bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal antibodies directed against rat tracheal epithelial cells transformed in vitro
Authors: Braslawsky Gary R. , Kennel Stephen J. , Hand R. E. , Nettesheim Paul
Published: February 2007

Cloned hybridoma cell lines were obtained by fusion of murine myeloma cells with spleen lymphocytes of either F344 rats or BALB/c mice immunized against the malignant F344 tracheal cell line, 2–10–1. Monoclonal antibodies were selected for their ability to bind to the immunizing cell line and not to normal tracheal epithelial cells. Results from quantitative binding assays indicated that such monoclonal antibodies recognized six epitopes. Each epitope was detected on four other malignant tracheal epithelial cell lines, and was also expressed during early preneoplastic cell passages (i.e. before the cells acquired the ability to produce carcinomas in vivo). Quantitative differences in epitope expression between non‐tumorigenic and tumorigenic passages of individual cell lines could not be detected for five of the epitope groups. However, two monoclonal antibodies, recognizing the same epitope, did show quantitative binding differences between non‐tumorigenic and tumorigenic cell passages on three of the five cell lines tested. Our results show that carcinogenaltered tracheal cell populations can be distinguished from non‐altered cells (by our current assay methods) by use of monoclonal antibodies. The suggest that the antigen expression is an early event associated with the transformation of rat tracheal epithelial cells in culture.
Age at first birth and breast atypia
Authors: Hsieh Chung‐Cheng , Walker Alexander M. , Trapido Edward J. , Crosson Ann W. , Macmahon Brian
Published: February 2007

The relation between age at first birth and the occurrence of fibrocystic breast disease of different atypia subtypes was evaluated using data from a cohort study of the health effects of oral‐contraceptive use. Multivariate case‐control analysis was performed on 218 parous women with biopsied fibrocystic disease and 928 parous controls. Fibrocystic breast disease, as a whole and as atypia subtypes, was found to be unrelated to age at first birth. Furthermore, the estimated effect of age at first birth did not vary from one atypia subtype to another. Women with high parity were found to be at decreased risk of fibrocystic breast disease compared to those with low parity. Age at completion of education, used as an indicator of socio‐economic status, was found to be moderately associated with fibrocystic breast disease. The estimated effect of parity and age at completion of education also did not vary among subtypes. More epidemiologic studies specific to histopathologic classifications of benign breast disease are called for.
The serologically unique cell surface antigen of zajdela ascitic hepatoma is also its tumor‐associated transplantation antigen
Authors: Srivastava Pramod K. , Das M. R.
Published: February 2007

A unique cell surface antigen of a chemically induced rat hepatoma (Zajdela Ascitic Hepatoma, ZAH) has been identified serologically and purified to apparent homogeneity. ZAH cells, when injected subcutaneously or intradermally into syngeneic hosts, elicit a weak humoral antibody response directed against a single cell surface antigen. In spite of prolonged and extensive immunization, the syngeneic anti‐tumor antibodies are solely of the IgM class. Antisera from such immunized animals lyse tumor cells in the presence of complement. These observations were utilized in developing methods for the identification and purification of the antigen. It was observed that administration of purified preparations of this antigen confers ZAH‐specific tumor immunity in syngeneic animals. Hence the serologically unique antigen is also the tumor‐associated transplantation antigen (TATA) of this tumor. This the first reported purification of a TATA from a rat tumor. There is considerable earlier evidence for the existence of tumor‐associated factors which elicit a strong suppressor‐cell response in tumor‐bearing rats. The availability of the purified TATA from a rat tumor provides, for the first time, a handle for the identification and further characterization of such molecular species.
Purification of a specific inhibitor of reverse transcriptase from human placenta
Authors: Leong Joann C. , Wood Scott O. , Lyford Arthur O. , Levy Jay A.
Published: February 2007

Human placental extracts contain a factor which specifically and reversibly inhibits the reverse transcriptase of mammalian retroviruses. This placental inhibitor has been partially purified and characterized. It elutes at 0.1–0.2 M phosphate on hydroxyapatite chromatography and can be further purified by phosphocellulose chromatography where it elutes at 0.4 M KCl. By these purification procedures, specific activities of 40–70,000 units of inhibitor per mg of protein were obtained. The size of the inhibitor is about 60–65,000 daltons as estimated by velocity sedimentation. The inhibitor purified by these techniques selectively inhibits the activity of purified reverse transcriptase from Rauscher murine leukemia virus and baboon endogenous virus. It is substantially less active against the reverse transcriptase of avian myeloblastosis virus. The specificity of this inhibitor for mammalian enzymes and particularly for the human placental reverse transcriptase suggests that it plays a role in the regulation of DNA synthesis in human placental development.
Binding of murine immunoglobulin to human tissues after immunotherapy with anticolorectal carcinoma monoclonal antibody
Authors: Shen Jun‐Wen , Atkinson Barbara , Koprowski Hilary , Sears Henry F.
Published: February 2007

