bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the growth inhibited substate induced in murine hepatic tumor cells during in vitro exposure to dimethylsulfoxide
Authors: Higgins Paul J.
Published: February 2007

Kinetic events associated with the dimethylsulfoxide (DMSO)‐induced inhibition of hepatic tumor cell proliferation were studied using established lines of murine liver tumor cells (BW77‐2 and Hepa‐1/A1) and conditions of polar solvent treatment (1–3% final concentration in the culture medium for a period of 4 days) previously shown to increase the expression of differentiated functions in BW77‐2 cells. Cell‐cycle substates of exponentially growing and DMSO‐treated liver tumor cell populations were compared by flow cytometric techniques employing recently developed cytochemical criteria to identify hepatocyte cell cycle compartments based on individual cellular RNA and DNA contents (Higgins, 1985). Suppression of hepatic tumor cell proliferation by DMSO (in non‐cytotoxic concentrations) persisted only for the duration of the exposure period. Resumption of cell division was readily observed following removal of the polar solvent from the culture medium. During DMSO treatment, BW77‐2 and Hepa‐1/A1 cells accumulated in the G, phase of the cell division cycle (low‐population‐density 3% DMSO‐treated cultures were composed of 88% G1cells compared to only 48% G1 DNA content cells in control cultures of similar population density) and exhibited a substantial shift to lower mean cellular RNA content. The relatively few S‐and G2+M‐phase cells in DMSO cultures also possessed lower RNA contents compared to the corresponding cell cycle compartments in exponentially growing cultures. The mean RNA contents for the G1, S, and G2+M compartments of DMSO‐treated cells approximated 63.8,78.6, and 74.4%, respectively, of the amounts observed in control cultures. Low‐RNA G1 cells in DMSO cultures expressed a continuum of RNA distributions similar in range variation to (but at lower mean cellular RNA content levels than) cycling G1 cells in log‐phase growth. Thus, G1 cells in 1% DMSO‐treated populations had a mean cellular RNA content of just 25 (arbitrary RNA) units compared to over 40 units for G1 cells in exponential phase growth. Low RNA content, non‐replicating, hepatic tumor cells in polar solvent‐treated cultures were designated as being in the “Qi” substate (DMSO‐induced quiescent‐type cells). Release of BW77‐2 cells from Qi, after replacement of the DMSO‐containlng growth medium by medium without the polar solvent, was characterized by an increase in mean G1 RNA content and recruitment into log‐phase growth. Since Qi cells predominate in DMSO‐treated hepatic tumor cell cultures (approximating 90% of the total population) and are unresolved, under control exponential‐phase growth conditions, it is likely that cells of the Qi phenotype participate in the augmentation of liver functions induced as a consequence of DMSO exposure.
EBV‐negative and ‐positive burkitt cell lines variably express receptors for B‐cell activation and differentiation
Authors: Favrot M. C. , Maritaz O. , Suzuki T. , Cooper M. , Philip I. , Philip T. , Lenoir G.
Published: February 2007

The expression of receptors for proliferation and differentiation factors was analyzed by indirect immunofluorescence on 29 Burkitt lymphoma (BL) cell lines previously Classified into 3 groups on the basis of their reactivity with 8 monoclonal antibodies (MAbs), including anti‐CALLA, BL13 and TÜ1. BL13 and HB5antibodies recognize different epitopes of the EBV/CR2 receptors. The determinant recognized by BL13has been previously shown to be expressed only on cell lines of the first two groups, supposed to derive from the germinal center and to be negative on a third group of lines of putative BM origin and established from sporadic cases of BL. In contrast, and as expected from its reactivity on normal B cells in the BM or in the lymph nodes, HB5 antibody reacts with all BL lines except one. The receptor for transferrin is expressed on the 29 lines. Two new MAbs, Bac‐1 and B1H5, could recognize respectively receptors for BCGF1 and BCGF2. Bac‐1 reacts with 15 of 17 BL lines belonging to the first two groups and 7 of 12 BL lines of the third group; 14 of 15 EBV+ lines express Bac‐1. No BL line expresses B1H5. The IL2 receptor is weakly expiressed on 5 EBV + cell lines and one EBV (−) line. All 6 are BCGF1‐positive. The almost constant expression of BCGFI receptor on EBV+ cell lines is the only strict relation between the expression of receptors for growth factors and their characteristics (i.e. EBV association, translocation, ethnic origin and clinical presentation). The maturation stage or the origin of BL cell lines in relation to the expression of growth factor receptors and the functional significance of these receptors will be discussed.
Specific inhibition of human natural killer cell‐mediated cytotoxicity by sialic acid and sialo‐oligosaccharides
Authors: van Rinsum Johanna , Smets Lou A. , van Rooy Henny , van den Eijnden Dirk H.
Published: February 2007

We have tried to identify carbohydrate structures involved in recognition and/or lysis of K562 target cells by human natural killer (NK) cells. Inhibition studies were performed with mono‐, di‐and trisaccharides, and with glycopeptides and glycoproteins of known carbohydrate composition. When tested with various monosaccharides, lysis of K562 cells was inhibited only by N‐acetylneuraminic acid (NeuAc). Di‐and trisaccharides and glycopeptides containing NeuAc or N‐glycolylneuraminic acid (NeuGc) all inhibited NK cell‐mediated lysis. Among the non‐sialylated carbohydrates tested, only Galβ(1→3)GalNAcol was effective. The inhibitory capacity of sialylated compounds appeared to be dependent on the linkage type of the sialic acid residue; carbohydrates containing α(2→6)‐linked sialic acids were more potent inhibitors than their α(2→3) isomers. Also the sugar to which the sialic acid residue was attached was of importance, NeuAcα(2→6)GalNAcol being more effective than NeuAcα(2→6)Galßl→R (where R= glucose or oligo‐saccharide‐peptide). Sialylated compounds and free sialic acid had minor or no effects on cell‐mediated cytotoxicity by allo‐sensitized cytotoxic T lymphocytes. The conjugation of target cells and NK effector cells was not inhibited by carbohydrates that effectively blocked the cytolytic response. These results may indicate that cell‐surface carbohydrates containing α(2→6)‐linked sialic acid are crucial structures in a post‐binding event in NK‐cell‐mediated lysis.
Control of human melanoma growth in nude mice by autologous allo‐activated peripheral blood lymphocytes
Authors: Balsari Andrea , Tona Gabriella , Colombo Mario P. , Fossaati Giuseppe , Parmiani Giorgio
Published: February 2007

