bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of the human T‐cell lymphotropic virus type I (HTLV‐I) in South‐Western Colombia
Authors: Maloney Elizabeth M. , Ramirez Hernan , Levin Arthur , Blattner William A.
Published: February 2007

To evaluate altitude of birthplace and residence as factors associated with geographic clustering of HTLV‐I infection in Colombia, we sampled a total of 670 current residents of the South Pacific coastal lowland and of upland regions (Cali and environs) of the Valle and Cauca Provinces, located at an altitude of 3,100 ft. Among the 255 lowland study subjects, 4.3% had antibody against HTLV‐I, compared to 0.9% of the 415 upland study subjects. A hypothesis emerging from this study is that the lower socio‐economic status of lowland residents and associated diseases, particularly untreated syphilis and other sexually transmitted diseases, may explain the increased HTLV‐I seropositivity rates in this population.
Epidermal growth factor receptors in spontaneous ovarian granulosa cell tumors of swr‐derived mice
Authors: Tennent Barbara J. , Beamer Wesley G. , Shultz Leonard D. , Adamson Eileen D.
Published: February 2007

Epidermal growth factor (EGF) receptor binding properties were examined in spontaneous ovarian granulosa cell (GC) tumors from SWR and SWR‐derived strains of mice. EGF binding was measured at room temperature in tissue ho‐mogenates from GC tumors and normal ovaries from adult randomly cycling mice. GC tumor tissue displayed significantly increased EGF binding and 2 receptor populations (Rl and R2). Normal ovarian tissue appeared to have only one receptor population with a dissociation constant (Kd) similar to the Rl (high‐affinity) receptor in GC tumors. In subsequent experiments, GC tumor and normal granulosa cells from immature mice were analyzed in primary cultures for EGF binding, immunofluorescence microscopy for receptors, and cell proliferation. After 24 hr in culture, the GC tumors bound 10‐fold more EGF/ug protein than did normal granulosa cells. GC tumor cells, but not normal granulosa cells, showed specific immunofluorescence when reacted with a polyclonal antibody to mouse EGFR. During 96 hr in culture, GC tumor cells, but not normal cells, showed a significant proliferative response to EGF. In conclusion, the EGF binding capacity is markedly increased in GC tumor cells and the proliferation data suggest that this growth factor supports tumor growth in the SWR model system.
Intraperitoneal and subcutaneous xenografts of human ovarian carcinoma in nude mice and their potential in experimental therapy
Authors: Massazza Gabriella , Tomasoni Antonella , Lucchini Valeria , Allavena Paola , Erba Eugenio , Colombo Nicoletta , Mantovani Alberto , D'Incalci Maurizio , Mangioni Costantino , Giavazzi Raffaella
Published: February 2007

Human ovarian carcinomas (HOC) were established s.c. and i.p. in nude mice and the biological characteristics were investigated for 4 xenografts. HOC8 and HOC 18, derived respectively from a primary tumor of the ovary and a pleural effusion (from 2 different patients) were established s.c. in nude mice. HOC10 and HOC22, derived from the ascites of 2 patients, were directly established as ascites after i.p. injection in nude mice. The s.c. and i.p. growth behavior of the 4 HOC lines was investigated. HOC18, HOC8 and HOC22 cells produced progressively growing tumor after s.c. injection but HOC10 ascites would not grow s.c. The cell suspension derived from HOC18 only produced carcinomatosis upon i.p. injection, while HOC8 cells produced both ascites and carcinomatosis. The 2 ascites HOC10 and HOC22 produced ascites in nude mice, but only HOC22 formed i.p. carcinomatosis. Histopathological characteristics of the patients' primary tumors persisted in nude mice, regardless of the site of tumor implantation. DNA histograms of the xenografts closely matched the patients' tumors and remained stable at different passages. Cisplatin, adriamycin and cyclophosphamide given i.v. were tested against HOC8 and HOC18 growing s.c. and HOC22 and HOC10 growing i.p. HOC8 showed a significant response to DDP and almost no sensitivity to ADR and CTX. HOC18 showed only moderate growth delay with all 3 drugs. Mice bearing HOC10 and HOC22 ascites had a prolonged survival time after DDP and ADR treatment.
Rabbit blastocoelic fluid regulation of tumor‐cell proliferation in vitro
Authors: Lambert Raymond D. , Gosselin Sylvie , Pothier Francois , Morin Cybele , Veilleux Raymonde , Roy Michel , Fortier Michel A.
Published: February 2007

To determine whether rabbit blastocoelic fluid could inhibit tumor‐cell proliferation, day‐9 and day‐12 embryonic fluids, together with autologous and homologous sera, were collected from pregnant or pseudopregnant rabbits and tested against 13 different cell lines and on human carcinoma cells in primary culture. An inhibitory effect on cell proliferation was observed in the presence of blastocoelic fluids, but not with homologous or heterologous sera. This suppression was higher with samples collected at day 12 than at day 9 of pregnancy. No such inhibition could be detected on one‐cell rabbit embryos or on freshly prepared uterine stromal or myometrial cells. In addition, the inhibitory activity on tumor cells was completely reversible upon removal of the fluids. Incorporation of 3H‐thymidine, 3H‐uridine and 35S‐methionine revealed that, in the presence of blastocoelic fluids, both DNA and RNA syntheses were rapidly inhibited. Inhibition of protein synthesis did not occur before 24 hr of treatment. We conclude that rabbit blastocoelic fluid suppresses the proliferation of tumor cells via inhibition of RNAand DNA synthesis by a process which may involve the expression of growth suppression gene(s).
Inhibition by cysteamine of hepatocarcinogenesis induced by N‐nitrosomorpholine in sprague‐dawley rats
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako
Published: February 2007

