bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligomannurarate Sulfate, a Novel Heparanase Inhibitor Simultaneously Targeting Basic Fibroblast Growth Factor, Combats Tumor Angiogenesis and Metastasis
Authors: Zhao Huajun , Liu Haiying , Chen Yi , Xin Xianliang , Li Jing , Hou Yongtai , Zhang Zhonghua , Zhang Xiongwen , Xie Chengying , Geng Meiyu , Ding Jian 
Published: September 2006

Abstract
Inhibitors of tumor angiogenesis and metastasis are increasingly emerging as promising agents for cancer therapy. Recently, heparanase inhibitors have offered a new avenue for such work because heparanase is thought to be critically involved in the metastatic and angiogenic potentials of tumor cells. Here, we report that oligomannurarate sulfate (JG3), a novel marine-derived oligosaccharide, acts as a heparanase inhibitor. Our results revealed that JG3 significantly inhibited tumor angiogenesis and metastasis, both in vitro and in vivo, by combating heparanase activity via binding to the KKDC and QPLK domains of the heparanase molecule. The JG3-heparanase interaction was competitively inhibited by low molecular weight heparin (4,000 Da) but not by other glycosaminoglycans. In addition, JG3 abolished heparanase-driven invasion, inhibited the release of heparan sulfate–sequestered basic fibroblast growth factor (bFGF) from the extracellular matrix, and repressed subsequent angiogenesis. Moreover, JG3 inactivated bFGF-induced bFGF receptor and extracellular signal–regulated kinase 1/2 phosphorylation and blocked bFGF-triggered angiogenic events by directly binding to bFGF. Thus, JG3 seems to inhibit both major heparanase activities by simultaneously acting as a substrate mimetic and as a competitive inhibitor of heparan sulfate. These findings suggest that JG3 should be considered as a promising candidate agent for cancer therapy. (Cancer Res 2006; 66(17): 8779-87)
Expression of Variant TMPRSS2/ERG Fusion Messenger RNAs Is Associated with Aggressive Prostate Cancer
Authors: Wang Jianghua , Cai Yi , Ren Chengxi , Ittmann Michael 
Published: September 2006

Abstract
Recent studies have reported that the majority of prostate cancers express fusion genes in which the 5′ region of the androgen-regulated TMPRSS2 gene is fused to an ETS family transcription factor, most commonly the ERG gene. We have characterized in detail the expression of TMPRSS2/ERG fusion mRNAs and correlated the isoforms expressed and expression levels with clinical outcome in cancers from men undergoing radical prostatectomy. Overall, 59% of clinically localized prostate cancers express the TMPRSS2/ERG fusion gene, confirming the initial observations of high frequency expression of this fusion mRNA in prostate cancer. There was significant variation in the alternatively spliced isoforms expressed in different cancers. Expression of an isoform, in which the native ATG in exon 2 of the TMPRSS2 gene is in frame with exon 4 of the ERG gene, was associated with clinical and pathologic variables of aggressive disease. Expression of other isoforms, in which the native ERG ATG in exon 3 was the first in-frame ATG, was associated with seminal vesicle invasion, which is correlated with poor outcome following radical prostatectomy. Cancers not expressing these isoforms tended to express higher levels of fusion mRNAs, and in this group, higher expression levels of fusion mRNA were present in cancers with early prostate-specific antigen recurrence. Thus, both the isoforms of TMPRSS2/ERG fusions expressed and expression level may affect prostate cancer progression. (Cancer Res 2006; 66(17): 8347-51)
Fatty Acid Binding Protein 6 Is Overexpressed in Colorectal Cancer
Authors: Ohmachi Takahiro , Inoue Hiroshi , Mimori Koshi , Tanaka Fumiaki , Sasaki Atsushi , Kanda Tatsuo , Fujii Hiroshi , Yanaga Katsuhiko , Mori Masaki 
Published: September 2006