Human peripheral blood lymphocytes (PBL) were activated in vitro by means of a pool of allogeneic PBL from normal donors and then evaluated for in vivo activity against human melanoma cells xenografted in splenectomized and irradiated athymic (nude) mice. The subcutaneous (s.c.) growth of human melanoma cells was inhibited by intravenous (i.v.) injection, 2 hr later, of such allo‐activated, autologous and allogeneic PBL in 7/8 and in 6/9 mice respectively. Unstimulated PBL were ineffective. When allo‐activated patients' lymphocytes were administered 3 days after s.c. implantation of autologous melanoma cells, inhibition of tumor growth was observed in 1/6 mice. A significant delay in tumor appearance was noted in the remaining animals. Unstimulated as well as allo‐activated, lymphokine‐releasing helper‐enriched human PBL had no effect on melanoma xenografts, indicating that the tumor inhibition by tumor‐cytotoxic allo‐activated PBL was not due to recruitment of murine immuno‐competent cells by human lymphokines. These results indicate that allo‐stimulated, tumor‐cytotoxic human PBL given i.v. to nude mice can circulate and inhibit the growth of autologous or allogeneic human melanoma cells implanted s.c.
Concordance of histological classification of lung cancer with special reference to adenocarcinoma in osaka, japan, and the north‐west region of england
Authors: Hanai A. , Whittaker J. S. , Tateishi R. , Sobin L. H. , Benn R. T. , Muir C. S.
Published: February 2007

In routinely collected data adenocarcinoma of the lung appeared to be 3 times more frequent in Osaka, Japan, than in the North‐Western (NW) Region of England (Manchester). Before embarking on comparative epidemiological studies, it was decided to investigate the comparability of histological diagnosis. Specimens from 60 NW Region lung cancer patients and 52 Osaka patients were exchanged and reviewed. The entire material was then independently assessed by the WHO Collaborating Center for Histological Classification of Tumours. The interpretation of the WHO Classification (WHO, 1981) by the NW Region and by Osaka was upheld by the WHO Collaborating Center in 89% and 93% of all cases and in 97% and 100% of adenocarcinoma cases respectively. Agreement between the 2 centres was 88% for the main cell types. Differences in the frequency of adenocarcinoma of lung between the NW Region and Osaka are thus not due to diagnostic artefact and require further exploration. The aetiological implications of the finding that many Chinese and Japanese women with lung adenocarcinoma do not smoke (77% in Osaka) are discussed.
Epidemiological and environmental evidence of the health effects of exposure to erionite fibres: A four‐year study in the cappadocian region of turkey
Authors: Baris I. , Artvinli M. , Saracci R. , Simonato L. , Pooley F. , Skidmore J. , Wagner C.
Published: February 2007

An environmental and epidemiological study has been carried out in Central Cappadocia, Turkey, aiming at investigating the relationship between exposure to naturally occurring erionite fibres and the reported high incidence of malignant mesotheliomas. Airborne fibre levels are generally low but show a higher proportion of erionite fibres in the villages affected by malignant disease than in a control village. The same pattern is confirmed by analysis of the fibre content in lung tissues of sheep from several villages, both affected and unaffected by malignant disease. The 3 villages with the highest proportion of erionite fibres have high rates of malignant pleural mesothelioma, malignant peritoneal mesothelioma and lung cancer. No case of malignancy for the same sites has been reported during the study period from the control village. The relationships between these findings and their consistency with the results from experimental studies indicate erionite fibres as a carcinogenic agent, although some aspects of the exposure are not fully clarified.
Surface markers of human lymphokine‐activated killer cells and their precursors. Analysis at the population and clonal level
Authors: Ferrini Silvano , Moretta Lorenzo , Pantaleo Giuseppe , Moretta Alessandro
Published: February 2007

Lymphokine‐activated killer (LAK) activity was first analyzed on PBL populations fractionated on the basis of the expression of TII or T3 antigen. LAK cell precursors were found to be present in both TII+ and TII‐ populations, but only in the T3‐ cell fraction. The generation of LAK activity in highly purified T3‐ populations of PBL was not accompanied by expression of T3 antigen during a 5‐day culture period. LAK activity was next analyzed at the level of limiting dilution clonal microcultures. TII+T3‐ and TII+T3+ cells, cloned under optimal culture conditions, gave a frequency of proliferating cells of approximately I cell in 1.25 for TII+T3+ and I cell in 10 for TII+T3‐ cells. Clones were screened for their ability to lyse fresh ovarian carcinoma cells and K562 target cells. The majority of LAK clones were derived from the TII+T3‐ cells; moreover, most of the clones derived from these cells displayed LAK activity. Clones displaying LAK activity lysed a panel of fresh or cultured tumor target cells, but failed to lyse PHA‐activated lymphoblasts. Surface marker analysis indicated that all the clones had maintained the original TII/T3 phenotype. Whereas 2 T3+ selected LAK clones expressed the T8+T4‐ phenotype, only I out of 9 T3‐ clones was T8+T4‐, all the others lacking both T4 and T8 antigens.
Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma
Authors: Trichopoulos Dimitrios , Tzonou Anastasia , Kaklamani Evangelia , Zavitsanos Xenophon , Koumantaki Yvonne , Day Nicholas E. , Muñoz Nubia , Trichopoulou Antonia
Published: February 2007

