bluuebunny/crossref_metadata_2025_split huggingface dataset:
2‐Methoxy‐2,4‐diphenyl‐3(2H)‐furanone‐labeled gelatin zymography and reverse zymography: A rapid real‐time method for quantification of matrix metalloproteinases‐2 and ‐9 and tissue inhibitors of metalloproteinases
Authors: Min Danqing , Lyons James Guy , Jia Junhong , Lo Lisa , McLennan Susan V. 
Published: December 2005

AbstractMeasurement of matrix metalloproteinases (MMPs) and their specific tissue inhibitors of metalloproteinases (TIMPs) by the techniques of zymography and reverse zymography provide useful information regarding the status of matrix accumulation or breakdown. This report describes the use of 2‐methoxy‐2,4‐diphenyl‐3(2H)‐furanone (MDPF), a fluorescent compound which can be used to label gelatin as a substrate for detection of the gelatin degrading MMP‐2 and ‐9 by zymography. In addition, a modification of the zymographic technique by addition of excess MMPs enables the use of the MDPF‐labeled gelatin substrate for the identification and quantification of TIMPs by reverse zymography. Both systems are real‐time sensitive reliable quantification techniques, easily used for measurement of these MMPs and TIMPs in clinical, biological, and tissue culture samples.
Separation performance of single‐stranded DNA electrophoresis in photopolymerized cross‐linked polyacrylamide gels
Authors: Lo Roger C. , Ugaz Victor M. 
Published: December 2005

AbstractConsiderable effort has been directed toward optimizing performance and maximizing throughput in ssDNA electrophoresis because it is a critical analytical step in a variety of genomic assays. Ultimately, it would be desirable to quantitatively determine the achievable level of separation resolution directly from measurements of fundamental physical properties associated with the gel matrix rather than by the trial and error process often employed. Unfortunately, this predictive capability is currently lacking, due in large part to the need for a more detailed understanding of the fundamental parameters governing separation performance (mobility, diffusion, and dispersion). We seek to address this issue by systematically characterizing electrophoretic mobility, diffusion, and dispersion behavior of ssDNA fragments in the 70–1000 base range in a photopolymerized cross‐linked polyacrylamide matrix using a slab gel DNA sequencer. Data are collected for gel concentrations of 6, 9, and 12%T at electric fields ranging from 15 to 40 V/cm, and resolution predictions are compared with corresponding experimentally measured values. The data exhibit a transition from behavior consistent with the Ogston model for small fragments to behavior in agreement with the biased reptation model at larger fragment sizes. Mobility data are also used to estimate the mean gel pore size and compare the predictions of several models.
Nitric oxide, adenosine deaminase, xanthine oxidase and superoxide dismutase in patients with panic disorder: alterations by antidepressant treatment
Authors: Herken Hasan , Akyol Omer , Yilmaz H. Ramazan , Tutkun Hamdi , Savas Haluk A. , Ozen M. Eren , Kalenderoglu Aysun , Gulec Mukaddes 
Published: December 2005

AbstractObjectiveIn the present study, we aimed to investigate whether nitric oxide (NO) levels and activities of xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA) are associated with Panic disorder (PD) as well as impact of psychopharmacological treatments on NO, SOD, ADA, and XO levels in PD.MethodIn this study, 32 patients and 20 healthy controls were included. The serum levels of NO, XO, SOD, and ADA were measured in the patients and controls. The patients were treated with antidepressant.ResultsADA and XO levels of the patients were significantly higher than the controls. SOD levels of the patients were significantly lower than the controls but the difference was not statistically significant. Although NO levels of the patients were higher than the controls, the difference was not statistically significant. There was no correlation between PAS and the parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of antidepressant treatment, ADA and SOD activities were increased whereas NO and XO levels decreased significantly.ConclusionADA, XO activity may have a pathophysiological role in PD, and prognosis of PD. Activity of these enzymes may be used to monitor effects of the antidepressant treatment. Copyright © 2005 John Wiley & Sons, Ltd.
Superiority of a cognitive education with photographs over ABCD criteria in the education of the general population to the early detection of melanoma: A randomized study
Authors: Girardi Sophie , Gaudy Caroline , Gouvernet Joanny , Teston Jacques , Richard Marie Aleth , Grob Jean‐Jacques 
Published: December 2005

