bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformation of rodent fibroblasts by herpes simplex virus: Presence of morphological transforming region 1 (MTR 1) is not required for the maintenance of the transformed state
Authors: Bauer Georg , Kahl Susanne , Sawhney Iva Singh , Höfler Petra , Gerspach Ralph , Matz Bertfried 
Published: February 2007

AbstractStudies on the mechanisms of transformation of mammalian cells by herpes simplex virus (HSV) in vitro have been prevented so far by the extremely low transformation frequencies obtained in monolayer culture. Here we present a transformation system that relies on the direct seeding in soft agar of infected single cells, thus avoiding negative interactions between normal and transformed cells. We took advantage of HSV‐1 temperature‐sensitive mutants at the UL9 locus, which codes for a DNA‐binding protein necessary for viral DNA replication. At the non‐permissive temperature, viral DNA synthesis and late gene expression are prevented. Viral gene expression is restricted to immediate early and early genes. Induction of transformation was highly efficient in our one‐step transformation system. It depended on intact viral particles and viral DNA. Immediate early and/or early viral gene expression was sufficient to induce transformation. Colonies were stably transformed and did not show any rescue of viable virus after temperature downshift and co‐cultivation with susceptible cells. Transformed cells maintained the transformed state in the absence of viral DNA. Our data therefore support the “hit‐and‐run” hypothesis for the transforming effect of HSV. © 1992 Wifey‐Liss, Inc.
Elevated stromelysin‐1 and reduced collagenase‐IV expression in invasive rat embryo fibroblasts expressing e1a deletion mutants + T24‐H‐ras
Authors: Engel Georg , Popowicz Przemyslaw , Marshall Heather , Norling Gertrud , Svensson Catharina , Auer Gert , Akusjärvi Göran , Linder Stig 
Published: February 2007

AbstractWe have studied the in vitro invasive properties of 3 cell lines derived from the co‐transfection of rat embryo fibroblasts (REF) with E1A genes deficient in exon 2 and T24‐ras. All 3 cell lines showed invasive properties at passage 10 after isolation. Invasive cells expressed elevated levels of stromelysin‐I and reduced levels of 68‐kDa type‐IV collagenase compared with untransfected REF. In 2 cell lines the invasive capacity increased during in vitro propagation. The expression of stromelysin‐I increased during this process, whereas 68‐kDa type‐IV collagenase was persistently expressed at reduced levels. In the third clone analyzed, the invasive capacity decreased during culture, in parallel with decreased expression of stromelysin‐I. The low level of stromelysin‐I expression observed in this cell line did not result from loss of AP‐I ‐transcription‐factor activity, and was not reversed by phorbol‐ester treatment. © 1992 Wifey‐Liss, Inc.
Fibroblast‐dependent tumorigenicity of melanoma xenografts in athymic mice
Authors: Gärtner Maria F. R. M. , Wilson E. Lynette , Dowdle Eugene B. 
Published: February 2007

AbstractTwo human melanoma cell lines, UCT‐Mel 2 and UCT‐Mel 3, were invariably tumorigenic in nude mice when inoculated s.c. in doses of 106 cells or higher; 105 cells or less did not give rise to tumours. In this report we show that otherwise sub‐tumorigenic inocula developed into vigorously growing tumour xenografts when co‐inoculated with normal fibroblasts. Fibroblasts derived from adult, neonatal or embryonic tissues all functioned as complementing cells, as did cells of human or murine origin. There was, however, a requirement for complementing cell viability, since ethanol‐killed fibroblasts were inefficacious. The fibroblast effect was dose‐dependent and was not observed if injections of fibroblasts and melanoma cells were separated anatomically or temporally. We have shown, by titrating admixtures of melanoma cells and fibroblasts, that fibroblasts are, in quantitative terms, more efficacious than melanoma cells as complementing cells. The system we describe provides a useful model for the study of stromal‐cell regulation of tumour growth. © 1992 Wifey‐Liss, Inc.
Arrest in late G2 or prophase of cell cycle induced by 4,4‐(l,2‐ethanediyl) bis (1‐isobutoxycarbonyloxymethyl 2, 6‐piperazinedione) (MST‐16) in cultured l1210 cells
Authors: Liu Yun‐Peng , Araya Shin‐Ichi , Nakamura Toru 
Published: February 2007

