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result(s) for
"Chen, Liguang"
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ROR1 Is Expressed in Human Breast Cancer and Associated with Enhanced Tumor-Cell Growth
2012
Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is expressed during embryogenesis and by certain leukemias, but not by normal adult tissues. Here we show that the neoplastic cells of many human breast cancers express the ROR1 protein and high-level expression of ROR1 in breast adenocarcinoma was associated with aggressive disease. Silencing expression of ROR1 in human breast cancer cell lines found to express this protein impaired their growth in vitro and also in immune-deficient mice. We found that ROR1 could interact with casein kinase 1 epsilon (CK1ε) to activate phosphoinositide 3-kinase-mediated AKT phosphorylation and cAMP-response-element-binding protein (CREB), which was associated with enhanced tumor-cell growth. Wnt5a, a ligand of ROR1, could induce ROR1-dependent signaling and enhance cell growth. This study demonstrates that ROR1 is expressed in human breast cancers and has biological and clinical significance, indicating that it may be a potential target for breast cancer therapy.
Journal Article
Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae
by
Yao, Bangxin
,
Zeng, Yigang
,
Li, Lisha
in
Anti-Bacterial Agents - therapeutic use
,
antibiotic resistance
,
Antibiotics
2020
We report a case of a 63-year-old female patient who developed a recurrent urinary tract infection (UTI) with extensively drug-resistant Klebsiella pneumoniae (ERKp). In the initial two rounds of phage therapy, phage resistant mutants developed within days. Although ERKp strains were completely resistant to sulfamethoxazole-trimethoprim, the combination of sulfamethoxazole-trimethoprim with the phage cocktail inhibited the emergence of phage resistant mutant in vitro, and the UTI of patient was successfully cured by this combination. Thus, we propose that non-active antibiotic and bacteriophage synergism (NABS) might be an alternative strategy in personalized phage therapy.
Journal Article
Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy
by
Zhang, Zhuhong
,
Widhopf, George F.
,
Wu, Rongrong
in
animal ovaries
,
Animals
,
Antibodies, Monoclonal - immunology
2014
Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1 . We found that ROR1-positive (ROR1 ⁺) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1 ᴺᵉᵍ) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial–mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1 ⁺ cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.
Significance This study demonstrates that the oncoembryonic surface antigen, receptor tyrosine kinase-like orphan receptor 1 (ROR1), is expressed on human ovarian cancer stem cells (CSCs), on which it seems to play a functional role in promoting migration/invasion or spheroid formation in vitro and tumor engraftment in immune-deficient mice. Treatment with a humanized mAb specific for ROR1 (UC-961) could inhibit the capacity of ovarian cancer cells to migrate, form spheroids, or engraft immune-deficient mice. Moreover, such treatment inhibited the growth of tumor xenografts, which in turn had a reduced capacity to engraft immune-deficient mice and were relatively depleted of cells with features of CSC, suggesting that treatment with UC-961 could impair CSC renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which may be targeted for anti-CSC therapy.
Journal Article
Response of the root morphological structure of Fokienia hodginsii seedlings to competition from neighboring plants in a heterogeneous nutrient environment
2024
Critical changes often occur in
seedlings during the process of growth owing to differences in the surrounding environment. The most common differences are heterogeneous nutrient environments and competition from neighboring plants.
In this study, we selected one-year-old, high-quality
seedlings as experimental materials. Three planting patterns were established to simulate different competitive treatments, and seedlings were also exposed to three heterogeneous nutrient environments and a homogeneous nutrient environment (control) to determine their effect on the root morphology and structure of
seedlings.
Heterogeneous nutrient environments, compared with a homogeneous environment, significantly increased the dry matter accumulation and root morphology indexes of the root system of
, which proliferated in nutrient-rich patches, and the P heterogeneous environment had the most significant enhancement effect, with dry matter accumulation 70.2%, 7.0%, and 27.0% higher than that in homogeneous and N and K heterogeneous environments, respectively. Homogeneous environments significantly increased the specific root length and root area of the root system; the dry matter mass and morphological structure of the root system of
.
with a heterospecific neighbor were higher than those under conspecific neighbor and single-plant treatments, and the root area of the root system under the conspecific neighbor treatment was higher than that under the heterospecific neighbor treatment, by 20% and 23%, respectively. Moreover, the root system under heterospecific neighbor treatment had high sensitivity; the heterogeneous nutrient environment increased the mean diameter of the fine roots of the seedlings of
and the diameter of the vascular bundle, and the effect was most significant in the P heterogeneous environment, exceeding that in the N and K heterogeneous environments. The effect was most significant in the P heterogeneous environment, which increased fine root diameter by 20.5% and 10.3%, respectively, compared with the homogeneous environment; in contrast, the fine root vascular ratio was highest in the homogeneous environment, and most of the indicators of the fine root anatomical structure in the nutrient-rich patches were of greater values than those in the nutrient-poor patches in the different heterogeneous environments; competition promoted most of the indicators of the fine root anatomical structure of
seedlings. According a principal component analysis (PCA), the N, Pm and K heterogeneous environments with heterospecific neighbors and the P heterogeneous environment with a conspecific neighbor had higher evaluation in the calculation of eigenvalues of the PCA.