AbstractMost education campaigns for melanoma (MM) detection in the general population have used the “ABCD” algorithm, although recognition of objects in the real life is based on a holistic image recognition rather than on analytic criteria. The objective was to compare analytic (ABCD) and cognitive (photographs) strategies for teaching self‐recognition of MM. A prospective 4‐arm stratified randomized trial in 255 individuals compared 3 realistic educative interventions by leaflets: 1) ABCD algorithm (“ABCD”), 2) a set of photographs chosen to stimulate recognition of MM among benign pigmented lesions (“Cog”), 3) photographs + explanations (“Cog‐Ex” arm) and 4) no intervention (“NI”). A 40‐slides test was performed before intervention (T0), 1 week after (T1) and after induction of anxiety (T2). In the “ABCD” arm, sensitivity slightly improved (80 to 83.8%, p = 0.04), but specificity dropped from 65.1 to 56.3% (p < 0.001), with no benefit in accuracy as compared to “NI”. In “Cog”arm, there was no change in sensitivity, but a strong increase in specificity (65.9 to 81.1%, p < 0.001) and accuracy (42.1 to 53.1%, p < 0.001). “Cog‐ex” resulted in similar although lower benefit. Under stress (T2), there was a dramatic loss of specificity and accuracy in “ABCD”arm (65.1 to 44.1%, p < 0.001 and 40.8% to 35.8%, p ≤ 0.001) without higher gain in sensitivity, while sensitivity and accuracy increased (p < 0.005) after “Cog” leaflet, without decreasing specificity. Finally, the “ABCD” message alone does not seem efficacious and is even worse in the context of anxiety, whereas a quick look at a few photographs is sufficient to improve the ability of the laymen to recognize a MM just by optimizing their spontaneous image recognition capacities. Education by photographs is a realistic strategy which should replace or complete “ABCD” message in the campaigns for self‐detection of MM. © 2005 Wiley‐Liss, Inc.
Chemokine receptors in head and neck cancer: Association with metastatic spread and regulation during chemotherapy
Authors: Muller Anja , Sonkoly Eniko , Eulert Christine , Gerber Peter Arne , Kubitza Robert , Schirlau Kerstin , Franken‐Kunkel Petra , Poremba Christopher , Snyderman Carl , Klotz Lars‐Oliver , Ruzicka Thomas , Bier Henning , Zlotnik Albert , Whiteside Theresa L. , Homey Bernhard , Hoffmann Thomas K. 
Published: December 2005

AbstractHead and neck carcinomas are histologically and clinically heterogeneous. While squamous cell carcinomas (SCC) are characterized by lymphogenous spread, adenoid cystic carcinomas (ACC) disseminate preferentially hematogenously. To study cellular and molecular mechanisms of organ‐specific metastasis, we used SCC and ACC cell lines and tumor tissues, obtained from patients with primary or metastatic disease. Comprehensive analysis at the mRNA and protein level of human chemokine receptors showed that SCC and ACC cells exhibited distinct and nonrandom expression profiles for these receptors. SCC predominantly expressed receptors for chemokines homeostatically expressed in lymph nodes, including CC chemokine receptor (CCR) 7 and CXC chemokine receptor (CXCR)5. No difference in expression of chemokine receptors was seen in primary SCC and corresponding lymph node metastases. In contrast to SCC, ACC cells primarily expressed CXCR4. In chemotaxis assays, ACC cells were responsive to CXCL12, the ligand for CXCR4. Exposure of ACC cells to cisplatin resulted in upregulation of CXCR4 on the cell surface, which was repressed by the transcriptional inhibitor, α‐amanitin. Treatment of ACC cells with CXCL12 resulted in the activation of Akt and ERK1/2 pathways. Furthermore, CXCL12 suppressed the rate of apoptosis induced by cisplatin in ACC cells, suggesting that signaling via CXCR4 may be part of a tumor cell survival program. Discrimination of the chemokine receptor profile in SCC and ACC in vitro and in tissues provided insights into their distinct biologic and clinical characteristics as well as indications that chemokine receptors might serve as future therapeutic targets in these malignancies. © 2005 Wiley‐Liss, Inc.
In vivo antitumor effect of the mTOR inhibitor CCI‐779 and gemcitabine in xenograft models of human pancreatic cancer
Authors: Ito Daisuke , Fujimoto Koji , Mori Tomohiko , Kami Kazuhiro , Koizumi Masayuki , Toyoda Eiji , Kawaguchi Yoshiya , Doi Ryuichiro 
Published: December 2005

