A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb.

Chimeric antigen receptor T-cell immunotherapy (CAR-T) has shown remarkable efficacy in treating tumors of lymphopoietic origin. Herein, we demonstrate an effective CAR-T cell treatment for recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL) has been demonstrated. The extracellular fragment gene sequences of CD30 were obtained from tumor tissues of PTCL patients and cloned into a plasmid vector to express the CD30 antigen. The CD30 targeting single-chain antibody fragment (scFv) was obtained from CD30-positive monoclonal hybridoma cells, which were obtained from CD30 antigen immunized mice. After a second-generation of CAR lentiviral construction, CD30 CAR T cells were produced and used to determine the cytotoxicity of this construct toward Karpas 299 cells. The results of CD30 CAR T-mediated cell lysis show that 9C11-2 CAR T cells could significantly promote the lysis of CD30-positive Karpas 299 cells in both LDH and real-time cell electronic sensing (RTCA) assays. In vivo data show that 9C11-2 CAR T cells effectively suppress the tumor growth in a Karpas 299 cell xenograft NCG mouse model. The CD30 CAR T cells exhibited an efficient cytotoxic effect after being co-cultured with the target cells and they also exhibited a significant tumor-inhibiting ability after being intravenously injected into PTCL xenograft tumors; these observations suggest that the new CD30 CAR-T cell may be a promising therapeutic candidate for cancer therapy.

Identification and functional characterization of JWA polymorphisms and their association with risk of gastric cancer and esophageal squamous cell carcinoma in a Chinese population.

Recently, a novel single nucleotide polymorphism (SNP) in the promoter of the JWA gene (-76G --> C) was identified that may alter the transcription activity and thus play a role in increased risk of bladder cancer. In this study, a screen for more novel variants in the JWA exons was undertaken by using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by a PCR-restriction fragment length polymorphism (PCR-RFLP) method and evaluating the functions of newl identified JWA -76G --> C using the reporter gene assay. In addition to the -76G --> C polymorphism, another novel SNP (723T --> G) in exon 3 of JWA was identified. In a case-control study of these two SNPs in 413 gastric cancer and 250 esophageal squamous-cell carcinoma (ESCC) patients and 814 cancer-free controls in a Chinese population, data showed that both SNPs were associated with enhanced risk of these cancers. The reporter gene assay showed that the -76C variant allele lost its response to benzo[a]pyrene (BaP) exposure, compared to the -76G allele. In addition, the JWA -76C allele was found to be associated with increased gastric and esophageal cancer risks in this study population. Further studies are needed to substantiate the biological significance and related mechanisms underlying the associations.

Single nucleotide polymorphism of the JWA gene is associated with risk of leukemia: a case-control study in a Chinese population.

The JWA gene was initially cloned as a novel cell differentiation-associated gene and was subsequently found to be an environmental responsive gene. The JWA gene also produced a marked effect during chemical-induced multidirectional differentiations of primary and human myeloid leukemia cells. Recently, a novel single nucleotide polymorphism (SNP) in exon2 of the JWA gene (454CA) was identified that may play a role in risk of bladder cancer. The aim of this study was to investigate the association between the 454CA (NM_006407.2) in JWA exon2 variants and risk of leukemia in a hospital-based case-control study of 202 leukemia patients and 289 cancer-free controls. Results indicated that 454A allele was found to associate with significantly increased risk of leukemia, although the 454CA is a synonymous polymorphism in coding region of the JWA gene. In conclusion, the potentially functional genetic polymorphism 454CA of the JWA gene appears to contribute to the risk of multiple kinds of leukemia in a south Chinese population.

Functional variations in the JWA gene are associated with increased odds of leukemias.

The association between the -76G>C in the 5'-flanking region and 723T>G in JWA exon three variants were examined for risk of leukemia development in a hospital-based case-control study of 201 leukemia patients and 243 cancer-free controls in a Chinese population. Studies showed that the -76C allele was associated with significantly increased odds of leukemia but the 723G allele was correlated with marked decreased odds of leukemia. Variation in the -76C allele resulted in almost complete loss of oxidative stress stimulated transcription activities of the promoter fragment.

[Influence of Qingdai compound on expression of bcr/abl and JWA in K562 cells].

To study the effects of Qingdai compound on proliferation and apoptosis of K562 cells, as well as the expression of bcr/abl and JWA mRNA, K562 cells were treated in culture with different concentrations of Qingdai compound (2.5, 5, 7.5, 10 and 20 mg/ml) and harvested at 24 hours. Then morphological changes were observed by light microscopy (LM); expressions of bcr/abl and JWA were detected with semi-quantitative RT-PCR. The results showed that morphological changes were observed as the increment of the Qingdai compound concentration. Inhibition effects on proliferation and apoptosis in K562 cells were seen. A concentration-dependent decreases were found in bcr-abl and JWA mRNA expression of K562 cells. Qingdai compound partially inhibited proliferation and induced apoptosis of K562 cells. Expressions of both bcr/abl and JWA, which took part in cell proliferation and apoptosis, were down-regulated in a dose dependent manner. In conclusion, Qingdai compound can partially inhibit the expressions of bcr/abl and JWA genes in K562 cells, and the clinical effect of Qingdai compound on CML may be associated with apoptosis of leukemic cells.

Effects of polyelectrolytes on reduction of model compounds via coagulation.

The objective of this research work was to evaluate the performance of enhanced coagulation by alum and polymer. Synthetic source waters containing high molecular weight humic acids, medium molecular weight tannic acids and low molecular weight p-hydroxybenzoic acid were formulated by adjusting the concentration of turbidity and pH; and jar tests were used to study the effect of various types and dosages of polymer on reducing the above model compounds. At a specific pH condition, the applied alum dosage would efficiently decrease the turbidity to 2 NTU follows the order: humic>tannic>p-hydroxybenzoic acid. Adjustment of pH influenced the performance of alum obviously but not of p-DADMAC. High p-DADMAC dosage overwhelming the effects of alum is less affected by pH adjustment. The results of this investigation reveal that enhanced coagulation with p-DADMAC was founded to be very effective for removing high-molecular-weight THM precursors, i.e., humic acid and tannic acid, and markedly reduced the alum dosages required for turbidity removal. The other two polymers, i.e., cationic PAM and non-ionic PAM, which had higher molecular weight but lower charge density than p-DADMAC, were not capable of removing organic precursors. It was thus concluded that enhanced coagulation with polymer, p-DADMAC, could be considered as a promising technique for removal of NOMs with hydrophobic and higher-molar-mass (>1K) in water treatment plants.