bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase inhibitor trichostatin a induces cell‐cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells
Authors: Yamashita Yo‐ichi , Shimada Mitsuo , Harimoto Norifumi , Rikimaru Tatsuya , Shirabe Ken , Tanaka Shinj , Sugimachi Keizo 
Published: December 2002

AbstractRemodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh‐7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh‐7. It inhibited cell proliferation in vitro and induced G0/G1 arrest in HepG2 and apoptosis in Huh‐7. Gene expression of liver‐specific functions and liver‐enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh‐7. Our results indicate that TSA can induce cell‐cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines. © 2002 Wiley‐Liss, Inc.
Detection of hematogenic and lymphogenic tumor cell dissemination in patients with medullary thyroid carcinoma by cytokeratin 20 and preprogastrin‐releasing peptide RT‐PCR
Authors: Weber Theresia , Lacroix Jeannine , Wörner Stefan , Weckauf Helgard , Winkler Steffi , Hinz Ulf , Schilling Tobias , Frank‐Raue Karin , Klar Ernst , Knebel Doeberitz Magnus von 
Published: December 2002

AbstractDespite an extensive surgical approach only 50% of the patients with medullary thyroid carcinoma (MTC) are biochemically cured. The failure to cure a larger number of patients is a result of the early dissemination of MTC. The present study evaluates two RT‐PCR based assays for the detection of disseminated tumor cells in blood, bone marrow and lymph node samples of patients with MTC. Frozen tissue and blood samples of 19 patients with MTC and 61 cervical lymph nodes of these patients were obtained intraoperatively during thyroidectomy and lymphadenectomy. Preoperative bone marrow samples were obtained from 8 patients with MTC. An expression of CK20 and preproGRP was found in all MTC tissue samples. Using CK20‐PCR, disseminated MTC cells were detected in 67% of the cervical lymph nodes of patients with MTC, compared to 72% involved lymph nodes, detected by preproGRP‐PCR. In 16 of 61 nodes (26%) each PCR‐system detected disseminated tumor cells in histologically tumor‐free lymph nodes. Disseminated tumor cells were detected with CK20‐PCR and preproGRP in 5 of 18 (28%) preoperative blood samples, each. The detection of a hematogenic tumor cell dissemination by preproGRP correlated significantly with the tumor stages (p = 0.019). Circulating MTC cells were found in 3 of 8 bone marrow samples with CK20‐PCR, compared to 1 of 8 samples with preproGRP‐PCR. Both PCR assays are highly sensitive to detect disseminated MTC cells in blood, bone marrow and lymph node samples. Our results of disseminated MTC cells in 26% of histologically tumor‐free cervical lymph nodes and in 28% of the blood samples of patients with MTC might therefore explain the low biochemical cure rates. © 2002 Wiley‐Liss, Inc.
Circulating interleukin‐6 predicts survival in patients with metastatic breast cancer
Authors: Salgado Roberto , Junius Sara , Benoy Ina , Van Dam Peter , Vermeulen Peter , Van Marck Eric , Huget Philippe , Dirix Luc Y. 
Published: December 2002

AbstractInterleukin‐6 (IL‐6) is a multifunctional cytokine produced by macrophages, T cells, B cells, endothelial cells and tumour cells. Interleukin‐6 is able to promote tumour growth by upregulating anti‐apoptotic and angiogenic proteins in tumour cells. In murine models it has been demonstrated that antibodies against IL‐6 diminish tumour growth. Several reports have highlighted the prognostic importance of IL‐6 in e.g., prostate and colon cancer. We addressed prospectively the prognostic significance of serum IL‐6 (sIL‐6), measured at diagnosis of metastasis, in 96 unselected and consecutive patients with progressive metastatic breast cancer before the initiation of systemic therapy. The median sIL‐6 value for the breast cancer population was 6.6 ± 2.1 pg/ml. Patients with 2 or more metastatic sites had higher sIL‐6 values compared to those with only 1 metastatic site (respectively 8.15 ± 1.7 pg/ml and 3.06 ± 6.6 pg/ml; p < 0.001). Patients with liver metastasis (8.3 ± 2.4 pg/ml), with pleural effusions (10.65 ± 9.9 pg/ml) and with dominant visceral disease (8.15 ± 3.3 pg/ml) had significantly higher values compared to those without liver metastases (4.5 ± 3.4 pg/ml; p = 0.001), without pleural effusions (5.45 ± 1.5 pg/ml; p = 0.0077) and with dominant bone disease (4.5 ± 1.4 pg/ml; p = 0.007) respectively. No correlation between sIL‐6 and age, menopausal status, performance status, tumour grade, body‐mass index, histology and hormone receptor status was found. Multivariate analysis showed that high levels of serum IL‐6 have independent prognostic value. We conclude that circulating IL‐6 is associated with worse survival in patients with metastatic breast cancer and is correlated with the extent of disease. © 2002 Wiley‐Liss, Inc.
Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer
Authors: Sienel Wulf , Hellers Joe , Morresi‐Hauf Alicia , Lichtinghagen Ralf , Mutschler Wolf , Jochum Marianne , Klein Christoph , Passlick Bernward , Pantel Klaus 
Published: December 2002

