bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progestin induction of 17β‐hydroxysteroid dehydrogenase enzyme protein in the t‐47D human breast‐cancer cell line
Authors: Poutanen M. , Isomaa V. , Kainulainen K. , Vihko R. 
Published: February 2007

AbstractSteroid regulation of 17β‐hydroxysteroid dehydrogenase (17‐HSD) was studied in the T‐47D human breast‐cancer cell line, using a radioimmunoassay. In addition, 3 mRNA species (2.4, 1.4, and 0.9 kb) specific for the enzyme were shown to be present in these cells. All the synthetic progestins tested (ORG 2058, R5020, medroxyprogesterone acetate) significantly increased the immunoreactive enzyme protein concentration, while other types of steroids, such as testosterone, oestradiol and dexamethasone, were ineffective. The progestin‐specific induction of 17‐HSD was dose‐related and was maximum in about 5 days. An antiprogestin, RU 486, when used in combination with synthetic progestins, blocked the progestin‐induced increase of 17‐HSD concentration very effectively. A good correlation was observed in the different experiments between the enzyme activity and the immunoreactive 17‐HSD concentration. We conclude that progestins induce 17‐HSD in T‐47D cells and that the induction occurs via an increased accumulation of enzyme protein.
Interleukin‐1 and interleukin‐2 control granulocyte‐ and granulocyte‐macrophage colony‐stimulating factor gene expression and cell proliferation in cultured acute myeloblastic leukemia
Authors: Cozzolino Federico , Torcia Maria , Bettoni Stefania , Aldinucci Donatella , Burgio Vito L. , Petti Maria C. , Rubartelli Anna , Barbui Tiziano , Rambaldi Alessandro 
Published: February 2007

AbstractIn vitro proliferation of leukemic cells purified from 10 cases of acute myeloblastic leukemia (AML) was analyzed in basal conditions or in the presence of exogenous recombinant (r) Interleukin (IL) I. In parallel, blasts from 5 of these patients were studied for granulocyte‐macrophage colonystimulating factor (GM‐CSF) or granulocyte‐CSF (G‐CSF) mRNA. IL‐I augmented the spontaneous AML cell proliferation in all cases and induced de novo expression or increased amounts of GM‐CSF and/or G‐CSF transcripts in 4 of the 5 cases evaluated. IL‐I‐induced AML cell proliferation was modulated by neutralizing anti‐GM‐CSF or anti‐G‐CSF antibodies in those cases in which CSF mRNAs were induced or increased by exogenous cytokine. In the same cases, biosynthetic labelling and immunoprecipitation studies using monospecific anti‐GM‐CSF antibodies showed that IL‐I also increased the levels of GM‐CSF protein synthesis. Addition of neutralizing anti‐IL‐I antibodies to AML cell cultures completely abolished ongoing GM‐CSF synthesis, suggesting that endogenous IL‐I is needed to maintain autocrine production of CSFs. The effects of rlL‐2 were investigated in a larger series of 21 patients. The cytokine reduced spontaneous AML cell proliferation in 8 cases. It caused complete disappearance of GM‐CSF mRNA in I case, and marked reduction of G‐CSF mRNA in 2 cases. Increased AML cell proliferation was observed in 2 of 21 cases. These findings suggest that expression of CSF genes and cell proliferation in AML are under the control of different cytokines acting in autocrine or paracrine fashion.
Oncogene expression of fanft‐ or BBN‐induced rat urothelial cells
Authors: Debiec‐Rychter Maria , Jones Richard F. , Zukowski Kim , Wang Ching Yung 
Published: February 2007