An anticolorectal carcinoma antibody, 17–1A, that is of gamma 2a isotype and has been used in previous immunotherapy trials, binds to an antigen on most human colon tumors. This antigen is destroyed by the fixative and embedding procedures employed for routine histologic evaluation of tissues. It can be demonstrated by the avidin/biotin‐labelled peroxidase complex (ABC) immunoperoxidase technique on briefly fixed, frozen sections of fresh human tissues. With this assay technique, the antibody is found to bind in vitro to both human colonic carcinoma and normal gastrointestinal epthelia. Tissues removed from patients having received the 17–1A antibody intravenously in an immunotherapy trial show bound antibody 1–2 after administration. This is no longer evident 3 weeks later though the antigen is present on the cell surface and is still capable of binding antibody in vitro.
Generation of crossreacting tumor antigens in ascitic derivatives from murine methylcholanthrene‐induced sarcomas
Authors: Law Lloyd W.
Published: February 2007

Sarcomas induced by the chemical carcinogen 3‐methyl‐cholanthrene (MC) in pedigreed BALB/c strain mice were studied for the existence and characteristics of tumorspecific antigens that induce protective immune defenses in syngeneic mice (TATA). It was found that each of the neoplasms expressed a unique immunogenicity that was stable and heritable over a period of 125 transfers in vivo. Common or crossreacting TATA were not observed. When converted to an ascitic form, two of these sarcomas, CII‐7 and CII‐10, were found to be crossreactive, presumably sharing TATA with each other and with the MC‐induced sarcoma Meth A. Two other neoplasms converted to the ascitic form, however, retained their unique TATA. Although the precise nature of unique and crossreacting TATA is not known, it is hoped that recent investigations in the purification of TATA of chemically induced neoplasms will shed light on the mechanisms responsible for the diversity of tumor‐specific antigens.
Patterns of lung cancer risk according to type of cigarette smoked
Authors: Lubin Jay H. , Blot William J. , Berrino Franco , Flamant Robert , Gillis Charles R. , Kunze Michael , Schmahl Dietrich , Visco Giuseppe
Published: February 2007

A case‐control study of lung cancer involving interviews with 7,804 cases and 15,207 hospital‐based controls was carried out in seven locations in Western Europe. The large study size permitted the calculation of precise estimates of the relative risk of lung cancer associated with smoking different types of cigarettes. Lifelong nonfilter smokers were at nearly twice the risk of lung cancer compared to lifelong filter smokers after controlling for duration of cigarette use and number smoked per day (RR = 1.7 for males and 2.0 for females). Lung cancer risks for filter, nonfilter and mixed smokers increased in proportion to intensity and duration of smoking and decreased with years since stopping smoking. The findings indicate that prevention activities should continue to emphasize smoking cessation, although switching to low‐tar cigarettes may also yield some reductions in lung cancer risk.
Humoral immune response to epstein‐barr virus antigens and immunoglobulin allotypes in African burkitt lymphoma patients
Authors: Biggar Robert J. , Pandey Janardan P. , Henle Werner , Nkrumah Francis K. , Levine Paul H.
Published: February 2007

We examined whether any immunoglobulin allotype was associated with an elevated risk of Burkitt's lymphoma because of the association between Burkitt's lymphoma and abnormalities of the immunoglobulin‐bearing chromosomes. The distribution of Gm and Km phenotypes among 56 Burkitt lymphoma cases and 25 age‐matched controls was unremarkable. Burkitt's lymphoma has also been associated with the Epstein‐Barr virus, and we therefore sought a relationship between immunoglobulin allotypes and antibody response to the component antigens of the Epstein‐Barr virus, VCA, EA‐D, EA‐R and EBNA. No immunoglobulin phenotype was associated with higher antibody titers against any antigen, but there appeared to be an interactive effect in which persons homozygous at both Gm and Km loci had elevated titers against several of the component antigens of the Epstein‐Barr virus. This is the first report of an interactive effet between immunoglobulin allotypes and viruses. Antibody titers against antigens of the Epstein‐Barr virus were higher in cases than in controls, as expected. However, female cases had significantly higher titers than male cases, a finding similar to that previously reported in healthy persons.
The effect of dietary factors on nitrosoproline levels in human urine
Authors: Stich Hans F. , Hornby A. Paul , Dunn Bruce P.
Published: February 2007

The effect of dietary components on the levels of nitro‐soproline (NPRO) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite‐preserved meats (85–170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European‐style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 μg/24 h, whereas the consumption of non‐preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 μg/24 h. The urinary NPRO levels of 22 vegetarians and 14 lactovegetarians averaged 0.8 and 1.4 μg/24 h, respectively. A change from a nitrite‐preserved meat diet to a vegetarian diet was accompanied by an approximately six‐fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite‐preserved meats could not be reduced by nitrite‐trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic‐containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO. An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.
Nyctohemeral changes in plasma prolactin levels and their relationship to breast cancer risk
Authors: Wang D. Y. , Sturzaker H. E. , Kwa H. G. , Verhofstad F. , Hayward J. L. , Bulbrook R. D.
Published: February 2007

