bluuebunny/crossref_metadata_2025 huggingface dataset:
Concentration and time‐dependent inter‐relationships for antitumour drug cytotoxicities against tumour cells in vitro
Authors: Rupniak H. Thomas , Whelan Richard D. H. , Hill Bridget T.
Published: February 2007

Cryopreserved tumour cells obtained from the ascitic fluid of a patient with an ovarian carcinoma were employed to determine the effect on in vitro drug cytotoxicities of varying both drug concentration and exposure time. Four antitumour drugs, in common clinical usage, were selected for study. Tumour‐cell survival following drug treatment was measured by colony‐forming ability in the soft‐agar assay developed by Courtenay et al. (1978). Treatment with cis‐platinum, adriamycin or vinblastine generated exponential survival curves with increasing cell kill resulting from either increasing drug concentrations or prolonging exposure times. In contrast, no detectable cell kill was elicited by treatment with hydroxyurea for short exposure times of 1 or 6 h, even at concentrations as high as 1 mg/ml, although continuous drug exposure resulted in a steep exponential survival curve. These results, obtained directly from biopsy material, are in close agreement with data from parallel studies employing a continuous human tumour‐cell line (COLO 205 derived from a colon carcinoma). Duration of exposure is therefore an important determinant of drug‐induced cytotoxicity under these assay conditions. The results with hydroxyurea, however, imply that prolonged incubation times are necessary to evaluate the cytotoxicity of certain agents and so the routinely employed 1 h exposure in most current human tumour drug sensitivity tests is inadequate for such drugs. These data therefore provide evidence that employing a single set of standard conditions of drug exposure to evaluate all antitumour drugs may be inappropriate.
Enhanced expression of human T‐cell leukemia/lymphoma virus in neoplastic T cells induced to proliferate by phorbol ester and interleukin‐2
Authors: Vyth‐Dreese Florry A. , De Vries Jan E.
Published: February 2007

Peripheral blood T cells from a patient with T‐cell chronic lymphocytic leukemia (T‐CLL) failed to respond to mitogenic lectins or alloantigens but could be induced to proliferate by the addition of exogenous interleukin‐2 (IL‐2). The T‐CLL cells also proliferated in response to 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA), or to TPA in combination with phytohemagglutinin (PHA). These TPA‐mediated proliferative responses were transient, and only small but significant amounts of IL‐2 activity were generated. In contrast, no IL‐2 activity was produced after the T‐CLL cells had been stimulated with PHA only. The T‐CLL cells that were induced to proliferate with PHA and exogenous IL‐2 could be maintained in continous culture by the addition of exogenous IL‐2 at regular intervals. These continuously proliferating T‐CLL cells failed to produce IL‐2 constitutively. However, they could be induced to produce IL‐2 activity by stimulation with TPA or TPA plus PHA. Irradiation of the proliferating T‐CLL cells prior to incubation with TPA or TPA plus PHA resulted in a 9‐fold increase in IL‐2 activity, suggesting that the proliferating T‐CLL cells were able to consume the IL‐2 they produced. Studies on the presence of human T‐cell leukemia/lymphoma virus (HTLV) in the fresh and proliferating T‐CLL cells revealed that 12% of the fresh cells expressed the HTLV p19 structural core protein. HTLV p19 expression was strongly enhanced in the T‐CLL cells induced to proliferate by TPA (66%) and in the continuously growing IL‐2‐dependent T‐CLL cells (82%). In the latter culture, but not in the fresh T‐CLL cells, type‐C virus particles were observed. These results indicate that HTLV expression correlates with T‐CLL cell proliferation but not with IL‐2 production by these cells.
Modulation of K562 cells with sodium butyrate. Association of impaired NK susceptibility with sialic acid and analysis of other parameters
Authors: Werkmeister Jerome A. , Pross Hugh F. , Roder John C.
Published: February 2007

Neuraminidase treatment of parental and butyrate‐induced K562 tumor cells was associated with an increase in natural killer (NK) susceptibility of these target cells. The degree of enhancement with neuraminidase was significantly greater for the NK‐resistant (NRR) butyrate‐differentiated K562 cells so that the relative difference between the parental NK‐sensitive (NKS) K562 line and its induced NKR variants, in terms of NK sensitivity, was no longer five‐ or six‐fold but only two‐fold. The predominant reason for the altered NK susceptibilities of the target cells after neuraminidase treatment was an increase in the target‐cell‐binding ability of these cells as assessed by a direct conjugate‐forming cell assay using Percoll‐enriched NK cells and cold target competition assays. The enhancement did not appear to be due simply to an increased membrane‐membrane attraction caused by a reduction of net negative cell surface charges since protamine sulphate, a positively charged molecule, had no effect on NK activity. Compared with the NKS parental K562 tumor cells, the NKR butyrate‐induced cells had 3.6‐to 4.0‐fold higher sialo‐transferase activities and were associated with significantly greater amounts of cell surface sialic acid detected both in sialyl glycoproteins (2.2‐ to 2.9‐fold higher) and particularly within ganglioside extracts (6.2‐ to 13.6‐fold higher). In conformity with the marked neuraminidase enhancement of NK‐mediated cytolysis of the butyrate‐induced targets, these NKR cells were associated with significantly enhanced levels of neuraminidase‐accessible sialic acid compared to the NKS parental K562 cell line. Other parameters such as sensitivity to superoxide radicals, intrinsic superoxide dismutase levels, altered membrane repair mechanisms and transferrin competition, were not significantly different between the NKS and NKR target phenotypes. Sugar inhibition studies demonstrated an enhanced inhibition against the butyrate‐induced cells with a variety of neutral sugars. The degree of inhibition with phosphorylated sugars was comparable between the parental and induced K562 tumor target cells and is consistent with our previous findings showing that these hexose phosphates may be inhibiting cytolysis at a step independent of target‐cell recognition.
In vitro production of rabbit macrophage tumor cell cytotoxin
Authors: Fisch Harvey , Gifford George E.
Published: February 2007