Tobacco smoking and alcohol drinking histories were obtained from 194 patients with hepatocellular carcinoma (HCC) and 456 hospital controls, and the results were analysed in conjunction with the results of serological determinations of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti‐HBs) and antibody to hepatitis B core antigen (anti‐HBc) in all subjects, as well as the presence or absence of cirrhosis in HCC patients. The relative risk (RR) of HCC (and 95% confidence interval) among HBsAg‐positive subjects was 13.7 (8.0–23.5), whereas the excess risk among antibody‐positive subjects was small and statistically non‐significant. In the presence of cirrhosis the RR for HBsAg‐positive subjects was considerably higher (30.7 vs. 7.1 among HBsAg‐positive subjects without cirrhosis) indicating that HBV may affect the development of HCC through at least two different and potentially multiplicative mechanisms (DNA integration and liver regeneration). Moderate ethanol consumption does not affect the risk of HCC, but there is a statistically significant and dose‐dependent association between tobacco smoking and HBsAg‐negative HCC. In most of the developed countries of Europe and North America, where the prevalence of HBsAg carrier state is very low and tobacco smoking very common, more cases of HCC may be due to tobacco smoking than to HBV, even though the RR for HCC is much higher among HBsAg carriers than among tobacco smokers.
Co‐expression of human cancer‐associated epitopes on mucin molecules
Authors: Lan Michael S. , Metzgar Richard S. , Bast Robert C. , Colnaghi Maria I. , Knapp Robert C. , Colcher David , Schlom Jeffrey
Published: February 2007

This work describes the immunochemical comparison of mucin‐like high‐molecular‐weight glycoproteins associated with human malignancies that are defined by murine MAbs, DU‐PAN‐2, 19‐9, OC‐125, B 72.3, and Mov 2. These MAbs were originally elicited to human adenocarcinomas from different organ sites such as pancreas, colon, ovary, and breast, respectively. Although each antibody recognizes an antigen on tumors of the same type as the tumor used for immunization, there is often considerable cross‐reactivity with adenocarcinomas from other organ sites. Additionally, these antigens have common properties of large molecular size, high carbohydrate content, and molecular size heterogeneity. Three antigens, CA 19‐9, Mov 2, and DU‐PAN‐2, demonstrated size heterogeneity on agarose gel immunoblotting with their respective antibodies and gave different migration patterns from sera, bile, and pancreatic juice of patients with pancreatic adenocarcinoma. Data from inhibitory double determinant analyses indicated that the DU‐PAN‐2, CA 19‐9, CA 125, TAG‐72, and Mov 2 epitopes are distinct and non‐cross‐reactive. However, immunoblotting and affinity chromatography indicated that both 19‐9 and DU‐PAN‐2 epitopes may be co‐expressed on the same mucin molecule in varying proportions.
Shedding of GD2 ganglioside by human neuroblastoma
Authors: Wu Zi‐Liang , Ladisch Stephan , Feig Stephen , Ulsh Lisa , Schwartz Eileen , Floutsis Grace , Wiley Frances , Lenarsky Carl , Seeger Robert
Published: February 2007

Substantial concentrations of the cell‐surface glycosphingolipid, the disialoganglioside GD2, are uniformly present in human neuroblastoma tumors. This ganglioside can also be detected in the plasma of patients with neuroblastoma by direct thin‐layer chromatographic analysis. Among 32 neuroblastoma patients in all clinical stages studied prior to the initiation of treatment, 27 (84%) showed measurably elevated plasma concentrations of GD2 (≥50 pmol/ml). The mean level (545 ± 108 pmol/ml) was more than 50 times the normal plasma GD2 concentration of ≤ 10 pmol/ml. Circulating GD2 was not detected in the plasma of patients with the related, more differentiated tumors, ganglioneuroblastoma and ganglioneuroma, indicating an association of the shedding of this ganglioside with the undifferentiated phenotype. Circulating GD2 diminished in patients in response to therapy, and reappeared in patients whose disease recurred. The results suggest that the sequential determination of circulating GD2 will be of value in monitoring individual patients with neuroblastoma.
In vitro effects of tamoxifen on UM‐SCC head and neck cancer cell lines: Correlation with the estrogen and progesterone receptor content
Authors: Carey Thomas , Grenman Reidar , Virolainen Erkki , Shapira Amnon
Published: February 2007

