Biomedical subjects

Xiao Yan

Publications and source records attributed to Xiao Yan.

17 recordsLinked to original sources

PubMed2026

Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults.

Essential thrombocythaemia (ET) in adolescents and young adults (AYA, 15-39 years) is a distinct entity with an incompletely defined prognosis. In this multicentre retrospective study, 1728 ET patients from 29 centres across China were stratified into AYA (n = 328) and non-AYA (≥40 years, n = 1400) cohorts. We compared their clinical profiles, genomic landscapes, long-term outcomes and risk factors for progression to post-ET myelofibrosis (MF). AYA patients had fewer cardiovascular risks and lower thrombosis rates, but higher rates of extreme thrombocytosis. Molecularly, AYA patients were enriched for calreticulin (CALR) mutations, whereas Janus kinase 2 (JAK2) predominated in older patients. The burden of non-driver mutations (tet methylcytosine dioxygenase 2 [TET2], DNA methyltransferase 3A [DNMT3A], ASXL transcriptional regulator 1 [ASXL1], SH2‑B adaptor protein 3 [SH2B3]) was lower in AYA patients. Consequently, AYA patients achieved superior long-term outcomes across all key survival endpoints, including overall, myelofibrosis-free and leukaemia-free survival. Analysis of post-ET MF progression risks identified age-specific patterns: CALR mutations are enriched in younger patients and show an age-specific association with MF progression. AYA-ET constitutes a unique clinicomolecular subtype with a favourable prognosis, supporting age-stratified management. The enrichment of CALR mutations and their specific link to MF progression in young patients underscore the urgent need for targeted therapies against CALR-mutant clones.

adolescents and young adults (AYA)↗

PubMed2006

[Biological response of B-cell lymphoma cells in vitro to 131I-rituximab].

OBJECTIVE: To study the biological response of B-cell lymphoma cells positive for CD20 expression to (131)I-labeled rituximab. METHODS: Anti-CD20 monoclonal antibody rituximab was labeled with (131)I by means of IODO-GEN method, and its effects on apoptosis of Raji cells were determined by Annexin-V/PI double-labeled cytometry. Its effects on the cell cycles was evaluated by cytometry with PI staining. RESULTS: The cell apoptosis rate measured by Annexin v-FITC/PI was 51.99% in (131)I-rituximab group, significantly higher than that in (131)I group, rituximab group and control group (42.71%, 29.42% and 26.17%, respectively, P<;0.05). The apoptosis rate by flow cytometry with PI staining was 4.32% in (131)I-rituximab group, also significantly higher than that in the other 3 groups (1.47%, 1.39% and 0.37%, respectively, P<0.05). Cell cycle alteration of Raji cells occurred in (131)I-rituximab group, and the majority of cells were arrested at G(1)/G(2) stage. CONCLUSION: (131)I-rituximab can regulate the cell cycle of Raji cells and induce their apoptosis to inhibit their proliferation.

Antibodies, Monoclonal↗

PubMed2006

[Killing effect of sequential Herceptin and adriamycin treatment on breast cancer cell line in vitro].

OBJECTIVE: To observe the killing effect of Herceptin and adriamycin sequentially applied on breast cancer cell line in vitro. METHODS: BT-474 human breast cancer cells in exponential growth phase were treated with Herceptin alone, adriamycin alone and their sequential administration (Herceptin before adriamycin and vice versa), respectively. Under optical microscope, the morphological changes of the cells were observed before and after drug administration. The expression rate and mean fluorescence intensity (MFI) of HER-2/neu and cell death rate were detected by flow cytometry. RESULTS: Microscopically, the cells treated with different protocols all exhibited such changes as darkening and increase of cellular debris with irregular cell morphology. Flow cytometry revealed no significant difference in the expression rate of HER-2/neu in each group before and after treatment, but the MFI of HER-2/neu and death rate of the treated cells were significant different from those of the control group (P<0.05). The cell death rate of Herceptin-pretreated cells was significantly higher than that of adriamycin-pretreated ones (P<0.05). CONCLUSION: Herceptin pretreatment enhances the killing effect of adriamycin on breast cancer cell line BT-474, which provides experimental evidence for designing clinical sequential biochemotherapy of breast cancer.

