bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matrix Metalloproteinase 3 Polymorphism
Authors: Blons Hélène , Gad Sophie , Zinzindohoué Franck , Manière Isabelle , Beauregard Janie , Tregouet David , Brasnu Daniel , Beaune Philippe , Laccourreye Ollivier , Laurent-Puig Pierre 
Published: September 2005

Abstract
Purpose: Treatment of head and neck cancer often associates different therapeutic modalities, including surgery, radiotherapy, and chemotherapy. In an attempt to optimize therapeutics, the identification of molecular markers linked to response to chemotherapy remains important. Recently, the involvement of metalloproteinases in resistance to chemotherapy was suggested through their interaction with the Fas/Fas ligand pathway. Indeed metalloproteinases enhance Fas ligand shedding modulating chemotherapy efficiency. On the basis of these findings, we tested the existence of a correlation between response to chemotherapy and four metalloproteinase polymorphisms in a prospective series of 148 head and neck cancer patients.
Experimental Design: Patients were genotyped using automated fragment analysis and 5′-nuclease allelic discrimination assay. Response to chemotherapy was clinically assessed without knowledge of the genotype status.
Results: A significant relation between the metalloproteinase type 3 (MMP3) −1612insA polymorphism and response to chemotherapy was identified. Indeed, patients with the 6A/6A genotype responded more frequently (86%) to treatment as compared with patients with the 5A/6A (65%) or 5A/5A (55%) genotypes (P = 0.04). A multivariate analysis, including tumor stage, gender, TP53 mutations, and MMP3 polymorphism, showed that the 6A/6A genotype was an independent factor of response to 5-fluorouracil-cisplatin chemotherapy in head and neck cancer patients with an odds ratio of 6.7 as compared with the 5A/5A genotype.
Conclusions: This work showed that genotyping the MMP3 gene enhancer polymorphism −1612insA could help predict chemosensitivity in head and neck cancer patients.
PC Cell-Derived Growth Factor Expression in Prostatic Intraepithelial Neoplasia and Prostatic Adenocarcinoma
Authors: Pan Chong-Xian , Kinch Michael S. , Kiener Peter A. , Langermann Solomon , Serrero Ginette , Sun Le , Corvera Joseph , Sweeney Christopher J. , Li Lang , Zhang Shaobo , Baldridge Lee Ann , Jones Timothy D. , Koch Michael O. , Ulbright Thomas M. , Eble John N. , Cheng Liang 
Published: September 2005

Abstract
Purpose: PCDGF (PC cell-derived growth factor), also called progranulin, is a Mr 88,000 glycoprotein precursor of granulin. It is a novel growth factor that stimulates cell proliferation, confers epithelial tumorigenesis, and promotes tumor invasion. Here we investigate the potential of PCDGF as a therapeutic target for prostate cancer.
Experimental Design: We studied the expression of PCDGF in invasive prostate cancer, adjacent high-grade prostatic intraepithelial neoplasia (PIN), and benign prostate tissue from 99 human prostate specimens. The level of PCDGF expression was correlated with various clinicopathological characteristics.
Results: Normal prostate tissue did not express (53/99), or expressed low levels (46/99) of PCDGF. In the 46 normal prostate specimens that expressed PCDGF, most of them had less than 10% of cells expressing PCDGF. PCDGF expression could be detected in more than 50% of cells in all specimens of PIN and invasive prostate cancer. The expression of PCDGF in normal prostate tissue was much less intense and in a smaller fraction of cells than in PIN and invasive adenocarcinoma (P &lt; 0.0001). There was no correlation of PCDGF expression with age, Gleason score, pathological stage, status of lymph node metastasis, extraprostatic extension, perineural invasion, surgical margins, and vascular invasion.
Conclusions: Our data suggest that the induction of PCDGF expression occurs during the development of PIN. PCDGF may be a new molecular target for the treatment and prevention of prostate cancer.
Alterations of
p16
and Prognosis in Biliary Tract Cancers from a Population-Based Study in China
Authors: Ueki Takashi , Hsing Ann W. , Gao Yu-Tang , Wang Bing-Sheng , Shen Ming-Chang , Cheng Jiarong , Deng Jie , Fraumeni Joseph F. , Rashid Asif 
Published: September 2005

