Dual epigenetic agents plus rituximab-gemcitabine-oxaliplatin as salvage treatment in relapsed/refractory diffuse large B-cell lymphoma patients failure of salvage chemotherapy.

Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) patients' failure of salvage chemotherapy had extremely worse prognoses. Herein, 14 R/R DLBCL patients failed to salvage chemotherapy were exposed to dual epigenetic agents (Chidamide 30 mg biw*2w and Decitabine 10 mg/m2 qd*d1-d5) and sequential R-GemOx (rituximab 375 mg/m2 qd d6; gemcitabine 1 g/m2 d7, d14; and oxaliplatin 100 mg/m2 d7) for further salvage chemotherapy. Finally, 11/14(78.6%) patients achieved overall response with 6/14(42.9%) achieving complete remission and 2-year overall survival (OS)/progression free survival (PFS) rate was 42.7%, extremely higher than reported previously. Further subgroup analysis demonstrated that 2-year OS/PFS rate was significantly higher in patients achieved complete/partial remission or with low international prognosis index (IPI 0-2) than that in patients with steady disease or high IPI (3-5). Common grade 3-4 adverse events were hematological toxicities. All toxicities were transient and reversible. Our report implicates that combination of dual epigenetic agents and R-GemOx is a safe and promising alternative for R/R DLBCL patients.

The Effects of HP0044 and HP1275 Knockout Mutations on the Structure and Function of Lipopolysaccharide in Helicobacter pylori Strain 26695.

Helicobacter pylori infection is associated with several gastric diseases, including gastritis, peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphatic tissue (MALT) lymphoma. Due to the prevalence and severeness of H. pylori infection, a thorough understanding of this pathogen is necessary. Lipopolysaccharide, one of the major virulence factors of H. pylori, can exert immunomodulating and immunostimulating functions on the host. In this study, the HP0044 and HP1275 genes were under investigation. These two genes potentially encode GDP-D-mannose dehydratase (GMD) and phosphomannomutase (PMM)/phosphoglucomutase (PGM), respectively, and are involved in the biosynthesis of fucose. HP0044 and HP1275 knockout mutants were generated; both mutants displayed a truncated LPS, suggesting that the encoded enzymes are not only involved in fucose production but are also important for LPS construction. In addition, these two gene knockout mutants exhibited retarded growth, increased surface hydrophobicity and autoaggregation as well as being more sensitive to the detergent SDS and the antibiotic novobiocin. Furthermore, the LPS-defective mutants also had significantly reduced bacterial infection, adhesion and internalization in the in vitro cell line model. Moreover, disruptions of the HP0044 and HP1275 genes in H. pylori altered protein sorting into outer membrane vesicles. The critical roles of HP0044 and HP1275 in LPS biosynthesis, bacterial fitness and pathogenesis make them attractive candidates for drug inventions against H. pylori infection.

Comparison and exploration of the prognostic value of the advanced lung cancer inflammation index, prognostic nutritional index, and systemic immune-inflammation index in newly diagnosed diffuse large B-cell lymphoma.

BACKGROUND: The international prognostic index (IPI) is widely used as an indicator for evaluating the clinical prognosis of diffuse large B-cell lymphoma (DLBCL). However, more precise prognostic indicators are needed. This study aimed to evaluate the prognostic significance of the advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) in DLBCL. METHODS: A total of 117 patients with newly diagnosed DLBCL were included in this study. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values for the ALI, PNI, and SII to predict survival, and patients were stratified into high and low groups. Cox regression analysis and the Kaplan-Meier method were used to assess the prognostic ability of these indexes. RESULTS: The optimal cut-offs for the ALI, PNI, and SII were 31.26, 36.48, and 486.76, respectively. The ALI had the highest area under the curve (AUC). The high ALI or PNI group had better 5-year overall survival (OS) than the low ALI (73% vs. 53%, P<0.001) or PNI (60% vs. 45%, P<0.001) group, and the low SII group had better 5-year OS than the high SII group (67% vs. 62%, P=0.034). Although all 3 parameters were associated with OS in univariate analyses, only the ALI and PNI were independent factors for OS in multivariate analyses. We found that when DLBCL patients were classified according to IPI combined with ALI, PNI, or SII, respectively, there were more obvious differences in OS among different types. CONCLUSIONS: The ALI and PNI may be easily available markers to predict clinical outcomes in DLBCL patients. SII predicted OS only in univariate analysis.

DRR1 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via regulating AKT activation.

