CAR T-Cell therapy for the management of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma (NHL) of mature B-cells characterized by translocation, which is typically due to excess expression of Cyclin D1. Although with the progress in our knowledge of the causes for MCL and available treatments for MCL, this cancer is still incurable. Age, male gender, rapid advancement, significant nodal involvement, elevated serum lactate dehydrogenase level, and prognostic indications including increased expression of Ki-67 and presence of TP53 mutation, are symbols of poor outcome. Advanced immunotherapy using chimeric antigen receptor (CAR)-T cells is advantageous for patients suffering from B-cell malignancies and MCL. Targeting B-cell antigens on the cell surface is a feasible approach in re-occurring (R/R) MCL because of significant responses obtained in other B-cell cancers. USFDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19), a novel CAR T-cell therapy to be used in patients with MCL who have not responded to previous treatments or have relapsed. The FDA approved this new treatment depending on the outcomes of the ZUMA-2 clinical trial. Serious adverse reactions, moderate anti-tumor activity, allergen withdrawal, antigen escape, limited tumor infiltration, and trafficking are major barriers to successful CAR T-cell therapy. This review is a brief synopsis of the development of CAR T-cell therapy for MCL.

Grb7 is over-expressed in cervical cancer and facilitate invasion and inhibit apoptosis in cervical cancer cells.

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34.2%, which was significantly higher than that in adjacent non-cancerous cervical tissue (0%, p<0.05). The expression of Grb7 was found to be correlated with age, tumor size, serosal invasion, differentiated degree, tumor stage, early or advanced stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with positive Grb7 protein expression had a lower overall survival rate than patients without Grb7 expression. In addition, Grb7 plays an important role in promoting tumor progression, including invasion and anti-apoptosis, in cervical cancer cell line. Down-regulation of Grb7 repressed the expression of MMP-9 and Bcl-2, and increased the expression of Bax in Grb7 knockdown Hela cells. Cell invasion assay showed decreased number of Grb7 knockdown Hela cells (18.7±2.1) compared to Hela cells (65.3±2.5, P<0.05). Our results indicated that Grb7 over-expression may facilitate invasion and inhibit apoptosis in cervical cancer and Grb7 is a potentially molecular target of cervical cancer chemotherapy.

[Analysis of Volatile Oils from Different Processed Products of Zingiber officinale Rhizome by GC-MS].

OBJECTIVE: To analyze the volatile components in different processed products of Zingiber officinale rhizome, and to make clear the effect of different heating degree on them. METHODS: The volatile components were extracted from four kinds of processed products by applying steam distillation, and then were analyzed by GC-MS. RESULTS: There were totally 43 components of volatile oil identified from four kinds of processed products of Zingiber officinale rhizome. Fresh product, dried product, and charcoal product of Zingiber officinale rhizome each had 27 components of volatile oil, while sand fried product contained 24 components. Fresh Zingiber officinale rhizome contained 22. 59% of zingiberene, 20. 87% of a-citral and 11. 01% of ß-phellandrene, respectively. After processing in different heating degree, the volatile components changed greatly in both of their quantity and quality, For instance, dried Zingiber officinale rhizome contained 40. 48% of α-citral and 8-phellandrene content was slightly lower at 10. 38%. 32.73% of 3,7,11-trimethyl-l, 6, 10-dodecatriene,16. 38% of murolan-3, 9 (11)-diene-10-peroxy and 3. 36% of cubebene newly emerged in the sand fried Zingiber officinale rhizome, and eudesm-4 (14) and ß-bisabolol, etc. However, ß-phellandrene content was only 1. 95%. The zingiberene and ß-sesquiphellandrene were the highest in charcoal product, besides, new components such as α-cedrene, decanal and γ-elemene appeared. CONCLUSION: Volatile components in different processed products of Zingiber officinale rhizome were different in both of their kinds and contents. This method is suitable for the analysis of volatile components in Zingiber officinale rhizome, and this study can provide the experimental evidence for quality evaluation and clinical application for ginger processed products.

[Optimization of wine-roasting technology of coptidis rhizoma using orthogonal design].

OBJECTIVE: To optimize the processing technology of Coptidis Rhizoma roasting with yellow rice wine. METHODS: The total content of four kinds of alkaloids was used as index. Orthogonal design was applied to study the processing technology of Coptidis Rhizoma roasting with yellow rice wine. L9 (3(4)) orthogonal table was decided with three factors: roasting temperature, roasting time and the amount of yellow rice wine. RESULTS: Of the three factors, only B factor (roasting time) had obvious effect on the total content of four kinds of alkaloids. CONCLUSION: The optimal processing technology is as follows: Coptidis Rhizoma should be roasted with 15% yellow rice wine for 30 min at 150 degrees C.

A novel and simple hollow-fiber assay for in vivo evaluation of nonpeptidyl thrombopoietin receptor agonists.

Preclinical in vivo assessment of the pharmacologic activity of nonpeptidyl thrombopoietin receptor (TPOR) agonists is very difficult because of the high species specificity of such agonists. In this study, we have developed a novel and simple in vivo hollow-fiber assay to preclinically evaluate TPOR agonists. The 32D-mpl cell line was generated by stable transfection of human TPOR into 32D lymphoblast cells and shown to be a specific model for nonpeptide TPOR agonists in vitro. Stably transfected 32D-mpl cells were then sealed in hollow fibers and implanted into nude mice. Cells in hollow fibers specifically responded to TPOR agonists, including thrombopoietin and eltrombopag, a nonpeptide small-molecule TPOR agonist, but not to granulocyte colony-stimulating factor or erythropoietin. Oral administration of eltrombopag stimulated 32D-mpl cell proliferation, prevented 32D-mpl cell apoptosis, and stimulated the phosphorylation of cellular signaling transducers and activators of transcription in a TPOR- and dose-dependent manner. These results indicate that the hollow-fiber assay is a specific and efficient model for rapidly evaluating the in vivo activity of small-molecule TPOR agonists.