bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Molecular and Biological Tumor Markers in Neuroblastoma
Authors: Riley Richard D. , Heney David , Jones David R. , Sutton Alex J. , Lambert Paul C. , Abrams Keith R. , Young Bridget , Wailoo Alan J. , Burchill Susan A. 
Published: September 2005

AbstractPurpose: The aim of this study was to conduct a systematic review, and where possible meta-analyses, of molecular and biological tumor markers described in neuroblastoma, and to establish an evidence-based perspective on their clinical value for the screening, diagnosis, prognosis, and monitoring of patients.Experimental Design: A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000.Results: A total of 428 papers studying the use of 195 different tumor markers in neuroblastoma were identified. Small sample sizes, poor statistical reporting, large heterogeneity across studies (e.g., in cutoff levels), and publication bias limited meta-analysis to the area of prognosis only; MYCN, chromosome 1p, DNA index, vanillylmandelic acid:homovanillic acid ratio, CD44, Trk-A, neuron-specific enolase, lactate dehydrogenase, ferritin, and multidrug resistance were all identified as potentially important prognostic tools.Conclusions: This systematic review forms a knowledge base of the tumor markers studied thus far in neuroblastoma, and has identified some of the most important prognostic markers, which should be considered in future research and treatment strategies. Importantly, the review has also highlighted some general problems across primary tumor marker studies, in particular poor and heterogeneous reporting. These need to be addressed to allow better clinical interpretation and enable more appropriate evidence-based reviews in the future. In particular, collaboration of cancer research groups is needed to enable bigger sample sizes, standardize methods of analysis and reporting, and facilitate the pooling of individual patient data.
Ki-67 Staining Index Predicts Distant Metastasis and Survival in Locally Advanced Prostate Cancer Treated With Radiotherapy
Authors: Li Rile , Heydon Kateri , Hammond M. Elizabeth , Grignon David J. , Roach Mack , Wolkov Harvey B. , Sandler Howard M. , Shipley William U. , Pollack Alan 
Published: September 2005

Abstract
Purpose: Proliferative activity defined by Ki-67 staining index (SI) has been correlated with progression and prognosis in a number of malignant tumors including prostate cancer. However, few studies have examined Ki-67 SI in pretreatment diagnostic material from patients treated with definitive radiotherapy. In a prior study, we found that a Ki-67 SI of &gt;3.5% was associated with poorer patient outcome. The goals of this analysis were to validate the prognostic value of Ki-67 SI and this cut point.
Experimental Design: Of 456 assessable patients in Radiation Therapy Oncology Group Protocol 86-10, diagnostic material from 108 patients was available for Ki-67 analysis using MIB-1 antibody. Sixty patients were treated with external beam radiotherapy (EBRT) alone, and 48 patients were treated with short-term androgen deprivation + EBRT. Median follow-up was 9 years for those living. The relationship of Ki-67 with distant metastasis (DM), disease-specific survival (DSS), and overall survival (OS) was examined.
Results: The median Ki-67 SI was 7.1% (range, 0.2–45.5%). The 7.1% cut point was associated with DM and DSS; however, the 3.5% cut point was as strong a determinant and was the focus of this analysis. In Cox proportional hazards regression, Ki-67 SI was independently associated with DM and DSS. When the Ki-67 SI was ≤3.5% and &gt;3.5%, the 5-year risk of DM was 13.5% and 50.8% (P = 0.0005), respectively, and the 5-year risk of DSS was 97.3% and 67.7% (P = 0.0039), respectively. No association of Ki-67 SI with OS was observed.
Conclusions: Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT.
Loss of CD55 Is Associated with Aggressive Breast Tumors
Authors: Madjd Zahra , Durrant Lindy G. , Bradley Richard , Spendlove Ian , Ellis Ian O. , Pinder Sarah E. 
Published: September 2005

