Biomedical subjects

Q Xiong

Publications and source records attributed to Q Xiong.

At least 19 recordsLinked to original sources

PubMed2001

Female patients with breast carcinoma age 30 years and younger have a poor prognosis: the M.D. Anderson Cancer Center experience.

BACKGROUND: The objective of this study was to analyze the outcome of treatment in young women with breast carcinoma who were treated at a single institution and to develop a clearer understanding of the natural history of the disease in these women. METHODS: One hundred eighty-five women age < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between October 1985 and September 1995 were identified in the Tumor Registry data base. Patient data were obtained by chart review. All female patients with breast carcinoma who were age > 30 years and who were identified in the same data base and received treatment during the same period served as the control population. The stage-stratified overall survival (OS) rate for the study patients was compared with the OS rate for both the control population and patients in the National Cancer Data Base (NCDB). RESULTS: Of 185 patients, 11% presented with Stage I disease, 45% presented with Stage II disease, 38% presented with Stage III disease, and 6% presented with Stage IV disease. Twenty-nine percent of patients with Stage I disease received adjuvant therapy, and 84% of patients with Stage II disease and 96% of patients with Stage III disease received either adjuvant or neoadjuvant chemotherapy. Among patients with Stage I disease, 8 patients underwent mastectomy and 13 patients underwent breast-conserving surgery (BCS). Among patients with Stage II disease, 66 patients underwent mastectomy and 17 patients underwent BCS. Among patients with Stage III disease, 65 patients underwent mastectomy and 5 patients underwent BCS. The 5-year OS rate was 87% for patients with Stage I disease, 60% for patients with Stage II disease, 42% for patients with Stage III disease, and 16% for patients with Stage IV disease. Compared with the control patients and those in the NCDB, there was a trend toward worse OS rates in women age < or = 30 years. CONCLUSIONS: Women who are diagnosed with breast carcinoma at an age < or = 30 years appear to have a poorer prognosis compared with that for their older counterparts.

Adolescent↗

PubMed2001

Genetic disruption of host interferon-gamma drastically enhances the metastasis of pancreatic adenocarcinoma through impaired expression of inducible nitric oxide synthase.

Synergistic induction of the inducible nitric oxide synthase (NOS II) gene requires a combination of interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). In this study, we determined whether the induction of IFN-gamma was required for NOS II-mediated antitumor activity in vivo. Highly metastatic H7 murine pancreatic adenocarcinoma cells were implanted into the subcutis, footpad, and pancreas of syngeneic IFN-gamma(+/+) and IFN-gamma(-/-) mice. These cells grew and produced metastases and ascites in IFN-gamma(+/+) mice. In sharp contrast, the same tumor cells grew much more aggressively, metastasized more extensively, and produced a larger amount of malignant ascites in IFN-gamma(-/-) mice. Also, induction of IFN-gamma correlated with NOS II gene expression and NO production in IFN-gamma(+/+) injected with the tumor cells but not in IFN-gamma(-/-) mice or IFN-gamma(+/+) mice without tumor challenge. In vitro, only LPS plus IFN-gamma induced a high level of NO production and cytotoxicity against H7 cells. These data suggested that the tumor cells stimulated IFN-gamma secretion from host cells, which in turn stimulated NO production by host cells and suppressed tumor growth and metastasis.

Adenocarcinoma↗

PubMed2001

Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells.

The influence of acidosis on the expression of the vascular endothelial growth factor (VEGF) gene was determined. FG human pancreatic adenocarcinoma cells were incubated for various time periods in media at a physiologically relevant pH level (6.7-7.4). The expression of VEGF mRNA and protein secretion was inversely correlated with pH in a pH- and time-dependent manner. Transient acidosis also activated the VEGF promoter/enhancer luciferase reporter, which was consistent with an increased VEGF gene transcription rate and VEGF mRNA half-life. These data indicated that acidosis transcriptionally and posttranscriptionally regulates VEGF expression, suggesting that an acidic tumor microenvironment contributes to tumor angiogenesis and progression.

3' Untranslated Regions↗

PubMed2001

Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma.

