bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1
Authors: Saleem Mohammad , Adhami Vaqar Mustafa , Zhong Weixiong , Longley B. Jack , Lin Chen-Yong , Dickson Robert B. , Reagan-Shaw Shannon , Jarrard David F. , Mukhtar Hasan 
Published: March 2006

Abstract
Background: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix, and in the progression of some epithelial cancers. Here, we establish the clinical significance of matriptase and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), during the progression of human prostate cancer (CaP).
Methods: The expression patterns of matriptase and HAI-1 were determined in primary cultures of normal human prostate epithelial (NHPE) cells, human CaP cells LNCaP, DU-145, CWR22Rν1, and PC-3, and in tissue samples of 172 patients with normal prostate, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma of different tumor grades.
Results: The protein and mRNA levels of matriptase were significantly higher in all carcinoma cells as compared with NHPE cells. Conversely, all CaP cells exhibited a reduced expression of HAI-1 as compared with NHPE cells. A progressive increase in the protein levels of matriptase was observed with increasing tumor grade in CaP specimens as compared with normal and BPH tissue specimens. Tissue samples of normal prostate exhibited a high constitutive protein level of HAI-1 compared with BPH and low-grade cancer with a progressive loss with increasing tumor grade.
Conclusion: The increased expression of matriptase and loss of HAI-1 may be an important event during the progression of CaP in humans. We suggest that the ratio of these two gene products may serve as a promising biomarker for CaP progression and a potential marker for establishing the efficacy of therapeutic and chemopreventive interventions. (Cancer Epidemiol Biomarkers Prev 2006;15(2):217–27)
Markers of Cutaneous Human Papillomavirus Infection in Individuals with Tumor-Free Skin, Actinic Keratoses, and Squamous Cell Carcinoma
Authors: Struijk Linda , Hall Lisa , van der Meijden Els , Wanningen Patrick , Bavinck Jan Nico Bouwes , Neale Rachel , Green Adèle C. , ter Schegget Jan , Feltkamp Mariet C.W. 
Published: March 2006

Abstract
Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC. (Cancer Epidemiol Biomarkers Prev 2006;15(3):529–35)
Influence of Estrogen Receptor α and Progesterone Receptor Polymorphisms on the Effects of Hormone Therapy on Mammographic Density
Authors: van Duijnhoven Fränzel J.B. , Peeters Petra H.M. , Warren Ruth M.L. , Bingham Sheila A. , Uitterlinden André G. , van Noord Paulus A.H. , Monninkhof Evelyn M. , Grobbee Diederick E. , van Gils Carla H. 
Published: March 2006

Abstract
Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch Prospect-EPIC and the English EPIC-Norfolk cohorts. Information on hormone therapy use was obtained through questionnaires at recruitment and after 5 years. Blood samples were collected and consecutive mammograms were available through breast cancer screening programs. For 795 hormone therapy users, one mammogram before and a second mammogram during hormone therapy use was included. For 781 never hormone therapy users, mammograms with similar time intervals were included. Mammographic density was assessed using a computer-assisted method. Changes in density were analyzed using linear regression. A statistically significant difference in percentage density change between hormone therapy users and never users was seen in women with the ESR1 PvuII Pp or pp genotype (2.24%; P &lt; 0.01), but not in those with the PP genotype (0.90%; P = 0.47). Similarly, effects of hormone therapy on percentage density were observed in women with the ESR1 XbaI Xx or xx genotype (2.20%; P &lt; 0.01), but not in those with the XX genotype (−0.65%; P = 0.70). Also, effects were seen in women with the PGR +331 GG genotype (2.04%; P &lt; 0.01), but not in those with the GA or AA genotype (0.98%; P = 0.53). The PGR PROGINS polymorphism did not seem to make women more susceptible to the effects of hormone therapy use. In conclusion, our results suggest that specific polymorphisms in the ESR1 and PGR genes may make women more susceptible to the effects of hormone therapy use on mammographic density. (Cancer Epidemiol Biomarkers Prev 2006;15(3):462–7)
Inflammatory Cytokine Gene Polymorphisms, Nonsteroidal Anti-Inflammatory Drug Use, and Risk of Adenoma Polyp Recurrence in the Polyp Prevention Trial
Authors: Sansbury Leah B. , Bergen Andrew W. , Wanke Kay L. , Yu Binbing , Caporaso Neil E. , Chatterjee Nilanjan , Ratnasinghe Luke , Schatzkin Arthur , Lehman Teresa A. , Kalidindi Aravind , Modali Ramakrishna , Lanza Elaine 
Published: March 2006

