bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a cocktail of monoclonal antibodies and human complement in selective killing of acute lymphocytic leukemia cells
Authors: Sugita Kenichi , Majdic Otto , Stockinger Hannes , Holter Wolfgang , Köller Ursula , Peschel Christian , Knapp Walter 
Published: February 2007

AbstractAutologous remission bone marrow is a potential source of repopulative stem cells after ablative chemoradiotherapy of tumor patients. Even with remission bone marrow, one major obstacle to use of autologous bone‐marrow support is the danger of reinfusing viable tumor cells. This report describes a purging protocol with human complement, which seems suitable for eliminating acute lymphatic leukemia (ALL) cells of the common ALL type. Lysis of ALL blasts is induced with a cocktail of 3 monoclonal antibodies of IgM type (termed VIB‐pool). These are directed against the CALLA (CD 10) antigen (VIL‐AI antibody) and against 2 different epitopes of the CD24 surface structure (VIB‐C5 and VIB‐E3 antibodies). The purging efficiency was evaluated with leukemic cell lines of the common ALL type (Reh‐6 and Nalm‐6) and with blast cells from common ALL patients. Optimal lysis was obtained with antibody and human serum concentrations as low as I μg/ml and 7% respectively. As a standard purging protocol we propose one 20‐min incubation at room temperature with antibody followed by two 30‐min incubations at 37°C with 25% human complement. In dye exclusion tests 99% purging efficiency and in clonogenic assays detecting elimination of up to 5 logs of clonogenic tumor cells 99.99% (= 4 logs) purging efficiency were achieved. Treatment with VIB‐pool and human complement had no negative effect on the growth of the normal hemopoietic progenitor cells CFU‐GM, CFU‐E and BFU‐E.
Synergistic antiproliferative effect of human interferons in combination with mismatched double‐stranded RNA on human tumor cells
Authors: Hubbell Howard R. 
Published: February 2007

AbstractFour human tumor cell lines were studied for their response to antiproliferative effects of various interferons (IFNs) alone and in combination with the novel mismatched dsRNA, r(I)n r(C12,U)n (Ampligen). RT4 cells (bladder carcinoma) were resistant to Ampligen alone, while A2182 (lung carcinoma), HT1080 C14 (fibrosarcoma) and RT112 (bladder carcinoma) cells were inhibited in a dose‐dependent manner. In contrast, RT4 cells were sensitive to the antitumor effects of IFNs as were HT1080 C14 and RT112 cells, while A2182 cells were resistant. In 3 of the 4 cell lines, the recombinant IFNs were less effective than the corresponding natural IFNs when compared by analysis of variance on an IRU/ml basis over a range of concentrations. In all cell lines, a synergistic antiproliferative effect was seen with all IFN preparations studied in combination with Ampligen, as calculated by the isobole method according to Berenbaum (1981). The antiproliferative effect of IFN was potentiated >3.3‐ to > 250‐fold, depending on the cell lines, IFN, and concentrations used. Varying the concentration of βser‐IFN while holding the Ampligen concentration constant gave synergy at all of the physiologically achievable concentrations tested in RT4 cells. These results indicate that: (1) Ampligen worked synergistically with all IFNs in all cell lines studied; (2) growth inhibition of cells resistant to IFNs can be potentiated by low doses of Ampligen; (3) the antiproliferative effect of IFNs can be potentiated by Ampligen in Ampligen‐resistant cells; and (4) Ampligen may work by a mechanism other than, or in addition to, the induction of IFNs.
Epstein‐Barr virus status and tumour cell phenotype in sporadic Burkitt's lymphoma
Authors: Rowe M. , Rooney C. M. , Edwards C. F. , Lenoir G. M. , Rickinson A. B. 
Published: February 2007