The amount of prolactin has been determined in serial blood samples taken over 24 h from 20 pre‐ and 9 post‐menopausal women volunteers. All women had a large increase in prolactin at night (24.00 h‐03.00 h). A much smaller rise in prolactin occurred in the evening (18.00 h‐20.00 h) which was just significantly different (p < 0.05) from levels found in the afternoon. Prolactin concentrations at any given time in the 29 women were linearly correlated with corresponding levels in either of the adjacent time intervals. This correlation was highly significant (p < 0.001) throughout 24 h, implying that a woman with a relatively high (or low) blood prolactin in the afternoon would have a similarly high (or low) concentration in the evening or at night. Premenopausal women had higher amounts of prolactin than postmenopausal volunteers throughout the day. Parity was found to be inversely related to prolactin levels in pre‐ and postmenopausal women; this effect was especially marked in the night peak of prolactin. In postmenopausal women an average of 33 years had elapsed since the birth of the last child, which implies that childbirth has a life‐long effect on reducing prolactin levels. Thus the protective effect of early childbearing and multiparity against developing breast cancer could be at least partly explained by these effects on serum prolactin levels.
Metastatic potential of murine fibrosarcoma cells is influenced by cell surface laminin
Authors: Malinoff Herbert L. , McCoy J. Philip , Varani James , Wicha Max S.
Published: February 2007

In order to examine the role of cell surface laminin in tumor metastasis we have utilized four well‐characterized murine fibrosarcoma cell lines. Two of these lines were highly metastatic when injected into syngeneic mice while the remaining two lines were significantly less metastatic. Using indirect immunofluorescence techniques, we detected cell surface laminin on the cell surface of both highly metastatic cell lines but not on the low‐metastatic cell lines. Although the low‐metastatic cell lines did not possess endogeneous cell surface laminin, they had the ability to specifically bind exogenous laminin to their surface in a time‐ and concentration‐dependent manner, indicating the presence of laminin receptors on these cells. Incubation of the low‐metastatic cells with exogenous laminin prior to injection into syngeneic animals significantly increased their metastatic potential. No such increase was observed when the highly metastatic lines were preincubated with exogenous laminin. On the basis of these results, we conclude that in this fibrosarcoma model, metastatic potential is influenced by cell surface laminin and that the presence of unbound laminin receptors on the cell surface is not alone sufficient to promote metastasis of these cells.
Interferon treatment of a transplantable rat colon adenocarcinoma: Importance of tumor site
Authors: Marquet R. L. , Westbroek D. L. , Jeekel J.
Published: February 2007

The effect of partially purified rat interferon (RIFN) was evaluated in CC531 colon tumor‐bearing rats. Tumor CC531 is a DMH‐induced, transplantable adenocarcinoma exhibiting weak immunogenicity. When small tumor fragments were implanted under the renal capsule, daily treatment with RIFN for 5 days led to a highly significant (p <0.001) inhibition of tumor growth, measured 7 days after implantation. Cyclic treatment with RIFN (105 units/kg/day, for 7 days in weeks 2, 4, 6 and 8) significantly retarded the development of artificial lung metastases, induced by intravenous (i.v.) injection of 5 × 105 colon tumor cells. The median survival time was 177 days in the RIFN group as compared to 116 days in the control group. Three of eight animals treated with RIFN showed no sign of lung metastases when they were killed 250 days after tumor cell injection. The same cyclic RIFN treatment which was effective in the lung metastases model had no influence on the growth of liver metastases evoked by the intraportal injection of 5 × 105 tumor cells. Laparotomy performed at days 30 and 50 after inoculation revealed equal numbers of liver metastases in the RIFN‐treated group and the control group. The mean survival times obtained in the two groups were 96±20 days and 108±14 days, respectively (0.05<p<0.10). The results indicate that (1) there is no inherent resistance of this solid tumor to RIFN therapy and (2) the effect of RIFN treatment is determined by the site of tumor development. The finding that the liver can provide a protective environment against tumor immunity may have important clinical implications.
Immunoglobulin A, G and E levels in egyptians with cancer: Influence of schistosomiasis
Authors: Pidcock N. B. , Cooper E. H. , El‐Aaser A. A. , El‐Sebai I.
Published: February 2007

The main patient series consisted of 415 Egyptians attending the Cairo Cancer Institute and comprising 286 bladder cancer, 97 breast cancer, 14 head and neck cancer and 18 gastrointestinal cancer cases. Also included in the study were 36 patients with active schistosomiasis and 89 healthy controls. Serum IgA, IgG, IgG subclasses, IgE, Schistosoma and Ascaris‐specific IgE (RAST) and the acute‐phase protein CRP were measured in all, or sub‐sets, of the main patient group. The well‐established increase in IgE and IgG levels, and the more recently reported increase in the levels of IgG3 and IgG4 subclasses in patients with schistosomiasis, were also found in bilharzial bladder cancer, indicating that humoral immunity persists in cancer‐bearing patients. However, the plasma protein profile in bilharzial bladder cancer is further modified by significant increases in the levels of IgA, IgG, IgGI, IgG2 and CRP when compared to levels in patients with Bilharzia in the absence of neoplastic change. Patients with cancers not associated with parasitic infestation also had significant increases in their serum levels of IgGI, IgG2, IgG, IgE and CRP when compared to healthy Egyptian controls, but 41% of these non‐bladder cancer patients showed IgE responses to previous parasitic infestations suggesting that any immunological response to cancer would be on the background of a variable non‐specific increase of IgE.
Antibody‐dependent cellular cytotoxicity and disease course in North American patients with nasopharyngeal carcinoma: A prospective study
Authors: Pearson Gary R. , Neel H. Bryan , Weiland Louis H. , Mulroney Susan E. , Taylor William , Goepfert Helmuth , Huang Andrew , Levine Paul , Lanier Anne , Pilch Ben , Goodman Max
Published: February 2007