Eleven squamous‐cell carcinoma (SCC) cell lines derived from patients with head and neck cancer were tested together with the MCF‐7 breast carcinoma cell line for in vitro growth inhibition by tamoxifen. MCF‐7 is known to contain cytosolic receptors for estrogen (ER), progesterone (PgR), androgen (AR) and glucocorticoid. We have previously reported the ER, PgR and AR contents of these 11 head‐and‐neck SCC cancer lines. Starting from day 3 or 4 after passage, cultures were fed daily with medium containing 5% dextran‐charcoal‐treated fetal bovine serum (D5) and 0, 1, 2.5, 5, 7.5 or 10 μm tamoxifen. Eight of the 11 SCC lines and MCF‐7 showed more than 60% growth inhibition when fed with 5 μm tamoxifen. Of these 8 SCC cell lines, 3 contained both ER and PgR, 4 contained only PgR, and one contained neither receptor. The 3 cell lines that were not inhibited by tamoxifen failed to express either ER or PgR. The action of tamoxifen on the cell lines was further investigated by examining the reversibility and the rate of recovery from tamoxifen‐induced growth inhibition in the presence or absence of estrogen. MCF‐7 and two ER‐ and PgR‐positive SCC cell lines, UM‐SCC‐12 and UM‐SCC‐9, recovered more rapidly when the tamoxifen was replaced with medium containing 17‐beta estradiol (E2) than when it was replaced with D5 medium alone. However, of the other tamoxifen‐inhibited cell lines studied, each recovered equally well whether the tamoxifen was replaced with D5 medium or with D5 medium containing E2. Furthermore, some cell lines spontaneously resumed growth within 4 to 5 days in the presence of tamoxifen if no new tamoxifen was added to the culture dish. This ability is specific for some cell lines, and further study is required to determine its significance.
Establishment and characterization of three new malignant lymphoid cell lines
Authors: Th'ng K. H. , Garewal G. , Kearney L. , Rassool F. , Melo J. V. , White H. , Catovsky D. , Foroni L. , Luzzatto L. , Goldman J. M.
Published: February 2007

We have established 3 new EBV‐negative cell lines, designated Sc‐1, Ri‐1 and Ci‐1, from patients with B‐cell lymphoma/leukemia. We characterized them by cytogenetics and by study of surface membrane antigens with a panel of monoclonal antibodies (MAbs), surface and cytoplasmic immunoglobulin (1g) expression and 1g heavy‐ and light‐chain genes. A11 3 lines had a 14q+ abnormality. Ri‐1 also had translocations involving chromosomes 2, 8 and 18. Ci‐1 also had abnormalities involving chromosomes 2, 8 and 22 and its karyotype was 46, XX, t(2;8), t(14;22). The t(2;8) had the same breakpoints as those reported in some cases of Burkitt's lymphoma. We also studied a classical Ph1‐positive cell line previously established by Pegoraro et al. (1983) and designated BV173. The phenotypes of these 4 lines based on 1g expression and marker studies correlated well with their respective genotypes. Our results are in keeping with the notion that leukaemic cell populations are clonal expansions of cells “frozen” at a particular stage in their differentiation. Specifically, BV173 cells are at an early stage of B‐cell differentiation, Ri‐1 and Ci‐1 cells are at intermediate stages and Sc‐1 cells are at a relatively late stage in the B‐cell lineage.
Alpha‐radiation‐induced amplification of integrated sv40 sequences is mediated by a trans‐acting mechanism
Authors: Lücke‐Huhle Christine , Herrlich Peter
Published: February 2007

Treatment of Chinese hamster embryo cells with alpha irradiation (4 MeV, emitted by 241americium) induces a 15‐fold amplification of integrated SV40 sequences. The extent of amplification depends on the dose of irradiation and on the presence of a functional T‐antigen encoded by the SV40 A gene. The inducing signal can be transmitted to a non‐irradiated nucleus following cell fusion. Amplification is therefore the result of some trans‐acting process, and this could explain how SV40 amplification can occur after doses of alpha irradiation that are too low to cause direct DNA damage within the SV40 replicon.
Reactive T cells in the immune repertoire: Self‐restricted and allo‐restricted helper T‐cell clones to epstein‐barr virus
Authors: Lai Patrick K. , Pauza Mary E. , Switzer Barbara L. , Smith Douglas , Purtilo David T.
Published: February 2007

Helper T‐cell clones were generated by stimulation with autologous or allogeneic lymphoblastoid B cells (B‐LCL) transformed by the Epstein‐Barr virus (EBV). Some of these T‐cell clones were allo‐reactive and others were specific to EBV‐transformed B‐LCL. Helper T‐cell clones specific to EBV‐transformed B‐LCL were restricted either by class‐1 or by class‐11 HLA molecules of self. T‐cell clones restricted by class‐1 HLA molecules were stained by OKT3 and OKT8 monoclonal antibodies (MAbs), whereas class‐11‐restricted clones stained with OKT3 and OKT4. Not all helper T‐cell clones specific to EBV‐transformed B‐LCL were restricted to self: one clone restricted by allo‐HLA antigen was established. This finding suggests that in humans, as in mice, some T cells in the T‐cell repertoire can be allo‐restricted. This allo restriction may represent cross‐reactivity of T cells, whereby “self + X” equals “allo + Y.” Activation of these cross‐reacting T cells restricted by allogeneic HLA molecules during infectious mononucleosis will give a T‐cell response which may appear unrestricted by self HLA molecules. This mechanism helps to explain, at least in part, the HLA unrestricted cytotoxicity to B‐LCL observed in infectious mononucleosis.
Characterization of a novel neuroglandular antigen (NGA) expressed on abnormal human melanocytes
Authors: Sikora L. K. J. , Demetrick D. J. , Dixon W. T. , Jerry L. M. , Pinto A. , Urbanski S. J. , Temple W.
Published: February 2007

