bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced expression of transforming growth factor‐β receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma
Authors: Fukai Yasuyuki , Fukuchi Minoru , Masuda Norihiro , Osawa Hidenobu , Kato Hiroyuki , Nakajima Takashi , Kuwano Hiroyuki 
Published: February 2003

AbstractTransforming growth factor‐β (TGF‐β) inhibits epithelial cell proliferation. Inactivation of the TGF‐β signaling pathway is thought to play a role in tumorigenesis. Our purpose was to clarify the correlation between TGF‐β receptors or TGF‐β1 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for TGF‐β type I receptor (TGF‐βR‐I), TGF‐βR‐II and TGF‐β1 was performed on surgical specimens obtained from 80 patients with esophageal SCC. Preoperative plasma TGF‐β1 levels were measured and correlated with pathologic features and clinical outcomes. Expression of TGF‐βR‐I and TGF‐βR‐II was reduced in 43 (53.8%) and 23 (28.8%) specimens, respectively. TGF‐β1 was overexpressed in 29 (36.3%). Reduced expression of TGF‐βR‐I and TGF‐βR‐II showed a significant association with depth of invasion (p = 0.0015 and p = 0.0012), lymph node metastasis (p = 0.0309 and p = 0.0059) and pathologic stage (p = 0.0103 and p = 0.0401). Overexpression of TGF‐β1 had a significant association with depth of invasion only (p = 0.0335). Reduced expression of TGF‐βR‐I and TGF‐βR‐II was correlated with cancer‐specific survival (p = 0.0324 and p = 0.0243). The mean preoperative plasma TGF‐β1 level was 10.5 ± 0.8 ng/ml in patients with esophageal carcinoma and was significantly higher compared to healthy controls (p < 0.01). We demonstrate that reduced expression of TGF‐β receptors in esophageal SCC appears to be correlated with depth of invasion, lymph node metastasis, pathologic stage and poor prognosis. TGF‐β receptor expression may play a key role in the progression of this cancer. © 2003 Wiley‐Liss, Inc.
Inhibition of heparanase activity and heparanase‐induced angiogenesis by suramin analogues
Authors: Marchetti Dario , Reiland Jane , Erwin Brad , Roy Madhuchhanda 
Published: February 2003

AbstractHeparanase, a heparan sulfate‐specific endo‐β‐D‐glucuronidase, plays an important role in tumor cell metastasis through the degradation of extracellular matrix heparan sulfate proteoglycans (ECM HSPG). Heparanase activity correlates with the metastatic propensity of tumor cells. Suramin, a polysulfonated naphthylurea, is an inhibitor of heparanase with suramin analogues shown to possess antiangiogenic and antiproliferative properties. We investigated the effects of selected suramin analogues (NF 127, NF 145 and NF 171) on heparanase activity and heparanase‐driven angiogenesis. Studies of the ability of cellular extracts and purified heparanase from human, highly invasive and brain‐metastatic melanoma (70W) cells revealed that heparanase expressed by these cells was effectively inhibited by suramin analogues in a dose‐dependent manner. These analogues possessed more potent heparanase inhibitory activities than suramin: The concentrations required for 50% heparanase inhibition (IC50) were 20–30 μM, or at least 2 times lower than that for suramin. One hundred percent inhibition was observed at concentrations of 100 μM and higher. Of relevance, these compounds significantly decreased (i) the invasive capacity of human 70W cells by chemoinvasion assays performed with filters coated with purified HSPG or Matrigel™, and (ii) blood vessel formation by in vivo angiogenic assays, thus linking their antiangiogenic properties with impedance of heparanase‐induced angiogenesis. Specifically, inhibition of invasion by NF 127, NF 145 and NF 171 was found at 10 μM concentrations of compounds with a significant decrease of invasive values at concentrations as low as 1.5 μM. In addition, NF 127, NF 145 and NF 171 promoted nearly complete inhibition of heparanase‐induced angiogenesis at values ranging from 236 μM (for NF 145) to 362 μM (for NF 127). These results further emphasize the importance of heparanase in invasive and angiogenic mechanisms and the potential clinical application of heparanase inhibitors such as suramin analogues in cancers and angiogenesis‐dependent diseases. © 2003 Wiley‐Liss, Inc.
α‐tocopherol protects against cisplatin‐induced toxicity without interfering with antitumor efficacy
Authors: Leonetti Carlo , Biroccio Annamaria , Gabellini Chiara , Scarsella Marco , Maresca Vittoria , Flori Enrica , Bove Loredana , Pace Andrea , Stoppacciaro Antonella , Zupi Gabriella , Cognetti Francesco , Picardo Mauro 
Published: February 2003

