bluuebunny/crossref_metadata_2025 huggingface dataset:
STLV‐I antibodies in feral populations of East African vervet monkeys (Cercopithecus aethiops)
Authors: Dracopoli Nicholas C. , Turner Trudy R. , Else James G. , Jolly Clifford J. , Anthony Robert , Gallo Robert C. , Saxinger W. Carl
Published: February 2007

Serum samples from feral populations of African green monkeys (Cercopithecus aethiops) were screened for antibodies to the simian T‐lymphotropic virus, type I (STLV‐I). Blood samples had been collected from 336 monkeys in 4 regions of central and southern Kenya in 1978 and 1979, from 114 monkeys in central Ethiopia in 1973, and from 85 monkeys from the Kampala region of Uganda in 1966. A total of 178/535 monkeys (33%) were seropositive (STLV‐I+). Only 4/114 monkeys (4%) from Ethiopia were seropositive compared to 25/85 Ugandan monkeys (29%) and 149/336 Kenyan monkeys (44%). Epidemiological analysis of the Kenyan monkeys showed that 37% of the males and 54% of the females were STLV‐I+, and that there was a progressive increase in the proportion of STLV‐1+ monkeys of both sexes with age, rising from an average of 16% in infants (< 9 months) to an average of 69% in adults (> 42 months). The proportion of STLV‐I+ monkeys was higher among females in each age category. Seropositivity for antibodies to STLV‐I had no apparent effect on the health of monkeys, and no association with the occurrence of Hepatocystis parasitemia was seen in this species. The analysis of data from infants of STLV‐I+ mothers showed that seroconversion had occurred in I of 3 cases, suggesting that vertical transmission of the STLV‐I virus is not an inevitable consequence for infants of seropositive mothers.
Identification of a cell‐surface glycoprotein mediating cell adhesion in EBV‐immortalized normal B cells
Authors: Patarroyo Manuel , Beatty Patrick G. , Nilsson Kenneth , Gahmberg Carl G.
Published: February 2007

Phorbol ester treatment markedly enhanced aggregation of Epstein‐Barr virus (EBV)‐immortalized normal B cells. Monoclonal antibody (MAb) 60.3, recognizing a leukocyte common antigen, completely inhibited intracellular adhesion, whereas MAbs reacting with leukocyte common antigen T200, C3b receptor, T‐cell‐associated antigen TA‐I, C3d (EBV) receptor, brain‐granulocyte/T‐lymphocyte antigen, transferrin receptor, surface immunoglobulin, Class‐I or Class‐II transplantation antigens or a B‐cell‐specific antigen (BI) showed no inhibitory effect. Both the spontaneous and phorbol‐ester‐enhanced cell aggregations were similarly inhibited by Fab fragments made from antibody 60.3. Phorbol esters also enhance binding between EBV‐immortalized normal B cells and autologous or allogeneic blood mononuclear cells depleted of B lymphocytes. This process, which is independent of immunity to EBV, was similarly blocked by the antibody fragments. Antibody 60.3 precipitated 3 non‐covalently associated surface gylcopolypeptides with apparent MW of 90, 130 and 160/kDa from EBV‐infected B cells. Although dissociation of a similar protein complex from granulocytes by sodium dodecyl sulfate treatment clearly indicated the presence of the epitope on the smallest component, the same treatment did not dissociate the protein complex from EBV‐immortalized normal B cells, ft is thus concluded that the 90‐kDa glycopolypeptide, either alone or associated with the larger glycopolypeptides, mediates cell adhesion of the B cells.
Specificity of a monoclonal antibody to drosophila melanogaster neoplastic hematopoietic cell surfaces as detected by immunofluorescence
Authors: Steinberg M. Gwen , Poodry Clifton A.
Published: February 2007

We have generated, and characterized the immunological specificity of, a monoclonal antibody (MAb) termed 2B3G8 that recognizes cell‐surface determinant(s) of D. melanogaster neoplastic hematopoietic tissue. This antibody was generated against antigens of a tumor line derived from neoplastic lymph glands, the hematopoietic organs, of a growth control mutant, Tumorous‐lethal (Turn1). 2B3G8 does not recognize any of a panel of normal Drosophila cells or transformed cell lines from mouse or human sources as assayed by indirect immunofluorescence. Enzymatic digests did not remove this antigen from neoplastic blood cells or uncover the antigen in normal blood cells. Thus, we have generated a MAb that serves as a marker for the neoplastic hematopoietic condition in Drosophila which is a model for vertebrate neoplasia. This antibody is potentially useful for the study of oncodevelopmental antigens in developing hematopoietic systems and for detecting the onset of the neoplastic condition.
Tumor‐associated glycoprotein (TAG‐72) detected in adenocarcinomas and benign lesions of the stomach
Authors: Ohuchi Noriaki , Thor Ann , Nose Masato , Fujita Jun , Kyogoku Masahisa , Schlom Jeffrey
Published: February 2007