AbstractProto‐oncogene expression by cultured urothelial cells prepared from the bladders of male F344 rats that had been treated with N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]‐formamide (FANFT) or N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) were examined. Although all of the cultured cells showed varying degrees of anchorage‐independent growth, only 9 of them were transplantable into nude mice. A Northern blot technique was employed for the detection of proto‐oncogene transcripts. The c‐Ha‐ras transcripts were detected in all the cultured urothelial cells prepared from the carcinogentreated rats and in normal urothelial cells. However, the transcript levels were several‐fold higlher in the former than in normal cells. Increased expression of p21, as determined by immunohistochemical techniques, was also observed in all the original bladder tissues from which the cultures were derived. c‐myc transcripts were detected in the cells from carcinogentreated rats but not in the normal cells. The presence of myc product in hyperplastic urothelial lesions and carcinomas of original bladder tissues was confirrned by immunohistochemical methods. Transcripts of mos, erb B, Ki‐ras, abl and src were not detected. Since increased expression of c‐myc and c‐Ha‐ras were present in both transplantable and non‐transplantable cell lines, and the expression of p21 occurs in preneoplastic cells, this suggests that elevated expression of these 2 genes may be an early genetic event during bladder carcinogenesis in the rat and further alteration of these 2 genes or mutation of additional genes may be required for the completion of malignant transformation.
Retardation of metastatic tumor growth after immunization with metastasis‐specific monoclonal antibodies
Authors: Reber S. , Matzku S. , Günthert U. , Ponta H. , Herrlich P. , Zöller M. 
Published: February 2007

AbstractThe influence of 4 murine monoclonal antibodies (MAbs) directed against surface determinants of a metastasizing rat adenocarcinoma (BSp73ASML) on metastatic spread was evaluated and compared to their in vivo binding as well as to the induction of a humoral anti‐MAb response, especially with respect to the development of anti‐idiotypic (ID) antibodies of the internal image type. In a protocol of explicit immunization, all 4 MAbs transiently inhibited metastatic growth. Survival was prolonged only with one MAb (4.4ASML). With another MAb (1.1ASML), directed against a new variant form of CD44, metastatic growth was accelerated after transient retardation. Retardation of metastatic growth correlated with the humoral anti‐MAb response. This accounted for the isotype‐ as well as for the idiotype‐specific response. An exception was noted after immunization with MAb 1.1ASML. Rats with high levels of anti‐1.1ASML antibodies, which inhibited binding to the tumor cells (internal image‐type antibodies) showed accelerated metastatic spread. Data are interpreted to mean that MAb‐induced inhibition of metastatic spread may be based on 2 independent mechanisms: blockade of metastasis‐associated epitopes (i. e., with MAb 1.1ASML) and induction of an anti‐mouse lg response. In the latter case it was irrelevant whether the response was isotype‐ or idiotype‐specific.
Increased sensitivity to two‐stage skin carcinogenesis of mice heterozygous for the repeated epilation mutation (Er)
Authors: Reddy A. Lakshma , Fialkow Philip J. 
Published: February 2007

AbstractMice heterozygous for repeated epilation mutation (Er) have cutaneous abnormalities that result in repeated loss of hair. Skin papillomas and carcinomas occur spontaneously in suchErl+ mice. BALB/c mice are generally resistant to induced skin cancers. We investigated whetherErl+ heterozygous mice of BALB/c genetic background exhibit increased susceptibility to spontaneous and induced skin tumors. Although none of theErl+ CXB(N5) mice spontaneously developed skin tumors, they exhibited increased sensitivity to the development of skin papillomas induced by an initiationpromotion regimen.Erl+ mice developed papillomas after 20 μg DMBA initiation in the absence of TPA promotion, but the same dose of DMBA was subtumorigenic in +/+ (sibling) mice. Although 15 weeks of TPA promotion resulted in similar tumor susceptibilities, tumor latencies and tumor frequencies in the 2 groups of initiated mice, the papillomas were qualitatively different.Erl+ mice, the developed more papillomas of the delayed promoter‐independent type, which occur after termination of promotion. In contrast, +/+ mice developed more promoter‐dependent papillomas, which regress after termination of promotion. ThereforeErl+ mice had a significantly higher number of papillomas than +/+ mice at the termination of the experiment. These results suggest that Er‐mutation‐induced skin defects not only lead to the repeated loss of hair, but also influence the mode of development of skin papillomas from carcinogen‐initiated cells.
The in vivo antimelanoma effect of 4‐S‐cysteaminylphenol and its N‐acetyl derivative
Authors: Miura Takako , Jimbow Kowichi , Ito Shosuke 
Published: February 2007

