bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testosterone and Dihydrotestosterone Tissue Levels in Recurrent Prostate Cancer
Authors: Titus Mark A. , Schell Michael J. , Lih Fred B. , Tomer Kenneth B. , Mohler James L. 
Published: September 2005

Abstract
Purpose: Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor–regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA.
Experimental Designs: Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry. Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received.
Results: Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P = 0.30). Dihydrotestosterone levels decreased 91% in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P &lt; 0.0001) although dihydrotestosterone levels in most specimens of recurrent prostate cancer were sufficient for androgen receptor activation. Testosterone or dihydrotestosterone levels were not related to metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P &gt; 0.2).
Conclusions: Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer.
Prognostic Impact of Immunohistochemical Expression of Ezrin in Highly Malignant Soft Tissue Sarcomas
Authors: Weng Wen-Hui , Åhlén Jan , Åström Kristina , Lui Weng-Onn , Larsson Catharina 
Published: September 2005

AbstractPurpose: Ezrin is a cytoskeleton linker protein that is actively involved in regulating the growth and metastatic capacity of cancer cells. It has recently been reported to be involved in dissemination of pediatric soft tissue sarcoma (STS).Experimental Design: To further evaluate the prognostic value of ezrin in STS progression, we screened 50 primary STSs of high malignancy grade using immunohistochemistry. At the initial surgery, all patients were without local or distant metastasis. The expression was then compared with the outcome during follow-up for at least 4 years or until the patients' death.Results: Twenty-five of the 50 STSs analyzed (50%) showed ezrin immunoreactivity in the membrane and cytoplasm of the tumor cells. A significant association was shown between positive expressions of ezrin and death in disease as well as overall survival (P = 0.014 and 0.007, respectively). Similarly, ezrin expression was significantly associated with development of distant metastasis during follow-up (P = 0.031), also excluding locally recurrent disease (P = 0.049). The relative abundance of metastasis in ezrin-positive cases was observed both over time and irrespective of time. In comparison with clinical, histopathologic, and genetic characteristics of the STSs, ezrin expression was found to correlate significantly with an infiltrative growth pattern outside the tumor capsule as well as with copy number gain of chromosomal region 9cen-q22.Conclusion: Our findings suggest that ezrin immunoreactivity could be valuable as an additional prognostic marker in highly malignant STSs and support a causative role of ezrin in STS tumor dissemination.
Identification of Novel Human CTL Epitopes and Their Agonist Epitopes of Mesothelin
Authors: Yokokawa Junko , Palena Claudia , Arlen Philip , Hassan Raffit , Ho Mitchell , Pastan Ira , Schlom Jeffrey , Tsang Kwong Y. 
Published: September 2005

AbstractPurpose: Mesothelin is overexpressed in many pancreatic and ovarian cancers, mesotheliomas, and other tumor types. Clinical trials are ongoing using immunotoxins to target mesothelin, and patients immunized with allogeneic pancreatic tumor cell lines have shown immune responses to previously defined mesothelin epitopes. The purpose of this study was to define novel mesothelin CTL epitopes and, more importantly, agonist epitopes that would more efficiently activate human T cells to more efficiently lyse human tumors.Experimental Design and Results: Two novel mesothelin HLA-A2 epitopes were defined. T-cell lines generated from one of these epitopes were shown to lyse pancreatic and ovarian tumor cells. Several agonist epitopes were defined and were shown to (a) have higher affinity and avidity for HLA-A2, (b) activate mesothelin-specific T cells from normal individuals or cancer patients to a greater degree than the native epitope in terms of induction of higher levels of IFN-γ and the chemokine lymphotactin, and (c) lyse several mesothelin-expressing tumor types in a MHC-restricted manner more effectively than T cells generated using the native peptide. External beam radiation of tumor cells at nontoxic levels was shown to enhance the expression of mesothelin and other accessory molecules, resulting in a modest but statistically significant increase in tumor cell lysis by mesothelin-specific T cells.Conclusions: The identification of novel CTL agonist epitopes supports and extends observations that mesothelin is a potential target for immunotherapy of pancreatic and ovarian cancers, as well as mesotheliomas.
Cytoplasmic CD24 Expression in Colorectal Cancer Independently Correlates with Shortened Patient Survival
Authors: Weichert Wilko , Denkert Carsten , Burkhardt Mick , Gansukh Tserenchunt , Bellach Joachim , Altevogt Peter , Dietel Manfred , Kristiansen Glen 
Published: September 2005