AbstractWe assessed the clinical impact of MMP‐9 expression on long‐term survival in patients with operable non‐small cell lung cancer (NSCLC). Primary tumors of 143 consecutive patients with NSCLC resected completely and without overt distant metastases (pT1‐4, pN0‐2, M0, R0) were examined for MMP‐9 expression using immunohistochemistry with a polyclonal, affinity‐purified rabbit antibody that recognizes both latent and active MMP‐9. Immunohistochemical staining of tumor cells was evaluated in comparison to normal bronchiolar epithelium that served as an internal positive control. MMP‐9 expression was categorized into negative, ≤5% tumor cells stained; heterogeneous, >5% and <95% tumor cells stained; and homogeneous, ≥95% tumor cells stained at least as intensively as bronchiolar epithelium. The median follow‐up period was 72 months (range = 12–144 months). Homogeneous expression of MMP‐9 was observed in 26 of 143 patients (18.2%) and did not correlate with clinicopathological parameters. Relapse defined as diagnosis of distant metastasis or local recurrence was observed in 78 of the 130 (60%) patients eligible for clinical follow up analysis. Relapse led to cancer‐related death in all of the 78 patients within the observation period. Kaplan‐Meier analysis showed a significant association between homogeneous MMP‐9 expression and shortened cancer‐related survival (log‐rank p = 0.016). Multivariate regression analysis including pT‐status, pN‐status, tumor histology and tumor grading showed an independence of this prognostic impact of homogeneous MMP‐9 expression (p = 0.045). Thus, immunohistochemical evaluation of MMP‐9 expression may provide a basis for the preselection of patients to be included in trials investigating specific protease inhibitor therapy after surgical resection of NSCLC. © 2002 Wiley‐Liss, Inc.
Experimental photodynamic therapy with MESO‐tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice
Authors: Ježek Petr , Nekvasil Milos , Škobisová Eva , Urbánková Eva , Jirsa Milan , Zadinová Marie , Poučková Pavla , Klepáček Ivo 
Published: December 2002

AbstractLiposomal meso‐tetrakis‐phenylporphyrin (TPP) was tested for photodynamic therapy (PDT) of human amelanotic melanomas implanted in nude mice. After intratumoural TPP application (15 mg.kg−1) followed by PDT lamp irradiation (600–700 nm, 635 nm peak), tumours retained their original volume up to the 23rd day post‐PDT, whereas volumes increased 6 times in controls. PDT with intravenously (i.v.) administered liposomal (3.2 mg.kg−1) TPP mostly disintegrated tumours to zero volumes. Melanoma remissions were accompanied by tumour surface necroses and were documented by the appearance of nontumourous cells with nonpycnotic nuclei. Spatial arrangement of capillaries in remissing tumour was the same as in healthy surrounding tissue. Lower TPP doses (1, 0.3 and 0.1 mg.kg−1) were more or equally efficient than hydrophilic TPPS4 (3.2 mg.kg−1, i.e., sulfonated TPP), i.v. administered also in liposomes. Liposomal TPPS4 only delayed the onset of subsequent tumour growth. Commercial Photosan 3 disintegrated tumours only in doses of approx. 7.5 mg.kg−1; in lower doses it was less efficient than TPPS4. The second PDT cycle (3.2 mg.kg−1 TPP or 7.5 mg.kg−1 Photosan 3), performed in a few unsuccessfully cured mice, predominantly led again to tumour remissions. Since the measured TPP and TPPS4 content in melanomas was similar, these results demonstrate the advantage of PDT with a hydrophobic photosensitizer such as TPP. Photophysical properties of TPP and TPPS4 are equal, but TPP has probably more favorable intracellular distribution, as documented by our studies, which leads to more efficient PDT. Consequently, liposomal TPP is suggested as a potentially suitable efficient preparation for PDT. © 2002 Wiley‐Liss, Inc.
Serum selenium and risk of prostate cancer in U.S. blacks and whites
Authors: Vogt Tara M. , Ziegler Regina G. , Graubard Barry I. , Swanson Christine A. , Greenberg Raymond S. , Schoenberg Janet B. , Swanson G. Marie , Hayes Richard B. , Mayne Susan T. 
Published: December 2002

