DNA amplification on chromosome 13q31.1 correlated with poor prognosis in colorectal cancer

Colorectal cancer is a leading cause of cancer deaths worldwide. Genetic markers involved in prognosis of colorectal cancer are still being elucidated. In this study, genetic alterations associated with prognosis of colorectal cancer were determined using arbitrarily primed polymerase chain reaction (AP-PCR) and analyzed quantitatively by real-time PCR. Seven different DNA sequences, mapped on chromosomes 13q31.1, 9q31.1, 1q24, 4q31.3, 10q21, 11q13.4, and 13q13.3, were identified. Among these sequences, seven cases (23%) harbored DNA amplification in chromosome 13q31.1, and 9 (29%) and 7 (23%) presented genetic alterations in chromosome 1q24 and 11q13.4, respectively. Multivariate analysis showed that only DNA amplification in chromosome 13q31.1 was associated with poor survival among patients with colorectal cancer, with median survival time for chromosome 13q31.1 amplification versus no amplification of 64 versus 268 weeks (P = 0.001). This genetic alteration may have a prognostic role in colorectal cancer.     

Polymorphism of glutathione S-transferase omega gene and risk of cancer

Polymorphic glutathione S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to cancer. Though polymorphisms have been reported in GSTO1 and GSTO2, their predisposition to cancer risk has not yet been explored. In this case control study, 28 cases of hepatocellular carcinoma, 30 cases of cholangiocarcinoma, 31 cases of colorectal cancer, 30 cases of breast cancer and 98 controls were compared for frequencies of GSTO1 and GSTO2 genotypes. The statistical analysis provided the support for the difference in genotypic distribution for GSTO1*A140D between hepatocellular carcinoma (OR 23.83, CI 95%: 5.07-127), cholangiocarcinoma (OR 8.5, CI 95%: 2.07-37.85), breast cancer (OR 3.71, CI 95%: 1.09-13.02) and control. With regards to GSTO2*N140D polymorphism, there was no difference in genotypic distribution between all the types of cancer and control. The study suggests that GSTO1*A140D polymorphism could play an important role as a risk factor for the development of hepatocellular carcinoma, cholangiocarcinoma and breast cancer.     

Distinct immunologic properties of Penicillium marneffei yeasts obtained from different in vitro growth conditions

A dimorphic fungus Penicillium marneffei is a causative agent of penicilliosis, a life-threatening disseminated disease in immunocompromised hosts predominantly found in southeast Asia and southern China. P. marneffei is the only known Penicillium that possesses a dimorphic characteristic. Since it is difficult to produce large amount of P. marneffei yeasts in vivo for experimentation purpose, yeast cells were produced in different in vitro conditions as alternatives. We interested in investigating the immunologic properties of yeast cells from different culture preparations. It was found that yeast cells obtained from brain heart infusion broth and Sabouraud dextrose broth did not resemble those resided in clinical specimens. A solution of 1% peptone, on the other hand, could induce a direct conidial transition into fission yeasts. Ability of yeast cells in each preparation to activate macrophages was determined by analyzing surface expression of CD40 and CD86 co-stimulatory molecules after two days of co-cultivation. Every P. marneffei yeast cell preparation demonstrated such ability. However, the ones from Sabouraud dextrose broth seemed to induce less phagocytosis. Additionally, although distinct antigenic profiles and lack of conformity in antigenic expression were observed among yeast cells from different culture conditions, most major immunogenic bands were present when Western analysis was performed using polyclonal antisera from penicilliosis patients. The results of the study raise attention on immunological and biochemical characteristics of P. marneffei yeasts if such preparations are to be used in future laboratory investigations.     

Effect of angiotensin type I[ndash ]receptor blockade on left ventricular remodeling in pressure overload hypertrophy

Background: The renin-angiotensin system is involved in cardiac remodeling. In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (AT₁)-receptor blockade on left ventricular (LV) hypertrophy and dysfunction is controversial. Methods and Results: Descending thoracic aorta[ndash ]banded and sham-operated guinea pigs were given either losartan (30 mg [middot] kg^{[minus ]1} [middot] day^{[minus ]1} intraperitoneally) or vehicle for 8 weeks (n = 7 in each group). LV end-diastolic and end-systolic dimensions and wall thicknesses were measured echocardiographically, and LV fractional shortening, relative wall thickness, and LV mass normalized by body weight were calculated. Isolated heart function (Langendorff perfusion) was studied 8 weeks after surgery, and LV performance was assessed by maximum LV pressure and [plusmn]dP/dt normalized by LV mass. Eight weeks after banding guinea pigs developed concentric LV hypertrophy and had decreased maximum LV pressure and [plusmn]dP/dt normalized by LV mass; LV end-diastolic dimension and LV fractional shortening were unchanged. In band-operated guinea pigs treatment with losartan had no significant effects on any of these measurements. Conclusions: In guinea pigs with descending aortic banding, treatment with losartan for 8 weeks neither attenuates progression of pressure overload hypertrophy nor significantly improves impaired mass-normalized pressure-derived indices of LV contraction and relaxation.     

