bluuebunny/crossref_metadata_2025 huggingface dataset:
Caffeine (1,3,7‐trimethylxanthine), a temperate promoter of DMBA‐induced rat mammary gland carcinogenesis
Authors: Welsch Clifford W. , Scieszka Karen M. , Senn Eric R. , Dehoog Jane V.
Published: February 2007

The administration of caffeine to the drinking water (250 mg/l and 500 mg/l) of female Sprague‐Dawley rats after treatment with 7,12‐dimethylbenzanthracene (DMBA) (5 mg i.g.) resulted in an increase in mammary carcinoma incidence. The confidence levels of statistical significance for the groups of rats receiving the 250‐mg and 500‐mg doses of caffeine were >0.70 and >0.99, respectively. This increase in mammary carcinoma incidence was observed when caffeine treatment was initiated commencing 3 days after DMBA treatment and continued for 21 weeks. This effect was also observed when caffeine treatment was initiated commencing 20 weeks after DMBA treatment and continued for 6 weeks in rats relatively refractory to carcinogen treatment (mammary tumor‐free at onset of treatment) and in rats relatively sensitive to the carcinogen (mammary tumor bearing at onset of caffeine treatment). Caffeine treatment of rats prior to and during carcinogen treatment did not significantly affect mammary carcinoma incidence. Thus caffeine consumption has been shown to significantly enhance the promoting phase but is without effect on the initiating phase of this carcinogenic process.
Murine non‐lymphoid tumors are lysed by a combination of NK and NC cells
Authors: Lattime Edmund C. , Pecoraro Gene A. , Cuttito Michael J. , Stutman Osias
Published: February 2007

Natural cell‐mediated cytotoxicity (NCMC) against a variety of tumor targets is mediated by a heterogeneous group of effector cells with the natural killer (NK) and natural cytotoxic (NC) cells being the predominant prototypes in mice. This report shows that non‐lymphoid tumor targets, mostly derived from chemically induced fibrosarcomas, are susceptible to either (I) NK‐mediated lysis with all the activity being the function of a poly‐IC augmentable Qa‐5+ effector cell; (2) NC‐mediated lysis with all activity being the function of a Qa‐5—cell not augmented by poly‐IC; and (3) a combination of NK‐and NC‐mediated lysis with activity being the function of both Qa‐5+ and Qa‐5‐ cells, the NK (Qa‐5+) augmented by poly‐IC. These studies further support the view that murine NC and NK cells are distinct and collectively make up the NCMC system, and also that the previous association of NK cells with lymphoid tumor lysis and NC cells with nonlymphoid tumor lysis is not a valid one.
Human papillomavirus type‐16‐related DNA in genital Bowen's disease and in bowenoid papulosis
Authors: Ikenberg Hans , Gissmann Lutz , Gross Gerd , Grussendorf‐Conen Elke‐Ingrid , Hausen Harald Zur
Published: February 2007

32P‐labelled DNA of HPV 16 which has been isolated and molecularly cloned from a cervical carcinoma (Dürst et al., 1983) was used to screen the cellular DNAs obtained from 20 different biopsies of Morbus Bowen or Bowenoid papulosis, respectively, by Southern blot analysis. Under conditions of differing stringency for the hybridization, HPV 16 DNA or related sequences were identified in 6 out of 10 cases of Morbus Bowen (4 out of 5 from a genital localization) and in 8 out of 10 biopsies from Bowenoid papulosis. One additional case of the latter disease contained DNA sequences of an HPV type not yet classified. There is evidence for the presence of another HPV DNA in two of the HPV‐16‐positive tumors. A large number of normal genital tissue samples were negative for HPV DNA.
Artificial sweeteners and absence of bladder cancer risk in Copenhagen
Authors: Møller‐Jensen O. , Knudsen J. B. , Sørensen B. L. , Clemmesen J.
Published: February 2007

During the years 1979 to 1981 a population‐based case‐control study of bladder cancer including papillomas was performed in Greater Copenhagen. After exclusions some 388 patients (290 males; 98 females) and an age‐and sex‐matched group of 787 controls (592 males; 195 females) remained for analysis. Controls were selected at random from the general population of the study area. All persons were interviewed concerning use of artificial sweeteners in addition to their exposure to a number of other known or suspected risk factors for bladder cancer. Fifty‐five male bladder cancer patients (19.4%) and 150 controls (25.7%) had at some time used artificial sweeteners regularly. Among females 27.1% of cases and 25.9% of controls regularly used sweeteners. In neither sex was the relative risk significantly increased in users compared with non‐users of artificial sweeteners. The relative risk of 0.78 in the two sexes combined was not significantly different from 1.0 (95% C.I.: 0.58‐1.05). There was no indication of a regular increase in risk with increasing daily consumption of table‐top sweeteners nor was there any indication of an increase in risk with a duration of regular use of artificial sweeteners. Taking into account a possible latency period between first regular use and bladder cancer development did not change the finding of an absence of association between use of artificial sweeteners and the risk of bladder cancer. Neither saccharine nor cyclamate users had an increased risk of bladder cancer. This population‐based case‐control investigation provides further evidence that it is highly unlikely that the consumption of artificial sweeteners has contributed to current bladder cancer rates in man.
Changes in lipid profiles of estrogen‐induced and transplanted renal carcinomas in Syrian hamsters
Authors: Talley Deanna J. , Sadowski James A. , Boler Sarah A. , Li Jonathan J.
Published: February 2007

