative chemotherapy-related anemia in elderly cancer patients].

OBJECTIVE: This study was conducted to investigate the correlation between anemia and postoperative chemotherapy in elderly cancer patients. METHODS: One hundred and fifty-seven elderly patients ( age ≥ 60) with pathologically confirmed breast, lung and digestive tract cancers, who had HGB ≥ 120 g/L and ECOG scores 0-2, were included in this study. We reviewed their clinicopathological data and analyzed the correlation of anemia in breast cancer patients after 1, 3 or 5 cycles and lung cancer patients after 1, 2 or 3 cycles of postoperative chemotherapy. RESULTS: Among the 157 cases, the overall proportion of anemia was 31.8% (50/157) , with 18.8% in male and 47.2% in female patients (P < 0.001). After three cycles of chemotherapy, the proportion of anemia was 57.9% in lung cancer, 34.5% in breast cancer, 26.3% in gastric cancer and 9.3% in colorectal cancer patients (P < 0.001). The proportion of anemia during 5 cycles chemotherapy (three cycles in lung cancer) was gradually increasing. In the lung cancer patients, anemia was observed in 66.7% of patients who received vinorelbine plus cispiatin regimen and 25.0% of cases who received vinorelbine regimen chemotherapy (P = 0.044). CONCLUSIONS: In most elderly patients with normal hemoglobin level and in good conditions, the chemotherapy-related anemia is mild and less frequent. Age should not limit the adjuvant chemotherapy in elderly cancer patients. Attention should be paid to the possibility of anemia in elderly female lung cancer patients receiving multiple cycle platinum-based chemotherapy regimens.

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway

Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC50 of 18.54 μM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway.

Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC50 of 18.54 µM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.