bluuebunny/crossref_metadata_2025_split huggingface dataset:
Internalization and excretion of epidermal growth factor‐dextran‐associated radioactivity in cultured human squamous‐carcinoma cells
Authors: Olsson Pär , Lindström Annelie , Carlsson Jörgen 
Published: February 2007

AbstractCertain tumour cells, such as squamous carcinomas and gliomas, can have an increased number of epidermal‐growth‐factor (EGF) receptors. The EGF receptors can in these cases be targets for toxic conjugates with specific binding. EGF‐based toxic conjugates are potential targeting agents. We have analyzed the internalization and excretion of 125I administered in the form of 125 I‐EGF‐dextran in squamous‐carcinoma A431 cells. 125I‐EGF without dextran was used for comparison. A431 cells have large numbers of EGF receptors and are capable both of recycling and of degradation of internalized receptor‐ligand complexes. The binding of 125I‐EGF‐dextran and 125I‐EGF was receptor‐specific, since both ligands competed with non‐radioactive EGF for binding. The amount of internalized 125I as a function of time increased continuously within 24 hr following administration of radioactivity as 125I‐EGF‐dextran. The time pattern was quite different when 125I‐EGF without dextran was applied. In the latter case, the amount of internalized radioactivity decreased already after a few hours, probably depending on degradation of EGF. Pre‐incubation of the cells with 125I‐EGF‐dextran or 125I‐EGF and analysis of retained and released 125I activity at different times after washing showed that the 125I activity was retained for longer periods of time when EGF‐dextran was used instead of EGF. About 30% of the internalized 125I activity was retained after 24 hr when EGF‐dextran was used, compared with excretion of nearly all the radioactivity within 5 hr when EGF was used. In some experiments a high concentration of non‐radioactive EGF, 5 μg/ml, was given to the cells after pre‐incubation with 125I‐EGF‐dextran. This changed the retention and excretion patterns, so that a larger amount of 125I was excreted in the macromolecular fraction and a smaller amount of 125I activity was retained in the cells. Gel chromatography of the 125I activity released into the culture medium showed that the variations in molecular weight were larger after administration of a high concentration of non‐radioactive EGF, most likely due to partial degradation of EGF‐dextran. The results regarding excretion are in conformity with a model of competition between recycling of EGF‐dextran‐EGF‐receptor complexes and “trapping” of EGF‐dextran in the lysosomes followed by slow degradation. For targeting purposes, it is worth noting that the radioactivity administered in the form of 125I‐EGF‐dextran had a longer retention time than when 125I‐EGF without dextran was used, and that the retention and excretion rates could be modified by post‐treatment with the receptor ligand itself.
Secretion of extracellular matrix‐degrading proteinases is increased in epithelial ovarian carcinoma
Authors: Moser Tammy L. , Young Timothy N. , Rodriguez Gustavo C. , Pizzo Salvatore V. , Bast Robert C. , Stack M. Sharon 
Published: February 2007

AbstractThe biochemical events associated with tumor invasion involve localized degradation of the basement membrane by tumor‐associated proteinases. In this study, we have characterized the proteinase secretion profiles of 5 ovarian epithelial carcinoma cell lines (DOV 13, OVCA 420, OVCA 429, OVCA 432, OVCA 433) as well as normal ovarian epithelial cells. Immunocapture assays demonstrated that all 5 carcinoma cell lines produce both secreted and surface‐associated plasminogen activator. Urinary‐type plasminogen activator (u‐PA) production was one order of magnitude greater than production of tissue‐type plasminogen activator (t‐PA). Furthermore, t‐PA secretion by normal ovarian epithelial cells was not detectable, whereas u‐PA production was 17‐to 38‐fold lower than in ovarian carcinoma cells. Western‐blotting analysis demonstrated that u‐PA was secreted as the single chain form (scu‐PA) when cells were cultured in serum‐free medium. Incubation of plasminogen with ovarian carcinoma cell‐conditioned medium resulted in direct activation of the Zymogen to plasmin. Furthermore, following incubation of cells with plasminogen, plasmin was eluted from the cell surface, indicating that ovarian carcinoma cells contain binding sites for plasminogen/plasmin which are accessible to surface‐associated plasminogen activators. In addition to plasminogen activators, metalloproteinases were also produced by DOV 13, OVCA 429 and OVCA 433 cells. DOV 13 cells produce a 68‐kDa metalloproteinase similar to matrix metalloproteinase 2 (MMP‐2) whereas a 92‐kDa enzyme similar to MMP‐9 is secreted by OVCA 429 and 433. Together, ovarian carcinoma‐associated plasminogen activators and metalloproteinases catalyze the hydrolysis of the major basement membrane protein components, type‐IV collagen, type‐IV gelatin, laminin and fibronectin. The enhanced proteolytic capability of ovarian carcinoma cells relative to normal ovarian epithelium suggests a biochemical mechanism by which invasion and spread of ovarian epithelial carcinoma may be mediated.
Foetal loss and infant deaths in families of children with soft‐tissue sarcoma
Authors: Hartley Ann L. , Birch Jillian M. , Blair Valerie , Kelsey Anna M. , Jones Patricia H. Morris 
Published: February 2007