Abstract
Purpose: Biliary tract cancer is an uncommon malignancy with a poor survival rate. We evaluated p16 gene alteration as a prognostic marker for this disease.
Experimental Design: We studied p16 gene alterations by sequencing, methylation, and loss of heterozygosity of chromosome 9p in 118 biliary tract carcinomas, including 68 gallbladder cancers, 33 extrahepatic bile duct cancers, and 17 ampullary cancers. Survival was evaluated in 57 patients with gallbladder carcinomas, 27 with bile duct carcinomas, and 16 with ampullary carcinomas with and without somatic p16 alterations detected by two different methods.
Results: p16 gene alterations including silent mutations were present in 61.8% gallbladder cancers, 54.5% bile duct cancers, and 70.6% ampullary cancers. p16 gene nonsilent mutations, p16 methylation, and loss of chromosome 9p21-22 that targets p14, p15, and p16 genes were present in 13 of 53 (24.5%), 8 of 54 (14.8%), and 32 of 44 (72.7%) gallbladder tumors; 5 of 25 (20.0%), 5 of 31 (16.1%), and 12 of 21 (57.1%) bile duct tumors; and 3 of 13 (23.1%), 6 of 15 (40.0%), and 8 of 16 (50.0%) ampullary tumors, respectively. The mean survival of patients with gallbladder cancers without p16 alterations was 21.5 ± 14.8 months compared with 12.1 ± 11.4 months for patients with p16 alterations (P = 0.02).
Conclusions: Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma, with more favorable survival rates associated with carcinomas lacking p16 gene alterations.
Induction of Apoptosis in Human Myeloid Leukemic Cells by 1′-Acetoxychavicol Acetate through a Mitochondrial- and Fas-Mediated Dual Mechanism
Authors: Ito Keisuke , Nakazato Tomonori , Murakami Akira , Yamato Kenji , Miyakawa Yoshitaka , Yamada Taketo , Hozumi Nobumichi , Ohigashi Hajime , Ikeda Yasuo , Kizaki Masahiro 
Published: September 2005

AbstractPurpose: The purpose of this investigation was to determine the antileukemic effects of 1′-acetoxychavicol acetate (ACA) obtained from rhizomes of the commonly used ethno-medicinal plant Languas galanga (Zingiberaceae).Experimental Design: We evaluated the effects of ACA on various myeloid leukemic cells in vitro and in vivo. We further examined the molecular mechanisms of ACA-induced apoptosis in myeloid leukemic cells.Results: Low-dose ACA dramatically inhibited cellular growth of leukemic cells by inducing apoptosis. Because NB4 promyelocytic leukemic cells were most sensitive to ACA, we used NB4 cells for further analyses. Production of reactive oxygen species triggered ACA-induced apoptosis. ACA-induced apoptosis in NB4 cells was in association with the loss of mitochondrial transmembrane potential (ΔΨm) and activation of caspase-9, suggesting that ACA-induced death signaling is mediated through a mitochondrial oxygen stress pathway. In addition, ACA activated Fas-mediated apoptosis by inducing of casapse-8 activity. Pretreatment with the thiol antioxidant N-acetyl-l-cysteine (NAC) did not inhibit caspase-8 activation, and the antagonistic anti-Fas antibody ZB4 did not block generation of reactive oxygen species, indicating that both pathways were involved independently in ACA-induced apoptosis. Furthermore, ACA had a survival advantage in vivo in a nonobese diabetic/severe combined immunodeficient mice leukemia model without any toxic effects.Conclusions: We conclude that ACA induces apoptosis in myeloid leukemic cells via independent dual pathways. In addition, ACA has potential as a novel therapeutic agent for the treatment of myeloid leukemia.
The Androgen Axis in Recurrent Prostate Cancer
Authors: Mohler James L. , Gregory Christopher W. , Ford O. Harris , Kim Desok , Weaver Catharina M. , Petrusz Peter , Wilson Elizabeth M. , French Frank S. 
Published: September 2005

