bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of autocrine mechanisms promoting motility in two metastatic cell lines: Human melanoma and ras‐transfected NIH3T3 cells
Authors: Seiki Motoharu , Sato Hiroshi , Liotta Lance A. , Schiffmann Elliott 
Published: February 2007

AbstractTumor‐cell migration plays an essential role in invasion into surrounding tissues and the formation of metastatic colonies in distant organs. Metastatic human A2058 melanoma and ras‐ transfected NIH3T3 cells produce autocrine motility factors (AMFs) which stimulate their own motility, and the A2058 cell AMF (AMF/A2058) has been purified. In this study, we partially purified the AMF produced by N‐ras‐transfected NIH3T3 cells (AMF/NIH3T3) and compared it with AMF/A2058. The two AMFs differed in their gel filtration patterns and heat stability, although both elicited migration of N‐ras‐transfected NIH3T3 cells. The receptor for AMF/A2058 in A2058 cells is linked to pertussis‐toxin‐sensitive GTP‐binding protein. Pre‐treatment of N‐ras‐transfected NIH3T3 cells with pertussis toxin also specifically blocked the promotion of motility by AMF/A2058, but did not affect the activity of AMF/NIH3T3. Stimulation of N‐ras‐transfected NIH3T3 cells by both AMFs elicited an additive response. Thus, the autocrine mechanisms of these two metastatic tumor cell lines are different with regard to the AMF molecules, receptors, and signal transduction pathways.
Increased growth adaptability to 5‐fluorouracil and methotrexate of HT‐29 sub‐populations selected for their commitment to differentiation
Authors: Lesuffleur Thécla , Kornowski Anne , Augeron Chantal , Dussaulx Elisabeth , Barbat Alain , Laboisse Christian , Zweibaum Alain 
Published: February 2007

AbstractAdaptation of the heterogeneous human colon carcinoma cell line HT‐29 to lethal concentrations of methotrexate (MTX) and 5‐fluorouracil (FUra) was shown to result in the emergence of sub‐populations of cells all stably committed to differentiation. It was postulated that these populations result from selection of a few cells present in the parental line which possess, associated with their ability to differentiate, particular advantages allowing them to adapt to adverse conditions such as MTX or FUra. The purpose of the present study was to further verify this hypothesis by investigating whether HT‐29 sub‐populations selected for the commitment of all cells to differentiation would spontaneously be more resistant and adaptable than the parental cells to MTX and FUra. This study included a mucus‐secreting clone (HT29‐16E), a transporting clone (HT29‐19A), and an enterocytic population selected by glucose deprivation (HT29‐Glc−/+). Although all 3 populations show only a slight increase in their spontaneous resistance to both drugs, as substantiated by the values of IC50, which are only less than 2‐fold higher than in parental cells, they are more adaptable as judged by growth curves, over a 50‐day culture period, under exposure to I μM FUra and 0.1 μM MTX. In sharp contrast to parental cells, which, at these concentrations, show a high rate of mortality, all 3 populations, although growing slowly, reach densities more or less close, depending on the drug and population concerned, to that of control untreated cells. These results show that, within population of cells of the same genetic origin, cells selected for their commitment to differentiation are more resistant and more adaptable to FUra and MTX than the parental population, which contains a majority (> 95%) of cells unable to differentiate.
The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors
Authors: Mizoguchi H. , Komiyama S. , Matsui K. , Hamanaka R. , Ono M. , Kiue A. , Kobayash M. , Shimizu N. , Welgus H. G. , Kuwano M. 
Published: February 2007

AbstractThree cancer cell lines, IMC‐2, IMC‐3 and IMC‐4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC‐2 in nude mice was markedly faster than that of the IMC‐3 and IMC‐4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC‐2 cells in response to EGF, but no change for IMC‐3 and IMC‐4 cells. We examined response to EGF of IMC‐2 cells with regard to expression of a growth‐related oncogene (c‐fos), proteinases and their inhibiton. Expression of c‐fos was transiently increased in IMC‐2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase‐type plasminogen activator and 72‐kDa type‐IV colla‐genase in IMC‐2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor‐I (PAI‐1) and tissue inhibitor of metalloproteinases‐1 (TIMP‐1) in IMC‐2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.
Active oxygen transforms murine myeloid progenitor cells in vitro
Authors: Crawford Dana R. , Greenberger Joel S. 
Published: February 2007