Rabbit pulmonary lavage cells, consisting mostly of macrophages (90–95%), cultured in the presence of LPS, secreted tumor cell cytotoxin that was similar to tumor necrosis serum cytotoxin. A similar cytotoxin was produced by phorbol‐ester‐pretreated rabbit bone marrow cells and by blood mononuclear cells when cultured in the presence of LPS. All cytotoxins had molecular weights of approximately 48,000 daltons by gel filtration and eluted from DEAE‐Sephadex between 0.28 and 0.32 m NaCl. All were stable to 56°C for 60 min, but labile to 70°C for 20 min. B16C3 melanoma cells and mouse embryo fibroblasts were resistant to the cytotoxins. By 3 h in culture, all effector cells secreted detectable cytotoxin levels. Kinetics of cytotoxin production differed for effector cells derived from the different tissues. No additional cytotoxin production could be demonstrated after 30 h in pulmonary lavage or bone marrow cell cultures, despite a change to fresh medium with LPS. Actinomycin D (1 μg/ml) added with LPS inhibited cytotoxin production (>95%) by pulmonary lavage cells. Delaying addition of actinomycin D after LPS treatment demonstrated that messenger RNA production for cytotoxin was completed by 2 to 6 h.
MHC imbalance and metastatic spread in Lewis lung carcinoma clones
Authors: Eisenbach Lea , Segal Shraga , Feldman Michael
Published: February 2007

Imbalance in the Kb and Db region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high‐metastatic clone show no expression of H‐2Kb products, while the non‐metastatic A9 clone expresses Kb products. Twenty‐nine new subclones of 3LL and A9 were analyzed for D‐end and K‐end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H‐2Kb to H‐2Db is correlated with metastatic properties of a given clone, but local tumor growth is not. A “low Kb/low D9” phenotype is nonmetastatic as is a “high Kb/high Db” phenotype; a “low Kb/high Db” is highly metastatic and a “medium Kb/high Db” is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both Kb and Db expression of A9 and D122 clones yet the net increase of Db was greater than Kb. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the Db gene product on the nonmetastatic A9, clone, without apparent changes in Kb expression. This treatment shifts the A9 to a high‐metastatic phenotype. The significance of this imbalance to the tumor — host relationship is discussed.
Plasminogen activator in normal and tumor‐bearing mice
Authors: Bruesch Margaret R. , Johnson Gail L. , Palackdharry Carol S. , Weber Michael J. , Carl Philip L.
Published: February 2007

The plasminogen activator levels of a series of murine tumors commonly used in cancer drug screening were determined and compared to the levels found in normal mouse tissues. Tumors high in plasminogen activator included the B16 and colon 26. The Lewis lung and M5076 carcinoma showed an intermediate level of activity, while the plasminogen activator activity in the L1210 leukemia and colon 38 was barely elevated above background. The specific activity of the enzyme (per μg protein) in extracts of B16 and colon 26 was three or four times higher than in the most active normal organs surveyed (kidney, lung, brain and intestine). The high level of plasminogen activator activity measured in extracts of the B16 tumor was reflected in a substantial elevation of the levels of fibrin degradation products in the serum of mice carrying this tumor. This result suggests that the tumor‐associated plasminogen activator activity is less subject to inhibitory controls in vivo than is the plasminogen activator of most normal tissues, since the total mass of the tumor was far less than the total mass of the fibrinolytically active tissues, and yet the bulk of the fibrin degradation products were caused by the tumor. We conclude that the high levels of plasminogen activator activity which are observed in many human tumors are found only in some of the transplantable murine tumors. Since this enzyme is active at an increased level in vivo in mice carrying the B16 tumor, plasminogen activator may be a suitable target for selective, enzyme‐activated chemotherapy with this tumor test system.
HLA and nasopharyngeal carcinoma in chinese —A further study
Authors: Chan S. H. , Day N. E. , Kunaratnam N. , Chia K. B. , Simons M. J.
Published: February 2007

This paper reports the results of 8 years of HLA typing of newly diagnosed nasopharyngeal carcinoma (NPC) patients among Chinese in Singapore, and compares the HLA profile of NPC cases with that of the normal Chinese population. Earlier results had indicated an association with A2 and BW46, but the heterogeneity of the earlier case series, which contained a proportion of long‐term survivors, obscured other aspects of the relationship. In this paper, the risk associated with A2 (relative risk = 1.5) and BW46 (relative risk = 1.9) is confirmed, showing a much higher relative risk in the presence of both antigens, and a risk is also demonstrated for B17 (relative risk = 2.1). Relative risks of less than unity are observed for All (relative risk = 0.5) and B13 (relative risk = 0.5). Data from family studies indicate the importance of the haplotype A2.BW46 in determining risk for NPC.
Protective effect of butylated hydroxytoluene against induction of gastric cancer by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in wistar rats
Authors: Tatsuta Masaharu , Mikuni Tomiko , Taniguchi Haruo
Published: February 2007

