bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene transfer to cervical cancer with fiber‐modified adenoviruses
Authors: Rein Daniel T. , Breidenbach Martina , Wu Hongju , Han Tie , Haviv Yosef S. , Wang Minghui , Kirby Tyler O. , Kawakami Yosuke , Dall Peter , Alvarez Ronald D. , Curiel David T. 
Published: May 2004

AbstractSuccessful adenoviral (Ad) vector–mediated strategies for cancer gene therapy mandate gene‐delivery systems that are capable of achieving efficient gene delivery in vivo. In many cancer types, in vivo gene‐transfer efficiency remains limited due to the low or highly variable expression of the primary Ad receptor, the coxsackie Ad receptor (CAR). In this study, we evaluated the expression of CAR on cervical cancer cells as well as CAR‐independent targeting strategies to integrins (Ad5.RGD), heparan sulfate proteoglycans (Ad5.pK7) or both (Ad5.RGD.pK7). We used a panel of established cervical cancer cell lines and primary cervical cancer cells isolated from patients to quantify the expression of CAR mRNA and to evaluate the gene‐transfer efficiency of fiber‐modified Ads. Of the fiber‐modified vectors, Ad5.pK7 and Ad5.RGD.pK7 displayed significantly enhanced gene‐transfer efficiency in vitro. Gene‐delivery efficiency in vivo was evaluated using an s.c. cervical cancer mouse model. Ad5.RGD.pK7 significantly improves tumor targeting in vivo, resulting in a significantly improved tumor/liver ratio in mice. Our results suggest that the double‐modified Ad5.RGD.pk7 vector enhances gene transfer to clinically relevant cervical cancer substrates, while the infectivity of nontarget cells in the mouse is not increased and comparable to Ad5. The fiber‐modified virus described here can help achieve higher clinical efficacy of cervical cancer gene therapy. © 2004 Wiley‐Liss, Inc.
Identification of a small peptide that inhibits the phosphorylation of ErbB2 and proliferation of ErbB2 overexpressing breast cancer cells
Authors: Pero Stephanie C. , Shukla Girja S. , Armstrong Amy L. , Peterson Daniel , Fuller Susan P. , Godin Katherine , Kingsley‐Richards Sarah L. , Weaver Donald L. , Bond Jeffrey , Krag David N. 
Published: May 2004

AbstractErbB2 is overexpressed in approximately 30% of breast cancer patients with a correlation to poor prognosis. ErbB2 has been identified as a useful receptor for molecular targeting. A cyclic 20 amino acid phage display random peptide library was constructed using the fUSE5 gene III system. The library was panned against 2 different purified forms of the external domain of ErbB2. This resulted in the identification of several ErbB2‐binding phage clones with variable binding to different ErbB2 preparations. One clone (EC‐1) bound all preparations of ErbB2 including live cells and fresh frozen human breast cancer specimens. The synthetic peptide based on the deduced sequence of the EC‐1 clone and its biotin‐conjugated form retained binding affinity for purified ErbB2 and ErbB2 overexpressing cell lysates. EC‐1 peptide was able to effectively inhibit the phosphorylation of ErbB2 on residues Y1248 and Y877 in a dose‐ and time‐dependent manner. Furthermore, EC‐1 peptide selectively inhibits the proliferation of ErbB2 overexpressing breast cancer cells. The linear portion of the cyclic EC‐1 peptide was shown to be essential for binding ErbB2. In addition, 4 biased phage libraries were constructed allowing 4 different regions of the EC‐1 peptide to have random sequence. Screening these EC‐1 biased libraries did not result in higher affinity peptides but did demonstrate the importance of amino acids at position 1–4 on the N‐terminal flanking arm and 11–15 within the cyclic ring. Interestingly, EC‐1 contains homologous motifs with known ErbB receptor family ligands. We have identified a small peptide that binds to the extracellular domain of ErbB2, inhibits ErbB2 autophosphorylation and inhibits the proliferation of ErbB2 overexpressing cells. This supports the notion that small peptides can bind to targets important in cancer therapy even if a target does not have a natural ligand. Continuing research with this peptide includes increasing its affinity to ErbB2, evaluation of pharmacokinetics and evaluation of anti‐proliferative effects with conjugate anti‐cancer agents. © 2004 Wiley‐Liss, Inc.
Frequent amplification and overexpression of CCND1 in male breast cancer
Authors: Bärlund Maarit , Kuukasjärvi Tuula , Syrjäkoski Kirsi , Auvinen Anssi , Kallioniemi Anne 
Published: May 2004