AbstractBurkitt's lymphoma (BL) biopsy cells and derived cell lines can be grouped according to their patterns of reactivity with 6 selected monoclonal antibodies (MAbs) against B cell‐associated surface antigens. Group I cells react only with MAbs J5 and 38.13, recognising the common acute lymphoblastic leukaemia antigen and a BL‐associated antigen respectively; group II cells react with J5 and 38.13 and with one or more of a set of MAbs (Ki‐24, MHM6, AC2, Ki‐I) against “lymphoblastoid” antigens; group III cells react only with these anti‐“lymphoblastoid” MAbs. Tumour biopsy cells from 17 cases of sporadic BL, 9 positive for the Epstein‐Barr (EB) virus genome and 8 negative, have been analysed during the process of cell line establishment in vitro. In early passage the EB virus‐negative BL cells showed either a group I phenotype or gave an additional reactivity with MAb Ki‐24 which placed them in group II; these phenotypes remained essentially stable with continued growth of the cell lines for up to 50 passages. By contrast the EB virus‐positive BL cells were much more susceptible to phenotypic change in vitro. Although such cells displayed a group I or group II phenotype in early passage, many of the lines soon moved into group III whilst retaining the karyotypic markers indicative of their malignant origin. These observations suggest that a resident EB virus genome can drive the in vitro progression of BL cells towards a more “lymphoblastoid” phenotype. This was confirmed in subsequent experiments where virus‐negative BL cell lines were converted to EB virus positivity by in vitro infection. Clearly, therefore, phenotypic analysis of long‐established lines can lead to false distinctions being drawn between the EB virus‐positive and ‐negative forms of sporadic BL; both may derive from the same sub‐population of target B cells in vivo.
Characteristics of in vitro transformed cells essential for their in vivo survival, selection and metastasizing activity
Authors: Deichman G. I. , Vendrov E. L. 
Published: February 2007

AbstractTwo questions were investigated: (1) the dynamics of in vivo selection of tumor cells possessing metastasizing activity (MA) at the time preceding the appearance of visible lung metastases, and (2) the possible connection of in vivo selection of metastatic tumor cells with their susceptibility to H2O2 produced by the cytotoxic oxidative burst of activated neutrophils, monocytes and macrophages. Spontaneously in vitro transformed Syrian hamster embryo cells (strain STHE), never selected in vivo and possessing low MA, were used as parental cells. STHE cells were injected i.v. and, after various time intervals (1 to 21 days), isolated from lungs of injected hamsters. A total of 43 STHE cell variants were isolated from individual animals. Their MA, natural‐resistance‐depressing (NRD) activity and susceptibility to H2O2 were determined.Selection of metastatic tumor cell variants capable of forming experimental metastasis (EM) begins a few hours after injection. The vast majority of injected cells die and the few cells which survive do not proliferate for a long period. The majority of variants isolated at days 5 to 6 after injection and later possess increased MA, depending on the duration of the in vivo selection, and varying among individual hosts. The ability to form spontaneous metastasis (SM) in the lungs and in other organs appears among cell variants isolated at days 10 to 21 after inoculation. This qualitatively new characteristic of cell variants correlates with the restoration of their proliferative activity and in most cases with their NRD activity.With respect to susceptibility to H2O2, (1) parental STHE cells and their 5 in vivo isolated cell variants, all possessing low MA, were highly susceptible to H2O2 injury; (2) 15 highly‐metastatic variants were 10 to 200 times more resistant; and (3) 4 variants obtained from s.c. transplants of parental cells were highly resistant to H2O2. Hamster embryo cells in vitro transformed with SV40 or bovine adenovirus type 3, were susceptible to high doses of H2O2 (14–28 mm) but resistant to lower doses. In contrast, the same cells, once passaged in vivo and the cells of tumors induced in vivo by the same viruses were resistant to high doses of H2O2. In vitro transformed cells and their in vivo selected variants thus appear to differ widely in terms of their susceptibility to H2O2. Extremely rare cell variants which are resistant to H2O2 and apparently present in the original populations of in vitro‐transformed cells possess an essential selective advantage in vivo, that is resistance to H2O2 appears necessary for in vivo survival of tumor cells and their growth in s.c. nodules and metastases.
Substrate‐dependent effect of epidermal growth factor on intercellular adhesion and synthesis of triton‐insoluble proteins in human carcinoma A431 cells
Authors: Rieber Manuel , Gil Francisco , Rieber Mary S. , Urbina Cecilia 
Published: February 2007

AbstractHuman epidermoid carcinoma A431 cells attach more rapidly to collagen type‐I and ‐IV substrates than to surfaces coated with laminin or fibronectin. The diminished intercellular interaction and rounding up manifested when these cells are exposed to epidermal growth factor (EGF) in tissue culture plastic or collagen films is not shown when the assay is performed on 3‐dimensional collagen. In the latter substrate, cells exposed to EGF reveal greater cell cohesion with interdigitations and desmosomal junctions, compared to the limited intercellular interaction detected in similarly treated cells assayed in tissue culture substrate. Although the protein synthesis inhibitor, cycloheximide, did not prevent these EGF‐mediated changes, metabolic labelling indicated a substrate‐dependent effect of EGF on the synthesis of proteins associated with the Triton‐insoluble cytoskeletal matrix. The involvement of cytoskeleton components in the EGF effects on intercellular adhesion was shown by its susceptibility to cytochalasin B, known to disorganize actin‐containing microfilaments. Some of the mechanisms of epithelial morphogenesis and the influence of extracellular matrix components on cell‐receptor/growth‐factor interactions may now be suitably analyzed by examining the EGF effects on A431 cells grown on different substrata.
Enhanced spontaneous metastasis of mouse carcinoma cells transfected with an activated c‐Ha‐ras‐1 gene
Authors: Vousden K. H. , Eccles S. A. , Purvies H. , Marshall C. J. 
Published: February 2007