AbstractPhenolic melanin precursors can be utilized for the development of anti‐melanoma agents. The sulphur homologue of tyrosine, 4‐S‐cysteinylphenol (CP) and its decarboxylation product, 4‐S‐cysteaminylphenol (CAP) were shown to be substrates of melanoma tyrosinase, forming melanin‐like pigment. Both, but in particular the 4‐S‐CAP, exhibited a significant in vivo depigmenting effect. Here, we report on the in vivo anti‐melanoma effect of 4‐S‐CP, and 4‐S‐CAP and its N‐acetyl derivative. In a previous in vitro study, it was shown that 4‐S‐CP and 4‐S‐CAP required a catalytic amount of dopa for optimal mammalian tyrosinase activity. To enhance the potential anti‐melanoma effect of these two compounds, L‐dopa and a decarboxylase inhibitor (carbidopa) were given concomitantly. We found that 4‐S‐CAP showed a significant growth inhibition of B16 melanoma inoculated S. C. into C57BL/6J mice. The anti‐melanoma effect was increased significantly by combination of L‐dopa and carbidopa. In addition, we tested the in vivo anti‐melanoma effect of an N‐acetyl derivative of 4‐S‐CAP (N‐Ac‐4‐S‐CAP). We found that N‐Ac‐4‐S‐CAP was the tyrosinase substrate and potent inhibitor of melanoma growth. N‐acetyl 4‐S‐CAP showed a marked increase in water solubility. We suggest that N‐Ac‐4‐S‐CAP may prove to be a valuable model for the development of anti‐melanoma agent using a metabolic pathway of melanin synthesis.
Expression of the epstein‐barr virus genome in a nasopharyngeal carcinoma epithelial tumor cell line
Authors: Zhang Hai‐Ying , Yao Kaitai , Zhu He‐Cheng , Glaser Ronald 
Published: February 2007

AbstractAn epithelial tumor cell line was recently established from a biopsy specimen of a nasopharyngeal carcinoma (NPC), and designated HONE‐1. Uncloned (parental) HONE‐1 and HONE‐1 clone (C)‐40 cells were found to contain latent Epstein‐Barr virus (EBV). Expression of the latent EBV genome in HONE‐1 C‐40 cells has been examined. It was possible to detect a small percentage of cells spontaneously synthesizing EBV early antigen (EA) and virus capsid antigen (VCA) by immunofluorescence (IF). In addition, the EBV nuclear antigens (EBNA‐I and EBNA‐2), as well as the EBV latent membrane protein (LMP) were detected in the HONE‐1 cells. Attempts were made to induce the latent EBV genome in these cells with iododeoxyuridine (IUdR). We observed a significant increase in the number of EA/VCA‐positive cells, an increase in EBV DNA, the synthesis of virus particles, and the rescue of infectious virus after treatment of HONE‐1 C‐40 cells with IUdR. The HONE‐1 C‐40 cells should facilitate studies of the expression and regulation of the EBV genome in NPC epithelial tumor cells, which have not previously been available.
Role of catalase and oxidative stress in hepatic peroxisome proliferator‐induced morphological transformation of syrian hamster embryo cells
Authors: Mikalsen Svein‐Ole , Kaalhus Olav , Reith Albrecht , Sanner Tore 
Published: February 2007