The effect of cysteamine (2‐aminoethanethiol hydrochloride) on hepatocarcinogenesis induced by N‐nitrosomor‐pholine (NNM) was investigated in male Sprague‐Dawley rats. Rats received alternate‐day s.c. injections of cysteamine, and beginning in experimental week 3 were given drinking water containing NNM for 8 weeks. Pre‐neoplastic and neoplastic lesions staining positive for gamma‐glutamyl transpeptidase (GGT) or glucose‐6‐phosphate dehydrogenase (G6PD) were examined by histochemical techniques. In week 18, quantitative histological analysis showed that prolonged administration of cysteamine resulted in a significant reduction in the number of GGT‐positive and G6PD‐positive hepatic lesions. Histologically, hepatocellular carcinomas were significantly fewer and smaller in GGT‐positive and G6PD‐positive lesions in rats treated with cysteamine than in untreated rats. Administration of cysteamine also caused a significant decrease in the liver norepinephrine concentration and in the labelling indices of pre‐neoplastic lesions and the surrounding liver. Our findings indicate that cysteamine inhibits hepatocarcinogenesis; this may be related to its reducing effect on norepinephrine concentration in the liver and its subsequent inhibition of cell proliferation in neoplastic lesions and surrounding hepatocvtes.
Two different anti‐erythroid monoclonal antibodies in immunodiagnosis of human leukemias: A comparative study
Authors: Tupitsyn N. N. , Mechetner E. B. , Baryschnikov A. Ju. , Drozdova T. S. , Frenkel M. A. , Ievleva E. S. , Kiselev A. V. , Perilov A. A. , Peterson I. S. , Probatova N. A. , Protasova A. K. , Rozinova E. N. , Tonevitsky A. G. , Volkova M. A.
Published: February 2007

To date, only anti‐glycophorin‐A monoclonal antibodies (MAbs) have been widely used as anti‐erythroid probes in the diagnosis of leukemias. We have examined blood, bone‐marrow and lymph‐node samples from 474 patients, adults and children, with different hemopoietic malignancies, using a panel of MAbs including 2 anti‐erythroid MAbs directed to glycophorin‐A and an antigen of erythroblasts, Ag‐Eb. MAb HAE9 directed against a human epitope of Ag‐Eb has earlier been shown to be highly specific for immature erythroid cells. Of all the patients, 2.7% demonstrated glycophorin‐A expression on blast cells, while anti‐Ag‐Eb MAb HAE9 reacted positively with cells from 6.0% of patients. Samples from 31 of 474 (6.5%) patients expressed one or both erythroid markers. Our results indicate that MAb HAE9 may be useful, in combination with anti‐glycophorin‐A MAbs, as an anti‐erythroid probe for immunophenotyping human leukemias.
Tumorigenic conversion of xeroderma pigmentosum lymphoblastoid cells without karyotypic alteration
Authors: Tachibana Akira , Toyoda Mariko , Mitani Hiroshi , Sasaki Masao S. , Arita Izumi , Takebe Hiraku , Tatsumi Kouichi
Published: February 2007

In order to examine the process of malignant transformation of human somatic cells, we studied the tumorigenic conversion of an Epstein‐Barr‐virus‐immortalized lymphoblas‐toid cell line (LCL) derived from a patient with xeroderma pigmentosum (XP) complementation group A. Repeated irradiation of the XP cells, XP7NI, with UV‐light and subsequent treatment with l2‐0‐tetradecanoylphorbol‐l3‐acetate (TPA) resulted in the acquisition of tumorigenicity in athymic nude mice. The tumorigenicity of XP7NI cells was also induced by TPA treatment alone. The tumors formed in athymic mice were of B‐cell lymphoma with characteristic histology, cell surface immunoglobulins and an antigen as detected by a B‐cell‐specific monoclonal antibody (MAb), CD20. The surface immunoglobulins and the HLA type of these tumor cells were identical with those of the parental cells. These malignantly transformed cells retained the same UV sensitivity, serum requirement, colony‐forming ability in soft agar, and normal human karyotype as the parental cells. Unlike other tumorigenic lymphoblastoid cell lines, this XP lympho‐blastoid cell line provides a unique case in that process(es) leading to tumorigenicity may be induced by UV and TPA without apparent karyotypic changes.
Bladder cancer and occupational exposure to polycyclic aromatic hydrocarbons
Authors: Bonassi Stcfano , Mfrlo Franco , Pearce Neil , Puntoni Riccardo
Published: February 2007

The association between occupational exposure to polycy‐clic aromatic hydrocarbons (PAH) and bladder cancer development was investigated in a population‐based case‐control study carried out in the Bormida valley, Italy. One hundred and twenty‐one male cases and 342 male controls, matched by age were collected from local hospitals. Occupational exposure to PAH and aromatic amines (AA) was evaluated by means of a job exposure matrix, constructed specifically for this study. Subjects considered as sharing a “definite exposure to PAH” showed an increased risk even after adjustment for cigarette smoking and exposure to AA (OR = 2.14, 95% CL 0.82‐5.60). No elevation in risk was found for the category “possible exposure to PAH” (OR = 1.05, 95% CL 0.45‐2.44). The findings of this study are consistent with previous studies indicating PAH as a risk factor for bladder cancer. A possible residual confounding effect due to AA impurities is discussed.
Bispecific antibodies reactive with the multidrug‐resistance‐related glycoprotein and CD3 induce lysis of multidrug‐resistant tumor cells
Authors: van Dijk J. , Tsuruo T. , Segal D. M. , Bolhuis R. L. H. , Colognola R. , van de Griendleuren R. J. , Fleuren G. J. , Warnaar S. O.
Published: February 2007