The lipid profiles of estrogen‐induced primary renal carcinomas and hormone‐dependent and ‐independent transplanted tumors were compared with those of both normal hamster kidneys and renal tissues of tumor‐bearing animals. Autonomous tumors had only one‐third the amount of triglycerides present in normal kidneys and hormone‐dependent tumors contained intermediate levels. Host kidneys of animals bearing either primary or transplanted tumors contained no more than 50–60% of the triglyceride level found in normal kidneys. In contrast to triglycerides, cholesteryl esters in primary tumors were 200 times higher than in normal kidneys, exhibited a successive decline in hormone‐dependent and ‐independent tumors, but remained 15 times higher in autonomous carcinomas than in normal kidneys. Cholesterol levels were similar in primary tumors, normal kidneys, and host kidneys of animals bearing renal tumors; however, both hormone‐dependent and ‐independent neoplasms had only one‐half to two‐thirds as much cholesterol as normal kidneys. Total phospholipid levels in primary and transplanted carcinomas were about one‐half those in normal kidneys. Host kidneys of animals bearing primary and transplanted, hormone‐dependent neoplasms also contained lower phospholipid levels than normal kidneys, but renal tissues from animals with autonomous tumors contained similar levels to those found in kidneys from normal hamsters. The phospholipid composition of primary and transplanted renal tumors was similar, but different from that of normal kidneys, mainly in increased percentages of phosphatidylcholine and decreased percentages of sphingomyelin.
T lymphoma variants with specifically altered growth in semi‐solid media
Authors: Claverie Jean‐Michel , Cohn Melvin
Published: February 2007

The relationship between the tumorigenic potential and the cloning efficiency of T lymphoma BW5147 in semi‐solid media has been studied. Two stable variants exhibiting a 30‐fold decrease of their cloning efficiencies in agarose an methycellulose media were independently isolated by negative selection with FuDr. These variants show no alteration of their growth properties in liquid medium and are still able to proliferate in liquid suspension over a bottom layer of agarose. This new phenotype is not correlated with any decreased tumorigenicity in syngeneic AKR/J mice.
Metastatic malignant melanoma: Regression induced by combined treatment with interferon [HuIFN‐α(Le)] and cimetidine
Authors: Flodgren P. , Borgström S. , Jönsson P. E. , Lindström C. , Sjögren H. O.
Published: February 2007

With the aim of potentiating the anti‐tumour effect of interferon in metastatic malignant melanoma by concomitant inhibition of suppressor T cells, oral cimetidine (histamine‐2 receptor antagonist) medication was added to interferon (HuIFN‐α(Le)) therapy in a series of 20 patients. While no objective tumour responses were recorded with interferon treatment alone administered intramuscularly or intratumorally, six patients had objective tumour regressions on subsequent combined therapy. Five out of eight patients with metastases confined to skin and subcutaneous tissue had complete tumour regressions while one patient with skin and lung metastases achieved an extensive partial regression of the skin tumour and a complete roentgenological regression of the lung metastasis. Three additional patients attained a stable disease status for prolonged periods of time. Histopathotogical examinations confirmed disappearance and/or degeneration of melanoma cells and demonstrated a marked lymphocyte infiltration in tumour sites of the patients with objective tumour regression.
Epstein‐Barr virus‐associated antibody pattern in untreated non‐Hodgkin lymphoma patients. Relationship to clinical variables and lymphocyte functions
Authors: Lindemalm C. , Biberfeld P. , Björkholm M. , Henle G. , Henle W. , Holm G. , Johansson B. , Klein G. , Mellstedt H.
Published: February 2007

Sera from 296 unselected and untreated patients with non‐Hodgkin lymphoma (NHL) classified according to the Rappaport and the Kiel systems were analzyed for antibodies to Epstein‐Barr virus (EBV). The aim of the study was to determine whether antibody spectra and liters to EBV‐coded antigens correlated to clinical and immunological variables and whether the liters were of any prognostic significance. Increased antibody titers to EB viral capsid antigen (VCA) and slightly raised titers to early antigens (EA) of the diffuse (D) and restricted (R) types were noted frequently. Anti‐VCA antibody titers correlated to clinical stage and age of the patients but not to histological. subgroups according to the Rappaport or the Kiel classification systems. However, and‐VCA titers ⩾ 1:2560 were seen only in diffuse lymphomas according to the Rappaport and in non‐follicle cell‐derived lymphomas according to the Kiel classifications. Patients with complement‐receptor‐positive diffuse lymphomas had higher anti‐VGA titers than complement‐receptor‐positive nodular cases. Anti‐VCA titers also correlated positively to serum IgG levels (p <0.01). Total number of lymphocytes separated from peripheral blood and mitogen induced (ConA, PWM) DNA synthesis were recorded before treatment in 54 of the patients. The patients exhibited a significant lymphocytopenia as well as a significantly reduced lymphocyte response to mitogens (p <0.001) compared to healthy controls. Elevated anti‐VCA titers and anti‐EA titers correlated to a good mitogen‐induced lymphocyte response (p <0.05). Only anti‐D 1:40 at diagnosis predicted a poor prognosis.
Differences in the peripheries of Lewis lung tumor cells growing in different sites in the mouse
Authors: Harlos James P. , Weiss Leonard
Published: February 2007

