bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical characterization and cellular localization of a formalin‐resistant melanoma‐associated antigen reacting with monoclonal antibody NKI/C‐3
Authors: Vennegoor C. , Calafat J. , Hageman Ph. , van Buitenen F. , Janssen H. , Kolk A. , Rümke Ph.
Published: February 2007

A monoclonal antibody (MAb NKI/C‐3) produced against a purified membrane preparation of human melanoma cells reacts preferentially with sections of formaldehyde‐fixed and paraffin‐embedded tissues of melanoma, nevocellular nevi, carcinoids and medullary carcinomas of the thyroid. NKI/C‐3 did not react with basal‐cell carcinoma, brain tissue or brain tumors, and in only 14/196 other tumors was a clear cross‐reactivity observed, e. g. with prostate carcinomas and a minority of primary breast, ovarian, lung and clear‐cell carcinomas. This antibody was used in an immuno‐electron microscopic study for the cellular localization of the antigen. The antigen was dispersed in the cytoplasm of melanoma cells, and more concentrated inside vacuoles and sometimes also on the melanosomes. Occasionally, the antigen was seen on the cell surface.

The nature of the antigen was determined in an enzyme immunoassay (EIA). It was found that the antigen is a glycoprotein with a disulfide‐dependent configuration that is essential for recognition by the MAb. The antigen was distributed heterogeneously during gel filtration as well as during SDS‐polyacrylamide gel electrophoresis in the region of 25–110 kd proteins. A purified antigen preparation that was obtained after affinity chromatography on a column of MAb NKI/C‐3 linked to Sepharose 4B contained a carbohydrate:protein ratio of 1:3.5.
The plasmin system in human colonic tumors: An immunofluorescence study
Authors: Burtin P. , Chavanel G. , Andre J.
Published: February 2007

We studied the plasmin system with specific antisera to plasminogen, its 2 activators (urokinase‐type and tissue‐type) and the 2 plasmin inhibitors, α2 anti‐plasmin and α2 macroglobulin on sections of 34 human colonic tumors by immunofluorescence. Anti‐plasmin ogen serum showed a clear‐cut reactivity at the surface of tumor cells, as it stained the contour of tumor glandular structures, foci, and isolated tumor cells. Intratumoral deposits and necrotic areas were stained as well, often strongly. Localization of plasminogen was quite different from that of fibrinogen, which was found only in peritumoral stroma, and never on tumor cells. Traces of both types of plasminogen activator were found, mainly on invasive tumor cells for urokinase type and on large tumor foci for tissue type. Images were weak and inconstant. Large amounts of both plasmin inhibitors were characterized in tumor stroma. Alpha‐2 anti‐plasmin was also found in intratumoral deposits and necrotic areas.

It seems likely that plasminogen exudes from blood capillaries (since anti‐plasminogen serum often stained the whole capillary wall), diffuses in the stroma and binds to tumor cells. Once formed, plasmin is likely to play a role in the invasion of surrounding tissues by tumor cells, in the dissociation of tumor cells from tumor glands and in the production of necrosis inside tumor areas.
Insulin binding by normal and neoplastic colon tissue
Authors: Wong M. , Holdaway I. M.
Published: February 2007

Insulin receptors in human colon tumours, normal colon tissue and mesenteric fat removed at surgery have been identified by measuring the binding of labelled insulin to cell membrane preparations. Insulin binding sites were readily detected in all tissues, with mean ± SD binding site concentrations of 43 ± 41, 44 ± 39, and 44 ± 35fmol/mg membrane protein, and dissociation constants of 0.73 ± 0.61, 0.66 ± 0.41, and 0.78 ± 0.58nM for microsomal plasma membrane preparations of tumour (n = 25), normal colon (n = 25) and fat (n = 23) respectively. The specificity of binding of labelled insulin was similar in tumour and normal colon samples. Binding in normal colon preparations was highest in the epithelium (84fmol/mg membrane protein) and lower in lamina propria (19fmol/mg), submucosa (26fmol/mg) and muscle wall (13fmol/mg). Degradation of labelled insulin was similar in tumour and normal colon preparations. Mean receptor levels were not significantly different between microsomal membrane preparations and plasma membranes partially purified on discontinuous sucrose gradients, quantitated against either unit membrane protein or unit 5′‐nucleotidase specific activity. There was a significant negative correlation between insulin binding to fat membranes and fasting serum insulin levels, but no significant relationship was seen between serum insulin and receptor levels in either colon tumour or tissue preparations from full‐thickness normal colon wall. An inverse correlation between serum insulin and receptor levels was, however, apparent in preparations of colonic musosa. These data indicate that although insulin receptors in colon tumours share the same biochemical characteristics as those present in the normal colon, receptors in tumour tissue are less sensitive to down‐regulation by ambient insulin than receptors in mesenteric fat cells and normal colonic mucosa.
Natural killer cell resistance in K‐562 cell sublines
Authors: Foster J. S. , Wust C. J. , Lozzio C. B. , Bamberger E. G. , Ichiki A. T.
Published: February 2007

Sublines of the hematopoietic stem cell line K‐562 were tested for their susceptibility to human natural killer (NK) cell activity. A correlation was found between the degree of NK‐mediated lysis and the presence or absence of particular chromosomal markers. K‐562 sublines susceptible to lysis by NK were found to express karyotypically a deletion 9‐ and a marker 8(tl : 18), whereas resistant sublines did not express these markers. A cloned K‐562 subline BIV was chosen as representative of a resistant subline. This subline was resistant to lysis even after prolonged incubation and activation of the NK cells with interferon. However, it was found that BIV was lysed by both antibody‐dependent, complement‐mediated and antibody‐dependent cellular mechanisms at levels comparable to those seen with NK‐sensitive K‐562 sublines. Subline BIV did compete poorly with NK‐sensitive K‐562 in cold‐target inhibition; however, conjugate‐formation assays demonstrated that the binding of NK cells to BIV cells is comparable to that of NK‐sensitive K‐562 cells. We suggest that cells of the cloned line BIV are recognized normally by NK cells but do not activate the lytic mechanism of the bound NK cell.