The effects of butylated hydroxytoluene (BHT) on the incidence and histology of gastric cancers induced by oral administration of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) were investigated in Wistar rats. Oral administration of 1.0% BHT in regular chow pellets during treatment with MNNG for 25 weeks significantly reduced the incidence of gastric cancers in experimental week 40. BHT had no influence on the histological type of adenocarcinomas induced in MNNG‐treated rats. BHT alone induced slight glandular hyperplasia, but not moderate glandular hyperplasia or gastric cancer.
Sodium butyrate produces concordant expression of “early placental” alkaline phosphatase, pregnancy‐specific beta1‐glycoprotein and human chorionic gonadotropin beta‐subunit in a newly established uterine cervical cancer cell line (SKG‐IIIa)
Authors: Nozawa Shiro , Engvall Eva , Kano Shojiro , Kurihara Soju , Fishman William H.
Published: February 2007

The production of early and term placental alkaline phosphatase (ALP), human chorionic gonadotropin betasubunit (β‐hCG) and pregnancy‐specific beta1‐glycoprotein (SP1) was confirmed in the newly established uterine cervical cancer call line SKG‐IIIa. Treatment of these cells in culture with sodium butyrate caused an increase of all of these oncodevelopmental proteins. On the other hand, prednisolone treatment enhanced only term placental ALP, while it reduced early placental ALP, β‐hCG and SP1. These data suggested that such oncotrophoblastic proteins as early placental ALP, β‐hCG and SP1 were con‐cordantly modulated by butyrate and prednisolone. These findings may support the possibility of the reex‐pression of sets of development phase‐specific genes in cancer cells.
Effect of 13‐cis‐retinoic acid and 4‐hydroxyphenyl‐all‐trans‐retinamide on human tumor colony formation in soft agar
Authors: Meyskens Frank L. , Alberts David S. , Salmon Sydney E.
Published: February 2007

We studied the effects of 13‐cis‐retinoic acid (13cRA) and 4‐hydroxyphenyl‐all‐trans‐retinamide (4HPR) on the proliferation of clonogenic human tumor colony‐forming units (TCFU) from patient biopsies in soft agar. Continuous exposure (5 × 10−6M) to 13cRA and 4HPR reduced colony formation to less than 50% of control in 49% and 31% of cases, respectively. This suggests that these retinoids have antiproliferative activity against TCFU. Continuous exposure to 13cRA reduced the number of TCFU to 30% of control in 22.6% of cases while 4HPR reduced colony formation to less than 30% of control in only 10% of patients tested. Prospective in vitro/in vivo correlations for 13cRA indicated that clinical resistance was correctly predicted in 4 of 4 cases treated while clinical response was predicted in 2 of 2 cases (one minor and one partial response). These data suggest that retinoids may have modest antitumor effects and that inhibition of TCFU growth in vitro may be used to screen for such activity.
Effects of anti‐transferrin receptor antibodies on growth of normal and malignant myeloid cells
Authors: Taetle Raymond , Honeysett J. Michael , Trowbridge Ian
Published: February 2007

The effects of three monoclonal antibodies (B3/25, 43/31, and 42/6) reactive with human transferrin (Tf) receptors on growth of normal and malignant myeloid cells were examined using in vitro culture techniques. When added directly to cultures, all three antibodies caused dose‐dependent inhibition of normal granulocyte/macrophage progenitor (CFU‐GM) growth. Monoclonal antibody 42/6 was by far the most potent of the three, with an ID50 of < 5μg/ml. Identical effects were seen on CFU‐GM from three patients with chronic myelogenous leukemia. Growth of colonies from two myeloid leukemia cells lines (KG‐1, HL60) was also inhibited by all three antibodies, and these cells were generally more sensitive than normal CFU‐GM. Blast colony‐forming cells from three patients with acute non‐lymphocytic leukemia were relatively resistant to the antibodies, and CFU‐GM from a patient with myeloid metaplasia were resistant (ID50 > 50 μg/ml) to 42/6. In liquid culture, growth of the leukemic cell lines was inhibited by saturating concentrations of the three antibodies, although in both liquid and colony culture recovery was seen even after exposure to antibody for periods of up to 72 h. Analysis of the cell‐cycle status of these cells showed that the antibodies did not cause accumulation of cells in any particular phase of the cell cycle. Addition to cultures of large quantities of human Tf failed to reverse the inhibitory effects of the antibodies. Competitive binding studies on the leukemia cell lines showed that only 42/6 inhibited binding of Tf to its receptor, although all three antibodies inhibited cell growth. Addition of Fe chelate (as ferric nitriloacetic acid, FeNTA) failed to reverse the inhibitory effects of the antibodies on CFU‐GM and HL60 cells, but had variable effects on KG‐1 cell growth. FeNTA fully reversed inhibitory effects of 42/6 on KG‐1 cells. We conclude that monoclonal antibodies to Tf receptors can inhibit growth of both normal and malignant myeloid cells. Overall, no selectivity for malignant vs normal cells is apparent, although malignant cells from one individual were more sensitive to colony inhibition by 43/31 monoclonal antibody than normal CFU‐GM.
A mouse hepatocyte carbohydrate‐specific receptor and its interaction with liver‐metastasizing tumor cells
Authors: Cheingsong‐Popov R. , Robinson P. , Altevogt P. , Schirrmacher V.
Published: February 2007