We describe the lysis of multidrug‐resistant (MDR) tumor cells by various lymphocytic effector cells, retargeted with bispecific antibodies (heteroconjugates). The Ab‐hetero‐conjugate used was prepared by chemically cross‐linking the OKT3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes, with the MRKI6 MAb, which recognizes the MDR‐associated P‐glycoprotein. Cloned TCRαβCD3+ T lymphocytes, OKT3‐activated peripheral‐blood mononuclear cells and peripheral‐blood mononuclear blood lymphocytes, stimulated with allogeneic irradiated cells in a mixed lymphocyte culture, could be induced to lyse MDR ovarian tumor cells in the presence of Ab‐heteroconjugate CD3/MRKI6, whereas the drug‐sensitive parental tumor cells lacking the P‐glycoprotein were not lysed by these retargeted effector cells. Cloned TCRγδ5/CD3+ T lymphocytes showed a high MHC‐unrestricted lysis of MDR tumor cells. Addition of Ab‐heteroconjugate CD3/MRKI6 could therefore not enhance target‐cell lysis. Melanoma tumor cells transfected with the mdr‐l gene which codes for the P‐glycoprotein were also efficiently lysed by Ab‐heteroconjugate retargeted cloned TCRαβ/CD3+ T cells. Tumor cell lines derived from organs known to express the P‐glycoprotein also were lysable by the retargeted effector cells.
Frequent clonal chromosomal changes in human non‐malignant tumors
Authors: Teyssier J. R. , Ferre D.
Published: February 2007

A cytogenetic analysis has been performed on 109 nonmalignant human solid tumors of various histological types after short‐term culture. These tumors were derived from epithelial, mesenchymal, embryonal and neurogenic tissues. The chromosome count was in the diploid range in virtually all specimens. Clonal chromosomal changes were found in 37% of tumors: 20% had numerical deviations, 12% structural rearrangements, and 5% both karyotypic alterations. Chromosome 7 was most frequently involved in 25% of abnormal specimens. Our results suggest that chromosomal changes contribute to non‐malignant tumorigenesis and that their analysis may provide information about the genetic events which shift benign tumor cells to malignant behavior.
Risk of cancer in women receiving hormone replacement therapy
Authors: Adami Hans‐Olov , Persson Ingemar , Hoover Robert , Schairer Catharine , Bergkvist Leif
Published: February 2007

Cancer risk following treatment with non‐contraceptive estrogens was studied in a population‐based cohort of 23,244 women. Complete follow‐up for an average of 6.7 years revealed 1,087 incident cancers versus 962.5 expected (relative risk/RR/= 1.13; 95% confidence interval 1.10–1.20). We confirmed the recent findings of a more detailed analysis of the same cohort, based on a I‐year shorter follow‐up period, namely: a markedly increased risk of endometrial cancer (RR = 1.8; 1.5–2.1), notably in women receiving potent estrogens, i.e., conjugated estrogens or estradiol (RR = 2.0; 1.6–2.4), and a slightly increased risk of breast cancer (RR = 1.1; 1.0–1.2). A slightly decreased risk of invasive cervical cancer (RR = 0.8; 0.5–1.2) is most likely due to more frequent smear taking than in the background population. There was no increase in the risk of cancer of ovary (RR = 1.0; 0.8‐1.2), pancreas (RR = 0.8; 0.5–1.2), large bowel (RR = 1.0; 0.8–1.2) or kidney (RR = 1.0; 0.7–1.4). The risk of developing cancer in liver or biliary tract was lower than expected (RR = 0.4; 0.2–0.7), particularly in women who had used potent estrogens (RR = 0.3; 0.1–0.6), an unexpected finding which warrants further studies. Increased risks of malignant melanoma (RR = 1.5; 1.0–2.1) and lung cancer (RR = 1.3; 0.9–1.7) need cautious interpretation because of their low magnitude, the absence of a biological gradient when subgroups were analyzed and the slightly higher prevalence of smokers in the cohort than in the background population.
Staurosporine stimulates expression of the urokinase‐type (u‐PA) plasminogen activator in LLC‐PK1 cells
Authors: Dierks‐Ventling Christa , Knesel Jaromir , Nagamine Yoshikuni , Hemmings Brian A. , Pehling Gundula , Fischer Franz , Fabbro Doriano
Published: February 2007

In LLC‐PK1 porcine epithelial cells, the urokinase‐type plasminogen activator (u‐PA) mRNA and protein can be induced either by stimulation of the protein kinase C (PKC) pathway using a tumor promoter (PMA) or by stimulation of the protein kinase A (PKA) pathway with calcitonin (SCT). By contrast, addition of 10−7 M staurosporine, an inhibitor of PKC, to LLC‐PK1 cells also stimulated urokinase production. In contrast to the in vitro situation (where staurosporine inhibited PKC activity), in the cell‐culture system the microbial agent caused an early translocation of PKC and inhibited PKA. Addition of staurosporine together with PMA or with SCT further increased urokinase mRNA and protein synthesis. Maximal stimulation was obtained when all 3 agents were added together. We thus assume that in LLC‐PK, cells the PKA and PKC signal‐transferring pathways can function independently.
Morphological and immunological characteristics of a rat choriocarcinoma
Authors: Verstuyf A. , Sobis H. , Vandeputte M.
Published: February 2007