Treatment of the resistant clone BIV with neura minidase did not lead to enhanced levels of lysis. Protein extracts of NK‐sensitive K‐562 sublines efficiently inhibited lysis by NK cells but extracts of the resistant clone, BIV, did not inhibit lysis, suggesting that the clone lacks cell surface determinants involved in the post‐recognitive activation of the NK cytolytic mechanism.
Characterization of a second Epstein‐Barr virus‐determined nuclear antigen associated with the BamHI WYH region of EBV DNA
Authors: Dillner Joakim , Kallin Bengt , Ehlin‐Henriksson Barbro , Timar Laszlo , Klein George
Published: February 2007

The Epstein‐Barr virus‐determined nuclear antigen (EBNA) is the only known virally‐determined compoment that is regularly associated with EBV‐transformed cells. A main component of EBNA, herein designated EBNA‐1, has been conclusively localized to the BamHI K fragment of the viral genome. EBNA‐1 is present in all EBV carrying cell lines so far studied. Our current study deals with a second component. We have found that the EBNA reaction detected by anticomplement immunofluorescence (ACIF) in Burkitt lymphoma lines Daudi, Jijoye, and P3HR‐1 could be completely removed by preabsorption of sera with any one of these 3 lines, when tested against any other of them. The same absorbed sera still gave a brilliant nuclear staining against other EBV‐carrying lines, e. g. Raji or B95‐8. The 3 lines in the first category carry EBV genomes that have delections in the BamHI WYH region of the EBV genome. This region is intact in the second group of lines. This result is interpreted as showing the existence of 2 different ACIF‐stainable EBV‐determined nuclear antigens, one of which is associated with the BamHI WYH region. We designate this antigen as EBNA‐2. We found that the two different EBNAs are different with regard to their association with metaphase chromosomes. In lines positive for both EBNA subtypes, metaphase chromosomes gave brilliant EBNA‐1 staining, but could not be stained for EBNA‐2, indicating differences in chromatin association of the two EBNAs. An 86 kd polypeptide was identified by immunoblotting of DNA‐binding proteins from EBV‐transformed lymphoid cell lines. EBV‐specificity of the polypeptide was demonstrated by the presence of antibodies against this polypeptide in antisera from a population of EBV‐seropositive donors, but not from seronegative donors, by the presence of the polypeptide itself in EBV‐carrying but not in EBV‐negative cell lines and by the appearance of antibodies against this polypeptide during the course of infectious mononucleosis (IM). The polypeptide was absent from the EBV‐carrying P3HR‐1, Daudi and Jijoye cell lines, which suggested that it may be encoded by the BamHI WYH region that is deleted from the viral substrains carried by these lines.
Isolation of simian retroviruses closely related to human T‐cell leukemia virus by establishment of lymphoid cell lines from various non‐human primates
Authors: Tsujimoto Hajime , Komuro Atsumi , Iijima Kumiko , Miyamoto Junko , Ishikawa Koh‐Ichi , Hayami Masanori
Published: February 2007

Simian retroviruses closely related to human T‐cell leukemia virus (HTLV) were isolated by establishing virus‐producing lymphoid cell lines from 7 species of non‐human primates. By co‐cultivation with human umbilical cord‐blood cells and/or in the presence of interleukin‐2, lymphoid cell lines were successfully established from the chimpanzee, African green monkey, pig‐tailed macaque, red‐faced macaque, Formosan monkey, Japanese monkey and bonnet monkey that had antibodies against HTLV antigens. These cell lines reacted with human sera of ATL patients and monoclonal antibodies against p19 and p24 of HTLV antigens. Cellular DNAs contained the provirus sequences homologous to HTLV‐I by Southern blot hybridization. Moreover, they produced extracellular type‐C virus particles and RNA‐dependent DNA polymerase. All of these lymphoid line cells had Tac antigen, interleukin‐2 receptor, and those of chimpanzee and red‐faced macaque had helper/inducer T‐cell markers, while those derived from African green monkey had suppressor/cytotoxic T‐cell markers. Furthermore, simian HTLV‐related viruses of pig‐tailed macaque, red‐faced macaque and Japanese monkey were transmitted to human lymphocytes on co‐cultivation.
Cutaneous melanoma in relation to intermittent and constant sun exposure—the western canada melanoma study
Authors: Elwood J. M. , Gallagher R. P. , Hill G. B. , Pearson J. C. G.
Published: February 2007

The histories of exposure to sun through occupational, recreational and vacation activities of 595 patients with newly incident cutaneous melanoma excluding lentigo maligna and acral lentiginous melanoma, were compared to those of comparison subjects drawn randomly from the same population and matched for age, sex and province of residence in Western Canada. Significant increases in risk were seen with increasing amount of sun exposure through outdoor activities associated with recreation and vacations; activities likely to involve more intense sun exposure were associated with greater increases in risk. While a moderate amount of occupational exposure was associated with increased risk, greater occupational exposure resulted in no further increase; in men a decrease in risk was seen. These findings were independent of the effects of hair and skin colour, freckles, ethnic origin and socio‐economic status. The results suggest that short‐term exposure to unusually intense sunlight increases the risk of melanoma, while long‐term constant exposure has no effect or may decrease risk. No simple relationship was seen between melanoma risk and total sunlight exposure. This study introduces new methods of assessing different types of sun exposure from retrospective data.
The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer: Relationships with metabolic clearance rates of oestradiol
Authors: Reed M. J. , Beranek P. A. , Cheng R. W. , Ghilchik M. W. , James V. H. T.
Published: February 2007