AbstractThe effects of MST‐16, a new antitumor agent derived from bis (2, 6‐dioxopiperazine), on cell growth, cell‐cycle progression and DNA synthesis, alone and in combination with other antitumor agents, were investigated in murine leukemia L1210 cells in vitro. The drug showed dose‐dependent inhibition of cell growth, and this effect was cell‐cycle phase‐specific. Flow cytometric analysis indicated that the drug could retard‐arrest the cells in late G2 phase or prophase and that it did not affect the progression from G1 to G2 phase. In the presence of MST‐16, the change in 3H‐thymidine incorporation was proportional to the retardation‐arrest of the cells, suggesting that MST‐16 has no direct action on DNA synthesis itself. MST‐16 could continuously retard the cells which were arrested by etoposide (VP‐16); and vincristine (VCR) could block the progression of the cells arrested by MST‐16, but not vice versa. The addition of MST‐16 followed by VCR was more effective than simultaneous addition of the 2 drugs on inhibition of cell growth. These results will be useful in designing a reasonable regimen of MST‐16 chemotherapy for malignancies. © 1992 Wifey‐Liss, Inc.
Metastatic phenotype of murine tumor cells expressing different cooperating oncogenes
Authors: Virone Angela , Monier Roger , Zerial Aurelio , Lavelle François , Feunteun Jean 
Published: February 2007

AbstractFour murine cellular tumor models expressing various combinations of oncogenes (SV40 large T and v‐Ha‐ras, SV40 large T and v‐src, SV40 large T and neu, adenovirus E1A and v‐Ha‐ras) induce sarcoma when they are inoculated s.c. into the DBA/2 syngenic mice. The metastatic patterns, distribution and fate of these tumor cells transplanted by two different routes into syngenic DBA/2 mice have been studied. All the tumor cell lines except E1A‐ras, induce massive overt artificial metastases principally in the lung after i.v. injection. In s.c. tumor‐bearing mice, a few resting cells colonize the lung as micrometastases. When removed from this tissue context and injected s.c. these cells regain their proliferative potential and grow as local tumors which again give rise to occult pulmonary micrometastases. © 1992 Wifey‐Liss, Inc.
Colon cancer in argentina. II: Risk from fibre, fat and nutrients
Authors: Iscovich J. M. , L'abbé K. A. , Castelleto R. , Calzona A. , Bernedo A. , Chopita N. A. , Jmelnitzsky A. C. , Kaldor J. , Howe G. R. 
Published: February 2007

AbstractA case‐control study has been conducted to investigate the relationship between total energy intake, fibre and nutrients and colon cancer in Argentina. Cases are 110 newly diagnosed patients from 10 hospitals between 1985 and 1986. Two neighbourhood controls per case were matched on age, sex and place of residence. The intake of calories, fibre and nutrients was estimated from the information collected on food consumption during the 5‐year period up to 6 months prior to interview of subjects, based on a pilot study and standard portion sizes in Argentina. In conditional regression models, dietary fibre is highly protective (odds ratio (OR) = 0.07 per 19.02 g/day; 95% confidence interval (CI): 0.02 to 0.25) and total energy intake increases risk (RR = 1.82 per 1000 kcal/day; 95% CI: 1.20 to 2.77), each with adjustment for the other. Analysis of caloric components (fat, protein and carbohydrates) reveals that carbohydrates are the most important factor driving the total energy effect. Other nutrients make little apparent contribution to risk.
Clustering of discrete cell properties essential for tumorigenicity and metastasis. III. Dissociation of the properties in N‐ras‐transfected rsv‐SR‐transformed cells
Authors: Deichman G. I. , Topol L. Z. , Kluchareva T. E. , Matveeva V. A. , Zakamaldina T. A. , Uvarova E. N. , Tatosyan A. G. 
Published: February 2007

