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Background/Aims: Idiopathic pneumonia syndrome (IPS) is a serious and life-threatening lung complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and currently no effective therapies exist. This study was designed to determine whether transplantation of allogeneic murine compact bone derived- mesenchymal stem cells (CB-MSCs) could prevent the development of IPS. Methods: We tested the effects of CB-MSCs transplantation on IPS using an established murine model of C57BL/6 (H-2b)→BALB/c (H-2d). Survival rates, body weight change, clinical GVHD scores, lung histological changes were assessed after IPS induction. Mechanistically, concentrations of cytokines (TNF-α, IFN-γ and IL-4) and chemokines (CCL5, CXCL9 and CXCL10) in bronchoalveolar lavage fluid (BALF) from the recipient mice were measured at different time point post-transplantation. CD4⁺CD25⁺Foxp3⁺ regulatory T cell (Treg) percentage, CCR5, CXCR3 and CCR7 expression on CD3⁺ T cells, and lung CXCR3, CCR5, CCR7, T-bet and GATA-3 mRNA levels were also evaluated at different time point post-transplantation. Results: Co-transplantation of CB-MSCs significantly attenuated the severity of lung injuries and increased survival rate of mice compared to non-cotransplanted mice. A higher Treg percentage, reduction of TNF-α, IFN-γ, CCL5, CXCL9 and CXCL10 levels, down-regulation of CXCR3 and CCR5, as well as up-regulation of CCR7, were observed in MSCs co-transplantation mice. Also, the prophylactic effect of CB-MSCs was associated with a shift of Th1/Th2 balance toward anti-inflammatory Th2 polarization. Conclusions: Allogeneic CB-MSCs effectively controlled the occurrence of IPS due to its profound immunomodulatory capacity. This may offer a novel prophylactic approach for IPS after allo-HSCT.

The human cervical cancer oncogene (HCCR) has been found to be overexpressed in a variety of human cancers. However, the level of expression of HCCR and its biological function in gastric cancer are largely unknown. In this study, we evaluated HCCR expression in several gastric cancer cell lines and in one normal gastric mucosal cell line. We established a 5-FU-resistant gastric cancer cell subline, and we evaluated its HCCR expression. HCCR expression levels were high in gastric cancer lines, and expression was significantly increased in the 5-FU-resistant cancer cell subline. HCCR expression affected cell growth by regulating apoptosis in the cancer cells, and it had a positive correlation with p-STAT3 expression. Western blot and luciferase reporter assays showed that the activation of STAT3 upregulated HCCR expression in a positive feedback loop model. In vivo and in vitro studies showed that HCCR plays an important role in the apoptosis induced by 5-FU. Our data demonstrate that HCCR is probably involved in apoptosis and cancer growth and that it functions as a p-STAT3 stimulator in a positive feedback loop model. In gastric cancer cells, HCCR confers a more aggressive phenotype and resistance to 5-FU-based chemotherapy.

The human cervical cancer oncogene (HCCR2) has been found to be overexpressed in a variety of human malignant tumors cells, and its function is related to cell cycle progression and survival. However, the molecular mechanisms of action of HCCR2 in leukemia remain unclear. In this study, we used the RNA interference strategy to investigate the effects of HCCR2 knockdown in the K562 leukemia cell line, and to explore the potential mechanisms involved. Following transfection with small interfering RNA (siRNA) targeting HCCR2 (HCCR2-siRNA), we examined the effects of HCCR2 knockdown on cell morphology, cell proliferation, cell cycle progression and apoptosis in K562 cells. Morphological changes were evaluated by Wright-Giemsa staining. Cell cycle progression and apoptosis were measured by flow cytometry. The expression levels of genes related to the cell cycle and apoptosis were detected by quantitative RT-PCR (qRT-PCR) and western blot analysis. HCCR2 expression at the mRNA and protein level was significantly decreased following transfection with plasmids expressing HCCR2-siRNA. Silencing HCCR2 expression significantly suppressed cell proliferation, induced G1 cell cycle arrest and promoted the apoptosis of K562 cells. Additionally, we found that the expression of Bax, p53 and p21 was significantly increased, while Bcl-2 expression was significantly decreased in the HCCR2-siRNA-transfected cells. However, the expression of p27 was not affected. These results suggest that the HCCR2 gene plays an important role in the tumorigenesis of leukemia, thus making it an attractive therapeutic target for acute leukemia.

The human cervical cancer oncogene (HCCR) has been shown to be over-expressed in some solid tumors, and its function is involved in negative regulation of p53 tumor suppressor gene. However, the roles of HCCR in leukemia remain unclear. The present study is to investigate whether the expression levels of HCCR mRNA are associated with clinical prognosis in patients with acute leukemia (AL) and to explore the potential use as a biomarker for monitoring minimal residual disease (MRD) in AL. The mRNA levels of HCCR1 and HCCR2 were quantified by real-time reverse transcription polymerase chain reaction in bone marrow samples from 80 adult de novo AL patients and 20 normal healthy donors. The expressions of HCCR1 and HCCR2 were significantly higher in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) than those in healthy donors (P < 0.01), but there was no significant difference between AML and ALL (P > 0.05). Besides white blood cell count, we did not find any significant correlation between HCCR expression and clinical characteristics, such as age, sex, CD34 antigen expression, and response to chemotherapy. HCCR was monitored in 12 cases during remission and/or relapse. Significant reductions of both HCCR1 and HCCR2 mRNA levels were observed in patients who had achieved complete remission after chemotherapy but not in patients with non-responsive. However, an increased HCCR expression was detected in these patients who relapsed. Our findings suggest that HCCR gene is over-expressed in AL patients and may be as a useful biomarker for monitoring MRD in AL.