bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Overexpression and Amplification of ABCF2 in Clear Cell Ovarian Adenocarcinomas by cDNA Microarray Analyses
Authors: Tsuda Hiroshi , Ito Yoichi M. , Ohashi Yasuo , Wong Kwong-Kwok , Hashiguchi Yasunori , Welch William R. , Berkowitz Ross S. , Birrer Michael J. , Mok Samuel C. 
Published: March 2006

Abstract
Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease.
Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance.
Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002).
Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.
Molecular Subtyping of Breast Cancer from Traditional Tumor Marker Profiles Using Parallel Clustering Methods
Authors: Ambrogi Federico , Biganzoli Elia , Querzoli Patrizia , Ferretti Stefano , Boracchi Patrizia , Alberti Saverio , Marubini Ettore , Nenci Italo 
Published: March 2006

Abstract
Purpose: Recent small-sized genomic studies on the identification of breast cancer bioprofiles have led to profoundly dishomogeneous results. Thus, we sought to identify distinct tumor profiles with possible clinical relevance based on clusters of immunohistochemical molecular markers measured on a large, single institution, case series.
Experimental Design: Tumor biological profiles were explored on 633 archival tissue samples analyzed by immunohistochemistry. Five validated markers were considered, i.e., estrogen receptors (ER), progesterone receptors (PR), Ki-67/MIB1 as a proliferation marker, HER2/NEU, and p53 in their original scale of measurement. The results obtained were analyzed by three different clustering algorithms. Four different indices were then used to select the different profiles (number of clusters).
Results: The best classification was obtained creating four clusters. Notably, three clusters were identified according to low, intermediate, and high ER/PR levels. A further subdivision in two biologically distinct subtypes was determined by the presence/absence of HER2/NEU and of p53. As expected, the cluster with high ER/PR levels was characterized by a much better prognosis and response to hormone therapy compared to that with the lowest ER/PR values. Notably, the cluster characterized by high HER2/NEU levels showed intermediate prognosis, but a rather poor response to hormone therapy.
Conclusions: Our results show the possibility of profiling breast cancers by means of traditional markers, and have novel clinical implications on the definition of the prognosis of cancer patients. These findings support the existence of a tumor subtype that responds poorly to hormone therapy, characterized by HER2/NEU overexpression.
Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene
Authors: Barclay Christie , Li Audrey W. , Geldenhuys Laurette , Baguma-Nibasheka Mark , Porter Geoffrey A. , Veugelers Paul J. , Murphy Paul R. , Casson Alan G. 
Published: March 2006

Abstract
Purpose: The basic fibroblast growth factor (FGF-2) gene is bidirectionally transcribed to generate overlapping sense and antisense (FGF-AS) mRNAs. FGF-AS has been implicated in the post-transcriptional regulation of FGF-2 expression. The aim of this study was to characterize FGF-2 and FGF-AS in esophageal cancer and to correlate their expression with clinicopathologic findings and outcome.
Experimental Design: Reverse transcription-PCR was used to study FGF-2 and FGF-AS mRNA expression (normalized to glyceraldehyde-3-phosphate dehydrogenase) in 48 esophageal cancers relative to matched histologically normal esophageal epithelia (internal control). We used Cox proportional hazards analysis to calculate hazard ratios for recurrence and survival of patients with underexpression relative to the overexpression of FGF-2 and/or FGF-AS.
Results: Overexpression of FGF-2 mRNA, by comparison with tumors underexpressing FGF-2, was associated with significantly increased risk for tumor recurrence (hazard ratio, 3.80; 95% confidence interval, 1.64-8.76) and reduced overall survival (hazard ratio, 2.11; 95% confidence interval, 1.0-4.58). When the effects of FGF-2 and FGF-AS were considered simultaneously, the association of FGF-2 mRNA overexpression with recurrence and mortality was even more pronounced, whereas FGF-AS mRNA overexpression was associated with reduced risk for recurrence and improved survival.
Conclusions: Overexpression of FGF-2 mRNA is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer and that these risks are reduced in tumors coexpressing the FGF-AS mRNA. These data support the hypothesis that FGF-AS is a novel tumor suppressor that modulates the effect of FGF-2 expression and may have potential clinical application to the development of novel therapeutic strategies.
Phase 1 Study of Weekly Polyethylene Glycol-Camptothecin in Patients with Advanced Solid Tumors and Lymphomas
Authors: Posey James A. , Saif M. Wasif , Carlisle Ronda , Goetz Andrew , Rizzo Jinee , Stevenson Suzanne , Rudoltz Marc S. , Kwiatek Joseph , Simmons Paul , Rowinsky Eric K. , Takimoto Chris H. , Tolcher Anthony W. 
Published: March 2006