AbstractWe have previously shown that RSV‐SR‐transformed hamster cells acquire high resistance to H2O2, i.e. the cytotoxic product of activated macrophages (H2OR2) and that they begin to secrete PGE (PGEs), thus inactivating the CTA of NK cells. Among normal cells, the same phenotype is expressed in activated macrophages. In all our RSV‐transformed cells these 2 properties were jointly expressed and correlated with high tumorige‐nicity and experimental metastasizing of these cells. We now show that transfection of 3 RSV‐SR‐transformed cell strains with activated N‐ras leads either to complete inhibition of the H2OR2 + PGES phenotype in all clones of one strain, or to inhibition of PGES only in the majority of clones of 2 other strains. Unexpectedly, the complete or partial inhibition of this phenotype did not alter the high tumorigenicity of 2 strains of these cells, but lower tumorigenicity was evident in almost all clones of the third strain (as well as in some gene‐neo‐transfected clones of these strains). The loss of PGES made these cells susceptible to the CTA of NK cells, while the loss of H2OR2 did not alter their resistance to the CTA of macrophages. Expression of the H2OR2 + PGES phenotype was retained in all cloned variants of control, gene‐neo‐transfected cells. The possible relation of the N‐ras gene to regulation of src gene activities in RSV‐SR‐transformed cells is discussed.
In vitro activity of novel antifolates against human squamous carcinoma cell lines of the head and neck with inherent resistance to methotrexate
Authors: van der Laan B. F. A. M. , Jansen G. , Kathmann G. A. M. , Westerhof G. R. , Schornagel J. H. , Hordijk G. J. 
Published: February 2007

AbstractA series of 7 human squamous carcinoma cell lines of the head and neck (HNSCC), grown in standard medium containing high folate concentrations and in “folate‐conditioned” medium containing nanomolar concentrations of folates, were all found to be sensitive (IC50: ⩽50 nM) in growth‐inhibition studies to methotrexate (MTX) following drug exposure for 7 days. However, when MTX exposure was limited to 24 hr, only 2 out of 7 HNSCC cell lines were sensitive to MTX (IC50: <500 nM), 2 were moderately sensitive (IC50: 1‐2 μM), and 3 exhibited inherent resistance to MTX (IC50: >250 μM). In these last 3 cell lines, the mechanism of resistance was not correlated with altered membrane transport of MTX or changes in dihydrofo‐late reductase activity, but rather was associated with a 3‐fold lower activity of intracellular folylpolyglutamate synthase (FPGS) activity compared to MTX‐sensitive HNSCC cells. The 3 cell lines exhibiting inherent resistance to a short exposure to MTX, however, did not show inherent cross‐resistance after exposure for 24 hr to one or more of 3 novel antifolate compounds. These compounds, which appear to be more efficiently transported and polyglutamylated than MTX, include: 10‐ethyl‐10‐deazaami‐nopterin (10‐EdAM), 2‐desamino‐2‐methyl‐N10‐propargyl‐5,8‐dideazafolic acid (ICI‐198,583), and 5, 10‐dideazatetrahydrofo‐lic acid (DDATHF). These results indicate that antifolate membrane transport and intracellular FPGS activity are important factors in determining sensitivity or resistance of HNSCC cells to short‐term antifolate compound exposures.
Physiological factors influencing radioantibody uptake: A study of four human colonic carcinomas
Authors: Blumenthal Rosalyn D. , Sharkey Robert M. , Kashi Rina , Natale Ana M. , Goldenberg David M. 
Published: February 2007

AbstractWe evaluated the accretion of 131l‐labeled NP‐4 anticarcinoembryonic antigen (CEA) into 4 size‐matched human colonic carcinomas grown s.c. in nude mice. Antibody uptake for LS174T and GW‐39 tumors was relatively high (19 to 23%ID/g on day 3), whereas moderate uptake was seen in the Moser tumor (7.5% on day 3) and low uptake was detected in the GS‐2 tumor (1.8% on day 3). Blood clearance of radioanti‐body was twice as fast in mice with GS‐2 tumors than in mice with GW‐39, LS174T or Moser tumors. Seven physiological parameters that might influence radioantibody accretion were evaluated in order to better understand the differences in observed tumor targeting: vascular volume, blood flow rate, vascular permeability, tumor antigen content, serum antigen content and complexation of radioantibody, intratumoral antigen distribution, and intracellular antigen distribution. Although marked variability in vascular physiology, antigen content and antibody complexation of the 4 tumors grown in the same host and site existed, it was insufficient to explain the differences in antibody uptake. However, intra‐tumoral distribution of antigen, and sub‐cellular accessibility of antigen for radioantibody were important considerations. GS‐2 tumors are well differentiated and have polarized cells. CEA in GS‐2 is largely inaccessible to radioantibody; most of the antigen is located in the lumen of the glands or on the apical surface of gland cells and most of the antibody distributes to the stromal region on the basolateral surface. The low antibody targeting in GS‐2 could therefore be explained by restricted intra‐tumor accessibility of antibody. Scatchard analysis of NP‐4 binding to Moser cells under non‐internalizing and internalizing conditions revealed that 90% of the antigen is found within the cell, unavailable to bind with the NP‐4 antibody, which is slow to internalize. In contrast, CEA in LS174T cells was almost entirely accessible. The reduced antibody targeting to Moser xenografts might therefore, be explained by restricted antibody accessibility at the cellular level.
Therapy of primary and metastatic mouse mammary carcinomas with doxorubicin encapsulated in long circulating liposomes
Authors: Vaage Jan , Mayhew Eric , Lasic Dan , Martin Frank 
Published: February 2007

