bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Vascular Endothelial Growth Factor (VEGF)-A Causes a Paradoxical Increase in Tumor Blood Flow and Up-Regulation of VEGF-D
Authors: Moffat Bradford A. , Chen Mark , Kariaapper Muhammed S.T. , Hamstra Daniel A. , Hall Daniel E. , Stojanovska Jadranka , Johnson Timothy D. , Blaivas Mila , Kumar Mahesh , Chenevert Thomas L. , Rehemtulla Alnawaz , Ross Brian D. 
Published: March 2006

Abstract
Purpose: Vascular endothelial growth factor (VEGF)-A is an important mediator of angiogenesis in almost all solid tumors. The aim of this study was to evaluate the effect of VEGF-A expression on tumor growth, perfusion, and chemotherapeutic efficacy in orthotopic 9L gliosarcomas.
Experimental Design: Stable 9L cell lines underexpressing and overexpressing VEGF-A were generated. Anatomic, susceptibility contrast, and continuous arterial spin-labeling magnetic resonance imaging were used to quantify the volume, blood volume, and blood flow of tumors orthotopically grown from these and wild-type 9L cells. Histologic, immunohistochemical, and quantitative reverse transcription-PCR analyses were also done on excised tumors. Finally, the effects of carmustine chemotherapy were also evaluated.
Results: Orthotopic tumors underexpressing VEGF-A had slower growth rates (increased median survival), greater blood flow, vessel density, and VEGF-D expression, but no statistical difference in blood volume and chemotherapeutic sensitivity, compared with tumors with wild-type levels of VEGF-A. Tumors overexpressing VEGF-A had faster growth rates, greater blood volume, vessel density, and blood flow but no statistical difference in VEGF-D expression and chemotherapeutic sensitivity compared with wild-type VEGF-A-expressing tumors.
Conclusion: Blood volume and blood flow are independent and different biomarkers of tumor perfusion. Therefore, both should be measured when characterizing the efficacy of antiangiogenic therapies. Underexpression of VEGF-A does not result in complete inhibition of angiogenesis. Moreover, these tumors have a different perfusion phenotype, suggesting that angiogenesis is mediated by an alternative pathway. The results indicate that VEGF-D is a plausible alternative mediator of this angiogenesis.
Comparison of Two Cancer Vaccines Targeting Tyrosinase: Plasmid DNA and Recombinant Alphavirus Replicon Particles
Authors: Goldberg Stacie M. , Bartido Shirley M. , Gardner Jason P. , Guevara-Patiño José A. , Montgomery Stephanie C. , Perales Miguel-Angel , Maughan Maureen F. , Dempsey JoAnn , Donovan Gerald P. , Olson William C. , Houghton Alan N. , Wolchok Jedd D. 
Published: March 2006

AbstractPurpose: Immunization of mice with xenogeneic DNA encoding human tyrosinase-related proteins 1 and 2 breaks tolerance to these self-antigens and leads to tumor rejection. Viral vectors used alone or in heterologous DNA prime/viral boost combinations have shown improved responses to certain infectious diseases. The purpose of this study was to compare viral and plasmid DNA in combination vaccination strategies in the context of a tumor antigen.Experimental Design: Using tyrosinase as a prototypical differentiation antigen, we determined the optimal regimen for immunization with plasmid DNA. Then, using propagation-incompetent alphavirus vectors (virus-like replicon particles, VRP) encoding tyrosinase, we tested different combinations of priming with DNA or VRP followed by boosting with VRP. We subsequently followed antibody production, T-cell response, and tumor rejection.Results: T-cell responses to newly identified mouse tyrosinase epitopes were generated in mice immunized with plasmid DNA encoding human (xenogeneic) tyrosinase. In contrast, when VRP encoding either mouse or human tyrosinase were used as single agents, antibody and T-cell responses and a significant delay in tumor growth in vivo were observed. Similarly, a heterologous vaccine regimen using DNA prime and VRP boost showed a markedly stronger response than DNA vaccination alone.Conclusions: Alphavirus replicon particle vectors encoding the melanoma antigen tyrosinase (self or xenogeneic) induce immune responses and tumor protection when administered either alone or in the heterologous DNA prime/VRP boost approaches that are superior to the use of plasmid DNA alone.
Correlations between Serum Monocyte Chemotactic Protein-1 Levels, Clinical Prognostic Factors, and HER-2/neu Vaccine-Related Immunity in Breast Cancer Patients
Authors: Dehqanzada Zia A. , Storrer Catherine E. , Hueman Matthew T. , Foley Rebecca J. , Harris Katie A. , Jama Yusuf H. , Kao Tzu-Cheg , Shriver Craig D. , Ponniah Sathibalan , Peoples George E. 
Published: March 2006