Challenging successive mosquito generations with a densonucleosis virus yields progressive survival improvement but persistent, innocuous infections

Research on cultivated shrimp suggests that they have the capability to tolerate viral pathogens in a highly specific manner by mechanisms currently unknown. The phenomenon is difficult to study in detail because they have a generation time of 1-2yr and lack continuous cell lines. Thus, we developed a mosquito-densovirus model to examine whether similar phenomena occur in insects. Serial challenge of five generations with a stock densovirus (AThDNV) resulted in progressive survival increases from 15% to 58%. Prevalence of AThDNV infection in surviving mosquito larvae (confirmed by PCR, histology, in situ hybridization and transmission electron microscopy) was relatively high (e.g. 36% in F2) but they grew normally to establish each succeeding generation. At the end of five generations, comparison of deduced amino acid sequences from genome fragments revealed a significantly higher (p=0.02) estimated prevalence of defective targets in the survivor virus population (29.7%+/-10.0 SD) than in the stored viral population (3.3%+/-5.8 SD). The results paralleled those reported for serially passaged C6/36 mosquito cell cultures infected with a densovirus. There, reduced infection rates are ascribed to the production of defective interfering particles (DIP). Thus, it is possible that the presence of prior AThDNV infections with a high level of DIP contributed to improved survival in our challenged F4 mosquito population. If so, it suggests that persistent viral infections in arthropods may serve in a specific, adaptive manner to reduce the incidence and severity of disease.     

Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery

Nanotechnology-based antigen delivery has been developing as a vaccine strategy due to its dose-sparing and prolonged antigen presentation features. In the current study, we examined the feasibility of nanoparticle (NP)-mediated delivery of antigenic peptides to efficiently induce cytotoxic T lymphocyte responses against tumor-associated self-antigens in C57BL/6 mouse models. The biodegradable poly(D,L-lactide-co-glycolide) nanoparticle (PLGA-NP) carrying murine melanoma antigenic peptides, hgp100(25-33) and TRP2(180-188), were prepared by double emulsion method. Efficient uptake of PLGA-NP by murine dendritic cells was shown in vitro and in vivo, using NP labeled with the fluorescent dye DiD. Intradermal injection of peptide-loaded PLGA-NP into mice induced antigen-specific T cell responses more strongly than the peptides mixed with Freund's adjuvant. More importantly, vaccination with PLGA-NP carrying both TRP2(180-188) and a toll-like receptor 4 agonist, monophosphoryl lipid A, significantly delayed growth of subcutaneously inoculated B16 melanoma cells in a prophylactic setting. Furthermore, the anti-tumor activity of NP-mediated peptide vaccination was significantly augmented by combined treatment with interferon-γ, which might prevent tumor escape through up-regulation of MHC class I expression on tumor cells. Our findings demonstrate the feasibility of NP-mediated antigen delivery for cancer immunotherapy, in particular when immune escape mechanisms of tumor cells are blocked simultaneously.     

Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants

OBJECTIVE: To determine the efficacy and safety of oral erythromycin (EM) for feeding intolerance in preterm infants < 35 weeks gestation. STUDY DESIGN: In this randomized, double-blinded, placebo-controlled trial, preterm infants with feeding intolerance were randomly allocated to a treatment group given EM ethyl succinate 10 mg/kg every 6 hours for 2 days, followed by 4 mg/kg every 6 hours for another 5 days, or to a control group given placebo. The primary outcome was time to full feeding (150 mL/kg/day) after the start of treatment. RESULTS: Each group comprised 23 preterm infants, almost all of whom were < 32 weeks gestation. Baseline characteristics were similar between the 2 groups. Times to full feeding were significantly shorter and the number of withheld feeds were significantly less in the EM group than the control group; the respective medians (interquartile ranges) were 7 days (6 to 9 days) versus 13 days (9 to 15 days) (P < .001) and 1 episode (0 to 2 episodes) versus 9 episodes (2 to 13 episodes) (P < .001). No significant differences in episodes of sepsis, necrotizing enterocolitis, and cholestasis were observed. CONCLUSIONS: Oral EM was effective and safe for treatment of feeding intolerance in preterm infants.