The distribution of oestradiol in plasma from post‐menopausal women with or without breast cancer has been measured and related to the metabolic clearance rates of oestradiol (MCR‐E2). All measurements were carried out preoperatively. No difference in the free fraction of oestradiol was found between women with breast cancer (1.8 ± 0.4%, mean ± sd) and normal women (1.6 ± 0.3%). Approximately 40% of oestradiol in plasma was bound to albumin with 60% bound to sex hormone binding globulin (SHBG), but values were similar for women with or without breast cancer. Concentrations of total unconjugated oestradiol and free oestradiol (2.4 ± 0.5 ng/100 ml and 44 ± 12 pg/100 ml respectively, mean ± sd, n = 9) were significantly higher in plasma from postmenopausal women with breast cancer compared with levels in plasma from normal postmenopausal women (1.8 ± 0.5 ng/100 ml and 27 ± 10 pg/100 ml, n = 8). A significant correlation was found between the free oestradiol fraction and MCR‐E2 (r = 0.53, p < 0.05). Correlations were also found between the fractions of oestradiol bound to albumin and MCR‐E2 (r = 0.45). From correlations between the binding capacity of SHBG and MCR‐E2 it appears that, for a given level of SHBG, MCR‐E2 may be higher in women with breast cancer.
Cell surface antigens of human trophoblast and choriocarcinoma defined by monoclonal antibodies
Authors: Rettig Wolfgang J. , Cordon‐Cardo Carlos , Koulos John P. , Lewis John L. , Oettgen Herbert F. , Old Lloyd J.
Published: February 2007

Six distinct cell surface antigens of human trophoblast and choriocarcinoma were defined with MAbs

Abbreviations: MAb, monoclonal antibody; ALP, alkaline phosphatase; MHA assay, mixed hemadsorption assay; PLAP, placental alkaline phosphatase.

. The distribution of the antigens was determined by MHA assays on 150 tumor cell lines and normal cell cultures and by immunofluorescence tests with a wide range of normal adult and fetal tissues and a tumor panel. Antigen LK26 is expressed on all cultured choriocarcinoma, teratocarcinoma and renal cancer lines but is absent from most cell lines derived from other tumor types and from cultures of normal kidney epithelium and fibroblasts. LK26 expression in normal tissues is restricted to the trophoblast. No other adult or fetal tissue was found to express the antigen, but choriocarcinoma and teratocarcinoma tissues were LK26+. SV19 is expressed on cultured choriocarcinomas and teratocarcinomas and on subsets of breast and colon cancer lines, but not on 120 additional cultures tested. In tissues, SV19 is detected in normal placenta, mammary gland and colon epithelium as well as in tumors of breast, colon and lung. Two antibodies, AbSV63 and AbK8, react with PLAP and Ab‐SV63 also reacts with the intestinal form of the enzyme. AbLK24 defines a heat‐stable determinant present on choriocarcinoma and breast cancer cell lines but absent from most other cultured cells. It is expressed on a small range of normal and malignant epithelial tissues, including normal trophoblast, normal breast epithelium and urothelium and tumors derived from these tissues. One antigen, K66, showed a wide distribution on cultured epithelial cells but was not found in any normal or malignant tissue. Finally, S4, a previously described marker of normal and malignant kidney epithelial cells, was also expressed on the choriocarcinoma cell lines. Four of the antigens are glycoproteins that could be immunoprecipitated from radiolabelled extracts of choriocarcinoma cells: LK26 (Mr 35,000), SV19 (Mr 40,000), PLAP (Mr 68,000) and S4 (Mr 160,000). The highly restricted distribution of LK26, SV19, S4, and PLAP in normal tissues and their expression in tumors make these antigens potential diagnostic markers of gestational choriocarcinoma and germ‐cell tumors and, possibly, targets for immunotherapy.
The generation of culture activated killer cells (AK) is interleukin‐2‐dependent and requires self‐ia recognition
Authors: Lattime Edmund C. , Stutman Osias
Published: February 2007

Cytotoxic cells which lack major histocompatibility restriction for lysis are generated when murine spleen cells are cultured in the presence of FCS

Abbreviations: AK, activated killer; C′, complement; CTL, cytotoxic T lymphocyte; FCS, fetal calf serum; IFN, interferon; IL‐2, interleukin‐2; MHC, major histocompatibility complex; NC, natural cytotoxic; NK, natural killer; NCMC, natural cellmediated cytotoxicity; NMS, normal mouse serum; MAb, monoclonal antibody.

with or without allogeneic stimulation. The studies reported show that, following 3 days of culture with FCS, murine spleen cell cultures contain at least two cytotoxic populations. The first (AK‐YAC), expresses an NK cell phenotype and target specificity while the second (AK‐WEHI) shares the characteristics of the NC cell. Generation of the AK‐YAC effector cell requires the presence of a pre‐AK cytotoxic cell (Qa‐5, LYT‐2‐plus;) and is dependent on the generation of interleukin‐2 (IL‐2) during the culture period, while the AK‐WEHI effector is independent of IL‐2 production. IL‐2 production in the cultures is shown to require syngeneic la recognition by an Lyt‐1+, L3T4+ T cell. These findings suggest a role for IL‐2 in the in vivo regulation of NCMC and describe a mechanism for its production in the absence of antigenic stimulation.
Further study of β‐tgfs released by virally transformed and non‐transformed cells
Authors: Krycéve‐Martinerie C. , Lawrence D. A. , Crochet J. , Jullien P. , Vigier P.
Published: February 2007

