bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferation, migration and invasion of human glioma cells exposed to antifolate drugs
Authors: Terzis A. J. A. , Arnold H. , Fiskerstrand T. , Refsum H. , Ueland P. M. , Bjerkvig R. 
Published: February 2007

AbstractThe present study describes the effects of 2 folate antagonists, methotrexate (MTX) and the lipophilic antifolate trimetrexate (TMX) on 2 permanent human glioma cell lines (GaMg and D‐54Mg) grown as monolayers and as multicellular tumor spheroids. In addition, the effects of drug exposure on tumor cell invasion was studied using a three‐dimensional organ co‐culture system. In monolayer cultures, TMX was a more potent inhibitor of cell growth than MTX, especially towards the GaMg cell line. The 2 drugs, however, showed similar cytotoxicity as assessed by the plating efficiency assay. Reduced ability of directional migration of cells on a plastic surface was seen by either antifolate usually at concentrations to 10‐fold higher than those exerting a cytotoxic effect in the plating efficiency assay. TMX was somewhat more potent than MTX as an inhibitor of spheroid growth. When tumor spheroids were exposed to MTX or TMX at concentrations that caused 65 to 70% inhibition of cell migration, there was a latent period of 4 to 5 days before inhibition of spheroid growth ensued. Invasion was investigated in a co‐culture system, where tumor spheroids were confronted with fetal rat brain cell aggregates. Neither drug reduced tumor cell invasion, although histological examination revealed toxic effects both in GaMg and in D‐54Mg spheroids. We conclude that spheroids from human glioma cells were less sensitive to the antifolates than monolayers. For both drugs a latency period was observed before inhibition of spheroid growth. The spheroids retained their ability to invade normal brain tissue when exposed to levels of folate antagonists inhibiting spheroid growth.
TGF‐β induces an inhibitory effect of normal cells directed against transformed cells
Authors: Höfler P. , Wehrle I. , Bauer G. 
Published: February 2007

AbstractCo‐cultivation of normal and transformed fibroblasts in the presence of exogenously added transforming growth factor type beta 1 (TGF‐β1) leads to a drastic reduction of colony‐forming transformed cells. This inhibitory effect is dependent both on the dose of TGF‐β applied and the density of normal cells. It does not reflect a direct action of TGF‐β on transformed cells, but is rather induced by TGF‐β in normal cells. In the absence of exogenously added TGF‐β, normal cells exhibit a basal inhibitory activity, which can be abrogated by anti‐TGF‐β. TGF‐β‐mediated inhibition of transformed cells by normal cells may be considered as a novel potent controlling step in carcinogenesis.
Abrogation of tumor‐inhibitory MRC‐OX8+ (CD8+) effector T‐cell generation in rats by selective depletion of neutrophils In vivo using a monoclonal antibody
Authors: Tanaka Eiichi , Sendo Fujiro 
Published: February 2007

AbstractThese studies were designed to examine the role of neutrophils in transplantation immunity to syngeneic rat tumors. We have earlier reported that specific transplantation immunity to syngeneic transplanted tumors is abrogated by selective depletion of peripheral‐blood neutrophils by administration of a monoclonal antibody (MAb) (RP‐3) at the time of immunization with X‐irradiated tumor cells. In order to elucidate the mechanisms of this phenomenon, we have now examined whether induction of the sensitized spleen cells that inhibit the growth of tumor cells is inhibited by RP‐3 treatment at the time of in vivo priming with tumor‐associated antigen (TAA). Neutrophils were required to induce the sensitized T cells responsible for tumor inhibition with Winn's assay. In addition, CD8+ T cells are proved to be effector cells in an assay system of tumor‐growth inhibition using a diffusion chamber. Our results indicate that neutrophils are required for priming rats with TAA to induce CD8+ effector T cells in tumor inhibition.
Expression of myc family oncoproteins in small‐cell lung‐cancer cell lines and xenografts
Authors: Rygaard Kåre , Spang‐Thomsen Mogens , Vindelø Lars L. 
Published: February 2007