AbstractDistribution of miscarriages, stillbirths and infant deaths in the families of a population‐based series of children with soft‐tissue sarcoma was examined in relation to index case histology (rhabdomyosarcoma or other soft‐tissue sarcoma) and to the possible presence of genetic predisposition to cancer in the families (Li‐Fraumeni syndrome or neurofibromatosis). Reproductive loss was not related to index histology (miscarriages, p = 0.3; all losses, p = 0.6) but was significantly higher in “genetic” rather than “sporadic” families (miscarriages, p = 0.02; all losses, p = 0.01). However, excess reproductive loss was not a feature of families with the Li‐Fraumeni syndrome, but appeared to be concentrated in the families affected by neurofibromatosis.
Serum micronutrients in relation to pre‐cancerous gastric lesions
Authors: Zhang Lian , Blot William J. , You Wei‐Cheng , Chang Yun‐Sheng , Liu Xian‐Qiu , Kneller Robert W. , Zhao Lei , Liu Wei‐Dong , Li Ji‐You , Jin Mao‐Lin , Xu Guang‐Wei , Fraumeni Joseph F. , Yang Chung S. 
Published: February 2007

AbstractSerum levels of retinol, beta‐carotene, ascorbic acid, alphatocopherol, selenium, ferritin, copper, and zinc were assayed for approximately 600 adults aged 35 to 64 with pre‐cancerous gastric lesions in an area of China with one of the world's highest rates of stomach cancer. Previous studies have shown that the cancers generally are preceded by chronic atropic gastritis (CAG), intestinal metaplasia (IM) and dysplasia. Concentrations of beta‐carotene and ascorbic acid were significantly lower among individuals with IM than among those whose most severe lesion was superficial gastritis or CAG. The associations with IM for these nutrients were strong and independent. In combination, the odds of CAG progressing to IM were only 1/6 as high among those with upper tertile levels of beta‐carotene and ascorbic acid as among those with lower tertile levels of both nutrients. The serum levels of beta‐carotene and ascorbic acid were similar for individuals having IM with or without accompanying dysplasia. Risk of IM was also somewhat increased among those with low serum ferritin, but no significant effects were observed in multivariate analyses for the other nutrients assayed. The findings point to a major influence of specific nutrient deficits in the mechanisms of gastric carcinogenesis in this high‐risk area.
p53 protein over‐expression and p53 gene abnormalities in HIV‐1‐related non‐Hodgkin's lymphomas
Authors: De Re Valli , Carbone Antonino , De Vita Salvatore , Gloghini Annunziata , Maestro Roberta , Gasparotto Daniela , Vukosavljevic Tamara , Boiocchi Mauro 
Published: February 2007

AbstractAlteration of the p53 tumor‐suppressor gene was studied in non‐Hodgkin's lymphomas (NHLs) from HIV‐I‐infected patients. p53 protein was over‐expressed in 10 out of the 45 (22%) cases analyzed, mainly clustering in the small‐non‐cleaved‐cell (SNC) (5/19) and Ki‐l+ anaplastic large‐cell (ALC) (3/8) subtypes, according to previous findings on HIV‐1 ‐unrelated NHLs. p53‐positive small‐non‐cleaved‐cell lymphomas presented a diffuse or clustered pattern of p53‐positive neoplastic cells consequent upon p53‐gene mutations. In contrast, in Ki‐1 + ALC lymphomas p53 immunohistochemical reactivity was limited to scattered tumor cells, and no p53‐gene alterations could be detected. These results suggest that p53‐gene alterations play a role in the lymphomagenetic process of a fraction of HIV‐I‐related SNC NHLs, however with a frequency no different from that observed in HIV‐I ‐unrelated NHLs of the same sub‐type. In HIV‐I‐related Ki‐I+ ALC lymphomas, mechanisms different from gene alterations might be implicated in over‐expression of p53 protein.
Cripto, a member of the epidermal growth factor family, is over‐expressed in human pancreatic cancer and chronic pancreatitis
Authors: Friess Helmut , Yamanaka Yoichiro , Büchler Markus , Kobrin Michael S. , Tahara Eiichi , Korc Murray 
Published: February 2007