A post‐gestational rat choriocarcinoma has been studied for its immunological and morphological characteristics. The tumor can be transplanted in syngeneic (WKA/H rats) as well as in allogeneic rats (BN, R/A). Even after immunization of the allogeneic hosts with tissues of the WKA/H rats, the development of the tumor was not inhibited. This neoplasm is composed of giant cells, surrounding spaces filled with blood, and of proliferating cytotrophoblasts. Ultrastructurally, these cells are very similar to those found in normal rat placenta. In some rats lung metastases were also observed. The tumor is hormonally active as demonstrated by proliferation of and secretions from the mammary glands in tumor‐bearing animals and by the presence of Δ5‐3β‐hydroxysteroid dehydrogenase in the giant cells of the neoplasms. These 2 findings indicate that the rat choriocarcinoma cells secrete lactogen and might produce progesterone, like cells of rat placenta. All the described features of this tumor point to its similarity to human choriocarcinoma.
Suppression of focus formation by bovine papilloma virus‐transformed cells by contact with non‐transformed cells: Involvement of sugar(S) and phosphorylation
Authors: Yoshikura H.
Published: February 2007

Focus formation by bovine papilloma virus‐transformed C127 cells was inhibited by direct contact with non‐transformed C127 cells. The suppressive capacity of C127 cells was abolished by introduction of the neomycin resistance gene (neor) but not by that of the hygromycin resistance gene (hygrr).Though both genes code for phosphotransferase which inactivates the aminoglycoside antibiotics, their substrates are different, i.e.,there is no cross‐resistance between them. As the neomycin phosphotransferase phosphorylates the specific hydroxyl group of the sugar in the aminoglycosides, such as 3′OH of the glucose residue of kanamycin A, some specific sugar(s) on the molecules exposed on the cell surface must be responsible for the suppressive signal and their phosphorylation must have resulted in the loss of that signai. The sugar must have the structure shared by kanamycin, neomycin or G418 but not by hygromycin B. Involvement of sugar was also suggested by the observation that conca‐navalin A partially abrogated the suppressive capacity of C127 cells.
Synergism of cisplatin and mitomycin C in sensitive and resistant cell subpopulations of a tumor model
Authors: Durand Ralph E.
Published: February 2007

Cisplatin is a widely‐used anti‐neoplastic agent with activity against a broad spectrum of human solid tumors. It is, however, seldom curative as a single agent. In an in vitro tumor model system, V79 spheroids, the non‐cycling, hypoxic cell subpopulations are most resistant to cisplatin, suggesting that combination chemotherapy with cisplatin and a drug which preferentially killed hypoxic cells might prove useful. Mitomycin C has the latter activity, and was thus evaluated. Not only was the expected complementary toxicity observed in combination treatments, but synergism between the drugs was found at clinically relevant drug doses. Further, both the net pattern of cell killing and the degree of interaction between the agents were a function of the dose ratios of the drugs in the combination treatments. The ability of mitomycin C to potentiate the response of cells resistant to cisplatin as a single agent may thus prove of value in clinical protocols.
Factors influencing the time and site of leukemic transformation of factor‐dependent cells after injection into irradiated recipient mice
Authors: Dührsen Ulrich , Metcalf Donald
Published: February 2007

After cells of the non‐tumorigenic‐factor‐dependent line FDC‐PI are injected into irradiated DBA/2 mice a progressive increase occurs in the number of engrafted FDC‐PI cells and eventually leukemic transformation occurs. Step‐wise increase in the number of cells injected led to an increasingly rapid accumulation of untransformed FDC‐PI cells in the hemopoietic organs and some shortening of the pre‐leukemic phase. FDC‐PI cells explanted from pre‐leukemic mice differed from primary FDC‐PI cells in that they were able to undergo leukemic transformation in non‐irradiated recipients after short latent periods. Pre‐leukemic populations contained FDC‐PI variants with an improved ability to proliferate in non‐irradiated tissues. Co‐injection of normal marrow cells delayed the leukemic transformation of injected FDC‐P cells. The accelerating effect of prior irradiation of the recipient on leukemia development was also abrogated when the injection of FDC‐PI cells was delayed by several weeks. No specific site of transformation could be determined in mice with very early leukemias. Proliferation of untransformed FDC‐PI cells and the emergence of variants with improved adaptation to in vivo conditions appear to be important and possibly necessary steps in the pathogenesis of the disease. Whether the host contributes actively to the final transformation process remains speculative.
Volatile nitrosamine levels and genotoxicity of food samples from high‐risk areas for nasopharyngeal carcinoma before and after nitrosation
Authors: Poirier S. , Bouvier G. , Malaveille C. , Ohshima H. , Shao Y. M. , Hubert A. , Zeng Y. , De Tehé G. , Bartsch H.
Published: February 2007