Vascular endothelial growth factor (VEGF) is a key angiogenic molecule that plays an important role in the growth and metastasis of many types of human cancer, including pancreatic adenocarcinoma. In this study, we explored the regulation of VEGF in human pancreatic cancer cells. Over 70% of the human pancreatic cancer cell lines studied in vitro secreted constitutively high levels of VEGF. High VEGF-secreting cells also generally expressed an elevated steady-state level of VEGF mRNA. Kinetic analysis revealed that the elevated steady-state level of VEGF mRNA was due to enhanced VEGF gene transcription and increased constitutive VEGF promoter activity. Deletive mutation analyses of the VEGF promoter revealed that the region from -109 to -38 bp was essential for constitutive VEGF promoter activity. Further deletion and point mutation analyses indicated that mutation of individual or all of the putative Sp1 binding sites reduced or eliminated the constitutive VEGF promoter activity and abrogated the differential activity of the promoter in high and low VEGF-expressing cells. Consistent with the constitutive VEGF transcription activation, a high level of constitutive Sp1 expression and activity was detected in pancreatic cancer cell lines and pancreatic cancer tissue specimens overexpressing VEGF. Collectively, our data demonstrated that constitutive Sp1 activation is essential for the differential overexpression of VEGF, which in turn plays an important role in the angiogenesis and progression of human pancreatic cancer.

Adenocarcinoma↗

PubMed2001

Genetic disruption of host nitric oxide synthase II gene impairs melanoma-induced angiogenesis and suppresses pleural effusion.

Our previous study showed that genetic disruption of nitric oxide (NO) synthase II (NOS II) expression inhibits the metastatic ability of non-immunogenic B16 melanoma cells in syngeneic mice. In the present study, the mechanisms for this metastasis suppression were determined. B16-BL6 and B16-F10 murine melanoma cells were injected i.v. into syngeneic wild-type (NOS II(+/+)) and NOS II-null (NOS II(-/-)) C57BL/6 mice. Both melanoma cells produced less and smaller experimental pulmonary metastases in NOS II(-/-) mice than in NOS II(+/+) mice. Moreover, less metastatic pleural effusion was observed in NOS II(-/-) mice than in NOS II(+/+) mice. Immunohistochemical analyses indicated that absence of NOS II expression was correlated with decreased vascular endothelial growth factor expression and tumor-associated vascular formation. After activation with lipopolysaccharide and IFN-gamma, neither melanoma cell line produced detectable levels of NO. Our data demonstrate that tumor-induced expression of host NOS II enhances melanoma metastasis and pleural effusion, at least in part, through regulation of vascular formation and vascular permeability.

Animals↗

PubMed2001

Intact nitric oxide synthase II gene is required for interferon-beta-mediated suppression of growth and metastasis of pancreatic adenocarcinoma.

Previous studies have shown that enforced expression of IFN-beta suppressed tumor growth and metastasis. In this report, we determined whether the induction of nitric oxide synthase II (NOS II) gene is required for IFN-beta-mediated antitumor activity using syngeneic mice with intact (NOS II+/+) or genetically disrupted (NOS II-/-) NOS II gene. PANC02-H7 highly metastatic murine pancreatic adenocarcinoma cells were transfected with an IFN-beta expression vector or a control pcDNA3 vector. The parental PANC02-H7, control vector-transfected, and IFN-beta-transfected cells were orthotopically implanted into the pancreas of syngeneic NOS II+/+ and NOS II-/- C57BL/6J mice. In NOS II+/+ C57BL/ 6J, both parental and control vector-transfected cells grew progressively in pancreas and produced numerous liver metastases and a large amount of malignant ascites, whereas IFN-beta-secreting cells did not. In NOS II-/- C57BL/6J mice, however, IFN-beta-secreting cells grew much more aggressively. Higher NO induction was detected in NOS II+/+ mice that received injections with IFN-beta-secreting cells than with the control cells, but it was not detected in NOS II-/- mice. These data suggested that IFN-beta secreted from tumor cells stimulates NO production by host cells and suppresses tumor growth and metastasis.

Adenocarcinoma↗

PubMed2001

Screening of Chinese herbal drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bungeanum.

Sixty-eight water and methanol extracts from 34 Chinese herbal drugs, most of which are used for inflammatory diseases, were screened for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated J774.1 macrophages and in LPS/interferon (IFN)-gamma-stimulated mouse peritoneal exudate macrophages. Among the extracts, methanol extracts of Myristica fragrans, Plantago asiatica, Rubia cordifolia, and Zanthoxylum bungeanum showed significant inhibition in J774.1 macrophages, while in mouse peritoneal exudate macrophages, water extracts of Ru. cordifolia and Scutellaria baicalensis and methanol extracts of Angelica megaphylla, My. fragrans, and Z. bungeanum inhibited the NO production. Among them, inhibition of water extract of Sc. baicalensis was found to be mainly due to direct scavenging of NO radicals, through an examination of its scavenging activity on PAPA NONOate-generated NO radicals, while water extract of Ru. cordifolia and methanol extracts of An. megaphylla, My. fragrans, P. asiatica, and Z. bungeanum showed inhibition on iNOS mRNA expression. At last, an inhibitory compound on iNOS mRNA expression was isolated from a methanol extract of Z. bungeanum and identified as 4-O-beta-D-glucopyranosyldihydroferulic acid by NMR spectral analyses and chemical synthesis.