Murine monoclonal antibody (MAb) B72.3, prepared against a membrane‐enriched extract of metastatic carcinoma and reactive with a high‐molecular‐weight determinant, designated tumor‐associated glycoprotein (TAG)‐72, was shown to be reactive immunohistochemically with 97% of a variety of primary adeno‐carcinomas of the stomach (n = 40). All “early” gastric carcinomas were reactive with MAb B72.3, although the average percentage cellular reactivity was lower than in “advanced” carcinomas. TAG‐72 antigen was detected in benign lesions (i.e. adenomatous polyps and hyperplastic polyps) with intestinal metaplasia. Dysplastic lesions characterized by cellular atypia, abnormal differentiation, and disorganized mucosal architecture demonstrated higher TAG‐72 expression than non‐dysplastic epithelia. In contrast, normal gastric mucosa was generally non‐reactive with MAb B72.3. Assays using serial sections of normal, benign and malignant gastric tissues with two MAbs (B1.1 and COL‐6) directed against distinct epitopes of carcinoembryonic antigen (CEA) demonstrated differential reactivity, confirming that TAG‐72 and CEA are distinct, non‐coordinately expressed antigens. Our results suggest that TAG‐72 antigen may be expressed in malignant and dysplastic epithelial cells, as well as in intestinalized epithelium of the stomach which has been closely related to subsequent carcinoma development. Hence, MAb B72.3 may be a useful immunohistochemical adjunct for detecting early foci of adenocarcinomas and premalignant lesions of the stomach.
Differential expression of cellular oncogenes in benign and malignant human breast tissue
Authors: Whittaker Joanne L. , Walker Rosemary A. , Varley Jennifer M.
Published: February 2007

We have examined 62 specimens of benign fibrocystic breast tissue, fibroadenomas, carcinomas and surrounding non‐malignant tissue excised from 50 patients to determine the level of expression of 4 cellular oncogenes, c‐myc, c‐H‐ras, c‐K‐ras, and c‐N‐ras. Our results demonstrate that in breast carcinoma the frequency and relative level of expression of these oncogenes are significantly greater than those found for benign breast tissue. However, some fibrocystic specimens having prominent hyperplastic features also exhibited enhanced oncogene expression. In view of the association between the increased frequency of carcinoma of the breast in women with a previous history of benign breast disease, it will be interesting to follow up donors of benign specimens to see if there is any relationship between the expression of oncogenes in such lesions and the development of carcinomas.
Formaldehyde and cancers of the pharynx, sinus and nasal cavity: I. Occupational exposures
Authors: Vaughan Thomas L. , Strader Clifton , Davis Scott , Daling Janet R.
Published: February 2007

A population‐based case‐control study was undertaken in 13 counties of western Washington to determine if occupational formaldehyde exposure was related to cancer of the oro‐ and hypopharynx (OHPC, N = 205), nasopharynx (NPC, N = 27) or sinus and nasal cavity (SNC, N = 53). Controls were selected by random digit dialing (N = 552). A telephone interview inquired about lifetime occupational history as well as a number of potential confounding factors, including smoking and drinking. Approximately half (N = 143) of the case interviews were with next‐of‐kin. Occupational formaldehyde exposures were assessed by application of job‐exposure matrix developed for this study which classified unique job codes into 4 categories based on judgement of likelihood and intensity of formaldehyde exposure. Exposure scores were calculated by weighting the number of years in a formaldehyde‐associated job by the assigned exposure level. The effects assuming a 15‐year induction period were also investigated. Logistic regression was used to estimate exposure odds ratios (OR) while taking into account multiple risk factors for each site. No significant associations were found between occupational formaldehyde exposure and any of the cancer sites under study. However, relative risk estimates associated with the highest exposure score categories were elevated for OHPC (OR = 1.3, 95% Confidence Interval = 0.6–3.1) and NPC (OR = 2.1, 95% CI = 0.4–10.0) when an induction period was accounted for. When only live interviews were considered, the odds ratios for OHPC and NPC increased to 1.7 and 3.1 respectively. Several limitations in the study tend to conservatively bias the results and must be taken into account in its interpretation.
Formaldehyde and cancers of the pharynx, sinus and nasal cavity: II. Residential exposures
Authors: Vaughan Thomas L. , Strader Clifton , Davis Scott , Daling Janet R.
Published: February 2007

To investigate the possible association between residential formaldehyde exposures and risk of cancer of the oro‐ and hypopharynx (OHPC, N = 205), nasopharynx (NPC, N = 27) and sinus and nasal cavity (SNC, N = 53), a population‐based case‐control investigation was carried out in 13 counties of western Washington. Controls (N = 552) were selected by random digit dialing. Subjects' residential histories, including type of dwelling, were determined from a structured telephone interview which also collected smoking, alcohol and demographic information. Multiple logistic regression was used to estimate exposure odds ratios (OR) while adjusting for known risk factors. A strong association was found between a history of having lived in a mobile home and NPC, but not OHPC or SNC. The NPC risk increased with the number of years lived in a mobile home: for those with I to 9 years the OR = 2.1 (95% confidence interval = 0.7–6.6), and for those with 10 or more years, the OR = 5.5 (95% CI = 1.6–19.4). No associations were found between any of the cancers and a history of exposure to new constructions containing particle board and plywood, or to urea‐formaldehyde foam insulation. The association found with living in a mobile home must be interpreted with caution since it is based on a small number of cases, and may be due to factors other than formaldehyde. This report emphasizes the need for additional studies focusing on potential associations between indoor air pollutants and respiratory cancers.
Suppression and re‐expression of transformed phenotype in hybrids of HA‐ras‐1 ‐transformed rat‐1 cells and early‐passage rat embryonic fibroblasts
Authors: Griegel S. , Traub O. , Willecke K. , Schäfer R.
Published: February 2007

Rat‐1 cells which had been transformed with the activated Ha‐ras‐1 gene from human EJ bladder carcinoma cells were fused with diploid embryonic rat fibroblasts. Four selected cell hybrids expressed the human transforming gene product p21 at levels of 10 to 30% compared to 100% in the transformed parental cells. The hybrid cells, however, exhibited normal morphology, anchorage requirement for proliferation, and largely extended latency periods of tumorigenicity in newborn rats. Tumorigenic hybrid derivatives contained lower numbers of chromosomes than the tetraploid parental hybrids. DNA of the non‐tumorigenic cell hybrids transformed Rat‐1 cells to anchorage‐independent proliferation as expected for the transforming human Ha‐ras gene present in the donor DNA. We conclude that the transforming properties of the activated Ha‐ras gene in Rat‐1 cells can be suppressed at the post‐translational level by the presence of the genome from diploid embryonic rat fibroblasts but additional controls of expression of the transforming gene are likely to exist. Normal cells contain suppressor gene(s) which safeguard these cells against transformation by the product of the transforming Ha‐ras‐1 oncogene.
Plasminogen activators, plasminogen activator inhibitors and procoagulant analyzed in twenty human tumor cell lines
Authors: Cajot Jean‐Franc̨ois , Kruithof Egbert K. O. , Schleuning Wolf‐Dieter , Sordat Bernard , Bachmann Fedor
Published: February 2007