Abstract
Purpose: CD55 is a complement regulatory protein expressed by cells to protect them from bystander attack by complement. CD55 is overexpressed on some tumor cell lines, and in colorectal carcinomas, it has been shown to be an indicator of poor prognostic.
Experimental Design: A large set of samples (480) from patients with primary operable breast cancer followed for 4–192 months were included in the present study. The prognostic significance of CD55 was then investigated in these tumors using an anti-CD55 monoclonal antibody (RM1) that we raised against a synthetic peptide and a standard immunohistochemistry method.
Results: Ninety-five percent of the breast carcinomas expressed CD55 (RM1) with intensity ranging from weak (51%) to strong (6%). High expression of CD55 was significantly associated with low-grade (grades 1 or 2; P = 0.001), lymph node negativity (P = 0.031), and good prognosis tumors (Nottingham Prognostic Index &lt; 3.4; P &lt; 0.001). Survival analysis showed CD55 overexpression was associated with a more favorable outcome and loss of CD55 being associated with poor survival (P = 0.001). Intensity of CD55 expression was significantly correlated (P = 0.002) with intensity of CD59 expression (as shown in a previous study) in these series of patients.
Conclusions: In conclusion, we found that loss of both CD55 and CD59 in breast carcinomas is associated with a worse prognosis.
Metabotropic Glutamate Receptor 4-Mediated 5-Fluorouracil Resistance in a Human Colon Cancer Cell Line
Authors: Yoo Byong Chul , Jeon Eunkyung , Hong Sung-Hye , Shin Young-Kyoung , Chang Hee Jin , Park Jae-Gahb 
Published: September 2005

Abstract
Purpose: 5-Fluorouracil (5-FU) has been the mainstay treatment for colorectal cancer for the past few decades. However, as with other cancers, development of 5-FU resistance has been a major obstacle in colorectal cancer chemotherapy. The purpose of this study was to gain further understanding of the mechanisms underlying 5-FU resistance in colorectal cancer cells.
Experimental Design: A 5-FU-resistant cell line was established from the human colon cancer cell line SNU-769A. Protein extracts from these two cell lines (parent and resistant) were analyzed using comparative proteomics to identify differentially expressed proteins.
Results: 5-FU-resistant human colon cancer cells were found to overexpress metabotropic glutamate receptor 4 (mGluR4). Other experiments showed cellular resistance to 5-FU (i.e., cell survival) was altered by the mGluR4 agonist l-2-amino-4-phosphonobutyric acid (L-AP 4), and by the mGluR4 antagonist (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP 4), in that L-AP 4 increased 5-FU resistance in SNU-769A cells, whereas MAP 4 ablated 5-FU resistance in 5-FU-resistant cells. However, there was no significant effect of L-AP 4 or MAP 4 on basal cAMP and thymidylate synthase levels. Interestingly, 5-FU down-regulated mGluR4 expression, and MAP 4 suppressed proliferation in both cell lines.
Conclusions: We here report mGluR4 expression in human colon cancer cell line, which provides further evidence for extra-central nervous system expression of glutamate receptors. Overexpression of mGluR4 may tentatively be responsible for 5-FU resistance and, although activation by agonist promotes cell survival in the presence of 5-FU, decreased mGluR4 expression or inactivation by antagonist contributes to cell death.
Humoral Responses to Peptides Correlate with Overall Survival in Advanced Cancer Patients Vaccinated with Peptides Based on Pre-existing, Peptide-Specific Cellular Responses
Authors: Mine Takashi , Sato Yuji , Noguchi Masanori , Sasatomi Teruo , Gouhara Rumi , Tsuda Naotake , Tanaka Shoko , Shomura Hiroki , Katagiri Kazuko , Rikimaru Touru , Shichijo Shigeki , Kamura Toshiharu , Hashimoto Takashi , Shirouzu Kazuo , Yamada Akira , Todo Satoru , Itoh Kyogo , Yamana Hideaki 
Published: September 2005

