bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Significance of Vascular Endothelial Growth Factor Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis
Authors: Kyzas Panayiotis A. , Cunha Isabella W. , Ioannidis John P.A. 
Published: September 2005

Abstract
Purpose: Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis. Various studies examining the relationship between VEGF protein overexpression with the clinical outcome in patients with head and neck squamous cell carcinoma have yielded inconclusive results.
Experimental Design: We conducted a meta-analysis of 12 studies (n = 1.002 patients) that evaluated the correlation between VEGF (detected by immunohistochemistry) and 2-year overall survival. The relation between VEGF and lymph node involvement (11 studies, n = 722) was also examined. Data were synthesized with random effect and fixed effect risk ratios.
Results: The estimated risk of death in 2 years was 1.88-fold higher in the VEGF-positive patients [95% confidence interval, 1.43-2.45; P &lt; 0.001 random effect calculations]. Between-study heterogeneity was nonsignificant (P = 0.15) but larger studies tended to provide more conservative estimates (P = 0.097). VEGF overexpression was not significantly associated with the presence of lymph node metastasis (risk ratio, 1.20; 95% confidence interval, 0.97-1.49; P = 0.087) and there was significant between-study heterogeneity (P = 0.08).
Conclusions: Although some modest bias cannot be excluded, VEGF positivity seems to be associated with worse overall survival in patients with head and neck squamous cell carcinoma.
B-Cell Lymphomas Differ in their Responsiveness to CpG Oligodeoxynucleotides
Authors: Jahrsdorfer Bernd , Mühlenhoff Lars , Blackwell Sue E. , Wagner Moritz , Poeck Hendrik , Hartmann Evelyn , Jox Ralf , Giese Thomas , Emmerich Bertold , Endres Stefan , Weiner George J. , Hartmann Gunther 
Published: September 2005

AbstractHuman B cells detect CpG motifs within microbial DNA via TLR9. Synthetic CpG oligodeoxynucleotides are currently being tested in clinical trials for the therapy of different types of B cell non-Hodgkin's lymphoma. However, there is only limited information on the CpG oligodeoxynucleotide sensitivity of primary malignant B cells of different non-Hodgkin's lymphoma entities. Here we found that most B-cell malignancies except plasmacytoma respond to CpG oligodeoxynucleotides by up-regulating expression of costimulatory and antigen-presenting molecules, by increasing expression of CD20, and by proliferation. In an in vitro analysis of 41 individual patient-derived primary tumor samples, B-cell chronic lymphocytic leukemia (B-CLL) and marginal zone lymphoma showed the strongest activation upon stimulation with CpG oligodeoxynucleotides. Small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and large cell lymphoma showed an intermediate response. Consistent with CpG oligodeoxynucleotides sensitivity, TLR9 mRNA was present in B-CLL but absent in plasmacytoma. Although CpG oligodeoxynucleotides induced proliferation in all CpG oligodeoxynucleotide–sensitive types of B-cell malignancies, proliferation was weaker than in normal B cells and at least for B-CLL was followed by increased apoptosis. In conclusion, B-cell malignancies show significant differences in their responsiveness to CpG oligodeoxynucleotides. Focusing clinical studies on patients with highly CpG oligodeoxynucleotide–sensitive B-cell malignancies may improve the clinical outcome of such trials.
Prognostic Validation of the International Classification of Immunoglobulin M Gammopathies: A Survival Advantage for Patients with Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance?
Authors: Gobbi Paolo G. , Baldini Luca , Broglia Chiara , Goldaniga Maria , Comelli Mario , Morel Pierre , Morra Enrica , Cortelazzo Sergio , Bettini Roberto , Merlini Giampaolo 
Published: September 2005

Abstract
Purpose: To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002).
Experimental Design: A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenström's macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and sex and over an equivalent period of follow-up (standardized mortality ratio, SMR).
Results: IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations.
Conclusions: Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.
Noninvasive Detection of Prostate Cancer by Quantitative Analysis of Telomerase Activity
Authors: Botchkina Galina I. , Kim Roger H. , Botchkina Inna L. , Kirshenbaum Alex , Frischer Zelik , Adler Howard L. 
Published: September 2005

