bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies of clonal cell lines developed from primary breast cancers indicate that the ability to undergo morphogenesis IN vitro is lost early in malignancy
Authors: Shearer Moira , Bartkova Jirina , Bartek Jiri , Berdichevsky Feodor , Barnes Diana , Millis Rosemary , Taylor‐Papadimitriou Joyce 
Published: February 2007

AbstractIn an attempt to obtain cell lines from the different components found in primary breast cancers, we used a low‐calcium medium to culture epithelial cells of mixed phenotype and a recombinant T antigen containing retrovirus to immortalize cells found in these cultures. In each case, the histology of the sample used for culture was examined in detail and the best growth was obtained from samples associated with a substantial in situ or benign component and from lobular rather than ductal carcinomas. Clonal cell lines were developed from each of 4 tumours: I infiltrating ductal (tumour number 2), 2 infiltrating lobular (tumours 3 and 5) and I mucoid (tumour 6). To try to identify the phenotype and origin of the cell lines, immunohis‐tochemical markers, histological analysis of tissue sections and behavioural markers were used. All the cell lines expressed mainly luminal epithelial cell markers, but the basal epithelial keratin, keratin 14, was also expressed homogeneously or heterogeneously. Growth in agar was seen with some but not all cell lines derived from only I tumour (tumour 5) and tumour development in nude mice was observed (with low efficiency) with cell lines from only I tumour (tumour 6). The data suggest that the cell lines obtained from the infiltrating ductal carcinoma (tumour 2) developed from cells cultured from the associated benign component, while the cell lines from tumours 3, 5 and 6 may each have developed from a cell in an early stage of malignancy. When tested for their ability to undergo morphogenesis on extracellular matrix components, celi lines from tumour 2 made well‐developed ductal‐alveolar‐like structures, while those from the other tumours did not.
Unique expression of integrin fibronectin receptors in human neuroblastoma cell lines
Authors: Yoshihara Takao , Esumi Noriko , Humphries Martin J. , Imashuku Shinsaku 
Published: February 2007

AbstractCultured human neuroblastoma cells can be classified morphologically into 3 types: neuroblastic (N), intermediate (I) and substrate adherent (S). Neuroblastoma cells of all types were found to attach and display distinct morphological characteristics on fibronectin, with S‐type cells attaching better than N‐type cells. Studies of the expression of integrin fibronectin receptors (α3βI, α4β I, α5β I and αVβ I) were carried out using a total of 26 morphologically distinct cell lines and their subpopu‐lations. Fluorescence‐activated cell sorting (FACS) analysis and immunoprecipitation revealed that all S‐type cells expressed abundant α5β I, while N‐type cells barely expressed this molecule. Although α3β I expression of S‐type cells was also higher than that of N‐type cells, some N‐type cells had significantly increased levels of this molecule. α4β I was found to be randomly expressed. All cell lines tested expressed αVβ I. Human neuroblastoma cells, the majority of which are N‐type cells with very low α5β I expression, are also contrasted with other childhood cancer cells (rhabdomyosarcoma, Ewing's sarcoma, and glioma), all of which expressed high levels of α5β I. The characteristic expression of integrin fibronectin receptors may account for the clinically unique tumor behavior, and the immunohistochemical staining for integrins may become a useful alternative to conventional histology in differential diagnosis and a marker for prognosis in neuroblastoma.
Dipyridamole enhances an anti‐proliferative effect of interferon in various types of human tumor cells
Authors: Suzuki Nobuo , Oiwa Yoko , Sugano Isamu , Inaba Noriyuki , Sekiya Souei , Fukazawa Ichio , Yoshida Jun , Takakubo Yoshiaki , Isogai Eriko , Saito‐Ebihara Mitsue 
Published: February 2007