We have analyzed the CM of 20 human tumor cell lines for the presence of PA, PA‐I and PC. Most of the cell lines expressed PA activity as measured by a ra‐dioiodinated fibrin plate assay. The urinary type and tissue‐type PA activities were specifically quantified by means of purified inhibitory antibodies. U‐PA and/ or t‐PA antigen, as measured by radioimmunoassays, were detected in all but 4 of the CM and were generally 10 times more concentrated than PA activity, indicating the presence of specific PA‐Is. Analysis of CM by electrophoresis followed by fibrin‐agarose zymog‐raphy demonstrated the presence not only of free but also of inhibitor‐complexed PA. Affinity purification demonstrated that 8/20 cell lines expressed detectable PA‐I activity. The PA‐I1 and PA‐I2 inhibitors were most frequently observed, while PN was recovered only from CM of the HT 1080 fibrosarcoma cell line. PC activity, as measured by the plasma recalcification time method, was found in 9/20 CM. It was of the thromboplastin tissue factor type since most of its activity was lost when assayed with a Factor VII‐deficient plasma.
Lymphoblastoid cell lines and burkitt‐lymphoma‐derivee cell lines differ in the expression of a second epstein‐barr virus encoded nuclear antigen
Authors: Ernberg Ingemar , Kallin Bengt , Dillner Joakim , Falk Kerstin , Ehlin‐Henriksson Barbro , Hammarskjöld Marie‐Louise , Klein George
Published: February 2007

Twenty‐seven Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cell lines and 27 EBV‐carrying Bur‐kitt‐lymphoma‐derived lines were analyzed for expression of the second EBV‐encoded nuclear antigen (EBNA‐2) by immunoblotting and anticomple‐ment immunofluorescence with EBNA‐2‐specific sera. While all lymphoblastoid cell lines expressed EBNA‐2, only 10 of the 27 BL lines were EBNA‐2‐positive. Comparison of the EBNA‐2 coding Bam HI W‐Y‐ and H‐fragments of EBV‐DNA in the different cell lines by restriction enzyme analysis suggests that EBNA‐2 negativity is due either to sequence diversity or to a deletion in the BamHI WYH region.
Oligoclonal tumours
Authors: Woodruff M. F. A. , Ansell J. D. , Hodson B. A. , Potts R. B.
Published: February 2007

Tumours are commonly classified as monoclonal or polyclonal. The question of how many clones are present in a polyclonal tumour is seldom asked; it is important, however, because the answer may show whether or not clones arise and develop independently, and whether the number of clones in tumours of a particular kind tends to increase or decrease with time. We have used two procedures to assess the clon‐ality of chemically‐induced murine fibrosarcomas, one based on the heterozygosity of the tumour hosts for an X‐linked marker, the other on the expression of tumour‐associated transplantation antigens (TATA) by the tumours. As we have reported previously, many of these tumours are pleoclonal. Evidence now presented suggests that the clones do not develop independently and that many of the tumours are biclonal.
Cysteine proteinases produced by cultured rabbit V2 carcinoma cells and rabbit skin fibroblasts
Authors: Baici Antonio , Knöpfel Margrit
Published: February 2007

Rabbit V2 carcinoma cells and normal rabbit skin fibroblasts produced cysteine proteinases with properties similar to those of purified rabbit liver cathepsin B. Both cell types secreted into the culture medium enzymes with an apparent Mr of 43,000, which reacted with synthetic substrates commonly used for cathepsin B. After limited proteolysis with pepsin or treatment at pH 3, the Mr = 43,000 species could be converted into forms with Mr = 34,000 and an increased specific activity. In the intracellular pool of both V2 carcinoma cells and fibroblasts, a cysteine proteinase with the same Mr of cathepsin B (27,000) was found. Despite the similarity in molecular size, substrate specificity and sensitivity to inhibitors, the tumor and fibroblast enzymes were not identical in their stability at pH ≧ 7 and were produced by the 2 cell types in considerably different amounts. In terms of enzyme units and normalized to an equal cell number, the ratios of fibroblast enzyme/tumor enzyme were as follows: secreted 130–150; intracellular, 150–180. The pH stability of the cysteine proteinases was determined quantitatively by measuring the half‐life of enzyme activity. At pH 8.0 and 25°C the secreted tumor cysteine proteinase had a half‐life of at least 5 hr, whereas the secreted fibroblast enzyme and liver cathepsin B had half‐lives of 8.8 min and 4.4 min, respectively.
Anti‐tumor effects of interferon in mice injected with interferon‐sensitive and interferon‐resistant friend leukemia cells. V. Comparisons with the action of tumor necrosis factor
Authors: Gresser I. , Belardelli F. , Tavernier J. , Fiers W. , Podo F. , Federico M. , Carpinelli G. , Duvillard P. , Prade M. , Maury C. , Bandit M.‐T. , Maunoury M.‐T.
Published: February 2007