AbstractGenetic events underlying the pathogenesis of breast cancer have been studied extensively and several clinically significant markers have been identified. For example, amplification and overexpression of the ERBB2 oncogene is associated with poor prognosis in breast cancer and ERBB2 serves as a target for antibody‐based therapy. Current knowledge on the pathogenesis of male breast cancer (MBC) is limited. The purpose of our study was to investigate the potential relevance of a series of genes known to be amplified in female breast cancer (FBC) in a the development and pathogenesis of MBC. To this end, we applied fluorescence in situ hybridization and immunohistochemistry to the analysis of 128 breast tumors from males. Amplification of ERBB2, MYC, PPM1D and ZNF217 was detected rarely (1–2% of tumors) indicating a considerably lower amplification frequency than in FBC. CCND1 amplification was observed in 12% of cases, being in good concordance with findings from FBC. In addition, CCND1 overexpression was detected in 63% of tumors and was associated with ER positivity (p < 0.0001). Our results indicate distinct differences in the genetic basis of MBC and FBC and suggest that marked differences exist in the pathogenesis of these diseases. The lack of ERBB2 involvement was especially unexpected and implies that ERBB2‐targeted therapies are unlikely to be beneficial in MBC. Furthermore, the high frequency of hormone receptor positivity and the association between ER positivity and CCND1 overexpression supports the notion that hormonal regulation is likely to be essential for the development of MBC. © 2004 Wiley‐Liss, Inc.
In vitro blockade of receptor activator of nuclear factor‐κB ligand prevents osteoclastogenesis induced by neuroblastoma cells
Authors: Granchi Donatella , Amato Ilaria , Battistelli Luca , Avnet Sofia , Capaccioli Sergio , Papucci Laura , Donnini Martino , Pellacani Andrea , Brandi Maria Luisa , Giunti Armando , Baldini Nicola 
Published: May 2004

AbstractProliferation and differentiation of osteoclasts are regulated by a cytokine system that includes RANKL, which binds 2 receptors: RANK, which activates osteoclast differentiation, and osteoprotegerin (OPG), a decoy receptor that limits RANKL action. We investigated the role of the OPG/RANKL/RANK network in the pathogenesis of skeletal metastasis in neuroblastoma. Four different neuroblastoma cell lines (NB100, CHP212, SH‐SY5Y, SJ‐NK‐P) showed a large amount of OPG and RANKL transcripts. Soluble RANKL was detectable in all cell lines, but poor release of OPG was observed. SH‐SY5Y showed the lowest OPG‐to‐RANKL ratio and promoted osteoclastic differentiation of FLG29.1 and peripheral mononuclear cells, inducing expression of the osteoclast markers RANK, c‐src, c‐fos, cathepsin‐K and TRAP. SJ‐N‐KP, which released both OPG and RANKL, did not show the same capability. OPG, neutralizing anti‐RANKL antibody and antisense oligonucleotides were evaluated for their ability to inhibit RANKL activity. The neutralizing antibody hampered osteoclastic differentiation by blocking both the juxtacrine and the paracrine activity of RANKL. Our findings confirm that neuroblastoma cells induce osteoclastogenesis via RANKL and suggest that the RANKL expression associated with lack of the decoy receptor OPG could be a peculiarity of some tumors that makes them able to induce metastatic osteolysis. Moreover, our results suggest that RANKL could be a relevant target in the adjuvant therapy of bone metastatic neuroblastoma as proper neutralization revokes completely osteoclastic differentiation. © 2004 Wiley‐Liss, Inc.
Non‐self‐discrimination as a driving concept in the identification of an immunodominant HMW‐MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients
Authors: Dummer Reinhard , Mittelman Abraham , Fanizzi Francesco P. , Lucchese Guglielmo , Willers Jörg , Kanduc Darja 
Published: May 2004

AbstractWe analyzed the sera of patients with melanoma to define the human humoral autoantibody profile towards HMW‐MAA. Computational proteome scanning using the non‐self‐discrimination principle as a guide led to the individuation of the low‐similarity HMW‐MAA781–789RATVWMLRL peptide fragment as an immunodominant B‐cell epitope. Linear B‐cell determinant individuation was experimentally validated by dot blot immunoassay and NMR spectroscopy analysis. Regulation of physiologic self‐reactivity by the non‐self‐discrimination principle is discussed. © 2004 Wiley‐Liss, Inc.
Clinical relevance of amphiregulin and VEGF in primary breast cancers
Authors: Desruisseau Sylvie , Palmari Jaqueline , Giusti Corinne , Romain Sylvie , Martin Pierre‐Marie , Berthois Yolande 
Published: May 2004