Murine monoclonal antibodies (MAbs) were produced with reactivity to human malignant melanoma. Six MAbs, 3 of the IgGI (LS113, LS140, LS152) and 3 of the IgG2a (LS59, LS62, LS76) subclasses, were selected for their binding, with an identical pattern of reactivity, to a novel melanoma‐associated antigen. As characterized by the enzyme‐linked immunosorbent assay (ELISA), these MAbs were found to be positive on n‐octyl‐β‐D‐glucopyranoside extracts of all 10 melanoma cell lines tested and on extracts of 22 metastatic melanoma tumors. The antibodies had minimal reaction with a panel of 14 normal adult tissue extracts. A degree of crossreactivity was observed with 50% of 39 non‐melanoma tumor extracts. The results obtained with the ELISA on cell line and tissue extracts were duplicated using the ABC method of peroxidase staining. The pattern of cross‐reactivity, as demonstrated by the intense staining of paraffin‐embedded and frozen tissue sections of normal, benign and malignant tissues, defines the recognized protein as a neuroglandular antigen (NGA). Immunoadsorbents made with the antibodies were used to purify the antigen shed from cultured melanomas. All 6 MAbs recognized this purified antigen while 5 other antimelanoma antibodies did not react with it. On gel electrophoresis this antigen is a highly glycosylated glycoprotein with a protein core of 21 kDa.
Measurements of passive smoking and estimates of lung cancer risk among non‐smoking chinese females
Authors: Koo Linda C. , Ho Ching‐Yee , Ho John H‐C. , Saw Daisy
Published: February 2007

Lifetime exposures to environmental tobacco smoke from the home or workplace for 88 “never‐smoked” female lung cancer patients and 137 “never‐smoked” district controls were estimated in Hong Kong to assess the possible causal relationship of passive smoking to lung cancer risk. Relative risks based on the husband's smoking habits, or lifetime estimates of total years, total hours, mean hours/day, or total cigarettes/day smoked by each household smoker did not show dose‐response results. Similarly, when such categories as mean hours/day, or earlier age of initial exposure, were combined with years of exposure, there were no apparent increases in relative risk. However, when the data were segregated by histological type and location of the primary tumor, it was seen that peripheral tumors in the middle or lower lobes, or, less strongly, squamous or small‐cell tumors in the middle or lower lobes, had increasing relative risks that might indicate some association with passive smoking exposure.
The plasmin system in human adenocarcinomas and their metastases. A comparative immunofluorescence study
Authors: Burtin P. , Chavanel O. , André‐Bougaran J. , Gentile A.
Published: February 2007

Components of the plasmin system were comparatively studied in lymph node metastases and corresponding primary tumors by immunofluorescence. Primary tumors, all adenocarcinomas, originated from large bowel (N = 12) or breast (N = 10). We used antisera against plasminogen (Pg), plasminogen activators (PA) such as urokinase (UK) and tissue type PA (t‐PA), plasmin inhibitors such as α2 anti‐plasmin (α2AP) and α2 macroglobulin (α2M), plasmin‐α2 anti‐plasmin complex (PAPC). Positivity with anti‐PAPC serum was considered as proving that plasmin was formed by Pg activation. The following results were obtained. 1) Breast adenocarcinomas were more strongly stained than colorectal adenocarcinomas using antisera against Pg, PAPC and PA, while their reactivity was much weaker with antisera against both plasmin inhibitors. 2) Lymph node metastases from colorectal adenocarcinomas were more strongly stained than primary tumors using antisera against PAPC and PA. Reactivity with anti‐Pg was similar, while that with antisera against plasmin inhibitors was much weaker. 3) Metastasis from breast adenocarcinomas, on the average, showed the same type of staining as primary tumors. However, there was a slight decrease in reactivity with anti‐Pg and PAPC in metastases. 4) Tumor cells invading lymphoid areas in metastatic lymph nodes were often strongly labeled using antisera against Pg and UK. Staining was less strong or less frequent using antisera against PAPC and t‐PA. These results favor the role of plasmin in the degradation of basement membrane and connective tissue components, thus implicating it in the invasiveness of tumor cells, at least in most primary tumors and metastases.
HLA studies of endemic african kaposi's sarcoma patients and matched controls: No association with hla‐DR5
Authors: Melbye Mads , Kestens Luc , Gigase Paul L. , Biggar Robert J. , Schreuder Geziena M. T.
Published: February 2007

In the search for a genetic factor involved in the etiology of Kaposi's sarcoma, several studies have recently focused on a significantly increased HLA determinant, DR5, as well as a decreased DR3, among patients with both the classical and the AIDS‐related form of Kaposi's sarcoma. To test the consistency of this phenomenon, we analysed the frequencies of HLA immunogenetic markers in 23 histologically confirmed Kaposi's sarcoma patients from Central Africa, where this tumor is endemic, and a local sex‐ and tribe‐matched control group. No definite association was observed for any of the HLA antigens, including DR5 and DR3. We were not able to support the hypothesis that the same HLA‐associated immune susceptibility factors are involved in all types of Kaposi's sarcoma.
Presence of circulating antibodies against cellular protein p53 in a notable proportion of children with B‐cell lymphoma
Authors: De Fromentel C. Caron , Chandrasekaran K. , May P. , May‐Levin F. , Mouriesse H. , Lemerle J.
Published: February 2007

Serum samples taken from children bearing a wide variety of tumors were screened for the presence of circulating antibodies against the cellular tumor antigen p53. There was a significant correlation (p<0.001, n = 119) between the presence of such antibodies and the occurrence of cancer; 12% of the sera tested were positive. These sera were derived from children with a wide range of tumor types. In particular, 21% of the sera obtained from children suffering from a B‐cell lymphoma contained anti‐p53 antibodies. We were not able to establish a correlation between the secretion of p53‐reactive antibodies and any other parameters, such as the age or sex of the child, presence of metastasis, stage or prognosis of disease, or treatment regimen. These results therefore show that the development of p53 immunogenicity is associated with a wide range of neoplastic diseases in children, and in particular with the presence of a B‐cell lymphoma.
Expression of B‐cell‐specific markers in different burkitt lymphoma subgroups
Authors: Ehlin‐Henriksson Barbro , Manneborg‐Sandlund Agneta , Klein George
Published: February 2007