Abstract
Background: Pro- and anti-inflammatory cytokine genes may be important in the maintenance and progression of colorectal cancer. It is possible that single-nucleotide polymorphisms in inflammatory genes may play a role in chronic colonic inflammation and development of colorectal adenomas. Furthermore, common variants in cytokine genes may modify the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colorectal cancer.
Methods: We examined the association between cytokine gene polymorphisms and risk of recurrent adenomas among 1,723 participants in the Polyp Prevention Trial. We used logistic regression to calculate odds ratios (OR) for the association between genotype, NSAID use, and risk of adenoma recurrence.
Results: Cytokine gene polymorphisms were not statistically significantly associated with risk of adenoma recurrence in our study. We observed statistically significant interactions between NSAID use, IL-10 −1082 G&gt;A genotype, and risk of adenoma recurrence (P = 0.01) and multiple adenoma recurrence (P = 0.01). Carriers of the IL-10 −1082 G&gt;A variant allele who were non-NSAID users had a statistically significant decreased risk of multiple adenoma recurrence (OR, 0.43; 95% confidence interval, 0.24-0.77) as well as a nonsignificant 30% decreased risk of any adenoma recurrence. In contrast, NSAID users who were carriers of the IL-10 −1082 G&gt;A variant allele were at an increased risk of any adenoma recurrence (OR, 1.55; 95% confidence interval, 1.00-2.43).
Conclusion: These findings suggest that individuals who are carriers of the IL-10 −1082 G&gt;A variant allele may not benefit from the chemoprotective effect of NSAIDs on adenoma polyp recurrence. (Cancer Epidemiol Biomarkers Prev 2006;15(3):494–501)
Cytogenetics of Hispanic and White Children with Acute Lymphoblastic Leukemia in California
Authors: Aldrich Melinda C. , Zhang Luoping , Wiemels Joseph L. , Ma Xiaomei , Loh Mignon L. , Metayer Catherine , Selvin Steve , Feusner James , Smith Martyn T. , Buffler Patricia A. 
Published: March 2006

Abstract
Epidemiologic studies of childhood leukemia have made limited use of tumor genetic characteristics, which may be related to disease etiology. We characterized the cytogenetics of 543 childhood leukemia patients (0-14 years of age) enrolled in the Northern California Childhood Leukemia Study, an approximately population-based study comprised primarily of Hispanics (42%) and non-Hispanic Whites (41%), and compared the cytogenetic profiles between these two ethnic groups. Subjects were classified by immunophenotype, conventional cytogenetic characteristics, and fluorescence in situ hybridization findings. The ploidy levels most frequently observed among acute lymphoblastic leukemia patients were high hyperdiploidy (51-67 chromosomes) and pseudodiploidy (34% and 27%, respectively). No ethnic differences in the frequency of 11q23/MLL rearrangements were observed between Hispanics and non-Hispanic Whites. Among B-lineage acute lymphoblastic leukemia patients, the percentage of TEL-AML1 translocations was significantly lower in Hispanics (13%) than in non-Hispanic Whites (24%; P = 0.01). This is the first time that this ethnic variation has been observed in a large number of patients in a defined geographic region, which is consistent with findings from smaller international studies. The mechanistic basis for this 2-fold variation in frequency of TEL-AML1 may be due to ethnic-specific risk factors or genetics and should be explored further. (Cancer Epidemiol Biomarkers Prev 2006;(15)3:578–81)
Reduction in Breast Cancer Mortality from the Organised Service Screening with Mammography: 2. Validation with Alternative Analytic Methods
Authors:   The Swedish Organised Service Screening Evaluation Group
Published: March 2006