AbstractOur aim was 2‐fold: to investigate the role of α‐tocopherol supplementation on the antitumor activity of DDP and to evaluate the effect of α‐tocopherol on the survival and neurotoxicity of DDP‐treated mice. Experiments performed on the M14 human melanoma line demonstrated that α‐tocopherol supplementation did not influence the efficacy of DDP; the inhibition of cell survival and of the in vivo tumor growth after treatment with α‐tocopherol and DDP combination was similar to that observed after DDP alone. Conversely, α‐tocopherol was also able to increase survival of mice treated with a high dose of DDP. While DDP alone produced death in about 70% of mice, the combination reduced deaths to about 30%. Analysis of oxidative stress markers and peroxidative damage in organs indicated that the protective effect of α‐tocopherol was mainly related to its antioxidant activity. A significant increase in the concentration of TBARS and decreased PUFAs and catalase activity were observed after DDP treatment, while with α‐tocopherol the levels of these markers were comparable to those observed in untreated mice. Histologic analysis performed on peripheral nerve revealed that α‐tocopherol also protected mice from severe neurologic damage induced by DDP treatment. In conclusion, our results demonstrate that α‐tocopherol protects against the systemic toxicity and neurotoxicity induced by DDP without interfering with its antitumor activity and suggest that this combination is a promising strategy to improve the therapeutic index of DDP‐based chemotherapy. © 2003 Wiley‐Liss, Inc.
Human papillomavirus infection among women in South and North Vietnam
Authors: Anh Pham Thi Hoang , Hieu Nguyen Trong , Herrero Rolando , Vaccarella Salvatore , Smith Jennifer S. , Thuy Nguyen Thi , Nga Nguyen Hoai , Duc Nguyen Ba , Ashley Rhoda , Snijders Peter J.F. , Meijer Chris J.L.M. , Muñoz Nubia , Parkin D. Max , Franceschi Silvia 
Published: February 2003

AbstractThe incidence rate of invasive cervical carcinoma (ICC) is 4‐fold higher in Ho Chi Minh City, in the South of Vietnam, than in Hanoi, in the North. Thus, we explored the prevalence of and the risk factors for human papillomavirus (HPV) infection in these 2 areas. A population‐based random sample of married women aged 15–69 years were interviewed and had a gynaecological examination in the urban district of Ho Chi Minh City and in a peri‐urban district in Hanoi. HPV DNA detection was performed using a GP5+/6+ primer‐mediated PCR enzyme immunoassay. A total of 922 women from Ho Chi Minh and 994 from Hanoi, for whom a Pap smear and HPV‐status were available, were evaluated. HPV DNA was detected among 10.9% of women in Ho Chi Minh City and 2.0% in Hanoi (age standardized prevalence, world standard population: 10.6% and 2.3%, respectively). In the 2 areas combined, 30 different HPV types were found, the most common being HPV 16 (in 14 single and 18 multiple infections), followed by HPV 58, 18 and 56. A peak of HPV DNA detection in women younger than age 25 was found in Ho Chi Minh City (22.3%) but not in Hanoi. Major risk factors for HPV DNA detection were indicators of sexual habits, most notably the presence of HSV‐2 antibodies, nulliparity and the current use of oral contraceptives. Women in Hanoi showed the lowest HPV prevalence ever reported so far, suggesting that HPV has not spread widely in this population. As expected, HPV prevalence in a population seemed to be closely correlated with ICC incidence rates. © 2003 Wiley‐Liss, Inc.
Mucosal immunoglobulin‐A and ‐G responses to oncogenic human papilloma virus capsids
Authors: Sasagawa Toshiyuki , Rose Robert C. , Azar Khadijeh K. , Sakai Akemi , Inoue Masaki 
Published: February 2003