Forty‐three Burkitt lymphoma (BL) lines were examined for the expression of 5 monoclonal antibody (MAb)‐identified B‐cell‐specific markers and immunoglobulin production. All (13) EBV‐negative BL lines were CALLA+LB‐I‐, whereas 30 EBV‐carrying lines showed a more heterogeneous pattern. In the EBV‐negative lines, the follicle mantle zone markers BA‐I and 35.IC5 were expressed concordantly, at a different level in each line. This coordination was disrupted in EBV‐carrying lines. In the EBV‐negative lines, there was also an inverted correlation between the expression of 35.IC5 and the germinal center marker BLA, suggesting that some etiologically important event, perhaps the translocation, had fixed the cells at different stages of their transition from one zone to the other. This inverted relationship was also disrupted in the EBV‐carrying lines, suggesting that EBV can interfere with the maturation program of the BL cell. This conclusion was also supported by a comparison between 5 EBV‐negative BL lines and their EBV‐converted sublines. All converted lines have undergone marker changes, but the degree and nature of these changes was different for each EBV‐BL line. Both the coordinated expression of BA‐I and 35.1C5 and the inverted relationship between CALLA and LB‐I were disrupted in several other convertants. We have reexamined our previous finding (Ehlin‐Henriksson and Klein, 1984) that the majority of the variant translocation‐carrying BL lines were CALLA‐LB‐I +, in contrast to the majority of the typical translocation carriers that were mostly CALLA+ LB‐I‐. All II EBV‐negative lines were CALLA+ LB‐I‐, irrespective of the type of translocation. Among the EBV‐carrying lines, 4 of 17 typical (8; 14) translocation carriers were CALLA‐LB‐I +, whereas 7 of the 12 variant translocation‐carrying lines were CALLA‐ LB‐I+. The remaining two expressed both antigens to some extent. The difference is statistically significant at the 0.03 level.
The inability of adoptive immunotherapy to eradicate tumor cells in radiation‐induced chimeric mice: The possible down‐regulation of intratumor immune amplification
Authors: Evans Robert , Duffy Theodore M.
Published: February 2007

Tumors were eradicated following adoptive immunotherapy of (C57BL/6J x DBA/2J) F1 (B6D2F1) hybrid mice bearing the C57B1/6J (B6) sarcoma, MCA/76‐9, by treatment with cyclophosphamide (CY) and adoptively transferred tumor‐sensitized B6D2F1 T cells. Identical treatment of B6→ B6D2F1 or DBA→ B6D2F1 chimeric tumor‐bearing mice resulted in temporary tumor regression only. Immunotherapy in both systems resulted in the appearance at the tumor site of large numbers of T lymphocytes and macrophages, which were shown to be derived from the adoptively transferred donor immune B6D2F1 cells or from the original reconstituting bone marrow respectively. The TAC and TAL isolated from either B6D2F1 or chimeric mice expressed potent toxicity in vitro towards tumor target cells. In addition, TAC from both systems inhibited tumor growth in a Winn assay in an immunologically specific manner. Suppressor cells detected in spleens 8 days after CY injection of normal B6, DBA, B6D2F1 hybrid and chimeric mice and also after adoptive immunotherapy of tumor‐bearing B6, B6D2F1 and chimeric mice and were shown to persist in the spleens of chimeric mice for at least 31 days after adoptive immunotherapy. In contrast, spleen cells taken 31 days after therapy of B6D2F1 mice did not contain detectable suppressor cells and were able to induce tumor eradication when adoptively transferred to CY‐treated tumor‐bearing B6D2F1 mice. The possibility is discussed that two forms of suppressor mechanisms are induced after adoptive immunotherapy of chimeric mice and that they may down‐regulate donor T cell responses at the tumor site.
Generation of activated killer cells in tumor‐bearing hosts
Authors: Ting Chou‐Chik , Hargrove Myrthel E. , Stephany David
Published: February 2007

Activated killer (AK) cells were generated in spleen‐cell cultures derived from tumor‐bearing hosts (TS) whereas, under the same conditions, cultured normal spleen cells (NS) gave little cytotoxicity. The AK effectors were primarily Thyl+, AGMI‐ and Lyt2‐ and thus were neither classic cytotoxic T lymphocyts (CTL) nor classic NK cells. These AK cells selectively killed tumor targets of different etiologic origins and did not kill concanavalin‐A‐induced lymphoblasts. The broad target‐cell reactivity of these AK cells was also confirmed by cold target‐inhibition experiments. Generation of AK cell correlated with interleukin‐2 (IL‐2) production, and the levels of AK cells generation paralleled those of IL‐2 production. Furthermore, the generation of AK cells was blocked by the anti‐IL‐2 receptor monoclonal antibody (MAb) (αIL‐2R), indicating that IL‐2 was involved, and thus these AK cells were lymphokine‐activated killer (LAK) cells. We previously showed that the expression of AGMI on LAK precursors disappeared when they differentiated into LAK effectors, indicating that the activated LAK cells lacked AGMI. When examining the serologic phenotype of the LAK precursors in tumor‐bearing hosts, we found that they lacked AGMI, which suggested that these LAK precursors were in an “activated” state. These cells were still Thyl‐, and were thus different from fully activated LAK effectors which were Thyl+ cells, indicating that the full differentiation of LAK cells in vivo was arrested in the tumor‐bearing hosts. We also found that the presence of small amounts of X‐irradiated tumor cells prevented the generation of AK cells. These findings suggest that, in the tumor‐bearing hosts, the presence of tumor cells triggers the activation of AK precursors; however, the same tumor cells may also be immunosuppressive, which prevents the full differentiation of AK precursors into AK effectors.
Characterization of an animal model of metastatic colon carcinoma
Authors: Dunnington Damien J. , Buscarino Charles , Gennaro Doris , Greig Russell , Poste George
Published: February 2007