Abstract
Purpose: To determine the maximal tolerated dose and dose-limiting toxicities (DLT) of pegamotecan (polyethylene glycol-camptothecin) in patients with advanced malignancies when administered in cycles of once weekly for 3 of 4 weeks.
Experimental Design: Eligible patients had advanced solid tumors that failed to respond to standard therapy or for which no standard therapy was available, including also the following criteria: measurable disease, Eastern Cooperative Oncology Group performance status of ≤2, and acceptable organ function. Pegamotecan was administered as a 60-minute infusion, with successive patient cohorts receiving escalating doses from 800 to 4,300 mg/m2. The primary end point was to determine the maximal tolerated dose. Other end points were toxicity, pharmacokinetics, pharmacodynamics, and efficacy. Pharmacokinetic analysis measured free camptothecin. Pharmacodynamic analysis correlated drug effects with pegamotecan dose and pharmacokinetic variables.
Results: Twenty-seven patients were enrolled. The maximal tolerated dose was 3,240 mg/m2. Grade 4 neutropenia, the DLT, was noted in two of four patients treated at 4,300 mg/m2. Other grade 3 and 4 toxicities were anemia, thrombocytopenia, fatigue, prolonged partial thromboplastin time, hemorrhagic cystitis, dysuria, and urinary frequency. Pharmacokinetic analysis showed the apparent terminal elimination half-life to be 46 ± 12.8 hours. Pharmacodynamic analysis showed that hematuria occurred in 8 of 15 patients with an area under the curve extrapolated to infinity (AUC0-∞) &gt; 20 ng h/mL and 0 of 10 patients with an AUC0-∞ ≤ 20 ng h/mL. Unconfirmed partial responses were observed in two patients, one with metastatic small bowel adenocarcinoma and the other with metastatic esophageal cancer.
Conclusions: The maximal tolerated dose of pegamotecan when administered weekly for 3 of 4 weeks is 3,240 mg/m2. The DLT was neutropenia. Among nonhematologic toxicities, the incidence of gastrointestinal toxicity was low, but genitourinary toxicity seems to occur in the same effective dose range as noted with native camptothecin in earlier trials (27-43 mg/m2). The observed antitumor activity suggests that pegamotecan has single-agent activity and merits further investigation in phase 2 studies.
A Phase I and Pharmacokinetic Study of Paclitaxel Poliglumex (XYOTAX), Investigating Both 3-Weekly and 2-Weekly Schedules
Authors: Boddy Alan V. , Plummer E. Ruth , Todd Radha , Sludden Julieann , Griffin Melanie , Robson Lesley , Cassidy James , Bissett Donald , Bernareggi Alberto , Verrill Mark W. , Calvert A. Hilary 
Published: March 2006