The root dry matter accumulation, root morphology, and anatomical structure of
.
seedlings in the heterogeneous nutrient environment were more developed than those in the homogeneous nutrient environment. The effect of the P heterogeneous environment was the most significant. The heterospecific neighbor treatment was more conducive to the expansion and development of root morphology of
seedlings than were the conspecific neighbor and single-plant treatments.
Journal Article
Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44
by
Wu, Rongrong
,
Wu, Christina C. N.
,
Cui, Bing
in
Animals
,
Antibodies, Monoclonal, Humanized - immunology
,
Apoptosis
2013
Chronic lymphocytic leukemia (CLL) cells express high levels of CD44, a cell-surface glycoprotein receptor for hyaluronic acid. We found that a humanized mAb specific for CD44 (RG7356) was directly cytotoxic for leukemia B cells, but had little effect on normal B cells. Moreover, RG7356 could induce CLL cells that expressed the zeta-associated protein of 70 kDa (ZAP-70) to undergo caspase-dependent apoptosis, independent of complement or cytotoxic effector cells. The cytotoxic effect of this mAb was not mitigated when the CLL cells were cocultured with mesenchymal stromal cells (MSCs) or hyaluronic acid or when they were stimulated via ligation of the B-cell receptor with anti-µ. RG7356 induced rapid internalization of CD44 on CLL cells at 37 °C, resulting in reduced expression of ZAP-70, which we found was complexed with CD44. Administration of this mAb at a concentration of 1 mg/kg to immune-deficient mice engrafted with human CLL cells resulted in complete clearance of engrafted leukemia cells. These studies indicate that this mAb might have therapeutic activity, particularly in patients with CLL that express ZAP-70.
Journal Article
Effects of Moso Bamboo (Phyllostachys edulis) Forest Stand Density on Root Growth and Soil Quality for Shoot Production Under a Long-Term Bamboo-Stocking Retention Model
2025
Bamboo forest density is a factor that critically impacts the growth of moso bamboo, soil quality, and productivity. In this study, four bamboo forest density treatment groups were established under a long-term bamboo-stocking retention model, namely 1200 ± 100, 1800 ± 100, 2400 ± 100, and 3000 ± 100 plants·hm−2, while a traditional management model focused on selective logging, with a bamboo forest density of 2100 ± 100 plants·hm−2 (CK), serving as the control group. The study aimed to investigate the impact of bamboo forest density on bamboo shoots, roots, and soil, identify key influencing factors, and determine the optimal management density for this management model. Under the novel management model, bamboo shoot yield and number exhibited a unimodal response to stand density. At a density of 2400 plants·hm−2, the bamboo shoot yield reached its highest value of 18,822 kg·hm−2, with 7080 shoots·hm−2. Under the density of 2400 plants·hm−2, the specific root length, specific root surface area and total nitrogen, phosphorus and potassium contents of 0–1 mm fine roots were higher, and the contents of soil organic matter, total nitrogen, available phosphorus and available potassium were also better. Correlation analysis showed that the bamboo shoot yield and the number of shoots were closely related to soil quality (water content, organic matter, total nitrogen, available phosphorus and available potassium), and the effect of root total nitrogen content on shoot yield was particularly significant (the explanation rate was 75.7%). The comprehensive growth status assessment (D3 > D4 > D2 > CK > D1) showed that there were differences in the performance of different density treatment groups. This information could help bamboo farmers improve yield while protecting soil quality.
Journal Article
Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a
2008
We examined the sera of six patients before and after i.v. infusions of autologous chronic lymphocytic leukemia (CLL) cells transduced ex vivo with an adenovirus encoding CD154 (Ad-CD154). Five patients made high-titer antibodies against adenovirus and three made IgG reactive with a leukemia-associated surface antigen, which we identified as ROR1. Anti-ROR1 antibodies were not detected in the sera of untreated patients. We generated anti-ROR1 mAbs and found they reacted specifically with the CLL cells of all patients, but not with nonleukemic leukocytes, a wide variety of normal adult tissues, or blood mononuclear cells, including CD5⁺ B cells of healthy adults. ROR1 could bind Wnt5a, which induced activation of NF-κB when coexpressed with ROR1 in HEK293 cells and enhanced the survival of CLL cells in vitro, an effect that could be neutralized by posttreatment anti-ROR1 antisera. We conclude that patients with CLL can break immune tolerance to ROR1, which is an oncofetal surface antigen and survival-signaling receptor in this neoplastic disease.