AbstractThe characterization of novel prognostic markers in breast cancer is necessary to improve the identification of high‐risk populations. In our study, the prognostic significance of VEGF and amphiregulin (AR) was investigated and compared to conventional prognostic factors in primary breast cancers. The analysis was performed using enzyme‐linked immuno‐assay in a series of 193 patients, and univariate and multivariate analysis were performed in the overall population as well as in pre‐ and post‐menopausal patients subdivided in node‐negative (N−) and node‐positive (N+) subsets. AR (median, 44.8 pg/mg protein) appeared strongly correlated with progesterone receptors (PgR) (p = 0.0018) in the premenopausal N+ population, and with uPA (p= 0.020) and VEGF (p= 0.0053) in the postmenopausal/N+ patients. Despite these attractive data, AR expression was not significant for recurrence or survival outcome. Data revealed strong correlation between VEGF and uPA, and PAI‐1, in the N+ population. Moreover, patients with high VEGF levels displayed poor outcome, with an increased risk for N+ subset. These data were confirmed by multivariate analysis that presented histologic grade (HR, 10.55, p = 0.001) and VEGF (HR, 3.89, p = 0.03) as the prominent prognostic markers for overall survival for the N+ population. Furthermore, infiltrating ductal carcinomas (IDC) were shown to express higher levels of both uPA (p < 0.0001) and VEGF (p = 0.002) than intralobular carcinomas. This retrospective study reinforces the pejorative biological role of VEGF in the progression of breast tumors. Our data also suggest that VEGF and uPA might play particular role in the biology and progression of IDC. © 2004 Wiley‐Liss, Inc.
Aerodigestive and gastrointestinal tract cancers and exposure to crocidolite (blue asbestos): Incidence and mortality among former crocidolite workers
Authors: Reid Alison , Ambrosini Gina , de Klerk Nicholas , Fritschi Lin , Musk Bill 
Published: May 2004

AbstractThe objective of this article was to assess the association between the incidence and mortality from aerodigestive cancers and exposure to crocidolite (blue asbestos). Our study is a cohort study of former workers of the now‐defunct crocidolite mining and milling operation at Wittenoom, Western Australia, who have been followed up since 1979 and on whom asbestos exposure and smoking information was known. Standardised mortality and incidence rates were used to compare former workers with the Western Australian male population. Cases were matched with up to 10 randomly assigned controls, and conditional logistic regression was used to examine the relationship between asbestos exposure, smoking status and cancer incidence. There were 129 incident cases from all cancers of interest and 57 deaths. Former workers had a significantly higher risk of mortality from upper aerodigestive cancers than the Western Australian male population. The incidence of upper and lower aerodigestive cancers was higher in the Wittenoom cohort but not significantly so. Cumulative exposure to asbestos did not appear to be associated with the incidence of stomach cancer, colorectal cancer or upper aerodigestive cancers. Smoking status was strongly associated with the incidence of upper aerodigestive cancers, with current smokers experiencing the greatest risk. Our study with longer and more complete follow‐up, smoking information and a stronger study design does not show an association between cumulative asbestos exposure and stomach cancer or other gastrointestinal cancers. The excess mortality from upper aerodigestive cancers seen in this cohort of former asbestos workers compared to the Western Australian male population does not appear to be associated with exposure to crocidolite. © 2004 Wiley‐Liss, Inc.
Breast cancer metastatic potential: Correlation with increased heterotypic gap junctional intercellular communication between breast cancer cells and osteoblastic cells
Authors: Kapoor Preeti , Saunders Marnie M. , Li Zhongyong , Zhou Zhiyi , Sheaffer Nate , Kunze Elaine L. , Samant Rajeev S. , Welch Danny R. , Donahue Henry J. 
Published: May 2004

AbstractThe breast cancer metastasis‐suppressor gene BRMS1 is downregulated in metastatic breast cancer cells. Previous reports have shown restoration of gap junctional intercellular communication (GJIC) in the metastatic human breast carcinoma cell line MDA‐MB‐435 (435) transfected with BRMS1 cDNA. Metastasis, to a large extent in most breast cancers, occurs to bone. However, the reason for this preferential metastasis is not known. We explored cell‐to‐cell communication between 435 carcinoma cells and a human osteoblastic cell line, hFOB1.19, to determine whether carcinoma cells can form gap junctions with bone cells and to explore the role of these heterotypic gap junctions and the BRMS1 gene in breast cancer metastasis to bone. 435 cells displayed greater cell‐to‐cell communication with hFOB 1.19 cells than with themselves. Transfection of BRMS1 into 435 cells increased homotypic gap junctional communication but did not significantly affect heterotypic communication with hFOBs. However, heterotypic communication of BRMS1 transfectants with hFOB cells was reduced relative to homotypic communication. In contrast, parental 435 cells displayed greater heterotypic communication with hFOBs relative to homotypic communication. Our results suggest that there are differences in the relative homotypic and heterotypic GJIC of metastasis‐capable and ‐suppressed cell lines. © 2004 Wiley‐Liss, Inc.
Childbirth and breast cancer prognosis
Authors: Rosenberg Lena , Thalib Lukman , Adami Hans‐Olov , Hall Per 
Published: May 2004