AbstractMammalian target of rapamycin (mTOR) is considered to be a major effector of cell growth and proliferation that controls protein synthesis through a large number of downstream targets. We investigated the expression of the phosphatidylinositol 3′‐kinase (PI3K)/mTOR signaling pathway in human pancreatic cancer cells and tissues, and the in vivo antitumor effects of the mTOR inhibitor CCI‐779 with/without gemcitabine in xenograft models of human pancreatic cancer. We found that the Akt, mTOR and p70 S6 kinase (S6K1) from the PI3K/mTOR signaling pathway were activated in all of the pancreatic cancer cell lines examined. When surgically resected tissue specimens of pancreatic ductal adenocarcinoma were examined, phosphorylation of Akt, mTOR and S6K1 was detected in 50, 55 and 65% of the specimens, respectively. Although CCI‐779 had no additive or synergistic antiproliferative effect when combined with gemcitabine in vitro, it showed significant antitumor activity in the AsPC‐1 subcutaneous xenograft model as both a single agent and in combination with gemictabine. Furthermore, in the Suit‐2 peritoneal dissemination xenograft model, the combination of these 2 drugs achieved significantly better survival when compared with CCI‐779 or gemcitabine alone. These results demonstrate promising activity of the mTOR inhibitor CCI‐779 against human pancreatic cancer, and suggest that the inhibition of mTOR signaling can be exploited as a potentially tumor‐selective therapeutic strategy. © 2005 Wiley‐Liss, Inc.
Silencing of APAF‐1 in B‐CLL results in poor prognosis in the case of concomitant p53 mutation
Authors: Sturm Isrid , Bosanquet Andrew G. , Radetzki Silke , Hummel Michael , Dörken Bernd , Daniel Peter T. 
Published: December 2005

AbstractApoptosis protease‐activating factor 1 (APAF‐1), a transcriptional target of p53, is a cytosolic adaptor protein that links the mitochondrial apoptosis pathway to the caspase cascade. Here, we aimed to study the impact of APAF‐1 expression levels on cell death induced by anticancer drugs or ionizing irradiation (IR) and disease prognosis in B‐type chronic lymphocytic leukemia (B‐CLL) patients. Samples from 138 patients with B‐CLL were investigated for APAF‐1 expression and p53 mutations. The results were related to survival data, in vitro cytotoxicity of various cytotoxic drugs and IR and clinico‐pathological data. Variable APAF‐1 expression was observed in all investigated B‐CLL samples. Reduction in APAF‐1 expression was observed at both mRNA and protein level indicating transcriptional silencing whereas mutation of p53 or the immunoglobulin heavy chain variable genes (IgHV) had no impact on APAF‐1 expression. Surprisingly, APAF‐1 loss did not result in resistance to cytotoxic therapies. Likewise, APAF‐1 downregulation on its own showed no impact on disease prognosis. Nevertheless, a poor prognosis was observed in patients with loss of APAF‐1 expression and additional p53 mutation. Thus, loss of APAF‐1 may become relevant when additional core apoptosis signaling components are disrupted. © 2005 Wiley‐Liss, Inc.
Tissue microarrays for comparing molecular features with proliferation activity in breast cancer
Authors: Ruiz Christian , Seibt Silvia , Kuraya Khawla Al , Siraj Abdul K , Mirlacher Martina , Schraml Peter , Maurer Robert , Spichtin Hanspeter , Torhorst Joachim , Popovska Savelina , Simon Ronald , Sauter Guido 
Published: December 2005