It has previously been reported that antibody‐dependent cellular cytotoxicity (ADCC) levels determined at diagnosis against Epstein‐Barr virus (EBV)‐specific membrane antigens (MA) are predictive of disease course following therapy in patients with nasopharyngeal carcinoma (NPC). In general, survival was significantly shorter following therapy in patients with low ADCC titers at diagnosis versus those with high titers. To examine this further, a prospective study on North Americans with different histopathological types of this disease was initiated approximately 5 years ago. The results to date tend to support the conclusions drawn from the retrospective study for patients with the more poorly differentiated types (WHO 2 and WHO 3) of this disease. Over the first 3 years of this study, approximately 75% of the patients in the “high” category have remained clinically disease‐free for 3 years or longer as opposed to approximately 35% of the patients in the “low” group. Disease progression rates were calculated to be approximately four times higher in the low group. Similar trends were noted in actual survival rates over a 3‐year period. ADCC titers were in general found to be relatively stable in sequential serum samples from the same patient, with some exceptions. With the exceptions, however, changes in ADCC titers also reflected disease course. These results indicate, therefore, that anti‐EBV ADCC titers are predictive of disease course in patients with the poorly differentiated types of NPC.
Antigenic heterogeneity of clones and subclones from human melanoma cell lines demonstrated by a panel of monoclonal antibodies and flow microfluorometry analysis
Authors: Cillo C. , Mach J.‐P. , Schreyer M. , Carrel S.
Published: February 2007

Cells from two melanoma cell lines, Me43 and GLL‐19, were cloned in methylcellulose cultures and 20 randomly selected colonies from each line were picked up by micro‐manipulation, expanded in liquid cultures, and considered as clones of the original cell lines. The antigenic cell surface phenotype of these clones defined by panel of 12 monoclonal antibodies (MAb) was analyzed by flow microfluoromery (FMF) using a fluorescence‐activated cell sorter (FACS II) and compared with the known stable phenotype of the parent cell line. The antibody panel consisted of eight MAb against melanoma‐associated antigens, two MAb against monomorphic determinants of HLA‐DR (la) and HLA‐ABC, respectively, one MAb against the common acute lymphoblastic leukemia antigen (CALLA) and one MAb against carcinoembryonic antigen used as control. A remarkable heterogeneity in terms of qualitative and quantitative expression of the cell surface antigens studied was observed among and within the different clones. The single‐cell origin of the clones was assessed by comparing the clonogenic cell frequency, determined by limiting dilutions in microculture plates, with the cloning efficiency observed in Petri dishes. Both techniques using methylcellulose medium gave the same percentages of growing colonies. Cells from four Me43 clones were recloned in methylcellulose and the phenotype of five randomly selected subclones from each clone was analysed using the same panel of monoclonal antibodies. Each subclone also displayed heterogeneity with individual phenotypes different from that of the original clone and from the parental Me43 cell line. The antigen expression by individual cells in situ within clones was analyzed on frozen sections from colonies using the same panel of MAb and a biotin‐avidin immunoperoxidase method. The results confirmed the marked heterogeneity of antigen expression within and among colonies, as indicated by the FMF analysis.
Multicellular spheroids grown directly from human tumour material
Authors: Wibe E. , Berg J. P. , M.Tveit K. , Nesland J. M. , Lunde S.
Published: February 2007

Human tumour cells from surgical material were grown as multicellular spheroids. In 16 out of 20 cultures spheroids with a diameter of more than 250 μm could be observed. In 6 out of 20 cultures more than 30 spheroids with a diameter of at least 300 üm were obtained, i.e. 30% of the cultures fulfilled the criterion for a possible chemosensitivity test on primary cell spheroids. A study of stained sections from the spheroids and the respective tumours, showed that the morphology of the spheroid was very similar that of the tumour from which the cells were derived. Samples from 9 malignant melanomas, 4 bladder carcinomas, 2 renal‐cell carcinomas, 2 ovarian carcinomas, 1 lymphoma, 1 colon carcinoma, and 1 schwannoma were tested for spheroid growth. Spheroids were obtained from at least one representative of all these tumour types. However, investigations involving larger numbers of tumours are needed to find out which tumour types are most suitable for further biological characterization of primary cell spheroids and tests for therapy respone.
Socio‐economic status, indoor and outdoor work, and malignant melanoma
Authors: Cooke K. R. , Skegg D. C. G. , Fraser J.
Published: February 2007

Among New Zealand non‐Maori men, professional, technical, administrative and managerial workers had the highest incidence and mortality rates for malignant melanoma of the skin; labourers and workers in production and transport had the lowest rates. Reclassification of occupations, in terms of both socio‐economic status and a three‐step scale of outdoor exposure during work, suggested that differences between occupational groups were determined by differences in socio‐economic status. Outdoor work exposure seemed to have little effect on the risk of melanoma.
Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue
Authors: Gudnason Vilmundur , Ingvarsson Sigurdur , Jonasdottir Adalbjörg , Andresdottir Valgerdur , Egilsson Valgardur
Published: February 2007

Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and I axillary metastatic growth) and 7 non‐pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions used were cytosol, mitochondria and microsomes. A comparison of two methods for detecting HK activity was made, yielding different results regarding HK II and HK III. A method based on the ability of NADPH to fluoresce in UV gave a constant pattern of HK isoenzymes. In non‐pathological breast tissue, only HK I was seen, i.e. in the cytosol and the microsomal fractions. HK I was also seen in all fractions of the cancers, but another more anodal band of HK I, as well as HK II and HK III, consistently appeared in the cytosol fractions. The more commonly used staining technique with tetrazolium dye revealed HK II in 45% and HK III in 50% of the samples. The pattern of HK isoenzymes in the cancers was the same irrespective of estrogen and progesterone cytosolic receptor contents and the histology of the tumors. The fluorescence method is, therefore, much more sensitive than the tetrazolium technique for detecting HK activity after electrophoresis and could explain difference in results obtained by various laboratories.
Geographical distribution of breast cancer in the USSR
Authors: Merabishvili V. M. , Semiglazov V. F. , Serova L. S. , Buslayeva M. M.
Published: February 2007

This work presents statistical data on breast cancer incidence in the population of the USSR and the Union republics (1970‐1980). Mortality rates for the population are also presented, together with trends in compilation of breast cancer patient contingents. The study was based on summarized data on breast cancer incidence and patient follow‐up carried out by oncological institutions.
Enhancement of lung‐colonizing ability of cloned low‐metastatic lewis lung carcinoma cells by treatment with highly polar compounds
Authors: Takenaga Keizo
Published: February 2007

Treatment of low‐metastatic Lewis lung carcinoma cells (P‐29) with dimethylsulfoxide (DMSO) in vitro enhanced their lung‐colonizing ability. The effects of other highly polar compounds on the lung‐colonizing ability of P‐29 cells were examined. The following compounds were found to enhance the lung‐colonizing ability of the cells: acetamide, N‐methylacetamide, N‐methylformamide, N,N‐dimethylformamide, piperidone and hexamethylphosphoric triamide. Treatment of P‐29 cells with DMSO or other polar compounds resulted in increases in activities of degradative enzymes, such as cathepsin B and plasminogen activator. The increases in cathepsin B and plasminogen activator activities were apparent after a 24 h treatment with DMSO and were suppressed by simultaneous treatment with cycloheximide, which suggested that they were due to syntheses of new proteins. DMSO‐treated P‐29 cells degraded [3H]leucine‐labelled subendothelial matrix much more than did untreated cells. P‐29 cells treated with DMSO or other polar compounds became attached to culture dishes more rapidly and were more resistant to detachment by trypsin treatment than untreated cells. A significant correlation was found between the degrees of adhesiveness of P‐29 cells treated with various polar compounds and their lung‐colonizing abilities.
Role of T suppressor cells in the cycling of the immune response against a murine fibrosarcoma
Authors: Payelle Béatrice , Lespinats Geneviève , Tlouzeau Sylvie
Published: February 2007

Antitumor immunity against a fibrosarcoma in C57BL/6 mice was obtained by means of a semi‐allogenic somatic hybrid cell derived from the fusion of this C57BL/6 fibrosarcoma (MCB6‐1) and A9 cells of C3H origin. In a Winn assay, this immunity could be transferred by T lymphocytes to normal C57BL/6 recipient mice during an early and a late phase after immunization. There appeared to be a transient non‐responsive period during which no immunity could be transferred. Injection of cyclophosphamide (CY) into mice before immunization increased the level of immunity during this period, and reconstitution of animals with normal spleen cells abolished the effect of CY. During the non‐responsive period, suppressor cells were demonstrated in the spleen: the i.v. transfer of these suppressor cells to normal mice significantly inhibited the induction of antitumor immunity; the suppressive effect was transferred by T lymphocytes of the Lyt‐2+ phenotype. No suppressive effect on antitumor protection was observed when suppressor cells were transferred simultaneously with immune T lymphocytes in the Winn assay. From these findings, it appears that T‐suppressor cells regulate the antitumor response, interfering with the afferent (induction) arm of the immune response.
Reversibility of the transformed and neoplastic phenotype. IV. Effects of long‐term interferon treatment of C3H/10T1/2 cells transformed by methylcholanthrene and SV40 virus
Authors: Brouty‐Boye D. , Wybier‐Franqui J. , Calvo C. , Feunteun J. , Gresser I.
Published: February 2007

The effects of long‐term treatment with mouse interferon on the phenotype of untransformed C3H/10TI/2 cells and cloned derivatives transformed by methylcholanthrene (MCA) and Simian virus 40 (SV40) were investigated. Continuous presence of interferon induced morphologic reversion, with the development of thick, submembranous filaments in MCA‐transformed cells, where as no morphological effects were detected in SV40‐transformed cells. Interferon inhibited the proliferation of all three cell lines and maintained low saturation densities. However, prolonged treatment of MCA‐transformed cells with interferon rendered them tolerant toward the antiproliferative and antiviral activities of interferon although 2‐A synthetase activity was induced. Interferon treatment reduced the capacity of both MCA and SV40‐transformed cells to form colonies in agar and decreased the tumorigenicity of MCA‐transformed but not SV40‐transformed cells in mice. These results indicate that the same cell type transformed by different means has different sensitivities to a number of interferon‐induced changes in the cell phenotype.
Occult melanoma in lymph nodes detected by antiserum to S‐100 protein
Authors: Cochran Alistair J. , Wen Duan‐Ren , Herschman Harvey R.
Published: February 2007