The peripheries of Lewis lung (3LL) tumor cells growing in different organs of the mouse were studied by cell electrophoresis and electron microscopic quantitation of colloid iron hydroxide (CIH) adsorption before and after incubation with neuraminidase. The results show that cells growing in the kidney after direct injection have significantly higher anodic mobilities than cells growing in the subcutaneous sites from which they were derived, or in intramuscular sites, liver or spleen. The proportional contributions of cell surface sialic acids were similar in all sites. Electron microscopy of cells reacted with CIH indicates that the increased surface charge density of the tumor cells growing in the kidney is due to the presence of increased densities of non‐CIH‐binding ionogenic groups. Before neuraminidase treatment, the surface distribution patterns of CIH were indistinguishably random for 3LL cells growing in all sites. After neuraminidase treatment, significantly more clustering of CIH particles was observed on 3LL cells with a history of growth in the kidney than in subcutaneous sites. The changes observed in the 3LL cells growing in the kidney were irreversible, and persisted on multiple back‐transplantation to subcutaneous sites. Detailed analysis of the results shows the changes to be due to the preferential selection of a subpopulation consisting of approximately 10% of the original (subcutaneous) tumor‐cell populaton. This evidence for an irreversible site‐induced selection of a pre‐existing sub‐population of 3LL cells contrasts with the reversible (modulation) site‐induced adaptation previously observed by us in Walker‐256 cancer cells, and therefore indicates that both selective and adaptive processes can occur. Even in the case of the 3LL cells, site‐specific selection is not general, since the changes were observed in tumors growing in the kidney but not in the other anatomic sites. At present we cannot comment on the relevance of these reported changes to naturally occurring metastasis.
Effects on metastases of drug therapy during developing and established tumor immunity
Authors: Vaage Jan , Costanza Mary E.
Published: February 2007

The effectiveness of treatment with cyclophosphamide, methotrexate and 5‐fluorouracil was studied during the s.c. and pulmonary growth of syngeneic C3H/He mammary carcinomas. Treatments with cyclophosphamide, methotrexate and 5‐fluorouracil during the primary induction of immunity against a mouse mammary carcinoma inhibited the growth of the tumor, but also inhibited the development of an effective immune resistance against subsequent implants of the same tumor. However, drug treatments of mice with estatablished tumor immunity gave added benefit without detectable depression of immune resistance.
Control of in vivo differentiation of myeloid leukemic cells. III. Regulation By T Lymphocytes And Inflammation
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

Mouse and human (HL‐60) MGI+D+ myeloid leukemic cells were induced to differentiate to mature cells in diffusion chambers implanted into the peritoneal cavity of normal mice when a xenogeneic source of serum was added to the diffusion chambers. Differentiation was inhibited in immune deficient mice including congenitally athymic nude and neonatally thymectomized mice, and mice treated with cyclophosphamide, hydrocortisone, or X‐irradiation. There was no such inhibition of differentiation in mice with various genetic defects in their B lymphocytes, granulocytes, erythrocytes and natural killer cells. Differentiation in cyclophosphamide‐treated mice was restored by a single intravenous injection of normal spleen cells highly enriched for T lymphocytes. Conditions permissive for differentiation were associated with a higher number of eosinophils in the peritoneum than conditions that inhibited differentiation. Intraperitoneal injections of inflammatory peritoneal exudate cells, peritoneal granulocytes, or the inflammation inducer sodium caseinate, restored the ability of defective mice to induce differentiation. Injections into defective mice of the normal mouse macrophage and granulocyte differentiation‐inducing protein (MGI‐2) restored differentiation of the mouse myeloid leukemic cells but not of the human myeloid leukemic cells. Differentiation of normal mouse bone marrow myeloid precursors to mature cells and of differentiation‐defective (MGI‐D‐) mouse myeloid leukemic cells to intermediate stages of differentiation were not affected by the conditions that inhibited differentiation of the MGI +D+ myeloid leukemic cells. The results indicate: 1) that the intraperitoneal accumulation of inflammatory cells, including eosinophils, can induce differentiation of MGI +D+ leukemic cells in the peritoneal cavity; 2) that this response requires T lymphocytes and can be regulated by xenogeneic serum in the chamber; 3) that in vivo diffentiation of normal and MGI +D+ myeloid leukemic cells can be regulated in different ways; and 4) that the in vivo differentiation of the mouse MGI +D+ leukemic cells, human MGI+D+ leukemic cells and mouse MGI−D− leukemic cells were induced by different compounds, so that differentiation of different types of leukemic cells may be differently regulated in vivo depending on which compounds induce differentiation.
Propagation of a poorly differentiated human pulmonary adenocarcinoma in nude athymic rats
Authors: Korsgaard Rolf , Lindén Carl‐Johan , Willén Roger , Willén Helena , Svensson Gunnar , Simonsson Bo G.
Published: February 2007