Chicken embryo fibroblasts sensitized by ts RSV respond to TGFs present in the media of non‐transformed FR3T3 and NRK‐4 rat cells and of the same cells transformed by KiMSV or RSV. They also respond to TGFs present in the media of BHK hamster cells transformed by MoMSV, PyV or RSV. Two other indicator rat cell lines, untransformed NRK‐4 and FR3T3, sensitized by ts KiMSV, respond to the same TGF‐containing media, and this response is increased by exogenous EGF. Normal FR3T3 cells failed to respond to any of the media. The most sensitive target cells were the ts KiMSV‐FR3T3 cells at the restrictive temperature (39.5°C). All the media tested on NRK‐49F target cells required EGF for their TGF activity which was essentially dependent on prior activation by acidification. These data show that the above media from non‐transformed or transformed cells contain β‐TGFs, with no detectable accompanying α‐TGF activity. The release of and the response to these TGFs are not interdependent. A function of ts mutant src and k‐ras viral oncogenes, still expressed at the restrictive temperature, can sensitize non‐responsive cells, without there being any specificity towards the TGF producer cells.
Directional motility in strongly malignant murine tumor cells
Authors: Varani James , Fligeil Suzanne E. G. , Perone Patricia
Published: February 2007

Laminin, fibronectin and 12‐0‐tetradecanoyl phorbol acetate (TPA) were examined for their ability to induce biological responses (cell‐to‐substrate adherence and motility) in a series of strongly malignant and weakly malignant murine fibrosarcoma cells. All three agents caused increased cell‐to‐substrate attachment of the cell lines. Laminin and fibronectin induced a slow but sustained response, whereas with TPA the response was rapid and transient. The 3 agents also stimulated motility in the same cells. Random motility was seen with all of the cells but directional motility was observed primarily in the strongly malignant cells. With TPA, the response was chemotactic but laminin and fibronectin induced cell migration by haptotaxis. Since laminin and fibronectin are constituents of the extracellular matrix and since malignant tumor cells must cross the extracellular space during invasion, those properties of cells which allow for migration across a substrate containing these materials may contribute to the expression of malignancy.
HLA and prognostic factors in primary breast cancer
Authors: Iaffaioli Rosario V. , Maio Michele , Ruggiero Giuseppina , De Felice Mario , Ungaro Achille , del Vecchio Luigi , Rosato Giovanni B. , Bianco A. Raffaele , Zappacosta Serfino
Published: February 2007

A group of 157 women with primary breast cancer (BC) were typed for HLA antigens, and gene frequencies were compared to those of 327 control healthy individuals. Diagnosis of BC was made for all patients on surgical mastectomy specimens; histologic grading, estrogen (ER) and progesterone (PgR) receptors were determined on all primary tumors. Typed antigens included the majority of the specificities controlled by the HLA‐A, ‐B and ‐C loci, according to the 8th International Histocompatibility Testing Workshop recommendations. No significant discrepancy in their frequencies was found in the undivided sample as compared to controls. The analysis of HLA gene frequency was extended to subsets of patients identified by the following prognostic features: (a) age at tumor diagnosis (pre‐menopause vs. post‐menopause); (b) receptor status (presence vs. absence of ER and PgR); (c) mammary gland dysplasia (presence vs. absence); (d) histologic grade (grade 3 vs. grades I and 2 combined); (e) time to relapse before or after (24 months following mastectomy). A moderate deviation from normal of some genes was found in several subsets, often affecting only one of the antithetical subgroups (feature present vs. feature absent). In the instance of B5, the increase in frequency of the gene in one of the subset pair (ER + subjects) was balanced by a decrease of the same gene in the counterpart (ER‐ subjects). Increased frequencies were found for the B7 gene in the following prognostic groups: (a) lack of ER (0.08); (b) lack of PgR (0.09); (c) absence of mammary dysplasia (0.075); (d) histologic grade 3 (0.10); and (e) premenopause (0.12). the last two showing significant divergence from normal. When features (d) and (e) on the one hand and (a), (b), (d) and (e) on the other were combined, B7 reached frequencies of 0.18 (p < 5 × 10−4) and of 0.29 (p < 5 × 10−6), respectively.
Occupation and bladder cancer in males: A case‐control study
Authors: Vineis Paolo , Magnani Corrado
Published: February 2007

A case‐control study of 512 male cases of bladder cancer and 596 male hospital controls (all living in the province of Turin, Northern Italy, an area with a high proportion of car workers) has been analyzed for occupations. Relative risks were 1.8 (95% c.1. 0.9–3.6) for the textile industry, 3.8 (1.3–11.5) for the leather industry, 1.8 (0.8–4.0) for printing, 8.8 (2.7–28.6) for dyestuff production, 1.2 (0.6–2.4) for tire production and 2.5 (1.0–6.0) for other rubber goods, 2.0 (0.9–4.5) for brickyards and related activities. A relative risk of 3.1 (0.9–10.5) was found for turners having started work before 1940 and with at least 10 years of activity. For truck drivers the relative risk was 1.2 (0.6–2.5). A job‐exposure matrix was developed for the development of new hypotheses; an association with bladder cancer was found for aromatic amines only. The attributable risk percent in the population was estimated as 10%, when only those occupations consistently associated with bladder cancer were considered.
Differential action of six human interferons against two human carcinomas growing in nude mice
Authors: Balkwill F. R. , Goldstein L. , Stebbing N.
Published: February 2007