AbstractThe purpose of our study was to compare the therapeutic effects of doxorubicin in 3 different formulations: (1) in PBS, (2) in conventional liposomes composed of egg phosphatidylglycerol/ egg phosphatidylcholine/cholesterol/dl‐α tocopherol, and (3) in sterically stabilized, long‐circulating “Stealth” liposomes composed of hydrogenated soy phosphatidylcholine/cholesterol/ polyethylene glycol‐distearoylphosphatidylethanolamine. The doxorubicin formulations were used to treat recently implanted and well‐established, growing primary mouse mammary carcinomas, and to inhibit the development of spontaneous metastases from intra‐mammary tumor implants. In the treatment of recently implanted primary tumors, the formulations were given in 3 i.v. injections over 15 days, starting 3 or 10 days after tumor implantation. In the treatment of well‐established primary tumors, the mice received 4 i.v. injections over 22 days, starting an average 38 days after tumor implantation. In the preventive treatment against metastases, the formulations were given in 4 i.v. injections over 22 days, starting 22 days or 58 days after primary tumor implantation. The Stealth liposome formulation was significantly more effective than the conventional liposome formulation or the free drug in reducing the incidence of metastases from intra‐mammary implants of tumor MC19 and tumor MC65, in curing mice with recent implants of tumor MC2A, tumor MC2B, and tumor MC65, and in increasing the 8‐week survival of mice with well‐established implants of tumor MC2B. It is concluded that the long circulation time of the Stealth liposome doxorubicin formulation accounts for its superior therapeutic effectiveness. © 1992 Wiley‐Liss, Inc.
Interferon‐α/β in virus‐induced mouse mammary carcinogenesis: Effects on the spontaneous process and on the progression of transplanted pre‐neoplastic lesions
Authors: Basolo F. , Fontanini G. , Serra C. , Dolei A. , Proietti E. , Belardelli F. , Conaldi P. G. , Bistocchi M. , Squartini F. , Toniolo A. 
Published: February 2007

AbstractLow levels of anti‐viral activity, mainly interferon α/β (IFN‐α/ β), are regularly found in lymphoid tissues of BALB/c mice infected with the C3H strain of mammary tumor virus. At the time of tumor development, significant amounts of anti‐viral activity were detected in homogenates of spleen and mammary tumors, but not in blood and normal mammary glands. This activity is pH2‐resistant and neutralized by antibody to IFN/ α‐β. The pathogenetic role of IFN in mammary carcinogenesis was investigated in 2 ways: (a) by treating virus‐infected newborn mice with antibody to IFN‐α/β, and (b) by giving either the latter antibody or IFN‐α/β to virus‐free animals transplanted with pre‐neoplastic lesions. Mice were treated only for 2 months, starting either I week after birth or immediately after tumor transplant. In case (a), treatment with antibody to IFN‐α/β shortened the incubation period of mammary carcinomas and decreased the mean survival time. In case (b), anti‐IFN antibody did not significantly affect the development of mammary tumors. However, exogenous IFN‐α/β markedly reduced both tumor incidence and mortality rate. These results indicate that endogenous IFN‐α/β plays a crucial role in the in vivo restriction of the early infectious phase of spontaneous carcinogenesis and that relatively high doses of IFN‐α/β may inhibit the progression of pre‐neoplastic lesions. © 1992 Wiley‐Liss, Inc.
Optimization of culture conditions for activation and large‐scale expansion of human T lymphocytes for bispecific antibody‐directed cellular immunotherapy
Authors: Lamers C. H. J. , van de Griend R. J. , Braakman E. , Ronteltap C. P. M. , Bénard J. , Stoter G. , Gratama J. W. , Bolhuis R. L. H. 
Published: February 2007