AbstractActive oxygen (AO) is ubiquitous in nature and its many forms can act as natural carcinogens. Their effect on the transformation of a mouse myeloid progenitor cell line was studied using anchorage‐independent colony formation in methylcellulose as the primary assay. Both cytotoxic and non‐toxic concentrations of t‐butylhydroperoxide, hydrogen peroxide and menadione were examined. At non‐cytotoxic concentrations, no AO transformation of these cells from interleukin‐3 dependence to factor independence (FI) was observed, even after as many as 25 treatments. At cytotoxic concentrations, however, all 3 classes of AO transformed the cells to FI growth. The most potent agent was t‐butyl hydroperoxide (43‐fold induction), followed by hydrogen peroxide and then menadione. As little as one exposure to cytotoxic levels of these oxidants induced significant transformation, with relative potencies the same as those observed for multiple exposures. These inductions were not due to general cytotoxic effects, since sodium fluoride and heat‐shock treatment gave minimal inductions. AO‐induced colonies in methylcellulose that were removed, examined and then injected into pre‐irradiated mice uniformly produced tumors. Control, non‐treated cells did not form tumors. Tumorigenic cells did not form colonies in methylcellulose at lower plating densities. Furthermore, low numbers of transformed cells supplemented to high density with normal cells showed a small but insufficient increase in colony number as compared with high‐density cultures of transformed cells. Our results suggest that the transformants depend upon a paracrine mechanism of growth that is mediated by the transformed cells. Studies on selected factor‐dependent cell lines and antibodies to interleukin‐3, interleukin‐4, granulocyte‐macrophage‐ and macrophage‐colony stimulating factors, suggest that this putative paracrine factor is unique.
Human tumor spontaneous metastasis in immunosuppressed newborn rats. II. Multiple selections of human melanoma metastatic clones and variants
Authors: Bailly Maryse , Doré Jean‐François 
Published: February 2007

AbstractUsing a recently developed model of human tumor spontaneous metastasis in immunosuppressed newborn rats, we selected variants with different metastatic abilities from the human melanoma cell line M4Be. We used 4 in vivo selection approaches, by direct serial tumor transplantations or by techniques involving in vitro reculture of the cells recovered from S.C. tumors or lung and lymph‐node metastases. In addition, 3 series of clones were derived in vitro from the M4Be cell line, either by limiting‐dilution or by cloning in semi‐solid agar and harvesting small and large colonies. A considerable amount of heterogeneity in tumorigenicity and metastatic ability was demonstrated among variants and clones following in vivo selections and in vitro cloning. Four main malignant phenotypes were identified among those expressed by the selected cells: poorly tumorigenic and poorly metastatic; poorly tumorigenic and highly metastatic; highly tumorigenic and poorly metastatic; and highly tumorigenic and highly metastatic. However, while malignant pheno‐type (i.e., tumorigenicity and metastatic ability) did not appear to be grossly influenced by in vitro cloning procedure, it appeared greatly influenced both by the in vivo selection procedure (direct transplantations or use of in vitro culture between the in vivo passages) and by the origin of the cells under selection (S.C. tumor or metastases). Our study provided us with a large panel of variants and clones with varying metastatic abilities, which represent a model of human melanoma spontaneous metastasis allowing the study of critical determinants in human tumor metastasis.
The role of alkaline reflux in esophageal carcinogenesis induced by N‐amyl‐N‐methylnitrosamine in rats
Authors: Seto Yasuyuki , Kobori Oichiro , Shimizu Toshio , Morioka Yasuhiko 
Published: February 2007

AbstractIt is now accepted that the incidence of esophageal carcinoma is highest in the middle thoracic region. Esophageal carcinoma after gastrectomy, however, has a tendency to develop in the lower thoracic region. These studies suggest a possible correlation between the development of esophageal carcinoma and gastrectomy, i.e., alkaline reflux into the esophagus. To elucidate this correlation, the role of alkaline reflux of duodenal contents in the development of esophageal squamous‐cell carcinoma induced by N‐amyl‐N‐methylnitrosamine (AMN) was investigated in Wistar rats. The animals were divided into 3 groups; gastrectomized rats with or without regurgitation of duodenal contents into the esophagus, and control rats without gastrectomy. All received low doses of AMN for 8 weeks and were subsequently killed for pathological examination. Esophageal squamous‐cell carcinomas were found only in gastrectomized rats with regurgitation. The carcinomas were found exclusively in areas of reflux esophagitis and were accompanied by severe dysplasia. Our results indicate that alkaline reflux of duodenal contents strongly contributes to the development of esophageal squamous‐cell carcinoma.
Infection of rats with HTLV‐1: A small‐animal model for HTLV‐1 carriers
Authors: Suga T. , Kameyama T. , Kinoshita T. , Shimotohno K. , Matsumura M. , Tanaka H. , Kushida S. , Ami Y. , Uchida M. , Uchida K. , Miwa M. 
Published: February 2007