Spontaneous high‐metastatic variants (ESb) of the DBA/2 mouse lymphoma L5178Y which show heavy liver involvement were found to form rosettes in vitro with isolated autologous hepatocytes, whilst low‐metastatic sublines of the same tumor (Eb) did not. An analysis of the molecules involved in the hepatocyte:tumor cell interaction was performed by affinity adsorption and SDS‐polyacrylamide gel electrophoresis of 125I‐labelled membrane components from either the hepatocytes or the tumor cells. The hepatocytes were found to bind ESb tumor cells through lectin‐like hepatic binding proteins (HBP) with molecular weights of 52, 56 and 110 Kd and specificity for D‐galactosyl and N‐acetyl‐D‐galactosaminyl residues. More than 10 different cell surface glycoproteins of ESb tumor cells and none of Eb‐type tumor cells served as ligands in the hepatocyte interaction. The low‐metastatic subline Eb formed hepatocyte rosettes only after neuraminidase pretreatment, indicating that lectin binding carbohydrate structures existed in a cryptic form masked on these cells by sialic acid. Although lectin‐car‐bohydrate interactions have been found to play a crucial role in many intercellular recognition processes, this apparently is the first molecular description of such an interaction between organ‐derived normal parenchymal cells and tumor cells. The possible relevance of such an interaction for cancer metastasis is suggested by the finding that spleen‐selected ESb sublines differed from liver‐selected ones in their organotropism as well as in their ability to form hepatocyte rosettes.
Studies of the mechanisms for the induction of in vivo tumor immunity. VII. Development of specific antitumor immunity in progressors and regressors
Authors: Ting Chou‐Chik , Zhang Shu‐Ren
Published: February 2007

The present study was aimed at comparing the development of specific antitumor immunity between hosts with progressively growing tumors and hosts with regressing tumors. The experiments were performed with a Friend virus‐induced leukemia FBL‐3 in syngeneic C57BL/6 mice. The specific antitumor immunity was determined by in vitro cell‐mediated cytotoxicity assay and in vivo tumor neutralization test. Both the systemic immunity (demonstrated in spleen) and immunity developed at tumor site were examined. For progressors, the tumor site was in the peritoneal cavity. For regressors, it was in a subcutaneous site of both flanks. Testing by the cell‐mediated cytotoxicity assay showed that immune hosts and regressors had higher levels of systemic immunity than the progressors. However, when lymphocytes isolated from tumor sites were assayed, it was found that there was no remarkable difference between lymphocytes from progressor tumors (PTL) and lymphocytes from regressor tumors (RTL). Both lymphocyte populations were similar in profile analysis; they were characterized as T cells and possessed the same antigenic specificity. Nevertheless, when in vivo tumor transplantation experiments were performed, RTL were found to give protection against FBL‐3 challenge whereas PTL consistently failed to do so. On cytomorphological examination, the PTL were seen to contain large amounts of macrophages. The presence of macrophages in PTL appeared to have an inverse relationship to the in vivo protective effect. After removal of macrophages from PTL by Petri dish adherence, the non‐adherent PTL were found to give in vivo protection. Furthermore, thymocytes from progressors and macrophages isolated from the progressor tumors were found to suppress the in vivo T‐cell‐mediated immunity. These findings demonstrated that suppressor T cells and suppressor macrophages were present in tumor‐bearing hosts. These suppressor cells could interfere with the function of immune T cells at the efferent arm of the immune response.
Sucrase‐isomaltase: A marker of foetal and malignant epithelial cells of the human colon
Authors: Zweibaum Alain , Triadou Nicole , Kedinger Michèle , Augeron Chantal , Robine‐Léon Sylvie , Pinto Moïse , Rousset Monique , Haffen Katy
Published: February 2007

The presence of sucrase‐isomaltase (SI), a glycoprotein hydrolase normally restricted to the brush border membrane of the enterocytes of the small intestine, was investigated in tumours which developed in nude mice inoculated with six human colon carcinoma cell lines (HT‐29, Caco‐2, HRT‐18, HCT‐8R, SW‐480, and CO‐115). Foetal and normal adult human small intestines and colons were used as controls. SI was studied by (I) immunofluores‐cence with rabbit antibodies raised against purified human small intestine SI; (2) polyacrylamide gel elec‐trophoresis and immunoblotting; and (3) determination of the enzyme activity. SI was antigenically present, and enzymatically active, in all the tumours derived from Caco‐2 and HT‐29 cells. The presence of the enzyme was associated with that of typical brush borders at transmission electron microscopy examination. SI was absent from the tumours developed with the other four cell lines, as well as from the normal adult colon mucosa. SI was also present and active in the colons of mid‐gestation foetuses, ranging in ages between 20 and 28 weeks; it was absent from the colons of late‐gestation foetuses. The presence of SI in tumours derived from two cell lines suggests that this enzyme is a marker, so far unsuspected, of certain human colon cancers, and that the differentiation pattern of these particular cancers closely resembles that of the foetal colon.
Chromosomal aberrations in a case of T‐cell CLL with concomitant IgA myeloma
Authors: Zech L. , Hammarström L. , Smith C. I. E.
Published: February 2007

Four consistent markers, involving chromosomes 8, 11, 14, 18, 21 and 22, were found in the majority of meta‐phases obtained after stimulation of peripheral blood and bone marrow from a patient with a T‐cell chronic lym‐phocytic leukemia (CLL) and a concomitant IgA/lambda myeloma with phytohemagglutinin (PHA), lipopolysac‐charide of E. coli(LPS) and S. aureus strain Cowan I bacteria (Cowan). A second malignant clone with three additional markers was observed after stimulation with Con‐canavalin A (Con A). A chromosome 14 aberration, inv(14) (q11‐q32), may be of significance in the T‐cell malignancy and may suggest a common clonal origin of the two tumors.
Ecotropic MuLV expression in radiation‐induced lymphomas of the RF, BALB/c and (BALB/c × RF)F1 mouse strains
Authors: Dorsch‐Häsler Karoline , Mayer Allen
Published: February 2007