AbstractPurpose: The aim of this study is to find a laboratory marker for overall survival in advanced cancer patients who were vaccinated with peptides based on pre-existing, peptide-specific CTL precursors in the circulation.Experimental Design: A group of 113 patients with advanced cancer (28 colorectal, 22 prostate, 15 lung, 14 gastric, and 34 other cancers) was enrolled in a Phase I clinical study of peptide vaccination in which peptide-specific CTL precursors of prevaccination peripheral blood mononuclear cells were measured, followed by vaccination with these peptides (maximum of four). For cellular responses, pre and postvaccination (sixth) peripheral blood mononuclear cells were provided for measurement of both peptide-specific CTL precursors by IFN-γ release assay and tumor reactivity by 51Cr release assay. Delayed type hypersensitivity was also measured. For humoral response, pre and postvaccination (sixth) sera were provided for measurement of peptide-reactive IgG by an ELISA.Results: The median survival time and 1-year survival rate of the total cases were 346 ± 64.9 days and 44.6%, respectively, and those of patients vaccinated more than six times (n = 91) were 409 ± 15 days and 54.4%, respectively. In these 91 patients, the overall survival of patients whose sera showed increased levels of peptide-reactive IgG (n = 60) was significantly more prolonged (P = 0.0003) than that of patients whose sera did not (n = 31), whereas none of cellular responses correlated with overall survival.Conclusions: Peptide-specific IgG in postvaccination sera could be a suitable laboratory maker for the prediction of prolonged survival in advanced cancer patients vaccinated with peptides based on pre-existing CTL precursors.
Missense Mutations of
MADH4
Authors: Iacobuzio-Donahue Christine A. , Song Jason , Parmiagiani Giovanni , Yeo Charles J. , Hruban Ralph H. , Kern Scott E. 
Published: September 2005

Abstract
Purpose and Experimental Design: The mutational spectrum of MADH4 (DPC4/SMAD4) opens valuable insights into the functions of this protein that confer its tumor-suppressive nature in human tumors. We present the MADH4 genetic status determined on a new set of pancreatic, biliary, and duodenal cancers with comparison to the mutational data reported for various tumor types.
Results: Homozygous deletion, followed by inactivating nonsense or frameshift mutations, is the predominant form of MADH4 inactivation in pancreatic cancers. Among the naturally occurring MADH4 missense mutations, the MH2 domain is the most frequent target (77%) of missense mutations in human tumors. A mutational hot spot resides within the MH2 domain corresponding to codons 330 to 370, termed the mutation cluster region (MCR). A relationship was found between the locations of the missense mutations (the MH1 domain, the MH2-MCR, and the MH2 outside of the MCR) and the tumor types, suggesting environmental or selective influences in the development of MADH4 mutations. Immunohistochemical studies for Madh4 protein in nine archival cancers (six pancreatic cancers, two duodenal cancers, and one biliary cancer) with known missense mutations indicated that all mutations within the MH1 or MH2 domain COOH-terminal to the MCR (seven of nine cases) had negative or weak labeling, whereas two cancers with mutations within the MCR had strong positive nuclear labeling for Madh4 protein.
Conclusions: These findings have important implications for in vitro functional studies, suggesting that the majority of missense mutations inactivate Madh4 by protein degradation in contrast to those that occur within the MCR.
Novel Poly(ADP-ribose) Polymerase-1 Inhibitor, AG14361, Restores Sensitivity to Temozolomide in Mismatch Repair-Deficient Cells
Authors: Curtin Nicola J. , Wang Lan-Zhen , Yiakouvaki Anthie , Kyle Suzanne , Arris Christine A. , Canan-Koch Stacie , Webber Stephen E. , Durkacz Barbara W. , Calvert Hilary A. , Hostomsky Zdenek , Newell David R. 
Published: September 2005

Abstract
Purpose: Mismatch repair (MMR) deficiency confers resistance to temozolomide, a clinically active DNA-methylating agent. The purpose of the current study was to investigate the reversal mechanism of temozolomide resistance by the potent novel poly(ADP-ribose) polymerase (PARP)-1 inhibitor, AG14361, in MMR-proficient and -deficient cells.
Experimental Design: The effects of AG14361, in comparison with the methylguanine DNA methyltransferase inhibitor, benzylguanine, on temozolomide-induced growth inhibition were investigated in matched pairs of MMR-proficient (HCT-Ch3, A2780, and CP70-ch3) and -deficient (HCT116, CP70, and CP70-ch2) cells.
Results: AG14361 enhanced temozolomide activity in all MMR-proficient cells (1.5–3.3-fold) but was more effective in MMR-deficient cells (3.7–5.2-fold potentiation), overcoming temozolomide resistance. In contrast, benzylguanine only increased the efficacy of temozolomide in MMR-proficient cells but was ineffective in MMR-deficient cells. The differential effect of AG14361 in MMR-deficient cells was not attributable to differences in PARP-1 activity or differences in its inhibition by AG14361, nor was it attributable to differences in DNA strand breaks induced by temozolomide plus AG14361. MMR-deficient cells are resistant to cisplatin, but AG14361 did not sensitize any cells to cisplatin. PARP-1 inhibitors potentiate topotecan-induced growth inhibition, but AG14361 did not potentiate topotecan in MMR-deficient cells more than in MMR-proficient cells.
Conclusions: MMR defects are relatively common in sporadic tumors and cancer syndromes. PARP-1 inhibition represents a novel way of selectively targeting such tumors. The underlying mechanism is probably a shift of the cytotoxic locus of temozolomide to N7-methylguanine and N3-methyladenine, which are repaired by the base excision repair pathway in which PARP-1 actively participates.
Predictive Value of Biological Markers for Hepatocellular Carcinoma Patients Treated with Orthotopic Liver Transplantation
Authors: Fiorentino Michelangelo , Altimari Annalisa , Ravaioli Matteo , Gruppioni Elisa , Gabusi Elena , Corti Barbara , Vivarelli Marco , Bringuier Pierre-Paul , Scoazec Jean-Yves , Grigioni Walter Franco , D’Errico-Grigioni Antonia 
Published: September 2005