Six different pure human interferons (IFNs). were tested for anti‐tumour effect against two human carcinomas, breast and bowel, growing in nude mice, in a total of 36 experiments. The IFN‐α mixture, analogue and subtypes showed the greatest activity, particularly against the breast cancer xenograft, whereas IFN‐β and IFN‐γ had little effect. However, circulating IFN could be found in the sera of mice treated with all 3 IFN types. In terms of amount of IFN protein, IFN‐αCon1, an IFN‐α analogue, was the most effective, a dose of 0.1 μg/mouse/day being sufficient to induce breast tumour regression, and IFN‐γ the least effective, a dose of 10 μg/mouse/day having no effect on the same tumour. A more detailed comparison of 2 IFN‐α subtypes showed that a daily dose of 1 μg IFN‐αA was more effective than the same dose of IFN‐αD, but as this IFN had approximately 30 times less antiviral activity on human cells than IFN‐αD, these IFNs were probably at least equally effective in terms of human cell units. IFN‐αD stimulated mouse spleen natural killer cell activity but it was not clear whether this stimulation was involved in anti‐tumour activity. We conclude that this model system is useful for investigating direct anti‐tumour activity of a wide range of IFN types and subtypes.
Purification from a human lung cancer cell line of a water soluble molecule mediating leukocyte adherence inhibition for patients with lung cancer
Authors: Thomson D. M. P. , Sutherland Mary , Durko Margaret , Dubois Tony , Scanzano Rosemarie , Labateya Nabil , Shenouda George
Published: February 2007

Soluble lung tumor activity as determined by LAI2 was enriched by physiocochemical methods from chemically ‐ defined spent medium of a lung cancer cell line (NCI‐H69). To identify the polypeptide carrying the antigenic determinant, splenic lymphocytes of BALB/c mice were immunized with the enriched isolate and hybridized with mouse plasmacytoma cells. Eight hybrids were cloned successfully and produced MAbs that immunoprecipitated principally a single chain of Mr 40,000 (p40) as well as minor chains of Mr 25,000 (p25) and Mr 13,000 (p13) which were probably degradation products of p40. On 2D gels, p40 was composed of 7 spots with a p1 of 6.3 to 7.6, which was not altered by neuraminidase digestion. Affinity chromatography with MAb anti‐p40 absorbed p40 and LAI activity. The bound and recovered fraction was enriched for p40 and LAI activity. Affinity‐purified p40 also contained the previously identified p25 and p13 as well as a Mr 32,000 peptide (p32). MAb anti‐p40 was directed to a common framework determinant on p40 since MAb anti‐p40 bound to cancer cells from other organs. The comparatively lung cancer organ‐specific determinant recognized by leukocytes from lung cancer patients was not recognized by the MAb. Affinity‐purified p40 triggered LAI for leukocytes from patients with lung cancer but not for leukocytes from control subjects or patients with colon cancer or malignant melanoma in rigorous blind testing. Crossreactivity was observed with leukocytes from patients with breast cancer. LAI activity of affinity‐purified p40 seems unlikely to result from an unidentified impurity. Thus a p40 molecule has been purified that is expressed on the membranes of lung cancer cells and triggers immunologically‐mediated LAI.
Therapeutic application of a radiolabelled monoclonal antibody in nude mice xenografted with human neuroblastoma: Tumoricidal effects and distribution studies
Authors: Jones D. H. , Goldman A. , Gordon I. , Pritchard J. , Gregory B. J. , Kemshead J. T.
Published: February 2007

Monoclonal antibody UJ13A radiolabelled with isotopes of iodine has been shown to selectively localize to human neuroblastoma xenografts. When 131I‐UJ13A conjugates were given to nude mice at high doses (100–150 μCi), tumours temporarily disappeared, only to regrow. No selection for neuroblastoma cells that were UJ13A. negative was observed. Distribution studies on mice receiving radiolabelled UJ13A demonstrated the antibody is rapidly lost from the blood of animals. This cannot be accounted for by selective uptake into xenografts or any other mouse organ examined. We concluded there is a rapid equilibration of isotope between intra‐and extravascular spaces in the animal. The rapid, biphasic loss of UJ13A from the blood of mice may explain why so little injected antibody can target to the human tumour xenografts.
Increased urokinase activity to antigen ratio in human renal‐cell carcinoma
Authors: Kirchheimer Johannes C. , Pflüger Heinz , Hienert Gregor , Binder Bernd R.
Published: February 2007

Eighteen patients with renal‐cell carcinoma have been investigated in an attempt to elucidate the ratio of active urokinase enzyme to urokinase antigen in the tumor and adjacent normal kidney. The tumor itself exhibited a significantly increased total fibrinolytic activity, an increase in the relative contribution of anti‐urokinase IgG‐inhibitable plasminogen activator activity and increased levels of urokinase antigen when compared to normal renal tissue. In tumor‐adjacent tissue total fibrinolytic activity was also, but not significantly, increased, this increase being completely due to tissue‐type plasminogen activator. Correlation of active urokinase‐type plasminogen activator with urokinase antigen revealed that in tumor tissue the enzyme was present to more than 70% in its active form whereas in tumor‐adjacent tissue and normal renal tissue only half of the enzyme appeared to be active. No correlation was obtained between urokinase antigen present in one of the 3 tissues investigated and plasma urokinase antigen.
Incidence of adult T‐cell leukemia‐lymphoma and its familial clustering
Authors: Kondo Toshifumi , Nonaka Hiroshi , Miyamoto Naoaki , Yoshida Ryoichi , Matsue Yasuhiro , Ohguchi Yoshito , Inouye Hiroo , Komoda Haruko , Hinuma Yono , Hanaoka Masao
Published: February 2007