Nude athymic rats of Rowett genetic background were injected subcutaneously with cells from a poorly differentiated human pulmonary adenocarcinoma, following propagation in nude mice. The tumour cells were obtained by thoracentesis and by pleural biopsy during thoracoscopy. So far, we have heterotransplanted 13 different malignant human tumours including malignant mesothelioma, pulmonary adenocarcinoma, malignant melanoma and malignant lymphoma. Subcutaneous tumour growth was seen in all inoculated animals, with an exponential tumour growth pattern and with tumour volume doubling times of approximately 8 days. After two initial passages in nude athymic mice of BALB/c genetic background, the human tumour so far has undergone 9 passages in athymic rats, i. e. collection of tumour material by biopsy from the preceding tumour‐bearing rat generation, processing and inoculation of tumour brei with subsequent tumour growth have been repeated 8 times. Four‐ to 8‐week‐old rats of both sexes were used throughout and tumour growth was controlled by palpation twice a week. Routine histopathological sections were prepared from the tumour at various passages to assess similarity to the original tumour in the patient. The growth pattern of the xenografts remained similar at all passages just as the remarkable similarity of the heterotransplanted tumours to the original adenocarcinoma was retained at all passages. No spontaneous regressions of heterotransplanted tumours could be demonstrated. Electron microscopical analysis revealed numerous blunt microvilli and lumina partly filled with conglomerates of mucigen granules and small glycocayceal bodies associated with external superficial microvilli. Scantiness of dark secretory granules together with free and membrane‐bound polyribosomes were seen in the cytoplasm. We believe that the nude athymic rat is a valuable research tool and that the permanently transplantable human tumour reported here could be of value in delineating further the mechanisms for tumour take, growth and control.
Forskolin: A potential antimetastatic agent
Authors: Agarwal Kailash C. , Parks Robert E.
Published: February 2007

Forskolin, a diterpene from the roots of an Indian plant, Coleus forskohlii, is a potent platelet aggregation inhibitor and has been examined for its effects on (a) tumor‐induced human platelet aggregation and (b) pulmonary tumor colonization in mice. These studies employed a subline of B16 murine melanoma, BI6‐FIO (highly meta‐static to lungs). Forskolin (2 μM) strongly inhibits the melanoma cell‐induced human platelet aggregation. A single dose of forskolin (82 μg/mouse) administered in‐ traperitoneally 30 or 60 min prior to tail vein injection of cultured BI6‐FIO cells (2 or 3 × 10s cells/mouse) reduced tumor colonization in the lungs by more than 70%. Similar results were obtained in three separate experiments. These findings raise the possibility that forskolin could prove of value in the clinic for the prevention of cancer metastasis.
Application of an in vitro assay for serum thymidine kinase: Results on viral disease and malignancies in humans
Authors: Gronowitz J. Simon , Källander Clas F. R. , Diderholm Hans , Hagberg Hans , Pettersson Ulf
Published: February 2007

An improved method for the detection of deoxythymidine kinase (TK) in human sera is reported. The method which utilizes 125I‐iododeoxyuridine (IdUrd) as a substrate was used to measure TK in sera from patients with different diseases. Sera collected during the acute stage of infectious mononucleosis were found to contain elevated levels of TK, in most cases 10–40 times the normal value. The serum TK activity disappeared gradually and reached a normal level within 4 weeks. Sera from patients with other viral infections contained in most cases normal serum TK levels except in connection with measles, rubella, varicella, herpes simplex virus and cytomegalovirus infections. Additional studies revealed that sera from patients with different types of advanced lymphomas, acute leukemias, chronic granulocytic leukemia and lung cancer of the small‐cell type with metastases, contained high TK level which fluctuated in parallel with alterations in activity of the disease. The TK activity in sera from patients with both mononucleosis and tumor disease was characterized by electrophoresis and by its ability to utilize cytidine triphosphate as the phosphate donor. The results showed that the serum TK has the same properties as the human cytosolar TK1, except in connection with varicella.
Steroid hormone receptors in human squamous carcinoma cell lines
Authors: Virolainen Erkki , Vanharanta Riitta , Carey Thomas E.
Published: February 2007

Specific estrogen, progesterone and androgen receptors were determined in 19 well‐characterized squamous‐cell carcinoma (SCC) cell lines. Ten of the lines were derived from patients with SCC of the larynx and nine were from patients with SCC originating in other areas of the head and neck. Estrogen receptors (ER) were found in seven of 10 cell lines derived from squamous cancers of the larynx (70%) but in only one of the nine SCC cell lines from sites other than larynx. Progesterone receptors (PGR) were more evenly distributed. Eight of the 10 laryngeal carcinoma cell lines (80%) and five of the nine non‐laryngeal SCC lines (55%) had progesterone receptors. Only one cell line, UM‐SCC‐10B (derived from a recurrent carcinoma of the larynx) was found to express androgen receptors (AR). Expression of specific estrogen receptors was not dependent on the sex of the patients since lines from both males and females contained receptors. These results establish that squamous carcinoma cell lines may express specific steroid hormone receptors and that cell lines from cancers of the larynx (an organ known to be androgen‐responsive) are more likely to express estrogen receptors than androgen receptors. From this initial survey it appears that there is a striking difference in estrogen and progesterone receptor content between SCC cell lines originating from larynx cancers and cell lines established from squamous carcinomas of other head and neck regions. The presence of estrogen receptors in a high proportion of laryngeal carcinoma cell lines suggests that hormonal therapy may be a useful adjunctive therapy in selected patients with cancer of the larynx.
Soft‐tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system
Authors: Trojani M. , Contesso G. , Coindre J. M. , Rouesse J. , Bui N. B. , De Mascarel A. , Goussot J. F. , David M. , Bonichon F. , Lagarde C.
Published: February 2007

The pathological features of 155 adult patients with soft‐tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft‐tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.
Enhanced chemotaxis of tumor‐derived and virus‐transformed cells to fibronectin and fibroblast‐conditioned medium
Authors: Mensing Hartwig , Albini Adriana , Krieg Thomas , Pontz Bertram F. , Müller Peter K.
Published: February 2007