Abstract
Purpose: To determine the safety, maximum tolerated dose, pharmacokinetics, and toxicities associated with administration of paclitaxel poliglumex (PPX, XYOTAX, Cell Therapeutics, Inc., Bresso, Italy) given on either 3-weekly or 2-weekly schedule.
Experimental Design: Nineteen patients were investigated on the 3-weekly phase Ia study and 11 patients on the 2-weekly phase Ib study. Dose escalation starting with 100% increments and one patient per dose level was modulated in accordance with the observed toxicities. Conjugated and unconjugated paclitaxel were measured in plasma.
Results: Dose-limiting toxicity of neutropenia was encountered at 266 mg/m2 (paclitaxel equivalents) in phase Ia and the maximum tolerated dose was 233 mg/m2. Neuropathy was dose-limiting in phase Ib with a maximum tolerated dose of 177 mg/m2. Pharmacokinetic investigations indicated a prolonged half-life of &gt;100 hours for conjugated taxanes. Plasma concentrations of unconjugated paclitaxel were similar to those following administration of an equivalent dose of Taxol. Two partial responses were observed, one in a patient with mesothelioma at 177 mg/m2 in phase Ia and one in a patient with gastric carcinoma at 175 mg/m2 in phase Ib.
Conclusion: PPX is a water-soluble paclitaxel-polymer conjugate with a prolonged half-life and limited volume of distribution. Dose-limiting toxicities were neutropenia and neuropathy. PPX showed activity in this patient population.
Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy
Authors: Yoshiura Kenta , Nakaoka Takashi , Nishishita Toshihide , Sato Katsuaki , Yamamoto Akifumi , Shimada Shinji , Saida Toshiaki , Kawakami Yutaka , Takahashi Tsuneo A. , Fukuda Hiroyuki , Imajoh-Ohmi Shinobu , Oyaizu Naoki , Yamashita Naohide 
Published: March 2006

AbstractTumor-associated antigens are promising candidates as target molecules for immunotherapy and a wide variety of tumor-associated antigens have been discovered through the presence of serum antibodies in cancer patients. We previously conducted dendritic cell therapy on 10 malignant melanoma patients and shrinkage or disappearance of metastatic tumors with massive necrosis occurred in two patients. In this study, we found a 29-kDa protein against which antibody was elicited by dendritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by two-dimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium–associated antigen in melanoma and other cancers, and elicitation of serum anti–CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction.
Heat-Induced Up-Regulation of NAD(P)H:Quinone Oxidoreductase Potentiates Anticancer Effects of β-Lapachone
Authors: Park Heon Joo , Choi Eun Kyung , Choi Jihyung , Ahn Ki-Jung , Kim Eun Jung , Ji In-Mi , Kook Yeon Hee , Ahn Seung-Do , Williams Brent , Griffin Robert , Boothman David A. , Lee Chung K. , Song Chang W. 
Published: March 2006

Abstract
Purpose: The purpose of the present study was to evaluate the efficacy of mild hyperthermia to potentiate the anticancer effects of β-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) by up-regulating NAD(P)H:quinone oxidoreductase (NQO1) in cancer cells.
Experimental Design: Effects of β-lapachone alone or in combination with mild heating on the clonogenic survival of FSaII fibrosarcoma cells of C3H mice and A549 human lung tumor cells in vitro was determined. Effects of heating on the NQO1 level in the cancer cells in vitro were assessed using Western blot analysis for NQO1 expression, biochemical determination of NQO1 activity, and immunofluorescence microscopy for NQO1 expression. Growth of FSaII tumors in the hind legs of C3H mice was determined after treating the host mice with i.p. injection of 45 mg/kg β-lapachone followed by heating the tumors at 42°C for 1 hour every other day for four times.
Results: Incubation of FSaII tumor cells and A549 tumor cells with β-lapachone at 37°C reduced clonogenic survival of the cells in dose-dependent and incubation time–dependent manner. NQO1 level in the cancer cells in vitro increased within 1 hour after heating at 42°C for 1 hour and remained elevated for &gt;72 hours. The clonogenic cell death caused by β-lapachone increased in parallel with the increase in NQO1 levels in heated cells. Heating FSaII tumors in the legs of C3H mice enhanced the effect of i.p.-injected β-lapachone in suppressing tumor growth.
Conclusion: We observed for the first time that mild heat shock up-regulates NQO1 in tumor cells. The heat-induced up-regulation of NQO1 enhanced the anticancer effects of β-lapachone in vitro and in vivo.
Histone Deacetylase Inhibitor FK228 Activates Tumor Suppressor Prdx1 with Apoptosis Induction in Esophageal Cancer Cells
Authors: Hoshino Isamu , Matsubara Hisahiro , Hanari Naoyuki , Mori Mikito , Nishimori Takanori , Yoneyama Yasuo , Akutsu Yasunori , Sakata Haruhito , Matsushita Kazuyuki , Seki Naohiko , Ochiai Takenori 
Published: March 2006