Antibiotics, Antineoplastic↗

PubMed2006

[Preparation of hematoporphyrin-herceptin photoimmunoconjugate for photoimmunotherapy].

OBJECTIVE: To prepare photoimmunoconjugate of hematoporphyrin (HP) and herceptin, and study its killing and apoptosis-inducing effect on tumor cells BT-474. METHODS: HP-herceptin photoimmunoconjugate was synthesized with EDCI as the condensator. After exposure of the cells to 630 nm laser, the killing effect of the conjugate and cell apoptosis were evaluated by MTT assay and flow cytometry. RESULTS: Compared with free HP at equivalent dose, the immune reactivity, killing effect and the apoptosis-inducing effect of HP-herceptin immunoconjugate on BT-474 cells was enhanced (P<0.05). CONCLUSION: The killing effect of HP-herceptin immunoconjugate is stronger than free HP on BT-474 cells.

Antibodies, Monoclonal↗

PubMed2006

[Preparation, quality control and biodistribution of 131I-herceptin in New Zealand rabbits].

OBJECTIVE: To study the immunoactivity,biodistribution and metabolic pattern of (131)I-Herceptin in rabbits. METHODS: Herceptin was radiolabelled with (131)I and its radiochemicalpurity (RCP) measured by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate to BT-474 cells was measured to evaluate the immunoactivity of (131)I-Herceptin. (131)I-herceptin (2.0 mCi/kg) was injected intravenously into New Zealand rabbits. Scintigraphy on emission computed tomography was performed at 3 h, 1, 3 and 5 days after injection, and the radiocounts of the heart, liver and kidney etc. were compared with that of the muscle to calculate the organ-to-muscle activity ratio (O/M). On the fifth day,the rabbits were killed and the blood, myocardium, lung and other organs were obtained for measuring the radiocounts on gamma-counter to calculate the uptake percentage per gram tissue (ID%/g). RESULTS: The labeling rate of (131)I-herceptin was 93% with RCP of 95% and binding rate to BT-474 cells of 36.9%. After injection of (131)I-herceptin, the heart, lung and liver displayed dense radioactive regions but not the muscles and intestines. Three hours after injection, the O/M ratio of the heart was significantly higher than that of the lung, kidney and intestine (P<0.05), but decreased significantly one day after injection (t=10.817, P<0.001) with further decrement on days 3 and 5 (P<0.05). The O/M ratio of liver on day 1, 3, and 5 reduced significantly in comparison with that at 3 h (P<0.05). The uptake percentage was higher in the blood (11.3 ID/g%) than in the liver (2.8 ID/g%) and the myocardium (1.8 ID/g%). CONCLUSIONS: (131)I-herceptin possesses high immunoactivity which distributes mainly in the blood, liver and kidney, but with low uptake in the myocardium.

Animals↗

PubMed2006

[Effects of interferon-gamma on Her-2/neu expression and antitumor activity of 131I-Herceptin in breast cancer cell lines].

