Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

A novel effect of imidazole derivative KK-42 on increasing survival of Aeromonas hydrophila challenged prawn Macrobrachium nipponense.

Imidazole derivative KK-42 is well known as the insect growth regulator. Here we find that KK-42 pretreatment could promote the survival of Macrobrachium nipponense infected with Aeromonas hydrophila, which is considered to be possibly related to the prophenoloxidase (proPO), a conserved copper-containing enzyme that plays an important role in defense against pathogens. In this study, a full-length of proPO gene from M. nipponense haemocytes, designated as MnproPO, was firstly cloned and characterized. The full-length cDNA contained 2428 bp with a 2013 bp open reading frame encoding a putative proPO protein of 671 amino acids with a predicted molecular mass of 76.5 kDa and pI of 7.31. It was predicted to possess all the expected features of proPO members, including two putative copper-binding sites with six histidine residues and a thiol ester-like motif. Sequence analysis showed that MnproPO exhibited the highest amino acid sequence similarity (93%) to a proPO of Macrobrachium rosenbergii. The gene was expressed highly in haemocytes and weakly in hepatopancreas. Real-time PCR analysis revealed that the MnproPO expression increased significantly at 3, 12 and 24 h after KK-42 treatment, the PO activity also importantly rose from 6 to 48 h in KK-42-treated prawns and reached the maximum at 24 h with a 2.3-fold higher than that in control group. Injection of A. hydrophila could stimulate the MnproPO transcription and PO activity whether or not the prawns were pretreated by KK-42, the mRNA level increased obviously only at 3 h and 6 h after the bacterium injection (challenged control), but increased constantly during the phase of experiment except at 6 h under the condition of KK-42 pretreatment (challenged treatment group). The change trend of PO activity was basically similar to that of MnproPO expression. Our present results demonstrate that the MnproPO expression as well as PO activity may be induced by KK-42, which is likely one of the molecular mechanisms of KK-42 acts for increasing survival of the prawn infected with A. hydrophila.

[Expression and Clinical Significance of C/EBPα Gene in Elderly Multiple Myeloma].

OBJECTIVE: To investigate the expression of C/EBPα gene in elderly patients with multiple myeloma （MM） and its prognostic significance. METHODS: Sixty-nine olderly patients with multiple myeloma (MM) treated in our hospital from February 2015 to October 2017 were selected and enrolled in the MM group, 38 healthy persons received physical examination were selected and enrolled in the control group. The bone marrow of 2 groups was collected and the mononuclear cells were isolated.The mRNA expression level of C/EBPα gene in mononuclear cells was determined by RT-PCR, the Western blot was used to detect the protin expression level of PBMNC C/EBPα, and the protein level of C/EBPα in bone marrow was detected by immunohistochemistry. The correlations of C/EBPα gene expression with the clinical characteristics and survival time in MM patients were analyzed. RESULTS: The expression level of mRNA and protein of C/EBPα in MM patients was significantly lower than that in the control group (P<0.05). The expression level of C/EBPα gene significantly correlated with the ISS stage, CRP, Calcium, ß2-MG, LDH and the percentage of myeloma cells in MM patients (P<0.05). The expression of C/EBPα gene was not correlate with sex, age, immunoglobulin typing, Hb in MM patients (P>0.05).Immunohistochemical staining showed that the bone marrow samples of the control group were stained more deeply, and the staining intensity in bone marrow samples of MM patients with CR, PR and relapse was successively descended. The protein level of C/EBPα in CR patients with MM was significantly higher than that in PR and relapsed patients by Western blot (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in the patients with high expression of C/EBPα gene were higher than those in low expression group (P<0.05). Multivariate Cox regression analysis showed that CRP,ratio of myeloma cells and C/EBPα gene were independent factors affecting OS and PFS (P<0.05). CONCLUSION: The expression level of C/EBPα gene in MM patients is low that may stimulate the genesis of MM, and the expression of C/EBPα gene closely relates with the development of MM disease.