Animals↗

PubMed2001

Regulation of interleukin-8 expression by nitric oxide in human pancreatic adenocarcinoma.

The regulation of interleukin-8 (IL-8) expression by nitric oxide (NO) was determined in human pancreatic cancer cell lines. CaPan-2 and FG human pancreatic adenocarcinoma cells were incubated for 24 h in medium alone or medium containing a cytokine mixture in the presence or absence of an NO synthase (NOS) inhibitor, N(G)-monomethyl-L-arginine (NMA). The NOS activity and level of IL-8 expression were determined. IL-8 expression was induced in the two cell lines. A low level of NOS activity was detectable only in CaPan-2 cells. Moreover, the presence of NMA did not reverse the induction of IL-8. The FG cells were then engineered to produce a physiologic level of NO and incubated in medium alone or medium containing 1 mM NMA. No significant IL-8 expression was induced in those producing a low level of NO, whereas IL-8 expression was induced in those producing a high level of NO. Inhibition of NO production by NMA reversed this effect. Incubation of FG cells with an NO donor, S-nitroso-D,L.-acetyl-penicillamine (SNAP), led to a concentration-dependent and time-dependent induction of IL-8 expression. This NO-mediated upregulation of IL-8 expression correlated with an increase in IL-8 gene transcription and mRNA stability. Our results indicate that NO is involved in the regulation of IL-8 expression in and contributes to the progression of human pancreatic cancer.

Adenocarcinoma↗

PubMed2001

Regulation of interleukin-8 expression by tumor-associated stress factors.

Tumor and host cells frequently express interleukin-8 (IL-8). IL-8 has been shown to be motogenic, mitogenic, and angiogenic and to play important roles in human tumor progression. IL-8 expression can be induced by numerous stress factors present in the tumor environment, such as hypoxia, acidosis, hyperglycemia, hyperosmotic pressure, high cell density, hyperthermia, radiation, and chemotherapeutic agents. Understanding the mechanisms of IL-8 expression and regulation will be helpful in designing potential therapeutic modalities targeting IL-8 to control tumor growth and metastasis.

Animals↗

PubMed2001

Mouse models of metastatic pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is a deadly disease. Its etiology is unknown, and metastatic disease kills the majority of patients who have it. Effective prevention is clearly the ultimate goal for eradicating this disease provided that the effects of environmental and genetic elements on pancreatic cancer development are fully understood. Currently, it appears that the control of pancreatic cancer metastasis is of immediate urgency. Fulfillment of this difficult task relies on knowledge of the cellular and molecular biology of metastasis. The use of relevant animal models will help define each aspect of this complicated process.

Adenocarcinoma↗

PubMed2001

A novel, clinically relevant animal model of metastatic pancreatic adenocarcinoma biology and therapy.

In this study, we report a metastatic model of Panc02 murine pancreatic adenocarcinoma. Parental Panc02 cells were orthotopically implanted into the pancreas of syngeneic C57BL/6 mice. Tumor cells were isolated from liver micrometastases 90 d after tumor implantation and established as a culture (Panc02-H1). The Panc02-H1 cells were then implanted into the pancreas of mice. Liver metastases were then collected and established as Panc02-H2 cells. This process was repeated until the Panc02-H7 cell line was established. These cells were extremely aggressive after implantation as manifested by progressive growth in the pancreas, peritoneal dissemination, and distant metastasis to multiple organs, including the liver and lungs. Moreover, Panc02-H7 cells expressed the inducible nitric oxide synthase gene at a very low level in culture and produced highly vascularized tumors having a large number of infiltrating macrophages. Collectively, this model system should be a valuable tool for investigating the molecular mechanisms governing pancreatic cancer growth and metastasis and exploring potential treatment modalities for this disease.

Adenocarcinoma↗

PubMed2001

[Cox proportional risk model analysis on the affecting factors of liver transplantation].