Abstract
Background: In our companion article, incidence-based mortality analysis of data from breast cancer screening programs in 13 areas in Sweden indicated a 40% to 45% reduction in incidence-based breast cancer mortality among women actually screened. In this article, we apply new analytic methods for the evaluation of breast cancer mortality, using all breast cancer deaths in the period under study.
Methods: Data were available from 13 areas on breast cancer mortality by year of diagnosis, year of death, and screening exposure. The period of study varied by area, the overall range of year of diagnosis being 1968 to 2001. We had data on 6,231 deaths and an average population of 555,676 women ages 40 to 69 years. Analysis of the effect of being screened was conducted using an alternative statistical analysis applied to all breast cancer deaths in the period of study, in addition to the incidence-based mortality analysis in our companion article. Data were analyzed using Poisson regression and adjusted for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.
Results: Using all deaths in the period of observation, a significant 42% reduction in breast cancer mortality was observed, adjusting for contemporaneous changes independent of screening [relative risk (RR), 0.58; 95% confidence interval (95% CI), 0.53-0.62]. After further adjustment for self-selection bias, the mortality reduction was 39% (RR, 0.61; 95% CI, 0.55-0.68), also highly significant.
Conclusions: These results indicate a reduction in breast cancer mortality of 39% in association with screening, after adjustment for contemporaneous changes and self-selection bias. These results confirm previous conclusions arrived at using incidence-based mortality analyses.
Gene Expression Profile Associated with Response to Doxorubicin-Based Therapy in Breast Cancer
Authors: Koike Folgueira Maria Aparecida Azevedo , Carraro Dirce Maria , Brentani Helena , da Costa Patrão Diogo Ferreira , Barbosa Edson Mantovani , Netto Mário Mourão , Caldeira José Roberto Fígaro , Katayama Maria Lucia Hirata , Soares Fernando Augusto , Oliveira Célia Tosello , Reis Luiz Fernando Lima , Kaiano Jane Haruko Lima , Camargo Luiz Paulo , Vêncio Ricardo Zorzetto Nicoliello , Snitcovsky Igor Moysés Longo , Makdissi Fabiana Baroni Alves , da Silva e Silva Paulo José , Góes João Carlos Guedes Sampaio , Brentani Maria Mitzi 
Published: March 2006

Abstract
Purpose: This study was designed to identify genes that could predict response to doxorubicin-based primary chemotherapy in breast cancer patients.
Experimental Design: Biopsy samples were obtained before primary treatment with doxorubicin and cyclophosphamide. RNA was extracted and amplified and gene expression was analyzed using cDNA microarrays.
Results: Response to chemotherapy was evaluated in 51 patients, and based on Response Evaluation Criteria in Solid Tumors guidelines, 42 patients, who presented at least a partial response (≥30% reduction in tumor dimension), were classified as responsive. Gene profile of samples, divided into training set (n = 38) and independent validation set (n = 13), were at first analyzed against a cDNA microarray platform containing 692 genes. Unsupervised clustering could not separate responders from nonresponders. A classifier was identified comprising EMILIN1, FAM14B, and PBEF, which however could not correctly classify samples included in the validation set. Our next step was to analyze gene profile in a more comprehensive cDNA microarray platform, containing 4,608 open reading frame expressed sequence tags. Seven samples of the initial training set (all responder patients) could not be analyzed. Unsupervised clustering could correctly group all the resistant samples as well as at least 85% of the sensitive samples. Additionally, a classifier, including PRSS11, MTSS1, and CLPTM1, could correctly distinguish 95.4% of the 44 samples analyzed, with only two misclassifications, one sensitive sample and one resistant tumor. The robustness of this classifier is 2.5 greater than the first one.
Conclusion: A trio of genes might potentially distinguish doxorubicin-responsive from nonresponsive tumors, but further validation by a larger number of samples is still needed.
PRL-3 Phosphatase Is Implicated in Ovarian Cancer Growth
Authors: Polato Federica , Codegoni Annamaria , Fruscio Robert , Perego Patrizia , Mangioni Costantino , Saha Saurabh , Bardelli Alberto , Broggini Massimo 
Published: March 2006