SV40 transformants of human embryo fibroblasts showed an enhanced chemotactic response to fibronectin and conditioned medium of fibroblasts in comparison to the non‐transformed cells. An even higher chemotactic response was characteristic for a malignant human fibrosarcoma cell line, whereas cells derived from low‐grade malignant dermatofibrosarcoma showed a normal response in the Boyden chamber assay. The high stimulation of chemotaxis is paralleled by a reduced synthesis and an altered deposition of fibronectin in the pericellular matrix of these cells. Both high chemotactic response and lack of deposition of fibronectin may play a role in tissue invasion and formation of metastasis by malignant tumors.
Role of nk cells in the antimetastatic effect of anticoagulant drugs
Authors: Gorelik Eliezer , Bere William W. , Herberman Ronald B.
Published: February 2007

The antimetastatic effects of heparin (40 units) and prostacylin (PGI2, 100 μ)1 were investigated in normal mice and in mice with depressed or activated natural killer (NK) cell activity. Both anticoagulants inhibited the formation of lung metastases after inoculation of the F1 or F10 sublines of B16 melanoma. Inhibition of NK activity by treatment of mice with anti‐asialo GM1 serum abrogated the antimetastatic effects of PGI2 or heparin. Conversely, augmentation of NK‐cell activity by poly I:C plus treatment with anticoagulants produced synergistic antimetastatic effects. A similar pattern of results was obtained with heparin treatment of mice challenged with the Madison lung carcinoma (M109), but PGI2 alone or in combination with theophylline had little or no detectable antimetastatic effect on M109 or on the parental B16 melanoma. Studies of the mechanism of the interaction between heparin nd NK cells revealed that the anticoagulant treatment did not affect splenic NK activity in vitro However, heparin treatment caused a significant increase in the clearance of radiolabelled tumor cells from the lungs of normal mice. Combined treatment of mice with poly I:C and heparin synergistically accelerated the elimination of radiolabelled tumor cells. In contrast, heparin did not affect the clearance of tumor cells from the lungs of mice with depressed NK activity. Thus the antimetastatic effects of heparin and PGI2 are dependent on levels of NK activity in the host. Platelet aggregation and fibrin coating of the surface of tumor cells may be among the mechanisms by which hematogenously spread tumor cells are protected from destruction by NK cells. Anticoagulant drugs may exert antimetastatic effects by making tumor cells more vulnerable to the cytotoxic effects of NK cells, rather than by blocking adherence of tumor cells to vascular endothelium.
Lysis of fld‐3 friend erythroleukemia cellsin vitroandin vivo: Effect of89sr treatment and friend virus infection
Authors: Lust John A. , Bennett Michael , Kumar Vinay
Published: February 2007

The effector cells from non‐immunized mice capable of lysing51Cr‐labelled FLD‐3 BALB/c Friend virus‐induced erythroleukemia cellsin vitroand cells capable of clearing FLD‐3 cells labelled with 5‐iodo‐2′‐deoxyuridine‐125I (125IdUrd) from the lungsin vivowere characterized and compared with natural killer (NK) cells reactive against YAC‐1 lymphoma cells. Unlike NK cells, the cells capable of lysing FLD‐3 cellsin vitrowere insensitive to antibodies directed agains NK‐2.1 or Thy‐1.2 antigens (plus complement) and to pretreatment of micein vivowith silica particles,89Sr or estradiol. Heat‐killedC. parvumorganism stimulated anti‐FLD‐3 effector cells without changing the slow rate (24 h) of lysisin vitro. The ability to clear FLD‐3 and YAC‐1 cells from the lung was normal and defective, respectively, in C57BL/6‐bg/bg(beige) mice and in mice pretreated with89Sr or estradiol. We conclude that natural cytotoxic (NC) cells lyse FLD‐3 cells.Fv‐2, which regulates resistance to leukemia induction by Friend virus, does not regulate NC(FLD‐3) activity, and the virus does not affect NC(FLD‐3) activity during the first several days of infection of normal genetically susceptible mice. However, infection of89Sr‐treated mice inhibits NC(FLD‐3) function owing to the activation of suppressor cells. These data suggest (but do not prove) that effector cells similar or identical to NC(FLD‐3) cells may functionin vivoto resist the proliferation/survival of certain leukemia cells.
Retinoic acid restores shape‐dependent growth control in neoplastic cells cultured on poly(2‐hydroxyethyl methacrylate)‐coated substrate
Authors: Lotan Reuben , Stolarsky Tamara , Lotan Dafna , Ben‐zeev Avri
Published: February 2007

The ability of retinoic acid to modulate cell‐shape‐dependent growth of untransformed (human skin fibroblasts and mouse embryo Swiss 3T3 fibroblasts) and neoplastic cells (human cervical carcinoma HeLa‐S3, osteosarcoma Hs791, and murine melanomas B16‐F1, S91‐C2 and S91‐C154) was examined. The cells were plated on tissue culture dishes coated with increasing concentrations of poly(2‐hydroxyethyl methacrylate), poly(HEMA) which cause a gradual decrease in substrate adhesiveness. Untreated cells as well as cells pretreated with 10 μM retinoic acid for 4 days displayed a similar graded series of cell shapes between flat and spherical on these modified substrata, with the exception of HeLa‐S3 cells which were rounded and loosely attached even on uncoated plastic dishes. A marked cell‐shape‐dependent decrease in DNA synthesis was observed in untransformed human skin fibroblasts, Swiss 3T3 fibroblasts and neoplastic human Hs791 cells 20 h following plating of untreated cells on poly(HEMA)‐coated substrates of decreasing adhesiveness. Conversely, in B16‐F1, HeLa‐S3 and S91‐C154 cells DNA synthesis was only slightly affected by changes in cell shape. Pretreatment with retinoic acid rendered DNA synthesis in Swiss 3T3, Hs791, B16‐F1 and S91‐C2 cells much more sensitive to changes in cell shape. In contrast, retinoic acid exerted only marginal effects on the sensitivity of DNA synthesis to changes in cell shape in untransformed human skin fibroblasts, in HeLa‐S3 cells and in the retinoic‐acid‐resistant S91‐C154 cells. The results suggest that retinoic acid can restore in certain tumor cells the tight coupling between cell shape and DNA synthesis that exists in untransformed cells.
Control of in vivo differentiation of myeloid leukemic cells. iv. inhibition of leukemia development by myeloid differentiation‐inducing protein
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

