bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Endothelial Growth Factor: A Therapeutic Target for Tumors of the Ewing's Sarcoma Family
Authors: Dalal Surita , Berry Andrea M. , Cullinane Catherine J. , Mangham D. Charles , Grimer Robert , Lewis Ian J. , Johnston Colin , Laurence Valerie , Burchill Susan A. 
Published: September 2005

Abstract
Purpose: We have reported previously that intratumoral microvessel density (MVD) is a significant prognostic indicator of event-free survival in the Ewing's sarcoma family of tumors (ESFT). Here, the angiogenic growth factor expression profile and its relationship with MVD has been investigated in ESFT.
Experimental Design and Results: Using ESFT model systems, the potential of these factors as therapeutic targets has been evaluated. A significant correlation (P = 0.02) was observed between vascular endothelial growth factor (VEGF) expression and MVD, consistent with the hypothesis that VEGF regulates the development of microvessels in ESFT. There was no correlation between MVD and any of the other growth factors studied. All six ESFT cell lines studied produced and secreted VEGF; five of six cell lines also secreted placental growth factor, one cell line (A673) at high levels. Tumor conditioned medium induced proliferation of human umbilical vein endothelial cells. Expression of VEGF receptors Flt-1 and Flk-1/KDR was heterogeneous across the cell lines. Both receptor tyrosine kinase inhibitors SU6668 (targets Flk-1/KDR, platelet-derived growth factor receptor-β, and fibroblast growth factor receptor 1) and SU5416 (targets Flk-1/KDR) as well as anti-VEGF agents rhuMAb-VEGF (bevacizumab) and VEGF Trap delayed s.c. growth of ESFT in mice compared with untreated groups: SU6668 (100 mg/kg/d), SU5416 (25 mg/kg/d), rhuMAb-VEGF (10 mg/kg twice weekly), and VEGF Trap (2.5 or 25 mg/kg twice weekly).
Conclusions: These data suggest that VEGF is the single most important regulator of angiogenesis in ESFT and may be exploited for therapeutic advantage.
Glutathione S-transferase P1 Genotype and Prognosis in Hodgkin's Lymphoma
Authors: Hohaus Stefan , Di Ruscio Annalisa , Di Febo Annalaura , Massini Giuseppina , D'Alo' Francesco , Guidi Francesco , Mansueto Giovanna , Voso Maria Teresa , Leone Giuseppe 
Published: September 2005

Abstract
Purpose: Glutathione S-transferase P1 (GSTP1) is a member of the GST enzyme superfamily that is important for the detoxification of several cytotoxic drugs and their by-products. A single nucleotide polymorphism results in the substitution of isoleucine (Ile) to valine (Val) at codon 105, causing a metabolically less active variant of the enzyme. We assessed the impact of the GSTP1 codon 105 genotype on treatment outcome in patients with Hodgkin's lymphoma.
Experimental Design: The Ile105Val polymorphism in the GSTP1 gene was analyzed using a PCR-RFLP technique. Ninety-seven patients with Hodgkin's lymphoma were included and associations with patient characteristics and treatment outcome were analyzed.
Results: The GSTP1 Ile105Val polymorphism was associated in a dose-dependent fashion with an improved failure-free survival in patients with Hodgkin's lymphoma (P = 0.02). The probability of 5-year survival for patients homozygous for the 105Val/105Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the 105Ile/105Ile genotype 43% (95% confidence interval, 23-61). The Cox multivariate analysis showed that GSTP1 codon 105 genotype was an independent prognostic factor.
Conclusions: The GSTP1 genotype predicts clinical outcome in patients with Hodgkin's lymphoma.
Differences in Smad4 Expression in Human Papillomavirus Type 16–Positive and Human Papillomavirus Type 16–Negative Head and Neck Squamous Cell Carcinoma
Authors: Báez Adriana , Cantor Alan , Fonseca Sharon , Marcos-Martinez Maria , Mathews Linda A. , Muro-Cacho Carlos A. , Muñoz-Antonia Teresita 
Published: September 2005