A number of similarities and dissimilarities in the anti‐tumor effects of TNF and interferon α/β have been observed in DBA/2 mice injected with Friend erythroleukemia cells (FLC). Mouse TNF exerted marked anti‐tumor effects in mice injected either s.c. or i.p. with FLC lines 3C 18 or 3 γR8 resistant in vitro to the cytotoxic effects of TNF. Likewise, mouse interferon α/β had anti‐tumor activity in mice injected with these FLC, resistant to the action of interferon α/β or γ in vitro. The results of histopathologic examination and 31P nuclear magnetic resonance analyses of 3C18 FLC s.c. tumors injected with TNF resembled the results previously obtained for 3C18 FLC tumors injected with interferon α/β, although the effects of TNF occurred more rapidly. Injection of mice with antibody to mouse interferon α/β or γ did not abrogate the anti‐tumor effects of TNF in mice injected i.p. with FLC. Our results suggest that in this experimental system the anti‐tumor effects of TNF, like interferon α/β, do not result from a direct effect on the tumor cells themselves but are host‐mediated.
Pharmacokinetics of methotrexate and its 7‐OH metabolite in cancer patients treated with different high‐methotrexate dosage regimens
Authors: Ei‐Yazigi Adnan , Amer Magid , Al‐Saleh Iman , Martin Cazemiro
Published: February 2007

The pharmacokinetics of methotrexate (MX) and 7‐OH methotrexate (MXOH) was studied in 18 cancer patients treated with 6‐hr intravenous (i.v.) infusion of 100 mg/kg (S), 80 mg/kg preceded by 30 mg/kg i.v. loading dose (C). Simultaneous analysis of MX and MXOH was performed by high‐performance liquid chromatography. The data for MX conformed to a 2‐compartment model with overall mean ± SD for beta k12, k21, and k13 of 0.225 ± 0.196, 1.33 ± 1.44, 0.954 ± 1.06, and 0.994 ± 1.28 hr−1, repectively. The total body clearance, Vc, and V‐beta were 0.123 ± 0.037 1/hr.kg, 0.15 ± 0.122 l/kg, and 0.965 ± 0.87 l/kg, respectively. No significant differences (p > 0.05) in these parameters, attributable to the difference in regimens, were observed. With regimens A, B and C, the maximum observed concentrations of MXOH occurred at 9.2, 11.5, and 9.2 hr and the mean ± SD values of these concentrations were 15.02 ± 14.91 ± 9.95 μm, respectively. With regimens A and C, maximum obserced concentration of MX equal to 231 ± 67.1 and 204 ± 69.5 μm, occurred at 0.5 and 6 hr, respectively. Only with regimen B was a steady‐state MX concnetration of 179 μm, achieved throughout infusion; this regimen is therefore highly advantageours for high‐dose MX treatment.
Diet and breast cancer: A case‐control study in Greece
Authors: Katsouyanni K. , Trichopoulos D. , Boyle P. , Xirouchaki E. , Trichopoulou A. , Lisseos B. , Vasilaros S. , Macmahon B.
Published: February 2007

A case‐control study of the role of diet in the etiology of breast cancer was conducted in Athens, Greece. There are reasons to believe that the diet of the Greek population is characterized by greater heterogeneity than that in most countries where such studies have been undertaken. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12‐month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Cases reported significantly less frequent consumption of vegetables as a group and, within that group, specifically of cucumber, lettuce and raw carrot. After adjustment for potential external confounding variables and for confounding between food categories, the odds ratio for persons in the highest quintile of vegetable consumers, relative to those in the lowest quintile, was 0.09 with 95% confidence limits 0.03–0.30. That is to say, the lowest quintile of vegetable consumers had about 10 times the breast cancer risk of the highest quintile. For a score based on consumption of only the 3 specified salad items the odds ratio over the extreme quartiles was 0.12 (0.05–0.32). There was no association with consumption of fats and oils, alcohol or coffee, and no significant association with any other major food category (including alcohol and coffee) after adjustment for confounding variables.
Evaluation of a mass screening program for stomach cancer with a case‐control study design
Authors: Oshima Akira , Hirata Noriko , Ubukata Takashi , Umeda Katstuhiko , Fujimoto Isaburo
Published: February 2007

In order to evaluate the effectiveness of a mass screening program for stomach cancer, a case‐control study was conducted in Nose town in Osaka, Japan. The case series consisted of all deaths from stomach cancer during the period 1969–1981 (54 in males and 37 in females). For each case, 3 controls of the same sex and from the same precinct as the case, and born within 5 years of the case birth‐year, were selected at random from Nose town residents alive at the date of death of the relevant case. We then investigated whether each case and corresponding controls had ever had screening tests before the date of diagnosis of the case. From the matched analysis of the distribution of screening in case‐control combination, the odds ratio of screened vs. unscreened among those who died from stomach cancer compared to those who did not was calculated as 0.595 (90% confidence interval: 0.338–1.045) among males and 0.382 (0.185–0.785) among females. When the screening tests conducted within 12 months of diagnosis were ignored on the presumption that they were symptom‐related, the odds ratio was calculated as 0.519 (0.297–0.905) among males and 0.486 (0.239–0.986) among females. These data strongly suggest that the mass screening program is effective in reducing stomach cancer mortality.
Plant‐derived diterpene esters enhance HTLV‐I‐induced colony formation of lymphocytes in co‐culture
Authors: Matsuda Shuichi , Nakao Yoshinobu , Ohigashi Hajime , Koshimizu Koichi , Ito Yohei
Published: February 2007