Abstract
Purpose: Prostate cancer is the most common male malignancy and the second leading cause of male cancer death; therefore, there is urgent necessity for noninvasive assays for early detection of prostate cancer. Obtaining prostate tumor samples surgically is problematic because the malignancy is heterogeneous and multifocal and early-stage tumors are nonpalpable. In contrast, exfoliated cells represent the cancer status of the entire gland better due to the general tendency of cancer cells to exfoliate into biological fluids. The purpose of this study was to clarify whether quantitative analysis of telomerase activity in exfoliated cells in urine could serve as a reliable molecular marker of prostate malignancy.
Experimental Design: We analyzed prospectively post-prostatic examination–exfoliated cells from the urine of 56 patients undergoing routine prostate screening. Epithelial cells were isolated and enriched by immunomagnetic separation. Telomerase activity was analyzed by quantitative real-time PCR telomeric-repeat amplification protocol assay using Opticon MJ research instrument.
Results: We report now that all prostate cancer patients revealed high levels of telomerase activity thereby showing 100% of the assay sensitivity. In contrast, the majority of patients with clinically confirmed benign prostatic hyperplasia (BPH) did not express any telomerase activity (70% of all BPH patients), most likely presenting cancer-free cases, or expressed low levels of activity (18%). However, about 12% of BPH patients revealed high levels of telomerase activity that potentially can reflect hidden prostate cancer.
Conclusions: We suggest that the quantitative analysis of telomerase activity can be useful for the selection of prostate cancer and cancer-free cases.
A Multicenter Phase II Trial of ZD6474, a Vascular Endothelial Growth Factor Receptor-2 and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients with Previously Treated Metastatic Breast Cancer
Authors: Miller Kathy D. , Trigo Jose Manuel , Wheeler Catherine , Barge Alan , Rowbottom Jacqui , Sledge George , Baselga Jose 
Published: September 2005

Abstract
Purpose: To determine the efficacy and safety of ZD6474, an orally available inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase with additional activity against the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously treated metastatic breast cancer.
Patients and Methods: Eligible patients had histologically confirmed metastatic breast cancer and had received prior treatment with an anthracycline and taxane; measurable disease was required. Patients were enrolled sequentially into one of two dose cohorts, 100 or 300 mg orally once daily; 28 days defined one cycle. The primary end point was objective response rate; pharmacokinetics and serial pharmacodynamic studies were obtained.
Results: Forty-six patients were enrolled between May 2002 and April 2003, and 44 were evaluable for response. Diarrhea was the most commonly reported toxicity and seemed dose related (grade ≥2: 4.5% and 37.5% in the 100 and 300 mg cohorts, respectively). Rash was reported by 26% of patients but was never worse than grade 2. Seven patients in the 300 mg cohort had asymptomatic grade 1 prolongation of the QTc interval. Hypertension requiring treatment was not reported. There were no objective responses; one patient in the 300 mg cohort had stable disease ≥24 weeks. All patients in the 300 mg cohort and 90% of patients in the 100 mg cohort achieved steady-state concentrations exceeding the IC50 for VEGF inhibition in preclinical models.
Conclusion: ZD6474 monotherapy was generally well tolerated but had limited monotherapy activity in patients with refractory metastatic breast cancer.
Heterogeneous Patterns of CEBPα Mutation Status in the Progression of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia to Acute Myelogenous Leukemia
Authors: Shih Lee-Yung , Huang Chein-Fuang , Lin Tung-Liang , Wu Jin-Hou , Wang Po-Nan , Dunn Po , Kuo Ming-Chung , Tang Tzung-Chih 
Published: September 2005

Abstract
Purpose: We aimed to assess the role of CEBPα mutations in the progression of myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML) and their cooperating mutations.
Experimental Design: Mutational analysis of CEBPα with direct sequencing for each PCR product was done on matched bone marrow samples obtained from 50 adult patients with MDS at diagnosis and at AML transformation. Cloning analysis was used to determine the allelic distribution.
Results: CEBPα mutations were identified in four patients at diagnosis of MDS, including one with refractory anemia with excess blasts and three with chronic myelomonocytic leukemia. At AML transformation, three patients retained the identical mutant clones as their initial diagnosis, three acquired the mutations, and one lost CEBPα mutation when she gained FLT3/ITD mutation. Together, seven patients had CEBPα mutations throughout the disease course; four patients had NH2-terminal mutations resulting in a frameshift and truncation of the protein, three of them had two different mutations either on the same alleles or on different alleles, two had missense mutations, and one had a deletion in the basic region leucine zipper domain. Except for one with coexistence of N-ras mutation, no sample harbored cooperating mutations with FLT3 or N-ras genes. CEBPα mutations had no influence on the time to AML progression or overall survival.
Conclusions: Our results show that CEBPα mutations play a role in a subset of patients with MDS, especially in chronic myelomonocytic leukemia. The mutation status was heterogeneous, exhibiting identical clone, clonal change, or clonal evolution during the progression to AML.
Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B
Authors: Govindan Ramaswamy , Kratzke Robert A. , Herndon James E. , Niehans Gloria A. , Vollmer Robin , Watson Dorothy , Green Mark R. , Kindler Hedy L. ,   on behalf of the Cancer and Leukemia Group B (CALGB 30101)
Published: September 2005