AbstractA number of genes have altered activity in small‐cell lung cancer (SCLC), but especially genes of the myc family (c‐myc, L‐myc and N‐myc) are expressed at high levels in SCLC. Most studies have explored expression at the mRNA level, whereas studies of myc family oncoprotein expression are sparse. We examined the expression of myc proto‐oncogenes at the mRNA and protein level in 23 cell lines or xenografts. In the cell lines, the doubling time and the cell‐cycle distribution, as determined by flow‐cytometric DNA analysis, were examined to establish whether the level of myc‐gene‐family expression correlated with proliferative parameters. All tumours expressed at least one myc family member at the mRNA level. Exclusive c‐myc mRNA expression was demonstrated in 8 tumours, L‐myc in 7 and N‐myc in I. Five tumours expressed both c‐myc and L‐myc, and 2 tumours expressed both c‐myc and N‐myc. In general, the level of expression of c‐myc and N‐myc was similar at the mRNA and the protein level. Expression of c‐myc was positively correlated with the proliferative index (sum of S and G2 + M phases) of cell lines, but not with the population doubling time. In general, L‐myc‐expressing cell lines had a low proliferative index. There was no systematic difference in myc expression between cell lines and xenografts of individual tumours.
Relationship between the anti‐HTLV‐1 antibody level, the number of abnormal lymphocytes and the viral‐genome dose in HTLV‐1‐infected individuals
Authors: Shinzato Osamu , Shiku Hiroshi , Nagata Yasuhiko , Nakayama Eiichi , Kamihira Shimeru , Ikeda Shuichi , Kondo Hisayoshi , Kanda Takcnao 
Published: February 2007

AbstractTwo distinct diseases, adult T‐cell leukemia (ATL) and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), develop in a minor population of HTLV‐1 carriers. We examined the relationship between the viral genome dose in the peripheral‐blood mononuclear cells and the serological response in HTLV‐1 carriers and patients with HAM/TSP. The antibody titer to HTLV‐1 gag and env proteins, as well as the frequency of an antibody response to viral protein p40tax and the titer, increased with increasing viral genome dose. However, the number of abnormal lymphocytes was not directly related to the host viral load. Patients with HAM/TSP generally showed a higher genome dose than healthy carriers and also had higher antibody titers than healthy carriers with the same HTLV‐1 load, supporting the existence of an augmented immune response in these patients. These findings suggest that the antibody titer to HTLV‐1 genome products, and not the number of abnormal lymphocytes, intimately reflects the approximate viral load in HTLV‐I ‐infected individuals.
Cell proliferation as a long‐term prognostic factor in diffuse large‐cell lymphomas
Authors: Silvestrini Rosella , Costa Aurora , Boracchi Patrizia , Giardini Roberto , Rilke Franco 
Published: February 2007

AbstractThe relevance of cell proliferation rate—defined as the 3H‐thymidine labeling index (3H‐dT LI)—in predicting response to treatment (complete remission, CR), freedom from progression (FFP) and overall survival (OS) was evaluated in 86 patients with diffuse large‐cell lymphoma (DLCL). The biologic variable was not associated with most of the established clinical factors, such as gender and age of the patient, performance status, B symptoms, tumor bulk, or extranodal disease, but was directly related to stage. 3H‐dT LI significantly predicted short‐ and long‐term clinical outcome. In fact, more patients with slowly proliferating DLCL reached CR and had longer median FFP and OS than patients with rapidly proliferating DLCL. Multiple‐regression analysis to evaluate the relative contribution of the different biologic and clinical variables in predicting CR, FFP and OS showed that 3H‐dT LI and Ann Arbor stage were the only 2 stable factors, which retained their prognostic significance even in the presence of other conventional factors, and that 3H‐dT LI was the most powerful as an indicator of risk of death in DLCL patients.
Oral contraceptives and endometrial cancer: Do other risk factors modify the association?
Authors: Stanford Janet L. , Brinton Louise A. , Hoover Robert N. , Berman Michael L. , Mortel Rodrigue , Twiggs Leo B. , Barrett Rolland J. , Wilbanks George D. 
Published: February 2007