Sections of 1,273 nodes from 58 patients with melanoma were stained in an immunoperoxidase assay using an antiserum to S‐100 protein and aminoethyl carbazole as indicator. By the hematoxylin and eosin (H. and E.) technique, 128 nodes were seen to contain melanoma (10%); by the anti‐S‐100 protein technique, 363 (29%) were found to be tumor‐positive. The additional tumor‐positive nodes contained single tumor cells or small groups of tumor cells and were adjacent to nodes that were partly or wholly replaced by melanoma. Penetration of nodes by single tumor cells was seldom seen in node groups containing no tumor that was visible on H. and E. staining. The anti‐S‐100 protein approach more accurately identified those patients who would die of their recurrent disease less than 5 years after lymphadectomy.
Modulation of anti‐tumour immunity induced by syngeneic mitomycin C‐treated murine tumour cells
Authors: Kearney R. , Harrop P.
Published: February 2007

Experiments were performed to examine the kinetics of delayed‐type hypersensitivity (DTH) to mitomycin‐C‐treated syngeneic murine fibrosarcomas inoculated into the footpads of mice. Evidence is presented to show that a “strongly” antigenic tumour, designated H7, elicits consecutive waves of footpad swelling in both primary and secondary responses. Periods of anti‐tumour resistance coincided with the expression of each successive wave of footpad swelling in normal and immune mice. The downregulation of the response, between the successive peaks of footpad swelling, was accompanied by active tumour growth. In contrast, the non‐cross‐reacting “weakly” antigenic tumour, designated HI, induced footpad swelling which was expressed only once after either primary or secondary sensitization. Unlike that induced by the “strongly” antigenic H7 tumour, the anti‐tumour immunity to the HI tumour was not sustained beyond its initial specific phase. Consequently, HI tumour cells which survived the initial phase of anti‐tumour immunity appeared to encounter no further resistance. Thus the distinctive feature of the “weakly” antigenic HI tumour was its inability to sustain consecutive waves of tumour resistance as exhibited by the “strongly” antigenic H7 tumour. It is proposed that “weakly” and “strongly” antigenic tumours are distinguished by their different abilities to down‐regulate the anti‐tumour immune response. The “weakly” antigenic tumour induces specific immunity which is rapidly down‐regulated while that induced by the “strongly” antigenic tumour is sustained by successive waves of antitumour activity of diminshing intensity. Suppression of some but not all waves of footpad swelling occurred in mice with growing H7 tumours.
Antitumor activity of murine tumor necrosis factor (TNF) against transplanted murine tumors and heterotransplanted human tumors in nude mice
Authors: Haranaka Katsuyuki , Satomi Nobuko , Sakurai Akiko
Published: February 2007

The antitumor activity of highly purified tumor necrosis factor (TNF) was tested against eight kinds of murine tumor and five kinds of human tumor heterotransplanted into nude mice. Mice were treated by intravenous or intratumoral injection of TNF, commencing when the tumors were well established. TNF showed an excellent curative effect against all kinds of murine and human tumors tested. Meth A sarcoma, Colon 26, Ehrlich, sarcoma 180, MM 46, MH 134, B16 melanoma, and Lewis lung tumors transplanted into mice underwent tumor necrosis and regression following a single injection of TNF. Sometimes a complete cure was observed in Meth A sarcoma, sarcoma 180, Ehrlich, and MM 46 tumors. Human cancers, SEKI, HMV‐I, KATO‐III, MKN 45, or KB, heterotransplanted into nude mice, also exhibited tumor necrosis and regression in size following several intratumoral injections of TNF. A great difference in curative effects of TNF was observed in Meth A sarcomas between those transplanted into BALB/c nu/+and into BALB/c nu/numice: following a single intravenous administration the effect was stronger in BALB/c nu/+ than in nu/nu mice. In contrast, tumor necrosis was almost the same in nu/+ and nu/nu mice following intratumoral administration. The present results thus indicate that TNF from mice had an antitumor activity against not only murine tumors but also human tumors. In addition to direct cytotoxicity against tumor cells, TNF induced a host‐mediated factor which contributed to the antitumor effects.
Interaction between feline leukaemia virus subgroups in the pathogenesis of erythroid hypoplasia
Authors: Jarrett Oswald , Golder Matthew C. , Toth Sarah , Onions David E. , Stewart Marianne F.
Published: February 2007

The interaction of feline leukaemia virus (FeLV) of subgroups A and C in the pathogenesis of erythroid hypoplasia in cats was studied. Weanling kittens infected with FeLV‐A became permanently viraemic but remained haematologically normal over a period of 36 weeks. Similar kittens inoculated with FeLV‐C, which produces erythroid hypoplasia when administered to newborn kittens, neither became viraemic nor developed the disease. However, weanling kittens inoculated with a mixture of FeLV‐A and C became viraemic, first with FeLV‐A and then additionally with FeLV‐C, and the emergence of FeLV‐C into the blood coincided with the advent of erythroid hypoplasia. When FeLV‐C was inoculated into five older cats which had been viraemic with FeLV‐A for several months previously, it appeared in the plasma of three of the cats and erythroid hypoplasia was diagnosed in two of these, 16‐20 weeks after infection with FeLV‐C. These results show that FeLV‐A enhances the growth of FeLV‐C in cats and overcomes their age‐related resistance to FeLV‐C. Also, the appearance of FeLV‐C in the plasma of cats viraemic with FeLV‐A indicates that erythroid hypoplasia will subsequently occur rapidly. These findings are relevant to the origin of FeLV‐C isolates and their occurrence in nature.
Evaluation of AFP glycosylation heterogeneity in cancer patients with AFP‐producing tumors
Authors: Vessella Robert L. , Santrach Marcia A. , Bronson David , Smith Carol J. P. , Klicka Michael J. , Lange Paul H.
Published: February 2007