AbstractTissue microarrays (TMAs) are potentially suited to find associations between molecular features and clinical outcome. Enhanced cell proliferation, as measured by Ki67 immunohistochemistry, is related to poor patient prognosis in many different tumor types. Ki67 expression shows considerable intratumoral heterogeneity. It is unclear if the TMA format is suitable for the analysis of potentially heterogeneous markers because of the small size of TMA spots. We have analyzed a breast cancer TMA containing 2,517 breast tissues, including 2,222 neoplastic and 295 normal or premalignant samples, for Ki67 labeling index (Ki67 LI) and additional markers with a known relationship to Ki67 LI by immunohistochemistry (ER, PR, Bcl‐2, Egfr, p16, p53) and Fluorescence in situ hybridization (HER2, MDM2, CCND1, MYC). A high Ki67 LI was linked to tumor phenotype including grade (p < 0.0001), stage (p < 0.0001), nodal stage (p = 0.0018), and patient prognosis (p < 0.0001), elevated protein levels of p53, p16 and Egfr, reduced levels of Bcl2, ER, and PR (p < 0.0001 each), as well as amplifications of HER2, MYC, CCND1 and MDM2 (p < 0.0001 each). In summary, all expected associations between Ki67 and the analyzed molecular markers could be reproduced with high statistical significance using a TMA containing only one tissue sample per tumor, measuring 0.6 mm in diameter. We conclude that associations with cell proliferation can be reliably analyzed in a TMA format. © 2005 Wiley‐Liss, Inc.
p16 expression in primary malignant melanoma is associated with prognosis and lymph node status
Authors: Mihic‐Probst Daniela , Mnich Christian D. , Oberholzer Patrick A. , Seifert Burkhardt , Sasse Bernd , Moch Holger , Dummer Reinhard 
Published: December 2005

AbstractLymph node (LN) status is an important prognostic factor in melanoma patients. p16 expression and proliferation rate (MIB‐1) of primary melanomas have been suggested as a marker of metastatic potential. In this study, the correlation of p16 expression and the proliferation rate (MIB‐1) with LN status and tumor‐specific survival was investigated in primary melanomas. MIB‐1 and p16 expression were analyzed by immunohistochemistry in 64 patients with primary cutaneous melanoma. Thirty four nevi were used as control. All patients underwent sentinel lymph node staging. Three different p16 staining patterns were observed: a combination of nuclear and cytoplasmic staining, only cytoplasmic staining and absence of p16 expression. All 34 nevi displayed a nuclear and cytoplasmic p16 staining, whereas p16 was negative in 14 of 64 (22%) melanomas. The level of p16 expression gradually decreased from benign nevi to melanoma without metastasis to melanoma with metastasis. There was a significant correlation between cytoplasmic p16 expression and absence of metastasis (p < 0.05). Death of disease correlated with absence of p16 immunostaining (p = 0.01). MIB‐1 expression was not associated with survival. These results confirm the relevance of p16 expression as a prognostic marker in melanoma patients. In addition, it was shown that cytoplasmic immunostaining for p16 in primary melanoma might serve as a predictor of the LN status. Therefore, immunohistochemical evaluation for p16 expression is of potential value for treatment planning in melanoma surgery. © 2005 Wiley‐Liss, Inc.
Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma
Authors: Kang Sokbom , Kim Jae Weon , Kang Gyeong Hoon , Lee Sun , Park Noh Hyun , Song Yong Sang , Park Sang Yoon , Kang Soon Beom , Lee Hyo Pyo 
Published: December 2005

AbstractThe incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite‐modification technique and methylation‐specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. © 2005 Wiley‐Liss, Inc.
Tobacco use, body mass index and the risk of malignantlymphomas—A nationwide cohort study in Sweden
Authors: Fernberg Pia , Odenbro Åsa , Bellocco Rino , Boffetta Paolo , Pawitan Y Yudi , Adami Johanna 
Published: December 2005

