Mouse models in liver cancer research： A review of current literature

Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma （HCC）, as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.     

Synthesis of new carbon-11 labeled naphthalene-sulfonamides for PET imaging of human CCR8.

Carbon-11 labeled naphthalene-sulfonamides, N-(4-(N-(4-[(11)C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)benzamide ([(11)C]5a), N-(4-(N-(4-[(11)C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-2-methylbenzamide ([(11)C]5b), N-(4-(N-(4-[(11)C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-3-methylbenzamide ([(11)C]5c), N-[(11)C]methyl-N-methyl-4-(4-benzamidonaphthalene-1-sulfonamido)piperidine-1-carboxamide ([(11)C]9a) and N-[(11)C]methyl-N-methyl-4-(4-(2-methylbenzamido)naphthalene-1-sulfonamido)piperidine-1-carboxamide ([(11)C]9b), have been synthesized as new potential positron emission tomography (PET) agents for imaging of human CCR8. The target tracers were prepared by either O-[(11)C]methylation or N-[(11)C]methylation of their corresponding precursors using [(11)C]CH(3)OTf and isolated by either a simplified solid-phase extraction (SPE) purification procedure or a high pressure liquid chromatography (HPLC) method in 30-50% radiochemical yields decay corrected to end of bombardment (EOB), 20-25min overall synthesis time, and 74-111GBq/mumol specific activity at end of synthesis (EOS).     

宁夏贝母化学成分的研究

从宁夏贝母(Frdillapia taipaiensis P. Y. Li var. ningxiaensis Y. K. Yang et. J. K. Wu)的鳞茎中分得六个异甾体生物碱成分,鉴定为宁贝素(taipaienine,Ⅰ)、川贝酮(chuanbeinone,Ⅱ)、西贝素(imperialine,Ⅲ)、贝母乙素(verticinone,Ⅳ)、贝母辛(peimissine,Ⅴ)和异贝母甲素(isoverticine,Ⅵ).其中T为一新C-去甲-D-高甾生物碱。应用波谱分析(IR,MS,¹HNMR和¹³CNMR)等确定了它们的化学结构。     

Computer graphics for digitally formatted images

The increasing use of digitally formatted imaging systems requires high-quality interactive gray-scale computer raster graphics systems for the management, display, and analog film recording of digital image and alphanumeric information. These systems are a combination of computer hardware and software and implement a set of graphics protocols. This paper describes a set of interactive graphics protocols that has been developed for clinical use.     

Studies of Swedish adjustable gastric band and Lap-Band: systematic review and meta-analysis

BACKGROUND: This is the first systematic review and meta-analysis of the large body of data describing the Swedish adjustable gastric band (SAGB) and Lap-Band (LB). METHODS: A systematic review was performed that included screening of studies published in any language (January 1, 1998 through April 30, 2006) identified through MEDLINE, Current Contents, or the Cochrane Library. Studies with > or =10 SAGB or LB patients reporting > or =30-day efficacy or safety outcomes were eligible for review; the data were extracted from the accepted studies. A weighted means analysis and random-effects meta-analysis of efficacy outcomes of interest were conducted. RESULTS: A total of 4592 bariatric surgery studies met the initial criteria. Of these studies, 129 (28,980 patients) were accepted (33 SAGB and 104 LB studies); most had a retrospective single-center design. For 4273 patients (36 treatment groups) in 33 SAGB studies and 24,707 patients (111 groups) in 104 LB studies, the mean baseline age (39.1-40.2 yr), body mass index (43.8-45.3 kg/m2), and gender (women 79.2-82.5%) were similar. A laparoscopic technique was used in > or =88% and a pars flaccida technique in > or =41% of both groups. Early mortality was equivalent for SAGB/LB (< or =.1%). The 3-year mean SAGB and LB excess weight loss (56.36% and 50.20%, respectively) and body mass index reduction (-11.99 and -11.81 kg/m2, respectively) from baseline were statistically significant (P <.05), as was the resolution of diabetes (61.45% and 60.29%, respectively) and hypertension (62.95% and 43.58%, respectively). Although scant and inconsistently reported data precluded direct statistical comparisons, the complication rates for the 2 devices appeared comparable. In 8 directly comparative studies, meta-analysis found a significantly greater absolute weight loss (P <.05) with the SAGB at 2 years (48.4 versus 41.9 kg, mean difference -4.84, 95% confidence interval -9.47 to -0.22), although no difference was found in the percentage of excess weight loss or change in body mass index. CONCLUSION: In a systematic review of the published world SAGB and LB data, at 1, 2, and 3 years, the weight loss, resolution of diabetes and hypertension, and complications appeared comparable.     

The effects of oncotype DX recurrence scores on chemotherapy utilization in a multi-institutional breast cancer cohort

The use of clinicopathologic features in decision-making in early stage estrogen receptor (ER)-positive breast cancer (BC) may lead to over or under treatment. We investigated the effect of the Oncotype Dx? (ODX) on chemotherapy (CTX) utilization in two cancer centers. 276 cases of node-negative ER-positive BC had ODX between 2005 and 2009. Age at diagnosis, tumor size, grade, and progesterone receptor (PR) status were abstracted from records and provided to two medical oncologists blinded to the ODX score. A recommendation for or against CTX was made based on clinicopathologic characteristics. Median age was 55 years. Mean tumor size was 1.6 cm. The median 10-year Adjuvant! Online (AO) mortality risk was 8. The median Nottingham Prognostic Index (NPI) was 3.3. The median ODX recurrence score was 17. Without knowledge of the ODX, oncologists were more likely to recommend CTX to younger women (P < 0.0001), women with negative PR status (P < 0.0001), higher NPI (P < 0.012), and tumors > 1 cm (P = 0.033). On average, CTX recommended patients had larger tumors (2.0 vs. 1.2 cm) and higher AO 10-year mortality (11.4 vs. 4.4%). ODX resulted in a change in management for 38% of women. Of 188 total patients who did not receive CTX, 71 had a recommendation favoring CTX by an oncologist blinded to the ODX score. In our multi-institutional cohort, the ODX score had a significant impact on the receipt of adjuvant CTX and altered management for 38% of women.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model.

The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses.     

Shape response of human erythrocytes to altered cell pH

Alteration of red blood cell (RBC) pH produces stomatocytosis (at low pH) and echinocytosis (at high pH). Cell shrinkage potentiates high pH echinocytosis, but shrinkage alone does not cause echinocytosis. Mechanisms for these shape changes have not been described. In this study, measured dependence of RBC shape on cell pH was nonlinear, with a broad pH range in which normal discoid shape was maintained. Transbilayer distribution of phosphatidylcholine and phosphatidylserine, measured by back-extraction of radiolabeled lipid, was the same in control and altered pH cells. Possible roles of pH- titratable inner monolayer phospholipids were examined by assessing pH- dependent shape in cells in which their levels had been perturbed. In metabolically depleted cells and calcium-treated cells, which have altered levels of phosphatidic acid, phosphatidylinositol-4-phosphate, and/or phosphatidylinositol-4,5-bisphosphate, low cell pH was stomatocytogenic and high cell pH was echinocytogenic, as in control cells. Thus, neither change in membrane lipid asymmetry nor normal levels of the pH-titratable inner monolayer lipids is necessary for cell pH-mediated shape change.