bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical and growth‐modulatory effects of the new S‐adenosylmethionine decarboxylase inhibitor CGP 48664 in malignant and immortalized normal human breast epithelial cells in culture
Authors: Manni Andrea , Badger Betty , Wechter Rita , Kunselman Susan , Rossini Anthony , Demers Laurence 
Published: February 2007

AbstractCGP 48664 [4‐aminoindanon‐1‐(2′‐amidino)hydrazone dihydrochloride monohydrate] is a newly introduced inhibitor of S‐adenosyltnethionine decarboxylase (SAMDC) with increased selectivity of action and reduced toxichy. We analyzed the biochemical and antiproliferative effects of this compound in a panel of hormone‐dependent (3 clones of MCF‐7, T47D) and ‐independent (MDA‐MB‐231, BT‐20) human breast cancer cell lines in culture. For comparison, we also tested its effects in the spontaneously immortalized human breast epithelial cell line MCF‐10A. All cell lines were highly sensitive to the growth‐inhibitory effect of CGP 48664 with an IC50 between 0.1 and 0.5 μM. A dose‐dependent bell‐shaped increase in SAMDC was observed in normal and malignant breast cells resulting from enzyme stabilization by the inhibitor as supported by Western blot analysis. While omithine decarboxylase (ODC) activity consistently increased, the effect of CGP 48664 on spermidine J. spermine N′acetyltransferase (SSAT) was variable in the breast cancer cell lines. In contrast, the inhibitor consistently reduced SSAT activity level in the MCF‐10A cell line and its derivative partially transformed by a mutated ras oncogene. As expected, cellular putrescine levels were markedly increased by CGP 48664 administration, whereas spermidine and spermine contents were reduced. However, the degree of reduction was usually only moderate. Furthermore, exogenous polyamine administration was relatively ineffective in rescuing the antiproliferative effect of CGP 48664 in MCF‐7 cells, while exerting a more complete rescue in the MDA‐MB‐231 cell line. We conclude that CGP 48664 exerts a potent growth‐inhibitory effect on mammary cells in culture. However, its action may not always be entirely mediated through the polyamine pathway. © 1995 Wiley‐Liss, Inc.
Oral contraceptives, menopausal estrogens, and the risk of breast cancer: A case‐control study in greece
Authors: Lipworth Loren , Katsouyanni Klea , Stuver Sherri , Samoli Evangelia , Hankinson Susan E. , Trichopoulos Dimitrios 
Published: February 2007

AbstractIn a hospital‐based case‐control study in Athens, we examined the association between the use of oral contraceptives and menopausal estrogens and the risk of breast cancer. Eight hundred and twenty patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to the cases by age and interviewer. The data were modeled through logistic regression, controlling for demographic and reproductive variables. Odds ratio patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not elevated among ever‐users of oral contraceptives, regardless of age at diagnosis of breast cancer, duration of oral contraceptive use or timing of use in relation to first full‐term pregnancy. Among peri‐ and post‐menopausal women who ever used menopausal estrogens, with never‐users as the baseline, a statistically significant elevated odds ratio was found after adjusting for age at menopause. © 1995 Wiley‐Liss, Inc.
An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines
Authors: Melani Cecilia , Pupa Serenella M. , Stoppacoaro Antonella , Ménard Sylvie , Colaghi Maria Ines , Parmiani Giorgio , Colombo Mario P. 
Published: February 2007

AbstractIn this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti‐tumor immune response. Two carcinoma cell lines, SK‐ OV‐3 ovary carcinoma and CALU‐3 lung carcinoma, were analyzed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), immunofluorescence and ELISA for the expression and in vrtro production of cytokines with chemotactic, pro‐ inflammatory and growth‐stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony‐stimulating factor (G‐CSF), granulocyte macrophage‐ CSF (GM‐CSF), M‐CSF, interleukin (IL‐) la and IL‐8, only CALU‐3 cell line expressed IL‐10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte‐ activating protein (MCP)‐I. MCP‐I and IL‐8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor‐released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK‐OV‐3 and of CALU‐3 tumor xenografts. While SK‐OV‐3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU‐3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18–24 hr. © 1995 Wiley‐Liss, Inc.
Analysis of the antibody response to immunization with purified O‐acetyl GD3 gangliosides in patients with malignant melanoma
Authors: Ritter Gerd , Ritter‐Boosfeld Erika , Adluri Rita , Calves Michele , Ren Shunlin , Yu Robert K. , Oettgen Herbert F. , Old Lloyd J. , Livingston Philip O. 
Published: February 2007