AbstractAlthough certain risk factors for breast cancer incidence may also effect survival, findings have been inconsistent and the long‐term role of childbirth is unknown. We studied the influence of number and timing of births on breast cancer prognosis prospectively. From 1958 to 1997, altogether 32,003 women, born 1932 or later, were notified to the Swedish Cancer Registry due to a primary invasive breast cancer. We obtained information on dates of all childbirths and achieved complete follow‐up through 1997 by means of linkage to other nation‐wide databases. Proportional hazards analyses were used to compute crude and multivariate hazard ratios (HR) with 95% confidence intervals (CI) of dying from breast cancer. We found a successively worse prognosis for women with a shorter delay between their last birth and breast cancer diagnosis (p for trend <0.0001). Compared to women with their last birth more than 10 years before diagnosis, the multivariate HR of breast cancer death was 1.39 (95% CI 1.17–1.67) for those with breast cancer diagnosis in the 3rd year after last birth and 1.72 (CI 95% 1.42–2.09) for those with diagnosis within 1 year after last birth. This adverse effect on prognosis of childbirth persisted beyond 10 years among women with a first birth before the age of 20 years. A pregnancy has marked adverse effects on the prognosis of a breast cancer diagnosed within 10 years after delivery. These findings suggest that pregnancy influences tumor biology. © 2004 Wiley‐Liss, Inc.
High BRAF mutation frequency does not characterize all melanocytic tumor types
Authors: Saldanha Gerald , Purnell David , Fletcher Alan , Potter Linda , Gillies Angela , Pringle J. Howard 
Published: May 2004

AbstractCutaneous melanoma (CM) is the most lethal form of skin cancer. Along with some benign melanocytic tumors, the majority shows BRAF or NRAS mutation, but it is not known whether these are essential to all forms of melanocytic neoplasia. We screened 79 melanocytic tumors of different types for BRAF and NRAS mutations and looked at MAPK pathway activity using immunohistochemistry in a subset. Significant differences in BRAF exon 15 mutation frequency were found: 14/16 (87.5%) in common acquired naevi (CANs), 9/12 (75%) in CMs, 0/26 in Spitz naevi and 3/25 (12%) in blue naevi (p < 0.01). We looked at whether Spitz and blue naevi showed a compensatory increase in BRAF exon 11 and/or NRAS exons 1 and 2 mutations to account for the low BRAF exon 15 mutation frequency. NRAS mutations were found in only 1/16 (6.3%) Spitz naevi and 0/15 blue naevi. In addition, NRAS mutations were found in 2/11 (18.2%) CANs and 3/12 (25%) CMs. None of the tumors showed BRAF exon 11 mutations. Despite their low combined BRAF and NRAS mutation frequency, Spitz naevi showed strong MAPK pathway activation as measured by cytoplasmic expression of dually phosphorylated ERK1/2, while blue naevi had weak pathway activation. We conclude that BRAF and NRAS mutations are not necessary for melanocytic tumor development and that some types of tumor must arise by alternative mechanisms. © 2004 Wiley‐Liss, Inc.
PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome
Authors: Lachmann Margit , Gelbmann Dieter , Kálmán Endre , Polgár Beata , Buschle Michael , von Gabain Alexander , Szekeres‐Barthó Júlia , Nagy Eszter 
Published: May 2004