AbstractOncogenic human papilloma virus (HPV) infection is the most important risk factor for developing cervical cancer. It is known that serum antibody responses against these viruses are associated with persistent infection. We conducted an epidemiological study of 627 women to detect cervical mucosal immunoglobulin (Ig)A and IgG responses to oncogenic HPV capsids. Antibody reactivity and cervical HPV infection genotypes were examined by enzyme‐linked immunosorbent assay (ELISA) using HPV types 16, 18, 31, and 45 virus‐like particles, and a polymerase chain reaction‐based method, respectively. HPV infection was defined as being positive for HPV DNA. Multivariate analysis revealed that a mucosal IgA response was associated with the HPV infection, whereas the IgG response was associated with high‐grade cervical squamous intraepithelial lesions (SIL)/squamous cell cancer (SCC) and subject age (40–49 years). IgA was positive in 72% of women with oncogenic HPV infections, whereas IgG was positive in 64% of women with high‐grade SIL/SCC. The longitudinal study demonstrated that the IgA response was elicited earlier than the IgG response, and the IgG response was barely induced in the preclinical HPV infection. However, once an IgG response was induced, it persisted longer after HPV clearance. The mucosal IgA response reflects current HPV infection, whereas an IgG response may be induced with the development of cervical lesions. © 2003 Wiley‐Liss, Inc.
Letrozole as a potent inhibitor of cell proliferation and expression of metalloproteinases (MMP‐2 and MMP‐9) by human epithelial breast cancer cells
Authors: Mitropoulou Theoni N. , Tzanakakis George N. , Kletsas Dimitris , Kalofonos Haralabos P. , Karamanos Nikas K. 
Published: February 2003

AbstractP450 aromatase catalyzes the conversion of androgens to estrogens and plays a key role in the cell growth of hormone‐dependent breast cancer in postmenopausal women. On the other hand, matrix metalloproteinases (MMPs), which can degrade almost all components of the extracellular matrix, play a crucial role in tumor cell invasion and cancer metastasis. In the present study the effect of letrozole on cell proliferation of estrogen receptor (ER)‐positive MCF‐7 human epithelial breast cancer and MCF‐12A human mammary epithelial cells was studied. The effect of letrozole on the in vitro release of MMPs, particularly type IV collagenases (MMP‐2 and MMP‐9), by the ER‐positive MCF‐7 cells was also investigated, using a solid‐phase method of high sensitivity and accuracy. Using RNA isolates from cell lines MCF‐7 and MCF‐12A, reverse transcriptase‐polymerase chain reaction analysis revealed that only MCF‐7 cells express the P450 aromatase gene. Study of the effects of letrozole alone and the hormones 17‐β‐estradiol, testosterone and 4‐androstene‐3, 17‐dione in the presence and absence of letrozole on cell growth at the DNA synthesis level showed that letrozole significantly suppressed the endogenous aromatase‐induced proliferation of MCF‐7 cells. The majority of MMPs secreted by MCF‐7 cells were identified in their pro‐forms, which was in accordance with the low metastatic potential determined for these cells. After treatment of cells with letrozole (10 nM) for 24 and 48 h, significant inhibition of MMP levels was obtained. Furthermore, concurrent treatment of MCF‐7 cells with 17‐β‐estradiol in the presence of letrozole significantly suppressed the estradiol‐induced stimulation of MMP levels. The data obtained suggest that letrozole is a potent in vitro inhibitor of cell proliferation and of type IV collagenases expressed by ER‐positive MCF‐7 cells and may be of value for suppressing breast tumor growth and invasiveness. © 2003 Wiley‐Liss, Inc.
The product of the candidate prostate cancer susceptibility gene ELAC2 interacts with the γ‐tubulin complex
Authors: Korver Wouter , Guevara Claudia , Chen Yang , Neuteboom Saskia , Bookstein Rob , Tavtigian Sean , Lees Emma 
Published: February 2003

AbstractELAC2 is a novel candidate cancer susceptibility gene located on chromosome 17p: Carriers of mutations in ELAC2 display a higher risk of developing prostate cancer. Overexpression of ELAC2 in tumor cells causes a delay in G2‐M progression characterized by accumulation of cyclin B levels. Consistent with a function in mitosis, further biochemical analysis revealed that ELAC2 physically interacts with the γ‐tubulin complex. This is the first biologic insight into the function of this new putative cancer susceptibility gene, providing clues of how perturbation of ELAC2 might promote tumorigenesis through irregular cell division. © 2003 Wiley‐Liss, Inc.
Differentially expressed transcripts in neoplastic hepatic nodules and neonatal rat liver studied by cDNA microarray analysis
Authors: Tellgren Åsa , Wood Timothy J.J. , Flores‐Morales Amilcar , Torndal Ulla‐Britta , Eriksson Lennart , Norstedt Gunnar 
Published: February 2003