AbstractGangliosides expressed in malignant melanoma are potential targets for immunotherapy. Immunization of melanoma patients with vaccines containing purified GM2 ganglioside has resulted in induction of GM2 antibodies, and high titers of GM2 antibodies have correlated with increased survival. Melanoma ganglioside 9‐O‐acetyl GD3 is another candidate for ganglioside vaccine construction because of its limited expression in normal human tissues. As purification of 9‐O‐acetyl GD3 from human melanoma (9‐O‐acetylated on the terminal sialic acid) is not practical for broad application, we investigated the antibody response of melanoma patients to O‐acetyl GD3 from several additional sources: hamster melanoma (7‐O‐acetyl GO3), bovine buttermilk (mixture of 7‐O‐acetyl GD3, 9‐O‐acetyl GD3 and 7,9‐di‐O‐acetyl GD3) and chemically modified GD3 from bovine brain (9‐O‐acetylated on the subterminal sialic acid). Only immunization with the buttermilk‐derived O‐acetyl GD3 preparation resulted in consistent production of IgM antibodies. However, the induced antibodies reacted with the immunogen and with 7‐O‐acetyl GO3 derived from hamster melanoma but not with 9‐O‐acetyl GD3 or human melanoma cells expressing 9‐O‐acetyl GD3 on their cell surface. In contrast, all O‐acetyl GD3 derivatives used for immunization were recognized by murine MAbs that reacted with 9‐O‐acetyl GD3, and immunization of mice with buttermilk‐derived O‐acetyl GD3 resulted in the production of antibodies that reacted with human melanoma cells expressing 9‐O‐acetyl GD3. Apparently, the human and murine immune systems preferentially recognize different epitopes on these molecules. © 1995 Wiley‐Liss, Inc.
Recurrent cytogenetic alterations of prostate carcinoma and amplification of c‐myc or epidermal growth factor receptor in subclones of immortalized pnt1 human prostate epithelial cell line
Authors: Degeorges Armelle , Hoffschir Françoise , Cussenot Olivier , Gauville Christiana , Le Duc Alain , Dutrillaux Bernard , Calvo Fabien 
Published: February 2007

AbstractTo develop an experimental prostate cancer model, we immortalized normal human prostate adult epithelial cells with SV40 large‐T antigen. Two sublines were derived in culture, namely PNTIA and PNTIB. They retained the characteristics of prostatic epithelial cells, but did not clone in soft agarose. PNTIA occasionally formed undifferentiated adenocarcinoma tumors in nude mice, but only in the presence of matrigel. PNTIA and PNTIB displayed common cytogenetic alterations: a 10q arm deletion, which is a recurrent alteration in prostate carcinoma, chromosome losses and a translocation involving chromosome 5. An extensive study of oncogenic alterations occurring in these cells showed that PNTIA displayed c‐myc gene amplification, forming an hsr on chromosome 4, as well as c‐myc mRNA overexpression, with a faster doubling time (25 hr); moreover, it seemed less sensitive to EGF than PNTIB. PNTIB had a doubling time identical to that of normal cells (48 hr) but displayed EGF receptor gene amplification accompanied by an increased number of EGF binding sites and sensitivity to EGF. Because both cell lines displayed cytogenetic and oncogenic alterations found in prostate cancer, as well as differing malignant potentials, they represent an interesting model for studying the progression of prostate tumors. © 1995 Wiley‐Liss, Inc.
Comparisons of colon–cancer survival among european countries: The eurocare study
Authors: Sant Milena , Capocaccia Riccardo , Verdecchia Arduino , Gatta Gemma , Micheli Andrea , Mariotto Angela , Hakulinen Timo ,   Franco Berrino The Eurocare Working Group
Published: February 2007