AbstractSeveral hepatic peroxisome proliferators (HHPs), such as di(2‐ethylhexyl)phthalate (DEHP), mono(2‐ethylhexyl)‐phthalate, clofibrate and tiadenol, induce morphological transformation of Syrian hamster embryo (SHE) cells in vitro. According to one hypothesis, the hepatocarcinogenic effect of HPPs is caused by an oxidative stress due to increased H2O2‐production from the strongly induced peroxisomal β‐oxidation of fatty acids. Thus, increased transformation frequencies by HPPs should be obtained when catalase was inhibited by 3‐amino‐1, 2, 4‐triazole (amitrole). However, coexposure to HPPs and amitrole did not enhance the transformation frequencies for any of the HPPs. The sensitivity of SHE cells for oxidative agents was studied by using menadione and H2O2. Menadione only induced transformation at a toxic concentration, while H2O2 induced transformation at non‐toxic concentrations. To study the generation of oxidative radicals in SHE cells, electron spin resonance was employed. No oxidative radical formation was detected in tiadenol‐ or DEHP‐exposed SHE cells. When menadione or H2O2 were added during the measurements, oxidative radicals were found. A transmission electron microscopic study showed a small number of peroxisomes, and did not reveal any increase in the number of peroxisomes in clofibrate treated SHE cells.
Expression of epstein‐barr virus‐encoded proteins and B‐cell markers in fatal infectious mononucleosis
Authors: Falk Kerstin , Ernberg Ingemar , Sakthivel Ramasamy , Davis Jack , Christensson Birger , Luka Janos , Okano Motohiko , Grierson Helen L. , Klein George , Purtilo David T. 
Published: February 2007

AbstractWe assessed 33 lymphoid tissues from 15 patients, including 7 with X‐linked lymphoproliferative disease (XLP) and 8 pa tients with sporadic fatal infectious mononucleosis (IM), to determine whether the cellular infiltrate had the immu nophenotype and expressed Epstein‐Barr virus (EBV)‐encoded proteins characteristic of either EBV‐immortalized lymphoblastoid cell lines (LCL) or EBV‐carrying Burkitt lymphoma (BL) cells. The results of these studies revealed that in 13 cases the proliferating B cells were polyclonal, LCL‐like, and in 2 cases they were monoclonal, malignant lymphomalike.
Number of children and death from hormone‐dependent cancers
Authors: Lund Eiliv 
Published: February 2007

AbstractThe association between number of children of current marriage reported by 431,604 women aged 45‐74 years at the Norwegian Census in 1970 and mortality, at follow‐up through 1985, from hormone‐dependent cancers, i. e., cancers of breast, corpus uteri and ovary combined, has been investigated. The reduction in age‐adjusted mortality was 9.6% (95% confidence interval; 8.3–10.9%) for each child with no deviation from linearity. Women with 8‐11 children had a relative risk of 0.34 (0.25–0.47) compared to nullipara. Adjustment for age at first birth slightly changed the effect of number of children on mortality to 9.3% per child. The reduction in mortality per child was for cancer of the breast 7.2%, corpus uteri 12.2% and ovary 12.7%. Our findings indicate that having few children is a major risk factor for death from the 3 hormone‐dependent cancers combined.
Cell‐surface antigens of human lung tumors detected by mouse monoclonal antibodies: Definition of blood‐group‐ and non‐blood‐group‐related antigenic systems
Authors: Feickert Hans‐Joachim , Anger Bernd R. , Cordon‐Cardo Carlos , Lloyd Kenneth O. 
Published: February 2007