AbstractThe molecular mechanisms underlying hepatocarcinogenesis remain unclear. Wistar rats treated with 2‐AAF develop hepatocarcinoma in histologically well‐characterised stages. In our study, cDNA microarrays were used to measure the expression of 3,000 genes during the progression of liver carcinogenesis in persistent neoplastic nodules. Because tumours frequently revert into a more poorly differentiated phenotype, we also studied the expression of the same set of transcripts in neonatal rat liver. Approximately 2,000 transcripts gave a detectable signal in experiments comparing gene expression in nodules and control tissue. Approximately 8% of these were identified as differentially expressed in liver nodules. The differentially expressed genes fell into several categories with putative or demonstrated roles in signal transduction, metabolism, detoxification, cell‐structure and transport. Many of the differentially expressed genes in nodules were not previously known to be regulated during liver carcinogenesis. A universal transcript profile for gene expression in hepatic liver nodules and neonatal liver has been created. © 2003 Wiley‐Liss, Inc.
Abnormal expression pattern of cyclin E in tumour cells
Authors: Erlandsson Fredrik , Wählby Carolina , Ekholm‐Reed Susanna , Hellström Ann‐Cathrin , Bengtsson Ewert , Zetterberg Anders 
Published: February 2003

AbstractThe expression pattern of cyclin E during the cell cycle was studied in normal and tumour cells in culture and in tumour biopsies. This pattern was found to be abnormal in tumour cells. A triple immunostaining protocol, digital microscopy and image analysis were used to find the position of the individual cells in the cell cycle and to measure the nuclear cyclin E levels. In normal cells, the number of cyclin E‐positive cells decreased rapidly when the cells entered the S‐phase. In the tumour cell lines, cyclin E was not downregulated in early S‐phase, as in normal cells. Instead the number of cyclin E‐positive cells remained high throughout S‐phase, and the cyclin E staining intensity per cell often increased during S‐phase. In about half of the analysed tumour cell lines, many cells stained positive for cyclin E even in the G2‐phase. This abnormal expression over the cell cycle of cyclin E was also found in tumour biopsies from cervical, breast and prostatic carcinomas, even though it varied greatly between individual tumours. In some tumours, the expression pattern of cyclin E was similar to that of normal cells in culture, whereas in others high cyclin E levels could be seen in S‐phase cells, as in the transformed cell lines. A high percentage of cells expressing cyclin E during S‐ or G2‐phase was found to be related to poor outcome (p < 0.025) in a small group of cervical carcinoma patients (n = 12). © 2003 Wiley‐Liss, Inc.
Structural analysis of the ErbB‐2 receptor using monoclonal antibodies: Implications for receptor signalling
Authors: Yip Yum L. , Novotny Jiri , Edwards Michael , Ward Robyn L. 
Published: February 2003

AbstractThe extracellular part of ErbB‐2 is formed by 4 domains, specifically, L1, L2 that adopt a β‐helical structure and S1, S2 that consist of several cysteine‐rich, EGF‐fold modules. These ectodomains mediate ErbB‐2 dimerisation with itself or with other members of the epidermal growth factor receptor (EGFR) family, events essential to both ErbB‐2 signaling and the development of certain malignancies. The anti‐ErbB‐2 monoclonal antibodies N12, N28 and L87 bind to the polypeptides C531‐A586, T216‐C235 and C220‐C235 respectively. In this study, glycine walking and random mutagenesis were used to further delineate the critical residues involved in antibody binding. A molecular model of ErbB‐2 ectodomains was then constructed based on the recently published coordinates of the EGFR (EGFR) model. This model rationalized successfully many features of our epitope mapping, including their location in modules within the S1 and S2 domains and the importance of Arg545, Gln548 and Leu561 for N12 binding. Further investigation of the functional effects of the anti‐ErbB‐2 monoclonal antibodies demonstrated that N28 strongly stimulated ErbB‐2 phosphorylation and MAPK activation whereas N12 had no effect. As bivalency is required for the action of these antibodies we propose that at least 2 different kinds of ErbB‐2 homodimers can be formed as relative rotational isomers and that the S1 and S2 domains are instrumental in determining the relative orientations of the ErbB‐2 homodimers, such that different signaling effects are induced. © 2003 Wiley‐Liss, Inc.
Anti‐tumor effect and increased survival after treatment with [177Lu‐DOTA0,Tyr3]octreotate in a rat liver micrometastases model
Authors: Breeman Wouter A.P. , Mearadji Amir , Capello Astrid , Bernard Bert F. , van Eijck Casper H.J. , Krenning Eric P. , de Jong Marion 
Published: February 2003