Although numerous animal tumor models have been used to study colon carcinoma, few display metastatic properties. We have characterized an animal tumor model that has 3 properties essential for the study of metastasis of colon carcinoma cells: epithelial cell origin; a reproducible pattern of metastatic behavior and the ability to be propagated both in vitro and in vivo to facilitate identification of biochemical correlates of metastasis. The KI2/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD‐IX rat strain. Transmission electron microscopy of KI2/TR cells demonstrated junctional complexes, desmosomes and surface microvilli characteristic of gastrointestinal epithelial cells. The epithelial cell origin of KI2/TR was confirmed by demonstrating the presence of keratin, a marker of epithelial cells, but not vimentin, a constituent of mesenchymal cells. Secretion of CEA and Ca19‐9 antigens by KI2/TR cells in vitro was below the sensitivity of the assays (1 ng/ml and 6 U/ml respectively). KI2/TR cells produced tumors following s.c. injection into syngeneic BD‐IX rats, allogeneic RNU/rnuDF rats and xenogeneic CRL:nu/nuBR mice. Macroscopic lung metastases were observed in animals from all 3 groups. Distal lymph node metastases were more frequent in BD‐IX rats than in nude rats or mice. The histological appearances of all tumors and metastases were similar, showing a moderate to poorly differentiated glandular carcinoma. Intrasplenic injections of KI2/TR cells in nude mice resulted in liver colonization. Preferential growth of tumor cells at sites of trauma was also observed. The results show that the KI2/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions.
Studies of skin tumorigenesis in pgk mosaic mice: Many promoter‐independent papillomas and carcinomas do not develop from pre‐existing promoter‐dependent papillomas
Authors: Reddy A. L. , Caldwell Mark , Fialkow Philip J.
Published: February 2007

The induction of mouse skin papillomas in two stages by initiation‐promotion protocols has been studied extensively. On the basis of kinetics of induction and morphological observations of apparent progression to carcinomas, it has been argued that the papillomas sequentially advance to carcinomas through promoter‐dependent and promoter‐independent premalignant stages. Although this hypothesis has been widely accepted, the step‐wise development of the same cell population from papilloma to carcinoma has not been established at the cellular level. We show here that some carcinomas which morphologically appear to result from progression of promoter‐dependent papillomas do not develop from sequential progression of the same cell population as was found in the original papillomas. Other initiated cells also participate during the growth of these tumors and may replace the original papilloma cells. We also present evidence that some tumors develop directly as promoter‐independent papillomas without going through an apparent promoter‐dependent papilloma stage.
Delta agent and the etiology of hepatocellular carcinoma
Authors: Trichopoulos Dimitrios , Tzonou Anastasia , Kaklamani Evangelia , Hatzakis Angelos , Day Nicholas E. , Muñoz Nubia , Hadziyannis Stefanos , Sparos Loukas
Published: February 2007

Sera from 87 patients with hepatitis B surface antigen (HBsAg)‐positive hepatocellular carcinoma (HCC) and from 29 HBsAg‐positive hospital controls were tested for delta (δ) antigen with an immunoenzymatic procedure and for anti‐δ antibody, hepatitis Be antigen (HBeAg) and antibody to HBeAg (anti‐HBe) by radioimmunoassay. All the sera, from both the HCC cases and the control patients, were negative for δ‐antigen. Among the HCC cases 9 were positive for serum anti‐δ (10%) whereas among the controls none was positive for this antibody (p = 0.067); the anti‐δ‐positive cases were found only among HCC patients negative for HBeAg. The lower prevalence of anti‐δ among HBsAg‐positive HCC patients, as compared to the corresponding prevalence among HBsAg‐positive patients with chronic active hepatitis or cirrhosis (reported in the literature) indicates that the pathogenesis of HCC is frequently independent of the pathogenesis of the other HBsAg‐positive common chronic liver diseases. By contrast, the higher prevalence of anti‐δ among HBsAg‐positive HCC cases than among HBsAg‐positive controls may reflect the longer average duration of the carrier state in HCC patients (until integration is accomplished and the induction period completed). Serum HBeAg was higher among HBsAg‐positive HCC patients with cirrhosis (23%) than among HBsAg‐positive HCC patients without cirrhosis (6%) or HBsAg‐positive controls (3%); thus, the conflicting results in the literature concerning the association of the HBeAg/anti‐HBe system with HCC may be accounted for, in part, by the variable association of HCC with an underlying cirrhosis.
Volatile nitrosamine levels in common foods from tunisia, south china and greenland, high‐risk areas for nasopharyngeal carcinoma (NPC)
Authors: Poirier S. , De‐Thé G. , Hubert A. , Ohshima H. , Bourgade M. C. , Bartsch H.
Published: February 2007

On the basis of anthropological pilot studies on diet in Tunisia, south China and Greenland, food items consumed frequently by these populations at high risk for NPC were analysed for volatile nitrosamines using gas chromatography combined with a thermal energy analyzer. Relatively high levels of N‐nitrosodimethylamine (NDMA), N‐nitrosopyrrolidine (NPYR) and N‐nitrosopiperidine (NPIP) were detected in Tunisian stewing base (“Touklia”) and dried mutton preserved in olive oil (“Qaddid”). NDMA was also detected at levels ranging from trace amounts to 133 μg/kg in several Chinese salted and dried marine fish and in Greenland dried, unsalted fish preparations. NPYR and NPIP were also occasionally detected in several vegetables fermented in brine collected in Tunisia and China. The possible role of nitrosamines in the etiology of NPC is discussed.
Monoclonal antibodies to human colorectal epithelium: Markers for differentiation and tumour characterization
Authors: Richman P. I. , Bodmer W. F.
Published: February 2007

A panel of monoclonal antibodies (MAbs) has been obtained, directed against determinants of normal human colorectal epithelium. BALB/c mice were immunized and boosted with mucosal scrapings and cell membrane preparations from normal large intestine. In one case boosting was also performed with HT29 colon carcinoma cells. Hybridoma supernatants were screened immunohistochemically on frozen sections of normal colorectal epithelium, leading to the selection of 12 MAbs which recognized determinants of the major epithelial cell lineages. These antibodies fall into two groups: group I antibodies react with mucus constituents, with or without other cell components; group 2 antibodies react only with non‐mucus components of cells.