Abstract
Purpose: The histone deacetylase inhibitor FK228 shows strong activity as a potent antitumor drug but its precise mechanism is still obscure. The purpose of this study is to reveal the effect of FK228 on gene expression in the cell and to determine the mechanism of the antitumor activity of FK228 for further clinical applications.
Experimental Design and Results: Microarray analysis was applied to verify the gene expression profiles of 4,608 genes after FK228 treatment using human esophageal squamous cell cancer cell lines T.Tn and TE2. Among them, peroxiredoxin 1 (Prdx1), a member of the peroxiredoxin family of antioxidant enzymes having cell growth suppression activity, as well as p21WAF1, were significantly activated by FK288. In addition, FK228 strongly inhibited the cell growth of T.Tn and TE2 by the induction of apoptosis. Further, chromatin immunoprecipitation analysis revealed that FK228 induced the accumulation of acetylated histones H3 and H4 in Prdx1 promoter, including the Sp1-binding site. In mouse xenograft models of T.Tn and TE2 cells, FK228 injection resulted in significant tumor regression as well as activated Prdx1 expression in tumor tissues. Prdx1 suppression by RNA interference hindered the antitumor effect of FK228.
Conclusion: Our results indicate that the antitumor effect of FK228 in esophageal cancer cells is shown at least in part through Prdx1 activation by modulating acetylation of histones in the promoter, resulting in tumor growth inhibition with apoptosis induction.
Expression of HER2 and the Coamplified Genes GRB7 and MLN64 in Human Breast Cancer: Quantitative Real-time Reverse Transcription-PCR as a Diagnostic Alternative to Immunohistochemistry and Fluorescence In situ Hybridization
Authors: Vinatzer Ursula , Dampier Brigitta , Streubel Berthold , Pacher Margit , Seewald Michael J. , Stratowa Christian , Kaserer Klaus , Schreiber Martin 
Published: March 2006

Abstract
Purpose: Accurate testing of HER2 is centrally important for breast cancer therapy and prognosis. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are current standard testing methods. As a potential alternative for assessment of HER2, we explored quantitative real-time reverse transcription-PCR (RT-PCR), a fast and inexpensive method yielding quantitative results insensitive to interobserver variability and amenable to standardized scoring.
Experimental Design: We assessed HER2 status at the DNA, mRNA, and protein levels with FISH, quantitative RT-PCR, and IHC in 136 tumor samples from 85 breast cancer patients. Expression of GRB7, MLN64, and p21, genes coregulated with HER2, was also quantified with quantitative RT-PCR and correlated with the overall survival (OS) and disease-free survival (DFS) individually and in combination with HER2.
Results: Twenty-nine percent and 19% of the patients scored HER2 positive with IHC and quantitative RT-PCR, respectively. In 18 of 19 cases, HER2 statuses in tumors and lymph node metastases were identical. HER2 status significantly correlated with DFS when determined by IHC (P &lt; 0.01), quantitative RT-PCR (P &lt; 0.003), but not with FISH (P = 0.09). The combination of HER2 with MLN64, but not with GRB7 or p21, enhanced the prognostic power for the DFS (P &lt; 0.00005) and OS (P &lt; 0.0008).
Conclusions: Quantitative RT-PCR seems to be clinically as useful in the assessment of HER2 status as IHC and FISH, yielding comparable correlations of HER2 status with the OS and DFS. Thus, quantitative RT-PCR analysis of HER2 or HER2 plus MLN64 is a promising complement or alternative to current methods for HER2 testing, particularly in laboratories lacking FISH or IHC technology.
The Relationship between Global Methylation Level, Loss of Heterozygosity, and Microsatellite Instability in Sporadic Colorectal Cancer
Authors: Matsuzaki Koji , Deng Guoren , Tanaka Hirofumi , Kakar Sanjay , Miura Soichiro , Kim Young S. 
Published: March 2006