BACKGROUND & OBJECTIVE: Herceptin plays an important role in treating metastatic breast cancer by targeting Her2/neu, therefore, combining Herceptin with iodine-131 (131I) might enhance its antitumor activity. This study was to up-regulate Her2/neu expression by interferon-gamma (IFN-gamma), and explore its effect on binding and antitumor activity of 131I-Herceptin in breast cancer cell lines MCF-7, SKBR-3 and BT-474. METHODS: MCF-7, SKBR-3 and BT-474 cells were cultured with or without IFN-gamma (500 U/ml) for 48 h. The positive rate and mean fluorescence intensity (MFI) of Her2/neu on the 3 cell lines were tested by flow cytometry. Herceptin was labeled with 131I by Iodogen method, and its radiochemical purity (RCP) was tested by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate of 131I-Herceptin on cells was measured by non-competitive saturation analysis, and its killing effect was estimated by colony-forming assay. The positive rate and MFI of Her2/neu, binding rate of 131I-Herceptin, and colony-forming rate were compared between IFN-gamma-induced group and control group by t test. RESULTS: For MCF-7 cells, the positive rate and MFI of Her2/neu were significantly higher in IFN-gamma-induced cells than in control cells [(15.2+/-4.7)% vs. (8.5+/-1.9)%, t=3.515, P<0.05; 121+/-17 vs. 38+/-7, t=7.823, P<0.002]; for SKBR-3 and BT-474 cells, no obvious difference of Her2/neu positive rate was observed between IFN-gamma-induced cells and control cells [(99.7+/-0.9)% vs. (98.9+/-1.1)%, P>0.05; (99.5+/-1.2)% vs. (98.1+/-0.9)%, P>0.05], but the MFI of Her2/neu was significantly higher in IFN-gamma-induced cells than in control cells (1,608+/-201 vs. 952+/-125, t=4.802, P<0.01; 1,968+/-192 vs. 1,020+/-98, t=7.614, P<0.002). The binding rates of Her2/neu were increased from (5.2+/-1.4)% to (12.3+/-3.4)% by 2.4 folds in MCF-7 cells, from (35.8+/-4.5)% to (48.9+/-7.1)% by 1.4 folds in SKBR-3 cells, and from (37.2+/-3.6)% to (59.5+/-8.7)% by 1.6 folds in BT-474 cells after inducement with IFN-gamma. The colony-forming rates were significantly lower in IFN-gamma-induced MCF-7, SKBR-3 and BT-474 cells than in control cells [(30+/-4)% vs. (49+/-3)%, t=6.574, P<0.05; (23+/-5)% vs. (37+/-6)%, t=3.105, P<0.05; (19+/-6)% vs. (34+/-5)%, t=3.323, P<0.05]. CONCLUSION: IFN-gamma can up-regulate Her-2/neu expression and increase the binding of 131I-Herceptin, hence, improve the inhibitory effect of 131I-Herceptin on proliferation of breast cancer cells.

Antibodies, Monoclonal↗

PubMed2005

Lack of response to all-trans retinoic acid supplementation in adult dogs following left pneumonectomy.

We showed previously that removing 55-58% of the lung by right pneumonectomy (R-PNX) in adult dogs triggers compensatory growth of the remaining lung, but removing 42-45% of the lung by left PNX (L-PNX) does not. We also showed that, following R-PNX, supplemental all-trans retinoic acid (RA) selectively enhances alveolar capillary endothelial cell volume (Yan X, Bellotto DJ, Foster DJ, Johnson RL, Jr., Hagler HH, Estrera AS, and Hsia CC. J Appl Physiol 96: 1080-1089, 2004). We hypothesized that RA supplementation might enhance compensation following L-PNX and tested this hypothesis by administering RA (2 mg.kg(-1).day(-1), 4 days/wk) or placebo orally to litter-matched adult foxhounds for 4 mo following L-PNX. Resting lung function was measured under anesthesia. Air and tissue volumes of the remaining lung were assessed by high-resolution computed tomography scan and by detailed postmortem morphometric analysis of the fixed lung. There was no significant difference in resting lung function, lung volume, alveolar structure, or septal ultrastructure between RA and placebo treatment groups. We conclude that RA supplementation does not induce post-PNX compensatory lung growth in the absence of existing cellular growth activities initiated by other primary signals.

Adaptation, Physiological↗

PubMed2005

Enhanced alveolar growth and remodeling in Guinea pigs raised at high altitude.

To examine the effects of chronic high altitude (HA) exposure on lung structure during somatic maturation, we raised male weanling guinea pigs at HA (3800m) for 1, 3, or 6 months, while their respective male littermates were simultaneously raised at low altitude (LA, 1200m). Under anaesthesia, airway pressure was measured at different lung volumes. The right lung was fixed at a constant airway pressure for morphometric analysis under light and electron microscopy. In animals raised at HA for 1 month, lung volume, alveolar surface area and alveolar-capillary blood volume (V(c)) were elevated above LA control values. Following 3-6 months of HA exposure, increases in lung volume and alveolar surface area persisted while the initial increase in V(c) normalized. Additional adaptation occurred, including a higher epithelial cell volume, septal tissue volume and capillary surface area, a lower alveolar duct volume and lower harmonic mean diffusion barrier resulting in higher membrane and lung diffusing capacities. These data demonstrate enhanced alveolar septal growth and progressive acinar remodeling during chronic HA exposure with long-term augmentation of alveolar dimensions as well as functional compensation in lung compliance and diffusive gas transport.

Altitude↗

PubMed2005

Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing.