OBJECTIVE: To analyze the relative factors affecting the survival time of liver transplantation and identify the main factors for the purpose of supply the reference evidence to the clinic. METHODS: The clinical data on preoperative condition, interoperation and liver function in 116 out of 128 recipients were quantified by the cox proportional risk model after liver transplantation. Their variables were calculated and analyzed by cox regression under the SAS 6.12 software. RESULTS: Z14 (FFP) was obvious at alpha = 0.05. After deleting the non-obvious factors from the model, regression coefficient, standard errors, wald, P and RR were 0.065, 0.024, 7.493, 0.006 and 1.067 respectively. There was no difference of survival time between living liver transplantation and cadaver liver transplantation. The relative dangerous degree in cadaver liver transplantation was 0.340 as much as that in living liver transplantation. CONCLUSIONS: Living liver transplantation shortens the waiting time of liver transplantation and alleviates patient's suffering. It suits for children and adult and supports a selective liver transplantation.

Adolescent↗

PubMed2001

[Detection of pathogenic Edwarsiella tarda].

25 Edwardsiella tarda(Et) strains had been detected both on their viruslent factor Excellular Product (ECP), including the hemolysin and extracellular protease (ECPase), and on their pathogenicity to mice and Xiphophorus helleri. ECP was detected by Dot-ELISA with rabbit antiserum against ECP of reference strain JEL4. The results showed that the animal pathogenicity of Et had good correlation with its hemolysin other than with ECPase. The agreement between Dot-ELISA of JEL4 ECP and pathogenicity to animal was up to 100%. It was desirable to establish a detecting method, which only need detect the ECP with plate assay (PA) and Dot-ELISA, but needn't have animal experiment. Furthermore it is possible to develop a diagnosis kit of application to simplify the detecting procedure of pathogenic Et.

Animals↗

PubMed2000

Inhibition of nitric oxide by phenylethanoids in activated macrophages.

Nitric oxide (NO) is one of the pro-inflammatory molecules. Some phenylethanoids have been previously shown to possess anti-inflammatory effects. Seven phenylethanoids from the stems of Cistanche deserticola, viz. isoacteoside, tubuloside B, acteoside, 2'-O-acetylacteoside, echinacoside, cistanoside A and tubuloside A, were tested for their effect on NO radical generation by activated murine macrophages. At the concentration of 100-200 microM, all the phenylethanoids reduced (6.3-62.3%) nitrite accumulation in lipopolysaccharide (0.1 microgram/ml)-stimulated J774.1 cells. At 200 microM, they inhibited by 32.2-72.4% nitrite accumulation induced by lipopolysaccharide (0.1 microgram/ml)/interferon-gamma (100 U/ml) in mouse peritoneal exudate macrophages. However, these compounds did not affect the expression of inducible nitric oxide (iNOS) mRNA, the iNOS protein level, or the iNOS activity in lipopolysaccharide-stimulated J774.1 cells. Instead, they showed a clear scavenging effect (6.9-43.9%) at the low concentrations of 2-10 microM of about 12 microM nitrite generated from an NO donor, 1-propanamine-3-hydroxy-2-nitroso-1-propylhydrazino (PAPA NONOate). These results indicate that the phenylethanoids have NO radical-scavenging activity, which possibly contributes to their anti-inflammatory effects.

Animals↗

PubMed2000

Influence of nitric oxide synthase II gene disruption on tumor growth and metastasis.

The relationship between nitric oxide (NO) synthase II (NOS II) expression and the metastatic ability of tumor cells is inconclusive. We determined the role of host NOS II expression in the growth and metastasis of the B16-BL6 murine melanoma and M5076 murine ovarian sarcoma cell lines. The cells were either s.c. or i.v. injected into syngeneic wild-type (NOS H+/+) and NOS II-null (NOS H-/-) C57BL/6 mice. Both cell lines produced slightly larger s.c. tumors in NOS H-/- mice than in NOS II+/+ mice. However, B16- BL6 cells produced more and larger experimental lung metastases in NOS II+/+ mice than in NOS II-/- mice, whereas M5076 cells produced fewer and smaller experimental lung metastases in NOS II+/+ mice than in NOS II-/- mice. After activation with IFN-gamma and lipopolysaccharide, macrophages isolated from NOS II+/+ C57BL/6 mice produced NO-dependent cytotoxicity in sarcoma cells, whereas macrophages from NOS II-/- C57BL/6 mice did not. In contrast, activated macrophages produced little to no NO-mediated cytotoxicity in melanoma cells. Immunostaining analyses indicated that NOS II expression was apparent in the metastases growing in NOS H+/+ mice and correlated with increased cell proliferation in B16-BL6 lung metastases but with decreased cell proliferation in M5076 liver metastases. Our data suggest that disruption of host NOS II expression enhanced the growth and metastasis of NO-sensitive tumor cells but suppressed the metastasis of NO-resistant tumor cells, proposing that host-derived NO may differentially modulate tumor progression.