Abstract
Purpose: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer.
Experimental Design: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles.
Results: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P &lt; 0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P &lt; 0.01), more often in the left colon (P &lt; 0.05), and had shallower invasion into the bowel wall (P &lt; 0.05) compared with those with low expression. There was no significant difference between high- and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P &lt; 0.05), more dominant proliferation (P &lt; 0.001), and less apoptosis than mock cells.
Conclusions: The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.
Molecular Heterogeneity of Inflammatory Breast Cancer: A Hyperproliferative Phenotype
Authors: Nguyen Dang M. , Sam Kathy , Tsimelzon Anna , Li Xiaoxian , Wong Helen , Mohsin Syed , Clark Gary M. , Hilsenbeck Susan G. , Elledge Richard M. , Allred D. Craig , O'Connell Peter , Chang Jenny C. 
Published: September 2006

Abstract
Purpose: Inflammatory breast cancer (IBC) is associated with very poor prognosis. The aims of this study are (a) to prospectively identify differential gene expression patterns associated with IBC and (b) to confirm these pathways using tissue arrays.
Experimental Design: For gene expression analysis, IBC (n = 14) was clinically defined as rapid-onset cancer associated with erythema and skin changes, whereas non-IBC patients (n = 20) had stage III breast cancers, and cDNA analysis was carried out using the Affymetrix (Santa Clara, CA) HG-U133A microarrays. Tissue arrays were constructed from paraffin-embedded material, and the molecular phenotype of 75 IBC was compared with results from &gt;2,000 non-IBC.
Results: Gene expression analyses indicated that IBC has higher expression of genes associated with increased metabolic rate, lipid signaling, and cell turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC had statistically higher Ki-67 (93% versus 11%; P &lt; 0.001). BAX expression, reflecting increased apoptosis and cell turnover, was significantly uniformly higher in almost all IBC (98% versus 66%; P &lt; 0.05), whereas the expression of Bcl-2 was not significantly different. IBC tumors were more likely to be steroid hormone receptor negative (estrogen receptor, 49% versus 30%; P = 0.002; progesterone receptor, 68% versus 42%; P = 0.001). The expression of tyrosine kinases was not significantly different. E-cadherin was found to be expressed in 87% of IBC, whereas the expression p53 was not significantly different.
Conclusion: This study is one of the largest molecular analyses of IBC. Both IBC and non-IBC are genetically heterogeneous with consistent differences in the molecular phenotype of IBC.
Antitumor Effects of a Novel Phenylbutyrate-Based Histone Deacetylase Inhibitor, (S)-HDAC-42, in Prostate Cancer
Authors: Kulp Samuel K. , Chen Chang-Shi , Wang Da-Sheng , Chen Ching-Yu , Chen Ching-Shih 
Published: September 2006

Abstract
Purpose: To assess the antitumor effects of a novel phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, (S)-HDAC-42, vis-à-vis suberoylanilide hydroxamic acid (SAHA) in in vitro and in vivo models of human prostate cancer.
Experimental Design: The in vitro effects of (S)-HDAC-42 and SAHA were evaluated in PC-3, DU-145, or LNCaP human prostate cancer cell lines. Cell viability, apoptosis, and indicators of HDAC inhibition were assessed. Effects on Akt and members of the Bcl-2 and inhibitor of apoptosis protein families were determined by immunoblotting. Immunocompromised mice bearing established s.c. PC-3 xenograft tumors were treated orally with (S)-HDAC-42 (50 mg/kg q.o.d. or 25 mg/kg q.d.) or SAHA (50 mg/kg q.d.) for 28 days. In vivo end points included tumor volumes and intratumoral changes in histone acetylation, phospho-Akt status, and protein levels of Bcl-xL and survivin.
Results: (S)-HDAC-42 was more potent than SAHA in suppressing the viability of all cell lines evaluated with submicromolar IC50 values. Relative to SAHA, (S)-HDAC-42 exhibited distinctly superior apoptogenic potency, and caused markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells. The growth of PC-3 tumor xenografts was suppressed by 52% and 67% after treatment with (S)-HDAC-42 at 25 and 50 mg/kg, respectively, whereas SAHA at 50 mg/kg suppressed growth by 31%. Intratumoral levels of phospho-Akt and Bcl-xL were markedly reduced in (S)-HDAC-42-treated mice, in contrast to mice treated with SAHA.
Conclusions: (S)-HDAC-42 is a potent orally bioavailable inhibitor of HDAC, as well as targets regulating multiple aspects of cancer cell survival, which might have clinical value in prostate cancer chemotherapy and warrants further investigation in this regard.
High-Dose Celecoxib and Metronomic “Low-dose” Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non–Hodgkin's Lymphoma
Authors: Buckstein Rena , Kerbel Robert S. , Shaked Yuval , Nayar Rakesh , Foden Cindy , Turner Ruth , Lee Christine R. , Taylor Diane , Zhang Liying , Man Shan , Baruchel Sylvain , Stempak Diana , Bertolini Francesco , Crump Michael 
Published: September 2006