Endogenous ecotropic viruses isolated from radiation‐induced lymphomatous tissue of BALB/c mice have been shown to consist of a collection of variants as assayed by the mobility of virion structural proteins p30, p15, p12 and gp70 on SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE) (Ellis et al., 1980a). In this study we show that a similar phenomenon occurs in RF mice, but only with regard to p15 and gp70, and not p30 and p12. Using the distinct and unvarying mobility of the RF viral p12 protein on SDS‐PAGE as a marker, we show that the RF‐derived ecotropic murine leukemia virus (MuLV) is expressed to the exclusion of the BALB/c‐derived ecotropic MuLV in F1 hybrid mice of the BALB/c X RF cross, and that variant viruses expressed in F1 radiation‐induced lymphomatous tissue display the pattern of variation characteristic of the RF, and not of the BALB/c, strain.
The use of cell fusion to analyse factors involved in tumour cell metastasis
Authors: Ramshaw I. A. , Carlsen S. , Wang H. C. , Badenoch‐Jones P.
Published: February 2007

Cell fusion has been used to study some of the factors involved in the process of metastasis. Highly metastatic rat mammary adenocarcinoma cells were fused with various non‐metastatic cells and the hybrid clones isolated. These were then tested for their metastatic potential either by injecting the cells intravenously and measuring lung colony formation or by injecting the cells subcutaneously and measuring their ability to form lymphatic metastases. With most hybrid clones tested, the metastatic potential was either inhibited or greatly suppressed; thus this phenotype is a recessive characteristic. We also monitored the hybrid cells' ability to produce plasminogen activator (PA) a serine proteinase thought to be involved in the formation of metastatic lung foci. Whilst the highly metastatic parent cells produced large quantities of PA, none could be detected in the non‐metastatic lines. Although the hybrid clones produced little PA activity this could not be correlated with their decreased metastatic potential in that one clone, after extensive in vitro culture, reverted to a more metastatic line without a concomitant increase in PA activity. The suppressed PA activity may be due to the presence of an inhibitor that is spontaneously produced by the hybrid cells.
Studies on chemically induced rat tumors. II. Partial protection against syngeneic lethal tumors by cloned syngeneic cytotoxic T lymphocytes
Authors: Binz Hans , Fenner Martin , Engel Robert , Wigzell Hans
Published: February 2007

In the present article we describe studies on a chemically induced sarcoma in DA rats. This tumor expresses a unique antigen which can be demonstrated by both syngeneic antibodies and cytotoxic T cells. We have established cytotoxic T‐cell lines (CTLs) specific for the tumor and with high efficient killing capacity in vitro. When testing for the ability of such CTLs to inhibit tumor outgrowth in vivo, we found that they had to be inoculated together with the tumor and in the presence of T‐cell growth factor to provide any significant degree of protection. We thus believe not only that there is a requirement for addition of CTL‐stimulating lymphokines in vivo, but also that the CTLs fail to move from one site in vivo to attack relevant tumor cells at another site. No evidence was obtained that the CTLs gradually could acquire such migratory ability in vivo.
High‐grade tumor‐specific immunity induced by L1210 leukemia variants obtained from the culture of L1210 cells fused with Lesch‐Nyhan fibroblasts
Authors: Kawashima K. , Nagura E. , Watanabe E. , Mizoguchi K. , Saga S. , Isobe K. , Nakashima I. , Yamada K. , Oikawa T. , Kojima K.
Published: February 2007

A highly immunogenic variant of the murine L1210 leukemia cell (L1210/LN‐1) for generation of tumor immunity has been obtained from culture of L1210 cells originally fused with human Lesch‐Nyhan fibroblasts. In L1210/LN‐1 cells, no human chromosomes were identified and chromosomes Ml and No. I carried by the parent L1210 cells were missing. L1210/LN‐1 cells displayed an intermediate morphology between L1210 cells and Lesch‐Nyhan fibroblasts. Most of the CDF1 mice that were inoculated with less than 2 × 106 L1210/LN‐1 cells survived over 60 days without evidence of tumor, whereas the original L1210 cells killed all the mice tested in about 2 weeks. When inoculated with more than 5 × 106 L1210/LN‐1 cells, CDF1 mice developed tumor. The CDF1 mice which rejeted 2 × 106 L1210/LN‐1 cells were protected very effectively against challenge of otherwise highly aggressive 1–5 × 105 L1210 leukemia cells; 40 out of 43 primed mice tested survived for 60 days or longer after the tumor challenge. Even the CDF1 mice primed with irradiated or mitomycin‐treated L1210/LN‐1 cells survived against a challenge of 10s L1210 leukemia cells. They were, however, not protected against P388 leukemia or Meth A sarcoma, indicating that the immunity was specific to L1210 leukemia. The immunity induced by L1210/LN‐1 cells was transplantable by immune spleen cells into syngeneic recipients. Thus, the L1210/LN‐1 cells we obtained seem to be very useful as an immunogen for generation of high‐grade tumor‐specific immunity against highly malignant L1210 leukemia.
Antibody formation against the cytotoxic proteins abrin and ricin in humans and mice
Authors: Godal Aslak , Fodstad Øystein , Pihl Alexander
Published: February 2007