AbstractCripto is a 188 amino‐acid protein containing a central segment that shares amino‐acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF‐α). The EGF receptor, EGF and TGF‐α are expressed in the normal human pancreas, and are over‐expressed in human pancreatic cancer. Therefore, in the present study we sought to determine whether cripto is found in the normal human pancreas and whether its expression is altered in pancreatic cancer. Because chronic pancreatitis (CP) is associated with interstitial fibrosis similar to that observed in pancreatic cancer, we also examined cripto expression in pancreatic tissues from patients with CP. In the normal pancreas, cripto immunoreactivity was found at moderate levels in most ductal cells and was present very faintly in a rare acinar cell. In 26 of 58 pancreatic cancers, cripto immunoreactivity was present in many cancer cells. Its presence was associated with advanced tumor stage, but not with shorter post‐operative survival. Cripto was also present in acinar and ductal cells adjacent to the cancer cells, and in many ductal and atrophic acinar cells in the CP samples. Northern blot analysis revealed a marked increase in cripto mRNA levels in the cancer and CP samples. By densitometry, there was a 11 ‐ and 4‐fold increase in cripto mRNA levels in pancreatic cancer and CP respectively. Southern blot analysis did not reveal an increase in gene copies encoding cripto either in cancer or in CP. These findings indicate that cripto expression may contribute to disease progression in pancreatic cancer, and implicate cripto in the histopathological alterations that occur in the pancreas both in cancer and in CP.
High density of somatostatin receptors in veins surrounding human cancer tissue: Role in tumor‐host interaction?
Authors: Reubi Jean Claude , Horisberger Ursula , Laissue Jean 
Published: February 2007

AbstractSomatostatin receptors were detected in peritumoral veins of various human cancer tissue specimens. Vascular and neoplastic tissue from 14 colonic adenocarcinomas, 13 carcinoids, 6 renal‐cell carcinomas and 7 malignant lymphomas were analyzed for somatostatin receptors by use of quantitative receptor autoradiography. In colonic carcinoma specimens, the peritumoral vessels expressed a high density of somatostatin receptors, whereas the neoplastic tissue itself was receptor‐negative in many cases. In contrast, the incidence and density of somatostatin receptors in peritumoral vessels was low in well‐differentiated gastrointestinal and bronchial carcinoids, in contrast to the high density of such receptors in the carcinoid tumor tissue. Autochthonous vessels surrounding other tumors such as renal‐cell carcinomas or malignant lymphomas also frequently expressed somatostatin receptors. In all cases, the somatostatin receptors were localized in veins, particularly in the smooth‐muscle cell layer. They exhibited specific and high‐affinity binding of somatostatin‐14, somatostatin‐28 and octreotide, suggesting a preferential expression of the SSTR2 receptor subtype. Since the vessels of normal non‐neoplastic human tissues, e.g. of intestine or lymphatic organs, have few somatostatin receptors, the increased somatostatin receptor expression in peritumoral vessels observed in this study may be linked to the neoplastic process itself. The results suggest that somatostatin and somatostatin receptors may play a regulatory role for hemodynamic tumor‐host interactions, possibly involving tumor stroma generation, tumor environment, angiogenesis and, particularly, vascular drainage of poorly differentiated neoplasms.
A fetal rat urogenital sinus mesenchymal cell line (rUGM): Accelerated growth and conferral of androgen‐induced growth responsiveness upon a human bladder cancer epithelial cell line IN VIVO
Authors: Zhau Haiyen E. , Hong Sung‐Joon , Chung Leland W. K. 
Published: February 2007