AbstractPurpose: CD24 is a cell adhesion molecule that has been implicated in metastatic tumor progression of various solid tumors. We aimed to clarify the expression patterns of CD24 in colorectal cancer and to correlate these to clinicopathologic variables including patient survival.Experimental Design: 147 colorectal carcinomas and two colon carcinoma cell lines were immunostained for CD24. Cytoplasmic and membranous immunoreactivity were semiquantitatively scored. Fisher's exact test, χ2 test for trends, Kaplan-Meier analysis, and Cox's regression were applied.Results: The cell line CX-2 showed only a minimal membranous CD24 immunoreactivity, in contrast to HT29, which stained strongly in the cytoplasm. In colorectal cancer, 68.7% of the tumors showed membranous CD24 staining, whereas 84.4% showed cytoplasmic staining. In 10% of cases, an exceptionally strong cytoplasmic CD24 expression was observed. The latter significantly correlated to higher tumor stages (Dukes and pT), nodal or systemic metastasis, and higher tumor grade. In survival analysis, strong cytoplasmic CD24 expression correlated significantly (Cox's regression: P = 0.012, relative risk = 3.7) to shortened patient survival in the group of cases without distant metastases.Conclusions: CD24 is commonly up-regulated in colorectal cancer and is a new independent prognostic marker which corroborates the importance of CD24 in tumor progression of this disease.
Metronomic Low-Dose Chemotherapy Boosts CD95-Dependent Antiangiogenic Effect of the Thrombospondin Peptide ABT-510: A Complementation Antiangiogenic Strategy
Authors: Yap Ronald , Veliceasa Dorina , Emmenegger Urban , Kerbel Robert S. , McKay Laura M. , Henkin Jack , Volpert Olga V. 
Published: September 2005

Abstract
Blocking angiogenesis is a promising approach in cancer therapy. Natural inhibitors of angiogenesis and derivatives induce receptor-mediated signals, which often result in the endothelial cell death. Low-dose chemotherapy, given at short regular intervals with no prolonged breaks (metronomic chemotherapy), also targets angiogenesis by obliterating proliferating endothelial cells and circulating endothelial cell precursors. ABT-510, a peptide derivative of thrombospondin, kills endothelial cell by increasing CD95L, a ligand for the CD95 death receptor. However, CD95 expression itself is unaffected by ABT-510 and limits its efficacy. We found that multiple chemotherapy agents, cyclophosphamide (cytoxan), cisplatin, and docetaxel, induced endothelial CD95 in vitro and in vivo at low doses that failed to kill endothelial cells (cytoxan &gt; cisplatin &gt; docetaxel). Thus, we concluded that some of these agents might complement each other and together block angiogenesis with maximal efficacy. As a proof of principle, we designed an antiangiogenic cocktail combining ABT-510 with cytoxan or cisplatin. Cyclophosphamide and cisplatin synergistically increased in vivo endothelial cell apoptosis and angiosuppression by ABT-510. This synergy required CD95, as it was reversible with the CD95 decoy receptor. In a mouse model, ABT-510 and cytoxan, applied together at low doses, acted in synergy to delay tumor take, to stabilize the growth of established tumors, and to cause a long-term progression delay of PC-3 prostate carcinoma. These antitumor effects were accompanied by major decreases in microvascular density and concomitant increases of the vascular CD95, CD95L, and apoptosis. Thus, our study shows a “complementation” design of an optimal cancer treatment with the antiangiogenic peptide and a metronomic chemotherapy.
Diagnostic Evaluation of HER-2 as a Molecular Target: An Assessment of Accuracy and Reproducibility of Laboratory Testing in Large, Prospective, Randomized Clinical Trials
Authors: Press Michael F. , Sauter Guido , Bernstein Leslie , Villalobos Ivonne E. , Mirlacher Martina , Zhou Jian-Yuan , Wardeh Rooba , Li Yong-Tian , Guzman Roberta , Ma Yanling , Sullivan-Halley Jane , Santiago Angela , Park Jinha M. , Riva Alessandro , Slamon Dennis J. 
Published: September 2005