Abstract
Purpose: The relationship between global hypomethylation, chromosomal instability (CIN), and microsatellite instability (MSI) remains unclear in colorectal cancer. The aim of this study was to investigate the relationship between global methylation status, loss of heterozygosity (LOH), and MSI in sporadic colorectal cancer.
Experimental Design: We determined global methylation levels in 80 sporadic colorectal cancers, 51 adjacent normal tissues, and 20 normal tissues using the long interspersed nucleotide elements–combined bisulfite restriction analysis method. We also analyzed 80 colorectal cancers for MSI status and LOH at chromosomes 5q21, 8p12-22, 17p13, and 18q21.
Results: We identified 14 cases of MSI (17.5%) and 58 cases of LOH (72.5%). LOH was observed more frequently in microsatellite stable (MSS) cancers than in MSI cancers at all loci. Colorectal cancers showed significantly lower global methylation levels than did normal tissues (41.0 ± 9.7% versus 54.3 ± 6.5%; P &lt; 0.001). MSS cancers showed significantly lower global methylation levels when compared with MSI cancers (39.5 ± 9.4% versus 48.2 ± 8.2%; P = 0.003). Tumors with global hypomethylation (with ≤40% of methylation levels) had a significantly increased number of chromosomal loci with LOH than did tumors without global hypomethylation (1.9 versus 0.9; P &lt; 0.001); 11 tumors (13.9%) lacked both MSI and LOH. This subgroup had significantly higher global methylation levels (46.8 ± 8.7%) than did MSS cancers with LOH (38.0 ± 9.0%; P = 0.006).
Conclusions: These data showed a significant association between global hypomethylation and chromosomal instability in sporadic colorectal cancer. This suggests that global hypomethylation plays an important role in inducing genomic instability in colorectal carcinogenesis.
MHC Class I–Related Chain A Conjugated to Antitumor Antibodies Can Sensitize Tumor Cells to Specific Lysis by Natural Killer Cells
Authors: Germain Claire , Larbouret Christel , Cesson Valérie , Donda Alena , Held Werner , Mach Jean-Pierre , Pèlegrin André , Robert Bruno 
Published: March 2006

Abstract
Purpose: As a first step for the development of a new cancer immunotherapy strategy, we evaluated whether antibody-mediated coating by MHC class I–related chain A (MICA) could sensitize tumor cells to lysis by natural killer (NK) cells.
Experimental Design: Recombinant MICA (rMICA) was chemically conjugated to Fab′ fragments from monoclonal antibodies specific for tumor-associated antigens, such as carcinoembryonic antigen, HER2, or CD20.
Results: Flow cytometry analysis showed an efficient coating of MICA-negative human cancer cell lines with the Fab-rMICA conjugates. This was strictly dependent on the expression of the appropriate tumor-associated antigens in the target cells. Importantly, preincubation of the tumor cells with the appropriate Fab-rMICA conjugate resulted in NK cell–mediated tumor cell lysis. Antibody blocking of the NKG2D receptor in NK cells prevented conjugate-mediated tumor cell lysis.
Conclusions: These results open the way to the development of immunotherapy strategies based on antibody-mediated targeting of MICA.