AbstractThe anti‐proliferative activity of human interferon (HulFN) was enhanced by dipyridamole, 2,6‐bis‐(diethanolamino)‐4,8‐dipiperidinopyrimido‐[5,4‐d]‐pyrimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC‐1, U251‐SP and T98 (glioma), HAC‐2 and SHIN‐3 (ovarian carcinoma), and MM‐1CB (melanoma). The enhancement occurred irrespective of the kind of HulFN used (α, β or γ) and the original degree of susceptibility of the cells to HulFN. Even low doses down to 0.01 μM of dipyridamole that had no intrinsic anti‐proliferative activity could enhance the effect of HulFN. The enhancement of HulFN effects seems not to be caused by induction of HulFN production, because neither anti‐viral activity nor HulFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HulFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HulFN by dipyridamole for HAC‐2 and SHIN‐3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC‐21 ovarian cancer cells nor HEC‐1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC‐1, U251‐SP, and HAC‐2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HulFN in combination with oral administration of dipyridamole than by the HulFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HulFN by dipyridamole varied among the cell lines examined.
Regulation of surface‐differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c‐Ha‐ras proto‐oncogene
Authors: Basolo F. , Serra C. , Ciardiello F. , Fiore L. , Russo J. , Campani D. , Dolei A. , Squartini F. , Toniolo A. 
Published: February 2007

AbstractSpontaneously immortalized human mammary epithelial cells MCF‐IOA were transfected with an activated c‐Ha‐ras oncogene. Transfected cells (MCF‐IOT) acquire a malignant pheno‐type, as already reported. Studies of l‐2′‐deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF‐α) showed that though MCF‐IOT had become almost independent on exogenous EGF and TGF‐α, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class‐I molecules, human milk‐fat‐globule‐1 antigen, and EGF receptor was reduced in ras‐transfected cells, although other differentiation markers were unchanged. Exogenous EGF down‐regulated the expression of functional EGF‐R, selectively in transformed cells. TGF‐α failed to modulate EGF‐R. In contrast, HC strongly stimulated the expression of EGF‐R while depressing MHC class‐l molecules. Thus, it appears that in vivo HC may co‐operate with TGF‐α and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers.
A single human colonic adenoma cell line can be converted IN VITRO to both A colorectal adenocarcinoma and A mucinous carcinoma
Authors: Paraskeva Christos , Hague Angela , Rooney Nicholas , Williams Ann C. , Harper Sara J. , Hanlon Katherine A. , Atkinson Rebecca J. , Corfield Anthony P. 
Published: February 2007

AbstractIn a previous study, using a chemical carcinogen, we converted in vitro a non‐tumorigenic cell line derived from a human colorectal diploid adenoma, designated PC/AA, into a tumori‐genic cell line which, when inoculated into athymic nude mice, produced progressively growing adenocarcinomas. We now report that continuous in vitro passage of the PC/AA adenoma cell line resulted in its spontaneous transformation to a mucinous carcinoma with a modal karyotype of 51, XY, + i( Iq), +8, +9, +13, +i(13q), ‐21, +mar. These studies show that a single adenoma can be converted along 2 independent pathways, giving rise to either a mucinous carcinoma or an adenocarcinoma, and provide further experimental evidence for the adenoma‐carcinoma sequence. Cytogenetic changes which occur along both pathways to tumorigenicity include abnormalities of chromosome I and multiple copies of chromosome 13. These abnormalities may be important in tumour development and progression in colorectal carcinogenesis.
Quantitative study of the growth of experimental hepatic tumors in rats by using magnetic resonance imaging
Authors: Qin Yunfeng , Van Cauteren Marc , Osteaux Michel , Willems Gérard 
Published: February 2007

AbstractPrecise estimation of the volume and growth rate of hepatic metastases would represent an important step forward not only in clinical oncology but also for the evaluation of experimental treatments in animal models. In the present study, an original method of volumetry of hepatic metastatic tumors in vivo has been tested in rats using magnetic resonance imaging (MRI). Three different hepatic tumor models mimicking liver metastases were established in syngeneic BDIX rats by injection of DHD/KI2 rat colon cancer cells either directly under the liver capsule or via the portal system. The liver tumor volumes were estimated in vivo by using MR imaging of the liverand summing the individual tumor volumes in the sequential MR liver sections. The values of the tumor volumes measured by MRI were compared with those determined by a classical method of water displacement in vitro after killing the animals and excising the tumors. At 3 weeks after tumor implantation, liver tumors as small as I mm in diameter could be detected by MRI. The difference between the tumor volumes estimated by MRI in vivo and those measured by water displacement in vitro was 9% for single liver tumors and 16% for multiple liver tumors. Close correlation between the values of the tumor volumes measured by MRI and those determined by water displacement was observed in solitary liver tumors (r = 0.985, p < 0.01) as well as in multiple liver tumors (r = 0.985, p < 0.01), indicating the high accuracy of MRI volumetry for liver tumors. Estimation of the liver tumor volumes by MRI in the same animals at successive time intervals made it possible to construct tumor growth curves and to calculate tumor growth parameters. These data suggest that MRI volumetry represents an effective means of evaluating the efficacy of experimental treatments in small animals and may have potentially important applications in clinical patients.
c‐myc amplification is an independent prognostic factor in postmenopausal breast cancer
Authors: Borg Åke , Baldetorp Bo , Fernö Mårten , Olsson Håkan , Sigurdsson Helgi 
Published: February 2007