AbstractPurpose. Prostate cancer that recurs during androgen deprivation therapy is referred to as androgen-independent. High levels of expression of androgen receptor and androgen receptor-regulated genes in recurrent prostate cancer suggest a role for androgen receptor and its ligands in prostate cancer recurrence.Experimental Design. Recurrent prostate cancer specimens from 22 men whose prostate cancer recurred locally during androgen deprivation therapy and benign prostate specimens from 48 men who had received no prior treatment were studied. Androgen receptor expression was measured using monoclonal antibody and automated digital video image analysis. Tissue androgens were measured using radioimmunoassay.Results. Epithelial nuclei androgen receptor immunostaining in recurrent prostate cancer (mean optical density, 0.284 ± SD 0.115 and percentage positive nuclei, 83.7 ± 11.6) was similar to benign prostate (mean optical density, 0.315 ± 0.044 and percentage positive nuclei, 77.3 ± 13.0). Tissue levels of testosterone were similar in recurrent prostate cancer (2.78 ± 2.34 pmol/g tissue) and benign prostate (3.26 ± 2.66 pmol/g tissue). Tissue levels of dihydrotestosterone, dehydroepiandrosterone, and androstenedione were lower (Wilcoxon, P = 0.0000068, 0.00093, and 0.0089, respectively) in recurrent prostate cancer than in benign prostate, and mean dihydrotestosterone levels, although reduced, remained 1.45 nm. Androgen receptor activation in recurrent prostate cancer was suggested by the androgen-regulated gene product, prostate-specific antigen, at 8.80 ± 10.80 nmol/g tissue.Conclusions. Testosterone and dihydrotestosterone occur in recurrent prostate cancer tissue at levels sufficient to activate androgen receptor. Novel therapies for recurrent prostate cancer should target androgen receptor directly and prevent the formation of androgens within prostate cancer tissue.
Camptothecin Analogs (Irinotecan or Topotecan) plus High-Dose Cyclophosphamide as Preparative Regimens for Antibody-Based Immunotherapy in Resistant Neuroblastoma
Authors: Kushner Brian H. , Kramer Kim , Modak Shakeel , Cheung Nai-Kong V. 
Published: September 2005

Abstract
Purpose: We used high-dose cyclophosphamide plus topotecan/vincristine (CTV) or irinotecan (C/I) in patients with resistant neuroblastoma. The aim was to use a regimen with little risk to major organs to (a) achieve or consolidate remission in heavily treated patients and to (b) induce an immunological state conducive to passive immunotherapy with the murine 3F8 antibody.
Experimental Design: CTV and C/I included cyclophosphamide 140 mg/kg (∼4200 mg/m2). With CTV, topotecan 2 mg/m2 was infused i.v. (30 min) on days 1–4 (total, 8 mg/m2), and vincristine 0.067 mg/kg was injected on day 1. With C/I, irinotecan, 50 mg/m2 was infused i.v. (1 h) on days 1–5 (total, 250 mg/m2). Mesna and granulocyte colony-stimulating factor were used.
Results: Twenty-nine patients received 38 courses of CTV, and 26 patients received 38 courses of C/I. All patients had previously received topotecan, a hemopoietic stem-cell transplant, and/or high-dose cyclophosphamide. CTV and C/I caused myelosuppression of comparably prolonged duration as follows: absolute neutrophil counts &lt;500/μl lasted 5–12 days in patients who had not previously received transplant and 7–21 days in patients who were post-transplant. Other significant toxicities included typhlitis (two CTV-treated patients, one C/I-treated patient) and hemorrhagic cystitis (one C/I-treated patient). Major responses were seen in 4 (15%) of 26 CTV and 4 (17%) of 24 C/I-treated patients with assessable disease. Bone marrow disease resolved in 5 (28%) of 18 CTV-treated patients and in 4 (27%) of 15 C/I-treated patients. 3F8 after CTV or C/I was not blocked by neutralizing antibodies, consistent with the desired immunosuppressive effect of high-dose cyclophosphamide.
Conclusions: CTV and C/I require transfusional and antibiotic support but otherwise entail tolerable morbidity. They have modest antineuroblastoma activity in heavily treated patients and are good preparative regimens for passive immunotherapy with monoclonal antibodies.
State of the Translational Science
Authors: Zelent Arthur , Waxman Samuel , Carducci Michael , Wright John , Zweibel James , Gore Steven D. 
Published: September 2005