Traditional life‐style, especially food habits, infection by Ep‐stein‐Barr virus (EBV) and genetic factors, have been associated with an increased risk of nasopharyngeal carcinoma (NPC). N‐Nitroso compounds and other carcinogens either present in food or formed endogenously, as well as food constituents that activate EBV, have been suspected as etiological factors in NPC pathogenesis. For their characterization preserved food items, frequently consumed in NPC endemic areas in Tunisia, South China and Greenland, were sampled and screened for the presence of mutagens and volatile nitro‐samines before and after nitrosation. Aqueous extracts as well as 2 organic extracts of the samples were assayed for genotoxicity in 2 Salmonella typhimurium strains and the SOS chromotest. The same extracts had previously been analyzed for volatile nitrosamines and for EBV‐activating substances in Raji cells. In our study, 13 out of 16 food samples showed a weak, directly‐acting genotoxicity in the SOS chromotest in at least one of the extracts, but only one sample from Greenland was found to be weakly mutagenic in Salmonella TA 98. Chemical nitrosation for 9 out of 15 samples of aqueous food extracts increased the genotoxic effect in the SOS chromotest. Levels of volatile nitrosamines were also elevated for 12 out of 15 samples; highest levels of N‐nitroso‐dimethylamine were found in hard salted and dried fish from China (1,200 μg/kg) and highest N‐nitrosopyrrolidine levels in a Tunisian spice (3,840 μg/kg). In non‐nitrosated aqueous food extracts, the level of volatile nitrosamines and genotoxic activities were not correlated with the EBV‐inducing activity of the same samples. After chemical nitrosation, EBV‐inducing activity was decreased or showed no change and was not correlated with increases in either the genotoxicity or the nitro‐samine levels. Our results suggest that EBV‐activating compounds belong to a different class of substances. However, there was an association between the changes in genotoxicity and nitrosamine levels due to nitrosation.
Measurement of 5′‐methylthioadenosine in patients with neoplasms
Authors: Kaneko Kiyoko , Fujimori Shin , Kanbayashi Takaaki , Miyazawa Yukihisa , Kumakawa Toshiro , Fujii Hisaichi , Miwa Shiro , Kamatani Naoyuki , Akaoka Leo
Published: February 2007

The amount of polyamines in urine from patients with various neoplasms is larger than in normal subjects. We have determined the concentration of 5′‐methylthioadenosine (MTA), a by‐product of the polyamine biosynthesis, in patients with malignancies as well as normal subjects. Our studies indicate that the amount of MTA in urine from patients with leukemias and malignant lymphomas was higher than in normal subjects (p <0.005). Urine samples from patients with other malignancies contained normal amounts of MTA. The levels of blood MTA in patients with leukemias before treatment or in relapse was higher than in control subjects (p <0.005), while in patients with other malignancies and leukemia in remission, the levels were not different from control subjects. Peripheral blood MTA levels clearly decreased after effective chemotherapy. The measurement of MTA levels in urine and blood may not be as useful as polyamine assays for the detection of malignancies, but blood levels of MTA may be useful as an indicator of the efficacy of chemotherapy in leukemic patients.
Chromosome aberrations in metastatic ovarian cancer: Relationship with abnormalities in primary tumors
Authors: Bello M. Josefa , Rey Juan A.
Published: February 2007

Twenty malignant effusions secondary to ovarian cancer have been cytogenetically analyzed directly and after short in vitro culture. With the exception of one sample characterized by trisomy 3, all cases displayed clonal structural rearrangements. Chromosomes 1 and 3 were most frequently involved in the genesis of markers. Abnormalities of chromosomes 5, 6, 9, 11 and 12 were also recurrently found, and double minutes (DM) were observed in 2 samples. Our results agree with previous findings on the preferential involvement of chromosomes 1, 3 and 6 in ovarian carcinomas, and suggest that rearrangements of certain chromosomes are non‐random but are secondary to the malignant progression of these tumors.
Murine spontaneous T‐cell leukemia constitutively expressing IL‐2 receptor—a model for human T‐cell malignancies expressing IL‐2 receptor
Authors: Lugasi Hefziba , Hajos Silvia , Murphy John R. , Strom Terry B. , Nichols Jean , Peñarroja Carlos , Naor David
Published: February 2007

We describe a new, spontaneously occurring BALB/c‐derived murine T‐cell leukemia. The leukemic cells, designated LB, grow rapidly and progressively in the syngeneic host with no signs of effective immunological resistance. LB cells expressed the Thy‐1+, Lyt‐2+, L3T4‐, CD3‐ class‐1+, CD25+ (IL‐2 receptor, IL‐2R), class‐II‐, gp70‐ phenotype. As LB cells express IL‐2, as indicated by staining with 2 distinct anti‐CD25 IL‐2R monoclonal antibodies (MAbs), the therapeutic efficacy of IL‐2‐diphtheria toxin‐related protein was tested on this leukemic model. IL‐2‐diphtheria toxin, but not diphtheria toxin, efficiently inhibited the proliferation of LB cells. The proliferation of a murine myeloma cell line, which does not express IL‐2R, was not inhibited by IL‐2‐diphtheria toxin. The possible implantation of this animal model in fundamental and practical studies is discussed.
A possible mechanism for increased breast cell proliferation by progestins through increased reductive 17β‐hydroxysteroid dehydrogenase activity
Authors: Coldham N. G. , James V. H. T.
Published: February 2007