It has been postulated that analysis of alpha‐fetoprotein (AFP) glycosylation heterogeneity in cancer patients whose AFP levels are elevated (e.g., non‐seminomatous ferm cell tumors, ovarian germ cell tumors and primary hepatocellular carcinoma) might provide useful clinical information. We undertook a study to determine whether scrutiny of AFP glycosylation heterogeneity in patients with non‐seminomatous germ cell tumors would provide information useful in diagnosis, staging, prognosis, or monitoring for recurrence of disease following therapy. While an analysis of AFP glycosylation heterogeneity using Concanavalin A lectin chromatography did not provide useful information in regard to staging or prognosis, it does supply unique information useful in discriminating between benign liver dysfunction (e.g. alcoholic hepatitis, chemotherapy‐related liver damage) and that due to nonsemininomatous germ cell tumors. It was also concluded that an analysis of Concanavalin A binding patterns is not sufficient to discriminate between recurrent non‐seminomatous germ cell tumor and primary hepatocellular carcinoma in patients with elevated serum AFP.
Tumour regression after intralesional injection of interleukin 2 (IL‐2) in bladder cancer. Preliminary report
Authors: Pizza Giancarlo , Severini Giuseppe , Menniti Domenico , De Vinci Caterina , Corrado Francesco
Published: February 2007

Six bladder cancer patients received intralesional injections by needle, under cystoscopic control, of 1969‐4046 units (U) of xenogeneic IL‐2 of high biological activity (324 U/ml; 397 μg/ml protein; 1.22 protein/U ratio). The treatment was spread over 7‐54 days and 0.5 ml was injected each time. In 3/6 patients complete tumour regression was seen 43, 60 and 105 respectively days after the first IL‐2 injection. In 2 a 70% regression was observed at days 45 and 75. In the last patient massive necrosis throughout the tumour mass was recorded on day 25 at radical cystectomy. In order to evaluate the minimum IL‐2 U required to obtain positive clinical results and/or to assess whether the anti‐tumour effect observed could be ascribed to the foreign protein of bovine origin contained in our IL‐2 preparation, 4 additional bladder cancer patients were treated in 7‐14 days with 156‐1404 U of a second IL‐2 lot with a much lower biological activity and similar protein content (52 U/ ml; 289 μg/ml of protein; 5.55 protein/U ratio). No clinical or histological improvement was noted over a 42‐ to 54‐day observation period. When we evaluated the 2 groups of patients by Student's t‐test for both total U injected and U/ kg of body weight (bw) we found a statistically significant differences (0.0025 p7<0.0005 and p<0.0005, respectively). In contrast, no difference was seen for the injected protein amounts. The reported observations are in favour of a dose‐dependent anti‐tumour action mediated by IL‐2 instead of foreign proteins. In none of the patients treated were any early or late adverse clinical side effects observed. Immunological monitoring (E, EAC, E‐active rosettes, mitogen lymphocyte stimulations and leukocyte migration inhibition in the presence of allogeneic bladder cancer cells) performed on the peripheral blood (PB) showed significant but contrasting modifications after IL‐2 injection. There was no clear correlation with the clinical course. The patients in whom we observed complete regression are still tumour free after 2, 4 and 7 months. In addition, in all the patients of the first group we observed an increase in tumour lymphoid infiltrate after IL‐2 injection and in 2 patients lymphoid pseudo‐follicles were also noted. In 2 of these patients we also observed scar‐like areas in the place of the tumours previously seen.
Incidence of double minutes, cytogenetic equivalents of gene amplification, in human carcinoma cells
Authors: Gebhart E. , Bruderlein S. , Tulusan A. H. , Maillot K. V. , Birkmann J.
Published: February 2007

Screening of the occurrence of double minutes (DM) was performed in more than 1,000 metaphases obtained from a total of 22 solid human breast tumors and more than 3,600 metaphases from a total of 55 malignant effusions (45 patients with different types of carcinomas). DM were observed in 15 of these breast tumor cases and in 34 of the effusions (obtained from 29 cancer patients). The percentage of cells exhibiting DM as well as the number of DM per respective cell varied widely. It could be seen that meta‐static cells from malignant effusions exhibited on the average more DM per cell than did cells of primary breast carcinomas. Differences in the incidence of DM could be observed between different carcinomas as well as between different age groups. In addition, it did not appear that DM could be induced by mutagenic tumor therapy. DM are thus not a rare finding in human solid tumors but, as cytogenetic equivalents of gene amplification, they rather represent a fundamental biological characteristic of tumor development.
Inhibition of experimentally‐induced murine metastases by recombinant alpha interferon: Correlation between the modulatory effect of interferon treatment on natural killer cell activity and inhibition of metastases
Authors: Brunda Michael J. , Rosenbaum Deborah , Stern Lorraine
Published: February 2007