Abstract
Purpose: To help stratify candidates with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT), biomarkers are needed that are capable of predicting recurrence of disease (ROD). We investigated the prognostic role in this setting of immunohistochemical markers reported previously to predict poor prognosis in HCC patients treated with resection.
Experimental Design: Eighty-three patients with HCC who underwent OLT between 1987 and 2001 with a minimum clinical follow up of 12 months were included in this retrospective study. We analyzed immunohistochemical expression of the adhesion molecules E-cadherin and β-catenin (membrane/nuclear localization), MIB-1 proliferative index and the cyclin-dependent kinase inhibitor p27, alongside the main clinical-pathological variables.
Results: At univariate analysis, vascular thrombosis, high MIB-1 index, lower membrane expression of E-cadherin and β-catenin, and nuclear β-catenin localization were associated with ROD. At multivariate analysis, only MIB-1 index, low equal E-cadherin (with respect to non-neoplastic surrounding tissue), and nuclear β-catenin appeared as independent predictors of ROD. The logistic regression analysis model indicated that detection of any one parameter was associated with at least 88% estimated risk of ROD (up to 99% for all three).
Conclusions: We propose these three molecular parameters as an additional tool for rational selection of OLT candidates among HCC patients (stratification according to the risk of ROD might help provide a similar life expectancy for cirrhotic candidates with and without HCC).
The Evaluation of Recombinant, Chimeric, Tetravalent Antihuman CD22 Antibodies
Authors: Meng Ruiqi , Smallshaw Joan E. , Pop Laurentiu M. , Yen Michael , Liu Xiaoyun , Le Lien , Ghetie Maria-Ana , Vitetta Ellen S. , Ghetie Victor 
Published: September 2005

AbstractPurpose: The purpose of this study was to prepare chimeric antihuman CD22 tetravalent monoclonal antibodies (MAbs) with high functional affinity, long persistence in the circulation, increased antitumor activity, and conserved effector function in vitro.Experimental Design: We investigated the association/dissociation rates of these tetravalent antibodies using CD22+ Daudi lymphoma cells. We then tested their ability to interact with Fc receptors on a human cell line (U937), to mediate antibody-dependent cellular cytotoxicity with human natural killer cells, to bind human C1q, to inhibit the in vitro growth of CD22 Daudi cells, and to persist in the circulation.Results: The rate of dissociation of the tetravalent MAbs versus the divalent antibody was considerably slower. These tetravalent MAbs inhibited the in vitro proliferation of CD22 Daudi cells at a concentration that was at least 100-fold lower than that of the divalent murine antibody. The tetravalent MAbs containing both the CH2 and CH3 domains and a chimeric recombinant divalent antibody bound similarly to Fc receptor, C1q, and mediate antibody-dependent cellular cytotoxicity equally well with human natural killer cells. The persistence in the circulation of chimeric tetravalent MAbs was considerably longer than that of chemical homodimers.Conclusions: The tetravalent anti-CD22 MAbs with intact Fc regions should make effective therapeutic agents for B-cell tumors.
Comprehensive Analysis of Matrix Metalloproteinase and Tissue Inhibitor Expression in Pancreatic Cancer
Authors: Jones Lucie E. , Humphreys Michelle J. , Campbell Fiona , Neoptolemos John P. , Boyd Mark T. 
Published: September 2005