The yearly incidence of ATLL in the Uwajima district is 6.6 patients per 100,000 inhabitants aged over 40. The yearly morbidity rate from ATLL of persons in this district who are positive for HTLV‐antibody and older than 40 is I patient per 1,631. Familial occurrence was observed in 9/38 families available for pedigree analyses. Even in the endemic area, the existence of positive HTLV antibody is remarkably high in ATLL families, suggesting that HTLV has been transmitted from generation to generation mainly within these particular families.
Regional variation in prevalence of antibody against human T‐lymphotropic virus types I and III in Kenya, East Africa
Authors: Biggar Robert J. , Johnson Bruce K. , Oster Charles , Sarin Prem S. , Ocheng David , Tukei Peter , Nsanze Herbert , Alexander Steven , Bodner Anne J. , Siongok Timothy Arap , Gallo Robert C. , Blattiner William A.
Published: February 2007

The prevalence of antibodies against HTLV—III and ‐I was studied among populations of 6 distinctly different regions of Kenya, an equatorial African country in which AIDS has rarely been observed. Overall, 21% of subjects had ELISA reactions suggesting the presence of antibody against HTLV‐III. The frequency of HTLV‐III antibodies was highest among the Turkana people (50%) and lowest among the Masai (8%). Prevalence increased with age but was not related to sex. The pattern of ELISA‐detected antibody against HTLV‐I was similar. The specificity of these antibodies was supported by Western blot analysis of a subset of sera with high and low ELISA ratios, in which 66% and 73% of those with ELISA ratios considered positive ( = > 5.0 in this study) also had a profile of bands consistent with HTLV‐III and HTLV‐I respectively. The antibodies detected were not cross‐reactive between HTLV‐III and HTLV—I on Western blot analysis. In a series of subjects with various parasitic and infectious diseases, patients with idiopathic splenomegaly and with schistosomiasis had a high proportion of antibodies against both HTLV‐III and HTLV‐I. This survey shows that reactivity in the ELISA HTLV‐III and HTLV‐I assays are common among Kenyans but vary considerably by region.
A monoclonal antibody to human transitional‐cell carcinoma of the bladder cross‐reacting with a differentiation antigen of neutrophilic lineage
Authors: Baricordi O. R. , Sensi A. , de Vinci Caterina , Melchiorri Loredana , Fabris G. , Marchetti Elisabetta , Corrado F. , Mattiuz P. L. , Pizza G.
Published: February 2007

A monoclonal antibody (MAb) to human transitional‐cell carcinoma of the bladder (TCCB) was obtained by immunization of a BALB/c mouse with formalin‐fixed TCCB cells and subsequent fusion of the spleen cells with SP2‐OAg14 myeloma line. GF 26.7.3 MAb was selected by indirect immunofluorescence (IIF) as reacting agent with target cells and negative with autologous lymphocytes and Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cell‐line. GF 26.7.3 reacts with a high percentage of bladder and colon carcinomas when examined by IIF and immunoperoxidase techniques and cross‐reacts with a determinant expressed on neutrophilic cell lineage. The IIF analysis performed on bone marrow and peripheral blood (PB) from healthy subjects and leukemic patients and on leukemic cell lines showed that the expression of the structure detected by GF 26.7.3 is restricted to the neutrophilic cell lineage and first expressed at the promyelocytic level. Immunoprecipitation and SDS‐polyacrylamide gel electrophoresis (PAGE) of 125 I‐labelled membrane proteins from target cells were performed, but no bands were detected by autoradiography. In addition, pronase insensitivity and periodate sensitivity suggest the possible involvement of a carbohydrate determinant.
The use of multicellular spheroids in establishing human sarcoma cell lines In vitro
Authors: Bruland Ø. , Fodstad Ø. , Pihl A.
Published: February 2007

By a new procedure stable monolayer cultures were derived from spheroids in 8 out of 17 different human sarcomas (16 soft‐tissue and I osteogenic sarcoma). Eleven of the sarcomas were obtained from patients undergoing surgery, and 6 from BALB/c nude mice carrying s. c. growing xenografts. The new procedure involves aggregation of single‐cell suspensions into spheroids and cultivation of these in agar‐coated flasks until the growth rate levels off, at which time the spheroids are transferred to uncoated flasks. Cells proliferating from the rim of adhering spheroids are trypsinized and aggregated to form new spheroids. By 3 to 5 such alternations, monolayer cultures were obtained that have now been subcultured for about 6 months. The cell lines all gave rise to colonies in a clonogenic soft‐agar system, and upon s. c. injection into athymic nude mice 3 lines tested formed growing tumors. The histology of spheroids formed from late monolayer passages closely resembled that of the original tumors. That the new procedure is superior to other methods of establishing sarcoma cell lines is indicated by the fact that a stable monolayer culture could be obtained directly from the tumors in only 1/8 cases where the above procedure was successful, and in only 2 instances from soft‐agar colonies derived from the tumors.
Antitumor effects of two polyamine antimetabolites combined with mitomycin C on human stomach cancer cells xenotransplanted into nude mice
Authors: Fujimoto Shigeru , Igarashi Kazuei , Shrestha Ram Dhoj , Miyazaki Masaru , Okui Katsuji
Published: February 2007