AbstractA human T‐cell line producing human T‐cell leukemia virus type 1 (HTLV‐1), MT‐2, was injected intravenously into female F344 rats aged 5 weeks to make HTLV‐1 carrier rats. Antibody against HTLV‐1 was detected at the 5th week after MT‐2 injection, and its titer reached a high plateau which continued from the 15th to the 27th week. The antibodies were against p 19, p24, p28 and p53 of HTLV‐1 antigens from MT‐2 cells. The gag, pX and LTR nucleotide sequences of HTLV‐1 provirus were demonstrated by using polymerase chain reaction (PCR) in the peripheral‐blood mononuclear cells of 3 rats at the 44th week and 2 at the 66th to 68th week out of 8 F344 rats injected with MT‐2 cells. Quantification of the HTLV‐1 proviral sequence revealed that 30 to 60 molecules were present in 105 peripheral‐blood mononuclear cells, indicating that the rats were chronically infected with HTLV‐1. HTLV‐1‐infected rats could serve as a small‐animal model for studying the pathophysiological state of HTLV‐1 carriers and also that of HTLV‐1 infection on various HTLV‐1‐related diseases, including adult T‐cell leukemia and HTLV‐1‐associated myelopathy.
Modulation of tumoricidal activity, induced in bone‐marrow‐derived mononuclear phagocytes by interferon γ or Corynebacterium parvum, by interferon β, tumor necrosis factor, prostaglandin E2, and transforming growth factor β
Authors: Keller Robert , Keist Ruth , van der Meide Peter H. 
Published: February 2007

AbstractAmong a series of agents, including various interleukins and growth factors, only interferon γ (IFNγ) and heat‐killed Corynebacterium parvum (CP) organisms were able to elicit, within 24 hr, tumoricidal activity in bone‐marrow‐derived mononuclear (BMM) phagocytes. In subsequent experiments, the abilities of interferon β (IFNβ), tumor necrosis factor α (TNFα), prostaglandin E2 (PGE2), and transforming growth factor β (TFGβ), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFNγ or CP, were compared. In concentrations secreted by macrophages under physiological conditions, these agents proved potent in modulating induction and/or expression of tumoricidal activity. However, their ability to interfere with tumoricidal activity varied considerably, depending on the extent of macrophage differentiation and/or functional responsiveness, the pathway of macrophage activation, the type, concentration and combination of the macrophage secretory molecules, and on whether the agents were present during induction and expression or only during expression of tumoricidal activity. In showing that IFNβ and TNFα were mostly enhancing and TGFβ mostly suppressive, whereas PGE2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage‐derived molecules have a key role in autocrine regulation of macrophage functional activities.
Neutral glycosphingolipid expression in B‐cell neoplasms
Authors: Kalisiak Angela , Minniti J. Gerald , Oosterwuk Egbert , Old Lloyd J. , Scheinberg David A. 
Published: February 2007

AbstractThe expression of neutral glycosphingolipids (GSL) in 37 B‐cell neoplasms [7 acute lymphocytic leukemia (ALL), 5 Burkitt's lymphoma (BL), 7 chronic lymphocytic leukemia (CLL), 5 diffuse, poorly differentiated lymphoma (DPDL), 6 diffuse histiocytic lymphoma (DHL), 3 hairy‐cell leukemia (HCL), and 4 multiple myeloma (MM)] was examined. Patterns of expression of simple (GlcCer, LacCer) and globo‐series GSL (Gb3, Gb4,) were found for each tumor type. In addition, pre‐B ALL expressed the neo‐lacto series GSL, paragloboside, which was not significantly seen at later stages of maturation. As a group, leukemias expressed about 10 times higher ratios of simple GSL to Globo‐series GSL as compared to lymphomas, regardless of stage of differentiation. Significant amounts of GSL of other series were not found except in one CLL which contained asialo‐GM2. GSL phenotype in these cells was not grossly affected by cell genotype since pre‐B ALL containing Philadelphia chromosome t(9q;22q) translocations were similar to other ALL; and DHL with t(8q;14q) translocations had GSL patterns similar to other DHL samples and dissimilar to GSL patterns found in Burkitt's lymphomas with t(8q;14q). Differences in GSL expression among the different types of B‐cell neoplasm suggested that GSL patterns form a phenotypic map that may complement the traditional glycoprotein immunophenotypic map and contribute to our understanding of the biology of these diseases and B‐cell differentiation.
PCR‐detected genital papillomavirus infection: Prevalence and association with risk factors for cervical cancer
Authors: Rohan Thomas , Mann Valerie , McLaughlin John , Harnish Delsworth G. , Yu He , Smith David , Davis Ruth , Shier R. Michael , Rawls William 
Published: February 2007