AbstractProstate cancer is the fourth most common cancer in men worldwide and the most common cancer in men in the United States, with reported incidence rates for U.S. blacks being the highest in the world. The etiology of prostate cancer and an explanation for the racial disparity in incidence in the United States remain elusive. Epidemiologic studies suggest that selenium, an essential trace element, may protect against the disease. To further explore this hypothesis, we measured serum selenium in 212 cases and 233 controls participating in a multicenter, population‐based case‐control study that included comparable numbers of U.S. black and white men aged 40–79 years. Serum selenium was inversely associated with risk of prostate cancer (comparing highest to lowest quartiles, OR = 0.71, 95% CI 0.39–1.28; p for trend = 0.11), with similar patterns seen in both blacks and whites. Cubic regression spline analysis of continuous serum selenium indicated a reduced risk of prostate cancer above concentrations of 0.135 μg/ml (median among controls) compared to a reference value set at the median of the lowest selenium quartile. Because both the selenoenzyme GPX and vitamin E can function as antioxidants, we also explored their joint effect. Consistent with other studies, the inverse association with selenium was strongest among men with low serum α‐tocopherol concentrations. In conclusion, our results suggest a moderately reduced risk of prostate cancer at higher serum selenium concentrations, a finding that can now be extended to include U.S. blacks. Since selenium exposure varies widely throughout the world, further research on optimal concentrations for cancer prevention is justified. © 2002 Wiley‐Liss, Inc.
Breast cancer revisited using DNA array‐based gene expression profiling
Authors: Bertucci François , Viens Patrice , Hingamp Pascal , Nasser Valery , Houlgatte Rémi , Birnbaum Daniel 
Published: December 2002

AbstractBreast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The resulting clinical heterogeneity makes current diagnostic and therapeutic strategies less than perfectly adapted to each patient. Pathological and clinical factors are insufficient to capture the complex cascade of events that drive the clinical behavior of tumors. High‐throughput molecular technologies provide novel tools to tackle this complexity. In particular, DNA arrays allow the simultaneous and quantitative analysis of the mRNA expression levels of thousands of genes in a single assay. Potential applications are multiple in the cancer field and the first research results are promising; comprehensive gene expression profiles of breast tumors are providing insights into mammary oncogenesis and are revealing new tumor subgroups previously indistinguishable. Significant advances will be the identification of new diagnostic, prognostic and predictive biomarkers as well as the discovery of new potential therapeutic targets. This review presents recent applications of DNA arrays in breast cancer research and discusses some issues to address in the near future to allow the technology to reach its full potential. © 2002 Wiley‐Liss, Inc.
CDKN2A region polymorphism and genetic susceptibility to melanoma in the melim swine model of familial melanoma
Authors: Le Chalony Catherine , Renard Christine , Vincent‐Naulleau Silvia , Crechet Françoise , Leplat Jean‐Jacques , Tricaud Yves , Horak Vratislav , Gruand Joseph , Le Roy Pascale , Frelat Gérard , Geffrotin Claudine 
Published: December 2002

AbstractSome herds of miniature swine are genetically predisposed to cutaneous melanoma. To test if swine melanoma susceptibility could be linked to the CDKN2A gene, which is involved in a proportion of 9p21‐linked human familial melanoma, we performed a genetic analysis of miniature pigs of the MeLiM strain. F1 and backcross animals were generated by crossing 1 MeLiM boar with healthy Duroc sows. We isolated the swine CDKN2A gene and characterized a linked informative microsatellite marker, the S0644 marker. Using this marker and 2 flanking markers, we analyzed the segregation of the CDKN2A gene in a 3‐generation pedigree. Allelic association, linkage analysis and haplotype analysis of these data led to exclusion of the CDKN2A gene as a candidate for melanoma susceptibility. Nonetheless, this analysis suggests an association with the swine 1q25 chromosomal region, which is homologous to the human 9p21 region. © 2002 Wiley‐Liss, Inc.
Prostaglandin J2 metabolites inhibit aromatase activity by redox‐sensitive mechanisms: Potential implications for breast cancer therapy
Authors: Winnett Georgia , van Hagen Daphne , Schrey Michael 
Published: December 2002

AbstractThe mechanisms by which prostaglandin (PG)J2 metabolites inhibit tumorigenicity are poorly understood but may involve thiol reactivity or peroxisome proliferator‐activated receptor (PPAR)‐dependent pathways. Because aromatase is an important therapeutic target in breast cancer treatment, we have investigated the effect of PGJ2 metabolites on aromatase activity and evaluated a potential role for redox status during PGJ2 metabolite action. 15‐deoxy‐Δ12,14PGJ2 (15d‐PGJ2) and 9‐deoxy‐Δ9,1213,14‐dihydroPGD2 (Δ12PGJ2) caused dose‐dependent inhibition of both pre‐induced aromatase activity in human breast fibroblasts and MDA MB 231 breast cancer cells and of constitutive aromatase activity in JEG‐3 choriocarcinoma cells. Structure‐activity studies showed that this inhibition was mimicked by 4‐cyclopentene‐1,3‐dione but not by the PPARγ agonist troglitazone nor the eicosanoids PGE2 or arachidonic acid. The thiol oxidants diamide and H2O2 simulated the inhibitory action of 15d‐PGJ2 on aromatase activity, whereas the glutathione (GSH) repletor and antioxidant N‐acetyl‐cysteine (NAC) reversed these actions of 15d‐PGJ2 and H2O2 on aromatase. 15d‐PGJ2 also caused a direct dose‐dependent inhibition of aromatase activity in JEG‐3 cell sonicates, which was also reversed in the presence of GSH. Kinetic analysis of this 15d‐PGJ2‐induced inhibition of cell‐free aromatase indicated the involvement of a non‐competitive mechanism possibly resulting from direct thiol‐targeted alkylation of the enzyme. These redox‐sensitive, PPARγ‐independent actions of 15d‐PGJ2 on aromatase activity demonstrate a novel therapeutic potential for such cyclopentenone PGs in breast cancer treatment. © 2002 Wiley‐Liss, Inc.
Regeneration of serous membrane on gelatin‐processed polyglycolic acid (PGA)‐human collagen membrane and its efficacy on the prevention of adhesion
Authors: Lee Yong Ho , Nakamura Tatsuo , Shimizu Yasuhiko , Yamamoto Yasumich , Kiyotani Tetsuya , Tsuda Touru , Teramachi Masayoshi , Takimoto Yukinobu 
Published: December 2002

AbstractWe prepared a complex membrane consisting of human amnion‐derived collagen membrane and polyglycolic acid (PGA), and then gelatin was crosslinked using heat on one side of the complex membrane to prepare a membrane that can prevent adhesion (gelatin‐processed PGA–human collagen membrane). Applying this membrane to a rabbit cecum‐abdominal‐wall‐adhesion model, the prevention of adhesion and tissue regeneration were investigated. The animals were sacrificed 2 and 12 weeks after surgery and then examined. The adhesion scores in the short‐term observation group (2 weeks after surgery) and long‐term observation group (12 weeks after surgery) were 1.0 ± 2.4 and 0.8 ± 2.0, respectively, showing a significant prevention of adhesion compared to the control value of 6.3 ± 2.5 (p < 0.01). Histologically, gelatin was not absorbed, and outgrowth of connective tissue accompanied by capillary blood vessels was observed between the sample and the cecum in the short‐term observation group. In the long‐term observation group, the sample was completely absorbed, and serous membrane was regenerated on the surface of connective tissue. Based on these findings, it is possible to use gelatin‐processed PGA–human collagen membrane as a filling material with both an adhesion‐preventing effect and tissue‐regenerating function. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 88–92, 2003
Preparation of epoxy–SiO2 hybrid sol–gel material for bone cement
Authors: Yang Jen Ming , Shih Chun Hsiung , Chang Chen‐Nen , Lin Feng Huei , Jiang Jian Ming , Hsu Ying Gev , Su Wen Yu , See Lai Chu 
Published: December 2002