Journal Article
Responses of Growth and Root Vitality of Fokienia hodginsii Seedling to the Neighbor Competition in Different Heterogeneous Nutrient Environments
2023
Fokienia hodginsii is characterized by shallow and developed lateral roots with no obvious taproot. It can be used as a pioneer tree species for opening up barren land and as a mixed species for creating plantation forests. During the growth process of F. hodginsii seedlings, they are often exposed to heterogeneous nutrient environments and competition for nutrients, water, and space from neighboring plants, which have significant impacts on the growth of F. hodginsii. These impacts are most directly reflected in the root vitality of F. hodginsii, whose physiological changes embody the plant’s adaptability to different heterogeneous nutrient environments and neighbor competition. Herein, high-quality one-year-old F. hodginsii seedlings were subjected to three planting patterns to simulate different competition patterns. The three planting patterns were also exposed to three heterogeneous nutrient environments and a homogeneous nutrient environment (control) to determine the differences in the F. hodginsii seedling growth and root vitality under different heterogeneous nutrient environments and planting patterns. The F. hodginsii seedling height, ground diameter (root neck diameter), and root biomass under the heterospecific neighbor condition were significantly higher than under the single-plant condition. Across heterogeneous nutrient environments, the average seedling height in the N heterogeneous environments was higher than in the P and K heterogeneous environments. The root biomass in the P heterogeneous environment was slightly higher than in the N heterogeneous environment and significantly higher than in the homogeneous and the K heterogeneous environments. Moreover, the average F. hodginsii seedling root vitality under the heterospecific neighbor was the highest, and the root vitality in the N heterogeneous environment was the highest under each planting pattern. The F. hodginsii root catalase (CAT) and peroxidase (POD) activities under the competition patterns were significantly higher than under the single-plant condition. Additionally, the superoxide dismutase (SOD) activity under single-plant was higher than under the competition patterns. At the same time, the F. hodginsii root malondialdehyde (MDA) content was the highest under the conspecific neighbor. Relative to the homogeneous environment, the root CAT, SOD, and POD activities were increased in the N and P heterogeneous environments. The CAT, SOD, and POD activities were highest in the P heterogeneous environment, while the K heterogeneous environment had the highest average MDA content. From the results of principal component analysis, when F. hodginsii seedlings were in N and P heterogeneous nutrient environments and heterospecific neighbor, their growth, root biomass accumulation, and root activity indexes reached better levels.
Journal Article
Composition of Species and Spatial Patterns of Phyllostachys edulis Mixed Forests in a Succession after Enclosure
2023
This paper investigates the changes in species diversity and the spatial pattern of the population of a moso bamboo (Phyllostachys edulis) forest community in the Wuyi Mountain Nature Reserve in Fujian Province, China. Using the method of space–time substitution, the composition of species and changes in the spatial patterns of different communities were analyzed by taking Phyllostachys edulis mixed forests after 0, 3, 5, 10, 15, and 40 years of enclosure as the survey object. The results showed that as the number of years of enclosure extended, the important values of the Japanese bay tree (Machilus thunbergii Sieb. & Zucc.), chinquapin (Castanopsis faberi Hance), and Masson’s pine (Pinus massoniana Lamb.) increased continuously. These trees became the dominant species of mature forest after 40 years of enclosure. The species diversity of mature and young trees in the community generally increased in parallel with the years of enclosure, and the species diversity of the shrubs generally increased first and then decreased as the number of years of enclosure increased. With the extension of enclosure years, the average diameter at breast height of the mature trees tended to increase, indicating that there were increasing advantages of mature growth as the time of enclosure increased. With the extension of enclosure years, the pattern of spatial distribution of the mature trees in the forest community was generally an aggregated distribution. The Phyllostachys edulis forest community under the prolonged enclosure conditions responded in a positive direction and ultimately formed a more stable Phyllostachys edulis mixed forest community.
Journal Article
Comparative Analysis of Arctic-Related Strategies at the National Level: Competition and Collaboration
2023
The melting of ice creates favorable conditions for the development of the Arctic by elevating the Arctic’s geostrategic value and stoking national competition. As a result, many states, both within and beyond the Arctic region, have recently released Arctic strategies or updated existing ones, clarifying their roles, interests, priorities, and policies for Arctic international cooperation. In this study, a database is generated with a collection of Arctic strategies from 16 states, and then grounded theory is applied to code the texts in these strategy documents. Using this code, word-frequency analysis, cross-tabulation, correlation analysis, and cooperative-network analysis are implemented to explore competition and collaboration in the Arctic among these 16 states. The results indicate that Arctic states are significantly concerned with governance, economic and social development, and security and stability, while environmental protection and scientific research are given more attention by non-Arctic states. In addition, the highest value of the Pearson correlation coefficient is identified as 0.85 for collaboration and Arctic public security affairs, which indicates that collaboration on Arctic security will dominate the development of Arctic affairs in the near future.
Journal Article