AbstractIn an investigation conducted in student health clinic patients, the polymerase chain reaction was used to detect human papillomavirus (HPV) DNA, thereby allowing measurement of the prevalence of HPV infection and study of the association between HPV infection and risk factors for cervical cancer. Of 159 women eligible to participate, 105 (66%) provided specimen of cervical cells for HPV typing, and also answered an interviewer‐administered questionnaire which sought information on risk factors for cervical cancer. Nucleic acid extracted from cervical cells was screened with primers for HPV types 6, 11, 16, 18, 33 and with an HPV Consensus primer. Overall, the prevalence of HPV infection was 18.1%, while for HPV‐6/11 it was 2.9% and for HPV‐16/18 it was 10.5%. There were statistically significant increases in risk of HPV infection with history of ever having smoked cigarettes (overall, and for HPV‐16 alone) and with a history of usually having sexual intercourse during menstrual periods (overall, but not for HPV‐16), and these associations were independent of the effects of age at first sexual intercourse and number of sexual partners. The latter 2 variables, as well as the total number of occasions of sexual intercourse, a history of anal intercourse, and a history of ever having used oral contraceptives, were not associated with statistically significant alterations in risk of HPV infection.
The interaction between HPV infection and estrogen metabolism in cervical carcinogenesis
Authors: Auborn Karen J. , Woodworth Craig , Dipaolo Joseph A. , Bradlow H. Leon 
Published: February 2007

AbstractCancer of the genital tract is the final outcome of some infections with human papillomavirus (HPVs), and the most estrogen‐sensitive cells are at greatest risk for the HPV‐related cancers. Therefore we investigated relationships between HPVs and estrogen metabolism in cells of the genital tract. Increased conversion of estradiol to 16α‐hydroxyestrone, known to be a risk factor for cancer in some other estrogen‐sensitive cells, was investigated in keratinocytes from the genital tract. Primary cells, particularly those explants from the transformation zone of the cervix, are able to 16α‐hydroxylate estradiol. Both cervical and foreskin cells immortalized with HPV‐16 are greatly enhanced in the 16αa‐hydroxylation of estradiol as compared with normal cells. We suggest a model whereby the combined action of 16α‐hydroxylation of estrogen and HPV work together to promote cell proliferation.
Prognostic scores combining clinical, histological and morphometric variables in assessment of the disease outcome in female breast cancer
Authors: Aaltomaa S. , Lipponen P. , Eskelinen M. , Kosma V‐M. , Marin S. , Alhava E. , Syrjänen K. 
Published: February 2007

AbstractClinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a Cox's model to assess their independent predictive power in a series of 517 breast cancer patients followed up for over 10 years. The volume‐corrected mitotic index (M/V index) (p< 0.001), axillary lymph‐node status (p= 0.002), the shortest nuclear axis (p= 0.006) and the degree of tubule formation (p= 0.02) predicted independently the recurrence‐free survival. In N−tumours (n = 293), the M/V index (p= 0.005), the degree of tubule formation (p= 0.016) and tumour size (p= 0.023) were independent prognostic predictors, whereas in N+tumours (n = 224), only the M/V index (p= 0.004) and the maximum nuclear axis (p= 0.004) had independent prognostic value. The corrected survival was predicted independently by the axillary lymph‐node status, degree of tubule formation, M/V index, tumour size (p< 0.001), age (p= 0.002) and year of treatment (p= 0.008). In N−tumours, the degree of tubule formation (p= 0.005) and intraductal growth pattern (p = 0.015) exhibited independent predictive value. In N+tumours, patient survival was related to the M/V index (p< 0.001), tumour size (p= 0.005) and patient age (p= 0.005). The results show that the assessment of the M/V index, axillary lymph‐node status, tumour size, intraductal growth pattern and tubule formation are reliable factors in predicting the prognosis of breast cancer. The conventional mitotic activity index (MAI) and histological grading should be replaced by the M/V index in histological assessment of malignancy in breast cancer. The prognostic scores combining the independent variables reflecting the proliferative rate and metastatic potential of the tumours are more accurate predictors of the recurrence‐free survival and overall survival (p< 0.0001) than the single variables used alone.
Humoral immune response in disease‐free advanced melanoma patients after vaccination with melanoma‐associated gangliosides
Authors: Portoukalian Jacques , Carrel Stefan , Doré Jean‐François 
Published: February 2007