AbstractTo investigate whether the presence of an activated ras oncogene influences the ability of tumour cells to metastasize, the c‐Ha‐ras‐1 oncogene cloned from EJ/T24 cells was introduced into MT1 C1.5/7 mouse mammary carcinoma cells. Since the MT1 C1.5/7 cells are already tumorigenic but have a low metastatic capacity, this experimental design allows a distinction to be made between the effects of the ras gene on metastasis and tumorigenicity. MT1 C1.5/7 containing the EJ c‐Ha‐ras‐1 metastasized more readily and to more tissue sites than control cells (2.8 sites/mouse vs 0.9 sites/mouse). The metastases expressed the EJ c‐Ha‐ras‐1 p21 ras proteins; however, one metastasis was discovered that had lost the expression of the c‐Ha‐ras‐1 gene. When these cells were re‐tested for metastasis, the rate of metastasis was indistinguishable from that of controls. This observation, coupled with a demonstration that lung colonization potential following intravenous inoculation is unaffected by the presence of the activated ras gene, argues that the effect of mutant ras genes is exerted on the ability of cells to escape from the primary tumour, rather than on a survival in the circulatory systems and ability to seed a second site.
The role of tumor‐cell surface carbohydrate in experimental metastasis
Authors: Stanford David R. , Starkey Jean R. , Magnuson James A. 
Published: February 2007

AbstractQuantitative studies on the binding of concanavalin A (Con A) and wheat‐germ agglutinin (WGA) to a series of rat hepatocarcinoma metastatic variants revealed a positive correlation between the amount of cell‐surface‐bound lectin and lung colonization potential. Scatchard analysis of Con A and WGA binding to 10 individual clones isolated from a subcutaneous (s.c.) tumor transplant and to tumor‐cell isolates from 10 individual spontaneous lung metastases from the same animal showed diverse binding characteristics for these cell populations. Nevertheless, the expression of Con A receptor sites accurately predicted the lung colonization potential of 3 isolates from the lung metastases. Higher lectin binding curves were observed for the clones from the subcutaneous tumor than for the isolates from lung metastases. These data suggest that a high Con‐A binding potential is indicative of a high lung colonization potential for these hepatocarcinoma cells, but that this phenotype may be rapidly lost during tumor outgrowth in the lungs. The binding of tumor cells to vascular endothelial cell monolayers was inhibited in the presence of Con A; however, no inhibition was observed with 2 other lectins. Attachment of tumor cells to endothelial cell monolayers was also inhibited by the monosaccharides methyl α‐D‐mannopyranoside and N‐acetyl‐D‐galactosamine. Other monosaccharides tested did not alter the attachment of tumor cells to endothelial cell monolayers.
Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T‐cell lymphotropic virus (HTLV‐III)/lymphadenopathy‐associated virus (LAV)
Authors: Balzarini Jan , Mitsuya Hiroaki , De Clercq Erik , Broder Samuel 
Published: February 2007

AbstractSuramin and various other selected compounds were evaluated for their in vitro inhibitory effects on the infectivity and replication of human T‐cell lymphotropic virus (HTLV/III)/iymphadenopathy‐associated virus (LAV). As parameters for infectivity and replication, respectively, we followed the cytopathic effect of HTLV‐III/LAV on ATH 8 cells, a T‐cell clone with high susceptibility to HTLV‐III/LAV, and the expression of HTLV‐III/LAV p24 gag protein in H9 cells infected with HTLV‐III/LAV. As the most effective inhibitors of HTLV‐III/LAV the following substances emerged (in order of decreasing activity): Evans Blue ⋍ suramin > phosphonoformic acid > Direct Yellow 50. Several purine nucleoside analogues including vidarabine, tubercidin, neplanocin A, dihydroxypropyladenine, pyrazofurin and ribavirin were not inhibitory to HTLV‐III/LAV. In our test systems, involving a high multiplicity of infection, HPA‐23, previously reported to be effective against LAV reverse transcriptase, showed no inhibitory effect on HTLV‐III/LAV infectivity for ATH 8 cells and proved only weakly inhibitory to HTLV‐III/LAV replication in H9 cells. Thus, among the anionic dyes that are structurally related to suramin, compounds were found which were as active as suramin itself, if not more so.
Cancer of the nasal cavity and paranasal sinuses, and formaldehyde exposure
Authors: Hayes Richard B. , Raatgever Jan W. , de Bruyn Arry , Gerin Michel 
Published: February 2007