We have investigated whether progestins may be able to regulate breast cell proliferation by altering the fraction of oestradiol relative to oestrone, using the human breast cancer cell line MCF‐7. The ability of the two oestrogens, oestradiol and oestrone, to stimulate breast tumour cell proliferation was investigated. Oestradiol in concentration was of 10‐fold greater proliferative potency than oestrone. The progestin MPA increased both reductive and oxidative 17β‐hydroxysteroid oxidoreductase activity when the tissue culture media pH indicator phenol red was included in the media. When phenol red was excluded from the tissue culture media, MPA increased predominantly the reductive 17β‐hydroxysteroid oxidoreductase activity, and to a far greater extent than in the presence of phenol red. Other progestins such as levonorgestrel, norethisterone and norethisterone acetate also increased predominantly reductive 17β‐hydroxysteroid oxidoreductase activity in the absence of phenol red. The action of MPA on reductive 17β‐hydroxysteroid oxidoreductase activity was increased by treatment with oestradiol to a small but significant extent. We propose that the progestational increase of reductive 17β‐hydroxysteroid oxidoreductase activity is a possible mechanism by which progestins may increase breast cell proliferation in vivo.
Screening for lung cancer in the middle‐aged
Authors: Berndt R. , Nischan P. , Ebeling K.
Published: February 2007

A screening programme for lung diseases has been in operation in the German Democratic Republic for more than 3 decades. The programme is based on biennial chest X‐rays (70 × 70 mm posterior‐anterior) of the population 40 years of age or over. With respect to lung cancer the results show that, for the population under 60 years of age, the adjusted relative risk of dying from lung cancer among subjects who took part in the last screening round compared with subjects who did not but were screened at least once during the preceding 10‐year period was 0.93 (95% confidence interval 0.65–1.33).
Procoagulant activity of mononuclear phagocytes from different anatomical sites in patients with gynecological malignancies
Authors: Semeraro N. , Montemurro P. , Conese M. , Giordano D. , Stella M. , Restaino A. , Cagnazzo G. , Colucci M.
Published: February 2007

Mononuclear phagocytes exhibit complex interactions with cancer cells and might contribute to fibrin formation associated with malignancy through the production of procoagulant activity (PCA). We have studied the PCA of peritoneal macrophages in 8 patients with advanced (stages III or IV) ovarian cancer and of macrophages from regional lymph nodes in 14 patients with limited (stages I or II) uterine cancer; peritoneal and lymph‐node macrophages from patients with benign gynecological tumors were used as reference cell populations. In all patients, PCA of blood monocytes was also studied. Peritoneal and lymph‐node macrophages obtained from patients with ovarian and uterine cancer, respectively, expressed far higher levels of basal PCA than the corresponding cell populations from patients with benign tumors (p <0.001). PCA of blood mononuclear cells from patients with ovarian, but not with uterine cancer, was significantly higher (p <0.001) than that of control cells. High levels of D‐dimer, a specific product derived from plasmin‐induced degradation of stabilized fibrin, were found in all ascitic fluids and in all plasma samples but one from patients with ovarian cancer. In contrast, all controls and all uterine cancer patients but one had normal plasma D‐dimer. Our findings suggest that local activation of host macrophages for PCA production might contribute to fibrin formation within the tumoral mass. In advanced cancer, blood monocytes may also be activated to produce PCA and thus contribute to activation of intravascular coagulation and, possibly, to thrombo‐embolic complications frequently associated with disseminated malignancy.
Deficient production of tumor necrosis factor by peripheral‐blood monocytes in chronic lymphocytic leukemia
Authors: Flieger Dimitri , Emmerich Berthold , Meyer Nicolette , Riethmüller Gert , Ziegler‐Heitbrock H. W. Löms
Published: February 2007

The production of tumor necrosis factor (TNF) by lipopolysaccharide (LPS)‐triggered peripheral‐blood mononuclear cells (PBM) was investigated in 23 patients with untreated B‐cell chronic lymphocytic leukemia (B‐CLL) and 14 control donors. Cells were stimulated at concentrations that reflect cell density in peripheral blood. Under these conditions, PBM from 11/23 of the CLL patients produced at least 10‐fold less TNF as compared with controls. Monocyte numbers were decreased in percentage, while absolute numbers (normal range 233 ± 120 × 103/mm3) were decreased only in 2, normal in 17 and increased in 4 patients indicating that the deficiency is not a result of monocytopenia in most patients. Cell separation experiments indicate that after removal of leukemic B cells, percentages of monocytes return to control range and TNF production is improved (7/7). In mixing experiments, we found a suppression of TNF production in control mononuclear cells by CLL cell samples (75 × 106 cells/ml) in 5/19 cases, while control cells from thymus exhibited no or little suppression in these conditions. In 2‐chamber experiments, leukemic samples suppress TNF production by normal monocytes across a 0.45μm membrane indicating that a soluble factor is responsible for suppression. The factor exhibits higher stability in serum‐free conditions and its molecular weight is below 20kDa. Prostaglandins are not involved, since indomethacin did not abrogate suppression.
Dietary factors and risk of lung cancer: Results from a case‐control study, toronto, 1981–1985
Authors: Jain M. , Burch J. D. , Howe G. R. , Risch H. A. , Miller A. B.
Published: February 2007

Associations between dietary factors and risk of lung cancer are reported from a study of 839 cases and 772 population‐based controls interviewed in metropolitan Toronto between 1981 and 1985. Increased consumption of vegetables is associated with a decreased relative risk of 0.60 (95% confidence limits =0.40 to 0.88) for those in the highest compared with the lowest quartile. Cholesterol intake is associated with increased risk, but this is restricted to those in the highest quartile for whom the relative risk is 1.58 (95% confidence limits =1.05 to 2.38) compared with those in the lowest quartile. The results of this study suggest that dietary factors may affect the risk of lung cancer, but identification of the specific constituents involved will require further research.
Protein kinase C‐mediated regulation of the expression of CD14 and CD11 /CD18 in U937 cells
Authors: Pedrinaci Susana , Ruiz‐Cabello Francisco , Gomez Ovidio , Collado Antonia , Garrido Federico
Published: February 2007

