Value of pretherapeutic DWI in evaluating prognosis and therapeutic effect in immunocompetent patients with primary central nervous system lymphoma given high-dose methotrexate-based chemotherapy: ADC-based assessment.

AIM: To investigate apparent diffusion coefficient (ADC) as a prognostic indicator in primary central nervous system lymphoma (PCNSL) by analysing patient clinical characteristics and pretherapeutic diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Clinical characteristics and pretherapeutic DWI were studied retrospectively in 28 patients receiving high-dose methotrexate (HD-MTX)-based chemotherapy. Mean (ADCmean), 95th percentile (ADC95%), and 5th percentile (ADC5%) ADC values of the enhancing tumour volume were measured. The influence of prognostic parameters on progression-free survival (PFS) was investigated by log-rank test and Cox regression analysis. Correlations between the variables and PFS or the level of Ki-67 expression were analysed. ADC and clinical features were analysed using an independent sample t-test between the complete response (CRi) and partial response (PRi) groups after initial four cycles of chemotherapy. Receiver operating characteristic (ROC) curves were constructed using ADC parameters. RESULTS: Patients with CRi, lower Ki-67 level, higher Karnofsky performance status (KPS), ADC5%, or ADCmean showed better PFS. The level of Ki-67 expression and ADC5% were independent risk factors. There was a positive correlation between KPS, ADC5%, and PFS, and negative correlation between ADC5%, PFS, and the level of Ki-67 expression. There was a significant difference for PFS, KPS, ADCmean, and ADC5% between CRi and non-CRi; however, ADC5% outperformed ADCmean because the area under the ROC curve (AUC) using ADC5% (0.983) was higher than the AUC using ADCmean (0.822). CONCLUSION: ADC measurements, especially ADC5%, are useful predictors for PFS and response to HD-MTX in PCNSL.

Visceral pleural invasion impacts the prognosis of non-small cell lung cancer: A meta-analysis.

BACKGROUND: In the 7th tumor, node, metastasis (TNM) classification, T1 tumors with visceral pleural invasion (VPI) are upgraded to T2a. The objective of this study was to evaluate the prognostic impact of VPI among patients with NSCLC and to propose a method of incorporating VPI into T-status classification in future staging systems. METHODS: A systematic electronic search was conducted from each database's date of inception to October 2015. The included studies were selected according to predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining. RESULTS: A total of 22 studies, published from 2003 to 2015, were included in this meta-analysis. In the subgroup analysis, we identified that VPI was a poor prognostic factor for tumor size ≤2 cm (2.34 [95% confidence interval (CI) 1.55-3.54; P < 0.0001]), 2-3 cm (1.81 [95% CI 1.56-2.10; P < 0.0001]), 3-5 cm (1.61 [95% CI 1.38-1.87; P < 0.0001]) and 5-7 cm (1.50 [95% CI 1.24-1.82; P < 0.0001]). In addition, we also found that there were no significant differences for the following comparisons of OS: tumor size ≤2 cm with VPI versus 3-5 cm without VPI (1.04 [95% CI 0.83-1.31; P = 0.34]); 2-3 cm with VPI versus 3-5 cm without VPI (1.04 [95% CI 0.96-1.13; P = 0.30]); 3-5 cm with VPI versus 5-7 cm without VPI (0.95 [95% CI 0.78-1.17; P = 0.66]); and 5-7 cm with VPI versus T3 status (1.03 [95% CI 0.93-1.14; P = 0.57]). CONCLUSIONS: In addition to the current TNM classification recommendations, consideration should be given to classifying the T2a tumors with VPI as T2b and classifying T2b with VPI as T3 in the next edition of the TNM Classification for Lung cancer.

Protective effects of sodium p-aminosalicylic acid on learning and memory via increasing the number of basal forebrain choline acetyltransferase neurons in manganese-exposed rats.

This study was conducted to investigate the protective effects of sodium p-aminosalicylic acid (PAS-Na) on learning and memory via increasing the number of basal forebrain choline acetyltransferase (ChAT) neurons in manganese (Mn)-exposed rats. Male Sprague Dawley rats were divided into following groups: the normal control I, II, and III groups, the model I, II, and III groups, low- and high-dose PAS-Na treatment (L- and H-PAS) group, PAS-Na prevention (PAS-P) group, and PAS-Na treatment (PAS-T) group. The model I, II, and III groups, L- and H-PAS, and PAS-T groups received intraperitoneal (i.p.) injection of 15 mg/kg manganese chloride tetrahydrate (MnCl2·4H2O) for 3 or 12 weeks, while the normal control I, II, and III groups received i.p. injection of an equal volume of saline; L- and H-PAS and PAS-T groups received back subcutaneous (s.c.) injection of PAS-Na (100 and 200 mg/kg) for the next 5 or 6 weeks, whereas model I and II group received back s.c. injection of an equal volume of saline. However, PAS-P group received back s.c. injection of 200 mg/kg PAS-Na + i.p. injection of 15 mg/kg MnCl2·4H2O for 12 weeks. Mn exposure significantly reduced the ability of spatial learning and memory capability, while PAS-Na prevention recovered it. Mn decreased the number of ChAT-positive neurons in vertical limb nucleus of the basal forebrain diagonal band/horizontal limb nucleus of the basal forebrain diagonal band and ChAT protein activity and treatment or prevention with PAS-Na restored those comparable with control. In brief, our results showed that PAS-Na may have protective effects on learning and memory against Mn via increasing the number of ChAT-positive neurons and activity of ChAT protein.

The Enzymatic Activity of Drosophila AWD/NDP Kinase Is Necessary but Not Sufficient for Its Biological Function

The Drosophila abnormal wing discs (awd) gene encodes the subunit of a protein that has nucleoside diphosphate kinase (NDP kinase) activity. Null mutations of the awd gene cause lethality after puparium formation. Larvae homozygous for such mutations have small imaginal discs, lymph glands, and brain lobes. Neither the imaginal discs nor the ovaries from such null mutant larvae are capable of further growth or normal differentiation when transplanted into suitable host larvae. This null mutant phenotype can be entirely rescued by one copy of a transgene that has 750 bp of awd upstream regulatory DNA fused to a full-length awd cDNA. Tissue-specific expression of AWD protein from this rescue transgene is identical to tissue-specific expression of beta-galactosidase from a reporter transgene that has the same regulatory region fused to the bacterial lac Z gene. However, this rescue transgene or reporter transgene expression pattern is only a subset of the endogenous pattern of expression detected by either in situ hybridization or immunohistochemistry. This suggests that awd is normally expressed in some tissues where it is not required. The null mutant phenotype cannot be rescued at all by a transgene that has 750 bp of awd upstream regulatory DNA fused to a full-length awd cDNA with a mutation that eliminates NDP kinase activity by replacement of the active site histidine with alanine. This suggests that the enzymatic activity of the AWD protein is necessary for its biological function. The human genes nm23-H1 and nm23-H2 encode NDP kinase A and B subunits, respectively. The protein subunit encoded by either human nm23 gene is 78% identical to that encoded by the Drosophila awd gene. Transgenes that have the 750-bp awd upstream regulatory DNA fused to human nm23-H2 cDNA but not to nm23-H1 cDNA can rescue the imaginal disc phenotype and the zygotic lethality caused by homozygosis for an awd null mutation as efficiently as an awd transgene. However, rescue of female sterility requires twice as much nm23-H2 expression as awd expression. This implies that the enzymatic activity of the AWD protein is not sufficient for its biological function. The biological function may require nonconserved residues of the AWD protein that allow it to interact with other proteins.