Abstract
Purpose: Angiogenesis is increased in aggressive histology non–Hodgkin's lymphoma and may be a target with selective cyclooxygenase-2 inhibition and metronomic chemotherapy.
Experimental Design: We assessed response, toxicity, and biomarkers of angiogenesis to low-dose cyclophosphamide (50 mg p.o. o.d.) and high-dose celecoxib (400 mg p.o. b.i.d.) in adult patients with relapsed or refractory aggressive non–Hodgkin's lymphoma in a multicenter phase II prospective study.
Results: Thirty-two of 35 patients (median age, 62 years) are evaluable for response. Patients had primarily relapsed diffuse large B-cell lymphoma (63%) were heavily pretreated (median of three regimens) and high risk (79% international prognostic index, ≥2) and 34% were relapsed after autologous stem cell transplant. With a median follow-up of 8.4 months, the overall best response rate is 37% (2 complete clinical response/complete clinical response unconfirmed and 9 partial response), with 22% achieving stable disease. Median overall and progression-free survivals are 14.4 and 4.7 months, respectively. The median response duration was 8.2 months. The most common toxicity was skin rash (40%); myelosuppression and gastrointestinal side effects were uncommon. Three patients developed deep vein thromboses and two heavily pretreated patients developed treatment-related acute myelogenous leukemia or myelodysplasia after 3.7 and 12 months of therapy. Circulating endothelial cells and their precursors declined and remained low in responders, whereas plasma vascular endothelial growth factor trended to decline in responding patients but increase in nonresponders. Trough celecoxib levels achieved targeted “antiangiogenic” levels.
Conclusions: Low-dose cyclophosphamide and high-dose celecoxib is well tolerated and active in pretreated aggressive non–Hodgkin's lymphoma. Close surveillance for arterial and venous thrombotic events is recommended. The decline in circulating endothelial cells and their precursors suggests that this combination may be working by inhibiting angiogenesis but should be validated in a larger patient sample.
DNA Repair Pathway Profiling and Microsatellite Instability in Colorectal Cancer
Authors: Yu Jinsheng , Mallon Mary A. , Zhang Wanghai , Freimuth Robert R. , Marsh Sharon , Watson Mark A. , Goodfellow Paul J. , McLeod Howard L. 
Published: September 2006

Abstract
Background: The ability to maintain DNA integrity is a critical cellular function. DNA repair is conducted by distinct pathways of genes, many of which are thought to be altered in colorectal cancer. However, there has been little characterization of these pathways in colorectal cancer.
Method: By using the TaqMan real-time quantitative PCR, RNA expression profiling of 20 DNA repair pathway genes was done in matched tumor and normal tissues from 52 patients with Dukes' C colorectal cancer.
Results: The relative mRNA expression level across the 20 DNA repair pathway genes varied considerably, and the individual variability was also quite large, with an 85.4 median fold change in the tumor tissue genes and a 127.2 median fold change in the normal tissue genes. Tumor-normal differential expression was found in 13 of 20 DNA repair pathway genes (only XPA had a lower RNA level in the tumor samples; the other 12 genes had significantly higher tumor levels, all P &lt; 0.01). Coordinated expression of ERCC6, HMG1, MSH2, and POLB (RS ≥ 0.60) was observed in the tumor tissues (all P &lt; 0.001). Apoptosis index was not correlated with expression of the 20 DNA repair pathway genes. MLH1 and XRCC1 RNA expression was correlated with microsatellite instability status (P = 0.045 and 0.020, respectively). An inverse correlation was found between tumor MLH1 RNA expression and MLH1 DNA methylation (P = 0.003).
Conclusion: Our study provides an initial characterization of the DNA repair pathways for understanding the cellular DNA damage/repair system in human colorectal cancer.
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting
Authors: Sok John C. , Coppelli Francesca M. , Thomas Sufi M. , Lango Miriam N. , Xi Sichuan , Hunt Jennifer L. , Freilino Maria L. , Graner Michael W. , Wikstrand Carol J. , Bigner Darell D. , Gooding William E. , Furnari Frank B. , Grandis Jennifer R. 
Published: September 2006