Abstract
The SMADs are a group of interrelated proteins that mediate transforming growth factor β (TGF-β) signaling. Upon TGF-β binding the TGF-β type I receptor phosphorylates Smad2 and Smad3, which then complex with Smad4 and translocate to the nucleus, with subsequent activation of target genes. Disruption of TGF-β signaling is thought to contribute to the development of head and neck squamous cell carcinomas (HNSCC). Alterations in the function of the DPC4/Smad4 tumor suppressor gene have been found to inactivate TGF-β signaling in several tumor types. For example, DPC4/Smad4 is lost or mutated in colorectal, pancreatic, and esophageal cancers. In addition, DPC4/Smad4 transcriptional activity and TGF-β ability to inhibit DNA synthesis is blocked by the E7 protein of the human papillomavirus type 16 (HPV16) in cervical carcinoma cell lines. HPV16 infection is a risk factor for the development of a subset of HNSCC. This study was undertaken to investigate a potential correlation between expression of components of the TGF-β signaling pathway and HPV16 status in HNSCC tumors. We examined the expression of TGF-β signaling proteins Smad2, Smad2-P, and Smad4 by immunohistochemistry in 27 HPV16-negative and 16 HPV16-positive HNSCCs. We compared the expression patterns and assessed their relationship to HPV16 status. No significant differences were detected between HPV16-positive and HPV16-negative tumors in the expression of Smad2 and Smad2-P. Smad4 expression, however, was decreased in 56% of the HPV16-positive tumors and in 39% of HPV16-negative tumors. This difference was statistically significant (P = 0.01) suggesting that loss of Smad4 expression may be involved in HPV16-induced carcinogenesis of HNSCC.
Expression Profile of Cancer-Testis Genes in 121 Human Colorectal Cancer Tissue and Adjacent Normal Tissue
Authors: Li Ming , Yuan Yan-Hua , Han Yan , Liu Yue-Xiang , Yan Li , Wang Yu , Gu Jin 
Published: September 2005

Abstract
Purpose: Among tumor antigens identified to date, cancer-testis (CT) antigens, which are coded by CT genes, are identified as a group of highly attractive targets for cancer vaccines. This study is the first to analyze the mRNA expression and possible correlation with pathologic characteristics of multiple CT genes in a large cohort of colorectal cancer (CRC) patients.
Experimental Design: The expression of 10 individual CT genes in 121 CRC and adjacent tissues were analyzed by RT-PCR method. The presence of autologous antibodies against NY-ESO-1 was examined in serum samples by ELISA. To confirm the protein expression, immunohistochemistry was done for detecting the NY-ESO-1 antigen in mRNA-positive CRC tissues.
Results: The CT genes were detected with various frequencies in CRC tissue, SCP-1, 1.7%; SSX-2, 2.5%; SSX-4, 2.5%; SSX-1, 5.0%; CT10, 6.6%; NY-ESO-1, 9.9%; MAGE-1, 11.6%; LAGE-1, 15.7%; MAGE-4, 22.3%; and MAGE-3, 27.3%. In 56.2% of tumor tissues examined in this study, at least one CT gene was detected. In contrast, no CT gene expression was found in cancer adjacent tissues. Among 10 CT genes investigated, NY-ESO-1 and LAGE-1 are of particular interest because their mRNA expression in CRC was rarely reported before. In our study, NY-ESO-1 mRNA was found to express in 9.9% of the samples, and also correlated significantly with stages (P = 0.041) and local lymph node metastasis (P = 0.002). In addition, we also identified one NY-ESO-1 antibody–positive serum sample. MAGE-4 mRNA was expressed at a high frequency in tumor tissues with vessel emboli samples (P = 0.025).
Conclusions: These results suggested that CT genes, especially NY-ESO-1 and LAGE-1, do express in CRC. More than 50% of the CRC patients in this study express at least one CT gene, making them eligible for CT vaccination. NY-ESO-1 gene may serve as a marker for local metastasis and advanced disease. MAGE-4 gene is significantly associated with the vessel emboli.
Induction of T-Cell Apoptosis in Rats by Genetically Engineered Glioma Cells Expressing Granulocyte-Macrophage Colony-Stimulating Factor and B7.1
Authors: Tseng Sheng-Hong , Chen Yun , Chang Chun-Jung , Tai Kuo-Feng , Lin Swei-Ming , Hwang Lih-Hwa 
Published: September 2005