AbstractUnder the aegis of Eurocare, a European Union project to assemble survival data from population‐based cancer registries and analyze them according to standardized procedures, we have investigated and compared colon‐cancer survival in 10 European countries. We analyzed 68,283 colon‐cancer cases diagnosed between 1978 and 1985 and followed for at least 6 years. After calculating relative survival, putative factors prognostic for survival were investigated by univariate and multiple‐regression analyses. Important intercountry colon‐cancer survival differences exist within Europe, which are not explained by methodological differences, nor by demographic confounders. In patients aged 60 to 69, the mean European 5‐year cumulative relative survival was 40%. Switzerland, Finland and The Netherlands had significantly higher 5‐year relative survival, while one area in the UK and Cracow in Poland had significantly lower survival than this European estimate. Prognosis improved over time: from 1978 to 1985, the risk of death was reduced by about 4% per year in all countries studied. Age at diagnosis is inversely related to prognosis. Differences in health provision and hence in quality of care and stage at presentation seem largely responsible for the differences in colon‐cancer survival found in the EUROCARE countries.
The prognostic value of DNA ploidy and S—phase estimate in primary breast cancer: A prospective study
Authors: Dieterich B. , Albe X. , Vassilakos P. , Wieser S. , Friedrich R. , Krauer F. 
Published: February 2007

AbstractIn this prospective study, the independent prognostic value of DNA ploidy in combination with the major clinico‐pathological characteristics (histological grade, nodal status, tumor size, estrogen and progesterone receptor status, number of tumors, multicentricity, lympho‐vascular infiltration) was evaluated in a series of 399 breast‐cancer patients. The mean follow‐up time was 4.5 years. The DNA content was measured using image cytometry on fresh tumor samples. The overall survival of tetraploid and slowly proliferating diploid cases was significantly different compared with that of aneuploid and rapidly proliferating diploid cases (p = 0.0002). Thus, DNA ploidy combined with S‐phase estimate (DNA histogram type) appeared to be good prognostic factors. In a multivariate survival analysis, DNA histogram type was not an independent prognostic factor unless the histological grade was excluded. This effect of DNA histogram type on survival was also observed among patients with grade‐l or ‐II tumors and patients with small tumors. In conclusion, DNA histogram type was a valuable prognostic factor in univariate analysis, and provided independent complementary information for patients considered at low or intermediate risk by classical pathological findings.
Increased risk of cancer in the descendants of syrian hamsters exposed prenatally to diethylnitrosamine (DEN)
Authors: Mohr U. , Emura M. , Kamino K. , Steinmann J. , Kohler M. , Morawietz G. , Dasenbrock C. , Tomatis L. 
Published: February 2007

AbstractTransmission of site‐specific tumorigenicity (papillomas in larynx and trachea) of diethylnitrosamine (DEN) to the 2 subsequent generations (F1 and F2) was studied using an out‐bred strain (Han:AURA) of pregnant Syrian golden hamsters (P generation), which were treated i.p. with 10 mg/kg b.w. of DEN on day 12, 13 or 14 of gestation. Laryngotracheal papillomas were induced by DEN in the P and F1 generations only, while these tumours did not occur in the F2 generation. Spontaneously occurring tumours, including uterine adenocarcinomas, lymphomas, and laryngotracheal neuro‐endocrine cell tumours, were observed at higher incidences among the F2 animals derived from the P generation hamsters treated with DEN only on day 13 or 14 of gestation. In the same animals, the ratio of malignant to benign tumours was considerably higher than in controls. In addition, the F2 hamsters derived from the DEN‐treated P generation showed more frequent multiple organ involvement in tumorigenesis than the F2 controls. Several uncommon malignant tumours were detected in the F2 offspring, possibly the result of damage caused to germ cells by the prenatal exposure of F1 Syrian hamsters to DEN.
Anti—vascular approaches to solid tumour therapy: Evaluation of vinblastine and flavone acetic acid
Authors: Hill Sally A. , Sampson Louise E. , Chaplin David J. 
Published: February 2007

AbstractSeveral agents have now been identified which exert their anti‐tumour effects in large part via the tumour vasculature; these include TNFα and flavone acetic acid (FAA). More recently, Vincristine and Vinblastine have also been shown to cause a prolonged and selective decrease in tumour perfusion. Vinblastine, unlike FAA, causes no increase in plasma TNFα levels in mice bearing the CaNT tumour, suggesting 2 distinct mechanisms of anti‐vascular activity for these structurally diverse agents. Since FAA and Vinblastine also show quite different normal tissue toxicities, which are separately dose‐limiting, we have examined the strategy of combining these 2 agents. When Vinblastine preceded FAA by 24 hr or less, tumour growth delay was significantly enhanced without a concomitant increase in toxicity. The level of enhancement was not significantly reduced by a 5‐fold decrease in Vinblastine dose, though any reduction in the dose of FAA caused a rapid reduction in treatment effectiveness. Investigation of the functional vasculature of treated tumours suggested that increased anti‐vascular effects may contribute to the enhanced growth inhibition of the combined treatment. Our results demonstrate the potential benefit of combining 2 different classes of antivas‐cular agent, using Vinblastine and FAA (or 5,6‐MeXAA) as prototype drugs.
Improved stage at diagnosis of cervical cancer with increased cancer awareness in a rural Indian population
Authors: Jayant Kasturi , Rao R. S. , Nene B. M. , Dale P. S. 
Published: February 2007