Abstract
Purpose: The PRL-3 phosphatase has been found expressed at higher levels in metastasis than in primary tumors of patients with colorectal cancer. In the present study, we evaluated the expression of PRL-3 in ovarian cancer tissue and its role in ovarian cancer cell growth.
Experimental Design: PRL-3 phosphatase expression was evaluated in 84 ovarian tumor samples. PRL-3 expression has been knocked down using specific small interfering RNAs to determine its role in ovarian cancer cell growth in vitro.
Results: In ovarian cancers, PRL-3 expression correlates with disease progression, being higher in advanced (stage III) than in early (stage I) tumors. In situ measurements of PRL-3 expression showed that it was confined to the epithelial neoplastic cells. The molecular mechanism underlying PRL-3 overexpression in ovarian cancers is independent from amplification of the corresponding genomic locus. Ovarian cancer cells growing in culture have high levels of expression of this phosphatase. PRL-3–specific knockdown using small interfering RNA severely impaired the growth of cells without affecting the expression of the closely related homologue PRL-1. Intriguingly, the growth of human colon carcinoma cells expressing lower levels of the PRL-3 was not affected by the PRL-3 knockdown.
Conclusions: Altogether, these results show that PRL-3 expression is associated with ovarian cancer progression and point to a key role for this phosphatase in the control of ovarian cancer cells growth. This strongly suggests that PRL-3 should be considered as a target for the discovery of new anticancer agents to be tested against this malignancy.
High Cyclooxygenase-2 Expression Following Neoadjuvant Radiochemotherapy Is Associated with Minor Histopathologic Response and Poor Prognosis in Esophageal Cancer
Authors: Xi Huan , Baldus Stephan E. , Warnecke-Eberz Ute , Brabender Jan , Neiss Susanne , Metzger Ralf , Ling Frederike C. , Dienes Hans P. , Bollschweiler Elfriede , Moenig Stefan , Mueller Rolf P. , Hoelscher Arnulf H. , Schneider Paul M. 
Published: March 2006

Abstract
Purpose: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapy- and radiotherapy-induced apoptosis. We analyzed the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal cancer.
Experimental Design: Fifty-two patients with resectable esophageal cancers (cT2-4, Nx, and M0) received neoadjuvant radiochemotherapy (cisplatin, 5-5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumor cells. RNA was isolated from endoscopic biopsies (paired tumor and normal tissue) before neoadjuvant treatment and quantitative real-time reverse transcriptase-PCR (Taqman) assays were done to determine COX-2 mRNA expression levels standardized for β-actin. COX-2 protein expression in pretreatment biopsies and post-therapeutic resection specimens was analyzed by immunostaining of tumor cells.
Results: Median COX-2 mRNA expression levels were significantly (P &lt; 0.0001) different between paired tumor (median, 2.2) and normal tissues (median, 0.159). Comparison of pre-therapeutic and posttherapeutic specimens showed a significant difference (P &lt; 0.006) in COX-2 protein expression. Twelve of 52 tumors showed down-regulation and 3 of 52 showed up-regulation of COX-2 protein expression during neoadjuvant radiochemotherapy. High COX-2 protein expression in post-therapeutic resection specimens was significantly associated with minor histopathologic response (P &lt; 0.04) and poor prognosis (5-year survival probabilities: 26.3 ± 8.2% for minor and 58.6% ± 12.9% for major histopathologic response; P &lt; 0.01).
Conclusion: High COX-2 protein expression following neoadjuvant radiochemotherapy in resection specimens is significantly associated with minor histopathologic response to neoadjuvant therapy and very poor prognosis.
In vitro and In vivo Targeting Properties of Iodine-123- or Iodine-131–Labeled Monoclonal Antibody 14C5 in a Non–Small Cell Lung Cancer and Colon Carcinoma Model
Authors: Burvenich Ingrid , Schoonooghe Steve , Cornelissen Bart , Blanckaert Peter , Coene Elisabeth , Cuvelier Claude , Mertens Nico , Slegers Guido 
Published: March 2006