AbstractThe c‐myc proto‐oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2‐5 copies). The adjacent pvt gene was co‐amplified with c‐myc in all tumors analyzed. C‐myc amplification was significantly correlated to a high S‐phase fraction and to amplification of the c‐erbB‐2 proto‐oncogene. Weak relationships were found between c‐myc amplification and the presence of lymph‐node metastasis, advanced stage, DNA non‐diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int‐2 amplification. C‐myc amplification, and especially a high gene copy number (>5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph‐node‐negative and node‐positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p > 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c‐myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c‐myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c‐myc activation in human breast cancer. However, the obvious instability of the c‐myc transcript and translate suggests that c‐myc is not a suitable prognostic marker for routine purposes. © 1992 Wifey‐Liss, Inc.
Study of fibronectin mRNA in human laryngeal and ectocervical carcinomas by IN SITU hybridization and image analysis
Authors: Moro Laura , Colombi Marina , Tosatti Maria Pia Molinari , Barlati Sergio 
Published: February 2007

AbstractThe expression of fibronectin (FN) mRNA was studied in histological sections of surgical biopsies from human laryngeal and ectocervical invasive carcinomas of different grading stages by in situ hybridization and image analysis. This approach made it possible to identify the cell types synthesizing FN mRNA in the tissue sections and to compare semi‐quantitatively the FN mRNA levels expressed in the different specimens. The carcinoma cells synthesized low levels of FN mRNA, comparable to those detected in control epithelia and connective‐tissue fibroblasts. Well‐differentiated (G1) laryngeal and ectocervical carcinomas induced the synthesis of FN mRNA—to levels 7 to 13 times higher than in control connective tissues—in the stromal fibroblasts surrounding the tumors. In carcinoma samples analysed, the amount of FN mRNA detected in the stroma decreased in relation to tumor grading (from G1 to G3) and the stromal destruction. FN mRNA was not detectable in the endothelial cells of venules while it was present in large amounts in those surrounding the capillaries present in the stroma. These data indicate that FN, usually observed around carcinomas, is produced by stromal fibroblasts, which are induced to express FN mRNA, presumably in response to diffusible factors produced by the tumor cells, and/or by endothelial cells of the infiltrating capillary vessels. The induction of FN mRNA, inversely proportional to the tumor grading, may be useful in evaluating the invasion potential of the tumor. © 1992 Wifey‐Liss, Inc.
Loss of heterozygosity for distal markers on 22q in human gliomas
Authors: Rey Juan A. , Bello M. Josefa , Jimenez‐lara Ana M. , Vaquero Jesus , Kusak M. Elena , de Campos José M. , Sarasa José L. , Pestana Angel 
Published: February 2007

AbstractLoss of constitutional heterozygosity as determined through the analysis of restriction‐fragment‐length polymorphism (RFLP) on tumoral and constitutional DNA has proven to be helpful to delimit the location of tumor‐suppressor genes in the human genome. In malignant gliomas this approach indicates that chromosomes 9p, 10, 17p, and 22 may contain genes of this category involved in its origin and/or progression. Regarding chromosome 22, the data so far provided by molecular studies confirmed those previously reported by cytogenetic studies, suggesting the existence of a sub‐group of malignant gliomas characterized by monosomy of this chromosome. However, the precise location of the putative glioma suppressor gene on chromosome 22 remains ambiguous. We have performed a combined cytogenetic and RFLP study on a series of 31 gliomas, looking for structural abnormalities of this chromosome. In 3 instances, terminal deletions of the long arm of chromosome 22 were observed by both methodologies, suggesting that the band q13 region distal to the D22S80 marker might be the critical domain non‐randomly involved in tumor suppression of gliomas. © 1992 Wifey‐Liss, Inc.
Cytostatic activity of new synthetic anti‐tumor aza‐alkyllysophospholipids
Authors: Sidoti Carole , Principe Paola , Vandamme Benedicte , Broquet Colette , Braquet Pierre 
Published: February 2007