The addition to culture dishes of 10–50 ng/ml of the essential diterpene ester of Sapium sebiferum, 12‐O‐hexadecanoylphorbol‐13‐acetate (HPA), increased colony formation of normal peripheral blood lymphocytes co‐cultured with γ‐irradiated HTLV‐1‐producing HUT102 cells. The cells in the stimulated colonies showed an approximately 3‐fold increase in the expression of interleukin‐2 (IL‐2) receptors and a 1.5‐to 2.0‐fold increase in human T‐lymphotropic virus type‐I (HTLV‐I) p19‐positive cells. This biological potency was analogous to that induced by the most potent tumor promoter 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and stronger than that of 12‐O‐hexade‐canoyl‐16‐hydroxyphorbol‐13‐acetate (HHPA) isolated from Aleurites fordii.
Establishment of a murine leukemia L1210‐specific T‐cell clone displaying novel in vivo anti‐tumor activity
Authors: Nagase Fumihiko , Ueda Kaoru , Nakashima Izumi , Kawashima Kohei , Isobe Ken‐Ichi , Nagura Ei‐Ichi , Yamada Kazumasa , Yokochi Takashi , Hasegawa Yoshinori , Yoshida Tomoaki , Ando Ko‐Ichi
Published: February 2007

The murine leukemia L1210‐specific cytotoxic T‐cell clone K7 was established by repeated antigenic stimulation of spleen cells of L1210‐immune CD2F, mice in long‐term culture. K7 possessed L1210‐specific cytolytic activity detectable by the 51Cr‐release test, but lost its cytolytic activity about 100 days after initiation of culture (designated as clone K7L). Clone K7L retained its L1210‐specific tumor‐growth‐inhibitory activity independently of culture supplementation with IL‐2. K7L possessed the cell‐surface antigenic phenotype of cytotoxic T cells, Thy‐1+, Lyt‐1+, Lyt‐2+. This clone K7L displayed surprisingly strong activity in specifically inhibiting In vivo tumor growth of L1210 by day 5 in the peritoneal cavity of CD2F1 mice when injected together with 105 tumor cells (more than 90% inhibition at E/T = 5), and prolonged survival times of most of the mice for more than 60 days, whereas control mice inoculated with L1210 alone died on day 9–17. This unique in vivo anti‐tumor activity was not correlated to the In vitro cytolytic activity. Nevertheless, bystander inhibitory effect on the growth of third‐party tumor cells (P388) was not seen in mice injected with a mixture of L1210 and P388 together with K7L, suggesting that K7L inhibited L1210 growth by direct cell‐to‐cell interaction. Host cells such as X‐irradiation (800R)‐sensitive lymphocytes and Carrageenan‐sensitive macrophages were not involved in the early growth inhibition of L1210 by K7L.
The differentiated form of nasopharyngeal carcinoma contains epstein‐barr virus DNA
Authors: Raab‐Traub Nancy , Flynn Kathy , Pagano Joseph , Pearson Gary , Huang Andrew , Levine Paul , Lanier Anne
Published: February 2007

Immunologic studies of Epstein‐Barr virus (EBV) have implicated EBV in undifferentiated and partially differentiated, non‐keratinizing nasopharyngeal carcinoma (NPC). Patients with the well‐differentiated, keratinizing form of NPC have EBV serologic patterns similar to those of control populations. In addition, viral DNA has not been detected in the differentiated tumors using viral cRNA probes to DNA immobilized on filters. In this study we have tested for EBV DNA using recombinant DNA probes to Southern blots of DNA from 33 NPC specimens. The 24 undifferentiated and 4 partially differentiated specimens generally contained a relatively high number of EBV genome equivalents, while the 5 well‐differentiated NPC all contained detectable EBV, but at low copy number. The viral DNA from one of the well‐differentiated specimens was cloned into a cosmid vector. Five recombinant clones representing the fused viral termini were obtained, indicating the presence of episomal, intracellular DNA in the tumor. These findings indicate that all histologic subsets of NPC contain EBV DNA.
Circulating tumour‐associated antigen detected by the monoclonal antibody HMFG2 in human epithelial ovarian cancer
Authors: Ward B. G. , Cruickshank D. J.
Published: February 2007

A radioimmunometric sandwich assay for the tumour‐associated antigen defined by the monoclonal antibody (MAb) HMFG2, has been used to measure serum levels of the antigen in 76 healthy controls, 38 ovarian carcinoma patients pre‐operatively, 98 patients 2 to 6 weeks after surgery and 36 patients at relapse or in complete remission at 12 months. HMFG2 antigen levels were elevated in 33% of stage‐I and 62% of II‐IV patients pre‐operatively; they reflected bulk of disease post‐surgically and were signficantly higher in patients in relapse than in those who were in complete remission. HMFG2 antigen levels predicted the clinical course of disease in the majority of patients.
Analysis of the inhibition of tumour metastasis by sulphated polysaccharides
Authors: Coombe Deirdre R. , Parish Christopher R. , Ramshaw Ian A. , Snowden John M.
Published: February 2007

Lung metastases resulting from the intravenous (i.v.) injection of cells from the rat mammary adenocarcinoma 13762 MAT were significantly reduced by a variety of sulphated polysaccharides, the most effective being heparin, fucoidan and Carrageenan lambda. Although all the inhibitory polysaccharides were anticoagulants, it is unlikely that anticoagulation is the total explanation of their antimetastatic effect because: (1) heparin preparations from 2 different suppliers, although exhibiting comparable anticoagulant activities, differed 10‐fold in their antimetastatic capability; (ii) certain sulphated polysaccharides consistently gave a 30% difference in the number of metastatic lesions, yet exhibited identical anticoagulant activity; and (iii) the entrapment of 13762 MAT cells in the lung was not impaired by heparin or fucoidan. It was more probable that the sulphated polysaccharides were interfering with the passaging of tumour cells across the capillary wall as heparin significantly inhibited metastasis when injected up to 3 hr after lodgement, and heparin and fucoidan caused a gradual loss of tumour cells from the lung which only became apparent greater than 1 hr following cell lodgement. The data did not eliminate the possibility that tumour cell adhesion to the endothelium occurred via sulphated polysaccharide recognition. A negative correlation existed between the sulphated polysaccharides that bound to the surface of the tumour cells and those that inhibited metastasis.
Purified colony stimulating factors (G‐CSF and GM‐CSF) induce differentiation in human HL60 leukemic cells with suppression of clonogenicity
Authors: Begley C. Glenn , Metcalf Donald , Nicola Nicos A.
Published: February 2007