AbstractIn the search for risk factors involved in the etiology of lymphoproliferative malignancies there is still inconsistent evidence regarding effects of smoking tobacco, and the role of smokeless tobacco is poorly investigated. New evidence indicates that excess body weight increases the risk of NHL and HD. To determine if tobacco use of various forms and high Body Mass Index (BMI) affect the occurrence of these neoplasms, we conducted a prospective cohort study on over 330,000 Swedish construction workers included in the Construction Industry Working Environment and Health program. Information on smoking, snuff dipping, height and weight was gathered by self administered questionnaires together with personal interviews. Cancer incidence was ascertained through the year 2000 by record linkage to the nationwide Swedish Cancer Registry, Migration Registry and Cause of Death Registry. At the end of follow up, 1,309 subjects had been diagnosed with NHL (including chronic lymphocytic leukemia) and 205 with HD respectively. Age adjusted incidence rate ratios were computed using Cox proportional Hazard regression modeling. Smoking cigarette, pipe or cigar was not associated with NHL or HD. There was no evidence indicating a relation between quantity and duration of smoking and NHL or HD risk. No link was found between NHL and usage of smokeless tobacco. Having a BMI of 30 or higher did not convey excess risk of developing NHL or HD compared to normal weight (BMI 18.6–24.9). We conclude that tobacco smoking and high BMI do not entail an increased risk of NHL and HD. Our findings of a relation between the duration of snuff dipping and HD need further investigation. © 2005 Wiley‐Liss, Inc.
Prognostic significance of osteopontin expression in human prostate cancer
Authors: Forootan Shiva S. , Foster Christopher S. , Aachi Vijay R. , Adamson Janet , Smith Paul H. , Lin Ke , Ke Youqiang 
Published: December 2005

AbstractTo test the hypothesis that expression of osteopontin (OPN), an integrin‐binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT‐2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du‐145 and PC‐3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 ± 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6‐fold to 5.9 ± 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (+). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (+) and 4 (11%) were unstained (−). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (+++), 20 (29%) stained moderately positive (++) and 19 (27%) stained weakly positive (+). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p = 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi‐square test, p < 0.0001). Kaplan‐Meier survival analysis showed that the increased level of OPN expression was significantly (n = 70, p = 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi‐square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival. © 2005 Wiley‐Liss, Inc.
Nuclear Maspin expression is associated with response to adjuvant 5‐fluorouracil based chemotherapy in patients with stage III colon cancer
Authors: Dietmaier Wolfgang , Bettstetter Marcus , Wild Peter J. , Woenckhaus Matthias , Rümmele Petra , Hartmann Arndt , Dechant Stefan , Blaszyk Hagen , Pauer Armin , Klinkhammer‐Schalke Monika , Hofstädter Ferdinand 
Published: December 2005

AbstractMaspin, a member of the Serpin protease inhibitor family, is overexpressed in poorly differentiated colorectal tumors and more frequently found in tumors with microsatellite instability. Immunohistochemical nuclear Maspin staining is predominantly seen in tumor cells at the invasion front of such cancers, suggesting that this molecule is associated with local tumor cell infiltration and aggressiveness. In a retrospective study, we studied nuclear Maspin expression as a potential prognostic tool in a total of 172 primary stage III colon cancers by immunohistochemistry. Of those 172 patients, 76 were treated by surgery only, and 96 patients received additional adjuvant 5‐fluorouracil (5‐FU) based chemotherapy. Nuclear Maspin expression was an independent adverse prognostic factor for overall survival in our patient cohort (hazard ratio 2.08; 95% CI, 1.13–3.81; p = 0.018). However, patients with primary tumors expressing Maspin in the nucleus showed a significant treatment benefit from 5‐FU chemotherapy (hazard ratio 0.384; 95% CI, 0.188–0.784; p = 0.009) compared to adjuvantly treated patients whose tumors did not express this molecule. Nuclear Maspin expression is highly predictive of 5‐FU chemotherapy response in patients with advanced stage colon cancer. Patients with negative immunhistochemical Maspin expression do not benefit from 5‐FU treatment and may be candidates for an alternative (non‐5‐FU based) adjuvant therapy regime. © 2005 Wiley‐Liss, Inc.