AbstractPIBF was previously identified as a 34 kDa immunomodulatory molecule secreted by pregnancy lymphocytes and is thought to play a crucial role in preventing rejection of the embryo by the maternal immune response. Recent data suggested that PIBF protein was also expressed by the progesterone receptor (PR) positive MCF‐7 breast tumor cell line. Therefore our study was designed to analyze the expression of PIBF in malignant cell lines and primary tumors both at the mRNA and protein levels. RNA expression analyses of several human cell lines with different tissue origin and paired human tumor/normal tissues, as well as of several PR+ and PR− breast tumors revealed that PIBF mRNA was overexpressed in highly proliferating cells independent of the presence of PR. In addition to the full‐length PIBF mRNA encoding for a 90 kDa protein, several alternatively spliced species were detected, all resulting from perfect exon skipping. The most frequently identified splice variant is predicted to encode for an approximately 35 kDa protein. Immunofluorescence microscopy revealed a centrosomal localization for the full‐length PIBF, while the 35 kDa form showed a diffuse cytoplasmic staining. These data, together with the identification of the PIBF gene in the chromosomal region associated with breast cancer susceptibility, reveal a strong parallel with known tumor suppressor proteins, such as BRCA1 and p53 having the same centrosomal localization. Given the notion that a number of proteins shown to be involved in tumorigenesis are associated with the centrosome and disturbed centrosome function causes unequal segregation of chromosomes, studies to evaluate whether or not PIBF that is highly expressed in tumors is directly involved in tumorigenesis are thus warranted. © 2004 Wiley‐Liss, Inc.
Amount of DNA in plasma and cancer risk: A prospective study
Authors: Gormally Emmanuelle , Hainaut Pierre , Caboux Elodie , Airoldi Luisa , Autrup Herman , Malaveille Christian , Dunning Alison , Garte Seymour , Matullo Giuseppe , Overvad Kim , Tjonneland Anne , Clavel‐Chapelon Francoise , Boffetta Paolo , Boeing Heiner , Trichopoulou Antonia , Palli Domenico , Krogh Vittorio , Tumino Rosario , Panico Salvatore , Bueno‐De‐Mesquita H. Bas , Peeters Petra H. , Lund Eiliv , Gonzalez Carlos A. , Martinez Carmen , Dorronsoro Miren , Barricarte Aurelio , Tormo M. Jose , Quiros J. Ramón , Berglund Goran , Hallmans Goran , Day Nicholas E. , Key Timothy J. , Veglia Fabrizio , Peluso Marco , Norat Teresa , Saracci Rodolfo , Kaaks Rudolf , Riboli Elio , Vineis Paolo 
Published: May 2004

AbstractLevels of plasma DNA concentrations in cancer patients have been shown to be higher than the plasma DNA concentrations found in healthy subjects. The value of plasma DNA levels for development of neoplastic or pulmonary disease was evaluated in a large prospective study. Plasma samples (n = 1,184) were analyzed from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx, larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease (COPD), including never smokers and ex‐smokers, from 9 countries across Europe. The amount of plasma DNA was variable across the European Prospective Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations in some centers might be due to the type of population recruited and/or the treatment of the samples. An elevated and statistically significant odds ratio (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06–6.02), while nonsignificant increased ORs were present for oral cancers, cancers of the pharynx and larynx and leukemia. When the analyses were stratified by time since recruitment (below or above 36 months), the increased ORs were limited to the more recent period of recruitment, i.e., a time elapsed between blood drawing and disease onset lower than 36 months. This was particularly true for COPD deaths (OR = 12.7; 95% CI = 1.57–103) and leukemia (OR = 2.37; 95% CI = 1.20–4.67). © 2004 Wiley‐Liss, Inc.
Increased expression of amyloid precursor protein in oral squamous cell carcinoma
Authors: Ko Shun‐Yao , Lin Shu‐Chun , Chang Kuo‐Wei , Wong Yong‐Kie , Liu Chung‐Ji , Chi Chin‐Wen , Liu Tsung‐Yun 
Published: May 2004

AbstractIn our previous study, we identified amyloid precursor protein (APP) in an oral squamous cell carcinoma (OSCC)‐enriching subtractive hybridization library. Our present study attempts to define the significance of APP expression in the genesis of OSCC. RT‐PCR analysis showed increase in APP mRNA expression for more than 2‐fold in 76% of OSCC (n = 55) relative to corresponding non‐cancerous matched tissues (NCMT). The majority of esophageal SCCs also had increase in APP mRNA expression. OSCC patients exhibiting increase in APP mRNA expression had significantly lower survival rate compared to patients exhibiting the opposite status. Western blotting analysis identified APP751 and APP770 as the major APP isoforms in oral keratinocytes. A high correlation between mRNA and protein expressions of APP was noted in OSCC/NCMT pairs. Immunohistochemistry further showed a remarkable increase of APP in OSCC tissue relative to NCMT. Treatment with an antisense oligonucleotide against APP reduced cellular and secreted APP as well as growth in an OSCC cell line. Our study provides novel clues that APP expression is involved in the proliferation and carcinogenesis of OSCC. Correlated with such pathogenesis was the survival of its victims. The degree of APP expression could serve as an invaluable marker for oral carcinogenesis. © 2004 Wiley‐Liss, Inc.