Abstract
Purpose: To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)–based clinical trials.
Experimental Design: Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies.
Results: HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [κ statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (κ statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (κ statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories.
Conclusions: Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.
A Comparison Study of Different PCR Assays in Measuring Circulating Plasma Epstein-Barr Virus DNA Levels in Patients with Nasopharyngeal Carcinoma
Authors: Le Quynh-Thu , Jones Carol D. , Yau Tsz-Kok , Shirazi Haider A. , Wong Priscilla H. , Thomas Ella N. , Patterson Bruce K. , Lee Anne W.M. , Zehnder James L. 
Published: September 2005

Abstract
Purpose: To compare the performance of three PCR assays in measuring circulating Epstein-Barr virus (EBV). DNA levels in nasopharyngeal carcinoma patients and to confirm its prognostic significance.
Experimental Design: Plasma from 58 newly diagnosed nasopharyngeal carcinoma patients were collected before, during, and every 3 to 6 months after radiotherapy. EBV DNA levels were determined by real-time quantitative PCR using primer/probe sets for polymerase-1 (Pol-1), latent membrane protein 2 (Lmp2), and BamHI-W. Pretreatment levels from the three assays were correlated with each other and serial measurements from the Pol-1 assay were correlated with clinical variables.
Results: Pol-1 was more accurate than BamHI-W in predicting EBV DNA concentrations in cell lines. Of the three assays, BamHI-W yielded the highest concentrations followed by Pol-1 in plasmas (n = 23). The correlation coefficient was 0.99 (P &lt; 0.0001) for Pol-1 and Lmp2, 0.66 (P &lt; 0.0001) for Pol-1 and BamHI-W, and 0.55 (P &lt; 0.0001) for BamHI-W and Lmp2. Elevated pretreatment DNA levels as detected by Pol-1 were correlated with advanced nodal stage (P = 0.04) and overall stage (P = 0.028). There was no correlation between pretreatment EBV DNA levels and freedom-from-relapse or overall survival; however, there was a significant correlation between posttreatment levels and these variables. The 2-year freedom-from-relapse and overall survival rates were 92% and 94% for patients with undetectable, and 37% and 55% for those with detectable, posttreatment levels (P &lt; 0.0001 and P &lt; 0.002).
Conclusions: The three PCR assays yielded similar results in detecting EBV DNA in plasmas. The Pol-1-detected posttreatment EBV DNA level was the strongest predictor for treatment outcomes.
Expression of Trefoil Factor Family Members Correlates with Patient Prognosis and Neoangiogenesis
Authors: Dhar Dipok Kumar , Wang Timothy C. , Tabara Hideki , Tonomoto Yasuhito , Maruyama Riruke , Tachibana Mitsuo , Kubota Hirofumi , Nagasue Naofumi 
Published: September 2005