AbstractThe joint effect of use of combination‐type oral contraceptives and other exposure factors on risk of endometrial cancer was examined in data from a multicenter case‐control study conducted in 5 areas of the United States. Cases were 405 women with histologically confirmed invasive epithelial endometrial cancer first treated at one of 7 participating hospitals. A total of 297 population‐based controls of similar age, race, and geographic area were selected as a comparison group. Information on exposure factors was derived from in‐person interviews. Combination‐type oral contraceptive (COC) use was associated with a significant reduction in risk of endometrial cancer, with an adjusted odds ratio (OR) of 0.4 (95% confidence interval 0.3 to 0.7) for ever compared to never use. Long‐term (≥ 10 years) users experienced a markedly lower risk (OR = 0.2). Women who discontinued COC use ≥20 years earlier remained at reduced risk (OR = 0.7) compared with non‐users. The negative association with COC use was apparent regardless of the presence or level of several other risk factors for endometrial cancer, including age, menopausal status, parity, obesity, ever‐use of menopausal estrogens, smoking history, or history of infertility. The magnitude of the negative association observed in COC users, however, was considerably diminished in women with no full‐term births and in women who subsequently used replacement estrogens for 3 or more years. These results provide new evidence that the protective effect of COC use lasts for 20 or more years after use is discontinued, and highlight several sub‐groups of users in whom the level of protection is attenuated by the presence of other risk factors for this disease.
HTLV‐I and HTLV‐II world‐wide distribution: Reanalysis of 4,832 immunoblot results
Authors: Madeleine Margaret M. , Wiktor Stefan Z. , Goedert James J. , Manns Angela , Levine Paul H. , Biggar Robert J. , Blattner William A. 
Published: February 2007

AbstractMapping the geographic distribution of human T‐lymphotro‐phic virus types 1 and 2 (HTLV‐I and ‐II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV‐I and HTLV‐II, we evaluated a convenience sample of 4,832 HTLV‐I immunoblot results from over 140,000 samples screened for HTLV‐I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV‐I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV‐I), type 2, p24 stronger than p 19 (presumptive HTLV‐II), or indeterminate (p 19 and p24 weakly positive or p19 weakly positive in the presence of p21e). Geographic areas could be grouped into 4 patterns. Patterns A (>75% type 1) and B (>75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous‐drug‐using and other populations in which both virus types have been reported. Pattern D (>10% indeterminate), suggests the presence of non‐specific reactivity, perhaps resulting from exposure to non‐virus‐related antigens or an HTLV‐related virus. HTLV‐I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro‐populations of the Western hemisphere. HTLV‐II clusters in Native American populations and among intravenous drug users. Pattern‐D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types.
Modulation of MDR‐1 expression by a H‐ras oncogene in a human colon carcinoma cell line
Authors: Kramer Robert , Arceci Robert , Weber Thomas K. , Morse Barry , Simpson Heather , Steele Glenn D. , Summerhayes Ian C. 
Published: February 2007

AbstractIn an established colon differentiation model, introduction of a c‐H‐ras‐1 oncogene into a poorly differentiated human colon carcinoma cell line (Clone A) results in changes associated with the acquisition of a more differentiated phenotype. Down‐regulation of mdr‐l mRNA was shown to accompany ras‐related differentiation events resulting in decreased Pgp synthesis and a significant reduction in membrane Pgp as detected by immunoprecipitation, Western‐blot and FACS analysis. Consistent with these observations was a reduction in Pgp‐mediated drug resistance associated with Clone‐A ras transfectants, with no alteration in drug sensitivity being observed with non‐MDR drugs in these cells. An alternative differentiation model involves exposure of Clone‐A cells to sodium butyrate. Under these conditions, differentiation‐related changes resulted in up‐regulation of mdr‐1 mRNA and Pgp synthesis, although no alteration in drug sensitivity was recorded. In agreement with this observation, the levels of membrane‐associated Pgp remained unchanged throughout the period of exposure to sodium butyrate. This study shows that modulation of Pgp expression in colon differentiation is dependent upon the differentiation induction agent used.
Dimethyl sulfoxide (DMSO) increases expression of sialyl lewis X antigen and enhances adhesion of human gastric carcinoma (NUGC4) cells to activated endothelial cells
Authors: Maehara Masanori , Isobe Yoshiaki , Nakagawara Gizo , Yagita Masato , Hoshino Takashi 
Published: February 2007