AbstractAlkyllysophospholipids are analogues of the naturally occurring 2‐lysophosphatidylcholine which have been reported to have selective in vitro/in vivo anti‐tumor activity. Their anti‐proliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of 2 newly synthetized aza‐alkyllysophospholipids (AALPs), the BN52205 and the BN52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. We used 3 different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the anti‐proliferative activity of the 2 AALPs. By applying the biparametric analysis of 5′‐bromo‐2‐deoxyuridine incorporation vs. DNA content we have been able to demonstrate that the 2 AALPs do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein vs. DNA content in isolated HT29 nuclei enabled us to exclude a block in the M phase of the ee cycle. Finally, stathmokinetic analysis enabled us to show that cytostatic activity of the 2 new AALPs is characterized by multiple “terminal points” as the drugs' action results in a G1 block, in a slow‐down of the transition from late S to G2 followed by an accumulation of HT29 cells in the G2 phase of the cell cycle. © 1992 Wifey‐Liss, Inc.
Modulation of neuroblastoma cell differentiation by the extracellular matrix
Authors: Matsushima Hiroshi , Bogenmann Emil 
Published: February 2007

AbstractThe effect of a complex in vitro synthesized extracellular matrix (ECM) and its components on growth and phenotypical differentiation of a human neuroblastoma (NB) cell line (HTLA230) was investigated. Rat smooth‐muscle‐cell (R22CIF)‐derived ECM composed of collagen, glycoproteins, and glycosaminoglycans (GAGs) promoted spontaneous neurite outgrowth of HTLA230 cells but did not alter their growth kinetic or cloning efficiency as compared with cells seeded onto gelatin‐coated dishes. The matrix significantly enhanced, quantitatively and qualitatively, the responsiveness of HTLA230 cells to retinoic acid (RA), and a substantially reduced growth rate was observed in the presence of RA with cells grown on the ECM. Biochemical modification of the composition of the R22CIF‐matrix by trypsin digestion and/or high‐salt extraction (4 M guanidinium) demonstrated that the ratio of chondroitin sulfate to hyaluronic acid (HA) present in the ECM determines the capacity of the matrix to promote NB differentiation. A human fibroblast (T‐1)‐derived ECM, which has a biochemical composition of the GAG component similar to that of the trypsinized R22 CIF‐matrix, but which has a high amount of glycoproteins, confirmed these results. Nerve‐growth‐factor (NGF)‐induced differentiation in a variant HTLA 230 cell line was inhibited when cells were grown on an ECM with a low ratio of chondroitin sulfate/HA. The composition of the ECM thus modulates the responsiveness to various differentiation‐inducing agents and alters the phenotype of NB cells. © 1992 Wifey‐Liss, Inc.
Phosphorylation and estradiol binding of estrogen receptor in hormone‐dependent and hormone‐independent GR mouse mammary tumors
Authors: Migliaccio Antimo , Pagano Michele , de Goeij Cornelis C. J. , Domenico Marina Di , Castoria Gabriella , Sluyser Mels , Auricchio Ferdinando 
Published: February 2007