AbstractThis case‐control study of nasal and paranasal sinus tumors, in males diagnosed between 1978 and 1981 in the Netherlands, was designed to identify environmental risk factors. Special attention was given to assessing any association between nasal cancer and an occupational history of possible formaldehyde exposure while taking into account histologic type of tumor, history of tobacco use, and occupational exposure to wood dust. Of the 116 cases and 259 controls identified, interviews were completed for 91 (78%) of the cases and 195 (75%) of the controls.Adenocarcinoma was strongly associated with a history of high wood dust exposure (RR = 27.0). Two independent assessments of the association between possible formaldehyde exposure and the risk for nasal cancer were carried out (Assessments A and B). By Assessment A the relative risk for nasal cancer associated with possible formaldehyde exposure was 2.5 and by Assessment B it was 1.9. The risk appeared to be most strongly associated with squamous‐cell carcinoma and could not be attributed to differences between cases and controls in age, smoking habits, or wood dust exposure. By its retrospective nature, the classification of formaldehyde exposure in this study is not based on known exposures to formaldehyde but on assessment of employment in jobs where formaldehyde exposure is thought possible. Given the limitations of the study, the authors do not consider that it provides conclusive evidence of a carcinogenic effect for formaldehyde, but that it indicates a need for further research–particularly into formaldehyde and squamous carcinoma of the nose.
Lysis of autologous tumor cells by high‐density lymphocytes is potentiated by the streptococcal preparation OK432 (picibanil)
Authors: Vánky Farkas , Uchida Atsushi , Klein Eva , Willems Jan 
Published: February 2007

AbstractIn experiments performed with tumor cells isolated from surgical specimens and lymphocytes collected at the time of surgery, tumor cells are often lysed by blood lymphocytes. Some of the effectors are present in the high‐density T‐cell subset. This population has little or no anti‐K562 activity. For the auto‐tumor lysis of T‐cells with high density, CD8‐positive cells are mainly responsible. OK432 pretreatment of the effectors potentiates the existing lytic function or induces it in cases in which the cells have no such function. In general, the potentiating effect reflects inherent patterns of cytotoxicity. In contrast to the lysis of autologous tumor cells, cells with low but not high density were induced to lyse K562.
Comparison of risk factors for cervical cancer in different populations
Authors: Rawls William E. , Lavery Carol , Marrett Loraine D. , Clarke E. Aileen , Adam Ervin , Melnick Joseph L. , Best Jennifer M. , Kraiselburd Edmundo , Benedet Louis J. , Brenes Maria M. , Quiroz Evelia , Reeves William C. 
Published: February 2007

AbstractThe incidence of cervical cancer has been found to vary between populations. Risk factors of cervical cancer include early age at first marriage, multiple marriages and antibodies to herpes simplex virus type 2 (HSV‐2). The interrelatedness of these risk factors was examined by comparing data collected from 428 cancer cases and 947 control women selected from 6 populations having standardized cervical cancer incidence rates varying from 9.3 to 85.1 per 100,000. Logistic regression analysis revealed that multiple marriages, early age at first marriage or pregnancy and HSV‐2 antibodies were all associated with significant risk when all 3 factors were entered into the model. Cervical cancer incidence rates were best predicted by the occurrence of HSV‐2 antibodies among control women. To further assess the relation between cervical cancer rates and HSV‐2 antibody, 2,306 additional sera representing an 0.8% random sample of females over 9 years of age residing in the Republic of Panama were assayed for antibodies to the virus, and the occurrence of antibodies was correlated with invasive crvical cancer rates specific to each Province. Data from both the random sample and the other study populations yielded a linear relation between the occurrence of HSV‐2 antibodies and the incidence of cervical cancer. An exception was found for women living in Herrera Province, Republic of Panama, who had a higher cancer rate than predicted by HSV‐2 antibody occurrence. The data suggested that infection with HSV‐2 is a co‐variable of venereal factors, although a role for the virus in the genesis of a certain proportion of cervical cancers is not excluded.
The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice
Authors: Ramani P. , Hart I. R. , Balkwill F. R. 
Published: February 2007