We used the U937 cell line to analyze CD14, CD11/CD18, HLA class‐I and DR antigen expression during PMA‐induced differentiation. Treatment of U937 cells with PMA markedly increased CD14, CDIIa, CDIIb and CDI8 antigen expression, and slightly increased CDIIc expression. Protein kinase C may play a major role in regulating the expression of these antigens. The protein kinase inhibitor H7 abrogated the inductive effect of PMA. Calcium ionophore, when added alone or in the presence of PMA, had no effect. The inhibitory effect of the calcium antagonist verapamil, EGTA, and of chlorpromazine, an antagonist of calcium‐binding proteins, supports a role for calcium‐dependent protein kinase C in the up‐regulation of CDI4 and CDII/CD18 surface expression. The specific calmodulin inhibitors R2457I and W7 had no effect on antigen expression. Our findings suggest that protein kinase C activation is an important step in the PMA‐induced differentiation of U937 cells.
Rat monoclonal antibodies to the external domain of the product of the C‐erbB‐2 proto‐oncogene
Authors: Styles Jennifer M. , Harrison Shona , Gusterson B. A. , Dean C. J.
Published: February 2007

With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 lgG2a and I IgA) have been prepared against the external domain of the product of the c‐erbB‐2 proto‐oncogene. All 4 antibodies stain frozen sections of tissues that over‐express the product of the c‐erbB‐2 proto‐oncogene, and competitive binding assays showed that the antibodies recognized 2 non‐overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190kDa protein from 35S‐methionine‐labelled breast carcinoma cells where the c‐erbB‐2 is amplified (BT 474 and MDA‐MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR 12 stains formolsaline‐fixed sections of breast carcinoma tissue that overexpresses the product of the c‐erbB‐2 proto‐oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio‐immunoscintigraphic and therapeutic applications.
Characterization of the synergistic effect of insulin and transferrin and the regulation of their receptors on a human colon carcinoma cell line
Authors: Watkins Linda F. , Lewis Laurie R. , Levine Alan E.
Published: February 2007

The human colon carcinoma cell line, HCT 116, can be grown in chemically defined media in the absence of exogenous growth factors. The addition of transferrin and insulin will significantly stimulate growth. The interaction of these growth factors with their receptors was studied to determine whether the synergistic action of insulin and transferrin on growth involved alterations in the growth‐factor receptors. Redistribution of the transferrin receptor occurred in the presence of transferrin or transferrin plus insulin. The presence of insulin in the growth media resulted in occupation of cell‐surface insulin receptors without a reduction in total insulin binding. Addition of transferrin with insulin resulted in a decrease in insulin binding to its receptor, with no alteration in receptor affinity. It appears that transferrin plays a role in regulating the insulin receptor and that this may contribute to the synergistic effect of insulin and transferrin on growth.
Cancer incidence among swedish brewery workers
Authors: Carstensen John M. , Bygren Lars Olov , Hatschek Thomas
Published: February 2007

In order to examine the risks of cancer, particularly of rectal cancer, among Swedish brewery workers, 6,230 men employed in the brewery industry in 1960 were followed‐up during 1961–79 by the Swedish Cancer Registry. Using all Swedish men as a reference group, relative risks (RR) were computed with standardization for year of birth, year of follow‐up, and geographic region. A total of 712 new cases of cancer were observed compared to 570.7 expected (p < 0.001). Significantly increased risks were seen for several cancer sites, e.g. esophagus (RR = 2.5, 95% confidence interval (Cl) = 1.5–3.8), rectum (RR = 1.7, Cl = 1.3–2.3), pancreas (RR= 1.7, C1=1.2‐2.3), and lung (RR = 1.4, Cl = 1.1–1.7). An excess risk of liver cancer was almost significant (p = 0.053, RR = 1.7, Cl = 1.0–2.8). The risk of colon cancer was not significantly increased (RR = 1.2, Cl = 0.9–1.5), and the difference between the relative risk of colon cancer and that of rectum cancer was nearly significant (p = 0.07). Our results support the hypothesis that high beer consumption is associated with an increased risk of rectal cancer.
Cytosolic NAD(P)H:(Quinone‐acceptor)oxidoreductase in human normal and tumor tissue: Effects of cigarette smoking and alcohol
Authors: Schlager John J. , Powis Garth
Published: February 2007