Abstract
A workshop was held in Baltimore, Maryland in January 2003 to discuss translational aspects of cancer therapies targeted at impacting aberrant gene transcription due to epigenetic changes. The mission of the meeting was the development of strategies for scientifically sound, clinically feasible applications targeting epigenetics in cancer therapy. Sessions included preclinical discussions of DNA methylation, the histone code, chromatin remodeling, and transcriptional control. Data on the histone deacetylase and DNA methyltransferase inhibitors under preclinical and clinical investigation were presented and discussed. The optimal correlative laboratory studies for monitoring clinical trials with these agents remain controversial. DNA methyltransferase and histone deacetylase inhibitors will be combined with each other to maximally re-express genes silenced through promoter methylation. Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs.
Decreased Nucleotide Excision Repair Activity and Alterations of Topoisomerase IIα Are Associated with thein VivoResistance of a P388 Leukemia Subline to F11782, a Novel Catalytic Inhibitor of Topoisomerases I and II
Authors: Kruczynski Anna , Barret Jean-Marc , van Hille Benoît , Chansard Nathalie , Astruc Jackie , Menon Yoann , Duchier Carole , Créancier Laurent , Hill Bridget T. 
Published: September 2005

AbstractPurpose: The purpose of the study was to investigate the mechanisms associated with antitumor activity and resistance to F11782, a novel dual catalytic inhibitor of topoisomerases with DNA repair-inhibitory properties.Experimental Design: For that purpose, an F11782-resistant P388 leukemia subline (P388/F11782) has been developed in vivo and characterized.Results: Weekly subtherapeutic doses of F11782 (10 mg/kg) induced complete resistance to F11782 after 8 weekly passages. This resistant P388/F11782 subline retained some in vivo sensitivity to several DNA-topoisomerase II and/or I complex-stabilizing poisons and showed marked collateral sensitivity to cisplatin, topotecan, colchicine, and Vinca alkaloids, while proving completely cross-resistant only to merbarone and doxorubicin. Therefore, resistance to F11782 did not appear to be associated with a classic multidrug resistance profile, as further reflected by unaltered drug uptake and no overexpression of resistance-related proteins or modification of the glutathione-mediated detoxification process. In vivo resistance to F11782 was, however, associated with a marked reduction in topoisomerase IIα protein (87%) and mRNA (50%) levels, as well as a diminution of the catalytic activity of topoisomerase IIα. In contrast, only minor reductions in topoisomerases IIβ and I levels were recorded. However, of major interest, nucleotide excision repair activity was decreased 3-fold in these P388/F11782 cells and was more specifically associated with a decreased (67%) level of XPG (human xeroderma pigmentosum group G complementing protein), an endonuclease involved in this DNA repair system.Conclusions: These findings suggest that both topoisomerase IIα and XPG are major targets of F11782 in vivo and further demonstrate the original mechanism of action of this novel compound.
Clinical Significance of Cellular Distribution of Moesin in Patients with Oral Squamous Cell Carcinoma
Authors: Kobayashi Hiroichi , Sagara Junji , Kurita Hiroshi , Morifuji Masayo , Ohishi Masamichi , Kurashina Kenji , Taniguchi Shun’ichiro 
Published: September 2005

Abstract
Purpose: Moesin is a linking protein of the submembraneous cytoskeleton and plays a key role in the control of cell morphology, adhesion, and motility. The aim of the present study was to elucidate the clinical significance of expression patterns of moesin in patients with oral squamous cell carcinoma (OSCC).
Experimental Design: Immunohistochemistry for moesin monoclonal antibody was performed on 103 paraffin-embedded specimens from patients with primary OSCC, including 30 patients with locoregional lymph node metastasis, and in the sections from nude mice transplanted with two cell lines derived from a single human tongue cancer (SQUU-A and SQUU-B).
Results: Expression patterns of moesin in OSCCs were divided into three groups: membranous pattern; mixed pattern; and cytoplasmic pattern. These expression patterns correlated with tumor size, lymph node metastasis, mode of invasion, differentiation, and lymphocytic infiltration. In about two-thirds of the patients with metastatic lymph node, homogeneous cytoplasmic expression was detected in the metastatic lymph nodes. In addition, SQUU-B with high metastatic potential showed more reduced levels of membrane-bound moesin than SQUU-A with low metastatic potential. A multivariate analysis demonstrated that expression patterns of moesin can be an independent prognostic factor.
Conclusions: Our results suggest that moesin expression contributed to discriminating between patients with the potentiality for locoregional lymph node metastasis and those with a better prognosis and might improve the definition of suitable therapy for each.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells
Authors: Ballestrero Alberto , Nencioni Alessio , Boy Davide , Rocco Ilaria , Garuti Anna , Mela Giuseppe Sandro , Van Parijs Luk , Brossart Peter , Wesselborg Sebastian , Patrone Franco 
Published: September 2005