Abstract
Purpose: We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast cancer patients in relationship to their clinicopathologic variables and immune response to a /neu E75 vaccine.
Experimental Design: We measured MCP-1 levels in 32 /neu+ breast cancer patients before and after vaccination with a /neu E75 peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical prognostic variables were collected. Vaccine-specific immunologic responses were monitored.
Results: Serum MCP-1 levels &gt;250 pg/mL (MCP-high) correlated with favorable prognostic variables. MCP-high patients compared with MCP-low (&lt;250 pg/mL) patients showed statistically significant later onset of disease, earlier stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high patients had increased levels of preexisting immunity when compared with MCP-low patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher inducible levels of MCP-1 compared with MCP-high patients (median increase, 41% versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with &gt;50% increase in MCP-1 levels (response-high) had worse clinical prognostic variables compared with patients with &lt;50% increase (response-low). Response-high patients had statistically significant more poorly differentiated tumors, later stage of disease, and higher percentage of large tumors. Patients with &gt;30% postvaccination MCP-1 increase also showed significant increases in E75-specific CD8+ T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination.
Conclusions: High serum MCP-1 levels in breast cancer patients correlate with favorable prognostic variables and increased preexisting /neu immunity. E75 vaccination induces the largest MCP-1 response in patients with unfavorable clinicopathologic variables. Therefore, low serum MCP-1 levels may identify patients with worse prognosis and those most likely to benefit from this vaccination.
Expression of Interleukin-9 in Nasal Natural Killer/T-Cell Lymphoma Cell Lines and Patients
Authors: Nagato Toshihiro , Kobayashi Hiroya , Kishibe Kan , Takahara Miki , Ogino Takeshi , Ishii Hideyuki , Oikawa Kensuke , Aoki Naoko , Sato Keisuke , Kimura Shoji , Shimizu Norio , Tateno Masatoshi , Harabuchi Yasuaki 
Published: March 2006

Abstract
Purpose: Nasal natural killer (NK)/T-cell lymphoma is associated with EBV and has distinct clinical and histologic features. However, little is known about its genetic features. In this study, we examined the genes expressed by SNK-6 and SNT-8 cells, which were established from nasal NK/T-cell lymphomas, and found that interleukin (IL)-9 was specifically expressed in these two cell lines.
Experimental Design: cDNA array was used to examine the genes expressed by SNK-6 and SNT-8 cells. Expression of IL-9 and IL-9 receptor was investigated by reverse transcription-PCR, ELISA, and flow cytometry. Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunohistologic staining and ELISA were used to examine IL-9 expression in biopsies and sera from patients, respectively.
Results: In cDNA array, expression of IL-9 mRNA was much higher in SNK-6 and SNT-8 cells than in NK-92 cells from non-nasal NK-cell lymphoma and peripheral blood mononuclear cells from healthy volunteers. Furthermore, IL-9 was specifically expressed by SNK-6 and SNT-8 cells but not by other NK-cell, NK-like T-cell, and T-cell lymphoma/leukemia cell lines. IL-9 receptor was also expressed on the surfaces of SNK-6 and SNT-8 cells. An IL-9-neutralizing antibody inhibited the growth of these two cell lines, whereas recombinant human IL-9 enhanced their growth. Most significantly, IL-9 was present in biopsies and sera from patients with this lymphoma.
Conclusions: These results suggest that IL-9 plays an important role in nasal NK/T-cell lymphoma possibly via an autocrine mechanism.
Reduced Expression ofCAMTA1Correlates with Adverse Outcome in Neuroblastoma Patients
Authors: Henrich Kai-Oliver , Fischer Matthias , Mertens Daniel , Benner Axel , Wiedemeyer Ruprecht , Brors Benedikt , Oberthuer André , Berthold Frank , Wei Jun Stephen , Khan Javed , Schwab Manfred , Westermann Frank 
Published: March 2006