The effect of a human recombinant hybrid alpha interferon (referred to as rHulFN‐alphaA/D) on pulmonary metastases induced by intravenous injection of B16 F10 melanoma cells in C57BL/6 mice was examined; rHulFN‐alphaA/D has been previously shown to have anti‐viral, anti‐proliferative and immunomodulatory activities in murine cells. Pretreatment of mice with 4 daily intra‐peritoneal injections of rHulFN‐alphaA/D resulted in a marked decrease in the number of pulmonary metastases. This inhibition was dose‐dependent but was not seen when mice were similarly treated with rHulFN‐alphaA, a human recombinant alpha interferon subtype which is inactive on murine cells. Treatment of mice with rHulFN‐alphaA/D following B16 F10 injection resulted in no significant inhibition of pulmonary metastases. Mice given a similar treatment regimen of rHulFN‐alphaA/D had elevated natural killer (NK) cell activity as measured by in vitro cytotoxicity against YAC‐1 or in vivo pulmonary clearance of B16 F10 cells. Pretreatment of mice with 10 daily injections of rHulFN‐alphaA/D resulted in decreased NK activity and less inhibition of metastases. Therefore, in this model system, rHulFN‐alphaA/D inhibits metastases when given in the appropriate treatment schedule. Furthermore, the data are consistent with the hypothesis that rHulFN‐alphaA/D‐induced inhibition is a consequence of the immunomodulation of NK cells, which prevent the establishment of pulmonary metastases.
Colony formation in the absence of added growth factors by peripheral blood T‐cell colony‐forming cells of patients with T‐cell malignancies
Authors: Georgoulias Vassilis , Bourinbaiar Aldar , Amesland Françoise , Canon Chantal , Auclair Huguette , Jasmin Claude
Published: February 2007

Clonogenic cells from peripheral blood of 13/16 patients with T‐cell malignancies generated colonies in methylcellulose in absence of added growth factors or mitogenic stimulation. Spontaneous colonies were also obtained from purified cell fractions (E−OKT3− and/or E+ cells) in 73% and 57% of the patients, respectively. No spontaneous colony growth was observed with mononuclear cells of patients with solid tumors, non‐T‐cell leukemias or normal subjects. Colonies consisted of acid‐phosphatase‐positive, myeloperoxidase‐and PAS‐negative lymphoblasts bearing T‐cell surface markers. Although the phenotype of pooled colony cells from either unfractionated mononuclear cells or E−OKT3−‐derived colonies varied from patient to patient, the colonies, like fresh leukemic cells, were mostly composed of relatively immature cells as assessed by the high proportion (>40%) of OKT6+ and OKT10+ cells and the low proportion (<40%) of OKT3+ and/or E+ cells. Cytogenetic analysis of colony cells revealed either normal metaphases or chromosome anomalies similar to those observed in fresh leukemic cells. Moreover, cells from primary colonies exhibited a capacity for self‐renewal in the absence of added growth factors.
Definition of three species‐specific monoclonal antibodies recognizing antigenic structures present on human embryonal carcinoma cells which undergo modulation during in vitro differentiation
Authors: Blaineau C. , Connan F. , Arnaud D. , Andrews P. , Williams L. , McIlhinney J. , Avner P.
Published: February 2007

Three novel species‐specific monoclonal antibodies 5.I.H, 8.7.D and 13.7.A raised against semi‐purified detergent solubilized fractions of the Tera I embryonal carcinoma (EC) cell line are restricted in their in vitro distribution to undifferentiated human EC cell lines. Competition experiments have established that distinct antigenic specificities are seen by the 3 different monoclonal antibodies. All 3 antigens 5.I.H, 8.7.D and 13.7.A, defined by these monoclonal antibodies, undergo developmental regulation and cease to be expressed on Tera 2 clones 5 and 12 after retinoic‐acid‐induced differentiation and on LICRLONHT 39/7 cells after phorbol‐ester‐induced differentiation. These results taken together with the extremely limited in vivo tissue distribution of the defined antigens suggest that the 5.I.H, 8.7.D and 13.7.A monoclonal antibodies define distinct onco‐foetal antigens.
Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice
Authors: Bennett Alice S.
Published: February 2007

Strain A/ST female mice maintained on a high fat (15%) diet in which stearic acid was the major lipid component developed initial spontaneous mammary adenocarcinomas at an older age than mice fed a low fat (4.5%) stock diet. Mice placed on the SA diet at weaning developed tumors at 15.7 ± 0.87 months compared to 12.7 ± 0.43 months for those retained on the stock diet (p<.05). Placing mice on the SA diet at 11.5 months resulted in a smaller but significant increase in the latency period (5.0 ± 0.86 vs 3.0 ± 0.57 months ± 0.57 mo), (p< .05). Fatty acid analyses of non‐tumorous mammary tissue from mid‐pregnant mice and of tumor tissues showed that feeding large amounts of 18:0 did not result in increases in the proportion of 18:0. Significant reductions in the percentages of polyun‐saturated fatty acids (PUFA) was found in tissues on mice fed the SA diet. The percentage of 18:2 was reduced in both types of tissues; 20:3 and 20:4 was reduced in tumor tissues. Distribution of C18 fatty acids in plasma membranes of tumors of mice fed the two diets were similar; percentages 18:2 was higher in plasma membranes of non‐tumorous tissues of mice fed the SA diet. These results suggest that dietary stearic acid interferes with the availability of certain PUFA required for tumor production.