The antitumor effects of alpha‐difluoromethylornithine (DFMO), methylglyoxal‐bis‐guanylhydrazone (MGBG) and mitomycin C (MMC), administered separately or in various combinations, on human stomach cancer cells xenotransplanted into BALB/c nude mice were studied using the protocol of Battelle's Columbus Laboratories (Ovejera et al., 1978). DFMO (1,000 mg/kg in 2 divided doses) and MGBG (50 mg/kg) were given Intraperitoneally (i. p.) for 7 consecutive days from the time when the tumor weighed about 100 mg. MMC (2 mg/kg) was given i. p. every other day from the same time. Animals treated with either DFMO or MGBG alone displayed tumor growth comparable to that seen in untreated controls. In mice treated with DFMO plus MGBG with or without MMC, or in mice treated only with MMC, tumor growth was significantly lower than in untreated mice. In the group which received only combined DFMO/MGBG there was a rapid regrowth of the tumor after termination of therapy. Tumor putrescine levels decreased within 4 days following the administration of DFMO; however, spermidine levels did not decline with either DFMO or MGBG treatment even after 7 days. When combined DFMO/MGBG was given, there was a significant decline in spermidine levels 7 days after the initiation of treatment. In contrast, when MMC alone was administered, putrescine and spermidine levels in the tumor did not differ from those in control mice. Spermine decreased markedly in tumor with the combined administration of DFMO/MGBG as well as with combined DFMO/MGBG/MMC, but decreased only slightly when MMC alone or MMC plus either DFMO or MGBG was administered. By the 7th treatment day, DNA biosynthesis in the tumor had dropped markedly in all groups except those receiving DFMO or MGBG alone.
The value of HLA phenotypes in the prognosis of Hodgkin's lymphoma
Authors: Hafez Mohamed M. , El‐Wehedy Gamal F. , El‐Kholy Nawal M. , El‐Shawaf Ibrahim M. , Gamil Tawakol M. , Mahmoud Mohamed Eissa A.
Published: February 2007

The study included 52 patients with Hodgkin's disease, 32 males and 20 females, whose ages ranged from 3 to 36 years (34 under and 18 over 15 years). All patients were carefully staged, and lymph‐node biopsies were taken for histopathological examination. HLA phenotype determinations were carried out, and the frequencies were statistically compared with those of normal Egyptian controls. We followed the patients for 3 years to monitor the effect of therapy. In order to determine the prognostic value of patients′ characteristics (age, stage, histologic pattern and HLA phenotypes), statistical analysis and retrospective stratification studies were performed. The frequency of HLA‐AI was significantly increased in our patients. The relative risk showed that persons carrying the Al antigen are 6 times more susceptible than those lacking it. There was no significant difference in the frequency of Al antigen in relation to the histopathologic subtypes. Furthermore, the results revealed a prognostic value of the HLA marker. In conclusion, we suggest that chemotherapy should be added to radiotherapy of marker‐positive patients at any stage.
The interaction of melanoma cells with fibroblasts and endothelial cells in three‐dimensional macromolecular matrices: A model for tumour cell invasion
Authors: Schor S. L. , Schor A. M. , Winn B. , Allen T. D.
Published: February 2007

Comparative quantitative data are presented concerning the adhesion, proliferation and invasive behaviour of RPMI‐3460 melanoma cells on (1) plain collagen gels, (2) monolayer cultures of fibroblasts and endothelial cells growing on the gel surface, and (3) the exposed endothelial and fibroblast extracellular matrices (ECMs). Both types of ECMs enhanced melanoma cell adhesion and proliferation (compared with plain gels) and had marked, but distinctive, effects on melanoma morphology. The thickness and composition of the ECMs was altered by treatment of the matrices with enzymes (trypsin, elastase and chondroitinase ABC) or by using ECMs produced by endothelial cells at various times after confluence. Variations in the thickness and composition of the ECMs had no effect on the behaviour of melanoma cells growing on these matrices; our results suggest that the glycoproteins and glycosaminoglycan ECM constituents removed by digestion with the enzymes do not play an important role in melanoma cell attachment, proliferation and migration. Melanoma cells plated on the surface of a plain collagen gel rapidly migrated down into the collagen matrix, with approximately 30% of the cells found within the gel after 6 days of incubation. Fibroblast and endothelial ECMs significantly and distinctively inhibited melanoma invasion into the underlying collagen gel. The extensive invasion of melanoma cells into the gel was not accompanied by hydrolysis of the collagen fibres. Conversely, fibroblast and endothelial ECMs, which acted as effective barriers, were extensively hydrolysed by the melanoma cells. The possible use of ECMs deposited on collagen in the study of melanoma local invasion (on fibroblast ECMs) and extravasation (on endothelial ECMs) is discussed.
Survey of a population with a high incidence of oral and oesophageal cancer
Authors: Zaridze David G. , Blettner Maria , Trapeznikov Nikolai N. , Kuvshinov Juri P. , Matiakin Eugene G. , Poljakov Boris P. , Poddubni Boris K. , Parshikova Svetlana M. , Rottenberg Vera I. , Chamrakulov Farchad S. , Chodjaeva Mamlakat C. , Stich Hans F. , Rosin Miriam P. , Thurnham David I. , Hoffmann Dietrich , Brunnemann Klaus D.
Published: February 2007

The results of a survey of a population with a high incidence of oral and oesophageal cancer are presented. The population under study appears to have several epidemiologic characteristics, some of which may be associated with a high incidence of oral and oesophageal cancer. A remarkably high proportion (41%) of the men surveyed were nass users and this habit, like the use of other types of tobacco mixtures, has been related to oral cancer. Oral leukoplakia and chronic oesophagitis (conditions thought to be precursors of oral and oesophageal cancer) have been diagnosed in 11% and 60%, respectively, of the persons examined. Analysis of the relationship between nass use, cigarette smoking, oral leukoplakia and oesophagitis revealed that the prevalence of oral leukoplakia is highest among cigarette smokers who use nass. It appears that nass use does not affect the frequency of occurrence of chronic oesophagitis. However, a slight elevation of the prevalence odds ratio was observed for current smokers and drinkers. Biochemical analysis of the blood of a random sample of the surveyed population revealed low levels of riboflavin, vitamin A and carotenoids—vitamins that most probably have a protective effect against the development of cancer. The mutagenicity test has shown that nass contains a chemical or chemicals that exert a genotoxic effect. Chemical analysis revealed the presence in nass of tobacco‐specific N‐nitroso compounds.
Differential responsiveness of cloned mammary carcinoma cell populations to the human recombinant leukocyte interferon enhancement of tumor antigen expression
Authors: Greiner John W. , Tobi Martin , Fisher Paul B. , Lancer Jerome A. , Pestka Sidney
Published: February 2007