AbstractPeptide receptor scintigraphy with [111In‐DTPA0]octreotide (a stabilized radiolabeled somatostatin (SS) analogue, OctreoScan®) is widely used for the visualization and staging of somatostatin receptor‐positive tumors. The application of likewise somatostatin analogues as vehicle for the deliverance of radionuclides to somatostatin receptor‐positive targets are now in use for peptide receptor‐targeted radionuclide therapy (PRRT). Currently preclinical and clinical investigation are ongoing trying to find the optimal combination of radionuclide and ligand. The anti‐tumoral effects of such combinations, like [90Y‐DOTA°, Tyr3]octreotide and [177Lu‐DOTA°, Tyr3]octreotate, on SSR‐positive solid tumors have been reported. In this study we present the anti‐tumor effects of 177Lu‐DOTA‐tate on: a) a single SSR‐positive cell model and b) on a SSR‐positive tumor in a rat liver micrometastatic model, mimicking disseminated disease. 177Lu‐DOTA‐tate showed anti‐tumoral effects in both cases and significant survival in the PRRT‐treated rats. 177Lu‐DOTA‐tate is a very promising new treatment modality for SSR‐positive tumors, including disseminated disease. © 2003 Wiley‐Liss, Inc.
A CD4+, HLA‐DR7‐restricted T‐helper lymphocyte clone recognizes an antigen shared by human malignant melanoma and glioma
Authors: Somasundaram Rajasekharan , Swoboda Rolf , Caputo Laura , Lee Allana , Jackson Naidine , Marincola Francesco M. , Guerry DuPont , Herlyn Dorothee 
Published: February 2003

AbstractCD4+ Th cells that are restricted by MHC class II molecules play an important role in the induction of antitumor immune responses. We have established a stable CD4+ Th cell clone (Th35‐1A) from the PBMCs of a patient with primary cutaneous melanoma. The Th cell clone is noncytolytic and proliferates specifically in the presence of irradiated autologous melanoma cells or autologous EBV‐transformed B cells pulsed with melanoma tumor cell lysates. Th35‐1A produces IFN‐γ (a Th1‐type cytokine) after autologous tumor cell stimulation, and its proliferative reactivity is HLA class II–restricted. Th cells showed helper activity for PWM responses of PBMCs. Using a panel of HLA class II–matched and unmatched EBV‐B cells as APCs and allogeneic melanoma tumor cell lysate as stimulant, DR7 was delineated as the HLA class II restriction element used by the Th cell clone. In agreement with these results, transfection of an allogeneic melanoma cell line with HLA‐DR7 isolated from autologous EBV‐B cells rendered the cell line stimulatory for Th35‐1A cells. Specificity studies using autologous EBV‐B cells (EBV‐B35) pulsed with a panel of allogeneic tumor cell lysates of various tissue origins indicated that the Th cell clone recognizes an antigen shared by melanoma and glioma cells. The availability of the Th cell clone may lead to the development of new therapies against melanoma, using adoptive Th cell transfer and/or active immunization with a shared Th cell antigen. © 2003 Wiley‐Liss, Inc.
The interaction between NK cells and dendritic cells in bacterial infections results in rapid induction of NK cell activation and in the lysis of uninfected dendritic cells
Authors: Ferlazzo Guido , Morandi Barbara , D'Agostino Antonella , Meazza Raffaella , Melioli Giovanni , Moretta Alessandro , Moretta Lorenzo 
Published: February 2003

AbstractNK and DC reciprocal interactions have only recently been investigated. In this study, we focused on the interplay between NK cells and DC in two models of bacterial infection. Immature monocyte‐derived DC were cultured in the presence of live Escherichia coli or bacillus Calmette–Guérin. Upon exposure to either extracellular or intracellular bacteria, DC underwent maturation as assessed by the increased levels of expression of CD80, CD86, and HLA molecules and the de novo expression of CD83 and CCR7. Significant amounts of TNF‐α and IL‐12 were released by DCupon infection, whereas IL‐2 and IL‐15 were barely detectable in culture supernatants. Both infected and uninfected DC were capable of inducing in fresh autologous NK cells the expression of CD69 and HLA‐DR and of inducing cell proliferation. Remarkably, however, infected DC were much stronger inducers of NK cell activation and proliferation than uninfected DC. Thus, after just 24 h of NK/DC coculture, only those NK cells that had been exposed to bacteria‐infected DC had acquired the ability to lyse autologous immature DC. In addition, infected DC were more resistant to NK‐mediated lysis as a consequence of the up‐regulation of HLA class I molecule expression on their surface. This study suggests a regulatory circuit involving NK cells and DC in which DC‐induced NK cell activationis effectively enhanced by the presence of pathogens. Activated NK cells, by limiting the supply of immature DC, may then exert a control on subsequent innate and adaptive immune responses.