Antibody formation may limit the therapeutic use of cancerostatic proteins. To study the significance of antibody formation against abrin and ricin, highly sensitive ELISA procedures for determination of anti‐abrin and anti‐ricin were developed. In mice treated weekly with therapeutic doses of ricin, antibodies appeared after 2–3 weeks and then rose rapidly, whereas after abrin treatment the antibody formation was slower. Ricin A‐chain was found to be more immunogenic than either intact ricin or human serum albumin (HSA). Cyclophosphamide inhibited the antibody response to both abrin and ricin and a combination of cyclophosphamide and prednisolone totally inhibited both anti‐abrin and anti‐ricin formation during the 6‐week observation period. In mice treated weekly with HSA, abrin treatment strongly reduced the anti‐HSA formation, showing that abrin has an immuno‐suppressive effect which appeared to be stronger than that of cyclophosphamide. The existence of circulating antigen‐antibody complexes could be demonstrated in the sera of toxin‐treated mice by precipitation with poly‐ethyleneglycol, whenever antibodies were detectable with ELISA. The life‐span of animals given lethal ricin doses was appreciably enhanced in animals having antibody levels in excess of 10–20 ng/ml. In cancer patients treated i. v. every second week with therapeutic toxin doses, the 10–20 ng/ml levels of anti‐ricin and anti‐abrin were reached 6–8 weeks and 7–10 weeks after the first injection of rkin and abrin, respectively. The data indicate that the effective therapeutic use of abrin and ricin as single agents may be limited to these time frames, but that the period of effective use may be substantially prolonged if the toxins are given together with conventional cytostatic agents having immuno‐suppressive activity.
Reactivity of purified GP40 antigen with antibodies from sera of patients with colorectal cancer: A follow‐up study
Authors: Gazitt Yair , Bentwich Z. , Shani A.
Published: February 2007

A glycoprotein antigen (GP40) was previously identified as a major component of immune complexes isolated from sera of patients with Burkitt's lymphoma. Its reactivity with antibodies from sera of patients with various types of cancer was described. In this presentation we describe the methods for further purification of GP40 from Burkitt's lymphoma sera. Radioiodinated purified GP40 was used in a double antibody precipitation assay, to measure the level of free anti‐GP40 antibodies in sera of patients with colorectal cancer. Follow‐up studies of patients at various stages of the disease revealed a close correlation between the level of free anti‐GP40 antibodies and the stage of the disease, namely, low levels in advanced stages (C‐D) and high levels in early stages (A‐B). Furthermore, patients in remission undergoing chemotherapy always had elevated levels of free antibodies. Similarly, patients in relapse had decreasing levels of free antibodies.
Estrogen and progesterone receptor titers in primary epithelial ovarian carcinomas
Authors: Jones L. A. , Edwards C. L. , Freedman R. S. , Tan M. T. , Gallager H. S.
Published: February 2007

Only 69% (42 of 61) of the documentated ovarian tumor specimens received between September 1981 and August 1982 contained 75% or more viable tumor. Of the 42 measured for estrogen receptors (ER) and progesterone receptors (PR), 34 (81%) had estrogen‐binding titers. ⩾1 fmol/mg of cytosol protein, while 18 (43%) had progesterone‐binding titers ⩾5 fmol/mg of cytosol protein. ER and PR titers were found to be independent of histologic grade, clinical stage, patient age, age at first pregnancy, age at menarche, age at menopause and number of pregnancies. The presence of ER and PR in malignant ovarian tumors suggests that assays positive for these hormones could aid in the selection of patients suitable for hormonal therapy.
Selection by trypsin of two sublines of rat colon cancer cells forming progressive or regressive tumors
Authors: Martin François , Caignard Anne , Jeannin Jean‐François , Leclerc Annick , Martin Monique
Published: February 2007

From an established cell culture line obtained from a chemically‐induced rat colon carcinoma, two sublines have been selected and isolated according to their susceptibility to trypsin‐mediated detachment from plastic surfaces. Subline TR, the most resistant to the detaching effect of trypsin, gave progressive tumors in most of the syngeneic rats in which it was inoculated. Subline TS, which was easily detached by trypsin, also gave tumors in the syngeneic rats, but all these tumors disappeared within 3 or 4 weeks. Both sublines gave progressive tumors when injected into nude mice. This suggests that the parent cell line is heterogeneous and contains cell variants differing in their susceptibility to trypsin‐mediated detachment from substrate and their sensitivity to host factors leading to acceptance or rejection of the inoculated tumor cells.
Tumor immunity to murine plasma‐cell tumors. VIII. Immunosuppression of the generation of cytotoxic T cells by murine plasma‐cell tumor lines
Authors: Giorgi Janis V. , Warner Noel L.
Published: February 2007

Previous studies have clearly established that murine plasmacytomas suppress B‐cell responses, but no effects on T‐cell responses have been noted by most investigators. However, in our investigation of the tumor‐associated antigens of plasmacytomas, we have found that immunosuppression plays an important role in the complex interaction between host immune T cells and tumor cells. In these investigations, varying the number of plas‐macytoma cells added to in vitro induction systems separated two different effects which these cells had on the generation of cytotoxic T cells. On the one hand, when appropriate numbers were present, tumor cells acted as immunogens and stimulated the generation of specific killer cells against tumor‐associated antigen or alloantigen which they expressed. In contrast, greater numbers of tumor cells exerted a profound inhibitory effect on the generation of cytotoxic activity when cells inactivated with irradiation were used. Mitomycin‐C inactivation of plasmacytoma cells abrogated this inhibitory activity. In further experiments, MPC‐11 cells that had been inactivated with Mitomycin C were able to prime T cells in vivo, whereas priming by live tumor cells could not be detected in the same situation. It is suggested that immunosuppression by the live tumor cells may account for their inability to prime T cells in vivo. These results indicate that immunosuppression by plasmacytomas may be one of the important variables which influence the generation of cytotoxic T cells against tumor‐associated antigens both in vivo and in vitro.
Increased antibody responses to Herpes virus papio (HVP) ANTIGENS IN PRE‐LYMPHOMATOUS BABOONS (Papio hamadryas) of the sukhumi high lymphoma stock
Authors: Voevodin A. F. , Yakovleva L. A. , Lapin B. A. , Ponomarjeva T. I.
Published: February 2007