Abstract
Purpose: Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where expression levels correlate with decreased survival. Therapies that block EGFR have shown limited efficacy in clinical trials and primarily when combined with standard therapy. The most common form of mutant EGFR (EGFRvIII) has been described in several cancers, chiefly glioblastoma. The present study was undertaken to determine the incidence of EGFRvIII expression in HNSCC and the biological consequences of EGFRvIII on tumor growth in response to EGFR targeting.
Experimental Design: Thirty-three HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for EGFRvIII expression. A representative HNSCC cell line was stably transfected with an EGFRvIII expression construct. EGFRvIII-expressing cells and vector-transfected controls were compared for growth rates in vitro and in vivo as well as chemotherapy-induced apoptosis and the consequences of EGFR inhibition using the chimeric monoclonal antibody C225/cetuximab/Erbitux.
Results: EGFRvIII expression was detected in 42% of HNSCC tumors where EGFRvIII was always found in conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased proliferation in vitro and increased tumor volumes in vivo compared with vector-transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed decreased apoptosis in response to cisplatin and decreased growth inhibition following treatment with C225 compared with vector-transfected control cells.
Conclusions: EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.
The Effect of Enzyme-Inducing Antiseizure Drugs on the Pharmacokinetics and Tolerability of Procarbazine Hydrochloride
Authors: Grossman Stuart A. , Carson Kathryn A. , Batchelor Tracy T. , Lesser Glenn , Mikkelsen Tom , Alavi Jane B. , Phuphanich Surasak , Hammour Tarek , Fisher Joy D. , Supko Jeffrey G. 
Published: September 2006

Abstract
Purpose: Procarbazine hydrochloride (PCB) is one of the few anticancer drugs with activity against high-grade gliomas. This study was conducted to determine if the maximum tolerated dose and pharmacokinetics of PCB are affected by the concurrent use of enzyme-inducing antiseizure drugs (EIASD).
Experimental Design: Adults with recurrent high-grade glioma were divided into cohorts who were (+) and were not (−) taking EIASDs. PCB was given orally for 5 consecutive days each month. Six patients were evaluated at each dose level beginning with 200 mg/m2/d and escalated using the modified continual reassessment method. Toxicity and response were assessed. Pharmacokinetic studies were done with a new electrospray ionization mass spectrometry assay.
Results: Forty-nine patients were evaluated. The maximum tolerated dose was 393 mg/m2/d for the +EIASD group and the highest dose evaluated in −EIASD patients was 334 mg/m2/d. Myelosuppression was the primary dose-limiting toxicity. Significant hepatic dysfunction occurred in three patients in the +EIASD cohort. Four partial responses (8%) and no complete responses were observed. PCB exhibited linear pharmacokinetics with no significant differences between the two cohorts. A marked increase in peak PCB levels was noted on day 5 relative to day 1, which was not attributable to drug accumulation.
Conclusions: This study suggests that (a) EIASD use does not significantly affect the pharmacokinetics of PCB; (b) changes in the peak plasma concentration of PCB, consistent with decreased apparent oral clearance due to autoinhibition of hepatic metabolism, occur with daily dosing; and (c) severe hepatic dysfunction may accompany this administration schedule.
Health behaviour modelling for prenatal diagnosis in Australia: a geodemographic framework for health service utilisation and policy development
Authors: Muggli Evelyne E , McCloskey David , Halliday Jane L 
Published: September 2006