AbstractThe pattern of antigen expression in human non‐small‐cell cancers of various histiological subtypes has been studied. Mouse monoclonal antibodies (MAbs) were generated following immunizations with cell lines of squamous, adeno‐ and anaplastic large‐cell carcinomas of the lung. Seven nonblood‐group‐related antigens were defined in addition to 5 antigens related to blood‐group determinants. Detailed specificity was established with a large panel of cultured cell lines and normal and neoplastic tissues. MAb F‐18 reacted in direct tests with the immunizing squamous lung carcinoma cell line, with 5 out of 5 choriocarcinoma cell lines, but with no other cell lines. No expression of F‐18 antigen was observed in any normal or malignant tissue examined. The other 6 nonblood‐group‐reactive MAbs (F‐7, F‐8, F‐11, F‐15, F‐16 and F‐17) could be distinguished by their reactivity on a panel of cultured cells and tissues. One MAb in this group (F‐17) reacted strongly with 19/35 lung tumor cell lines, 32/76 other tumor‐derived cell lines, cultured normal kidney cells and fetal lung fibroblasts. This antibody did not react with any normal adult tissues examined, but did react with several cancer tissues including 1/17 lung tumors, 2/4 ovarian cancers and 1/5 colon tumors. Immunoprecipitation tests revealed that 5 of the antigens were glycoproteins: F‐18 (Mr > 200,000), F‐15 (Mr 44,000), F‐16 (Mr 90,000), F‐17 (Mr 95,000) and F‐8 (Mr 95,000). Four MAbs detected Y blood‐group antigen (Ley), only 2 of which were able to agglutinate O erythrocytes. Another antibody detected X blood‐group antigen (Lex).
Mitogenic peptides in breast cyst fluid: Relationship with intracystic electrolyte ratios
Authors: Lai L. C. , Ghatei M. A. , Takahashi K. , Patel K. V. , Schrey M. P. , Ghilchik M. W. , Bloom S. R. , James V. H. T. 
Published: February 2007

AbstractWomen with palpable breast cysts which are lined with apocrine epithelium may be at higher risk of developing breast cancer than women with breast cysts which are lined with flattened epithelium, the former group being characterized by intracystic sodium to potassium ratios below 3, while the latter group has intracystic sodium to potassium ratios above 3. In this study the distribution of intracystic concentrations of the mitogenic peptides, epidermal growth factor, endothelin and gastrin‐releasing peptide in the 2 groups of breast cysts were compared to see whether differences in concentrations between the 2 cyst groups might provide an explanation for the higher risk of breast cancer observed in women with “apocrine” breast cysts. The concentrations of epidermal growth factor and gastrin‐releasing peptide were significantly higher in the low electrolyte ratio group (p < 0.001). There was no difference in endothelin concentrations between the 2 groups. Negative correlations were found between epidermal growth factor concentrations and Na+/K+ and between gastrin‐releasing peptide concentrations and Na+/K+ (p < 0.001). A positive correlation was found between gastrin‐releasing peptide and epidermal growth factor concentrations in breast cyst fluid (p < 0.001). The significantly higher intracystic concentrations of both epidermal growth factor and gastrin‐releasing peptide in the low‐electrolyte‐ratio group may provide an explanation for the higher risk of breast cancer which has been observed in women with “apocrine” breast cysts.
Lymphokine‐activated killer cell cytotoxicity against human colon carcinomas enhanced by monoclonal antibody D612
Authors: Pendurthi Tribhuvan K. , Parker Ricardo , Schlom Jeffrey , Primus F. James 
Published: February 2007

AbstractThe antibody‐dependent cellular cytotoxicity (ADCC) properties of a murine monoclonal antibody (MAb), designated D612 (IgG2a), which reacts with human colon carcinomas, was studied using normal human peripheral blood lymphocytes (PBMNC). Although the level of ADCC of PBMNC with D612 varied among different donors, it was 20 to 30 times higher than the lytic activity of control cultures containing isotype‐matched control MAb. Incubation of PBMNC with recombinant interleukin‐2 (IL‐2) resulted in a 2‐ to 5‐fold augmentation in the cytotoxicity of effector cells exposed to MAb. This augmentation was apparent after subtracting nonspecific cellular cytotoxicity from the total cytotoxicity mediated by activated effector cells in the presence of D612. Optimal stimulation of specific ADCC with IL‐2 appeared after 24 hr of culture in 500 U/ml of IL‐2, resulting in a 3.8 ± 1.7 fold increase in lytic units. However, stimulation of ADCC was also evident at 10 U/ml of IL‐2. Furthermore, antibody dose titrations with untreated and IL‐2 activated effectors showed that the threshold dose of MAb needed for efficient ADCC was reduced by 200‐fold with IL‐2. Depletion of FcRγIII‐positive lymphoid cells markedly reduced D612 ADCC, demonstrating the participation of NK/LAK cells in D612‐mediated ADCC. Low levels of ADCC activity were found associated with adherent cells, either untreated or following their activation with γ‐interferon, while D612 was most active with non‐adherent effectors. The specificity and ADCC properties of the D612 MAb suggest that it should be considered as a candidate for immunotherapy of colon cancer, particularly when used in combination with IL‐2 plus LAK cell treatment.
Expression of messenger RNAs for platelet‐derived growth factor and its receptors in human sarcoma cell lines
Authors: Leveen P. , Claesson‐Welsh L. , Heldin C. H. , Westermark B. , Betsholtz C. 
Published: February 2007