It is shown that a 5‐day schedule of two injections per day of the myeloid differentiation‐inducing protein MGI‐2 inhibited the in vivo development of leukemia in SL and SJL/J mice with different syngeneic MGI+D+ clones of myeloid leukemic cells. With this schedule of treatment high levels of MGI‐2 were maintained in the serum for long periods. In contrast to these results with MGI‐2, the same schedule of injections of the myeloid growth‐inducing protein MGI‐1 did not affect the in vivo development of leukemia in mice with MGI+D+ myeloid leukemic cells, but stimulated normal myelopoiesis in the bone marrow. Different forms of MGI‐1 including MGI‐1M and MGI‐1G had different serum half‐lives, and the form of MGI‐1 with the shortest serum half‐life showed the smallest in vivo effect on normal myelopoiesis. MGI‐2 injections did not inhibit the in vivo development of differentiation‐defective WEHI‐3B myelomonocytic leukemic cells or YAC lymphoma cells. The results indicate that the in vivo inhibitory effect of MGI‐2 on the development of myeloid leukemia correlated with its differentiation‐inducing potential on the leukemic cells. It is concluded that this approach of inhibiting leukemia development by inducing differentiation should also be applied to human leukemic patients, whose cells have been shown to be inducible for differentiation in culture by human MGI‐2 or by other differentiation‐inducing compounds.
A fetal glycolipid expressed on adenocarcinomas of the colon
Authors: Blaszczyk Magdalena , Ross Alonzo H. , Ernst Carolyn S. , Marchisio Marino , Atkinson Barbara F. , Pak Koon Yan , Steplewski Zenon , Koprowski Hilary
Published: February 2007

Reactivity of neuraminidase‐treated colorectal carcinoma cells with antibodies that detect the X‐carbohydrate structure was greater than the reactivity of untreated cells. The same results were obtained with glycolipid extracts of meconium, a colorectal carcinoma cell line, three freshly excised human adenocarcinomas, and normal bronchial mucosa. The glycolipid was either not expressed or expressed in smaller quantities on the corresponding normal colon tissue. Further study showed that the major sialo‐X glycolipid has six sugars including a single sialic acid which blocks X‐antigenicity. These glycolipids were further analyzed by ion‐exchange high‐pressure liquid chromatography and thin‐layer chromatography. These monosialo‐X glycolipid antigens might serve as potential tumor markers.
SV40 immortalization of adult human mesenchymal cells from neuroretina. Biological, functional and molecular characterization
Authors: Daya‐Grosjean L. , Azzarone B. , Maunoury R. , Zaech P. , Elia G. , Zaniratti S. , Benedetto A.
Published: February 2007

Human adult mesenchymal cells from neuroretina (human choroid cells, HC) have acquired an infinite lifespan, following phenotypic transformation with a wild‐type SV40. Immortalized cells (HC/SV40) contain high numbers of free circular viral DNA, and integrated molecules in a head‐to‐tail array in the cellular DNA. HC/SV40 cells express both the virus‐coded “T” antigens and the cell‐coded p53 transformation‐associated protein. The transformed phenotype was further characterized by loss of contact inhibition of cell division, inability to induce the retraction of a fibrin clot and to spread within fibrin and the existence of an altered distribution of acutin cables. For the first time we also describe a coupling of the immunofluorescence and the quantitative cytofluorometric analyses, a new transformation parameter, since we show that SV40 transformation causes reorganization of the cell membrane by inducing the unmasking of the antigen recognized by the 4F2 monoclonal antibody, which is present in a “cryptic” form in the untransformed cells. Though the HC/SV40 cells have been continuously passaged over a 3‐year period, they have not yet achieved a fully malignant phenotype, since they retain serum‐dependency and the presence of a well developed fibronectin pericellular network, and they are not tumorigenic in nude mice. Thus this human immortal cell line constitutes a very useful tool for studying the progression toward full malignancy and the relationships between evolution of transformation parameters and changes in the viral and cellular genome interplay.
Initial clinical evaluation of an immunoradiometric assay for CA 19‐9 using the nci serum bank
Authors: Ritts Roy E. , del Villano Bert C. , Go V. L. W. , Herberman Ronald B. , Klug Thomas L. , Zurawski Vincent R.
Published: February 2007