AbstractDimethyl sulfoxide (DMSO) exerts a number of biological effects including the promotion of cell differentiation in cultured cells. In this study, we examined the effect of DMSO on the adhesion of tumor cells to endothelial cells. In vitro treatment of human gastric adenocarcinoma (NUGC4) cells with DMSO resulted in increased adhesion to interleukin‐1 (IL‐l)‐activated human endothelial cells compared with DMSO‐untreated NUGC4 cells. In flow cytometry, treating NUGC4 cells with DMSO enhanced the expression of sialyl Lewis x (sialyl Lex) and sialyl dimeric Lex antigens on their surface. Also, the binding of Limulus polyphemus agglutinin (LPA), which specifically binds to cell‐surface sialic acids, was increased by DMSO. The adhesion of DMSO‐treated NUGC4 cells to activated endothelial cells was blocked by neuraminidase pre‐treatment of tumor cells or by antibody against either endothelial leukocyte adhesion molecule‐1 (ELAM‐I) or sialyl Lex. Thus, it is suggested that enhanced adhesion following DMSO treatment is mediated by the interaction of sialyl Lex expressed on NUGC4 cells with ELAM‐I of endothelial cells. The modulation of sialyl Lex antigen by DMSO provides a useful system for studying the regulatory mechanism of Lewis‐related carbohydrate antigens and also for understanding the metastatic properties of cancer cells.
Anomalous expression of P‐glycoprotein in highly drug‐resistant human KB cells
Authors: Dolci Elizabeth D. , Abramson Robin , Xuan Yongzhi , Siegfried Jennifer , Yuenger Kristin A. , Yassa David S. , Tritton Thomas R. 
Published: February 2007

AbstractKB‐AI and KB‐A10 are 2 multi‐drug‐resistant cell lines which are 100‐ and 1,000‐fold resistant to Adriamycin, respectively. We have examined the expression of P‐glycoprotein at the molecular and cellular levels in these human carcinoma cells. Both MDR cell lines, when compared to the parental KB‐3–1, show characteristic increases in mdr l gene copy number, an increase in mdr l mRNA expression, a corresponding increase in transcription rate and a consequent over‐expression of P‐glycoprotein. However, the more highly resistant KB‐A 10 cells have a lower gene copy number, express less mdr l mRNA and contain less P‐glycoprotein than the AI cell line. To determine whether higher levels of cellular resistance were attributable to enhanced efficacy of P‐glycoprotein or to other cellular regulatory mechanisms, we examined other major cellular properties known to be associated with the mdr phenotype. Both the KB‐AI and KB‐A 10 lines exhibit similar increases in protein kinase C activity as compared to the drug‐sensitive parent. In addition, neither glutathione‐S‐transferase nor topoisomerase II activities account for enhanced resistance of the KB‐A 10 cells. The above observations are contrary to the premise that the level of drug resistance is necessarily proportional to expression of P‐glycoprotein or to other common factors thought to participate in drug insensitivity; consequently, new mechanisms of resistance must be in operation in these cells.
A study of cross‐resistance pattern and expression of molecular markers of multidrug resistance in a human small‐cell lung‐cancer cell line selected with doxorubicin
Authors: Supino Rosanna , Binaschi Monica , Capranico Giovanni , Gambetta Romolo A. , Sala Elena , Zunino Franco , Prosperi Ennio 
Published: February 2007

AbstractA doxorubicin‐resistant variant of the human small‐cell lung‐cancer cell line N592 was selected by in vitro continuous exposure to increasing drug concentrations. The aim of this study was to examine the cross‐resistance pattern, cellular pharmacokinetics of doxorubicin and expression of molecular factors of resistance. The sub‐line N592/DX exhibited a multidrug‐resistance phenotype, which was somewhat atypical, since it included cisplatin. Development of doxorubicin resistance could not be attributed to differential doxorubicin uptake or retention. Verapamil partially reverted doxorubicin resistance without affecting cellular pharmacokinetics. These findings are consistent with undetectable levels of mdr‐1 ‐gene expression in these cells. A molecular analysis of other putative mechanisms of multidrug resistance indicated no alterations in GSH levels or GSH‐related enzymes, but a marginal reduction of topoisomerase II α expression in the resistant sub‐line. This reduction, which was associated with an increase in topoisomerase I, does not explain the high degree of resistance. This study supports the view that alternative, unidentified mechanisms, which may be of clinical relevance, must be involved in the development of multidrug resistance of small‐cell lung cancer.
Somatostatin receptor‐positive primary breast tumors: Genetic, patient and tumor characteristics
Authors: Bootsma A. H. , Lamberts S. W. J. , Van Eijck C. , Schouten K. K. , De Klein A. , Reubi J. C. , Waser B. , Foekens J. A. , Van Pel R. , Zwarthoff E. C. 
Published: February 2007