AbstractPurpose: To evaluate antitumor effects on intracerebral gliomas of genetically engineered tumor vaccines expressing granulocyte-macrophage colony-timulating factor (GM-CSF), B7.1, or both (combination).Experimental Design: A rat glioma cell line, RT-2, was engineered with a retroviral vector to express GM-CSF, B7.1, or combination. Tumorigenicity of engineered cells and therapeutic effects of s.c. given irradiated or live tumor vaccines on parental intracerebral gliomas were studied. Immune cell infiltration induced at vaccine and tumor sites was examined by histologic and immunohistochemical staining. Apoptosis of T cells from vaccine sites was analyzed with fluorescence-activated cell sorting.Results: Engineered RT-2 cells exhibited reduced s.c. tumorigenicity in rats with reduced tumor growth and prolonged animal survival time compared with control rats. Rats with intracerebral gliomas s.c. treated with irradiated or live GM-CSF-expressing vaccines had 60% and 100% survival rates, respectively, significantly better than the control groups (P &lt; 0.05). In contrast, rats treated with vaccines expressing B7.1 or the combination had no or mild therapeutic effects. Studies revealed less T-cell infiltration at both vaccine and tumor sites in rats treated with vaccines expressing B7.1 or the combination than in rats treated with a vaccine expressing GM-CSF. Cell sorting analyses revealed higher proportions of apoptotic T cells at vaccine sites of rats treated with the combination than those treated with vaccine expressing GM-CSF.Conclusions: Combination of GM-CSF- and B7.1-expressing tumor vaccines exerted no synergistic, or even worse, therapeutic effects on gliomas compared with single GM-CSF-secreting tumor vaccine. The worse therapeutic effects of the GM-B7.1-expressing tumor vaccine than the GM-CSF-expressing tumor vaccine were related to the reduced T-cell amount and increased T-cell apoptosis in the former.
Telomere Shortening and Telomerase Reverse Transcriptase Expression in Preinvasive Bronchial Lesions
Authors: Lantuejoul Sylvie , Soria Jean Charles , Morat Luc , Lorimier Philippe , Moro-Sibilot Denis , Sabatier Laure , Brambilla Christian , Brambilla Elisabeth 
Published: September 2005

Abstract
Purpose: Telomerase, a ribonucleoprotein complex whose activity is related to the expression of its catalytic subunit human telomerase reverse transcriptase (hTERT), restores telomere length in tumor cells and enables immortality after p53/Rb inactivation has been achieved. To determine the timing of hTERT derepression during bronchial carcinogenesis and its relationship with telomere shortening and the p53/Rb pathway alterations, we did an immunohistochemical and in situ hybridization study in preinvasive and invasive bronchial lesions.
Experimental Design: hTERT, P53, P16, cyclin D1, Bax-to-Bcl2 ratio, and Ki67 immunostainings were done in 106 preneoplastic lesions and in paired lung carcinoma and normal bronchial mucosae. Concomitantly, hTERT mRNA levels and qualitative telomere shortening were assessed by in situ hybridization and fluorescence in situ hybridization, respectively, in a subset of preneoplastic and neoplastic lesions.
Results: Telomerase was increasingly expressed from normal epithelium to squamous metaplasia, dysplasia, and carcinoma in situ, and decreased in invasive carcinoma (P &lt; 0.0001), with a direct correlation between protein and mRNA levels of expression (P &lt; 0.0001). hTERT expression was directly correlated with P53, Ki67, and Bcl2-to-Bax ratio, suggesting a coupling between telomerase reactivation, proliferation, and resistance to apoptosis. Telomere signals significantly decreased as early as squamous metaplasia and progressively increased over the spectrum of preneoplastic lesions.
Conclusions: Telomere shortening represents an early genetic abnormality in bronchial carcinogenesis, preceding telomerase expression and p53/Rb inactivation, which predominate in high-grade preinvasive lesions.
Expression of CXCR4 and Its Down-Regulation by IFN-γ in Head and Neck Squamous Cell Carcinoma
Authors: Katayama Akihiro , Ogino Takeshi , Bandoh Nobuyuki , Nonaka Satoshi , Harabuchi Yasuaki 
Published: September 2005