More than 1,600 coded sera obtained from blood donors and the NCI/Mayo Clinic Serum Bank were analyzed with an improved immunoradiometric assay for the carbohydrate antigenic determinant, CA 19‐9. Results indicated that CA 19‐9 is elevated in a large fraction of sera (67%) from patients with advanced adenocarcinomas of the upper gastrointestinal (GI) tract, including those with pancreatic, hepatobiliary and gastric carcinomas. Several of these sera had CA 19‐9 exceeding 300,000 U/ml. A smaller fraction (18%) of patients with carcinomas of the large bowel had elevated serum CA 19‐9 levels, the majority among patients with metastatic disease. In contrast, none of the healthy donors from the serum bank and only 4 of 1,023 of the blood donor specimens (0.4%) had CA 19‐9 levels greater than or equal to 40 U/ml. Three of 235 sera (1.3%) from benign disease patients had levels of CA 19‐9 in excess of 40 U/ml. These data suggest that the improved CA 19‐9 immunoradiometric assay may have clinical utility as a diagnostic adjunct for adenocarcinoma of the upper GI tract and that the assay also may have some value in monitoring patients with advancing colorectal carcinoma, particularly in combination with CEA determinations. Rigorous prospective clinical trials will be necessary to verify these hypotheses.
Detection of the granulocyte‐specific antigen 3‐fucosyl‐N‐acetyl‐lactosamine on leukemic cells after neuraminidase treatment
Authors: Tetteroo P. A. T. , Van Veer M. B. T , Tromp J. F. , von dem Borne A. E. G. Kr
Published: February 2007

The carbohydrate antigen 3‐fucosyl‐N‐acetyl‐lactos‐amine (FAL) is expressed on human granulocytes and is detected by a monoclonal antibody B4.3. After neuraminidase treatment, this structure can also be detected on monocytes and on the cells of nearly all acute myeloid leukemia patients (38/39). It is then also present on the cells of a number of CALLA‐positive lymphatic leukemias (8/18), but not on T‐ALL and B‐ALL cells. On cells of patients with AUL, the antigen is then detected in many TdT+ cases, but not in TdT− cases.
Reduced levels of fibronectin in ataxia‐telangiectasia lymphoblastoid cells
Authors: Lavin Martin F. , Seymour G. J.
Published: February 2007

In this study Epstein‐Barr virus‐transformed lymphoblastoid cells were shown to contain fibronectin. A marked difference in the number of fibronectin‐positive cells was observed in control and ataxia‐telangiectasia lymphoblastoid cells. Three control cell lines varied between 60% and 80% in the number of cells containing fibronectin. Only a small percentage of ataxia‐telangiectasia cells (1–5%) had fibronectin present. Control and ataxia‐telangiectasia fibroblasts had similar amounts and distributions of fibronectin. An asymmetric distribution of fibronectin was evident in many control and ataxia‐telangiectasia lymphoblastoid cells. The increased frequency of fibronectin‐containing cells in the control populations cannot be accounted for by different growth rates or variation in the various phases of the cell cycle in the two cell types.
Identification of a surface antigen, common to murine lung and lewis lung carcinoma, by monoclonal antibody
Authors: Hadas Eran , Hurwitz Esther , Eshhar Zelig
Published: February 2007

Lewis lung carcinoma (3LL) is a spontaneous murine lung carcinoma which preferentially metastasizes into the lung. Monoclonal antibodies (MAb) against 3LL cells were prepared by fusing spleen cells from rats immunized with 3LL and the P3‐NSI/I‐Ag4 (NSI) plasmacytoma. Two hybridomas were selected which secreted antibodies capable of preferential binding to 3LL cells and not to other malignant cells. Immunohistochemical staining of sections prepared from various mouse organs with one of the MAbs (22.2), revealed exclusive staining of the lung tissue. The data suggest that a lung‐specific, 3 LL‐associated antigen, is detected by the 22.2 MAb on 3LL cells. The 22.2 antigen is a surface molecule, and is stable following trypsin treatment and fixation by glutaraldehyde or picric acid. Cells that were prepared from a subcutaneous tumor or from lung metastases express high amounts of 22.2 antigen compared to cells of the culture 3LL line (3LLC). Upon reinoculation of 3LLC cells into mice there was a gradual increase in 22.2 antigen expression. It was possible to select from the heterogeneous 3LLC cell population several clones which express high amounts of antigen. These clones differed also in their metastatic patterns. However, the metastatic capacity of these clones did not correlate with expression of the 22.2 antigen. Thus, it appears that expression of the 22.2 antigen is not a necessary condition for formation of lung metastases by 3LL.
Phenotypes associated with tumor rejection mediated by cyclophosphamide and syngeneic tumor‐sensitized t lymphocytes: Potential mechanisms of action
Authors: Evans Robert
Published: February 2007

The phenotypes of the affector and effector cell populations involved during the induction of permanent tumor regression by combined therapy using cyclophosphamide (CY) and immune spleen cells were identified. Permanent tumor regression was dependent on the presence of Thy‐1+ Lyt‐2+ lymphocytes in the immune spleen cell population that was injected i.v. 2‐4 h after an intraperitoneal injection of CY (240 mg/kg) into C57BL/6J mice bearing 1.0‐1.5 g. MCA/76‐9 or MCA/76‐64 sarcomas. Histological evaluation after the combined treatment indicated an intense influx of putative lymphocytes 6‐10 days after the combined treatment, over and above the inflammatory response involving macrophages and neutrophils induced by CY treatment alone. These infiltrating cells were shown to be T lymphocytes, most of them having the Lyt‐1 and Lyt‐2 antigens on their cell membrane. Isolated MCA/76‐9 or 76‐64 tumor‐associated cells (TAC), lymphocytes (TAL) and macrophages (TAM) inhibited MCA/76‐9 or 76‐64 tumor growth respectively in a Winn test in an immunologically specific manner, having no effect on the growth of the B6 sarcoma cells, MCA/76‐45 and 77‐23. The tumor‐free mice from the Winn test were not resistant to a subsequent challenge inoculum of either MCA/76‐9 or 76‐64 cells. Isolated TAC were usually non‐specifically cytotoxic in vitro, while TAL and TAM showed some degree of specificity. The overall data indicated that the ultimate rejection of those tumor cells remaining after the direct anti‐tumor action of CY had been dissipated was probably mediated by the combined action of TAL and TAM.
Further characterization of marek's disease virus‐infected lymphocytes. II. In vitro infection
Authors: Calnek B. W. , Schat K. A. , Ross L. J. N. , Chen C‐L. H.
Published: February 2007