We have previously shown that a recombinant human leukocyte interferon (IFN‐αA)5 can mediate an increase in cell surface tumor antigen expression in human carcinoma cells but not normal cells (Greiner et al., 1984). Such a biological response modifier may prove useful in circumventing the problem of antigenic heterogeneity and could increase the effectiveness of monoclonal antibodies (MAbs) for detection and/or therapy of human carcinoma lesions. These studies also revealed that, within populations of human carcinoma cells, there exist subpopulations which are unresponsive to the antigen‐enhancing properties of IFN‐αA. Utilizing cloned cell populations from the MCF‐7 human breast carcinoma cell line, we now report the differential responsiveness to the tumor antigen enhancing and antiproliferative actions of IFN‐αA. Binding of MAb B72.3 to the 220‐400 kd tumor antigen, TAG‐72, is increased by IFN‐αA treatment on the surface of the parental MCF‐7 cell line and 2 cloned cell populations. A third MCF‐7 clone does not express this antigen either before or after IFN‐αA treatment, but does express a 90 kd tumor antigen and carcinoembryonic antigen which bind MAbs B6.2 and BI. I, respectively. The level of expression of these 2 surface tumor antigens remained unchanged upon interferon treatment. The growth of the parental MCF‐7 cells and the 3 cloned cell lines was, however, inhibited IFN‐αA. These cell lines also exhibited approximately the same number of interferon receptors with similar binding affinities for IFN‐αA. The results demonstrate a dissociation of two biological actions of IFN‐αA‐antiproliferative activity and enhancement of tumor antigen expression within a cloned human carcinoma cell line. Our studies also indicate that the differential response of cloned MCF‐7 cells to tumor antigen modulation by interferon involves alterations in the transduction of signals occurring distal to receptor occupancy within the biochemical pathways responsible for the actions of this biological response modifier. In addition, the clonal cell lines we have isolated which differ in their responsiveness to interferon should prove valuable in analyzing the molecular basis of interferon actions and may provide insights into the mechanism by which this compound confers its anti‐tumor activity.
Elevated expression of the cellular SRC gene in tumors of differing etiologies in xiphophorus
Authors: Schartl Manfred , Schmidt Carl‐Rudolf , Anders Annerose , Barnekow Angelika
Published: February 2007

In the fish Xiphophorus we have detected elevated levels of pp60c‐src kinase activity in a variety of tumors (n = 34) of neurogenic, epithelial, and mesenchymal origin either of hereditary etiology or induced by carcinogens. This elevation ranged from 2‐fold up to 50‐fold compared to the corresponding non‐tumorous tissue and up to 6‐fold compared to the highest activities found in any of the normal organs. The level of elevation parallels the degree of malignancy in melanoma and in tumors of mesenchymal origin. In fish bearing tumors of hereditary etiology kinase activity was also elevated in the non‐tumorous brain, while in fish bearing induced tumors, kinase activity was elevated only in the cells of the neoplasia.
Humoral response against murine lymphoma cells xenogenized by drug treatment in vivo
Authors: Romani L. , Mage M. G. , Puccetti P. , Fioretti M. C.
Published: February 2007

Treatment of murine lymphomas with triazene derivatives may lead to the appearance of novel drugmediated tumor antigens, a phenomenon known as chemical xenogenization. Such antigens, which are capable of eliciting specific transplantation resistance in histocompatible mice, have been previously detected by in vivo and in vitro cell‐mediated immune responses. In the present report we address the question of the humoral antibody response to a chemically xenogenized lymphoma. Histocompatible mice were given several injections of live cells of the xenogenized tumor. Ten days after each immunization, pooled sera from different animals were analyzed for Ab content by means of flow microfluorometry analysis and CELISA assay. The results reveal that antibodies of both IgG and IgM classes capable of binding the xenogenized tumor can already be detected after one single sensitization. However, the Ab titer gradually increases through subsequent immunizations, reaching a peak level after 3–4 injections at a time when most of the humoral response is made up of antibodies of IgG class. The specificity of the anti‐xenogenized tumor hyperimmune sera was subsequently investigated by its reaction with the parental, nonxenogenized line and with normal tissue cells of the same or allogeneic haplotypes. The data obtained point out that cross‐reactivity with the parental line could be completely removed by absorption of the hyperimmune sera on parental cells, which removed most of the IgM antibodies. Moreover, the presence of an excess of anti‐parental antibodies on the xenogenized tumor cells does not prevent the subsequent binding of the hyperimmune absorbed serum, thus indicating that the novel determinant(s) recognized on xenogenized cells are not spatially related to those shared with the original parental tumor. In addition, the hyperimmune absorbed serum does not crossreact with normal hemopoietic or lymphoid cells of the same (H‐r, or allogeneic H‐t> and H‐r haplotypes. Furthermore, no alien histocompatibility antigens of H‐t> or H‐r haplotypes could be detected on the xenogenized tumor cell surface. Taken together, these data provide evidence that chemical xenogenization of a murine lymphoma leads to the appearance of novel determinant(s) detectable by specific antibodies.