Metastatic invasion is the primary cause of treatment failure for GBM. EMT is one of the most important events in the invasion of GBM; therefore, understanding the molecular mechanisms of EMT is crucial for the treatment of GBM. In this study, high expression of DRR1 was identified to correlate with a shorter median overall and relapse-free survival. Loss-of-function assays using shDRR1 weakened the invasive potential of the GBM cell lines through regulation of EMT-markers. The expressions of p-AKT were significantly decreased after DRR-depletion in SHG44 and U373 cells. Moreover, the invasion was inhibited by the AKT inhibitor, MK-2206. The expression of Vimentin, N-cadherin, MMP-7, snail and slug was significantly inhibited by MK-2206, while the expression of E-cadherin was upregulated. Our results provide the first evidence that DRR1 is involved in GBM invasion and progression possibly through the induction of EMT activation by phosphorylation of AKT.

Preoperative serum C-reactive protein levels and early breast cancer by BMI and menopausal status.

Serum C-reactive protein (CRP), a sensitive marker of systemic inflammation, has been reported to be associated with the risk of a number of cancers including breast cancer. However, the results are inconsistent. To investigate the association between serum CRP levels and early breast cancer, we conducted a hospital-based case-control study among 506 newly diagnosed breast cancer patients and 506 controls with benign breast diseases matched by age and menopausal status. Odds ratios (ORs) were computed with unconditional logistic regression models, adjusted for major confounding factors. Relative to women with the lowest quartile of CRP level, women with the highest quartile had 1.65-fold increased breast cancer risk (OR: 1.65, 95% CI: 1.12-2.42) in a significant dose-response manner (p(trend) = .011). Stratification analysis revealed a positive association only for overweight postmenopausal women (highest CRP quartile versus lowest CRP quartile: OR: 2.78, 95% CI: 1.18-6.6). Multinominal logistic regression analysis showed that only hormonal receptor (HR) positive and human epidemiological receptor 2 (HER2) negative breast cancers had elevated serum CRP levels. We observed that elevated serum CRP levels are positively associated with early breast cancer, predominantly among overweight and postmenopausal women. This study provided epidemiological evidence that chronic inflammation might mediate the association between obesity and postmenopausal breast cancer. Although a positive association between serum CRP and HR positive/HER2 negative breast cancer is intriguing, further epidemiological studies are needed to confirm such findings.

Twist expression associated with the epithelial-mesenchymal transition in gastric cancer.

This study aimed to investigate the expression of Twist in gastric cancer tissues and its correlation between Twist and the epithelial-mesenchymal transition (EMT). By means of RT-PCR and Western blot, the mRNA and protein expressions of Twist, E-cadherin, and Vimentin in 61 gastric cancer tissues and adjacent normal tissues were detected. The positive rates of Twist, E-cadherin, and Vimentin mRNA expression in gastric cancer tissues were 73.9. 40.6, and 60.9 %, respectively; compared to the expression of these genes in adjacent normal tissues (2.9, 75.4, and 27.5 %), the differences were significant (p < 0.05). The E-cadherin protein expression level in gastric cancer tissues was significantly lower than that in the adjacent normal tissues (p < 0.05). After the transfection of Twist siRNA into the MKN45 cells, the protein expression of Twist was significantly reduced (p < 0.05), the protein expression of E-cadherin was significantly increased, and the number of cells that passed through the Transwell chamber was significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). Twist may be associated with the epithelial-mesenchymal transition in gastric cancer and the tumorigenesis, invasion, and metastasis of gastric cancer.

[Study of 161 chronic idiopathic myelofibrosis patients for clinicopathological staging].

OBJECTIVE: To investigate the significance of clinicopathological stage of chronic idiopathic myelofibrosis (CIMF) in WHO classification of 2001. METHODS: Histopathological analysis of bone marrow biopsy plastic-embedded sections stained with H-G-E and Gomori's stains and clinical features of 113 cases previously diagnosed as primary myelofibrosis (PMF) and 48 cases MPD-U (total of 161 cases which including male 79 and female 82) were studied retrospectively. RESULTS: There was no significant differences on the clinical features among the cellular phase, collagen fiber phase, sclerotic phase and osteomyelosclerosis of 113 previously diagnosed patients. According to WHO classification 2001 of CIMF, previously diagnosis in 48 cases with MPD-U was WHO pre-CIMF, and in 113 cases with PMF was WHO CIMF-Fs. There were significant differences between of WHO pre-CIMF and WHO CIMF-Fs about clinicopathological features except age. The percentage of immature granulocytes, normoblasts, lymphocytes in peripheral blood, the size of hepatosplenomegaly, and the percent age of tear drop-like red blood cells in pre-CIMF were significantly lower than those in CIMF-Fs (P < 0.05). However, the number of hemoglobin and platelets in patients with pre-CIMF were significantly higher than that with CIMF-Fs (P < 0.01). CONCLUSION: pre-CIMF and CIMF-Fs in clinical and histopathological features were different development stage of CIMF, while osteomyelosclerosis is a variant of CIMF, but not an independent disease.