AbstractPurpose: The functional expression of CXCR4, which plays roles in cell migration and proliferation in response to its unique ligand stromal cell–derived factor-1 (SDF-1), has been reported in variety of carcinomas. However, CXCR4 expression and its functional role in head and neck squamous cell carcinomas (HNSCC) remain unclear. In this study, we investigated CXCR4 expression and analyzed its functions in HNSCC cell lines. We also attempted to regulate CXCR4 expression using cytokines, such as interleukin-1β, tumor necrosis factor-α, and IFN-γ. Finally, we investigated correlation between CXCR4 expression and clinical features in patients with HNSCC.Experimental Design: Six HNSCC cell lines were used in this study. Reverse transcription-PCR and flow cytometry analysis were shown for CXCR4 expressions with or without stimulations of cytokines. SDF-1-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. The SDF-1-mediated cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The SDF-1-mediated signaling pathways were analyzed by Western blot analysis. Biopsy specimens from 56 patients with HNSCC were used for immunohistologic analysis.Results: The significant CXCR4 expression was found in HSQ-89, IMC-3, and Nakamura cells. The SDF-1-mediated cell migration and proliferation were observed in CXCR4-positive cells. SDF-1 also promoted rapid phosphorylation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways in CXCR4-positive cells. The SDF-1-mediated cell migration and proliferation of CXCR4-positive cells were inhibited by neutralization of CXCR4. Among three cytokines tested, IFN-γ significantly reduced CXCR4 expression and SDF-1-induced cell migration and proliferation of CXCR4-positive cells. Immunohistologic analysis revealed that patients with advanced neck status and patients who developed distant metastases showed significantly higher CXCR4 expression, and the cause-specific survival of patients with CXCR4-expression was significantly shorter. Furthermore, multivariate analysis confirmed that CXCR4 positive was the independent factor for cause-specific death.Conclusion: Our results may provide an insight into future therapeutic agent that inhibits tumor metastasis and progression via down-regulating CXCR4 expression in patients with HNSCC.
Evaluation of a Panel of Tumor Markers for Molecular Detection of Circulating Cancer Cells in Women with Suspected Breast Cancer
Authors: Reinholz Monica M. , Nibbe Andrea , Jonart Leslie M. , Kitzmann Kathleen , Suman Vera J. , Ingle James N. , Houghton Raymond , Zehentner Barbara , Roche Patrick C. , Lingle Wilma L. 
Published: September 2005

Abstract
Purpose: We examined the feasibility of using molecular characterization of circulating tumor cells as a method for early detection of breast cancer.
Research Design: Women without a prior history of cancer who had a breast abnormality detected on imaging followed by a breast biopsy were enrolled in this study. Density gradient centrifugation and immunomagnetic capture were used to enrich for epithelial cells from ∼20 mL of blood. Real-time reverse transcription-PCR was used to quantitate the expression levels of the highly breast-specific genes, mammaglobin, γ-aminobutyric acid type A receptor π subunit (GABA Aπ), B305D-C, and B726P in the epithelial cell–enriched samples.
Results: The assay was technically feasible in 154 of 199 accrued patients. From their clinical assessment, 100 patients had benign breast disease, 10 patients had ductal carcinoma in situ, and 44 patients had invasive breast cancer. We constructed a diagnostic test that classified patients with mammaglobin levels of at least 32.2 copies/pg β-actin (units) in their circulating epithelial cells as positive for invasive breast cancer. This resulted in a sensitivity and specificity of 63.3% and 75.0%, respectively. A diagnostic test that classified patients as positive for invasive breast cancer when either mammaglobin levels were &gt;46.3 units or B305D-C levels were &gt;11.6 units increased the sensitivity and specificity to 70.5% and 81.0%, respectively. In the latter test, 12 of the 14 node-positive breast cancer patients were correctly identified. Including GABA Aπ and B726P in the test did not increase its diagnostic potential.
Conclusions: These results suggest that molecular characterization of circulating epithelial cells using mammaglobin and B305D-C offers potential for early detection of invasive breast cancer.
Recombinant Sendai Virus Vector Induces Complete Remission of Established Brain Tumors through Efficient Interleukin-2 Gene Transfer in Vaccinated Rats
Authors: Iwadate Yasuo , Inoue Makoto , Saegusa Takashi , Tokusumi Yumiko , Kinoh Hiroaki , Hasegawa Mamoru , Tagawa Masatoshi , Yamaura Akira , Shimada Hideaki 
Published: September 2005