AbstractPurpose: A distal portion of 1p is frequently deleted in human neuroblastomas, and it is generally assumed that this region harbors at least one gene relevant for neuroblastoma development. A 1p36.3 commonly deleted region, bordered by D1S2731 and D1S214 has been defined. The present study surveys whether expression of genes mapping to this region is associated with tumor behavior.Experimental Design: Candidate genes localized within the deleted region were identified by sequence data analysis. Their expression was assessed in a cohort of 49 primary neuroblastomas using cDNA microarray analysis. Gene expression patterns associated with known prognostic markers and patient outcome were further evaluated by quantitative real-time reverse transcription-PCR in a cohort of 102 neuroblastomas.Results: The commonly deleted region spans 261 kb and encompasses two genes, FLJ10737 and CAMTA1. We found no evidence for an association of FLJ10737 expression with established prognostic variables or outcome. In contrast, low CAMTA1 expression characterized tumors with 1p deletion, MYCN amplification, and advanced tumor stages 3 and 4. Moreover, low CAMTA1 expression was significantly associated with poor outcome (P &lt; 0.001). In multivariate analysis of event-free survival, the prognostic information of low CAMTA1 expression was independent of 1p status, MYCN status, tumor stage, and age of the patient at diagnosis (hazard ratio, 3.52; 95% confidence interval, 1.21-10.28; P = 0.02).Conclusions: Our data suggest that assessment of CAMTA1 expression may improve the prognostic models for neuroblastoma and that it will be important to define the biological function of CAMTA1 in this disease.
Inclusion of Vasculature-Related Variables in the Dukes Staging System of Colon Cancer
Authors: Koukourakis Michael I. , Giatromanolaki Alexandra , Sivridis Efthimios , Gatter Kevin C. , Harris Adrian L. ,   for Tumour and Angiogenesis Research Group
Published: March 2006

Abstract
Purpose: The Dukes stage is used to stratify colorectal cancer patients into groups of different prognosis and need of adjuvant radiotherapy and chemotherapy. However, ∼80% of patients with Dukes stage C colorectal cancer receive cytotoxic therapy without any expected benefit, for such patients would either not relapse without adjuvant therapy or they would inevitably do so because of tumor resistance to the available regimens. On the other hand, as 20% of Dukes stage B patients would relapse after surgery, adjuvant therapy could improve their survival. Improvement of the Dukes stage predictive accuracy is necessary to better assign patients for adjuvant therapies, especially nowadays when antiangiogenic agents are being incorporated in the clinical practice.
Patients and Methods: In this study, we examined the prognostic role of Dukes staging system in parallel with three vasculature-related variables (vascular invasion, tumor angiogenic activity, and vascular survival ability) in a series of 130 stage B/C patients with colorectal cancer treated with surgery alone (without adjuvant radiotherapy or chemotherapy).
Results: Inclusion of vasculature-related variables in the Dukes staging system significantly improved the prognostic categorization of patients, identifying subgroups of B-stage and C-stage patients with an up to 40% and 60% 5-year survival difference, respectively.
Conclusions: Preliminary results show that the prognostic value of Dukes staging system is significantly improved after taking into account vasculature-related variables, which may be useful in stratifying patients for adjuvant therapies, highlighting also subgroups that may benefit the most from antiangiogenic agents.
Adoptive transfer of allogeneic cytotoxic T lymphocytes equipped with a HLA-A2 restricted MART-1 T-cell receptor: a phase I trial in metastatic melanoma.
Authors: Duval Lone , Schmidt Henrik , Kaltoft Keld , Fode Kirsten , Jensen Jens Jorgen , Sorensen Steen Mellerup , Nishimura Michael I , von der Maase Hans 
Published: March 2006