Purified recombinant human granulocyte‐macrophage colony‐stimulating factor (rHGM‐CSF) and purified native murine granulocyte‐CSF (G‐CSF) both induced differentiation in HL60 cells as evidenced by expression of granulocyte and macrophage membrane antigens, although this was not accompanied by morphological evidence of differentiation. Both types of CSF suppressed clonogenic HL60 cells with evidence of complete clonal extinction. The suppression of clonogenic HL60 cells was preceded in some experiments by CSF‐stimulated proliferation of HL60 cells, and this was most evident in cultures containing low concentrations of fetal calf serum (FCS).
Surveillance, latency and the two levels of MCA‐induced tumor immunogenicity
Authors: Prehn Richmond T. , Bartlett Gerald L.
Published: February 2007

Among 154 different, MCA‐induced mouse sarcomas, the immunogenicities of those tumors that had had the shortest original latencies in their autochthonous hosts were of an intermediate level with relatively little scatter. This fact is not predicted by the theory of immunological surveillance, but does fit the predictions of the immunological facilitation theory of oncogenesis. The frequency distribution of the tumor immunogenicities showed 2 peaks; the cluster of higher immunogenicity had a shorter latency than did the cluster of lower immunogenicity. The data for tumors initiated within in vivo diffusion chambers also showed 2 immunogenicity clusters, suggesting that the discrete clusters were not caused by host immunity. However, immunity apparently reduced the mean latency of the more immunogenic cluster and/or lengthened the mean latency of the less immunogenic, a result also inconsistent with the theory of immunological surveillance.
EL‐4 metastases in spleen and bone marrow suppress the nk activity generated in these organs
Authors: Sarzotti Marcella , Baron Samuel , Klimpel Gary R.
Published: February 2007

The relationship between metastatic cells in the spleen and bone marrow of tumor‐bearing mice and the NK activity generated in vitro by cells obtained from these organs was investigated. EL‐4 lymphoma and B16 melanoma cells injected intraperitoneally into syngeneic mice (106 cells/animal) killed the recipients in 16 days. These tumors had a different metastatic profile: EL‐4 metastasized to the spleen and bone marrow while B16 did not. The number of metastatic cells was evaluated by plating spleen or bone‐marrow cells of tumorbearing mice in agarose cultures; in parallel, the ability of spleen and bone‐marrow cells to generate NK activity in vitro was assessed. The presence of 105 EL‐4 cells/106 spleen or bone‐marrow cells correlated with a total lack of NK activity in these organs; in contrast, no decrease in NK activity was evident in the spleen or bone marrow of B16‐bearing mice. The removal of metastatic EL‐4 cells (by antibody and complement) from the spleen or bone marrow did not rescue the NK activity. The lack of NK activity in spleen and bone marrow colonized by metastatic cells was not due to induction of a suppressor cell in the host. Metastatic EL‐4 cells appeared to have a direct and irreversible suppressive effect on the generation of NK activity by spleen or bone marrow. A possible cause‐effect relationship between metastatic colonization of lymphoid organs and suppression of local NK activity is considered.
Patterns of nasopharyngeal cancer mortality in the united states
Authors: Levine Paul H. , McKay Frank W. , Connelly Roger R.
Published: February 2007

We examined the geographic pattern of nasopharyngeal cancer (NP cancer) mortality in the United States using economic sub‐regions (ESRs) as the basis for analysis. The distribution of 15,145 deaths from NP cancer over the years 1950‐1979 revealed clustering in the 119 ESRs that was not detected in analyses of distribution by the 48 states, 506 state economic areas or 3,056 counties or combinations of counties of the coterminous United States. NP cancer mortality among white males was concentrated on the south‐east Atlantic and Gulf coasts. This newly described pattern is not due to any recent changes in mortality rates and should provide leads to further epidemiologic study.
Pretreatment prognostic factors and scoring system in 407 small‐cell lung cancer patients
Authors: Cerny T. , Anderson H. , Bramwell V. , Thatcher N. , Blair V.
Published: February 2007

In 407 patients with small‐cell lung cancer (SCLC), 61 pretreatment variables were evaluated in a Cox multiple regression analysis to assess their prognostic value. All patients received short‐term intensive regimens (cyclophosphamide, etoposide and methotrexate or ifosfamide and etoposide, both followed by thoracic irradiation if complete response was noted). Lactate dehydrogenase (p = 0.0001), tumour stage (p = 0.0001), serum sodium (p = 0.0009), pretreatment Karnofsky performance score (p = 0.0121), alkaline phosphatase (p = 0.0186) and serum bicarbonate (p = 0.0321) were the important prognostic factors. Once these variables were taken into account no other variable provided additional prognostic information. A simple scoring system (“Manchester Score”) using these variables was established and shows little loss of information compared to the Cox analysis. The score distinguishes 3 prognostic groups, the best of which contains all long‐term survivors, whereas the bad prognostic group contains no patient surviving longer than one year. The scoring system may help to design new treatment strategies and may also facilitate the comparison of different studies.
Progenitor and pre‐B lymphocytes transformed by epstein‐barr virus
Authors: Ernberg Ingemar , Falk Kerstin , Hansson Mona
Published: February 2007