Abstract
Purpose: Sendai virus (SeV), a murine parainfluenza virus type I, replicates independent of cellular genome and directs high-level gene expressions when used as a viral vector. We constructed a nontransmissible recombinant SeV vector by deleting the matrix (M) and fusion (F) genes from its genome (SeV/ΔMΔF) to enhance its safety. We also estimated the therapeutic efficacy of the novel vector system against a rat glioblastoma model.
Experimental Design: We administered the recombinant SeV vector carrying the lacZ gene or the human interleukin-2 (hIL-2) gene into established 9L brain tumors in vivo simultaneous with peripheral vaccination using irradiated 9L cells. Sequential monitoring with magnetic resonance imaging was used to evaluate the therapeutic efficacy.
Results: We found extensive transduction of the lacZ gene into the brain tumors and confirmed sufficient amounts of interleukin 2 (IL-2) production by hIL2-SeV/ΔMΔF both in vitro and in vivo. The magnetic resonance imaging study showed that the intracerebral injection of hIL2-SeV/ΔMΔF brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The 51Cr release assay showed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that CD4+ T cells and CD8+ T cells were abundantly infiltrated in the target tumors.
Conclusion: The present results show that the recombinant nontransmissible SeV vector provides efficient in vivo gene transfer that induces significant regression of the established brain tumors and suggest that it will be a safe and useful viral vector for the clinical practice of glioma gene therapy.
Serum Human Telomerase Reverse Transcriptase Messenger RNA as a Novel Tumor Marker for Hepatocellular Carcinoma
Authors: Miura Norimasa , Maeda Yoshiko , Kanbe Takamasa , Yazama Hiroaki , Takeda Yohei , Sato Reina , Tsukamoto Tomoe , Sato Emi , Marumoto Akira , Harada Tomomi , Sano Akiko , Kishimoto Yosuke , Hirooka Yasuaki , Murawaki Yoshikazu , Hasegawa Junichi , Shiota Goshi 
Published: September 2005

Abstract
Purpose: We previously reported the usefulness of a qualified highly sensitive detection method for human telomerase reverse transcriptase (hTERT) mRNA in serum with 89.7% sensitivity for hepatocellular carcinoma (HCC). In this study, we developed a quantitative detection method for serum hTERT mRNA and examined the clinical significance in HCC diagnosis.
Experimental Background: In 64 patients with HCC, 20 with liver cirrhosis, 20 with chronic hepatitis, and 50 healthy individuals, we measured serum hTERT mRNA by using the newly developed real-time quantitative reverse transcription-PCR with SYBR Green I. We examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical variables by using multivariate analyses.
Results: Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression was shown to be independently correlated with clinical variables such as tumor size, number, and degree of differentiation (P &lt; 0.001, each). The sensitivity/specificity of hTERT mRNA and alpha;-fetoprotein (AFP) mRNA in HCC diagnosis were 88.2%/70.0% for hTERT and 71.6%/67.5% for AFP, respectively. hTERT mRNA proved to be superior to AFP mRNA, AFP, and des-γ-carboxy prothrombin in HCC diagnosis. Furthermore, hTERT mRNA in serum was associated with that in HCC tissue.
Conclusions: The usefulness of hTERT mRNA expression in HCC diagnosis and its superiority to conventional tumor markers were shown. Therefore, serum hTERT mRNA is a novel and available marker for HCC diagnosis.
Nonapical and Cytoplasmic Expression of Interleukin-8, CXCR1, and CXCR2 Correlates with Cell Proliferation and Microvessel Density in Prostate Cancer
Authors: Murphy Catherine , McGurk Maryalice , Pettigrew Johanna , Santinelli Alfredo , Mazzucchelli Roberta , Johnston Patrick G. , Montironi Rodolfo , Waugh David J.J. 
Published: September 2005

Abstract
Purpose: We characterized interleukin-8 (IL-8) and IL-8 receptor expression (CXCR1 and CXCR2) in prostate cancer to address their significance to this disease.
Experimental Design: Immunohistochemistry was conducted on 40 cases of human prostate biopsy containing histologically normal and neoplastic tissue, excised from patients with locally confined or invasive androgen-dependent prostate cancer, and 10 cases of transurethral resection of the prostate material from patients with androgen-independent disease.
Results: Weak to moderate IL-8 expression was strictly localized to the apical membrane of normal prostate epithelium. In contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer. Each of IL-8, CXCR1, and CXCR2 were also increasingly localized to the cytoplasm of cancer cells in correlation with advancing stage of disease. Cytoplasmic expression (but not apical membrane expression) of IL-8 in Gleason pattern 3 and 4 cancer correlated with Ki-67 expression (R = 0.79; P &lt; 0.001), cyclin D1 expression (R = 0.79; P &lt; 0.001), and microvessel density (R = 0.81; P &lt; 0.001). In vitro studies on androgen-independent PC3 cells confirmed the mitogenic activity of IL-8, increasing the rate of cell proliferation through activation of both CXCR1 and CXCR2 receptors.
Conclusions: We propose that the concurrent increase in IL-8 and IL-8 receptor expression in human prostate cancer induces autocrine signaling that may be functionally significant in initiating and promoting the progression of prostate cancer by underpinning cell proliferation and angiogenesis.