AbstractAs part of its strategy to identify cancer cases in a rural population, the cancer registry of Barshi, India, has developed a methodology which includes education of the population about likely symptoms of cancer, and motivation of symptomatic individuals to undergo medical investigation. Patients with cervical cancer from the registry area who attended Barshi Cancer Hospital (84% of the total) showed a significant improvement in stage at diagnosis between 1988–1989 (38% in stages I and II) and 1990–1992 (51% in stages I and II). No change was observed in those attending the same hospital from a control area (38% vs. 34%). Among a random sample of the population of the registry area, 76% of women were aware of the symptoms of cervical cancer, compared with 25% of the population of control areas. It is suggested that action to raise awareness of symptoms of cancer, and to encourage medical consultation, should form an important initial component of cervical‐cancer control programmes.
Trypsinogen expression in human ovarian carcinomas
Authors: Hirahara Fumiki , Miyagi Yohei , Miyagi Etsuko , Yasumitsu Hidetaro , Koshikawa Naohiko , Nagashima Yoji , Kitamura Hitoshi , Minaguchi Hiroshi , Umeda Makoto , Miyazaki Kaoru 
Published: February 2007

AbstractIncreased secretion of matrix metalloproteinases and serine proteinases is well known to be associated with cancer invasion and metastasis. We aimed to elucidate the implication of trypsin, a serine proteinase and a representative digestive enzyme in invasion and metastasis of human carcinomas. Northern blot, RT‐PCR and Western blot analyses and immunohisto‐chemical studies were performed to detect and analyze trypsinogen expression in 5 ovarian carcinoma cell lines and 10 human ovarian carcinoma tissues using a DNA probe for trypsinogen I, and monoclonal and polyclonal antibodies to human trypsin I. Among the 5 ovarian carcinoma cell lines, only the MCAS (mucinous cystadenocarcinoma) cell line showed a high level of trypsinogen production and mRNA expression by Western and Northern blot analyses, respectively. However, Southern blot analysis of RT‐PCR products could detect considerable levels of trypsinogen mRNA in all ovarian cancer cell lines. In Northern analysis of ovarian cancer tissues, all advanced cancer samples showed trypsinogen gene expression. Serous cystadenocarcinomas exhibited particularly high levels of gene expression. Immunohistochemical staining also detected trypsin in ovarian carcinoma tissues. In contrast, normal ovaries and tumors with low malignant potential did not show trypsinogen expression. Our results demonstrate the extra‐pancreatic production and distribution of trypsinogen in human ovarian carcinomas.
HLA‐A2 allelic microvariants in nasopharyngeal carcinoma
Authors: Ren E. C. , Law Grace C. T. , Chan S. H. 
Published: February 2007

AbstractHLA‐A2‐positive nasopharyngeal carcinoma (NPC; n = 38) and normal control (n = 51) populations were analysed by high‐resolution oligotyping to identify A2 allelic microvariants. Within the control group, A*0207 was found to be the most common allele, accounting for 50% of the A2 frequency in normals. In contrast, this allele was found to be present in only 23% of NPC cases, suggesting a protective effect. Of these 9 NPC patients with A*0207, all were associated with B46, unlike in the control group, where it can be found associated with non‐B46 antigens. Another allele, A*0201, which was thought to be protective against NPC was in fact present in 39.5% of NPC patients, more than twice the frequency in controls. These data confirm that A*0201 is not a protective allele for NPC, and other factors such as the A*0207, non‐B46 haplotype are of greater importance.
A recombinant vaccinia virus expressing human prostate‐specific antigen (PSA): Safety and immunogenicity in a non‐human primate
Authors: Hodge James W. , Schlom Jeffrey , Donohue Susan J. , Tomaszewski Joseph E. , Wheeler Clyde W. , Levine Barry S. , Gritz Linda , Panicali Dennis , Kantor Judy A. 
Published: February 2007