AbstractWe investigated the optimal culture conditions (i.e., activation procedure, medium composition and type of culture vessel) for rapid in vitro expansion of large numbers (>5 × 109) of blood T lymphocytes. These expanded lymphocytes can be targeted to be cytotoxic to ovarian carcinoma cells with a bispecific monoclonal antibody (BsAb) specific for CD3 and for the ovarian carcinoma‐associated antigen MOvl8. Both phytohemagglutinin (PHA) and monoclonal antibody (MAb) CD3 induced rapid T‐cell proliferation, although the growth kinetics after PHA activation were slightly faster. A 50‐fold increase in cell number was obtained after 14 and 16 days for PHA and CD3 MAb, respectively. The induction of BsAb‐directed cytolysis was faster after CD3 MAb than after PHA activation of lymphocytes, but became similar around day 20. A mixture of media consisting of 78% RPMI 1640, 20% AIM‐V and 2% human plasma (Mix‐med) yielded better results than 100% AIM‐V medium. Culture of lymphocytes in polyolefin bags, compared with tissue culture flasks, or cryopreservation did not affect lymphocyte yield and function. In most cultures the proportion of CD8+lymphocytes increased, suggesting a growth advantage of CD8+over CD4+ lymphocytes in this culture system. A protocol employing PHA activation, Mix‐med and polyolefin bags has been used successfully to activate and expand blood lymphocytes for the first 5 patients entered into a phase‐l/ll clinical trial for the intraperitoneal treatment of ovarian carcinoma using CD3 x anti‐MOv 18 BsAb‐directed T lymphocytes. © 1992 Wiley‐Liss, Inc.
Expression of histo‐blood‐group‐A/B‐gene‐defined glycosyltransferases in normal and malignant epithelia: Correlation with A/B‐carbohydrate expression
Authors: Mandel Ulla , Langkilde Niels C. , Osrntoft Torben F. , Therkildsen Marianne Hamilton , Karkov Jens , Reibel Jesper , White Thayer , Clausen Henrik , Dabelsteen Erik 
Published: February 2007

AbstractMalignant transformation of oral and bladder epithelia is often associated with loss of histo‐blood‐group‐A‐ and ‐B‐carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A‐ and B‐carbohydrate antigens with that of the A/B‐gene‐defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti‐A/B‐transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A‐ and B‐carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B‐transferees proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A‐ and B‐carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes. © 1992 Wiley‐Liss, Inc.
Expression of p53 protein in cutaneous melanoma
Authors: Akslen Lars A. , Mørkve Odd 
Published: February 2007

AbstractThe purpose of the present study was to examine the expression of p53 protein in malignant melanomas of the nodular sub‐type, with special reference to the role of p53 alterations in the development of metastases. Increased expression of p53 protein was found in 29 of 30 cases using PAb 1801 monoclonal antibody (MAb) and flow‐cytometric detection on archival material. A large proportion of the cells were positive in a majority of the cases. The level of expression was not correlated to DNA ploidy or to subsequent development of local metastases. However, a significant decrease in p53 protein expression was observed in metastatic lesions, as compared with the corresponding primary tumors. Our results indicate that p53 alterations may be an early event in melanoma development, since almost all cases were affected, and that metastatic spread appears to be parallelled by decreased p53 protein expression. © 1992 Wiley‐Liss, Inc.
Aspects of medical history and exocrine carcinoma of the pancreas: A population‐based case‐control study in The Netherlands
Authors: De Mesquita H. B. Bueno , Maisonneuve P. , Moerman C. J. , Walker A. M. 
Published: February 2007

AbstractDuring 1984–88 a population‐based case‐control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. We observed an inverse relationship between medical treatment for allergy‐ related conditions and the development of pancreatic cancer (30 cases vs. 130 controls, OR 0.57, 95% Cl 0.36 to 0.90). A history of gallbladder problems, gallstones, cholecystectomy, stomach or duodenal ulcer, pancreatitis, appendicitis, diabetes or tonsillectomy was not related to risk. In direct responses, compared with once daily, a positive relationship was seen for stool frequency, 10 years ago, of less than once daily (18 cases vs. 40 controls, OR 2.10, 95% Cl 1.09 to 4.04). In men, diabetes treated with insulin and diagnosed more than 1 year previously was significantly and positively related to risk (5 cases vs. 1 control, OR 11.66, 95% 1.28 to 105.95). In brief, the results of the present study suggest that a history of allergy‐related conditions may protect, whereas a past stool frequency of less than once daily may enhance the risk of cancer of the pancreas. Other elements of the medical history were not consistently related to risk. © 1992 Wiley‐Liss, Inc.