AbstractAn organic–inorganic hybrid material, epoxy–SiO2, was prepared by incorporating epoxy structure units covalently into a SiO2 glass network via the sol–gel approach. The precursor was obtained by the reaction of diglycidyl ether of bisphenol A (DGEBA) with 3‐aminopropyl trimethoxysilane (APTS). The precursor was then hydrolyzed and co‐condensated with tetraethyl orthosilicate (TEOS) in tetrahydrofuran (THF) at room temperature to yield epoxy–SiO2 hybrid sol–gel material having a 50 wt % SiO2 content. Thermal properties of the hybrid material were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The hybrid sol–gel material epoxy–SiO2 was the solid, powder component of bone cement. The liquid component contains bis‐phenol‐A glycidyl methacrylate (Bis‐GMA), triethyleneglycol dimethacrylate (TEGDMA), and methyl methacrylate (MMA) with 25, 55, and 20 vol %, respectively. We discuss the comparison between the new epoxy–SiO2 bone cement and the commercial Simplex® P bone cement. Mechanical properties such as Young's modulus, compressive strength, hardness, and impact strength of the new epoxy–SiO2 bone cement exceeded those of SimplexR P bone cement. The tensile and bending strengths of the new epoxy–SiO2 bone cement were approximately the same as those of Simplex® P bone cement. In order to evaluate the biocompatibility of the new bone cement, an MTT test and optical microscopy were conducted in cell culture. Results indicated that the new epoxy–SiO2 bone cement exhibits very low cytotoxicity compared with Simplex® P bone cement. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 138–146, 2003
Quantitative analysis of binary adsorbed protein films by time of flight secondary ion mass spectrometry
Authors: Wagner M. S. , Shen M. , Horbett T. A. , Castner David G. 
Published: December 2002

AbstractTime of flight secondary ion mass spectrometry (ToF‐SIMS) is an ideal technique for the analysis of adsorbed protein films because of its surface sensitivity and chemical specificity. In this study, we examined ToF‐SIMS with the multivariate calibration method partial least squares regression (PLSR) for the determination of the relative abundance of the components in binary protein films adsorbed onto mica, PTFE, and heptyl amine plasma polymer substrates. These results have been compared with independently measured 125I‐radiolabeled protein adsorption experiments. By applying PLSR to the ToF‐SIMS data, the relative abundance of the components in the binary adsorbed protein films was quantified, and the agreement between the ToF‐SIMS and 125I‐radiolabeling data was measured by the root mean square prediction error (RMSPE). Differences in protein quantification by PLSR and 125I‐radiolabeling ranged from 5 to 25 mass % RMSPE and were highly dependent on the structure of the adsorbed protein film, the substrate surface chemistry and morphology, and the number of latent variables retained in the PLSR model. The limit of detection for the minor component in the adsorbed protein film was found to be approximately 10 mass %. This study demonstrates that the combination of ToF‐SIMS and multivariate calibration provide complementary information to 125I‐radiolabeling about the composition and structure of binary adsorbed protein films. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 1–11, 2003
Development of new hydroactive dressings based on chitosan membranes: Characterization and in vivo behavior
Authors: de Queiroz Alvaro Antonio Alençar , Ferraz Humberto Gomes , Abraham Gustavo Abel , del Mar Fernández María , Bravo Antonio López , Román Julio San 
Published: December 2002

AbstractDifferent poly(vinyl alcohol) (PVA)/chitosan lactate (ChL)‐blended hydrogels containing nitrofurazone as a local anti‐infective drug were prepared by the phase‐inversion technique. The swelling degree, surface free energy, mechanical properties, and nitrofurazone release of these membranes were determined. Blood compatibility of these systems was evaluated by the open‐static platelet adhesion test with whole human blood. The results showed that water absorption into the PVA/ChL membranes slowed down, governed by the rate at which the dressing interacted with the physiological fluid. Swelling degree values up to 200% were observed. The rate of release of nitrofurazone seemed to depend on the ChL percentage on the blend as well as the pH of the solution. The surface free energy values were in the range of 20–30 dynes/cm, which was appropriate for a favorable interaction with blood. From the Young's module curve, it could be seen that elastic hydrogels were obtained with increment of ChL in the PVA/ChL blends. Values of platelet adhesion and whole blood clotting times for the PVA/ChL blends as well as the increase of ChL, which appears to reduce the fibrinogen adsorption on the PVA/ChL membranes, demonstrated that the blood compatibility of PVP/ChL blends is superior to that separated polymers. The results of in vivo experiments in rats were in very good agreement with these observations, suggesting that PVA/ChL may serve as a new type of potential wound‐dressing material. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 147–154, 2003