AbstractProstate‐specific antigen (PSA) is. a serine protease secreted by prostatic epithelial cells and is widely used as a marker for prostate cancer. The tissue specificity of PSA makes it a potential target for active specific immunotherapy, especially in prostate cancer patients who have undergone prostatectomy and in whom the only PSA‐expressing tissue in the body resides in metastatic deposits. We report here the cloning, construction and immunological consequences of immunization of rhesus monkeys with a recombinant vaccinia virus expressing human PSA (designated rV‐PSA). The prostate gland of the rhesus is structurally and functionally similar to the human prostate. While rodent and other mammalian species do not share homology with human PSA, there is 94% homology between the amino acid sequences of rhesus and human PSA. Immunization of rhesus monkeys with wild‐type vaccinia virus or rV‐PSA elicited the usual low‐grade constitutional symptoms of vaccinia virus infection. There was no evidence of any adverse effects in any immunized monkeys. A short‐lived PSA‐specific IgM antibody response was noted in all rV‐PSA immunized monkeys regardless of dose level. All monkeys receiving the 108pfu dose of rV‐PSA demonstrated PSA‐specific T‐cell responses that were maintained up to 270 days. No differences in anti‐PSA immune responses or toxicity were observed in animals that received prostatectomy prior to immunization. Our results thus demonstrate the safety and immunogenicity of rV‐PSA in a non‐human primate and have implications for potential specific immunotherapy protocols using PSA as a target.
Protein tyrosine kinase expression during the estrous cycle and carcinogenesis of the mammary gland
Authors: Andres Anne‐Catherine , Zuercher Gisela , Djonov Valentin , Flueck Martin , Ziemiecki Andrew 
Published: February 2007

AbstractThe susceptibility of the mammary epithelium to neoplastic transformation is linked to the exposure to estrogen during the estrous cycle. The effects of the estrous cycle on the mouse mammary gland have been investigated by analyzing <3>H‐thymidine incorporation, milk protein gene expression and DNA fragmentation. We found that the mammary epithelium undergoes limited proliferation, differentiation and apoptosis in a cycle‐dependent manner. The estrous‐responsive regulators of the mammary epithelium are unknown; however, considering the integral role of protein tyrosine kinases (PTKs) in the control of normal and malignant development, members of this family of enzymes are likely candidates for such regulatory molecules. Using a RT‐PCR‐based cloning strategy, we have undertaken a survey of PTKs expressed in the mammary gland at defined stages of development, with special emphasis on the estrous cycle. We identified 21 known and 4 novel PTKs. Their expression was analyzed throughout mammary gland development and in mammary neoplasias using a transgenic mouse model for invasive and non‐invasive carcinogenesis. Most of the identified PTKs showed highest expression during the estrous cycle and were down‐regulated during pregnancy and lactation. Deregulated expression was rarely observed in the non‐invasive mammary tumors. In contrast, 10 of 19 PTKs expressed during the estrous cycle were also over‐expressed in the invasive carcinomas, mostly involving members of the receptor family of PTKs.
Molecular heterogeneity of tumor rejection antigen/heat shock protein GP96
Authors: Feldweg Anna M. , Srivastava Pramod K. 
Published: February 2007

AbstractGlycoproteins of 96 kDa (gp96) have been shown to mediate tumor‐specific immunogenicity of a number of murine sarcomas. The purity of gp96 preparations used in these studies was originally demonstrated by their homogeneity on silver‐stained gels and the observation that a single amino acid terminus was detected by micro‐sequencing. Results reported here show that gp96 preparations consist of 3–4 closely spaced bands. However, each of the bands is recognized by well‐characterized monoclonal or monospecific antibodies to gp96. We have obtained purified preparations of a slowly migrating 110‐kDa and a faster migrating 96‐kDa band of the gp96 cluster from the Meth A sarcoma and have observed both species to be immunogenic in a dose‐restricted manner. In addition to the size‐based heterogeneity, purified 96‐kDa molecules are found to contain 2 major populations, which share the same amino and carboxy termini but differ in the region recognized by an anti‐grp94 monoclonal antibody (MAb). The heterogeneity in gp96 preparations does not result from differences in glycosylation but may result from differential phosphorylation, conformation or the antigenic peptides associated with gp96. It has been suggested that the tumor‐specific immunogenicity of gp96 preparations does not derive from gp96 but from a 110‐kDa protein which co‐purifies with gp96 and is distinct from it. Our observations show instead that the presence of a number of bands in purified gp96 preparations is due to heterogeneity within gp96 molecules rather than to contamination with unrelated proteins.