AIM: To explore the impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines. METHODS: The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed. RESULTS: The alpha/ beta and repair half-time (T(1/2)) of HepG2 and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min, while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols. CONCLUSION: The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.

Carcinoma, Hepatocellular↗

PubMed2005

[Killing effect of 131I-Herceptin on breast cancer cell lines in vitro].

OBJECTIVE: To study the specific killing effect of (131)I-labeled Herceptin on breast cancer cell lines positive for Her-2 expression. METHODS: Anti-Her-2 monoclonal antibody Herceptin was labeled with (131)I by means of IODO-GEN, and the killing effects of Herceptin on SK-BR-3, MCF-7 and A549 cell lines expressing Her-2 were evaluated with MTT assay. RESULTS: (131)I-Herceptin had immunoactivity had to that of Herceptin but possessed stronger killing effects on the cell lines expressing Her-2 than Herceptin and (131)I used alone (P<0.05). Its killing effect on cell lines negative or only weakly positive for Her-2 expression was similar to that of (131)I and Herceptin. CONCLUSION: (131)I-Herceptin can specifically kill Her-2-positive cancer cells in vitro.

Antibodies, Monoclonal↗

PubMed2004

[Three patterns of interaction between soil and non-point source P-pollutants in agricultural watershed].

Typical agricultural watershed was selected to study the interactions between soil matrix and non-point source P-pollutants in surface runoff under simulative conditions. The soil samples were taken in different spatial locations in this watershed and were under different degree of human disturbance. The results showed that the interactions between different soil matrix and phosphorus could be divided into three patterns:retention, release and combination of retention and release. Soil of retention pattern has strong adsorption capacity of phosphate and will retain phosphorus from polluted runoff. Soil of release pattern has significant desorption capacity of phosphate and will release phosphorus to the runoff. Soil of retention and release combination pattern will retain or release phosphorus according to the phosphate concentration in the polluted runoff. These results showed that soil matrix in different spatial locations in the agricultural watershed have different ecological functions and environmental values under the processing of natural conditions and human disturbance. From the view of occurrence of non-point source pollution, these soils could become the sink of pollutants as well as the source of pollutants. Under some conditions, there has a conversion between sink and source of them. These results are valuable for control of non-point source pollution on watershed level, identification of key source area of pollutants and improvement of efficiency of control measures.

Crops, Agricultural↗

PubMed2003

Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) enhances compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 4 mo, the remaining lung was fixed by tracheal instillation of fixatives at a constant airway pressure for detailed morphometric analysis. After RA treatment compared with placebo, lung volume was slightly but not significantly lower. Volume density of septum to lung was 37% higher because of a 50 and 25% higher volume density of capillary and septal tissue, respectively. Mean septal thickness was 27% higher. Absolute volumes of endothelial cells and capillary blood were 31-37% higher, whereas epithelial and interstitial volumes were not different between groups. Absolute alveolar-capillary surface areas did not differ between groups, and alveolar septal surface-to-volume ratio was 20% lower in RA-treated animals. RA treatment exaggerated interlobar differences in morphometric indexes and caused alveolar capillary morphology to revert to a more immature state. Thus RA treatment during early post-R-PNX adaptation preferentially enhanced alveolar capillary and endothelial cell volumes consistent with formation of new capillaries, but the associated septal distortion precluded a corresponding increase in gas-exchange surface or morphometric estimates of lung diffusing capacity.

Animals↗

PubMed2003

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

Animals↗

PubMed2003

Density-dependent reduction of nitric oxide diffusing capacity after pneumonectomy.

Airway lengthening after pneumonectomy (PNX) may increase diffusive resistance to gas mixing (1/D(G)); the effect is accentuated by increasing acinar gas density but is difficult to detect from lung CO-diffusing capacity (Dl(CO)). Because lung NO-diffusing capacity (Dl(NO)) is three- to fivefold that of Dl(CO), whereas 1/D(G) for NO and CO are similar, we hypothesized that a density-dependent fractional reduction would be greater for Dl(NO) than for Dl(CO). We measured Dl(NO) and Dl(CO) at two tidal volumes (Vt) and with three background gases [helium (He), nitrogen (N(2)), and sulfur hexafluoride (SF(6))] in immature dogs 3 and 9 mo after right PNX (5 and 11 mo of age). At maturity (11 mo), background gas density had no effect on Dl(NO), Dl(CO), or Dl(NO)-to-Dl(CO) ratio in sham controls. In PNX animals, Dl(NO) declined 25-50% in SF(6) relative to He and N(2), and Dl(NO)/Dl(CO) declined approximately 50% in SF(6) relative to He at a Vt of 15 ml/kg, consistent with a significant 1/D(G). At 5 mo of age, Dl(NO)/Dl(CO) declined 25-45% in SF(6) relative to He and N(2) in both groups, but Dl(CO) increased paradoxically in SF(6) relative to N(2) or He by 20-60%. Findings suggest that SF(6), besides increasing 1/D(G), may redistribute ventilation and/or enhance acinar penetration of the convective front.