Abstract
Purpose: The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma.
Experimental Design: Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity.
Results: The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression.
Conclusions: Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.
Polymorphisms in ERCC1 and Grade 3 or 4 Toxicity in Non–Small Cell Lung Cancer Patients
Authors: Suk Rebecca , Gurubhagavatula Sarada , Park Sohee , Zhou Wei , Su Li , Lynch Thomas J. , Wain John C. , Neuberg Donna , Liu Geoffrey , Christiani David C. 
Published: September 2005

Abstract
Purpose: ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity.
Experimental Design: Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 polymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non–small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen.
Results: There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95% confidence interval, 1.07-5.05; P = 0.03).
Conclusions: Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a &gt;2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non–small cell lung cancer patients.
Generation of PRL-3- and PRL-1-Specific Monoclonal Antibodies as Potential Diagnostic Markers for Cancer Metastases
Authors: Li Jie , Guo Ke , Koh Vicki Wei Chyi , Tang Jing Ping , Gan Bin Qi , Shi Hong , Li Hui Xiang , Zeng Qi 
Published: September 2005

Abstract
Purpose: The PRL-3 mRNA is consistently elevated in metastatic samples derived from colorectal cancers. We sought to generate a specific PRL-3 monoclonal antibody (mAb) that might serve as a potential diagnostic marker for colorectal cancer metastasis.
Experimental Design: PRL-3 is one of three members (PRL-1, PRL-2, and PRL-3) in a unique protein-tyrosine phosphatase family. Because the three PRLs are 76% to 87% identical in their amino acid sequences, it poses a great challenge to obtain mAbs that are specific for respective phosphatase of regenerating liver (PRL) but not for the other two in the family. We screened over 1,400 hybridoma clones to generate mAbs specific to each PRL member.
Results: We obtained two hybridoma clones specifically against PRL-3 and another two clones specifically against PRL-1. These antibodies had been evaluated by several critical tests to show their own specificities and applications. Most importantly, the PRL-3 mAbs were assessed on 282 human colorectal tissue samples (121 normal, 17 adenomas, and 144 adenocarcinomas). PRL-3 protein was detected in 11% of adenocarcinoma samples. The PRL-3- and PRL-1-specific mAbs were further examined on 204 human multiple cancer tissues. The differential expressions of PRL-3 and PRL-1 confirmed the mAbs' specificity.
Conclusions: Using several approaches, we show that PRL-3- or PRL-1-specific mAbs react only to their respective antigen. The expression of PRL-3 in &gt;10% of primary colorectal cancer samples indicates that PRL-3 may prime the metastatic process. These mAbs will be useful as markers in clinical diagnosis for assessing tumor aggressiveness.
Predicting Response to Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Neoadjuvant Chemotherapy for Bladder Cancers through Genome-Wide Gene Expression Profiling
Authors: Takata Ryo , Katagiri Toyomasa , Kanehira Mitsugu , Tsunoda Tatsuhiko , Shuin Taro , Miki Tsuneharu , Namiki Mikio , Kohri Kenjiro , Matsushita Yasushi , Fujioka Tomoaki , Nakamura Yusuke 
Published: September 2005

