[Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma].

Objective: The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively. Methods: A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis. Results: The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively (P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively (P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion: The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy.

BACKGROUND: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC. METHODS: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed. RESULTS: Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042). CONCLUSIONS: Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).

[Quantities and function of NK cells in patients with positive BMMNC-Coombs test and cytopenia].

OBJECTIVE: To test NK cell quantities and function in patients with positive BMMNC-Coombs test (CBCPC) and cytopenia and to explore how NK cell participate in the progress of this disease. METHODS: The percentage of CD3(-)CD56(+) NK cell in peripheral blood lymphocytes, the expression of activating receptor (NKG2D, NKp46, NKp44), inhibitory receptor (CD158a, CD158b), perforin and granzyme-ß were detected by flow cytometry. All samples were taken from 42 patients (22 newly diagnosed and 20 in remission) and 12 healthy volunteers. The correlation between the above parameters and patients' clinical profile were evaluated. RESULTS: ①The percentage of CD3(-)CD56(+) NK cell in new diagnosed and remission CBCPC patients were significantly lower than that in healthy control [(10.04 ± 5.33)% vs (19.94 ± 7.38)%; (11.62 ± 6.80)% vs (19.94 ± 7.38)%, all P<0.01]. ② The expression of activating receptor NKG2D in new diagnosed CBCPC patients was significantly higher than that in remission group and healthy control [(74.03±18.24)% vs (45.97±29.45)%; (74.03±18.24)% vs (41.89± 15.34)% , P <0.01]. ③The expression of inhibitory receptor CD158a in new diagnosed CBCPC patients was significantly lower than that in remission group and healthy control (median: 3.72% vs 16.10%, P= 0.015; 3.72% vs 11.04%, P=0.025). ④The expression of perforin in new diagnosed and remitted CBCPC patients were significantly higher than that in healthy controls [(75.71±10.14) % vs (57.20±18.85)%, P= 0.018; (77.88±22.82)% vs (57.20±18.85)%, P=0.008]. ⑤The product of NK cell percentage and perforin expression in new diagnosed and remission CBCPC patient were significantly lower than that in healthy control [(7.68±4.54)% vs (12.13±5.19)%, P=0.011; (8.24±5.80)% vs (12.13±5.19)%, P=0.023]. The product of NK cell percentage and granzyme-ß expression in the new diagnosed and remission CBCPC patient were significantly lower than that in healthy control [(7.83±5.26)% vs (14.79±8.37)%, P=0.008; (8.37 ± 6.83)% vs (14.79±8.37)%, P=0.012]. CONCLUSION: Deceased quantities and impaired total NK function might play a role in pathogenesis of CBCPC.

Prognosis of advanced hepatocellular carcinoma patients enrolled in clinical trials can be classified by current staging systems.

BACKGROUND: Patients enrolled in clinical trials of advanced hepatocellular carcinoma (HCC) are usually required to have good liver reserve and organ function. However, their outcomes are still highly variable. We aimed to examine whether current staging systems can predict the survival of these highly selected patients. METHODS: Patients from clinical trials involving first-line anti-angiogenic therapy were assigned to different stage groups using the American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), China integrated score, Cancer of the Liver Italian Program (CLIP) score, Chinese University Prognostic Index (CUPI), Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH), Japan Integrated Staging (JIS) score, Okuda, Tokyo score, and a new staging system recently proposed. Survival prediction by the 10 systems was then compared by both univariate and multivariate analyses. RESULTS: A total of 157 patients were selected for this study. In univariate analysis, all staging systems can predict patient survival except AJCC, BCLC, and JIS score. Concordance indexes for CLIP score, CUPI, and GETCH (0.752, 0.775, and 0.791, respectively) were significantly higher than those obtained for other staging systems. In multivariate analysis, the CLIP score and CUPI (P<0.001 and 0.009, respectively) predicted survival more accurately than did the other tested staging systems. Hepatitis B infection and poor performance status were also associated with poor survival. CONCLUSION: Several HCC staging systems, especially the CLIP score and CUPI, can predict prognosis of patients who are enrolled in clinical trials of advanced HCC.

Construction of a broad-host-range promoter-probing vector and cloning of promoter fragments of Xanthomonas campestris.

A broad-host-range promoter-probing vector, pMY3 (8.0 kb), was constructed for cloning of DNA fragments containing promoter sequences of Xanthomonas campestris pv. campestris. This vector (pMY3) consists of the RK2 replicon, promoterless luxAB genes, the thr attenuator to block the transcription of RNA into the luxAB region, and multiple cloning sites for cloning of the fragment carrying promoter sequences. The feasibility of using pMY3 as a promoter-probing vector in both E. coli and Xc17 was demonstrated by using the lac promoter of E. coli, and the amy promoter of X. campestris in Xc17. Among the 63 promoter-containing fragments cloned from Xc17, only 9 were able to express in E. coli. It appears that X. campestris can recognize most E. coli type promoters, but, E. coli can recognize only a small portion of the X. campestris type promoters.

A fluorometric, high-performance liquid chromatographic assay for transglutaminase activity.

A fluorometric, high-performance liquid chromatographic assay for transglutaminase activity is described. The method uses the small synthetic peptide benzyloxycarbonyl-L-glutaminylglycine and the fluorescent amine monodansylcadaverine as substrates. Very small amounts of substrates and enzyme are required for this assay. The reaction product is separated from substrates on a reversed-phase, C-18 column, using an isocratic elution solvent consisting of 50% methanol in water, and is detected fluorometrically with didansylcadaverine as standard. A detection limit of 31 pmol of product per injection was measured. An apparent Km of 34.7 +/- 2.4 mM was determined for the peptide substrate with purified guinea pig liver enzyme. Using this assay, a series of alkyl aldehydes was shown to inhibit transglutaminase. Modification of this assay using either gradient or isocratic elution with various proportions of acetonitrile (0.1% trifluoroacetic acid)/water (0.1% trifluoroacetic acid) afforded assays for a series of glutamine-containing peptides including substance P, alpha-endorphin, and two small, synthetic peptides. The assay is suitable for measurement of transglutaminase activity with purified enzyme or with crude preparations. This method provides a sensitive, quantitative assay for the determination of substrate and inhibitor properties of small peptides toward transglutaminases.

Improvements in the determination of penicillin analogues by HPLC separation and laser-based polarimetric detection.

The combination of HPLC separation and laser-based polarimetric detection is shown to provide unique advantages when applied to the study of penicillin analogues. The mass delectability for penicillin G is 5 ng with this system, which is an order-of-magnitude improvement over other techniques. More importantly, the polarimetric system can provide specific rotation information about eluting species. Individual specific rotations are reported for the (10R)- and (10S)-epimers of both carbenicillin and ticarcillin. These results demonstrate the sensitivity of specific rotation to the arrangement of atoms at or near the chiral centre, suggesting that specific rotation may be used to identify closely related penicillin analogues.

Specific rotation measurements from peak height data, with a Gaussian peak model.

A method is described whereby a sensitive laser-based polarimeter can be used to make very accurate and precise specific rotation measurements on microgram quantities of optically active materials. Flow-injection or liquid chromatography systems provide reproducible introduction of the sample into the polarimetric system. If a Gaussian distribution of the analyte concentration is assumed, the peak height can be used in the determination of specific rotation. This method provides a direct calibration with an absolute standard which yields more accurate and precise results than those obtainable by using peak area.