By rosetting with SRBC coupled to rabbit‐anti‐human IgM, the surface IgM‐negative cells of human fetal bone marrow were enriched, and subsequently infected and transformed by Epstein‐Barr virus (EBV). Single clones of the transformed cells were obtained. Ninety percent of the resulting cell clones were surface‐immunoglobulin‐negative, and of 8 clones which were further studied, 5 lacked intracellular, cytoplasmic Ig as measured by immunofluorescence. Control cell clones derived from the same material without pre‐selection expressed surface Ig and also secreted Ig. Utilization of a panel of B‐cell‐specific monoclonal antibodies (MAbs) showed no difference between the cell clones expressing surface Ig and those that did not. The progenitor B‐cell lines did not show a phenotype resembling that of cell lines derived from B‐cell malignancies, such as high agarose clonability. In spite of their immature Ig‐phenotype, these clones showed rearrangement of at least one heavy chain Ig‐allele. Efforts to induce differentiation in these clones were unsuccessful. These clones may represent progenitor B cells, or B cells with faulty heavy‐chain rearrangement. EBV can apparently be used as a tool to derive cell lines representing different levels of B‐cell differentiation, and can also transform immature B cells, which may be useful in the analysis of B‐cell differentiation.
HTLV‐III infection of EBV‐genome‐positive B‐lymphoid cells with or without detectable T4 antigens
Authors: Salahuddin S. Z. , Hunter E. A. , Sturzenegger S. , Markham P. D. , Gallo R. C. , Ablashi D. V. , Gonda M. A.
Published: February 2007

The infection of a number of new and established B‐cell lines by human T‐cell lymphotropic virus III (HTLV‐III) was investigated. The B lymphocytes differed in their expression of T4 antigens detected by specific monoclonal antibodies (MAbs) and the presence of Epstein Barr virus (EBV)‐DNA or antigens. The presence of the EBV genome was the only requirement for infection of B‐lymphocytes by HTLV‐III, although its presence did not ensure infection. Two EBV genome and T4 antigen‐positive B‐cell lines, lacking EBV early antigens (EA) and viral capsid antigens (VCA), could be productively infected with no induction of known EBV antigens. Two other EBV genome‐positive cell lines, lacking T4, EA, and VCA could also be infected. Another genome‐positive cell line (P3HR‐I) that was EBV‐EA, VCA‐positive and produced non‐transforming EBV, could also be infected by HTLV‐III. However, 3 EBV genome‐ and T4 antigen‐negative B‐cell lines could only be infected with HTLV‐III after successful conversion to an EBV‐genome‐positive state by pre‐infection with EBV. Five other EBV‐genome‐positive B‐cell lines lacking T4 antigens were not infectible with HTLV‐III even after superinfection with EBV. Incomplete inhibition of the HTLV‐III infection of a T4‐positive (LDV‐7) and a T4‐negative (Craig) was obtained by preadsorption with specific MAb to T4 (OKT4A and Leu 3A). From these observations, it is not clear whether the presence of T4 antigen on the cell surface is needed for the infection of B lymphoblastoid cells; however, successful infection does depend upon the presence of the EBV genome. The mechanism of interaction of HTLV‐III and EBV‐infected B‐cell lines permitting this infection is not fully understood. Although the clinical implications of these observations remain to be determined, it is possible that infection of EBV‐positive B‐cells may contribute to aberrant humoral responses and/or increased frequency of B‐cell malignancies observed in HTLV‐III‐infected individuals.
Establishment and characterisation of three new human ovarian carcinoma cell lines and initial evaluation of their potential in experimental chemotherapy studies
Authors: Hill Bridget T. , Whelan Richard D. H. , Gibby Elizabeth M. , Hosking Louise K. , Thomas Rupniak H. , Sheer Denise , Shellard Sharon A.
Published: February 2007

Three new human cell lines have been established from biopsy specimens of ovarian cystadenocarcinomas: line JA‐I was derived from a primary “solid” tumour from an untreated patient, whilst the other lines were derived from ascites from patients previously treated with chlorambucil plus either cyclophosphamide (TR175) or cisplatin (TR170). Their in vitro characteristics are compared with those of the established SK‐OV‐3 line of similar origin. Each line has a distinct morphology and expresses a unique isozyme profile and karyotype. All 4 lines have comparable population doubling times of 28–38 hr. Only 3 lines reproducibly form colonies in soft agar, but the JA‐I line, which failed to clone, readily produces xenografts in nude mice. Drug sensitivity testing, using clonogenic or growth‐inhibition assays, shows that these lines express a wide range of sensitivities to cisplatin (> 20‐fold), with the TR175 cells proving particularly sensitive, but a narrower range of sensitivity (≤ 10‐fold) to adriamycin. Following 6 24‐hr pulsed exposures in vitro to drug concentrations between IC50 and IC90 values, significant resistance develops to adriamycin in each line tested. In contrast, with cisplatin treatment, all lines retain their original sensitivities, except for TR170 cells exposed to the highest concentration, which express cisplatin resistance.
The immune basis of dosage‐induced reversal of the rank‐order of strain susceptibility to MCA
Authors: Prehn Liisa M. , Lawler Ellen M.
Published: February 2007

Even AHH‐inducible mouse strains vary in their susceptibilities to MCA sarcomagenesis. Previous work showed that the rank‐order of strain susceptibility depended upon the dosage of MCA; the strain most susceptible to a high dose became the least susceptible to a low one and vice versa. We now confirm our previous findings and test the hypothesis that the reversal, with dosage, of the rank‐order of relative strain‐susceptibility has an immunological basis. This was tested in two ways: by examining the effect of immunosuppression on strain‐susceptibility to sarcomagenesis and by transplanting parental bone marrow into irradiated F1 hybrid to see if the relative MCA‐susceptibility characteristics of the parental donors could be transferred. The results of both studies suggest that the rank‐order‐reversal phenomenon is caused, at least in part, by differences in the immunological reactivities of the strains. Inasmuch as immunosuppression inhibited the response of the C3 mice to a high dose of carcinogen, but facilitated carcinogenesis among the B6, the level of innate immune capacity most conducive to high‐dose carcinogenesis is apparently intermediate between the levels of these two strains.
Effects of DL‐α‐difluoromethylornithine on the growth and metastasis of b16 melanoma in vivo
Authors: Kubota Shunichiro , Ohsawa Nakaaki , Takaku Fumimaro
Published: February 2007