Abstract
PURPOSE: We did a phase I dose-escalation trial to evaluate the feasibility and safety of intratumoral injections of C Cure 709, an allogeneic, continuous CTL cell line that, restricted by HLA-A2, recognizes MART-1-positive tumor cells through transduction with a T-cell receptor encoding gene. EXPERIMENTAL DESIGN: Cells were administered intratumorally in four dose levels ranging from 10(8) to 10(9) cells/d on days 1, 4, 7, 10, 14, and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1-positive tumor cells, and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without progressive disease were offered up to three treatment cycles. RESULTS: Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709. Toxicity was minor to moderate and most common injection site reactions were fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient obtained a partial response, encompassing both metastases used and not used for intratumoral injections. Remaining patients did not achieve an overall response. In addition, we observed local regression of metastases used for injection in two patients and of metastases not used for injection in one patient. CONCLUSION: Intratumoral injections of C Cure 709 are feasible, safe, and capable of inducing tumor regression. Further investigation in a phase II setting is warranted.
Expression of EphA2 and Ephrin A-1 in Carcinoma of the Urinary Bladder
Authors: Abraham Shaji , Knapp Deborah W. , Cheng Liang , Snyder Paul W. , Mittal Suresh K. , Bangari Dinesh S. , Kinch Michael , Wu Lan , Dhariwal Jay , Mohammed Sulma I. 
Published: March 2006

Abstract
Purpose: The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer.
Experimental Design: EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system.
Results: Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P &lt; 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (Ta-T4). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between Ta stage and T1-T2 (P &lt; 0.04) and Ta and T3-T4 stages (P &lt; 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells.
Conclusion: EphA2 may serve as a novel target for bladder cancer therapy.
ZAP-70 Expression in Normal Pro/Pre B Cells, Mature B Cells, and in B-Cell Acute Lymphoblastic Leukemia
Authors: Crespo Marta , Villamor Neus , Giné Eva , Muntañola Ana , Colomer Dolors , Marafioti Teresa , Jones Margaret , Camós Mireia , Campo Elias , Montserrat Emili , Bosch Francesc 
Published: March 2006

Abstract
Purpose: The ZAP-70 gene is normally expressed in T and natural killer cells, where it is required for the T-cell receptor (TCR) signaling. More recently, it has been described that ZAP-70 contributes to the B-cell development at early stages of B-cell differentiation in mice. The purpose was to investigate the presence of ZAP-70 in normal pro/pre B cells and mature B cells and in tumoral cells from B-acute lymphoblastic leukemias (B-ALL).
Experimental Design: ZAP-70 expression was ascertained by flow cytometry, immunofluorescence, Western blot, and quantitative reverse transcription-PCR. Analysis of ZAP-70 and other signaling proteins of the pre-TCR/TCR was done by Western blot.
Results: ZAP-70 was expressed in pro/pre B cells but not in normal mature B cells derived from bone marrow, peripheral blood, or tonsil. Among tumoral cells, ZAP-70 was expressed in 56% of B-ALLs with pro/pre B-cell phenotype and in 4 of 6 Burkitt/ALL lymphomas. In B-ALL cells, expression of CD38 protein correlated with ZAP-70 expression (P = 0.05). Mutational analysis of the ZAP-70 gene revealed the absence of mutations in cases lacking ZAP-70 expression. Moreover, other elements of the pre-TCR/TCR signaling pathway, like LAT and Lck, were also found in B-ALL cells.
Conclusions: Among normal B-cell subsets, ZAP-70 was found expressed in normal pro/pre B cells but not in a significant proportion of normal B cells with mature phenotype. Moreover, the presence of ZAP-70 in B-ALLs probably reflects their cellular origin. The lack of ZAP-70 expression in normal mature B cells suggests that its expression in mature-derived neoplasms with different cellular origin, such as Burkitt's lymphoma and chronic lymphocytic leukemia, might be due to an aberrant phenomenon.
Plasma Levels of Trefoil Factors are Increased in Patients with Advanced Prostate Cancer
Authors: Vestergaard Else Marie , Borre Michael , Poulsen Steen Seier , Nexø Ebba , Tørring Niels 
Published: March 2006