Lymphocyte cultures from chicken spleens had been shown to be susceptible to in vitro infection by Marek's disease virus (MDV)4 in an earlier report from this laboratory. In that study, virus infection was evidenced by virus isolation and detection of viral internal antigen (VIA) 2 days post inoculation (DPI), and serial passage was accomplished by adding fresh spleen cells at 2‐day intervals. The susceptible cells were identified as bursa‐derived lymphocytes (B cells). Using a dual fluorescence technique to identify surface markers for B cells, thymus‐derived lymphocytes (T cells) or la antigen on VIA‐positive cells, we have now shown that a small proportion (generally less than 10%) of VIA‐positive cells observed 2 DPI are T cells, and that a low level of infection can be maintained by serial passage of MDV in cultures totally free of B cells. Most infected T cells in this study had Ia antigen. As the incubation period for infected cultures was extended from 2 to 4 or 5 days, the average number of viable cells decreased but the percentage of viable cells infected with MDV (VIA‐positive) increased. Also, both the proportion and the actual number of infected T cells increased, significantly more so in cultures from genetically susceptible P‐2 donors than from resistant N‐2 donors. Spleen‐cell cultures from resistant Line 6 chickens were markedly less susceptible than those from susceptible Line 7 chickens to in vitro MDV infection, as assessed by numbers of VIA‐positive cells at 5 DPI.
The long‐term prognostic significance of the thymidine labelling index in breast cancer
Authors: Tubiana M. , Pejovic M. H. , Chavaudra N. , Contesso G. , Malaise E. P.
Published: February 2007

A prospective study of the prognostic significance of the labelling index (LI) was undertaken in 1972. The LI of the primary tumor was measured consecutively on 128 patients with mammary carcinoma at the time of initial treatment, followingin vitroincubation of specimens with tritiated thymidine. The follow‐up for all patients has now extended over 10 years. Relapse‐free survival and total survival are significantly higher in patients with a low LI. A multivariate analysis of the prognostic factors, carried out with Cox's model, showed that Li is the most predictive indicator with respect to survival. The size of the tumor is the second most predictive indicator, while histological grading and the number of involved lymph nodes are less predictive. These results strongly suggest that proliferative activity as assessed by LI is directly related to metastatic dissemination probability, independent of other prognostic factors.
Chemosensitivity of human melanoma xenografts in immunocompetent mice and its histological evaluation
Authors: Dumont P. , Esch E. P. Vander , Jabri M. , Lejeune F. , Atassi G.
Published: February 2007

In the subrenal capsule assay, the immuno‐competent mice used have a host immune response to the graft which may introduce a bias in the determination of tumour size. A study was therefore conducted to verify the quality of the correlation that could exist between “macroscopical” and “microscopical” evaluation. A histological study of 12 different tumours treated with cis‐Pt, L‐PAM, DTIC, vindesine, BCNU or TGU demonstrated that a cellular host immune response was observed in 11 out of the 12 control groups and was uneven in the treated groups. The “microscopical” and “macroscopical” evaluations of tumour‐take were 100 and 95% respectively. Although there was a fair correlation between the “microscopic” and “macroscopic” parameters, tumour variations in absence of host reaction ‐ which reflect pure chemosensitivity of the treated tissue ‐ could be measured in 50% of the cases. It was possible to determine abase‐line for rejection of the test results when the control group showed a decrease in mean tumour size exceeding 20% of its initial size on day 0. If the decrease is less than 20%, then the histological evaluation appears to be of considerable additional value.
Distinction between burkitt lymphoma subgroups by monoclonal antibodies: Relationships between antigen expression and type of chromosomal translocation
Authors: Ehlin‐Henriksson Barbro , Klein George
Published: February 2007

Twenty‐six lines derived from 22 Burkitt lymphoma patients were examined for cytoplasmic vs. surface immunoglobulin and the expression of the monoclonal‐antibody‐detected BLA, CALLA and LB‐I antigens. Six of the lines carried the variant translocations 8;2 or 8;22 (three each), 17 lines had the typical 8;14 translocation, I was translocation‐negative (BJAB) and 2 were not examined cytogenetically. Depending on their immunoglobulin and surface marker expression, the BL lines could be subdivided into several subgroups. There was a strong inverse correlation between the expression of the CALLA and the LB‐I marker. All BLA‐lines were CALLA‐, whereas the CALLA+ lines could be either BLA‐ or BLA+. All six variant translocations belonged to the CALLA‐BLA‐LB‐I + category. Only one set of three lines, derived from the patient with the 8;14 translocation, belonged to the same subgroup. This suggests that the typical vs. the variant translocation freezes the BL cell at a different stage of differentiation. The variant translocation‐carrying subtypes represent probably a somewhat more advanced stage of differentiation.