AbstractThe effect of phosphorylation on the hormone‐binding capacity of the estrogen receptor (ER) was investigated in hormone‐dependent (HD) and hormone‐independent (HI) mammary carcinomas of GR mice. Tumor cytosols were incubated with ATP under conditions previously used to study the tyrosine kinase which confers hormone binding to phosphatase‐treated or in vitro‐synthesized ER. The ATP‐dependent increases in hormone‐binding capacity of 8 out of 20 HI tumors ranged from values of 23 to 124 fmol/mg cytosol protein. The enhancement by ATP of hormone binding to ER was significantly less marked in HD and HR tumors than in HI tumors. In only 3 out of 13 HD and HR tumors was an increase ranging from 15 to 20 fmol/mg protein detected. Analysis by Scatchard plot of estradiol binding to ER showed that cytosol incubation of HI tumors with ATP markedly increased the hormone binding without any change in affinity. The data suggest that ER of HI tumors is less phosphorylated in vivo than the ER of HD/HR tumors, so that the receptor of HI tumors is more susceptible to γ32P‐ATP phosphorylation and ATP‐induced hormone binding in vitro. Western blot of ER with antiphosphotyrosine antibody showed that, in HI tumors, the large ATP‐induced increase in hormone binding to ER was associated with phosphorylation on tyrosine of the receptor itself. Our findings indicate that the process of activation‐inactivation of binding through tyrosine‐phosphorylation/ phosphotyrosine‐dephosphorylation of ER observed in estrogen target tissues is altered in some HI mammary tumors. © 1992 Wifey‐Liss, Inc.
Malignant transformation of NIH‐3T3 cells after subcutaneous co‐injection with a reconstituted basement membrane (matrigel)
Authors: Fridman Rafael , Sweeney Thomas M. , Zain Mona , Martin George R. , Kleinman Hynda K. 
Published: February 2007

AbstractNIH‐3T3 cells are non‐tumorigenic when injected into athymic mice. If these cells are mixed with an extract of basement‐membrane proteins (matrigel) and injected s.c., they form locally invasive and highly vascularized tumors. Cells cultured from the NIH‐3T3‐matrigel‐induced tumors showed a transformed phenotype and lacked contact inhibition. When cultured in a gel of matrigel, they proliferated and formed branched and invasive colonies. In contrast, the parental NIH‐3T3 cells cultured on matrigel remained as cell aggregates and were not invasive. I.V. injections of the tumor‐derived NIH‐3T3 cells produced many colonies on the surface of the lungs, whereas the parental NIH‐3T3 cells were not metastatic. Zymographic analysis of the conditioned media obtained from both the tumor‐derived and parental NIH‐3T3 cells demonstrated higher amounts of the 72‐kDa gelatinase (type‐IV collagenase) enzyme in the tumor‐derived cells. Also, tumorderived NIH‐3T3 cells, but not parental NIH‐3T3 cells, secreted the 92‐kDa type‐IV collagenase. These studies suggest that the interaction of pre‐malignant NIH‐3T3 cells with extracellular matrix components may contribute to the process of tumor progression. © 1992 Wifey‐Liss, Inc.
Putative invasion‐specific proteins in mouse T‐cell hybridomas that differ in invasive and metastatic potential
Authors: La Rivière Geertje , Schipper Cor A. , Klein Gebbinck Jacqueline W. T. M. , Koch Guus , Kuhn Lotte , Lefkovits Ivan , Roos Ed 
Published: February 2007

AbstractFusion of invasive, activated T‐lymphocytes with non‐invasive BW5147 T‐lymphoma cells mainly yields highly invasive (HI), highly metastatic T‐cell hybridomas. In addition, several noninvasive (NI), non‐metastatic hybrids have been obtained, probably due to loss of involved gene(s) by chromosome segregation. Here we have compared a panel of HI and NI hybrids in a search for proteins specifically expressed by either cell type. MAbs were raised against HI hybrids, but out of more than 1,000 none bound exclusively to HI cells. Furthermore, polyclonal rat, rabbit and chicken antisera did not immunopre‐cipitate specific proteins from total lysates, and the expression of 18 (T‐cell) surface markers did not correlate with invasiveness. These results indicated that the number of differences between HI and NI hybridomas was surprisingly small. This notion was confirmed by 2‐dimensional gel electrophoresis. Among 1,000 detectable spots, we found only 2 clear‐cut differences between HI and NI T‐cell hybridomas, whereas multiple differences were found between individual hybrids. One protein (p130) was expressed at much higher levels by HI than by NI hybrids in this panel, whereas the other (p 15) was only seen in NI hybrids. These proteins are primary candidates for a role in invasion. © 1992 Wifey‐Liss, Inc.