AbstractA recombinant human hybrid alpha interferon (rIFN‐α A/D) with antiviral, immunomodulating and cell‐growth‐inhibitory activity on murine cells strongly inhibited the development of experimental pulmonary metastases of the Colo 26 adenocarcinoma in BALB/c mice. Twenty‐one days after i.v. injection of 5 × 104 cells, 8/8 control mice had >200 lung tumour nodules whereas 1/6 mice receiving 500 ng rIFN‐α A/D had one lung tumour nodule and the other 5 mice were tumour‐free. Equally strong inhibition was seen in immunodeficient BALB/c nu/nu (athymic) and beige nu/nu (athymic and NK‐deficient) mice. Scheduling experiments in vivo showed that the most important time of IFN treatment was from the day of tumour cell injection to day 5, although statistically significant reductions in lung tumour nodule number and lung weight were seen even when IFN treatment was started 7 days after cell injection. rIFN‐α A/D was cytostatic to Colo 26 in vitro, causing 50% or more inhibition of cell growth or colony number at IFN levels that could be achieved in the sera of IFN‐treated mice. Although rIFN‐α A/D stimulated NK‐cell activity in BALB/c mice, Colo 26 cells were resistant in vitro to such cells whether from control or IFN treated mice.
Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects
Authors: Heicappell R. , Schirrmacher V. , von Hoegen P. , Ahlert T. , Appelhans B. 
Published: February 2007

AbstractEffective anti‐metastatic therapy was achieved in a mouse tumor model by combining surgery with postoperative immunotherapy using virus‐modified autologous tumor cells. No therapeutic effect was observed when using for immunotherapy the nonmodified autologous tumor ESb, which is only weakly immunogenic and highly metastatic. The viral modification was achieved by infecting the tumor with an avirulent strain of Newcastle disease virus (NDV), which led to expression of viral antigens and to an increase in the tumor cells' immunogenicity. Parameters which were of decisive influence for success or failure of therapy were the time of operation of the primary tumor and the dose of virus which was admixed to a standard dose of irradiated tumor cells. There was a low dose optimum of NDV at about 100 hemagglutinating units per 25 × 106 tumor cells. The therapeutic effect observed was less pronounced if the virus was given separately from the tumor cells. Postoperative immunotherapy with NDV‐modified tumor cells had the following therapeutic effects: (1) disappearance of micrometastases from visceral organs as ascertained by a sensitive bioassay; (2) life prolongation in virtually all animals when compared to controls (operated only); (3) cures in about 50% of the treated animals. The possible mechanism of this therapeutic effect and its potential for clinical application are discussed.
Chemosensitivity profiles of human cancers assessed by the 6‐day SRC assay on serially xenografted tumors
Authors: Aamdal Steinar , Fodstad Øystein , Kaalhus Olav , Pihl Alexander 
Published: February 2007

AbstractTo assess the potential value of the 6‐day subrenal capsule (SRC) assay in preclinical evaluation of new drugs using serially xenografted human tumors as source of tumor tissue, we studied the response of 31 human tumor lines (8 malignant melanomas, 12 sarcomas, 9 lung carcinomas and 2 colon carcinomas) to relevant standard drugs and to a new imidazotetrazine, Mitozolomide. Mitozolomide was found to be the most active drug tested in 50% of the lung carcinomas and as active as CCNU in melanomas. The activity of the standard anticancer drugs against subrenal grafts closely resembled the patterns seen with the same tumors in the clinic. In further attempts to validate the procedure, sensitivity profiles of some tumors were concurrently determined in the subcutaneous (s.c.) nude mouse model. In 11 out of the 12 tumors, the two assays selected the same drug as being the most active and in most of these tumors the two procedures gave the same ranking for the different drugs. Also, when the relative sensitivities of a series of melanoma xenografts to each of two drugs (DTIC and CCNU) were tested, the two assays gave the same ranking of the xenografts for each drug. The concordance between the two assays and the fact that the s.c. nude mouse assay reflects the chemosensitivity of the parent tumor in patients, suggest that the application of the 6‐day SRC assay to xenografted tumors is a valid and useful procedure permitting rapid preclinical evaluation of new drugs to be carried out at relatively low cost.