Antibody responses to Herpes virus papio (HVP) antigens were studied in 21 pre‐lymphoma baboons (which subsequently died of malignant lymphoma), 21 paired controls, i.e. age‐, sex‐ and population‐matched healthy baboons, and 185 randomly selected healthy baboons of the same population. The sera were all collected at the same time and were tested blind in the fixed‐cell indirect immunofluorescence test against HVP viral capsid antigen (VCA)‐positive, early antigen (EA)‐positive cell targets before and after absorption with HVP. Eleven of the pre‐lymphoma sera were anti‐EA‐positive whereas none of the paired controls contained anti‐EA. Anti‐VCA titers of pre‐lymphoma sera were higher than those of paired controls in thirteen cases. Only in four cases were anti‐VCA titers of pre‐lymphoma sera lower than those of paired controls. Qualitatively, the same results were obtained when anti‐VCA and anti‐EA titers of pre‐lymphoma sera were compared with respective mean population values. The differences between pre‐lymphoma group and control groups, especially in the case of anti‐EA, were statistically highly significant. Thus, elevated anti‐HVP titers in healthy baboons of the Sukhumi lymphoma‐prone stock can be considered as a marker of high risk for development of malignant lymphoma.
Deoxyribonucleic acid (DNA) content of carcinomas and prognosis in human breast cancer
Authors: Deshpande N. , Mitchell Irene , Allen Diane , Millis Rosemary
Published: February 2007

DNA content was estimated in 705 breast carcinomas from patients with stage I or stage II disease undergoing mastectomy, to investigate whether it would predict the clinical course of the disease. The patients were then followed for up to 84 months during which time 166 of them developed recurrences. There were no statistically significant differences in the DNA content of carcinomas between stage I and stage II patients or between those with various numbers of involved nodes. The tumours from pre‐menopausal patients as a group had significantly higher DNA content than those from post‐menopausal cases. There was a gradual rise in DNA content with the malignancy grade of the carcinoma which showed significant differences between Grades I and III and between II and III. Life‐table analyses showed that the measurement of DNA would not be an aid to prognosis. Furthermore, when the data were stratified according to menopausal status, stage, malignancy grade or numbers of lymph nodes involved, the results indicated that these estimation do not add significantly to the information obtained through established prognostic factors. Survival data were available on 111 patients with recurrent disease. There were no significant differences in tumour DNA content between short‐ and long‐term survivors. It is concluded that these measurements seem unlikely to be a prognostic factor in human breast cancer.
Childhood cancer incidence: Geographical and temporal variations
Authors: Breslow N. E. , Langholz B.
Published: February 2007

Data from the first four volumes of Cancer Incidence in Five Continents (CI‐5) and from the first 5 years of the US Surveillance, Epidemiology and End Results (SEER) program were analyzed for evidence of geographical and temporal variations in the incidence of selected childhood tumors. Only lymphoid leukemia and glial neoplasms are common enough for the observed differences between US registries to be distinguished from sampling variation. Internationally, kidney and eye tumors and leukemia show less geographical variation than do lymphomas and brain tumors, but for none of the tumors examined is the incidence constant Wilms' tumor rates among Japanese, Singapore Chinese and Indians (Bombay) are approximately 60% of the rates in North America and Britain, whereas in Scandinavia the rates are up to 30% higher. This lessens the status of Wilms' tumor as an “index tumor” of childhood. Areas or countries with especially high or low rates of other tumors are identified. Rates for glial neoplasms (SEER data) and Hodgkin's disease (CI‐S) are increasing with time in the US, while brain tumors are being diagnosed more frequently worldwide. However, the results for brain tumors may largely reflect changes in pathology diagnosis or reporting practices, and those for Hodgkin's disease may reflect improvements in case ascertainment. Otherwise, there is a remarkable stability in the incidence of selected childhood cancers over time.
Endotoxin‐induced in vitro release of interleukin‐1 by cancer patients' monocytes: Relation to stage of disease
Authors: Pollack Simon , Micali Anita , Kinne David W. , Enker Warren E. , Geller Nancy , Oettgen Herbert F. , Hoffmann Michael K.
Published: February 2007

The in vitro release of IL‐I by monocytcs in response to endotoxin was subnormal in many patients with breast cancer, malignant melanoma or colorectal cancer but not in patients with benign tumors of the breast or colon. In each of these groups, IL‐I release was low in patients with early cancer, normal in patients with regional metastases, and low in patients with disseminated cancer.
Transformation of different phenotypic types of human bone marrow T‐lymphocytes by htlv‐1
Authors: Markham Phillip D. , Salahuddin S. Zaki , Macchi Beatrice , Robert‐Guroff Marjorie , Gallo Robert C.
Published: February 2007