Abstract
Purpose: Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer.
Experimental Design: In 79 patients with prostate cancer, 23 patients with benign prostatic hyperplasia, and 44 healthy individuals plasma TFF1, TFF2, and TFF3 were determined with ELISAs and compared with clinical stage and prostate-specific antigen (PSA) values. Plasma levels of TFF were compared with the immunohistochemical expression of TFF and chromogranin A in 30 prostate cancer tissue samples.
Results: Patients with advanced prostate cancer had significantly higher plasma concentrations of TFF1, TFF2, and TFF3 (P &lt; 0.01) compared with patients with localized disease. Using a cutoff of 200 pmol/L, the sensitivity and specificity of plasma TFF3 in differentiating between patients with localized and advanced disease was 74% (59-85%) and 81% (66-91%). Plasma levels of TFF3 were highest in patients with bone metastases (P = 0.008). Patients with serum PSA &gt;10 μg/L had significantly higher plasma TFF3 values than patients with serum PSA &lt;10 μg/L (P = 0.03) and TFF3 levels were higher in patients with Gleason sums of ≥7 (P = 0.02). Expression of TFF1 and TFF3 determined by immunohistochemistry was increased in patients with prostate cancer but did not correlate with plasma trefoil factor values.
Conclusions: Plasma levels of trefoil factors are increased in patients with advanced prostate cancer. Prospective studies are needed to confirm the predictive utility of trefoil factors in prostate cancer.
Reduced Toxicity and Superior Therapeutic Activity of a Mitomycin C Lipid-Based Prodrug Incorporated in Pegylated Liposomes
Authors: Gabizon Alberto A. , Tzemach Dinah , Horowitz Aviva T. , Shmeeda Hilary , Yeh Jerry , Zalipsky Samuel 
Published: March 2006

Abstract
Purpose: A lipid-based prodrug of mitomycin C [MMC; 2,3-(distearoyloxy)propane-1-dithio-4′-benzyloxycarbonyl-MMC] was designed for liposome formulation. The purpose of this study was to examine the in vitro cytotoxicity, pharmacokinetics, in vivo toxicity, and in vivo antitumor activity of this new lipid-based prodrug formulated in polyethylene glycol–coated (pegylated) liposomes.
Experimental Design: MMC was released from the MMC lipid–based prodrug (MLP) by thiolytic-induced cleavage with a variety of thiol-containing reducing agents. MLP was incorporated with nearly 100% efficiency in cholesterol-free pegylated liposomes with hydrogenated phosphatidylcholine as the main component and a mean vesicle size of ∼90 nm. This formulation was used for in vitro and in vivo tests in rodents.
Results: In vitro, the cytotoxic activity of pegylated liposomal MLP (PL-MLP) was drastically reduced compared with free MMC. However, in the presence of reducing agents, such as cysteine or N-acetyl-cysteine, its activity increased to nearly comparable levels to those of free MMC. Intravenous administration of PL-MLP in rats resulted in a slow clearance indicating stable prodrug retention in liposomes and long circulation time kinetics, with a pharmacokinetic profile substantially different from that of free MMC. In vivo, PL-MLP was ∼3-fold less toxic than free MMC. The therapeutic index and absolute antitumor efficacy of PL-MLP were superior to that of free MMC in the three tumor models tested. In addition, PL-MLP was significantly more active than a formulation of doxorubicin in pegylated liposomes (DOXIL) in the M109R tumor model, a mouse tumor cell line with a multidrug-resistant phenotype.
Conclusions: Delivery of MLP in pegylated liposomes is a potential approach for effective treatment of multidrug-resistant tumors while significantly buffering the toxicity of MMC.