AbstractBackgroundDespite the wide availability of prenatal screening and diagnosis, a number of studies have reported no decrease in the rate of babies born with Down syndrome. The objective of this study was to investigate the geodemographic characteristics of women who have prenatal diagnosis in Victoria, Australia, by applying a novel consumer behaviour modelling technique in the analysis of health data.MethodsA descriptive analysis of data on all prenatal diagnostic tests, births (1998 and 2002) and births of babies with Down syndrome (1998 to 2002) was undertaken using a Geographic Information System and socioeconomic lifestyle segmentation classifications.ResultsMost metropolitan women in Victoria have average or above State average levels of uptake of prenatal diagnosis. Inner city women residing in high socioeconomic lifestyle segments who have high rates of prenatal diagnosis spend 20% more on specialist physician's fees when compared to those whose rates are average. Rates of prenatal diagnosis are generally low amongst women in rural Victoria, with the lowest rates observed in farming districts. Reasons for this are likely to be a combination of lack of access to services (remoteness) and individual opportunity (lack of transportation, low levels of support and income). However, there are additional reasons for low uptake rates in farming areas that could not be explained by the behaviour modelling. These may relate to women's attitudes and choices.ConclusionA lack of statewide geodemographic consistency in uptake of prenatal diagnosis implies that there is a need to target health professionals and pregnant women in specific areas to ensure there is increased equity of access to services and that all pregnant women can make informed choices that are best for them. Equally as important is appropriate health service provision for families of children with Down syndrome. Our findings show that these potential interventions are particularly relevant in rural areas.Classifying data to lifestyle segments allowed for practical comparisons of the geodemographic characteristics of women having prenatal diagnosis in Australia at a population level. This methodology may in future be a feasible and cost-effective tool for service planners and policy developers.
Awareness and practice of patient's rights law in Lithuania
Authors: Ducinskiene Danute , Vladickiene Jurgita , Kalediene Ramune , Haapala Irja 
Published: September 2006

AbstractBackgroundPatient's rights law is intended to secure good medical practice, but it can also serve to improve understanding between patients and medical staff if both were aware of their rights.MethodsAwareness and practice of the new patient's rights law in Lithuanian health care institutions was explored through a survey of 255 medical staff and 451 patients in the four Kaunas city medical units in 2002. Participation rates were 74% and 66%, respectively.ResultsMajority of the medical staff (85%) and little over one half of the patients (56%) had heard or read about the Law on Patient's Rights (p < 0.001). Only 50% of professionals compared to 69% of patients thought information for patients about diagnosis, treatment results and alternative treatments is necessary (p < 0.001). A clear discrepancy was indicated between physicians informing the patients (80% – 98% of physicians) and patients actually knowing (37% – 54%) their treatment prognosis, disease complications or possible alternative treatment methods.ConclusionThese results suggest a need for awareness-raising among patients to improve the practical implementation of the Patient's Rights Law in Lithuania.
Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1 replication and persistence
Authors: Cassol Edana , Alfano Massimo , Biswas Priscilla , Poli Guido 
Published: September 2006

Abstract
HIV infection of mononuclear phagocytes (MP), mostly as tissue macrophages, is a dominant feature in the pathogenesis of HIV disease and its progression to AIDS. Although the general mechanism of infection is not dissimilar to that of CD4+ T lymphocytes occurring via interaction of the viral envelope with CD4 and a chemokine receptor (usually CCR5), other features are peculiar to MP infection. Among others, the long-term persistence of productive infection, sustained by the absence of substantial cell death, and the capacity of the virions to bud and accumulate in intracellular multivescicular bodies (MVB), has conferred to MP the role of “Trojan horses” perpetuating the chronic state of infection. Because the investigation of tissue macrophages is often very difficult for both ethical and practical reasons of accessibility, most studies of in vitro infection rely upon monocyte-derived macrophages (MDM), a methodology hampered by inter-patient variability and lack of uniformity of experimental protocols. A number of cell lines, mostly Mono Mac, THP-1, U937, HL-60, and their derivative chronically infected counterparts (such as U1 and OM-10.1 cell lines) have complemented the MDM system of infection providing useful information on the features of HIV replication in MP. This article describes and compares the most salient features of these different cellular models of MP infection by HIV.