Abstract
Purpose: Overexpression of antiapoptotic Bcl-2 family members has recently been related to resistance to chemo/radiotherapy in several human malignancies, particularly lymphomas. Hence, innovative approaches bypassing this resistance mechanism are required in the therapeutic approach. This study evaluated whether chemoresistance associated with Bcl-2 and Bcl-xL overexpression would be overcome by activating the death receptor pathway by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the Jurkat cell model
Experimental Design: We made use of genetically modified Jurkat cells to evaluate the effect of Bcl-2 or Bcl-xL overexpression on the cytotoxic effect produced by the anticancer drugs doxorubicin, etoposide, and oxaliplatin and TRAIL. Caspase activation was detected by cleavage of caspase-8 and -3. The mitochondrial transmambrane potential was assessed by staining with DiOC6 and flow cytometry. Caspase activity was blocked by the broad-spectrum caspase inhibitor zVAD-fmk.
Results: Bcl-2 and Bcl-xL overexpression but not lack of caspase-8 protects the Jurkat cells from the anticancer drug-induced cytolysis. However, Bcl-2/Bcl-xL Jurkat cells retained some susceptibility to TRAIL-induced cytolysis. A highly synergistic cytotoxic effect of the combination of TRAIL with any of the antiblastic used in this study was detected in the chemoresistant cells. This effect was associated with mitochondrial disassemblage and dependent on caspase activation
Conclusions: The combination of TRAIL with conventional anticancer drugs may prove to be useful in the treatment of antiapoptotic Bcl-2 family proteins-expressing malignancies.
Correlation of Osteopontin Protein Expression and Pathological Stage across a Wide Variety of Tumor Histologies
Authors: Coppola Domenico , Szabo Marianna , Boulware David , Muraca Patrick , Alsarraj Marwan , Chambers Ann F. , Yeatman Timothy J. 
Published: September 2005

Abstract
Purpose: Osteopontin (OPN) is an integrin-binding protein overexpressed in various experimental models of malignancy and appears to be involved in tumorigenesis and metastasis. Although various studies have assessed OPN protein levels in several tumor types, a broad survey of OPN expression in human neoplasia under the same experimental conditions has not been carried out.
Experimental Design: We used immunohistochemistry to detect OPN in a selection of 350 human tumors and 113 normal tissues, from a variety of body sites, using stage-oriented human cancer tissue arrays. Tumors included malignancies from breast (26), ovary (22), endometrium (14), esophagus (10), stomach (11), pancreas (16), bile duct (1), liver (9), colon (20), kidney (53), bladder (33), prostate (28), head and neck (60), salivary glands (14), lung (17), skin (6), and brain (10).
Results: High cytoplasmic OPN staining was observed in 100% of gastric carcinomas, 85% of colorectal carcinomas, 82% of transitional cell carcinomas of the renal pelvis, 81% of pancreatic carcinomas, 72% of renal cell carcinomas, 71% of lung and endometrial carcinomas, 70% of esophageal carcinomas, 58% of squamous cell carcinomas of the head and neck, and 59% of ovarian carcinomas. Although OPN expression was identified in a good number of bladder, prostate, and brain tumors, the majority of 6 skin cancers, 11 of 14 salivary gland cancers, 2 thyroid carcinomas, and 23 of 26 breast cancers revealed low OPN positivity or were negative. When considering all sites, OPN expression significantly correlated with tumor stage (Spearman’s correlation coefficient, P = 0.0002). OPN score and stage were also significantly correlated for specific cancer sites including bladder (P = 0.01), colon (P = 0.004), kidney (P = 0.0001), larynx (P = 0.035), mouth (P = 0.046), and salivary gland (P = 0.011).
Conclusions: This study reports the broad distribution of OPN in human tumors from different body sites, suggesting involvement of this protein in tumor formation. The strong correlation between pathological stage and OPN across multiple tumor types suggests a role for OPN in tumor progression.