Abstract
Purpose: Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), can improve the resectability of larger neoplasms for some patients and offer a better prognosis. However, some suffer severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting response to the M-VAC therapy.
Experimental Design: We analyzed gene expression profiles of biopsy materials from 27 invasive bladder cancers using a cDNA microarray consisting of 27,648 genes, after populations of cancer cells had been purified by laser microbeam microdissection.
Results: We identified dozens of genes that were expressed differently between nine “responder” and nine “nonresponder” tumors; from that list we selected the 14 “predictive” genes that showed the most significant differences and devised a numerical prediction scoring system that clearly separated the responder group from the nonresponder group. This system accurately predicted the drug responses of 8 of 9 test cases that were reserved from the original 27 cases. Because real-time reverse transcription–PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative reverse transcription–PCR–based prediction system that could be feasible for routine clinical use.
Conclusions: Our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of “personalized therapy” for treatment of this disease.
Detection of Melanoma Cells Displaying Multiple Genomic Changes in Histopathologically Negative Sentinel Lymph Nodes
Authors: Ulmer Anja , Fischer Jörg R. , Schanz Stefan , Sotlar Karl , Breuninger Helmut , Dietz Klaus , Fierlbeck Gerhard , Klein Christoph A. 
Published: September 2005

Abstract
Purpose: Improved detection of early-disseminated melanoma cells may eventually translate into more effective patient care. We present a novel strategy for detection of melanoma cells in sentinel lymph nodes and confirm their malignant descent by genomic characterization.
Experimental Design: In sentinel lymph nodes from 358 melanoma patients, we prospectively compared the rates of tumor cell detection between immunocytochemistry using HMB45 and Melan A antibodies on disaggregated lymph node samples and standard histopathology (H&E staining and immunostaining on tissue sections). Immunocytochemical melanoma cell detection was controlled by testing lymph node samples from 59 nonmelanoma patients and by isolation and comparative genomic analysis of 30 antigen-positive cells.
Results: Of the 358 patients, 43 (12%) were positive by standard histopathology, whereas HMB45 immunocytochemistry detected 159 of 358 (44%) positive patients. None of the control samples reacted with the HMB45 antibody. Reexamination of samples that were classified as negative by histopathology revealed that extensive serial sectioning would be necessary to achieve sensitivity similar to HMB45 immunocytochemistry. Interestingly, both the number of immunocytochemically positive samples and the number of positive cells in the sentinel node correlated with the thickness of the primary tumor (r = 0.34; P = 0.001 and P &lt; 0.0001, respectively). Twenty-four of 30 isolated immunocytochemically positive cells (80%) displayed chromosomal aberrations, some of which were isolated from histopathologically negative nodes.
Conclusion: Immunocytochemical detection of melanoma cells in sentinel lymph nodes is superior to standard histopathology. It remains to be determined whether the detection and genomic characterization of isolated melanoma cells in sentinel lymph nodes will provide relevant prognostic information.
Fluorodeoxyglucose Positron Emission Tomography as an Outcome Measure for Castrate Metastatic Prostate Cancer Treated with Antimicrotubule Chemotherapy
Authors: Morris Michael J. , Akhurst Timothy , Larson Steven M. , Ditullio Marisa , Chu Elaina , Siedlecki Karen , Verbel David , Heller Glenn , Kelly W. Kevin , Slovin Susan , Schwartz Lawrence , Scher Howard I. 
Published: September 2005

Abstract
Purpose: Standard imaging studies are limited as outcome measures for patients with metastatic prostate cancer. We tested the hypothesis that serial fluorodeoxyglucose positron emission tomography (FDG-PET) scans can serve as an outcome measure for patients with castrate metastatic prostate cancer treated with antimicrotubule chemotherapy.
Experimental Design: FDG-PET scans were done at baseline, 4, and 12 weeks of treatment. The average maximum standardized uptake value (SUVmaxavg) was measured in up to five lesions and was tested as the quantitative outcome measure. Prostate-specific antigen (PSA) at 4 weeks and PSA, bone scan, and soft tissue imaging at 12 weeks were considered standard outcome measures. The change in SUVmaxavg that distinguished clinically assessed progression from nonprogression was sought.
Results: Twenty-two PET scans were reviewed and compared with PSA at 4 weeks; 18 PETs were compared at 12 weeks with standard outcome measures. Applying the PSA Working Group Consensus Criteria guideline that a 25% PSA increase constitutes progression to the SUVmaxavg, PET correctly identified the clinical status of 20 of 22 patients (91%) at 4 weeks and 17 of 18 patients at 12 weeks (94%). The accuracy of PET could be further optimized if a &gt;33% increase in PSA and SUVmaxavg were used to define progression.
Conclusion: FDG-PET is promising as an outcome measure in prostate cancer. As a single modality, it can show treatment effects that are usually described by a combination of PSA, bone scintigraphy, and soft tissue imaging. Preliminarily, a &gt;33% increase in SUVmaxavg or the appearance of a new lesion optimally dichotomizes patients as progressors or nonprogressors.