To utilize Bifidobacterium longum (B. longum) as a safe and stable delivery system for endostatin in cancer gene therapy, we constructed pBV22210 vector combining a chloramphenicol-resistance gene (Cm r ) from pBCSK( þ ) plasmid, a cryptic plasmid pMB1 from B. longum strain with pBV222. Endostatin was cloned directly downstream of an N terminal His6-tag sequence in the pBV22210, so that the endostatin protein expressed in B. longum could be purified with Ni-binding resin. The results indicated that the plasmid electroporated into B. longum was maintained stably in the absence of selective antibiotics and did not significantly affect biological characteristics of B. longum. In addition, the plasmid in B. longum showed a strong inhibitory effect on the growth of mouse solid liver tumor in vivo. These results suggested that this new plasmid may be a stable vector in B. longum for transporting anti-cancer genes in cancer gene therapy.

In our previous study, we have shown that vector pBV22210 containing a chloramphenicol resistance and a cryptic plasmid pMB1 from Bifidobacterium longum strain could stably replicate and did not significantly affect the biological characteristics of B. longum. In this study, B. longum was transfected by electroporation with pBV22210 encoding the extracellular domain of TRAIL (B. longum-pBV22210-TRAIL) and its carbohydrate fermentation and growth curve were determined, and its location and inhibitory effect on tumor xenografts in mice were also examined. The results further proved that gene transfection did not change the main biochemical characteristics of B. longum. The results also showed that B. longum-pBV22210-TRAIL resulted in selective location in tumors and exhibited a definite antitumor effect on S180 osteosarcoma. In addition, when a low dosage of Adriamycin (5 mg kg À1 ) or B. longum-pBV22210-endostatin was combined, the antitumor effect was significantly enhanced. The successful inhibition of S180 tumor growth suggested a stable vector in B. longum for transporting anticancer genes combined with low-dose chemotherapeutic drugs or other target genes is a promising approach in cancer gene therapy.

ABSTRACT. In this study, the relationship between CYP19 gene polymorphisms and breast cancer in Xinjiang Uigur women was investigated. A case-control study was designed to compare 112 Uigur breast cancer patients with 139 Uigur healthy controls. Individuals were genotyped for the CYP19 rs10046 polymorphism using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Accordingly, the relationship between the rs10046 polymorphism and the susceptibility of Xinjiang Uigur women to breast cancer was analyzed. Given that the allele at the rs10046 site varies between C and T within the CYP19 gene, the frequency distribution of the C and T allele in breast cancer subjects were 48.2 and 51.8% respectively, and 47.5 and 52.5% in control cases. Moreover, the frequency distribution of the TC, CC, and TT genotype were 26.8, 42.9, and 30.4% in breast (2015) cancer cases, but 18.0, 59.0, and 23.0% in control cases (P < 0.05). Risk factors within the Uigur population for breast cancer included an age ≥ 50 years old, a BMI ≥ 25 kg/m 2 , and a parity ≥ 2. Conversely, an abortion and the CYP19 rs10046 TC genotype were protective factors. Menopause was another independent risk factor for breast cancer in Uigur women after the correction for age, BMI, age at first parity, pregnancy, and breastfeeding. In conclusion, breast cancer in Xinjiang Uigur women is closely connected with the age, BMI, parity, abortion, and CYP19 rs10046 polymorphisms. The TC genotype and an abortion can reduce the risk of the breast cancer disease in Uigur women.

Extensive experimental evidence has shown that thymic hormones (or factors) affect and regulate the differentiation and function of T lymphocytes. However, little is known about the action, if any, of thymic hormones on B lymphocytes. This paper reports the results of an investigation of the effect of a calf thymic peptide preparation (TP) prepared in our laboratory, on the proliferation and differentiation of human B lymphocytes. TP at concentrations higher than 1 micrograms (protein)/ml inhibited the proliferative responses of human B lymphocytes to the stimulation by Staphylococcus aureus Cowen strain I (SAC) and F(ab')2 fragments of goat anti-human IgM, mu chain specific antibody (anti-mu). TP itself had neither toxic nor mitogenic effect on B cells. TP at concentrations of 60 and 100 micrograms/ml did not affect the differentiation of B cells driven by SAC and PWM in a reverse PFC assay, but appeared to suppress the production in some individuals of total IgG and IgM in culture supernatants in a PWM system. Preculture of B cells with 60 micrograms/ml of TP for 40 hrs showed a suppression of the proliferative response to SAC and anti-mu stimulation, suggesting that TP might act on cells directly and persistently for some time. When TP was added to the culture on day 0 or on day 1, a similar decrease of inhibition of B cell proliferation was observed. A decrease in monocytes from 15-17% to 5% did not appreciably influence the suppression of SAC- or anti-mu-induced proliferation of B cells by TP. These preliminary results suggest that a calf thymic peptides preparation might have some direct effect on B lymphocytes.