[Correlations of S100A4 and MMP9 expressions to infiltration, metastasis and prognosis of non-small cell lung cancer].

OBJECTIVE: To observe the expressions of metastasis-associated protein (S100A4) and matrix metalloproteinase 9 (MMP9) in human non-small cell lung cancer (NSCLC) and investigate their correlations to the infiltration, metastasis and prognosis of NSCLC. METHODS: The expressions of S100A4 and MMP9 were detected in 41 NSCLC specimens and 6 normal lung tissue specimens using immunohistochemistry with SP method. Univariate and multivariate survival analysis were used to analyze the correlations of S100A4 and MMP9 to the clinicopathological characteristics and progrnosis of NSCLC. RESULTS: Compared with normal lung tissues, NSCLC showed significantly increased positivity for S100A4 and MMP9 expression (P<0.05); their expression were significantly higher in adenocarcinoma than in squamous cell carcinoma (P<0.01), and higher in metastatic NSCLC than in that without lymphatic metastasis (P<0.01). The positive expression rates of S100A4 and MMP9 were significantly higher in tumors in TNM stages III +IV than in stages II+I (P<0.05). S100A4 expression was positively correlated to tumor size (P<0.001), while MMP9 was inversely correlated to tumor differentiation (P<0.05). The expressions of S100A4 and MMP9 were both correlated to lymphatic metastasis, TNM stages and pathological types (P<0.05), and they also showed a mutual correlation (P<0.01). Univariate survival analysis confirmed the effects of histological types, lymphatic metastasis, clinical TNM stages and expressions of S100A4 and MMP9 on the survival time of NSCLC patients (P<0.001). Multivariate survival analysis identified clinical TNM stages and expressions of S100A4 and MMP9 as the independent factors affecting the prognosis of NSCLC (P<0.05). CONCLUSION: The expressions of S100A4 and MMP9 are up-regulated in NSCLC and have significant correlations to the clinical and biological behaviors of NSCLC. S100A4 and MMP9 status are independent prognostic predictors of NSCLC, and detection of their expressions may help evaluate the prognosis of NSCLC.

[Correlations of S100A4 protein expression to invasion and metastasis of non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Metastasis-associated protein S100A4 is overexpressed in many malignant tumor cells; it may play a pivotal role in invasion and metastasis of malignant tumors. This study was to determine the expression of S100A4 in human non-small cell lung cancer (NSCLC), and to investigate its correlations to invasion and metastasis of NSCLC. METHODS: The expression of S100A4 in 41 specimens of NSCLC and 6 specimens of normal lung tissues was detected by SP immunohistochemistry. The correlations of S100A4 to clinicopathologic features of NSCLC were analyzed. RESULTS: The positive rate of S100A4 was significantly higher in NSCLC than in normal lung tissues (70.7% vs. 16.7%, P<0.05), and was significantly higher in adenocarcinoma than in squamous cell carcinoma (90.0% vs. 52.4%, P<0.01). The positive rate of S100A4 was significantly higher in stage III-IV than in stage II and stage I NSCLC (100.0% vs. 66.7% and 30.0%, P<0.01), while there was no obvious difference between the latter 2 groups (P>0.05). The positive rate of S100A4 was significantly higher in NSCLC with lymphatic metastasis than in NSCLC without lymphatic metastasis (90.0% vs. 52.4%, P<0.01), and significantly higher in NSCLC with tumor size of > or = 3 cm than in NSCLC with tumor size of < 3 cm (91.3% vs. 44.4%, P<0.001). The expression of S100A4 was closely related to lymphatic metastasis (r=0.480, P=0.001), and tumor size (r=0.288, P=0.017). No significant correlation was found between the expression of S100A4 and pathologic grade of NSCLC (P>0.05). CONCLUSION: S100A4 expression is up-regulated in NSCLC, and closely related to lymphatic metastasis, TNM stage and tumor size, which suggest an important role of S100A4 in the invasion and metastasis of NSCLC.