AbstractA cell‐cell interaction model was developed to examine the intercellular communication between mesenchymal and epithelial cells in vivo, and to define the role of androgen and paracrine growth factors in promoting growth and differentiation of the target epithelial cells. Using this model system, we have demonstrated that, in the presence of andrqgenic steroids, a fetal urogenital sinus mesenchymal cell line exhibited androgen‐induced growth responses which resulted in an induction of growth of a non‐androgen target epithelial cell line derived from human urinary bladder. Our results show that: (1) a rat fetal urogenital sinus mesenchyme‐derived cell line (rUGM) accelerated growth and conferred androgen‐induced growth responsiveness upon a non‐androgen target cell line, WH, derived from a human bladder transitional‐cell carcinoma (TCC); this induction of epithelial tumor growth in vivo occurred in a fibroblast‐specific manner; (2) live fetal rUGM cells are required to promote WH tumor growth in vivo, which suggests that continuous production of factors that may serve as mediators for paracrine/autocrine pathways are responsible for androgen stimulation of WH tumor growth in vivo; and (3) although WH tumor growth, mediated by the presence of rUGM cells, was markedly accelerated by the presence of androgen in vivo, androgen and rUGM cells failed to promote the expression of a human prostate‐specific antigen (PSA) by WH tumors in vivo. Our results emphasize the importance of organ‐specific fibroblasts that promote tumor growth and mediate androgen‐induced growth responses; the accelerated growth of the bladder epithelium was not accompanied by the expression of PSA, a known differentiated gene product produced by human prostatic epithelial cells. This report also discusses the potential significance of mesenchymal‐epithelial cellular interaction which mediates androgen action and may play an important role by influencing human prostate tumor growth, progression and differentiation.
Effect of immunomodulators on specific tumor immunity induced by liposome‐encapsulated tumor‐associated antigens
Authors: Bergers Joep J. , Den Otter Willem , Dullens Hub F. J. , De Groot Jan Willem , Steerenberg Peter A. , Filius Margreet P. G. , Crommelin Daan J. A. 
Published: February 2007

AbstractReconstituted membranes consist of liposomal structures formed by removal of detergent from solubilized membrane constituents. The membrane‐like configuration of reconstituted membranes makes them attractive as vehicles for presentation of tumor‐associated antigens and induction of immune responses. In this study the potential of immunomodulators was assessed to enhance the specific immune response induced by immunization with reconstituted membranes prepared from SL2 lymphosarcoma cells. Reconstituted membranes containing muramyl tripeptide phosphatidylethanolamine (MTP‐PE) provided better protection against a challenge with SL2 cells than did reconstituted membranes containing alternative immunomodulators. Local administration of IL‐2 at the immunization sites further augmented the protection induced by reconstituted membranes with MTP‐PE, but was ineffective when administered with plain reconstituted membranes. Immunity elicited by the triple modality of reconstituted SL2 membranes with MTP‐PE and IL‐2 was specific for SL2 cells. Systemic immunity was obtained against a challenge with a 100‐fold higher number of SL2 cells than was reached after immunization with reconstituted membranes alone (105 vs. 10 SL2 cells). Macrophages isolated from the peritoneal cavity of immunized mice 5 to 7 days after tumor challenge expressed high In vitro cytotoxicity. However, in contrast to the observed specificity of the systemic immunity, macrophages killed both SL2 cells and non‐related P815 cells. Neither major cytotoxic lymphocyte activity nor substantial cytotoxic antibody tilers were detectable. These results clearly indicate that the approach using reconstituted membranes combined with particular immunomodulators warrants further exploration for the development of safe, well‐characterized cancer vaccines.
RT‐PCR detection of fibronectin EDA+ and EDB+ mRNA isoforms: Molecular markers for hepatocellular carcinoma
Authors: Tavian Daniela , De Petro Giuseppina , Colombi Marina , Portolani Nazario , Giulini Stefano Maria , Gardella Rita , Barlati Sergio 
Published: February 2007

AbstractAlternative splicing of fibronectin pre‐mRNA has been shown to be independently regulated at the EDA and EOB regions in a tissue and developmental stage‐specific manner. In this study, RT‐PCR approaches were developed for the detection of EDA and EDB FN mRNA isoforms in hepatocarcinoma cells (SK‐Hep‐I) grown in vitro and in human liver biopsies. While EDA+ and EDB+ isoforms were not present in control adult liver, they were detectable in the hepatocarcinoma cells and in fetal liver. The RT‐PCR analysis, extended to biopsies of malignant and non‐malignant hepatic tissues, showed that FN mRNAs containing the EDA and EDB sequences were present in the 14 hepatocelfular carcinomas (HCCs) tested but absent in the non‐tumorous liver tissues (i.e., normal parenchyma, nonspecific reactive and chronic hepatitis, steatosis). The EDB+ FN mRNA isoforms were also detected in 3 cases of benign neoplasm (hepatocellular adenoma, HCA, I; nodular focal hyperplasia, NFH, 2), while the EDA+ was only detectable in I of the 2 cases of NFH. In addition, both EDA+ and EDB+ isoforms were expressed in 5 out of 9 cirrhotic livers surrounding the tumors. This molecular analysis, which can also be performed on small liver biopsies (2 mg), may therefore be a useful additional tool in the diagnosis of HCC.
Expression of mage genes by non‐small‐cell lung carcinomas
Authors: Weynants P. , Lethé B. , Brasseur F. , Marchand M. , Boon T. 
Published: February 2007