AbstractSeveral studies have shown that melanoma‐associated gangliosides are immunogenic in melanoma patients and that antibodies against them have a favorable prognostic effect. Our study aims at characterizing the humoral immune response in disease‐free, advanced melanoma patients vaccinated with a total ganglioside fraction extracted from pooled metastases of human melanoma, containing as major gangliosides GM3 and GD3, and as minor ones GM2 and GD2. Prior to vaccination, all patients were made disease‐free by surgical removal of skin, lymph‐node or other distant metastases. Repeated vaccinations were carried out intradermally with gangliosides either in the native form in buffered solution, or in the form of liposomes. Serum samples were collected at regular intervals and assayed by ELISA for the presence of specific IgG and IgM antiganglioside antibodies. Selected samples were tested by immunostaining on thin‐layer plates to specify the ganglioside species involved in the reactivity. Out of 32 evaluable patients, 17 presented a significant increase in antibody titer, mostly of the IgG isotype, which was maximal between 2 and 4 months after starting injections of gangliosides, and gradually disappeared within 1 year. No significant difference could be seen between the group of 20 patients treated with native gangliosides and the group of 12 vaccinated with the gangliosides in liposomes. All gangliosides seemed to be immunogenic, but GM2 and GD2 were somewhat more reactive. The disease‐free intervals for the patients who showed an antibody response to the treatment were significantly higher (p < 0001) than those of the non‐responding group, as compared by the Kaplan‐Meier method.
Estrogen inhibition of MPA‐Induced mouse mammary tumor transplants
Authors: Kordon Edith , Lanari Claudia , Molinolo Alfredo A. , Elizalde Patricia V. , Charreau Eduardo H. , Pasqualini Christiane Dosne 
Published: February 2007

AbstractEstrogen compounds were used to treat mice bearing syngeneic transplants of medroxyprogesterone acetate(MPA)‐induced BALB/c mammary adenocarcinomas. Both MPA‐dependent and MPA‐independent tumor lines were used. These lines expressed estrogen (ER) and progesterone receptors (PR). We demonstrate that different doses of estradiol benzoate (EB) and 17‐β‐estradiol (E2) inhibit tumor growth and induce tumor regression in both MPA‐independent and ‐dependent tumors, even in the presence of MPA or progesterone (P). EB was unable to induce regression of (ER‐) hormone‐independent tumor lines. A few MPA‐dependent tumors became resistant to the estrogenic treatment; in subsequent passages some of these tumors retained their MPA‐responsiveness, although estrogen sensitivity was not recovered.
Differential mRNA levels of c‐myc, c‐fos and MHC class I in several clones of a murine fibrosarcoma
Authors: Gaforio J. J. , Pérez M. , Algarra I. , Mialdea M. J. , Ljunggren H. G. , Garrido F. 
Published: February 2007

AbstractWe have evaluated the relationship between MHC class‐I, c‐myc and c‐fos proto‐oncogene expression in several clones of a methylcholanthrene‐induced fibrosarcoma (GR9) which originated in a BALB/c mouse. These clones represent a heterogeneous population and differ markedly with regard to H‐2 class‐I cell‐surface expression, local tumor growth, NK sensitivity and metastatic potential. In the present study we show that cell‐surface expression of MHC class‐I antigens correlates inversely with levels of c‐myc mRNA transcripts, On the other hand, mRNA levels of c‐fos are correlated directly with the amount of mRNA of MHC class I. Treatment of the B9 clone with gamma interferon increased mRNA transcription and surface expression of H‐2 class‐I antigens, while c‐myc transcription was simultaneously down‐regulated. In contrast, c‐fos mRNA levels remained unaltered.