NAD(P)H:(quinone‐acceptor)oxidoreductase (QAO), previously known as DT‐diaphorase, catalyzes the reduction of qui‐nones to hydroquinones. Enhanced activity of the enzyme has been suggested to protect cells against the cellular toxicity and carcinogenicity of quinones, but may activate some cyto‐toxic anti‐tumor quinones. Cytosolic levels of QAO, carbonyl reductase (CR) and total quinone reductase activity have been measured in normal and tumorous human tissues. QAO was the major component of the total cytosolic quinone reductase activity in all the tissues investigated. CR represented 10 to 28% of the total cytosolic quinone reductase activity in normal tissue. Normal tissue QAO was high in the stomach and kidney, and lower in the lung, liver, colon and breast. Primary tumor from lung, liver, colon and breast had elevated levels of QAO compared to normal tissue, while tumor from kidney and stomach had lower levels. CR was not significantly altered in tumor tissue, except in the case of lung and colon tumor which showed an increase compared to normal tissue. A major determinant of the variability of human lung tumor QAO was the cigarette‐smoking history of the donor. Non‐smokers and past smokers had high levels of tumor QAO compared to normal tissue. Smokers had levels of tumor QAO that were not significantly different from those of normal tissue QAO. Smokers had a small increase in normal lung QAO compared to non‐smokers. Alcohol use was associated with an increase in lung tumor QAO but had no effect on QAO in normal lung. The function of QAO in tumors is not known but the elevated activity of QAO in some tumors and the apparent depressant effect of smoking could influence the response of these tumors to quinone drugs or toxic agents that are metabolized by QAO.
Cervical‐cancer screening: Attendance and cost‐effectiveness
Authors: Koopmanschap Marc A. , van Oortmarssen Gerrit J. , van Agt Heleen M. A. , van Ballegooijen Marjolein , Habbema J. Dik F. , Lubbe Koos Th. N.
Published: February 2007

The influence of attendance on the health effects and cost‐effectiveness of cervical‐cancer screening was studied, both for organized screening programmes and for spontaneous screening. The asymmetric distribution of smears among the female population and the higher risk incurred by women who never or only occasionally attend screening appear crucial in determining the health effects of screening. An increase in attendance rate induces a substantial rise in health effects and a less than proportionate rise in costs, thus improving cost‐effectiveness. Wider screening coverage, in order to increase the number of life‐years saved, is achieved more efficiently by encouraging a greater number of women to attend than by inviting the same number of women to attend more often, i.e., with a shorter interval between successive screens. Spontaneous screening is characterized by high coverage for younger women and low coverage for middle‐aged and older women. This leads to a small amount of health effects and poor cost‐effectiveness as compared with organized screening.
Hodgkin's disease in adults: Association with social factors and age at tonsillectomy. A case‐control study
Authors: Bonelli Luigina , Vitale Vito , Bistolfi Franco , Landucci Marco , Bruzzi Paolo
Published: February 2007

The relationship between socio‐economic characteristics, previous tonsillectomy, family history of cancer and risk of Hodgkin's disease (HD) was investigated in a case‐control study. One hundred and sixty patients, aged 15–78, with histologically confirmed HD, and 185 hospital controls were interviewed. A statistically significant decrease in risk of HD was observed among subjects with large sibship size (RR = 0.63, C.I. 0.46–0.86) and among those who underwent tonsillectomy prior to the age of 10 (RR = 0.46, C.I. 0.22–0.94). High educational level was associated with an increased risk of HD (RR = 6.68, C.I. 1.94–23.08). Analysis by age‐group (15–39 yrs and 40 yrs or more) confirmed the role of high educational level as a risk factor in both young and old subjects, while the protective effect of tonsillectomy at an early age seems to be confined to young subjects. Analysis by histological subtype showed a statistically significant decrease in risk of HD in large sibship size for both nodular sclerosis (NS) and mixed‐cell subtypes; the role of education and tonsillectomy was observed only for NS. These data confirm the role of social factors in HD risk and suggest a protective effect of tonsillectomy performed early in life that needs to be confirmed in larger population‐based studies.
Expression of the p185 encoded by her2 oncogene in normal and transformed human tissues
Authors: Natali Pier G. , Nicotra Maria R. , Bigotti Aldo , Venturo Irene , Slamon Dennis J. , Fendly Brian M. , Ullrich Axel
Published: February 2007

The human homolog of the rat neu oncogene, HER2 (also termed c‐erbB2) has been demonstrated in amplified form in human breast tumors with poor prognosis. Although amplification of the gene correlates with expression of a 185‐kDa transmembrane glycoprotein, no extensive information is available regarding the extent of tissue and tumor specificity of this gene product. We have addressed this issue by immunohistochemically evaluating the expression of p185 HER2 in normal tissue and various tumors using monoclonal antibodies (MAbs) to distinct epitopes of its extracellular domain. No detectable levels of p185 HER2 were found in fetal tissues analyzed, with the exception of renal tubules in 2 out of 3 specimens tested and in intestinal epithelium. In adult tissues, detectable levels of this glycoprotein were found in a restricted number of cell types, the expression being heterogeneous among individuals and cell histotypes. Among the neoplasms assayed p185 HER2 was expressed in 46% of primary breast cancers, in 28% of ovarian tumors and in 30% of colon rectum malignancies. No male breast adenocarcinomas were p185‐positive. A large number of other tumors tested revealed only a low incidence of expression of the p185. In metastatic breast tumors p185 HER2 was demonstrated homogeneously among multiple autologous lesions and almost invariably (80%) the expression of p185 in the primary lesion correlated with that of the deriving metastases. Our findings indicate that the expression of the p185 HER2 represents a tumor marker of clinical relevance in breast cancer. Whether this holds true for other malignancies remains to be explored.
Heavy water enhances the antineoplastic effect of 5‐fluoro‐uracil and bleomycin in nude mice bearing human carcinoma
Authors: Altermatt Hans Jörg , Gebbers Jan‐Olaf , Laissue Jean Albert
Published: February 2007

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven‐week‐old BALB/c‐nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous‐cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5‐Fluoro‐uracil (5‐FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5‐FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5‐125I‐Iodo‐2′deoxyuridine, and of Ki‐67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium‐induced prolongation of tumor‐cell cycle times and a reduction of the growth fraction.