AbstractHuman gene MAGE‐1 codes for an antigen that is recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). This antigen is potentially useful as a target for cancer immunotherapy because gene MAGE‐1 is not expressed in any normal tissues except the testis. We tested 46 surgical samples of non‐small‐cell lung carcinomas and observed MAGE‐1 expression in 16 of them (35%). Genes MAGE‐2 and 3, which are closely related to MAGE‐1, were expressed by a similar proportion of these tumors. Some small‐cell lung tumors also express MAGE genes. The proportion of tumors expressing MAGE‐1 suggests that lung tumor patients may constitute the largest group of patients potentially eligible for pilot studies involving MAGE‐1 immunization.
Retroviral‐mediated transduction of p53 gene increases TGF‐β expression in a human glioblastoma cell line
Authors: Fujiwara Toshiyoshi , Mukhopadhyay Tapas , Cai De Wei , Morris Danna K. , Roth Jack A. , Grimm Elizabeth A. 
Published: February 2007

AbstractTransforming growth factor‐β (TGF‐β) has been implicated as a potent growth regulator; the degree of responses to it, whether positive or negative, generally correlates with the stage of cell differentiation in various cell types. We examined the effect of the p53 gene, which participates in the control of cell‐cycle progression, on the expression of human TGF‐β. The human glioblastoma cell line SNB‐19, which expresses the latent form of TGF‐β, was transfected with a retroviral vector containing wild‐type p53 (wt‐p53) or p53 with a mutation (mut‐p53) at codon 273. Stable G418‐resistant SNB‐19 clones were isolated. The growth kinetics of wt‐p53 transfectants were suppressed compared with those of parental cells, vector transfectants, or mut‐p53 transfectants, as assayed by growthcurve measurements and H‐thymidine incorporation; how‐, ever, RNA dot blot and Western blot analyses demonstrated that wt‐p53 and mut‐p53 transfectants expressed higher amounts of TGF‐β1 and TGF‐β2 mRNA and intracellular TGF‐β isoform proteins, respectively, than parental cells. By means of the biological assay for active TGF‐β (MvlLu cell‐growth‐inhibition assay), we observed that both transfectants produced active TGF‐β, whereas the parental cells produced only the latent form. These results suggest that, while only the wt‐p53 gene inhibits tumor‐cell progression, both wt‐p53 and codon 273‐mutated p53 can cause increased TGF‐β expression.
Cytotoxicity and characterization of an active metabolite of benzamide riboside, a novel inhibitor of IMP dehydrogenase
Authors: Gharehbaghi Kamran , Paull Kenneth D. , Kelley James A. , Barchi Joseph J. , Marquez Victor E. , Cooney David A. , Monks Anne , Scudiero Dominic , Krohn Karsten , Jayaram Hiremagalur N. 
Published: February 2007

AbstractBenzamide riboside exhibits significant cytotoxicity against a variety of human tumor cells in culture. On the basis of metabolic studies, the primary target of this drug's action appears to be IMP dehydrogenase (IMPDH). Incubation of human myelogenous leukemia K562 cells with an IC50 concentration of benzamide riboside resulted in an expansion of IMP poofs (5.9‐fold), with a parallel reduction in the concentration of GMP (90%), GDP (63%), GTP (55%) and dGTP (40%). On kinetic grounds, it was deduced that benzamide riboside (whose Ki versus IMPDH is 6.4 mM, while that of its 5′‐monophosphate is 3.9 mM) or its 5′‐monophosphate were unlikely to be responsible for inhibition of this target enzyme, IMPDH, since only micromolar concentrations of benzamide riboside were needed to exert potent inhibition of tumor‐cell growth. Studies on the metabolism of this C‐nucleoside have revealed the presence of a new peak eluting in the nucleoside diphosphate area on HPLC. Treatment of this peak with venom phosphodiesterase degraded it and concurrently nullified its inhibitory activity versus IMPDH; alkaline phosphatase, on the other hand, totally failed to digest the anabolite. These results suggest that the metabolite in question is the phosphodiester, benzamide adenine dinucleotide (BAD). Evidence that the inhibitor was an analog of NAD, wherein the nicotinamide moiety has been replaced by benzamide, was provided by both NMR and mass spectrometric analysis and confirmed by enzymatic synthesis. Further insight into the nature of the active principle was obtained from kinetic studies, which established that BAD competitively inhibited NAD utilization by partially purified IMPDH from K562 cells with a Ki of O.118 μM. In concert, these studies establish that benzamide riboside exhibits potent antiproliferative activity by inhibiting IMPDH through BAD.