Abstract
Purpose: Trefoil factor family (TFF) peptides are thought to contribute to epithelial protection and restitution by virtue of their protease-resistant nature and their strong affinity for mucins. However, they are often overexpressed in tumors, where they seem to be negative prognostic factors, possibly contributing to tumor spread, although the precise mechanisms have not been defined.
Experimental Design: Tissue sections from 111 patients with curatively resected advanced gastric carcinoma were immunohistochemically stained for TFF2, ITF (TFF3), and CD34. Microvessel density was expressed as number and area of microvessels. Results were correlated with clinicopathological characteristics and patient survival.
Results: Forty-nine (44.1%) and 41 (36.9%) tumors were immunohistochemically positive for TFF3 and TFF2, respectively. Among the various clinicopathologic variables, overexpression of TFF3 had a significant correlation with patient age only. In addition, a significantly higher prevalence of positive TFF2 staining was detected in large, diffuse tumors and in tumors with lymph node metastasis. The number of microvessels had a significant correlation with both TFF3 and TFF2 staining, whereas the area of microvessels had a significant correlation only with TFF3 staining. Both TFF3 and TFF2 were independent predictors of a worse disease-free survival. TFF3 had a gender-specific negative survival advantage, with a 91.3% disease-free survival in female patients with TFF3-negative advanced gastric carcinoma.
Conclusions: Induction of increased tumor vascularity might be one of the mechanisms by which TFFs confer metastatic phenotype and frequent disease recurrence in gastric carcinomas. Female patients with TFF3-negative advanced gastric carcinoma have comparable survival as that reported for patients with early gastric carcinoma.
Quantitation of Minimal Residual Disease in Acute Myeloid Leukemia by Tryptase Monitoring Identifies a Group of Patients with a High Risk of Relapse
Authors: Sperr Wolfgang R. , Mitterbauer Margit , Mitterbauer Gerlinde , Kundi Michael , Jäger Ulrich , Lechner Klaus , Valent Peter 
Published: September 2005

Abstract
Purpose: Recent data suggest that tryptase is produced by blast cells in a group of patients with acute myeloid leukemia (AML). In these patients, serum tryptase levels are elevated at diagnosis and decrease to normal (&lt;15 ng/mL) or near normal values in those achieving complete hematologic remission (CR) after chemotherapy.
Patients: In this study, we examined the value of tryptase as a marker of minimal residual AML. In 61 patients with de novo AML exhibiting elevated serum tryptase (&gt;15 ng/mL) at diagnosis, tryptase levels were measured serially during and after chemotherapy by a fluoroenzyme immunoassay.
Results: Of the 61 patients, 42 (68.9%) entered hematologic CR in response to induction chemotherapy. Twenty-nine of these 42 patients also entered biochemical remission (BR) defined by a decrease of tryptase levels to normal (&lt;15 ng/mL). The remaining 13 patients exhibited elevated enzyme levels despite of hematologic CR. As assessed by multivariate analysis, the elevated tryptase in CR was found to be an independent prognostic variable concerning disease-free survival. Thus, AML relapses occurred in 15 of 29 patients with CR + BR (52%) and in 12 of 13 patients with CR without BR (92%), resulting in a significantly reduced probability of continuous CR for patients with CR without BR (P &lt; 0.05). In all patients with continuous hematologic CR, tryptase levels remained constantly normal, whereas a recurrent elevation of tryptase in CR was invariably followed by a hematologic relapse.
Conclusion: A persistently elevated tryptase level in AML in CR is indicative of minimal residual AML and associated with a high risk of relapse.
Approval Summary for Erlotinib for Treatment of Patients with Locally Advanced or Metastatic Non–Small Cell Lung Cancer after Failure of at Least One Prior Chemotherapy Regimen
Authors: Johnson John R. , Cohen Martin , Sridhara Rajeshwari , Chen Yeh-Fong , Williams Gene M. , Duan John , Gobburu Jogarao , Booth Brian , Benson Kimberly , Leighton John , Hsieh Li Shan , Chidambaram Nallalerumal , Zimmerman Paul , Pazdur Richard 
Published: September 2005