AbstractIn a series of 87 primary breast tumors, somatostatin receptor (SSR) expression was detected by in vitro autoradiography in 58 tumors. In 41 tumors the SSR expression was homogeneous and in 17 it was heterogeneous. Although the tumors were not selected by the investigators upon entry in the study, examination of the tumor and patient characteristics showed that a pre‐selection had taken place for small tumors. Eighty percent of the tumors were classified as stage pTI or pT2 tumors. This small tumor size and the large size of the tumor sections used for autoradiography can explain the high incidence of somatostatin expression in our series. Forty‐three of these tumors, 30 SSR‐positive and 13 SSR‐negative, were tested for morphological and (immuno)histochemical markers of neuroendocrine differentiation. Three SSR‐positive tumors were also positive for 2 or more other markers of neuroendocrine differentiation, suggesting that neuroendocrine breast tumors and SSR‐positive breast tumors are overlapping, but independent, subgroups of tumors. To test whether specific genetic alterations are associated with SSR‐positive or SSR‐negative breast tumors, we examined in a selected series of 47 SSR‐positive and 32 SSR‐negative breast tumors a number of known genetic markers by Southern blotting. Deletions or rearrangements of the retinoblastoma (RB) tumor‐suppressor gene were observed in 5 SSR‐positive and 5 SSR‐negative tumors. In 4 SSR‐positive and also in 4 SSR‐negative tumors an amplification of the neu oncogene was observed. Amplifications of the int‐2 oncogene were found in 2 SSR‐positive and I SSR‐negative breast tumor. In one SSR‐positive tumor an amplification of the c‐myc oncogene was observed and in another SSR‐positive tumor a rearrangement of the L‐myc oncogene was found.
p53 Mutations in sporadic adrenocortical tumors
Authors: Ohgaki H. , Kleihues P. , Heitz P. U. 
Published: February 2007

AbstractNon‐familial human adrenocortical adenomas and carcinomas were screened for mutations in exons 5–8 of the p53 tumor suppressor gene by single‐strand‐conformation‐polymorphism (SSCp) analysis, followed by direct sequencing of PCR‐amplified DNA. point mutations in codons 12, 13 and 61 in H‐ras, K‐ras and N‐ras proto‐oncogenes were similarly assessed by direct DNA sequencing. Three out of 15 primary adrenocortical carcinomas (20%) contained a mis‐sense point mutation in the conserved regions (exons 5 and 8) of the p53 gene. Mutations were located in codon 157 (GTC → TTC; Val → phe), codon 163 (TAC → AAC; Tyr → Asn), and codon 273 (CGT → TGT; Arg → Cys). The mutation in codon 157 was detected in the primary tumor as well as in brain and lymph‐node metastases. Among 18 adrenocortical adenomas, there was only a single non‐miscoding mutation in codon 295 (CCT → CCC; pro → pro). These data suggest that mutational inactivation of the p53 gene occurs in a minority (20%) of sporadic adrenocortical carcinomas and that these mutations constitute a late event in the multi‐step process of malignant transformation. No ras mutations were detected in any of these tumors, suggesting that these genes are not involved in the development of tumors originating from the adrenal cortex.
Biodistribution study of 99mTc‐labeled LDL in B16‐melanoma‐bearing mice. Visualization of a preferential uptake by the tumor
Authors: Ponty Emmanuelle , Carton Michel , Soula Georges , Favre Gillcs , Benaniba Rachid , Boneu Andrée , Lucot Henriette 
Published: February 2007

AbstractSince there is strong evidence of a preferential LDL accumulation in tumor cells, LDL might be of interest for tumor imaging. We have tested the ability of 99mTc‐LDL in tumor imaging with B16‐melanoma‐bearing mice as a model for further applications in human studies. The LDL fixation rate was higher with 99mTc‐labeled LDL than with 125I labeled LDL. Since technetium‐99m remains trapped in the cells, 99mTc‐LDL is a well‐adapted radioligand because of information given by this radiotracer on the receptor metabolism. We observed that, at early growth stages, the tumor took up the LDL at a maximal rate, suggesting differences in cholesterol metabolism as a function of tumor growth. Accumulation of label in the tumor area was perfectly observable in tumor‐bearing mice on scintigraphic images. Computerized quantification of the regions of interest (as well as biodistribution studies including killing of the animals) showed a 1.81 ‐fold increase in uptake by the tumor as compared to the liver and a 28‐fold increase as compared with corresponding normal tissue (muscle of the left leg) at day 8 of tumor growth. These data give strong support to the value of this non‐invasive method in visualizing and quantifying the tissue LDL uptake in vivo, including the precise information provided by nuclear scintigraphy on the distribution of the radiolabeled LDL in the different tissues. 99mTc‐LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients.