[Diffuse hemangiomatosis of the skeleton, liver, kidney and soft tissues].
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Angiomatosis↗
Biomedical subjects
D Yu
Publications and source records attributed to D Yu.
Role of endothelium in the control of mouse yolk sac stem cell differentiation.
Studies in our laboratory have shown that as early as day 8.5 of development, mouse yolk sac cells can generate T cells when placed in a thymic microenvironment. At this stage, yolk sac cells can also differentiate into myeloid cells in vitro. B cell differentiation in vitro was achieved with day 9 yolk sac by providing a bone marrow stromal feeder layer. We have now established endothelial cell lines and clones from yolk sacs of day 8-12 mouse embryos. These vary in their ability to support stem cell maintenance and differentiation. Our principal work has been carried out with day 12 cloned endothelial cell lines. One clone supported the > 100 fold expansion of yolk sac hematopoietic stem cells that subsequently could generate B cells, T cells and myeloid cells both in vitro and in vivo. Preliminary experiments with endothelial cells from younger embryos are also described.
Animals↗
Air pollution and daily mortality in Shenyang, China.
The authors analyzed daily mortality data in Shenyang, China, for calendar year 1992 to identify possible associations with ambient sulfur dioxide and total suspended particulates. Both total suspended particulate concentrations (mean = 430 microg/m3, maximum = 1,141 microg/m3) and sulfur dioxide concentrations (mean 197 = microg/m3, maximum = 659 microg/m3) far exceeded the World Health Organization's recommended criteria. An average of 45.5 persons died each day. The lagged moving averages of air-pollution levels, calculated as the mean of the nonmissing air-pollution levels of the concurrent and 3 preceding days, were used for all analyses. Locally weighted regression analysis, including temperature, humidity, day of week, and a time variable, showed a positive association between daily mortality and both total suspended particulates and sulfur dioxide. When the authors included total suspended particulates and sulfur dioxide separately in the model, both were highly significant predictors of daily mortality. The risk of all-cause mortality increased by an estimated 1.7% and 2.4% with a 100-microg/m3 concomitant increase in total suspended particulate and sulfur dioxide, respectively. When the authors analyzed mortality separately by cause of death, the association with total suspended particulates was significant for cardiovascular disease (2.1%), but not statistically significant for chronic obstructive pulmonary diseases (2.6%). In contrast, the association with sulfur dioxide was significant for chronic obstructive pulmonary diseases (7.4%), but not for cardiovascular disease (1.8%). The mortality from cancer was not associated significantly with total suspended particles or with sulfur dioxide. The correlation between sulfur dioxide and total suspended particulates was high (correlation coefficient = .66). When the authors included sulfur dioxide and total suspended particulates simultaneously in the model, the association between total suspended particulates and mortality from all causes and cardiovascular diseases remained significant. Sulfur dioxide was associated significantly with increased mortality from chronic obstructive pulmonary diseases and other causes. The results of the current study reveal increased mortality associated with both total suspended particulates and sulfur dioxide.
Air Pollution↗
Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma.
This report describes a phase I study of the adoptive transfer of cloned melanoma antigen-specific T lymphocytes for therapy of patients with advanced melanoma. Clones were derived from peripheral blood lymphocytes or tumor-infiltrating lymphocytes of patients who had received prior immunization with the melanoma-associated antigen, gpl00. In response to its cognate antigen, each clone used for treatment secreted large amounts of interferon-gamma and granulocyte-macrophage colony-stimulating factor, lesser amounts of interleukin (IL)-2 and tumor necrosis factor-alpha, and little or no IL-4 and IL-10. Clones also demonstrated recognition of human leukocyte antigen-matched melanomas using cytokine secretion and lysis assays. Twelve patients received 2 cycles of cells alone; 11 patients received additional cycles of cells and were randomized between two schedules of IL-2 (125,000 IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg intravenously every 8 h for 4 days). A total of 51 cycles of cells were administered, with an average of 1 x 10(10) cells per cycle. Peripheral blood samples were analyzed for persistence of transferred cells by T-cell receptor-specific polymerase chain reaction. Transferred cells reached a maximum level at 1 h after transfer but rapidly declined to undetectable levels by 2 weeks. One minor response and one mixed response were observed (both in the high-dose IL-2 arm). This report demonstrates the safety and feasibility of cloned T-cell transfer as a therapy for patients with cancer. The lack of clinical effectiveness of this protocol suggests that transfer of different or additional cell types or that modulation of the recipient host environment is required for successful therapy.
Adult↗
Advances in the understanding of human soft tissue sarcomas: molecular biology and therapeutic strategies (Review).
Soft tissue sarcomas comprise a group of exceedingly rare and histologically diverse malignancies. A multidisciplinary approach utilizing surgery, radiation therapy, and chemotherapy has evolved to address the challenge of effective treatment. Pertinent to this clinical goal are efforts to understand the molecular mechanisms underlying the etiology, proliferation, and metastatic phenotype of these tumors. This review describes the specific research efforts of our laboratory, which focus on the role of tumor suppressor genes and angiogenic factors as drivers of malignant behavior in soft-tissue sarcomas. By enlarging our knowledge of basic sarcoma tumor biology, it may be possible to identify important molecular mechanisms that can guide the design of future molecularly based therapies for this disease.
Cell Division↗
Increased hyaluronidase expression in more aggressive prostate adenocarcinoma.
Tumor metastasis involves a complex sequence of cellular and biochemical events of which tumor cell penetration through the basement membrane is an essential component. Disruption of basement membrane integrity by hyaluronidase has been implicated in the development of locally advanced and metastatic carcinoma. This investigation correlates hyaluronidase expression with pathologic prognostic variables for prostate adenocarcinoma. Paraffin samples (n=9) of patients receiving prostatectomies for clinical stage B adenocarcinoma were evaluated. RT-PCR was utilized to detect the presence of hyaluronidase. These results were correlated with the histological assessment of each sample. Gleason score was significantly higher in patients with RT-PCR detectable hyaluronidase (mean +/- SD 7.25+/-1.8 versus 4.17+/-1.0; p<0.05). Histological evidence of perineural invasion was seen in 83% of the specimens with detectable hyaluronidase, whereas none was found in hyaluronidase negative samples (p<0.05). A trend was seen between hyaluronidase and capsular invasion with 33% hyaluronidase positive tumor exhibiting evidence of capsular invasion, while no evidence in the hyaluronidase negative tumor. These data suggest that hyaluronidase may be involved in prostate adenocarcinoma progression and metastasis.
Biomarkers, Tumor↗
Alteration of nuclear matrix protein composition of neuroblastoma cells after arsenic trioxide treatment.
The aims of the present study were to assess the effects of arsenic trioxide on the nuclear matrix protein profiles of mouse neuroblastoma cells. Arsenic trioxide induces apoptosis of acute promyelocytic leukemia cells. Our results demonstrated that 2 microM As2O3 could significantly inhibit the growth of Neuro-2a cells. As early as 24 hours after As2O3 treatment, we began to observe the alteration of nuclear matrix proteins and apoptosis in tumor cells by TUNEL assay but not by DNA ladder. An increase expression of Hsc in nuclear matrix proteins of 2 microM As2O3 treated cells was also noted. Our results also showed that before a mass range of apoptosis occurred, the composition of nuclear matrix proteins had altered. Hence the alteration of nuclear matrix proteins, such as increased expression of Hsc, may be a sensitive indicator for the detection of early apoptosis.
Animals↗
The effect of arsenic trioxide on the expression of Hsc and HNF4 in nuclear matrix proteins in HepG2 cells.
Anticancer agents interfere with the proliferation and survival of tumor cells by a variety of mechanisms. An important factor in the development of a cytotoxic effect by certain anticancer agents is the localization of drug-induced lesions within the cell nucleus. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by some of these agents. Arsenic trioxide (As2O3) was identified as a very potent anti-leukemic agent by inducing apoptosis. The present study shows that As2O3 significantly inhibits the growth of hepatoblastoma cell line, HepG2, changes the composition of nuclear matrix proteins and reduces the expression of Hsc 70 and HNF4 in HepG2, which in turn initiate a cascade of events that compromise multiple nuclear functions and, ultimately, cell survival.
Antigens, Nuclear↗
Evaluation of the European Spondyloarthropathy Study Group (ESSG) classification criteria in a Chinese population.
OBJECTIVE: To evaluate for thefirst time in a Chinese population, the usefulness of the European Spondyloarthropathy Study Group (ESSG) criteria. METHODS: A total of 193 clinically diagnosed SpA patients were compared to 166 patients with other types of arthritis, using the parameters listed in the ESSG criteria. RESULTS: The sensitivity and specificity of the ESSG criteria in this Chinese population were high at 85.4% and 96.4% respectively. CONCLUSION: The use of ESSG criteria for classifying SpA in Chinese will not lead to significant omission of SpA patients or inclusion of patients who do not have SpA.
China↗
[Lymphography in bladder carcinoma].
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Adult↗
Up-regulation of urokinase-type plasminogen activator expression by the HER2/neu proto-oncogene.
The HER2/neu (c-erbB2) protooncogene, which encodes a transmembrane receptor (p185neu), contributes to tumor cell invasion/metastasis through mechanism(s) which are, at present, poorly defined. Since basement membrane degradation is a prerequisite for tumor progression, we undertook a study to determine if the expression of urokinase, a key protease implicated in extracellular matrix proteolysis, was regulated by this oncogene. Stable overexpression of a cDNA encoding HER2/neu in H460 lung cancer cells led to elevated secretion of urokinase which was a consequence of a higher level of protease mRNA. Transfection of the HER2/neu-overexpressing B 104-1 cells with a CAT reporter construct driven by the urokinase promoter, gave rise to increased CAT activity when compared with parental NIH3T3 cells, which have low levels of HER2/neu, suggesting that the protooncogene can enhance urokinase promoter activity. Since the enhanced expression of HER2/neu results in increased tumor invasion/metastasis (1), these data suggest that, at least in vitro, HER2/neu-induced expression of urokinase may contribute to tumor progression in p185neu-positive cancers.
3T3 Cells↗
A multivariate analysis of the relationship between work ability and S. japonicum infection in Dongting Lake region, in China.
A cross-sectional case-control study on the association between the reduced work ability and S. japonicum infection was carried out in a moderate endemic area for schistosomiasis japonica in the southern part of Dongting lake in China. A total of 120 cases with reduced work ability and 240 controls paired to the case by age, sex, occupation and without reduced work ability, participated in the study. The mean age for individuals was 37.6 years old (21-60), the ratio of male:female was 60:40, the prevalence of S. japonicum in the individuals was 28.3%. The results obtained in this study showed that the infection of S. japonicum in case and control groups was 49.2% (59/120) and 17.9% (43/240), respectively. Odds ratio for reduced work ability among those who had schistosomiasis was 4.34 (95%), confidence interval was 2.58-7.34, and among those who had S. japonicum infection (egg per gram > 100) was up to 12.67 (95%), confidence interval was 3.64-46.39. After odds ratio was adjusted by multiple logistic regression, it was confirmed that heavier intensity of S. japonicum infection and splenomegaly due to S. japonicum infection were the main risk factors for reduced work ability in the population studied.
Adult↗
Mutant SV40 large T antigen as a therapeutic agent for HER-2/neu-overexpressing ovarian cancer.
The HER-2/neu gene is frequently amplified and/or its protein product, p185, is overexpressed in a number of human cancers. Overexpression of p185 correlates with poor prognosis and low survival rates in ovarian cancer patients. We previously found that the K1 mutant of SV40 large T antigen inhibits rat neu promoter and suppresses mutation-activated rat neu transformation in mouse fibroblasts. We show here that K1 also inhibits human HER-2/neu promoter in human ovarian cancer cells. To investigate whether K1 can suppress HER-2/neu transformation and thus is a potential therapeutic agent, we used an orthotopic ovarian cancer model in which mice were injected intraperitoneally with HER-2/neu-overexpressing human ovarian cancer cells to induce tumor development. The tumor-bearing mice were then treated with K1-liposome complex weekly. We found that liposome-mediated K1 gene transfer decreased the p185 protein level by K1 expression in these cancer cells and significantly prolonged mice survival; about 40% of these treated mice were alive for more than 1 year without any tumor development. On the other hand, the animals from control groups that did not receive this gene therapy all developed tumors and died within 7 months. The results indicate that liposome-mediated K1 gene transfer is able to suppress tumor development from HER-2/neu-overexpressing ovarian cancer cells in mice.
Animals↗