Fresh bone marrow mononuclear leukocytes were used as a target for infection by human T‐cell leukemia‐lymphoma virus subgroup 1 (HTLV‐1) by co‐cultivation with virus‐positive cell lines. The lines were established from T‐cell leukemia‐lymphoma patients or HTLV‐1‐transformed human umbilical cord‐blood T cells. Clumps of transformed cells became visible by 2–3 weeks after infection and developed at a high frequency (>90%) in the bone marrow samples used. Stimulation of target cells with lymphocyte mitogens facilitated this process but was not absolutely required. Unlike fresh or cultured cells from HTLV‐1‐positive adult leukemia‐lymphoma patients and HTLV‐1‐transformed cord‐blood T cells, which usually have an OKT 4/leu 3a surface phenotype, the transformed bone marrow cells frequently fell into one of three categories based on their reactivity with cell‐specific monoclonal antibodies. These included populations of cells that were predominantly; (1) OKT 4/leu 3a‐positive, (2) OKT 8/leu 2a‐positive, and (3) cells expressing neither phenotype. Fresh bone marrow provided a rapid and efficient system for the assessment of HTLV‐1 infection. The type of bone marrow cells transformed in vitro suggests that HTLV‐1 can infect several subsets of T lymphocytes, possibly including immature cells or that these cells can undergo phenotypic modulation.
Estrogen binding sites on membranes from human laryngeal papilloma
Authors: Essman Eric J. , Abramson Alan
Published: February 2007

Estrogen binding sites were identified on plasma membranes from biopsy materials (N=16) of normal human larynx; such binding was found to be specific. In tissue from 22 cases of laryngeal papilloma, membrane binding of 17‐beta‐estradiol was also specific. Although such binding occurred for papilloma membranes at a comparable affinity, it was clear that all membranes from the papillomatous tissue possessed a 148% greater estrogen binding capacity; there were at least 17 times more estrogen binding sites for each mg of receptor protein on papilloma membrane than for normal laryngeal epithelium. These findings suggest a possible receptor marker for the detection and/or prediction of recurrence of laryngeal papilloma.
Heterogeneity of murine mammary adenocarcinoma cell subpopulations. in vitro and in vivo resistance to macrophage cytotoxicity and its association with metastatic capacity
Authors: Yamamura Yasuhiro , Fischer Beth C. , Harnaha J. B. , Proctor Julian W.
Published: February 2007

Properties of Ts, a long‐term tissue culture line of T1699 mammary adenocarcinoma of DBA/2 mice, and two of its sublines – TR2 and TL1–1 – were comparatively studied. Ts tumors produced no spontaneous metastases, nor did i.v. injection of up to 1 × 106 Ts cells produce a lung tumor nodule. Ts cells were susceptible to macrophage cytotoxicity in vitro and i.v. injected cells were rapidly destroyed in the lungs. TL1–1 tumors spontaneously metastasized to the lungs, and i.v. injection of 1 × 103 TL1–1 cells produced approximately 15 lung nodules per animal. TL1–1 cells were least susceptible to both macrophage‐mediated cytolysis in vitro and in vivo host antitumor mechanisms. TR2 cells were intermediate with respect to all these properties. Differences in their susceptibility to macrophage cytotoxicity were recognized not only by normal peritoneal macrophages but also by murine macrophage lines. On the other hand, all the subpopulations were uniformily resistance to NK activity in vitro. These findings suggest that resistance of tumor cells in vitro to macrophage cytotoxicity corresponds with their in vivo metastatic potential.
Monoclonal antibody against a cryptic carbohydrate antigen of murine and human lymphocytes. I. antigen expression in non‐cryptic or unsubstituted form on certain murine lymphomas, on a spontaneous murine mammary carcinoma, and on several human adenocarcinomas
Authors: Michael Longenecker B. , Raisur Rahman A. F. , Barrington Leigh J. , Purser Ross A. , Greenberg Arnold H. , Willans D. J. , Keller O. , Petrik P. K. , Thay T. Y. , Suresh M. R. , Noujaim A. A.
Published: February 2007

This paper describes an IgM monoclonal antibody (49H.8) which was produced following immunization of BALB/c mice with human neuraminidase‐treated erythrocytes (NE‐RBC). 49H.8 reacts with NE‐RBC, neuraminidase‐treated T lymphocytes (NE‐T) and NE B lymphocytes of both human and murine origin. Little or no reactivity with untreated T or B cells could be detected. Thus the 49H.8 antigen is ‚cryptic’︁ in most normal lymphocytes of both humans and mice. In contrast, the 49H.8 antigen was detected in non‐cryptic or unsubstituted form on many non‐treated murine lymphomas of both B‐ and T‐cell origin, on the spontaneous murine mammary carcinoma, TA3‐HA and on serveral human adenocarcinomas. The 49H.8 antigen appears to be related to the previously described 49H.24 antigen as shown by sugar inhibition experiments. 49H.24 reacts most strongly with the synthetic disaccharide (betaGal (1→3)alphaGalNAc) but not at all with betaGal (1→3)betaGalNac, 49H.24 does not react with any of the murine or human tumors tested. 49H.8 reacts with both the alpha and beta forms of the disaccharide but reacts most strongly with phenyl‐betagalactoside‐containing compounds. In contrast, phenylalpha‐galactoside‐containing compounds produced no reaction. The natural determinant detected by this antibody was not determined but various possibilities are considered. 49H.8 was used to detected antigen apparently shed from growing TA3‐Ha cells into the serum and ascites of tumor‐bearing mice. These observations suggest that the 49H.8 monoclonal antibody will be valuable as a specific reagent for a common tumor‐associated antigen shared by certain murine and human tumors, and as a means of assaying shed tumor antigen in circulation as in the TA3‐Ha mammary adenocarcinoma model.