AbstractPurpose: To enable the design of improved inhibitors of matrix metalloproteinases (MMPs) for the treatment of pancreatic cancer, the expression profiles of a range of MMPs and tissue inhibitors of MMPs (TIMPs) were determined.Experimental Design: Nine MMPs (MMPs 1–3, 7–9, 11, 12, and 14) and three TIMPs (TIMPs 1–3) were examined in up to 75 pancreatic ductal adenocarcinomas and 10 normal pancreata by immunohistochemistry. Eighteen additional pancreatic ductal adenocarcinomas and an additional eight normal pancreata were also analyzed by real-time reverse transcription-PCR and additionally for MMP-15.Results: There was increased expression by immunohistochemistry for MMPs 7, 8, 9, and 11 and TIMP-3 in pancreatic cancer compared with normal pancreas (P &lt; 0.0001, 0.04, 0.0009, 0.005, and 0.0001, respectively). Real-time reverse transcription-PCR showed a significant increase in mRNA levels for MMP-11 in tumor tissue compared with normal pancreatic tissue (P = 0.0005) and also significantly reduced levels of MMP-15 (P = 0.0026). Univariate analysis revealed that survival was reduced by lymph node involvement (P = 0.0007) and increased expression of MMP-7 (P = 0.005) and (for the first time) MMP-11 (P = 0.02) but not reduced by tumor grade, tumor diameter, positive resection margins, adjuvant treatment, or expression of the remaining MMPs and TIMPs. On multivariate analysis, only MMP-7 predicted shortened survival (P &lt; 0.05); however, increased MMP-11 expression was strongly associated with lymph node involvement (P = 0.0073).Conclusions: We propose that the principle specificity for effective inhibitors of MMPs in pancreatic cancer should be for MMP-7 with secondary specificity against MMP-11. Moreover, these studies indicate that MMP-7 expression is a powerful independent prognostic indicator and potentially of considerable clinical value.
Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry
Authors: Koopmann Jens , Zhang Zhen , White Nicole , Rosenzweig Jason , Fedarko Neal , Jagannath Sanjay , Canto Marcia I. , Yeo Charles J. , Chan Daniel W. , Goggins Michael 
Published: September 2005

Abstract
Purpose: Each year in the United States, ∼ 30,000 people die from pancreatic cancer. Fewer than 5% of patients survive &gt;5 years after diagnosis, because most patients present with advanced disease. Early diagnosis may improve the prognosis of patients with pancreatic cancer.
Experimental Design: In an attempt to improve on current approaches to the serological diagnosis of pancreatic cancer, we analyzed serum samples from patients with and without pancreatic cancer using surface-enhanced laser desorption and ionization (SELDI) protein chip mass spectrometry. Using a case-control study design, serum samples from 60 patients with resectable pancreatic adenocarcinoma were compared with samples from 60 age- and sex-matched patients with nonmalignant pancreatic diseases, as well as 60 age- and sex-matched healthy controls. To increase the number of proteins potentially identifiable, serum was fractionated using anion exchange and profiled on two ProteinChip surfaces (metal affinity capture and weak cation exchange).
Results: We determined a minimum set of protein peaks able to discriminate between patient groups and used the unified maximum separability algorithm to compare the performance of the individual marker panels alone or in conjunction with CA19–9. Among the peaks identified by SELDI profiling that had the ability to distinguish between patient groups, the 2 most discriminating protein peaks could differentiate patients with pancreatic cancer from healthy controls with a sensitivity of 78% and specificity of 97%. These 2 markers performed significantly better than the current standard serum marker, CA19–9 (P &lt; 0.05). The diagnostic accuracy of the 2 markers was improved by using them in combination with CA 19-9. Similarly, a combination of 3 SELDI markers and CA19–9 was superior to CA19–9 alone in distinguishing individuals with pancreatic cancer from the combined pancreatic disease controls and healthy subject groups (P = 0.078). SELDI markers were also better than CA19–9 in distinguishing patients with pancreatic cancer from those with pancreatitis.
Conclusion: SELDI profiling of serum can be used to accurately differentiate patients with pancreatic cancer from those with other pancreatic diseases and from healthy controls.