The normal tissue distribution of the antibody panel has been characterized immunohistochemically. Three of the mucus‐reactive group‐1 antibodies, PR.4D4, PR.5D5 and PR.3A5, and also PR. IA3 of group 2, have a very restricted distribution. In all 4 cases, their reactivity outside the gastrointestinal tract is mainly confined to tracheal epithelium.

A series of benign and malignant colorectal tumours has been studied with the antibody panel. The antibodies of group 1, and PR. 1A3 from group 2, show a marked heterogeneity in their reactions with malignant cells and seem to be defining patterns of functional differentiation, independently of standard histological criteria. The reactivity of 6 colorectal carcinoma cell lines has also been assessed with the antibodies. The group‐1 antibodies and PR.1A3 identify those cell lines which have retained some capacity for differentiation.
Sister chromatid exchange induction by benzo(a)pryene in cultured peripheral blood lymphocytes of lung cancer patients and healthy individuals with or without familial history of neoplasms
Authors: Dosaka Hirotoshi , Miyamoto Hiroshi , Kawakami Yoshikazu , Abe Syuiti , Sasaki Motomichi
Published: February 2007

The inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene (BP) was studied in cultured peripheral blood lymphocytes of 15 untreated lung cancer patients and 25 healthy persons including 11 high‐ and 14 low‐cancer‐risk individuals tentatively classified by the familial history of lung cancer and other neoplasms. The baseline SCE frequency in cultured lymphocytes was significantly high in lung cancer patients, as compared with all healthy persons or low‐cancer‐risk individuals. Following exposure to BP, the lymphocytes of lung‐cancer patients and high‐cancer‐risk individuals exhibited significantly greater SCE yields than those of persons at low risk, although no significant difference was observed in the lymphocyte SCE yields when the levels of lung cancer patients were compared with those of all healthy persons. A comparison of the net SCE increase (ΔSCE) in BP‐exposed lymphocytes among the study groups, however, revealed a significant difference in ΔSCE values only between high‐ and low‐cancer‐risk individuals. The present findings on both the observed SCE yields and ΔSCE values suggest that lymphocytes of high‐risk individuals may be more susceptible to BP‐induced DNA damage than those of persons at low risk, and that such a chromosomal hypersensitivity to genotoxins may be associated with a high risk of neoplasms.
High incidence of egf receptor hyperproduction in esophageal squamous‐cell carcinomas
Authors: Ozawa Soji , Ueda Masakazu , Ando Nobutoshi , Abe Osahiko , Shimizu Nobuyoshi
Published: February 2007

EGF receptor levels were investigated in esophageal squa‐mous‐cell carcinoma tissues from 31 patients. Twenty‐two (71%) of these cancer tissues exhibited significantly higher 125I‐EGF binding activity than normal mucosa in the adjacent noncancerous tissues. These EGF receptor levels were then compared on the basis of pathological findings including lymph‐node metastasis, depth of invasion, differentiation type, vascular invasion, infiltration and location of the lesion. Unlike previous reports on breast and bladder cancers, our study showed no obvious correlation between these pathological characteristics and the EGF receptor levels in esophageal carcinomas. Immunohistochemical staining with the anti‐EGF receptor monoclonal antibody detected EGF receptors in squamous cells of the cancer tissues as well as in the basal cells of nearby normal epithelium. Since the basal cells have proliferative potential in the esophagus, the increase in EGF receptor levels in these cells may possibly be associated with the development of human esophageal squamous‐cell cancer.
Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5‐azacytidine
Authors: Ishikawa Makoto , Okada Futoshi , Hamada Jun‐Ichi , Hosokawa Masuo , Kobayashi Hiroshi
Published: February 2007

The effect of quercetin, a flavonoid derivative, on the transplantability (tumorigenicity) and metastatic behavior of mouse tumor cells was studied. BMT‐11 cl‐9 fibrosarcoma cells were treated in vitro with quercetin, and after cloning by limiting dilution, cell suspensions of each clone were injected subcuta‐neously (s.c.) into syngeneic C57BL/6 mice at a dose of 2 × 105 cells per mouse. Out of 17 clones examined, 8 were nontumorigenic in normal mice (“regressor” clones), whereas these clones were able to grow in immunosuppressed (600‐rad‐irradiated) mice. Furthermore, 1 out of 9 tumorigenic clones metastasized spontaneously to the lungs despite the very low metastatic potential of the parent BMT‐11 cl‐9 cells. In contrast, all 15 clones selected from the untreated parental line grew progressively in normal mice with no evidence of metastases. The appearance of both regressor and metastatic clones was also observed after treatment with a DNA hypomethylating agent, 5‐azacytidine. These altered phenotypes resulting from treatment with both chemicals, however, were not necessarily stable if maintained in culture for several months. The data suggest that quercetin may be a useful new material for obtaining regressor or metastatic clones from parental tumor lines.