The effects of DL‐α‐difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, on the growth of experimental mouse B16‐F10 melanoma cells were investigated. DFMO (3%) in drinking water was administered to B16‐F10 melanoma‐bearing mice. At 24 days, B16‐F10 melanomas in DFMO‐fed mice weighed 75% less than those in control mice (p < 0.001). DFMO reduced putrescine and spermidine levels in B16‐F10 melanoma by 98% and 84%, respectively, and prolonged the mean survival time from 25.9 ± 1.2 to 35.7 ± 2.2 days (p < 0.001). The effects of DFMO on experimental metastasis were also investigated. DFMO treatment resulted in a significant decrease in pulmonary metastasis induced by i.v. injection of B16‐F10 melanoma cells.
Anti‐tumor effects of tumor necrosis factor in combination with chemotherapeutic agents
Authors: Regenass Urs , Müller Marcel , Curschellas Enrico , Matter Alex
Published: February 2007

The anti‐tumor activity of partially purified tumor necrosis factor (TNF) was analysed in combination with chemotherapeutic drugs against intradermally transplanted Meth A sarcoma. Tumors were allowed to grow until they reached an average diameter of about 8 mm. TNF was given once i.v. (16,000 units as determined on L‐M cells) and the chemotherapeutic agents adriamycin (1‐10 mg/kg), 5‐FU (3‐100 mg/kg), cyclophosphamide (50–200 mg/kg) were applied once i.p. 4 hr after TNF injection. The strongest anti‐tumor effects in normal BALB/c mice were observed when TNF was combined with the following doses of chemotherapeutic agents: cyclophosphamide 100 mg/kg, adriamycin 5 mg/kg, 5‐FU 30‐100 mg/kg. The most effective combinations induced complete regressions. When TNF was combined with varying doses of adriamycin and cyclophosphamide, bell‐shaped dose‐response curves were obtained. Experiments were repeated in Meth A sarcoma‐bearing BALB/c nu/nu mice. In this case TNF combinations with cyclophosphamide and 5‐FU did not induce tumor regressions. The highest dose of the chemotherapeutic agent was the most effective in drug combinations. Histological analysis revealed a potentiation of the TNF‐induced necrosis by cyclophosphamide. Increased hyperemia and extravasation of erythrocytes could be found in tumors of animals treated with the drug combination.
Tobacco and occupation as risk factors in bladder cancer: A case‐control study in southern belgium
Authors: Schifflers Eugéne , Jamart Jacques , Renard Véronique
Published: February 2007

A pilot case‐control study on bladder cancer, with population‐based controls matched for each of 74 cases, has been conducted in two industrial areas of Southern Belgium in order to analyze the influence of tobacco use and occupation. Observed bladder cancer risk for smokers is more than 5 times higher than that for non‐smokers, and the risk for people having an a priori hazardous occupation is about 3.5 times higher than that of other subjects. A dose‐response relationship was found for tobacco exposure and duration of employment. It seems that the risk is increased in a log‐linear way by these variables. Population attributable risks show that in 20 cases of bladder cancer, 17 could be explained by the two factors combined. This study also reveals an increased risk for metal workers, truck and engine drivers, coal‐miners, and rubber and coal‐tar workers. The risk for metal workers is specially high in the case of turners, metal fitters, blacksmiths, stokers and workers exposed to hot metal.
Characterization of human ovarian carcinoma‐associated antigens defined by novel monoclonal antibodies with tumor‐restricted specificity
Authors: Miotti S. , Canevari S. , Ménard S. , Mezzanzanica D. , Porro G. , Pupa S. M. , Regazzoni M. , Tagliabue E. , Colnaghi M. I.
Published: February 2007

Three new monoclonal antibodies (MAbs) (MOv16, MOv18 and MOv19) were raised against human ovarian carcinoma. To obtain more specific reagents than those produced so far, we adopted the following experimental approach which consisted of: (1) the selection of a poorly differentiated ovarian carcinoma which was unreactive with all the MAb previously selected in our laboratory; and (2) the application of a particular immunization protocol. The reactivity of the selected MAbs was studied by solid‐phase RIA on live and fixed cells from tumor cell lines and by immunofluorescence on frozen sections from surgical specimens. The MAb MOv16 reacted with 60% of ovarian carcinomas as well as with a high percentage of other carcinomas and with some normal tissues. In contrast, MOv18 and MOv19 appeared to have restricted specificities for ovarian carcinomas and cystadenomas. Reactivity on other carcinomas was only observed in a few cases and no reactivity was found on non‐epithelial tumors or normal tissues. Immunoprecipitation experiments indicated that MOv16 recognizes a 48‐50‐kDA protein, whereas MOv18 and MOv19 both identify a 38‐40 kDA glycoprotein band. Cross‐competition experiments, together with a double‐determinant immunoradiometric assay which uses MOv18 as catcher and MOv19 as tracer, suggested that they recognize different epitopes carried by the same molecule. The affinity constants of MOv18 and MOv19 were estimated to be in the range of 108 ‐ 109 M‐1. Taken together, the properties of these antibodies, their restricted ovarian tumor specificities and relative high affinity constants, suggest that they could represent promising tools for in vivo applications.