Abstract
Purpose: To describe the Food and Drug Administration (FDA) review and approval of erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) for treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen.
Experimental Design: The FDA reviewed raw data in electronic format from a randomized controlled clinical trial comparing erlotinib with placebo in patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.
Results: Patients were randomized in a 2:1 ratio (erlotinib, n = 488 and placebo, n = 243). Erlotinib was superior to placebo for survival, progression-free survival, and tumor response rate. Exploratory analyses indicate that epidermal growth factor receptor status may be an important predictor of the erlotinib survival effect. Rash (75% versus 17%) and diarrhea (54% versus 18%) in the erlotnib and placebo group respectively were the most common adverse events. Severe rash occurred in 9% and severe diarrhea in 6% of erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reductions were required for 10% of patients with rash and 4% of patients with diarrhea.
Conclusions: On November 18, 2004, the FDA granted erlotinib regular approval for treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. The applicant has committed to conduct post-marketing clinical trials to assess further the effect of epidermal growth factor receptor expression, measured with immunohistochemical staining, on erlotinib treatment effect.
The −251T Allele of the Interleukin-8 Promoter Is Associated with Increased Risk of Gastric Carcinoma Featuring Diffuse-Type Histopathology in Chinese Population
Authors: Lee Wei-Ping , Tai Dar-In , Lan Keng-Hsin , Li Anna Fen-Yau , Hsu Hou-Ching , Lin En-Ju , Lin Yi-Ping , Sheu Meei-Ling , Li Chung-Pin , Chang Full-Young , Chao Yee , Yen Shang-Heu , Lee Shou-Dong 
Published: September 2005

AbstractPurpose: Persistent interleukin-8 (IL-8) production contributes to chronic inflammation of the stomach. The proinflammatory IL-1β polymorphisms, which enhance the cytokine production, are associated with increased risk of gastric cancer. The −251A/T polymorphism of the IL-8 promoter is involved in several human diseases. Particularly, the −251A is associated with decreased risk of colorectal cancer. We aimed to determine whether the −251 allele resulting in high IL-8 expression was associated with increased risk of gastric carcinoma.Experimental Design: The −251A/T promoters were cloned and analyzed by luciferase assay. Binding of nuclear proteins to the −251A/T promoters was analyzed by electrophoretic mobility shift assay. The −251A/T promoters were differentiated by PCR-RFLP. Comparison of gastric cancer risk between the −251A/T promoters was done by a case-control study.Results: The −251T allele possessed transcriptional activity 2- to 5-fold stronger than the −251A counterpart. Electrophoretic mobility shift assay showed that the −251A promoter had strong ability to bind to an unknown protein or multiprotein complex. The −251T allele was associated with increased risk of noncardia (Ptrend = 0.012) and cardia (Ptrend = 0.029) carcinomas. Gastric carcinoma patients with the low-risk AA genotype had a tendency to sustain intestinal-type carcinomas (χ2 = 6.816; P = 0.033); however, the high-risk −251T allele was associated with &gt;2-fold increased risk of diffuse-type (AA versus AT + TT: odds ratio, 2.52; 95% confidence interval, 1.16-5.49; P = 0.017) and mixed-type (AA versus AT + TT: odds ratio, 2.22; 95% confidence interval, 1.12-4.40; P = 0.019) carcinomas.Conclusions: The IL-8 −251T allele is significantly associated with increased risk of gastric carcinoma, particularly the diffuse and mixed types in Chinese population.
Limitations of Screening for Lung Cancer with Low-Dose Spiral Computed Tomography
Authors: Jett James R. 
Published: September 2005

Abstract
Past lung cancer screening trials in the United States with chest X-ray and sputum cytology were not able to show any decrease in lung cancer mortality; however, these trials are over 20 years old. Recent follow-up of the Mayo Lung Project showed a better survival from lung cancer in the screened arm, but no difference in overall mortality, suggesting an overdiagnosis of nonfatal cancers. Recent reports of low radiation dose spiral computed tomography (CT) chest screening for lung cancer have shown that CT screening detects cancers at a smaller size than chest X-rays. To date, there have been no randomized trials of CT versus observation or chest radiographs for screening purposes. All data available thus far on CT screening are from phase II proof-of-principle trials. The major limitations of CT screening, discussed here, include (a) a high rate of nodule detection: over 50% of participants will have at least one noncalcified nodule; (b) resulting follow-up CT scans, associated with increased costs; (c) cost and morbidity of biopsy or resection of benign noncalcified nodule (20-25% of such procedures in several trials); and (d) a small, but difficult to quantify, risk of cancer associated with multiple follow-up CT scans.