Abstract
Purpose: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs. The aim of this study was to investigate the in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 as a novel agent for radioimmunodetection and radioimmunotherapy.
Experimental Design: Internalization of mAb 14C5 was investigated with 125I-labeled mAb 14C5 and by confocal laser scanning microscopy. Biodistribution studies of 131I-labeled mAb 14C5 and planar gamma imaging were done in nude mice bearing an A549 (non–small cell lung carcinoma) or a LoVo (colon carcinoma) tumor.
Results: Internalization studies with both A549 and LoVo cells showed that 125I-labeled mAb 14C5 is slowly internalized with ∼30% of the initially bound mAb 14C5 internalized after 2 hours at 37°C. Internalization of mAb 14C5 could be visualized with confocal laser scanning microscopy. In vivo, radioisotope uptake peaked at 24 hours for both tumor models (n = 5) with no significant difference in percentage of injected dose/g tissue (A549 10.4 ± 0.8 and LoVo 9.3 ± 0.8). Via planar gamma camera imaging, A549 lung tumors as well as LoVo colon tumors could be clearly visualized.
Conclusions: The in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 are promising and could provide a new antibody-based agent for radioimmunodetection and radioimmunotherapy of patients bearing antigen 14C5–expressing tumors.
Novel Phase I Dose De-escalation Design Trial to Determine the Biological Modulatory Dose of the Antiangiogenic Agent SU5416
Authors: Dowlati Afshin , Robertson Kelly , Radivoyevitch Tomas , Waas John , Ziats Nicholas P. , Hartman Paul , Abdul-Karim Fadi W. , Wasman Jay K. , Jesberger Jack , Lewin Jonathan , McCrae Keith , Ivy Percy , Remick Scot C. 
Published: March 2006

Abstract
Purpose: To determine the biological modulatory dose of SU5416, we employed a novel trial design, where “dose de-escalation” was based on demonstrable biological changes observed at the maximum tolerated dose. If such an effect was shown, dose de-escalation to a predefined dose level would occur to determine if the lower dose exhibited the same amount of pharmacodynamic effect as the higher dose.
Experimental Design: Ten patients with advanced solid tumors were enrolled at each dose level. One of the following pharmacodynamic effects was considered significant: (a) a 35% decrease in microvessel density in sequential tumor biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, and plasma vascular endothelial growth factor were measured sequentially.
Results: Nineteen patients were enrolled. Sequential tumor biopsies in all evaluable patients showed an increase in microvessel density. Only one patient met the intended pharmacodynamic end point of &gt;35% reduction in blood flow. There was a significant increase in both soluble E-selectin and soluble intercellular adhesion molecule levels pretreatment versus levels at the time of removal of patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum fibrinogen rose with therapy. There was a trend toward increase in plasma vascular endothelial growth factor levels.
Conclusion: SU5416 does not result in decreased blood flow in tumors or a decrease in microvessel density. This corresponds to the lack of clinical activity seen with this agent. Our clinical trial design termed dose de-escalation is a novel approach to determine the in vivo biological effects of targeted therapies in cancer patients.