Aging↗

PubMed2002

Variation of lung volume after fixation when measured by immersion or Cavalieri method.

Organ volume is a critical parameter in morphometric analysis. The special problems of the lung as a nonsolid organ are overcome by tracheal instillation of fixatives at a constant airway pressure (P(aw)). Lung volume can change significantly after fixation as P(aw) change. To determine the variation of lung volume after fixation, we measured the volume of intact fixed lungs by serial immersion in saline (V(imm)) at selected time points, compared with measurements obtained by point counting [Cavalieri Principle (V(cav))] after tissue sectioning to release P(aw). V(imm) was systematically higher than V(cav) by 25% in dog lungs and 13% in guinea pig lungs (P = 0.0003 between species). This size-dependent variability reflects residual elastic recoil, refolding and/or crumpling of alveolar septa after fixation. V(imm) remained 14% higher than V(cav) in dog lungs even after pressure release. V(cav)/V(imm) was systematically lower in the upper than the lower strata of the same lung. We conclude that V(cav) measured on lung slices after relaxation of P(aw) more precisely represents the state of the tissue to be used for subsequent morphometric analysis, particularly for large lungs.

Animals↗

PubMed2002

Expression of epidermal growth factor and surfactant proteins during postnatal and compensatory lung growth.

We examined whether lung growth after pneumonectomy (PNX) invokes normal signaling pathways of postnatal development. We qualitatively and quantitatively assessed the immunoexpression of epidermal growth factor (EGF), its receptor (EGFR), surfactant proteins (SP) [SP-A and -D and surfactant proproteins (proSP)-B and -C] and proliferating cell nuclear antigen (PCNA) in immature and mature dog lung. We also assayed these proteins in lungs of immature dogs 3 wk or 10 mo after they underwent right PNX compared with simultaneous matched sham controls. During maturation, alveolar cell proliferation is regionally regulated in parallel with EGF and EGFR levels and inversely correlated with SP-A and proSP-C levels. In contrast, post-PNX lung growth is not associated with EGF or EGFR upregulation but with markedly increased SP-A level and moderately increased SP-D level; proSP-B and proSP-C levels did not change. We conclude that 1) signaling of EGF axis and differential regulation of SPs persist during postnatal lung development, 2) post-PNX lung growth is not a simple recapitulation of maturational responses, and 3) SP-A and SP-D may modulate post-PNX lung growth.

Aging↗

PubMed2002

Glatiramer acetate (Copaxone) therapy induces CD8(+) T cell responses in patients with multiple sclerosis.

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine that is used therapeutically in patients with multiple sclerosis (MS). To investigate the mechanism of the drug's immunomodulatory effect, we used immunophenotypic approaches to characterize the precise nature of GA-induced T cell responses. We demonstrate here that healthy individuals and untreated MS patients exhibit prominent T cell proliferative responses to GA. However, these responses are different in distinct subsets of T cells. Whereas GA-induced CD4(+) T cell responses are comparable in healthy individuals and MS patients, CD8(+) T cell responses are significantly lower in untreated MS patients. Treatment with GA results in upregulation of these CD8(+) responses with restoration to levels observed in healthy individuals. Both CD4(+) and CD8(+) GA-specific responses are HLA-restricted. GA therapy also induces a change in the cytokine profile of GA-specific CD4(+) and CD8(+) T cells. This study provides the first direct immunophenotypic evidence, to our knowledge, of GA-specific CD8(+) T cell responses and their upregulation during the course of therapy, which may suggest a role for these responses in the immunomodulatory effects of the drug.

Adjuvants, Immunologic↗