AbstractGrowth factors of the platelet‐derived growth factor (PDGF) family have been thought to possess autocrine functions in certain neoplasms of mesenchymal and glial origin. This notion has been based on observations that these tumors express PDGF genes and produce PDGF‐like growth factors. Corresponding data on PDGF receptor expression in sarcoma cell lines is essentially lacking. The cloning of cDNA for 2 distinct PDGF receptors with different abilities to recognize the members of the PDGF family and availability of recombinant PDGF for binding studies have recently made it possible to study the expression of both receptor types in tumor cell lines. We present here a study on 8 human sarcoma cell lines, and show a large variability and independency in the expression of the 2 PDGF receptor types as well as of the genes encoding the corresponding ligands.
Transfection of a non‐metastatic diploid rat mammary epithelial cell line with the oncogenes for EJ‐RAS‐1 and polyoma large T antigen
Authors: Jamieson Susan , Barraclough Roger , Rudland Philip S. 
Published: February 2007

AbstractTransfection of rat mammary (Rama) 37 epithelial cells which yield non‐metastasizing adenomas in syngeneic Wistar‐Furth rats with a drug resistance plasmid containing both the neo gene and EJ‐ras‐I (pSV2neo‐ras) or with pSV2neo and a plasmid encoding the large T Antigen (pLT214) of polyoma virus yields drug‐resistant transformants with a frequency of 10−5. Representative transformants have been propagated in neo‐selecting medium to yield various cell lines. The 7 lines transfected with pSV2neo‐ras (EJI set) and the 10 lines cotransfected with pSV2neo and pLT214 (LTI set) all produce tumours at subcutaneous (s. c.) sites with a shorter median latent period than tumours produced by the parental Rama 37 cells. In addition, the LTI set: of transformants yields a higher incidence of tumours than the Rama 37 cells. No metastases are produced when any of the oncogene transformants are inoculated s. c. into rats. However, when an EJi representative is inoculated intravenously (i. v.), tumour deposits are found in the lungs of the host animals. In contrast, other Rama 37 variants that metastasize from s. c. sites fail to produce any metastases when inoculated i. v. The oncogene transfectants contain integrated DNA that hybridizes to neo and to the requisite oncogenic DNAs; the pattern of hybridizing bands to the transfected genes and their expression as mRNA is complex, and is presented in detail.
A fluorouridine‐anti‐CEA immunoconjugate is therapeutically effective in a human colonic cancer xenograft model
Authors: Shih Lisa B. , Xuan Hong , Sharkey Robert M. , Goldenberg David M. 
Published: February 2007

Abstract5‐fluorouridine (FUR), an antineoplastic agent, was sitespecifically conjugated to the carbohydrate moiety of a anticarcinoembryonic antigen (CEA) monoclonal antibody (MAb) by using amino‐dextran as the intermediate carrier. The final immunoconjugate contains approximately 30‐35 molecules of FUR per molecule of immunoglobulin, has immunoreactivity retained as examined by flow cytometry, and is cytotoxic to the target cells as examined by 75selenomethionine incorporation studies. In the GW‐39/nude mouse model, the conjugate remained efficient in targeting the human colonic tumor and possessed greater inhibitory growth effects on the subcutaneous tumor than free FUR or an irrelevant antibody conjugate. In addition, the reduced host toxicity of the conjugate may permit the use of this agent in a high‐dose therapy of this tumor system.