Animals↗

PubMed2000

Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare.

Five new triterpene glucosides, quadranosides I-V (1-5), have been isolated from a MeOH extract of the seeds of Combretum quadrangulare, together with 13 known compounds. The structures of compounds 1-5 were elucidated on the basis of spectroscopic analysis. Among the new triterpene glucosides, three compounds (1, 2, 5) showed significant hepatoprotective effects against D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes.

Africa↗

PubMed2000

Hepatoprotective effect of Apocynum venetum and its active constituents.

The leaves of Apocynum venetum L. are used as a tea material in north China and Japan. A water extract (500 mg/kg/day, one week administration) of the leaves of A. venetum showed protective effects against carbon tetrachloride (CCl4, 30 microliters/mouse) or D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 20 micrograms/kg)-induced liver injury in mice. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is the most crucial mediator in the D-GalN/LPS-induced liver injury model. The extract had no significant inhibition on the increase of serum TNF-alpha (1169 +/- 132 pg/ml vs. 1595 +/- 314 pg/ml of control), but exhibited a complete inhibition at the concentration of 100 micrograms/ml on TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized mouse hepatocytes. Further activity-guided fractionation resulted in the isolation of fifteen flavonoids viz. (-)-epicatechin (1), (-)-epigallocatechin (2), isoquercetin (3), hyperin (4), (+)-catechin (5), (+)-gallocatechin (6), kaempferol-6'-O-acetate (7), isoquercetin-6'-O-acetate (8), catechin-[8,7-e]-4 alpha-(3,4-dihydroxpyhenyl)-dihydro-2(3H)-pyranone (9), apocynin B (10), apocynin A (11), cinchonain Ia (12), apocynin C (13), apocynin D (14) and quercetin (15). All the compounds showed inhibitory effects on TNF-alpha-induced cell death with different intensities. The flavonol glycosides 3, 4, 7 and 8 and the phenylpropanoid-substituted flavan-3-ols 11 and 12 showed potent inhibitory effects on TNF-alpha-induced cell death with IC50 values of 37.5, 14.5, 31.2, 55.1, 71.9 and 41.2 microM, respectively. In contrast, the clinically used 5 and its analogues 1, 2 and 6 showed apparent activity only at 80 microM. These flavonoids appeared to be the hepatoprotective principles of the leaves of A. venetum. The hepatoprotective effects exhibited by the extract and its constituents suggest a validation of the leaves as a tea material.

Animals↗

PubMed2000

Molecular regulation of constitutive expression of interleukin-8 in human pancreatic adenocarcinoma.

Recent studies have shown that interleukin-8 (IL-8) plays an important role in the growth and metastasis of human pancreatic cancer. In the present study, we determined the molecular regulation of constitutive IL-8 expression in human pancreatic cancer cells. Various human pancreatic cancer cell lines were incubated in vitro. Sixty-seven percent of the cell lines constitutively secreted high levels of IL-8, as determined using enzyme-linked immunosorbent assay. Consistently, these cells constitutively expressed high levels of IL-8 mRNA, as determined using Northern blot analysis. To determine the mechanisms of the high steady-state levels of IL-8 mRNA, the IL-8 half-life and transcription rate were measured. There was no significant difference in IL-8 half-life between cells expressing high and low levels of IL-8. However, higher transcription rates and increased IL-8 promoter activity were observed in the cells constitutively expressing high levels of IL-8. Detailed IL-8 promoter analysis using deletion mutation revealed that the region from -85 to -133 bp was essential for the constitutive IL-8 promoter activity. Also, point-mutation analysis indicated that mutation of NF-kappaB, AP-1, or NF-IL-6 binding sites significantly reduced or eliminated the constitutive IL-8 promoter activity. Consistent with the constitutive IL-8 transcription activity, high levels of constitutive NF-kappaB and AP-1 activity were detected in the cells overexpressing IL-8, as determined using electrophoretic mobility shift assay. In addition, transfection of a dominant-negative I-kappaBalpha expression vector (I-kappaBalphaM) inhibited constitutive NF-kappaB activity and IL-8 expression in pancreatic cancer cells. Collectively, our data demonstrated that constitutive NF-kappaB and AP-1 activation contributes to the overexpression of IL-8, which in turn plays an important role in tumor angiogenesis and contributes to the aggressive biology of human pancreatic cancer.

Adenocarcinoma↗